Toxins, Vol. 8, Pages 11: Determination of Gonyautoxin-4 in Echinoderms and Gastropod Matrices by Conversion to Neosaxitoxin Using 2-Mercaptoethanol and Post-Column Oxidation Liquid Chromatography with Fluorescence Detection

Paralytic Shellfish Toxin blooms are common worldwide, which makes their monitoring crucial in the prevention of poisoning incidents. These toxins can be monitored by a variety of techniques, including mouse bioassay, receptor binding assay, and liquid chromatography with either mass spectrometric or pre- or post-column fluorescence detection. The post-column oxidation liquid chromatography with fluorescence detection method, used routinely in our laboratory, has been shown to be a reliable method for monitoring paralytic shellfish toxins in mussel, scallop, oyster and clam species. However, due to its high sensitivity to naturally fluorescent matrix interferences, when working with unconventional matrices, there may be problems in identifying toxins because of naturally fluorescent interferences that co-elute with the toxin peaks. This can lead to erroneous identification. In this study, in order to overcome this challenge in echinoderm and gastropod matrices, we optimized the conversion of Gonyautoxins 1 and 4 to Neosaxitoxin with 2-mercaptoethanol. We present a new and less time-consuming method with a good recovery (82.2%, RSD 1.1%, n = 3), requiring only a single reaction step.

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Healthcare, Vol. 4, Pages 2: Sustainability as an Ethical Principle: Ensuring Its Systematic Place in Professional Nursing Practice

Alongside the central focus on the persons requiring nursing care in professional nursing practice, the perspective of the sustainability of interventions and the use of materials (for example, nursing aids and hygiene articles) is gaining prominence in nursing decision-making processes. This contribution makes the principle of sustainability concrete and delineates its importance in the context of professional nursing practice and decision-making. It further suggests the development of an ethical policy in order to systematically ensure that sustainability has a place in ethical reflection and decision-making, and describes the elements involved. Finally, a synthesis is made between the importance of the principle of sustainability, suggested ethical policies (system of ethical reflection) as they affect nursing practice and professional reflection, decision-making, and practice.

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Cancers, Vol. 8, Pages 4: Studies of Tumor Suppressor Genes via Chromosome Engineering

The development and progression of malignant tumors likely result from consecutive accumulation of genetic alterations, including dysfunctional tumor suppressor genes. However, the signaling mechanisms that underlie the development of tumors have not yet been completely elucidated. Discovery of novel tumor-related genes plays a crucial role in our understanding of the development and progression of malignant tumors. Chromosome engineering technology based on microcell-mediated chromosome transfer (MMCT) is an effective approach for identification of tumor suppressor genes. The studies have revealed at least five tumor suppression effects. The discovery of novel tumor suppressor genes provide greater understanding of the complex signaling pathways that underlie the development and progression of malignant tumors. These advances are being exploited to develop targeted drugs and new biological therapies for cancer.

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JCM, Vol. 5, Pages 4: Pathogenesis of Type 2 Epithelial to Mesenchymal Transition (EMT) in Renal and Hepatic Fibrosis

Epithelial to mesenchymal transition (EMT), particularly, type 2 EMT, is important in progressive renal and hepatic fibrosis. In this process, incompletely regenerated renal epithelia lose their epithelial characteristics and gain migratory mesenchymal qualities as myofibroblasts. In hepatic fibrosis (importantly, cirrhosis), the process also occurs in injured hepatocytes and hepatic progenitor cells (HPCs), as well as ductular reaction-related bile epithelia. Interestingly, the ductular reaction contributes partly to hepatocarcinogenesis of HPCs, and further, regenerating cholangiocytes after injury may be derived from hepatic stellate cells via mesenchymal to epithelia transition, a reverse phenomenon of type 2 EMT. Possible pathogenesis of type 2 EMT and its differences between renal and hepatic fibrosis are reviewed based on our experimental data.

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Catalysts, Vol. 6, Pages 5: Electrocatalytic Oxidation of Cellulose to Gluconate on Carbon Aerogel Supported Gold Nanoparticles Anode in Alkaline Medium

The development of high efficient and low energy consumption approaches for the transformation of cellulose is of high significance for a sustainable production of high value-added feedstocks. Herein, electrocatalytic oxidation technique was employed for the selective conversion of cellulose to gluconate in alkaline medium by using concentrated HNO3 pretreated carbon aerogel (CA) supported Au nanoparticles as anode. Results show that a high gluconate yield of 67.8% and sum salts yield of 88.9% can be obtained after 18 h of electrolysis. The high conversion of cellulose and high selectivity to gluconate could be attributed to the good dissolution of cellulose in NaOH solution which promotes its hydrolysis, the surface oxidized CA support and Au nanoparticles catalyst which possesses high amount of active sites. Moreover, the bubbled air also plays important role in the enhancement of cellulose electrocatalytic conversion efficiency. Lastly, a probable mechanism for electrocatalytic oxidation of cellulose to gluconate in alkaline medium was also proposed.

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Materials, Vol. 9, Pages 14: Ferroelectrics under the Synchrotron Light: A Review

Currently, an intensive search for high-performance lead-free ferroelectric materials is taking place. ABO3 perovskites (A = Ba, Bi, Ca, K and Na; B = Fe, Nb, Ti, and Zr) appear as promising candidates. Understanding the structure–function relationship is mandatory, and, in this field, the roles of long- and short-range crystal orders and interactions are decisive. In this review, recent advances in the global and local characterization of ferroelectric materials by synchrotron light diffraction, scattering and absorption are analyzed. Single- and poly-crystal synchrotron diffraction studies allow high-resolution investigations regarding the long-range average position of ions and subtle global symmetry break-downs. Ferroelectric materials, under the action of electric fields, undergo crystal symmetry, crystallite/domain orientation distribution and strain condition transformations. Methodological aspects of monitoring these processes are discussed. Two-dimensional diffraction clarify larger scale ordering: polycrystal texture is measured from the intensities distribution along the Debye rings. Local order is investigated by diffuse scattering (DS) and X-ray absorption fine structure (XAFS) experiments. DS provides information about thermal, chemical and displacive low-dimensional disorders. XAFS investigation of ferroelectrics reveals local B-cation off-centering and oxidation state. This technique has the advantage of being element-selective. Representative reports of the mentioned studies are described.

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Education Sciences, Vol. 6, Pages 1: The ‘Lifeblood’ of Science and Its Politics: Interrogating Epistemic Curiosity as an Educational Aim

Social- and virtue-epistemologies connect intellectual and moral concerns in ways significant for education and its theory. For most educationists, epistemic and ethical virtues are no longer dissociated. However, many political framings or operations of epistemic virtues and vices remain neglected in educational discourses. This article illustrates why a politicization of epistemic issues is relevant to education through reference to political performances of a curiosity typically considered educationally valuable. Curiosity bore political connotations from antiquity to late modernity whose exploration may add critical nuance to educational-philosophical conceptions of epistemic desire. This leads us to the main argument of the article, which is that such politicization helps us interrogate unqualified, uniform, and glorifying treatments of curiosity as an educational aim.

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Biliary reconstruction with or without an intraductal removable stent in liver transplantation: study protocol for a randomized controlled trial

Background: The incidence of biliary complications following liver transplantation (LT) remains high, ranging from 10 to 50 % of patients, especially when the diameter of the bile duct is smaller than 7 mm. Biliary reconstruction is most often performed by duct-to-duct anastomosis. In a preliminary study (n = 20), we previously reported a technique of biliary reconstruction using an intraductal stent tube followed by its endoscopic removal and showed both the feasibility and safety of this innovative procedure. The next step is to validate the potential benefit of this procedure in a randomized controlled trial.DesignThis is a multicenter randomized controlled trial in France comparing the efficacy of biliary reconstruction with or without a removable intraductal stent on reducing biliary complications. Inclusion and randomization are performed during LT when a duct-to-duct biliary anastomosis smaller than 7 mm in diameter is envisioned. In the intraductal stent group, a custom-made segment of a T-tube is placed into the bile duct and removed endoscopically 4 to 6 months later. The surgical technique is described in a video during randomization and is available on the secure website used for inclusion and randomization. The primary endpoint is the occurrence of biliary complications, including biliary fistulae and strictures, during the 6 months of follow-up. Secondary evaluation criteria are the incidence of complications related to the stent placement and its extraction by endoscopy. The inclusion of 248 patients in total has been determined based on an expected incidence of biliary complications of 25 % in the non-IST group and a 60 % reduction of biliary complications (10 %) in the IST group.DiscussionBiliary complications following LT are significant causes of morbidity, retransplantation, and mortality. Although controversial, the use of a T-tube has been proven to be useless and even responsible for specific complications related to the external part of the tube in many studies, including several randomized trials. However, several studies have identified a small bile duct diameter as a risk factor for biliary stenosis. A threshold of 7 mm was found to be significantly associated with biliary stenosis. Our team published a preliminary study that included 20 patients using a new technique of intraductal stenting. Only four complications were reported in the overall study population, whereas no biliary complication occurred in the subgroup of patients who received a whole graft LT. Moreover, no technical failures and no procedure-related complications were noted before and during the drain removal. Although an intraductal stent tube in duct-to duct biliary anastomosis seems feasible and safe, a multicenter randomized controlled trial is needed to validate its benefit as a protective tool against the occurrence of biliary complications. One original aspect of this protocol is the video demonstration of the surgical procedure, which is available on the web to standardize and homogenize the technique. The surgical community may be inspired by this type of tool in the future to minimize technical bias related to technical issues.Trial registrationNCT02356939, date of registration 2 February 2015.

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Musculoskeletal care stratification Stratification of Treatment in A Community-Based Musculoskeletal Service: A Mixed-Methods Study to Assess Predictors of Requiring Complex Care

Publication date: Available online 29 December 2015
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Christine Comer, Jennie Glover, Jennifer Richardson, Rachel Yaseen, Steven Foster, Neil M. Wolfenden, Gareth J. Hughes
ObjectiveTo explore factors that might be relevant when designing a triage toolDesignA mixed-methods study using multivariable logistic regression analysis to identify significant factors associated with requiring different levels of care and qualitative focus groups exploring views of patients and physiotherapy clinicians regarding case complexity.SettingA community-based adult Musculoskeletal Service delivering Tier One (standard physiotherapy) and Tier Two care (complex care beyond the scope of standard physiotherapy) and providing onward referral to orthopaedic clinics (Tier Three).ParticipantsQuantitative data was extracted from a random sample of 484 patients who had received treatment for musculoskeletal conditions. Patients and physiotherapists who had received care or who worked in the service participated in focus groups.Main outcome measuresThemes which emerged from focus groups were compared against predictors of requiring complex care found to be significant (P<0.05) following quantitative data analysis.Results184 patients (38.0%, 95% confidence interval: 33.8–42.4) received complex care. Peripheral joint problems, unclear diagnosis, and symptoms affecting sleep were significant independent predictors of requiring complex care. These data supported some of the main themes raised at focus groups.ConclusionsA substantial proportion of patients receive Tier Two level complex care. Further studies are needed to evaluate whether the predictive factors found to be significant in our study might be useful for developing a tool for more effective triage to the most appropriate tier of musculoskeletal care.



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Pembrolizumab With Locally Delivered Radiation Therapy for the Initial Treatment of Metastatic Esophageal Cancers

Conditions:   Esophageal Neoplasms;   Esophageal Cancer;   Cancer of the Esophagus
Interventions:   Drug: Pembrolizumab;   Radiation: Brachytherapy;   Procedure: Endoscopic biopsy;   Procedure: Ultrasound-guided biopsy;   Procedure: Computed tomography-guided biopsy;   Procedure: Peripheral blood collection
Sponsors:   Washington University School of Medicine;   Merck Sharp & Dohme Corp.
Not yet recruiting - verified December 2015

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Individualized Elective Neck Irradiation Based on MRI in NPC Patients

Condition:   Nasopharyngeal Carcinoma
Interventions:   Radiation: Elective neck irradiation;   Radiation: Whole neck irradiation
Sponsor:   Sun Yat-sen University
Not yet recruiting - verified December 2015

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Deep Neuromuscular Relaxation in Patients for Thoraco-laparoscopic Esophagectomy

Conditions:   Neuromuscular Block;   Esophageal Cancer;   Surgery
Intervention:   Drug: Rocuronium
Sponsors:   Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA);   Merck Sharp & Dohme Corp.
Recruiting - verified December 2015

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Entropy, Vol. 18, Pages 15: Thermal Characteristics of a Primary Surface Heat Exchanger with Corrugated Channels

This paper presents the heat transfer and pressure drop characteristics of a primary surface heat exchanger (PSHE) with corrugated surfaces. The PSHE was experimentally investigated for a Reynolds number range of 156–921 under various flow conditions on the hot and cold sides. The inlet temperature of the hot side was maintained at 40 °C, while that of the cold side was maintained at 20 °C. A counterflow was used as it has a higher temperature proximity in comparison with a parallel flow. The heat transfer rate and pressure drop were measured for various Reynolds numbers on both the hot and cold sides of the PSHE, with the heat transfer coefficients for both sides computed using a modified Wilson plot method. Based on the results of the experiment, both Nusselt number and friction factor correlations were suggested for a PSHE with corrugated surfaces.

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Remote Sensing, Vol. 8, Pages 21: Modeling and Mapping Agroforestry Aboveground Biomass in the Brazilian Amazon Using Airborne Lidar Data

Agroforestry has large potential for carbon (C) sequestration while providing many economical, social, and ecological benefits via its diversified products. Airborne lidar is considered as the most accurate technology for mapping aboveground biomass (AGB) over landscape levels. However, little research in the past has been done to study AGB of agroforestry systems using airborne lidar data. Focusing on an agroforestry system in the Brazilian Amazon, this study first predicted plot-level AGB using fixed-effects regression models that assumed the regression coefficients to be constants. The model prediction errors were then analyzed from the perspectives of tree DBH (diameter at breast height)—height relationships and plot-level wood density, which suggested the need for stratifying agroforestry fields to improve plot-level AGB modeling. We separated teak plantations from other agroforestry types and predicted AGB using mixed-effects models that can incorporate the variation of AGB-height relationship across agroforestry types. We found that, at the plot scale, mixed-effects models led to better model prediction performance (based on leave-one-out cross-validation) than the fixed-effects models, with the coefficient of determination (R2) increasing from 0.38 to 0.64. At the landscape level, the difference between AGB densities from the two types of models was ~10% on average and up to ~30% at the pixel level. This study suggested the importance of stratification based on tree AGB allometry and the utility of mixed-effects models in modeling and mapping AGB of agroforestry systems.

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Religions, Vol. 7, Pages 5: Religion, Race/Ethnicity, and Norms of Intergenerational Assistance among Older Adults

Using data on adults ages 55 and over from the second wave of the National Survey of Families and Households (NSFH-2), this study models the main and interactive effects of religious involvement and race/ethnicity on four items of attitudes towards intergenerational assistance. Results indicate that African Americans and Hispanics tend to express stronger support for intergenerational assistance than non-Hispanic Whites. Conservative Protestants, Mormons, and Catholics are more likely than others to believe that adult children should offer co-residence to their aging parents. In addition, theological conservatism is positively associated with support for each type of intergenerational aid, and the net effect of theological conservatism is stronger for African Americans than for non-Hispanic Whites. However, religious attendance is statistically unrelated to norms of intergenerational assistance. It is concluded that religious factors are important in shaping norms of intergenerational support, particularly within minority communities.

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Diagnostics, Vol. 6, Pages 3: Hepatocellular Carcinoma, Fibrolamellar Variant: Diagnostic Pathologic Criteria and Molecular Pathology Update. A Primer

Fibrolamellar hepatocellular carcinoma (FL-HCC) is generally a fairly rare event in routine pathology practice. This variant of hepatocellular carcinoma (HCC) is peculiarly intriguing and,in addition, poorly understood. Young people or children are often the target individuals with this type of cancer. Previously, I highlighted some pathology aspects of FL-HCC, but in this review, the distinctive clinico-pathologic features of FL-HCC and the diagnostic pathologic criteria of FL-HCC are fractionally reviewed and expanded upon. Further, molecular genetics update data with reference to this specific tumor are particularly highlighted as a primer for general pathologists and pediatric histopathologists. FL-HCC may present with metastases, and regional lymph nodes may be sites of metastatic spread. However, peritoneal and pulmonary metastatic foci have also been reported. To the best of our knowledge, FL-HCC was initially considered having an indolent course, but survival outcomes have recently been updated reconsidering the prognosis of this tumor. Patients seem to respond well to surgical resection, but recurrences are common. Thus, alternative therapies, such as chemotherapy and radiation, are ongoing. Overall, it seems that this aspect has not been well-studied for this variant of HCC and should be considered as target for future clinical trials. Remarkably, FL-HCC data seem to point to a liver neoplasm of uncertain origin and unveiled outcome. A functional chimeric transcript incorporating DNAJB1 and PRKACA was recently added to FL-HCC. This sensational result may give remarkable insights into the understanding of this rare disease and potentially provide the basis for its specific diagnostic marker. Detection of DNAJB1-PRKACA seems to be, indeed, a very sensitive and specific finding in supporting the diagnosis of FL-HCC. In a quite diffuse opinion, prognosis of this tumor should be reconsidered following the potentially mandatory application of new molecular biological tools.

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Membranes, Vol. 6, Pages 5: YSZ-Reinforced Alumina Multi-Channel Capillary Membranes for Micro-Filtration

The combined phase-inversion and sintering method not only produces ceramic hollow fibre membranes with much lower fabrication costs than conventional methods, but these membranes can also be designed to have greatly reduced transport resistances for filtration processes. The bottleneck of this technique is the weak mechanical property of the fibres, due to the small dimensions and the brittle nature of the ceramic materials. In this study, yttrium stabilised zirconia (YSZ) reinforced alumina seven-channel capillary microfiltration membranes were prepared with a pore size of ~230 nm and their mechanical property and permeation characteristics were studied. It is found that the addition of YSZ can effectively enhance the mechanical property of the membrane and also increase pure water permeation flux. The Al2O3-YSZ seven-channel capillary membranes could reach a fracture load of 23.4 N and a bending extension of 0.54 mm when being tested with a 6 cm span, to meet the requirements for most industrial microfiltration applications.

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Resources, Vol. 5, Pages 1: Typology of Options for Metal Recycling: Australia’s Perspective

While Australia has traditionally relied on obtaining metals from primary sources (namely mined natural resources), there is significant potential to recover metals from end-of-life-products and industrial waste. Although any metals recycling value chain requires a feasible technology at its core, many other non-technical factors are key links in the chain, which can compromise the overall viability to recycle a commodity and/or product. The "Wealth from Waste" Cluster project funded by the Commonwealth Scientific Industrial Research Organisation (CSIRO) Flagship Collaboration Fund and partner universities is focusing on identifying viable options to "mine" metals contained in discarded urban infrastructure, manufactured products and consumer goods. A key aspect of this research is to understand the critical non-technical barriers and system opportunities to enhance rates of metals recycling in Australia. Work to date has estimated the mass and current worth of metals in above ground resources. Using these outcomes as a basis, a typology for different options for (metal) reuse and recycling has been developed to classify the common features, which is presented in this article. In addition, the authors investigate the barriers and enablers in the recycling value chain, and propose a set of requirements for a feasible pathway to close the material loop for metals in Australia.

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Actuators, Vol. 5, Pages 2: Non-Resonant Magnetoelectric Energy Harvesting Utilizing Phase Transformation in Relaxor Ferroelectric Single Crystals

Recent advances in phase transition transduction enabled the design of a non-resonant broadband mechanical energy harvester that is capable of delivering an energy density per cycle up to two orders of magnitude larger than resonant cantilever piezoelectric type generators. This was achieved in a [011] oriented and poled domain engineered relaxor ferroelectric single crystal, mechanically biased to a state just below the ferroelectric rhombohedral (FR)-ferroelectric orthorhombic (FO) phase transformation. Therefore, a small variation in an input parameter, e.g., electrical, mechanical, or thermal will generate a large output due to the significant polarization change associated with the transition. This idea was extended in the present work to design a non-resonant, multi-domain magnetoelectric composite hybrid harvester comprised of highly magnetostrictive alloy, [Fe81.4Ga18.6 (Galfenol) or TbxDy1-xFe2 (Terfenol-D)], and lead indium niobate–lead magnesium niobate–lead titanate (PIN-PMN-PT) domain engineered relaxor ferroelectric single crystal. A small magnetic field applied to the coupled device causes the magnetostrictive element to expand, and the resulting stress forces the phase change in the relaxor ferroelectric single crystal. We have demonstrated high energy conversion in this magnetoelectric device by triggering the FR-FO transition in the single crystal by a small ac magnetic field in a broad frequency range that is important for multi-domain hybrid energy harvesting devices.

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Catalysts, Vol. 6, Pages 6: Hydrogenation of Levulinic Acid over Nickel Catalysts Supported on Aluminum Oxide to Prepare γ-Valerolactone

Four types of nickel catalysts supported on aluminum oxide (Ni/Al2O3) with different nickel loadings were synthesized using the co-precipitation method and were used for the hydrogenation of levulinic acid (LA) to prepare γ-valerolactone (GVL). The synthesized Ni/Al2O3 catalysts exhibited excellent catalytic activity in dioxane, and the activity of the catalysts was excellent even after being used four times in dioxane. The catalytic activity in dioxane as a solvent was found to be superior to the activity in water. Nitrogen physisorption, X-ray diffraction, and transmission electron microscopy were employed to characterize the fresh and used catalysts. The effects of the nickel loading, temperature, hydrogen pressure, and substrate/catalyst ratio on the catalytic activity were investigated.

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Polymers, Vol. 8, Pages 6: Crosslinked Poly(2-oxazoline)s as “Green” Materials for Electronic Applications

Poly(2-nonyl-2-oxazoline)80-stat-poly(2-dec-9′-enyl-2-oxazoline)20 and poly(2-dec-9′-enyl-2-oxazoline)100 can be synthesized from the cationic ring-opening polymerization of monomers that can be derived from fatty acids from renewable resources. These (co)poly(2-oxazoline)s can be crosslinked with di- and trifunctional mercapto compounds using the UV-induced thiol-ene reaction. The complex permittivity of the corresponding networks increases with the temperature and decreases with the network density. In a frequency range from 10−2 to 106 Hz and at temperatures ranging from −20 to 40 °C, the changes of the real part of the complex permittivity as well as the loss factor can be explained by interfacial polarization within the material. At a temperature of 20 °C and a frequency of 50 Hz, the permittivity of the crosslinked (co)poly(2-oxazoline)s covers a range from 4.29 to 4.97, and the loss factors are in the range from 0.030 to 0.093. The electrical conductivities of these polymer networks span a range from 5 × 10−12 to 8 × 10−9 S/m, classifying these materials as medium insulators. Notably, the values for the permittivity, loss factor and conductivity of these copoly(2-oxazoline)s are in the same range as for polyamides, and, hence, these copoly(2-oxazoline)-based networks may be referred to as "green" alternatives for polyamides as insulators in electronic applications.

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Minerals, Vol. 6, Pages 3: Uranium-Series Disequilibria in the Groundwater of the Shihongtan Sandstone-Hosted Uranium Deposit, NW China

Uranium (U) concentration and the activities of 238U, 234U, and 230Th were determined for groundwaters, spring waters, and lake water collected from the Shihongtan sandstone-hosted U ore district and in the surrounding area, NW China. The results show that the groundwaters from the oxidizing aquifer with high dissolved oxygen concentration (O2) and oxidation-reduction potential (Eh) are enriched in U. The high U concentration of groundwaters may be due to the interaction between these oxidizing groundwaters and U ore bodies, which would result in U that is not in secular equilibrium. Uranium is re-precipitated as uraninite on weathered surfaces and organic material, forming localized ore bodies in the sandstone-hosted aquifer. The 234U/238U, 230Th/234U, and 230Th/238U activity ratios (ARs) for most water samples show obvious deviations from secular equilibrium (0.27–2.86), indicating the presence of water-rock/ore interactions during the last 1.7 Ma and probably longer. The 234U/238U AR generally increases with decreasing U concentrations in the groundwaters, suggesting that mixing of two water sources may occur in the aquifer. This is consistent with the fact that most of the U ore bodies in the deposit have a tabular shape originati from mixing between a relatively saline fluid and a more rapidly flowing U-bearing meteoric water.

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Biomedicines, Vol. 4, Pages 1: Synthesis and Preliminary Biological Evaluations of Fluorescent or 149Promethium Labeled Trastuzumab-Polyethylenimine

Background: Radioimmunotherapy utilize a targeting antibody coupled to a therapeutic isotope to target and treat a tumor or disease. In this study we examine the synthesis and cell binding of a polymer scaffold containing a radiotherapeutic isotope and a targeting antibody. Methods: The multistep synthesis of a fluorescent or 149Promethium-labeled Trastuzumab-polyethyleneimine (PEI), Trastuzumab, or PEI is described. In vitro uptake, internalization and/or the binding affinity to the Her2/neu expressing human breast adenocarcinoma SKBr3 cells was investigated with the labeled compounds. Results: Fluorescent-labeled Trastuzumab-PEI was internalized more into cells at 2 and 18 h than fluorescent-labeled Trastuzumab or PEI. The fluorescent-labeled Trastuzumab was concentrated on the cell surface at 2 and 18 h and the labeled PEI had minimal uptake. DOTA-PEI was prepared and contained an average of 16 chelates per PEI; the compound was radio-labeled with 149Promethium and conjugated to Trastuzumab. The purified 149Pm-DOTA-PEI-Trastuzumab had a radiochemical purity of 96.7% and a specific activity of 0.118 TBq/g. The compound demonstrated a dissociation constant for the Her2/neu receptor of 20.30 ± 6.91 nM. Conclusion: The results indicate the DOTA-PEI-Trastuzumab compound has potential as a targeted therapeutic carrier, and future in vivo studies should be performed.

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Toxins, Vol. 8, Pages 12: Alkaloids from Veratrum taliense Exert Cardiovascular Toxic Effects via Cardiac Sodium Channel Subtype 1.5

Several species of the genus Veratrum that produce steroid alkaloids are commonly used to treat pain and hypertension in China and Europe. However, Veratrum alkaloids (VAs) induce serious cardiovascular toxicity. In China, Veratrum treatment often leads to many side effects and even causes the death of patients, but the pathophysiological mechanisms under these adverse effects are not clear. Here, two solanidine-type VAs (isorubijervine and rubijervine) isolated from Veratrum taliense exhibited strong cardiovascular toxicity. A pathophysiological study indicated that these VAs blocked sodium channels NaV1.3–1.5 and exhibited the strongest ability to inhibit NaV1.5, which is specifically expressed in cardiac tissue and plays an essential role in cardiac physiological function. This result reveals that VAs exert their cardiovascular toxicity via the NaV1.5 channel. The effects of VAs on NaV1.3 and NaV1.4 may be related to their analgesic effect and skeletal muscle toxicity, respectively.

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Algorithms, Vol. 9, Pages 4: A Novel Complex-Valued Encoding Grey Wolf Optimization Algorithm

Grey wolf optimization (GWO) is one of the recently proposed heuristic algorithms imitating the leadership hierarchy and hunting mechanism of grey wolves in nature. The aim of these algorithms is to perform global optimization. This paper presents a modified GWO algorithm based on complex-valued encoding; namely the complex-valued encoding grey wolf optimization (CGWO). We use CGWO to test 16 unconstrained benchmark functions with seven different scales and infinite impulse response (IIR) model identification. Compared to the real-valued GWO algorithm and other optimization algorithms; the CGWO performs significantly better in terms of accuracy; robustness; and convergence speed.

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Membranes, Vol. 6, Pages 4: The Effect of Microporous Polymeric Support Modification on Surface and Gas Transport Properties of Supported Ionic Liquid Membranes

Microporous polymers based on anionic macroinitiator and toluene 2,4-diisocyanate were used as a support for 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]) and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([emim][Tf2N]) immobilization. The polymeric support was modified by using silica particles associated in oligomeric media, and the influence of the modifier used on the polymeric structure was studied. The supported ionic liquid membranes (SILMs) were tested for He, N2, NH3, H2S, and CO2 gas separation and ideal selectivities were calculated. The high values of ideal selectivity for ammonia-based systems with permanent gases were observed on polymer matrixes immobilized with [bmim][PF6] and [emim][Tf2N]. The modification of SILMs by nanosize silica particles leads to an increase of NH3 separation relatively to CO2 or H2S.

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Micromachines, Vol. 7, Pages 4: Particulate Blood Analogues Reproducing the Erythrocytes Cell Free Layer in a Microfluidic Device Containing a Hyperbolic Contraction

The interest in the development of blood analogues has been increasing recently as a consequence of the increment in the number of experimental hemodynamic studies and the difficulties associated with the manipulation of real blood in vitro because of ethical, economical or hazardous issues. Although one-phase Newtonian and non-Newtonian blood analogues can be found in the literature, there are very few studies related to the use of particulate solutions in which the particles mimic the behaviour of the red blood cells (RBCs) or erythrocytes. One of the most relevant effects related with the behaviour of the erythrocytes is a cell free layer (CFL) formation, which consists in the migration of the RBCs towards the center of the vessel forming a cell depleted plasma region near the vessel walls, which is known to happen in in vitro microcirculatory environments. Recent studies have shown that the CFL enhancement is possible with an insertion of contraction and expansion region in a straight microchannel. These effects are useful for cell manipulation or sorting in lab-on-chip studies. In this experimental study we present particulate Newtonian and non-Newtonian solutions which resulted in a rheological blood analogue able to form a CFL, downstream of a microfluidic hyperbolic contraction, in a similar way of the one formed by healthy RBCs.

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New Trends in Instrumentation and Complex Techniques in Spine Surgery

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After Myocardial Ischemia-Reperfusion, miR-29a, and Let7 Could Affect Apoptosis through Regulating IGF-1

Cardiovascular and cerebrovascular ischemic disease is a large class of diseases that is harmful to human health. The primary treatment for the ischemic disease is to recover the blood perfusion and relieve the tissue hypoxia and the shortage of the nutrients in the supply of nutrients. In recent years, investigations found that IGF-1 has a protective effect on cardiovascular disease, especially in myocardial ischemia-reperfusion injury. Investigation into molecular mechanism of ischemia-reperfusion injury may offer potential targets for the development of novel diagnostic strategies. In this study we defined IGF-1 was differentially expressed in the I/R model of the Mus musculus and IGF-1 was the target gene of miR-29a and Let7f. After ischemia-reperfusion, the expression of miR-29a and Let7f increased, while the expression of IGF-1 decreased significantly in the animal model assay. Further studies have found that IGF-1 could inhibit cell apoptosis signaling pathway, thus protecting the reperfusion injury. These results provide new understanding of ischemia-reperfusion injury, with the hope of offering theoretical support for future therapeutic studies.

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IJMS, Vol. 17, Pages 47: Innovative Target Therapies Are Able to Block the Inflammation Associated with Dysfunction of the Cholesterol Biosynthesis Pathway

The cholesterol pathway is an essential biochemical process aimed at the synthesis of bioactive molecules involved in multiple crucial cellular functions. The end products of this pathway are sterols, such as cholesterol, which are essential components of cell membranes, precursors of steroid hormones, bile acids and other molecules such as ubiquinone. Several diseases are caused by defects in this metabolic pathway: the most severe forms of which cause neurological involvement (psychomotor retardation and cerebellar ataxia) as a result of a variety of cellular impairments, including mitochondrial dysfunction. These pathologies are induced by convergent mechanisms in which the mitochondrial unit plays a pivotal role contributing to defective apoptosis, autophagy and mitophagy processes. Unraveling these mechanisms would contribute to the development of effective drug treatments for these disorders. In addition, the development of biochemical models could have a substantial impact on the understanding of the mechanism of action of drugs that act on this pathway in multifactor disorders. In this review we will focus in particular on inhibitors of cholesterol synthesis, mitochondria-targeted drugs and inhibitors of the inflammasome.

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IJMS, Vol. 17, Pages 48: Notch Signaling in Pancreatic Development

The Notch signaling pathway plays a significant role in embryonic cell fate determination and adult tissue homeostasis. Various studies have demonstrated the deep involvement of Notch signaling in the development of the pancreas and the lateral inhibition of Notch signaling in pancreatic progenitor differentiation and maintenance. The targeted inactivation of the Notch pathway components promotes premature differentiation of the endocrine pancreas. However, there is still the contrary opinion that Notch signaling specifies the endocrine lineage. Here, we review the current knowledge of the Notch signaling pathway in pancreatic development and its crosstalk with the Wingless and INT-1 (Wnt) and fibroblast growth factor (FGF) pathways.

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IJMS, Vol. 17, Pages 45: Effect of Greenhouse Gases Dissolved in Seawater

A molecular dynamics simulation has been performed on the greenhouse gases carbon dioxide and methane dissolved in a sodium chloride aqueous solution, as a simple model of seawater. A carbon dioxide molecule is also treated as a hydrogen carbonate ion. The structure, coordination number, diffusion coefficient, shear viscosity, specific heat, and thermal conductivity of the solutions have been discussed. The anomalous behaviors of these properties, especially the negative pressure dependence of thermal conductivity, have been observed in the higher-pressure region.

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IJMS, Vol. 17, Pages 50: Pharmacotherapy Treatment Options for Insomnia: A Primer for Clinicians

Insomnia is a prevalent disorder with deleterious effects such as decreased quality of life, and a predisposition to a number of psychiatric disorders. Fortunately, numerous approved hypnotic treatments are available. This report reviews the state of the art of pharmacotherapy with a reference to cognitive behavioral therapy for insomnia (CBT-I) as well. It provides the clinician with a guide to all the Food and Drug Administration (FDA) approved hypnotics (benzodiazepines, nonbenzodiazepines, ramelteon, low dose sinequan, and suvorexant) including potential side effects. Frequently, chronic insomnia lasts longer than 2 years. Cognizant of this and as a result of longer-term studies, the FDA has approved all hypnotics since 2005 without restricting the duration of use. Our manuscript also reviews off-label hypnotics (sedating antidepressants, atypical antipsychotics, anticonvulsants and antihistamines) which in reality, are more often prescribed than approved hypnotics. The choice of which hypnotic to choose is discussed partially being based on which segment of sleep is disturbed and whether co-morbid illnesses exist. Lastly, we discuss recent label changes required by the FDA inserting a warning about "sleep-related complex behaviors", e.g., sleep-driving for all hypnotics. In addition, we discuss FDA mandated dose reductions for most zolpidem preparations in women due to high zolpidem levels in the morning hours potentially causing daytime carry-over effects.

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Remote Sensing, Vol. 8, Pages 20: Remote Sensing Based Simple Models of GPP in Both Disturbed and Undisturbed Piñon-Juniper Woodlands in the Southwestern U.S.

Remote sensing is a key technology that enables us to scale up our empirical, in situ measurements of carbon uptake made at the site level. In low leaf area index ecosystems typical of semi-arid regions however, many assumptions of these remote sensing approaches fall short, given the complexities of the heterogeneous landscape and frequent disturbance. Here, we investigated the utility of remote sensing data for predicting gross primary production (GPP) in piñon-juniper woodlands in New Mexico (USA). We developed a simple model hierarchy using climate drivers and satellite vegetation indices (VIs) to predict GPP, which we validated against in situ estimates of GPP from eddy-covariance. We tested the influence of pixel size on model fit by comparing model performance when using VIs from RapidEye (5 m) and the VIs from Landsat ETM+ (30 m). We also tested the ability of the normalized difference wetness index (NDWI) and normalized difference red edge (NDRE) to improve model fits. The best predictor of GPP at the undisturbed PJ woodland was Landsat ETM+ derived NDVI (normalized difference vegetation index), whereas at the disturbed site, the red-edge VI performed best (R2adj of 0.92 and 0.90 respectively). The RapidEye data did improve model performance, but only after we controlled for the variability in sensor view angle, which had a significant impact on the apparent cover of vegetation in our low fractional cover experimental woodland. At both sites, model performance was best either during non-stressful growth conditions, where NDVI performed best, or during severe ecosystem stress conditions (e.g., during the girdling process), where NDRE and NDWI improved model fit, suggesting the inclusion of red-edge leveraging and moisture sensitive VI in simple, data driven models can constrain GPP estimate uncertainty during periods of high ecosystem stress or disturbance.

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Marine Drugs, Vol. 14, Pages 9: Specific Metabolites in a Phaeodactylum tricornutum Strain Isolated from Western Norwegian Fjord Water

We have searched for special characteristics in growth, protein expression, fatty acids and volatile organic compounds (VOCs) in a local Phaeodactylum tricornutum Bohlin strain (Bergen Marine Biobank), by comparing it with a common accession strain (CCAP). Differences in growth and expressed proteins were detected between the BMB strain and the CCAP strain, and the BMB strain reached the highest cell densities under the given growth conditions. Fatty acid (FA) analyses showed highest relative eicosapentaenoic acid (EPA) levels in the exponential phase (25.73% and 28.31%), and highest levels of palmitoleic acid (16:1 n-7) in the stationary phase (46.36% and 43.66%) in the BMB and CCAP strain, respectively. The most striking finding of the VOCs analyses was the relatively high levels of ectocarpene, 6-((1E)-butenyl)-1,4-cycloheptadiene, hormosirene, and desmarestene and structurally related compounds, which were exclusively detected in the BMB strain. Many of the VOCs detected in the CCAP and, in particular, in the BMB strain have been reported as antimicrobial agents. We suggest that the array of pheromones and antimicrobial substances could be part of an allelopathic strategy of the BMB strain, dominated by oval cells, thus reflecting the benthic life stage of this morphological form. These findings show the potential for bioactive metabolites in the BMB strain.

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Marine Drugs, Vol. 14, Pages 8: Structures and Activity of New Anabaenopeptins Produced by Baltic Sea Cyanobacteria

Anabaenopeptins, bioactive cyclic hexapeptides, were isolated by preparative reversed-phase high performance liquid chromatography from an extract of Baltic Sea cyanobacterial bloom material composed of Nodularia spumigena (50%), Aphanizomenon flos-aquae (40%) and Dolichospermum spp. (10%). Five new anabaenopeptins and nine previously known anabaenopeptins were isolated, and their putative structures were determined by tandem mass spectrometry. The activity of the peptides against carboxypeptidase A and protein phosphatase 1 as well as chymotrypsin, trypsin and thrombin was tested. All anabaenopeptins inhibited carboxypeptidase A (apart from one anabaenopeptin variant) and protein phosphatase 1 with varying potency, but no inhibition against chymotrypsin, trypsin and thrombin was observed.

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Remote Sensing, Vol. 8, Pages 22: Mapping Fractional Cropland Distribution in Mato Grosso, Brazil Using Time Series MODIS Enhanced Vegetation Index and Landsat Thematic Mapper Data

Mapping cropland distribution over large areas has attracted great attention in recent years, however, traditional pixel-based classification approaches produce high uncertainty in cropland area statistics. This study proposes a new approach to map fractional cropland distribution in Mato Grosso, Brazil using time series MODIS enhanced vegetation index (EVI) and Landsat Thematic Mapper (TM) data. The major steps include: (1) remove noise and clouds/shadows contamination using the Savizky–Gloay filter and temporal resampling algorithm based on the time series MODIS EVI data; (2) identify the best periods to extract croplands through crop phenology analysis; (3) develop a seasonal dynamic index (SDI) from the time series MODIS EVI data based on three key stages: sowing, growing, and harvest; and (4) develop a regression model to estimate cropland fraction based on the relationship between SDI and Landsat-derived fractional cropland data. The root mean squared error of 0.14 was obtained based on the analysis of randomly selected 500 sample plots. This research shows that the proposed approach is promising for rapidly mapping fractional cropland distribution in Mato Grosso, Brazil.

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Remote Sensing, Vol. 8, Pages 18: The Morphology, Dynamics and Potential Hotspots of Land Surface Temperature at a Local Scale in Urban Areas

Current characterization of the Urban Heat Island (UHI) remains insufficient to support the effective mitigation and adaptation of increasing temperatures in urban areas. Planning and design strategies are restricted to the investigation of temperature anomalies at a city scale. By focusing on Land Surface Temperature of Wuhan, China, this research examines the temperature variations locally where mitigation and adaptation would be more feasible. It shows how local temperature anomalies can be identified morphologically. Technically, the MODerate-resolution Imaging Spectroradiometer satellite image products are used. They are first considered as noisy observations of the latent temperature patterns. The continuous latent patterns of the temperature are then recovered from these discrete observations by using the non-parametric Multi-Task Gaussian Process Modeling. The Multi-Scale Shape Index is then applied in the area of focus to extract the local morphological features. A triplet of shape, curvedness and temperature is formed as the criteria to extract local heat islands. The behavior of the local heat islands can thus be quantified morphologically. The places with critical deformations are identified as hotpots. The hotspots with certain yearly behavior are further associated with land surface composition to determine effective mitigation and adaptation strategies. This research can assist in the temperature and planning field on two levels: (1) the local land surface temperature patterns are characterized by decomposing the variations into fundamental deformation modes to allow a process-based understanding of the dynamics; and (2) the characterization at local scale conforms to planning and design conventions where mitigation and adaptation strategies are supposed to be more practical. The weaknesses and limitations of the study are addressed in the closing section.

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Marine Drugs, Vol. 14, Pages 7: Determination of FVIIa-sTF Inhibitors in Toxic Microcystis Cyanobacteria by LC-MS Technique

The blood coagulation cascade involves the human coagulation factors thrombin and an activated factor VII (fVIIa). Thrombin and fVIIa are vitamin-K-dependent clotting factors associated with bleeding, bleeding complications and disorders. Thrombin and fVIIa cause excessive bleeding when treated with vitamin-K antagonists. In this research, we explored different strains of toxic Microcystis aeruginosa and cyanobacteria blooms for the probable fVIIa-soluble Tissue Factor (fVIIa-sTF) inhibitors. The algal cells were subjected to acidification, and reverse phase (ODS) chromatography-solid phase extraction eluted by water to 100% MeOH with 20%-MeOH increments except for M. aeruginosa NIES-89, from the National Institute for Environmental Studies (NIES), which was eluted with 5%-MeOH increments as an isolation procedure to separate aeruginosins 89A and B from co-eluting microcystins. The 40%–80% MeOH fractions of the cyanobacterial extract are active against fVIIa-sTF. The fVIIa-sTF active fractions from cultured cyanobacteria and cyanobacteria blooms were subjected to liquid chromatography-mass spectrometry (LC-MS). The 60% MeOH fraction of M. aeruginosa K139 exhibited an m/z 603 [M + H]+ attributed to aeruginosin K139, and the 40% MeOH fraction of M. aeruginosa NIES-89 displayed ions with m/z 617 [M − SO3 + H]+ and m/z [M + H]+ 717, which attributed to aeruginosin 89. Aeruginosins 102A/B and 298A/B were also observed from other toxic strains of M. aeruginosa with positive fVIIa-sTF inhibitory activity. The active fractions contained cyanobacterial peptides of the aeruginosin class as fVIIa-sTF inhibitors detected by LC-MS.

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Viruses, Vol. 8, Pages 1: Development of Novel Vaccines against Enterovirus-71

The hand, foot and mouth disease is caused by a group of Enteroviruses such as Enterovirus 71 (EV-A71) and Coxsackievirus CV-A5, CV-A8, and CV-A16. Mild symptoms of EV-A71 infection in children range from high fever, vomiting, rashes and ulcers in mouth but can produce more severe symptoms such as brainstem and cerebellar encephalitis, leading up to cardiopulmonary failure and death. The lack of vaccines and antiviral drugs against EV-A71 highlights the urgency of developing preventive and treatment agents against EV-A71 to prevent further fatalities. Research groups have developed experimental inactivated vaccines, recombinant Viral Protein 1 (VP1) vaccine and virus-like particles (VLPs). The inactivated EV-A71 vaccine is considered the safest viral vaccine, as there will be no reversion to the infectious wild type strain. The recombinant VP1 vaccine is a cost-effective immunogen, while VLPs contain an arrangement of epitopes that can elicit neutralizing antibodies against the virus. As each type of vaccine has its advantages and disadvantages, increased studies are required in the development of such vaccines, whereby high efficacy, long-lasting immunity, minimal risk to those vaccinated, safe and easy production, low cost, dispensing the need for refrigeration and convenient delivery are the major goals in their design.

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Entropy, Vol. 18, Pages 16: Stochastic Reorder Point-Lot Size (r,Q) Inventory Model under Maximum Entropy Principle

This paper takes into account the continuous-review reorder point-lot size (r,Q) inventory model under stochastic demand, with the backorders-lost sales mixture. Moreover, to reflect the practical circumstance in which full information about the demand distribution lacks, we assume that only an estimate of the mean and of the variance is available. Contrarily to the typical approach in which the lead-time demand is supposed Gaussian or is obtained according to the so-called minimax procedure, we take a different perspective. That is, we adopt the maximum entropy principle to model the lead-time demand distribution. In particular, we consider the density that maximizes the entropy over all distributions with given mean and variance. With the aim of minimizing the expected total cost per time unit, we then propose an exact algorithm and a heuristic procedure. The heuristic method exploits an approximated expression of the total cost function achieved by means of an ad hoc first-order Taylor polynomial. We finally carry out numerical experiments with a twofold objective. On the one hand we examine the efficiency of the approximated solution procedure. On the other hand we investigate the performance of the maximum entropy principle in approximating the true lead-time demand distribution.

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Noninvasive prenatal testing in the general obstetric population: clinical performance and counseling considerations in over 85,000 cases

Abstract

Objective

The primary goal of this study was to provide clinically relevant information for appropriate patient counseling.

Method

Demographics and test metrics were reviewed for 86,658 clinical cases. Outcome information was requested for samples reported as aneuploidy detected or suspected for chromosomes 21, 18, or 13; voluntary outcome reporting was encouraged for all discordant outcomes.

Results

Of 86,658 cases, 85,298 (98.4%) met inclusion criteria for result reporting. Of the 1,360 (1.6%) cancellations, only 101 (0.1%) were for technical reasons. Average time to result was 3.3 business days. Aneuploidy was detected or suspected in 2,142 (2.5%) samples. For aneuploidy detected cases with known clinical outcomes, the overall PPV was 83.5% (608/728); observed PPVs for trisomies 21, 18, and 13 ranged from 50.0–92.8%. As individual PPVs are determined by a patient's prior risk, we developed a chart for counseling patients on positive predictive value (PPV) based on maternal age.

Conclusion

This large-scale report reinforces that NIPT is a highly accurate screen for fetal aneuploidy in the general obstetric population. Test improvements have facilitated a reduction in failure rates, time to result, and borderline results/unclassifiable results. We have developed a PPV counseling tool to ensure appropriate patient education, counseling, and clinical utilization. This article is protected by copyright. All rights reserved.

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