Dying for Money: The Effects of Global Health Initiatives on NGOs Working with Gay Men and HIV/AIDS in Northwest China.
Drawing on 17 months of ethnographic fieldwork (2007-2011), this article critically examines the consequences of two global health initiatives (GHIs), the Global Fund and the Gates Foundation, on NGOs engaged in HIV/AIDS prevention and treatment among gay men in northwest China. I argue that a short-term surge in funding provided by GHIs between 2008 and 2010 exacerbated preexisting conflicts between NGOs by promoting a neoliberal process in which the state outsourced public health services to civil society organizations, deliberately encouraging a climate of competition among NGOs. I also show how GHIs encouraged the bureaucratization and medicalization of one grassroots gay NGO, channeling its activities away from broader political and social objectives and compelling the group to develop a narrower and more entrepreneurial emphasis on HIV testing and treatment. This article contributes to a deeper ethnographic understanding of the complex and perhaps unintended consequences of GHIs.


Alcohol intake and risk of coronary heart disease in younger, middle-aged, and older adults.
Light to moderate alcohol consumption is associated with a reduced risk of coronary heart disease. This protective effect of alcohol, however, may be confined to middle-aged or older individuals. Coronary heart disease incidence is low in men <40 years of age and in women <50 years of age; for this reason, study cohorts rarely have the power to investigate the effects of alcohol on coronary heart disease risk in younger adults. This study examined whether the beneficial effect of alcohol on coronary heart disease depends on age. In this pooled analysis of 8 prospective studies from North America and Europe including 192,067 women and 74,919 men free of cardiovascular diseases, diabetes, and cancers at baseline, average daily alcohol intake was assessed at baseline with a food frequency or diet history questionnaire. An inverse association between alcohol and risk of coronary heart disease was observed in all age groups; hazard ratios among moderately drinking men (5.0 to 29.9 g/d) 39 to 50, 50 to 59, and >or=60 years of age were 0.58 (95% confidence interval [CI], 0.36 to 0.93), 0.72 (95% CI, 0.60 to 0.86), and 0.85 (95% CI, 0.75 to 0.97) compared with abstainers. However, the analyses indicated a smaller incidence rate difference between abstainers and moderate consumers in younger adults (incidence rate difference, 45 per 100,000; 90% CI, 8 to 84) than in middle-aged (incidence rate difference, 64 per 100,000; 90% CI, 24 to 102) and older (incidence rate difference, 89 per 100,000; 90% CI, 44 to 140) adults. Similar results were observed in women. Alcohol is also associated with a decreased risk of coronary heart disease in younger adults; however, the absolute risk was small compared with middle-aged and older adults.


Effects of hypoxia on embryonic development in two Ambystoma and two Rana species.
Oxygen available to amphibian embryos fluctuates widely and is often very low. We investigated the effects of oxygen partial pressure (1. 3-16.9 kPa) on embryonic development and hatching of two salamander (Ambystoma) and two frog (Rana) species. In Ambystoma, chronic hypoxia resulted in slowed development, delayed hatching, and embryos that were less developed at the time of hatching. Although hypoxia was not lethal to embryos, temporary developmental abnormalities were observed in Ambystoma at oxygen partial pressures of 3.8 kPa and below. Posthatching survival decreased below 3.3 kPa. In Rana, hypoxia did not affect developmental rate, presumably because hatching occurs at a very early stage of development relative to Ambystoma. However, Rana embryos hatched sooner in hypoxia than in normoxia, resulting in less developed embryos at the time of hatching. The results suggest that embryonic hypoxia may negatively affect survival and fitness in these species.


[Is there a causal link between idiopathic intracranial hypertension and the use of lithium? A case-study and a review of the literature].
The first case-study of idiopathic intracranial hypertension (IIH) linked to the use of lithium appeared in 1978. Since then several new case-studies have been published sporadically. A recurrent problem for therapists seems to be whether to continue or discontinue treatment with lithium. To review the literature on the alleged link between IIH and the use of lithium. We performed a systematic review of published papers relating to the use of lithium in the treatment of IIH. We found 16 cases. The typical clinical picture of IIH was present in most of the cases. There was a large variation in the course of the illness. In many cases the nature of the link (coincidental or causal) remained unclear. Strong arguments in favour of a causal link were found in only two cases. IIH linked to the use of lithium is a very rare condition. In most cases it is not clear whether the link is coincidental or causal. If a patient being treated with lithium is definitely diagnosed with IIH and no other more plausible cause is found, then it is advisable to discontinue treatment with lithium. However, the therapist should feel free to re-start treatment with lithium in certain circumstances, for instance if patients have clearly benefited from lithium in previous maintenance treatment, if there is an unclear association between lithium and the onset and course of pseudotumour cerebri (PTC), or if the patient's condition has clearly deteriorated after lithium treatment has been discontinued.


Effect of immersion in water on linear expansion and strength of three base/liner materials.
The purpose of this study was to characterize three base/liner materials in the initial stage of setting, i.e., dual-cured (light-activated glass ionomer), light-cured (light-activated glass ionomer analogue), and chemically-cured (conventional glass ionomer) materials. Changes in dimension, weight and flexural strength were examined from immediately after setting to the end of one week following immersion in water. The results obtained from these three types of material differed from each other, and showed a statistically significant correlation between changes in dimension and weight. This may be attributed to hygroscopic expansion. They also showed different flexural strength, indicating differences in the polymerization system. From these results, it appeared that marginal gaps following setting would be compensated for by hygroscopic expansion during immersion in water for one day or more. Physical properties would be favourably improved following the setting process which continues to advance during immersion in water.


Antigen-specific activities of CD8+ T cells in the nasal mucosa of patients with nasal allergy.
The prevalence of chronic rhinitis is increasing rapidly. Its pathogenesis is not fully understood but immune inflammation is one plausible causative factor. Antigen specific CD8+ T cells play a critical role in the induction of chronic inflammation. This study aims to investigate the role of antigen specific CD8+ T cells in the pathogenesis of chronic AR. Nasal mucosal epithelial samples obtained by the surface of the nasal mucosaof patients with AR complicated with inferior turbinate hypertrophy. Exosomes were purified from the scratching samples and examined by immune gold electron microscopy. Cell culture models were employed to evaluate the effect of exosomes on modulating CD8+ T cell activity. Exosomes purified from patients with chronic AR carried microbial products, Staphylococcal enterotoxin B (SEB), and airborne antigen, Derp1. Dendritic cells pulsed by SEB/Derp1-carrying exosomes showed high levels of CD80, CD86 and the major histocompatibility class I (MHCI). Exosome-pulsed dendritic cells could induce naive CD3+ T cells to differentiate into CD8+ T cells. Upon exposure to a specific antigen, the CD8+ T cells released granzyme B and perforin and more than 30% antigen specific CD8+ T cells proliferated. Antigen specific CD8+ T cells play an important role in the pathogenesis of chronic AR complicated with inferior turbinate hypertrophy.


Characterization of mutations in patients with autoimmune polyglandular syndrome type 1 (APS1).
Autoimmune polyglandular syndrome type 1 (APS1), also known as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), is an autosomal recessive disorder characterized by the failure of several endocrine glands as well as nonendocrine organs. The autoimmune regulator (AIRE) gene responsible for APS1 on chromosome 21q22.3 has recently been identified. Here, we have characterized mutations in the AIRE gene by direct DNA sequencing in 16 unrelated APS1 families ascertained mainly from the USA. Our analyses identified four different mutations (a 13-bp deletion, a 2-bp insertion, one nonsense mutation, and one potential splice/donor site mutation) that are likely to be pathogenic. Fifty-six percent (9/16) of the patients contained at least one copy of a 13-bp deletion (1094-1106del) in exon 8 (seven homozygotes and two compound heterozygotes). A nonsense mutation (R257X) in exon 6 was also found in 31.3% (5/16) of the USA patients. These data are important for genetic diagnosis and counseling for families with autoimmune endocrine syndromes.


Hospitalist handoffs: a systematic review and task force recommendations.
Handoffs are ubiquitous to Hospital Medicine and are considered a vulnerable time for patient safety. To develop recommendations for hospitalist handoffs during shift change and service change. PubMed (through January 2007), Agency for Healthcare Research and Quality (AHRQ) Patient Safety Network, white papers, and hand search of article bibliographies. Controlled studies evaluating interventions to improve in-hospital handoffs (n = 10). Studies were abstracted for design, setting, target, outcomes (including patient-level, staff-level, or system-level outcomes), and relevance to hospitalists. Although there were no studies of hospitalist handoffs, the existing literature from related disciplines and expert opinion support the use of a verbal handoff supplemented with written documentation in a structured format or technology solution. Technology solutions were associated with a reduction in preventable adverse events, improved satisfaction with handoff quality, and improved provider identification. Nursing studies demonstrate that supplementing verbal exchange with a written medium leads to improved retention of information. White papers characterized effective verbal exchange, as focusing on ill patients and actions required, with time for questions and minimal interruptions. In addition, content should be updated daily to ensure communication of the latest clinical information. Using this literature, recommendations for hospitalist handoffs are presented with corresponding levels of evidence. Recommendations were reviewed by hospitalists at the Society of Hospital Medicine (SHM) Annual Meeting and by an interdisciplinary team of expert consultants and were endorsed by the SHM governing board. The systematic review and resulting recommendations provide hospitalists a starting point from which to improve in-hospital handoffs.


A guideline-based decision support for pharmacological treatment can improve the quality of hyperlipidemia management.
The Institute of Medicine has identified both Computerized Physician Order Entry (CPOE) and Electronic Prescription (EP) as key in reducing medication errors and improving safety. Many computerized clinical decision support systems (CDSSs) improve practitioner performance. However, the development of CDSSs involves a long cycle time that makes it difficult to apply in a wider scope. In this study, we integrated the hyperlipidemia treatment guideline ATP III (Adult Treatment Panel III) in a CPOE of a medical center. The first 200 consecutive patients followed up more than 1 year were recorded for analysis. Our study revealed that 130 (65%) patients reached the LDL-C (low density lipoprotein-cholesterol) goal in 1 year. For those who with CDSS finished, 74% reached the LDL-C goal. For those who with CDSS exited, 57% reached the LDL-C goal. The odds ratio is 2.1 (1.2, 3.8) (p=0.022), which means for those who with CDSS finished can have 2 times of chance to reach the LDL-C goal. The mean of days to attain the LDL-C goal level after initiation of antihyperlipidemia therapy was 175+/-98 days. 11,806 prescribing records from 8023 patients were collected for analyzing the reasons of prematurely exiting the CDSS. The most frequent reason for exiting the system is "too busy to use". We conclude that a CPOE with CDSS integrated may let more hyperlipidemia patients reach the LDL-C goal. However, data also showed the total prescribing time may increase. The results of a preliminary evaluation are presented to illustrate that the CDSSs can improve the quality of hyperlipidemia management.


Preschool teachers' perspective on how high noise levels at preschool affect children's behavior.
Early-age exposure to noise may have long-term health implications of which we have little knowledge of today. Age-specific hearing, learning inadequate coping strategies, and alterations in biological stress regulatory responses could play a role in the long-term health impacts. In Sweden about half a million children in the age between 1-5 years attend preschool. The noise exposure at preschools is intermittent and unpredictable and levels reach up to 84 dB LAeq (time indoors) with maximum levels of 118 dB LAF, mostly due to child activity. To increase the overall understanding of the possible implications of preschool noise environments for children, this paper describes children's behavioral and emotional reactions to and coping with their everyday sound environment from a teachers perspective. A postal questionnaire study performed in 2013-2014 with answers from 3,986 preschool teachers provided the data. Content analysis was combined with quantitative analysis. Eighty-two percent of the personnel considered that children's behavior was affected rather or very much by preschool noise. The most prevalent behaviors were categorized into: be heard, be distracted, show negative internal emotions, crowd, avoid, withdraw, be exhausted, and learning. The quantitative analyses confirmed an association between the perceived loudness and noise annoyance at preschool and affirmative reporting on noise affecting the children´s behavior. Age of the personnel, with the youngest age group reporting noise related behavior less often, and age distribution of the class, with 1-5 years old seeming less affected by noise, were also indicated, while pedagogic orientation was not a significant factor. Future studies should address the long-term health effects of these behaviors.


OsALMT7 Maintains Panicle Size and Grain Yield in Rice by Mediating Malate Transport.
Panicle size is a critical determinant of grain yield in rice (Oryza sativa) and other grain crops. During rice growth and development, spikelet abortion often occurs at either the top or the basal part of the panicle under unfavorable conditions, causing a reduction in fertile spikelet number and thus grain yield. In this study, we report the isolation and functional characterization of a panicle abortion mutant named panicle apical abortion1-1 (paab1-1). paab1-1 exhibits degeneration of spikelets on the apical portion of panicles during late stage of panicle development. Cellular and physiological analyses revealed that the apical spikelets in the paab1-1 mutant undergo programmed cell death, accompanied by nuclear DNA fragmentation and accumulation of higher levels of H2O2 and malondialdehyde. Molecular cloning revealed that paab1-1 harbors a mutation in OsALMT7, which encodes a putative aluminum-activated malate transporter (OsALMT7) localized to the plasma membrane, and is preferentially expressed in the vascular tissues of developing panicles. Consistent with a function for OsALMT7 as a malate transporter, the panicle of the paab1-1 mutant contained less malate than the wild type, particularly at the apical portions, and injection of malate into the paab1-1 panicle could alleviate the spikelet degeneration phenotype. Together, these results suggest that OsALMT7-mediated transport of malate into the apical portion of panicle is required for normal panicle development, thus highlighting a key role of malate in maintaining the sink size and grain yield in rice and probably other grain crops.


The discovery of dust trails in the orbits of periodic comets.
Analysis of data from the Infrared Astronomical Satellite has yielded evidence for narrow trails of dust coincident with the orbits of periodic comets Tempel 2, Encke, and Gunn. Dust was found both ahead of and behind the orbital positions of these comets. This dust was produced by the low-velocity ejection of large particles during perihelion passage. More than 100 additional dust trails are suggested by the data, almost all near the detection limits of the satellite. Many of these dust trails may be derived from previously unobserved comets.


Adalimumab in combination with methotrexate for refractory uveitis associated with juvenile idiopathic arthritis: a RCT.
Children with juvenile idiopathic arthritis (JIA) are at risk of uveitis. The role of adalimumab (Humira®; AbbVie Inc., Ludwigshafen, Germany) in the management of uveitis in children needs to be determined. To compare the efficacy, safety and cost-effectiveness of adalimumab in combination with methotrexate (MTX) versus placebo with MTX alone, with regard to controlling disease activity in refractory uveitis associated with JIA. This was a randomised (applying a ratio of 2 : 1 in favour of adalimumab), double-blind, placebo-controlled, multicentre parallel-group trial with an integrated economic evaluation. A central web-based system used computer-generated tables to allocate treatments. A cost-utility analysis based on visual acuity was conducted and a 10-year extrapolation by Markov modelling was also carried out. The setting was tertiary care centres throughout the UK. Patients aged 2-18 years inclusive, with persistently active JIA-associated uveitis (despite optimised MTX treatment for at least 12 weeks). All participants received a stable dose of MTX and either adalimumab (20 mg/0.8 ml for patients weighing < 30 kg or 40 mg/0.8 ml for patients weighing ≥ 30 kg by subcutaneous injection every 2 weeks based on body weight) or a placebo (0.8 ml as appropriate according to body weight by subcutaneous injection every 2 weeks) for up to 18 months. A follow-up appointment was arranged at 6 months. Primary outcome - time to treatment failure [multicomponent score as defined by set criteria based on the Standardisation of Uveitis Nomenclature (SUN) criteria]. Economic outcome - incremental cost per quality-adjusted life-year (QALY) gained from the perspective of the NHS in England and Personal Social Services providers. Full details of secondary outcomes are provided in the study protocol. A total of 90 participants were randomised (adalimumab, n = 60; placebo, n = 30). There were 14 (23%) treatment failures in the adalimumab group and 17 (57%) in the placebo group. The analysis of the data from the double-blind phase of the trial showed that the hazard risk (HR) of treatment failure was significantly reduced, by 75%, for participants in the adalimumab group (HR 0.25, 95% confidence interval 0.12 to 0.51; p < 0.0001 from log-rank test). The cost-effectiveness of adalimumab plus MTX was £129,025 per QALY gained. Adalimumab-treated participants had a much higher incidence of adverse and serious adverse events. Adalimumab in combination with MTX is safe and effective in the management of JIA-associated uveitis. However, the likelihood of cost-effectiveness is < 1% at the £30,000-per-QALY threshold. A clinical trial is required to define the most effective time to stop therapy. Prognostic biomarkers of early and complete response should also be identified. Current Controlled Trials ISRCTN10065623 and European Clinical Trials Database number 2010-021141-41. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 15. See the NIHR Journals Library website for further project information. This trial was also funded by Arthritis Research UK (grant reference number 19612). Two strengths of adalimumab (20 mg/0.8 ml and 40 mg/0.8 ml) and a matching placebo were manufactured by AbbVie Inc. (the Marketing Authorisation holder) and supplied in bulk to the contracted distributor (Sharp Clinical Services, Crickhowell, UK) for distribution to trial centres.


Enhanced biodegradation of hexachlorocyclohexane (HCH) in contaminated soils via inoculation with Sphingobium indicum B90A.
Soil pollution with hexachlorocyclohexane (HCH) has caused serious environmental problems. Here we describe the targeted degradation of all HCH isomers by applying the aerobic bacterium Sphingobium indicum B90A. In particular, we examined possibilities for large-scale cultivation of strain B90A, tested immobilization, storage and inoculation procedures, and determined the survival and HCH-degradation activity of inoculated cells in soil. Optimal growth of strain B90A was achieved in glucose-containing mineral medium and up to 65% culturability could be maintained after 60 days storage at 30 degrees C by mixing cells with sterile dry corncob powder. B90A biomass produced in water supplemented with sugarcane molasses and immobilized on corncob powder retained 15-20% culturability after 30 days storage at 30 degrees C, whereas full culturability was maintained when cells were stored frozen at -20 degrees C. On the contrary, cells stored on corncob degraded gamma-HCH faster than those that had been stored frozen, with between 15 and 85% of gamma-HCH disappearance in microcosms within 20 h at 30 degrees C. Soil microcosm tests at 25 degrees C confirmed complete mineralization of [(14)C]-gamma-HCH by corncob-immobilized strain B90A. Experiments conducted in small pits and at an HCH-contaminated agricultural site resulted in between 85 and 95% HCH degradation by strain B90A applied via corncob, depending on the type of HCH isomer and even at residual HCH concentrations. Up to 20% of the inoculated B90A cells survived under field conditions after 8 days and could be traced among other soil microorganisms by a combination of natural antibiotic resistance properties, unique pigmentation and PCR amplification of the linA genes. Neither the addition of corncob nor of corncob immobilized B90A did measurably change the microbial community structure as determined by T-RFLP analysis. Overall, these results indicate that on-site aerobic bioremediation of HCH exploiting the biodegradation activity of S. indicum B90A cells stored on corncob powder is a promising technology.


Reticulospinal neurons receive direct spinobulbar inputs during locomotor activity in lamprey.
Reticulospinal neurons of the lamprey brain stem receive rhythmic input from the spinal cord during locomotor activity. The goal of the present study was to determine whether such spinal input has a direct component to reticulospinal neurons or depends on brain stem interneurons. To answer this question, an in vitro lamprey brain stem-spinal cord preparation was used with a diffusion barrier placed caudal to the obex, separating the experimental chamber into two baths. Locomotor activity was induced in the spinal cord by perfusion of d-glutamate or N-methyl-dl-aspartate into the spinal cord bath. The brain stem bath was first perfused with normal Ringer solution followed by a high-Ca(2+), -Mg(2+) solution, which reduced polysynaptic transmission. The amplitudes of membrane potential oscillations of reticulospinal neurons in the posterior and middle rhombencephalic reticular nuclei (PRRN and MRRN, respectively) recorded with sharp intracellular microelectrodes did not significantly change from normal to high-divalent solution. This finding suggests a large part of the spinal input creating the oscillations is direct to the reticulospinal neurons. Application of strychnine to the high-Ca(2+), -Mg(2+) solution decreased membrane potential oscillation amplitude, and injection of Cl(-) reversed presumed inhibitory postsynaptic potentials, indicating a role for direct spinal inhibitory inputs. Although reduced, the persistence of oscillations in strychnine suggests that spinal excitatory inputs also contribute to the oscillations. Thus it was concluded that both excitatory and inhibitory spinal neurons provide direct rhythmic inputs to reticulospinal cells of the PRRN and MRRN during locomotor activity. These inputs provide reticulospinal cells with information regarding the activity of the spinal locomotor networks.


Safety and Use of Anticoagulation After Aortic Valve Replacement With Bioprostheses: A Meta-Analysis.
The American College of Cardiology guidelines recommend 3 months of anticoagulation after replacement of the aortic valve with a bioprosthesis. However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether anticoagulation in the setting of a new bioprosthesis was associated with improved outcomes or greater risk of bleeding. We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed anticoagulation with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa Scale, and random effects analysis was used to pool the data from the available studies. I(2) testing was done to assess the heterogeneity of the included studies. After screening through 170 articles, a total of 13 studies (cases=6431; controls=18210) were included in the final analyses. The use of warfarin was associated with a significantly increased risk of overall bleeding (odds ratio, 1.96; 95% confidence interval, 1.25-3.08; P<0.0001) or bleeding risk at 3 months (odds ratio, 1.92; 95% confidence interval, 1.10-3.34; P<0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke, or transient ischemic attack) at 3 months, no significant difference was seen with warfarin (odds ratio, 1.13; 95% confidence interval, 0.82-1.56; P=0.67). Moreover, anticoagulation was also not shown to improve outcomes at time interval >3 months (odds ratio, 1.12; 95% confidence interval, 0.80-1.58; P=0.79). Contrary to the current guidelines, a meta-analysis of previous studies suggests that anticoagulation in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable effect on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.


Treatment of inflammatory diseases with mesenchymal stem cells.
Human mesenchymal stem cells (hMSCs) are rare progenitor cells present in adult bone marrow that have the capacity to differentiate into a variety of tissue types, including bone, cartilage, tendon, fat, and muscle. In addition to multilineage differentiation capacity, MSCs regulate immune and inflammatory responses, providing therapeutic potential for treating diseases characterized by the presence of an inflammatory component. The availability of bone marrow and the ability to isolate and expand hMSCs ex vivo make these cells an attractive candidate for drug development. The low immunogenicity of these cells suggests that hMSCs can be transplanted universally without matching between donors and recipients. MSCs universality, along with the ability to manufacture and store these cells long-term, present a unique opportunity to produce an "off-the-shelf" cellular drug ready for treatment of diseases in acute settings. Accumulated animal and human data support MSC therapeutic potential for inflammatory diseases. Several phase III clinical trials for treatment of acute Graft Versus Host Disease (GVHD) and Crohn's disease are currently in progress. The current understanding of cellular and molecular targets underlying the mechanisms of MSCs action in inflammatory settings as well as clinical experience with hMSCs is summarized in this review.


Knowledge-based identification of sleep stages based on two forehead electroencephalogram channels.
Sleep quality is important, especially given the considerable number of sleep-related pathologies. The distribution of sleep stages is a highly effective and objective way of quantifying sleep quality. As a standard multi-channel recording used in the study of sleep, polysomnography (PSG) is a widely used diagnostic scheme in sleep medicine. However, the standard process of sleep clinical test, including PSG recording and manual scoring, is complex, uncomfortable, and time-consuming. This process is difficult to implement when taking the whole PSG measurements at home for general healthcare purposes. This work presents a novel sleep stage classification system, based on features from the two forehead EEG channels FP1 and FP2. By recording EEG from forehead, where there is no hair, the proposed system can monitor physiological changes during sleep in a more practical way than previous systems. Through a headband or self-adhesive technology, the necessary sensors can be applied easily by users at home. Analysis results demonstrate that classification performance of the proposed system overcomes the individual differences between different participants in terms of automatically classifying sleep stages. Additionally, the proposed sleep stage classification system can identify kernel sleep features extracted from forehead EEG, which are closely related with sleep clinician's expert knowledge. Moreover, forehead EEG features are classified into five sleep stages by using the relevance vector machine. In a leave-one-subject-out cross validation analysis, we found our system to correctly classify five sleep stages at an average accuracy of 76.7 ± 4.0 (SD) % [average kappa 0.68 ± 0.06 (SD)]. Importantly, the proposed sleep stage classification system using forehead EEG features is a viable alternative for measuring EEG signals at home easily and conveniently to evaluate sleep quality reliably, ultimately improving public healthcare.


The epidemiology of malignant mesothelioma in women: gender differences and modalities of asbestos exposure.
The epidemiology of gender differences for mesothelioma incidence has been rarely discussed in national case lists. In Italy an epidemiological surveillance system (ReNaM) is working by the means of a national register. Incident malignant mesothelioma (MM) cases in the period 1993 to 2012 were retrieved from ReNaM. Gender ratio by age class, period of diagnosis, diagnostic certainty, morphology and modalities of asbestos exposure has been analysed using exact tests for proportion. Economic activity sectors, jobs and territorial distribution of mesothelioma cases in women have been described and discussed. To perform international comparative analyses, the gender ratio of mesothelioma deaths was calculated by country from the WHO database and the correlation with the mortality rates estimated. In the period of study a case list of 21 463 MMs has been registered and the modalities of asbestos exposure have been investigated for 16 458 (76.7%) of them. The gender ratio (F/M) was 0.38 and 0.70 (0.14 and 0.30 for occupationally exposed subjects only) for pleural and peritoneal cases respectively. Occupational exposures for female MM cases occurred in the chemical and plastic industry, and mainly in the non-asbestos textile sector. Gender ratio proved to be inversely correlated with mortality rate among countries. The consistent proportion of mesothelioma cases in women in Italy is mainly due to the relevant role of non-occupational asbestos exposures and the historical presence of the female workforce in several industrial settings. Enhancing the awareness of mesothelioma aetiology in women could support the effectiveness of welfare system and prevention policies.


Presence of viremia during febrile neutropenic episodes in patients undergoing chemotherapy for malignant neoplasms.
The importance of viral infections as a leading cause of morbidity and mortality is well documented in severely immunosuppressed patients undergoing allogeneic stem cell transplantation. By contrast, viral infections generally receive less attention in patients with malignant disorders undergoing chemotherapy, where the onset of neutropenic fever is mostly associated with bacterial or fungal infections, and screening for viral infections is not routinely performed. To address the occurrence of invasive viral infections in a clinical setting commonly associated with less pronounced immunosuppression, we have prospectively screened 237 febrile neutropenic episodes in pediatric (n = 77) and adult (n = 69) patients undergoing intensive chemotherapy, primarily for treatment of acute leukemia. Serial peripheral blood specimens were tested by RQ-PCR assays for the presence and quantity of the clinically relevant viruses CMV, EBV, HHV6 and HAdV, commonly reactivated in highly immunocompromised patients. Viremia was documented in 36 (15%) episodes investigated, including the detection of HHV6 (n = 14), EBV (n = 15), CMV (n = 6), or HAdV (n = 1). While low or intermediate levels of viremia (<104 virus copies/mL) were commonly associated with bacterial or fungal co-infection, viremia at higher levels (>104 copies/mL) was documented in patients without evidence for other infections, raising the possibility that at least in some instances the onset of fever may have been attributable to the virus detected. The observations suggest that viral infections, potentially resulting from reactivation, might also play a clinically relevant role in patients receiving chemotherapy for treatment of malignant neoplasms, and routine screening for viremia in this clinical setting might be warranted.


In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6).
We investigated the cellular tropism of human B-lymphotropic virus (HBLV) (also designated Human Herpesvirus-6) in vitro by infecting fresh MN cells from normal human adult peripheral blood, umbilical cord blood, bone marrow, tonsil, and thymus. Cultures from all the sources examined contained infectable cells, as shown by the appearance of characteristic enlarged, round-shaped, short-lived cells expressing HBLV-specific markers. Detailed immunological analysis demonstrated that the vast majority of these cells expressed T cell-associated antigens (i.e., CD7, CD5, CD2, CD4, and to a lesser extent, CD8). The CD3 antigen and the TCR-alpha/beta heterodimer were not detectable on the surface membrane, but were identified within the cytoplasm of HBLV-infected cells, by both immunofluorescence and radioimmunoprecipitation assay. A proportion of the HBLV-infected cell population also expressed the CD15 and class II MHC DR antigens. By means of immunoselection procedures it was possible to show that a consistent proportion of HBLV-infectable cells were contained within the CD3-depleted immature T cell population, while the depletion of CD2+ cells completely abrogated the infectability of the cultures. Northern blot analysis confirmed the T cell origin of HBLV-infected cells, demonstrating the expression of full size TCR-alpha and -beta chain mRNA. In addition to fresh T cells, HBLV was able to infect normal T lymphocytes expanded in vitro with IL-2 for greater than 30 d. These results indicate that HBLV is selectively T cell tropic in the course of the in vitro infection of normal mononuclear cells and may therefore be directly involved in the pathogenesis of T cell related hematological disorders. In particular, in light of the cytopathic effect exerted in vitro on CD4+ T lymphocytes, a possible role of HBLV in immune deficiency conditions should be considered.


Retinal rods and cones have distinct G protein beta and gamma subunits.
Guanine nucleotide-binding proteins (G proteins) involved in transmembrane signal-transduction processes are heterotrimers composed of alpha, beta, and gamma subunits. The alpha subunit shows great diversity and is thought to confer functional specificity to a particular G protein. By contrast, the beta and gamma subunits appear much less diverse; in particular, the beta subunit is believed to have no role in G protein specificity. Using immunocytochemistry, we found distinct distribution patterns for different beta and gamma subunits in the retina. In particular, rod and cone photoreceptors, which both subserve phototransduction but differ in light-response properties, have different beta and gamma subunits in their outer segments. Thus, the G protein mediating phototransduction shows cell-specific forms of the beta and gamma subunits in addition to the alpha subunit. This surprising finding supports the hypothesis that these subunits may also contribute to functional specificity of a G protein.


Barton's forceps deliveries at Paarl Hospital.
Experience in using Barton's forceps for mid-pelvic arrest of the fetal head in 348 cases has proved that this instrument is both easy to apply and safe for the baby, provided rigid adherence to safety criteria are observed. As modern obstetric practice is favourably disposed towards mid-pelvic forceps vaginal delivery, the particular advantages of Barton's forceps should be more widely extolled. Their use is an invaluable addition to the obstetrician's armamentarium. Training in their use should, however, be thorough and extensive and under the guidance of a skilled senior obstetrician.


Shared understanding and idiosyncratic expression in early vocabularies.
To what extent do toddlers have shared vocabularies? We examined CDI data collected from 14,607 infants and toddlers in five countries and measured the amount of variability between individual lexicons during development for both comprehension and production. Early lexicons are highly overlapping. However, beyond 100 words, toddlers share more words with other toddlers in comprehension than in production, even when matched for lexicon sizes. This finding points to a structural difference in early comprehension and production: Toddlers are generalists in comprehension but develop a unique, expressive voice. Variability in production decreases after two years of age, suggesting convergence to a common expressive core vocabulary. We discuss potential exogenous and endogenous contributions to the inverted U-shaped development observed in young children's expressive lexical variability.


Reconstructing plumage evolution in orioles (Icterus): repeated convergence and reversal in patterns.
Several empirical studies suggest that sexually selected characters, including bird plumage, may evolve rapidly and show high levels of convergence and other forms of homoplasy. However, the processes that might generate such convergence have not been explored theoretically. Furthermore, no studies have rigorously addressed this issue using a robust phylogeny and a large number of signal characters. We scored the appearance of 44 adult male plumage characters that varied across New World orioles (Icterus). We mapped the plumage characters onto a molecular phylogeny based on two mitochondrial genes. Reconstructing the evolution of these characters revealed evidence of convergence or reversal in 42 of the 44 plumage characters. No plumage character states are restricted to any groups of species higher than superspecies in the oriole phylogeny. The high frequency of convergence and reversal is reflected in the low overall retention index (RI = 0.66) and the low overall consistency index (CI = 0.28). We found similar results when we mapped plumage changes onto a total evidence tree. Our findings reveal that plumage patterns and colors are highly labile between species of orioles, but highly conserved within the oriole genus. Furthermore, there are at least two overall plumage types that have convergently evolved repeatedly in the three oriole clades. This overall convergence leads to significant conflict between the molecular and plumage data. It is not clear what evolutionary processes lead to this homoplasy in individual characters or convergence in overall pattern. However, evolutionary constraints such as developmental limitations and genetic correlations between characters are likely to play a role. Our results are consistent with the belief that avian plumage and other sexually selected characters may evolve rapidly and may exhibit high homoplasy. The overall convergence in oriole plumage patterns is an interesting evolutionary phenomenon, but it cautions against heavy reliance on plumage characters for constructing phylogenies.


Novel Trajectories for Identifying Asthma Phenotypes: A Longitudinal Study in Korean Asthma Cohort, COREA.
Unbiased cluster analysis has identified several asthma phenotypes. However, these phenotypes did not consistently predict disease prognosis and reflect temporal variability in airway inflammation. We aimed to identify longitudinal trajectories in terms of pulmonary function parameters and investigated whether the trajectories are associated with prognosis. Data were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). Three-year pulmonary function test results were used to apply finite mixture models for group-based trajectory in 486 patients with eligible data set. Two main sets of longitudinal trajectories were identified in terms of FEV1% predicted, and FEV1 variability. In the 4 trajectories determined with FEV1% predicted, the pulmonary function showed a consistent course in 4 stratified levels during 3 years of follow-up, which was associated with unexpected hospital visits and the use of steroid bursts due to exacerbation. The variability in pulmonary function showed 3 different patterns, and we found that higher blood and sputum eosinophil levels were associated with the higher variability in pulmonary function and more exacerbations. Trajectory analysis is a novel method that provides longitudinal asthma phenotypes and aids in prediction of future risk of exacerbation. Further analysis is needed to validate the usefulness of these trajectories in an independent population.


Testing for Constant Nonparametric Effects in General Semiparametric Regression Models with Interactions.
We consider the problem of testing for a constant nonparametric effect in a general semi-parametric regression model when there is the potential for interaction between the parametrically and nonparametrically modeled variables. The work was originally motivated by a unique testing problem in genetic epidemiology (Chatterjee, et al., 2006) that involved a typical generalized linear model but with an additional term reminiscent of the Tukey one-degree-of-freedom formulation, and their interest was in testing for main effects of the genetic variables, while gaining statistical power by allowing for a possible interaction between genes and the environment. Later work (Maity, et al., 2009) involved the possibility of modeling the environmental variable nonparametrically, but they focused on whether there was a parametric main effect for the genetic variables. In this paper, we consider the complementary problem, where the interest is in testing for the main effect of the nonparametrically modeled environmental variable. We derive a generalized likelihood ratio test for this hypothesis, show how to implement it, and provide evidence that our method can improve statistical power when compared to standard partially linear models with main effects only. We use the method for the primary purpose of analyzing data from a case-control study of colorectal adenoma.


Pressure induced photoluminescence modulation in a wide range and synthesis of monodispersed ternary AgCuS nanocrystal based on Ag2S nanocrystals.
Binary Ag2S nanocrystals (NCs) have many potential optical applications because of their low toxicity, narrow direct band gaps and near-infrared photoluminescence (PL) with high emission efficiency. However, due to its small exciton Bohr radius (2.2 nm), the PL spectra of Ag2S NCs can only be modulated below ∼1200 nm with increasing particle size. Meanwhile, ternary silver copper chalcogenides (AgCuX, X = S, Se) have also attracted increased attention in recent years. Temperature-dependent structural phase transformation leads electrical transport to exhibit fascinating transitions between p and n type conduction, which makes AgCuS and AgCuSe ideal materials for diode or transistor devices. Nevertheless, the traditional method to synthesize these materials is mainly through melting the mixture of Ag, Cu and S/Se powder under extremely high reaction temperatures (973-1373 K) and long reaction time, forming a bulk product. Therefore, the synthesis of high quality monodispersed and size-tunable AgCuS or AgCuSe NCs is still a challenge. To address these issues, in this paper, we report using Ag2S NCs as a template, a method to synthesize monodispersed and size-tunable β-AgCuS NCs via ion exchange and diffusion processes. Similarly, monodispersed β-AgCuSe NCs were also synthesized by this simple and reproducible strategy. This synthetic method opens new avenues for investigating the size-, morphology- and temperature-dependent phase transitions of these ternary AgCuS and AgCuSe materials. Thus, the corresponding electrical transport between p and n type conduction can be studied in the future. Furthermore, we systematically investigated the pressure-dependent PL properties and band gap modulation of monodispersed Ag2S NCs using in situ high pressure PL and absorption spectroscopy. We found that the PL peak of 6.0 nm for Ag2S NCs could be easily adjusted from ∼1200 to 1900 nm with increasing pressure from 0 to 5.1 GPa, which greatly extends the wavelength range of the PL peak beyond that of other approaches.


Reinstatement in honeybees is context-dependent.
During extinction animals experience that the previously learned association between a conditioned stimulus (CS) and an unconditioned stimulus (US) no longer holds true. Accordingly, the conditioned response (CR) to the CS decreases. This decrease of the CR can be reversed by presentation of the US alone following extinction, a phenomenon termed reinstatement. Reinstatement and two additional phenomena, spontaneous recovery and renewal, indicate that the original CS-US association is not lost through extinction but can be reactivated through different processes. In honeybees (Apis mellifera), spontaneous recovery, i.e., the time-dependent return of the CR, has been demonstrated, suggesting that also in these insects the original CS-US association is not lost during extinction. To support this notion, we ask whether honeybees show reinstatement after extinction. In vertebrates reinstatement is context-dependent, so we examined whether the same holds true for honeybees. We demonstrate reinstatement in restrained honeybees and show that reinstatement is context-dependent. Furthermore, we show that an alteration of the color of light illuminating the experimental setup suffices to indicate a contextual change. We conclude that in honeybees the initially formed CS-US memory is not lost after extinction. Rather, honeybees might learn about the context during extinction. This enables them to adequately retrieve one of the two opposing memories about the CS that have been formed after extinction.


Latent class analysis of child behavior checklist anxiety/depression in children and adolescents.
Comorbidity of psychiatric problems such as anxiety and depression poses challenges to treatment and research. This study tested whether problem items from the Anxious/Depressed scale of the Child Behavior Checklist (CBCL) can be separated into distinct anxiety and depression classes or are continuously distributed throughout a population. A CBCL was completed by a parent or guardian of each of 1,987 children and adolescents selected to represent nonreferred children in the United States, as well as by a parent or guardian of each of a demographically matched sample of 1,987 clinically referred children and adolescents. Problem items from the Anxious/Depressed scale of the CBCL were subjected to latent class analysis. Analyses revealed three levels of problem presentation in both samples. Children in the nonreferred sample were classified as having no problems, mild problems, or moderate anxiety/depression problems. Children and adolescents in the referred group were classified as having mild, moderate, or severe levels of problems. No pure anxiety or depression classes were found, only classes containing a mixture of both anxiety and depressive problems. Age, gender, and sample differences were found in class groupings, with nonreferred adolescent girls showing elevated levels of problems. Results suggest that the comorbid conditions of anxiety and depression, as assessed by the CBCL anxiety/depression problem items, can be thought of as part of the same continuum of problems. Implications for assessment and treatment utilization are discussed.


Coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood and atherosclerosis later in life: the CARDIA study.
To determine the association of coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood with the presence and progression of coronary artery calcified (CAC) plaque and carotid intima-media thickness later in life. The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a cohort of 5115 white and black adults who were aged 18 to 30 years when they completed a baseline clinic examination from 1985 to 1986. Subsequent examinations were conducted 2, 5, 7, 10, 15, and 20 years later. After multivariable adjustment, no association was observed between average coffee, decaffeinated coffee, or caffeine consumption (years 0 and 7) and presence of CAC (score, >0 Agatston units at year 15 or 20), CAC progression (incident CAC at year 20 or increase in CAC score by ≥20 Agatston units), or high carotid intima-media thickness (>80th percentile, year 20). However, tea consumption displayed a nonsignificant trend for an inverse association with CAC (P=0.08 for trend) and an inverse association with CAC progression (P=0.04 for trend) but no association with high carotid intima-media thickness (P>0.20 for trend). Stratification of the coffee analyses by sex, race, or smoking yielded similar nonsignificant patterns. We observed no substantial association between coffee or caffeine intake and coronary and carotid atherosclerosis. However, our results suggested an inverse association between tea and CAC but not carotid atherosclerosis.


Robust label-free biosensing using microdisk laser arrays with on-chip references.
Whispering-gallery mode (WGM) microdisk lasers show great potential for highly sensitive label-free detection in large-scale sensor arrays. However, when used in practical applications under normal ambient conditions, these devices suffer from temperature fluctuations and photobleaching. Here we demonstrate that these challenges can be overcome by a novel referencing scheme that allows for simultaneous compensation of temperature drift and photobleaching. The technique relies on reference structures protected by locally dispensed passivation materials, and can be scaled to extended arrays of hundreds of devices. We prove the viability of the concept in a series of experiments, demonstrating robust and sensitive label-free detection over a wide range of constant or continuously varying temperatures. To the best of our knowledge, these measurements represent the first demonstration of biosensing in active WGM devices with simultaneous compensation of both photobleaching and temperature drift.


Screening value of the Center for epidemiologic studies - depression scale among people living with HIV/AIDS in Ho Chi Minh City, Vietnam: a validation study.
Depression is believed to be under-diagnosed and under-treated in people living with HIV/AIDS (PLHIV). Early screening and referral to mental health services for treatment has been shown to enhance HIV patients' health during the course of HIV treatment. A lack of psychiatric specialist services for PLHIV at outpatient clinics (OPC) in Vietnam leads to insufficient identification of depression. However, alternative approaches are available such as the use of screening scales. This study investigated the psychometric properties of the Center for Epidemiologic Studies - Depression scale (CES-D) in Vietnamese HIV positive outpatients. A cross-sectional survey of 400 HIV positive outpatients was conducted in Ho Chi Minh City, Vietnam. Participants completed a self-reported questionnaire that included the CES-D. Participants were also interviewed independently by a psychiatrist who assessed for symptoms of major depressive disorder. CES-D reliability was measured by Cronbach's alpha. Criterion validity was evaluated by ROC analysis, Kappa index and the percentage of agreement between the CES-D and psychiatrists' interview. Construct validity was investigated by confirmatory factor analysis. The reliability for the whole scale was good (Cronbach α = 0.81). The four sub-scales of the CES-D had lower levels of internal consistency with Cronbach alpha of 0.71, 0.73, 0.71 and 0.58 for somatic complaints, depressive affect, positive affect and interpersonal problems respectively. CES-D has adequate construct validity with CFI = 0.926, IFI = 0.927, GFI = 0.930 and RMSEA = 0.045 (90% CI = 0.037-0.053) in the final four-factor model. Area under curve was 0.88 indicating good criterion validity. At the cutoff of 16, the sensitivity and specificity were 79.8% and 83.0% respectively while the percentage of agreement between the CES-D and psychiatrists' interview was 82.0% with Kappa index at 0.60. The CES-D was shown to be acceptable, reliable and valid for screening symptoms of depression in Vietnamese HIV outpatient clinic settings where mental health specialists are not always available. Routine use of the CES-D at HIV outpatient clinics, in combination with the availability of free-for-all national mental health services, is likely to be beneficial in improving the lives of PLHIV in Vietnam who have depression.


Molecular mechanisms of recombination restriction in the envelope gene of the human immunodeficiency virus.
The ability of pathogens to escape the host's immune response is crucial for the establishment of persistent infections and can influence virulence. Recombination has been observed to contribute to this process by generating novel genetic variants. Although distinctive recombination patterns have been described in many viral pathogens, little is known about the influence of biases in the recombination process itself relative to selective forces acting on newly formed recombinants. Understanding these influences is important for determining how recombination contributes to pathogen genome and proteome evolution. Most previous research on recombination-driven protein evolution has focused on relatively simple proteins, usually in the context of directed evolution experiments. Here, we study recombination in the envelope gene of HIV-1 between primary isolates belonging to subtypes that recombine naturally in the HIV/AIDS pandemic. By characterizing the early steps in the generation of recombinants, we provide novel insights into the evolutionary forces that shape recombination patterns within viral populations. Specifically, we show that the combined effects of mechanistic processes that determine the locations of recombination breakpoints across the HIV-1 envelope gene, and purifying selection acting against dysfunctional recombinants, can explain almost the entire distribution of breakpoints found within this gene in nature. These constraints account for the surprising paucity of recombination breakpoints found in infected individuals within this highly variable gene. Thus, the apparent randomness of HIV evolution via recombination may in fact be relatively more predictable than anticipated. In addition, the dominance of purifying selection in localized areas of the HIV genome defines regions where functional constraints on recombinants appear particularly strong, pointing to vulnerable aspects of HIV biology.


Predicting accident frequency at their severity levels and its application in site ranking using a two-stage mixed multivariate model.
Accident prediction models (APMs) have been extensively used in site ranking with the objective of identifying accident hotspots. Previously this has been achieved by using a univariate count data or a multivariate count data model (e.g. multivariate Poisson-lognormal) for modelling the number of accidents at different severity levels simultaneously. This paper proposes an alternative method to estimate accident frequency at different severity levels, namely the two-stage mixed multivariate model which combines both accident frequency and severity models. The accident, traffic and road characteristics data from the M25 motorway and surrounding major roads in England have been collected to demonstrate the use of the two-stage model. A Bayesian spatial model and a mixed logit model have been employed at each stage for accident frequency and severity analysis respectively, and the results combined to produce estimation of the number of accidents at different severity levels. Based on the results from the two-stage model, the accident hotspots on the M25 and surround have been identified. The ranking result using the two-stage model has also been compared with other ranking methods, such as the naïve ranking method, multivariate Poisson-lognormal and fixed proportion method. Compared to the traditional frequency based analysis, the two-stage model has the advantage in that it utilises more detailed individual accident level data and is able to predict low frequency accidents (such as fatal accidents). Therefore, the two-stage mixed multivariate model is a promising tool in predicting accident frequency according to their severity levels and site ranking.


CD28 costimulation prevents cell death during primary T cell activation.
CD28 has been demonstrated to play an important role in augmenting T cell proliferation and effector function. Costimulation through CD28 has also been reported to enhance human T cell survival. in this report, we have further investigated the role of CD28 in regulating T cell survival by comparing the survival characteristics of T cells from wild-type and CD28-deficient mice. CD28 costimulation of anti-CD3-activated cells augmented the viability of T cells from wild-type but not from CD28-deficient mice. CTLA4Ig treatment reduced wild-type T cell viability to a level comparable with CD28-deficient T cells. The ability of CD28 to enhance survival during T cell activation correlated positively with its ability to up-regulate the protein product of the cell survival gene bcl-xL. No differences in the expression of either Bcl-2 or Fas were observed between wild-type and CD28-deficient T cells. The CD28-dependent enhancement of cell survival during in vitro activation was found to be independent of Fas expression, as CD28 costimulation enhanced T cell survival to comparable levels in both wild-type and lpr animals. Cell death in CD28-deficient animals and in wild-type animals treated with CTLA4Ig displayed the morphologic characteristics of apoptosis. Additionally, inhibitors of ICE proteases could reverse cell death induced by TCR engagement in the absence of CD28 costimulation. Thus, CD28 costimulation not only enhances the proliferative expansion of cells activated through the TCR but also increases the likelihood that individual cells survive during T cell activation.


Methods used to address fidelity of receipt in health intervention research: a citation analysis and systematic review.
The American Behaviour Change Consortium (BCC) framework acknowledges patients as active participants and supports the need to investigate the fidelity with which they receive interventions, i.e. receipt. According to this framework, addressing receipt consists in using strategies to assess or enhance participants' understanding and/or performance of intervention skills. This systematic review aims to establish the frequency with which receipt is addressed as defined in the BCC framework in health research, and to describe the methods used in papers informed by the BCC framework and in the wider literature. A forward citation search on papers presenting the BCC framework was performed to determine the frequency with which receipt as defined in this framework was addressed. A second electronic database search, including search terms pertaining to fidelity, receipt, health and process evaluations was performed to identify papers reporting on receipt in the wider literature and irrespective of the framework used. These results were combined with forward citation search results to review methods to assess receipt. Eligibility criteria and data extraction forms were developed and applied to papers. Results are described in a narrative synthesis. 19.6% of 33 studies identified from the forward citation search to report on fidelity were found to address receipt. In 60.6% of these, receipt was assessed in relation to understanding and in 42.4% in relation to performance of skill. Strategies to enhance these were present in 12.1% and 21.1% of studies, respectively. Fifty-five studies were included in the review of the wider literature. Several frameworks and operationalisations of receipt were reported, but the latter were not always consistent with the guiding framework. Receipt was most frequently operationalised in relation to intervention content (16.4%), satisfaction (14.5%), engagement (14.5%), and attendance (14.5%). The majority of studies (90.0%) included subjective assessments of receipt. These relied on quantitative (76.0%) rather than qualitative (42.0%) methods and studies collected data on intervention recipients (50.0%), intervention deliverers (28.0%), or both (22.0%). Few studies (26.0%) reported on the reliability or validity of methods used. Receipt is infrequently addressed in health research and improvements to methods of assessment and reporting are required.


Exploring educational disparities in risk of preterm delivery: a comparative study of 12 European birth cohorts.
An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data. The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22-36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs). Singleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts. Educational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences.


SERPINB3-MYC axis induces the basal-like/squamous subtype and enhances disease progression in pancreatic cancer.
Pancreatic ductal adenocarcinoma (PDAC) exhibits distinct molecular subtypes: classical/progenitor and basal-like/squamous. Our study aimed to identify genes contributing to the development of the basal-like/squamous subtype, known for its aggressiveness. Transcriptome analyses revealed consistent upregulation of SERPINB3 in basal-like/squamous PDAC, correlating with reduced patient survival. SERPINB3 transgene expression in PDAC cells enhanced in vitro invasion and promoted lung metastasis in a mouse PDAC xenograft model. Metabolome analyses unveiled a metabolic signature linked to both SERPINB3 and the basal-like/squamous subtype, characterized by heightened carnitine/acylcarnitine and amino acid metabolism, associated with poor prognosis in patients with PDAC and elevated cellular invasiveness. Further analysis uncovered that SERPINB3 inhibited the cysteine protease calpain, a key enzyme in the MYC degradation pathway, and drove basal-like/squamous subtype and associated metabolic reprogramming through MYC activation. Our findings indicate that the SERPINB3-MYC axis induces the basal-like/squamous subtype, proposing SERPINB3 as a potential diagnostic and therapeutic target for this variant.


Localization of the cellular-fibronectin-specific epitope recognized by the monoclonal antibody IST-9 using fusion proteins expressed in E. coli.
Here we report on a monoclonal antibody (IST-9) which distinguishes between human cellular and plasma fibronectin. Using beta-galactosidase-fibronectin fusion proteins expressed in E. coli we have demonstrated that this monoclonal antibody is specific for a fibronectin segment (ED) which can be included or omitted from the molecule depending on the pattern of splicing of the mRNA precursors. Furthermore, using the same fusion proteins we have been able to localize precisely the epitopes of two other monoclonal antibodies (IST-1 and IST-2), specific for the heparin-binding domain 5 of fibronectin.


Age-related changes in cortical blood flow activation during visual processing of faces and location.
We examined age-related changes in object and spatial visual processing in two separate experiments. Regional cerebral blood flow (rCBF) was measured in young and old subjects with positron emission tomography and H2(15)O during tests of face matching, location matching, and a control task. The task demands in the two experiments were identical, but the stimuli in Experiment II were constructed to equalize stimulus complexity across all three tasks. The old subjects performed more slowly than the young subjects in both experiments, and showed significantly slower reaction times during location matching compared to face matching in Experiment II. Both young and old subjects showed occipitotemporal rCBF activation during face matching and occipitoparietal activation during location matching when these conditions were compared to the control task. However, in both experiments and in both tasks, young subjects showed greater activation of prestriate cortex (Brodmann's area 18), and old subjects had larger rCBF increases in occipitotemporal cortex (area 37). Areas in prefrontal cortex, as well as in inferior and medial parietal cortex, were more activated in the old subjects during location matching in both experiments. These results demonstrate that reliable age-related changes during visual processing can be found in rCBF patterns, suggesting more efficient use of occipital visual areas by younger subjects and more reliance by older subjects on one or more cortical networks, particularly for spatial vision, perhaps to compensate for reduced processing efficiency of occipital cortex. Both the differentially increased reaction times and the more widespread prefrontal activation in the old subjects during location matching suggest that spatial vision may be affected to a greater degree by aging than is object vision.


Geographic distribution and adaptive significance of genomic structural variants: an anthropological genetics perspective.
Anthropological geneticists have successfully used single-nucleotide and short tandem repeat variations across human genomes to reconstruct human history. These markers have also been used extensively to identify adaptive and phenotypic variation. The recent advent of high-throughput genomic technologies revealed an overlooked type of genomic variation: structural variants (SVs). In fact, some SVs may contribute to human adaptation in substantial and previously unexplored ways. SVs include deletions, insertions, duplications, inversions, and translocations of genomic segments that vary among individuals from the same species. SVs are much less numerous than single-nucleotide variants but account for at least seven times more variable base pairs than do single-nucleotide variants when two human genomes are compared. Moreover, recent studies have shown that SVs have higher mutation rates than single-nucleotide variants when the affected base pairs are considered, especially in certain parts of the genome. The null hypothesis for the evolution of SVs, as for single-nucleotide variants, is neutrality. Hence, drift is the primary force that shapes the current allelic distribution of most SVs. However, due to their size, a larger proportion of SVs appear to evolve under nonneutral forces (mostly purifying selection) than do single-nucleotide variants. In fact, as exemplified by several groundbreaking studies, SVs contribute to anthropologically relevant phenotypic variation and local adaptation among humans. In this review, we argue that with the advent of affordable genomic technologies, anthropological scrutiny of genomic structural variation emerges as a fertile area of inquiry to better understand human phenotypic variation. To motivate potential studies, we discuss scenarios through which structural variants (SVs) affect phenotypic variation among humans within an anthropological context. We further provide a methodological workflow in which we analyzed 1000 Genomes deletion variants and identified 16 exonic deletions that are specific to the African continent. We analyzed two of these deletion variants affecting the keratin-associated protein (KAP) cluster in a locus-specific manner. Our analysis revealed that these deletions may indeed affect phenotype and likely evolved under geography-specific positive selection. We outline all the major software and data sets for these analyses and provide the basic R and Perl codes we used for this example workflow analysis. Overall, we hope that this review will encourage and facilitate incorporation of genomic structural variation in anthropological research programs.


Spillover effects of HIV testing policies: changes in HIV testing guidelines and HCV testing practices in drug treatment programs in the United States.
To examine the extent to which state adoption of the Centers for Disease Control and Prevention (CDC) 2006 revisions to adult and adolescent HIV testing guidelines is associated with availability of other important prevention and medical services. We hypothesized that in states where the pretest counseling requirement for HIV testing was dropped from state legislation, substance use disorder treatment programs would have higher availability of HCV testing services than in states that had maintained this requirement. We analyzed a nationally representative sample of 383 opioid treatment programs from the 2005 and 2011 National Drug Abuse Treatment System Survey (NDATSS). Data were collected from program directors and clinical supervisors through telephone surveys. Multivariate logistic regression models were used to measure associations between state adoption of CDC recommended guidelines for HIV pretest counseling and availability of HCV testing services. The effects of HIV testing legislative changes on HCV testing practices varied by type of opioid treatment program. In states that had removed the requirement for HIV pretest counseling, buprenorphine-only programs were more likely to offer HCV testing to their patients. The positive spillover effect of HIV pretest counseling policies, however, did not extend to methadone programs and did not translate into increased availability of on-site HCV testing in either program type. Our findings highlight potential positive spillover effects of HIV testing policies on HCV testing practices. They also suggest that maximizing the benefits of HIV policies may require other initiatives, including resources and programmatic efforts that support systematic integration with other services and effective implementation.


Effectiveness of a novel mobile health education intervention (Peek) on spectacle wear among children in India: study protocol for a randomized controlled trial.
Uncorrected refractive errors are the commonest cause of visual loss in children despite spectacle correction being highly cost-effective. Many affected children do not benefit from correction as a high proportion do not wear their spectacles. Reasons for non-wear include parental attitudes, overprescribing and children being teased/bullied. Most school programmes do not provide health education for affected children, their peers, teachers or parents. The Portable Eye Examination Kit (Peek) will be used in this study. Peek has applications for measuring visual acuity with software for data entry and sending automated messages to inform providers and parents. Peek also has an application which simulates the visual blur of uncorrected refractive error (SightSim). The hypothesis is that higher proportion of children with uncorrected refractive errors in schools allocated to the Peek educational package will wear their spectacles 3-4 months after they are dispensed, and a higher proportion of children identified with other eye conditions will access services, compared with schools receiving standard school screening. Cluster randomized, double-masked trial of children with and without uncorrected refractive errors or other eye conditions. Government schools in Hyderabad, India will be allocated to intervention (Peek) or comparator (standard programme) arms before vision screening. In the intervention arm Peek will be used for vision screening, SightSim images will be used in classroom teaching and will be taken home by children, and voice messages will be sent to parents of children requiring spectacles or referral. In both arms the same criteria for recruitment, prescribing and dispensing spectacles will be used. After 3-4 months children dispensed spectacles will be followed up to assess spectacle wear, and uptake of referrals will be ascertained. The cost of developing and delivering the Peek package will be assessed. The cost per child wearing their spectacles or accessing services will be compared. Educating parents, teachers and children about refractive errors and the importance of wearing spectacles has the potential to increase spectacle wear amongst children. Innovative, potentially scalable mobile technology (Peek) will be used to screen, provide health education, track spectacle wear and adherence to follow-up amongst children referred. Controlled-Trials.com, ISRCTN78134921 . Registered on 29 June 2016.


Is the theory of collectivity of drinking cultures valid across educational groups?
To explore whether Skog's theory of collectivity of drinking cultures is valid across groups with different socioeconomic position (SEP). Individual-level information on alcohol consumption and SEP for the years 2004-2014 were retrieved from the Monitoring Project; a nationally representative monthly alcohol use survey. The analytical sample consisted of 162 369 respondents aged 25-79 years. SEP was measured by education level. Alcohol use was measured by yearly volume of consumption and frequency of heavy episodic drinking (HED). Respondents were divided into six SEP-groups based on their education level and sex. Mean yearly volume consumption and prevalence of monthly HED was calculated for each group and graphically plotted against the overall mean volume of consumption. The yearly changes in overall mean consumption during the study period reflected a collective shift in drinking across groups with basic, intermediate and high education. There were also indications that changes in overall mean consumption reflected collective shifts in the prevalence of HED across the SEP-groups. Moreover, while the magnitude of the associations for both average volume and HED differed somewhat in strength across the SEP-groups, they were clearly in the same, positive, direction. Our findings add support for including a socioeconomic dimension to Skog's theory of collectivity of drinking cultures. Future studies should replicate our analyses on cases and periods with more tangible changes in the price and availability of alcohol.


Integrating copy number polymorphisms into array CGH analysis using a robust HMM.
Array comparative genomic hybridization (aCGH) is a pervasive technique used to identify chromosomal aberrations in human diseases, including cancer. Aberrations are defined as regions of increased or decreased DNA copy number, relative to a normal sample. Accurately identifying the locations of these aberrations has many important medical applications. Unfortunately, the observed copy number changes are often corrupted by various sources of noise, making the boundaries hard to detect. One popular current technique uses hidden Markov models (HMMs) to divide the signal into regions of constant copy number called segments; a subsequent classification phase labels each segment as a gain, a loss or neutral. Unfortunately, standard HMMs are sensitive to outliers, causing over-segmentation, where segments erroneously span very short regions. We propose a simple modification that makes the HMM robust to such outliers. More importantly, this modification allows us to exploit prior knowledge about the likely location of "outliers", which are often due to copy number polymorphisms (CNPs). By "explaining away" these outliers with prior knowledge about the locations of CNPs, we can focus attention on the more clinically relevant aberrated regions. We show significant improvements over the current state of the art technique (DNAcopy with MergeLevels) on previously published data from mantle cell lymphoma cell lines, and on published benchmark synthetic data augmented with outliers. Source code written in Matlab is available from http://www.cs.ubc.ca/~sshah/acgh.


Minimal incision surgery as a risk factor for early failure of total hip arthroplasty.
Minimal incision total hip arthroplasty (MI THA) techniques were developed to decrease postoperative pain and recovery time. Although these techniques have increased in popularity, the long-term survivorship of these procedures is unknown. We therefore investigated whether the time to revision in our referral practice was shorter for patients who underwent primary MI THA compared to primary traditional THA. We retrospectively reviewed 46 revision THAs performed during a 3-year period. We excluded revisions performed for infection and rerevisions. Patients with incisions less than or equal to 10 cm were defined as having had MI THA. Fifteen of the 46 patients (33%) had undergone primary MI THA. At the time of primary index THA, the mean ages of the MI and non-MI patients were 65 years and 55 years, respectively. The mean time to revision was 1.4 years for the MI patients compared with 14.7 years for the non-MI patients. Twelve of the 15 patients having MI THA required revision within 2 years of primary THA compared to 4 of the 31 patients without MI surgery (OR = 26.5, 95% CI 4.4-160.0). There were no differences between the groups with regard to age, gender, or body mass index. The most common reasons for revision in the MI THA group were intraoperative fracture and failure of femoral component osseointegration. Our data suggest MI THA may be a risk factor for early revision surgery and the long-term survival therefore may be lower than that for non-MI surgery. Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Kv Channel S1-S2 Linker Working as a Binding Site of Human β-Defensin 2 for Channel Activation Modulation.
Among the three extracellular domains of the tetrameric voltage-gated K(+) (Kv) channels consisting of six membrane-spanning helical segments named S1-S6, the functional role of the S1-S2 linker still remains unclear because of the lack of a peptide ligand. In this study, the Kv1.3 channel S1-S2 linker was reported as a novel receptor site for human β-defensin 2 (hBD2). hBD2 shifts the conductance-voltage relationship curve of the human Kv1.3 channel in a positive direction by nearly 10.5 mV and increases the activation time constant for the channel. Unlike classical gating modifiers of toxin peptides from animal venoms, which generally bind to the Kv channel S3-S4 linker, hBD2 only targets residues in both the N and C termini of the S1-S2 linker to influence channel gating and inhibit channel currents. The increment and decrement of the basic residue number in a positively charged S4 sensor of Kv1.3 channel yields conductance-voltage relationship curves in the positive direction by ∼31.2 mV and 2-4 mV, which suggests that positively charged hBD2 is anchored in the channel S1-S2 linker and is modulating channel activation through electrostatic repulsion with an adjacent S4 helix. Together, these findings reveal a novel peptide ligand that binds with the Kv channel S1-S2 linker to modulate channel activation. These findings also highlight the functional importance of the Kv channel S1-S2 linker in ligand recognition and modification of channel activation.


Stretch-induced complexation reaction between poly(vinyl alcohol) and iodine: an in situ synchrotron radiation small- and wide-angle X-ray scattering study.
Fibrillation and the complexation reaction between poly(vinyl alcohol) (PVA)-iodine (i) complexes have been studied with in situ synchrotron radiation small- and wide-angle X-ray scattering (SAXS and WAXS) during the uniaxial stretching of PVA films in KI/I2 aqueous solution. SAXS results show that stretching induces the formation of nanofibrils, which pack periodically in the later stage of stretching with an average inter-fibrillar distance of around 10 nm. The onset strains for fibrillation and the appearance of periodicity of nanofibrils are located at the beginning and the end of the stress plateau, and decrease with increasing iodine concentration. In the stretching process as a whole, the presence of iodine ions reduces the crystallinity of the PVA crystal but favors the formation of a PVA-I complex. The complexation reaction is promoted by the synergistic effect of stretch and iodine ions, during which stretching drives the formation of polyiodine via the effect of entropic reduction while iodine concentration dictates crystallization of PVA-I3- co-crystals through the role of chemical potential. A morphological and structural phase diagram is constructed in the strain-iodine concentration space, which defines the regions for fibrillation and complexation reactions and may serve as a roadmap for the industrial processing of PVA polarizer.


Rapid and robust enzymatic sensing and quantitation of 3,6-Anhydro-L-galactose in a heterogeneous sugar mixture.
3,6-Anhydro-L-galactose (L-AHG) is a rare sugar found in agar polysaccharides. L-AHG has been used as a bioactive compound over the past few years. While the chromatographic or mass-spectrometric quantitation of L-AHG is quite sensitive and accurate, these methods require a reference standard and an intensive sample preparation procedure. We developed an enzymatic assay for rapid and robust quantitation of L-AHG using anhydrogalactose dehydrogenase cloned from Vibrio sp. EJY3 (VejAHGD). VejAHGD is a NADP+ - dependent enzyme which catalyzes the oxidation of L-AHG with a stoichiometric ratio of 1:1. Kinetic characterization of the enzyme showed a Km value of 0.19 ± 0.01 mM. The activity of the enzyme was optimum at 20 °C and pH 8.0. The half-life of enzymatic activity was 12 h under optimum condition. VejAHGD was highly specific to L-AHG, such that the reaction was not interfered by a variety of mono- or oligo-sugars in a heterogeneous mixture. Except transition metal ions, other cations or chelating agents did not affect the activity of the enzyme. Detection limit of the assay was 0.2 mM at 340 nm in the spectrophotometry. The assay was so rapid to give the result less than 5 min, requiring neither separation nor pretreatment of samples. We suggest application of the assay for detection and quantitation of L-AHG in commercial products and biosensor development.


Ultrafast optical manipulation of atomic arrangements in chalcogenide alloy memory materials.
A class of chalcogenide alloy materials that shows significant changes in optical properties upon an amorphous-to-crystalline phase transition has lead to development of large data capacities in modern optical data storage. Among chalcogenide phase-change materials, Ge2Sb2Te5 (GST) is most widely used because of its reliability. We use a pair of femtosecond light pulses to demonstrate the ultrafast optical manipulation of atomic arrangements from tetrahedral (amorphous) to octahedral (crystalline) Ge-coordination in GST superlattices. Depending on the parameters of the second pump-pulse, ultrafast nonthermal phase-change occurred within only few-cycles (≈1 picosecond) of the coherent motion corresponding to a GeTe4 local vibration. Using the ultrafast switch in chalcogenide alloy memory could lead to a major paradigm shift in memory devices beyond the current generation of silicon-based flash-memory.


The effect of free chlorine on Burkholderia pseudomallei in potable water.
Chlorine is widely used in public water supplies to provide a disinfection barrier. The effect of chlorine disinfection on the water-borne pathogen Burkholderia pseudomallei was assessed using multiple techniques. After exposure to chlorine viable bacteria were undetectable by conventional plate count techniques; however, persistence of B. pseudomallei was verified by flow cytometry and bacteria were recoverable following a simple one-step broth procedure. The minimum residual chlorine concentration and contact time as prescribed by potable water providers in Australia was insufficient to reduce a B. pseudomallei population by more than 2 log(10). Chlorine had a bacteriostatic effect only on B. pseudomallei; viable bacteria were recovered from water containing up to 1000 ppm free chlorine. This finding has practical implications for water treatment in regions where B. pseudomallei is endemic. Future work to assess the effect of alternative water disinfection processes either singly or in sequence is necessary.


The dynamics of smallholder farmers' acquisition and distribution of sweetpotato vines in the Lake Victoria Zone Region, Tanzania.
This paper offers new insights into smallholder farmer's practices regarding acquisition and distribution of sweetpotato planting material in the Mwanza and Mara regions of Tanzania by examining three specific issues: (i) farmers' sources of planting material; (ii) factors that influence farmers' sourcing of planting materials outside their own farms and (iii) the types of transactions and social relations involved in farmers' acquisition and distribution of sweetpotato planting material. Data were collected using mixed methods, including a survey of 621 households across nine districts, semi-structured key informant interviews with 28 women sweetpotato farmers, and six focus group discussions. Findings show that farmers in the study area rely almost exclusively on informal seed systems, and that the majority (> 56%) produce their own planting material. Individual, household and community level factors influence farmers' acquisition of planting materials outside their own farms. The sources and mode of transaction related to acquisition/distribution of planting material are strongly influenced by the type of social relationship between the parties involved. Strong social ties facilitate the majority of local planting material acquisitions/distributions, and favor provision of locally available planting material as a gift/without payment.Weak social ties are primarily associated with the transaction modality of purchase/sale, and frequently help facilitate acquisition of new or exotic planting material. The findings provide entry points both for entities that seek to enhance small-scale farmers' access to improved, high quality sweetpotato germplasm, as well as broader efforts to strengthen research and development strategies for integrating formal and informal seed systems.


Allogeneic hematopoietic stem cells from sources other than bone marrow: biological and technical aspects.
Identification and characterization of hematopoietic stem cells in peripheral blood (PB) and cord blood (CB) have suggested feasible alternatives to conventional allogeneic bone marrow (BM) transplantation. The growing interest in this use of allogeneic stem cells has prompted the Working Group on CD34-positive Hematopoietic Cells to review this subject by analyzing its biological and technical aspects. The method used for preparing this review was informal consensus development. Members of the Working Group met three times, and the participants at these meetings examined a list of problems previously prepared by the chairman. They discussed the individual points in order to reach an agreement on the various concepts, and eventually approved the final manuscript. Some of the authors of the present review have been working in the field of hematopoietic stem cell biology and processing, and have contributed original papers published in peer-reviewed journals. In addition, the material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. Several studies have now shown that hematopoietic stem cells collected from peripheral blood after the administration of G-CSF, or from cord blood upon delivery, are capable of supporting rapid and complete reconstitution of BM function in allogeneic recipients. Perhaps more importantly, reinfusion of large numbers of HLA-matched T-cells from PB collections or T-cells with various degrees of HLA disparity from CB did not result in a higher incidence or greater severity of acute graft-versus-host disease than expected with BM. Based on the data reviewed, operative guidelines for mobilization, collection and graft processing are provided. It should be remembered that despite the growing interest, these procedures must be still considered as advanced clinical research and should be included in formal clinical trials aimed at demonstrating their definitive role in stem cell transplantation. In this regard, a large European randomized study is currently comparing PB and BM allografts. However, the possibility of collecting large quantities of hematopoietic progenitor-stem cells, perhaps with reduced allo-reactivity, offers an exciting perspective for widening the number of potential stem cell donors and greater leeway for graft manipulation than is possible with BM.


Muscle metaboreceptors modulate postexercise sweating, but not cutaneous blood flow, independent of baroreceptor loading status.
We examined whether sustained changes in baroreceptor loading status during prolonged postexercise recovery can alter the metaboreceptors' influence on heat loss. Thirteen young males performed a 1-min isometric handgrip exercise (IHG) at 60% maximal voluntary contraction followed by 2 min of forearm ischemia (to activate metaboreceptors) before and 15, 30, 45, and 60 min after a 15-min intense treadmill running exercise (>90% maximal heart rate) in the heat (35°C). This was repeated on three separate days with continuous lower body positive (LBPP, +40 mmHg), negative (LBNP, -20 mmHg), or no pressure (Control) from 13- to 65-min postexercise. Sweat rate (ventilated capsule; forearm, chest, upper back) and cutaneous vascular conductance (CVC; forearm, upper back) were measured. Relative to pre-IHG levels, sweating at all sites increased during IHG and remained elevated during ischemia at baseline and similarly at 30, 45, and 60 min postexercise (site average sweat rate increase during ischemia: Control, 0.13 ± 0.02; LBPP, 0.12 ± 0.02; LBNP, 0.15 ± 0.02 mg·min(-1)·cm(-2); all P < 0.01), but not at 15 min (all P > 0.10). LBPP and LBNP did not modulate the pattern of sweating to IHG and ischemia (all P > 0.05). At 15-min postexercise, forearm CVC was reduced from pre-IHG levels during both IHG and ischemia under LBNP only (ischemia: 3.9 ± 0.8% CVCmax; P < 0.02). Therefore, we show metaboreceptors increase postexercise sweating in the middle to late stages of recovery (30-60 min), independent of baroreceptor loading status and similarly between skin sites. In contrast, metaboreflex modulation of forearm but not upper back CVC occurs only in the early stages of recovery (15 min) and is dependent upon baroreceptor unloading.


Dynamin-2 function and dysfunction along the secretory pathway.
Dynamin-2 is a ubiquitously expressed mechano-GTPase involved in different stages of the secretory pathway. Its most well-known function relates to the scission of nascent vesicles from the plasma membrane during endocytosis; however, it also participates in the formation of new vesicles from the Golgi network, vesicle trafficking, fusion processes and in the regulation of microtubule, and actin cytoskeleton dynamics. Over the last 8 years, more than 20 mutations in the dynamin-2 gene have been associated to two hereditary neuromuscular disorders: Charcot-Marie-Tooth neuropathy and centronuclear myopathy. Most of these mutations are grouped in the pleckstrin homology domain; however, there are no common mutations associated with both disorders, suggesting that they differently impact on dynamin-2 function in diverse tissues. In this review, we discuss the impact of these disease-related mutations on dynamin-2 function during vesicle trafficking and endocytotic processes.


The inter-relationship among economic activities, environmental degradation, material consumption and population health in low-income countries: a longitudinal ecological study.
The theory of ecological unequal exchange explains how trade and various forms of economic activity create the problem of environmental degradation, and lead to the deterioration of population health. Based on this theory, our study examined the inter-relationship among economic characteristics, ecological footprints, CO2 emissions, infant mortality rates and under-5 mortality rates in low-income countries. A longitudinal ecological study design. Sixty-six low-income countries from 1980 to 2010 were included in the analyses. Data for each country represented an average of 23 years (N=1497). Data were from the World Development Indicators, UN Commodity Trade Statistics Database, Global Footprint Network and Polity IV Project. Linear mixed models with a spatial power covariance structure and a correlation that decreased over time were constructed to accommodate the repeated measures. Statistical analyses were conducted separately by sub-Saharan Africa, Latin America and other regions. After controlling for country-level sociodemographic characteristics, debt and manufacturing, economic activities were positively associated with infant mortality rates and under-5 mortality rates in sub-Saharan Africa. By contrast, export intensity and foreign investment were beneficial for reducing infant and under-5 mortality rates in Latin America and other regions. Although the ecological footprints and CO2 emissions did not mediate the relationship between economic characteristics and health outcomes, export intensity increased CO2 emissions, but reduced the ecological footprints in sub-Saharan Africa. By contrast, in Asia, the Middle East and North Africa, although export intensity was positively associated with the ecological footprints and also CO2 emissions, the percentage of exports to high-income countries was negatively associated with the ecological footprints. This study suggested that environmental protection and economic development are important for reducing infant and under-5 mortality rates in low-income countries.


Spontaneous splenic artery aneurysm rupture: mimicking acute myocardial infarct.
Spontaneous splenic artery aneurysm (SAA) is a rare but a life-threatening condition. Thus, early diagnoses may increase the chance of survival. A 52-year-old female patient was admitted to the emergency department with a pain that starts from the chest and epigastric region and radiates to back and left arm. The patient prediagnosed as having acute myocardial infarct and was under observation when acute abdomen and hemorrhagic shock developed. After further investigation, the patient was diagnosed as having SAA and has undergone a successful surgery. The patient was fully cured and discharged from the hospital on the seventh postoperative day. The patient originally presented with SAA, although she was primarily observed in the emergency department with acute myocardial infarct diagnosis because of similar symptoms and clinical findings to cardiovascular diseases. When changes in the clinical picture occurred, the patient was reevaluated and had undergone an operation because of SAA rupture. Therefore, physicians should take into consideration of aneurysm rupture in the differential diagnosis of the cardiovascular conditions; otherwise, the patient may lose his/her life.