New Late Cretaceous microvertebrate assemblage from the Campanian-Maastrichtian Williams Fork Formation, northwestern Colorado, USA, and its paleoenvironmental implications

We describe a microvertebrate assemblage from the J&amp;M site, of the Upper Cretaceous (Campanian&ndash;Maastrichtian) Williams Fork Formation. Breakdown of fossil bearing matrix was achieved with the use of heated dimethyl sulfoxide. Nine of the recovered taxa are new to both the J&amp;M site and the Williams Fork Formation. The sharks Lonchidion griffisi, Chiloscyllium sp., and Cantioscyllium markaguntensis are the first non-batoid elasmobranchs reported from the Williams Fork Formation and are all represented by teeth. The rays Cristomylus and Psuedomyledaphus are also newly reported from teeth. The most common identifiable fossils were teeth of indeterminate amiids, most likely belonging to Melvius. Osteichthyan fossils new to the Williams Fork Formation include teeth of Paralbula, an indeterminate pycnodontid tooth plate fragment, and an indeterminate lungfish tooth fragment. A tooth of the teiid Peneteius is also the first reported from within the Williams Fork Formation. Alligatoroid teeth are relatively common and are extremely similar to those of the contemporaneous durophage Brachychampsa but are generically indeterminate. Terrestrial taxa were recovered in much smaller numbers. Theropod dinosaur fossils included isolated tooth fragments belonging to an indeterminate dromaeosaurid and, possibly, to Richardoestesia. We recovered both multituberculate and metatherian fossils in the form of isolated teeth. Some of these taxa are known from marine and estuarine deposits and, given that so many of these marine associated taxa have been recovered together, it seems likely that the J&amp;M site is recording marine or estuarine influence within at least part of its depositional history. The mammalian taxa suggest a Judithian&ndash;Lancian age for the site, while records of the squamate Peneteius and the ray Myledaphus, suggest that the J&amp;M site may be temporally transitional between other late Campanian and late Maastrichtian-aged localities. &nbsp;</p

Security and privacy requirements for a multi-institutional cancer research data grid: an interview-based study

<p>Abstract</p> <p>Background</p> <p>Data protection is important for all information systems that deal with human-subjects data. Grid-based systems – such as the cancer Biomedical Informatics Grid (caBIG) – seek to develop new mechanisms to facilitate real-time federation of cancer-relevant data sources, including sources protected under a variety of regulatory laws, such as HIPAA and 21CFR11. These systems embody new models for data sharing, and hence pose new challenges to the regulatory community, and to those who would develop or adopt them. These challenges must be understood by both systems developers and system adopters. In this paper, we describe our work collecting policy statements, expectations, and requirements from regulatory decision makers at academic cancer centers in the United States. We use these statements to examine fundamental assumptions regarding data sharing using data federations and grid computing.</p> <p>Methods</p> <p>An interview-based study of key stakeholders from a sample of US cancer centers. Interviews were structured, and used an instrument that was developed for the purpose of this study. The instrument included a set of problem scenarios – difficult policy situations that were derived during a full-day discussion of potentially problematic issues by a set of project participants with diverse expertise. Each problem scenario included a set of open-ended questions that were designed to elucidate stakeholder opinions and concerns. Interviews were transcribed verbatim and used for both qualitative and quantitative analysis. For quantitative analysis, data was aggregated at the individual or institutional unit of analysis, depending on the specific interview question.</p> <p>Results</p> <p>Thirty-one (31) individuals at six cancer centers were contacted to participate. Twenty-four out of thirty-one (24/31) individuals responded to our request- yielding a total response rate of 77%. Respondents included IRB directors and policy-makers, privacy and security officers, directors of offices of research, information security officers and university legal counsel. Nineteen total interviews were conducted over a period of 16 weeks. Respondents provided answers for all four scenarios (a total of 87 questions). Results were grouped by broad themes, including among others: governance, legal and financial issues, partnership agreements, de-identification, institutional technical infrastructure for security and privacy protection, training, risk management, auditing, IRB issues, and patient/subject consent.</p> <p>Conclusion</p> <p>The findings suggest that with additional work, large scale federated sharing of data within a regulated environment is possible. A key challenge is developing suitable models for authentication and authorization practices within a federated environment. Authentication – the recognition and validation of a person's identity – is in fact a global property of such systems, while authorization – the permission to access data or resources – mimics data sharing agreements in being best served at a local level. Nine specific recommendations result from the work and are discussed in detail. These include: (1) the necessity to construct separate legal or corporate entities for governance of federated sharing initiatives on this scale; (2) consensus on the treatment of foreign and commercial partnerships; (3) the development of risk models and risk management processes; (4) development of technical infrastructure to support the credentialing process associated with research including human subjects; (5) exploring the feasibility of developing large-scale, federated honest broker approaches; (6) the development of suitable, federated identity provisioning processes to support federated authentication and authorization; (7) community development of requisite HIPAA and research ethics training modules by federation members; (8) the recognition of the need for central auditing requirements and authority, and; (9) use of two-protocol data exchange models where possible in the federation.</p

A π-Extended Donor-Acceptor-Donor Triphenylene Twin linked via a Pyrazine-bridge

Beta-amino triphenylenes can be accessed via palladium catalyzed amination of the corresponding triflate using benzophe-none imine. Transformation of amine 6 to benzoyl amide 18 is also straightforward and its wide mesophase range demon-strates that the new linkage supports columnar liquid crystal formation. Amine 6 also undergoes clean aerobic oxidation to give a new twinned structure linked through an electron-poor pyrazine ring. The new discotic liquid crystal motif contains donor and acceptor fragments, and is more oval in shape rather than disk-like. It forms a wide range columnar mesophase. Absorption spectra are strong and broad; emission is also broad and occurs with a Stokes shift of ca. 0.7 eV, indicative of charge-transfer characte

Adiponectin reduces glomerular endothelial glycocalyx disruption and restores glomerular barrier function in a mouse model of type 2 diabetes

Adiponectin has vascular anti-inflammatory and protective effects. Although adiponectin protects against the development of albuminuria, historically, the focus has been on podocyte protection within the glomerular filtration barrier (GFB). The first barrier to albumin in the GFB is the endothelial glycocalyx (eGlx), a surface gel-like barrier covering glomerular endothelial cells (GEnCs). In diabetes, eGlx dysfunction occurs before podocyte damage; hence, we hypothesized that adiponectin could protect from eGlx damage to prevent early vascular damage in diabetic kidney disease (DKD). Globular adiponectin (gAd) activated AMPK signaling in human GEnCs through AdipoR1. It significantly reduced eGlx shedding and the TNF-α–mediated increase in syndecan-4 (SDC4) and MMP2 mRNA expression in GEnCs in vitro. It protected against increased TNF-α mRNA expression in glomeruli isolated from db/db mice and against expression of genes associated with glycocalyx shedding (namely, SDC4, MMP2, and MMP9). In addition, gAd protected against increased glomerular albumin permeability (Ps’alb) in glomeruli isolated from db/db mice when administered intraperitoneally and when applied directly to glomeruli (ex vivo). Ps’alb was inversely correlated with eGlx depth in vivo. In summary, adiponectin restored eGlx depth, which was correlated with improved glomerular barrier function, in diabetes

Real-World Cost-Effectiveness of Pulmonary Vein Isolation for Atrial Fibrillation: A Target Trial Approach

OBJECTIVES Randomized controlled trials of pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have proven the procedure's efficacy. Studies assessing its empirical cost-effectiveness outside randomized trial settings are lacking. We aimed to evaluate the effectiveness and cost-effectiveness of PVI versus medical therapy for AF. METHODS We followed a target trial approach using the Swiss-AF cohort, a prospective observational cohort study that enrolled patients with AF between 2014 and 2017. Resource utilization and cost information were collected through claims data. Quality of life was measured with EQ-5D-3L utilities. We estimated incremental cost-effectiveness ratios (ICERs) from the perspective of the Swiss statutory health insurance system. RESULTS Patients undergoing PVI compared with medical therapy had a 5-year overall survival advantage with a hazard ratio of 0.75 (95% CI 0.46-1.21; P = .69) and a 19.8% SD improvement in quality of life (95% CI 15.5-22.9; P < .001), at an incremental cost of 29 604 Swiss francs (CHF) (95% CI 16 354-42 855; P < .001). The estimated ICER was CHF 158 612 per quality-adjusted life-year (QALY) gained within a 5-year time horizon. Assuming similar health effects and costs over 5 additional years changed the ICER to CHF 82 195 per QALY gained. Results were robust to the sensitivity analyses performed. CONCLUSIONS Our results show that PVI might be a cost-effective intervention within the Swiss healthcare context in a 10-year time horizon, but unlikely to be so at 5 years, if a willingness-to-pay threshold of CHF 100 000 per QALY gained is assumed. Given data availability, we find target trial designs are a valuable tool for assessing the cost-effectiveness of healthcare interventions outside of randomized controlled trial settings

Jupiter's X-ray Emission 2007 Part 2:Comparisons with UV and Radio Emissions and In-Situ Solar Wind Measurements

We compare Chandra and XMM‐Newton X‐ray observations of Jupiter during 2007 with a rich multi‐instrument dataset including: upstream in‐situ solar wind measurements from the New Horizons spacecraft, radio emissions from the Nançay Decametric Array and Wind/Waves, and UV observations from the Hubble Space Telescope. New Horizons data revealed two corotating interaction regions (CIRs) impacted Jupiter during these observations. Non‐Io decametric bursts and UV emissions brightened together and varied in phase with the CIRs. We characterise 3 types of X‐ray aurorae: hard X‐ray bremsstrahlung main emission, pulsed/flared soft X‐ray emissions and a newly identified dim flickering (varying on short‐timescales, but quasi‐continuously present) aurora. For most observations, the X‐ray aurorae were dominated by pulsed/flaring emissions, with ion spectral lines that were best fit by Iogenic plasma. However, the brightest X‐ray aurora was coincident with a magnetosphere expansion. For this observation, the aurorae were produced by both flickering emission and erratic pulses/flares. Auroral spectral models for this observation required the addition of solar wind ions to attain good fits, suggesting solar wind entry into the outer magnetosphere or directly into the pole for this particularly bright observation. X‐ray bremsstrahlung from high energy electrons was only bright for one observation, which was during a forward shock. This bremsstrahlung was spatially coincident with bright UV main emission (power> 1TW) and X‐ray ion spectral line dusk emission, suggesting closening of upward and downward current systems during the shock. Otherwise, the bremsstrahlung was dim and UV main emission power was also lower(<700 GW), suggesting their power scaled together

Real-world cost-effectiveness of pulmonary vein isolation for atrial fibrillation: a target trial approach.

OBJECTIVES Randomized controlled trials of pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have proven the procedure's efficacy. Studies assessing its empirical cost-effectiveness outside randomized trial settings are lacking. We aimed to evaluate the effectiveness and cost-effectiveness of PVI versus medical therapy for AF. METHODS We followed a target trial approach using the Swiss AF cohort, a prospective observational cohort study that enrolled AF patients between 2014 and 2017. Resource utilization and cost information was collected through claims data. Quality-of-life was measured with EQ-5D-3L utilities. We estimated incremental cost-effectiveness ratios from the perspective of the Swiss statutory health insurance system. RESULTS Patients undergoing PVI compared to medical therapy had a 5-year overall survival advantage with a hazard ratio of 0.75 (95%CI 0.46-1.21, p=0.69), a 19.8% standard deviation improvement in quality-of-life (95%CI 15.5-22.9%, p<0.001), at an incremental cost of 29,604 (95%CI 16,354-42,855, p<0.001) Swiss Francs (CHF). The estimated incremental cost-effectiveness ratio was CHF 158,612 per quality-adjusted life-year (QALY) gained within a 5-year time horizon. Assuming similar health effects and costs over 5 additional years changed the incremental cost-effectiveness ratio to CHF 82,195 per QALY gained. Results were robust to the sensitivity analyses performed. CONCLUSIONS Our results show that PVI might be a cost-effective intervention within the Swiss healthcare context in a 10-year time horizon, but unlikely to be so at 5-years, if a willingness-to-pay threshold of CHF100,000 per QALY gained is assumed. Given data availability, we find target trial designs are a valuable tool for assessing the cost-effectiveness of healthcare interventions outside of RCT settings

‘Why would we not want to keep everybody safe?’ The views of family members of people who use drugs on the implementation of drug consumption rooms in Scotland

BackgroundPeople who use drugs in Scotland are currently experiencing disproportionately high rates of drug-related deaths. Drug consumption rooms (DCRs) are harm reduction services that offer a safe, hygienic environment where pre-obtained drugs can be consumed under supervision. The aim of this research was to explore family member perspectives on DCR implementation in Scotland in order to inform national policy.MethodsScotland-based family members of people who were currently or formerly using drugs were invited to take part in semi-structured interviews to share views on DCRs. An inclusive approach to ‘family’ was taken, and family members were recruited via local and national networks. A convenience sample of 13 family members were recruited and interviews conducted, audio-recorded, transcribed, and analysed thematically using the Structured Framework Technique.ResultsFamily members demonstrated varying levels of understanding regarding the existence, role, and function of DCRs. While some expressed concern that DCRs would not prevent continued drug use, all participants were in favour of DCR implementation due to a belief that DCRs could reduce harm, including saving lives, and facilitate future recovery from drug use. Participants highlighted challenges faced by people who use drugs in accessing treatment/services that could meet their needs. They identified that accessible and welcoming DCRs led by trusting and non-judgemental staff could help to meet unmet needs, including signposting to other services. Family members viewed DCRs as safe environments and highlighted how the existence of DCRs could reduce the constant worry that they had of risk of harm to their loved ones. Finally, family members emphasised the challenge of stigma associated with drug use. They believed that introduction of DCRs would help to reduce stigma and provide a signal that people who use drugs deserve safety and care.ConclusionsReporting the experience and views of family members makes a novel and valuable contribution to ongoing public debates surrounding DCRs. Their views can be used to inform the implementation of DCRs in Scotland but also relate well to the development of wider responses to drug-related harm and reduction of stigma experienced by people who use drugs in Scotland and beyond

Jupiter's X-ray Emission During Solar Minimum

The 2007–2009 solar minimum was the longest of the space age. We present the first of two companion papers on Chandra and XMM‐Newton X‐ray campaigns of Jupiter through February–March 2007. We find that low solar X‐ray flux during solar minimum causes Jupiter's equatorial regions to be exceptionally X‐ray dim (0.21 GW at minimum; 0.76 GW at maximum). While the Jovian equatorial emission varies with solar cycle, the aurorae have comparably bright intervals at solar minimum and maximum. We apply atomic charge exchange models to auroral spectra and find that iogenic plasma of sulphur and oxygen ions provides excellent fits for XMM‐Newton observations. The fitted spectral S:O ratios of 0.4–1.3 are in good agreement with in situ magnetospheric S:O measurements of 0.3–1.5, suggesting that the ions that produce Jupiter's X‐ray aurora predominantly originate inside the magnetosphere. The aurorae were particularly bright on 24–25 February and 8–9 March, but these two observations exhibit very different spatial, spectral, and temporal behavior; 24–25 February was the only observation in this campaign with significant hard X‐ray bremsstrahlung from precipitating electrons, suggesting this may be rare. For 8–9 March, a bremsstrahlung component was absent, but bright oxygen O6+ lines and best‐fit models containing carbon, point to contributions from solar wind ions. This contribution is absent in the other observations. Comparing simultaneous Chandra ACIS and XMM‐Newton EPIC spectra showed that ACIS systematically underreported 0.45‐ to 0.6‐keV Jovian emission, suggesting quenching may be less important for Jupiter's atmosphere than previously thought. We therefore recommend XMM‐Newton for spectral analyses and quantifying opacity/quenching effects