Commissioning and Sensitivity Studies for the SuperNEMO Demonstrator Module

The SuperNEMO experiment will search for neutrinoless double- beta decay. It is a tracker-calorimeter detector, designed to reach a 0νββ half life sensitivity of T1/2 > 1026 years, corresponding to an effective Majorana neutrino mass of 50 - 100 meV. Successful operation of the SuperNEMO tracker requires a pre- cise mixture of gases to be supplied continuously to the detector volume. The purpose of the gas system is to control the fractions of gases, at a given flow rate. Improvements have been made to meet the basic requirements of a safe, radio-pure, remotely moni- tored and controlled gas-delivery system. The SuperNEMO demonstrator module is the first phase of the experiment, with 7 kg of 82Se. Construction and commissioning of the module is well underway, with first data expected in 2022. In preparation for data taking, sensitivity studies have been per- formed on simulated data. Results of the sensitivity and relative errors of two key back- grounds, 208Tl and 214Bi, for the demonstrator module will be presented here. The enhancement of the gas system and integra- tion with slow control will also be presented

Decimation by sea star wasting disease and rapid genetic change in a keystone species, \u3cem\u3ePisaster ochraceus\u3c/em\u3e

Standing genetic variation enables or restricts a population’s capacity to respond to changing conditions, including the extreme disturbances expected to increase in frequency and intensity with continuing anthropogenic climate change. However, we know little about how populations might respond to extreme events with rapid genetic shifts, or how population dynamics may influence and be influenced by population genomic change. We use a range-wide epizootic, sea star wasting disease, that onset in mid-2013 and caused mass mortality in Pisaster ochraceus to explore how a keystone marine species responded to an extreme perturbation. We integrated field surveys with restriction site-associated DNA sequencing data to (i) describe the population dynamics of mortality and recovery, and (ii) compare allele frequencies in mature P. ochraceus before the disease outbreak with allele frequencies in adults and new juveniles after the outbreak, to identify whether selection may have occurred. We found P. ochraceus suffered 81% mortality in the study region between 2012 and 2015, and experienced a concurrent 74-fold increase in recruitment beginning in late 2013. Comparison of pre- and postoutbreak adults revealed significant allele frequency changes at three loci, which showed consistent changes across the large majority of locations. Allele frequency shifts in juvenile P. ochraceus (spawned from premortality adults) were consistent with those seen in adult survivors. Such parallel shifts suggest detectable signals of selection and highlight the potential for persistence of this change in subsequent generations, which may influence the resilience of this keystone species to future outbreaks

MR-guided radiotherapy for liver malignancies

MR guided radiotherapy represents one of the most promising recent technological innovations in the field. The possibility to better visualize therapy volumes, coupled with the innovative online adaptive radiotherapy and motion management approaches, paves the way to more efficient treatment delivery and may be translated in better clinical outcomes both in terms of response and reduced toxicity. The aim of this review is to present the existing evidence about MRgRT applications for liver malignancies, discussing the potential clinical advantages and the current pitfalls of this new technology

Effectiveness of a Heads-Up Adaptive Lane Deviation Warning System for Middle-Aged and Older Adults

46 participants (24 younger and 22 older) completed at least one out of four simulated drives designed to test the effectiveness of an Adaptive Lane Deviation Warning (LDW) system, and they drove through both a warnings-on and warnings-off version of each drive. Findings showed that LDW was effective in reducing reaction time for lane deviation corrections for both older (by 1.2 seconds) and younger drivers (by 1.6 seconds). The older and younger drivers did not differ in correction RTs when the warnings were turned off. But older drivers showed slower correction RTs than younger drivers in the warning-on drives. The data indicate that these benefits were specific to LDW rather than general improvement in driving performance. Cognitive processing speed emerged as a particularly robust predictor of benefits from the LDW compared to other domains of cognitive function

Refining an Ecological Momentary Assessment Study of Binge Eating Among Sexual Minority and Heterosexual Young Women: A Mixed Methods Pilot Study

Background: Ecological momentary assessment (EMA) is used to capture daily lived experiences, states, and environments. Although EMA is commonly used in behavioral health research, there remains a dearth of literature on how researchers account for design considerations of EMA techniques when designing studies. The goal of this formative mixed methods study was to elicit feedback on EMA study procedures and materials from the target populations for a larger study about binge eating among sexual minority and heterosexual young women, in which data are collected entirely remotely. Methods: Sexual minority (n=12) and heterosexual (n=9) women ages 18–30 who binge ate took part in a pilot EMA study and exit interview and survey. As part of the consent and orientation process, participants reviewed video and written materials describing the study purpose and procedures. Using a smartphone app, for seven consecutive days they completed a survey each morning, 5 random surveys per day, and self-initiated a survey each time they binge ate. Participants then provided feedback on the study via a 1-hour virtual interview and online survey. Interviews were transcribed and reviewed by two coders to identify themes on the acceptability and feasibility of the EMA procedures with a focus on: (I) the training and study description materials; (II) general smartphone app and survey preferences; and (III) specific EMA survey question content and wording. Results: The qualitative and quantitative data converged to suggest participants were able to easily download and use the app to complete surveys and report on binge eating events. Participants provided feedback that was incorporated into revisions on general study procedures, the training video content, and EMA question content for binge eating, identity-related stressors, and appearance-related pressures. No systematic themes in the quantitative or qualitative data emerged to suggest questions were perceived differently by sexual minority and heterosexual young women. Conclusions: These findings provide evidence for the feasibility of conducting a remote EMA study to assess young women’s experiences around binge eating. This formative study provides an example of how a mixed methods approach can be used to refine EMA study methods and questions to improve study design

Rationale and Design of an Ecological Momentary Assessment Study Examining Predictors of Binge Eating Among Sexual Minority and Heterosexual Young Women: Protocol for the Health and Experiences in Real Life (HER Life) Study

Background: Previous research has identified health disparities between sexual minority and heterosexual women, including increased rates of obesity and binge eating in sexual minority women. Established predictors of binge eating behavior include negative emotions and sociocultural processes; however, these studies are generally conducted in samples of young women where sexual identity is not known or reported. There is a dearth of research evaluating how sexual minority–specific factors (eg, minority stress and connectedness to the lesbian, gay, bisexual, transgender, and queer community) may affect binge eating in sexual minority women. In addition, no studies have examined these processes in racially diverse samples or considered how intersecting minority identities (eg, Black and sexual minority) may affect eating behaviors. Objective: The Health and Experiences in Real Life (HER Life) Project aims to clarify real-world predictors of binge eating in young heterosexual and sexual minority women using ecological momentary assessment. The role of affective, social, and health behavior factors in binge eating will be examined for all women (aim 1), and sexual minority–specific predictors will also be considered for sexual minority women participants (aim 2). Person-level moderators of race, body- and eating-related factors, and sexual minority–specific factors will also be examined to better understand how real-world binge eating predictors may differ for various demographic groups (aim 3). Methods: Researchers aim to recruit 150 sexual minority and 150 heterosexual women from across the United States, including at least 50 Black women for each group, using web-based recruitment methods. The eligibility criteria include identifying as a woman, being aged between 18 and 30 years, and having had at least two binge eating episodes in the last 2 weeks. Participants must endorse being only or mostly attracted to men (considered heterosexual) or only or mostly attracted to women or having a current or most recent female partner (considered sexual minority). Eligible participants complete an initial web-based baseline survey and then 14 days of ecological momentary assessment involving the completion of a morning and before-bed survey and 5 prompted surveys per day as well as a user-initiated survey after binge eating episodes. The data will be analyzed using a series of multilevel models. Results: Data collection started in February 2021. We have currently enrolled 129 sexual minority women and 146 heterosexual women. Data collection is expected to conclude in fall 2022. Conclusions: The Health and Experiences in Real Life Project aims to elucidate potential differences between sexual minority and heterosexual women in within-person factors predicting binge eating and inform eating disorder interventions for sexual minority women. The challenges in recruiting sexual minority women, including the determination of eligibility criteria and considerations for remote data collection, are discussed. International Registered Report Identifier (IRRID): DERR1-10.2196/4119

Mental health among healthcare workers and other vulnerable groups during the COVID-19 pandemic and other coronavirus outbreaks: A rapid systematic review.

INTRODUCTION: Although most countries and healthcare systems worldwide have been affected by the COVID-19 pandemic, some groups of the population may be more vulnerable to detrimental effects of the pandemic on mental health than others. The aim of this systematic review was to synthesise evidence currently available from systematic reviews on the impact of COVID-19 and other coronavirus outbreaks on mental health for groups of the population thought to be at increased risk of detrimental mental health impacts. MATERIALS AND METHODS: We conducted a systematic review of reviews on adults and children residing in a country affected by a coronavirus outbreak and belonging to a group considered to be at risk of experiencing mental health inequalities. Data were collected on symptoms or diagnoses of any mental health condition, quality of life, suicide or attempted suicide. The protocol for this systematic review was registered in the online PROSPERO database prior to commencing the review (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=194264). RESULTS: We included 25 systematic reviews. Most reviews included primary studies of hospital workers from multiple countries. Reviews reported variable estimates for the burden of symptoms of mental health problems among acute healthcare workers, COVID-19 patients with physical comorbidities, and children and adolescents. No evaluations of interventions were identified. Risk- and protective factors, mostly for healthcare workers, showed the importance of personal factors, the work environment, and social networks for mental health. CONCLUSIONS: This review of reviews based on primary studies conducted in the early months of the COVID-19 pandemic shows a lack of evidence on mental health interventions and mental health impacts on vulnerable groups in the population

BACE1 Overexpression Reduces SH-SY5Y Cell Viability Through a Mechanism Distinct from Amyloid-β Peptide Accumulation:Beta Prime-Mediated Competitive Depletion of sAβPPα

Background: The Alzheimer’s disease (AD)-associated amyloid-beta protein precursor (AβPP) can be cleaved by β-site AβPP cleaving enzyme 1 (BACE1) and the γ-secretase complex to yield neurotoxic amyloid-β (Aβ) peptides. However, AβPP can also be cleaved in a ‘non-amyloidogenic’ manner either by α-secretase to produce soluble AβPP alpha (sAβPPα) (a fragment with neuroprotective/neurogenic functions) or through alternative BACE1-mediated ‘beta prime’ activity yielding soluble AβPP beta prime (sAβPPβ’). Objective: To determine whether sAβPPα depletion, as opposed to Aβ peptide accumulation, contributes to cytotoxicity in AD-relevant SH-SY5Y neuroblastoma cell models. Methods: AβPP proteolysis was characterized by immunoblotting in mock-, wild-type AβPP (wtAβPP)-, BACE1-, and Swedish mutant AβPP (SweAβPP)-transfected cells. AβPP beta prime cleavage was confirmed through secretase inhibitor studies and C-terminal fragment analysis. The roles of sAβPPα and sAβPPβ’ in cell viability were confirmed by overexpression studies. Results: Despite producing enhanced Aβ peptide levels, wtAβPP- and SweAβPP-transfected cells did not exhibit reduced viability whereas BACE1-transfected cells did. sAβPPα generation in SH-SY5Y-BACE1 cells was virtually ablated in lieu of BACE1-mediated sAβPPβ’ production. sAβPPα overexpression in SH-SY5Y-BACE1 cells restored viability whereas sAβPPβ’ overexpression decreased viability further. The anti-AβPP 6E10 antibody was shown to cross-react with sAβPPβ’. Conclusion: sAβPPα depletion and/or sAβPPβ’ accumulation, but not elevated Aβ peptide levels, represent the cytotoxic mechanism following BACE1 overexpression in SH-SY5Y cells. These data support the novel concept that competitive sAβPPα depletion by BACE1 beta prime activity might contribute to AD. The cross-reactivity of 6E10 with AβPPβ’also questions whether previous studies assessing sAβPPα as a biomarker using this antibody should be revisited

Acute impact of conventional and eccentric cycling on platelet and vascular function in patients with chronic heart failure.

Evidence-based guidelines recommend exercise therapy for patients with chronic heart failure (CHF). Such patients have increased atherothrombotic risk. Exercise can transiently increase platelet activation and reactivity and decrease vascular function in healthy participants, although data in CHF is scant. Eccentric (ECC) cycling is a novel exercise modality which may be particularly suited to patients with CHF, but the acute impacts of ECC on platelet and vascular function are currently unknown. Our null hypothesis was that ECC and concentric (CON) cycling, performed at matched external workloads, would not induce changes in platelet or vascular function in patients with CHF. Eleven patients with heart failure with reduced ejection fraction (HFrEF) took part in discrete bouts of ECC and CON cycling. Before and immediately after exercise, vascular function was assessed by measuring diameter and flow mediated dilation (FMD) of the brachial artery. Platelet function was measured by the flow cytometric determination of glycoprotein IIb/IIIa activation and granule exocytosis in the presence and absence of platelet agonists. ECC increased baseline artery diameter (pre: 4.0±0.8mm vs post: 4.2±0.7mm, P=0.04) and decreased FMD%. When changes in baseline artery diameter were accounted for the decrease in FMD post-ECC was no longer significant. No changes were apparent after CON. Neither ECC nor CON resulted in changes to any platelet function measures (all P>0.05). These results suggest both ECC and CON cycling at a moderate intensity and short duration can be performed by patients with HFrEF, without detrimental impacts on vascular or platelet function