HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Sensory wellbeing workshops for inpatient and day-care patients with anorexia nervosa.

BACKGROUND: The wellbeing of patients with eating disorders is one of the priorities in the "bigger picture" of treatment for eating disorders. Sensory soothing strategies for sensory sensitivities are supportive tools which could be useful in day-care and inpatient clinical programmes. METHODS: Evaluation of multiple separate sensory wellbeing workshops consisting of psychoeducation and experiential components delivered in inpatient and intensive day-care services was performed. Participants' self-report questionnaires were evaluated pre- and post-workshop. Additionally, patients' comments and qualitative feedback was collected after completion of the workshop. RESULTS: There was strong evidence that self-reported awareness of sensory wellbeing, awareness of strategies to enhance sensory wellbeing, and confidence in managing sensory wellbeing increased after the workshops with positive qualitative feedback from participants. The feedback questionnaires highlighted that patients found the sessions useful and were able to use some of the skills and strategies they learned in the workshop. CONCLUSION: This pilot work on sensory wellbeing workshops with a protocol-based format was feasible and beneficial for the patient group. Preliminary evidence suggests that delivery of similar workshops could be sensible in addition to treatment as usual in inpatient and day-care programmes.

Brief trauma therapy for occupational trauma-related PTSD/CPTSD in UK police.

BACKGROUND: Police are frequently exposed to occupational trauma, making them vulnerable to post-traumatic stress disorder (PTSD) and other mental health conditions. Through personal and occupational trauma police are also at risk of developing Complex PTSD (CPTSD), associated with prolonged and repetitive trauma. Police Occupational Health Services require effective interventions to treat officers experiencing mental health conditions, including CPTSD. However, there is a lack of guidance for the treatment of occupational trauma. AIMS: To explore differences in demographics and trauma exposure between police with CPTSD and PTSD and compare the effectiveness of brief trauma-focused therapy between these diagnostic groups. METHODS: Observational cohort study using clinical data from the Trauma Support Service, providing brief trauma-focused therapy for PTSD (cognitive behavioural therapy/eye movement desensitization and reprocessing) to UK police officers. Demographics, trauma exposure, baseline symptom severity and treatment effectiveness were compared between police with PTSD and CPTSD. Changes in PTSD, depression and anxiety symptoms were used to measure treatment effectiveness. RESULTS: Brief trauma therapy reduced symptoms of PTSD, depression and anxiety. Treatment effectiveness did not differ between CPTSD and PTSD groups. Police with CPTSD exposed to both primary and secondary occupational trauma had poorer treatment outcomes than those exposed to a single occupational trauma type. CONCLUSIONS: Brief trauma-focused interventions are potentially effective in reducing symptoms of PTSD, depression and anxiety in police with CPTSD and PTSD. Further research is needed to establish whether additional CPTSD symptoms (affect dysregulation, self-perception and relational difficulties) are also reduced.

Pre-diagnostic genotyping identifies T1D subjects with impaired Treg IL-2 signaling and an elevated proportion of FOXP3+IL-17+ cells.

T-regulatory cells (Tregs) are essential for immune tolerance, and animal studies implicate their dysfunction in type 1 diabetes (T1D) pathogenesis. Tregs require interleukin-2 (IL-2) for their suppressive function, and variants in IL-2/IL-2R pathway genes have been associated with T1D. We previously reported that recent-onset T1D subjects have an increased population of FOXP3lo Tregs that secrete the pro-inflammatory cytokine, interleukin-17 (IL-17). We hypothesize that IL-2 signaling defects may drive T1D development by skewing protective Tregs towards an inflammatory Th17 phenotype. Overall, we found that the proportion of FOXP3+IL-17+ cells in T1D subjects pre-diagnosis was unchanged compared with healthy controls. However, stratification by IL2RA single-nucleotide polymorphisms revealed that T1D subjects with the rs3118470 CC risk variant have Tregs with IL-2 signaling defects and an increased proportion of FOXP3+IL-17+ cells before diagnosis. These data suggest a potential mechanism for genetically controlled loss of Treg function via dysfunctional IL-2 signaling in T1D.

Evaluating the success of a marine protected area: A systematic review approach.

Marine Protected Areas (MPAs), marine areas in which human activities are restricted, are implemented worldwide to protect the marine environment. However, with a large proportion of these MPAs being no more than paper parks, it is important to be able to evaluate MPA success, determined by improvements to biophysical, socio-economic and governance conditions. In this study a systematic literature review was conducted to determine the most frequently used indicators of MPA success. These were then applied to a case study to demonstrate how success can be evaluated. The fifteen most frequently used indicators included species abundance, level of stakeholder participation and the existence of a decision-making and management body. Using the indicator framework with a traffic light system, we demonstrate how an MPA can be evaluated in terms of how well it performs against the indicators using secondary data from the literature. The framework can be used flexibly. For example, where no MPA data currently exist, the framework can be populated by qualitative data provided by local stakeholder knowledge. This system provides a cost-effective and straightforward method for managers and decision-makers to determine the level of success of any MPA and identify areas of weakness. However, given the variety of motivations for MPA establishment, this success needs to be determined in the context of the original management objectives of the MPA with greater weighting being placed on those objectives where appropriate.

Extracellular vesicles such as prostate cancer cell fragments as a fluid biopsy for prostate cancer.

Extracellular vesicles (EVs) are cell-derived vesicles generated through a process of cell membrane shedding or storage vesicle release, as occurs during apoptosis, necrosis or exocytosis. Initially perceived as cellular by-products or 'dust' of insignificant biological importance, recent research has shed light on the role of EVs as mediators of intercellular communication, blood coagulation and disease progression. The prostate is a source of EVs and their abundance in complex biological fluids such as plasma, serum and urine make them compelling entities for a 'fluid biopsy'. As such, prostate cancer cell fragments (PCCF) are EVs generated by the tumor resident within the prostate and are also present in blood, expressing a portion of biomarkers representative of the primary tumor. High-throughput analytical techniques to determine biomarker expression on EVs is the last hurdle towards translating the full potential of prostate EVs for clinical use. We describe current state-of-the-art methods for the analysis of prostate-derived EVs in patient fluids such as plasma and the challenges that lie ahead in this emerging field of translational research.

Clinical dietetic practice in the treatment of severe acute malnutrition in a high HIV setting.

BACKGROUND: In Sub-Saharan Africa, children commonly present with severe acute malnutrition (SAM) complicated by HIV/AIDS. In 2005, the South African Department of Health implemented the World Health Organization (WHO) Ten Step programme for the inpatient treatment of SAM. Dietary management with F75 and F100 (where the terms F75 and F100 refer to a mixture of milk, sugar, oil and a vitamin and mineral mix) may not be appropriate for relatively well resourced settings such as South Africa. METHODS: A structured questionnaire aiming to determine current clinical practice was e-mailed to all dietitians working in hospitals (n = 53) in KwaZulu-Natal who routinely treated SAM. RESULTS: When initially refeeding with no diarrhoea (ND), F75 was used exclusively by 16% of dietitians to treat infants, and by 42% of dietitians to treat children. If diarrhoea, 16% of dietitians used F75 to treat infants/children. Acidified infant formula (IF) was given if ND and lactose-free IF was given if diarrhoea. Children were often started on a lactose-free F100 equivalent omitting cautious refeeding. Some gave reduced amounts for cautious refeeding; however, the feeds osmolality was too high. The use of partially hydrolysed feeds increased if the child/infant presented with diarrhoea and/or hypoalbuminea. In the post-initial feeding phase, approximately 14% of dietitians used F100 to treat infants/children. Most gave F100 equivalents as high-energy infant/paediatric formulas. CONCLUSIONS: The dietetic practices for infants with SAM followed current expert opinion closely rather than the WHO protocol. The omission of cautious refeeding follows neither current expert opinion, nor the WHO protocol, and may predispose to the refeeding syndrome. Limited evidence indicates that partially hydrolysed formulas are less effective than low lactose low osmolality feeds in the treatment of SAM.

Bacterial water quality and network hydraulic characteristics: a field study of a small, looped water distribution system using culture-independent molecular methods.

AIMS: To determine the spatial and temporal variability in the abundance, structure and composition of planktonic bacterial assemblages sampled from a small, looped water distribution system and to interpret results with respect to hydraulic conditions. METHODS AND RESULTS: Water samples were collected from five sampling points, twice a day at 06:00 h and 09:00 h on a Monday (following low weekend demand) and a Wednesday (higher midweek demand). All samples were fully compliant with current regulated parameter standards. This study did not show obvious changes in bacterial abundance (DAPI count) or community structure Denaturing gradient gel electrophoresis analysis with respect to sample site and hence to water age; however, the study did show temporal variability with respect to both sampling day and sample times. CONCLUSIONS: Data suggests that variations in the bacterial assemblages may be associated with the local system hydraulics: the bacterial composition and numbers, over short durations, are governed by the interaction of the bulk water and the biofilm influenced by the hydraulic conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates general stability in bacterial abundance, community structure and composition within the system studied. Trends and patterns supporting the transfer of idealized understanding to the real world were evident. Ultimately, such work will help to safeguard potable water quality, fundamental to public health.

Performance of influenza rapid antigen testing in influenza in emergency department patients.

BACKGROUND: The use of rapid antigen tests to triage specimens for polymerase chain reaction (PCR) testing from emergency department patients with influenza-like illness during surveillance for novel influenza viruses has been suggested. OBJECTIVE: To measure the observed sensitivity and specificity for a widely used rapid antigen test (Binax) using a PCR-based assay (Medical Diagnostic Laboratories). METHODS: Nasopharyngeal samples were taken with flocked swabs (Copan Diagnostics) from patients presenting to the emergency department of a community hospital. Samples were analysed using a rapid antigen and a PCR-based test. PCR testing was used as the criterion reference. Sensitivity and specificity were calculated for influenza and influenza A. Positive predictive values were calculated over a range of possible prevalence. RESULTS: Samples from 566 unique patients were tested using both methods. Sensitivity was 69.1% (95% CI 58.9% to 78.1%) and specificity was 97.7% (95% CI 95.8% to 98.8%) for the detection of any influenza and 75.3% (95% CI 64.7% to 84.0%) and 97.8% (95% CI 95.9% to 98.9%), respectively, for influenza A only. The resultant positive predictive value ranges from 23% to 77% when the prevalence ranges from 1% to 10%. CONCLUSION: When planning early outbreak surveillance, provision of adequate PCR testing capacity rather than triaging specimens using rapid antigen testing for influenza is advisable.

Community pharmacist-initiated screening program for osteoporosis: randomized controlled trial.

SUMMARY: This study evaluated the effect of a multifaceted intervention (screening and patient education) by community pharmacists on testing or treatment of osteoporosis. One hundred and twenty-nine patients randomized to receive the intervention were compared to 133 patients who did not receive the intervention. Twice as many patients who got the intervention received further testing or treatment for osteoporosis. INTRODUCTION: The objective of this study was to determine the effect of a community pharmacist screening program on testing and treatment of osteoporosis. METHODS: In this randomized, controlled trial, 262 patients meeting bone mineral density (BMD) testing guidelines [men or women aged > or = 65 years or 50-64 years with one major risk factor including previous fracture, family history of osteoporosis, glucocorticoids for > 3 months, or early menopause] were allocated to intervention (129) or control (133). Intervention consisted of printed materials, education, and quantitative ultrasound. Primary outcome was a composite endpoint of BMD or prescription for osteoporosis medication within 4 months. RESULTS: Primary endpoint of BMD or osteoporosis treatment was achieved by 28 intervention patients (22%) compared with 14 controls (11%) (RR 2.1, 95% CI 1.1-3.7). This was driven by BMD testing (28 (22%) vs. 13 (10%) for controls, p = 0.011). Calcium intake increased more among intervention patients than controls (30% vs. 19%, RR 1.6, 95% CI 1.0-2.5). There was no effect on knowledge or quality of life. CONCLUSION: A pharmacist screening program doubled the number of patients tested for osteoporosis. Nevertheless, many patients eligible for BMD did not receive appropriate care suggesting more intensive interventions are needed.

Bacterial quorum sensing and cell surface electrokinetic properties.

The hypothesis tested in this paper is that quorum sensing influences the microbial surface electrokinetic properties. Escherichia coli MG1655 and MG1655 LuxS- mutant (lacking quorum-sensing gene for Autoinducer synthase AI-2) were used for this study. AI-2 production (or lack of) in both strains was analyzed using the Vibrio harveyi bioassay. The levels of extracellular AI-2 with and without glucose in the growth medium were consistent with previously published work. The surface electrokinetic properties were determined for each strain of E. coli MG1655 by measuring the electrophoretic mobility using a phase amplitude light-scattering (PALS) Zeta potential analyser. The findings show that the surface charge of the cells is dependent upon the stage in the growth phase as well as the ability to participate in quorum sensing. In addition, significant differences in the electrophoretic mobility were observed between both strains of E. coli. These findings suggest that quorum sensing plays a significant role in the surface chemistry of bacteria during their growth.

Role of nonadsorbing polymers in bacterial aggregation.

Bacteria exhibit properties similar to those of nonbiological colloids and can display pairwise attractions when in close proximity. This interaction is governed by the surface chemistry of the cells. We seek to understand bacterial aggregation at the cellular level using Escherichia coli (E. coli) AB1157. Aggregation studies were carried out using 0.5 to 2.5 wt% E. coli AB1157 harvested in different growth phases with varying concentrations of a nonadsorbing polymer, sodium polystyrene sulfonate (SPS). The electrophoretic mobility of E. coli AB1157 in different growth phases was determined using phase-amplitude light scattering. E. coli AB1157 was found to be negatively charged, and the cell surface properties changed in different growth phases. The electrokinetic results correlated well with the different concentrations of nonadsorbing polymer needed to induce depletion aggregation. This shows that a difference in aggregation properties is due to changes in the bacteria electrokinetic properties during their growth.

Investigating the effect of storm events on the particle size distribution in a combined sewer simulator.

The changes in particle size of sewer sediment particles rapidly eroded from a previously deposited sediment bed are described, using a rotating annular flume as a laboratory scale sewer simulator. This is the first time that particle size distributions of eroded sewer sediments from a previously deposited sediment bed have been monitored in such a controlled experimental environment. Sediments from Loenen, The Netherlands and Dundee, UK were used to form deposits in the base of the annular flume (WL Delft Netherlands) with varying conditions for consolidation in order to investigate the effect of changing consolidation time, temperature and sediment type on the amount and size of particles eroded from a bed under conditions of increasing shear. The median size of the eroded particles did not change significantly with temperature, although the eroded suspended solids concentration was greater for the higher temperature under the same shear stresses, indicating a weaker bed deposit. An increase in consolidation time caused an increase in median size of eroded solids at higher bed shear stresses, and this was accompanied by higher suspended solids concentrations. As the shear stress increased, the solids eroded from the bed developed under a longer consolidation time (56 hours) tended towards a broad unimodal distribution, whilst the size distribution of solids eroded from beds developed under shorter consolidation times (18 or 42 hours) retained a bi- or tri-modal distribution. Using different types of sediment in the flume had a marked effect on the size of particles eroded.

Modelling the effect of shear history on activated sludge flocculation.

The aim of this paper is to investigate the effect of shear history on activated sludge flocculation dynamics and to model the observed relationships using population balances. Activated sludge flocs are exposed to dramatic changes in the shear rate within the treatment process, as they pass through localised high and low mixing intensities within the aeration basin and are cycled through the different unit operations of the treatment process. We will show that shear history is a key factor in determining floc size, and that the floc size varies irreversibly with changes in shear rate. A population balance model of the flocculation process is also introduced and evaluated.

Reproductive life events and sexual functioning in women: case reports.

Are reproductive life events in women associated with an increased risk of sexual dysfunction? Female sexual dysfunction effects up to 40% of women in the United States between 18 and 59 years of age. Sexual dysfunction may be accompanied by fluctuations in gonadal hormone secretion, making women more vulnerable to sexual symptoms, especially during times of reproductive life events. Reproductive life events, such as the use of birth control pills, various phases of the menstrual cycles, postpartum and lactation states, and perimenopause, are highly correlated with changes in sex steroids. As an understanding of the role of sex steroids on sexual functioning is elucidated, clinicians will be able to offer more specific and effective treatment options for women during various phases of reproductive life. Several case studies are presented to illustrate the unique clinical considerations that a clinician must consider when treating the biologic component of female sexual dysfunction.

Modelling the activated sludge flocculation process combining laser light diffraction particle sizing and population balance modelling (PBM).

A technique based on laser light diffraction is shown to be successful in collecting on-line experimental data. Time series of floc size distributions (FSD) under different shear rates (G) and calcium additions were collected. The steady state mass mean diameter decreased with increasing shear rate G and increased when calcium additions exceeded 8 mg/l. A so-called population balance model (PBM) was used to describe the experimental data. This kind of model describes both aggregation and breakage through birth and death terms. A discretised PBM was used since analytical solutions of the integro-partial differential equations are non-existing. Despite the complexity of the model, only 2 parameters need to be estimated; the aggregation rate and the breakage rate. The model seems, however, to lack flexibility. Also, the description of the floc size distribution (FSD) in time is not accurate.

Activated sludge flocculation: direct determination of the effect of calcium ions.

The effect of calcium on activated sludge flocculation dynamics is investigated using a unique experimental technique. The technique allows on-line analysis of the size of activated sludge flocs during flocculation and provides valuable insight into the mechanisms of flocculation. Activated sludge samples were firstly sonicated for 3 minutes at 50 W and then stirred at 100 rpm. The floc size was subsequently measured on-line using a Malvern Mastersizer/E. For concentrations of calcium less than 4 meq/L no significant increase in final floc size was observed even though an increase in the initial rate of change of floc size could be seen. Addition of calcium greater than 4 meq/L resulted in a dramatic increase in floc size. Results from this investigation support the theory that cations are involved in flocculation through cationic bridging, and will be used in ongoing investigations to model the flocculation process.

Practice-based research: lessons from community pharmacist participants.

We designed this project to determine community pharmacists' opinions regarding the challenges and motivations of their recent participation in a pharmacy practice-based research study At the conclusion of a randomized, multicenter study, 87 community pharmacist-investigators were sent a questionnaire that explored four areas: motivating factors to participate, barriers to participation, communication tools used by study coordinators, and design issues for future studies. Fifty-eight (67%) completed questionnaires were returned. Key factors motivating participation in the study were desire to improve the profession and opportunity to learn. Time was the greatest barrier to participation. Pharmacy practice-based research has two distinct advantages. First, it translates clinical knowledge into direct application in the community. Second, it provides needed data to demonstrate the value of enhanced pharmacy practice. Thorough understanding of pharmacists' opinions is necessary to optimize the design of future studies.

Women's regrets after bilateral prophylactic mastectomy.

BACKGROUND: Primary prevention strategies such as chemopreventive agents (e.g., tamoxifen) and bilateral prophylactic mastectomy (PM) have received increasingly more attention as management options for women at high risk of developing breast cancer. METHODS: A total of 370 women, who had registered in the Memorial Sloan-Kettering Cancer Center National Prophylactic Mastectomy Registry, reported having undergone a bilateral PM. Twenty-one of these women expressed regrets about their decision to have a PM. A psychiatrist and psychologist interviewed 19 of the women about their experiences with the PM. RESULTS: A physician-initiated rather than patient-initiated discussion about the PM represented the most common factor in these women. Psychological distress and the unavailability of psychological and rehabilitative support throughout the process were the most commonly reported regrets. Additional regrets about the PM related to cosmesis, perceived difficulty of detecting breast cancer in the remaining breast tissue, surgical complications, residual pain, lack of education about the procedure, concerns about consequent body image, and sexual dysfunction. CONCLUSIONS: Although a PM statistically reduces the chances of a woman developing breast cancer, the possibility of significant physical and psychological sequelae remains. Careful evaluation, education, and support both before and after the procedure will potentially reduce the level of distress and dissatisfaction in these women. We discuss recommendations for the appropriate surgical and psychiatric evaluation of women who are considering a PM as risk-reducing surgery.

Dual effects of L-3,4-dihydroxyphenylalanine on aromatic L-amino acid decarboxylase, dopamine release and motor stimulation in the reserpine-treated rat: evidence that behaviour is dopamine independent.

The comparative effects of L-3,4-dihydroxphenylalanine (L-DOPA) on dopamine synthesis, release and behaviour were studied in the reserpine-treated rat. Acute administration of L-DOPA (25-200 mg/kg) dose-dependently inhibited the activity of aromatic L-amino acid decarboxylase (AADC) in the substantia nigra and corpus striatum. The antiparkinsonian drugs budipine (10 mg/kg) and amantadine (40 mg/kg) enhanced AADC activity in these regions, and prevented or reversed AADC inhibition by L-DOPA. Dual probe dialysis revealed that low doses of L-DOPA (25-50 mg/kg) dose-dependently stimulated the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in nigra and striatum, whilst high doses of L-DOPA (100-200 mg/kg) completely suppressed the release of dopamine, but not DOPAC. Sulpiride (50 microM) administered via the probes antagonized dopamine release in response to 25 mg/kg L-DOPA, but greatly facilitated release by 200 mg/kg L-DOPA. Dopamine release was blocked by the centrally acting AADC inhibitor NSD 1015, but facilitated by the central AADC activator budipine. In behavioural tests L-DOPA (plus benserazide, 50 mg/kg) only reversed akinesia at 200 mg/kg, and not at 25-100 mg/kg. Pretreatment with either NSD 1015 (100 mg/kg) or budipine (10 mg/kg) markedly potentiated the motor stimulant action of a threshold dose of L-DOPA (100 mg/kg). A combination of NSD 1015 (100 mg/kg) and benserazide (50 mg/kg) potentiated L-DOPA behaviour more effectively than either inhibitor alone. NSD 1015-facilitated L-DOPA behaviour was antagonized by sulpiride (100 mg/kg) and not by SCH 23390 (1 mg/kg), whereas budipine-facilitated L-DOPA behaviour was fully antagonized by SCH 23390 and only partially by sulpiride. These results show that behaviourally active doses of L-DOPA in the reserpinized rat are not accompanied by significant increases in extracellular dopamine and are therefore probably not dopamine mediated. We propose that L-DOPA is capable of directly stimulating dopamine D2 and possibly non-dopamine receptors, thereby inhibiting dopamine efflux presynaptically and promoting motor activation postsynaptically. A stimulant action of L-DOPA on motor behaviour, preferentially mediated by D1 > D2 receptors, suggests that L-DOPA may also be capable of yielding a dopamine-like response in the absence of detectable dopamine release. These findings are incorporated into a new model of L-DOPA's actions in the reserpinized rat, and their possible implications for our understanding of L-DOPA in Parkinson's disease are discussed.