SNOWPACK CONTROLS ON HYDROLOGIC RESPONSE TO EXTREME RAIN-ON-SNOW EVENTS IN THE NORTHERN SIERRA NEVADA

Continuous, near-real time predictions of winter flooding are critical to balancing the protection of life and property with providing water resources for consumptive use in California’s northern Sierra Nevada. Rain-on-snow (ROS) events are a major cause of floods in the region and are expected to increase as a result of climate change. During ROS, the amount of terrestrial water input (TWI) draining from the snowpack is the major driver of floods and depends on the snowpack's capacity to refreeze liquid water, its transmissivity, and the magnitude of snow melt during the event. The outcome is an interplay between (1) the amount and intensity of precipitation, (2) the antecedent conditions of the snowpack and (3) the potential for incoming energy to melt snow and drain additional water. An incomplete understanding and insufficient measurement of these interacting processes limits the skill of flood prediction in mountain regions. In this study, antecedent snowpack conditions, specifically cold content, density, liquid water content and SWE, are examined to understand how these factors modulate TWI during ROS. Data from three SNOTEL stations, common in the Western U.S., across a 500 m elevation gradient on the eastern side of California’s Sierra Nevada mountains are used as input to a physically-based model that simulates liquid water drainage explicitly (SNOWPACK). Hourly forcing parameters were developed to calibrate and validate the SNOWPACK model to the SNOTEL stations spanning water years 1981-2019 and 149 ROS events. During the 149 historical events, the snowpack mitigated TWI for 80% of events, 13% had no mitigation, and 7% had conditions for active melt. Mean TWI increased 32% from the lowest elevation (58 mm of water) to the highest elevation (85 mm of water). As expected, the amount of TWI depends on total rainfall, however, that events with TWI/rain ratios>1.0 produce the largest event streamflows. When antecedent conditions were varied in reasonable ways, total TWI response varies 46% on average across eight extreme events. A key result is that snowpack cold content explains the majority of TWI variability. Riper snowpacks generated the highest TWI values for most events, with a 1 MJ decrease in cold content corresponding to 0.74 more TWI. Our results highlight the importance of cold content in TWI response across realistic antecedent conditions. Cold content is rarely measured and effectively not included in operational flood forecast models. As ROS becomes increasingly frequent in a warming climate, enhanced observations of cold content and modeling could have important implications for improved flood forecasting

[Beta]-tubulin Genes and Benzimidazole Resistance in 'Trichostrongylus colubriformis'

This thesis describes the characterisation of the β-tubulin gene family in 'Trichostrongylus colubriformis' and the role of a particular β-tubulin locus (tcb-1) in BZ resistance and the subsequent development of a PCR (Polymerase Chain Reaction) based assay that can be used to genotype individual 'T. colubriformis' for a marker associated with a BZ resistance allele. This is the first genotypic assay for the detection of a drug resistance allele in this species of nematode and one of only two (the other detects BZ resistance in Haemonchus contortus) genotypic assays for the detection of a drug resistance gene in parasitic nematodes of sheep. The assay detects a polymorphism in a 13-tubulin allele shown to be involved in BZ resistance in an RFLP analysis. Sequence analysis of this allele revealed striking sequence homology to a β-tubulin allele shown to be involved in BZ resistance in the closely related nematode 'H. contortus' suggesting that these genes have functional homology. Comparison of these sequences with other nematode 13-tubulins suggested that the gene responsible for BZ resistance in these parasitic nematodes was closely related to the ben-1 gene in the free-living nematode 'Caenorhabditis elegans', the product of which has been shown to be responsible for BZ susceptibility in that nematode. When the PCR assay was applied to a BZ naive strain (McMaster susceptible) the resistance allele could be readily detected and the allele frequency of the resistance allele was shown to be in Hardy-Weinberg equilibrium. This suggests that the resistance allele was present in the unselected population as a natural polymorphism and that no deleterious effects were associated with the resistance allele. The assay was also applied successfully to a number of independently selected BZ resistant populations implying that the same allele was selected in each population. Clones for an additional three 'T. colubriformis' β-tubulin genes were obtained. Sequence analysis of the variable 3' ends of these genes showed that the sequence of the loci vary within 'T. colubriformis' but are highly conserved between closely related nematodes species. This degree of homology between species has only been reported for vertebrates and this is the first example of conservation of isotypic classes for β-tubulins in invertebrates

Mandatory Disclosure of Pharmaceutical Industry-Funded Events for Health Professionals

David Henry and colleagues examine compliance with new disclosure requirements of Medicines Australia, the pharmaceutical industry representative body, and argue that they fall short and instead more comprehensive reporting standards are needed

"Watch Me Grow- Electronic (WMG-E)" surveillance approach to identify and address child development, parental mental health, and psychosocial needs : study protocol

Background: The COVID-19 pandemic and the associated economic recession has increased parental psychosocial stress and mental health challenges. This has adversely impacted child development and wellbeing, particularly for children from priority populations (culturally and linguistically diverse (CALD) and rural/regional communities) who are at an already increased risk of health inequality. The increased mental health and psychosocial needs were compounded by the closure of in-person preventive and health promotion programs resulting in health organisations embracing technology and online services. Watch Me Grow- Electronic (WMG-E) – developmental surveillance platform- exemplifies one such service. WMG-E was developed to monitor child development and guide parents towards more detailed assessments when risk is identified. This Randomised Controlled Trial (RCT) aims to expand WMG-E as a digital navigation tool by also incorporating parents’ mental health and psychosocial needs. Children and families needing additional assessments and supports will be electronically directed to relevant resources in the ‘care-as-usual’ group. In contrast, the intervention group will receive continuity of care, with additional in-person assessment and ‘warm hand over’ by a ‘service navigator’ to ensure their needs are met. Methods: Using an RCT we will determine: (1) parental engagement with developmental surveillance; (2) access to services for those with mental health and social care needs; and (3) uptake of service recommendations. Three hundred parents/carers of children aged 6 months to 3 years (recruited from a culturally diverse, or rural/regional site) will be randomly allocated to the ‘care-as-usual’ or ‘intervention’ group. A mixed methods implementation evaluation will be completed, with semi-structured interviews to ascertain the acceptability, feasibility and impact of the WMG-E platform and service navigator. Conclusions: Using WMG-E is expected to: normalise and de-stigmatise mental health and psychosocial screening; increase parental engagement and service use; and result in the early identification and management of child developmental needs, parental mental health, and family psychosocial needs. If effective, digital solutions such as WMG-E to engage and empower parents alongside a service navigator for vulnerable families needing additional support, will have significant practice and policy implications in the pandemic/post pandemic period. Trial registration: The trial (Protocol No. 1.0, Version 3.1) was registered with ANZCTR (registration number: ACTRN12621000766819) on July 21st, 2021 and reporting of the trial results will be according to recommendations in the CONSORT Statement

The Management of Disclosure in Children’s Accounts of Domestic Violence: Practices of Telling and Not Telling

Children and young people who experience domestic violence are often represented as passive witnesses, too vulnerable to tell the stories of their own lives. This article reports on findings from a 2 year European research project (Understanding Agency and Resistance Strategies, UNARS) with children and young people in Greece, Italy, Spain and the UK, who had experienced domestic violence. It explores children and young people’s understandings of their own capacity to reflect on and disclose their experiences Extracts from individual interviews with 107 children and young people (age 8–18) were analysed. Three themes are presented, that illustrate children and young people’s strategies for managing disclosure: (1) “Being silenced or choosing silence?”, explores children and young people’s practices of self-silencing; (2) “Managing disclosures: Finding ways to tell” outlines how children and young people value self-expression, and the strategies they use to disclose safely; and in (3) “Speaking with many voices” considers how children and young people’s accounts of their experiences are constituted relationally, and are often polyvocal. The article concludes that children and young people can be articulate, strategic and reflexive communicators, and that good support for families struggling with domestic violence must enable space for children and young people’s voice to be heard. This is possible only in an integrated framework able to encompass multiple layers and perspectives, rather than privileging the adult point of view. Practitioners who work with families affected by domestic violence need to recognize that children and young people are able to reflect on and speak about their experiences. This requires that attention is paid to the complexity of children and young people’s communication practices, and the relational context of those communications

The community-based prevention of diabetes (ComPoD) study: A randomised, waiting list controlled trial of a voluntary sector-led diabetes prevention programme

© 2019 The Author(s). Objective: This two-site randomised trial compared the effectiveness of a voluntary sector-led, community-based diabetes prevention programme to a waiting-list control group at 6 months, and included an observational follow-up of the intervention arm to 12 months. Methods: Adults aged 18-75 years at increased risk of developing type 2 diabetes due to elevated blood glucose and being overweight were recruited from primary care practices at two UK sites, with data collected in participants' homes or community venues. Participants were randomised using an online central allocation service. The intervention, comprising the prototype "Living Well, Taking Control" (LWTC) programme, involved four weekly two-hour group sessions held in local community venues to promote changes in diet and physical activity, plus planned follow-up contacts at two, three, six, nine and 12 months alongside 5 hours of additional activities/classes. Waiting list controls received usual care for 6 months before accessing the programme. The primary outcome was weight loss at 6 months. Secondary outcomes included glycated haemoglobin (HbA1c), blood pressure, physical activity, diet, health status and well-being. Only researchers conducting analyses were blinded. Results: The target sample of 314 participants (157 each arm) was largely representative of local populations, including 44% men, 26% from ethnic minorities and 33% living in deprived areas. Primary outcome data were available for 285 (91%) participants (141 intervention, 144 control). Between baseline and 6 months, intervention participants on average lost more weight than controls (- 1.7 kg, 95% CI - 2.59 to - 0.85). Higher attendance was associated with greater weight loss (- 3.0 kg, 95% CI - 4.5 to - 1.5). The prototype LWTC programme more than doubled the proportion of participants losing > 5% of their body weight (21% intervention vs. 8% control, OR 2.83, 95% CI 1.36 to 5.90) and improved self-reported dietary behaviour and health status. There were no impacts on HbA1c, blood pressure, physical activity and well-being at 6 months and, amongst intervention participants, few further changes from six to 12-months (e.g. average weight re-gain 0.36 kg, 95% CI - 0.20 to 0.91). There were no serious adverse events but four exercise-related injuries were reported in the intervention arm. Conclusions: This voluntary sector-led diabetes prevention programme reached a broad spectrum of the population and had modest effects on weight-related outcomes, but limited impacts on other diabetes risk factors. Trial registration: Trial registration number: ISRCTN70221670, 5 September 2014 Funder (National Institute for Health Research School for Public Health Research) project reference number: SPHR-EXE-PES-COM

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension