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International wild Atlantic salmon management priorities have moved from exploitation to conservation since the 1990s, recognizing the need to protect diversity and abundance at individual river levels amid widespread declines. Here we review international salmon-stock assessments and describe a simple, transferable catch-advice framework, established for management of fisheries that conforms to international obligations. The risk assessment approach, applied at the river scale, jointly incorporates uncertainty in estimated and forecasted returning salmon numbers with the level of uncertainty around spawning requirements (Conservation Limits). Outputs include quantification of risk of stocks not attaining conservation limits (CL) and surpluses above CL on stocks able to support sustainable exploitation via total allowable catches (TAC), with monitoring by rod catch or fish counter. Since management implementation and cessation of at-sea mixed-stock fisheries, there has been a deterioration in the performance of many individual stocks, without any sustained increase in fisheries open to harvest. Given declines in mid-latitude Atlantic salmon populations over 30 years, the novel framework presented provides an approach to protect stocks failing to meet spawning thresholds while supporting sustainable exploitation of those achieving them. On-going management policy of adopting scientific advice and allowing exploitation only on stocks exceeding CLs is central to the objective of protecting salmon stocks. [ABSTRACT FROM AUTHOR]

Malignant mesothelioma (MM) is an incurable cancer of the serosal lining that is often caused by exposure to asbestos. Therefore, novel agents for the prevention and treatment of this disease are urgently needed. Asbestos induces the release of pro-inflammatory cytokines such as IL-1β and IL-6, which play a role in MM development. IL-6 is a component of the JAK-STAT3 pathway that contributes to inflammation-associated tumorigenesis. Glycoprotein 130 (gp130), the signal transducer of this signaling axis, is an attractive drug target because of its role in promoting neoplasia via the activation of downstream STAT3 signaling. The anticancer drug, SC144, inhibits the interaction of gp130 with the IL-6 receptor (IL6R), effectively blunting signaling from this inflammatory axis. To test whether the inflammation-related release of IL-6 plays a role in the formation of MM, we evaluated the ability of SC144 to inhibit asbestos-induced carcinogenesis in a mouse model. The ability of sulindac and anakinra, an IL6R antagonist/positive control, to inhibit MM formation in this model was tested in parallel. Asbestos-exposed Nf2 +/− ;Cdkn2a +/− mice treated with SC144, sulindac or anakinra showed significantly prolonged survival compared to asbestos-exposed vehicle-treated mice. STAT3 activity was markedly decreased in MM specimens from SC144-treated mice. Furthermore, SC144 inhibited STAT3 activation by IL-6 in cultured normal mesothelial cells, and in vitro treatment of MM cells with SC144 markedly decreased the expression of STAT3 target genes. The emerging availability of newer, more potent SC144 analogs showing improved pharmacokinetic properties holds promise for future trials, benefitting individuals at high risk of this disease. [ABSTRACT FROM AUTHOR]

Exceptional times call for exceptional measures—this formula is all too familiar in the domestic setting. Governments have often played loose with their state's constitution in the name of warding off an urgent threat. But after decades of increasing interconnectedness and emerging transnational governance, today one sees new forms of emergency politics that are cross-border in range. From the European Union to the World Health Organization, from supranational institutions to state governments acting in concert, the logic of emergency is embraced in international contexts, with Covid-19 the latest occasion. This Forum offers an entry-point into this emerging phenomenon. Taking as its point of departure two recent books, it examines the origins, forms, effects and normative stakes of emergency politics beyond the state. Among the matters discussed are the concept of emergency politics, the historical context of its contemporary forms, the patterns of decision-making associated with it, the implications for the legitimacy of transnational institutions, and the constitutional and political ways in which it might be contained. Transnational emergency politics seems likely to remain a central feature of the coming years, and our aim is to further its study in international relations. [ABSTRACT FROM AUTHOR]

Objective: Distinguishing normal pressure hydrocephalus (NPH) from Alzheimer's disease (ad) would aid patient selection for lumbar drain trials (LDT). Cerebrospinal fluid (CSF) ad biomarkers are altered in NPH, limiting interpretation. This study examines the utility of CSF ad biomarkers in predicting gait and cognitive outcomes in patients undergoing LDT. Methods: 127 patients underwent LDT. CSF ad biomarkers from Mayo Clinic Laboratories (MCL) or Athena Diagnostics were used to classify patients as ad, non-ad, or indeterminate. MCL indeterminate results were further classified as suspected ad, non-ad, or suspected NPH (sNPH) using a derived p-tau threshold (>15 pg/mL & Aß42 <=1026 pg/mL)1. Cognitive improvement was determined using reliable change indices for Trail Making Test A&B and Hopkins Verbal Learning Test-Revised. Physical therapists (PT) utilized the Berg Balance Scale and/or the Timed Up and Go to determine gait improvements. Chi-square tests investigated relationships between diagnostic groups, PT and cognitive improvements, and eventual shunting for the whole sample and then stratified by the two laboratory assays. Results: The sNPH group had the highest percentage of PT (63%–70%) and cognitive (9% -11%) improvement (see Table 1), while the ad group had the lowest (50% and 3%, respectively). The sNPH group underwent shunting more (56%–68%) compared to the ad and non-ad groups (47%). Relationships, however, were not statistically significant (p > 0.05). Conclusion: Patients with sNPH CSF ad biomarker profiles demonstrated clinically meaningful physical improvements and underwent shunting more frequently than those with ad or non-ad biomarker profiles. This highlights the potential for CSF ad biomarkers in predicting NPH treatment response. [ABSTRACT FROM AUTHOR]

As our understanding of the pathogenesis of SpA improves, focus has turned to the role janus kinase (JAK)-mediated signal transduction and inhibiting its actions as a therapeutic mechanism. Small molecule inhibitors of JAK exist, with variable selectivity for the different JAK isoforms. Less selective JAK inhibitors have variable efficacy and safety profiles, prompting the investigation of selective JAK1 inhibition. In this review, we summarize the current phase 2 and 3 clinical trial data, evaluating the use of JAK1 selective inhibitors in the treatment of SpA, particularly AS and PsA. Selective JAK1 inhibition offers a promising therapeutic approach, however further longer-term trials are needed to fully establish their efficacy and safety at higher doses, and their use in the greater continuum of SpA. [ABSTRACT FROM AUTHOR]

OBJECTIVES We performed a prospective randomized study comparing the clinical performance of the Carpentier–Edwards supra-annular valve (CE-SAV) (Edwards Lifesciences, Irvine, CA, USA) and the newer Mosaic (Medtronic Corporation, Minneapolis, MN, USA) porcine bioprostheses in the aortic position over a 10-year period. METHODS Between January 2001 and March 2005, 394 patients undergoing bioprosthetic aortic valve replacement were randomized to receive either the CE-SAV (n  = 191) or the Mosaic (n  = 203) prosthesis. The preoperative demographics, EuroSCORE and intraoperative characteristics concerning cardiopulmonary bypass of the 2 groups were comparable. All patients were followed annually for 10 years. RESULTS There were 77 (40.3%) deaths in the CE-SAV group and 93 (45.8%) deaths in the Mosaic group. The 10-year survival rate in the 2 groups was 59.7% and 54.2%, respectively (P  = 0.27). There were no statistically significant differences between the 2 groups in terms of structural valve deterioration (P  = 0.08), endocarditis (P  = 0.95), thromboembolism (P  = 0.06) and major bleeds (P  = 0.09). However, the incidence of paravalvular leaks and valve-related reoperations were higher in the Mosaic group, with 5 leaks and 6 reoperations when compared to none in the CE-SAV group, (P  = 0.02) and (P  = 0.01) respectively. CONCLUSIONS At 10 years after implantation, freedom from reoperation was greater in the CE-SAV group with no incidences of paravalvular leaks. There were no other statistically significant differences between CE-SAV and Mosaic aortic prostheses. Clinical trial registration clinicaltrial.gov ID 1301 (NCT03346044). [ABSTRACT FROM AUTHOR]

Background Hospital standardized mortality rates (HSMRs) are considered to identify unsafe hospital care, but are criticized for disregarding unmeasured variations of both coding practice and outside of hospital palliative provision. Methods The validity of HSMR methods is explored by examining whether the additional deaths implied by a Primary Care Trust (PCT) HSMR, as supplied by Dr Foster, are (i) detectable in English PCT mortality data and (ii) correlated with the percentage of PCT deaths out of hospital. Results Higher PCT HSMRs were positively associated with higher area mortality, although this effect was significantly smaller than the HSMR model implies. There was a significant negative association between PCT HSMR and the percentage of deaths outside of hospital. Conclusions This evidence suggests that the PCT HSMR is associated with all-cause area mortality, but it overstates the in-hospital mortality attributed to unsafe care. It also suggests that this overstatement is partially explained by the PCT HSMR reflecting the adverse case mix associated with a high share of deaths in hospital, i.e. the HSMR does not only reflect quality failings. Policy analyses that compare HSMRs to measure quality change may be biased by unbalanced samples of hospital patients. [ABSTRACT FROM AUTHOR]

Following advice fromthe International Council for the Exploration of the Seas and North Atlantic Salmon Conservation Organization, Irish salmon stocks have been managed on a river-by-river basis since 2007 with biological reference points (BRPs) based on maximum sustainable yield (MSY). A method for estimating BRPs at the river scale and the associated variability arising from observed variability in population structures and fecundities is presented here. Calculations of BRPs (referred to as conservation limits, CLs) were updated and their natural variability was included. Angling logbooks provided new river specific weight data to give sea age and fecundity ranges, and improved estimates of river-wetted areas, to account for available nursery habitat for juveniles and river-specific carrying capacities, were introduced. To transport BRPs, Bayesian stock-recruitment analysis was re-run with an updated list of monitored rivers and smolt ages. Results were converted to salmon numbers per river in Monte Carlo simulations incorporating the variability in sea ages and fecundities. Minimum sample size rules were implemented to reduce sampling error effects. Results showed that average total CL increased by 7%, average one sea-winter (1SW) CL decreased by 5%and average multi-sea-winter (MSW) CL increased by 157%.Differences were attributed to increases in wetted areas, MSW proportions, and changes inboth 1SW and MSW fecundities. While some changes were large, we believe that these updated CLs provide more accurate estimates and with associated confidence limits they are more robust, river-specific, and readily incorporated into stock assessments. As a significant improvement on their predecessors, they represent a major development for the conservation and management of salmon stocks. Additionally, the approach described is portable across stocks and has the potential to be implemented in other jurisdictions to improve the management of Atlantic salmon. Finally, this method of incorporating variation has application for the development of BRPs and management of other species. [ABSTRACT FROM AUTHOR]

Methylseleno-L-cysteine (L-SeMC) is a naturally occurring amino acid analogue used as a general dietary supplement and is being explored as a chemopreventive agent. As a known dietary supplement, L-SeMC is not regulated as a pharmaceutical and there is a paucity of analytical methods available. To address the lack of methodology, a stability-indicating method was developed and validated to evaluate L-SeMC as both the bulk drug and formulated drug product (400 μg Se/capsule). The analytical approach presented is a simple, nonderivatization method that utilizes HPLC with ultraviolet detection at 220 nm. AC18 column with a volatile ion-pair agent and methanol mobile phase was used for the separation. The method accuracywas 99-100% from 0.05 to 0.15 mg/mL L-SeMC for the bulk drug, and 98-99% from 0.075 to 0.15 mg/mL L-SeMC for the drug product. Method precision was <1% for the bulk drug and was 3% for the drug product. The LOQ was 0.1 μg/mL L-SeMC or 0.002 μg L-SeMC on column. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Since 1999 important widely publicized issues have affected morale in UK cardiothoracic (CT) surgery. Because more surgeons are needed, we sought to investigate whether these events have affected recruitment and demographic change in the specialty between 1999 and 2014. METHODS: We collected information on UK consultant CT surgeons using the SCTS public portal, the GMC Specialist Register and the NHS Annual Workforce Census via the Health & Social Care Information Centre. We analysed the demographics of UK CT surgeons with regard to country of primary medical qualification and ethnicity between 1999 and 2014. We compared the changes with other surgical specialties, cardiology and respiratory medicine. RESULTS: There has been a worrying decline in UK medical graduates entering the specialty and a 4-fold increase (282%) in consultant appointments from Europe. Whilst consultant numbers expanded by 83% overall, 59% of congenital heart surgeons, 46% of thoracic surgeons and 36% of adult cardiac surgeons are overseas graduates. It is found that 5% are female. Currently, only 32% of trainee surgeons are UK graduates. Of those receiving UK Certificate of Completion of Training in 2013, only 18% were UK graduates compared with 68% in 2000. Comparison with other specialties shows fewer UK graduates in CT surgery with the exception of Obstetrics and Gynaecology (52%). In cardiology, 77% are UK graduates with only 8% from Europe. CONCLUSIONS: Repeated negative messages have had a detrimental influence on recruitment. Because 55% of UK medical graduates, but less than 5% of CT surgeons are female, recruitment problems may worsen. Action is needed to restore interest in the specialty. [ABSTRACT FROM AUTHOR]

We developed a hierarchical Bayesian integrated life cycle model for Atlantic salmon that improves on the stock assessment approach currently used by ICES and provides some interesting insights about the population dynamics of a stock assemblage. The model is applied to the salmon stocks in eastern Scotland. It assimilates a 40-year (1971–2010) time-series of data compiled by ICES, including the catches in the distant water fisheries at Faroes and West Greenland and estimates of returning fish abundance. Our model offers major improvements in terms of statistical methodology for A. salmon stock assessment. Uncertainty about inferences is readily quantified in the form of Bayesian posterior distributions for parameters and abundance at all life stages, and the model could be adapted to provide projections based on the uncertainty derived from the estimation phase. The approach offers flexibility to improve the ecological realism of the model. It allows the introduction of density dependence in the egg-to-smolt transition, which is not considered in the current ICES assessment method. The results show that this modifies the inferences on the temporal dynamics of the post-smolt marine survival. In particular, the overall decrease in the marine survival between 1971 and 2010 and the sharp decline around 1988–1990 are dampened when density dependence is considered. The return rates of smolts as two-sea-winter (2SW) fish has declined in a higher proportion than return rates as one-sea-winter (1SW) fish. Our results indicate that this can be explained either by an increase in the proportion maturing as 1SW fish or by an increase in the mortality rate at sea of 2SW fish, but the data used in our analyses do not allow the likelihood of these two hypotheses to be gauged. [ABSTRACT FROM PUBLISHER]

A correction is provided for the article "Randomized Trial of the Carpentier–Edwards Supra-Annular Prosthesis Versus the Medtronic Mosaic Aortic Prosthesis: 10-year Results" which appears in a 2018 issue of the journal.

A review of the website "Memorable Days: The Emilie Davis Diaries," featuring the U.S. Civil War-era diary of African American seamstress Emilie Davis of Philadelphia, Pennsylvania, created and maintained by Judith Giesberg, and available at http://davisdiaries.villanova.edu/, is presented.