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The active bacterial community able to utilize benzoate under denitrifying conditions was elucidated in two coastal sediments using stable-isotope probing (SIP) and nosZ gene amplification. The SIP method employed samples from Norfolk Harbor, Virginia, and a Long-Term Ecosystem Observatory (no. 15) off the coast of Tuckerton, New Jersey. The SIP method was modified by use of archaeal carrier DNA in the density gradient separation. The carrier DNA significantly reduced the incubation time necessary to detect the 13C-labeled bacterial DNA from weeks to hours in the coastal enrichments. No denitrifier DNA was found to contaminate the archaeal 13C-carrier when [12C]benzoate was used as a substrate in the sediment enrichments. Shifts in the activity of the benzoate-utilizing denitrifying population could be detected throughout a 21-day incubation. These results suggest that temporal analysis using SIP can be used to illustrate the initial biodegrader(s) in a bacterial population and to document the cross-feeding microbial community. [ABSTRACT FROM AUTHOR]

AIM OF THE STUDY: To present the results of evaluation research investigating a successful community development project. RATIONALE: Many governments, health care agencies, and organizations require community participation in health care. As a result, nurses and other health professionals are often required to practice using a philosophy of community development. Although the theoretical, philosophical, and practical components of community development are well articulated, there is little evidence that exemplifies the experience of initiating and participating in a community development project. This paper provides evidence of how one organization successfully engaged the broader community on a respite care project. METHOD: Using qualitative research methods and guided by the principles and practices of participatory action research, this evaluation engaged with the community in data collection, analysis, dissemination of finding, and in promoting effective change. RESULTS: Four themes emerged that provide insight into how one HIV/AIDS organization successfully undertook community development. These themes include: (a) identifying a community need; (b) addressing the various components identified in the community development process; (c) highlighting the strategies used to engage in successful community development; and (d) attending to factors that influence community development. CONCLUSION: The results of this research contribute to the body of knowledge related to engaging in the process of community development. By highlighting the experiences of one community group, it is hoped that nurses can learn and incorporate this knowledge into practice. [ABSTRACT FROM AUTHOR]

Participatory action research (PAR) has been heralded as an important research methodology to address issues of research relevance, community involvement, democracy, emancipation and liberation. Increasingly, nurse researchers are turning to PAR as a method of choice. Although nursing interest in PAR is expanding little is known about how to successfully involve the community in research. This article attends to this dearth of information by presenting the results of a study investigating the significant elements of community involvement in PAR. Through the use of qualitative research methods, five themes emerged that describe the community participation process: (a) planning for participation, (b) the structural components of community participation, (c) living the philosophy, (d) enhancing the credibility, and (e) the type of leadership required to facilitate community participation. It is hoped that by sharing these results others may consider the knowledge gleaned from this project as they plan and proceed with the challenges and rewards inherent in PAR. [ABSTRACT FROM AUTHOR]

Spins of negatively charged nitrogen-vacancy (NV−) defects in diamond are among the most promising candidates for solid-state qubits. The fabrication of quantum devices containing these spin-carrying defects requires position-controlled introduction of NV− defects having excellent properties such as spectral stability, a long spin coherence time, and a stable negative charge state. Nitrogen ion implantation and annealing enable the positioning of NV− spin qubits with high precision, but to date, the coherence times of qubits produced this way are short, presumably because of the presence of residual radiation damage. In the present work, we demonstrate that a high-temperature annealing at 1000 ∘C allows 2 ms coherence times to be achieved at room temperature. These results were obtained for implantation-produced NV− defects in a high-purity, 99.99% 12C-enriched single crystal chemical vapor deposited diamond. We discuss these long coherence times in the context of the thermal behavior of residual defect spins. [ABSTRACT FROM AUTHOR]

Lay Abstract: During a conversation, on average, autistic individuals are often more likely than non-autistic people to provide an off-topic comment and/or to pause for longer before providing a response. One possible explanation for this is that autistic individuals prefer, or are more tolerant of, unconventional communication styles. To explore this possibility, we investigated whether autistic and non-autistic 9-13-year-olds find off-topic or delayed responding a deterrent to friendship or interaction. Participants listened to scripted conversations and then rated social desirability statements, such as 'I would enjoy chatting to the [target speaker]'. We also examined the prevalence of these behaviours in children's own conversational responses. We found that autistic children were just as likely as non-autistic children to dis-prefer unconventional conversational responding. Both groups indicated that they were less likely to want to be friends with the speaker, or to chat with them, when they provided off-topic or delayed responses. However, despite their judgements of others, the same autistic children were more likely to provide off-topic responses themselves than their non-autistic peers, as well as giving fewer on-topic responses which facilitate back-and-forth conversation. Overall, this is problematic for autistic children, as our findings suggest that the tendency to exhibit unconventional conversational behaviours will have negative social consequences, even when interacting with other autistic peers., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study investigated the effects of diet and stage of lactation (SOL) on sensory profiles, texture, volatile profiles, and colour of Cheddar cheese. Cheddar cheese was manufactured from early-, mid-, and late-lactation milk obtained from seasonally calved cows (n = 54). Cows were assigned a diet; group 1: perennial ryegrass (GRS), group 2: total mixed ration (TMR), and group 3: partial mixed ration (PMR). Instrumental analysis was performed at 270 days (mature Cheddar). Sensory evaluation took place after 548 days (extra mature Cheddar). Toluene was the only volatile compound that was significantly influenced by diet. The trained panel rated early-lactation cheese as stronger than mid- and late- for cowy/barny flavour and late-lactation cheese as sweeter than early- and mid-lactation cheese. Mid-lactation cheese was liked least overall. Early-lactation cheeses were rated higher for 'crumbly' texture than mid- and late. Diet affected consumer ratings, with GRS and PMR cheese rated as more intense than TMR for flavour, aftertaste, and saltiness. Consumers reported that TMR cheese was lighter in colour compared to GRS cheese, which was supported by instrumental analysis. Consumers perceived GRS as more springy and less crumbly than TMR and PMR, while Texture Profile Analysis indicated that TMR was harder than GRS. Consumer segmentation was observed with two clear preference groups, one preferring GRS and one preferring TMR. For both groups, 'taste' seemed to be the main driver of liking, highlighting that consumer preference is most impacted by individual taste preferences., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [E.D.O’R and E.L.F have received research funding through the Food for Health Ireland project, funded by Enterprise Ireland and industry partners, grant number TC20180025. L.MG and M.T are supported by the Food for Health Ireland project, funded by Enterprise Ireland and industry, grant number TC20180025. E.L.F has previously received travel expenses and /or speaking honoraria from the National Dairy Council and the European Milk Forum. The funders had no role in the analyses or interpretation of data in the writing of the manuscript, or in the decision to publish the findings.]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Context: Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease., Objective: To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic lymphadenopathy in men with penile cancer., Evidence Acquisition: EMBASE, MEDLINE, the Cochrane Database of Systematic Reviews, and other databases were searched from 1990 to July 2022. Randomised controlled trials (RCTs), nonrandomised comparative studies (NRCSs), and case series (CSs) were included., Evidence Synthesis: We identified 107 studies, involving 9582 patients from two RCTs, 28 NRCSs, and 77 CSs. The quality of evidence is considered poor. Surgery is the mainstay of LN disease management, with early inguinal LN dissection (ILND) associated with better outcomes. Videoendoscopic ILND may offer comparable survival outcomes to open ILND with lower wound-related morbidity. Ipsilateral pelvic LN dissection (PLND) in N2-3 cases improves overall survival in comparison to no pelvic surgery. Neoadjuvant chemotherapy in N2-3 disease showed a pathological complete response rate of 13% and an objective response rate of 51%. Adjuvant radiotherapy may benefit pN2-3 but not pN1 disease. Adjuvant chemoradiotherapy may provide a small survival benefit in N3 disease. Adjuvant radiotherapy and chemotherapy improve outcomes after PLND for pelvic LN metastases., Conclusions: Early LND improves survival in nodal disease in penile cancer. Multimodal treatments may provide additional benefit in pN2-3 cases; however, data are limited. Therefore, individualised management of patients with nodal disease should be discussed in a multidisciplinary team setting., Patient Summary: Spread of penile cancer to the lymph nodes is best managed with surgery, which improves survival and has curative potential. Supplementary treatment, including the use of chemotherapy and/or radiotherapy, may further improve survival in advanced disease. Patients with penile cancer with lymph node involvement should be treated by a multidisciplinary team., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Multiple myeloma is an incurable plasma cell malignancy with only a 53% 5-year survival rate. There is a critical need to find new multiple myeloma vulnerabilities and therapeutic avenues. Herein, we identified and explored a novel multiple myeloma target: the fatty acid binding protein (FABP) family. In our work, myeloma cells were treated with FABP inhibitors (BMS3094013 and SBFI-26) and examined in vivo and in vitro for cell cycle state, proliferation, apoptosis, mitochondrial membrane potential, cellular metabolism (oxygen consumption rates and fatty acid oxidation), and DNA methylation properties. Myeloma cell responses to BMS309403, SBFI-26, or both, were also assessed with RNA sequencing (RNA-Seq) and proteomic analysis, and confirmed with western blotting and qRT-PCR. Myeloma cell dependency on FABPs was assessed using the Cancer Dependency Map (DepMap). Finally, MM patient datasets (CoMMpass and GEO) were mined for FABP expression correlations with clinical outcomes. We found that myeloma cells treated with FABPi or with FABP5 knockout (generated via CRISPR/Cas9 editing) exhibited diminished proliferation, increased apoptosis, and metabolic changes in vitro. FABPi had mixed results in vivo, in two pre-clinical MM mouse models, suggesting optimization of in vivo delivery, dosing, or type of FABP inhibitors will be needed before clinical applicability. FABPi negatively impacted mitochondrial respiration and reduced expression of MYC and other key signaling pathways in MM cells in vitro. Clinical data demonstrated worse overall and progression-free survival in patients with high FABP5 expression in tumor cells. Overall, this study establishes the FABP family as a potentially new target in multiple myeloma. In MM cells, FABPs have a multitude of actions and cellular roles that result in the support of myeloma progression. Further research into the FABP family in MM is warrented, especially into the effective translation of targeting these in vivo., Competing Interests: MF, HF, MK, AD, CM, CF, RP, AC, JD, LM, CG, RI, EJ, VD, CV No competing interests declared, CM GRAIL Inc: Research Funding; JBF Legal: Consultancy, MR Reviewing editor, eLife, (© 2023, Farrell et al.)

Introduction: Protecting and promoting the mental health of youth under 30 years of age is a priority, globally. Yet investment in mental health promotion, which seeks to strengthen the determinants of positive mental health and wellbeing, remains limited relative to prevention, treatment, and recovery. The aim of this paper is to contribute empirical evidence to guide innovation in youth mental health promotion, detailing the early outcomes of Agenda Gap, an intervention centering youth-led policy advocacy to influence positive mental health for individuals, families, communities and society., Methods: Leveraging a convergent mixed methods design, this study draws on data from n = 18 youth (ages 15 to 17) in British Columbia, Canada, who contributed to pre- and post-intervention surveys and post-intervention qualitative interviews following their participation in Agenda Gap from 2020-2021. These data are supplemented by qualitative interviews with n = 4 policy and other adult allies. Quantitative and qualitative data were analyzed in parallel, using descriptive statistics and reflexive thematic analysis, and then merged for interpretation., Results: Quantitative findings suggest Agenda Gap contributes to improvements in mental health promotion literacy as well as several core positive mental health constructs, such as peer and adult attachment and critical consciousness. However, these findings also point to the need for further scale development, as many of the available measures lack sensitivity to change and are unable to distinguish between higher and lower levels of the underlying construct. Qualitative findings provided nuanced insights into the shifts that resulted from Agenda Gap at the individual, family, and community level, including reconceptualization of mental health, expanded social awareness and agency, and increased capacity for influencing systems change to promote positive mental health and wellbeing., Discussion: Together, these findings illustrate the promise and utility of mental health promotion for generating positive mental health impacts across socioecological domains. Using Agenda Gap as an exemplar, this study underscores that mental health promotion programming can contribute to gains in positive mental health for individual intervention participants whilst also enhancing collective capacity to advance mental health and equity, particularly through policy advocacy and responsive action on the social and structural determinants of mental health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jenkins, Daly, McAuliffe, McGuinness, Richardson, Hill, Goodyear, Lind, Barbic, Rivers and Haines-Saah.)

The COVID-19 pandemic is adversely impacting suicidality at a population level, with consequences resulting from a variety of pandemic-driven disruptions, including social activities and connectedness. This paper uses a single case study design to explore how members of the Reddit r /COVID19_support community create a sense of connectedness among those who have suicidal thoughts due to the pandemic. Data were gathered from posts to the r/COVID19_support subreddit forum from February 2020 through December 2020. The second step of Klonsky and May's (2015) Three-Step Theory (3ST) of suicide, connectedness as a key protective factor , was used as the theoretical framework. This study explored r/COVID19_support 's constructed environment, users' dialogical interactions, and the four primary tenets of connectedness as proposed by Klonsky and May - Purpose and Meaning, Relationships, Religiosity, and Employment. Findings demonstrate a deep sense of connectedness for online community members. Relationships and Purpose and Meaning featured as the most salient sources of connectedness within this subreddit, whereas Religiosity was rarely discussed, and Employment was often spoken of in negative terms (i.e., creating mental distress, rather than facilitating connectedness). Contributors' responses offered various opportunities for connectedness both on- and off-line. Safe online spaces, such as r/COVID19_support , can serve as a protective factor amid suicidality, facilitating connectedness, and thereby helping to curtail suicidal thoughts from advancing to suicidal actions. This subreddit and similar online spaces can benefit specific populations who may otherwise find it challenging to access services or who wish to remain anonymous., Competing Interests: None declared., (© 2022 The Author(s).)

Objective: The COVID-19 pandemic has had a complex impact on risks of suicide and non-fatal self-harm worldwide with some evidence of increased risk in specific populations including women, young people, and people from ethnic minority backgrounds. This review aims to systematically address whether SARS-CoV-2 infection and/or COVID-19 disease confer elevated risk directly., Method: As part of a larger Living Systematic Review examining self-harm and suicide during the pandemic, automated daily searches using a broad list of keywords were performed on a comprehensive set of databases with data from relevant articles published between January 1, 2020 and July 18, 2021. Eligibility criteria for our present review included studies investigating suicide and/or self-harm in people infected with SARS-CoV-2 with or without manifestations of COVID-19 disease with a comparator group who did not have infection or disease. Suicidal and self-harm thoughts and behaviour (STBs) were outcomes of interest. Studies were excluded if they reported data for people who only had potential infection/disease without a confirmed exposure, clinical/molecular diagnosis or self-report of a positive SARS-CoV-2 test result. Studies of news reports, treatment studies, and ecological studies examining rates of both SARS-CoV-2 infections and suicide/self-harm rates across a region were also excluded., Results: We identified 12 studies examining STBs in nine distinct samples of people with SARS-CoV-2. These studies, which investigated STBs in the general population and in subpopulations, including healthcare workers, generally found positive associations between SARS-CoV-2 infection and/or COVID-19 disease and subsequent suicidal/self-harm thoughts and suicidal/self-harm behaviour., Conclusions: This review identified some evidence that infection with SARS-CoV-2 and/or COVID-19 disease may be associated with increased risks for suicidal and self-harm thoughts and behaviours but a causal link cannot be inferred. Further research with longer follow-up periods is required to confirm these findings and to establish whether these associations are causal.

Background: Patients experiencing concurrent disorders (i.e., co-occurring mental health and substance use disorders) are prevalent in mental health settings and their health and social outcomes are often poor. This reflects persistent stigma as well as inadequate preparatory training or continuing education for healthcare professionals, including nurses., Objective: To explore the impacts of the 1-day 'Enhancing Concurrent Disorder Care Intervention' on nurses' and student nurses' capacity to deliver care, grounded in current evidence, to patients with concurrent disorders in inpatient mental health settings., Design: A Quasi-experimental intervention design was used with pre- and post t -test components, guided by the STROBE checklist for observational studies., Settings: Five acute mental health units across two hospitals in British Columbia, Canada, as well as two schools of nursing representing students completing clinical practicum rotations within these settings., Participants: Seventy-six nurses (Registered Nurses and Registered Psychiatric Nurses) and student nurses practicing in inpatient mental health care., Methods: This educational intervention was informed by a pilot study, which included content validation from international concurrent disorder experts, and further refined through collaborative processes with lived experience and nurse partners. Intervention impacts were examined using online surveys conducted prior to the intervention and within two weeks post-intervention. Surveys assessed knowledge and attitudes about concurrent disorders using a validated instrument and questions developed by the study team. Descriptive statistics alongside paired and independent t-tests and two-way ANOVAs were used to compare survey scores before and after the intervention., Results: Findings indicate that the intervention was effective in improving participants' knowledge and attitudes toward patients with concurrent disorders across participant groups., Conclusions: Enhancing care and outcomes for patients with concurrent disorders is a global priority. Brief educational interventions aimed at nurses can provide an effective, low-barrier mechanism to address knowledge gaps that contribute to harmful care and adverse outcomes., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Adverse mental health impacts of the COVID-19 pandemic are well documented; however, there remains limited data detailing trends in mental health at different points in time and across population sub-groups most impacted. This paper draws on data from three rounds of a nationally representative cross-sectional monitoring survey to characterize the mental health impacts of COVID-19 on adults living in Canada ( N = 9,061). Methods: Descriptive statistics were used to examine the mental health impacts of the pandemic using a range of self-reported measures. Multivariate logistic regression models were then used to quantify the independent risks of experiencing adverse mental health outcomes for priority population sub-groups, adjusting for age, gender, and survey round. Results: Data illustrate significant disparities in the mental health consequences of the pandemic, with inequitable impacts for sub-groups who experience structural vulnerability related to pre-existing mental health conditions, disability, LGBTQ2+ identity, and Indigenous identity. Conclusion: There is immediate need for population-based approaches to support mental health in Canada and globally. Approaches should attend to the root causes of mental health inequities through promotion and prevention, in addition to treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jenkins, Slemon, Richardson, Pumarino, McAuliffe, Thomson, Goodyear, Daly, McGuinness and Gadermann.)

Background: The COVID-19 pandemic is having considerable impacts on population-level mental health, with research illustrating an increased prevalence in suicidal thoughts due to pandemic stressors. While the drivers of suicidal thoughts amid the pandemic are poorly understood, qualitative research holds great potential for expanding upon projections from pre-pandemic work and nuancing emerging epidemiological data. Despite calls for qualitative inquiry, there is a paucity of qualitative research examining experiences of suicidality related to COVID-19. The use of publicly available data from social media offers timely and pertinent information into ongoing pandemic-related mental health, including individual experiences of suicidal thoughts. Objective: To examine how Reddit users within the r/COVID19_support community describe their experiences of suicidal thoughts amid the COVID-19 pandemic. Methods: This study draws on online posts from within r/COVID19_support that describe users' suicidal thoughts during and related to the COVID-19 pandemic. Data were collected from creation of this subreddit on February 12, 2020 until December 31, 2020. A qualitative thematic analysis was conducted to generate themes reflecting users' experiences of suicidal thoughts. Results: A total of 83 posts from 57 users were included in the analysis. Posts described a range of users' lived and living experiences of suicidal thoughts related to the pandemic, including deterioration in mental health and complex emotions associated with suicidal thinking. Reddit users situated their experiences of suicidal thoughts within various pandemic stressors: social isolation, employment and finances, virus exposure and COVID-19 illness, uncertain timeline of the pandemic, news and social media, pre-existing mental health conditions, and lack of access to mental health resources. Some users described individual coping strategies and supports used in attempt to manage suicidal thoughts, however these were recognized as insufficient for addressing the multilevel stressors of the pandemic. Conclusions: Multiple and intersecting stressors have contributed to individuals' experiences of suicidal thoughts amid the COVID-19 pandemic, requiring thoughtful and complex public health responses. While ongoing challenges exist with self-disclosure of mental health challenges on social media, Reddit and other online platforms may offer a space for users to share suicidal thoughts and discuss potential coping strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Slemon, McAuliffe, Goodyear, McGuinness, Shaffer and Jenkins.)

Evidence on the population-level mental health impacts of COVID-19 are beginning to amass; however, to date, there are significant gaps in our understandings of whose mental health is most impacted, how the pandemic is contributing to widening mental health inequities, and the coping strategies being used to sustain mental health. The first wave of a repeated cross-sectional monitoring survey was conducted between May 14-29, 2020 to assess the mental health impacts of the pandemic and to identify the disproportionate impacts on populations or groups identified as experiencing increased risks due to structural vulnerability and pre-existing health and social inequities. Respondents included a nationally representative probability sample (n = 3000) of Canadian adults 18 years and older. Overall, Canadian populations are experiencing a deterioration in mental health and coping due to the pandemic. Those who experience health, social, and/or structural vulnerabilities due to pre-existing mental health conditions, disability, income, ethnicity, sexuality, and/or gender are more likely to endorse mental health deterioration, challenging emotions, and difficulties coping. This monitoring study highlights the differential mental health impacts of the pandemic for those who experience health, social, and structural inequities. These data are critical to informing responsive, equity-oriented public health, and policy responses in real-time to protect and promote the mental health of those most at risk during the pandemic and beyond., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

To better address the mental health and substance use crises facing youth globally, a comprehensive approach, inclusive of mental health promotion is needed. A key component of mental health promotion is policy intervention to address the social and structural determinants of health. Importantly, youth should be engaged in these efforts to maximize relevancy and impact. Yet, while there is growing interest in the inclusion of youth in the policymaking process, there is a paucity of guidance on how to do this well. This environmental scan reports findings from a comprehensive search of academic and grey literature that was conducted using the electronic databases: CINAHL, ERIC, MEDLINE, PsycINFO, Google Scholar, and Google. Search terms included variations of 'youth*', 'educat*', 'engage*', 'policy' and 'policy training'. Thirteen English language training programmes met inclusion criteria. Analysis identified marked differences in programme philosophy and focus by geographic region and highlights the need for enhanced evaluation and impact measurement moving forward. This paper makes a needed contribution to the evidence-base guiding this key mental health promotion strategy, which holds the potential to address critical gaps in approaches to youth mental health and substance use., (© The Author(s) 2019. Published by Oxford University Press.)

Background: Mental health challenges are a leading health concern for youth globally, requiring a comprehensive approach incorporating promotion, prevention and treatment within a healthy public policy framework. However, the broad enactment of this vision has yet to be realized. Further, mental health promotion evidence specific to youth is still emerging and has not yet focused at a policy level. This is a critical gap, as policy is a key mental health promotion lever that can alter the social and structural conditions that contribute to shaping youth mental health outcomes for all youth, across the full spectrum of need. Responsive to this research and intervention priority, our prototype study intervention-the Agenda Gap-is comprised of an innovative, multi-media engagement intervention, developed in collaboration with youth. This intervention aims to equip youth and build capacity for them to lead meaningful policy change reflective of the mental health needs of diverse communities of youth, including those who experience structural vulnerability and who would not typically have had their voice represented in policymaking processes., Methods: This study will use a multiple case study design and mixed methods grounded in a realist approach and will be conducted in three sites across two Canadian provinces (British Columbia and Alberta). In an earlier phase of this research, we collaboratively designed the prototype intervention with youth, community and policy partners. In this phase of the study, the intervention will be implemented and further tested with new groups of youth collaborators (n = 10-15/site). Outcome data will be collected through realist qualitative interviews, validated questionnaires [i.e., Child and Youth Resilience Measure (CYRM-12), General Self-Efficacy (GSE) Scale, and the Critical Consiousness Scale (CCS)] and additional survey items developed by our study team. Analysis will focus on identification of key context-mechanism-outcome configurations to provide comprehensive insights into how this intervention works, for whom, and in what context., Discussion: This study is unique in its "upstream" focus on youth-engaged policymaking as a tool for improving the social and structural conditions that influence youth mental health across socioecological levels. Through the implementation and testing of the Agenda Gap intervention with diverse youth, this study will contribute to the evidence base on youth-engaged policymaking as a novel and innovative, mental health promotion strategy., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Objective: Several challenges have been identified for patients with concurrent disorders and the providers that care for them, contributing to a pressing need for interventions to improve outcomes, particularly within inpatient mental health settings. Methods: A systematic search of peer-reviewed literature was conducted using four online databases: CINAHL, MEDLINE (Ovid), PsycInfo and Web of Science. Articles were selected based on inclusion criteria and additional articles were identified through hand searches. Study details were charted and qualitative synthesis was conducted. Results: Thirty two articles met inclusion criteria. A substantial focus within the literature was education, with higher levels of education shown to improve healthcare provider attitudes and practices. Within this overarching focus, four themes were identified: 1) education as an intervention to improve attitudes and increase confidence and knowledge; 2) strategies to support practice change, including interventions aimed at clinical leaders and methods to address substance use among inpatients; 3) frameworks to guide care; and 4) opportunities to expand nursing scope of practice. Conclusions: Given the substantial evidence indicating that education improves nurses' knowledge, attitudes and practices, there is great promise in expanding educational intervention opportunities for nurses to improve care and outcomes for patients with concurrent disorders-a priority patient population.

Background: To limit the spread of SARS-CoV-2, an evidence-based understanding of the symptoms is critical to inform guidelines for quarantining and testing. The most common features are purported to be fever and a new persistent cough, although the global prevalence of these symptoms remains unclear. The aim of this systematic review is to determine the prevalence of symptoms associated with COVID-19 worldwide., Methods: We searched PubMed, Embase, CINAHL, AMED, medRxiv and bioRxiv on 5th April 2020 for studies of adults (>16 years) with laboratory test confirmed COVID-19. No language or publication status restrictions were applied. Data were independently extracted by two review authors into standardised forms. All datapoints were independently checked by three other review authors. A random-effects model for pooling of binomial data was applied to estimate the prevalence of symptoms, subgrouping estimates by country. I2 was used to assess inter-study heterogeneity., Results: Of 851 unique citations, 148 articles were included which comprised 24,410 adults with confirmed COVID-19 from 9 countries. The most prevalent symptoms were fever (78% [95% CI 75%-81%]; 138 studies, 21,701 patients; I2 94%), a cough (57% [95% CI 54%-60%]; 138 studies, 21,682 patients; I2 94%) and fatigue (31% [95% CI 27%-35%]; 78 studies, 13,385 patients; I2 95%). Overall, 19% of hospitalised patients required non-invasive ventilation (44 studies, 6,513 patients), 17% required intensive care (33 studies, 7504 patients), 9% required invasive ventilation (45 studies, 6933 patients) and 2% required extra-corporeal membrane oxygenation (12 studies, 1,486 patients). The mortality rate was 7% (73 studies, 10,402 patients)., Conclusions: We confirm that fever and cough are the most prevalent symptoms of adults infected by SARS-CoV-2. However, there is a large proportion of infected adults which symptoms-alone do not identify., Competing Interests: The authors have declared that no competing interests exist.

Polychlorinated dibenzo- p -dioxins (PCDDs) are released into the environment from a variety of both anthropogenic and natural sources. While highly chlorinated dibenzo- p -dioxins are persistent under oxic conditions, in anoxic environments, these organohalogens can be reductively dechlorinated to less chlorinated compounds that are then more amenable to subsequent aerobic degradation. Identifying the microorganisms responsible for dechlorination is an important step in developing bioremediation approaches. In this study, we demonstrated the use of a DNA-stable isotope probing (SIP) approach to identify the bacteria active in dechlorination of PCDDs in river sediments, with 1,2,3,4-tetrachlorodibenzo- p -dioxin (1,2,3,4-TeCDD) as a model. In addition, pyrosequencing of reverse transcribed 16S rRNA of TeCDD dechlorinating enrichment cultures was used to reveal active members of the bacterial community. A set of operational taxonomic units (OTUs) responded positively to the addition of 1,2,3,4-TeCDD in SIP microcosms assimilating 13 C-acetate as the carbon source. Analysis of bacterial community profiles of the 13 C labeled heavy DNA fraction revealed that an OTU corresponding to Dehalococcoides mccartyi accounted for a significantly greater abundance in cultures amended with 1,2,3,4-TeCDD than in cultures without 1,2,3,4-TeCDD. This implies the involvement of this Dehalococcoides mccartyi strain in the reductive dechlorination of 1,2,3,4-TeCDD and suggests the applicability of SIP for a robust assessment of the bioremediation potential of organohalogen contaminated sites.

We develop theoretically and demonstrate experimentally a universal dynamical decoupling method for robust quantum sensing with unambiguous signal identification. Our method uses randomization of control pulses to simultaneously suppress two types of errors in the measured spectra that would otherwise lead to false signal identification. These are spurious responses due to finite-width π pulses, as well as signal distortion caused by π pulse imperfections. For the cases of nanoscale nuclear-spin sensing and ac magnetometry, we benchmark the performance of the protocol with a single nitrogen vacancy center in diamond against widely used nonrandomized pulse sequences. Our method is general and can be combined with existing multipulse quantum sensing sequences to enhance their performance.

Objectives: Hepatitis C (HCV) knowledge gaps are associated with lower levels of engagement in (HCV) care which contributes to HCV-related morbidity and mortality. Knowledge gaps may be exacerbated by rapid changes in HCV care/treatment. Cost-effective, timely and easy-to-implement education is needed to address knowledge gaps and foster HCV engagement., Methods: We developed a free, one-hour, online course for patients and providers. Online and facilitated course events were evaluated. Outcome measures included: pre/post-scores, perceived knowledge gains and increased capacity to educate/encourage engagement in HCV care., Results: Total pre-post-test gains were significant (p < .001) across groups. Over 50% of participants reported: perceived knowledge gains of "A lot" or higher; the course increased their capacity to educate and encourage client engagement in care by "A lot" or higher., Conclusions: The evaluation confirmed ongoing patient and provider HCV knowledge gaps, significantly reduced those gaps, and increased provider's capacity to educate and encourage client engagement in HCV care., Practice Implications: The course is an effective tool to address knowledge gaps that might lower engagement in care. It is available to patients to use in the privacy of their own home or for providers for their personal use, to use with individuals or patient groups., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A growing body of evidence suggests that lysosomes, which have traditionally been regarded as degradative organelles, can function as Ca 2+ stores, regulated by the second messenger nicotinic acid adenine dinucleotide phosphate (NAADP). We previously demonstrated that in hippocampal pyramidal neurons, activity-dependent Ca 2+ release from these stores triggers fusion of the lysosome with the plasma membrane. We found that the physiological role of this Ca 2+ -dependent fusion was to maintain the long-term structural enlargement of dendritic spines induced by synaptic activity. Here, we examined the pathophysiological consequences of lysosomal dysfunction in hippocampal pyramidal neurons by chronically inhibiting lysosomal Ca 2+ signalling using the NAADP antagonist, NED-19. We found that within just 20 hours, inhibition of lysosomal function led to a profound intracellular accumulation of lysosomal membrane. This was accompanied by a significant change in dendritic spine structure, which included a lengthening of dendritic spines, an increase in the number of filipodia, and an overall decrease in spine number. Inhibition of lysosomal function also inhibited wound healing in neurons by preventing lysosomal fusion with the plasma membrane. Neurons were therefore more susceptible to injury. Our findings suggest that dysfunction in lysosomal Ca 2+ signalling and lysosomal fusion with the plasma membrane may contribute to the loss of dendritic spines and neurons seen in neurological disorders, such as Niemann-Pick disease type C1, in which lysosomal function is impaired.

Background: Alcohol dependence is common and serious cause of social and physical harm. However, the optimal management of those with moderate and severe alcohol dependence in primary and community care after detoxification remains unclear. The aim of this review is to evaluate the effectiveness of interventions for maintaining abstinence in people with alcohol dependence following detoxification., Methods: We will systematically search electronic databases and clinical trial registries for randomized controlled trials (RCTs) examining the effectiveness of pharmacological and/or psychosocial interventions for maintaining abstinence in recently detoxified, alcohol-dependent adults. The searches will be complemented by checking references and citations from included studies and other relevant systematic reviews. No limitation on language, year, or publication status will be applied. RCTs will be selected using prespecified criteria. Descriptive information, study characteristics, and results of eligible RCTs will be extracted. A revised version of the Cochrane Risk of Bias tool (RoB 2.0) will be used to assess the risk of bias in eligible RCTs. Results will be synthesized and analyzed using network meta-analysis (NMA). Overall strength of the evidence and publication bias will be evaluated. Subgroup and sensitivity analysis will also be performed., Discussion: This network meta-analysis aims to appraise and summarize the total evidence of therapeutic interventions for alcohol-dependent patients that require support for detoxification and can be treated in the community. The evidence will determine which combination of interventions are most promising for current practice and further investigation., Systematic Review Registration: PROSPERO CRD42016049779.

Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function as Ca 2+ stores. Here we examined the function of these stores in hippocampal pyramidal neurons. We found that back-propagating action potentials (bpAPs) could elicit Ca 2+ release from lysosomes in the dendrites. This Ca 2+ release triggered the fusion of lysosomes with the plasma membrane, resulting in the release of Cathepsin B. Cathepsin B increased the activity of matrix metalloproteinase 9 (MMP-9), an enzyme involved in extracellular matrix (ECM) remodelling and synaptic plasticity. Inhibition of either lysosomal Ca 2+ signaling or Cathepsin B release prevented the maintenance of dendritic spine growth induced by Hebbian activity. This impairment could be rescued by exogenous application of active MMP-9. Our findings suggest that activity-dependent exocytosis of Cathepsin B from lysosomes regulates the long-term structural plasticity of dendritic spines by triggering MMP-9 activation and ECM remodelling., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Background: There is a broad literature suggesting that cognitive difficulties are associated with violence across a variety of groups. Although neurocognitive and social cognitive deficits are core features of schizophrenia, evidence of a relationship between cognitive impairments and violence within this patient population has been mixed., Methods: We prospectively examined whether neurocognition and social cognition predicted inpatient violence amongst patients with schizophrenia and schizoaffective disorder (n = 89; 10 violent) over a 12 month period. Neurocognition and social cognition were assessed using the MATRICS Consensus Cognitive Battery (MCCB)., Results: Using multivariate analysis neurocognition and social cognition variables could account for 34 % of the variance in violent incidents after controlling for age and gender. Scores on a social cognitive reasoning task (MSCEIT) were significantly lower for the violent compared to nonviolent group and produced the largest effect size. Mediation analysis showed that the relationship between neurocognition and violence was completely mediated by each of the following variables independently: social cognition (MSCEIT), symptoms (PANSS Total Score), social functioning (SOFAS) and violence proneness (HCR-20 Total Score). There was no evidence of a serial pathway between neurocognition and multiple mediators and violence, and only social cognition and violence proneness operated in parallel as significant mediators accounting for 46 % of the variance in violent incidents. There was also no evidence that neurocogniton mediated the relationship between any of these variables and violence., Conclusions: Of all the predictors examined, neurocognition was the only variable whose effects on violence consistently showed evidence of mediation. Neurocognition operates as a distal risk factor mediated through more proximal factors. Social cognition in contrast has a direct effect on violence independent of neurocognition, violence proneness and symptom severity. The neurocognitive impairment experienced by patients with schizophrenia spectrum disorders may create the foundation for the emergence of a range of risk factors for violence including deficits in social reasoning, symptoms, social functioning, and HCR-20 risk items, which in turn are causally related to violence.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an accepted treatment for motor symptoms in a subset of Parkinson's disease (PD) patients. The mechanisms why DBS is effective are incompletely understood, but previous studies show that DBS targeted in brain structures other than the STN may modify the microvasculature. However, this has not been studied in PD subjects who have received STN-DBS. Here we investigated the extent and nature of microvascular changes in post-mortem STN samples from STN-DBS PD patients, compared to aged controls and PD patients who had not been treated with STN-DBS. We used immunohistochemical and immunofluorescent methods to assess serial STN-containing brain sections from PD and STN-DBS PD cases, compared to similar age controls using specific antibodies to detect capillaries, an adherens junction and tight junction-associated proteins as well as activated microglia. Cellular features in stained sections were quantified by confocal fluorescence microscopy and stereological methods in conjunction with in vitro imaging tools. We found significant upregulation of microvessel endothelial cell thickness, length and density but lowered activated microglia density and striking upregulation of all analysed adherens junction and tight junction-associated proteins in STN-DBS PD patients compared to non-DBS PD patients and controls. Moreover, in STN-DBS PD samples, expression of an angiogenic factor, vascular endothelial growth factor (VEGF), was significantly upregulated compared to the other groups. Our findings suggest that overexpressed VEGF and downregulation of inflammatory processes may be critical mechanisms underlying the DBS-induced microvascular changes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Emitters of indistinguishable single photons are crucial for the growing field of quantum technologies. To realize scalability and increase the complexity of quantum optics technologies, multiple independent yet identical single-photon emitters are required. However, typical solid-state single-photon sources are inherently dissimilar, necessitating the use of electrical feedback or optical cavities to improve spectral overlap between distinct emitters. Here we demonstrate bright silicon vacancy (SiV(-)) centres in low-strain bulk diamond, which show spectral overlap of up to 91% and nearly transform-limited excitation linewidths. This is the first time that distinct single-photon emitters in the solid state have shown intrinsically identical spectral properties. Our results have impact on the application of single-photon sources for quantum optics and cryptography.

This descriptive qualitative study examined the patient, provider, and institutional factors contributing to nonattendance for hepatitis C (HCV) care throughout the disease course. Eighty-four patients and health and social care providers were interviewed. Thematic analysis of the data yielded 6 interrelated nonattendance themes: self-protection, determining the benefits, competing priorities, knowledge gaps, access to services, and restrictive policies. Factors within the themes varied with the disease course, type of provider/service, and patient context. Nonattendance could span months to years and most frequently began at diagnosis where providers either advised that followup was not necessary or did not recommend any followup. The way services were organized (low barrier access) and delivered (nonjudgmental approach) and higher HCV knowledge levels of patients and providers encouraged attendance. This is the first study to explore the reasons for nonattendance for HCV care throughout the disease course and validate them from multiple perspectives. There are missed opportunities for providers to encourage attendance throughout the disease course beginning at diagnosis. Interventions required include development of integrated health and social service delivery models; mechanisms to improve knowledge dissemination of the disease, its management, and treatment; and implementation of standardized followup protocols for liver disease monitoring in primary care.

A rise in [Ca(2+)](i) provides the trigger for neurotransmitter release at neuronal boutons. We have used confocal microscopy and Ca(2+) sensitive dyes to directly measure the action potential-evoked [Ca(2+)](i) in the boutons of Schaffer collaterals. This reveals that the trial-by-trial amplitude of the evoked Ca(2+) transient is bimodally distributed. We demonstrate that "large" Ca(2+) transients occur when presynaptic NMDA receptors are activated following transmitter release. Presynaptic NMDA receptor activation proves critical in producing facilitation of transmission at theta frequencies. Because large Ca(2+) transients "report" transmitter release, their frequency on a trial-by-trial basis can be used to estimate the probability of release, p(r). We use this novel estimator to show that p(r) increases following the induction of long-term potentiation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Aims and Objectives: Based on a secondary analysis of data from a large qualitative study on cancer care communication, we address the question: what do patients with advanced cancer identify as helpful in their communication encounters with health care providers?, Background: Communication is of critical importance to the care of patients with advanced cancer. A better understanding of what such patients identify as helpful in their communication encounters with nurses and other health care providers seems critical to creating evidence-informed recommendations for best practices., Design: Secondary analysis of qualitative interview data., Methods: Data from 18 participants interviewed individually and 16 focus group participants, with advanced cancer in the palliative phase of care. Interpretive description methodology informed data collection and analysis., Results: Findings suggest four key elements are critically important to consider in communications with patients in an advanced or palliative phase - respecting the importance of time, demonstrating caring, acknowledging fear and balancing hope and honesty in the provision of information., Conclusions: Communication is an important element in the provision of advanced cancer care., Relevance to Clinical Practice: Findings emphasise the complex meanings inherent in cancer care communication and identify central themes that are fundamental to effective cancer care communication., (© 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.)

For infectious prion protein (designated PrP(Sc)) to act as a template to convert normal cellular protein (PrP(C)) to its distinctive pathogenic conformation, the two forms of prion protein (PrP) must interact closely. The neuronal receptor that rapidly endocytoses PrP(C) is the low-density lipoprotein receptor-related protein 1 (LRP1). We show here that on sensory neurons LRP1 is also the receptor that binds and rapidly endocytoses smaller oligomeric forms of infectious prion fibrils, and recombinant PrP fibrils. Although LRP1 binds two molecules of most ligands independently to its receptor clusters 2 and 4, PrP(C) and PrP(Sc) fibrils bind only to receptor cluster 4. PrP(Sc) fibrils out-compete PrP(C) for internalization. When endocytosed, PrP(Sc) fibrils are routed to lysosomes, rather than recycled to the cell surface with PrP(C). Thus, although LRP1 binds both forms of PrP, it traffics them to separate fates within sensory neurons. The binding of both to ligand cluster 4 should enable genetic modification of PrP binding without disrupting other roles of LRP1 essential to neuronal viability and function, thereby enabling in vivo analysis of the role of this interaction in controlling both prion and LRP1 biology.

Sandy or permeable sediment deposits cover the majority of the shallow ocean seafloor, and yet the associated bacterial communities remain poorly described. The objective of this study was to expand the characterization of bacterial community diversity in permeable sediment impacted by advective pore water exchange and to assess effects of spatial, temporal, hydrodynamic, and geochemical gradients. Terminal restriction fragment length polymorphism (TRFLP) was used to analyze nearly 100 sediment samples collected from two northeastern Gulf of Mexico subtidal sites that primarily differed in their hydrodynamic conditions. Communities were described across multiple taxonomic levels using universal bacterial small subunit (SSU) rRNA targets (RNA- and DNA-based) and functional markers for nitrification (amoA) and denitrification (nosZ). Clonal analysis of SSU rRNA targets identified several taxa not previously detected in sandy sediments (i.e., Acidobacteria, Actinobacteria, Chloroflexi, Cyanobacteria, and Firmicutes). Sequence diversity was high among the overall bacterial and denitrifying communities, with members of the Alphaproteobacteria predominant in both. Diversity of bacterial nitrifiers (amoA) remained comparatively low and did not covary with the other gene targets. TRFLP fingerprinting revealed changes in sequence diversity from the family to species level across sediment depth and study site. The high diversity of facultative denitrifiers was consistent with the high permeability, deeper oxygen penetration, and high rates of aerobic respiration determined in these sediments. The high relative abundance of Gammaproteobacteria in RNA clone libraries suggests that this group may be poised to respond to short-term periodic pulses of growth substrates, and this observation warrants further investigation.

Boutons are specialised presynaptic compartments that lie along the axons of central neurons. Release of neurotransmitter from boutons is tightly regulated by the level of intracellular calcium [Ca2+]i. A rise in Ca2+ level may be generated in several ways; entry of extracellular Ca2+ via voltage gated calcium channels (VGCCs), entry via ligand-operated channels (LOCs) or the release of Ca2+ from intracellular Ca2+ stores. The role of Ca2+ stores in boutons remains poorly understood, despite recent work indicating that the release of Ca2+ from the endoplasmic reticulum (ER) may contribute to transmitter release. In this study we assess whether the lysosome or a closely related organelle functions as a Ca2+ store in the boutons of hippocampal pyramidal neurones. Lysosomes are small acidic organelles more commonly known for their role in degrading redundant cellular constituents. Using a fluorescent lysosomal marker, we show that lysosomes are located in the axons of hippocampal CA3 neurones. Selective pharmacological lysis of the lysosomes with glycyl-phenylalanine 2-naphthylamide (GPN) generates rapid, highly focal Ca2+ transients within the axon and increases the frequency of spontaneous miniature excitatory post-synaptic currents (mEPSCs), revealing that the organelle contains Ca2+ at a concentration sufficient to evoke transmitter release. Confocal laser scanning microscopy, combined with electrophysiology is used to monitor the action potential evoked increases in [Ca2+]i in boutons. We show that disruption of lysosomes compromises action potential evoked [Ca2+]i but this effect is occluded if the ER is discharged. Conversely, disruption of the lysosome does not appear to impact on the capacity of the ER to release Ca2+. These results suggest that the lysosome may serve as a Ca2+ store within hippocampal boutons, with a Ca2+ signalling role that is unique from that of the ER.