Mortality in hepatitis C patients who achieve a sustained viral response compared to the general population

Background & Aims: The number of people living with previous hepatitis C infection that have attained a sustained viral response (SVR) is expected to grow rapidly. So far, the prognosis of this group relative to the general population is unclear. Methods: Individuals attaining SVR in Scotland in 1996–2011 were identified using a national database. Through record-linkage, we obtained cause-specific mortality data complete to Dec 2013. We calculated standardised mortality ratios (SMRs) to compare the frequency of mortality in SVR patients to the general population. In a parallel analysis, we used Cox regression to identify modifiable patient characteristics associated with post-SVR mortality. Results: We identified 1824 patients, followed on average for 5.2 years after SVR. In total, 78 deaths were observed. Overall, all-cause mortality was 1.9 times more frequent for SVR patients than the general population (SMR: 1.86; 95% confidence interval (CI): 1.49–2.32). Significant cause-specific elevations were seen for death due to primary liver cancer (SMR: 23.50; 95% CI: 12.23–45.16), and death due to drug-related causes (SMR: 6.58, 95% CI: 4.15–10.45). Together these two causes accounted for 66% of the total excess death observed. All of the modifiable characteristics associated with increased mortality were markers either of heavy alcohol use or injecting drug use. Individuals without these behavioural markers (32.8% of cohort) experienced equivalent survival to the general population (SMR: 0.70; 95% CI: 0.41–1.18) Conclusions: Mortality in Scottish SVR patients is higher overall than the general population. The excess was driven by death from drug-related causes and liver cancer. Health risk behaviours emerged as important modifiable determinants of mortality in this population. Lay summary: Patients cured of hepatitis C through treatment had a higher mortality rate overall than the general population. Most of the surplus mortality was due to drug-related causes and death from liver cancer. A history of heavy alcohol and injecting drug use were associated with a higher mortality risk

Canvass: a crowd-sourced, natural-product screening library for exploring biological space

NCATS thanks Dingyin Tao for assistance with compound characterization. This research was supported by the Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH). R.B.A. acknowledges support from NSF (CHE-1665145) and NIH (GM126221). M.K.B. acknowledges support from NIH (5R01GM110131). N.Z.B. thanks support from NIGMS, NIH (R01GM114061). J.K.C. acknowledges support from NSF (CHE-1665331). J.C. acknowledges support from the Fogarty International Center, NIH (TW009872). P.A.C. acknowledges support from the National Cancer Institute (NCI), NIH (R01 CA158275), and the NIH/National Institute of Aging (P01 AG012411). N.K.G. acknowledges support from NSF (CHE-1464898). B.C.G. thanks the support of NSF (RUI: 213569), the Camille and Henry Dreyfus Foundation, and the Arnold and Mabel Beckman Foundation. C.C.H. thanks the start-up funds from the Scripps Institution of Oceanography for support. J.N.J. acknowledges support from NIH (GM 063557, GM 084333). A.D.K. thanks the support from NCI, NIH (P01CA125066). D.G.I.K. acknowledges support from the National Center for Complementary and Integrative Health (1 R01 AT008088) and the Fogarty International Center, NIH (U01 TW00313), and gratefully acknowledges courtesies extended by the Government of Madagascar (Ministere des Eaux et Forets). O.K. thanks NIH (R01GM071779) for financial support. T.J.M. acknowledges support from NIH (GM116952). S.M. acknowledges support from NIH (DA045884-01, DA046487-01, AA026949-01), the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program (W81XWH-17-1-0256), and NCI, NIH, through a Cancer Center Support Grant (P30 CA008748). K.N.M. thanks the California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board for support. B.T.M. thanks Michael Mullowney for his contribution in the isolation, elucidation, and submission of the compounds in this work. P.N. acknowledges support from NIH (R01 GM111476). L.E.O. acknowledges support from NIH (R01-HL25854, R01-GM30859, R0-1-NS-12389). L.E.B., J.K.S., and J.A.P. thank the NIH (R35 GM-118173, R24 GM-111625) for research support. F.R. thanks the American Lebanese Syrian Associated Charities (ALSAC) for financial support. I.S. thanks the University of Oklahoma Startup funds for support. J.T.S. acknowledges support from ACS PRF (53767-ND1) and NSF (CHE-1414298), and thanks Drs. Kellan N. Lamb and Michael J. Di Maso for their synthetic contribution. B.S. acknowledges support from NIH (CA78747, CA106150, GM114353, GM115575). W.S. acknowledges support from NIGMS, NIH (R15GM116032, P30 GM103450), and thanks the University of Arkansas for startup funds and the Arkansas Biosciences Institute (ABI) for seed money. C.R.J.S. acknowledges support from NIH (R01GM121656). D.S.T. thanks the support of NIH (T32 CA062948-Gudas) and PhRMA Foundation to A.L.V., NIH (P41 GM076267) to D.S.T., and CCSG NIH (P30 CA008748) to C.B. Thompson. R.E.T. acknowledges support from NIGMS, NIH (GM129465). R.J.T. thanks the American Cancer Society (RSG-12-253-01-CDD) and NSF (CHE1361173) for support. D.A.V. thanks the Camille and Henry Dreyfus Foundation, the National Science Foundation (CHE-0353662, CHE-1005253, and CHE-1725142), the Beckman Foundation, the Sherman Fairchild Foundation, the John Stauffer Charitable Trust, and the Christian Scholars Foundation for support. J.W. acknowledges support from the American Cancer Society through the Research Scholar Grant (RSG-13-011-01-CDD). W.M.W.acknowledges support from NIGMS, NIH (GM119426), and NSF (CHE1755698). A.Z. acknowledges support from NSF (CHE-1463819). (Intramural Research Program of the National Center for Advancing Translational Sciences, National Institutes of Health (NIH); CHE-1665145 - NSF; CHE-1665331 - NSF; CHE-1464898 - NSF; RUI: 213569 - NSF; CHE-1414298 - NSF; CHE1361173 - NSF; CHE1755698 - NSF; CHE-1463819 - NSF; GM126221 - NIH; 5R01GM110131 - NIH; GM 063557 - NIH; GM 084333 - NIH; R01GM071779 - NIH; GM116952 - NIH; DA045884-01 - NIH; DA046487-01 - NIH; AA026949-01 - NIH; R01 GM111476 - NIH; R01-HL25854 - NIH; R01-GM30859 - NIH; R0-1-NS-12389 - NIH; R35 GM-118173 - NIH; R24 GM-111625 - NIH; CA78747 - NIH; CA106150 - NIH; GM114353 - NIH; GM115575 - NIH; R01GM121656 - NIH; T32 CA062948-Gudas - NIH; P41 GM076267 - NIH; R01GM114061 - NIGMS, NIH; R15GM116032 - NIGMS, NIH; P30 GM103450 - NIGMS, NIH; GM129465 - NIGMS, NIH; GM119426 - NIGMS, NIH; TW009872 - Fogarty International Center, NIH; U01 TW00313 - Fogarty International Center, NIH; R01 CA158275 - National Cancer Institute (NCI), NIH; P01 AG012411 - NIH/National Institute of Aging; Camille and Henry Dreyfus Foundation; Arnold and Mabel Beckman Foundation; Scripps Institution of Oceanography; P01CA125066 - NCI, NIH; 1 R01 AT008088 - National Center for Complementary and Integrative Health; W81XWH-17-1-0256 - Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program; P30 CA008748 - NCI, NIH, through a Cancer Center Support Grant; California Department of Food and Agriculture Pierce's Disease and Glassy Winged Sharpshooter Board; American Lebanese Syrian Associated Charities (ALSAC); University of Oklahoma Startup funds; 53767-ND1 - ACS PRF; PhRMA Foundation; P30 CA008748 - CCSG NIH; RSG-12-253-01-CDD - American Cancer Society; RSG-13-011-01-CDD - American Cancer Society; CHE-0353662 - National Science Foundation; CHE-1005253 - National Science Foundation; CHE-1725142 - National Science Foundation; Beckman Foundation; Sherman Fairchild Foundation; John Stauffer Charitable Trust; Christian Scholars Foundation)Published versionSupporting documentatio

Superconductivity in Compositionally-Complex Cuprates with the YBa2_2Cu3_3O7−x_{7-x} Structure

High-temperature superconductivity is reported in a series of compositionally-complex cuprates with varying degrees of size and spin disorder. Three compositions of Y-site alloyed YBa$_2$Cu$_3$O$_{7-x}$, i.e., (5Y)BCO, were prepared using solid-state methods with different sets of rare earth ions on the Y-site. Synchrotron X-ray diffraction and energy-dispersive X-ray spectroscopy confirm these samples have high phase-purity and homogeneous mixing of the Y-site elements. The superconducting phase transition was probed using electrical resistivity and AC magnetometry measurements, which reveal the transition temperature, T$_C$, is greater than 91 K for all series when near optimal oxygen doping. Importantly, these T$_C$ values are only $\approx$1$\%$ suppressed relative to pure YBCO (T$_C$ = 93 K). This result highlights the robustness of pairing in the YBCO structure to specific types of disorder. In addition, the chemical flexibility of compositionally-complex cuprates allows spin and lattice disorder to be decoupled to a degree not previously possible in high-temperature superconductors. This feature makes compositionally-complex cuprates a uniquely well-suited materials platform for studying proposed pairing interactions in cuprates.Comment: 6 pages, 3 figures, 1 tabl

Pennsylvania Folklife Vol. 34, No. 4

• Coverlets • Sign Painting • Reverse Painting on Glass • Kites • Snake Lore • Horncraft • Weathervanes and Country Signs • Festival Focus • Sheep Shearing & Natural Knits • Bread Baking Among the Pennsylvania Dutch • The Craft of Rushing • Toy Soldier Casting • Pennsylvania Dutch Humor • Fireside Brooms and Whirligigs • Springerlehttps://digitalcommons.ursinus.edu/pafolklifemag/1108/thumbnail.jp

A StrongREJECT for Empty Jailbreaks

Most jailbreak papers claim the jailbreaks they propose are highly effective, often boasting near-100% attack success rates. However, it is perhaps more common than not for jailbreak developers to substantially exaggerate the effectiveness of their jailbreaks. We suggest this problem arises because jailbreak researchers lack a standard, high-quality benchmark for evaluating jailbreak performance, leaving researchers to create their own. To create a benchmark, researchers must choose a dataset of forbidden prompts to which a victim model will respond, along with an evaluation method that scores the harmfulness of the victim model\u27s responses. We show that existing benchmarks suffer from significant shortcomings and introduce the StrongREJECT benchmark to address these issues. StrongREJECT\u27s dataset contains prompts that victim models must answer with specific, harmful information, while its automated evaluator measures the extent to which a response gives useful information to forbidden prompts. In doing so, the StrongREJECT evaluator achieves state-of-the-art agreement with human judgments of jailbreak effectiveness. Notably, we find that existing evaluation methods significantly overstate jailbreak effectiveness compared to human judgments and the StrongREJECT evaluator. We describe a surprising and novel phenomenon that explains this discrepancy: jailbreaks bypassing a victim model\u27s safety fine-tuning tend to reduce its capabilities. Together, our findings underscore the need for researchers to use a high-quality benchmark, such as StrongREJECT, when developing new jailbreak attacks. We release the StrongREJECT code and data at https://strong-reject.readthedocs.io/en/latest/.Code and data at https://strong-reject.readthedocs.io/en/latest

The iDiabetes Platform: Enhanced Phenotyping of Patients with Diabetes for Precision Diagnosis, Prognosis and Treatment - study protocol for a cluster-randomised controlled study in Tayside, Scotland

Introduction and aim Diabetes is a global health emergency with increasing prevalence and diabetes-associated morbidity and mortality. One of the challenges in optimising diabetes care is translating research advances in this heterogeneous disease into clinical care. A potential solution is the introduction of precision medicine approaches into diabetes care.We aim to develop a digital platform called ‘intelligent Diabetes’ (iDiabetes) to support a precision diabetes care model in Scotland and assess its impact on the primary composite outcome of all-cause mortality, hospitalisation rate, renal function decline and glycaemic control.Methods and analysis The impact of iDiabetes will be evaluated through a cluster-randomised controlled study, recruiting up to 22 500 patients with diabetes. Primary care general practices (GPs) in the National Health Service (NHS) Scotland Tayside Health Board are the units (clusters) of randomisation. Each primary care GP will form one cluster (approximately 400 patients per cluster), with up to 60 clusters recruited. Randomisation will be to iDiabetes (guideline support), iDiabetesPlus or usual diabetes care (control arm). Patients of participating primary care GPs are automatically enrolled on the study when they attend for their annual diabetes screening or are newly diagnosed with diabetes. A composite hierarchical primary outcome, evaluated using Win-Ratio statistical methodology, will consist of (1) all-cause mortality, (2) all-cause hospitalisation rate, (3) proportion with &gt;40% estimated glomerular filtration rate [eGFR] reduction from baseline or new development of end-stage renal disease, (4) proportion with absolute HbA1C reduction &gt;0.5%. Outcomes will be evaluated after a 2-year median follow-up period. Comprehensive qualitative and health economic analyses will be conducted, assessing the cost-effectiveness, budget impact and user acceptability of the iDiabetes platform.Ethics and dissemination This study was reviewed by the NHS Health Research Authority and approved by the East of Scotland Research Ethics Committee (reference: 23/ES/0008). Study findings will be disseminated via publications, presented at scientific conferences and shared with patients and the public on the study website and social media.<br/

Beating Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes on Porcine Extracellular Matrix

Despite modern technology and developments in heart disease treatment and prevention, heart disease remains the number one cause of death in America. With an inability to meet an ever-increasing demand for heart transplants and the dangers of immunosuppressant drugs, any potential alternative to cardiac transplantation must be pursued. The end goal of this research is to engineer biocompatible tissues that are fully functional to repair or replace damaged portions of the heart following the loss of cardiac function. This research investigates the effect of porcine extracellular matrix as the scaffold for beating IPS-differentiated cardiomyocytes

The Developing Human Connectome Project neonatal data release

The Developing Human Connectome Project has created a large open science resource which provides researchers with data for investigating typical and atypical brain development across the perinatal period. It has collected 1228 multimodal magnetic resonance imaging (MRI) brain datasets from 1173 fetal and/or neonatal participants, together with collateral demographic, clinical, family, neurocognitive and genomic data from 1173 participants, together with collateral demographic, clinical, family, neurocognitive and genomic data. All subjects were studied in utero and/or soon after birth on a single MRI scanner using specially developed scanning sequences which included novel motion-tolerant imaging methods. Imaging data are complemented by rich demographic, clinical, neurodevelopmental, and genomic information. The project is now releasing a large set of neonatal data; fetal data will be described and released separately. This release includes scans from 783 infants of whom: 583 were healthy infants born at term; as well as preterm infants; and infants at high risk of atypical neurocognitive development. Many infants were imaged more than once to provide longitudinal data, and the total number of datasets being released is 887. We now describe the dHCP image acquisition and processing protocols, summarize the available imaging and collateral data, and provide information on how the data can be accessed

DU Undergraduate Showcase: Research, Scholarship, and Creative Works

DU Undergraduate Showcase: Research, Scholarship, and Creative Work