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Tuberculosis (TB) in children is a critical public health issue. In Bohol, Philippines, we found a high tuberculin skin test (TST)-positive prevalence (weighted prevalence = 6.4%) among 5476 children (<15 years) from 184 villages, with geographically isolated communities having prevalence as high as 29%. Therefore, we conducted a geospatial and hot spot analysis to examine the association between villages with high TST-positive prevalence (⩾6.5%) and access to medical care (distance (in kilometres and minutes of travel time) to the municipal Rural Health Units (RHU)), access to healthcare resources (distance to Provincial Health Office (PHO)) and socioeconomic determinants of health. Hot spot analysis revealed significant clusters of TST-positive prevalence in villages farthest from the PHO. Based on univariate analysis, the following variables associated with high prevalence were included in the multivariate model: minutes of travel time to the PHO, distance to the PHO, island villages and total deprivation based on socioeconomic indicators. In the final model, only distance to PHO in minutes was significant (P = 0.005). When evaluated further, greater than 1-hour drive significantly increased risk for TST-positivity (P = 0.003). Distance to healthcare resources likely increases the risk of TB transmission within the community. Expanding TB control efforts to geographically isolated areas is critical.
Epidemiological studies have reported that the increased risk of developing psychosis in cannabis users is dose related. In addition, experimental research has shown that the active constituent of cannabis responsible for its psychotogenic effect is Delta-9-Tetrahydrocannabinol (THC) (Murray et al, 2007). Recent evidence has suggested an increased in potency (% TCH) in the cannabis seized in the UK (Potter et al, 2007).
We predicted that first episode psychosis patients are more likely to use higher potency cannabis and more frequently than controls.
We collected information concerning socio-demographic, clinical characteristics and cannabis use (age at first use, frequency, length of use, type of cannabis used) from a sample of 191 first-episode psychosis patients and 120 matched healthy volunteers. All were recruited as part of the Genetic and Psychosis (GAP) study which studied all patients who presented to the South London and Maudsley Trust.
There was no significant difference in the life-time prevalence of cannabis use or age at first use between cases and controls. However, cases were more likely to be regular users (p=0.05), to be current users (p=0.04) and to have smoked cannabis for longer (p=0.01). Among cannabis users, 86.8% of 1st Episode Psychosis Patients preferentially used Skunk/Sinsemilla compared to 27.7% of Controls. Only 13.2 % of 1st Episode psychosis Patients chose to use Resin/Hash compared to 76.3% of controls. The concentration of TCH in these in South East London, ranges between 8.5 and 14 % (Potter et al, 2007). Controls (47%) were more likely to use Hash (Resin) whose average TCH concentration is 3.4% (Potter et al, 2007).
Patients with first episode psychosis have smoked higher potency cannabis, for longer and with greater frequency, than healthy controls.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
Different manufacturers recommend different levels of disinfection for oxygen nipple and nut adaptors, also known as Christmas-tree adaptors (CTAs). We aimed to determine the bacterial contamination rates of CTAs before and after clinical use and whether disinfection wipes effectively eliminate bacteria from CTAs.
CTAs were swabbed for bacteria directly from the shipment box or after use in a medical intensive care unit to determine levels of contamination. CTAs were also inoculated in the laboratory with a variety of bacteria and disinfected with either 0.5% hydrogen peroxide (Oxivir 1) or 0.25% tetra-ammonium chloride with 44.50% isopropyl alcohol (Super Sani-Cloth), and the effectiveness of each wipe was determined by comparing the bacterial recovery before and after disinfection.
CTAs exhibit low levels of bacterial burden before and after clinical use. Both disinfecting wipes were effective at removing bacteria from the CTAs.
Low-level disinfection of CTAs is appropriate prior to redeployment in the clinical setting.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
This paper reports on: (1) an evaluation of a common elements treatment approach (CETA) developed for comorbid presentations of depression, anxiety, traumatic stress, and/or externalizing symptoms among children in three Somali refugee camps on the Ethiopian/Somali border, and (2) an evaluation of implementation factors from the perspective of staff, lay providers, and families who engaged in the intervention.
This project was conducted in three refugee camps and utilized locally validated mental health instruments for internalizing, externalizing, and posttraumatic stress (PTS) symptoms. Participants were recruited from either a validity study or from referrals from social workers within International Rescue Committee Programs. Lay providers delivered CETA to youth (CETA-Youth) and families, and symptoms were re-assessed post-treatment. Providers and families responded to a semi-structured interview to assess implementation factors.
Children who participated in the CETA-Youth open trial reported significant decreases in symptoms of internalizing (d = 1.37), externalizing (d = 0.85), and posttraumatic stress (d = 1.71), and improvements in well-being (d = 0.75). Caregivers also reported significant decreases in child symptoms. Qualitative results were positive toward the acceptability and appropriateness of treatment, and its feasibility.
This project is the first to examine a common elements approach (CETA: defined as flexible delivery of elements, order, and dosing) with children and caregivers in a low-resource setting with delivery by lay providers. CETA-Youth may offer an effective treatment that is easier to implement and scale-up versus multiple focal interventions. A fullscale randomized clinical trial is warranted.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
Violence against women and girls (VAWG) is an urgent global health problem. Root causes for VAWG include the individual- and family-level factors of alcohol abuse, mental health problems, violence exposure, and related adverse experiences. Few studies in low- and middle-income countries (LMIC) have assessed the effectiveness of psychological interventions for reducing VAWG. This randomized controlled trial, part of the What Works to Prevent Violence Against Women and Girls consortium, examines the effectiveness of a common elements treatment approach (CETA) for reducing VAWG and comorbid alcohol abuse among families in Zambia.
Study participants are families consisting of three persons: an adult woman, her male husband or partner, and one of her children aged 8–17 (if available). Eligibility criteria include experience of moderate-to-severe intimate partner violence by the woman and hazardous alcohol use by her male partner. Family units are randomized to receive CETA or treatment as usual. The primary outcome is VAWG as measured by the Severity of Violence Against Women Scale, assessed along with secondary outcomes at 24 months post-baseline. Interim assessments are also conducted at 4–5 months (following CETA completion) and 12 months post-baseline.
This ongoing trial is one of the first in sub-Saharan Africa to evaluate the use of an evidence-based common elements approach for reducing VAWG by targeting a range of individual- and family-level factors, including alcohol abuse. Results of this trial will inform policy on what interventions work to prevent VAWG in LMIC with local perspectives on scale up and wider implementation.
Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.
We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.
Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.
Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
Studies from low- and middle-income countries (LMIC) indicate that the use of audio computer-assisted self-interviewing (ACASI) is associated with more accurate reporting of sensitive behaviors (e.g. substance use and sexual risk behaviors) compared with interviewer-administered questionnaires. There is a lack of published information on the process of designing, developing, and implementing ACASI in LMIC. In this paper we describe our experience implementing an ACASI system for use with a population of orphans and vulnerable children in Zambia.
A questionnaire of mental health, substance use, and HIV risk behaviors was converted into an ACASI system, tested in pilot and validity studies, and implemented for use in a randomized controlled trial. Successes, barriers, and challenges associated with each stage in the development and implementation of ACASI are described.
We were able to convert a lengthy and complex survey into an ACASI system that was feasible for use in Zambia. Lessons learned include the importance of: (1) piloting the written and electronic versions; (2) proper and extensive training for study assessors to use ACASI and for those doing voice recordings; and (3) attention to logistics such as appropriate space, internet, and power.
We found that ACASI was feasible and acceptable in Zambia with proper planning, training, and supervision. Given mounting evidence indicating that ACASI provides more accurate self-report data and immediate data download compared with interview-administered measures, it may be an effective and economical alternative for behavioral health research studies in LMIC.
Driven by the unprecedented wealth of high quality data that is accumulating for the Frontier Fields, they are becoming some of the best-studied strong lensing clusters to date, and probably the next few years. As will be discussed intensively in this focus meeting, the FF prove transformative for many fields: from studies of the high redshift Universe, to the assembly and structure of the clusters themselves. The FF data and the extensive collaborative effort around this program will also allow us to examine and improve upon current lens modeling techniques. Strong lensing is a powerful tool for mass reconstruction of the cores of galaxy clusters of all scales, providing an estimate of the total (dark and seen) projected mass density distribution out to 0.5 Mpc. Though SL mass may be biased by contribution from structures along the line of sight, its strength is that it is relatively insensitive to assumptions on cluster baryon astrophysics and dynamical state. Like the Frontier Fields clusters, the most “famous” strong lensing clusters are at the high mass end; they lens dozens of background sources into multiple images, providing ample lensing constraints. In this talk, I will focus on how we can leverage what we learn from modeling the FF clusters in strong lensing studies of the hundreds of clusters that will be discovered in upcoming surveys. In typical clusters, unlike the Frontier Fields, the Bullet Cluster and A1689, we observe only one to a handful of background sources, and have limited lensing constraints. I will describe the limitations that such a configuration imposes on strong lens modeling, highlight measurements that are robust to the richness of lensing evidence, and address the sources of uncertainty and what sort of information can help reduce those uncertainties. This category of lensing clusters is most relevant to the wide cluster surveys of the future.
Overvaluation of body shape/weight is thought to be the core psychopathology underlying eating disorders, which propels engagement in non-compensatory weight-control behaviors. In turn, these behaviors lead to binge eating and/or maintenance of low weight thereby reinforcing overvaluation. The present study investigated the reciprocal relationship between overvaluation and engagement in non-compensatory weight-control behaviors (defined in two ways: restrictive eating and compulsive exercise) among women diagnosed with anorexia nervosa or bulimia nervosa (N = 237).
Participants completed clinical interviews in which weekly eating disorder symptoms and behaviors were assessed over 2 years.
Overvaluation on a given week was associated with greater engagement in non-compensatory weight-control behaviors during the following week. Further, engagement in non-compensatory weight-control behaviors on a given week was associated with greater overvaluation during the following week. These findings held true regardless of participants’ shape/weight concerns (feelings of fatness and fat phobia), and eating disorder diagnosis.
Our data provide empirical support for key aspects of the transdiagnostic cognitive-behavioral model of eating disorders and suggest that targeting non-compensatory weight-control behaviors in treatment may help alleviate overvaluation and shape/weight concerns.
Depression is characterized by poor executive function, but – counterintuitively – in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study.
One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials).
Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r = −0.28, p = 0.007).
Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.
A novel influenza virus emerged in the United States in spring 2009, rapidly becoming a global pandemic. Children were disproportionally affected by the novel influenza A(H1N1) pandemic virus [A(H1N1)pdm]. This retrospective electronic medical record review study aimed to identify clinical predictors of disease severity of influenza A(HIN1)pdm infection in paediatric patients. Disease severity was defined on an increasing three-level scale from non-hospitalized, hospitalized, and admitted to the intensive care unit (ICU). From April 2009 to June 2010, 696 children presented to Texas Children's Hospital's emergency department, 38% were hospitalized, and 17% were admitted to the ICU. Presenting symptoms associated with severe influenza were dyspnoea [odds ratio (OR) 5·82], tachycardia (OR 2·61) and fatigue (OR 1·96). Pre-existing health conditions associated with disease severity included seizure disorder (OR 4·71), obesity (OR 3·28), lung disease (OR 2·84), premature birth (OR 2·53), haematological disease (OR 2·22), and developmental delay (OR 2·20). According to model fitness tests, presenting symptoms were more likely to predict severe influenza than underlying medical conditions. However, both are important risk factors. Recognition of clinical characteristics associated with severe disease can be used for triaging case management of children during future influenza outbreaks.
Growing evidence supports the use of Western therapies for the treatment of depression, trauma, and stress delivered by community health workers (CHWs) in conflict-affected, resource-limited countries. A recent randomized controlled trial (Bolton et al. 2014a) supported the efficacy of two CHW-delivered interventions, cognitive processing therapy (CPT) and brief behavioral activation treatment for depression (BATD), for reducing depressive symptoms and functional impairment among torture survivors in the Kurdish region of Iraq.
This study describes the adaptation of the CHW-delivered BATD approach delivered in this trial (Bolton et al. 2014a), informed by the Assessment–Decision–Administration-Production–Topical experts–Integration–Training–Testing (ADAPT–ITT) framework for intervention adaptation (Wingood & DiClemente, 2008). Cultural modifications, adaptations for low-literacy, and tailored training and supervision for non-specialist CHWs are presented, along with two clinical case examples to illustrate delivery of the adapted intervention in this setting.
Eleven CHWs, a study psychiatrist, and the CHW clinical supervisor were trained in BATD. The adaptation process followed the ADAPT–ITT framework and was iterative with significant input from the on-site supervisor and CHWs. Modifications were made to fit Kurdish culture, including culturally relevant analogies, use of stickers for behavior monitoring, cultural modifications to behavioral contracts, and including telephone-delivered sessions to enhance feasibility.
BATD was delivered by CHWs in a resource-poor, conflict-affected area in Kurdistan, Iraq, with some important modifications, including low-literacy adaptations, increased cultural relevancy of clinical materials, and tailored training and supervision for CHWs. Barriers to implementation, lessons learned, and recommendations for future efforts to adapt behavioral therapies for resource-limited, conflict-affected areas are discussed.
Mass spectrometry is one of the primary analysis techniques for biological analysis but there are technological barriers in sampling scale that must be overcome for it to be used to its full potential on the size scale of single cells. Current mass spectrometry imaging methods are limited in spatial resolution when analyzing large biomolecules. The goal of this project is to use atomic force microscope (AFM) tip enhanced laser ablation to remove material from cells and tissue and capture it for subsequent mass spectrometry analysis. The laser ablation sample transfer system uses an AFM stage to hold the metal-coated tip at a distance of approximately 10 nm from a sample surface. The metal tip acts as an antenna for the electromagnetic radiation and enables the ablation of the sample with a spot size much smaller than a laser focused with a conventional lens system. A pulsed nanosecond UV or visible wavelength laser is focused onto the gold-coated silicon tip at an angle nearly parallel with the surface, which results in the removal of material from a spot between 500 nm and 1 µm in diameter and 200 and 500 nm deep. This corresponds to a few picograms of ablated material, which can be captured on a metal surface for MALDI analysis. We have used this approach to transfer small peptides and proteins from a thin film for analysis by mass spectrometry as a first step toward high spatial resolution imaging.