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Using growth rings observed in statoliths, the size-at-age relationship was modeled for waved whelk (Buccinum undatum) populations within the Mid-Atlantic Bight. A total of 45 sites in the Mid-Atlantic were sampled between 2016 and 2019 using a scallop dredge, and a subset of the whelk collected were aged (n = 318). Lab-reared individuals and back-calculation methods were used to fill missing juvenile observations. The Mid-Atlantic Bight population appears to differ in the fit of growth curves, compared to other assessed populations, due to a timing difference in hatching. Growth curves for whelk from the Mid-Atlantic Bight show that maturity is reached between 4 and 6 years of age. A statolith chronology spanning a 10-year period was developed using a mixed-effects modeling approach. The chronology was used to explore the influence of temperature variation on growth during ecologically relevant periods. Growth increased with higher annual temperatures however specific seasonal bottom temperature had varying effects on growth. Increasing bottom temperature during summer, the anticipated egg-development and hatching period in this region, resulted in an age-dependent decline in growth with a positive effect on younger whelk and a negative effect on older whelk growth. Higher summer temperatures provide larger time-windows for growth, facilitating increased growth in early life stages. It appears that whelk in this region possess sufficient growth plasticity to adapt to warmer conditions throughout the year, but increased warming during specific seasons may depress growth in older individuals, potentially affecting fitness and population persistence. Understanding these temperature-growth dynamics are critical for disentangling the effects of climate change on whelk growth, allowing for population predictions in the future.

Using growth rings observed in statoliths, the size-at-age relationship was modeled for waved whelk (Buccinum undatum) populations within the Mid-Atlantic Bight. A total of 45 sites in the Mid-Atlantic were sampled between 2016 and 2019 using a scallop dredge, and a subset of the whelk collected were aged (n = 318). Lab-reared individuals and back-calculation methods were used to fill missing juvenile observations. The Mid-Atlantic Bight population appears to differ in the fit of growth curves, compared to other assessed populations, due to a timing difference in hatching. Growth curves for whelk from the Mid-Atlantic Bight show that maturity is reached between 4 and 6 years of age. A statolith chronology spanning a 10-year period was developed using a mixed-effects modeling approach. The chronology was used to explore the influence of temperature variation on growth during ecologically relevant periods. Growth increased with higher annual temperatures however specific seasonal bottom temperature had varying effects on growth. Increasing bottom temperature during summer, the anticipated egg-development and hatching period in this region, resulted in an age-dependent decline in growth with a positive effect on younger whelk and a negative effect on older whelk growth. Higher summer temperatures provide larger time-windows for growth, facilitating increased growth in early life stages. It appears that whelk in this region possess sufficient growth plasticity to adapt to warmer conditions throughout the year, but increased warming during specific seasons may depress growth in older individuals, potentially affecting fitness and population persistence. Understanding these temperature-growth dynamics are critical for disentangling the effects of climate change on whelk growth, allowing for population predictions in the future.

Background: Since the 1918 influenza pandemic, non-randomised studies and small clinical trials have suggested that convalescent plasma or anti-influenza hyperimmune intravenous immunoglobulin (hIVIG) might have clinical benefit for patients with influenza infection, but definitive data do not exist. We aimed to evaluate the safety and efficacy of hIVIG in a randomised controlled trial. Methods: This randomised, double-blind, placebo-controlled trial was planned for 45 hospitals in Argentina, Australia, Denmark, Greece, Mexico, Spain, Thailand, UK, and the USA over five influenza seasons from 2013–14 to 2017–18. Adults (≥18 years of age) were admitted for hospital treatment with laboratory-confirmed influenza A or B infection and were randomly assigned (1:1) to receive standard care plus either a single 500-mL infusion of high-titre hIVIG (0·25 g/kg bodyweight, 24·75 g maximum; hIVIG group) or saline placebo (placebo group). Eligible patients had a National Early Warning score of 2 points or greater at the time of screening and their symptoms began no more than 7 days before randomisation. Pregnant and breastfeeding women were excluded, as well as any patients for whom the treatment would present a health risk. Separate randomisation schedules were generated for each participating clinical site using permuted block randomisation. Treatment assignments were obtained using a web-based application by the site pharmacist who then masked the solution for infusion. Patients and investigators were masked to study treatment. The primary endpoint was a six-category ordinal outcome of clinical status at day 7, ranging in severity from death to resumption of normal activities after discharge. The choice of day 7 was based on haemagglutination inhibition titres from a pilot study. It was analysed with a proportional odds model, using all six categories to estimate a common odds ratio (OR). An OR greater than 1 indicated that, for a given category, patients in the hIVIG group we

Science should provide solutions for societal transformations toward sustainability in the face of global environmental change. Land system science, as a systemic science focused on complex socio-ecological interactions around land use and associated trade-offs and synergies, is well placed to contribute to this agenda. This goal requires a stronger engagement with the normative implications of scientific practice, research topics, questions and results. We identify concerns as well as three concrete steps for land system science to more deeply contribute in normative issues. In particular, we encourage land system scientists to discuss explicitly the normative questions, values, perspectives and assumptions already present in our research, as well as to identify key normative research questions to contribute to societal transformations. (c) 2019 Elsevier B.V.

© 2019 Elsevier B.V. Science should provide solutions for societal transformations toward sustainability in the face of global environmental change. Land system science, as a systemic science focused on complex socio-ecological interactions around land use and associated trade-offs and synergies, is well placed to contribute to this agenda. This goal requires a stronger engagement with the normative implications of scientific practice, research topics, questions and results. We identify concerns as well as three concrete steps for land system science to more deeply contribute in normative issues. In particular, we encourage land system scientists to discuss explicitly the normative questions, values, perspectives and assumptions already present in our research, as well as to identify key normative research questions to contribute to societal transformations.

Science should provide solutions for societal transformations toward sustainability in the face of global environmental change. Land system science, as a systemic science focused on complex socio-ecological interactions around land use and associated trade-offs and synergies, is well placed to contribute to this agenda. This goal requires a stronger engagement with the normative implications of scientific practice, research topics, questions and results. We identify concerns as well as three concrete steps for land system science to more deeply contribute in normative issues. In particular, we encourage land system scientists to discuss explicitly the normative questions, values, perspectives and assumptions already present in our research, as well as to identify key normative research questions to contribute to societal transformations. (c) 2019 Elsevier B.V.

Science should provide solutions for societal transformations toward sustainability in the face of global environmental change. Land system science, as a systemic science focused on complex socio-ecological interactions around land use and associated trade-offs and synergies, is well placed to contribute to this agenda. This goal requires a stronger engagement with the normative implications of scientific practice, research topics, questions and results. We identify concerns as well as three concrete steps for land system science to more deeply contribute in normative issues. In particular, we encourage land system scientists to discuss explicitly the normative questions, values, perspectives and assumptions already present in our research, as well as to identify key normative research questions to contribute to societal transformations. (c) 2019 Elsevier B.V.

Background. Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. Methods. We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1) pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. Results. We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13-0.40) than controls (0.12; IQR, 0.09-0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21-0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25-43.90). Conclusions. High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration.

Background: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4 + counts compared to no therapy. Methodology: Participants not on continuous ART with ≥300 CD4 + cells/mm 3 were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4 + counts, HIV RNA, and HIV progression events were collected monthly. Principal Findings: A total of 267 participants were randomized. At week 32, the mean CD4 + count was 134 cells greater in the IL-2 alone group (p < 0.001), and 133 cells greater in the IL-2 plus ART group (p < 0.001) compared to the no therapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group assigned to no therapy experienced an opportunistic event or died (HR 5.84, CI: 0.59 to 43.57; p = 0.009). Conclusions: IL-2 alone or with peri-cycle HAART increases CD4 + counts but was associated with a greater number of opportunistic events or deaths compared to no therapy. These results call into question the immunoprotective significance of IL-2-induced CD4 + cells. Trial Registration: ClinicalTrials.gov NCT00110812.