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Δευτέρα 15 Φεβρουαρίου 2016

HIV counselling and testing practices for children seen in an urban emergency department of a tertiary referral hospital in Dar es Salaam, Tanzania: a retrospective cross-sectional study

Objectives

To describe the HIV counselling and testing practices for children presenting to an emergency department (ED) in a low-income country.

Setting

The ED of a large east African national referral hospital.

Participants

This retrospective review of all paediatric (<18 years old) ED visits in 2012 enrolled patients who had an HIV test ordered and excluded those without testing. Files were available for 5540/5774 (96%) eligible patients and 1632 (30%) were tested for HIV, median age 1.3 years (IQR 9 months to 4 years), 58% <18 months old and 61% male.

Primary and secondary outcome measures

The primary outcome measure was documentation of pretest and post-test counselling, or deferral of counselling, for children tested for HIV in the ED. Secondary measures included the overall rate of HIV testing, rate of counselling documented in the inpatient record when deferred in the ED, rate of counselling documented when testing was initiated by the inpatient service, rate of counselling documented by test result (positive vs negative) and the rate of referral to follow-up HIV care among patients testing positive.

Results

Of 418 patients tested in the ED, counselling, or deferral of counselling, was documented for 70 (17%). When deferred to the ward, subsequent counselling was documented for 15/42 (36%). Counselling was documented in 33% of patients testing positive versus 1.1% patients testing negative (OR 43 (95% CI 23 to 83). Of 199 patients who tested positive and survived to hospital discharge, 76 (38%) were referred for follow-up at the HIV clinic on discharge.

Conclusions

Physicians documented the provision, or deferral, of counselling for <20% of children tested for HIV in the ED. Counselling was much more likely to be documented when the test result was positive. Less than 40% of those testing positive were referred for follow-up care.



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The Box Plots Alternative for Visualizing Quantitative Data

Although bar charts are popular among researchers and are ubiquitous in quantitative software packages, they do not always provide the best visualization for a dataset. This column discusses a simple, alternative graphical method that is often underappreciated: the box plot, also known as the box-and-whisker plot. The basic elements of the box plot are presented, along with how to correctly interpret box plots, variations that are available to provide more information, and free online software that researchers can use to create box plots for publication.

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Aqueous humor SIRT1 in cataract

Kondo A, Goto M, Mimura T, Matsubara M

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Vagus Nerve Stimulation For Tinnitus


People suffering from severe tinnitus have a hard time finding helpful therapies. Now, a new treatment using vagus nerve stimulation for tinnitus relief is showing promising results for many people with this frustrating and debilitating condition.

Tinnitus is a medical condition in which a person hears ringing, whooshing, or buzzing sounds inside their head and ears. Many people experience short episodes of tinnitus symptoms from time to time. People with bad cases of tinnitus hear these sounds all the time, causing severe distraction, discomfort, and annoyance.

The Wandering Vagus Nerve

The vagus nerve is actually a long pair of nerves wandering throughout the body. (The origin of the word vagus means wanderer.) Much of the work done by the vagus nerve involves sending messages from bodily organs to the brain, alerting the brain about what the body is experiencing.

The vagus nerve is part of the parasympathetic nervous system starting in the 10th cranial nerve in the spinal cord and extending to the heart, stomach and other organs, and into the brain. The parasympathetic nervous system is composed of the nerves and hormonal receptors which quiet the body down after 'fight or flight' messages from the sympathetic nervous system.

Artificial stimulation of the vagus nerve has been in use for many years by researchers and medical professionals as a treatment for severe epilepsy. Now, new technology has been developed for stimulating the vagus nerve for tinnitus treatment, and many tinnitus sufferers are finding help with this therapy.

How Vagus Nerve Stimulation for Tinnitus Works

This therapy for tinnitus works by implanting a small electrical stimulator into the patient's neck. The devise attaches to the vagus nerve close to the point where it enters the auditory cortex. The patient then puts on a set of headphones and listens to a series of tones specifically designed to train their brain to ignore the tinnitus frequencies.

During a session of using vagus nerve stimulation for tinnitus therapy, the patient hears frequencies above and below the frequency of the bothersome tinnitus tones. Over time, the person's brain learns to ignore the tinnitus sounds, restoring normal activity in the auditory cortex.

For many people using vagus nerve stimulation for tinnitus treatment, the bothersome tinnitus sounds go away or subside considerably for several weeks after a treatment session. The treatment can then be repeated as needed in the patient's home using headphones and the digital audio application.

Sources:
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The cost-utility of integrated cervical cancer prevention strategies in the Ontario setting – Can we do better?

Publication date: Available online 15 February 2016
Source:Vaccine
Author(s): Beate Sander, William W.L. Wong, Man Wah Yeung, Orges Ormanidhi, Karen Atkin, Joan Murphy, Murray Krahn, Shelley L. Deeks
IntroductionA universal, publicly funded, school-based human papillomavirus (HPV) vaccination program in grade eight girls was initiated in Ontario in 2007. We present a cost-utility analysis of integrated cervical cancer prevention programs from the healthcare payer perspective.MethodsOur analysis was based on linked HPV transmission and disease history models. We obtained data from the literature, provincial surveys and Ontario population-based linked health administrative datasets. We modeled combinations of vaccination and screening strategies. We considered vaccination based on the Ontario experience, as well as conservative and optimistic scenarios, varying coverage, vaccine effectiveness and duration of protection. We considered 900 screening scenarios (screening start age: 21–70 years, screening interval: 3–20 years; 1-year time steps). The current schedule screens every 3 years starting at age 21 years. We examined (1) first vaccinated cohort (low herd-immunity), and (2) steady state, i.e. all cohorts were vaccinated (high herd-immunity).ResultsAdding vaccination to the current screening schedule was cost-effective (<C$10,000/quality-adjusted life year (QALY)) across all scenarios. Delaying screening start and/or extending screening intervals increased both expected QALYs and cost, and increased overall NHB for screening schedules with a start age of 25–35 years and 3–10-year intervals for most scenarios.ConclusionDelaying screening start age and/or extending screening intervals in vaccinated cohorts is likely to be cost-effective. Consideration should be given to both the short- and long-term implications of health policy decisions, particularly for infectious disease interventions that require long time intervals to reach steady state.



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Trends in differences between births and surviving infants reported for immunization program planning and external data sources in Eastern and Southern Africa 2000–2013

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Publication date: 24 February 2016
Source:Vaccine, Volume 34, Issue 9
Author(s): Reinhard Kaiser, Jethro M. Chakauya, Messeret E. Shibeshi
To inform our WHO team's support for immunization programs in Member States in Eastern and Southern Africa, we compared annual trends from 2000 to 2013 in target populations reported by Member States through the WHO-UNICEF joint reporting form with United Nations (UN) population projections and modeled infant mortality estimates from the UN Inter-agency Group for Child Mortality Estimation. Our findings indicated a tendency of underestimating births and surviving infants used by Member States as denominators for administrative immunization coverage rates, resulting in or contributing to overestimation of coverage. The difference with UN estimates appeared to be more pronounced for surviving infants than births. Measures of central tendency for individual country differences indicated that those differences decreased over time. Comparing trends of births and surviving infants with external sources can help monitoring progress in efforts to provide accurate and reliable target population estimates and sampling frames.



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Editorial Board/Aims and Scope

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Publication date: 24 February 2016
Source:Vaccine, Volume 34, Issue 9





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HPV vaccine: Less is more

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Publication date: Available online 15 February 2016
Source:Vaccine
Author(s): Rachel Caskey, Steven Andes, Surrey Walton




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The Patient-Centered Medical Home and Associations With Health Care Quality and Utilization A 5-Year Cohort Study

Background:
Effects of the patient-centered medical home (PCMH) are unclear. Previous studies had relatively short follow-up and may not have distinguished effects of the PCMH (which involves electronic health records [EHRs] plus organizational changes) from those of EHRs alone.
Objective:
To determine effects of the PCMH on health care quality and utilization compared with paper records alone and EHRs alone, with extended follow-up.
Design:
Prospective cohort study (2008 to 2012), including 3 years after PCMH implementation. (ClinicalTrials.gov: NCT00793065)
Setting:
The Hudson Valley, a multipayer, multiprovider region in New York.
Participants:
438 primary care physicians in 226 practices, with 136 480 patients across 5 health plans.
Intervention:
Level III PCMH, as defined by the National Committee for Quality Assurance.
Measurements:
Claims-based outcomes included 8 quality and 7 utilization measures. Generalized estimating equations were used to compare adjusted differences in rates of change across study groups.
Results:
Patterns of quality were fairly similar across groups. Utilization patterns were similar across groups from 2008 to 2011 but showed modest differences between the PCMH and control groups on most measures in 2012. For example, hospitalizations were relatively stable from 2008 to 2011 (approximately 3.9 to 5.2 per 100 patients per year) but decreased in the PCMH group in 2012 (incidence rate ratio, 0.79 [95% CI, 0.69 to 0.90] compared with paper records). Emergency department visits were highest for the PCMH group (16.7 per 100 patients at baseline and 15.4 per 100 patients at the end of the study period) and lowest for the paper group (14.3 per 100 patients at baseline and 12.2 per 100 patients at the end of the study period), but the rate of change did not differ across groups.
Limitation:
Possible unmeasured confounding.
Conclusion:
The PCMH was associated with modest changes in most utilization measures and provided similar quality compared with EHRs and paper records.
Primary Funding Source:
The Commonwealth Fund and the New York State Department of Health.

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Innovation in Analysis of Respiratory Sounds

It is difficult to describe the sounds of breathing, especially when different types of sound are present at the same time. The authors propose the use of an electronic stethoscope with innovative software to solve this problem and use videos to illustrate its possibilities.

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Framing Financial Incentives to Increase Physical Activity Among Overweight and Obese Adults A Randomized, Controlled Trial

Background:
Financial incentive designs to increase physical activity have not been well-examined.
Objective:
To test the effectiveness of 3 methods to frame financial incentives to increase physical activity among overweight and obese adults.
Design:
Randomized, controlled trial. (ClinicalTrials.gov: NCT 02030119)
Setting:
University of Pennsylvania.
Participants:
281 adult employees (body mass index ≥27 kg/m2).
Intervention:
13-week intervention. Participants had a goal of 7000 steps per day and were randomly assigned to a control group with daily feedback or 1 of 3 financial incentive programs with daily feedback: a gain incentive ($1.40 given each day the goal was achieved), lottery incentive (daily eligibility [expected value approximately $1.40] if goal was achieved), or loss incentive ($42 allocated monthly upfront and $1.40 removed each day the goal was not achieved). Participants were followed for another 13 weeks with daily performance feedback but no incentives.
Measurements:
Primary outcome was the mean proportion of participant-days that the 7000-step goal was achieved during intervention. Secondary outcomes included mean proportion of participant-days achieving the goal during follow-up and mean daily steps during intervention and follow-up.
Results:
The mean proportion of participant-days achieving the goal was 0.30 (95% CI, 0.22 to 0.37) in the control group, 0.35 (CI, 0.28 to 0.42) in the gain-incentive group, 0.36 (CI, 0.29 to 0.43) in the lottery-incentive group, and 0.45 (CI, 0.38 to 0.52) in the loss-incentive group. In adjusted analyses, only the loss-incentive group had a significantly greater mean proportion of participant-days achieving the goal than control (adjusted difference, 0.16 [CI, 0.06 to 0.26]; P = 0.001), but the adjusted difference in mean daily steps was not significant (861 [CI, 24 to 1746]; P = 0.056). During follow-up, daily steps decreased for all incentive groups and were not different from control.
Limitation:
Single employer.
Conclusion:
Financial incentives framed as a loss were most effective for achieving physical activity goals.
Primary Funding Source:
National Institute on Aging.

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What Do You Mean by Medical Home?

Keeping up with the medical home is difficult. Researchers have published dozens of studies on medical homes over the past few years, including an article in this week's Annals by Kern and colleagues, and we can expect dozens more. To complicate matters, these studies frequently disagree with each other. Some have found that medical homes have modest or no effects, whereas others have found desirable changes in quality, utilization, and costs of care. The editorialist believes that to better understand the contribution of each new medical home study, we must first ask how the researchers defined "medical home."

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The Effect of Erythropoietin-Stimulating Agents on Health-Related Quality of Life in Anemia of Chronic Kidney Disease A Systematic Review and Meta-analysis

Background:
The efficacy of erythropoietin-stimulating agents (ESAs) for improving health-related quality of life (HRQOL) in anemia of chronic kidney disease (CKD) is unclear.
Purpose:
To determine the effect of ESAs on HRQOL at different hemoglobin targets in adults with CKD who were receiving or not receiving dialysis.
Data Sources:
Searches of PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov from inception to 1 November 2015, supplemented with manual screening.
Study Selection:
Randomized, controlled trials that evaluated the treatment of anemia with ESAs, including erythropoietin and darbepoetin, targeted higher versus lower hemoglobin levels, and used validated HRQOL metrics.
Data Extraction:
Study characteristics, quality, and data were assessed independently by 2 reviewers. Outcome measures were scores on the 36-item Short-Form Health Survey (SF-36), Kidney Dialysis Questionnaire (KDQ), and other tools.
Data Synthesis:
Of 17 eligible studies, 13 reported SF-36 outcomes and 4 reported KDQ outcomes. Study populations consisted of patients not undergoing dialysis (n = 12), those undergoing dialysis (n = 4), or a mixed sample (n = 1). Only 4 studies had low risk of bias. Pooled analyses showed that higher hemoglobin targets resulted in no statistically or clinically significant differences in SF-36 or KDQ domains. Differences in HRQOL were further attenuated in studies at low risk of bias and in subgroups of dialysis recipients.
Limitation:
Statistically significant heterogeneity among studies, few good-quality studies, and possible publication bias.
Conclusion:
ESA treatment of anemia to obtain higher hemoglobin targets does not result in important differences in HRQOL in patients with CKD.
Primary Funding Source:
KRESCENT and Manitoba Health Research Council Establishment.

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Patient and Public Risks of Powdered Alcohol: A Citywide Case Study to Prevent Abuse

The U.S. Alcohol and Tobacco Tax and Trade Bureau recently approved a formulation of powdered alcohol for sale. The authors discuss the paucity of data available on the safety of this product, its potential harms on an individual and public health basis, and how local advocacy led to a ban of its sale and distribution in Baltimore, Maryland.

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Colorimetric Strategy for Highly Sensitive and Selective Simultaneous Detection of Histidine and Cysteine Based on G-Quadruplex-Cu(II) Metalloenzyme

TOC Graphic

Analytical Chemistry
DOI: 10.1021/acs.analchem.5b04796
ancham?d=yIl2AUoC8zA


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Self-Partitioned Droplet Array on Laser-Patterned Superhydrophilic Glass Surface for Wall-less Cell Arrays

TOC Graphic

Analytical Chemistry
DOI: 10.1021/acs.analchem.5b03764
ancham?d=yIl2AUoC8zA


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ABPTS Specialist Certification: Pediatrics

Maximize your PT potential by becoming a specialist in pediatrics. Learn more at www.abpts.org.



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ABPTS Specialist Certification: Sports Physical Therapy

Maximize your PT potential by becoming a specialist in sports physical therapy. Learn more at www.abpts.org.



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ABPTS Specialist Certification: Clinical Electrophysiology

Maximize your PT potential by becoming a specialist in clinical electrophysiology. Learn more at www.abpts.org.



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ABPTS Specialist Certification: Orthopaedics

Maximize your PT potential by becoming a specialist in orthopaedics. Learn more at www.abpts.org.



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ABPTS Specialist Certification: Cardiovascular & Pulmonary

Maximize your PT potential by becoming a specialist in cardiovascular and pulmonary. Learn more at www.abpts.org.



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ABPTS Specialist Certification: Neurology

Maximize your PT potential by becoming a specialist in neurology. Learn more at www.abpts.org.



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ABPTS Specialist Certification: Geriatrics

Maximize your PT potential by becoming a specialist in geriatrics. Learn more at www.abpts.org.



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ABPTS Specialist Certification: Women’s Health

Maximize your PT potential by becoming a specialist in women's health. Learn more at www.abpts.org.



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Maximize Your PT Potential With ABPTS Specialist Certification

ABPTS offers board-certification in 8 areas: cardiovascular and pulmonary, clinical electrophysiology, geriatrics, neurology, orthopaedics, pediatrics, sports, and women's health.

Learn more at www.abpts.org.



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In abstinent adults with type 2 diabetes, a daily glass of wine (vs mineral water) improved cardiometabolic factors



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Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies

Background:
Controversy persists about optimal mammography screening strategies.
Objective:
To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer.
Design:
Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality.
Setting:
United States.
Patients:
Average-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity.
Intervention:
Eight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years.
Measurements:
Benefits (breast cancer–specific mortality reduction, breast cancer deaths averted, life-years, and quality-adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens.
Results:
Biennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar benefits, but more harms than other strategies). For groups with a 2- to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years.
Limitation:
Other imaging technologies, polygenic risk, and nonadherence were not considered.
Conclusion:
Biennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the decision makers' weight given to the harms and benefits of screening.
Primary Funding Source:
National Institutes of Health.

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Annals for Educators - 16 February 2016



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Factors Associated With Rates of False-Positive and False-Negative Results From Digital Mammography Screening: An Analysis of Registry Data

Background:
Women screened with digital mammography may receive false-positive and false-negative results and subsequent imaging and biopsies. How these outcomes vary by age, time since the last screening, and individual risk factors is unclear.
Objective:
To determine factors associated with false-positive and false-negative digital mammography results, additional imaging, and biopsies among a general population of women screened for breast cancer.
Design:
Analysis of registry data.
Setting:
Participating facilities at 5 U.S. Breast Cancer Surveillance Consortium breast imaging registries with linkages to pathology databases and tumor registries.
Patients:
405 191 women aged 40 to 89 years screened with digital mammography between 2003 and 2011. A total of 2963 were diagnosed with invasive cancer or ductal carcinoma in situ within 12 months of screening.
Measurements:
Rates of false-positive and false-negative results and recommendations for additional imaging and biopsies from a single screening round; comparisons by age, time since the last screening, and risk factors.
Results:
Rates of false-positive results (121.2 per 1000 women [95% CI, 105.6 to 138.7]) and recommendations for additional imaging (124.9 per 1000 women [CI, 109.3 to 142.3]) were highest among women aged 40 to 49 years and decreased with increasing age. Rates of false-negative results (1.0 to 1.5 per 1000 women) and recommendations for biopsy (15.6 to 17.5 per 1000 women) did not differ greatly by age. Results did not differ by time since the last screening. False-positive rates were higher for women with risk factors, particularly family history of breast cancer; previous benign breast biopsy result; high breast density; and, for younger women, low body mass index.
Limitations:
Confounding by variation in patient-level characteristics and outcomes across registries and regions may have been present. Some factors, such as numbers of first- and second-degree relatives with breast cancer and diagnoses associated with previous benign biopsy results, were not examined.
Conclusion:
False-positive mammography results and additional imaging are common, particularly for younger women and those with risk factors, whereas biopsies occur less often. Rates of false-negative results are low.
Primary Funding Source:
Agency for Healthcare Research and Quality and National Cancer Institute.

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In patients with hypertension, β-blockers in the 120 d before noncardiac surgery were linked to CV events and death



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The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model

Background:
Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown.
Objective:
To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments.
Design:
Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status).
Data Sources:
Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry.
Target Population:
U.S. women aged 50 to 74 years.
Time Horizon:
10 and 25 years.
Perspective:
Population.
Intervention:
Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab.
Outcome Measures:
Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups.
Results of Base-Case Analysis:
At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10 000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10 000 women.
Results of Sensitivity Analysis:
Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%.
Limitation:
Disease models simplify reality and cannot capture all breast cancer subtypes.
Conclusion:
Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival.
Primary Funding Source:
University of Washington and National Cancer Institute.

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In patients with SBP ≥ 130 mm Hg and CV risk, intensive vs standard BP control reduced CV events and mortality



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Effectiveness of Breast Cancer Screening: Systematic Review and Meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation

Background:
In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years.
Purpose:
To review studies of the effectiveness of breast cancer screening in average-risk women.
Data Sources:
MEDLINE and Cochrane databases to 4 June 2015.
Study Selection:
English-language randomized, controlled trials and observational studies of screening with mammography, magnetic resonance imaging, and ultrasonography that reported breast cancer mortality, all-cause mortality, or advanced breast cancer outcomes.
Data Extraction:
Investigators extracted and confirmed data and dual rated study quality; discrepancies were resolved through consensus.
Data Synthesis:
Fair-quality evidence from a meta-analysis of mammography trials indicated relative risks (RRs) for breast cancer mortality of 0.92 for women aged 39 to 49 years (95% CI, 0.75 to 1.02) (9 trials; 3 deaths prevented per 10 000 women over 10 years); 0.86 for those aged 50 to 59 years (CI, 0.68 to 0.97) (7 trials; 8 deaths prevented per 10 000 women over 10 years); 0.67 for those aged 60 to 69 years (CI, 0.54 to 0.83) (5 trials; 21 deaths prevented per 10 000 women over 10 years); and 0.80 for those aged 70 to 74 years (CI, 0.51 to 1.28) (3 trials; 13 deaths prevented per 10 000 women over 10 years). Risk reduction was 25% to 31% for women aged 50 to 69 years in observational studies of mammography screening. All-cause mortality was not reduced with screening. Advanced breast cancer was reduced for women aged 50 years or older (RR, 0.62 [CI, 0.46 to 0.83]) (3 trials) but not those aged 39 to 49 years (RR, 0.98 [CI, 0.74 to 1.37]) (4 trials); less evidence supported this outcome.
Limitations:
Most trials used imaging technologies and treatments that are now outdated, and definitions of advanced breast cancer were heterogeneous. Studies of effectiveness based on risk factors, intervals, or other modalities were unavailable or methodologically limited.
Conclusion:
Breast cancer mortality is generally reduced with mammography screening, although estimates are not statistically significant at all ages and the magnitudes of effect are small. Advanced cancer is reduced with screening for women aged 50 years or older.
Primary Funding Source:
Agency for Healthcare Research and Quality.

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In acute low back pain, adding oxycodone/acetaminophen or cyclobenzaprine to naproxen did not improve pain or function



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Harms of Breast Cancer Screening: Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation

Background:
In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years.
Purpose:
To review studies of screening in average-risk women with mammography, magnetic resonance imaging, or ultrasonography that reported on false-positive results, overdiagnosis, anxiety, pain, and radiation exposure.
Data Sources:
MEDLINE and Cochrane databases through December 2014.
Study Selection:
English-language systematic reviews, randomized trials, and observational studies of screening.
Data Extraction:
Investigators extracted and confirmed data from studies and dual-rated study quality. Discrepancies were resolved through consensus.
Data Synthesis:
Based on 2 studies of U.S. data, 10-year cumulative rates of false-positive mammography results and biopsies were higher with annual than biennial screening (61% vs. 42% and 7% vs. 5%, respectively) and for women aged 40 to 49 years, those with dense breasts, and those using combination hormone therapy. Twenty-nine studies using different methods reported overdiagnosis rates of 0% to 54%; rates from randomized trials were 11% to 22%. Women with false-positive results reported more anxiety, distress, and breast cancer–specific worry, although results varied across 80 observational studies. Thirty-nine observational studies indicated that some women reported pain during mammography (1% to 77%); of these, 11% to 46% declined future screening. Models estimated 2 to 11 screening-related deaths from radiation-induced cancer per 100 000 women using digital mammography, depending on age and screening interval. Five observational studies of tomosynthesis and mammography indicated increased biopsies but reduced recalls compared with mammography alone.
Limitations:
Studies of overdiagnosis were highly heterogeneous, and estimates varied depending on the analytic approach. Studies of anxiety and pain used different outcome measures. Radiation exposure was based on models.
Conclusion:
False-positive results are common and are higher for annual screening, younger women, and women with dense breasts. Although overdiagnosis, anxiety, pain, and radiation exposure may cause harm, their effects on individual women are difficult to estimate and vary widely.
Primary Funding Source:
Agency for Healthcare Research and Quality.

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In atrial fibrillation, the ATRIA risk score better predicted stroke than CHADS 2 and CHA 2 DS 2 -VASc scores



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Optimal parameters for laccase-mediated destaining of Coomassie Brilliant Blue R-250-stained polyacrylamide gels

Publication date: June 2016
Source:Data in Brief, Volume 7
Author(s): Jie Yang, Xiaodan Yang, Xiuyun Ye, Juan Lin
The data presented in this article are related to the research article entitled "Destaining of Coomassie Brilliant Blue R-250-stained polyacrylamide gels with fungal laccase" [1]. Laccase is a class of multicopper oxidases that can catalyze oxidation of recalcitrant dyestuffs. This article describes optimal parameters for destaining of polyacrylamide gels, stained with Coomassie Brilliant Blue R-250, with laccase from basidiomycete Cerrena sp. strain HYB07. Effects of laccase activity, mediator type and concentration, temperature and time on destaining of polyacrylamide gels were evaluated with respect to gel background intensity and protein band signals, and the optimal destaining effects were obtained with 15UmL−1 laccase and 2μM ABTS at 37°C after 2h.



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Characterization of rhamnolipids by liquid chromatography/mass spectrometry after solid-phase extraction

Abstract

Rhamnolipids are surface-active agents with a broad application potential that are produced in complex mixtures by bacteria of the genus Pseudomonas. Analysis from fermentation broth is often characterized by laborious sample preparation and requires hyphenated analytical techniques like liquid chromatography coupled to mass spectrometry (LC-MS) to obtain detailed information about sample composition. In this study, an analytical procedure based on chromatographic method development and characterization of rhamnolipid sample material by LC-MS as well as a comparison of two sample preparation methods, i.e., liquid-liquid extraction and solid-phase extraction, is presented. Efficient separation was achieved under reversed-phase conditions using a mixed propylphenyl and octadecylsilyl-modified silica gel stationary phase. LC-MS/MS analysis of a supernatant from Pseudomonas putida strain KT2440 pVLT33_rhlABC grown on glucose as sole carbon source and purified by solid-phase extraction revealed a total of 20 congeners of di-rhamnolipids, mono-rhamnolipids, and their biosynthetic precursors 3-(3-hydroxyalkanoyloxy)alkanoic acids (HAAs) with different carbon chain lengths from C8 to C14, including three rhamnolipids with uncommon C9 and C11 fatty acid residues. LC-MS and the orcinol assay were used to evaluate the developed solid-phase extraction method in comparison with the established liquid-liquid extraction. Solid-phase extraction exhibited higher yields and reproducibility as well as lower experimental effort.

Graphical Abstract



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Qualitative identification of growth hormone-releasing hormones in human plasma by means of immunoaffinity purification and LC-HRMS/MS

Abstract

The use of growth hormone-releasing hormones (GHRHs) is prohibited in sports according to the regulations of the World Anti-Doping Agency (WADA). The aim of the present study was to develop a method for the simultaneous detection of four different GHRHs and respective metabolites from human plasma by means of immunoaffinity purification and subsequent nano-ultrahigh performance liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry. The target analytes included Geref (Sermorelin), CJC-1293, CJC-1295, and Egrifta (Tesamorelin) as well as two metabolites of Geref and CJC-1293, which were captured from plasma samples using a polyclonal GHRH antibody in concert with protein A/G monolithic MSIA™ D.A.R.T.'S® (Disposable Automation Research Tips) prior to separation and detection. The method was fully validated and found to be fit for purpose considering the parameters specificity, linearity, recovery (19–37 %), lower limit of detection (<50 pg/mL), imprecision (<20 %), and ion suppression/enhancement effects. The analytes' stability and metabolism were elucidated using in vitro and in vivo approaches. EDTA blood samples were collected from rats 2, 4, and 8 h after intravenous administration of GHRH (one compound per test animal). All intact substances were detected for at least 4 h but no anticipated metabolite was confirmed in laboratory rodents' samples; conversely, a Geref metabolite (GHRH3-29) was found in a human plasma sample collected after subcutaneous injection of the drug to a healthy male volunteer. The obtained results demonstrate that GHRHs are successfully detected in plasma using an immunoaffinity-mass spectrometry-based method, which can be applied to sports drug testing samples. Further studies are however required and warranted to account for potential species-related differences in metabolism and elimination of the target analytes

Graphical abstract

GHRH immunoaffinity purification by means of anti-GHRH antibody coated protein A/G D.A.R.T.'S


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Label-free and sensitive aptasensor based on dendritic gold nanostructures on functionalized SBA-15 for determination of chloramphenicol

Abstract

A highly sensitive and low-cost electrochemical aptasensor was developed for the determination of chloramphenicol (CAP). The system was based on a CAP-binding aptamer, a molecular recognition element, and 1,4-diazabicyclo[2.2.2]octane (DABCO)-supported mesoporous silica SBA-15 on the surface of a screen-printed graphite electrode for formation of dendritic gold nanostructures and improving the performance and conductivity of the biosensor. Hemin has been applied as an electrochemical indicator which interacted with the guanine bases of the aptamer. In the absence of CAP, hemin binds to the aptamer and produces a weak differential pulse voltammetric (DPV) signal. The presence of CAP led to stabilization of the folded aptamer, which generated an amplified DPV signal. The peak current of hemin increased linearly with the concentration of CAP. Under optimal conditions, two linear ranges were obtained from 0.03 to 0.15 μM and 0.15 to 7.0 μM, respectively, and the detection limit was 4.0 nM. The prepared biosensor has good selectivity against other non-target drugs. Thus, the sensor could provide a promising platform for the fabrication of aptasensors. The feasibility of using this aptasensor was demonstrated by determination of CAP in a human blood serum sample.



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Quantification of a peptide standard using the intrinsic fluorescence of tyrosine

Abstract

Absolute quantification of peptides is typically achieved using amino acid analysis, elemental analysis or derivatisation chemistry. Impurities, if present, may be accounted for using analytical high-performance liquid chromatography (HPLC) with detection of the peptide bond ultraviolet (UV) absorbance. To do this, peak areas from a UV chromatogram are used to estimate percentage purity on a mass basis, and this purity value is used as a correction. However, because the approach assumes that UV absorbance is uniformly proportional to mass, the result may be only semi-quantitative. Here, an alternative approach involving HPLC with detection of intrinsic tyrosine fluorescence is described. The fluorescence properties of a 21-residue synthetic peptide corresponding to an S-carbamidomethylated tryptic fragment of human serum albumin were characterised, and a method involving quantification relative to a non-peptidic calibrant, N-acetyl-l-tyrosine ethyl ester, was established. The method was used to quantify the thiol form of the peptide, and the results were compared with a parallel analysis involving derivatisation of the same material with Ellman's reagent. When differences in fluorescence response (analyte versus calibrant) were accounted for, the measurements obtained via the two methods were in good agreement. Contributions from peptidic impurities were also considered, and their influence on the validity of the conclusions was evaluated. Despite some ambiguities introduced by the impurities, and the identification of some other potential sources of error, the results demonstrate that use of Tyr fluorescence is a promising solution to the challenging problem of absolute peptide quantification.

Graphical Abstract

A low-molecular-weight tyrosine derivative was used as a generic fluorescence calibrant for the quantification of a 21-residue peptide


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Fluoroquinolone prophylaxis in preventing BK polyomavirus infection after renal transplant: A systematic review and meta-analysis

Publication date: Available online 15 February 2016
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Tu-Run Song, Zheng-Sheng Rao, Yang Qiu, Jin-Peng Liu, Zhong-Li Huang, Xian-Ding Wang, Tao Lin
Previous studies regarding the prevention of BK viremia following renal transplantation with fluoroquinolone have yielded conflicting results. The purpose of this systematic review was to examine the evidence regarding the efficacy of fluoroquinolone in preventing BK polyomavirus infection following renal transplantation. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for research articles published prior to January 2015 using keywords such as "fluoroquinolone," "BK viremia," and "renal transplantation." We extracted all types of study published in English. The primary outcome was BK viremia and viruria at 1 year post-transplantation. Secondary outcomes were BK virus-associated nephropathy (BKVN), graft failure, and fluoroquinolone-resistant infection. We identified eight trials, including a total of 1477 participants with a mean duration of fluoroquinolone prophylaxis of >1 month. At 1 year, fluoroquinolone prophylaxis was not associated with a decreased incidence of BK viremia [risk ratio (RR), 0.84; 95% confidence interval (95% CI), 0.58–1.20). No significant differences in BKVN (RR, 0.88; 95% CI, 0.37–2.11), risk of graft failure due to BKVN (RR, 0.68; 95% CI, 0.29–1.59), or fluoroquinolone-resistant infection (RR, 1.08; 95% CI, 0.64–1.83) were observed between the fluoroquinolone prophylaxis and control groups. The results of this study suggest that fluoroquinolone is ineffective in preventing BK polyomavirus infection following renal transplantation.



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In Situ Characterization of Hydrated Proteins in Water by SALVI and ToF-SIMS

53708fig1.jpg

This work presents a protocol for liquid handling and sample introduction to a microchannel for in situ time-of-flight secondary ion mass spectrometry analysis of protein biomolecules in an aqueous solution.

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Development of a Specific Monoclonal Antibody for the Quantification of Artemisinin in Artemisia annua and Rat Serum

TOC Graphic

Analytical Chemistry
DOI: 10.1021/acs.analchem.5b04058
ancham?d=yIl2AUoC8zA


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What do we know about homocysteine and exercise? A review from the literature

Journal Name: Clinical Chemistry and Laboratory Medicine (CCLM)
Issue: Ahead of print


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Plasma total C-terminal agrin fragment (tCAF) as a marker for kidney function in patients with chronic kidney disease

Journal Name: Clinical Chemistry and Laboratory Medicine (CCLM)
Issue: Ahead of print


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History dependence of the electromyogram: Implications for isometric steady-state EMG parameters following a lengthening or shortening contraction

Publication date: April 2016
Source:Journal of Electromyography and Kinesiology, Volume 27
Author(s): Alexis A. Jones, Geoffrey A. Power, Walter Herzog
Residual force enhancement (RFE) and force depression (FD) refer to an increased or decreased force following an active lengthening or shortening contraction, respectively, relative to the isometric force produced at the same activation level and muscle length. Our intent was to determine if EMG characteristics differed in the RFE or FD states compared with a purely isometric reference contraction for maximal and submaximal voluntary activation of the adductor pollicis muscle. Quantifying these alterations to EMG in history-dependent states allows for more accurate modeling approaches for movement control in the future. For maximal voluntary contractions (MVC), RFE was 6–15% (P<0.001) and FD was 12–19% (P<0.001). The median frequency of the EMG was not different between RFE, FD and isometric reference contractions for the 100% and 40% MVC intensities (P>0.05). However, root mean square EMG (EMGRMS) amplitude for the submaximal contractions was higher in the FD and lower in the RFE state, respectively (P<0.05). For maximal contractions, EMGRMS was lower for the FD state but was the same for the RFE state compared to the isometric reference contractions (P>0.05). Neuromuscular efficiency (NME; force/EMG) was lower in the force depressed state and higher in the force enhanced state (P<0.05) compared to the isometric reference contractions. EMG spectral properties were not altered between the force-enhanced and depressed states relative to the isometric reference contractions, while EMG amplitude measures were.



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The impact of state of bladder fullness on tonic and phasic activation of the pelvic floor muscles in women

Publication date: Available online 13 February 2016
Source:Journal of Electromyography and Kinesiology
Author(s): Linda McLean, Catherine Normandeau, Joanne Hodder
PurposeWe aimed to determine if state of bladder fullness affects pelvic floor muscle activation in healthy women without urogenital symptoms.Materials and MethodsTwenty-three nulliparous, continent female participants were recruited to participate. Women were randomized to begin the protocol with either an empty (EF) or a full (FE) bladder. Tonic and maximal voluntary pelvic floor muscle electromyographic activity were measured in three states of bladder fullness (empty, full and uncomfortably full). Electromyographic signal amplitudes were compared among bladder states using separate two-way repeated-measures analyses of variance including bladder state and test order as main effects as well as the interaction between bladder state and test order.ResultsTonic activity of the pelvic floor muscles was significantly higher in the full and uncomfortably full bladder states compared to when the bladder was empty (p<0.005). Maximum voluntary electromyographic activation was unaffected by state of bladder fullness (p=0.713).ConclusionsConsistent with studies in which the bladder was filled through saline infusion, these results suggest that tonic activity of the PFMs is higher when the bladder is full compared to when it is empty. However once the bladder is moderately full, tonic PFM activity does not increase with increases in bladder volume.



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Effect of kinesthetic illusion induced by visual stimulation on muscular output function after short-term immobilization

Publication date: Available online 12 February 2016
Source:Journal of Electromyography and Kinesiology
Author(s): Toru Inada, Fuminari Kaneko, Tatsuya Hayami
Kinesthetic illusions by visual stimulation (KiNVIS) enhances corticomotor excitability and activates motor association areas. The purpose of this study was to investigate the effect of KiNVIS induction on muscular output function after short-term immobilization. Thirty subjects were assigned to 3 groups: an immobilization group, with the left hand immobilized for 12 h (immobilization period); an illusion group, with the left hand immobilized and additionally subjected to KiNVIS of the immobilized part during the immobilization period; and a control group with no manipulation. The maximum voluntary contraction (MVC), fluctuation of force (force fluctuation) during a force modulation task, and twitch force were measured both before (pre-test) and after (post-test) the immobilization period. Data were analyzed by performing two-way (TIME × GROUP) repeated measures ANOVA. The MVC decreased in the immobilization group only (pre-test; 37.8 ± 6.1 N, post-test; 32.8 ± 6.9 N, p < 0.0005) after the immobilization period. The force fluctuation increased only in the immobilization group (pre-test; 2.19 ± 0.54 %, post-test; 2.78 ± 0.87 %, p = 0.007) after the immobilization period. These results demonstrate that induction of KiNVIS prevents negative effect on MVC and force fluctuation after 12 h of immobilization.



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Construction and Systematical Symmetric Studies of a Series of Supramolecular Clusters with Binary or Ternary Ammonium Triphenylacetates

53418fig1.jpg

This article describes construction of a series of hydrogen-bonding supramolecular clusters in crystals using primary ammonium triphenylacetates, which are recrystallized from non-polar solvents. This selective construction of the supramolecular clusters leads to effective systematical symmetric studies about a correlation between the supramolecular clusters and their components.

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Forests, Vol. 7, Pages 41: Development of Ash Dieback in South-Eastern Germany and the Increasing Occurrence of Secondary Pathogens

Since its first identification in Poland in 2006, the ascomycete Hymenoscyphus fraxineus has caused massive dieback of Fraxinus excelsior in the countries of eastern, northern and central Europe. This work shows the development, expansion, and severity of the disease in south-eastern Germany for a period of four years, starting in 2010. Differences between habitats, as well as age classes have been captured. The presence and the amount of potentially resistant trees were proven over the years, to determine how high the resistance level might be. Typical disease symptoms are the wilting of leaves, necrotic lesions in the bark and reddish discolorations of branches and stems. In addition, stem necroses also appear by infection with species of Armillaria. Therefore, special attention has been given to Armillaria species in affected ash stands but also to other secondary pathogens, like ash bark beetles. It is shown that breeding galleries of Hylesinus fraxini are only found in trees that have recently died and thus Hylesinus fraxini is still acting as a secondary opportunistic pathogen. In contrast, Armillaria spp. can be considered as serious pathogens of weakened ash trees. In different ash stands, typical symptoms of infection can be found. A relationship between stem base necrotic lesions and vitality was examined. It is shown that necrotic lesions severely contribute to accelerating the mortality of ash trees. In addition to the high infection pressure by H. fraxineus, the high inoculum of Armillaria in the soil facilitates further infections and, thus, likewise endangers the survival of potentially resistant trees. In the following years, forest conversion and seed harvest in affected ash stands will have to be urgently considered to avoid tree gaps on a large scale. Furthermore, infection assays of potentially resistant trees with ensuing breeding programmes should be initially started for the conservation of this ecologically and economically important tree species.

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Molecules, Vol. 21, Pages 212: Synthetic Strategy and Anti-Tumor Activities of Macrocyclic Scaffolds Based on 4-Hydroxyproline

A series of novel 13- to 15-member hydroxyproline-based macrocycles, which contain alkyl-alkyl ether and alkyl-aryl ether moieties, have been synthesized by the strategy of macrocyclization utilising azide-alkyne cycloaddition, Mitsunobu protocol and amide formation. Their anti-tumor activities towards A549, MDA-MB-231 and Hep G2 cells were screened in vitro by an MTT assay. The results indicated that 13-member macrocycle 33 containing alkene chain showed the best results, exhibiting the highest inhibitory effects towards lung cancer cell line A549, which was higher than that of the reference cisplatin (IC50 value = 2.55 µmol/L).

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Reconciling RDoC and DSM approaches in clinical psychophysiology and neuroscience

Abstract

The Research Domain Criteria (RDoC) initiative endeavors to foster a science of psychopathology based around dimensions of brain-behavior relationships as opposed to subjectively based diagnostic categories. A rapidly accumulating array of transdiagnostic commonalities, across multiple objective and subjective measures, underscores the clear potential of this initiative. At the same time, a road map for guiding future RDoC research efforts is needed that draws upon the wealth of extant disorder-specific findings. In this issue, Hamm and colleagues provide an example of conceptualizing within-disorder processes in terms of dimensional brain-behavior relationships that advances the understanding of panic disorder with agoraphobia beyond the conventional nosological framework. Their findings and conceptual model are reviewed and discussed in terms of broader transdiagnostic implications.



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Applying Research Domain Criteria (RDoC) to the study of fear and anxiety: A critical comment

Abstract

The goal of the Research Domain Criteria (RDoC) is to develop an interdisciplinary science of psychopathology, forming a template for research and disconnecting conceptual and empirical questions from traditional diagnostic entities. In this article, we review some of the challenges in the implementation of this framework within the field of pathological fear and anxiety, specifically commenting on the article by Hamm and colleagues (2016). The study of pathological fear and anxiety has had considerable, yet stalled, success in its understanding of underlying mechanisms, prevention, and treatment. With a shift toward RDoC, it is unclear what to do with the existing diagnostic labels, and the importance of defining and measuring phenotypes becomes paramount. Additional concerns include the role of psychological constructs and mechanisms, the use of self-report measures, the examination of replication and clinical utility, and the measurement of the role of the environment. Though a laudable and potentially necessary shift in focus, it remains to be seen whether new overall insights into psychopathology will emerge from focusing on small units of analyses and piecing them together and whether these insights will directly translate into the prevention of psychopathology, more efficacious treatments, and improved lives of patients.



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Taking an RDoC lens to the study of panic disorder: A commentary on Hamm et al. and other thoughts on RDoC

Abstract

The Research Domain Criteria (RDoC) initiative put forth by the National Institute of Mental Health represents an exciting new framework in which to study psychopathology. The article by Hamm et al. (2016) is an interesting application of an "RDoC lens" toward a program of research on panic disorder. This commentary highlights the many strengths of the Hamm et al. (2016) study—most notably the article's application of a well-studied animal model of anxiety (Fanselow's, , threat imminence model) to humans, utilization of an interesting behavioral paradigm (as an analog for avoidance behaviors in panic disorder), and using RDoC to examine predictors of treatment response. This commentary also discusses several questions about RDoC that arise out of Hamm et al. For example, (a) How should participants be selected for RDoC studies? (b) Are RDoC constructs risk factors (and risk factors for what)? (c) Besides Hamm et al.'s, approach, how else can RDoC be used in treatment studies? In sum, Hamm et al. is a very good example of an RDoC study, and in this early phase of the initiative, more examples for how the approach plays out are needed.



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The error-related negativity: A transdiagnostic marker of sustained threat?

Abstract

The creation of the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) project has been the driving force behind the reconceptualization of the pathogenesis of psychiatric disorders. In this commentary, I explore whether the error-related negativity can be considered as a transdiagnostic marker of sustained threat based on findings from Weinberg, Meyer et al.'s (2016) study in relation to current findings in the literature. Potential alternative study designs, use of a multimodal approach to the assessment of a specific phenotype of clinical phenomenon, and the importance of integrating a neurodevelopmental perspective are also discussed.



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Psychobiological operationalization of RDoC constructs: Methodological and conceptual opportunities and challenges

Abstract

NIMH's Research Domain Criteria (RDoC) project seeks to advance the diagnosis, prevention, and treatment of mental disorders by promoting psychobiological research on dimensional constructs that might cut across traditional diagnostic boundaries (Kozak & Cuthbert, ). At the core of this approach is the notion that these dimensional constructs can be assessed across different units of analysis (e.g., genes, physiology, behavior), enriching the constructs and providing more complete explanations of clinical problems. While the conceptual aspects of RDoC have been discussed in several prior papers, its methodological aspects have received comparatively less attention. For example, how to integrate data from different units of analysis has been relatively unclear. Here, we discuss one means of psychobiologically operationalizing RDoC constructs across different units of analysis (the psychoneurometric approach; Yancey et al., ), highlighting ways in which this approach might be refined in future iterations. We conclude that there is much to be learned from this technique; however, greater attention to scale-development methods and to psychometrics will likely benefit this and other methodological approaches to combining measurements across multiple units of analysis.



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Achieving success with the Research Domain Criteria (RDoC): Going beyond the matrix

Abstract

Achieving Research Domain Criteria (RDoC) goals depends in part on how well scientists can grasp its principles and execute studies within its framework. Ford provides an exemplary illustration of a research program that aligns with RDoC guidelines. The future success of RDoC depends not just on research like that of Ford and colleagues. RDoC also must inspire the development of reliable neurobehavioral measures with demonstrable clinical validity that produce replicable findings leading to the establishment of neurocircuit-based behavioral dimensions that inform clinical work. Large samples not typically attainable in a clinical neuroscience laboratory or easily imagined within the confines of the RDoC matrix will be required if RDoC is to develop the insights and tools needed to establish incremental value over the DSM. Innovation that goes beyond reliance on the RDoC matrix and measures of neurocircuitry can help facilitate achievement of RDoC's goal of developing a science of psychopathology based on neurobiological systems.



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Psychophysiology as a core strategy in RDoC

Abstract

The Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health shows great promise in providing guidance for research on mental illness but has prompted considerable controversy. Papers by Yancey, Venables, and Patrick and Kozak and Cuthbert illustrate and clarify a number of important features of RDoC. The present commentary evaluates the former paper in light of the latter paper and addresses several common misunderstandings about RDoC. The concept of endophenotypes and diverse psychophysiological approaches will likely be central in RDoC-inspired research.



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The NIMH Research Domain Criteria initiative and error-related brain activity

Abstract

Research on the neural response to errors has an important role in the Research Domain Criteria (RDoC) project, since it is likely to link psychopathology to the dysfunction of neural systems underlying basic behavioral functions, with the error-related negativity (ERN) appearing as a unit of measurement in three RDoC domains. A recent report builds on previous research by examining the ERN as a measure of the sustained threat construct and providing evidence that the ERN may reflect sensitivity more specifically to endogenous threat. Data from 515 adolescent females indicate that the ERN was enlarged primarily in older adolescents with self-reported checking behaviors, although it was blunted in adolescents with depressive symptoms regardless of age. Potential future studies for replicating and extending the research on the ERN and obsessive-compulsive (OC) behaviors are discussed, including studies that more fully characterize OC symptom dimensions, studies that integrate other measures of error-related brain activity and use computational modeling, studies that combine longitudinal, family, and molecular genetic measures, and interventional studies that specifically modulate error-related brain activity in individuals with OC behaviors.



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Panic disorder with agoraphobia from a behavioral neuroscience perspective: Applying the research principles formulated by the Research Domain Criteria (RDoC) initiative

Abstract

In the current review, we reconceptualize a categorical diagnosis—panic disorder and agoraphobia—in terms of two constructs within the domain "negative valence systems" suggested by the Research Domain Criteria initiative. Panic attacks are considered as abrupt and intense fear responses to acute threat arising from inside the body, while anxious apprehension refers to anxiety responses to potential harm and more distant or uncertain threat. Taking a dimensional view, panic disorder with agoraphobia is defined with the threat-imminence model stating that defensive responses are dynamically organized along the dimension of the proximity of the threat. We tested this model within a large group of patients with panic disorder and agoraphobia (N = 369 and N = 124 in a replication sample) and found evidence that panic attacks are indeed instances of circa strike defense. This component of the defensive reactivity was related to genetic modulators within the serotonergic system. In contrast, anxious apprehension—characterized by attentive freezing during postencounter defense—was related to general distress and depressive mood, as well as to genetic modulations within the hypothalamic-pituitary-adrenal (HPA) axis. Patients with a strong behavioral tendency for active and passive avoidance responded better to exposure treatment if the therapist guides the patient through the exposure exercises.



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Using the NIMH Research Domain Criteria (RDoC) in human and nonhuman primate research

Abstract

In this article, we provide a commentary on Kozak and Cuthbert ()'s theoretical paper discussing the NIMH Research Domain Criteria (RDoC) initiative and on Latzman et al. (2016)'s empirical investigation of the RDoC negative valence systems domain in chimpanzees, conducted with experimental procedures across genetic, neurobiological, and behavioral levels of analysis. We discuss the pros and cons of the RDoC approach to research on mental illness as well as the strengths and weaknesses of the implementation of this approach in the chimpanzee study.



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Issue Information



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Psychophysiology of threat response, paradigm shifts in psychiatry, and RDoC: Implications for genetic investigation of psychopathology

Abstract

Two articles in this issue seek to further the goal of NIMH's Research Domain Criteria (RDoC) initiative to develop new approaches for investigating mental disorders, using fundamental dimensions that cut across traditional disorder categories and align more closely with mechanisms that underlie psychopathology. One article, by Lang, McTeague, and Bradley, describes the construction of such a disorder cross-crossing dimension of fear response. The other, by Kozak and Cuthbert, expounds upon the basis and conceptualization of research targets under RDoC. Possible implications of these developments for psychiatric genetics research are discussed.



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Toxins, Vol. 8, Pages 44: An Insight into the Triabin Protein Family of American Hematophagous Reduviids: Functional, Structural and Phylogenetic Analysis

A transcriptomic analysis of the saliva of T. pallidipennis together with a short proteomic analysis were carried out to reveal novel primary structures of the lipocalin/triabin protein families in this reduviid. Although triabins share some structural characteristics to lipocalins and they are classified as in the calcyn/lipocalin superfamily, triabins differ from lipocalins in the direction of β-strands in the general conformation of the β-barrel. The triabin protein family encompasses a wide variety of proteins, which disrupt the hemostasis of warm-blooded animals. Likewise, the function of proteins classified as triabins includes proteins that are carriers of small molecules, protease inhibitors, binders of specific cell-surface receptors as well as proteins that form complexes with other macromolecules. For example, triabin and pallidipin from the saliva of T. pallidipennis are thrombin and platelet aggregation inhibitors, respectively; triplatin from T. infestans binds to thromboxane A2; and nitrophorin from Rhodnius prolixus carries nitric oxide. Therefore, based on 42 new transcriptome sequences of triabins from the salivary glands of T. pallidipennis reported at present, and on triabin sequences of other American hematophagous reduviids already reported in the literature, subfamilies of triabins were proposed following phylogenetic analyses and functional characterization of triabin members. Eight subfamilies of proteins were recognized with known functions, which were the nitrophorin and amine binding proteins, Rhodnius prolixus aggregation inhibitor, triafestin, triatin, dipetalodipin and pallidipin, triplatin and infestilin, dimiconin and triabin, and procalin subfamilies. Interestingly, 70% of the analyzed sequences came from these eight subfamilies because there was no biological function associated with them, implying the existence of a vast number of proteins with potential novel biological activities.

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IJMS, Vol. 17, Pages 236: miR-9-5p, miR-675-5p and miR-138-5p Damages the Strontium and LRP5-Mediated Skeletal Cell Proliferation, Differentiation, and Adhesion

This study was designed to evaluate the effects of strontium on the expression levels of microRNAs (miRNAs) and to explore their effects on skeletal cell proliferation, differentiation, adhesion, and apoptosis. The targets of these miRNAs were also studied. Molecular cloning, cell proliferation assay, cell apoptosis assay, quantitative real-time PCR, and luciferase reporter assay were used. Strontium altered the expression levels of miRNAs in vitro and in vivo. miR-9-5p, miR-675-5p, and miR-138-5p impaired skeletal cell proliferation, cell differentiation and cell adhesion. miR-9-5p and miR-675-5p induced MC3T3-E1 cell apoptosis more specifically than miR-138-5p. miR-9-5p, miR-675-5p, and miR-138-5p targeted glycogen synthase kinase 3 β (GSK3β), ATPase Aminophospholipid Transporter Class I Type 8A Member 2 (ATP8A2), and Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (EIF4EBP1), respectively. Low-density lipoprotein receptor-related protein 5 (LRP5) played a positive role in skeletal development. miR-9-5p, miR-675-5p, and miR-138-5p damage strontium and LRP5-mediated skeletal cell proliferation, differentiation, and adhesion, and induce cell apoptosis by targeting GSK3β, ATP8A2, and EIF4EBP1, respectively.

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IJERPH, Vol. 13, Pages 216: Pathogens in Ornamental Waters: A Pilot Study

In parks, ornamental waters of easy access and populated with animals are quite attractive to children and yet might hide threats to human health. The present work focuses on the microbiota of the ornamental waters of a Lisboa park, characterized during 2015. The results show a dynamic microbiota integrating human pathogens such as Klebsiella pneumoniae, Aeromonas spp. and Enterobacter spp., and also antibiotic resistant bacteria. K. pneumoniae and Aeromonas spp. were present as planktonic and biofilm organized bacteria. In vitro K. pneumoniae and Aeromonas spp. showed an enhanced ability to assemble biofilm at 25 °C than at 37 °C. Bacteria recovered from biofilm samples showed an increased antibiotic resistance compared to the respective planktonic counterparts.

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Nutrients, Vol. 8, Pages 79: Suppression of Endogenous Glucose Production by Isoleucine and Valine and Impact of Diet Composition

Leucine has been shown to acutely inhibit hepatic glucose production in rodents by a mechanism requiring its metabolism to acetyl-CoA in the mediobasal hypothalamus (MBH). In the early stages, all branched-chain amino acids (BCAA) are metabolized by a shared set of enzymes to produce a ketoacid, which is later metabolized to acetyl-CoA. Consequently, isoleucine and valine may also modulate glucose metabolism. To examine this possibility we performed intrahypothalamic infusions of isoleucine or valine in rats and assessed whole body glucose kinetics under basal conditions and during euglycemic pancreatic clamps. Furthermore, because high fat diet (HFD) consumption is known to interfere with central glucoregulation, we also asked whether the action of BCAAs was affected by HFD. We fed rats a lard-rich diet for a short interval and examined their response to central leucine. The results showed that both isoleucine and valine individually lowered blood glucose by decreasing liver glucose production. Furthermore, the action of the BCAA leucine was markedly attenuated by HFD feeding. We conclude that all three BCAAs centrally modulate glucose metabolism in the liver and that their action is disrupted by HFD-induced insulin resistance.

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Nutrients, Vol. 8, Pages 88: Micronutrient Fortified Condiments and Noodles to Reduce Anemia in Children and Adults—A Literature Review and Meta-Analysis

Micronutrient deficiencies impose a considerable burden of disease on many middle and low income countries. Several strategies have been shown to be effective in improving micronutrient deficiencies. However, the impact of fortified condiments as well as fortified noodles is less well documented. We aimed to investigate existing evidence on the impact of micronutrient fortified condiments and noodles on hemoglobin, anemia, and functional outcomes in children and adults (age: 5 to 50 years). We conducted a literature review in electronic databases. In addition, we screened the homepages of relevant organizations and journals. We included randomized controlled trials (RCT). Of 1046 retrieved studies, 14 RCT provided data for the meta-analysis. Micronutrient fortification of condiments and noodles increased hemoglobin concentrations by 0.74 g/dL (95%-confidence intervals (95%-CI): 0.56 to 0.93; 12 studies) and 0.3 g/dL (95%-CI: 0.12 to 0.48; 1 study), respectively. Micronutrient fortification also led to a reduced risk of having anemia (risk ratio 0.59 (95%-CI 0.44 to 0.80)). Ferritin concentrations increased with fortified condiments. Functional outcomes were rarely assessed and showed mixed results. The use of micronutrient fortified condiments can be a strategy to reduce anemia in children and adults due to micronutrient deficiencies. The effect of fortified noodles seems to be smaller.

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Nutrients, Vol. 8, Pages 54: Profile of Free Fatty Acids and Fractions of Phospholipids, Cholesterol Esters and Triglycerides in Serum of Obese Youth with and without Metabolic Syndrome

The study evaluated the profile of circulating fatty acids (FA) in obese youth with and without metabolic syndrome (MetS) to determine its association with nutritional status, lifestyle and metabolic variables. A cross-sectional study was conducted in 96 young people, divided into three groups: obese with MetS (OBMS), obese (OB) and appropriate weight (AW). FA profiles were quantified by gas chromatography; waist circumference (WC), fat folds, lipid profile, high-sensitivity C-reactive protein, glucose, insulin, the homeostasis model assessment (HOMA index), food intake and physical activity (PA) were assessed. The OBMS group had significantly greater total free fatty acids (FFAs), palmitic-16:0 in triglyceride (TG), palmitoleic-16:1n-7 in TG and phospholipid (PL); in the OB group, these FAs were higher than in the AW group. Dihomo-gamma-linolenic (DHGL-20:3n-6) was higher in the OBMS than the AW in PL and FFAs. Linoleic-18:2n-6 in TG and PL had the lowest proportion in the OBMS group. WC, PA, total FFA, linoleic-18:2n-6 in TG and DHGL-20:3n-6 in FFAs explained 62% of the HOMA value. The OB group presented some higher proportions of FA and biochemical values than the AW group. The OBMS had proportions of some FA in the TG, PL and FFA fractions that correlated with disturbances of MetS.

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IJERPH, Vol. 13, Pages 212: Chronic Stress and Suicidal Thinking Among Medical Students

Introduction: The subject of chronic stress and ways of dealing with it are very broad. The aim of this study was to analyze stress and anxiety and their influence on suicidal thinking among medical students. Materials and Methods: The study was conducted in the years 2014 to 2015 in Poland, at the Medical University—Nicolaus Copernicus University, Collegium Medicum. The objective of this study was to assess chronic stress and suicidal thinking among students and how students cope with this huge problem. Descriptive statistics and chi-square analyses were conducted to detect differences. Results: Analyses showed that students' life is full of stressors. Students toward the end of their education cope better with stress than students starting their university studies. Chronic stress has a strong impact on mental health and suicidal thinking among students. Conclusions: The results of the study confirmed that chronic stress and anxiety have a negative influence on mental health and also confirm a relation to suicidal thinking in medical students. Students cope with stress by listening to music, talking to relatives or people close to them, resting or engaging in sports, with cycling, running and swimming being the most common methods used to affect suicidal thinking.

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A method to construct a points system to predict cardiovascular disease considering repeated measures of risk factors

Current predictive models for cardiovascular disease based on points systems use the baseline situation of the risk factors as independent variables. These models do not take into account the variability of the risk factors over time. Predictive models for other types of disease also exist that do consider the temporal variability of a single biological marker in addition to the baseline variables. However, due to their complexity these other models are not used in daily clinical practice. Bearing in mind the clinical relevance of these issues and that cardiovascular diseases are the leading cause of death worldwide we show the properties and viability of a new methodological alternative for constructing cardiovascular risk scores to make predictions of cardiovascular disease with repeated measures of the risk factors and retaining the simplicity of the points systems so often used in clinical practice (construction, statistical validation by simulation and explanation of potential utilization). We have also applied the system clinically upon a set of simulated data solely to help readers understand the procedure constructed.

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Influence of whole-wheat consumption on fecal microbial community structure of obese diabetic mice

The digestive tract of mammals and other animals is colonized by trillions of metabolically-active microorganisms. Changes in the gut microbiota have been associated with obesity in both humans and laboratory animals. Dietary modifications can often modulate the obese gut microbial ecosystem towards a more healthy state. This phenomenon should preferably be studied using dietary ingredients that are relevant to human nutrition. This study was designed to evaluate the influence of whole-wheat, a food ingredient with several beneficial properties, on gut microorganisms of obese diabetic mice. Diabetic (db/db) mice were fed standard (obese-control) or whole-wheat isocaloric diets (WW group) for eight weeks; non-obese mice were used as control (lean-control). High-throughput sequencing using the MiSeq platform coupled with freely-available computational tools and quantitative real-time PCR were used to analyze fecal bacterial 16S rRNA gene sequences. Short-chain fatty acids were measured in caecal contents using quantitative high-performance liquid chromatography photo-diode array analysis. Results showed no statistical difference in final body weights between the obese-control and the WW group. The bacterial richness (number of Operational Taxonomic Units) did not differ among the treatment groups. The abundance of Ruminococcaceae, a family containing several butyrate-producing bacteria, was found to be higher in obese (median: 6.9%) and WW-supplemented mice (5.6%) compared to lean (2.7%, p = 0.02, Kruskal-Wallis test). Caecal concentrations of butyrate were higher in obese (average: 2.91 mmol/mg of feces) but especially in WW-supplemented mice (4.27 mmol/mg) compared to lean controls (0.97 mmol/mg), while caecal succinic acid was lower in the WW group compared to obese but especially to the lean group. WW consumption was associated with ∼3 times higher abundances of Lactobacillus spp. compared to both obese and lean control mice. Analysis of weighted UniFrac distances revealed a distinctive clustering of lean microbial communities separately from both obese and WW-supplemented mice (p = 0.001, ANOSIM test). Predictive metagenome analysis revealed significant differences in several metabolic features of the microbiota among the treatment groups, including carbohydrate, amino acids and vitamin metabolism (p

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Apparent source levels and active communication space of whistles of free-ranging Indo-Pacific humpback dolphins (Sousa chinensis) in the Pearl River Estuary and Beibu Gulf, China

Background. Knowledge of species-specific vocalization characteristics and their associated active communication space, the effective range over which a communication signal can be detected by a conspecific, is critical for understanding the impacts of underwater acoustic pollution, as well as other threats. Methods. We used a two-dimensional cross-shaped hydrophone array system to record the whistles of free-ranging Indo-Pacific humpback dolphins (Sousa chinensis) in shallow-water environments of the Pearl River Estuary (PRE) and Beibu Gulf (BG), China. Using hyperbolic position fixing, which exploits time differences of arrival of a signal between pairs of hydrophone receivers, we obtained source location estimates for whistles with good signal-to-noise ratio (SNR ≥10 dB) and not polluted by other sounds and back-calculated their apparent source levels (ASL). Combining with the masking levels (including simultaneous noise levels, masking tonal threshold, and the Sousa auditory threshold) and the custom made site-specific sound propagation models, we further estimated their active communication space (ACS). Results. Humpback dolphins produced whistles with average root-mean-square ASL of 138.5 ± 6.8 (mean ± standard deviation) and 137.2 ± 7.0 dB re 1 µPa in PRE (N = 33) and BG (N = 209), respectively. We found statistically significant differences in ASLs among different whistle contour types. The mean and maximum ACS of whistles were estimated to be 14.7 ± 2.6 (median ± quartile deviation) and 17.1± 3.5 m in PRE, and 34.2 ± 9.5 and 43.5 ± 12.2 m in BG. Using just the auditory threshold as the masking level produced the mean and maximum ACSat of 24.3 ± 4.8 and 35.7 ± 4.6 m for PRE, and 60.7 ± 18.1 and 74.3 ± 25.3 m for BG. The small ACSs were due to the high ambient noise level. Significant differences in ACSs were also observed among different whistle contour types. Discussion. Besides shedding some light for evaluating appropriate noise exposure levels and information for the regulation of underwater acoustic pollution, these baseline data can also be used for aiding the passive acoustic monitoring of dolphin populations, defining the boundaries of separate groups in a more biologically meaningful way during field surveys, and guiding the appropriate approach distance for local dolphin-watching boats and research boat during focal group following.

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Effects of early and late cheiloplasty on anterior part of maxillary dental arch development in infants with unilateral complete cleft lip and palate

Objectives. The objective of this study is to compare the impact of early and late reconstruction of complete unilateral cleft lip and palate on the growth and development of the front of the dentoalveolar arch. Methods. This study was carried out in the years 2012–2015 at the Clinic of Plastic, Reconstructive and Aesthetic Surgery in Banska Bystrica. Infants with unilateral complete cleft lip and palate were divided into 2 groups according to the timing of lip reconstruction. Group A consisted of infants with early lip reconstruction–realised in the first 14 days of life. Group B consisted of infants with later lip reconstruction–realised in the third month of age. Maxillary dental casts were obtained for each child in four periods–in the first 14 days of life, in the third month, in the sixth month and in the age of one year. These were followed by the identification, measurement and evaluation of anthropometric parameters. Results. Significant differences were occurred after the reconstruction of the lips in linear and angle measurements between infants in the A and B groups. Conclusion. The early surgical reconstruction of the lips in the first 14 days of life has a positive effect on the growth and development of the anterior segment of the dentoalveolar arch. Early lip reconstruction forms a continuous pressure on the frontal segment, resulting in the earlier remedy of anatomical properties and creates appropriate conditions for the best development of this area.

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Spatial structure arising from neighbour-dependent bias in collective cell movement

Mathematical models of collective cell movement often neglect the effects of spatial structure, such as clustering, on the population dynamics. Typically, they assume that individuals interact with one another in proportion to their average density (the mean-field assumption) which means that cell–cell interactions occurring over short spatial ranges are not accounted for. However, in vitro cell culture studies have shown that spatial correlations can play an important role in determining collective behaviour. Here, we take a combined experimental and modelling approach to explore how individual-level interactions give rise to spatial structure in a moving cell population. Using imaging data from in vitro experiments, we quantify the extent of spatial structure in a population of 3T3 fibroblast cells. To understand how this spatial structure arises, we develop a lattice-free individual-based model (IBM) and simulate cell movement in two spatial dimensions. Our model allows an individual's direction of movement to be affected by interactions with other cells in its neighbourhood, providing insights into how directional bias generates spatial structure. We consider how this behaviour scales up to the population level by using the IBM to derive a continuum description in terms of the dynamics of spatial moments. In particular, we account for spatial correlations between cells by considering dynamics of the second spatial moment (the average density of pairs of cells). Our numerical results suggest that the moment dynamics description can provide a good approximation to averaged simulation results from the underlying IBM. Using our in vitro data, we estimate parameters for the model and show that it can generate similar spatial structure to that observed in a 3T3 fibroblast cell population.

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Bodily action penetrates affective perception

Fantoni & Gerbino (2014) showed that subtle postural shifts associated with reaching can have a strong hedonic impact and affect how actors experience facial expressions of emotion. Using a novel Motor Action Mood Induction Procedure (MAMIP), they found consistent congruency effects in participants who performed a facial emotion identification task after a sequence of visually-guided reaches: a face perceived as neutral in a baseline condition appeared slightly happy after comfortable actions and slightly angry after uncomfortable actions. However, skeptics about the penetrability of perception (Zeimbekis & Raftopoulos, 2015) would consider such evidence insufficient to demonstrate that observer's internal states induced by action comfort/discomfort affect perception in a top-down fashion. The action-modulated mood might have produced a back-end memory effect capable of affecting post-perceptual and decision processing, but not front-end perception. Here, we present evidence that performing a facial emotion detection (not identification) task after MAMIP exhibits systematic mood-congruent sensitivity changes, rather than response bias changes attributable to cognitive set shifts; i.e., we show that observer's internal states induced by bodily action can modulate affective perception. The detection threshold for happiness was lower after fifty comfortable than uncomfortable reaches; while the detection threshold for anger was lower after fifty uncomfortable than comfortable reaches. Action valence induced an overall sensitivity improvement in detecting subtle variations of congruent facial expressions (happiness after positive comfortable actions, anger after negative uncomfortable actions), in the absence of significant response bias shifts. Notably, both comfortable and uncomfortable reaches impact sensitivity in an approximately symmetric way relative to a baseline inaction condition. All of these constitute compelling evidence of a genuine top-down effect on perception: specifically, facial expressions of emotion are penetrable by action-induced mood. Affective priming by action valence is a candidate mechanism for the influence of observer's internal states on properties experienced as phenomenally objective and yet loaded with meaning.

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Bagworm bags as portable armour against invertebrate predators

Some animals have evolved the use of environmental materials as "portable armour" against natural enemies. Portable bags that bagworm larvae (Lepidoptera: Psychidae) construct using their own silk and plant parts are generally believed to play an important role as a physical barrier against natural enemies. However, no experimental studies have tested the importance of bags as portable armour against predators. To clarify the defensive function, I studied the bagworm Eumeta minuscula and a potential predator Calosoma maximoviczi (Coleoptera: Carabidae). Under laboratory conditions, all bagworm larvae were attacked by carabid adults, but successfully defended themselves against the predators' mandibles using their own bags. The portable bags, which are composed mainly of host plant twigs, may function as a physical barrier against predator mandibles. To test this hypothesis, I removed the twig bags and replaced some with herb leaf bags; all bag-removed larvae were easily caught and predated by carabids, while all bag-replaced larvae could successfully defend themselves against carabid attacks. Therefore, various types of portable bags can protect bagworm larvae from carabid attacks. This is the first study to test the defensive function of bagworm portable bags against invertebrate predators.

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Effectiveness of adaptive silverware on range of motion of the hand

Background. Hand function is essential to a person's self-efficacy and greatly affects quality of life. Adapted utensils with handles of increased diameters have historically been used to assist individuals with arthritis or other hand disabilities for feeding, and other related activities of daily living. To date, minimal research has examined the biomechanical effects of modified handles, or quantified the differences in ranges of motion (ROM) when using a standard versus a modified handle. The aim of this study was to quantify the ranges of motion (ROM) required for a healthy hand to use different adaptive spoons with electrogoniometry for the purpose of understanding the physiologic advantages that adapted spoons may provide patients with limited ROM. Methods. Hand measurements included the distal interphalangeal joint (DIP), proximal interphalangeal joint (PIP), and metacarpophalangeal joint (MCP) for each finger and the interphalangeal (IP) and MCP joint for the thumb. Participants were 34 females age 18–30 (mean age 20.38 ± 1.67) with no previous hand injuries or abnormalities. Participants grasped spoons with standard handles, and spoons with handle diameters of 3.18 cm (1.25 inch), and 4.45 cm (1.75 inch). ROM measurements were obtained with an electrogoniometer to record the angle at each joint for each of the spoon handle sizes. Results. A 3 × 3 × 4 repeated measures ANOVA (Spoon handle size by Joint by Finger) found main effects on ROM of Joint (F(2, 33) = 318.68, Partial η2 = .95, p

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Sorted gene genealogies and species-specific nonsynonymous substitutions point to putative postmating prezygotic isolation genes in Allonemobius crickets

In the Allonemobius socius complex of crickets, reproductive isolation is primarily accomplished via postmating prezygotic barriers. We tested seven protein-coding genes expressed in the male ejaculate for patterns of evolution consistent with a putative role as postmating prezygotic isolation genes.Our recently diverged species generally lacked sequence variation. As a result, ω-based tests were only mildly successful. Some of our genes showed evidence of elevated ω values on the internal branches of gene trees. In a couple genes these internal branches coincided with both species branching events of the species tree, between A. fasciatus and the other two species, and between A. socius and A. sp. nov. Tex. In comparison, more successful approaches were those that took advantage of the varying degrees of lineage sorting and allele sharing among our young species. These approaches were particularly powerful within the contact zone. Among the genes we tested we found genes with genealogies that indicated relatively advanced degrees of lineage sorting across both allopatric and contact zone alleles. Within a contact zone between two members of the species complex, only a subset of genes maintained allelic segregation despite evidence of ongoing gene flow in other genes. The overlap in these analyses was arginine kinase (AK) and apolipoprotein A-1 binding protein (APBP). These genes represent two of the first examples of sperm maturation, capacitation, and motility proteins with fixed non-synonymous substitutions between species-specific alleles that may lead to postmating prezygotic isolation. Both genes express ejaculate proteins transferred to females during copulation and were previously identified through comparative proteomics. We discuss the potential function of these genes in the context of the specific postmating prezygotic isolation phenotype among our species, namely conspecific sperm precedence and the superior ability of conspecific males to induce oviposition in females.

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RNA-Seq of the Caribbean reef-building coral Orbicella faveolata (Scleractinia-Merulinidae) under bleaching and disease stress expands models of coral innate immunity

Climate change-driven coral disease outbreaks have led to widespread declines in coral populations. Early work on coral genomics established that corals have a complex innate immune system, and whole-transcriptome gene expression studies have revealed mechanisms by which the coral immune system responds to stress and disease. The present investigation expands bioinformatic data available to study coral molecular physiology through the assembly and annotation of a reference transcriptome of the Caribbean reef-building coral, Orbicella faveolata. Samples were collected during a warm water thermal anomaly, coral bleaching event and Caribbean yellow band disease outbreak in 2010 in Puerto Rico. Multiplex sequencing of RNA on the Illumina GAIIx platform and de novo transcriptome assembly by Trinity produced 70,745,177 raw short-sequence reads and 32,463 O. faveolata transcripts, respectively. The reference transcriptome was annotated with gene ontologies, mapped to KEGG pathways, and a predicted proteome of 20,488 sequences was generated. Protein families and signaling pathways that are essential in the regulation of innate immunity across Phyla were investigated in-depth. Results were used to develop models of evolutionarily conserved Wnt, Notch, Rig-like receptor, Nod-like receptor, and Dicer signaling. O. faveolata is a coral species that has been studied widely under climate-driven stress and disease, and the present investigation provides new data on the genes that putatively regulate its immune system.

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IJMS, Vol. 17, Pages 237: Implications of MicroRNAs in the Treatment of Gefitinib-Resistant Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) represents about 85% of the reported cases of lung cancer. Acquired resistance to targeted therapy with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, is not uncommon. It is thus vital to explore novel strategies to restore sensitivity to gefitinib. Provided that microRNAs (miRNAs) negatively regulate their gene targets at the transcriptional level, it is speculated that miRNA mimetics may reduce the expression, activity and signal transduction of EGFR so that sensitization of tumour sites to gefitinib-induced cytotoxicity can be achieved. Indeed, a growing body of evidence has shown that the manipulation of endogenous levels of miRNA not only attenuates the EGFR/PI3K/Akt phosphorylation cascade, but also restores apoptotic cell death in in vitro models of experimentally-induced gefitinib resistance and provoked tumour regression/shrinkage in xenograft models. These data are in concordant with the clinical data showing that the differential expression profiles of miRNA in tumour tissues and blood associate strongly with drug response and overall survival. Furthermore, another line of studies indicate that the chemopreventive effects of a variety of natural compounds may involve miRNAs. The present review aims to discuss the therapeutic capacity of miRNAs in relation to recent discoveries on EGFR-TKI resistance, including chronic drug exposure and mutations.

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