Intravenous zoledronic acid to prevent osteoporosis in a veteran population with multiple risk factors for bone loss on androgen deprivation therapy.
Androgen deprivation therapy for prostate cancer is associated with osteoporosis and increased fracture risk. Previous studies of zoledronic acid demonstrated bone loss prevention in patients initiating androgen deprivation therapy. There are limited data on patients on prolonged androgen deprivation therapy or in Veterans Affairs patients with multiple risk factors for osteoporosis. We randomized 93 patients with M0 prostate cancer in this placebo controlled trial in the Veterans Affairs health care system. Preplanned strata included 50 patients on androgen deprivation therapy for less than 1 year (stratum 1) and 43 on androgen deprivation therapy for greater than 1 year (stratum 2). In each stratum patients were randomized to 4 mg zoledronic acid intravenously every 3 months for 4 treatments or intravenous placebo. The primary end point was the percent change in bone mineral density at the lumbar spine at 12 months. Age, race, body mass index and osteoporosis risk factors were similar for the 2 treatments. Most patients were former smokers, had moderate alcohol intake, were not on calcium/vitamin D supplements and were relatively sedentary at baseline. In stratum 1 spine bone mineral density increased 5.95% in the zoledronic acid arm and decreased 3.23% in the placebo arm (p = 0.0044). In stratum 2 spine bone mineral density increased 6.08% in the zoledronic acid arm and only increased 1.57% in the placebo arm (p = 0.0005). Treatment was well tolerated with minimal impact on renal function. Zoledronic acid improved bone mineral density in patients with M0 prostate cancer on androgen deprivation therapy for 1 year or less, or greater than 1 year. This finding indicates that bisphosphonate therapy remains effective when initiated later in the course of androgen deprivation therapy and is efficacious in Veterans Affairs patients with multiple risk factors for osteoporosis.


Diabetic ketoacidosis among obese African-American adolescents with NIDDM.
To determine whether ketosis at the time of presentation occurs among African-American adolescents with NIDDM. We reviewed the charts of all islet cell antibody (ICA) negative patients diagnosed with NIDDM at Children's Hospital Medical Center (CHMC) between 1982 and 1995. Between 1982 and 1985, 70 adolescents were diagnosed with NIDDM. Of these, ICA determinations were available and negative on 42 subjects (28 African-American, 12 white). Twelve of 28 (42%) African-American patients presented with ketonuria, and seven of 28 (25%) presented with DKA. In comparison, none of the 12 white adolescents with NIDDM had ketonuria at presentation or during their subsequent course. Mean follow-up time for patients with ketosis at presentation was 24 months. There was no difference between the age, BMI, or sex distribution of patients with and without ketosis. Previously diagnosed hypertension was present in 42% of patients presenting with ketosis, compared with 17% of the general NIDDM population at CHMC. We conclude that ketosis may occur among African-American adolescents with NIDDM, as has been previously reported among African-American adults with NIDDM. Therefore, ketosis in obese young African-American patients with new-onset diabetes does not necessarily imply the presence of IDDM and insulin dependence.


Dioxin and cancer: a critical review.
2,3,7,8-tetrachlordibenzo-p-doxin (TCDD) would not have been designated as a Group 1 carcinogen by IARC had there not been a change in the criteria used for inclusion in this category. Furthermore, there is no precedent for indicating, as did IARC, that a single chemical acts as a pluripotential carcinogen by modestly increasing human risk for all cancer while not increasing the risk for any single cancer at least moderately. IARC moved TCDD to Group 1 based on mechanistic considerations focusing on the Ah receptor. However, while occupancy of the Ah receptor by TCDD may be necessary for its toxicity, it is not sufficient for toxicity or for potential carcinogenicity. Animal evidence relating TCDD exposure to cancer is much stronger than that for humans. However, the large inter-species variation in the relevant dose-response slopes severely limits generalizations from animals to humans. The epidemiologic studies of occupational exposures, pesticide applicators, and community exposures following industrial accidents, notably Seveso, have generated overall relative risks of all cancer of about 1.0. Only case-control studies of soft-tissue sarcoma and non-Hodgkin's lymphoma, all by the same investigator, reported elevated risk from TCDD exposure. However, these results have not been replicated. The representation that a chemical compound (TCDD) would be a late-stage carcinogen for all types of cancer has no precedent and lacks biological foundation. Virtually all late-stage or promoting carcinogens (e.g., hepatitis-C virus, asbestos, and estrogens) cause a very limited number of forms of cancer. The exposure-response meta-analysis of TCDD and cancer developed by the United States Environmental Protection Agency (USEPA) is seriously compromised by its failure to adequately fit the data. The studies used by the USEPA also likely underestimate TCDD body burdens and may be confounded by smoking and other occupational exposures. Furthermore, the use of a linear dose-response model by the USEPA is scientifically unjustified since the underlying model of TCDD as a human carcinogen is based primarily on its supposed receptor-mediated, non-genotoxic (or promotional) mode of action. There are few examples of an agent being suspected as a human carcinogen for decades and then eventually moving into the category of "known" human carcinogens. In contrast, there are hundreds of compounds that remain for decades on lists of "suspected" human carcinogens despite the lack of confirming evidence. The long-term accumulation of negative, weak, and inconsistent findings suggests that TCDD eventually will be recognized as not carcinogenic for humans.


A 3-D Force and Moment Motor for Small-Scale Biomechanics Experiments.
The inability to identify 3-D force and moment components for actuators and sensors is a major limiting factor in the study of 3-D force interactions with small-scale biological structures. While recent advances have been made in the measurement of stimulating forces using load cells and atomic-force microscopy in experimental preparations of biological structures such as mammalian temporal bones, these techniques have mostly been limited to one or two dimensions. In this paper, a method is described for stimulating biological structures using a small magnet (2 mg Sm(2)Co(17)) and a nearby current-conducting coil (46 gauge, 50 turns), that allows the 3-D Lorentz forces and moments acting on the magnet to be calculated. To make these calculations possible, the dimensions and placements of the magnet and coil are accurately determined (within 10 μm for in vitro preparations) using high-resolution micro-CT imaging. This noncontact force motor method has been used to study the mechanics of the malleus-incus complex in the mammalian middle ear in addition to basilar membrane mechanics and fluid flow inside the cochlea, and it can also be applied to the study of other biomechanical structures.


Measuring Regional Eco-Efficiency in China (2003-2016): A "Full World" Perspective and Network Data Envelopment Analysis.
Eco-efficiency enhancement is an inherent requirement of green development and an important indicator of high-quality development in general. It aims to achieve the coordinated development of nature, the economy, and society. Therefore, eco-efficiency measurements should focus on not only total factor input, but also process analysis. Based on the "full world" model in ecological economic theory, this study constructed a theoretical framework for a composite economic-environmental-social system that reflects human welfare and sustainability. To this end, using network data envelopment analysis (DEA), this study established a staged eco-efficiency evaluation model that uses economic, environmental, and social factors to measure the overall and staged eco-efficiency of China's provinces from 2003 to 2016 and analyze its spatiotemporal characteristics. A geographically weighted regression (GWR) model was also used to analyze the influencing factors of eco-efficiency changes and the spatial differentiation in their effect intensity. The findings were as follows: (1) China's overall eco-efficiency is still at a low level. It varies significantly from region to region, and only three regions are at the frontier of production. The eastern region has the highest eco-efficiency, followed by the central region, and the gap between the central and western regions has gradually narrowed. In terms of staged efficiency, the level of eco-efficiency in the production stage is less than in the environmental governance stage, which is less than that in the social input stage. (2) In terms of the efficiency of each stage, the efficiency level of the production stage showed a downward trend throughout the entire process, and the decline in the central and western regions was more obvious. The social input stage and the environmental governance stage both showed upward trends. The social input stage showed a higher level, and the increase was relatively flat during the period of study. Efficiency continued to rise during the environmental governance stage from 2003 to 2010 and rose overall, but with some fluctuations from 2011 to 2016. (3) Geographically weighted regression showed that the effects of the influencing factors on eco-efficiency had obvious spatial heterogeneity. The factors affecting overall, production stage, and social input eco-efficiency were, in order of effect intensity from high to low, economic growth level, marketization level, and social input level. In terms of environmental governance, social input level had the greatest impact, followed by economic growth; marketization level did not show a significant impact.


Metabolic syndrome among Caribbean-born persons living in the U.S. Virgin Islands.
To determine the frequency of the metabolic syndrome (MS) among four subpopulations in the United States Virgin Islands and to estimate the risk for the MS that is associated with waist circumference cutpoints among overweight and obese individuals. In a study undertaken from 1995 to 1999, data on demographic characteristics, anthropometric measurements, blood pressure measurements, and a blood sample were obtained from a population-based cohort of 893 Caribbean-born persons from four population subgroups who were living on Saint Croix (the largest island of the U.S. Virgin Islands) and who did not have a history of diagnosed diabetes. The four subpopulations were: (1) Hispanic white, (2) Hispanic black, (3) non-Hispanic black born in the U.S. Virgin Islands, and (4) non-Hispanic black born elsewhere in the Caribbean. Fasting blood samples were analyzed for glucose, insulin, triglycerides, and high-density lipoprotein cholesterol (HDL-C). National Cholesterol Education Program Adult Treatment Panel III guidelines were used to identify the MS. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR) method. The overall prevalence of the MS in the sample was 20.5% (95% confidence interval (CI) = 15.3%-25.7%). Persons who had classified themselves as both Hispanic and black had the highest frequency (27.8% (95% CI = 16.3%-39.3%)) of the MS and the highest HOMA-IR scores. After controlling for lifestyle factors and HOMA-IR, Hispanic ethnicity was independently associated with an increased risk of having the MS (odds ratio (OR) = 1.82, (95% CI = 1.07-3.07)), high triglycerides (OR = 3.66 (95% CI = 2.18-6.15)), and low HDL-C (OR = 1.60 (95% CI = 1.04-2.45)). A waist circumference of > 88 cm was associated with an increased risk of metabolic abnormalities among overweight and obese women. The frequency of the MS among Caribbean-born persons in the U. S. Virgin Islands is comparable to the frequency of the MS among the general population on the mainland of the United States. Among Caribbean-born persons living in the U.S. Virgin Islands, those who are Hispanic blacks may have a greater risk of cardiovascular disease than do other groups.


Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review.
To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV. Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences.


Three Distinct Nanoviruses, One of Which Represents a New Species, Infect Faba Bean in Ethiopia.
In all, 70 of 296 leaf samples (23.6%) collected from faba bean (Vicia faba) plants showing leaf yellowing and stunting in Ethiopia gave nanovirus-positive reactions when studied by triple-antibody sandwich enzyme-linked immunosorbent assay using broad-spectrum monoclonal antibodies (MAbs) specific to nanoviruses. Further analysis of these samples with seven discriminating MAbs revealed contrasting epitope profiles that were categorized into roughly three serogroups, designated A, B, and C. Serogroup A was found in 89% of the nanovirus-positive samples whereas serogroups B and C were infrequently encountered. Sequence analysis of DNA-S and DNA-U1 of serogroup A, B, and C isolates suggested that each represents a distinct nanovirus species. Serogroup A comprised isolates of Faba bean necrotic stunt virus reported earlier only from Ethiopia and Morocco. The DNA-R, -S, -U1, and -U2 sequences of a serogroup B isolate closely resembled those of Faba bean necrotic yellows virus, providing first molecular evidence for its occurrence in Ethiopia. Sequence analysis of the eight genomic DNAs of a representative serogroup C isolate (Eth-231) showed that it shared overall nucleotide and amino acid sequence identities of only ≤70 and ≤74%, respectively, with other nanoviruses. This suggests that Eth-231 represents a new nanovirus species, for which the name faba bean yellow leaf virus is proposed.


Stable and exacerbation period serum cytokine and periostin levels of the five distinct phenotypes of severe asthma.
The differences in molecular mechanisms during stable period and the changes in the inflammatory responses during exacerbations between distinct severe asthma phenotypes remain unclear. In this study, we aimed to characterize stable and exacerbation period serum cytokine and periostin levels of 5 different pre-defined severe asthma phenotypes with real-life data. Changes in the viral infection-induced exacerbations were also analyzed. Serum levels of 8 cytokines and periostin were measured from the sera obtained from the adult patients with five different severe asthma phenotypes based on the presence/absence of aeroallergen sensitivity, peripheral eosinophilia and chronic rhinosinusitis with nasal polyposis (CRSwNP) during stable and exacerbation periods, and from the matched controls. Serum IL-13, IL-25, TSLP and periostin levels were similar between the patient and the control groups during stable and exacerbation periods. Serum IL-25 and TSLP levels, and peripheral eosinophil count and periostin level showed a strong correlation. Stable period periostin levels were significantly higher in eosinophilic patients and eosinophilic patients without long-term systemic steroid therapy had higher IL-13 levels. Compared to stable period, exacerbation period serum periostin levels found significantly lower [5853 (2309-8427) pg/mL vs. 4479 (2766-6495) pg/mL; p=0.05] and periostin levels were much more lower in viral infection-induced exacerbations [2913 (893-4770) pg/mL vs. 7094 (4782-9596) pg/mL; p=0.022]. Our study showed that serum periostin levels were decreased in viral infection-induced exacerbations and increased in the presence of eosinophilia independent from atopy and it can help to differentiate eosinophilia even if the patient is under long-term systemic steroid therapy. Also, serum IL-13 levels may reflect peripheral eosinophilia in patients without long term systemic steroid use.


Aspirin Intolerance: Experimental Models for Bed-to-Bench.
Aspirin is the oldest non-steroidal anti-inflammatory drug (NSAID), and it sometimes causes asthma-like symptoms known as aspirin-exacerbated respiratory disease (AERD), which can be serious. Unwanted effects of aspirin (aspirin intolerance) are also observed in patients with food-dependent exercise-induced anaphylaxis, a type I allergy disease, and aspirin-induced urticaria (AIU). However the target and the mechanism of the aspirin intolerance are still unknown. There is no animal or cellular model of AERD, because its pathophysiological mechanism is still unknown, but it is thought that inhibition of cyclooxygenase by causative agents leads to an increase of free arachidonic acid, which is metabolized into cysteinyl leukotrienes (cysLTs) that provoke airway smooth muscle constriction and asthma symptoms. As the bed-tobench approach, to confirm the clinical discussion in experimental cellular models, we have tried to develop a cellular model of AERD using activated RBL-2H3 cells, a rat mast cell like cell line. Indomethacin (another NSAID and also causes AERD), enhances in vitro cysLTs production by RBL-2H3 cells, while there is no induction of cysLTs production in the absence of inflammatory activation. Since this suggests that all inflammatory cells with activation of prostaglandin and cysLT metabolism should respond to NSAIDs, and then I have concluded that aspirin intolerance should be separated from subsequent bronchoconstriction. Evidence about the cellular mechanisms of NSAIDs may be employed for development of in vitro AERD models as the approach from bench-to-bed.


Spontaneous Intracerebral Hematoma in Low-Grade Glioma After 14 Years of Follow-Up.
We are reporting the case of a 53-year old woman presenting to our hospital with a hemorrhagic low-grade glioma (LGG). She was admitted to a nearby general hospital where she had presented with aphasia, right hemiplegia and change of mental status. Computer tomography (CT) images showed a left temporo-parietal hemorrhage with mass effect. She was transferred to our hospital neuro-intensive care unit where emergency craniotomy was performed. A tumor with hematoma was removed and further histopathology analysis revealed tumor progression. We reviewed the literature reporting cases of central nervous system tumors hemorrhage and found that these types of events are exquisitely rare in adults with LGG. However these events are possible, suggesting that it should be included in the differential diagnosis of any patient presenting with intracranial hemorrhage. This case raises questions regarding the benefit of early versus late intervention for patients known to have LGG.


Addressing the Issue of Microplastics in the Wake of the Microbead-Free Waters Act-A New Standard Can Facilitate Improved Policy.
The United States Microbead-Free Waters Act was signed into law in December 2015. It is a bipartisan agreement that will eliminate one preventable source of microplastic pollution in the United States. Still, the bill is criticized for being too limited in scope, and also for discouraging the development of biodegradable alternatives that ultimately are needed to solve the bigger issue of plastics in the environment. Due to a lack of an acknowledged, appropriate standard for environmentally safe microplastics, the bill banned all plastic microbeads in selected cosmetic products. Here, we review the history of the legislation and how it relates to the issue of microplastic pollution in general, and we suggest a framework for a standard (which we call "Ecocyclable") that includes relative requirements related to toxicity, bioaccumulation, and degradation/assimilation into the natural carbon cycle. We suggest that such a standard will facilitate future regulation and legislation to reduce pollution while also encouraging innovation of sustainable technologies.


Modulation of tissue factor protein expression in experimental venous bypass grafts.
Vein graft failure is a major limitation of coronary artery and peripheral vascular surgery. Tissue factor (TF), a transmembrane glycoprotein, generates thrombin by initiating the extrinsic coagulation cascade and plays a major role in the response to arterial injury. This study was designed to examine changes in TF protein expression in response to venous bypass grafting. New Zealand White rabbits underwent interposition bypass grafting of the common carotid artery via the ipsilateral external jugular vein. The contralateral control jugular veins (n = 6), early vein grafts (1 or 3 days after grafting, n = 18), and late vein grafts (14 or 28 days after grafting, n = 8) were examined by immunohistochemistry. The presence or absence of TF immunostaining in the intima was assessed in each vessel quadrant. In control veins, intimal TF staining was present in 5 of 24 vessel quadrants. In early vein grafts, TF staining was markedly increased in the intima (72 of 72 quadrants, P < .001 vs control veins), and TF immunostaining colocalized with CD18-positive leukocytes but not with endothelial cells, vascular smooth muscle cells, or RAM11-positive macrophages. In late vein grafts with intimal hyperplasia, TF expression was low or absent in the intima (6 of 32 quadrants, P < .001 vs early vein grafts; P = NS vs control veins), although medial smooth muscle cells expressed TF. Marked changes in TF expression occur in vein grafts. In early vein grafts, TF protein was greatly increased in the intima for at least 3 days and was associated with CD18-positive leukocytes. In late vein grafts with intimal hyperplasia, however, TF protein was not seen in the intima. These findings may have important implications for the development of therapeutic strategies to limit vein graft failure.


PD-L1 testing, fit for routine evaluation? From a pathologist's point of view.
Tumours with high somatic mutation rates escape immune surveillance by upregulating receptors and ligands such as programmed death receptor-1 and its ligand (PD-1/PD-L1). Checkpoint inhibitors (ICI) provide encouraging therapeutic results in non-small cell lung cancers (NSCLC) and may soon be used in 2nd or 1st line therapy. Currently PD-L1 immunohistochemistry (IHC) expression assessed on tumour cells is used as a predictive biomarker, since better patient outcomes are often, but not always associated with increased tumour cell PD-L1 IHC expression. However pre-analytical variables, different anti-PD-L1 clones used on different staining platforms, different specimens types, as well as intra- and interobserver variability influence the results. We will only understand PD-L1 expression on tumour cells if we accept that PD-L1 is an inducible pathophysiological factor with variable levels of PD-L1 expression depending on the immunological status. Should we test PD-L1 during initial diagnostic work up before, or at the point when immune checkpoint therapy is considered? Taking all arguments into account the value of PD-L1 as a predictive biomarker is questionable. Other predictive biomarkers such as high mutation burden, mRNA expression, neo-antigens and the diversity of tumour antigen-specific T cells should be evaluated in the future. Here we review results presented in 30 journal articles and three reviews covering this topic in the last 3 years.


Sensitivity Analysis of Upper Limb Musculoskeletal Models During Isometric and Isokinetic Tasks.
Sensitivity coefficients are used to understand how errors in subject-specific musculoskeletal model parameters influence model predictions. Previous sensitivity studies in the lower limb calculated sensitivity using perturbations that do not fully represent the diversity of the population. Hence, the present study performs sensitivity analysis in the upper limb using a large synthetic dataset to capture greater physiological diversity. The large dataset (n = 401 synthetic subjects) was created by adjusting maximum isometric force, optimal fiber length, pennation angle, and bone mass to induce atrophy, hypertrophy, osteoporosis, and osteopetrosis in two upper limb musculoskeletal models. Simulations of three isometric and two isokinetic upper limb tasks were performed using each synthetic subject to predict muscle activations. Sensitivity coefficients were calculated using three different methods (two point, linear regression, and sensitivity functions) to understand how changes in Hill-type parameters influenced predicted muscle activations. The sensitivity coefficient methods were then compared by evaluating how well the coefficients accounted for measurement uncertainty. This was done by using the sensitivity coefficients to predict the range of muscle activations given known errors in measuring musculoskeletal parameters from medical imaging. Sensitivity functions were found to best account for measurement uncertainty. Simulated muscle activations were most sensitive to optimal fiber length and maximum isometric force during upper limb tasks. Importantly, the level of sensitivity was muscle and task dependent. These findings provide a foundation for how large synthetic datasets can be applied to capture physiologically diverse populations and understand how model parameters influence predictions.


Antagonism of profound cisatracurium and rocuronium block: the role of objective assessment of neuromuscular function.
The purpose of this study is to determine the incidence of significant (train-of-four [TOF] ratio <0.70), but clinically undetectable (TOF ratio >0.40), residual neuromuscular block after neostigmine antagonism of profound cisatracurium (CIS) or rocuronium (ROC) block. Prospective, randomized, open-label study. University hospital. Forty ASA physical status I and II undergoing elective surgical procedures. Anesthesia was induced with propofol 1.5 to 2.5 mg/kg IV plus fentanyl 2 to 4 mug/kg and maintained with N(2)O/desflurane plus narcotic supplementation. The electromyographic response of the adductor pollicis was recorded. Train-of-four stimulation was given every 20 seconds. Twitch height (T1) and TOF fade ratio were continuously recorded. In group 1 (n = 20), neuromuscular block was induced with CIS 0.10 mg/kg, and T1 was maintained at 5% of control by a constant infusion of CIS until the end of surgery. One minute after the termination of the infusion, neostigmine 0.05 mg/kg was administered. T1 and TOF values were monitored continuously for the next 20 minutes. Group 2 (n = 20) is identical to group 1 except that the initial drug was ROC 0.60 mg/kg, and paralysis was maintained with an infusion of ROC. There were no significant differences in the recovery patterns of CIS vs ROC. The duration (bolus to end of infusion) in both groups averaged 2.7 hours, and the mean cumulative dose of relaxant approximated 4 x the ED(95). T1 at the time of reversal was 6% (4%-10%) of control. Mean TOF ratios at 10, 15, and 20 minutes were 0.55, 0.71, and 0.0.81, respectively. Return to a TOF ratio >0.40 was always achieved in 15 minutes or less. However, at 20 minutes postreversal, 5 of 40 subjects had TOF ratios <0.70 and only 11 individuals had recovered to a TOF ratio of 0.90 or greater. Most clinicians cannot detect tactile fade once the TOF ratio exceeds 0.40. When reversing profound block, an objective monitor of neuromuscular function is required if the extent of residual block is to be assessed with any confidence.


Biphasic Pulmonary Blastoma Associated with Cerebral Metastasis.
Pulmonary blastoma is a very rare malignant tumor of the lungs. A biphasic pulmonary blastoma was histologically diagnosed by a characteristic finding as it was mainly constituted of immature tumor tissue that had both epithelial and mesenchymal components. We present a case of a 68-year-old man with biphasic pulmonary blastoma. The patient underwent cranial metastatectomy and left lung upper lobectomy. Although the tumor was resected, there was rapid metastasis to the cranial, liver, kidney and multiple bones. Although radiotherapy and chemotherapy were administrated, the patient died about 6 months postoperatively. Close follow-up and aggressive chemotherapy should be considered for such tumours. In the light of this case, the authors review the pathologic, clinical, radiological and therapeutic features of this very rare malignant lung tumor.


Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation.
The present study investigated the clinical and mutational spectrum of aniridia in a cohort of 17 affected individuals from six families from Cyprus. Each proband was initially evaluated for copy number variants at the PAX6 locus and subsequently underwent PAX6 mutation screening. Sequence analysis of FOXC1 and PITX2 was performed in patients who did not carry a PAX6 mutation. The most common clinical features in the group of aniridia patients associated with aniridia were nystagmus, cataracts and glaucoma. PAX6 pathogenic mutations were identified in five out of six families (a diagnostic yield of 84%). Previously reported pathogenic mutations in PAX6 were identified in four families, which comprise p.R203*, p.R240* and p.R317*. In addition, a novel pathogenic variant (p.E220Gfs*23) was identified in a single family. No pathogenic mutations were detected in PAX6, FOXC1 or PITX2 in the only patient with a sporadic form of aniridia‑like phenotype, confirming the genetic heterogeneity associated with this disease. To the best of our knowledge this is the first report on the mutational spectrum of PAX6 in aniridia patients of Cypriot ancestry. Mutational screening of PAX6 serves a crucial role in distinguishing isolated from syndromic forms of aniridia, and it may therefore eliminate the need for renal ultrasound scan surveillance, delineate the phenotype and improve genetic counseling.


Toxicity prediction of compounds from turmeric (Curcuma longa L).
Turmeric belongs to the ginger family Zingiberaceae. Currently, cheminformatics approaches are not employed in any of the spices to study the medicinal properties traditionally attributed to them. The aim of this study is to find the most efficacious molecule which does not have any toxic effects. In the present study, toxicity of 200 chemical compounds from turmeric were predicted (includes bacterial mutagenicity, rodent carcinogenicity and human hepatotoxicity). The study shows out of 200 compounds, 184 compounds were predicted as toxigenic, 136 compounds are mutagenic, 153 compounds are carcinogenic and 64 compounds are hepatotoxic. To cross validate our results, we have chosen the popular curcumin and found that curcumin and its derivatives may cause dose dependent hepatotoxicity. The results of these studies indicate that, in contrast to curcumin, few other compounds in turmeric which are non-mutagenic, non-carcinogenic, non-hepatotoxic, and do not have any side-effects. Hence, the cost-effective approach presented in this paper could be used to filter toxic compounds from the drug discovery lifecycle.


Modulating light propagation in ZnO-Cu₂O-inverse opal solar cells for enhanced photocurrents.
The advantages of employing an interconnected periodic ZnO morphology, i.e. an inverse opal structure, in electrodeposited ZnO/Cu2O devices are presented. The solar cells are fabricated using low cost solution based methods such as spin coating and electrodeposition. The impact of inverse opal geometry, mainly the diameter and thickness, is scrutinized. By employing 3 layers of an inverse opal structure with a 300 nm pore diameter, higher short circuit photocurrents (∼84% improvement) are observed; however the open circuit voltages decrease with increasing interfacial area. Optical simulation using a finite difference time domain method shows that the inverse opal structure modulates light propagation within the devices such that more photons are absorbed close to the ZnO/Cu2O junction. This increases the collection probability resulting in improved short circuit currents.


A GABAergic neural circuit in the ventromedial hypothalamus mediates chronic stress-induced bone loss.
Homeostasis of bone metabolism is regulated by the central nervous system, and mood disorders such as anxiety are associated with bone metabolism abnormalities, yet our understanding of the central neural circuits regulating bone metabolism is limited. Here, we demonstrate that chronic stress in crewmembers resulted in decreased bone density and elevated anxiety in an isolated habitat mimicking a space station. We then used a mouse model to demonstrate that GABAergic neural circuitry in the ventromedial hypothalamus (VMH) mediates chronic stress-induced bone loss. We show that GABAergic inputs in the dorsomedial VMH arise from a specific group of somatostatin neurons in the posterior region of the bed nucleus of the stria terminalis, which is indispensable for stress-induced bone loss and is able to trigger bone loss in the absence of stressors. In addition, the sympathetic system and glutamatergic neurons in the nucleus tractus solitarius were employed to regulate stress-induced bone loss. Our study has therefore identified the central neural mechanism by which chronic stress-induced mood disorders, such as anxiety, influence bone metabolism.


Are MuSK antibodies the primary cause of myasthenic symptoms?
To investigate the morphologic, electrophysiologic, and molecular correlates of muscle-specific tyrosine kinase-seropositive [MuSK(+)] myasthenia gravis (MG). Anti-MuSK antibodies are detected in some of acetylcholine receptor-seronegative [AChR(-)] patients with MG with prominent facial, bulbar, and respiratory muscle involvement. The morphologic and electrophysiologic correlates of MuSK(+) MG have not been investigated to date. Immunohistochemistry, electron microscopy, and in vitro electrophysiology studies were performed on an intercostal muscle specimen of a patient with MuSK(+) MG and in control subjects. MUSK was directly sequenced, and the nucleotide changes were traced with allele-specific PCR in control subjects. A man aged 34 years has had facial weakness since childhood and progressive bulbar and respiratory muscle weakness and intermittent diplopia since age 21 years. He has thin temporalis and masseter muscles, a high-arched palate, and an atrophic tongue. EMG shows a 36% decrement in facial muscles. His mother has similar facial features. His endplates (EPs) show no AChR or MuSK deficiency, but the amplitudes of the miniature EP potentials and currents are reduced to 35% and 55% of normal, respectively. EP ultrastructure is well preserved, but some junctional folds immunostain faintly for immunoglobulin G. Mutation analysis of MUSK reveals one rare and two common DNA polymorphisms. 1) The circulating anti-muscle-specific tyrosine kinase antibodies caused neither muscle-specific tyrosine kinase nor acetylcholine receptor deficiency at the endplates; 2) the reduced intercostal miniature endplate potential and current amplitudes were not accounted for by acetylcholine receptor deficiency; 3) the faint immunoglobulin G deposits at the endplates may or may not represent anti-muscle-specific tyrosine kinase antibodies; and 4) the anti-muscle-specific tyrosine kinase antibodies may not be the primary cause of myasthenic symptoms in this patient.


Low subcutaneous degradation and slow absorption of insulin in insulin-dependent diabetic patients during continuous subcutaneous insulin infusion at basal rate.
As information on the absorption kinetics and local degradation of infused insulin is relevant to programming strategies for continuous subcutaneous insulin infusion, we examined the time relationship of systemic insulin appearance and quantitated subcutaneous degradation during a near-basal rate of continuous subcutaneous insulin infusion in five insulin-dependent diabetic patients. Plasma free insulin was monitored for 8 h during and 3 h after a subcutaneous (abdominal wall) infusion of neutral insulin at 2.4 U/h. An identical intravenous infusion (2-4 h) was given on a separate occasion. Plateau levels of free insulin were not significantly different during the subcutaneous (37 +/- 8 mU/l) and intravenous (40 +/- 7 mU/l) infusions. Fitting of the free insulin data to our two-pool model of the subcutaneous space gave a mean estimate of 9.2 units insulin (= 3.8 h infusion) for the subcutaneous depot after 8 h. Model estimates of systemic insulin appearance, as a percentage of subcutaneous infusion rate, were 59% and 93% after 4 and 8 h respectively, and 76% 2 h after cessation of infusion. In insulin-dependent diabetic patients subcutaneous degradation of infused insulin is negligible but local accumulation in the subcutaneous space is considerable. The delay in absorption has important clinical implications for interruption and resumption of continuous subcutaneous insulin infusion and also for programming of variable basal rates.


Assessment of the Midwifery Students' Clinical Competency Before Internship Program in the Field Based on the Objective Structured Clinical Examination.
One of the important goals of clinical education is to promote the level of students' clinical skills. About 50% of the midwifery education is focused on clinical education, which has a great importance in shaping the professional skills of the students. The aim of this study was to determine the ability of students in some practical skills, before internship program in the field, using objective structured clinical examination (OSCE). This research was a descriptive cross-sectional study with a single-stage, multivariate prospective design. Twenty-seven midwifery students from the Isfahan University of Medical Sciences who were in their sixth semester were selected by convenience sampling during the second semester of 2015-2016 educational year. OSCE was executed at skill laboratories in 8 stations during one day, and researcher-made checklists were used; their content and face validity were approved and their reliability was confirmed by a Cronbach's alpha coefficient of 0.97. Data analysis was performed by SPSS19. Results showed that the level of students' skills at pelvic exam station was 39.97%, at bladder catheterization was 66.92%, at Leopold was 42.7%, at fetal ECG interpretation was 50.49%, at physical examination was 21.30%, at fetal resuscitation was 48.81%, at breast examination was 56.32%, and at answering the questions was 23.49%. Results show that students gained a score of less than 50% in most skills. Therefore, they are not efficiently skilled for these essential clinical skills. Nonetheless, these procedures need the minimum skills that are required from students after graduation and before entering the working environment in hospitals and health centers. Therefore, more attention should be paid to these skills while planning internship programs before students enter the field. Also, more attention is required while teachers teach these skills and students are supposed to regard their weaknesses in these skills.


Letter and word identification in the fovea and parafovea.
We investigated the extent to which accuracy in word identification in foveal and parafoveal vision is determined by variations in the visibility of the component letters of words. To do so we measured word identification accuracy in displays of three three-letter words, one on fixation and the others to the left and right of the central word. We also measured accuracy in identifying the component letters of these words when presented at the same location in a context of three three-letter nonword sequences. In the word identification block, accuracy was highest for central targets and significantly greater for words to the right compared with words to the left. In the letter identification block, we found an extended W-shaped function across all nine letters, with greatest accuracy for the three central letters and for the first and last letter in the complete sequence. Further analyses revealed significant correlations between average letter identification per nonword position and word identification at the corresponding position. We conclude that letters are processed in parallel across a sequence of three three-letter words, hence enabling parallel word identification when letter identification accuracy is high enough.


Exogenous attention facilitates perceptual learning in visual acuity to untrained stimulus locations and features.
Visual perceptual learning (VPL) refers to the improvement in performance on a visual task due to practice. A hallmark of VPL is specificity, as improvements are often confined to the trained retinal locations or stimulus features. We have previously found that exogenous (involuntary, stimulus-driven) and endogenous (voluntary, goal-driven) spatial attention can facilitate the transfer of VPL across locations in orientation discrimination tasks mediated by contrast sensitivity. Here, we investigated whether exogenous spatial attention can facilitate such transfer in acuity tasks that have been associated with higher specificity. We trained observers for 3 days (days 2-4) in a Landolt acuity task (Experiment 1) or a Vernier hyperacuity task (Experiment 2), with either exogenous precues (attention group) or neutral precues (neutral group). Importantly, during pre-tests (day 1) and post-tests (day 5), all observers were tested with neutral precues; thus, groups differed only in their attentional allocation during training. For the Landolt acuity task, we found evidence of location transfer in both the neutral and attention groups, suggesting weak location specificity of VPL. For the Vernier hyperacuity task, we found evidence of location and feature specificity in the neutral group, and learning transfer in the attention group-similar improvement at trained and untrained locations and features. Our results reveal that, when there is specificity in a perceptual acuity task, exogenous spatial attention can overcome that specificity and facilitate learning transfer to both untrained locations and features simultaneously with the same training. Thus, in addition to improving performance, exogenous attention generalizes perceptual learning across locations and features.


Induced abortion and risk for breast cancer: reporting (recall) bias in a Dutch case-control study.
In general, no association has been found between spontaneous abortion (naturally occurring termination of a pregnancy) and the risk for breast cancer. With respect to induced abortion (termination of a pregnancy by artificial means), the results have been more inconclusive. A positive association was found in five studies, no association was found in six studies, and a negative association was found in the only cohort study. It is thought that part of the inconsistency of the reported results may be attributable to reporting (recall) bias, since all but two studies on induced abortion used the case-control design and were based only on information obtained from study subjects. In comparison with breast cancer case patients, healthy control subjects may be more reluctant to report on a controversial, emotionally charged subject such as induced abortion. Thus, differential underreporting may be a cause of spurious associations in case-control studies. Our goal was threefold: 1) to evaluate the relationship between a history of induced or spontaneous abortion and the risk for breast cancer in a Dutch population-based, case-control study; 2) to examine reporting bias by comparing risks between two geographic areas (i.e., western regions and southeastern regions in The Netherlands that differ in prevalence of and attitudes toward induced abortion); and 3) to compare reporting bias in data on induced abortion with reporting bias in data on oral contraceptive use. Data analyzed in this study were obtained from 918 women (20-54 years of age at diagnosis) who were diagnosed with invasive breast cancer during the period from 1986 through 1989 and had been initially enrolled in a population-based, case-control study investigating oral contraceptive use and breast cancer risk. The women resided in one of four geographic areas that were covered by Regional Cancer Registries: two western regions (Amsterdam and West) and two southeastern regions (East and Eindhoven). Each case patient was pair-matched, on the basis of age (within 1 year) and region, with a control subject who was randomly selected from municipal registries that fully covered the Dutch population. Both the case patients and the control subjects were interviewed at home by the same trained interviewer, who used a structured questionnaire. Reporting bias was examined indirectly by comparing risks between the western and the southeastern regions of the country, which differ in the prevalence of and attitude toward induced abortion. Multivariate conditional logistic regression methods for individually matched case-control studies were used to estimate relative risks (RRs). Reported P values are two-sided. Among parous women, a history of induced abortion was associated with a 90% increased risk for breast cancer (adjusted RR = 1.9; 95% confidence interval [CI] = 1.1-3.2). Among nulliparous women, no association between induced abortion and breast cancer was found. Neither among parous women nor among nulliparous women was a history of spontaneous abortion related to the risk for breast cancer. The association between induced abortion and breast cancer was stronger in the southeastern regions of the country, which have a predominantly Roman Catholic population, than in the western regions (adjusted RR = 14.6 [95% CI = 1.8-120.0] versus adjusted RR = 1.3 [95% CI = 0.7-2.6], respectively; test of difference between regions, P = .017), suggesting reporting bias. Support for reporting bias as an explanation for the regional differences was also found in data supplied by both study subjects and their physicians on the use of oral contraceptives. In comparison with physicians, control subjects in the southeastern regions underreported the duration of their oral contraceptive use by 6.3 months more than control subjects in the western regions (P = .007)...


Suicide in married couples in Sweden: Is the risk greater in same-sex couples?
Minority sexual orientation is a predictor of suicide ideation and attempts, though its association with suicide mortality is less clear. We capitalize on Sweden's extensively linked databases, to investigate whether, among married individuals, same-sex marriage is associated with suicide. Using a population-based register design, we analyzed suicide risk among same-sex married women and men (n = 6456), as compared to different-sex married women and men (n = 1181723) in Sweden. We selected all newly partnered or married individuals in the intervening time between 1/1/1996 and 12/31/2009 and followed them with regard to suicide until 12/31/2011. Multivariate Poisson regression was used to calculate adjusted incidence risk ratios (IRR) with 95 % confidence intervals (CI). The risk of suicide was higher among same-sex married individuals as compared to different-sex married individuals (IRR 2.7, 95 % CI 1.5-4.8), after adjustment for time at risk and socioeconomic confounding. Sex-stratified analyses showed a tentatively elevated risk for same-sex married women (IRR 2.5, 95 % CI 0.8-7.7) as compared to different-sex married women. Among same-sex married men the suicide risk was nearly three-fold greater as compared to different-sex married (IRR 2.895 % CI 1.5-5.5). This holds true also after adjustment for HIV status. Even in a country with a comparatively tolerant climate regarding homosexuality such as Sweden, same-sex married individuals evidence a higher risk for suicide than other married individuals.


Vacuum-ultraviolet photochemically initiated modification of polystyrene surfaces: morphological changes and mechanistic investigations.
Vacuum-ultraviolet (VUV) irradiation (lambda(exc): 172 +/- 12 nm) of polystyrene films in the presence of oxygen produced not only oxidatively functionalized surfaces, but generated also morphological changes. Whereas OH- and C=O-functionalized surfaces might be used for e.g. secondary functionalization, enhanced aggregation or printing, processes leading to morphological changes open new possibilities of microstructurization. Series of experiments made under different experimental conditions brought evidence of two different reaction pathways: introduction of OH- and C=O-groups at the polystyrene pathways is mainly due to the reaction of reactive oxygen species (hydroxyl radicals, atomic oxygen, ozone) produced in the gas phase between the VUV-radiation source and the substrate. However, oxidative fragmentation leading to morphological changes, oxidation products of low molecular weight and eventually to mineralization of the organic substrate is initiated by electronic excitation of the polymer leading to C-C-bond homolysis and to a complex oxidation manifold after trapping of the C-centred radicals by molecular oxygen. The pathways of oxidative functionalization or fragmentation could be differentiated by FTIR-ATR analysis of irradiated polystyrene surfaces before and after washing with acetonitrile and microscopic fluorescence analysis of the surfaces secondarily functionalized with the N,N,N-tridodecyl-triaza-triangulenium (TATA) cation. Ozonization of the polystyrene leads to oxidative functionalization of the polymer surface but cannot initiate the fragmentation of the polymer backbone. Oxidative fragmentation is initiated by electronic excitation of the polymer (contact-mode AFM analysis), and evidence of the generation of intermediate C-centred radicals is given e.g. by experiments in the absence of oxygen leading to cross-linking (solubility effects, optical microscopy, friction-mode AFM) and disproportionation (fluorescence).


Genetic polymorphism of pharmacogenomic VIP variants in the Deng people from the Himalayas in Southeast Tibet.
Little is known about polymorphic distribution of pharmacogenes among ethnicities, including the Deng people. In this study, we recruited 100 unrelated, healthy Deng people and genotyped them with respect to 76 different single-nucleotide polymorphisms by the PharmGKB database. Our results first indicated that the polymorphic distribution of pharmacogenes of the Deng people is most similar to CHD, suggesting that Deng people have a closest genetic relationship with CHD. Our data will enrich the database of pharmacogenomics and provide a theoretical basis for safer drug administration and individualized treatment plans, promoting the development of personalized medicine.


An analysis of birth weight by gestational age in Canada.
Birth-weight-gestational-age standards help to identify infants in need of special care and to determine causes and means for preventing retardation of intrauterine growth. Previously published standards either were based on small samples, data several decades old or characteristics of subpopulations in the United States or they were not specific for type of birth and sex. We compared the data for live births in 1972 with those in 1986 to develop current Canadian standards for type of birth (singleton or twin) and sex. We found that the 10th, 50th and 90th percentile figures for weight were slightly higher in 1986 than in 1972 for term deliveries (at 37 weeks' gestation or later), but the figures were virtually unchanged for preterm deliveries. The availability of reliable population-based standards should enhance the clinician's ability to identify true cases of retardation or acceleration of intrauterine growth.


Consequences of a simulated rapid ocean acidification event for benthic ecosystem processes and functions.
Whilst the biological consequences of long-term, gradual changes in acidity associated with the oceanic uptake of atmospheric carbon dioxide (CO2) are increasingly studied, the potential effects of rapid acidification associated with a failure of sub-seabed carbon storage infrastructure have received less attention. This study investigates the effects of severe short-term (8days) exposure to acidified seawater on infaunal mediation of ecosystem processes (bioirrigation and sediment particle redistribution) and functioning (nutrient concentrations). Following acidification, individuals of Amphiura filiformis exhibited emergent behaviour typical of a stress response, which resulted in altered bioturbation, but limited changes in nutrient cycling. Under acidified conditions, A. filiformis moved to shallower depths within the sediment and the variability in occupancy depth reduced considerably. This study indicated that rapid acidification events may not be lethal to benthic invertebrates, but may result in behavioural changes that could have longer-term implications for species survival, ecosystem structure and functioning.


Comparison of outcomes between complete and incomplete congenital duodenal obstruction.
Congenital duodenal obstruction (CDO) can be complete (CCDO) or incomplete (ICDO). To date there is no outcome analysis available that compares both subtypes. To quantify and compare the association between CCDO and ICDO with outcome parameters. We retrospectively reviewed all patients who underwent operative repair of CCDO or ICDO in our tertiary care institution between January 2004 and January 2017. The demographics, clinical presentation, preoperative diagnostics and postoperative outcomes of 50 patients were compared between CCDO (n = 27; atresia type 1-3, annular pancreas) and ICDO (n = 23; annular pancreas, web, Ladd´s bands). In total, 50 patients who underwent CDO repair were enrolled and followed for a median of 5.2 and 3.9 years (CCDO and ICDO, resp.). CCDO was associated with a significantly higher prenatal ultrasonographic detection rate (88% versus 4%; CCDO vs ICDO, P < 0.01), lower gestational age at birth, lower age and weight at operation, higher rate of associated congenital heart disease (CHD), more extensive preoperative radiologic diagnostics, higher morbidity according to Clavien-Dindo classification and comprehensive complication index (all P ≤ 0.01). The subgroup analysis of patients without CHD and prematurity showed a longer time from operation to the initiation of enteral feeds in the CCDO group (P < 0.01). CCDO and ICDO differ with regard to prenatal detection rate, gestational age, age and weight at operation, rate of associated CHD, preoperative diagnostics and morbidity. The degree of CDO in mature patients without CHD influences the postoperative initiation of enteral feeding.


Black-white inequalities in mortality and life expectancy, 1933-1999: implications for healthy people 2010.
Optimistic predictions for the Healthy People 2010 goals of eliminating racial/ethnic disparities in health have been made based on absolute improvements in life expectancy and mortality. This study sought to determine whether there is evidence of relative improvement (a more valid measure of inequality) in life expectancy and mortality, and whether such improvement, if demonstrated, predicts future success in eliminating disparities. Historical data from the National Center for Health Statistics and the Census Bureau were used to predict future trends in relative mortality and life expectancy, employing an Autoregressive Integrated Moving Average (ARIMA) model. Excess mortality and time lags in mortality and life expectancy for blacks relative to whites were also estimated. Based on data for 1945 to 1999, forecasts for relative black:white age-adjusted, all-cause mortality and white:black life expectancy at birth showed trends toward increasing disparities. From 1979, when the Healthy People initiative began, to 1998, the black:white ratio of age-adjusted, gender-specific mortality increased for all but one of nine causes of death that accounted for 83.4% of all US mortality in 1998. From 1980 to 1998, average numbers of excess deaths per day among American blacks relative to whites increased by 20%. American blacks experienced 4.3 to 4.5 million premature deaths relative to whites in 1940-1999. The rationale that underlies the optimistic Healthy People 2010 forecasts, that future success can be built on a foundation of past success, is not supported when relative measures of inequality are used. There has been no sustained decrease in black-white inequalities in age-adjusted mortality or life expectancy at birth at the national level since 1945. Without fundamental changes, most probably related to the ways medical and public health practitioners are trained, evaluated, and compensated for prevention-related activities, as well as further research on translating the findings of prevention studies into clinical practice, it is likely that simply reducing disparities in access to care and/or medical treatment will be insufficient. Millions of premature deaths will continue to occur among African Americans.


Frequency, viral loads, and serotype identification of enterovirus infections in Scottish blood donors.
Enteroviruses are non-enveloped, frequently pathogenic RNA viruses infecting humans. Infection is potentially transmissible through blood or blood component transfusion from donor in the viremic phase before seroconversion for antibody. To investigate the threat to blood safety from enteroviruses, a large-scale survey of frequency and levels of viremia in blood donors was conducted. Blood donations from Scotland over a period of 22 calendar months were screened for enterovirus RNA sequences by PCR. Positive samples were quantified, and serotypes were identified by nucleotide sequencing of VP1. From a total of 3658 pools of 95 donations tested, 73 samples that were enterovirus-positive were identified (corrected annual frequency 0.024% or 1 in 4000). The highest rates of viremia were in late summer months (e.g., 0.055%, 1 in 1800 in July) and lowest from January to May (0.009 and 0.012%). Viral loads ranged from 500 (the lower cutoff of the assay) to greater than 100,000 amplifiable enterovirus template copies per mL. Coxsackievirus A16, echoviruses 11 and 30, and enterovirus 71 were most often identified. The detection of enterovirus-positive blood units indicates the potential for enteroviral transmission by blood components. Although the infrastructure established for PCR-based screening for HCV RNA would allow parallel screening for enteroviruses, any decision concerning donor testing would require further information on the outcome of transfusion-acquired enterovirus infections.


The microenvironment in the Hirschsprung's disease gut supports myenteric plexus growth.
The transplantation of neural crest derived stem cells (NCSC) is a potent alternative for the treatment of Hirschsprung's disease (HSCR). Cells to be transplanted should find an appropriate microenvironment to survive and differentiate. Influences of HSCR-smooth-muscle-protein extracts upon isolated myenteric plexus cells, dissociated dorsal root ganglia and NCSC were studied in vitro to investigate the quality of this microenvironment effects. Postnatal human gut from children undergoing colonic resection due to HSCR was divided in segments. Smooth muscle was dissected and homogenized. Glial-cell-line-derived-neurotrophic-factor (GDNF) and transforming-growth-factor-β-1 (TGFβ-1) concentration were measured in the homogenates from the individual segment using ELISA. Myenteric plexus and dissociated dorsal root ganglia (DRG) cultures, as well as NCSCs were exposed to protein extracts derived from ganglionic and aganglionic HSCR segments, and their effect upon neurite outgrowth, survival, and branching was evaluated. The amount of the factors varied considerably between the individual segments and also from patient to patient. Four major expression patterns could be detected. While all extracts tested lead to a significant increase in neurite outgrowth compared to the control, extracts from proximal segments tended to have more prominent effects. In one experiment, extracts from all individual segments of a single patient were tested. Neurite outgrowth, neuronal survival, and branching pattern varied from segment to segment, but all HSCR-muscle-protein extracts increased neuronal survival and network formation. Smooth muscle protein from aganglionic bowel supports the survival and outgrowth of myenteric neurons and NCSCs and is so an appropriate target for neural stem cell treatment.


Effect of population size on the mating system in a self-compatible, autogamous plant, aquilegia canadensis (Ranunculaceae)
In self-compatible plants, small populations may experience reduced outcrossing owing to decreased pollinator visitation and mate availability. We examined the relation between outcrossing and population size in eastern Ontario populations of Aquilegia canadensis. Experimental pollinations showed that the species is highly self-compatible, and can achieve full seed-set in the absence of pollinators via automatic self-pollination. We estimated levels of outcrossing (t) and parental inbreeding coefficients (F) from allozyme variation in naturally pollinated seed families for 10 populations ranging in size from 32 to 750 reproductive individuals. The proportion of seeds produced through outcrossing was generally low (mean = 0.29 +/- 0.02 SE) and varied widely among populations (range = 0.00-0.83). Accordingly, estimates of F were large (mean = 0.26 +/- 0.05) and significantly greater than zero in seven populations. As expected, four small populations (N < 40) outcrossed less (0.17 +/- 0.03) than six large populations (N > 90; 0.38 +/- 0. 03). However, parental plants were not significantly more inbred in small than large populations (P = 0.18). There was no difference in the germination of seeds from hand self- and cross-pollinations. However, population genetic estimates of inbreeding depression for survival expressed from seed to reproductive maturity were very high (mean delta = 1 - relative fitness of selfed seed = 0.88 +/- 0.14). The combination of self-compatibility and automatic self-pollination makes the mating system of A. canadensis sensitive to variation in ecological factors that affect the likelihood of cross-pollination.


Neuropathologic basis of white matter hyperintensity accumulation with advanced age.
To determine which vascular pathology measure most strongly correlates with white matter hyperintensity (WMH) accumulation over time, and whether Alzheimer disease (AD) neuropathology correlates with WMH accumulation. Sixty-six older persons longitudinally followed as part of an aging study were included for having an autopsy and >1 MRI scan, with last MRI scan within 36 months of death. Mixed-effects models were used to examine the associations between longitudinal WMH accumulation and the following neuropathologic measures: myelin pallor, arteriolosclerosis, microvascular disease, microinfarcts, lacunar infarcts, large-vessel infarcts, atherosclerosis, neurofibrillary tangle rating, and neuritic plaque score. Each measure was included one at a time in the model, adjusted for duration of follow-up and age at death. A final model included measures showing an association with p < 0.1. Mean age at death was 94.5 years (5.5 SD). In the final mixed-effects models, arteriolosclerosis, myelin pallor, and Braak score remained significantly associated with increased WMH accumulation over time. In post hoc analysis, we found that those with Braak score 5 or 6 were more likely to also have high atherosclerosis present compared with those with Braak score 1 or 2 (p = 0.003). Accumulating white matter changes in advanced age are likely driven by small-vessel ischemic disease. Additionally, these results suggest a link between AD pathology and white matter integrity disruption. This may be due to wallerian degeneration secondary to neurodegenerative changes. Alternatively, a shared mechanism, for example ischemia, may lead to both vascular brain injury and neurodegenerative changes of AD. The observed correlation between atherosclerosis and AD pathology supports the latter.


Prevalence of HIV-related thrombocytopenia among clients at Mbarara Regional Referral Hospital, Mbarara, southwestern Uganda.
We aimed to determine the prevalence and correlates of thrombocytopenia among people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and to assess occurrence of antiplatelet antibodies, among thrombocytopenic HIV clients at Mbarara Regional Referral Hospital, southwestern Uganda. This was a retrospective review of hematologic results at enrollment to HIV care from 2005 to 2013. The prevalence and correlates of thrombocytopenia were estimated based on the Immune Suppressed Syndrome (ISS) Clinic electronic database. A cross-sectional study determined the occurrence of antiplatelet antibodies, using the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) technique. We reviewed 15,030 client records. The median age was 35.0 (range 18-78; interquartile range [IQR] 28-42) years, and there were 63.2% (n=9,500) females. The overall prevalence of thrombocytopenia was 17.4% (95% confidence interval [CI]: 16.8%-18.0%). The prevalence of thrombocytopenia was 17.8% (95% CI: 17.1%-18.4%) among antiretroviral therapy (ART)-naïve clients (n=2,675) and was 13.0% (95% CI: 0.3%-21.9%) for clients who were on ART (n=6). The study found a significant association between thrombocytopenia and other cytopenias, CD4 counts, ART, and deteriorating HIV stage (P<0.05). Two of the 40 participants (5.0%) had antiplatelet antibodies. This study has showed a high prevalence of HIV-related thrombocytopenia. Antiplatelet antibodies were found in 5.0% of HIV-infected thrombocytopenic participants. Our study shows a significant association of thrombocytopenia burden in a high-HIV study population (Southwest Uganda); therefore, there is need to monitor platelet counts and initiate platelet transfusion in our blood banking practices, to avert possible risks of bleeding.


Alcohol and the developing fetus--a review.
Fetal alcohol syndrome (FAS) is a collection of signs and symptoms seen in some children exposed to alcohol in the prenatal period. It is characterized mainly by physical and mental retardation, craniofacial anomalies and minor joint abnormalities. However, with the increasing incidence of FAS, there is a great variation in the clinical features of FAS. This article describes in detail these clinical features. Due to ethical reasons it is not possible to perform experiments on pregnant women. Hence to study the effects of alcohol, various animal and avian experimental models have been chosen. The various experimental findings and human correlation are described. The exact mechanism by which alcohol induces its teratogenic effects is not known. The possible mechanisms are discussed. Measures to prevent the occurrence of FAS have been suggested.


Body integrity identity disorder: deranged body processing, right fronto-parietal dysfunction, and phenomenological experience of body incongruity.
Body integrity identity disorder (BIID) is characterised by profound experience of incongruity between the biological and desired body structure. The condition manifests in "non-belonging" of body parts, and the subsequent desire to amputate, paralyse or disable a limb. Little is known about BIID; however, a neuropsychological model implicating right fronto-parietal and insular networks is emerging, with potential disruption to body representation. We argue that, as there is scant systematic research on BIID published to date and much of the research is methodologically weak, it is premature to assume that the only process underlying bodily experience that is compromised is body representation. The present review systematically investigates which aspects of neurological processing of the body, and sense of self, may be compromised in BIID. We argue that the disorder most likely reflects dysregulation in multiple levels of body processing. That is, the disunity between self and the body could arguably come about through congenital and/or developmental disruption of body representations, which, together with altered multisensory integration, may preclude the experience of self-attribution and embodiment of affected body parts. Ulimately, there is a need for official diagnostic criteria to facilitate epidemiological characterisation of BIID, and for further research to systematically investigate which aspects of body representation and processing are truly compromised in the disorder.


The Satisfaction and Use of Research Ethics Board Information Systems in Canada.
This article reports findings from a national survey of Research Ethics Board (REB) personnel across Canada on the satisfaction and use of information systems that support the review and administration of research ethics protocols. Findings indicate that though a wide variety of REB systems are utilized, the majority fall short of desired characteristics. Despite these shortcomings, most respondents are satisfied with their current REB systems. Satisfaction is dependent on the volume of protocols processed in relation to the robustness of the system. Boards with higher volumes are more satisfied with full-fledged systems; however, the satisfaction of REBs with lower volumes is not affected by the robustness of the REB system used. Recommendations are provided.


Systems biology applied to vaccine and immunotherapy development.
Immunotherapies, including vaccines, represent a potent tool to prevent or contain disease with high morbidity or mortality such as infections and cancer. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the induction of protective immune responses.Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules; among those is a growing appreciation for the role the innate immunity (i.e. pathogen recognition receptors - PRRs) plays in determining the nature and duration (immune memory) of adaptive T and B cell immunity. The complex network of interactions between immune manipulation of the host (immunotherapy) on one side and innate and adaptive responses on the other might be fully understood only employing the global level of investigation provided by systems biology. In this framework, the advancement of high-throughput technologies, together with the extensive identification of new genes, proteins and other biomolecules in the "omics" era, facilitate large-scale biological measurements. Moreover, recent development of new computational tools enables the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review recent progress in using systems biology to study and evaluate immunotherapy and vaccine strategies for infectious and neoplastic diseases. Multi-parametric data provide novel and often unsuspected mechanistic insights while enabling the identification of common immune signatures relevant to human investigation such as the prediction of immune responsiveness that could lead to the improvement of the design of future immunotherapy trials. Thus, the paradigm switch from "empirical" to "knowledge-based" conduct of medicine and immunotherapy in particular, leading to patient-tailored treatment.


The chemical biology of nitric oxide--an outsider's reflections about its role in osteoarthritis.
Excess formation of nitric oxide (NO) has been invoked in the development of osteoarthritis and blamed for triggering chondrocyte apoptosis and matrix destruction. Much of the evidence for a deleterious role of NO in disease progression has been obtained indirectly and inferred from the measurement of nitrite/nitrate and nitrotyrosine concentrations as well as iNOS expression in biopsy specimen, cartilage explants and cytokine-stimulated cells in culture. While these results clearly indicate an involvement of NO and suggest additional contributions from oxidative stress-related components they do not necessarily establish a cause/effect relationship. Many NO metabolites are not mere dosimeters of local NO production but elicit potent down-stream effects in their own right. Moreover, oxygen tension and other experimental conditions typical of many in vitro studies would seem to be at odds with the particular situation in the joint. Recent insight into the chemical biology of NO, in particular with regard to cellular redox-regulation, mitochondrial signaling and nitration reactions, attest to a much richer network of chemical transformations and interactions with biological targets than hitherto assumed. In conjunction with the emerging biology of nitrite and nitrate this information challenges the validity of the long-held view that "too much NO" is contributing to disease progression. Instead, it suggests that part of the problem is a shift from NO to superoxide-dominated chemistries triggering changes in thiol-dependent redox signaling, hypoxia-induced gene expression and mitochondrial function. This essay aims to provide a glimpse into research areas that may hold promise for future investigations into the underlying causes of osteoarthritis.


Reporting Helicopter Emergency Medical Services in Major Incidents: A Delphi Study.
Research on helicopter emergency medical services (HEMS) in major incidents is predominately based on case descriptions reported in a heterogeneous fashion. Uniform data reported with a consensus-based template could facilitate the collection, analysis, and exchange of experiences. This type of database presently exists for major incident reporting at www.majorincidentreporting.net. This study aimed to develop a HEMS-specific major incident template. This Delphi study included 17 prehospital critical care physicians with current or previous HEMS experience. All participants interacted through e-mail. We asked these experts to define data variables and rank which were most important to report during an immediate prehospital medical response to a major incident. Five rounds were conducted. In the first round, the experts suggested 98 variables. After 5 rounds, 21 variables were determined by consensus. These variables were formatted in a template with 4 main categories: HEMS background information, the major incident characteristics relevant to HEMS, the HEMS response to the major incident, and the key lessons learned. Based on opinions from European experts, we established a consensus-based template for reporting on HEMS responses to major incidents. This template will facilitate uniformity in the collection, analysis, and exchange of experience.


Why clowns taste funny: the relationship between humor and semantic ambiguity.
What makes us laugh? One crucial component of many jokes is the disambiguation of words with multiple meanings. In this functional MRI study of normal participants, the neural mechanisms that underlie our experience of getting a joke that depends on the resolution of semantically ambiguous words were explored. Jokes that contained ambiguous words were compared with sentences that contained ambiguous words but were not funny, as well as to matched verbal jokes that did not depend on semantic ambiguity. The results confirm that both the left inferior temporal gyrus and left inferior frontal gyrus are involved in processing the semantic aspects of language comprehension, while a more widespread network that includes both of these regions and the temporoparietal junction bilaterally is involved in processing humorous verbal jokes when compared with matched nonhumorous material. In addition, hearing jokes was associated with increased activity in a network of subcortical regions, including the amygdala, the ventral striatum, and the midbrain, that have been implicated in experiencing positive reward. Moreover, activity in these regions correlated with the subjective ratings of funniness of the presented material. These results allow a more precise account of how the neural and cognitive processes that are involved in ambiguity resolution contribute to the appreciation of jokes that depend on semantic ambiguity.


Decreased visual acuity associated with cystoid macular edema in neovascular age-related macular degeneration.
To determine the prevalence and visual significance of cystoid macular edema (CME) in eyes with subfoveal neovascular age-related macular degeneration using optical coherence tomography (OCT). The medical records of 61 consecutive patients initially seen with nondisciform subfoveal neovascular age-related macular degeneration were retrospectively reviewed. All patients underwent fluorescein angiography and OCT imaging. Eyes with intraretinal hyporeflective spaces in the macula in the OCT images were considered to have CME. Twenty-eight (46%) of 61 eyes demonstrated CME on the OCT images. The presence of CME and increased foveal thickness correlated with decreased visual acuity, but not with the duration of symptoms. Twenty-six (93%) of 28 eyes with CME contained classic choroidal neovascularization, whereas 16 (48%) of 33 eyes without CME contained classic choroidal neovascularization. Cystoid macular edema is a common finding in patients with choroidal neovascularization associated with age-related macular degeneration. The presence of CME and foveal thickening is associated with worse visual acuity in these patients. Cystoid macular edema is more common with choroidal neovascularization containing classic component. The OCT is a useful test to detect the presence of CME in these patients since CME may be difficult to identify on fluorescein angiogram.


Interventional tool tracking using discrete optimization.
This work presents a novel scheme for tracking of motion and deformation of interventional tools such as guide-wires and catheters in fluoroscopic X-ray sequences. Being able to track and thus to estimate the correct positions of these tools is crucial in order to offer guidance enhancement during interventions. The task of estimating the apparent motion is particularly challenging due to the low signal-to-noise ratio (SNR) of fluoroscopic images and due to combined motion components originating from patient breathing and tool interactions performed by the physician. The presented approach is based on modeling interventional tools with B-splines whose optimal configuration of control points is determined through efficient discrete optimization. Each control point corresponds to a discrete random variable in a Markov random field (MRF) formulation where a set of labels represents the deformation space. In this context, the optimal curve corresponds to the maximum a posteriori (MAP) estimate of the MRF energy. The main motivation for employing a discrete approach is the possibility to incorporate a multi-directional search space which is robust to local minima. This is of particular interest for curve tracking under large deformation. This work analyzes feasibility of employing efficient first-order MRFs for tracking. In particular it shows how to achieve a good compromise between energy approximations and computational efficiency. Experimental results suggest to define both the external and internal energy in terms of pairwise potential functions. The method was successfully applied to the tracking of guide-wires in fluoroscopic X-ray sequences of several hundred frames which requires extremely robust techniques. Comparisons with state-of-the-art guide-wire tracking algorithms confirm the effectiveness of the proposed method.


Intersex (testicular oocytes) in smallmouth bass from the Potomac River and selected nearby drainages.
Intersex, or the presence of characteristics of both sexes, in fishes that are normally gonochoristic has been used as an indicator of exposure to estrogenic compounds. In 2003, during health assessments conducted in response to kills and a high prevalence of skin lesions observed in smallmouth bass Micropterus dolomieu in the South Branch of the Potomac River, the presence of immature oocytes within testes was noted. To evaluate this condition, a severity index (0-4) was developed based on the distribution of oocytes within the testes. Using gonad samples collected from 2003 to 2005, the number of histologic sections needed to accurately detect the condition in mature smallmouth bass was statistically evaluated. The reliability of detection depended on the severity index and the number of sections examined. Examining five transverse sections taken along the length of the gonad resulted in a greater than 90% probability of detecting testicular oocytes when the severity index exceeded 0.5. Using the severity index we compared smallmouth bass collected at selected sites within the South Branch during three seasons in 2004. Seasonal differences in severity and prevalence were observed. The highest prevalence and severity were consistently noted during the prespawn-spawning season, when compared with the postspawn season. In 2005, smallmouth bass were collected at selected out-of-basin sites in West Virginia where fish kills and external skin lesions have not been reported, as well as at sites in the Shenandoah River, Virginia (part of the Potomac drainage), where kills and lesions occurred in 2004-2005. The prevalence of testicular oocytes is discussed in terms of human population and agricultural intensity.


Costs of postpartum care: examining associations from the Ontario mother and infant survey.
A cross-sectional survey of 1,250 mothers of "normal" newborn infants was conducted to assess mother and infant characteristics as well as the costs of health and social services used in the first 4 weeks after discharge from hospital in the province of Ontario, Canada. Each mother was asked to recall use of services for herself and her infant. This utilization was multiplied by the unit cost of each service and summed to arrive at the total cost of services used. Although re-admission rates were low (1% for mothers, 4% for infants), costs associated with hospital and emergency room care ($194 on average per mother/infant dyad) accounted for the greatest proportion of total health-care costs. Physician or midwife visits, which were received by almost all mothers, were the next most costly service ($128 on average per dyad). Mothers with incomes under $20,000 had more medical costs than those with higher incomes. Costs of community nursing care ($86 on average per dyad) were higher for mothers with more than 5 self-identified learning needs (e.g., infant feeding, infant care and behaviour, emotional changes in self, signs of illness in infant); perception of their own health as poor; perception of inadequate help and support at home; many signs and symptoms of depression; and postpartum hospital stay of 48 hours or less. Costs for social work visits were higher for mothers with depression and mothers with low incomes. Total health and social service costs were double for mothers with family incomes under $20,000 ($788 vs. $399 on average per dyad) and for mothers with clinical depression ($845 vs. $413). Specifically, nursing care costs were greater for mothers with high depression scores ($135 vs. $81).


3-dimensional examination of the adult mouse subventricular zone reveals lineage-specific microdomains.
Recent studies suggest that the subventricular zone (SVZ) of the lateral ventricle is populated by heterogeneous populations of stem and progenitor cells that, depending on their exact location, are biased to acquire specific neuronal fates. This newly described heterogeneity of SVZ stem and progenitor cells underlines the necessity to develop methods for the accurate quantification of SVZ stem and progenitor subpopulations. In this study, we provide 3-dimensional topographical maps of slow cycling "stem" cells and progenitors based on their unique cell cycle properties. These maps revealed that both cell populations are present throughout the lateral ventricle wall as well as in discrete regions of the dorsal wall. Immunodetection of transcription factors expressed in defined progenitor populations further reveals that divergent lineages have clear regional enrichments in the rostro-caudal as well as in the dorso-ventral span of the lateral ventricle. Thus, progenitors expressing Tbr2 and Dlx2 were confined to dorsal and dorso-lateral regions of the lateral ventricle, respectively, while Mash1+ progenitors were more homogeneously distributed. All cell populations were enriched in the rostral-most region of the lateral ventricle. This diversity and uneven distribution greatly impede the accurate quantification of SVZ progenitor populations. This is illustrated by measuring the coefficient of error of estimates obtained by using increasing section sampling interval. Based on our empirical data, we provide such estimates for all progenitor populations investigated in this study. These can be used in future studies as guidelines to judge if the precision obtained with a sampling scheme is sufficient to detect statistically significant differences between experimental groups if a biological effect is present. Altogether, our study underlines the need to consider the SVZ of the lateral ventricle as a complex 3D structure and define methods to accurately assess neural stem cells or progenitor diversity and population sizes in physiological or experimental paradigms.


Mindfulness-based stress reduction for HIV treatment side effects: a randomized, wait-list controlled trial.
Advances in antiretroviral therapy (ART) for HIV offer life-extending benefit; however, the side effects associated with ART use negatively impact quality of life and medication adherence among people living with HIV. This study tested the efficacy of Mindfulness-Based Stress Reduction (MBSR) for reducing ART symptoms and bother/distress related to ART side effects. Secondary aims were to test the impact of MBSR on medication adherence and psychological functioning. Seventy-six people living with HIV who were actively taking ART and reported distress from ART-related side effects were randomly assigned to an MBSR program or a wait-list control (WLC) standard care condition. We measured side effects, ART adherence, perceived stress, depression, positive and negative affect, and mindfulness at three time points: baseline, three-month follow-up, and six-month follow-up. Side effects and related distress were assessed separately from other symptoms. Compared with a WLC, participants in the MBSR condition experienced a reduction in the frequency of symptoms attributable to ARTs at three months post-intervention (mean difference=0.33; 95% confidence interval [CI]=0.01, 0.66; t(132)=2.04, P=0.044) and six months post-intervention (mean difference=0.38; 95% CI=0.05, 0.71; t(132)=2.27, P=0.025). MBSR participants also experienced a reduction in distress associated with those symptoms at three months post-intervention (mean difference=0.47; 95% CI=0.003, 0.94; t(132)=1.99, P=0.048) compared with the WLC condition. MBSR is a promising approach for reducing HIV treatment-related side effects.


Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta42.
It has long been assumed that the C-terminal motif, NPXY, is the internalization signal for beta-amyloid precursor protein (APP) and that the NPXY tyrosine (Tyr743 by APP751 numbering, Tyr682 in APP695) is required for APP endocytosis. To evaluate this tenet and to identify the specific amino acids subserving APP endocytosis, we mutated all tyrosines in the APP cytoplasmic domain and amino acids within the sequence GYENPTY (amino acids 737-743). Stable cell lines expressing these mutations were assessed for APP endocytosis, secretion, and turnover. Normal APP endocytosis was observed for cells expressing Y709A, G737A, and Y743A mutations. However, Y738A, N740A, and P741A or the double mutation of Y738A/P741A significantly impaired APP internalization to a level similar to that observed for cells lacking nearly the entire APP cytoplasmic domain (DeltaC), arguing that the dominant signal for APP endocytosis is the tetrapeptide YENP. Although not an APP internalization signal, Tyr743 regulates rapid APP turnover because half-life increased by 50% with the Y743A mutation alone. Secretion of the APP-derived proteolytic fragment, Abeta, was tightly correlated with APP internalization, such that Abeta secretion was unchanged for cells having normal APP endocytosis but significantly decreased for endocytosis-deficient cell lines. Remarkably, secretion of the Abeta42 isoform was also reduced in parallel with endocytosis from internalization-deficient cell lines, suggesting an important role for APP endocytosis in the secretion of this highly pathogenic Abeta species.


Linking memory and language: Evidence for a serial-order learning impairment in dyslexia.
The present study investigated long-term serial-order learning impairments, operationalized as reduced Hebb repetition learning (HRL), in people with dyslexia. In a first multi-session experiment, we investigated both the persistence of a serial-order learning impairment as well as the long-term retention of serial-order representations, both in a group of Dutch-speaking adults with developmental dyslexia and in a matched control group. In a second experiment, we relied on the assumption that HRL mimics naturalistic word-form acquisition and we investigated the lexicalization of novel word-forms acquired through HRL. First, our results demonstrate that adults with dyslexia are fundamentally impaired in the long-term acquisition of serial-order information. Second, dyslexic and control participants show comparable retention of the long-term serial-order representations in memory over a period of 1 month. Third, the data suggest weaker lexicalization of newly acquired word-forms in the dyslexic group. We discuss the integration of these findings into current theoretical views of dyslexia.


Web-Based Intervention for Teachers of Elementary Students With ADHD: Randomized Controlled Trial.
To test the acceptability, satisfaction, and effectiveness of a web-based intervention for teachers of elementary school-aged children with ADHD. Elementary classroom teachers (N = 58), along with their students with ADHD, participated in a randomized controlled trial. The program consisted of six sessions that included evidence-based intervention strategies for reducing ADHD symptoms and impairment in the classroom setting. Teachers also had access to a moderated Discussion Board and an online ADHD coach. Questionnaire data were electronically collected from teachers and parents pre-intervention, post-intervention (6 weeks), and after an additional 6-week follow-up. Intent-to-treat analyses found significant improvements based on teacher (but not parent) reports of core ADHD symptoms and impairment for the Teacher Help for ADHD treatment group. Teachers reported a high level of acceptability and satisfaction. Web-based ADHD interventions have the potential to reduce the barriers to treatment utilization and implementation that are common problems for school-based ADHD interventions.


Preoperative exercise therapy in lung surgery patients: A systematic review.
The impact of postoperative complications after lung surgery for cancer is substantial, with the increasing age of patients and the presence of comorbidities. This systematic review summarises the effects of Preoperative Exercise Therapy (PET) in patients scheduled for lung surgery on aerobic capacity, physical fitness, postoperative complications, length of hospital stay, quality of life and recovery. A systematic search on PET prior to lung surgery was conducted. The methodological quality of the included studies was rated using the Physiotherapy Evidence Database (PEDro) scale. The agreement between the reviewers was assessed with Cohen's kappa. A total of eleven studies were included with a methodological quality ranging from poor to good. The agreement between the reviewers, assessed with the Cohen's kappa, was 0.79. Due to substantial heterogeneity in the interventions across the included studies, it was impossible to conduct a meta-analysis. The most important finding of this systematic review was that PET based on moderate to intense exercise in patients scheduled for lung surgery has beneficial effects on aerobic capacity, physical fitness and quality of life. Also PET may reduce postoperative complications and length of hospital stay. PET may have beneficial effects on various physical fitness variables and postoperative complications in patients with lung cancer scheduled for surgery. Future research must focus on developing patient tailored exercise programs and investigate the influence of co-existing comorbidities on the outcome measures. Definitions of PET, including timing, (acceptable) duration, intensity and exercise training methods should be determined and compared.


Biochemical measurements of beef are a good predictor of untrained consumer sensory scores across muscles.
The ability of the biochemical measurements, haem iron, intramuscular fat (IMF%), moisture content, and total, soluble and insoluble collagen contents, to predict untrained consumer sensory scores both across different muscles and within the same muscle from different carcasses were investigated. Sensory scores from 540 untrained French consumers (tenderness, flavour liking, juiciness and overall liking) were obtained for six muscles; outside (m. biceps femoris), topside (m. semimembranosus), striploin (m. longissimus thoracis), rump (m. gluteus medius), oyster blade (m. infraspinatus) and tenderloin (m. psoas major) from each of 18 French and 18 Australian cattle. The four sensory scores were weighted and combined into a single score termed MQ4, which was also analysed. All sensory scores were highly correlated with each other and with MQ4. This in part reflects the fact that MQ4 is derived from the consumer scores for tenderness, juiciness, flavour and overall liking and also reflects an interrelationship between the sensory scores themselves and in turn validates the use of the MQ4 term to reflect the scope of the consumer eating experience. When evaluated across the six different muscles, all biochemical measurements, except soluble collagen, had a significant effect on all of the sensory scores and MQ4. The average magnitude of impact of IMF%, haem iron, moisture content, total and insoluble collagen contents across the four different sensory scores are 34.9, 5.1, 7.2, 36.3 and 41.3, respectively. When evaluated within the same muscle, only IMF% and moisture content had a significant effect on overall liking (5.9 and 6.2, respectively) and flavour liking (6.1 and 6.4, respectively). These results indicate that in a commercial eating quality prediction model including muscle type, only IMF% or moisture content has the capacity to add any precision. However, all tested biochemical measurements, particularly IMF% and insoluble collagen contents, are strong predictors of eating quality when muscle type is not known. This demonstrates their potential usefulness in extrapolating the sensory data derived from these six muscles to other muscles with no sensory data, but with similar biochemical parameters, and therefore reducing the amount of future sensory testing required.