On the Relation between Solar Activity and Clear-Sky Terrestrial Irradiance

The Mauna Loa Observatory record of direct-beam solar irradiance measurements for the years 1958-2010 is analysed to investigate the variation of clear-sky terrestrial insolation with solar activity over more than four solar cycles. The raw irradiance data exhibit a marked seasonal cycle, extended periods of lower irradiance due to emissions of volcanic aerosols, and a long-term decrease in atmospheric transmission independent of solar activity. After correcting for these effects, it is found that clear-sky terrestrial irradiance typically varies by about 0.2 +/- 0.1% over the course of the solar cycle, a change of the same order of magnitude as the variations of the total solar irradiance above the atmosphere. An investigation of changes in the clear-sky atmospheric transmission fails to find a significant trend with sunspot number. Hence there is no evidence for a yet unknown effect amplifying variations of clear-sky irradiance with solar activity.Comment: 16 pages, 7 figures, in press at Solar Physics; minor changes to the text to match final published versio

Energy landscape, two-level systems and entropy barriers in Lennard-Jones clusters

We develop an efficient numerical algorithm for the identification of a large number of saddle points of the potential energy function of Lennard- Jones clusters. Knowledge of the saddle points allows us to find many thousand adjacent minima of clusters containing up to 80 argon atoms and to locate many pairs of minima with the right characteristics to form two-level systems (TLS). The true TLS are singled out by calculating the ground-state tunneling splitting. The entropic contribution to all barriers is evaluated and discussed.Comment: 4 pages, RevTex, 2 PostScript figure

Deletion of Sirt3 does not affect atherosclerosis but accelerates weight gain and impairs rapid metabolic adaptation in LDL receptor knockout mice: implications for cardiovascular risk factor development.

Sirt3 is a mitochondrial NAD(+)-dependent deacetylase that governs mitochondrial metabolism and reactive oxygen species homeostasis. Sirt3 deficiency has been reported to accelerate the development of the metabolic syndrome. However, the role of Sirt3 in atherosclerosis remains enigmatic. We aimed to investigate whether Sirt3 deficiency affects atherosclerosis, plaque vulnerability, and metabolic homeostasis. Low-density lipoprotein receptor knockout (LDLR(-/-)) and LDLR/Sirt3 double-knockout (Sirt3(-/-)LDLR(-/-)) mice were fed a high-cholesterol diet (1.25 % w/w) for 12 weeks. Atherosclerosis was assessed en face in thoraco-abdominal aortae and in cross sections of aortic roots. Sirt3 deletion led to hepatic mitochondrial protein hyperacetylation. Unexpectedly, though plasma malondialdehyde levels were elevated in Sirt3-deficient mice, Sirt3 deletion affected neither plaque burden nor features of plaque vulnerability (i.e., fibrous cap thickness and necrotic core diameter). Likewise, plaque macrophage and T cell infiltration as well as endothelial activation remained unaltered. Electron microscopy of aortic walls revealed no difference in mitochondrial microarchitecture between both groups. Interestingly, loss of Sirt3 was associated with accelerated weight gain and an impaired capacity to cope with rapid changes in nutrient supply as assessed by indirect calorimetry. Serum lipid levels and glucose tolerance were unaffected by Sirt3 deletion in LDLR(-/-) mice. Sirt3 deficiency does not affect atherosclerosis in LDLR(-/-) mice. However, Sirt3 controls systemic levels of oxidative stress, limits expedited weight gain, and allows rapid metabolic adaptation. Thus, Sirt3 may contribute to postponing cardiovascular risk factor development

Comparative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccine Among Patients Receiving Maintenance Hemodialysis

Rationale & Objective: Studies of patients on maintenance dialysis therapy suggest that standard-dose influenza vaccine (SDV) may not prevent influenza-related outcomes. Little is known about the comparative effectiveness of SDV versus high-dose influenza vaccine (HDV) in this population. Study Design: Cohort study using data from the US Renal Data System. Setting & Participants: 507,552 adults undergoing in-center maintenance hemodialysis between the 2010 to 2011 and 2014 to 2015 influenza seasons. Exposures: SDV and HDV. Outcomes: All-cause mortality, hospitalization due to influenza or pneumonia, and influenza-like illness during the influenza season. Analytic Approach: Patients were eligible for inclusion in multiple yearly cohorts; thus, our unit of analysis was the influenza patient-season. To examine the relationship between vaccine dose and effectiveness outcomes, we estimated risk differences and risk ratios using propensity score weighting of Kaplan-Meier functions, accounting for a wide range of patient- and facility-level characteristics. For nonmortality outcomes, we used competing-risk methods to account for the high mortality rate in the dialysis population. Results: Within 225,215 influenza patient-seasons among adults 65 years and older, 97.4% received SDV and 2.6% received HDV. We observed similar risk estimates for HDV and SDV recipients for mortality (risk difference, −0.08%; 95% CI, −0.85% to 0.80%), hospitalization due to influenza or pneumonia (risk difference, 0.15%; 95% CI, −0.69% to 0.93%), and influenza-like illness (risk difference, 0.00%; 95% CI, −1.50% to 1.08%). Our findings were similar among adults younger than 65 years, as well as within other subgroups defined by influenza season, age group, dialysis vintage, month of influenza vaccination, and vaccine valence. Limitations: Residual confounding and outcome misclassification. Conclusions: The HDV does not appear to provide additional protection beyond the SDV against all-cause mortality or influenza-related outcomes for adults undergoing hemodialysis. The additional cost and side effects associated with HDV should be considered when offering this vaccine. Future studies of HDV and other influenza vaccine strategies are warranted

Influenza vaccine effectiveness in patients on hemodialysis: An analysis of a natural experiment

Background Although the influenza vaccine is recommended for patients with end-stage renal disease, little is known about its effectiveness. Observational studies of vaccine effectiveness (VE) are challenging because vaccinated subjects may be healthier than unvaccinated subjects. Methods Using US Renal Data System data, we estimated VE for influenza-like illness, influenza/pneumonia hospitalization, and mortality in adult patients undergoing hemodialysis by using a natural experiment created by the year-to-year variation in the match of the influenza vaccine to the circulating virus. We compared vaccinated patients in matched years (1998, 1999, and 2001) with a mismatched year (1997) using Cox proportional hazards models. Ratios of hazard ratios compared vaccinated patients between 2 years and unvaccinated patients between 2 years. We calculated VE as 1 − effect measure. Results Vaccination rates were less than 50% each year. Conventional analysis comparing vaccinated with unvaccinated patients produced average VE estimates of 13%, 16%, and 30% for influenza-like illness, influenza/pneumonia hospitalization, and mortality, respectively. When restricted to the preinfluenza period, results were even stronger, indicating bias. The pooled ratio of hazard ratios comparing matched seasons with a placebo season resulted in a VE of 0% (95% CI, −3% to 2%) for influenza-like illness, 2% (−2% to 5%) for hospitalization, and 0% (−3% to 3%) for death. Conclusions Relative to a mismatched year, we found little evidence of increased VE in subsequent well-matched years, suggesting that the current influenza vaccine strategy may have a smaller effect on morbidity and mortality in the end-stage renal disease population than previously thought. Alternate strategies (eg, high-dose vaccine, adjuvanted vaccine, and multiple doses) should be investigated

Prenatal Tdap immunization and risk of maternal and newborn adverse events

Many countries recommend combined tetanus toxoid, reduced diphtheria toxoid and acellular pertussis immunization (Tdap) during pregnancy to stimulate transplacental transmission of pertussis antibodies to newborns. The immune system can be altered during pregnancy, potentially resulting in differing immunization risks in pregnant women. The safety of widespread Tdap immunization during pregnancy needs to be established. Our objective was to assess whether prenatal Tdap immunization was associated with adverse birth outcomes, and to evaluate the effect of timing of Tdap administration on these outcomes. We identified pregnancies at delivery in a large insurance claims database (2010–2014). Tdap immunization was categorized as optimal prenatal (27 + weeks), early prenatal (<27 weeks), postpartum (≤7 days post-delivery), or none. Medical claims were searched to identify maternal adverse immunization reactions (e.g. anaphylaxis, fever, Guillian-Barre syndrome [GBS]), adverse birth outcomes (e.g. preeclampsia/eclampsia, premature rupture or membranes, chorioamnionitis) and newborn outcomes (e.g. respiratory distress, pulmonary hypertension, neonatal jaundice). Women with optimal or early prenatal Tdap were compared to those not immunized in pregnancy, using propensity score-weighted log-binomial regression and Cox proportional hazards models to estimate risk ratios (RR) and hazard ratios (HR). We identified 1,079,034 deliveries and 677,075 linked newborns; 11.5% were immunized optimally and 2.3% immunized early. There were 1 case of post-immunization anaphylaxis, and 12 cases of maternal encephalopathy (all post- delivery); there were no cases of GBS. Optimally-timed immunization was associated with small increased relative risks of: chorioamnionitis [RR = 1.11, (95% CI: 1.07–1.15), overall risk = 2.8%], and postpartum hemorrhage [RR = 1.23 (95% DI: 1.18–1.28), overall risk = 2.4%]; however, these relative increases corresponded to low absolute risk increases. Tdap was not associated with increased risk of any adverse newborn outcome. Overall, prenatal Tdap immunization was not associated with newborn adverse events, but potential associations with chorioamnionitis consistent with one previous study and postpartum hemorrhage require further investigation

Assessment of self-contamination during removal of personal protective equipment for Ebola patient care

OBJECTIVE Ebola virus disease (EVD) places healthcare personnel (HCP) at high risk for infection during patient care, and personal protective equipment (PPE) is critical. Protocols for EVD PPE doffing have not been validated for prevention of viral self-contamination. Using surrogate viruses (non-enveloped MS2 and enveloped Φ6), we assessed self-contamination of skin and clothes when trained HCP doffed EVD PPE using a standardized protocol. METHODS A total of 15 HCP donned EVD PPE for this study. Virus was applied to PPE, and a trained monitor guided them through the doffing protocol. Of the 15 participants, 10 used alcohol-based hand rub (ABHR) for glove and hand hygiene and 5 used hypochlorite for glove hygiene and ABHR for hand hygiene. Inner gloves, hands, face, and scrubs were sampled after doffing. RESULTS After doffing, MS2 virus was detected on the inner glove worn on the dominant hand for 8 of 15 participants, on the non-dominant inner glove for 6 of 15 participants, and on scrubs for 2 of 15 participants. All MS2 on inner gloves was observed when ABHR was used for glove hygiene; none was observed when hypochlorite was used. When using hypochlorite for glove hygiene, 1 participant had MS2 on hands, and 1 had MS2 on scrubs. CONCLUSIONS A structured doffing protocol using a trained monitor and ABHR protects against enveloped virus self-contamination. Non-enveloped virus (MS2) contamination was detected on inner gloves, possibly due to higher resistance to ABHR. Doffing protocols protective against all viruses need to incorporate highly effective glove and hand hygiene agents

A Test of Rank-Dependent Utility in the Context of Ambiguity

Experimental investigations of non-expected utility have primarily concentrated on decision under risk (probability triangles). The literature suggests, however, that ambiguity is one of the main causes for deviations from expected utility (EU). This article investigates the descriptive performance of rank-dependent utility (RDU) in the context of choice under ambiguity. We use the axiomatic difference between RDU and EU to critically test RDU against EU. Surprisingly, the RDU model does not provide any descriptive improvement over EU. Our data suggest other framing factors that do provide descriptive improvements over EU

Effectiveness of Prenatal Tetanus, Diphtheria, Acellular Pertussis Vaccination in the Prevention of Infant Pertussis in the U.S.

Introduction: It is recommended that all pregnant women in the U.S. receive tetanus, diphtheria, acellular pertussis (Tdap) immunization to prevent infant pertussis. This study's objective was to examine the clinical effectiveness of prenatal Tdap, and whether effectiveness varies by gestational age at immunization. Methods: A nationwide cohort study of pregnant women with deliveries in 2010–2014 and their infants was performed. Commercial insurance claims data were analyzed in 2016–2017 to identify Tdap receipt by the pregnant women, and hospitalizations and outpatient visits for pertussis in their infants until the infants reached 18 months of age. Pertussis occurrence was compared between infants of mothers who received prenatal Tdap (overall and stratified by gestational age at administration) and infants of unvaccinated mothers. Results: There were 675,167 mother–infant pairs in the cohort. Among infants whose mothers received prenatal Tdap, the rate of pertussis was 43% lower (hazard ratio=0.57, 95% CI=0.35, 0.92) than infants whose mothers did not receive prenatal or postpartum Tdap; this reduction was consistent across pertussis definitions (hazard ratio for inpatient-only pertussis=0.32, 95% CI=0.11, 0.91). Pertussis rates were also lower for infants whose mothers received Tdap during the third trimester. Infants whose mothers received Tdap at <27 weeks of gestation did not experience reductions in pertussis rates (hazard ratio for pertussis=1.10, 95% CI=0.54, 2.25). Conclusions: Infants of mothers who received prenatal Tdap experienced half the rate of pertussis as compared with infants of unimmunized mothers. These results do not provide evidence to support changing the currently recommended timing of Tdap administration in pregnancy