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BackgroundIn trials conducted in India, recombinant granulocyte colony stimulating factor (GCSF) improved survival in alcohol-associated hepatitis (AH). The aim of this trial was to determine the safety and efficacy of pegfilgrastim, a long-acting recombinant GCSF, in patients with AH in the United States.MethodsThis prospective, randomized, open label trial conducted between March 2017 and March 2020 randomized patients with a clinical diagnosis of AH and a Maddrey discriminant function score ≥32 to standard of care (SOC) or SOC+pegfilgrastim (0.6 mg subcutaneously) on Day 1 and Day 8 (clinicaltrials.gov NCT02776059). SOC was 28 days of either pentoxifylline or prednisolone, as determined by the patient's primary physician. The second injection of pegfilgrastim was not administered if the white blood cell count exceeded 30,000/mm3 on Day 8. Primary outcome was survival at Day 90. Secondary outcomes included the incidence of acute kidney injury (AKI), hepatorenal syndrome (HRS), hepatic encephalopathy, or infections.FindingsThe study was terminated early due to COVID19 pandemic. Eighteen patients were randomized to SOC and 16 to SOC+pegfilgrastim. All patients received prednisolone as SOC. Nine patients failed to receive a second dose of pegfilgrastin due to WBC > 30,000/mm3 on Day 8. Survival at 90 days was similar in both groups (SOC: 0.83 [95% confidence interval [CI]: 0.57-0.94] vs. pegfilgrastim: 0.73 [95% CI: 0.44-0.89]; p > 0.05; CI for difference: -0.18-0.38). The incidences of AKI, HRS, hepatic encephalopathy, and infections were similar in both treatment arms and there were no serious adverse events attributed to pegfilgrastim.InterpretationThis phase II trial found no survival benefit at 90 days among subjects with AH who received pegfilgrastim+prednisolone compared with subjects receiving prednisolone alone.Fundingwas provided by the United States National Institutes of Health and National Institute on Alcohol Abuse and Alcoholism U01-AA021886 and U01-AA021884.

Little is known about the ecological importance of low-order tidal marsh channels to fishes in the San Francisco Estuary, California. We conducted a passive mark-recapture study to compare residency, site fidelity, and movement patterns of fishes in a small intertidal channel (0.1 km2) in a large tidal marsh reserve (4.25 km2). We coupled continuous, high-frequency data on movements of fish tagged with Passive Integrated Transponder (PIT) tags and abiotic conditions from a PIT-detector and datasonde, respectively. Novel insights were gained by employing TidalTrend, a software program that characterizes tidal time-series data for ecological interpretation. Overall, we found that fishes exhibited different patterns of intertidal habitat use: the resident species, tule perch (Hysterocarpus traski), consistently spent more time per visit, per day, and per season using the intertidal channel, except during the reproductive window in spring; the transient species, Sacramento splittail (Pogonichthys macrolepidotus) and striped bass (Morone saxatilis), were more opportunistic and exhibited higher individual variation in movement patterns. Generalized additive mixed models indicated that tide height, rate of change in tide height, tidal inequality, time of day, lunar phase, and water temperature better predicted fish detections than other variables, but their effects varied across species. Based on our findings, we posit that time, through tides, allows habitat partitioning among fish species and individuals with different life-history types. Furthermore, functional connectivity between subtidal and intertidal channels in tidal marshes is a feature of the estuarine mosaic that should be integrated into habitat restoration designs in the San Francisco Estuary.

In December 2020, 11 months after identifying the first laboratory-confirmed case of COVID-19 in the United States, the U.S. Food and Drug Administration authorized emergency use of two COVID-19 vaccines. To prepare the public for a large-scale vaccination campaign and build confidence in COVID-19 vaccines, the U.S. Centers for Disease Control and Prevention (CDC) funded more than 200 partners and developed a national Vaccinate with Confidence (VwC) COVID-19 framework to support Americans in their decision to get vaccinated. The evolving nature of the pandemic and highly variable confidence in vaccines across populations has resulted in many unique complexities and challenges to reaching universally high vaccination coverage. Here, we describe how 23 professional health associations and national partner organizations, focused solely on building vaccine confidence, operationalized CDC's VwC COVID-19 framework from February 2021 to March 2022. Capturing how partners deployed and adapted their activities to meet a shifting pandemic landscape, which began with high demand for vaccines that waned over time, is an important first step to understanding how this new strategy was utilized and could be implemented for future surges in COVID-19 cases and other routine immunization efforts. Going forward, evaluation of partner activities should be prioritized to capture learnings and assess VwC program effectiveness. [ABSTRACT FROM AUTHOR]

The conditions that govern academic research vary greatly from country to country and research in the Republic of Ireland was and remains markedly different from that of its larger European neighbours and the United States. Despite the quality of its education system and the excellent reputation of its universities, until recently Ireland had relatively low levels of academic research. Pinnacles of excellence could be found in certain disciplines, but state funding was low and issues relating to industrial collaborations, international partnerships, commercialisation, and the exploitation of Intellectual Property (IP) rarely arose. Even today the Irish Government's spending on academic research, though only slightly less than the European average based on GNP, is dwarfed by the Research and Development (R&D) budgets of individual multinational companies. Nonetheless, rapid economic growth has led to a heightened awareness of the need for strategically planned research. The "Lisbon Objective" proposes to make Europe "the most dynamic knowledge-driven economy in the world by 2010." Consequently, research is heavily influenced by this policy and so a range of unfamiliar problems are posed for managers of Irish academic research. Key to successful operational planning and growth is the need to reconcile a number of contradictions at the heart of R&D in Third Level Institutes.