Marine mammal distribution and abundance in an offshore sub-region of the northeastern Chukchi Sea during the open-water season

AbstractThis paper describes the distribution and abundance of marine mammals during the open-water season within and near three offshore oil and gas prospects in the northeastern Chukchi Sea, known as the Klondike, Burger, and Statoil study areas. We collected vessel-based marine mammal data during July–October 2008–2010 along line transects oriented in a north–south direction. Over this period, we surveyed ~18,600km of on-transect effort in the three study areas. Sightings of cetaceans were rare. The bowhead whale was the primary cetacean species sighted and was mostly observed in October (33 of 35 animals). Pinnipeds were the most abundant marine mammals in the study area, with 980 seals and 367 walruses recorded on transect. Most seals were observed as solitary animals, while walruses were often observed in aggregations. We calculated seal and walrus densities using species-specific detection functions corrected for probability of detection. There was high interannual variability in the abundance of seals and walruses that for some species may be related to interannual differences in ice conditions. Notwithstanding this variation, the distribution data suggest that benthic-feeding bearded seals and walruses generally were more common in the Burger and Statoil study areas, which can be characterized as more benthic-dominated ecosystems. The distribution of ringed/spotted seals did not show any statistically significant differences among the study areas, although a slight preference for the Klondike and Statoil study areas was suggested. Both of these study areas are affected by Bering Sea Water from the Central Channel and have a stronger pelagic component than the Burger study area. Continued sampling of these areas will help establish whether the observed trends in marine mammal distribution and abundance are persistent

Bostonia: The Boston University Alumni Magazine. Volume 9

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Testing approaches to sharing trial results with participants : The Show RESPECT cluster randomised, factorial, mixed methods trial

Funding: The Show RESPECT study was funded by the Medical Research Council through core grants to MRS at the MRC CTU at UCL for Trial Conduct Methodology (MC_UU12023/24 and MC_UU_00004/08) https://mrc.ukri.org/. The funder had no role in the study design, the collection, analysis and interpretation of data, the writing of the report and the decision to submit the article for publication. All authors had full access to the study data, including statistical reports and tables, and can take responsibility for the integrity of the data and the accuracy of the data analysis. Acknowledgments We are very thankful to the patients who participated in this study and the people who contributed to our Patient and Public Involvement activities. We are very grateful for the work of the Show RESPECT site teams in carrying out this study. A list of team members from sites can be found in S10 Table. We thank Eva Burnett, who is a patient representative on the Study Steering Group for Show RESPECT and ICON8, for her input on the design and conduct of this study and for her comments on this manuscript, and Amanda Hunn for her contributions to the steering group. We also acknowledge the hard work and diligence of Sierra Santana and Ania Spurdens, who were data managers for Show RESPECT. We also wish to thank the ICON8 trial team for their support of this project, particularly Andrew Clamp, Babasola Popoola, Francesca Schiavone, Jonathan Badrock, and Rick Kaplan. We also thank Julia Bailey for her advice and guidance on the qualitative aspect of this study.Peer reviewedPublisher PD

Tandem quadruplication of HMA4 in the zinc (Zn) and cadmium (Cd) hyperaccumulator noccaea caerulescens

Zinc (Zn) and cadmium (Cd) hyperaccumulation may have evolved twice in the Brassicaceae, in Arabidopsis halleri and in the Noccaea genus. Tandem gene duplication and deregulated expression of the Zn transporter, HMA4, has previously been linked to Zn/Cd hyperaccumulation in A. halleri. Here, we tested the hypothesis that tandem duplication and deregulation of HMA4 expression also occurs in Noccaea. A Noccaea caerulescens genomic library was generated, containing 36,864 fosmid pCC1FOSTM clones with insert sizes ~20–40 kbp, and screened with a PCR-generated HMA4 genomic probe. Gene copy number within the genome was estimated through DNA fingerprinting and pooled fosmid pyrosequencing. Gene copy numbers within individual clones was determined by PCR analyses with novel locus specific primers. Entire fosmids were then sequenced individually and reads equivalent to 20-fold coverage were assembled to generate complete whole contigs. Four tandem HMA4 repeats were identified in a contiguous sequence of 101,480 bp based on sequence overlap identities. These were flanked by regions syntenous with up and downstream regions of AtHMA4 in Arabidopsis thaliana. Promoter-reporter b-glucuronidase (GUS) fusion analysis of a NcHMA4 in A. thaliana revealed deregulated expression in roots and shoots, analogous to AhHMA4 promoters, but distinct from AtHMA4 expression which localised to the root vascular tissue. This remarkable consistency in tandem duplication and deregulated expression of metal transport genes between N. caerulescens and A. halleri, which last shared a common ancestor >40 mya, provides intriguing evidence that parallel evolutionary pathways may underlie Zn/Cd hyperaccumulation in Brassicaceae

Healthcare systems data in the context of clinical trials - A comparison of cardiovascular data from a clinical trial dataset with routinely collected data

BACKGROUND: Routinely-collected healthcare systems data (HSD) are proposed to improve the efficiency of clinical trials. A comparison was undertaken between cardiovascular (CVS) data from a clinical trial database with two HSD resources. METHODS: Protocol-defined and clinically reviewed CVS events (heart failure (HF), acute coronary syndrome (ACS), thromboembolic stroke, venous and arterial thromboembolism) were identified within the trial data. Data (using pre-specified codes) was obtained from NHS Hospital Episode Statistics (HES) and National Institute for Cardiovascular Outcomes Research (NICOR) HF and myocardial ischaemia audits for trial participants recruited in England between 2010 and 2018 who had provided consent. The primary comparison was trial data versus HES inpatient (APC) main diagnosis (Box-1). Correlations are presented with descriptive statistics and Venn diagrams. Reasons for non-correlation were explored. RESULTS: From 1200 eligible participants, 71 protocol-defined clinically reviewed CVS events were recorded in the trial database. 45 resulted in a hospital admission and therefore could have been recorded by either HES APC/ NICOR. Of these, 27/45 (60%) were recorded by HES inpatient (Box-1) with an additional 30 potential events also identified. HF and ACS were potentially recorded in all 3 datasets; trial data recorded 18, HES APC 29 and NICOR 24 events respectively. 12/18 (67%) of the HF/ACS events in the trial dataset were recorded by NICOR. CONCLUSION: Concordance between datasets was lower than anticipated and the HSD used could not straightforwardly replace current trial practices, nor directly identify protocol-defined CVS events. Further work is required to improve the quality of HSD and consider event definitions when designing clinical trials incorporating HSD

Root exudates of the hyperaccumulator Thlaspi caerulescens do not enhance metal mobilization

To examine whether root exudates of the Zn/Cd hyperaccumulator Thlaspi caerulescens play a role in metal hyperaccumulation, we compared the metal mobilization capacity of root exudates collected from two ecotypes of T. caerulescens, and from the nonaccumulators wheat (Triticum aestivum) and canola (Brassica napus). Plants were grown hydroponically and three treatments (control, -Fe and -Zn) were later imposed for 2 wk before collection of root exudates. On a basis of root d. wt, the total soluble organic C in the root exudates of T. caerulescens was similar to that of wheat, and significantly higher than that of canola. In all treatment, the root exudates of T. caerulescens and canola mobilized little Cu and Zn from Cu- or Zn-loaded resins, and little Zn, Cd, Cu or Fe from a contaminated calcareous soil. By contrast, the root exudates of wheat generally mobilized more metals from both resin and soil. In particular, the -Fe treatment, and to a lesser extent the -Zn treatment, elicited large increases in the metal mobilization capacity of the root exudates from wheat. We conclude that root exudates from T. caerulescens do not significantly enhance mobilization of Zn and Cd, and therefore are not involved in Zn and Cd hyperaccumulation. (C) New Phytologist (2001)

BDSM Disclosure and Stigma Management: Identifying Opportunities for Sex Education

While participation in the activities like bondage, domination, submission/sadism, masochism that fall under the umbrella term BDSM is widespread, stigma surrounding BDSM poses risks to practitioners who wish to disclose their interest. We examined risk factors involved with disclosure to posit how sex education might diffuse stigma and warn of risks. Semi-structured interviews asked 20 adults reporting an interest in BDSM about their disclosure experiences. Most respondents reported their BDSM interests starting before age 15, sometimes creating a phase of anxiety and shame in the absence of reassuring information. As adults, respondents often considered BDSM central to their sexuality, thus disclosure was integral to dating. Disclosure decisions in nondating situations were often complex considerations balancing desire for appropriateness with a desire for connection and honesty. Some respondents wondered whether their interests being found out would jeopardize their jobs. Experiences with stigma varied widely

Accessing routinely collected health data to improve clinical trials: recent experience of access.

BACKGROUND: Routinely collected electronic health records (EHRs) have the potential to enhance randomised controlled trials (RCTs) by facilitating recruitment and follow-up. Despite this, current EHR use is minimal in UK RCTs, in part due to ongoing concerns about the utility (reliability, completeness, accuracy) and accessibility of the data. The aim of this manuscript is to document the process, timelines and challenges of the application process to help improve the service both for the applicants and data holders. METHODS: This is a qualitative paper providing a descriptive narrative from one UK clinical trials unit (MRC CTU at UCL) on the experience of two trial teams' application process to access data from three large English national datasets: National Cancer Registration and Analysis Service (NCRAS), National Institute for Cardiovascular Outcomes Research (NICOR) and NHS Digital to establish themes for discussion. The underpinning reason for applying for the data was to compare EHRs with data collected through case report forms in two RCTs, Add-Aspirin (ISRCTN 74358648) and PATCH (ISRCTN 70406718). RESULTS: The Add-Aspirin trial, which had a pre-planned embedded sub-study to assess EHR, received data from NCRAS 13 months after the first application. In the PATCH trial, the decision to request data was made whilst the trial was recruiting. The study received data after 8 months from NICOR and 15 months for NHS Digital following final application submission. This concluded in May 2020. Prior to application submission, significant time and effort was needed particularly in relation to the PATCH trial where negotiations over consent and data linkage took many years. CONCLUSIONS: Our experience demonstrates that data access can be a prolonged and complex process. This is compounded if multiple data sources are required for the same project. This needs to be factored in when planning to use EHR within RCTs and is best considered prior to conception of the trial. Data holders and researchers are endeavouring to simplify and streamline the application process so that the potential of EHR can be realised for clinical trials

Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme

Background Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. Methods PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. Findings Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4–7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80–1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86–1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001). Interpretation Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer. Funding Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London

Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme

Background: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. Methods: PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. Findings: Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4–7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80–1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86–1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001). Interpretation: Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer. Funding: Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London