Evaluating the influence of marine protected areas on surf zone fish.

Marine protected areas (MPAs) globally serve conservation and fisheries management goals, generating positive effects in some marine ecosystems. Surf zones and sandy beaches, critical ecotones bridging land and sea, play a pivotal role in the life cycles of numerous fish species and serve as prime areas for subsistence and recreational fishing. Despite their significance, these areas remain understudied when evaluating the effects of MPAs. We compared surf zone fish assemblages inside and outside MPAs across 3 bioregions in California (USA). Using seines and baited remote underwater videos (BRUVs), we found differences in surf zone fish inside and outside MPAs in one region. Inside south region MPAs, we observed higher abundance (Tukey's honest significant difference [HSD] = 0.83, p = 0.0001) and richness (HSD = 0.22, p = 0.0001) in BRUVs and greater biomass (HSD = 0.32, p = 0.0002) in seine surveys compared with reference sites. Selected live-bearing, fished taxa were positively affected by MPAs. Elasmobranchs displayed greater abundance in BRUV surveys and higher biomass in seine surveys inside south region MPAs (HSD = 0.35, p = 0.0003 and HSD = 0.23, p = 0.008, respectively). Although we observed no overall MPA signal for Embiotocidae, abundances of juvenile and large adult barred surfperch (Amphistichus argenteus), the most abundant fished species, were higher inside MPAs (K-S test D = 0.19, p < 0.0001). Influence of habitat characteristics on MPA performance indicated surf zone width was positively associated with fish abundance and biomass but negatively associated with richness. The south region had the largest positive effect size on all MPA performance metrics. Our findings underscored the variability in species richness and composition across regions and survey methods that significantly affected differences observed inside and outside MPAs. A comprehensive assessment of MPA performance should consider specific taxa, their distribution, and the effects of habitat factors and geography.

Evaluación de la influencia de las áreas marinas protegidas sobre los peces de la zona de rompientes Resumen Las áreas marinas protegidas (AMP) cumplen los objetivos de conservación y manejo de pesquerías a nivel mundial, lo que genera efectos positivos en algunos ecosistemas marinos. Las zonas de rompientes y las playas arenosas, ecotonos importantes que conectan la tierra con el mar, tienen un papel esencial en el ciclo de vida de varios peces y fungen como áreas óptimas para la pesca recreativa y de sustento. A pesar de su importancia, estas áreas están poco estudiadas con respecto a la evaluación del efecto de las AMP. Comparamos la composición de peces del área de rompientes dentro y fuera de las AMP de tres bioregiones de California, EUA. Usamos chinchorros y videos submarinos con carnada (BRUVs) y descubrimos diferencias en los peces de la zona de rompientes dentro y fuera de las AMP en una región. Dentro de las AMP de la región sur observamos una mayor abundancia (diferencia significativa honesta de Tukey [DSH]  =  0.83, p = 0.0001) y riqueza (DSH  =  0.22, p = 0.0001) en los BRUV y una mayor biomasa (DSH  =  0.32, p = 0.0002) en los censos con chinchorro en comparación con los sitios de referencia. Los taxones seleccionados de peces de sustento fueron afectados de manera positiva por las AMP. Los elasmobranquios mostraron una mayor abundancia en los BRUV y una mayor biomasa en los censos con chinchorro dentro de las AMP de la región sur (DSH  =  0.35, p = 0.0003 y DSH  =  0.23, p = 0.008, respectivamente). Aunque no observamos una señal generalizada de las AMP para la familia Embiotocidae, la abundancia de Amphistichus argenteus juveniles y adultos, la especie pescada más abundante, fue mayor dentro de las AMP (prueba K­S D  =  0.19, p < 0.0001). La influencia de las características del hábitat sobre el desempeño de las AMP indicó que el ancho de la zona de rompientes está asociado de forma positiva con la abundancia y biomasa de los peces, pero de forma negativa con la riqueza. La región sur tuvo el mayor tamaño de efecto positivo sobre todas las medidas de desempeño de las AMP. Nuestros hallazgos destacan la variabilidad en la riqueza y composición de especies en todas las regiones y los censos que afectan significativamente las diferencias observadas dentro y fuera de las AMP. Una evaluación completa del desempeño de las AMP debe considerar taxones específicos, su distribución y el efecto de los factores de hábitat y la geografía.

Fetal exome sequencing for isolated increased nuchal translucency: should we be doing it?

OBJECTIVE: To evaluate the utility of prenatal exome sequencing (ES) for isolated increased nuchal translucency (NT) and to investigate factors that increase diagnostic yield. DESIGN: Retrospective analysis of data from two prospective cohort studies. SETTING: Fetal medicine centres in the UK and USA. POPULATION: Fetuses with increased NT ≥3.5 mm at 11-14 weeks of gestation recruited to the Prenatal Assessment of Genomes and Exomes (PAGE) and Columbia fetal whole exome sequencing studies (n = 213). METHODS: We grouped cases based on (1) the presence of additional structural abnormalities at presentation in the first trimester or later in pregnancy, and (2) NT measurement at presentation. We compared diagnostic rates between groups using Fisher exact test. MAIN OUTCOME MEASURES: Detection of diagnostic genetic variants considered to have caused the observed fetal structural anomaly. RESULTS: Diagnostic variants were detected in 12 (22.2%) of 54 fetuses presenting with non-isolated increased NT, 12 (32.4%) of 37 fetuses with isolated increased NT in the first trimester and additional abnormalities later in pregnancy, and 2 (1.8%) of 111 fetuses with isolated increased NT in the first trimester and no other abnormalities on subsequent scans. Diagnostic rate also increased with increasing size of NT. CONCLUSIONS: The diagnostic yield of prenatal ES is low for fetuses with isolated increased NT but significantly higher where there are additional structural anomalies. Prenatal ES may not be appropriate for truly isolated increased NT but timely, careful ultrasound scanning to identify other anomalies emerging later can direct testing to focus where there is a higher likelihood of diagnosis.

Evolving fetal phenotypes and clinical impact of progressive prenatal exome sequencing pathways: cohort study.

OBJECTIVES: To determine (1) the diagnostic yield and turnaround time (TAT) of two consecutive prenatal exome sequencing (ES) pathways, (2) the evolution of the fetal phenotype and (3) the clinical impact of detecting causative pathogenic variants and incidental findings. METHODS: This was a retrospective cohort analysis of prospectively collected fetal cases that underwent trio ES in the presence of a structural anomaly and normal chromosomal microarray testing in the West Midlands Regional Genetics Laboratory, Birmingham, UK. The study included two phases: (1) between July 2018 and October 2020, the clinical pathway from the Prenatal Assessment of Genomes and Exomes (PAGE) study was adopted and involved prenatal trio ES based on a panel of 1542 development disorder genes and case selection by a multidisciplinary team; (2) between October 2020 and July 2021, prenatal trio ES investigation was based on the National Health Service (NHS) England R21 pathway, with definitive inclusion criteria and a panel of 1205 prenatally relevant genes. Deep phenotyping was performed throughout pregnancy and postnatally. RESULTS: A total of 54 cases were included. The diagnostic yield before vs after R21 pathway implementation was 28.0% (7/25) and 55.2% (16/29), respectively (P = 0.04). The respective values for mean TAT were 54.0 days (range, 14-213 days) and 14.2 days (range, 3-29 days). In cases in which a causative pathogenic variant was identified and in which the pregnancy reached the third trimester, additional anomalies were detected between the second and third trimesters in 73.3% (11/15) of cases, predominantly secondary to progressive hydropic features (3/11 (27.3%)), arthrogryposis (3/11 (27.3%)) or brain anomaly (2/11 (18.2%)). In three cases, a variant of uncertain significance was reclassified to likely pathogenic based on postnatal information. Detection of a causative pathogenic variant had a significant clinical impact in 78.3% (18/23) of cases, most frequently affecting decision-making regarding the course of the pregnancy and neonatal management (7/18 (38.9%)). CONCLUSIONS: Prenatal ES using the NHS England R21 pathway showed great promise when applied to this cohort, allowing a genetic diagnosis to be made in over half of preselected cases with a fetal structural anomaly on ultrasound. Monitoring and real-time updating of fetal phenotype and reclassification of variants based on postnatal findings is vital to increase the clinical impact that is already evident from this emerging genomic technology. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Disease-driven mass mortality event leads to widespread extirpation and variable recovery potential of a marine predator across the eastern Pacific.

The prevalence of disease-driven mass mortality events is increasing, but our understanding of spatial variation in their magnitude, timing and triggers are often poorly resolved. Here, we use a novel range-wide dataset comprised 48 810 surveys to quantify how sea star wasting disease affected Pycnopodia helianthoides, the sunflower sea star, across its range from Baja California, Mexico to the Aleutian Islands, USA. We found that the outbreak occurred more rapidly, killed a greater percentage of the population and left fewer survivors in the southern half of the species's range. Pycnopodia now appears to be functionally extinct (greater than 99.2% declines) from Baja California, Mexico to Cape Flattery, Washington, USA and exhibited severe declines (greater than 87.8%) from the Salish Sea to the Gulf of Alaska. The importance of temperature in predicting Pycnopodia distribution rose more than fourfold after the outbreak, suggesting latitudinal variation in outbreak severity may stem from an interaction between disease severity and warmer waters. We found no evidence of population recovery in the years since the outbreak. Natural recovery in the southern half of the range is unlikely over the short term. Thus, assisted recovery will probably be required to restore the functional role of this predator on ecologically relevant time scales.

Stereotactic body radiotherapy for synchronous early stage non-small cell lung cancer.

INTRODUCTION: In patients with non-small cell lung cancer (NSCLC) who present with multiple pulmonary nodules, it is often difficult to distinguish metastatic disease from synchronous primary lung cancers (SPLC). We sought to evaluate clinical outcomes after stereotactic body radiotherapy (SBRT) alone to synchronous primary lesions. MATERIAL AND METHODS: Patients with synchronous AJCC 8th Edition Stage IA-IIA NSCLC and treated with stereotactic body radiation therapy (SBRT) to all lesions between 2009-2018 were reviewed. SPLC was defined as patients having received two courses of SBRT within 180 days for treatment of separate early stage tumors. In total, 36 patients with 73 lesions were included. Overall survival (OS), progression-free survival (PFS), cumulative incidence of local failure (LF), and regional/distant failure (R/DF) were estimated and compared with a control cohort of solitary early stage NSCLC patients. RESULTS: Median PFS was 38.8 months (95% CI 14.3-not reached [NR]); 3-year PFS rates were 50.6% (35.6-72.1). Median OS was 45.9 months (95% CI: 35.9-NR); 3-year OS was 63.0% (47.4-83.8). Three-year cumulative incidence of LF and R/DF was 6.6% (3.7-13.9) and 35.7% (19.3-52.1), respectively. Patients with SPLC were compared to a control group (n = 272) of patients treated for a solitary early stage NSCLC. There was no statistically significant difference in PFS (p = .91) or OS (p = .43). Evaluation of the patterns of failure showed a trend for worse cumulative incidence of R/DF in SPLC patients as compared to solitary early stage NSCLC (p = .06). CONCLUSION: SBRT alone to multiple lung tumors with SPLC results in comparable PFS, OS, and LF rates to a cohort of patients treated for solitary early stage NSCLC. Those with SPLC had non-significantly higher R/DF. Patients with SPLC should be followed closely for failure and possible salvage therapy.

Influence of protogynous sex change on recovery of fish populations within marine protected areas.

Marine protected areas (MPAs) are increasingly implemented as a conservation tool worldwide. In many cases, they are managed adaptively: the abundance of target species is monitored, and observations are compared to some model-based expectation for the trajectory of population recovery to ensure that the MPA is achieving its goals. Most previous analyses of the transient (short-term) response of populations to the cessation of fishing inside MPAs have dealt only with gonochore (fixed-sex) species. However, many important fishery species are protogynous hermaphrodites (female-to-male sex-changing). Because size-selective harvest will predominantly target males in these species, harvesting not only reduces abundance but also skews the sex ratio toward females. Thus the response to MPA implementation will involve changes in both survival and sex ratio, and ultimately reproductive output. We used an age-structured model of a generic sex-changing fish population to compare transient population dynamics after MPA implementation to those of an otherwise similar gonochore population and examine how different features of sex-changing life history affect those dynamics. We examined both demographically open (most larval recruitment comes from outside the MPA) and demographically closed (most larval recruitment is locally produced) dynamics. Under both scenarios, population recovery of protogynous species takes longer when fishing was more intense pre-MPA (as in gonochores), but also depends heavily on the mating function, the degree to which the sex ratio affects reproduction. If few males are needed and reproduction is not affected by a highly female-biased sex ratio, then population recovery is much faster; if males are a limiting resource, then increases in abundance after MPA implementation are much slower than for gonochores. Unfortunately, the mating function is largely unknown for fishes. In general, we expect that most protogynous species with haremic mating systems will be in the first category (few males needed), though there is at least one example of a fish species (though not a sex-changing species) for which males are limiting. Thus a better understanding of the importance of male fish to population dynamics is needed for the adaptive management of MPAs.

Combining spore germination and heat inactivation to decontaminate materials contaminated with Bacillus anthracis spores.

AIMS: To add a spore germination step in order to reduce decontamination temperature and time requirements compared to the current hot, humid air decontamination parameters, which are 75-80°C, ≥72 h, 70-90% RH, down to ≤60°C and ≤24 h total decontamination time. METHODS AND RESULTS: Bacillus anthracis spore germination with l-alanine+inosine+calcium dipicolinate (CaDPA) was quantified at 0-40°C, several time points and spore concentrations of 5-9 log10 per ml. Germination efficiency at 0-40°C was >99% at <8 log10 spores per ml. The temperature optimum was 20°C. Germination efficiency was significantly higher but slower at 0°C compared to ≥30°C at ≥8 log10 spores per ml. A single germinant application followed by 60°C, 1-h treatment consistently inactivated >2 log10 (>99%) of spores. However, a repeat application of germinant was needed to achieve the objective of ≥6 log10 spore inactivation out of a 7 log10 challenge (≥99·9999%) for ≤24 h total decontamination time for nylon and aircraft performance coating. CONCLUSIONS: l-alanine+inosine+CaDPA stimulated germination across wide temperature and spore concentration ranges. SIGNIFICANCE AND IMPACT OF THE STUDY: Germination expands the scope of spore decontamination to include materials from any industry sector that can be sprayed with an aqueous germinant solution.

Supporting mental health service users to stop smoking: findings from a process evaluation of the implementation of smokefree policies into two mental health trusts.

BACKGROUND: Life expectancy is 10-20 years lower among people with a severe mental health disorder. Most of these early deaths are due to chronic conditions, including cardiovascular and respiratory diseases. Smoking is a major risk factor for these conditions and introducing smokefree policies has been recommended to mental health service providers in England by the National Institute for Health and Care Excellence (NICE), in their Public Health Guideline 48: Smoking: acute, maternity and mental health services. This paper reports a process evaluation of introducing these policy recommendations, which were updated in 2013. METHOD: Process data were collected through semi-structured interviews with staff (n = 51), members of partnering organisations (n = 5), service users (n = 7) and carers (n = 2) between November 2016 - April 2017. Normalization Process Theory (NPT) was used to design the data collection tools and analyse the data. A framework approach was taken with the analysis, using the four concepts of NPT: coherence, cognitive participation, collective action and reflexive monitoring. RESULTS: The policy made sense to some staff, patients and carers (coherence) who 'bought-into' the idea (cognitive participation) but other participants disagreed. Although smokefree policies were operationalised (collective action), sometimes they were opposed. Progress was made, especially in some units, but continued to be resisted in others. Informal appraisal of progress (reflexive monitoring) presented a varied picture. CONCLUSION: Some progress has been made in terms of changing an entrenched, smoking culture into one that is smokefree on Trust sites across the region. Perseverance and resourcing over the long-term is required to establish a non-smoking culture in on-site provision of mental health services.

Securing access to personnel and materials in transboundary animal disease responses.

A lack of human and material resources can limit effective responses to animal disease emergencies. Drawing upon examples from Australia and New Zealand, this paper proposes a framework for identifying human and material resources and securing the necessary personnel and materials before or during an animal disease emergency. This staged process involves: a) assessing the nature of the risks to be managed, b) identifying the types of resources required, c) assessing available resources and identifying gaps and d) developing arrangements to ensure availability of resources. It discusses the advantages and disadvantages of different strategies to secure access to human and material resources, including whole-of-government arrangements to access other government resources, national and international reserve models for responders, just-in-time employment and purchase of materials, and purchase of stockpiles.

La disponibilité insuffisante des ressources tant humaines que matérielles peut limiter l'efficacité des interventions en cas d'urgence zoosanitaire. À partir de l'expérience acquise par l'Australie et la Nouvelle-Zélande, les auteurs proposent un cadre permettant d'inventorier les ressources humaines et matérielles et de garantir la disponibilité des personnels et des équipements nécessaires avant ou pendant une urgence zoosanitaire. Le processus par étapes proposé prévoit : a) d'évaluer la nature des risques qu'il conviendra de traiter ; b) d'identifier les types de ressources à mobiliser ; c) d'évaluer les ressources disponibles et les lacunes ; d) de prendre les dispositions nécessaires pour garantir la disponibilité opérationnelle des ressources. Les auteurs examinent les avantages et les inconvénients respectifs de diverses stratégies visant à se doter des ressources humaines et matérielles nécessaires, en particulier les dispositions gouvernementales permettant de réquisitionner d'autres ressources publiques, les schémas nationaux et internationaux d'intervenants réservistes, les dispositifs d'emploi et d'achats de matériel à flux tendus et la constitution de stocks stratégiques.

La cantidad de recursos humanos y materiales disponibles puede ser un factor limitante a la hora de responder eficazmente a las emergencias zoosanitarias. Partiendo de ejemplos tomados de Australia y Nueva Zelanda, los autores proponen un marco de referencia para determinar los recursos humanos y materiales necesarios y asegurarse de contar con ellos antes o en el curso de una emergencia zoosanitaria. Se trata de un proceso por etapas, que pasa por: a) evaluar la naturaleza de los riesgos que hay que manejar; b) determinar los tipos de recursos que se requieren; c) determinar los recursos disponibles y los faltantes; y d) concebir e implantar disposiciones para asegurarse de tener disponibles todos esos recursos. Los autores pasan revista a las ventajas e inconvenientes de distintos procedimientos para asegurarse el acceso a recursos humanos y materiales, tales como: la aplicación de disposiciones que, abarcando todas las instancias gubernamentales, garanticen el acceso a recursos de otras instancias públicas; los modelos de personal reservista nacional e internacional; los métodos de contratación y compra de material «justo a tiempo¼ (just-in-time); o la adquisición por adelantado de existencias de reserva.

Ado-trastuzumab emtansine (T-DM1) in patients with HER2-amplified tumors excluding breast and gastric/gastroesophageal junction (GEJ) adenocarcinomas: results from the NCI-MATCH trial (EAY131) subprotocol Q.

BACKGROUND: The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) is a national precision medicine study incorporating centralized genomic testing to direct refractory cancer patients to molecularly targeted treatment subprotocols. This treatment subprotocol was designed to screen for potential signals of efficacy of ado-trastuzumab emtansine (T-DM1) in HER2-amplified histologies other than breast and gastroesophageal tumors. METHODS: Eligible patients had HER2 amplification at a copy number (CN) >7 based on targeted next-generation sequencing (NGS) with a custom Oncomine AmpliSeq™ (ThermoFisher Scientific) panel. Patients with prior trastuzumab, pertuzumab or T-DM1 treatment were excluded. Patients received T-DM1 at 3.6 mg/kg i.v. every 3 weeks until toxicity or disease progression. Tumor assessments occurred every three cycles. The primary end point was centrally assessed objective response rate (ORR). Exploratory end points included correlating response with HER2 CN by NGS. The impact of co-occurring genomic alterations and PTEN loss by immunohistochemistry were also assessed. RESULTS: Thirty-eight patients were enrolled and 36 included in efficacy analysis. Median prior therapies in the metastatic setting was 3 (range 0-9; unknown in one patient). Median HER2 CN was 17 (range 7-139). Partial responses were observed in two (5.6%) patients: one mucoepidermoid carcinoma of parotid gland and one parotid gland squamous cell cancer. Seventeen patients (47%) had stable disease including 8/10 (80%) with ovarian and uterine carcinomas, with median duration of 4.6 months. The 6-month progression-free survival rate was 23.6% [90% confidence interval 14.2% to 39.2%]. Common toxicities included fatigue, anemia, fever and thrombocytopenia with no new safety signals. There was a trend for tumor shrinkage with higher levels of gene CN as determined by the NGS assay. CONCLUSION: T-DM1 was well tolerated. While this subprotocol did not meet the primary end point for ORR in this heavily pre-treated diverse patient population, clinical activity was seen in salivary gland tumors warranting further study in this tumor type in dedicated trials.

Utility of a molecular prescreening program in advanced colorectal cancer for enrollment on biomarker-selected clinical trials.

BACKGROUND: Incorporation of multiple enrichment biomarkers into prospective clinical trials is an active area of investigation, but the factors that determine clinical trial enrollment following a molecular prescreening program have not been assessed. PATIENTS AND METHODS: Patients with 5-fluorouracil-refractory metastatic colorectal cancer at the MD Anderson Cancer Center were offered screening in the Assessment of Targeted Therapies Against Colorectal Cancer (ATTACC) program to identify eligibility for companion phase I or II clinical trials with a therapy targeted to an aberration detected in the patient, based on testing by immunohistochemistry, targeted gene sequencing panels, and CpG island methylation phenotype assays. RESULTS: Between August 2010 and December 2013, 484 patients were enrolled, 458 (95%) had a biomarker result, and 157 (32%) were enrolled on a clinical trial (92 on biomarker-selected and 65 on nonbiomarker selected). Of the 458 patients with a biomarker result, enrollment on biomarker-selected clinical trials was ninefold higher for predefined ATTACC-companion clinical trials as opposed to nonpredefined biomarker-selected clinical trials, 17.9% versus 2%, P < 0.001. Factors that correlated positively with trial enrollment in multivariate analysis were higher performance status, older age, lack of standard of care therapy, established patient at MD Anderson, and the presence of an eligible biomarker for an ATTACC-companion study. Early molecular screening did result in a higher rate of patients with remaining standard of care therapy enrolling on ATTACC-companion clinical trials, 45.1%, in contrast to nonpredefined clinical trials, 22.7%; odds ratio 3.1, P = 0.002. CONCLUSIONS: Though early molecular prescreening for predefined clinical trials resulted in an increase rate of trial enrollment of nonrefractory patients, the majority of patients enrolled on clinical trials were refractory to standard of care therapy. Within molecular prescreening programs, tailoring screening for preidentified and open clinical trials, temporally linking screening to treatment and optimizing both patient and physician engagement are efforts likely to improve enrollment on biomarker-selected clinical trials. CLINICAL TRIALS NUMBER: The study NCT number is NCT01196130.

Effect of niacin on triglyceride-rich lipoprotein apolipoprotein B-48 kinetics in statin-treated patients with type 2 diabetes.

AIM: To investigate the effects of extended-release (ER) niacin on apolipoprotein B-48 (apoB-48) kinetics in statin-treated patients with type 2 diabetes (T2DM). METHODS: A total of 12 men with T2DM were randomized to rosuvastatin or rosuvastatin plus ER niacin for 12 weeks and then crossed to the alternate therapy. Postprandial metabolic studies were performed at the end of each treatment period. D3-leucine tracer was administered as subjects consumed a high-fat liquid meal. ApoB-48 kinetics were determined using stable isotope tracer kinetics with fractional catabolic rates (FCRs) and secretion rates derived using a non-steady-state compartmental model. Area-under-the-curve (AUC) and incremental AUC (iAUC) for plasma triglyceride and apoB-48 were also calculated over the 10-h period after ingestion of the fat meal. RESULTS: In statin-treated patients with T2DM, apoB-48 concentration was lower with ER niacin (8.24 ± 1.98 vs 5.48 ± 1.14 mg/l, p = 0.03) compared with statin alone. Postprandial triglyceride and apoB-48 AUC were also significantly lower on ER niacin treatment (-15 and -26%, respectively; p < 0.05), without any change to triglyceride and apoB-48 iAUC. ApoB-48 secretion rate in the basal state (3.21 ± 0.34 vs 2.50 ± 0.31 mg/kg/day; p = 0.04) and number of apoB-48-containing particles secreted in response to the fat load (1.35 ± 0.19 vs 0.84 ± 0.12 mg/kg; p = 0.02) were lower on ER niacin. ApoB-48 FCR was not altered with ER niacin (8.78 ± 1.04 vs 9.17 ± 1.26 pools/day; p = 0.79). CONCLUSIONS: ER niacin reduces apoB-48 concentration by lowering fasting and postprandial apoB-48 secretion rate. This effect may be beneficial for lowering atherogenic postprandial lipoproteins and may provide cardiovascular disease risk benefit in patients with T2DM.

Viewpoint survey of mental health service users' experiences of discrimination in England 2008-2014.

OBJECTIVE: Discrimination reported by mental health service users in England is high. The study aims to determine changes in mental health-related discrimination from 2008 to 2014. METHODS: Samples of mental health service users were interviewed from 2008 to 2014 using the Discrimination and Stigma Scale version 12. Social capital in terms of access to social resources is a marker of discrimination in terms of effects on social connections, and so from 2011, social capital also measured using the Resource Generator-UK. RESULTS: Fewer participants reported discrimination in one or more life areas in 2014 compared to 2008 (OR: 0.58, 95% CI 0.36 to 0.94 P = 0.03). A weighted multiple regression model found a decrease in overall discrimination in 2014 compared to 2008 (mean difference: -13.55, 95% CI: -17.32 to -9.78, P < 0.001). There was not a consistent in discrimination decline between each year. No differences in access to social resources were found. CONCLUSIONS: Discrimination has fallen significantly over 2008-2014, although there was not a consistent decline between years. There is no evidence that social capital has increased.

The economic costs of mental health-related discrimination.

OBJECTIVE: To estimate and compare the economic costs of mental health-related discrimination in the domains of health care, relationships and participation in leisure activities in England between 2011 and 2014. METHOD: A subsample of the Viewpoint survey was interviewed using the Costs of Discrimination Assessment Questionnaire in 2011 and 2014. Information on the impact of discrimination on healthcare use, help seeking from family and friends and participation in leisure activities was recorded. Pattern of contacts, costs and predictor of costs were examined. RESULTS: Our findings showed higher costs of health service use for individuals who reported experiences of discrimination in healthcare settings in 2011 compared with those who did not (mean difference £625, P-value 0.019). Individuals who reported experiences of discrimination in relationships in 2014 had higher healthcare costs than those who did not (mean difference £418, P -value 0.034). There was some evidence of a reduction in overall levels of healthcare use, leisure activities and support from families over time. Discrimination did not significantly affect help seeking from family/friends or leisure activities. CONCLUSION: There is some evidence that discrimination is related to increased healthcare costs. A prospective study is needed to better understand the consequences of these effects.

Qualitative analysis of mental health service users' reported experiences of discrimination.

OBJECTIVE: To better understand mental health service users' experiences of stigma and discrimination in different settings. METHOD: An annual telephone survey of people with a mental health diagnosis conducted to evaluate the Time to Change antistigma campaign in England. Of 985 people who participated in 2013, 84 took part in a qualitative interview which was audio recorded. Of these, 50 interviews were transcribed and thematically analysed to explore accounts of discrimination. We analysed common types of behaviour; motivations ascribed to the discriminators; expectations of what fair treatment would have been; and the impact of discrimination on participants. RESULTS: Discrimination was most common in five contexts: welfare benefits, mental health care, physical health care, family and friends. Participants often found it hard to assess whether a behaviour was discriminatory or not. Lack of support, whether by public services or by friends and family, was often experienced as discrimination, reflecting an expectation that positive behaviours and reasonable adjustments should be offered in response to mental health needs. CONCLUSION: The impact of discrimination across different settings was often perceived by participants as aggravating their mental health, and there is thus a need to treat discrimination as a health issue, not just a social justice issue.

Increasing of blastocyst rate and gene expression in co-culture of bovine embryos with adult adipose tissue-derived mesenchymal stem cells.

PURPOSE: Despite advances in the composition of defined embryo culture media, co-culture with somatic cells is still used for bovine in vitro embryo production (IVEP) in many laboratories worldwide. Granulosa cells are most often used for this purpose, although recent work suggests that co-culture with stem cells of adult or embryonic origin or their derived biomaterials may improve mouse, cattle, and pig embryo development. MATERIALS AND METHODS: In experiment 1, in vitro produced bovine embryos were co-cultured in the presence of two concentrations of bovine adipose tissue-derived mesenchymal cells (b-ATMSCs; 103 and 104 cells/mL), in b-ATMSC preconditioned medium (SOF-Cond), or SOF alone (control). In experiment 2, co-culture with 104 b-ATMSCs/mL was compared to the traditional granulosa cell co-culture system (Gran). RESULTS: In experiment 1, co-culture with 104 b-ATMSCs/mL improved blastocyst rates in comparison to conditioned and control media (p < 0.05). Despite that it did not show difference with 103 b-ATMSCs/mL (p = 0.051), group 104 b-ATMSCs/mL yielded higher results of blastocyst production. In experiment 2, when compared to group Gran, co-culture with 104 b-ATMSCs/mL improved not only blastocyst rates but also quality as assessed by increased total cell numbers and mRNA expression levels for POU5F1 and G6PDH (p < 0.05). CONCLUSIONS: Co-culture of bovine embryos with b-ATMSCs was more beneficial than the traditional co-culture system with granulosa cells. We speculate that the microenvironmental modulatory potential of MSCs, by means of soluble substances and exosome secretions, could be responsible for the positive effects observed. Further experiments must be done to evaluate if this beneficial effect in vitro also translates to an increase in offspring following embryo transfer. Moreover, this study provides an interesting platform to study the basic requirements during preimplantation embryo development, which, in turn, may aid the improvement of embryo culture protocols in bovine and other species.

Factors associated with experienced discrimination among people using mental health services in England.

BACKGROUND: Research has found considerable variation in how far individuals with a diagnosis of mental illness experience discrimination. AIMS: This study tested four hypotheses: (i) a diagnosis of schizophrenia will be associated with more discrimination than depression, anxiety or bipolar disorder; (ii) people with a history of involuntary treatment will report more discrimination than people without; (iii) higher levels of avoidance behaviour due to anticipated discrimination will be associated with higher levels of discrimination and (iv) longer time in contact with services will be associated with higher levels of discrimination. METHOD: Three thousand five hundred and seventy-nine people using mental health services in England took part in structured telephone interviews about discrimination experiences. RESULTS: A multiple regression model found that study year, age, employment status, length of time in mental health services, disagreeing with the diagnosis, anticipating discrimination in personal relationships and feeling the need to conceal a diagnosis from others were significantly associated with higher levels of experienced discrimination. CONCLUSION: Findings suggest that discrimination is not related to specific diagnoses but rather is associated with mental health problems generally. An association between unemployment and discrimination may indicate that employment protects against experiences of discrimination, supporting efforts to improve access to employment among people with a diagnosis of mental illness.

Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. METHODS: Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. RESULTS: We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). CONCLUSIONS: This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH.

Viewpoint survey of mental health service users' experiences of discrimination in England 2008-2012.

PURPOSE: Research suggests levels of discrimination among mental health service users in England are high, but fell over the course of the first phase of the Time to Change programme to reduce stigma and discrimination (2008-2011). The aim of this study was to determine changes in discrimination levels, both overall and by the area of life in which discrimination is experienced, since Time to Change began and over the first year of its second phase (2011-2012). METHOD: Separate samples of mental health service users were interviewed annually from 2008 to 2012 using the Discrimination and Stigma Scale. In 2011 and 2012, social capital was also measured using the Resource Generator-UK. RESULTS: Sample percentages of participants reporting the experience of discrimination in one or more life areas for years 2008-2012 were 91.4, 86.5, 86.2, 87.9 and 91.0 %, respectively. A multivariable logistic regression model was performed to test for significant differences by study year, weighted to match the study population and adjusted for employment status and diagnosis as potential confounding factors. The odds of reporting discrimination in one or more life areas were significantly lower as compared to 2008 for all subsequent years except for 2012 (0.76, 95 % CI 0.49-1.19). However, a weighted multiple regression model provided evidence of decreased mean overall discrimination in 2012 as compared to 2008 (mean decrease -7.57, 95 % CI -11.1 to -4.0, p < 0.001). The weighted mean number of social resources was 13.5 in 2012 as compared to 14.0 in 2011 (mean difference -0.60, 95 % CI -1.25 to 0.06). CONCLUSIONS: While the overall level of discrimination across the life areas studied has fallen over 2008-2012, there is no evidence that more people using mental health services experience no discrimination. We suggest that the pattern suggesting a recent rise in discrimination following an earlier reduction may be linked to economic austerity. Further, the welfare benefits system has become an increasing source of discriminatory experience.