Health care transition: youth, family, and provider perspectives.
This study examined the process of health care transition (HCT) posing the following questions: What are the transition experiences of youths and young adults with disabilities and special health care needs, family members, and health care providers? What are promising practices that facilitate successful HCT? What are obstacles that inhibit HCT? A qualitative approach was used to investigate these questions. Focus group interviews were conducted. Content and narrative analyses of interview transcripts were completed using ATLAS.ti. Thirty-four focus groups and interviews were conducted with 143 young adults with disabilities and special health care needs, family members, and health care providers. Content analysis yielded 3 content domains: transition services, which presents a chronological understanding of the transition process; health care systems, which presents differences between pediatric and adult-oriented medicine and how these differences inhibit transition; and transition narratives, which discusses transition experience in the broader context of relationships between patients and health care providers. This study demonstrated the presence of important reciprocal relationships that are based on mutual trust between providers and families and are developed as part of the care of chronically ill children. Evidence supports the need for appropriate termination of pediatric relationships as part of the transition process. Evidence further supports the idea that pediatric and adult-oriented medicines represent 2 different medical subcultures. Young adults' and family members' lack of preparation for successful participation in the adult health care system contributes to problems with HCT.


Insulin's direct hepatic effect explains the inhibition of glucose production caused by insulin secretion.
Insulin can inhibit hepatic glucose production (HGP) by acting directly on the liver as well as indirectly through effects on adipose tissue, pancreas, and brain. While insulin's indirect effects are indisputable, their physiologic role in the suppression of HGP seen in response to increased insulin secretion is not clear. Likewise, the mechanisms by which insulin suppresses lipolysis and pancreatic α cell secretion under physiologic circumstances are also debated. In this study, insulin was infused into the hepatic portal vein to mimic increased insulin secretion, and insulin's indirect liver effects were blocked either individually or collectively. During physiologic hyperinsulinemia, plasma free fatty acid (FFA) and glucagon levels were clamped at basal values and brain insulin action was blocked, but insulin's direct effects on the liver were left intact. Insulin was equally effective at suppressing HGP when its indirect effects were absent as when they were present. In addition, the inhibition of lipolysis, as well as glucagon and insulin secretion, did not require CNS insulin action or decreased plasma FFA. This indicates that the rapid suppression of HGP is attributable to insulin's direct effect on the liver and that its indirect effects are redundant in the context of a physiologic increase in insulin secretion.


Serum cortisol concentrations in dogs with pituitary-dependent hyperadrenocorticism and atypical hyperadrenocorticism.
Atypical hyperadrenocorticism (AHAC) is considered when dogs have clinical signs of hypercortisolemia with normal hyperadrenocorticism screening tests. To compare cortisol concentrations and adrenal gland size among dogs with pituitary-dependent hyperadrenocorticism (PDH), atypical hyperadrenocorticism (AHAC), and healthy controls. Ten healthy dogs, 7 dogs with PDH, and 8 dogs with AHAC. Dogs were prospectively enrolled between November 2011 and January 2013. Dogs were diagnosed with PDH or AHAC based on clinical signs and positive screening test results (PDH) or abnormal extended adrenal hormone panel results (AHAC). Transverse adrenal gland measurements were obtained by abdominal ultrasound. Hourly mean cortisol (9 samplings), sum of hourly cortisol measurements and adrenal gland sizes were compared among the 3 groups. Hourly (control, 1.4 ± 0.6 μg/dL; AHAC, 2.9 ± 1.3; PDH, 4.3 ± 1.5) (mean, SD) and sum (control, 11.3 ± 3.3; AHAC, 23.2 ± 7.7; PDH, 34.7 ± 9.9) cortisol concentrations differed significantly between the controls and AHAC (P < .01) and PDH (P < .01) groups. Hourly (P < .01) but not sum (P = .27) cortisol concentrations differed between AHAC and PDH dogs. Average transverse adrenal gland diameter of control dogs (5.3 ± 1.2 mm) was significantly less than dogs with PDH (6.4 ± 1.4; P = .02) and AHAC (7.2 ± 1.5; P < .01); adrenal gland diameter did not differ (P = .18) between dogs with AHAC and PDH. Serum cortisol concentrations in dogs with AHAC were increased compared to controls but less than dogs with PDH, while adrenal gland diameter was similar between dogs with AHAC and PDH. These findings suggest cortisol excess could contribute to the pathophysiology of AHAC.


Morphological and nanostructural features of porous silicon prepared by electrochemical etching.
Porous layers were produced on a p-type (100) Si wafer by electrochemical anodic etching. The morphological, nanostructural and optical features of the porous Si were investigated as functions of the etching conditions. As the wafer resistivity was increased from 0.005 to 15 Ω·cm, the etched region exhibited 'sponge', 'mountain' and 'column'-type morphologies. Among them, the sponge-type structured sample showed the largest surface area per unit volume. Silicon nanocrystallites, 2.0 to 5.3 nm in size, were confirmed in the porous layers. The photoluminescence peaks varied in the wavelength range of 615 to 722 nm. These changes in the maximum peak position were related to the size distribution of the Si crystallites in the porous silicon. The doping levels of the wafers significantly affect the size distribution of the Si crystallites as well as the light-emitting behavior of the etched Si, which contains nanoscale Si crystallites.


Evolutionary dynamics of giant viruses and their virophages.
Giant viruses contain large genomes, encode many proteins atypical for viruses, replicate in large viral factories, and tend to infect protists. The giant virus replication factories can in turn be infected by so called virophages, which are smaller viruses that negatively impact giant virus replication. An example is Mimiviruses that infect the protist Acanthamoeba and that are themselves infected by the virophage Sputnik. This study examines the evolutionary dynamics of this system, using mathematical models. While the models suggest that the virophage population will evolve to increasing degrees of giant virus inhibition, it further suggests that this renders the virophage population prone to extinction due to dynamic instabilities over wide parameter ranges. Implications and conditions required to avoid extinction are discussed. Another interesting result is that virophage presence can fundamentally alter the evolutionary course of the giant virus. While the giant virus is predicted to evolve toward increasing its basic reproductive ratio in the absence of the virophage, the opposite is true in its presence. Therefore, virophages can not only benefit the host population directly by inhibiting the giant viruses but also indirectly by causing giant viruses to evolve toward weaker phenotypes. Experimental tests for this model are suggested.


Scaling up prevention of mother-to-child HIV transmission programs in sub-Saharan African countries: a multilevel assessment of site-, program- and country-level determinants of performance.
Uptake of prevention of mother-to-child HIV transmission (PMTCT) programs remains challenging in sub-Saharan Africa because of multiple barriers operating at the individual or health facility levels. Less is known regarding the influence of program-level and contextual determinants. In this study, we explored the multilevel factors associated with coverage in single-dose nevirapine PMTCT programs. We analyzed aggregate routine data collected within the framework of the Viramune(®) Donation Programme (VDP) from 269 sites in 20 PMTCT programs and 15 sub-Saharan countries from 2002 to 2005. Site performance was measured using a nevirapine coverage ratio (NCR), defined as the reported number of women receiving nevirapine divided by the number of women who should have received nevirapine (observed HIV prevalence x number of women in antenatal care [ANC]). Data on program-level determinants were drawn from the initial application forms, and country-level determinants from the Demographic and Health Surveys (DHS) and the World Bank (World Development Indicators). Multilevel linear mixed models were used to identify independent factors associated with NCR at the site-, program- and country-level. Of 283,410 pregnant women attending ANC in the included sites, 174,312 women (61.5%) underwent HIV testing after receiving pre-test counselling, of whom 26,700 tested HIV positive (15.3%), and 22,591 were dispensed NVP (84.6%). Site performance was highly heterogeneous between and within programs. Mean NCR by site was 43.8% (interquartile range: 19.1-63.9). Multilevel analysis identified higher HIV prevalence (Beta coefficient: 25.1, 95% confidence interval [CI] 18.7 to 31.6), higher proportion of persons with knowledge of PMTCT (8.3; CI 0.5 to 16.0), higher health expenditure as a proportion of Gross Domestic Product (3.9 per %; CI 2.0 to 5.8) and lower percentage of rural population (-0.7 per %; CI -1.0 to -0.5) as significant country-level predictors of higher NCR at the p<0.05 level. A medium ANC monthly activity (30-100/month) was the only site-level predictor found (-7.6; CI -15.1 to -0.1). Heterogeneity of nevirapine coverage between sites and programs was high. Multilevel analysis identified several significant contextual determinants, which may warrant additional research to further define important multi-level and potentially modifiable determinants of performance of PMTCT programs.


An Exemplar-Based Multi-View Domain Generalization Framework for Visual Recognition.
In this paper, we propose a new exemplar-based multi-view domain generalization (EMVDG) framework for visual recognition by learning robust classifier that are able to generalize well to arbitrary target domain based on the training samples with multiple types of features (i.e., multi-view features). In this framework, we aim to address two issues simultaneously. First, the distribution of training samples (i.e., the source domain) is often considerably different from that of testing samples (i.e., the target domain), so the performance of the classifiers learnt on the source domain may drop significantly on the target domain. Moreover, the testing data are often unseen during the training procedure. Second, when the training data are associated with multi-view features, the recognition performance can be further improved by exploiting the relation among multiple types of features. To address the first issue, considering that it has been shown that fusing multiple SVM classifiers can enhance the domain generalization ability, we build our EMVDG framework upon exemplar SVMs (ESVMs), in which a set of ESVM classifiers are learnt with each one trained based on one positive training sample and all the negative training samples. When the source domain contains multiple latent domains, the learnt ESVM classifiers are expected to be grouped into multiple clusters. To address the second issue, we propose two approaches under the EMVDG framework based on the consensus principle and the complementary principle, respectively. Specifically, we propose an EMVDG_CO method by adding a co-regularizer to enforce the cluster structures of ESVM classifiers on different views to be consistent based on the consensus principle. Inspired by multiple kernel learning, we also propose another EMVDG_MK method by fusing the ESVM classifiers from different views based on the complementary principle. In addition, we further extend our EMVDG framework to exemplar-based multi-view domain adaptation (EMVDA) framework when the unlabeled target domain data are available during the training procedure. The effectiveness of our EMVDG and EMVDA frameworks for visual recognition is clearly demonstrated by comprehensive experiments on three benchmark data sets.


Characteristics of hip fractures among hospitalized elder Mexican American Black and White Medicare beneficiaries in the Southwestern United States.
Hip fractures are a major cause of morbidity and mortality in the older adult population. The evidence of the incidence of morbidity and mortality in Mexican Americans compared to other ethnic groups is mixed. This study aims to examine characteristics and utilization patterns of older Mexican Americans compared to Whites and Blacks, hospitalized for hip fracture in the Southwestern United States. Retrospective analysis of the Medicare and Medicaid claims data for the southwestern states of California, Arizona, Colorado, New Mexico and Texas. All Medicare beneficiaries aged 65 and above, hospitalized for non-pathologic hip fractures, participated in the study. Mexican Americans were directly identified from the H-EPESE database. The primary outcome measures were length of stay, total charges and number of diagnoses. The total proportion of hospital encounters related to hip fractures within each ethnic group was 3.7% for Whites, 2.0% for Mexican Americans and 1.2% for Blacks. The mean patient age for the hip fracture was 82.5 years while the non-hip fractures encounters had a mean age of 76.6 years. A higher percentage of Mexican Americans who suffered fracture were female. Although length of stay for Mexican Americans was equivalent to Whites, comparative total charges for Mexican Americans were lower. Mexican Americans also have lower mean number of diagnoses at admission than the other groups (MA=5.5, B=6.2, W=5.9: p<0.001). Mexican American elders in the southwestern United States who are hospitalized for hip fractures are more likely to be female, relatively healthier, and have lower health care costs when compared to Whites and especially to Blacks in the same region.


Lano, a novel LAP protein directly connected to MAGUK proteins in epithelial cells.
Protein networks asymetrically distributed to basolateral and apical epithelial membranes maintain cell polarity and homeostasis of epithelial tissues. Genetic studies in non-vertebrates assigned two families of basolateral proteins, MAGUK (membrane-associated and guanylate kinase) and LAP (leucine-rich repeats and PDZ) proteins, to a common pathway crucial for the epithelial architecture and acting as a gatekeeper to malignancy. In mammals, three LAP proteins have been described, Densin-180, Erbin, and hScribble. Here, we identify a protein called Lano (LAP and no PDZ) only present in vertebrates and presenting strong identities with LAP proteins. Despite the lack of PDZ domain, Lano is located at the basolateral side of epithelial cells in a similar manner to Erbin and hScribble. Using in vitro and in vivo experiments, we demonstrate that Lano directly interacts with the PDZ domains of MAGUK proteins, including hDLG (human disc large), in epithelial cells. A second pool of Lano is complexed to Erbin. These LAP-MAGUK protein complexes coexist at the basolateral side of epithelial cells. We provide evidence for a direct interaction between LAP and MAGUK proteins, and we propose that various LAP-MAGUK networks targeted to the basolateral side of epithelial cells participate to homeostasis of epithelial tissues and tumor growth.


Quantum Hall effect in a bulk antiferromagnet EuMnBi2 with magnetically confined two-dimensional Dirac fermions.
For the innovation of spintronic technologies, Dirac materials, in which low-energy excitation is described as relativistic Dirac fermions, are one of the most promising systems because of the fascinating magnetotransport associated with extremely high mobility. To incorporate Dirac fermions into spintronic applications, their quantum transport phenomena are desired to be manipulated to a large extent by magnetic order in a solid. We report a bulk half-integer quantum Hall effect in a layered antiferromagnet EuMnBi2, in which field-controllable Eu magnetic order significantly suppresses the interlayer coupling between the Bi layers with Dirac fermions. In addition to the high mobility of more than 10,000 cm(2)/V s, Landau level splittings presumably due to the lifting of spin and valley degeneracy are noticeable even in a bulk magnet. These results will pave a route to the engineering of magnetically functionalized Dirac materials.


Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides.
The goal was to examine the association between urinary concentrations of dialkyl phosphate metabolites of organophosphates and attention-deficit/hyperactivity disorder (ADHD) in children 8 to 15 years of age. Cross-sectional data from the National Health and Nutrition Examination Survey (2000-2004) were available for 1139 children, who were representative of the general US population. A structured interview with a parent was used to ascertain ADHD diagnostic status, on the basis of slightly modified criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. One hundred nineteen children met the diagnostic criteria for ADHD. Children with higher urinary dialkyl phosphate concentrations, especially dimethyl alkylphosphate (DMAP) concentrations, were more likely to be diagnosed as having ADHD. A 10-fold increase in DMAP concentration was associated with an odds ratio of 1.55 (95% confidence interval: 1.14-2.10), with adjustment for gender, age, race/ethnicity, poverty/income ratio, fasting duration, and urinary creatinine concentration. For the most-commonly detected DMAP metabolite, dimethyl thiophosphate, children with levels higher than the median of detectable concentrations had twice the odds of ADHD (adjusted odds ratio: 1.93 [95% confidence interval: 1.23-3.02]), compared with children with undetectable levels. These findings support the hypothesis that organophosphate exposure, at levels common among US children, may contribute to ADHD prevalence. Prospective studies are needed to establish whether this association is causal.


Altered urinary porphyrins and mercury exposure as biomarkers for autism severity in Egyptian children with autism spectrum disorder.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects social, communication, and behavioral development. Recent evidence supported but also questioned the hypothetical role of compounds containing mercury (Hg) as contributors to the development of ASD. Specific alterations in the urinary excretion of porphyrin-containing ring catabolites have been associated with exposure to Hg in ASD patients. In the present study, the level of urinary porphyrins, as biomarkers of Hg toxicity in children with ASD, was evaluated, and its correlation with severity of the autistic behavior further explored. A total of 100 children was enrolled in the present study. They were classified into three groups: children with ASD (40), healthy controls (40), and healthy siblings of the ASD children (20). Children with ASD were diagnosed using DSM-IV-TR, ADI-R, and CARS tests. Urinary porphyrins were evaluated within the three groups using high-performance liquid chromatography (HPLC), after plasma evaluation of mercury (Hg) and lead (Pb) in the same groups. Results showed that children with ASD had significantly higher levels of Hg, Pb, and the porphyrins pentacarboxyporphyrin, coproporphyrin, precoproporphyrin, uroporphyrins, and hexacarboxyporphyrin compared to healthy controls and healthy siblings of the ASD children. However, there was no significant statistical difference in the level of heptacarboxyporphyrin among the three groups, while a significant positive correlation between the levels of coproporphyrin and precoproporphyrin and autism severity was observed. Mothers of ASD children showed a higher percentage of dental amalgam restorations compared to the mothers of healthy controls suggesting that high Hg levels in children with ASD may relate to the increased exposure to Hg from maternal dental amalgam during pregnancy and lactation. The results showed that the ASD children in the present study had increased blood Hg and Pb levels compared with healthy control children indicating that disordered porphyrin metabolism might interfere with the pathology associated with the autistic neurologic phenotype. The present study indicates that coproporphyrin and precoproporhyrin may be utilized as possible biomarkers for heavy metal exposure and autism severity in children with ASD.


A meta-analysis of leukaemia risk from protracted exposure to low-dose gamma radiation.
More than 400,000 workers annually receive a measurable radiation dose and may be at increased risk of radiation-induced leukaemia. It is unclear whether leukaemia risk is elevated with protracted, low-dose exposure. We conducted a meta-analysis examining the relationship between protracted low-dose ionising radiation exposure and leukaemia. Reviews by the National Academies and United Nations provided a summary of informative studies published before 2005. PubMed and Embase databases were searched for additional occupational and environmental studies published between 2005 and 2009. We selected 23 studies that: (1) examined the association between protracted exposures to ionising radiation and leukaemia excluding chronic lymphocytic subtype; (2) were a cohort or nested case-control design without major bias; (3) reported quantitative estimates of exposure; and (4) conducted exposure-response analyses using relative or excess RR per unit exposure. Studies were further screened to reduce information overlap. Random effects models were developed to summarise between-study variance and obtain an aggregate estimate of the excess RR at 100 mGy. Publication bias was assessed by trim and fill and Rosenthal's file drawer methods. We found an ERR at 100 mGy of 0.19 (95% CI 0.07 to 0.32) by modelling results from 10 studies and adjusting for publication bias. Between-study variance was not evident (p=0.99). Protracted exposure to low-dose gamma radiation is significantly associated with leukaemia. Our estimate agreed well with the leukaemia risk observed among exposed adults in the Life Span Study (LSS) of atomic bomb survivors, providing increased confidence in the current understanding of leukaemia risk from ionising radiation. However, unlike the estimates obtained from the LSS, our model provides a precise, quantitative summary of the direct estimates of excess risk from studies of protracted radiation exposures.


Stepwise observation and quantification and mixed matrix membrane separation of CO2 within a hydroxy-decorated porous host.
The identification of preferred binding domains within a host structure provides important insights into the function of materials. State-of-the-art reports mostly focus on crystallographic studies of empty and single component guest-loaded host structures to determine the location of guests. However, measurements of material properties (e.g., adsorption and breakthrough of substrates) are usually performed for a wide range of pressure (guest coverage) and/or using multi-component gas mixtures. Here we report the development of a multifunctional gas dosing system for use in X-ray powder diffraction studies on Beamline I11 at Diamond Light Source. This facility is fully automated and enables in situ crystallographic studies of host structures under (i) unlimited target gas loadings and (ii) loading of multi-component gas mixtures. A proof-of-concept study was conducted on a hydroxyl-decorated porous material MFM-300(VIII) under (i) five different CO2 pressures covering the isotherm range and (ii) the loading of equimolar mixtures of CO2/N2. The study has successfully captured the structural dynamics underpinning CO2 uptake as a function of surface coverage. Moreover, MFM-300(VIII) was incorporated in a mixed matrix membrane (MMM) with PIM-1 in order to evaluate the CO2/N2 separation potential of this material. Gas permeation measurements on the MMM show a great improvement over the bare PIM-1 polymer for CO2/N2 separation based on the ideal selectivity.


Health Literacy and Outcomes Among Patients With Heart Failure: A Systematic Review and Meta-Analysis.
The purpose of this study was to determine if health literacy is associated with mortality, hospitalizations, or emergency department (ED) visits among patients living with heart failure (HF). Growing evidence suggests an association between health literacy and health-related outcomes in patients with HF. We searched Embase, MEDLINE, PsycINFO, and EBSCO CINAHL from inception through January 1, 2019, with the help of a medical librarian. Eligible studies evaluated health literacy among patients with HF and assessed mortality, hospitalizations, and ED visits for all causes with no exclusion by time, geography, or language. Two reviewers independently selected studies, extracted data, and assessed the methodological quality of the identified studies. We included 15 studies, 11 with an overall high methodological quality. Among the observational studies, an average of 24% of patients had inadequate or marginal health literacy. Inadequate health literacy was associated with higher unadjusted risk for mortality (risk ratio [RR]: 1.67; 95% confidence interval [CI]: 1.18 to 2.36), hospitalizations (RR: 1.19; 95% CI: 1.09 to 1.29), and ED visits (RR: 1.17; 95% CI: 1.03 to 1.32). When the adjusted measurements were combined, inadequate health literacy remained statistically associated with mortality (RR: 1.41; 95% CI: 1.06 to 1.88) and hospitalizations (RR: 1.12; 95% CI: 1.01 to 1.25). Among the 4 interventional studies, 2 effectively improved outcomes among patients with inadequate health literacy. In this study, the estimated prevalence of inadequate health literacy was high, and inadequate health literacy was associated with increased risk of death and hospitalizations. These findings have important clinical and public health implications and warrant measurement of health literacy and deployment of interventions to improve outcomes.


Microvascular blood flow, volume, and velocity measured by laser Doppler techniques in IDDM.
A laser Doppler device with the capability to simultaneously measure skin blood flow, microvascular volume, and erythrocyte velocity was used to assess blood flow changes in 35 insulin-dependent diabetes mellitus (IDDM) subjects, mean age 33 +/- 1 yr, with average duration of diabetes 14 +/- 1 yr, and in a nondiabetic control group. Blood flow was determined at 35 and 44 degree C at several sites on the upper and lower extremities with a temperature-regulated probe. Blood flow was highest at both temperatures on the pulps of the index finger and the first toe, regions of high density of arteriovenous anastomoses. There was significantly greater blood flow at most locations for the nondiabetic than the diabetic group at 35 degree C, and the differences between the two groups were substantially larger at 44 degree C. At 44 degree C, blood flow in the control group was approximately 40% greater in the upper extremity and 50% greater in the lower extremity than it was in the diabetic subjects. The differences were attributed to decreases of both microvascular volume and velocity in the diabetic group. In the upper extremity, volumes in the diabetic patients were 10-15% lower and velocities 10-40% lower than in the nondiabetic subjects. In the lower extremity, volumes were 20-25% lower and velocities 40-50% lower. We conclude that laser Doppler techniques can be used to assess microvascular changes in the skin of diabetic patients. This approach may be useful to evaluate and model diabetic microangiopathy.


Placental barrier to coagulation factors: its relevance to the coagulation defect at birth and to haemorrhage in the newborn.
The placental barrier to coagulation factors was assessed by measuring their levels in maternal venous and neonatal umbilical arterial and venous blood and was found to be largely complete. Detailed coagulation assessments in a large number of term and premature neonates showed that term neonates had a mild coagulation deficiency at birth. Premature neonates had a more definite deficiency, which became more severe with increasing prematurity. Mortality in low birth weight premature infants was associated with a severe coagulation deficiency, and was frequently due to cerebral haemorrhage. It is suggested that the coagulation system of low birth weight infants should be assessed to enable prophylactic treatment of those with a severe deficiency.


The HIV care cascade: Japanese perspectives.
Japan has been known as a low HIV-prevalence country with a concentrated epidemic among high-risk groups. However, it has not been determined whether Japan meets the 90-90-90 goals set by the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO). Moreover, to date, the HIV care cascade has not been examined. We estimated the total number of diagnosed people living with HIV/AIDS (PLWHA) (n = 22,840) based on legal reports to the Ministry of Health, Labour and Welfare by subtracting the number of foreigners who left Japan (n = 2,273) and deaths (n = 2,321) from the cumulative diagnosis report (n = 27,434). The number of total undiagnosed PLWHA was estimated by age and sex specific HIV-positive rates observed among first-time blood donors between 2011-2015 in Japan. Our estimates show that 14.4% (n = 3,830) of all PLWHA (n = 26,670) were undiagnosed in Japan at the end of 2015. The number of patients retained in care (n = 20,615: 77.3% of PLWHA), the percentage of those on antiretroviral therapy (n = 18,921: 70.9% of PLWHA) and those with suppressed viral loads (<200 copies/mL; n = 18,756: 70.3% of PLWHA) were obtained through a questionnaire survey conducted in the AIDS Core Hospitals throughout the country. According to these estimates, Japan failed to achieve the first two of the three UNAIDS/WHO targets (22,840/26,670 = 85.6% of HIV-positive cases were diagnosed; 18,921/22,840 = 82.8% of those diagnosed were treated; 18,756/18,921 = 99.1% of those treated experienced viral suppression). Although the antiretroviral treatment uptake and success after retention in medical care appears to be excellent in Japan, there are unmet needs, mainly at the surveillance level before patients are retained in care. The promotion of HIV testing and treatment programs among the key affected populations (especially men who have sex with men) may contribute to further decreasing the HIV epidemic and achieving the UNAIDS/WHO targets in Japan.


Quality assurance initiative at one institution for minimally invasive breast biopsy as the initial diagnostic technique.
In 2005, the American College of Surgeons Consensus Conference issued a statement about the diagnostic workup of image-detected breast abnormalities. Guidelines include use of image-guided percutaneous needle biopsy as the gold standard for diagnosing image-detected breast abnormalities. In this study, we evaluate a method to audit use of excisional biopsy among different breast surgeons at our institution. From March to September 2007, 465 patients undergoing breast operation for benign or malignant lesions at our institution were interviewed by a surgical resident or physician's assistant. If an excisional biopsy was scheduled for initial diagnosis, the patient and surgeon were asked whose preference it was to perform the operation. Three attending groups were designated: academic breast surgeons, private practice breast surgeons on clinical faculty, and general surgeons who perform breast operations in addition to other procedures. Use of excisional biopsy was compared between these groups. Compliance for preoperative interview completion was 79%, differing substantially between surgeon groups with rates of 91%, 74%, and 58% for the academic breast, private practice, and general surgeons, respectively. Excisional biopsy for diagnosis made up 10%, 35%, and 37% of the case load for academic breast, private practice, and general surgeons, respectively. Patient and surgeon agreed 85% of the time for preference of performing diagnostic excisional biopsies. Excisional biopsies continue to be performed as the initial diagnostic procedure for 40% of patients. Tracking biopsy practices by surgeon can improve adherence with current recommendations.


Movement variability in the golf swing of male and female skilled golfers.
Despite the complexity of movement, the swings of skilled golfers are considered to be highly consistent. Interestingly, no direct investigation of movement variability or coupling variability during the swings of skilled golfers has occurred. To determine whether differences in movement variability exist between male and female skilled golfers during the downswing of the full golf swing. Three-dimensional thorax, pelvis, hand, and clubhead data were collected from 19 male (mean ± SD: age = 26 ± 7 yr) and 19 female (age = 25 ± 7 yr) skilled golfers. Variability of segmental movement and clubhead trajectory were examined at three phases of the downswing using discrete (SD) and continuous analyses (spanning set), whereas variability of intersegment coupling was examined using average coefficient of correspondence. Compared with males, females exhibited higher thorax and pelvis variability for axial rotation at the midpoint of the downswing and ball contact (BC). Similarly, thorax-pelvis coupling variability was higher for females than males at both the midpoint of the downswing and BC. Regardless of thorax and pelvis motion, the variability of hand and clubhead trajectory sequentially decreased from the top of the backswing to BC for both males and females. Male and female skilled golfers use different upper body movement strategies during the downswing while achieving similarly low levels of clubhead trajectory variability at BC. It is apparent that the priority of skilled golfers is to progressively minimize hand and clubhead trajectory variability toward BC, despite the individual motion or coupling of the thorax and pelvis.


Lyme borreliosis in laboratory animals: effect of host species and in vitro passage of Borrelia burgdorferi.
The susceptibility of several common laboratory animal species to a known pathogenic isolate of Borrelia burgdorferi (N40) was evaluated following intraperitoneal (ip) inoculation of 10(6-8) spirochetes into 3-day-old Lewis rats, CD-1 mice, Syrian hamsters, and 3-week-old American Dutch rabbits. At 30 days, tissues were cultured for spirochetes and examined histologically. All species developed multisystemic infection as well as arthritis and carditis, but disease was most severe in rats and mice. In order to evaluate the effect of in vitro passage on the pathogenicity of B. burgdorferi, 3-day-old Lewis rats were inoculated ip with borreliae passaged in culture 2, 5, 11, 17, 21, 26, and 31 times, and evaluated at 30 days by culture, histology, and ELISA antibody titers. Based upon these parameters, B. burgdorferi (N40) lost its virulence at 17-21 passages. This study demonstrated that B. burgdorferi was infectious for infant rats, mice, hamsters, and 3-week-old rabbits, although pathogenicity was modulated by host species and the in vitro passage history of the spirochete. Of the 4 laboratory animal species evaluated in this study, rats and mice appear to have the most potential for further use as animal models of Lyme disease.


Is Kinesio Taping to Generate Skin Convolutions Effective for Increasing Local Blood Circulation?
BACKGROUND It is unclear whether traditional application of Kinesio taping, which produces wrinkles in the skin, is effective for improving blood circulation. This study investigated local skin temperature changes after the application of an elastic therapeutic tape using convolution and non-convolution taping methods (CTM/NCTM). MATERIAL AND METHODS Twenty-eight pain-free men underwent CTM and NCTM randomly applied to the right and left sides of the lower back. Using infrared thermography, skin temperature was measured before, immediately after application, 5 min later, 15 min later, and after the removal of the tape. RESULTS Both CTM and NCTM showed a slight, but significant, decrease in skin temperature for up to 5 min. The skin temperature at 15 min and after the removal of the tape was not significantly different from the initial temperature for CTM and NCTM. There were also no significant differences in the skin temperatures between CTM and NCTM. CONCLUSIONS Our findings do not support a therapeutic effect of wrinkling the skin with elastic tape application as a technique to increase local blood flow.


Novel organic solvents for electrochemistry at the liquid/liquid interface.
Two-phase voltammetry has been carried out using a reverse cell configuration, i.e. with the lower density organic solvent on the top of the aqueous solution in the cell, where the organic solvents contain either nitrile or ketone functional groups. The transfer of tetraphenylarsonium TPAs(+), tetrabutylammonium TBA(+), tetrapropylammonium TPrA(+), and perchlorate CIO4(-) ions across these liquid/liquid interfaces has been observed. The standard Gibbs energies of ion partition from water to di-n-butyl ketone (5-nonanone) were calculated and compared with the previously reported 2-heptanone/water interface. Ion transfer (IT) and electron transfer (ET) were also investigated at the 5-nonanone/water interface. ET was exemplified using the ferri/ferrocyanide redox couple as the aqueous phase couple and the 7,7,8,8-tetracyanoquinodimethane (TCNQ) as the organic species.


Dual enhancement of T and NK cell function by pulsatile inhibition of SHIP1 improves antitumor immunity and survival.
The success of immunotherapy in some cancer patients has revealed the profound capacity for cytotoxic lymphocytes to eradicate malignancies. Various immunotherapies work by blocking key checkpoint proteins that suppress immune cell activity. The phosphatase SHIP1 (SH2-containing inositol polyphosphate 5-phosphatase) limits signaling from receptors that activate natural killer (NK) cells and T cells. However, unexpectedly, genetic ablation studies have shown that the effector functions of SHIP1-deficient NK and T cells are compromised in vivo. Because chronic activation of immune cells renders them less responsive to activating signals (a host mechanism to avoid autoimmunity), we hypothesized that the failure of SHIP1 inhibition to induce antitumor immunity in those studies was caused by the permanence of genetic ablation. Accordingly, we found that reversible and pulsatile inhibition of SHIP1 with 3-α-aminocholestane (3AC; "SHIPi") increased the antitumor response of NK and CD8+ T cells in vitro and in vivo. Transient SHIP1 inhibition in mouse models of lymphoma and colon cancer improved the median and long-term tumor-free survival rates. Adoptive transfer assays showed evidence of immunological memory to the tumor in hematolymphoid cells from SHIPi-treated, long-term surviving mice. The findings suggest that a pulsatile regimen of SHIP1 inhibition might be an effective immunotherapy in some cancer patients.


Downregulation of miRNA-424: a sign of field cancerisation in clinically normal tongue adjacent to squamous cell carcinoma.
The overall survival for patients with squamous cell carcinoma of the tongue is low and the search for early diagnostic and prognostic markers is thus essential. MicroRNAs have been suggested as potential prognostic and diagnostic candidates in squamous cell carcinoma of head and neck in general. On the basis of the known differences between sub-sites within the oral cavity, we investigated the expression and role of microRNA-424 in squamous cell carcinoma arising in tongue. MicroRNA levels were measured by qRT-PCR in both tissue and plasma samples. Levels of microRNA-424 were upregulated in tongue squamous cell carcinoma, but not in tumours originating from gingiva or floor of the mouth. Interestingly, microRNA-424 was downregulated in clinically normal tongue tissue next to tumour compared with completely healthy tongue, indicating that microRNA-424 could be a marker of field cancerisation in this tumour type. However, expression of microRNA-424 in a tongue-derived epithelial cell line revealed no significant changes in the expression profile of proteins and genes. Our patient data show that microRNA-424 alterations are a marker of field cancerisation specific for tongue tumourigenesis, which also could have a role in development of tongue squamous cell carcinoma.


Visual approach computation in feeding hoverflies.
On warm sunny days, female hoverflies are often observed feeding from a wide range of wild and cultivated flowers. In doing so, hoverflies serve a vital role as alternative pollinators, and are suggested to be the most important pollinators after bees and bumblebees. Unless the flower hoverflies are feeding from is large, they do not readily share the space with other insects, but instead opt to leave if another insect approaches. We used high-speed videography followed by 3D reconstruction of flight trajectories to quantify how female Eristalis hoverflies respond to approaching bees, wasps and two different hoverfly species. We found that, in 94% of the interactions, the occupant female left the flower when approached by another insect. We found that compared with spontaneous take-offs, the occupant hoverfly's escape response was performed at ∼3 times higher speed (spontaneous take-off at 0.2±0.05 m s-1 compared with 0.55±0.08 m s-1 when approached by another Eristalis). The hoverflies tended to take off upward and forward, while taking the incomer's approach angle into account. Intriguingly, we found that, when approached by wasps, the occupant Eristalis took off at a higher speed and when the wasp was further away. This suggests that feeding hoverflies may be able to distinguish these predators, demanding impressive visual capabilities. Our results, including quantification of the visual information available before occupant take-off, provide important insight into how freely behaving hoverflies perform escape responses from competitors and predators (e.g. wasps) in the wild.


Motor function of the opossum sphincter of Oddi.
We studied the opossum sphincter of Oddi (SO) because in this species the SO is approximately 3 cm in length and its extraduodenal location permits recording of motor activity with negligible interference from duodenal motor activity. The SO segment of 120 animals was evaluated by one or more of the following: (a) intraluminal manometry; (b) electromyography; (c) common bile duct (CBD) flow monitored by a drop counter; (d) cineradiography of intraductal contrast medium; and (e) histologic examination. SO pull-throughs using an infused catheter of 0.6-mm o.d. invariably showed a high pressure zone (HPZ) of 18 +/- 3 SE mm Hg in the terminal 4-5 mm of the SO segment. This HPZ had a narrow lumen, 0.5-0.7 mm in diam, and prominent circular muscle. The HPZ in the terminal SO had both active and passive components. HPZ with minimal amplitude and a paucity of underlying smooth muscle were present inconstantly at the junction of the SO segment with the CBD and pancreatic duct, respectively. The dominant feature of the SO segment was rhythmic peristaltic contractions that originated in the proximal SO and propagated toward the duodenum. These contractions occurred spontaneously at a rate of 2-8/min, ranged up to 200 mm Hg in magnitude, had a duration of approximately 5 s and were not abolished by tetrodotoxin. Concurrent myoelectric and manometric recordings showed that each phasic contraction was immediately preceded by an electrical spike burst. Simultaneous recordings of cineradiography, CBD inflow of contrast medium, SO manometry, and SO electromyography indicated that rhythmic peristaltic contractions stripped contrast medium from the SO into the duodenum. During SO systole, CBD emptying was transiently interrupted, whereas SO filling occurred during the diastolic interval between SO peristaltic contractions. SO distention increased the frequency of SO peristalsis. We conclude that (a) the dominant feature of the opossum SO is rhythmic peristaltic contractions that originate in the proximal SO and propagate toward the duodenum; (b) these forceful SO peristaltic contractions are myogenic in origin and serve as a peristaltic pump that actively empties the SO segment; (c) CBD outflow occurs passively during SO diastole, but is interrupted transiently during each SO peristaltic contraction; and (d) a short HPZ with active as well as passive components exists in the distal SO segment and acts as a variable resistor to SO outflow.


Quality assurance of axillary radiotherapy in the EORTC AMAROS trial 10981/22023: the dummy run.
To assess and if needed improve the compliance of participating institutions to the radiotherapy guidelines of the EORTC AMAROS trial 10981/22023 comparing axillary radiotherapy to axillary surgery in sentinel node positive patients with early stage breast cancer. A transverse contour and a frontal view radiograph of the axillary region of a 'dummy' patient were sent to all institutions intending to participate in the trial with the request to produce a radiotherapy treatment plan according to the protocol guidelines. Additional information on dose prescription, the treatment technique and field matching with breast fields and internal mammary lymph node fields was requested in a questionnaire. Eighteen institutions have performed the dummy run. At first assessment, the dose was not specified according to the protocol in seven cases, while two institutions did not comply with the dose prescription of 50 Gy in 25 fractions. Dose heterogeneity was over 20% in 10 institutions, caused by the use of a two-field technique in eight cases. Ten institutions did not apply special techniques to obtain non-overlapping match planes. In 10 cases, one or more field borders or blocks were positioned incorrectly. Following recommendations from the quality assurance committee given to the participating institutions on an individual basis, 10 institutions adapted their technique. Thereafter, 16 institutions could be accepted for trial participation. A number of potential protocol deviations were found at first assessment. Since recommendations led to a large number of adaptations by the participants, a considerable improvement in protocol compliance and inter-institutional consistency was achieved.


Expression of the Bs2 pepper gene confers resistance to bacterial spot disease in tomato.
The Bs2 resistance gene of pepper specifically recognizes and confers resistance to strains of Xanthomonas campestris pv. vesicatoria that contain the corresponding bacterial avirulence gene, avrBs2. The involvement of avrBs2 in pathogen fitness and its prevalence in many X. campestris pathovars suggests that the Bs2 gene may be durable in the field and provide resistance when introduced into other plant species. Employing a positional cloning strategy, the Bs2 locus was isolated and the gene was identified by coexpression with avrBs2 in an Agrobacterium-mediated transient assay. A single candidate gene, predicted to encode motifs characteristic of the nucleotide binding site-leucine-rich repeat class of resistance genes, was identified. This gene specifically controlled the hypersensitive response when transiently expressed in susceptible pepper and tomato lines and in a nonhost species, Nicotiana benthamiana, and was designated as Bs2. Functional expression of Bs2 in stable transgenic tomatoes supports its use as a source of resistance in other Solanaceous plant species.


Comprehensive risk analysis of postoperative complications in patients with rheumatoid arthritis for the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.
To examine the risk factors of surgical site infection (SSI), delayed wound healing, and death after orthopedic surgery in patients with rheumatoid arthritis (RA). We identified articles indexed in the Cochrane Library, PubMed, and Japan Centra Revuo Medicina Web published from 2013 to 2019 and other articles. Articles fulfilling the predefined inclusion criteria were reviewed systematically and their quality was appraised according to the Grading of Recommendations Assessment, Development, and Evaluation system with some modifications. After inclusion and exclusion by full-text review, 29 articles were analyzed. Use of biological disease modifying antirheumatic drugs was a risk factor of SSI (risk ratio 1.66, 95% confidence interval 1.25-2.19), but not of delayed wound healing. RA itself was a risk factor of SSI, and oral glucocorticoid use was a risk factor of SSI in three of the four studies analyzed and of postoperative death. Age, male sex, comorbidities such as diabetes mellitus and chronic obstructive pulmonary disease, surgical factors such as foot/ankle and spine surgery and longer operative time were risk factors of those postoperative complications. Patients with those factors should be dealt with appropriate cautions to strike a risk-benefit balance of orthopedic surgeries.


Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis.
To evaluate the feasibility, safety, and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stem cells (MSCs) (also called mesenchymal stromal cells) in patients with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). A phase 1/2 open-safety clinical trial. Patients Fifteen patients with MS (mean [SD] Expanded Disability Status Scale [EDSS] score, 6.7 [1.0]) and 19 with ALS (mean [SD] Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS] score, 20.8 [8.0]) were enrolled. Intervention After culture, a mean (SD) of 63.2 × 10(6) (2.5 × 10(6)) MSCs was injected intrathecally (n = 34) and intravenously (n = 14). In 9 cases, MSCs were magnetically labeled with the superparamagnetic iron oxide ferumoxides (Feridex). The main outcome measure was the recording of side effects. Follow-up (≤25 months) included adverse events evaluation, neurological disability assessment by means of the EDSS, magnetic resonance imaging to exclude unexpected pathologies and track the labeled stem cells, and immunological tests to assess the short-term immunomodulatory effects of MSC transplantation. Twenty-one patients had injection-related adverse effects consisting of transient fever, and 15 reported headache. No major adverse effects were reported during follow-up. The mean ALSFRS score remained stable during the first 6 months of observation, whereas the mean (SD) EDSS score improved from 6.7 (1.0) to 5.9 (1.6). Magnetic resonance imaging visualized the MSCs in the occipital horns of the ventricles, indicating the possible migration of ferumoxides-labeled cells in the meninges, subarachnoid space, and spinal cord. Immunological analysis revealed an increase in the proportion of CD4(+)CD25(+) regulatory T cells, a decrease in the proliferative responses of lymphocytes, and the expression of CD40(+), CD83(+), CD86(+), and HLA-DR on myeloid dendritic cells at 24 hours after MSC transplantation. Transplantation of MSCs in patients with MS and ALS is a clinically feasible and relatively safe procedure and induces immediate immunomodulatory effects. Trial Registration clinicaltrials.gov Identifier: NCT00781872.


CuO single crystal with exposed {001} facets--a highly efficient material for gas sensing and Li-ion battery applications.
Single crystal copper oxide nanoplatelets with a high percentage of {001} facets were synthesized by a facile hydrothermal approach. The as-prepared materials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, and high resolution transmission microscopy. Via density functional theory calculations, it was found that the {001} facets are active crystal planes. When the single crystal CuO nanoplatelets were applied as an anode material in Li-ion batteries, they demonstrated outstanding electrochemical performance with high lithium storage capacity, satisfactory cyclability, and excellent high rate capacity. When used as a sensing material in gas sensors, they exhibited a superior sensitivity towards toxic and flammable gases.


A fast generalizable solution method for glucose control algorithms.
In critical care tight control of blood glucose levels has been shown to lead to better clinical outcomes. The need to develop new protocols for tight glucose control, as well as the opportunity to optimize a variety of other drug therapies, has led to resurgence in model-based medical decision support in this area. One still valid hindrance to developing new model-based protocols using so-called virtual patients, retrospective clinical data, and Monte Carlo methods is the large amount of computational time and resources needed. This paper develops fast analytical-based methods for insulin-glucose system model that are generalizable to other similar systems. Exploiting the structure and partial solutions in a subset of the model is the key in finding accurate fast solutions to the full model. This approach successfully reduced computing time by factors of 5600-144000 depending on the numerical error management method, for large (50-164 patients) virtual trials and Monte Carlo analysis. It thus allows new model-based or model-derived protocols to be rapidly developed via extensive simulation. The new method is rigorously compared to existing standard numerical solutions and is found to be highly accurate to within 0.2%.


Interdisciplinary communication in the intensive care unit.
Patient safety research has shown poor communication among intensive care unit (ICU) nurses and doctors to be a common causal factor underlying critical incidents in intensive care. This study examines whether ICU doctors and nurses have a shared perception of interdisciplinary communication in the UK ICU. Cross-sectional survey of ICU nurses and doctors in four UK hospitals using a previously established measure of ICU interdisciplinary collaboration. A sample of 48 doctors and 136 nurses (47% response rate) from four ICUs responded to the survey. Nurses and doctors were found to have differing perceptions of interdisciplinary communication, with nurses reporting lower levels of communication openness between nurses and doctors. Compared with senior doctors, trainee doctors also reported lower levels of communication openness between doctors. A regression path analysis revealed that communication openness among ICU team members predicted the degree to which individuals reported understanding their patient care goals ((adj)R(2) = 0.17). It also showed that perceptions of the quality of unit leadership predicted open communication. Members of ICU teams have divergent perceptions of their communication with one another. Communication openness among team members is also associated with the degree to which they understand patient care goals. It is necessary to create an atmosphere where team members feel they can communicate openly without fear of reprisal or embarrassment.


Ultrafast hydrogen-bond dynamics in the infrared spectroscopy of water.
We investigated rearrangements of the hydrogen-bond network in water by measuring fluctuations in the OH-stretching frequency of HOD in liquid D2O with femtosecond infrared spectroscopy. Using simulations of an atomistic model of water, we relate these frequency fluctuations to intermolecular dynamics. The model reveals that OH frequency shifts arise from changes in the molecular electric field that acts on the proton. At short times, vibrational dephasing reflects an underdamped oscillation of the hydrogen bond with a period of 170 femtoseconds. At longer times, vibrational correlations decay on a 1.2-picosecond time scale because of collective structural reorganizations.


Cardiovascular benefits of probiotics: a review of experimental and clinical studies.
The microbiota inhabiting the human gastro-intestinal tract is reported to have a significant impact on the health of an individual. Recent findings suggest that the microbial imbalance of the gut may play a role in pathogenesis of cardiovascular diseases (CVD). Therefore, several studies have delved into the aspect of altering gut microbiota with probiotics as an approach to prevent and/or treat CVD. The World Health Organization defines probiotics as live microorganisms that, when consumed in adequate amounts, have a positive influence on the individual's health. The present review focuses on strategies of human dietary intervention with probiotic strains and their impact on cardiovascular risk factors like hypercholesterolemia, hypertension, obesity and type-2 diabetes. Accumulating evidence shows probiotics to lower low density lipoproteins (LDL)-cholesterol and improve the LDL/high density lipoproteins (HDL) ratio, as well as lower blood pressure, inflammatory mediators, blood glucose levels and body mass index. Thus, probiotics have the scope to be developed as dietary supplements with potential cardiovascular health benefits. However, there is not only ambiguity regarding the exact strains and dosages of the probiotics that will bring about positive health effects, but also factors like immunity and genetics of the individual that might influence the efficacy of probiotics. Therefore, further studies are required not only to understand the mechanisms by which probiotics may beneficially affect the cardiovascular system, but also to rule out any of their probable negative effects on health. The present review aims to critically appraise the complexity of the available data with regard to the cardiovascular benefits of probiotics.


Kinetic and HPV infection effects on cross-type neutralizing antibody and avidity responses induced by Cervarix(®).
We previously demonstrated that Cervarix(®) elicits antibody responses against vaccine-related types for which clinical efficacy was demonstrated (HPV-31 and -45). Here, we evaluated the kinetics of neutralization titers and avidity of Cervarix(®)-induced antibodies up to 36 months of follow-up in unexposed and HPV infected women. A subset of women who participated in the Cost Rica HPV-16/18 Vaccine Trial had pre- and post-vaccination sera tested for antibody responses to HPV-16, -18, -31, -45, and -58 using a pseudovirion-based neutralization assay, and HPV-16 antibody avidity using an HPV-16 L1 VLP (virus-like particle)-based ELISA developed in our laboratory. In uninfected women, neutralizing antibody titers did not reach significance until after the 3rd dose for HPV-31 (month 12, p=0.009) and HPV-45 (month 12, p=0.003), but then persisted up to month 36 (HPV-31, p=0.01; HPV-45, p=0.002). Individuals infected with HPV-16 or HPV-31 at enrollment developed a significantly higher median antibody response to the corresponding HPV type after one dose, but there was not a difference between median titers after three doses compared to the HPV negative group. Median HPV-16 antibody avidity and titer increased over time up to month 12; however, the HPV-16 avidity did not correlate well with HPV-16 neutralizing antibody titers at each time point examined, except for month 6. The median avidity levels were higher in HPV-16 infected women at month 1 (p=0.04) and lower in HPV-16 infected women at month 12 (p=0.006) compared to the HPV negative women. The persistence of cross-neutralization titers at month 36 suggests cross-reactive antibody responses are likely to persist long-term and are not influenced by infection status at enrollment. However, the weak correlation between avidity and neutralization titers emphasizes the need for examining avidity in efficacy studies to determine if high avidity antibodies play a critical role in protection against infection.


Postservice mortality among Vietnam veterans. The Centers for Disease Control Vietnam Experience Study.
The postservice mortality (through December 1983) of a cohort of 9324 US Army veterans who served in Vietnam was compared with that of 8989 Vietnam-era Army veterans who served in Korea, Germany, or the United States. Over the entire follow-up period, total mortality in Vietnam veterans was 17% higher than for other veterans. The excess mortality occurred mainly in the first five years after discharge from active duty (rate ratio, 1.45; 95% confidence interval, 1.08 to 1.96) and involved motor vehicle accidents, suicide, homicide, and accidental poisonings. Thereafter, mortality among Vietnam veterans was similar to that of other Vietnam-era veterans, except for drug-related deaths, which continued to be elevated. An unexpected finding was a deficit in deaths from diseases of the circulatory system among Vietnam veterans. The excess in postservice mortality due to external causes among Vietnam veterans is similar to that found among men returning from combat areas after World War II and the Korean War.


Demand and supply for psychological help in general practice in different European countries: access to primary mental health care in six European countries.
The general practitioner is usually the first health care contact for mental problems. The position of a general practitioner may vary between health care systems, depending on the referral system (gatekeepers versus directly accessible specialists), presence of fixed lists and the payment system. This may influence patients' expectations and requests for help and GPs' performance. In this paper the effects of working in different health care systems on demand and supply for psychological help were examined. Data were collected in six European countries with different health care system characteristics (Belgium, Germany, The Netherlands, Spain, Switzerland and the UK). For 15 consecutive contacts with 190 GPs in the six countries, each patient completed questionnaires concerning reason for visit and expectations (before) and evaluation (after consultation). General practitioners completed registration forms on each consultation, indicating familiarity with the patient and diagnosis. General practitioners completed a general questionnaire about their personal and professional characteristics as well. Practices in different countries differed considerably in the proportion of psychological reasons for the visit by the patient and psychological diagnoses by the GP. Agreement between patients' self-rated problems and GPs' diagnoses also varied. Patients in different countries evaluated their GPs' psychological performance differently as well, but evaluation was not correlated with agreement between request for help and diagosis. In gatekeeping countries, patients had more psycho-social requests, GPs made more psychological diagnoses and agreement between both was relatively high. Evaluation, however, was more positive in non-gatekeeping countries. Individual characteristics of doctors and patients explained only a relatively small part of variance. Health care system characteristics do affect GPs' performance in psycho-social care.


The Importance of Wildlife Disease Monitoring as Part of Global Surveillance for Zoonotic Diseases: The Role of Australia.
Australia has a comprehensive system of capabilities and functions to prepare, detect and respond to health security threats. Strong cooperative links and coordination mechanisms exist between the human (public health) and animal arms of the health system in Australia. Wildlife is included in this system. Recent reviews of both the animal and human health sectors have highlighted Australia's relative strengths in the detection and management of emerging zoonotic diseases. However, the risks to Australia posed by diseases with wildlife as part of their epidemiology will almost certainly become greater with changing land use and climate change and as societal attitudes bring wildlife, livestock and people into closer contact. These risks are not isolated to Australia but are global. A greater emphasis on wildlife disease surveillance to assist in the detection of emerging infectious diseases and integration of wildlife health into One Health policy will be critical in better preparing Australia and other countries in their efforts to recognize and manage the adverse impacts of zoonotic diseases on human health. Animal and human health practitioners are encouraged to consider wildlife in their day to day activities and to learn more about Australia's system and how they can become more involved by visiting www.wildlifeheathaustralia.com.au.


Brain Imaging Studies on the Cognitive, Pharmacological and Neurobiological Effects of Cannabis in Humans: Evidence from Studies of Adult Users.
Cannabis is the most widely used illicit drug worldwide. Regular cannabis use has been associated with a range of acute and chronic mental health problems, such as anxiety, depression, psychotic symptoms and neurocognitive impairments and their neural mechanisms need to be examined. This review summarizes and critically evaluates brain-imaging studies of cannabis in recreational and regular cannabis users between January 2000 and January 2016. The search has yielded eligible 103 structural and functional studies. Regular use of cannabis results in volumetric, gray matter and white matter structural changes in the brain, in particular in the hippocampus and the amygdala. Regular use of cannabis affects cognitive processes such as attention, memory, inhibitory control, decision-making, emotional processing, social cognition and their associated brain areas. There is evidence that regular cannabis use leads to altered neural function during attention and working memory and that recruitment of activity in additional brain regions can compensate for it. Similar to other drugs of abuse, cannabis cues activated areas in the reward pathway. Pharmacological studies showed a modest increase in human striatal dopamine transmission after administration of THC in healthy volunteers. Regular cannabis use resulted in reduced dopamine transporter occupancy and reduced dopamine synthesis but not in reduced striatal D2/D3 receptor occupancy compared with healthy control participants. Studies also showed different effects of Δ-9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on emotion, cognition and associated brain regions in healthy volunteers, whereby CBD protects against the psychoactive effects of THC. Brain imaging studies using selective high-affinity radioligands for the imaging of cannabinoid CB1 receptor availability in Positron Emission Tomography (PET) showed downregulation of CB1 in regular users of cannabis. In conclusion, regular use of the cannabinoids exerts structural and functional changes in the human brain. These changes have profound implications for our understanding of the neuropharmacology of cannabis and its effects on cognition, mental health and the brain.


Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Term Breech Trial Collaborative Group.
For 3-4% of pregnancies, the fetus will be in the breech presentation at term. For most of these women, the approach to delivery is controversial. We did a randomised trial to compare a policy of planned caesarean section with a policy of planned vaginal birth for selected breech-presentation pregnancies. At 121 centres in 26 countries, 2088 women with a singleton fetus in a frank or complete breech presentation were randomly assigned planned caesarean section or planned vaginal birth. Women having a vaginal breech delivery had an experienced clinician at the birth. Mothers and infants were followed-up to 6 weeks post partum. The primary outcomes were perinatal mortality, neonatal mortality, or serious neonatal morbidity; and maternal mortality or serious maternal morbidity. Analysis was by intention to treat. Data were received for 2083 women. Of the 1041 women assigned planned caesarean section, 941 (90.4%) were delivered by caesarean section. Of the 1042 women assigned planned vaginal birth, 591 (56.7%) delivered vaginally. Perinatal mortality, neonatal mortality, or serious neonatal morbidity was significantly lower for the planned caesarean section group than for the planned vaginal birth group (17 of 1039 [1.6%] vs 52 of 1039 [5.0%]; relative risk 0.33 [95% CI 0.19-0.56]; p<0.0001). There were no differences between groups in terms of maternal mortality or serious maternal morbidity (41 of 1041 [3.9%] vs 33 of 1042 [3.2%]; 1.24 [0.79-1.95]; p=0.35). Planned caesarean section is better than planned vaginal birth for the term fetus in the breech presentation; serious maternal complications are similar between the groups.


Current developments in immunotherapy in the treatment of multiple myeloma.
Multiple myeloma (MM) is the second most common hematologic malignancy and represents approximately 10% of all hematological neoplasms. Standard therapy consists of induction therapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) or, if ASCT cannot be performed, standard doublet, triplet, or quadruplet, novel agent-containing induction treatment until progression. Although MM is still regarded as mostly incurable by current standards, the development of several novel compounds, combination therapies, and immunotherapy approaches has raised great hopes about transforming MM into an indolent, chronic disease and possibly achieving a cure for individual patients. Several new inhibitory and immunological agents have been approved or are under intensive investigation and may lead to new therapeutic options for patients with relapsed/refractory MM, for patients ineligible for ASCT, and for patients after ASCT. Especially in the field of immunotherapy, including monoclonal antibodies, checkpoint inhibition, and chimeric antigen receptor T cells, current advances are rapid and highly promising. This review aims to summarize the newest and most promising immunotherapeutic agents for MM, their clinical efficacy, their adverse event (AE) profiles, and the ways in which these AEs can best be overcome or avoided. Cancer 2018;124:2075-85. © 2018 American Cancer Society.


Performance of AHEAD Score in an Asian Cohort of Acute Heart Failure With Either Preserved or Reduced Left Ventricular Systolic Function.
AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score has been related to clinical outcomes of acute heart failure. However, the prognostic value of the AHEAD score in acute heart failure patients with either reduced or preserved left ventricular ejection fraction (HFrEF and HFpEF) remain to be elucidated. The study population consisted of 2143 patients (age 77±12 years, 68% men, 38% HFrEF) hospitalized primarily for acute heart failure with a median follow-up of 23.75 months. The performance of the AHEAD score (atrial fibrillation, hemoglobin <13 mg/dL for men and 12 mg/dL for women, age >70 years, creatinine >130 μmol/L, and diabetes mellitus) was evaluated by Cox's regression analysis for predicting cardiovascular and all-cause mortality. The mean AHEAD scores were 2.7±1.2 in the total study population, 2.6±1.3 in the HFrEF group, and 2.7±1.1 in the HFpEF group. After accounting for sex, sodium, uric acid, and medications, the AHEAD score remained significantly associated with all-cause and cardiovascular mortality (hazard ratio and 95% CI: 1.49, 1.38-1.60 and 1.48, 1.33-1.64), respectively. The associations of AHEAD score with mortality remained significant in the subgroups of HFrEF (1.63, 1.47-1.82) and HFpEF (1.34, 1.22-1.48). Moreover, when we calculated a new AHEAD-U score by considering uric acid (>8.6 mg/dL) in addition to the AHEAD score, the net reclassification was improved by 19.7% and 20.1% for predicting all-cause and cardiovascular mortality, respectively. The AHEAD score was useful in predicting long-term mortality in the Asian acute heart failure cohort with either HFrEF or HFpEF. The new AHEAD-U score may further improve risk stratification.


Self-initiated versus externally triggered movements. II. The effect of movement predictability on regional cerebral blood flow.
Event-related potential studies in man suggest a role for the supplementary motor area (SMA) in movement preparation, particularly when movements are internally generated. In a previous study combining PET with recording of movement-related cortical potentials, we found similar SMA activation and early pre-movement negativity during self-initiated and predictably paced index finger extensions. Early pre-movement negativity was absent when finger movements were paced by unpredictable cues. We postulated that preparation preceding self-initiated and predictably cued movements was responsible for equivalent levels of SMA activation in these two conditions. To test this, we have performed further studies on six normal volunteers with H2(15)O-PET. Twelve measurements of regional cerebral blood flow were made in each subject under three conditions: rest; self-initiated right index finger extension at a variable rate of once every 2-7 s; and finger extension triggered by pacing tones at unpredictable intervals (at a rate yoked to the self-initiated movements). Activation associated with these conditions was compared using analysis of covariance and t statistics. Compared with rest, unpredictably cued movements activated the contralateral primary sensorimotor cortex, caudal SMA and contralateral putamen. Self-initiated movements additionally activated rostral SMA, adjacent anterior cingulate cortex and bilateral dorsolateral prefrontal cortex (DLPFC). Direct comparison of the two motor tasks confirmed significantly greater activation of these areas and of caudal SMA in the self-initiated condition. These results, combined with our previous data, suggest that rostral SMA plays a primary role in movement preparation while caudal SMA is a motor executive area. In this experiment and in our earlier study, DLPFC was activated only during the self-initiated task, in which decisions were required about the timing of movements.


Pharmacogenetics of antipsychotic response in the CATIE trial: a candidate gene analysis.
The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Phase 1 Schizophrenia trial compared the effectiveness of one typical and four atypical antipsychotic medications. Although trials such as CATIE present important opportunities for pharmacogenetics research, the very richness of the clinical data presents challenges for statistical interpretation, and in particular the risk that data mining will lead to false-positive discoveries. For this reason, it is both misleading and unhelpful to perpetuate the current practice of reporting association results for these trials one gene at a time, ignoring the fact that multiple gene-by-phenotype tests are being carried out on the same data set. On the other hand, suggestive associations in such trials may lead to new hypotheses that can be tested through both replication efforts and biological experimentation. The appropriate handling of these forms of data therefore requires dissemination of association statistics without undue emphasis on select findings. Here we attempt to illustrate this approach by presenting association statistics for 2769 polymorphisms in 118 candidate genes evaluated for 21 pharmacogenetic phenotypes. On current evidence it is impossible to know which of these associations may be real, although in total they form a valuable resource that is immediately available to the scientific community.


Outcomes for depression and anxiety in primary care and details of treatment: a naturalistic longitudinal study.
There is little evidence as to whether or not guideline concordant care in general practice results in better clinical outcomes for people with anxiety and depression. This study aims to determine possible associations between guideline concordant care and clinical outcomes in general practice patients with depression and anxiety, and identify patient and treatment characteristics associated with clinical improvement. This study forms part of the Netherlands Study of Depression and Anxiety (NESDA).Adult patients, recruited in general practice (67 GPs), were interviewed to assess DSM-IV diagnoses during baseline assessment of NESDA, and also completed questionnaires measuring symptom severity, received care, socio-demographic variables and social support both at baseline and 12 months later. The definition of guideline adherence was based on an algorithm on care received. Information on guideline adherence was obtained from GP medical records. 721 patients with a current (6-month recency) anxiety or depressive disorder participated. While patients who received guideline concordant care (N=281) suffered from more severe symptoms than patients who received non-guideline concordant care (N=440), both groups showed equal improvement in their depressive or anxiety symptoms after 12 months. Patients who (still) had moderate or severe symptoms at follow-up, were more often unemployed, had smaller personal networks and more severe depressive symptoms at baseline than patients with mild symptoms at follow-up. The particular type of treatment followed made no difference to clinical outcomes. The added value of guideline concordant care could not be demonstrated in this study. Symptom severity, employment status, social support and comorbidity of anxiety and depression all play a role in poor clinical outcomes.


Selection of RNA aptamers that bind HIV-1 LTR DNA duplexes: strand invaders.
RNA that can specifically bind to double-stranded DNA is of interest because it might be used as a means to regulate transcription of the target genes. To explore possible interactions between RNA and duplex DNA, we selected for RNA aptamers that can bind to the long terminal repeats (LTRs) of human immunodeficiency virus type 1 DNA. The selected aptamers were classified into four major groups based on the consensus sequences, which were found to locate in the non-stem regions of the predicted RNA secondary structures, consistent with roles in target binding. Analysis of the aptamer consensus sequences suggested that the conserved segments could form duplexes via Watson-Crick base-pairing with preferred sequences in one strand of the DNA, assuming the aptamer invaded the duplex. The aptamer binding sites on the LTR were experimentally determined to be located preferentially at these sites near the termini of double-stranded target DNA, despite selection schemes that were designed to minimize preferences for termini. The results presented here show that aptamer RNAs can be selected in vitro that strand-invade at preferred DNA duplex sequences to form stable complexes.


High levels of mortality, malnutrition, and measles, among recently-displaced Somali refugees in Dagahaley camp, Dadaab refugee camp complex, Kenya, 2011.
Following a rapid influx of over 200,000 displaced Somalis into the Dadaab refugee camp complex in Kenya, Médecins Sans Frontières conducted a mortality and nutrition survey of the population living in Bulo Bacte, a self-settled area surrounding Dagahaley camp (part of this complex). The survey was conducted between 31st July and 10th August 2011. We exhaustively interviewed representatives from all households in Bulo Bacte, collecting information on deaths, births, and population movements during the recall period (15th February 2011 to survey date), in order to provide estimates of retrospective death rates. We recorded the mid-upper arm circumference and presence or absence of bipedal oedema of all children of height 67-<110 cm to provide estimates of global and severe acute malnutrition. The surveyed population included 26,583 individuals, of whom 6,488 (24.4%) were children aged under 5 years. There were 360 deaths reported during the 177 days of the recall period, of which 186 (52%) were among children aged under 5 years. The crude death rate for the entire recall period was 0.8 per 10,000 person-days. The under-5 death rate was 1.8 per 10,000 person-days. More than two-thirds of all deaths were reported to have been associated with diarrhoea (25%), cough or other breathing difficulties (24%), or with fever (19%). Measles accounted for a reported 17% of all deaths; this was due to a measles outbreak that occurred between June and October 2011.Global acute malnutrition was observed in 13.4%, and severe acute malnutrition in 3.0%, of children measuring 67-<110 cm. Among children measuring 110-< 140 cm, 9.8% met the admission criteria for entry into the nutritional programme. Trends of decreasing death rates and malnutrition prevalence with length of stay in Bulo Bacte were observed. We report high death rates and prevalence of malnutrition among this population, reflecting at least a partial failure of the various humanitarian and governmental actors to adequately safeguard the welfare of this population. An outbreak of measles and long delays before registration should not have occurred. The recommendations for measles vaccination among crisis-affected populations should be revised to take into account the epidemiologic context. Organisations must be sensitive and reactive to changes in the health status of the populations they assist.


Effect of tree nuts on metabolic syndrome criteria: a systematic review and meta-analysis of randomised controlled trials.
To provide a broader evidence summary to inform dietary guidelines of the effect of tree nuts on criteria of the metabolic syndrome (MetS). We conducted a systematic review and meta-analysis of the effect of tree nuts on criteria of the MetS. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library (through 4 April 2014). We included relevant randomised controlled trials (RCTs) of ≥3 weeks reporting at least one criterion of the MetS. Two or more independent reviewers extracted all relevant data. Data were pooled using the generic inverse variance method using random effects models and expressed as mean differences (MD) with 95% CIs. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I(2) statistic. Study quality and risk of bias were assessed. Eligibility criteria were met by 49 RCTs including 2226 participants who were otherwise healthy or had dyslipidaemia, MetS or type 2 diabetes mellitus. Tree nut interventions lowered triglycerides (MD=-0.06 mmol/L (95% CI -0.09 to -0.03 mmol/L)) and fasting blood glucose (MD=-0.08 mmol/L (95% CI -0.16 to -0.01 mmol/L)) compared with control diet interventions. There was no effect on waist circumference, high-density lipoprotein cholesterol or blood pressure with the direction of effect favouring tree nuts for waist circumference. There was evidence of significant unexplained heterogeneity in all analyses (p<0.05). Pooled analyses show a MetS benefit of tree nuts through modest decreases in triglycerides and fasting blood glucose with no adverse effects on other criteria across nut types. As our conclusions are limited by the short duration and poor quality of the majority of trials, as well as significant unexplained between-study heterogeneity, there remains a need for larger, longer, high-quality trials. NCT01630980.


The use of self-report measures to examine changes in perception in response to fittings using different signal processing parameters.
Clinicians have long used self-report methods to assess hearing aid benefit. However, there are fewer data as to whether self-report instruments can be used to compare differences between signal processing settings. This study examined how self-perceived performance varied as a function of modifications in signal processing using two self-report measures. Data were collected as part of a double-blind randomised crossover clinical trial. Participants were fit with two fittings: mild processing (slow time constants, disabled frequency lowering) and strong processing (fast time constants, frequency lowering enabled). The speech, spatial, and qualities of hearing (SSQ) questionnaire and the Effectiveness of Auditory Rehabilitation (EAR) questionnaire were collected at multiple time points. Older adults with sensorineural hearing loss who had not used hearing aids within the previous year participated (49 older adults were consented; 40 were included in the final data analyses). Findings show that listeners report a difference in perceived performance when hearing aid features are modified. Both self-report measures were able to capture this change in perceived performance. Self-report measures provide a tool for capturing changes in perceived performance when hearing aid processing features are modified and may enhance provision of an evidence-based hearing aid fitting.


Behavioral activation, inhibition and mood symptoms in early-onset bipolar disorder.
Hypomania/mania and depression are hypothesized to correspond to high and low expressions of behavioral activation system (BAS) activity, respectively, in bipolar individuals. In contrast, behavioral inhibition system (BIS) activity is hypothesized to regulate anxiety. The aim of the present study was to examine whether self-reported levels of BAS functioning in bipolar adolescents corresponded with levels of concurrent manic and depressive symptomatology. The secondary aim was to investigate whether self-reported BIS levels were associated with self-reported anxiety symptoms. Twenty-five adolescents diagnosed with bipolar I, II or not otherwise specified were recruited from a treatment-development study. Adolescents were interviewed using the Depression and Mania Rating Scales of the Kiddie Schedule for Affective Disorders and Schizophrenia and given the Self-Report for Childhood Anxiety Related Disorders. Next, they completed the Behavioral Inhibition/Activation Scales. Contrary to hypotheses, adolescents with higher BAS levels exhibited less severe concurrent mania symptoms. Furthermore, levels of BAS sensitivity were not associated with concurrent levels of depression. As predicted, BIS scores correlated positively with self-reported anxiety scores. Adolescents reporting higher levels of the motor activity symptoms of mania also reported higher levels of anxiety symptoms. The conclusions are based upon cross-sectional analyses in a small sample. In bipolar adolescents, mania and depression appear to be independent of self-reported behavioral activation levels. However, mood symptoms in adolescent patients are closely tied to components of anxiety, which may lead to diminished approach behaviors.


Ecological integrity of streams related to human cancer mortality rates.
Assessments of ecological integrity have become commonplace for biological conservation, but their role for public health analysis remains largely unexplored. We tested the prediction that the ecological integrity of streams would provide an indicator of human cancer mortality rates in West Virginia, USA. We characterized ecological integrity using an index of benthic macroinvertebrate community structure (West Virginia Stream Condition Index, SCI) and quantified human cancer mortality rates using county-level data from the Centers for Disease Control and Prevention. Regression and spatial analyses revealed significant associations between ecological integrity and public health. SCI was negatively related to age-adjusted total cancer mortality per 100,000 people. Respiratory, digestive, urinary, and breast cancer rates increased with ecological disintegrity, but genital and oral cancer rates did not. Smoking, poverty, and urbanization were significantly related to total cancer mortality, but did not explain the observed relationships between ecological integrity and cancer. Coal mining was significantly associated with ecological disintegrity and higher cancer mortality. Spatial analyses also revealed cancer clusters that corresponded to areas of high coal mining intensity. Our results demonstrated significant relationships between ecological integrity and human cancer mortality in West Virginia, and suggested important effects of coal mining on ecological communities and public health. Assessments of ecological integrity therefore may contribute not only to monitoring goals for aquatic life, but also may provide valuable insights for human health and safety.


Inhibition of biofilm development of uropathogens by curcumin - an anti-quorum sensing agent from Curcuma longa.
Urinary tract infection is caused primarily by the quorum sensing (QS)-dependent biofilm forming ability of uropathogens. In the present investigation, an anti-quorum sensing (anti-QS) agent curcumin from Curcuma longa (turmeric) was shown to inhibit the biofilm formation of uropathogens, such as Escherichia coli, Pseudomonas aeruginosa PAO1, Proteus mirabilis and Serratia marcescens, possibly by interfering with their QS systems. The antibiofilm potential of curcumin on uropathogens as well as its efficacy in disturbing the mature biofilms was examined under light microscope and confocal laser scanning microscope. The treatment with curcumin was also found to attenuate the QS-dependent factors, such as exopolysaccharide production, alginate production, swimming and swarming motility of uropathogens. Furthermore, it was documented that curcumin enhanced the susceptibility of a marker strain and uropathogens to conventional antibiotics.


Analysis of peripheral nerve expression profiles identifies a novel myelin glycoprotein, MP11.
The myelin sheath insulates axons and allows for rapid salutatory conduction in the nervous system of all vertebrates. The formation of peripheral myelin requires expression of the transcription factor Egr2, which is responsible for inducing such essential myelin-associated genes as Mpz, Mbp, Pmp22, and Mag. Using microarray analysis to compare gene expression patterns in peripheral nerve during development, during remyelination after nerve injury, and in a congenital hypomyelinating mouse model, we identified an evolutionarily conserved novel component of myelin called Mp11 (myelin protein of 11 kDa). The Mp11 genomic locus contains multiple conserved Egr binding sites, and Mp11 induction is regulated by the expression of Egr2. Similar to other Egr2-dependent genes, it is induced during developmental myelination and remyelination after nerve injury. Mp11 is a glycoprotein expressed preferentially in the myelin of the peripheral nervous system versus CNS and is specifically localized to the Schmidt-Lanterman incisures and paranodes of peripheral nerve. The Mp11 protein contains no identifiable similarity to other known protein domains or motifs. However, like other myelin genes, strict Mp11 expression levels are a requirement for the in vitro myelination of DRG neurons, indicating that this previously uncharacterized gene product is a critical component of peripheral nervous system myelin.


Understanding attention, memory and social biases in fragile X syndrome: Going below the surface with a multi-method approach.
Fragile X syndrome (FXS) is characterised by atypical social behaviours, such as gaze aversion. However, it remains unclear whether, or if so how, these behaviours affect cognitive processing and influence memory. We asked children with FXS (N = 16) and typically developing children (TD; N = 46) to explore naturalistic scenes containing social and non-social salient items unrelated to their task at hand (searching for a simple target object). We also assessed children's memory for target locations. We complemented behavioural responses with eye-tracking data for the subset of participants who managed to comply with calibration and the demands of the experimental testing session (6 children with FXS and 43 TD children). Children with FXS performed well at the experimental task, and showed similar accuracy and speed in locating targets in natural scenes to children of equivalent verbal abilities. They also learned target locations over blocks, but their memory of target locations was not as precise as that of comparison children. In addition, children with FXS initially directed few first looks to salient social items within the scenes, but these looks increased over blocks. Like TD children, children with FXS also dwelled gaze upon social items while recalling target locations from memory. Individual differences in everyday social characteristics also related to gaze and behavioural measures. In conclusion, experimental approaches can highlight cognitive underpinnings of atypical social behaviour in FXS, pinpointing both similarities and differences to TD individuals.


Old focus of cysticercosis in a senegalese village revisited after half a century.
The objective of this epidemiological study was to determine whether cysticercosis and especially neurocysticercosis is endemic in Soutou village about half a century after the 1962 outbreak. This study was carried out from September 2009 to February 2010. It involved a questionnaire administration, serology, treatment, coproscopy and neuro-imaging. Four hundred and three serum samples were collected from the village people, which covered 94% of the village population. By using a parallel combination of the antigen-detection ELISA and the enzyme-linked immunoelectrotransfer blot (EITB) a cysticercosis seroprevalence of 11.9% (95% CI: 8.9-15.4%) was found. Cerebral CT-scans showed that 23.3% (10/43) of the seropositives were affected by neurocysticercosis. Four out of these 43 (9.3%) were tapeworm carriers. Seropositivity was significantly associated to older age groups (41-60 years old; p=0.001 and 61-91 years old; p=0.028) and absence of a household toilet (p=0.001). It can be concluded that Soutou village is an active focus of Taenia solium cysticercosis about 50 years after the first reported epidemic outbreak.


Scientific research publications in dengue: A global and Indian bibliometric analysis from 1997 to 2018.
Dengue fever is common in tropical and subtropical countries of the world and its present impact is 30 times more than what it was 50 yr ago. The aim of the study was to analyze the research output/publications on dengue across the world as well as in India, using the Web of Science database. Literature search was done using the keyword 'dengue' in the title field to find global and Indian publications on dengue from 1 June 1997 to 20 July 2018. Bibliometric analysis was done on the basis of the magnitude of research output; year, type and language of publications; citations and h-index, impact factor, keywords, most productive institutes etc. Descriptive analysis was performed using MS Office, Word Cloud Generator and SPSS software. The analysis of the records obtained indicated that globally 11,742 articles were published on dengue during the period of 21 yr of which 1114 were Indian. The country with highest number of publications was United States (3449; 29.37%) while India ranked third (1114; 9.48%). Majority of the published articles where in the American Journal of Tropical Medicine and Hygiene (1366; 11.63%) and the leading journal in India was Indian Journal of Medical Research (56; 5.02%) followed by the Journal of Vector Borne Diseases (42; 3.77%). The most productive Institute at global level was 'Mahidol University, Thailand' while in the Indian context it was 'All India Institute of Medical Sciences, New Delhi'. The elevated metrics of citation, impact factor, and h-index are based on the magnitude of scientific research outputs. Increasing trend in the number of publications over the years both globally as well as in India indicates overall growth in dengue research. Even though it is a good sign of productivity it is still significantly related to the magnitude of occurrence of dengue cases across the globe. Further, it is a good indication that the scientific community is dynamic and responding well in bringing out the regional scenarios to the public for health promotion.


Efficacy of pharmacological therapies in patients with IBS with diarrhoea or mixed stool pattern: systematic review and network meta-analysis.
Over half of patients with IBS have either diarrhoea (IBS-D) or a mixed stool pattern (IBS-M). The relative efficacy of licenced pharmacological therapies is unclear in the absence of head-to-head trials. We conducted a network meta-analysis to resolve this uncertainty. We searched MEDLINE, Embase, Embase Classic, the Cochrane central register of controlled trials, and Clinicaltrials.gov through January 2019 to identify randomised controlled trials (RCTs) assessing the efficacy of licenced pharmacological therapies (alosetron, eluxadoline, ramosetron and rifaximin) in adults with IBS-D or IBS-M. Trials included in the analysis reported a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of all pharmacological therapies were reported as a pooled relative risk with 95% CIs to summarise the effect of each comparison tested. Treatments were ranked according to their p score. We identified 18 eligible RCTs (seven alosetron, five ramosetron, two rifaximin and four eluxadoline), containing 9844 patients. All were superior to placebo for the treatment of IBS-D or IBS-M at 12 weeks, according to the Food and Drug Administration (FDA)-recommended endpoint for trials in IBS. Alosetron 1 mg twice daily was ranked first for efficacy, based on the FDA-recommended composite endpoint of improvement in both abdominal pain and stool consistency, effect on global symptoms of IBS and effect on stool consistency. Ramosetron 2.5µg once daily was ranked first for effect on abdominal pain. Total numbers of adverse events were significantly greater with alosetron 1 mg twice daily and ramosetron 2.5µg once daily, compared with placebo. Rifaximin 550 mg three times daily ranked first for safety. Constipation was significantly more common with all drugs, except rifaximin 550 mg three times daily. In a network meta-analysis of RCTs of pharmacological therapies for IBS-D and IBS-M, we found all drugs to be superior to placebo, but alosetron and ramosetron appeared to be the most effective.