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Summary 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 were more likely to be in a better category than those in the placebo group. Prespecified primary analyses for safety and efficacy were based on patients who received an infusion and for whom eligibility could be confirmed. This trial is registered with ClinicalTrials.gov , NCT02287467 . Findings 313 patients were enrolled in 34 sites between Dec 11, 2014, and May 28, 2018. We also used data from 16 patients enrolled at seven of the 34 sites during the pilot study between Jan 15, 2014, and April 10, 2014. 168 patients were randomly assigned to the hIVIG group and 161 to the placebo group. 21 patients were excluded (12 from the hIVIG group and 9 from the placebo group) because they did not receive an infusion or their eligibility could not be confirmed. Thus, 308 were included in the primary analysis. hIVIG treatment produced a robust rise in haemagglutination inhibition titres against influenza A and smaller rises in influenza B titres. Based on the proportional odds model, the OR on day 7 was 1·25 (95% CI 0·79–1·97; p=0·33). In subgroup analyses for the primary outcome, the OR in patients with influenza A was 0·94 (0·55–1·59) and was 3·19 (1·21–8·42) for those with influenza B (interaction p=0·023). Through 28 days of follow-up, 47 (30%) of 156 patients in the hIVIG group and in 45 (30%) of 152 patients in the placebo group had the composite safety outcome of death, a serious adverse event, or a grade 3 or 4 adverse event (hazard ratio [HR] 1·06, 95% CI 0·70–1·60; p=0·79). Six (4%) patients in the hIVIG group and five (3%) in the placebo group died, but these deaths were not necessarily related to treatment. Interpretation When administered alongside standard care (most commonly oseltamivir), hIVIG was not superior to placebo for adults hospitalised with influenza infection. By contrast with our prespecified subgroup hypothesis that hIVIG would result in more favourable responses in patients with influenza A than B, we found the opposite effect. The clinical benefit of hIVIG for patients with influenza B is supported by antibody affinity analyses, but confirmation is warranted. Funding NIAID and NIH. Partial support was provided by the Medical Research Council (MRC_UU_12023/23) and the Danish National Research Foundation.

Alterations in the neurohumoral regulation of the upper intestine may change rhythmicity and pattern of ghrelin and obestatin, the latter presumably antagonizing ghrelin effects. Five nongastroparetic diabetic patients and five with gastroparesis were investigated. Over 390 min including breakfast and lunch, ghrelin was significantly lower in patients with gastroparesis compared with in those without (P = 0.015). Ghrelin subsequent to lunch decreased significantly (P = 0.011) in patients without gastroparesis, but not in gastroparetic patients (P = 0.669). Obestatin was similar in both groups and unchanged. No significant differences in ghrelin-to-obestatin ratio were observed (P = 0.530). Loss of rhythmicity in the ghrelin levels of gastroparetic diabetics highlights the importance of integrity of the neurohumoral-intestinal axis. Stable diurnal obestatin levels do not support the concept of interaction between ghrelin and obestatin in terms of regulation of food intake and gastric emptying.

Thiolatecobalt carbonyls RSCo(CO)4, 1 (R = Me, a, Et, b, PhCH2, c, Ph, d) and RSCo(CO)3PPh3, 2 (R = Et, a, PhCH2, b) were prepared. Complexes 1 were obtained from Co2(CO)8 or ICo(CO)4 and RS− or from Co2(CO)8 and RSSR, complexes 2 were prepared by substitution of 1 by PPh3 or by the reaction of ICo(CO)3PPh3 with RS−. Complexes 1 yield desulfuration products and/or polynuclear sulfur containing cobalt carbonyl clusters. Einkernige Thiolatcobaltcarbonyl-Komplexe Thiolatcobaltcarbonyle RSCo(CO)41 (R = Me, a; Et, b; PhCH2, c; Ph, d) und RSCo(CO)3PPh32 (R = Et, a; PhCH2, b) wurden dargestellt. Die Komplexe 1 wurden von Co2(CO)8 bzw. ICo(CO)4 und RS− oder von Co2(CO)8 und RSSR erhalten; die Komplexe 2 wurden durch Substitution von 1 mit PPh3 oder durch Umsetzung von ICo(CO)3PPh3 mit RS− dargestellt. Die Komplexe 1 ergeben desulfurierte Produkte und/oder mehrkernige schwefelhaltige Cobaltcarbonyl-Cluster.

Thiolatecobalt carbonyls RSCo(CO)4, 1 (R = Me, a, Et, b, PhCH2, c, Ph, d) and RSCo(CO)3PPh3, 2 (R = Et, a, PhCH2, b) were prepared. Complexes 1 were obtained from Co2(CO)8 or ICo(CO)4 and RS− or from Co2(CO)8 and RSSR, complexes 2 were prepared by substitution of 1 by PPh3 or by the reaction of ICo(CO)3PPh3 with RS−. Complexes 1 yield desulfuration products and/or polynuclear sulfur containing cobalt carbonyl clusters. Einkernige Thiolatcobaltcarbonyl-Komplexe Thiolatcobaltcarbonyle RSCo(CO)41 (R = Me, a; Et, b; PhCH2, c; Ph, d) und RSCo(CO)3PPh32 (R = Et, a; PhCH2, b) wurden dargestellt. Die Komplexe 1 wurden von Co2(CO)8 bzw. ICo(CO)4 und RS− oder von Co2(CO)8 und RSSR erhalten; die Komplexe 2 wurden durch Substitution von 1 mit PPh3 oder durch Umsetzung von ICo(CO)3PPh3 mit RS− dargestellt. Die Komplexe 1 ergeben desulfurierte Produkte und/oder mehrkernige schwefelhaltige Cobaltcarbonyl-Cluster.

Ohmic contacts of AuBe to p-ZnTe show a minimum specific contact resistance of 3.0/spl times/10/sup -6/ /spl Omega/ cm/sup 2/ for a p-doping level of 1.6/spl times/10/sup 19/ cm/sup -3/ and at an annealing temperature of 200/spl deg/C. The beryllium is very effective at improving the electrical properties of p-type contacts to ZnTe.