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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Recent infection testing algorithms (RITA) for HIV combine serological assays with epidemiological data to determine likely recent infections, indicators of ongoing transmission. In 2016, we integrated RITA into national HIV surveillance in Ireland to better inform HIV prevention interventions. We determined the avidity index (AI) of new HIV diagnoses and linked the results with data captured in the national infectious disease reporting system. RITA classified a diagnosis as recent based on an AI < 1.5, unless epidemiological criteria (CD4 count <200 cells/mm3; viral load <400 copies/ml; the presence of AIDS-defining illness; prior antiretroviral therapy use) indicated a potential false-recent result. Of 508 diagnoses in 2016, we linked 448 (88.1%) to an avidity test result. RITA classified 12.5% of diagnoses as recent, with the highest proportion (26.3%) amongst people who inject drugs. On multivariable logistic regression recent infection was more likely with a concurrent sexually transmitted infection (aOR 2.59; 95% CI 1.04–6.45). Data were incomplete for at least one RITA criterion in 48% of cases. The study demonstrated the feasibility of integrating RITA into routine surveillance and showed some ongoing HIV transmission. To improve the interpretation of RITA, further efforts are required to improve completeness of the required epidemiological data.
New excavations at the Jebel Moya cemetery in Sudan reveal extensive evidence for Meroitic-era occupation, providing valuable data on contemporaneous diet, migration, exchange and population composition in sub-Saharan Africa.
Using multilevel models, we examined mother-, father-, and child-reported (N = 1,336 families) externalizing behavior problem trajectories from age 7 to 14 in nine countries (China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States). The intercept and slope of children's externalizing behavior trajectories varied both across individuals within culture and across cultures, and the variance was larger at the individual level than at the culture level. Mothers’ and children's endorsement of aggression as well as mothers’ authoritarian attitudes predicted higher age 8 intercepts of child externalizing behaviors. Furthermore, prediction from individual-level endorsement of aggression and authoritarian attitudes to more child externalizing behaviors was augmented by prediction from cultural-level endorsement of aggression and authoritarian attitudes, respectively. Cultures in which father-reported endorsement of aggression was higher and both mother- and father-reported authoritarian attitudes were higher also reported more child externalizing behavior problems at age 8. Among fathers, greater attributions regarding uncontrollable success in caregiving situations were associated with steeper declines in externalizing over time. Understanding cultural-level as well as individual-level correlates of children's externalizing behavior offers potential insights into prevention and intervention efforts that can be more effectively targeted at individual children and parents as well as targeted at changing cultural norms that increase the risk of children's and adolescents’ externalizing behavior.
Functional circuits of the human brain emerge and change dramatically over the second half of gestation. It is possible that variation in neural functional system connectivity in utero predicts individual differences in infant behavioral development, but this possibility has yet to be examined. The current study examines the association between fetal sensorimotor brain system functional connectivity and infant postnatal motor ability. Resting-state functional connectivity data was obtained in 96 healthy human fetuses during the second and third trimesters of pregnancy. Infant motor ability was measured 7 months after birth using the Bayley Scales of Infant Development. Increased connectivity between the emerging motor network and regions of the prefrontal cortex, temporal lobes, posterior cingulate, and supplementary motor regions was observed in infants that showed more mature motor functions. In addition, females demonstrated stronger fetal-brain to infant-behavior associations. These observations extend prior longitudinal research back into prenatal brain development and raise exciting new ideas about the advent of risk and the ontogeny of early sex differences.
Foodborne non-typhoidal salmonellosis causes approximately 1 million illnesses annually in the USA. In April 2015, we investigated a multistate outbreak of 65 Salmonella Paratyphi B variant L(+) tartrate(+) infections associated with frozen raw tuna imported from Indonesia, which was consumed raw in sushi. Forty-six (92%) of 50 case-patients interviewed ate sushi during the week before illness onset, and 44 (98%) of 45 who specified ate sushi containing raw tuna. Two outbreak strains were isolated from the samples of frozen raw tuna. Traceback identified a single importer as a common source of tuna consumed by case-patients; this importer issued three voluntary recalls of tuna sourced from one Indonesian processor. Four Salmonella Weltevreden infections were also linked to this outbreak. Whole-genome sequencing was useful in establishing a link between Salmonella isolated from ill people and tuna. This outbreak highlights the continuing foodborne illness risk associated with raw seafood consumption, the importance of processing seafood in a manner that minimises contamination with pathogenic microorganisms and the continuing need to ensure imported foods are safe to eat. People at higher risk for foodborne illness should not consume undercooked animal products, such as raw seafood.
We report on the results of coherent X-ray diffraction imaging (CXDI) and ptychography measurements of two individual core-shell-shell GaAs/(In,Ga)As/GaAs nanowires (NWs) grown by molecular beam epitaxy (MBE) on patterned Si(111) substrate. CXDI at the axial GaAs 111 Bragg reflection was applied at different positions along the NW axis in order to characterize the NWs in terms of structural homogeneity along the radial directions. At each positon 3D reciprocal space maps have been recoded and inverted using phase retrieval algorithms. The CXDI were complemented by 2D ptychography measurements at GaAs 111 Bragg reflection probing the same NWs with respect to their structural homogeneity. Both methods provide structural homogeneity for NW1 and NW2 except at the bottom part of the NWs. In case of NW2 CXDI and ptychography show changes in the structure of the top part of the NW indicated by 60° rotation of the indicated three-fold rotational symmetry in the observed diffraction patterns and changes in the strain field reconstructed from ptychography.
Endogenous melatonin is a hormone secreted by pineal gland; it has several roles in metabolism, reproduction, and remarkable antioxidant properties. Studies on the melatonin effect on the adrenal glands which are important endocrine organs, controlling essential physiological functions, are still deficient. In this study, we attempted to investigate the effect of exogenous melatonin treatment on the adrenal cortex and medulla using several approaches. Adrenal glands of 15 Soay ram were examined to detect the effect of melatonin treatment. Our results revealed that the cells of adrenal cortex of the treated animals were separated by wide and numerous blood sinusoids and showed signs of increase steroidogenic activity, which are evidenced by functional hypertrophy with increase profiles of mitochondria, smooth endoplasmic reticulum, and lipid droplets. The most striking ultrastructural features in the medulla of the treated group were the engorgement of chromaffin cells with enlarged secretory granules enclosed within a significantly increased diameter of these cells. The cytoplasm of these cells showed numerous mitochondria, rough endoplasmic reticulum (rER), Golgi apparatus, lysosomes, and glycogen granules. Exocytosis of secretory granules to the lumen of blood vessels was evident in the treated group. Piecemeal degranulation mode of secretion was recorded after melatonin treatment. Chromaffin cells in the control group expressed moderate immunoreactivity to Synaptophysin and tyrosine hydroxylase, compared with intensified expression after melatonin treatment. The ganglion cells of the melatonin-treated group showed a significant increase in diameter with numerous rER. The most interesting feature in this study is the presence of small granule chromaffin cells (SGC) and telocytes (TCs) for the first time in the adrenal glands of sheep. Moreover, these SGC cells, Schwann cells, fibroblasts, and progenitor stem cells showed a stimulatory response. The TCs were small branched cells scattered in the adrenal glands around cortical cells, chromaffin cells, nerve fibers, and blood vessels. These cells increased significantly in number, length of their telopodes, and secretory activity after melatonin treatment. In addition, multiple profiles of unmyelinated nerve fibers were demonstrated in all treated specimens. These results indicated that melatonin treatment caused a stimulatory action on all cellular and neuronal elements of the adrenal gland. This study may act as a new direction for treatment of adrenal insufficiency.
Using data from 1,177 families in eight countries (Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States), we tested a conceptual model of direct effects of childhood family adversity on subsequent externalizing behaviors as well as indirect effects through psychological mediators. When children were 9 years old, mothers and fathers reported on financial difficulties and their use of corporal punishment, and children reported perceptions of their parents’ rejection. When children were 10 years old, they completed a computerized battery of tasks assessing reward sensitivity and impulse control and responded to questions about hypothetical social provocations to assess their hostile attributions and proclivity for aggressive responding. When children were 12 years old, they reported on their externalizing behavior. Multigroup structural equation models revealed that across all eight countries, childhood family adversity had direct effects on externalizing behaviors 3 years later, and childhood family adversity had indirect effects on externalizing behavior through psychological mediators. The findings suggest ways in which family-level adversity poses risk for children's subsequent development of problems at psychological and behavioral levels, situated within diverse cultural contexts.
In this paper, we study the kinematic effects of number of legs in 6-DOF UPS parallel manipulators. A group of 3-, 4-, and 6-legged mechanisms are evaluated in terms of the kinematic performance indices, workspace, singular configurations, and forward kinematic solutions. Results show that the optimum number of legs varies due to priorities in kinematic measures in different applications. The non-symmetric Wide-Open mechanism enjoys the largest workspace, while the well-known Gough–Stewart (3–3) platform retains the highest dexterity. Especially, the redundantly actuated 4-legged mechanism has several important advantages over its non-redundant counterparts and different architectures of Gough–Stewart platform. It has dramatically less singular configurations, a higher manipulability, and at the same time less sensitivity. It is also shown that the forward kinematic problem has 40, 16, and 1 solution(s), respectively for the 6-, 3-, and the 4-legged mechanisms. Superior capabilities of the 4-legged mechanism make it a perfect candidate to be used in more challenging 6-DOF applications in assembly, manufacturing, biomedical, and space technologies.
This article reports investigation of the effects of high-rate stochastic micro-mechanics on the produced particulate size distribution during ball milling of reactive bimetallic foils (nanoheaters), by experimental and computational modeling. In particular, Ni-Al foils are ball-milled at various load charges, revolution rates and process durations, and the resulting particulate geometries are characterized by micrograph statistical analysis. Numerical simulation of the evolving particulate structure is based on coalescence and fragmentation of flexible monometallic ellipsoidal primitives, impacted by milling balls and vial walls with kinetic theory-based kinematics. Particulates are constrained by discrete compliant and continuum media and undergo conceptual ideal elastic transformations modeled by strain energy methods, and recast into inelastic frictional and plasticity-driven welding and fracture events. Finally the theoretical model predictions of particulate size distribution are validated against laboratory microscopy observations.
The effect of feeding two levels of Saccharomyces cerevisiae on the performance of crossbred Friesian calves was investigated. Twenty-four neonatal male Friesian × Baladi calves (35·5 ± 0·25 kg of initial body weight) were randomly assigned in a completely randomized design into three experimental groups for 90 days (eight calves per group). Calves fed their diets without yeast (S. cerevisiae) were considered as Control, while the diets of other calves were supplemented daily either with 2·5 g (YL diet) or with 5 g (YH diet) of yeast per calf. Calves fed the YH diet showed increased feed intake, while dry matter and fibre digestibilities were increased in calves fed YH and YL diets. Calves fed YL and YH diets showed lower ruminal ammonia-N and higher total volatile fatty acids, acetate and propionate concentrations than Control calves. Both YH and YL calves showed increased plasma concentrations of total protein, globulin and glucose and decreased cholesterol and triglycerides concentrations. Calves’ final weight and daily gain were increased with S. cerevisiae yeast supplemented diets. After 42 days of experiment, Clostridium spp., Escherichia coli and Enterobacteria spp. counts were down to undetectable levels in the faeces of calves fed S. cerevisiae additive. It could be concluded that adding S. cerevisiae to milk-fed calves increased feed utilization and improved pre-weaned calf performance and health status, reducing faecal pathogenic bacteria.
Radio survey datasets comprise an increasing number of individual observations stored as sets of multidimensional data. In large survey projects, astronomers commonly face limitations regarding: 1) interactive visual analytics of sufficiently large subsets of data; 2) synchronous and asynchronous collaboration; and 3) documentation of the discovery workflow. To support collaborative data inquiry, we present encube, a large-scale comparative visual analytics framework. encube can utilise advanced visualization environments such as the CAVE2 (a hybrid 2D and 3D virtual reality environment powered with a 100 Tflop/s GPU-based supercomputer and 84 million pixels) for collaborative analysis of large subsets of data from radio surveys. It can also run on standard desktops, providing a capable visual analytics experience across the display ecology. encube is composed of four primary units enabling compute-intensive processing, advanced visualisation, dynamic interaction, parallel data query, along with data management. Its modularity will make it simple to incorporate astronomical analysis packages and Virtual Observatory capabilities developed within our community. We discuss how encube builds a bridge between high-end display systems (such as CAVE2) and the classical desktop, preserving all traces of the work completed on either platform – allowing the research process to continue wherever you are.
In temperate zones, human respiratory syncytial virus (HRSV) outbreaks typically occur in cold weather, i.e. in late autumn and winter. However, recent outbreaks in Japan have tended to start during summer and autumn. This study examined associations of meteorological conditions with the numbers of HRSV cases reported in summer in Japan. Using data from the HRSV national surveillance system and national meteorological data for summer during the period 2007–2014, we utilized negative binomial logistic regression analysis to identify associations between meteorological conditions and reported cases of HRSV. HRSV cases increased when summer temperatures rose and when relative humidity increased. Consideration of the interaction term temperature × relative humidity enabled us to show synergistic effects of high temperature with HRSV occurrence. In particular, HRSV cases synergistically increased when relative humidity increased while the temperature was ⩾28·2 °C. Seasonal-trend decomposition analysis using the HRSV national surveillance data divided by 11 climate divisions showed that summer HRSV cases occurred in South Japan (Okinawa Island), Kyushu, and Nankai climate divisions, which are located in southwest Japan. Higher temperature and higher relative humidity were necessary conditions for HRSV occurrence in summer in Japan. Paediatricians in temperate zones should be mindful of possible HRSV cases in summer, when suitable conditions are present.
This paper is based on a report commissioned by the United Nations High Commissioner for Refugees, which aims to provide information on cultural aspects of mental health and psychosocial wellbeing relevant to care and support for Syrians affected by the crisis. This paper aims to inform mental health and psychosocial support (MHPSS) staff of the mental health and psychosocial wellbeing issues facing Syrians who are internally displaced and Syrian refugees.
We conducted a systematic literature search designed to capture clinical, social science and general literature examining the mental health of the Syrian population. The main medical, psychological and social sciences databases (e.g. Medline, PubMed, PsycInfo) were searched (until July 2015) in Arabic, English and French language sources. This search was supplemented with web-based searches in Arabic, English and French media, and in assessment reports and evaluations, by nongovernmental organisations, intergovernmental organisations and agencies of the United Nations. This search strategy should not be taken as a comprehensive review of all issues related to MHPSS of Syrians as some unpublished reports and evaluations were not reviewed.
Conflict affected Syrians may experience a wide range of mental health problems including (1) exacerbations of pre-existing mental disorders; (2) new problems caused by conflict related violence, displacement and multiple losses; as well as (3) issues related to adaptation to the post-emergency context, for example living conditions in the countries of refuge. Some populations are particularly vulnerable such as men and women survivors of sexual or gender based violence, children who have experienced violence and exploitation and Syrians who are lesbian, gay, bisexual, transgender or intersex. Several factors influence access to MHPSS services including language barriers, stigma associated with seeking mental health care and the power dynamics of the helping relationship. Trust and collaboration can be maximised by ensuring a culturally safe environment, respectful of diversity and based on mutual respect, in which the perspectives of clients and their families can be carefully explored.
Sociocultural knowledge and cultural competency can improve the design and delivery of interventions to promote mental health and psychosocial wellbeing of Syrians affected by armed conflict and displacement, both within Syria and in countries hosting refugees from Syria.
This study advances understanding of predictors of child abuse and neglect at multiple levels of influence. Mothers, fathers, and children (N = 1,418 families, M age of children = 8.29 years) were interviewed annually in three waves in 13 cultural groups in nine countries (China, Colombia, Italy, Jordan, Kenya, Philippines, Sweden, Thailand, and the United States). Multilevel models were estimated to examine predictors of (a) within-family differences across the three time points, (b) between-family within-culture differences, and (c) between-cultural group differences in mothers' and fathers' reports of corporal punishment and children's reports of their parents' neglect. These analyses addressed to what extent mothers' and fathers' use of corporal punishment and children's perceptions of their parents' neglect were predicted by parents' belief in the necessity of using corporal punishment, parents' perception of the normativeness of corporal punishment in their community, parents' progressive parenting attitudes, parents' endorsement of aggression, parents' education, children's externalizing problems, and children's internalizing problems at each of the three levels. Individual-level predictors (especially child externalizing behaviors) as well as cultural-level predictors (especially normativeness of corporal punishment in the community) predicted corporal punishment and neglect. Findings are framed in an international context that considers how abuse and neglect are defined by the global community and how countries have attempted to prevent abuse and neglect.
Pollen assemblages from the base of silty alluvium in three wadi-fills in Cyrenaica are described. They show evidence for forest clearance and cultivation, including the likely cultivation of olive. This suggests that the samples are broadly of Graeco-Roman age, and that the silty alluvium started to accumulate in these wadis as the result of the landscape impact of agricultural expansion.
This study examined whether parents’ social information processing was related to their subsequent reports of their harsh discipline. Interviews were conducted with mothers (n = 1,277) and fathers (n = 1,030) of children in 1,297 families in nine countries (China, Colombia, Italy, Jordan, Kenya, the Philippines, Sweden, Thailand, and the United States), initially when children were 7 to 9 years old and again 1 year later. Structural equation models showed that parents’ positive evaluations of aggressive responses to hypothetical childrearing vignettes at Time 1 predicted parents’ self-reported harsh physical and nonphysical discipline at Time 2. This link was consistent across mothers and fathers, and across the nine countries, providing support for the universality of the link between positive evaluations of harsh discipline and parents’ aggressive behavior toward children. The results suggest that international efforts to eliminate violence toward children could target parents’ beliefs about the acceptability and advisability of using harsh physical and nonphysical forms of discipline.