Administration of Acts Act Amendment Act, 1979, No. 56

It has been suggested that childhood obsessive-compulsive disorder (OCD) may be a risk factor for the development of an eating disorder (ED) later in life, but prospective studies are lacking. We aimed to determine the prevalence of ED at follow-up and clinical predictors in a longitudinal clinical sample of adolescents/young adults diagnosed with OCD in childhood. All contactable (n=231) young people with OCD assessed over 9 years at a national and specialist paediatric OCD clinic were included in this study. At follow-up, 126 (57%) young people and parents completed the ED section of the Developmental and Well-being Assessment. Predictors for ED were investigated using logistic regression. In total, 16 participants (12.7%) had a diagnosis of ED at follow-up. Having an ED was associated with female gender and persistent OCD at follow-up. There was a trend for family history of ED being predictive of ED diagnosis. Five (30%) of those who developed an ED at follow-up had ED symptoms or food-related obsessions/compulsions at baseline. A difference in predictors for an ED versus other anxiety disorders at follow-up was identified. This study provides initial evidence that baseline clinical predictors such as female gender and family history of ED might be specific to the later development of ED in the context of childhood OCD. Clinicians should be alert to ED subthreshold symptoms in young girls presenting with OCD. Future longitudinal studies are needed to clarify the relationship between childhood OCD and later ED

Instrumental performance and results from testing of the BLAST-TNG receiver, submillimeter optics, and MKID arrays

Polarized thermal emission from interstellar dust grains can be used to map magnetic fields in star forming molecular clouds and the diffuse interstellar medium (ISM). The Balloon-borne Large Aperture Submillimeter Telescope for Polarimetry (BLASTPol) flew from Antarctica in 2010 and 2012 and produced degree-scale polarization maps of several nearby molecular clouds with arcminute resolution. The success of BLASTPol has motivated a next-generation instrument, BLAST-TNG, which will use more than 3000 linear polarization sensitive microwave kinetic inductance detectors (MKIDs) combined with a 2.5m diameter carbon fiber primary mirror to make diffraction-limited observations at 250, 350, and 500 $\mu$m. With 16 times the mapping speed of BLASTPol, sub-arcminute resolution, and a longer flight time, BLAST-TNG will be able to examine nearby molecular clouds and the diffuse galactic dust polarization spectrum in unprecedented detail. The 250 $\mu$m detector array has been integrated into the new cryogenic receiver, and is undergoing testing to establish the optical and polarization characteristics of the instrument. BLAST-TNG will demonstrate the effectiveness of kilo-pixel MKID arrays for applications in submillimeter astronomy. BLAST-TNG is scheduled to fly from Antarctica in December 2017 for 28 days and will be the first balloon-borne telescope to offer a quarter of the flight for "shared risk" observing by the community.Comment: Presented at SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy VIII, June 29th, 201

Genetic Predisposition for Immune System, Hormone, and Metabolic Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Study

Introduction: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a multifactorial illness of unknown etiology with considerable social and economic impact. To investigate a putative genetic predisposition to ME/CFS we conducted genome-wide single-nucleotide polymorphism (SNP) analysis to identify possible variants.Methods: 383 ME/CFS participants underwent DNA testing using the commercial company 23andMe. The deidentified genetic data was then filtered to include only non-synonymous and nonsense SNPs from exons and microRNAs, and SNPs close to splice sites. The frequencies of each SNP were calculated within our cohort and compared to frequencies from the Kaviar reference database. Functional annotation of pathway sets containing SNP genes with high frequency in ME/CFS was performed using over-representation analysis via ConsensusPathDB. Furthermore, these SNPs were also scored using the Combined Annotation Dependent Depletion (CADD) algorithm to gauge their deleteriousness.Results: 5693 SNPs were found to have at least 10% frequency in at least one cohort (ME/CFS or reference) and at least two-fold absolute difference for ME/CFS. Functional analysis identified the majority of SNPs as related to immune system, hormone, metabolic, and extracellular matrix organization. CADD scoring identified 517 SNPs in these pathways that are among the 10% most deleteriousness substitutions to the human genome

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Background Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19. Methods In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days. Patients were randomly assigned via a central web-based randomisation system (TruST). Randomisation was stratified by site and age (65 years or ≥65 years), and within each stratum, blocks were of random sizes of two, four, or six patients. Participants in both groups continued to receive other therapies required to manage their condition. Participants, study staff, and investigators were masked to the study assignment. The primary outcome was the 7-point WHO ordinal scale for clinical status at day 29 after random assignment. The intention-to-treat population included all patients who were randomly assigned and met the enrolment criteria. The safety population included all participants who received at least one dose of study medication. This study was registered with the ISRCTN registry, ISRCTN30564012. Findings Between June 5, 2020, and Jan 25, 2021, 406 patients were randomly assigned to brensocatib or placebo; 192 (47·3%) to the brensocatib group and 214 (52·7%) to the placebo group. Two participants were excluded after being randomly assigned in the brensocatib group (214 patients included in the placebo group and 190 included in the brensocatib group in the intention-to-treat population). Primary outcome data was unavailable for six patients (three in the brensocatib group and three in the placebo group). Patients in the brensocatib group had worse clinical status at day 29 after being randomly assigned than those in the placebo group (adjusted odds ratio 0·72 [95% CI 0·57–0·92]). Prespecified subgroup analyses of the primary outcome supported the primary results. 185 participants reported at least one adverse event; 99 (46%) in the placebo group and 86 (45%) in the brensocatib group. The most common adverse events were gastrointestinal disorders and infections. One death in the placebo group was judged as possibly related to study drug. Interpretation Brensocatib treatment did not improve clinical status at day 29 in patients hospitalised with COVID-19

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Dynamics of Multicultural Social Networks

Historically human endeavors around the globe are in search of bilateral relationships. Knowledge and commerce has played a very significant role in increasing the ability for humans to connect for the betterment of the human species. As the means of communication improve, mutual benefits to the community as a whole also increase. Moreover, the benefits are filtered down to members of the overall community. Recent advancement in electronic communication technologies and in knowledge, in particular, physical, chemical, engineering and medical sciences and philosophies, have facilitated nearly instantaneous multi-cultural interactions. Local problems and solutions have become global. This has generated a need for cooperation, coordination, and co-management at local and global levels. This instant communication and easy access to almost all members of the global community, with minimal cost and effort, causes an increase in uncertainty and lack of clarity in communication and misunderstanding between the members of the community. This leads to a fuzzy and stochastic environment. In short, the 21st century has seen a significant increase in the need to consider all human endeavors as being subject to random environmental fluctuations. More precisely, currently the human species is highly mobile. In this work, an attempt is made (1) to balance communities working cooperatively and cohesively with one another while preserving member ability to retain individuality and fostering an environment of cultural state diversity. We develop (2) constructive analytic algorithms that provide tools to study qualitative and quantitative properties of multicultural diverse dynamic social networks. Under network parametric space/set conditions (3) cohesion and co-existence of members of multicultural dynamic network are insured. The parametric conditions (4) are algebraically simple, easy to verify, and robust. Moreover, the presented study of parametric representations of cohesion, co-existence and consensus attributes and robustness of multicultural dynamic networks provides a quantitative tool for planning, policy and performance of human mobility processes for members of a multicultural dynamic network. We develop and investigate (5) a deterministic dynamic multicultural network. To exhibit the significance of the analysis, ideas, the complexity and limitations, we present a specific prototype model. This serves to establish the framework for finding explicit sufficient conditions in terms of system parameters for studying a complex dynamic network. Further, we decompose the cultural state domain into invariant subsets (6) and consider the behavior of members within each cultural state subset. Moreover, we analyze the relative cultural affinity between individual members relative to the center of the social network. We then (7) outline the general method for investigating a multicultural cultural network. We also demonstrate the degree of conservatism of the estimates using Euler type numerical approximation schemes. We are then able to consider how changes in the various parametric effects are reflected on the dynamics of the network. The deterministic multicultural dynamic model and analysis is extended (8) to a multicultural dynamic network under random environmental perturbations. We present a detailed prototype model for the purpose of investigation. Introducing the concept of stochastic cohesion and consensus in the context of probabilistic modes of convergence (9), the explicit sufficient conditions in terms of system parameters are given to exhibit the cohesive property of the stochastic network. The effects of random fluctuations are characterized. We then extend the stochastic model (10) to a multicultural hybrid stochastic dynamic network model. By considering a hybrid dynamic, we can explore the properties of a multicultural dynamic under the influence of both continuous-time and discrete-time cultural dynamic systems. This model captures external influences and internal changes that may have an impact on the members and system parameters of the dynamic network. We extend the ideas of global cohesion and consensus to local cohesion and consensus (11). Again, the detailed study is focused on a prototype hybrid multicultural dynamic network. Using the ideas and tools developed from the stochastic network (12), we are able to establish conditions on the network parameters for which the cultural network is locally cohesive. Using Euler-Maruyama type numerical approximation schemes to model the network, we better understand to what extent the analytically developed estimates are feasible

Parent experiences of attending a specialist clinic for assessment of their child's obsessive compulsive disorder

Background: There are few published studies that have examined parental satisfaction with child mental health assessment. This study reports parental satisfaction with assessment in a national and specialist Child and Adolescent Mental Health Service for obsessive-compulsive disorder (OCD) and related disorders. Method: Forty parents completed a specially developed questionnaire designed to assess expectations and experiences of attending a specialist assessment. Results: High levels of satisfaction were reported. Common expectations of the assessment included: advice or information about the treatment of OCD, a diagnosis or understanding of the child's problems, and an offer of treatment. Conclusions: The majority of parents reported that their expectations were met, and some suggestions for improvement to the service were noted. © 2011 The Authors. Child and Adolescent Mental Healt