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Τετάρτη 7 Φεβρουαρίου 2018

The effect of the heights and thicknesses of the remaining root segments on buccal bone resorption in the socket-shield technique: An experimental study in dogs

Abstract

Background

To date only a few studies have been done on the use of the socket-shield technique for preserving the resorption of the buccal bone in aesthetically sensitive sites. Besides, there have been no further studies on the effect of the heights and thicknesses of the remaining root segments on buccal bone resorption when using this method.

Purpose

The aim of this study was to evaluate the effect of different heights and thicknesses of the remaining root segments on bone resorption in the socket-shield technique.

Materials and Methods

Four healthy female beagle dogs were used in this study. The third premolar (P3) and the fourth premolar (P4) on both sides of the mandible were hemisected in the buccal-lingual direction, and the clinical crown of the distal root was beheaded. In the experimental groups, the roots were worn down in the apical direction until they were located at the buccal crestal level (Group A) or 1 mm higher than that level (Group B). In the control group, the distal root segments were extracted. Then, implant placement was performed into the distal root. After 3 months of healing, the specimens were prepared for histological diagnosis.

Results

There was no difference between Group A and Group B when using the socket-shield technique, but the results of both groups were better than those of the control group.

Conclusions

The height of the root segments has little effect on the bone absorption of alveolar bone, while the bone absorption was strongly influenced by the thickness of the root segments. More precisely, the absorption may decrease if the thickness of the root fragment increases, when the thickness of the root plate is in the 0.5-1.5 mm range.



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Unusual Cause of Acute Scrotal Pain-Inflammatory Noncommunicating Hydrocele: A Pediatric Case Report

The etiology of scrotal pain is clinically classified in terms of the necessity for emergency surgery. Lately, color Doppler ultrasonography has reduced unnecessary surgeries, but there are still some cases that require immediate exploration because of an uncertain diagnosis. Here, we describe the case of a 14-month-old boy, who could not deliver his complaint accurately, presenting with a grumpy mood and a red swollen scrotum. Emergency surgery revealed that the cause was intense inflammation of the hydrocele wall, which typically does not cause acute scrotum. We also reviewed rare etiologies of scrotal pain for general physicians to develop the differential diagnosis.

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Brain tissue plasticity: protein synthesis rates of the human brain

Abstract
All tissues undergo continuous reconditioning via the complex orchestration of changes in tissue protein synthesis and breakdown rates. Skeletal muscle tissue has been well studied in this regard, and has been shown to turnover at a rate of 1–2% per day in vivo in humans. Few data are available on protein synthesis rates of other tissues. Because of obvious limitations with regard to brain tissue sampling no study has ever measured brain protein synthesis rates in vivo in humans. Here, we applied stable isotope methodology to directly assess protein synthesis rates in neocortex and hippocampus tissue of six patients undergoing temporal lobectomy for drug-resistant temporal lobe epilepsy (Clinical trial registration: NTR5147). Protein synthesis rates of neocortex and hippocampus tissue averaged 0.17 ± 0.01 and 0.13 ± 0.01%/h, respectively. Brain tissue protein synthesis rates were 3–4-fold higher than skeletal muscle tissue protein synthesis rates (0.05 ± 0.01%/h; P < 0.001). In conclusion, the protein turnover rate of the human brain is much higher than previously assumed.

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Femoral Artery Bypass Graft Pseudoaneurysm Rupture in a Transfemoral Amputee: A Case Report

We describe the case of a patient with an actively bleeding pseudoaneurysm associated with remnants of a polytetrafluoroethylene (PTFE) femoral bypass graft in their transfemoral residual limb. Initial graft placement was due to peripheral arterial disease. During subsequent transfemoral amputation, remnants of the non-patent graft were retained in the residuum. Following four years of lower limb prosthesis use, a proximal anastomosis pseudoaneurysm developed (with avulsion of graft remnants). The patient presented to clinic with a 5-day history of increased left groin fullness and largely non-radiating pain (rated 10/10). He was diagnosed with a pseudoaneurysm (1.9 cm) originating from the left common femoral artery and an associated hematoma (8 cm) on CT; this required emergent reoperation. This case highlights the importance surrounding the decision to leave or explant neovascularization materials, which may carry significant risk for infection or physical disruption complications in residual limbs. Corresponding Author Information: Jonathan Dallas, 1303 Wade Avenue, Nashville, TN 37212. jonathan.c.dallas@vanderbilt.edu The authors report no competing interests, funding for this report, or financial benefits. The material in this manuscript has not been previously described or presented. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Preliminary use of the PANESS for detecting subtle motor signs in adolescents with sport-related concussion: a brief report

Sensitive examination tools are needed to optimize evaluation after sport-related concussion (SRC). We preliminarily examined the Physical and Neurological Examination of Subtle Signs (PANESS) for sensitivity to motor changes in a pilot cohort of adolescents aged 13-17 with SRC. 15 Adolescents (5 females) with SRC were evaluated up to 3 times: within 2 weeks of injury, approximately 1 month later (mean 35 days between visits), and for those not recovered at the second visit, again following clinical recovery (mean 70 days between first and last visits for all participants). Comparison data were acquired from 20 age and sex-matched never-concussed healthy control athletes with no history of concussion who were evaluated twice (mean 32 days apart). Main effects of group, time, and interaction effects were evaluated with an analysis of covariance which controlled for socioeconomic status, times tested, and days between testing sessions. Adolescents with concussion had poorer PANESS performance than controls at all time points. Performance improved between visits within the concussion group with no change within the control group. These findings suggest that the PANESS merits additional study in larger cohorts and in combination with other markers of injury to facilitate an enhanced understanding of sports-related concussion and recovery. *Work was conducted while Dr. Stephens was at Kennedy Krieger Institute and Johns Hopkins; she has since moved to Colorado State University. Corresponding Author: Stacy Suskauer, Kennedy Krieger Institute, 7007 N. Broadway, Baltimore, MD, 21205. Email: suskauer@kennedykrieger.org Disclosures: There are no competing interests or financial benefit to the authors to report. Study Funding This research was supported by the National Institutes of Health (J.S. 5T32HD007414); (T.M. & S.S., R21HD080378). Prior Presentation of the Research Prior presentations of this work have been limited to talks given by the senior author (S.S.). Acknowledgements: We thank Dr. Jennifer Reesman for assistance with study design and management. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Issue Information



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Erratum



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Issue Information



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Clinical and Novel Biomarkers in the Management of Prostate Cancer

Opinion statement

Clinical outcomes in prostate cancer after initial screening and treatment for organ-confined disease and in advanced stage after drug intervention can be heterogeneous. Serum prostate-specific antigen which has a modest value as a screening biomarker while widely used in practice in all subsequent stages has limitations for prognostication or prediction of drug efficacy. Recent advances in genomic sciences and the identification of the mutational landscape of organ-confined and advanced-stage disease have contributed to the development of molecular biomarker profiling in addition to serum prostate-specific antigen. Genomic biomarkers are in development for application to screening for lethal disease subtypes, monitoring of disease recurrence after initial treatments, prognostication, as well as for prediction of drug efficacy. The application of translational molecular profiling in prostate cancer has the potential to enhance clinical management and outcomes in the future. Molecular biomarkers in development in organ-confined disease include both DNA- and RNA-based candidate and pathway-based biomarkers. In advanced-stage disease, molecular biomarker profiling has emerged for identifying therapeutic targets, prediction of drug efficacy, and for prognostication of survival that includes germline single nucleotide profiling and somatic aberrations including copy number variation and mutations and RNA-based profiling. This review summarizes the current state of clinical biomarkers used in practice, their limitations, and novel molecular biomarkers being developed for several clinical endpoints in early- and late-stage cancer.



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Options for Adjuvant Therapy for Uterine Leiomyosarcoma

Opinion statement

Uterine leiomyosarcoma (uLMS) is a rare disease; in the data from the SEER database, 3165 cases of uLMS were diagnosed between January 2000 and December 2012. While a majority of patients (60%) are diagnosed with early stage disease, recurrence rates are high. Five-year disease-specific survival is 76% for patients with FIGO stage I and 60% for patients with FIGO stage II disease. Adjuvant treatments, including radiation therapy, chemotherapy, and combined modality approaches, have been explored with the goal of demonstrating improved survival. However, heterogeneous patient populations, small sample sizes, and lack of no-treatment control arms have limited the interpretation and reliability of the results from these studies. A randomized trial of adjuvant pelvic radiation compared to no additional treatment showed that adjuvant radiation did not improve recurrence or survival outcomes for early-stage uterine LMS. To date, no prospective, randomized trial has been completed comparing adjuvant chemotherapy to observation. A recent well-designed retrospective study showed that women treated with adjuvant gemcitabine-docetaxel had no improvement in progression-free or overall survival compared to women who received no additional treatment. Thus, current data support our recommendation against adjuvant radiation or chemotherapy treatment for patients with non-morcellated, completely resected, and uterine-confined leiomyosarcoma. We recommend that these patients be observed with periodic surveillance imaging and physical examinations.



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Second Malignancies after Hematopoietic Stem Cell Transplantation

Opinion statement

Second malignancies are a rare but well-defined late complication after autologous and allogeneic hematopoietic stem-cell transplantation (SCT). Solid malignancies occur in up to 15% of patients 15 years after SCT with myeloablative conditioning, with no plateau in the incidence rates. They are responsible for 5–10% of late deaths after SCT. The incidence is increased with advanced age at SCT. The major risk factors are the use of total body irradiation, which is associated with adenocarcinomas and with chronic graft-versus-host disease which is associated with squamous cell cancers. There is less data on the incidence of second malignancies after reduced-intensity conditioning, but it may not be lower. The types of solid tumors reported in excess include melanoma and other skin cancers; cancers of the oral cavity and head and neck, brain, liver, uterine cervix, thyroid, breast, lung; and possibly gastrointestinal cancers. Therapy-related myeloid neoplasms (t-MN) are more common after autologous SCT and may be related mostly to pre-transplant therapies. Post-transplant lymphoproliferative disease is donor-cell-derived lymphoma that is more common after allogeneic SCT with T-cell depletion or intensive immune-suppression state. Second malignancies are most often treated similarly to the standard therapy for similar malignancies. Lifelong cancer screening and prevention interventions are required for all transplantation survivors.



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Novel Therapies for Older Adults With Acute Lymphoblastic Leukemia

Abstract

Purpose of Review

Older adults with acute lymphoblastic leukemia (ALL) have worse survival compared to their younger counterparts. Here, we review the reasons for the poorer outcomes of older patients with ALL and also summarize the current and future therapeutic approaches to ALL in the elderly population.

Recent Findings

The poor outcomes of older adults with ALL are driven largely by lack of tolerance to standard-dose chemotherapy, which leads to unacceptably high rates of myelosuppression-related deaths. Recent studies have shown promising results with the use of low-intensity or chemotherapy-free regimens in older patients with ALL, which are able to retain efficacy without excess toxicity.

Summary

Novel antibody constructs such as inotuzumab ozogamicin and blinatumomab as well as potent later-generation tyrosine kinase inhibitors such as ponatinib hold significant promise in the management of ALL in the older adult. Innovative combination strategies may further improve the outcomes of these patients.



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Face stimulus eliminates antisaccade-cost: gaze following is a different kind of arrow

Abstract

When a person suddenly looks in a certain direction, others seem to shift their attention to the same, looked-at, location. This common observation, that gaze-of-another seems to trigger reflexive shifts of attention within an observer, has been demonstrated in various studies. Yet just how reflexive it truly is, is an on-going controversy. Unlike most studies in which gaze cues were distractors in a cueing paradigm, the current study used gaze cues as triggers in a mixed pro- and anti-saccade task and a Posner-like discrimination task. In a set of two experiments, we investigated whether attention triggered by gaze-of-another differs from attention triggered by peripheral (exogenous) and arrow stimuli. In the first experiment, gaze cues resulted in slowed saccadic responses and in the elimination of the anti-saccade-cost associated with reflexive orienting. Pro-saccades triggered by peripheral cues had significantly fewer errors and shorter reaction times than anti-saccades. However, there was no significant difference between pro and anti-saccades triggered by gaze cues. Thus, counter to expectations, gaze did not produce reflexive shifts of overt attention. The second experiment showed that attention triggered by gaze cues is no different from attention triggered by biologically irrelevant arrow cues. They both eliminated the anti-saccade-cost and displayed prolonged reaction times. However, manual discrimination RTs showed no significant differences between gaze and peripheral cues. Together, these results suggest that neither gaze nor arrow cues trigger reflexive shifts of overt attention.



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Genetic profiling of cell-free DNA from cerebrospinal fluid: opening the barrier to leptomeningeal metastasis in EGFR-mutant NSCLC



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Final Validation of the ProMisE Molecular Classifier for Endometrial Carcinoma in a Large Population-based Case Series.

Abstract
Introduction
Based on The Cancer Genome Atlas, we previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). ProMisE identifies four prognostically distinct molecular subtypes, and can be applied to diagnostic specimens (biopsy/curettings), enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier prior to clinical application.
Patients and Methods
We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003-13. Primary outcomes of overall, disease-specific and progression-free survival were evaluated for clinical, pathological, and molecular features.
Results
Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 – 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB (89 (19.7%)), stage II (26 (5.8%)), and stage III/IV (61 (13.5%)). ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognostic marker for progression-free (P=0.001) and disease-specific (P=0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, kappa 0.88.
Discussion
We have developed, confirmed and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.

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Epigenetic modifiers as new immunomodulatory therapies in solid tumours

Abstract
Background
Immune therapies have revolutionized cancer treatment over the last few years by allowing improvements in overall survival. However, the majority of patients is still primary or secondary resistant to such therapies, and enhancing sensitivity to immune therapies is therefore crucial to improve patient outcome. Several recent lines of evidence suggest that epigenetic modifiers have intrinsic immunomodulatory properties, which could be of therapeutic interest.
Material and Methods
We reviewed preclinical evidence and clinical studies which describe or exploit immunomodulatory properties of epigenetic agents. Experimental approaches, clinical applicability and corresponding ongoing clinical trials are described.
Results
Several epigenetic modifiers, such as histone deacetylase inhibitors, DNA methyl transferase inhibitors, bromodomain inhibitors, lysine-specific histone demethylase 1 inhibitors and enhancer of zeste homolog 2 inhibitors, display intrinsic immunomodulatory properties. The latter can be achieved through the action of these drugs either on cancer cells (e.g. presentation and generation of neoantigens, induction of immunogenic cell death, modulation of cytokine secretion), on immune cells (e.g. linage, differentiation, activation status and antitumor capability), or on components of the microenvironment (e.g. regulatory T cells and macrophages). Several promising combinations, notably with immune checkpoint blockers or adoptive T cell therapy, can be envisioned. Dedicated clinically-relevant approaches for patient selection and trial design will be required to optimally develop such combinations.
Conclusion
In an era where immune therapies are becoming a treatment backbone in many tumour types, epigenetic modifiers could play a crucial role in modulating tumours' immunogenicity and sensitivity to immune agents. Optimal trial design, including window of opportunity trials, will be key in the success of this approach, and clinical evaluation is ongoing.

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Inequalities in the risk of disability due to traffic injuries in the Spanish adult population, 2009-2010

Publication date: Available online 7 February 2018
Source:Injury
Author(s): Rocío Palmera-Suárez, Teresa López-Cuadrado, Rafael Fernández-Cuenca, Enrique Alcalde-Cabero, Iñaki Galán
BackgroundAlthough traffic injuries (TIs) are an important cause of disability the related factors are little known. We aimed to estimate the differences in risk of TI-related disability according to individual characteristics that might generate health inequalities.MethodsCross-sectional study using a representative Spanish population sample drawn from the European Health Interview Survey 2009/2010. We calculated traffic crashes in the preceding year which resulted in injuries. Disability was measured using the Global Activity Limitation Indicator and four indicators of limitations (sensory, physical functional, self-care and domestic activities). Principal socio-demographic and behavioural/lifestyle variables were studied. We used multivariate logistic regression to estimate the risk (ORs) of TI-related disability in the sample as whole and disability-related factors in persons who had experienced TIs.ResultsPersons with TIs had a higher risk of global disability (OR = 1.61; 95%CI:1.17–2.20), physical functional limitations (OR = 1.96; 95%CI:1.33–2.89) and self-care limitations (OR = 1.73; 95%CI:0.98–3.05). Among persons with TIs, GALI-related risk was higher in women (OR = 3.06, p = 0.002) and persons aged over 30 years (OR31-45years = 6.81, p < 0.001; OR46–64years = 5.96, p = 0.011; OR>64years = 4.54, p = 0.047). Lower risk was observed among persons with a higher educational level (OR = 0.22, p = 0.003). The risk of disability among persons with TIs who consumed illegal drugs was OR = 3.9 (p = 0.023).ConclusionsTraffic injuries in the preceding year are associated with higher risk of disability, which is unevenly distributed. Individual (women and persons over 30 years), socio-economic (lower educational level) and behavioural (illegal drug use) factors are involved. Actions aimed at changing the unequal risk among vulnerable subgroups and providing health, social and protective services should be implemented.



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Identification of a novel lethal form of autosomal recessive ichthyosis caused by UDP-glucose ceramide glucosyltransferase deficiency

Thumbnail image of graphical abstract

UGCG:NM_003358:exon2:c.142dupA;p.(Ser48Lysfs*18).



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Anti-aging potential of extracts from Sclerocarya birrea (A. Rich.) Hochst and its chemical profiling by UPLC-Q-TOF-MS

Degradation of components of the extracellular matrix such as elastin and collagen by elastase and collagenase accelerates skin aging. Phytochemicals that inhibit the activity of these enzymes can be developed...

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Tumor necrosis and >20 mitoses per 50 high-power fields can distinguish ‘very high-risk’ and ‘highest-risk’ within ‘high-risk’ gastric gastrointestinal stromal tumor

Future Oncology, Ahead of Print.


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Why does a high-fat diet increase cancer risk?

Future Oncology, Ahead of Print.


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High-fat diet and colorectal cancer: myths and facts

Future Oncology, Ahead of Print.


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The immediate and short-term effects of bilateral intrahippocampal depth electrodes on verbal memory

Summary

In contrast to previous studies, Ljung et al. provide evidence of permanent cognitive consequences of bilateral intrahippocampal depth electrodes for verbal memory in patients who were not operated or operated in the right temporal lobe. Stimulated by this, we provide historical confirmatory and supplementary evidence of the detrimental effect of bilateral depth electrodes implanted along the longitudinal axis of the hippocampus on verbal learning and especially on delayed verbal memory and recognition performance. This is demonstrated in 31 patients with memory assessments before implantation, after explantation, and 3 months later after left/right temporal lobe surgery. After surgery, significant recovery from postimplantation impairment is found in right temporal patients. Left temporal resection patients stay on the level seen after implantation and do not recover. Surgery, however, has its own effects in addition to the implantation. Intracranial electrodes for electroencephalographic monitoring or electrical stimulation are commonly and increasingly used for diagnosis or treatment in pharmacoresistant epilepsies. Thus, the monitoring of invasive stereotactic approaches is recommended to find safe procedures for the patients. In response to the findings, we restricted indications and used different implantation schemes, different trajectories, and targets to minimize the risk of additional damage.



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Can Work Be Required in the Medicaid Program?

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On January 11, 2018, a new policy encouraging states to develop work requirements in their Medicaid programs was issued by the Centers for Medicare and Medicaid Services (CMS). Under this policy, states can require nonelderly, nondisabled adults to work or engage in community service to qualify for…

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First international TNBC conference meeting report

Abstract

Recently, Georgia State University's Centennial Hall was the premier location for the 2017 International Conference on Triple Negative Breast Cancer (TNBC): Illuminating Actionable Biology, which was held from Sept. 18 to 20, 2017, in Atlanta, USA. The conference featured a stellar line-up of domestic and international speakers and diverse participants including TNBC survivors, luminaries in breast cancer research, medical students and fellows, clinicians, translational researchers, epidemiologists, biostatisticians, bioinformaticians, and representatives from the industry. This report distills the burning questions that spiked the event and summarizes key themes, findings, unique opportunities and future directions that emerged from this confluence of thought leaders.



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Metastatic Prostate Cancer

Care for men with prostate cancer is a major global health care challenge, compounded by an aging population and increasing frequency of diagnosis. The priorities today are similar to those in the recent past: minimizing overtreatment of indolent disease and improving outcomes for patients with…

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Editorial Board



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Contents



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Editorial: a novel technology for the assessment of non-alcoholic fatty liver disease

Linked content

This article is linked to Eddowes et al paper. To view this article visit https://doi.org/10.1111/apt.14469.



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Editorial: weighing the global risk of cancer with thiopurines in inflammatory bowel disease—Authors' reply

Linked content

This article is linked to Lu et al and Laharie and Riviere papers. To view these articles visit https://doi.org/10.1111/apt.14436 and https://doi.org/10.1111/apt.14475.



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Letter: innovative use of the alfapump system to treat a small hepatocellular carcinoma

Linked content

This article is linked to Stirnimann et al and Stirnimann and De Gottardi papers. To view these articles visit https://doi.org.10.1111/apt.14331 and https://doi.org.10.1111/apt.14500.



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Letter: the efficacy and safety of rifaximin for the prophylaxis of spontaneous bacterial peritonitis in cirrhotic patients

Linked content

This article is linked to Goel et al paper. To view this article visit https://doi.org/10.1111/apt.14361.



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Editorial: looking for patients at risk of cirrhosis in the general population—many needles in a haystack

Linked content

This article is linked to Harman et al paper. To view this article visit https://doi.org/10.1111/apt.14463.



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Letter: nutritional benefits of rifaximin in cirrhotic patients

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This article is linked to Kang et al paper. To view this article visit https://doi.org/10.1111/apt.14275.



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Letter: what gastroenterologists should know about VSL#3

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This article is linked to McIlroy et al paper. To view this article visit https://doi.org/10.1111/apt.14384.



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Letter: innovative use of the alfapump system to treat small hepatocellular carcinoma – authors' reply

Linked content

This article is linked to Stirnimann et al and Weil et al papers. To view these articles visit https://doi.org/10.1111/apt.14331 and https://doi.org/10.1111/apt.14440.



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Editorial: weighing the global risk of cancer with thiopurines in inflammatory bowel disease

Linked content

This is article is linked to Lu et al and Qui et al papers. To view these articles visit https://doi.org/10.1111/apt.14436 and https://doi.org/10.1111/apt.14498.



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Oncogenic HSP60 regulates mitochondrial oxidative phosphorylation to support Erk1/2 activation during pancreatic cancer cell growth

Oncogenic HSP60 regulates mitochondrial oxidative phosphorylation to support Erk1/2 activation during pancreatic cancer cell growth

Oncogenic <i>HSP60</i> regulates mitochondrial oxidative phosphorylation to support Erk1/2 activation during pancreatic cancer cell growth, Published online: 07 February 2018; doi:10.1038/s41419-017-0196-z

Oncogenic HSP60 regulates mitochondrial oxidative phosphorylation to support Erk1/2 activation during pancreatic cancer cell growth

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Regenerative potential of tonsil mesenchymal stem cells on surgical cutaneous defect

Regenerative potential of tonsil mesenchymal stem cells on surgical cutaneous defect

Regenerative potential of tonsil mesenchymal stem cells on surgical cutaneous defect, Published online: 07 February 2018; doi:10.1038/s41419-017-0248-4

Regenerative potential of tonsil mesenchymal stem cells on surgical cutaneous defect

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Regulation of senescence escape by the cdk4–EZH2–AP2M1 pathway in response to chemotherapy

Regulation of senescence escape by the cdk4–EZH2–AP2M1 pathway in response to chemotherapy

Regulation of senescence escape by the cdk4–EZH2–AP2M1 pathway in response to chemotherapy, Published online: 07 February 2018; doi:10.1038/s41419-017-0209-y

Regulation of senescence escape by the cdk4–EZH2–AP2M1 pathway in response to chemotherapy

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Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death

Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death

Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death, Published online: 07 February 2018; doi:10.1038/s41419-017-0252-8

Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death

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bFGF plays a neuroprotective role by suppressing excessive autophagy and apoptosis after transient global cerebral ischemia in rats

bFGF plays a neuroprotective role by suppressing excessive autophagy and apoptosis after transient global cerebral ischemia in rats

bFGF plays a neuroprotective role by suppressing excessive autophagy and apoptosis after transient global cerebral ischemia in rats, Published online: 07 February 2018; doi:10.1038/s41419-017-0229-7

bFGF plays a neuroprotective role by suppressing excessive autophagy and apoptosis after transient global cerebral ischemia in rats

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Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling

Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling

Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling, Published online: 07 February 2018; doi:10.1038/s41419-017-0230-1

Bone morphogenetic protein 2 promotes human trophoblast cell invasion by upregulating N-cadherin via non-canonical SMAD2/3 signaling

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miR-27b-3p inhibits proliferation and potentially reverses multi-chemoresistance by targeting CBLB/GRB2 in breast cancer cells

miR-27b-3p inhibits proliferation and potentially reverses multi-chemoresistance by targeting CBLB/GRB2 in breast cancer cells

miR-27b-3p inhibits proliferation and potentially reverses multi-chemoresistance by targeting CBLB/GRB2 in breast cancer cells, Published online: 07 February 2018; doi:10.1038/s41419-017-0211-4

miR-27b-3p inhibits proliferation and potentially reverses multi-chemoresistance by targeting CBLB/GRB2 in breast cancer cells

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Homocysteine activates autophagy by inhibition of CFTR expression via interaction between DNA methylation and H3K27me3 in mouse liver

Homocysteine activates autophagy by inhibition of CFTR expression via interaction between DNA methylation and H3K27me3 in mouse liver

Homocysteine activates autophagy by inhibition of <i>CFTR</i> expression via interaction between DNA methylation and H3K27me3 in mouse liver, Published online: 07 February 2018; doi:10.1038/s41419-017-0216-z

Homocysteine activates autophagy by inhibition of CFTR expression via interaction between DNA methylation and H3K27me3 in mouse liver

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In This Issue



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Table of Contents



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Masthead



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Editorial board



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Audit of 117 otoplasties for prominent ear by one surgeon using a cartilage-cutting procedure

Background

The plethora of surgical procedures for prominent ear correction reflects lack of satisfaction with outcomes achieved. This paper describes a cartilage-cutting otoplasty procedure and reports an audit of its outcomes.

Methods

Discharge coding was used to retrospectively identify patients who had undergone the otoplasty of interest at Middlemore Hospital, Auckland, during the 5 years from March 2010 to the end of February 2015. Hospital records were accessed. Demographic, procedure and patient satisfaction data were recorded and analysed (PASW/SPSS Statistics 18.0). Chi-square test and t-test were used to assess associations, with significance accepted at two-sided P < 0.05.

Results

Sixty-four patients underwent the specified otoplasty (54.7% females: mean age 9.5 years (standard deviation, SD: 4.2; range: 4–20)), of whom 93.8% had bilateral procedures with mean surgical time of 61 min (SD: 14; range: 34–94). This was significantly shorter (P < 0.001) than for bilateral surgeries by all other techniques and surgeons in the review period. None of the 117 procedures of interest subsequently had suture extrusion or revision surgery. Mean time from surgery to satisfaction determination was 993 days (SD: 521; range: 111–1850) for 43 (67.2%) patients. 23.3% believed that there had been aesthetically insignificant partial recurrence of prominence, typically of one ear only. This was insufficient for all but one patient to consider repeat otoplasty. Surgery outcome was rated 'very satisfactory' and 'satisfactory' by 90.7% and 9.3% of patients/parents, respectively. All would recommend the surgery to others.

Conclusion

With infrequent complications and recurrence requiring revision, and without long-term reliance on sutures, the otoplasty reported is time-efficient, safe and generates high patient satisfaction.



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Uterine colorectal metastatic disease: a rare occurrence



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Clinical characteristics affecting length of stay in patients with cellulitis

Background

This study aimed to profile the clinical characteristics of patients presenting to Middlemore Hospital with cellulitis in order to identify factors that are associated with an increased length of stay (LOS).

Methods

Retrospective clinical data were collected for all patients aged 18 and above who were admitted with cellulitis to Middlemore Hospital General Surgical Department between 1 January and 31 March 2014. Comorbidities, laboratory results and medical conditions were included in the investigation.

Results

The study included 201 patients. Significant factors associated with increased LOS include type 2 diabetes mellitus (P < 0.012), obesity (P < 0.001), raised C-reactive protein (P < 0.0001), raised white cell count (P < 0.0001), raised temperature (P < 0.0001), septic shock (P < 0.003), multiorgan failure (P < 0.01), extended-spectrum beta-lactamases or methicillin-resistant Staphylococcus aureus colonization (P < 0.04) and intensive care unit admission (P < 0.0004).

Conclusion

This single-centre, retrospective clinical study has identified several factors that are significantly associated with an increased LOS. These factors provide a basis for future studies that may facilitate identification and timely medical optimization of high-risk patients.



http://ift.tt/2GYdMxU

The Association of Digit Ratio (2D : 4D) with Cancer: A Systematic Review and Meta-Analysis

Objective. Intrauterine sex hormone environment as indicated by the second to the fourth digit ratio (2D : 4D) can be associated with cancer risk. This systematic review and meta-analysis aimed to evaluate the association of 2D : 4D with cancer diagnosis, malignancy, and age at presentation. Methods. Studies that evaluated the association of 2D : 4D with cancer risk were collected from Pubmed/MEDLINE and Clarivate Analytics databases. Nineteen studies were included in the qualitative analysis. Results. The 2D : 4D ratio was studied in prostate cancer, breast cancer, testicular cancer, gastric cancer, oral cancer, brain tumors, and cervical intraepithelial neoplasia. Low 2D : 4D was associated with prostate cancer, gastric cancer, and brain tumors, while high 2D : 4D, with breast cancer risk and cervical dysplasia. The 2D : 4D ratio was not associated with prostate, breast, and gastric cancer stage. Greater 2D : 4D ratio was associated with younger presentation of breast cancer and brain tumors. The meta-analyses demonstrated that testicular cancer was not associated with right-hand 2D : 4D ratio () and gastric cancer was not associated with right-hand () and left-hand () 2D : 4D ratio. Conclusions. Sex hormone environment during early development is associated with cancer risk later in life. Further studies exploring the link between intrauterine hormone environment and cancer risk are encouraged.

http://ift.tt/2nPzcV6

EXTRAESOPHAGEAL SYMPTOMS AND DISEASES ATTRIBUTED TO GERD: Where is the pendulum swinging now?

The purpose of this review is to outline the recent developments in the field of extraesophageal reflux disease and provide clinically relevant recommendations.

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A new marker for severity of alcoholic hepatitis



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Risk of Oral and Upper Gastrointestinal Cancers in Persons With Positive Results From a Fecal Immunochemical Test in a Colorectal Cancer Screening Program

European guidelines recommend screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT), with follow-up colonoscopies for individuals with positive test results. However, more than half of participants with positive results from the FIT are not found to have advanced neoplasia in the colonoscopy examination. Fecal occult blood might also come from the upper gastrointestinal (GI) tract, so perhaps we should consider esophagogastroduodenoscopy (EGD), to detect upper GI cancers.

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A hard nut to crack: Bouveret's syndrome



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Increased Waitlist Mortality and Lower Rate for Liver Transplantation in Hispanic Patients with Primary Biliary Cholangitis

Data on the differences in ethnicity and race among patients with primary biliary cholangitis (PBC) awaiting liver transplantation (LT) are limited. We evaluated liver transplant waitlist trends and outcomes based on ethnicity and race in patients with PBC in the United States.

http://ift.tt/2BgHyO0

Predictors of Late Palliative Care Referral in Children with Cancer

Early integration of palliative care (PC) in the management of children with high-risk cancer is widely endorsed by patients, families, clinicians, and national organizations. However, optimal timing for PC consultation is not standardized, and variables that influence timing of PC integration for children with cancer remain unknown.

http://ift.tt/2BJSjt3

Can Work Be Required in the Medicaid Program?

New England Journal of Medicine, Ahead of Print.


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Metastatic Prostate Cancer

New England Journal of Medicine, Ahead of Print.


http://ift.tt/2siNBhU

Can Work Be Required in the Medicaid Program?

New England Journal of Medicine, Ahead of Print.


http://ift.tt/2EqGmcN

Metastatic Prostate Cancer

New England Journal of Medicine, Ahead of Print.


http://ift.tt/2siNBhU

Semi-automated ultrasound guidance applied to nasogastrojejunal tube replacement for enteral nutrition in critically ill adults

At present, the enteral nutrition approaches via nose and duodenum (or nose and jejunum) are the preferred method of nutritional support in the medical engineering field, given the superiority of in line with ...

http://ift.tt/2nJMVh8

Advances in intelligent diagnosis methods for pulmonary ground-glass opacity nodules

Pulmonary nodule is one of the important lesions of lung cancer, mainly divided into two categories of solid nodules and ground glass nodules. The improvement of diagnosis of lung cancer has significant clinic...

http://ift.tt/2nQ3QgZ

Clinical relevance of oncologic prognostic factors in the decision-making of pre-hepatectomy chemotherapy for colorectal cancer hepatic metastasis: the priority of hepatectomy

Abstract

Background

Although liver resection (LR) provides the best chance of long-term survival for patients with colorectal cancer (CRC) hepatic metastasis, concerns regarding chemotherapy before liver resection remain unresolved.

Methods

A retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and February 2016 was performed. Outcome relevance based on oncologic prognostic factors and chemotherapy prior to liver resection was assessed.

Results

Patients who had received pre-hepatectomy chemotherapy for CRC hepatic metastasis and delayed liver resection had a worse outcome in terms of CRC recurrence following liver resection. The hazard ratio (HR) of pre-hepatectomy chemotherapy in patients with minor oncologic prognostic factors was 1.55 (confidence interval, CI = 1.07–2.26, p = 0.021) for CRC recurrence after liver resection for hepatic metastasis, whereas the HR of pre-hepatectomy chemotherapy was 1.34 (CI = 0.99–1.81, p = 0.062) for CRC recurrence in patients with multiple oncologic prognostic factors.

Conclusion

The administration of pre-hepatectomy chemotherapy and delaying liver resection seems not to be an optimal strategy to provide a clinical benefit for patients with CRC hepatic metastasis. Hence, liver resection should be attempted without delay at the initial detection of CRC hepatic metastasis whenever possible.



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High density of M2-macrophages in acral lentiginous melanoma compared to superficial spreading melanoma

Abstract

Aims

Acral lentiginous melanoma (ALM) is the most common type of melanoma in people with darker skin phototypes. There is some evidences that the etiology, pathogenesis, risk factors, and natural history of ALM differ from those of superficial spreading melanoma (SSM). ALM behaves more aggressively than SSM, but the biological explanation for these differences remains unknown.

The presence of one subtype of macrophages, termed M2-macrophage (M2-M), has been found to be related to local progression, metastasis, and poor prognosis in several neoplasms. The aim of this study was to compare the density of M2-Ms in ALMs versus SSMs, and to examine whether the density of M2-Ms is associated with histopathological features predictive of adverse prognosis in cutaneous melanoma (CM), as well as development of metastasis.

Methods and results

Sixty-seven ALMs and 67 SSMs cases were analyzed. The tumors were classified according to thickness, ulceration, mitosis and metastasis. M2-M quantity was evaluated using immunohistochemistry with anti-CD163 and anti-CD206 antibodies. M2-Ms were increased in ALM compared with SSM, and were related to the histopathological features predictive of adverse prognosis in CM, such as thickness >1.0 mm, ulceration, and mitotic activity, and the development of metastasis.

Conclusions

Our study is the first to demonstrate increased presence of M2-Ms in ALM compared with SSM. Our findings suggest that the increased M2-Ms in ALM is associated with the main histopathological features predictive of adverse prognosis in CM, as well as the presence of metastasis and that these cells can be related with the aggressive behavior seen in ALMs.

This article is protected by copyright. All rights reserved.



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IgG4-related sclerosing oesophagitis in a 9-year-old girl

Abstract

Immunoglobulin G4 (IgG4)-related disease is a fibroinflammatory disorder characterised by a histopathological pattern of dense lymphoplasmocytic inflammation, fibrosis, obliterative phlebitis, and demonstration of dominance of IgG4-positive plasmocytes. Recognition of the disease entity is vital due its frequent misdiagnosis as a malignant tumour, which can result in unnecessary treatment measures including surgery. Despite recent insights into the mechanisms behind IgG4-related disease, a review of the literature yields only 13 (adult) cases of IgG4-related disease occuring within the oesophagus.

This article is protected by copyright. All rights reserved.



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Can Perceptual Experiences Be Rational?

The Rationality of Perception, by SiegelSusanna. Oxford: Oxford University Press, 2018. Pp. xxv + 221.

http://ift.tt/2FROzDV

Judgements about Thought Experiments

Abstract
Thought experiments invite us to evaluate philosophical theses by making judgements about hypothetical cases. When the judgements and the theses conflict, it is often the latter that are rejected. But what is the nature of the judgements such that they are able to play this role? I answer this question by arguing that typical judgements about thought experiments are in fact judgements of normal counterfactual sufficiency. I begin by focusing on Anna-Sara Malmgren's defence of the claim that typical judgements about thought experiments are mere possibility judgements. This view is shown to fail for two closely related reasons: it cannot account for the incorrectness of certain misjudgements, and it cannot account for the inconsistency of certain pairs of conflicting judgements. This prompts a reconsideration of Timothy Williamson's alternative proposal, according to which typical judgements about thought experiments are counterfactual in nature. I show that taking such judgements to concern what would normally hold in instances of the relevant hypothetical scenarios avoids the objections that have been pressed against this kind of view. I then consider some other potential objections, but argue that they provide no grounds for doubt.

http://ift.tt/2GZiCuH

The Boundary Stones of Thought: An Essay in the Philosophy of Logic, by Ian Rumfitt

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The Boundary Stones of Thought: An Essay in the Philosophy of Logic, by RumfittIan. Oxford: Clarendon Press, 2014. Pp. xiv + 345. H/b £40.00.

http://ift.tt/2FROv79

Dark Ghettos: Injustice, Dissent, and Reform, by Tommie Shelby

Dark Ghettos: Injustice, Dissent, and Reform, by ShelbyTommie. Cambridge, MA: Belknap Press of Harvard University Press, 2016. Pp. xii + 352.

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Causation & Free Will, by Carolina Sartorio

Causation & Free Will,, by SartorioCarolina. Oxford: Oxford University Press, 2016. Pp. viii + 188.

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The Aesthetics of Argument, by Martin Warner

The Aesthetics of Argument, by WarnerMartin. Oxford: Oxford University Press, 2016. Pp. xvii + 318.

http://ift.tt/2GZiw6j

Between Logic and the World, by Bernhard Nickel

Between Logic and the World, by NickelBernhard. Oxford: Oxford University Press, 2016. Pp. 286.

http://ift.tt/2FROnob

What is Reasoning?

Abstract
Reasoning is a certain kind of attitude-revision. What kind? The aim of this paper is to introduce and defend a new answer to this question, based on the idea that reasoning is a goodness-fixing kind. Our central claim is that reasoning is a functional kind: it has a constitutive point or aim that fixes the standards for good reasoning. We claim, further, that this aim is to get fitting attitudes. We start by considering recent accounts of reasoning due to Ralph Wedgwood and John Broome, and argue that, while these accounts contain important insights, they are not satisfactory: Wedgwood's rules out too much, and Broome's too little. We then introduce and defend our alternative account, discuss some of its implications and attractions, and, finally, consider objections.

http://ift.tt/2GZihYX

Backwards Causation and the Chancy Past

Abstract
I argue that the past can be objectively chancy in cases of backwards causation, and defend a view of chance that allows for this. Using a case, I argue against the popular temporal view of chance, according to which (i) chances are defined relative to times, and (ii) all chancy events must lie in the future. I then state and defend the causal view of chance, according to which (a) chances are defined relative to causal histories, and (b) all chancy events must lie causally downstream. The causal view replicates the intuitively correct results of the temporal view in cases of ordinary forwards causation, while correctly handling cases of backwards causation. I conclude that objective chance is more closely related to the direction of causation than it is to the direction of time.

http://ift.tt/2FVnUWZ

Frege on Judgement and the Judging Agent

Abstract
How is Frege able to claim that the notion of judgement is essential to his logic without introducing a form of psychologism? I argue first that Frege's logical notion of judgement is to be distinguished from an empirical notion of judgement, that it cannot be understood as an abstract, idealized notion, and that there are doubts concerning a transcendental reading of Frege's writings. Then, I explain that the logical notion of judgement has to be understood from a first-person perspective, to be contrasted with a third-person perspective, in which judgement is understood as an empirical, psychological phenomenon. Frege's logic is essentially a first-person engagement, as each of us can make use of the ideography as a science of logic only if we ourselves have made the relevant judgements. Finally, I claim that the judging agent as conceived by Frege can, after all, be understood as a transcendental ego.

http://ift.tt/2GYPJP8

Intuitions are Used as Evidence in Philosophy

Abstract
In recent years a growing number of philosophers writing about the methodology of philosophy have defended the surprising claim that philosophers do not use intuitions as evidence. In this paper I defend the contrary view that philosophers do use intuitions as evidence. I argue that this thesis is the best explanation of several salient facts about philosophical practice. First, philosophers tend to believe propositions which they find intuitive. Second, philosophers offer error theories for intuitions that conflict with their theories. Finally, philosophers are more confident in rejecting theories to the extent that they have several (intuitive) counter examples involving diverse cases. I argue that these facts are better explained by philosophers' using intuitions as evidence than by any plausible contrary explanations. I further argue that aspects of philosophical practice that my thesis may initially seem ill-suited to explain are in fact unsurprising whether or not my thesis is true.

http://ift.tt/2FS4mmf

The Things We Do with Identity

Abstract
Cognitive partitions are useful. The notion of numerical identity helps us induce them. Consider, for instance, the role of identity in representing an equivalence relation like taking the same train. This expressive function of identity has been largely overlooked. Other possible functions of the concept have been over-emphasized. It is not clear that we use identity to represent individual objects or quantify over collections of them (numerically or otherwise). Understanding what the concept is good for looks especially urgent in light of the fact that numerical identities themselves are tangibly trifling.

http://ift.tt/2GXXnJQ

Will done Better: Selection Semantics, Future Credence, and Indeterminacy

Abstract
Statements about the future are central in everyday conversation and reasoning. How should we understand their meaning? The received view among philosophers treats will as a tense: in 'Cynthia will pass her exam', will shifts the reference time forward. Linguists, however, have produced substantial evidence for the view that will is a modal, on a par with must and would. The different accounts are designed to satisfy different theoretical constraints, apparently pulling in opposite directions. We show that these constraints are jointly satisfied by a novel modal account of will. On this account, will is a modal but doesn't work as a quantifier over worlds. Rather, the meaning of will involves a selection function similar to the one used by Stalnaker in his semantics for conditionals. The resulting theory yields a plausible semantics and logic for will and vindicates our intuitive views about the attitudes that rational agents should have towards future-directed contents.

http://ift.tt/2FS4i5Z

Kierkegaard on Truth: One or Many?

Abstract
This paper re-examines Kierkegaard's work with respect to the question whether truth is one or many. I argue that his famous distinction between objective and subjective truth is grounded in a unitary conception of truth as such: truth as self-coincidence. By explaining his use in this context of the term 'redoubling' [Fordoblelse], I show how Kierkegaard can intelligibly maintain that truth is neither one nor many, neither a simple unity nor a complex multiplicity. I further show how these points shed much-needed light on the relationship between objective and subjective truth, conceived not as different kinds or species of truth but as different ways in which truth manifests itself as a standard of success across different contexts of inquiry.

http://ift.tt/2GVF5Jj

Self-management and liver allograft rejection in adolescence and beyond

We read with interest the study by Annunziato et al on self-management and allograft rejection in pediatric liver transplant recipients.1 A vexing challenge in pediatric organ transplantation is the "high-risk window" of graft failure and mortality as transplant recipients age into young adulthood.2-4 Changing patterns of treatment adherence and self-management during this time offer an intuitive explanation for the increase in risk.3 Provocatively, the present study demonstrates that greater self-management predicted an increased risk of liver allograft rejection in children and adolescents 9-17 years of age.

http://ift.tt/2BfuhVS

Neonatal Parotitis

A 6-day-old boy presented with restlessness and swelling of the right pre-auricular area. The patient was born by spontaneous vaginal delivery after a full-term gestation with birth weight of 3805 g. On examination, vital signs and weight were normal, and his temperature was 37.5°C. He had a firm, erythematous, and tender swelling of the right pre-auricular area that extended to the angle of the mandible. Purulent material was expressed from the orifice of the Stensen's duct by massaging the parotid gland (Figure).

http://ift.tt/2BegJtM

Reply

We are grateful to Tumin et al for their comments. In response, we offer the following points. The purpose of our study was to provide empirically based suggestions for the assessment of transition. We agree that age plays an important part in transition; we in fact examined 2 different age groups, pre-adolescents and adolescents. As shown by the analyses within each group, age may well interact with patients' confidence that they have "got this" when it comes to self-management. We agree, too, that improving self-management skills remains an important goal, but as a first step, a thorough assessment of the adolescent's capacity for self-management is indicated to inform such efforts.

http://ift.tt/2BKoOra

Congenital Absence of Skin on Scalp

A male preterm infant born via cesarean delivery, with a gestational age of 364/7 weeks and birth weight of 3040 g, presented with a 2.0 × 2.3 cm skin defect over his scalp vertex after birth (Figure 1). The mother had preeclampsia and a history of systemic lupus erythematosus. The physical examination did not show any other abnormalities. Hematological and biochemical data were all within normal limits. Brain sonogram revealed no abnormalities. The microarray-based comparative genomic hybridization study was normal.

http://ift.tt/2BLfenT

High Sustained Antibody Titers in Patients with Classic Infantile Pompe Disease Following Immunomodulation at Start of Enzyme Replacement Therapy

To evaluate whether immunomodulation at start of enzyme replacement therapy induces immune tolerance to recombinant human acid alpha-glucosidase (rhGAA) in patients with classic infantile Pompe disease.

http://ift.tt/2BhboBZ

New Thiophene-Acridine Compounds: Synthesis, Antileishmanial Activity, DNA Binding, Chemometric and Molecular Docking Studies

Abstract

In the present study, we synthesized eight new compounds containing the 2-amino-cycloalkyl[b]thiophene and acridine moieties (ACT01 and ACS01-ACS07). None tested compounds presented human erythrocyte cytotoxicity. The new compounds presented antipromastigote activity, where ACS01 and ACS02 derivatives presented significant antileishmanial activity, with better performance than the reference drugs (tri and pentavalent antimonials), with respective IC50 values of 9.60±3.19 and 10.95±3.96 μM. Additionally, these two derivatives were effective against antimony-resistant L. (L.) amazonensis strains. In addition, binding and fragmentation DNA assays were performed. It was observed that the antileishmanial activity of ACS01 is not associated to DNA fragmentation of the promastigote forms. However, it interacted with DNA with a binding constant of 104 M−1. In partial least-squares (PLS) studies, it was observed that the most active compounds (ACS01 and ACS02) showed lower values of amphiphilic moment descriptor, but there was a correlation between the lipophilicity of the molecules and antileishmanial activity. Furthermore, the docking molecular studies showed interactions between thiophene-acridine derivatives and the active site of pyruvate kinase enzyme with the major contribution of asparagine 152 residue for the interaction with thiophene moiety. Thus, the results suggested that the new thiophene-acridine derivatives are promising molecules as potential drug candidates.

This article is protected by copyright. All rights reserved.

Thumbnail image of graphical abstract

The new compounds presented antileishmanial activity, with better performance than the reference drugs (ACS01 and ACS02), without to present human erythrocyte cytotoxicity.

The best compound ACS01 interacted with DNA. However, the antileishmanial activity of ACS01 is not associated to DNA fragmentation of the promastigote forms.

Theoretical studies showed lower values of amphiphilic moment descriptor, but there was a correlation between the lipophilicity of the molecules and antileishmanial activity. In addition, the docking molecular studies showed interactions between thiophene-acridine derivatives and the active site of pyruvate kinase enzyme.



http://ift.tt/2EL6tJ7

Synthesis and Evaluation of Pyridinium-Hydrazone Derivatives as Potential Antitumoral Agents

Abstract

The hydrazones of 4-hydrazinylpyridinium bearing alkylphenyl groups on pyridinium nitrogen were synthesized and evaluated for their cytotoxic activity against MCF-7, PC3, U2OS and HEK293 cell lines by Wst1 cell proliferation assay.

Cytotoxic activity results indicated that d derivatives having butylene chain; 4 and 5 series having naphthalene and anthracene ring systems, showed high cytotoxic activity (IC50= 3.27-8.54 μM) on cancer cells. 3d (4-(2-(4-hydroxybenzylidene)hydrazinyl)-1-(4-phenylbutyl)pyridinium bromide) was the most cytotoxic compound with IC50 value of 3.27 μM against MCF-7. The most active derivatives (1d, 2d, 3d, 4 and 5 series) were selected to investigate for the effects on autophagy by analyzing the expression of autophagy marker proteins. The conversion of LC3-I to its lipidated form LC3-II is essential for autophagy and related to autophagosomes. According to our results, all tested compounds except for 3d, induced lipidated form LC3-II accumulation. Then, the effects of the compounds on p62 protein level were also analyzed by the immunoblotting since the autophagy inhibition results in accumulation of p62.

Further molecular mechanistic studies including morphological analysis and live death assays indicated that all tested compounds (1d, 2d, 3d, 4 and 5 series) are potent antitumoral molecules and all except for 3d have potential to inhibit autophagic flux.

This article is protected by copyright. All rights reserved.

Thumbnail image of graphical abstract

A series of pyridinium-hydrazones was evaluated for their cytotoxic activity. Among the tested compounds, derivatives with the highest cytotoxicity (1d, 2d, 3d, 4 and 5 series) were found to have potent antitumoral activity and all except for 3d have potential to inhibit autophagic flux.



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Recombinant Collagen I Peptide Microcarriers for Cell Expansion and Their Potential Use As Cell Delivery System in a Bioreactor Model

57363fig1.jpg

We propose a cell expansion protocol on macroporous microcarriers and their use as delivery system in a perfusion bioreactor to seed a decellularized tissue matrix. We also include different techniques to determine cell proliferation and viability of cells cultured on microcarriers. Furthermore, we demonstrate functionality of cells after bioreactor cultures.

http://ift.tt/2ENnMcJ

Imaging Approaches to Assessments of Toxicological Oxidative Stress Using Genetically-encoded Fluorogenic Sensors

This manuscript describes the use of genetically-encoded fluorogenic reporters in an application of live-cell imaging for the examination of xenobiotic-induced oxidative stress. This experimental approach offers unparalleled spatiotemporal resolution, sensitivity, and specificity while avoiding many of the shortcomings of conventional methods used for the detection of toxicological oxidative stress.

http://ift.tt/2EbJnuk

Ratiometric Calcium Imaging of Individual Neurons in Behaving Caenorhabditis Elegans

This protocol describes the use of genetically encoded Ca2+ reporters to record changes in neural activity in behaving Caenorhabditis elegans worms.  

http://ift.tt/2EMn27B

Questions Regarding Statistical Inferences, Quality of Life, and Conclusions From the COBRA Study

No abstract available

http://ift.tt/2nDhiG0

Prevent the Bleed: How Surgeons Can Lead the National Conversation About Firearm Safety Forward

In the 5 years since the Sandy Hook elementary school shooting that claimed the lives of 20 children and 6 of their teachers, we have witnessed intolerably more mass shooting events. In the intervening years, over 150,000 Americans have died because of firearm violence, 3 times the number who lost their lives during the Revolutionary war. In the last 2 months, we have been left reflecting on 2 more tragedies. The first came on October 1 in Las Vegas, at the Route 91 music festival where 58 were killed and over 500 injured by a single gunman. The second, on November 5, took place in Sutherland Springs, Texas (population 600) near San Antonio and claimed the lives of 26 men women and children while they prayed. As was witnessed in Orlando and San Bernardino, these most recent mass casualty incidents strained first responders, law enforcement, and the state's trauma systems to their breaking point. Once again, we were left searching for the reasons behind these tragedies asking predictable questions: who did this and why? Was it part of a terrorist plot or a lone psychopath with a grudge? Were the weapons obtained legally, and why would anyone need so many? How can we stop this from happening again?

http://ift.tt/2scVxkP

Stent Reconstruction of Carotid Tonsillar Loop Dissection Using Telescoping Peripheral Stents

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Background: Endovascular treatment options for internal carotid artery (ICA) dissection with tandem intracranial occlusion are evolving. We report 2 cases of stent reconstruction of carotid loop dissections. Methods: Two patients with symptomatic ICA dissections of true 360° tonsillar loops and tandem intracranial occlusions were treated with manual aspiration thrombectomy (MAT) and telescoping Zilver self-expanding peripheral stents. Patient demographics, clinical presentations, endovascular techniques, and clinical outcomes were reviewed. Results: In both cases, MAT achieved modified Treatment in Cerebral Ischemia scale 2B reperfusion, and complete endovascular reconstruction of the dissected extracranial loop was performed. Both patients had improved pre- to postintervention National Institutes of Health Stroke Scale scores (16 to 0 and 14 to 0), and both had modified Rankin scale scores of 1 at 3-month follow-up. Conclusions: Stent reconstruction of complex cerebrovascular anatomy is increasingly feasible with advancements in stent technology and catheter support system design. This technique may be of use to neuroendovascular surgeons who encounter variant ICA anatomy.
Intervent Neurol 2018;7:189–195

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A Review of Pre-Intervention Prognostic Scores for Early Prognostication and Patient Selection in Endovascular Management of Large Vessel Occlusion Stroke

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Background: Endovascular therapy (ET) has emerged as a highly effective treatment for acute large vessel occlusion stroke (LVOS). Tools that facilitate optimal patient selection of patients for ET are needed in order to maximize therapeutic benefit in a cost-effective manner. Several pre-intervention prognostic scores for prediction of outcomes in LVOS patients and patient selection for ET have been developed and validated, but their clinical use has been limited. Here, we review existing pre-intervention prognostic scores, compare their prognostic accuracies and levels of validation and identify gaps in current knowledge. Summary: We have reviewed published literature pertinent to development, validation, and implementation of pre-intervention prognostic scores for LVOS. Using receiver operating characteristic curve analysis, the prognostic accuracies of validated pre-interventional scores (Pittsburgh Response to Endovascular therapy [PRE], Totaled Health Risks in Vascular Events [THRIVE], Houston Intra-Arterial Therapy-2 (HIAT-2), Stroke Prognostication using Age and NIHSS [SPAN-100]) were compared in published work. Pre-intervention scores predicted functional out comes at 3 months with moderate prognostic accuracies (area under the receiver operator characteristic curve range 0.68–0.73). Using successful reperfusion (mTICI 2B/3) as the therapeutic objective of ET and 3-month modified Rankin Score 0–2 as good clinical outcome, patients most likely to clinically benefit from endovascular reperfusion can be identified using the PRE and HIAT-2 scores. Scores that incorporate collateral imaging or perfusion-based estimation of core and penumbra have not been published. Existing scores are predominantly limited to anterior circulation LVOS, and implementation studies of pre-interventional scores are lacking. Key Messages: Pre-intervention prognostic scores can serve as useful adjuncts for patient selection in ET for acute LVOS. Pre-intervention scores including HIAT-2, THRIVE, SPAN-100, and PRE have comparable moderate prognostic accuracies for good 3-month outcomes and can identify patients who derive maximal benefit from successful reperfusion. Improvements in prognostic accuracy may be achieved by incorporating variables such as collateral status and perfusion imaging data. Implementation and impact studies using pre-intervention scores are needed to guide clinical application.
Intervent Neurol 2018;7:171–181

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CRISPR/Cas9: A tool for immunological research

The CRISPR/Cas9-system was originally identified as part of the adaptive immune system in bacteria and has since been adapted for the genetic manipulation of eukaryotic cells. The technique is of particular value for biomedical sciences, as it enables the genetic manipulation of cell lines and primary cells as well as whole organisms with unprecedented ease and efficiency. Furthermore, the CRISPR/Cas9-technology has the potential for future therapeutic applications in the clinic. Here, we discuss the use of CRISPR/Cas9 for the genetic modification of haematopoietic cells and the generation of mouse models for immunological research. Additionally, we explain how the technique can be applied as a screening-tool to identify genes involved in different immunological processes. Moreover, we will talk about recent extensions of using the CRISPR/Cas9 technology, such as a transcriptional activator or repressor. Finally, we discuss the first clinical trials that use CRISPR/Cas9 and discuss potential future applications.

This article is protected by copyright. All rights reserved



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Severe Toxicity in Nonhuman Primates and Piglets with Systemic High-Dose Administration of Adeno-Associated Virus Serotype 9–Like Vectors: Putting Patients First

Human Gene Therapy , Vol. 0, No. 0.


http://ift.tt/2C2U5Bt

Late-onset postoperative Mycobacterium haemophilum endophthalmitis masquerading as inflammatory uveitis: a case report

Although atypical mycobacteria had been increasingly found in various ocular infections in the past decades, a slow-growing Mycobacterium haemophilum (M. haemophilum) was scarcely reported. Similar to tuberculous...

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Transmission dynamics for Methicilin-resistant Staphalococous areus with injection drug user

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial pathogen resistance to antibiotics including methicillin. The resistance first emerged in 1960 in a healthcare setting only after two years of ...

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Balloon-based Injury to Induce Myointimal Hyperplasia in the Mouse Abdominal Aorta

This article demonstrates a murine model to study the development of myointimal hyperplasia (MH) after aortic balloon injury.

http://ift.tt/2BOFSwa

A statewide program providing colorectal cancer screening to the uninsured of South Carolina

BACKGROUND

Cancer screening rates are lowest in those without insurance or a regular provider. Since 2008, the Colorectal Cancer Prevention Network (CCPN) has provided open access colonoscopy to uninsured residents of South Carolina through established, statewide partnerships and patient navigation. Herein, we describe the structure, implementation, and clinical outcomes of this program.

METHODS

The CCPN provides access to colonoscopy screening at no cost to uninsured, asymptomatic patients aged 50-64 years (African Americans age 45-64 years are eligible) who live at or below 150% of the poverty line and seek medical care in free medical clinics, federally qualified health centers, or hospital-based indigent practices in South Carolina. Screening is performed by board-certified gastroenterologists. Descriptive statistics and regression analysis are used to describe the population screened, and to assess compliance rates and colonoscopy quality metrics.

RESULTS

Out of >4000 patients referred to the program, 1854 were deemed eligible, 1144 attended an in-person navigation visit, and 1030 completed a colonoscopy; 909 were included in the final sample. Nearly 90% of participants exhibited good-to-excellent bowel preparation. An overall cecal intubation rate of 99% was measured. The polyp detection rate and adenoma detection rate were 63% and 36%, respectively, with male sex and urban residence positively associated with adenoma detection. Over 13% of participants had an advanced polyp, and 1% had a cancer diagnosis or surgical intervention.

CONCLUSION

The CCPN program is characterized by strong collaboration with clinicians statewide, low no-show rates, and high colonoscopy quality. Future work will assess the effectiveness of the navigation approach and will explore the mechanisms driving higher adenoma detection in urban participants. Cancer 2018. © 2018 American Cancer Society.



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Pentax Medical Duodenoscope Model ED-3490TK: FDA Safety Communication - Updated Design and Labeling Cleared

Audience: Gastroenterology, Nursing, Risk Manager [Posted 02/07/2018] ISSUE: Pentax issued an Urgent Medical Device Correction and Removal notification informing customers of its voluntary recall of all ED-3490TK duodenoscopes in order to replace...

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The effect of a medication reconciliation program in two intensive care units in the Netherlands: a prospective intervention study with a before and after design

Medication errors occur frequently in the intensive care unit (ICU) and during care transitions. Chronic medication is often temporarily stopped at the ICU. Unfortunately, when the patient improves, the restar...

http://ift.tt/2nQFROK

Direct serogrouping of Dichelobacter nodosus from Victorian farms using conventional multiplex polymerase chain reaction

Dichelobacter nodosus is the causative agent of footrot in sheep. Ovine footrot is a major problem in Australia that results in large economic losses and a represents a very significant animal welfare issue. D. n...

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Double non-contiguous fractures in a patient with spondylo-epiphyseal dysplasia with spinal ankylosis treated with open and percutaneous spinal fixation technique: a case report

Patients with ankylosing spines are susceptible to developing spinal fractures even with minor trauma and can develop early or late neurological injuries. These fractures require early and aggressive surgical ...

http://ift.tt/2E8hNlA

Incidence of acute lymphocytic leukemia in Calgary, Alberta, Canada: a retrospective cohort study

Acute lymphocytic leukemia (ALL) is a rare malignant neoplasm that develops from abnormal lymphoid stem cells. ALL incidence is highest among children and declines towards adolescence. There is limited data on...

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Discrimination between some Mycoplasma spp. and Acholeplasma laidlawii in bovine milk using high resolution melting curve analysis

This study aimed to provide a rapid, accurate and cost-effective diagnostic real time polymerase chain reaction-high resolution melting curve assay (PCR-HRM) to identify and distinguish between four different ...

http://ift.tt/2Eay4ql

Cryptosporidium infection in bovine calves: prevalence and potential risk factors in northwest Ethiopia

Cryptosporidium is an enteric protozoan organism that causes gastrointestinal disorders in different animals, mainly in calves. The parasite has also a zoonotic importance of children and immunocompromised patien...

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Pentax Medical Duodenoscope Model ED-3490TK: FDA Safety Communication - Updated Design and Labeling Cleared

Audience: Gastroenterology, Nursing, Risk Manager [Posted 02/07/2018] ISSUE: Pentax issued an Urgent Medical Device Correction and Removal notification informing customers of its voluntary recall of all ED-3490TK duodenoscopes in order to replace...

http://ift.tt/2BhjXwn

miR-155 Affects Osteosarcoma MG-63 Cell Autophagy Induced by Adriamycin Through Regulating PTEN-PI3K/AKT/mTOR Signaling Pathway

Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.


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Polluted Air May Pollute Our Morality

Exposure to air pollution, even imagining exposure to air pollution, may lead to unethical behavior, according to findings published in Psychological Science, a journal of the Association for Psychological Science. A combination of archival and experimental studies indicates that exposure to air pollution, either physically or mentally, is linked with unethical behavior such as crime and cheating. The experimental findings suggest that this association may be due, at least in part, to increased anxiety.

"This research reveals that air pollution may have potential ethical costs that go beyond its well-known toll on health and the environment," says behavioral scientist Jackson G. Lu of Columbia Business School, the first author of the research. "This is important because air pollution is a serious global issue that affects billions of people—even in the United States, about 142 million people still reside in counties with dangerously polluted air."

Previous studies have indicated that exposure to air pollution elevates individuals' feelings of anxiety. Anxiety is known to correlate with a range of unethical behaviors. Lu and colleagues hypothesized that pollution may ultimately increase criminal activity and unethical behavior by increasing anxiety.

In one study, the researchers examined air pollution and crime data for 9,360 US cities collected over a 9-year period. The air pollution data, maintained by the Environmental Protection Agency, included information about six major pollutants, including particulate matter, carbon monoxide, nitrogen dioxide, and sulfur dioxide. The crime data, maintained by the US Federal Bureau of Investigation, included information about offenses in seven major categories, including murder, aggravated assault, and robbery.

The researchers found that cities with higher levels of air pollution also tended to have higher levels of crime. This association held even after the researchers accounted for other potential factors, including total population, number of law enforcement employees, median age, gender distribution, race distribution, poverty rate, unemployment rate, unobserved heterogeneity among cities (e.g., city area, legal system), and unobserved time-varying effects (e.g., macroeconomic conditions).

To establish a direct, causal link between the experience of air pollution and unethical behavior, the researchers also conducted a series of experiments. Because they could not randomly assign participants to physically experience different levels of air pollution, the researchers manipulated whether participants imagined experiencing air pollution.

In one experiment, 256 participants saw a photo featuring either a polluted scene or a clean scene. They imagined living in that location and reflected on how they would feel as they walked around and breathed the air.

On a supposedly unrelated task, they saw a set of cue words (e.g., sore, shoulder, sweat) and had to identify another word that was linked with each of the cue words (e.g., cold); each correct answer earned them $0.50. Due to a supposed computer glitch, the correct answer popped up if the participants hovered their mouse over the answer box, which the researchers asked them not to do. Unbeknownst to the participants, the researchers recorded how many times the participants peeked at the answer.

The results showed that participants who thought about living in a polluted area cheated more often than did those who thought about living in a clean area.

Polluted scenes from Beijing

Polluted scenes from Beijing (Lu et al. Psychological Science)

Nonpolluted scenes from Beijing

Nonpolluted scenes from Beijing (Lu et al. Psychological Science)

In two additional experiments, participants saw photos of either polluted or clean scenes taken in the exact same locations in Beijing, and they wrote about what it would be like to live there. Independent coders rated the essays according to how much anxiety the participants expressed.

In one of the experiments conducted with university students in the US, the researchers measured how often participants cheated in reporting the outcome of a die roll; in the other experiment with adults in India, they measured participants' willingness to use unethical negotiation strategies.

Again, participants who wrote about living in a polluted location engaged in more unethical behavior than did those who wrote about living in a clean location; they also expressed more anxiety in their writing. As the researchers hypothesized, anxiety level mediated the link between imagining exposure to air pollution and unethical behavior.

Together, the archival and experimental findings suggest that exposure to air pollution, whether physical or mental, is linked with transgressive behavior through increased levels of anxiety.

Lu and colleagues note that there may be other mechanisms besides anxiety that link air pollution and unethical behavior. They also acknowledge that imagining experiencing air pollution is not equivalent to experiencing actual air pollution. They highlight these limitations as avenues for further research.

Ultimately, the research reveals another pathway through which a person's surroundings can affect his or her behavior:

"Our findings suggest that air pollution not only corrupts people's health, but also can contaminate their morality," Lu concludes.

Co-authors on the research include Julia J. Lee of the Stephen M. Ross School of Business at the University of Michigan, Francesca Gino at Harvard Business School, and Adam D. Galinsky at Columbia Business School.

All materials have been made publicly available via the Open Science Framework. The design and analysis plans for Study 3b were preregistered. The complete Open Practices Disclosure for this article is available online. This article has received badges for Open Materials and Preregistration.



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Intrathoracic versus cervical anastomosis and predictors of anastomotic leakage after oesophagectomy for cancer

Background

Studies comparing the anastomotic leak rate in patients with an intrathoracic versus a cervical anastomosis after oesophagectomy are equivocal. The aim of this study was to compare clinical outcome after oesophagectomy in patients with an intrathoracic or cervical anastomosis, and to identify predictors of anastomotic leakage in a nationwide audit.

Methods

Between January 2011 and December 2015, all consecutive patients who underwent oesophagectomy for cancer were identified from the Dutch Upper Gastrointestinal Cancer Audit. For the comparison between an intrathoracic and cervical anastomosis, propensity score matching was used to adjust for potential confounders. Multivariable logistic regression modelling with backward stepwise selection was used to determine independent predictors of anastomotic leakage.

Results

Some 3348 patients were included. After propensity score matching, 654 patients were included in both the cervical and intrathoracic anastomosis groups. An intrathoracic anastomosis was associated with a lower leak rate than a cervical anastomosis (17·0 versus 21·9 per cent; P = 0·025). The percentage of patients with recurrent nerve paresis was also lower (0·6 versus 7·0 per cent; P < 0·001) and an intrathoracic anastomosis was associated with a shorter median hospital stay (12 versus 14 days; P = 0·001). Multivariable analysis revealed that ASA fitness grade III or higher, chronic obstructive pulmonary disease, cardiac arrhythmia, diabetes mellitus and proximal oesophageal tumours were independent predictors of anastomotic leakage.

Conclusion

An intrathoracic oesophagogastric anastomosis was associated with a lower anastomotic leak rate, lower rate of recurrent nerve paresis and a shorter hospital stay. Risk factors for anastomotic leak were co-morbidities and proximal tumours.



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Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei of appendicular and extra-appendicular origin

Background

The prognostic value of the primary neoplasm responsible for pseudomyxoma peritonei (PMP) remains poorly studied. The aim of this study was to determine the prognosis for patients with extra-appendicular PMP (EA-PMP) treated optimally with complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

All patients treated for PMP with CCRS and HIPEC between 1994 and 2016 were selected retrospectively from a French multicentre database. Patients with EA-PMP had pathologically confirmed non-neoplastic appendices and were matched in a 1 : 4 ratio with patients treated for appendicular PMP (A-PMP), based on a propensity score.

Results

Some 726 patients were identified, of which 61 (EA-PMP group) were matched with 244 patients (A-PMP group). The origins of primary tumours in the EA-PMP group included the ovary (45 patients), colon (4), urachus (4), small bowel (1), pancreas (1) and unknown (6). The median peritoneal carcinomatosis index was comparable in EA-PMP and A-PMP groups (15·5 versus 18 respectively; P = 0·315). In-hospital mortality (3 versus 2·9 per cent; P = 1·000) and major morbidity 26 versus 25·0 per cent; P = 0·869) were also similar between the two groups. Median follow-up was 66·9 months. The 5-year overall survival rate was 87·8 (95 per cent c.i. 83·2 to 92·5) per cent in the A-PMP group and 87 (77 to 96) per cent in the EA-PMP group. The 5-year disease-free survival rate was 66·0 (58·7 to 73·4) per cent and 70 (53 to 83) per cent respectively.

Conclusion

Overall and disease-free survival following treatment with CCRS and HIPEC is similar in patients with pseudomyxoma peritonei of appendicular or extra-appendicular origin.



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Meta-analysis of delayed gastric emptying after pylorus-preserving versus pylorus-resecting pancreatoduodenectomy

Background

Delayed gastric emptying (DGE) is a frequent complication after pylorus-preserving pancreatoduodenectomy. Recent studies have suggested that resection of the pylorus is associated with decreased rates of DGE. However, superiority of pylorus-resecting pancreatoduodenectomy was not shown in a recent RCT. This meta-analysis summarized evidence of the effectiveness and safety of pylorus-preserving compared with pylorus-resecting pancreatoduodenectomy.

Methods

RCTs and non-randomized studies comparing outcomes of pylorus-preserving and pylorus-resecting pancreatoduodenectomy were searched systematically in MEDLINE, Web of Science and CENTRAL. Random-effects meta-analyses were performed and the results presented as weighted odds ratios (ORs) or mean differences with their corresponding 95 per cent confidence intervals. Subgroup analyses were performed to account for interstudy heterogeneity between RCTs and non-randomized studies.

Results

Three RCTs and eight non-randomized studies with a total of 992 patients were included. Quantitative synthesis across all studies showed superiority for pylorus-resecting pancreatoduodenectomy regarding DGE (OR 2·71, 95 per cent c.i. 1·48 to 4·96; P = 0·001) and length of hospital stay (mean difference 3·26 (95 per cent c.i. −1·04 to 5·48) days; P = 0·004). Subgroup analyses including only RCTs showed no significant statistical differences between the two procedures regarding DGE, and for all other effectiveness and safety measures.

Conclusion

Pylorus-resecting pancreatoduodenectomy is not superior to pylorus-preserving pancreatoduodenectomy for reducing DGE or other relevant complications.



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Reaching out to the surgical community in China



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Use of aspirin and bleeding-related complications after hepatic resection

Background

The operative risk of hepatectomy under antiplatelet therapy is unknown. This study sought to assess the outcomes of elective hepatectomy performed with or without aspirin continuation in a well balanced matched cohort.

Methods

Data were retrieved from a multicentre prospective observational study. Aspirin and control groups were compared by non-standardized methods and by propensity score (PS) matching analysis. The main outcome was severe (Dindo–Clavien grade IIIa or more) haemorrhage. Other outcomes analysed were intraoperative transfusion, overall haemorrhage, major morbidity, comprehensive complication index (CCI) score, thromboembolic complications, ischaemic complications and mortality.

Results

Before matching, there were 118 patients in the aspirin group and 1685 in the control group. ASA fitness grade, cardiovascular disease, previous history of angina pectoris, angioplasty, diabetes, use of vitamin K antagonists, cirrhosis and type of hepatectomy were significantly different between the groups. After PS matching, 108 patients were included in each group. There were no statistically significant differences between the aspirin and control groups in severe haemorrhage (6·5 versus 5·6 per cent respectively; odds ratio (OR) 1·18, 95 per cent c.i. 0·38 to 3·62), intraoperative transfusion (23·4 versus 23·7 per cent; OR 0·98, 0·51 to 1·87), overall haemorrhage (10·2 versus 12·0 per cent; OR 0·83, 0·35 to 1·94), CCI score (24 versus 28; P = 0·520), major complications (23·1 versus 13·9 per cent; OR 1·82, 0·92 to 3·79) and 90-day mortality (5·6 versus 4·6 per cent; OR 1·21, 0·36 to 4·09)

Conclusion

This observational study suggested that aspirin continuation is not associated with a higher rate of bleeding-related complications after elective hepatic surgery.



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Surgical treatment of multiple ipsilateral breast cancers

Towards more breast conservation?



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The concentration of programmed cell death-ligand 1 in the peripheral blood is a useful biomarker for esophageal squamous cell carcinoma

Abstract

Background

We determined the serum concentrations of Programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2) in patients with esophageal squamous cell carcinoma (ESCC).

Methods

Blood samples were collected from 85 patients with histologically proved ESCC. Serum levels of PD-1, PD-L1, and PD-L2 were measured using enzyme linked immunosorbent assays. Correlations between serum PD-1, PD-L1, and PD-L2 concentration and tumor depth, number of lymph node metastases, organ metastasis status, or disease stage were assessed and five-year survival rates according to clinicopathological characteristics were calculated.

Results

The concentration of PD-1 was not differed according to tumor progression. On the other hand, the average concentration of PD-L1 in patients with T3/T4 disease was 15.6 (12.2–18.3) pg/mL (25–75%), and this was significantly higher than that in patients with Tis/T1/T2 disease (p = 0.020). Similarly, PD-L1 levels were significantly higher in patients with positive lymph nodes than in cases with negative lymph node involvement (p = 0.006) and were higher in patients with organ metastasis (p = 0.123) and in more advanced stage (p = 0.006). Similar tendency was observed regarding PD-L2 concentrations. PD-L2 concentration was higher in T3, T4 cases (p = 0.008), in LN positive cases (p = 0.032), and in more advanced stage (p = 0.024).

Conclusion

Our data showed that a concentration of PD-L1 in peripheral blood was high in advanced cancer and high concentration of PD-L1 predicted disease progression and also poor survival in patients with ESCC.



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Diagnosing Neoplastic Hematoma: Role of MR Perfusion

Abstract

Background

The imaging appearance of neoplastic hematoma can be complicated by the presence of a large hematoma, even on magnetic resonance imaging (MRI). We describe the role of MR perfusion (MRP) in detecting neoplastic hematomas in patients with intraparenchymal hematoma (IPH).

Material and Methods

A retrospective review was performed for consecutive patients with IPH, where MRP was performed. Routine, post-gadolinium MRI and MRP were analyzed. All patients were either operated on for evacuation of IPH or followed up on imaging. The MRP parameters of cerebral blood volume (CBV) and cerebral blood flow (CBF) and pattern of enhancement (peripheral linear vs. nodular) were recorded. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated for these parameters for diagnosing neoplastic hematoma.

Results

Of 116 patients with MRP, 16 patients (male 8; mean age—65.5 years) had IPH on their initial MRI. For diagnosing neoplastic hematoma, the sensitivity, specificity, PPV and NPV for increased CBF and CBV were 100%, 88.9%, 87.5%, and 100%; for peripheral linear enhancement were 100%, 28.6%, 50%, 100% and for nodular enhancement were 85.7%, 77.8%, 75% and 12.5%, respectively. The combination of peripheral linear enhancement and increased CBF and CBV showed 100% sensitivity, specificity, PPV and NPV.

Conclusion

In our small series, the combination of peripheral linear enhancement and increased CBF and CBV showed 100% sensitivity, specificity, PPV and NPV for diagnosing a neoplastic hematoma. These findings need to be validated in a larger study.



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Correction to: SEOM clinical guidelines for endometrial cancer (2017)

In the original version of this article Figure 1 was shown incorrectly. The correct Figure 1 is shown here:



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Visualization of endothelial cell cycle dynamics in mouse using the Flt-1/eGFP-anillin system

Abstract

Endothelial cell proliferation is a key process during vascular growth but its kinetics could only be assessed in vitro or ex vivo so far. To enable the monitoring and quantification of cell cycle kinetics in vivo, we have generated transgenic mice expressing an eGFP-anillin construct under control of the endothelial-specific Flt-1 promoter. This construct labels the nuclei of endothelial cells in late G1, S and G2 phase and changes its localization during the different stages of M phase, thereby enabling the monitoring of EC proliferation and cytokinesis. In Flt-1/eGFP-anillin mice, we found eGFP+ signals specifically in Ki67+/PECAM+ endothelial cells during vascular development. Quantification using this cell cycle reporter in embryos revealed a decline in endothelial cell proliferation between E9.5 to E12.5. By time-lapse microscopy, we determined the length of different cell cycle phases in embryonic endothelial cells in vivo and found a M phase duration of about 80 min with 2/3 covering karyokinesis and 1/3 cytokinesis. Thus, we have generated a versatile transgenic system for the accurate assessment of endothelial cell cycle dynamics in vitro and in vivo.



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Axial reflexes are present in older subjects and may contribute to balance responses

Abstract

We studied the response to axial taps (mini-perturbations) of a group of 13 healthy older subjects (mean age 63 ± 12 years, 7 females, 6 males), 12 of whom were also studied using larger applied (macro-) perturbations requiring active postural responses. The mini-perturbation consisted of a brief impulsive force produced by a mini-shaker applied to the trunk at the level of the shoulders and anteriorly at the upper sternum which was perceived as a tap. Acceleration, force platform, and EMG measurements were made. The average peak accelerations for the mini-perturbations were 108 mG (anterior) and − 78.9 mG (posterior). Responses overall were very similar to those previously reported for younger subjects: the perturbation evoked short latency responses in leg muscles, modulated by degree and direction of lean, and were largest for the muscle most relevant for the postural correction. The increases in the amplitude for the main agonist were greater than the increase in tonic activity. With both anterior and posterior lean, co-contraction responses were present. The size of the EMG response to the mini-perturbations correlated with the corresponding earliest EMG responses (0–100, 100–200 ms intervals) to the larger postural perturbations, timing which corresponds to balance responses. The balance responses evoked by the larger imposed postural perturbations may, therefore, receive a contribution through the reflex pathway mediating the axial tap responses, whose efferent limb appears to be the reticulospinal tract.



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