Treatment outcomes 12 months after antiretroviral therapy initiation in Oman: a nationwide study from the Middle East.

ABSTRACTWe used routinely collected programme data on people living with HIV in Oman who started ART in 2014-2018 to assess retention on ART, viral suppression, attrition (mortality or loss to follow-up [LTFU]) and treatment failure (attrition or HIV viral load of > 1000 copies/mL) 12 months after antiretroviral therapy (ART) initiation. We identified 726 patients; 72% were male. Overall, 12 months retention on ART and viral suppression (intention-to-treat [ITT] analysis) were 85.7% and 74.5%, respectively. Attrition occurred in 14.3% (mortality of 7% and LTFU of 7.3%). Retention increased from 78.8% (93/118) to 90.6% (144/159) among patients who started ART in 2014 and 2018, respectively. Similarly, ITT and on-treatment analyses revealed that viral suppression 12 months after ART initiation increased from 57.6% (68/118) and 73.1% (68/93) among patients who initiated therapy in 2014-80.5% (128/159) and 88.8% (128/144) among patients started treatment in 2018, respectively. On multivariate analysis, older age, having "Other" as an HIV risk factor (compared to heterosexual) and receiving HIV care outside the capital Muscat independently predicted both attrition and treatment failure. Our findings have been useful in identifying factors at the individual and programme level that influenced the risk of attrition and treatment failure.

Strong neutrino cooling by cycles of electron capture and ß- decay in neutron star crusts.

The temperature in the crust of an accreting neutron star, which comprises its outermost kilometre, is set by heating from nuclear reactions at large densities, neutrino cooling and heat transport from the interior. The heated crust has been thought to affect observable phenomena at shallower depths, such as thermonuclear bursts in the accreted envelope. Here we report that cycles of electron capture and its inverse, ß(-) decay, involving neutron-rich nuclei at a typical depth of about 150 metres, cool the outer neutron star crust by emitting neutrinos while also thermally decoupling the surface layers from the deeper crust. This 'Urca' mechanism has been studied in the context of white dwarfs and type Ia supernovae, but hitherto was not considered in neutron stars, because previous models computed the crust reactions using a zero-temperature approximation and assumed that only a single nuclear species was present at any given depth. The thermal decoupling means that X-ray bursts and other surface phenomena are largely independent of the strength of deep crustal heating. The unexpectedly short recurrence times, of the order of years, observed for very energetic thermonuclear superbursts are therefore not an indicator of a hot crust, but may point instead to an unknown local heating mechanism near the neutron star surface.

The first pilot study of expanded newborn screening for inborn errors of metabolism and survey of related knowledge and opinions of health care professionals in Hong Kong.

INTRODUCTION: Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM. METHODS: The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling. RESULTS: In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years. CONCLUSION: The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.

Separating the wheat from the chaff: systematic identification of functionally relevant noncoding variants in ADHD.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable psychiatric condition with negative lifetime outcomes. Uncovering its genetic architecture should yield important insights into the neurobiology of ADHD and assist development of novel treatment strategies. Twenty years of candidate gene investigations and more recently genome-wide association studies have identified an array of potential association signals. In this context, separating the likely true from false associations ('the wheat' from 'the chaff') will be crucial for uncovering the functional biology of ADHD. Here, we defined a set of 2070 DNA variants that showed evidence of association with ADHD (or were in linkage disequilibrium). More than 97% of these variants were noncoding, and were prioritised for further exploration using two tools-genome-wide annotation of variants (GWAVA) and Combined Annotation-Dependent Depletion (CADD)-that were recently developed to rank variants based upon their likely pathogenicity. Capitalising on recent efforts such as the Encyclopaedia of DNA Elements and US National Institutes of Health Roadmap Epigenomics Projects to improve understanding of the noncoding genome, we subsequently identified 65 variants to which we assigned functional annotations, based upon their likely impact on alternative splicing, transcription factor binding and translational regulation. We propose that these 65 variants, which possess not only a high likelihood of pathogenicity but also readily testable functional hypotheses, represent a tractable shortlist for future experimental validation in ADHD. Taken together, this study brings into sharp focus the likely relevance of noncoding variants for the genetic risk associated with ADHD, and more broadly suggests a bioinformatics approach that should be relevant to other psychiatric disorders.

The molecular genetic architecture of attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral condition which affects 2-10% of school age children worldwide. Although the underlying molecular mechanism for the disorder is poorly understood, familial, twin and adoption studies suggest a strong genetic component. Here we provide a state-of-the-art review of the molecular genetics of ADHD incorporating evidence from candidate gene and linkage designs, as well as genome-wide association (GWA) studies of common single-nucleotide polymorphisms (SNPs) and rare copy number variations (CNVs). Bioinformatic methods such as functional enrichment analysis and protein-protein network analysis are used to highlight biological processes of likely relevance to the aetiology of ADHD. Candidate gene associations of minor effect size have been replicated across a number of genes including SLC6A3, DRD5, DRD4, SLC6A4, LPHN3, SNAP-25, HTR1B, NOS1 and GIT1. Although case-control SNP-GWAS have had limited success in identifying common genetic variants for ADHD that surpass critical significance thresholds, quantitative trait designs suggest promising associations with Cadherin13 and glucose-fructose oxidoreductase domain 1 genes. Further, CNVs mapped to glutamate receptor genes (GRM1, GRM5, GRM7 and GRM8) have been implicated in the aetiology of the disorder and overlap with bioinformatic predictions based on ADHD GWAS SNP data regarding enriched pathways. Although increases in sample size across multi-center cohorts will likely yield important new results, we advocate that this must occur in parallel with a shift away from categorical case-control approaches that view ADHD as a unitary construct, towards dimensional approaches that incorporate endophenotypes and statistical classification methods.

Female Sexual Function Index Short Version: A MsFLASH Item Response Analysis.

The Female Sexual Function Index (FSFI) is a psychometrically sound and popular 19-item self-report measure, but its length may preclude its use in studies with multiple outcome measures, especially when sexual function is not a primary endpoint. Only one attempt has been made to create a shorter scale, resulting in the Italian FSFI-6, later translated into Spanish and Korean without further psychometric analysis. Our study evaluated whether a subset of items on the 19-item English-language FSFI would perform as well as the full-length FSFI in peri- and postmenopausal women. We used baseline data from 898 peri- and postmenopausal women recruited from multiple communities, ages 42-62 years, and enrolled in randomized controlled trials for vasomotor symptom management. Goals were to (1) create a psychometrically sound, shorter version of the FSFI for use in peri- and postmenopausal women as a continuous measure and (2) compare it to the Italian FSFI-6. Results indicated that a 9-item scale provided more information than the FSFI-6 across a spectrum of sexual functioning, was able to capture sample variability, and showed sufficient range without floor or ceiling effects. All but one of the items from the Italian 6-item version were included in the 9-item version. Most omitted FSFI items focused on frequency of events or experiences. When assessment of sexual function is a secondary endpoint and subject burden related to questionnaire length is a priority, the 9-item FSFI may provide important information about sexual function in English-speaking peri- and postmenopausal women.

MsFLASH participants' priorities for alleviating menopausal symptoms.

OBJECTIVE: To describe self-reported menopausal symptom priorities and their association with demographics and other symptoms among participants in an intervention trial for vasomotor symptoms (VMS). METHODS: Cross-sectional study embedded in the MsFLASH 02 trial, a three-by-two factorial design of yoga vs. exercise vs. usual activity and omega-3-fatty acid vs. placebo. At baseline, women (n = 354) completed hot flush diaries, a card sort task to prioritize symptoms they would most like to alleviate, and standardized questionnaires. RESULTS: The most common symptom priorities were: VMS (n = 322), sleep (n = 191), concentration (n = 140), and fatigue (n = 116). In multivariate models, women who chose VMS as their top priority symptom (n = 210) reported significantly greater VMS severity (p = 0.004) and never smoking (p = 0.012), and women who chose sleep as their top priority symptom (n = 100) were more educated (p ≤ 0.001) and had worse sleep quality (p < 0.001). ROC curves identified sleep scale scores that were highly predictive of ranking sleep as a top priority symptom. CONCLUSIONS: Among women entering an intervention trial for VMS and with relatively low prevalence of depression and anxiety, VMS was the priority symptom for treatment. A card sort may be a valid tool for quickly assessing symptom priorities in clinical practice and research.

A multifaceted pharmacist intervention to improve antihypertensive adherence: a cluster-randomized, controlled trial (HAPPy trial).

WHAT IS KNOWN AND OBJECTIVES: About half of all patients taking antihypertensives discontinue treatment by 12 months. There is potential for substantial health gains at both individual and population levels through improved treatment adherence. The objective was to evaluate a community pharmacist intervention to improve adherence with antihypertensive medicines with a view to improving blood pressure (BP) control. DESIGN: prospective, non-blinded, cluster-randomized, controlled trial. PARTICIPANTS: adults with primary hypertension who obtained antihypertensives in the previous 6 months. Patients with poor refill adherence were preferentially identified with the help of a purpose-built software application. INTERVENTION: package comprising BP monitor; training on BP self-monitoring; motivational interviewing; medication use review; prescription refill reminders. FOLLOW-UP: six months. PRIMARY OUTCOME: change in proportion self-reporting medication adherence. Secondary outcome: BP changes. RESULTS: Participants (n = 395; intervention - 207; control - 188) had a mean age of 66.7 years; 51.1% were males. The proportion of adherent participants increased in both groups but was not significantly different between groups [57·2% to 63·6% (control) vs. 60·0% to 73·5% (intervention), P = 0·23]. The mean reduction in systolic BP was significantly greater in the intervention group (10·0 mmHg vs. 4·6 mmHg; P = 0·05). The proportion of patients who were non-adherent at baseline and adherent at 6 months was 22·6% (95%CI 5·1-40·0%) higher in the intervention group (61·8% vs. 39·2%, P = 0·007). Among participants with baseline BP above target, reduction of systolic BP was significantly greater in the intervention group [by 7·2 mmHg (95%CI 1·6-12·8 mmHg); (P = 0·01)]. Among participants non-adherent at baseline and above target BP, the proportion reporting adherence at 6 months was significantly greater in the intervention group [56·8% vs. 35·9%, P = 0·039). WHAT IS NEW AND CONCLUSION: This community pharmacist intervention resulted in improved adherence to antihypertensive medication and reduced systolic BP.

The relationship between the size and asymmetry of the lateral ventricles and cortical myelin content in individuals with mood disorders.

Background: Although enlargement of the lateral ventricles was previously observed in individuals with mood disorders, the link between ventricular size and asymmetry with other indices of brain structure remains underexplored. In this study, we examined the association of lateral ventricular size and asymmetry with cortical myelin content in individuals with bipolar (BD) and depressive (DD) disorders compared to healthy controls (HC). Methods: Magnetic resonance imaging (MRI) was used to obtain T1w and T2w images from 149 individuals (age=27.7 (SD=6.1) years, 78% female, BD=38, DD=57, HC=54). Cortical myelin content was calculated using the T1w/T2w ratio. Elastic net regularized regression identified brain regions whose myelin content was associated with ventricular size and asymmetry. A post-hoc linear regression examined how participants' diagnosis, illness duration, and current level of depression moderated the relationship between the size and asymmetry of the lateral ventricles and levels of cortical myelin in the selected brain regions. Results: Individuals with mood disorders had larger lateral ventricles than HC. Larger ventricles and lower asymmetry were observed in individuals with BD who had longer lifetime illness duration and more severe current depressive symptoms. A greater left asymmetry was observed in participants with DD than in those with BD (p<0.01). Elastic net revealed that both ventricular enlargement and asymmetry were associated with altered myelin content in cingulate, frontal, and sensorimotor cortices. In BD, but not other groups, ventricular enlargement was related to altered myelin content in the right insular regions. Conclusions: Lateral ventricular enlargement and asymmetry are linked to myelin content imbalance, thus, potentially leading to emotional and cognitive dysfunction in mood disorders.

Emission lines due to ionizing radiation from a compact object in the remnant of Supernova 1987A.

The nearby Supernova 1987A was accompanied by a burst of neutrino emission, which indicates that a compact object (a neutron star or black hole) was formed in the explosion. There has been no direct observation of this compact object. In this work, we observe the supernova remnant with JWST spectroscopy, finding narrow infrared emission lines of argon and sulfur. The line emission is spatially unresolved and blueshifted in velocity relative to the supernova rest frame. We interpret the lines as gas illuminated by a source of ionizing photons located close to the center of the expanding ejecta. Photoionization models show that the line ratios are consistent with ionization by a cooling neutron star or a pulsar wind nebula. The velocity shift could be evidence for a neutron star natal kick.

Identification of a novel HLA-DRB1*11:129 allele in a Chinese individual by sequence-based typing.

The new DRB1*11:129 allele differs from the closest matching allele HLA-DRB1*11:06:01 by one nucleotide substitution in exon 3 at position 623 (G→A).

Dairy products and colorectal cancer risk: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Previous studies of the association between intake of dairy products and colorectal cancer risk have indicated an inverse association with milk, however, the evidence for cheese or other dairy products is inconsistent. METHODS: We conducted a systematic review and meta-analysis to clarify the shape of the dose-response relationship between dairy products and colorectal cancer risk. We searched the PubMed database for prospective studies published up to May 2010. Summary relative risks (RRs) were estimated using a random effects model. RESULTS: Nineteen cohort studies were included. The summary RR was 0.83 (95% CI [confidence interval]: 0.78-0.88, I2=25%) per 400 g/day of total dairy products, 0.91 (95% CI: 0.85-0.94, I2=0%) per 200 g/day of milk intake and 0.96 (95% CI: 0.83-1.12, I2=28%) per 50 g/day of cheese. Inverse associations were observed in both men and women but were restricted to colon cancer. There was evidence of a nonlinear association between milk and total dairy products and colorectal cancer risk, P<0.001, and the inverse associations appeared to be the strongest at the higher range of intake. CONCLUSION: This meta-analysis shows that milk and total dairy products, but not cheese or other dairy products, are associated with a reduction in colorectal cancer risk.

Carbohydrates, glycemic index, glycemic load, and colorectal cancer risk: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Dietary carbohydrate, glycemic index, and glycemic load are thought to influence colorectal cancer risk through hyperinsulinemia. We review and quantitatively summarize in a meta-analysis the evidence from prospective cohort studies. METHODS: We searched the PubMed database for prospective studies of carbohydrate, glycemic index, and glycemic load and colorectal cancer risk, up to October 2011. Summary relative risks were estimated by the use of a random effects model. RESULTS: We identified 14 cohort studies that could be included in the meta-analysis of carbohydrate, glycemic index, and glycemic load and colorectal cancer risk. The summary RR for high versus low intake was 1.00 (95% CI: 0.87-1.14, I2 = 31%) for carbohydrate, 1.07 (95% CI: 0.99-1.16, I2 = 28%) for glycemic index, and 1.00 (95% CI: 0.91-1.10, I2 = 39%) for glycemic load. In the dose-response analysis, the summary RR was 0.95 (95% CI: 0.84-1.07, I2 = 58%) per 100 grams of carbohydrate per day, 1.07 (95% CI: 0.99-1.15, I2 = 39%) per 10 glycemic index units, and 1.01 (95% CI: 0.95-1.08, I2 = 47%) per 50 glycemic load units. Exclusion of one or two outlying studies reduced the heterogeneity, but the results were similar. CONCLUSION: This meta-analysis of cohort studies does not support an independent association between diets high in carbohydrate, glycemic index, or glycemic load and colorectal cancer risk.

Discontinuation of angiotensin-converting enzyme inhibitors: a cohort study.

WHAT IS KNOWN AND OBJECTIVE: Angiotensin-converting enzyme inhibitors (ACEI) are among the most commonly used antihypertensive agents worldwide. Factors associated with their discontinuation in clinical practice are not well defined as studies undertaken in different ethnic populations have yielded conflicting result. We aimed to identify predictors of ACEI discontinuation among Chinese patients. METHODS: We used a validated clinical database for this cohort study. We included all adult patients aged ≥ 18 years who visited any primary care clinic in one Territory of Hong Kong and who were prescribed an ACEI from January 2004 to June 2007. The cumulative incidence of discontinuation 180 days after prescription of an ACEI was measured. Factors associated with discontinuation were evaluated by multiple regression analyses. RESULTS: Among 9398 eligible patients, 14·0% discontinued their prescriptions. After controlling for patient's age, gender, socio-economic status, service type, district of residence, visit type and number of comorbidities, patients aged 70 or above [adjusted odds ratio (AOR) = 1·27, 95% CI 1·04-1·56, P = 0·022], male subjects (AOR = 1·21, 95% CI 1·05-1·40, P = 0·008), new visitors (AOR = 0·64, 95% CI 0·55-0·75, P < 0·001), patients who obtained their prescriptions in Family Medicine Specialist Clinic (FMSC) (AOR = 1·43, 95% CI 1·14-1·79, P = 0·002), patients who lived in the less urbanized district (AOR = 1·96, 95% CI 1·55-2·48, P < 0·001) and the most rural district (AOR = 1·24, 95% CI 1·03-1·49, P = 0·027), and patients with no comorbidity, were more likely to discontinue their medications. WHAT IS NEW AND CONCLUSION: Physicians should pay attention to adherence problems particularly when prescribing ACEI to male patients, those who are older than 70 years, have no comorbidity, live in less urbanized or more rural areas, qualify for fee-waiver, are new attendees of consultations or obtain their ACEI prescriptions in FMSC. Future research should evaluate the reasons for ACEI discontinuation among these higher-risk groups.

Time-of-flight mass measurements for nuclear processes in neutron star crusts.

We present results from time-of-flight nuclear mass measurements at the National Superconducting Cyclotron Laboratory that are relevant for neutron star crust models. The masses of 16 neutron-rich nuclei in the scandium-nickel range were determined simultaneously, with the masses of (61)V, (63)Cr, (66)Mn, and (74)Ni measured for the first time with mass excesses of -30.510(890) MeV, -35.280(650) MeV, -36.900(790) MeV, and -49.210(990) MeV, respectively. With these results the locations of the dominant electron capture heat sources in the outer crust of accreting neutron stars that exhibit super bursts are now experimentally constrained. We find the experimental Q value for the (66)Fe→(66)Mn electron capture to be 2.1 MeV (2.6σ) smaller than predicted, resulting in the transition occurring significantly closer to the neutron star surface.

Disparities between HIV patient subgroups in Oman: An analysis of the 2019 cascade of care.

BACKGROUND: The HIV cascade of care is a framework for monitoring HIV care, identifying gaps and informing appropriate interventions. This study aimed to describe the cascade of care in Oman in 2019 and highlight disparities at the sub-population level. METHODS: We used the UNAIDS Spectrum modelling software to estimate the number of people living with HIV. A national HIV surveillance database was used to identify Omani people (≥13 years old) diagnosed with HIV from 1984 through December 2019. We calculated the cascade indicators as of 31 December 2019 stratified by sex, age, HIV risk factor, residence, and region of HIV care. We also performed multivariate logistic regression to determine the predictors of attrition at linkage, retention, on ART, and viral suppression. RESULTS: As of December 2019, the estimated number of people living with HIV in Oman was 2440. Out of the estimated number of people living with HIV, 69% were diagnosed, 66% were linked to care, 61% were retained in care, 60% were on ART, and 55% were virally suppressed. Of the 1673 diagnosed individuals, 96% were linked to care, 88% were retained in care, 87% were on ART, and 81% were virally suppressed. People who received HIV care outside Muscat had the largest attrition (11% loss) in the transition from linkage (97%) to retention (86%). Similarly, people aged 13-24 years had the largest attrition (13% loss) from "on ART" (88%) to viral suppression (75%). Logistic regression showed that both not reporting a specific HIV risk factor and receipt of HIV care outside Muscat independently predicted attrition at each cascade stage from linkage to care through viral suppression. CONCLUSIONS: Our findings identified substantial disparities across various subpopulations along the cascade of care in Oman. This analysis will be invaluable in informing future interventions targeting patient subgroups who are at the highest risk of attrition.

Effects of sea-level rise on physiological ecology of populations of a ground-dwelling ant.

INTRODUCTION: Sea-level rise is a consequence of climate change that can impact the ecological and physiological changes of coastal, ground-dwelling species. Sea-level rise has a potential to inundate birds, rodents, spiders, and insects that live on the ground in coastal areas. Yet, there is still much to be learned concerning the specifics of these impacts. The red imported fire ant Solenopsis invicta (Buren) excavates soil for its home and is capable of surviving flooding. Because of their ground-dwelling life history and rapid reproduction, fire ants make an ideal model for discovery and prediction of changes that may be due to sea-level rise. There are up to 500,000 individuals in a colony, and these invasive ants naturally have a painful sting. However, observations suggest that colonies of fire ants that dwell in tidally-influenced areas are more aggressive with more frequent stings and more venom injected per sting (behavioral and physiological changes) than those located inland. This may be an adaption to sea-level rise. Therefore, the objective of this study is to elucidate differences in inland and coastal defensiveness via micro-dissection and comparison of head width, head length, stinger length, and venom sac volume. But first because fire ants' ability to raft on brackish tidal water is unknown, it had to be determined if fire ants could indeed raft in brackish water and examine the behavior differences between those flooded with freshwater vs. saltwater. METHODS: To test the coastal-aggression hypothesis, inland colonies and coastal colonies, which experience relatively greater amounts of flooding, specifically regular tidal and windblown water and oscillations (i.e. El Nino Southern Oscillation) from the Gulf of Mexico, were collected. To mimic sea-level rise, the colonies were flooded in salinities that correspond to both their collection site and conditions found in a variety of locales and situations (such as storm surge from a tropical storm). Individual ants were immediately taken from each colony for dissection before flooding, 1-hour into flooding, and 24-hours into flooding. RESULTS AND DISCUSSION: Fire ants use their venom to defend themselves and to communicate alarm or aggression. Dissections and measurement of heads, venom sacs, and stingers revealed both coastal and inland colonies experience an increase in venom sac volume after 24 hours; in fact coastal colonies increased their venom volume by 75% after 24 h of flooding Whether this venom sac enlargement is due to diffusion of water or venom sac production is unknown. These ground-dwelling ants exhibit physiological and behavioral adaptations to ongoing sea-level rise possibly indicating that they are responding to increased flooding. Fire ants will raft on high-salinity water; and sea-level rise may cause stings by flooded ants to be more severe because of increased venom volume.