Perceptions of trends in Seychelles artisanal trap fisheries: comparing catch monitoring, underwater visual census and fishers' knowledge

Fisheries scientists and managers are increasingly engaging with fishers' knowledge (FK) to provide novel information and improve the legitimacy of fisheries governance. Disputes between the perceptions of fishers and scientists can generate conflicts for governance, but can also be a source of new perspectives or understandings. This paper compares artisanal trap fishers' reported current catch rates with landings data and underwater visual census (UVC). Fishers' reports of contemporary 'normal' catch per day tended to be higher than recent median landings records. However, fishers' reports of 'normal' catch per trap were not significantly different from the median CPUE calculated from landings data, and reports of 'good' and 'poor' catch rates were indicative of variability observed in landings data. FK, landings and UVC data all gave different perspectives of trends over a ten-year period. Fishers' perceptions indicated greater declines than statistical models fitted to landings data, while UVC evidence for trends varied between sites and according to the fish assemblage considered. Divergence in trend perceptions may have resulted from differences in the spatial, temporal or taxonomic focus of each dataset. Fishers may have experienced and understood behavioural changes and increased fishing power, which may have obscured declines from landings data. Various psychological factors affect memory and recall, and may have affected these memory-based estimates of trends, while different assumptions underlying the analysis of both interview data and conventional scientific data could also have led to qualitatively different trend perceptions. Differing perspectives from these three data sources illustrate both the potential for 'cognitive conflicts' between stakeholders who do not rely on the same data sources, as well as the importance of multiple information sources to understand dynamics of fisheries. Collaborative investigation of such divergence may facilitate learning and improve fisheries governance

Rho GTPase gene expression and breast cancer risk:A Mendelian randomization analysis

The Rho GTPase family consists of 20 genes encoding intracellular signalling proteins that influence cytoskeletal dynamics, cell migration and cell cycle progression. They are implicated in breast cancer progression but their role in breast cancer aetiology is unknown. As aberrant Rho GTPase activity could be associated with breast cancer, we aimed to determine the potential for a causal role of Rho GTPase gene expression in breast cancer risk, using two-sample Mendelian randomization (MR). MR was undertaken in 122,977 breast cancer cases and 105,974 controls, including 69,501 estrogen receptor positive (ER+) cases and 105,974 controls, and 21,468 ER negative (ER−) cases and 105,974 controls. Single nucleotide polymorphisms (SNPs) underlying expression quantitative trait loci (eQTLs) obtained from normal breast tissue, breast cancer tissue and blood were used as genetic instruments for Rho GTPase expression. As a sensitivity analysis, we undertook co-localisation to examine whether findings reflected shared causal variants or genomic confounding. We identified genetic instruments for 14 of the 20 human Rho GTPases. Using eQTLs obtained from normal breast tissue and normal blood, we identified evidence of a causal role of RHOD in overall and ER+ breast cancers (overall breast cancer: odds ratio (OR) per standard deviation (SD) increase in expression level 1.06; (95% confidence interval (CI) 1.03, 1.09; P = 5.65 × 10(–5)) and OR 1.22 (95% CI 1.11, 1.35; P = 5.22 × 10(–5)) in normal breast tissue and blood respectively). There was a consistent direction of association for ER− breast cancer, although the effect-estimate was imprecisely estimated. Using eQTLs from breast cancer tissue and normal blood there was some evidence that CDC42 was negatively associated with overall and ER + breast cancer risk. The evidence from colocalization analyses strongly supported our MR results particularly for RHOD. Our study suggests a potential causal role of increased RHOD gene expression, and, although the evidence is weaker, a potential protective role for CDC42 gene expression, in overall and ER+ breast cancers. These finding warrant validation in independent samples and further biological investigation to assess whether they may be suitable targets for drug targeting

Environmental Heterogeneity Generates Fluctuating Selection on a Secondary Sexual Trait

SummaryIn any population in which resources are limiting, the allocation of resources toward increased reproductive success may generate costs to survival [1–8]. The relationship between a sexually selected trait and fitness will therefore represent a balance between its relative associations with fecundity versus viability [3, 6, 7]. Because the risk of mortality in a population is likely to be heavily determined by ecological conditions, survival costs may vary as a function of the prevailing environment [7]. As a result, for populations experiencing heterogeneous ecological conditions, there may not be a single optimal level of allocation toward reproduction versus survival [9]. Here, we show that early viability and fecundity selection act in opposing directions on a secondary sexual trait and that their relative magnitude depends upon ecological conditions, generating fluctuating selection. In a wild population of Soay sheep (Ovis aries), phenotypic and genetic associations between male horn growth and lifetime reproductive success were positive under good environmental conditions (because of increased breeding success) and negative under poor environmental conditions (because of reduced survival). In an unpredictable environment, high allocation to early horn growth is a gamble that will only pay off if ensuing conditions are favorable. Such fluctuating selection may play an important role in preventing the erosion of genetic variance in secondary sexual traits

The organisational and human resource challenges facing primary care trusts : protocol of a multiple case study

BACKGROUND: The study is designed to assess the organisational and human resource challenges faced by Primary Care Trusts (PCTs). Its objectives are to: specify the organisational and human resources challenges faced by PCTs in fulfilling the roles envisaged in government and local policy; examine how PCTs are addressing these challenges, in particular, to describe the organisational forms they have adopted, and the OD/HR strategies and initiatives they have planned or in place; assess how effective these structures, strategies and initiatives have been in enabling the PCTs to meet the organisational and human resources challenges they face; identify the factors, both internal to the PCT and in the wider health community, which have contributed to the success or failure of different structures, strategies and initiatives. METHODS: The study will be undertaken in three stages. In Stage 1 the key literature on public sector and NHS organisational development and human resources management will be reviewed, and discussions will be held with key researchers and policy makers working in this area. Stage 2 will focus on detailed case studies in six PCTs designed to examine the organisational and human resources challenges they face. Data will be collected using semi-structured interviews, group discussion, site visits, observation of key meetings and examination of local documentation. The findings from the case study PCTs will be cross checked with a Reference Group of up to 20 other PCG/Ts, and key officers working in organisational development or primary care at local, regional and national level. In Stage 3 analysis of findings from the preparatory work, the case studies and the feedback from the Reference Group will be used to identify practical lessons for PCTs, key messages for policy makers, and contributions to further theoretical development

Access to shops: The views of low-income shoppers

Concern is mounting as the retail stranglehold upon access to food grows. Research on the implications of restructuring retailing and health inequality has failed to involve low-income consumers in this debate. This paper reports on an exercise conducted for the UK Government's, Social Exclusion Unit's Policy Action Team on Access to Shops. The survey provides a useful baseline of the views of low-income groups in England. The choices that people on low income can make were found to be dominated by certain factors such as income and, most importantly, transport. Consumers reported varying levels of satisfaction with retail provision. The findings suggest gaps between what people have, what they want and what the planning process does and does not offer them. Better policy and processes are needed to include and represent the interests of low-income groups

Implementation of a Cardiogenic Shock Protocol and Data Review Process is Associated With Improved In-Hospital Survival

Background: Despite increasing use of mechanical circulatory support devices (MCS), cardiogenic shock (CS) mortality is persistently high, with worsening outcomes in later stages of CS. Delays in diagnosis and practice variation may contribute to in-hospital mortality. Methods: In June 2018, we devised and implemented a CS protocol at two hospitals from one health system in Portland, OR. The CS protocol was designed to promote early CS recognition, rapid notification of a multi-disciplinary specialty team lead by a heart failure cardiologist, invasive hemodynamic evaluation, and institution of MCS as appropriate. CS was defined by widely accepted clinical and hemodynamic criteria. Patient demographics, disease severity, process metrics, and clinical outcomes were prospectively collected and reviewed monthly by a multi-disciplinary CS task force. M&Ms were conducted routinely to identify improvement opportunities. The task force continually refined data collection, implemented protocol improvements, and educated providers and clinical staff in the emergency department, critical care, intermediate care, and cardiac telemetry units. Education centered on early recognition of CS, protocol for activation, and the time-sensitivity of CS outcomes. Results: From June 1, 2018 to October 1, 2019, identification of CS patients grew from five to 55 patients per month, with 311 total patients identified. Education initially emphasized CS identification and team activation, then expanded to definition of CS stages and hospital-specific protocols. Over 10 months, the CS mortality rate decreased by 30%. Ongoing optimization includes stratifying patients by primary discharge diagnosis, consistently documenting shock stages in the electronic medical record, and refining the transfer process from other hospitals. Conclusions: Implementation of a CS protocol with emphasis on early recognition, hemodynamic assessment, and implementation of MCS is associated with improved survival. Multi-disciplinary education and team engagement in data review are integral to continual process improvement. Character count: 1,818 Clinical Implications: A protocolized, multi-disciplinary approach can improve the outcome of CS

Rapid, ultra low coverage copy number profiling of cell-free DNA as a precision oncology screening strategy.

Current cell-free DNA (cfDNA) next generation sequencing (NGS) precision oncology workflows are typically limited to targeted and/or disease-specific applications. In advanced cancer, disease burden and cfDNA tumor content are often elevated, yielding unique precision oncology opportunities. We sought to demonstrate the utility of a pan-cancer, rapid, inexpensive, whole genome NGS of cfDNA approach (PRINCe) as a precision oncology screening strategy via ultra-low coverage (~0.01x) tumor content determination through genome-wide copy number alteration (CNA) profiling. We applied PRINCe to a retrospective cohort of 124 cfDNA samples from 100 patients with advanced cancers, including 76 men with metastatic castration-resistant prostate cancer (mCRPC), enabling cfDNA tumor content approximation and actionable focal CNA detection, while facilitating concordance analyses between cfDNA and tissue-based NGS profiles and assessment of cfDNA alteration associations with mCRPC treatment outcomes. Therapeutically relevant focal CNAs were present in 42 (34%) cfDNA samples, including 36 of 93 (39%) mCRPC patient samples harboring AR amplification. PRINCe identified pre-treatment cfDNA CNA profiles facilitating disease monitoring. Combining PRINCe with routine targeted NGS of cfDNA enabled mutation and CNA assessment with coverages tuned to cfDNA tumor content. In mCRPC, genome-wide PRINCe cfDNA and matched tissue CNA profiles showed high concordance (median Pearson correlation = 0.87), and PRINCe detectable AR amplifications predicted reduced time on therapy, independent of therapy type (Kaplan-Meier log-rank test, chi-square = 24.9, p < 0.0001). Our screening approach enables robust, broadly applicable cfDNA-based precision oncology for patients with advanced cancer through scalable identification of therapeutically relevant CNAs and pre-/post-treatment genomic profiles, enabling cfDNA- or tissue-based precision oncology workflow optimization

Artists on the edge of the world : an integrated approach to the study of Magdalenian engraved stone plaquettes from Jersey (Channel Islands)

Excavations at Les Varines were funded by Jersey Heritage through the States of Jersey Tourism Development Fund (https://www.gov.je/Leisure/Events/TourismDevelopmentFundTDF/pages/abouttdf.aspx) in 2013-15 and in 2017 (BS received the funding), by the British Museum research fund in 2016-18 (https://www.britishmuseum.org/research) (Grant nos EC164/EC208) (BS received the funding), in 2016 by British Academy (https://www.thebritishacademy.ac.uk) small grant SG152868 (CC received the funding) and Society of Antiquaries (https://www.sal.org.uk/) Research Grants R121086 in 2017 and BH181355 in 2018 (CC received the funding). Funding from the Universities of Manchester, Southampton and UCL supported student training at the excavation. Silvia Bello’s work was part of the ‘Human Behaviour in 3D’ Project funded by the Calleva Foundation. Beccy Scott’s work was also supported by the Calleva foundation (Pathways to Ancient Britain project).The Upper Palaeolithic is characterised by the appearance of iconographic expressions most often depicting animals, including anthropomorphic forms, and geometric signs. The Late Upper Palaeolithic Magdalenian saw a flourishing of such depictions, encompassing cave art, engraving of stone, bone and antler blanks and decoration of tools and weapons. Though Magdalenian settlement exists as far northwest as Britain, there is a limited range of art known from this region, possibly associated with only fleeting occupation of Britain during this period. Stone plaquettes, flat fragments of stone engraved on at least one surface, have been found in large quantities at numerous sites spanning the temporal and geographical spread of the Magdalenian, but they have been absent so far from the archaeological record of the British Isles. Between 2015 and 2018, ten fragments of stone plaquettes extensively engraved with abstract designs were uncovered at the Magdalenian site of Les Varines, Jersey, Channel Islands. In this paper, we report detailed analyses of these finds, which provide new evidence for technologies of abstract mark-making, and their significance within the lives of people on the edge of the Magdalenian world. These engraved stone fragments represent important, rare evidence of artistic expression in what is the far northern and western range of the Magdalenian and add new insight to the wider significance of dynamic practices of artistic expression during the Upper Palaeolithic.Publisher PDFPeer reviewe

“I was a full time proper smoker”: A qualitative exploration of smoking in the home after childbirth among women who relapse postpartum

Background: Many women stop smoking during pregnancy but relapse shortly afterwards, potentially putting their infants at risk of secondhand smoke (SHS) exposure. Women who were able to stop during pregnancy may be a motivated group, receptive to making behaviour changes postpartum to protect their infant from SHS exposure. Understanding more about their experiences of relapse, and if this influences home smoking behaviours and children’s exposure to SHS in the home may help to inform intervention development to prevent infant SHS exposure. Methods: Guided by interpretative phenomenological methodology we conducted and analysed nine semi-structured interviews with women who quit smoking during pregnancy, but relapsed ≤3 months postpartum. Findings: Central to mothers’ accounts of their smoking behaviours during pregnancy and postpartum was their desire to be a ‘responsible mother’. Mothers described using strategies to protect their infant from SHS exposure, and held strong negative attitudes towards other smoking parents. After relapsing, mothers appeared to reposition themselves as ‘social’ or ‘occasional’ smokers rather than ‘regular’ smokers Conclusions: Findings suggest that interventions to prevent/reduce infants' home SHS exposure should build on mothers' intentions to be responsible parents. As mothers who relapse principally view themselves as ‘social’ or ‘occasional’ smokers, interventions that are highlighted as relevant for women with these types of smoking patterns may be more likely to be responded to, and, ultimately, be effective

Nitric oxide-mediated posttranslational modifications control neurotransmitter release by modulating complexin farnesylation and enhancing its clamping ability.

Nitric oxide (NO) regulates neuronal function and thus is critical for tuning neuronal communication. Mechanisms by which NO modulates protein function and interaction include posttranslational modifications (PTMs) such as S-nitrosylation. Importantly, cross signaling between S-nitrosylation and prenylation can have major regulatory potential. However, the exact protein targets and resulting changes in function remain elusive. Here, we interrogated the role of NO-dependent PTMs and farnesylation in synaptic transmission. We found that NO compromises synaptic function at the Drosophila neuromuscular junction (NMJ) in a cGMP-independent manner. NO suppressed release and reduced the size of available vesicle pools, which was reversed by glutathione (GSH) and occluded by genetic up-regulation of GSH-generating and de-nitrosylating glutamate-cysteine-ligase and S-nitroso-glutathione reductase activities. Enhanced nitrergic activity led to S-nitrosylation of the fusion-clamp protein complexin (cpx) and altered its membrane association and interactions with active zone (AZ) and soluble N-ethyl-maleimide-sensitive fusion protein Attachment Protein Receptor (SNARE) proteins. Furthermore, genetic and pharmacological suppression of farnesylation and a nitrosylation mimetic mutant of cpx induced identical physiological and localization phenotypes as caused by NO. Together, our data provide evidence for a novel physiological nitrergic molecular switch involving S-nitrosylation, which reversibly suppresses farnesylation and thereby enhances the net-clamping function of cpx. These data illustrate a new mechanistic signaling pathway by which regulation of farnesylation can fine-tune synaptic release