Steady-state gain and saturation flux measurements in a high efficiency, electron-beam-pumped, Ar-Xe laser

Flat-top, Ar-Xe laser pulses at 1.73 ,um have been achieved by pumping the laser medium with a constant-current electron beam for pulse durations of up to 2.5 ms. The 220 keV electron beam pumped an active volume of 50X 8X6 cm3 at power loadings of 6-100 W/cm3. Small signal gain, saturation flux, and nonsaturable absorption were determined as a function of Xe concentration, total gas pressure, and pump power density by a Rigrod analysis. In the experimental regime investigated, the small signal gain increased as the total laser pressure decreased and as the partial pressure of Xe decreased. The Xe concentration was varied from 0.5% to 2.0% and the total pressure was varied from 250 to 860 Torr. The results are consistent with Xe quenching of the upper laser level being the dominant deexcitation process and with the collisional broadening dominating the linewidth. The peak intrinsic efficiency observed was 2.2%

Biased efficacy estimates in phase-III dengue vaccine trials due to heterogeneous exposure and differential detectability of primary infections across trial arms.

Vaccine efficacy (VE) estimates are crucial for assessing the suitability of dengue vaccine candidates for public health implementation, but efficacy trials are subject to a known bias to estimate VE toward the null if heterogeneous exposure is not accounted for in the analysis of trial data. In light of many well-characterized sources of heterogeneity in dengue virus (DENV) transmission, our goal was to estimate the potential magnitude of this bias in VE estimates for a hypothetical dengue vaccine. To ensure that we realistically modeled heterogeneous exposure, we simulated city-wide DENV transmission and vaccine trial protocols using an agent-based model calibrated with entomological and epidemiological data from long-term field studies in Iquitos, Peru. By simulating a vaccine with a true VE of 0.8 in 1,000 replicate trials each designed to attain 90% power, we found that conventional methods underestimated VE by as much as 21% due to heterogeneous exposure. Accounting for the number of exposures in the vaccine and placebo arms eliminated this bias completely, and the more realistic option of including a frailty term to model exposure as a random effect reduced this bias partially. We also discovered a distinct bias in VE estimates away from the null due to lower detectability of primary DENV infections among seronegative individuals in the vaccinated group. This difference in detectability resulted from our assumption that primary infections in vaccinees who are seronegative at baseline resemble secondary infections, which experience a shorter window of detectable viremia due to a quicker immune response. This resulted in an artefactual finding that VE estimates for the seronegative group were approximately 1% greater than for the seropositive group. Simulation models of vaccine trials that account for these factors can be used to anticipate the extent of bias in field trials and to aid in their interpretation

Anne E. Perkins, MD Correspondence

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Oxidative Stress in Oocytes during Midprophase Induces Premature Loss of Cohesion and Chromosome Segregation Errors

In humans, errors in meiotic chromosome segregation that produce aneuploid gametes increase dramatically as women age, a phenomenon termed the maternal age effect. During meiosis, cohesion between sister chromatids keeps recombinant homologs physically attached and premature loss of cohesion can lead to missegregation of homologs during meiosis I. A growing body of evidence suggests that meiotic cohesion deteriorates as oocytes age and contributes to the maternal age effect. One hallmark of aging cells is an increase in oxidative damage caused by reactive oxygen species (ROS). Therefore, increased oxidative damage in older oocytes may be one of the factors that leads to premature loss of cohesion and segregation errors. To test this hypothesis, we used an RNAi strategy to induce oxidative stress in Drosophila oocytes and measured the fidelity of chromosome segregation during meiosis. Knockdown of either the cytoplasmic or mitochondrial ROS scavenger superoxide dismutase (SOD) caused a significant increase in segregation errors, and heterozygosity for an smc1 deletion enhanced this phenotype. FISH analysis indicated that SOD knockdown moderately increased the percentage of oocytes with arm cohesion defects. Consistent with premature loss of arm cohesion and destabilization of chiasmata, the frequency at which recombinant homologs missegregate during meiosis I is significantly greater in SOD knockdown oocytes than in controls. Together these results provide an in vivo demonstration that oxidative stress during meiotic prophase induces chromosome segregation errors and support the model that accelerated loss of cohesion in aging human oocytes is caused, at least in part, by oxidative damage

Is the incidence of depressive disorders increased following cerebral concussion?

Q: Is the incidence of depressive disorders increased following cerebral concussion? Evidence-based answer: yes, in some populations. Youth and adolescents with self-reported history of concussion had increased risk of depressive disorders (strength of recommendation [SOR]: B, based on a prospective cohort study and a retrospective cohort study). Evidence was inconsistent for college athletes. Athletes with ≥ 3 concussions exhibited more depressive disorders, but no association was observed for those with 1 or 2 concussions compared to nonconcussion injuries (SOR: B, based on a cross-sectional study, a small prospective cohort study, and a case-control study). In semiprofessional and professional athletes, evidence was variable and may be sport related. Retired rugby players with a history of concussion showed no increase in depression compared to controls with no concussion history (SOR: B, based on a case-control study). Retired football players with previous concussions displayed increased incidence of depression, especially after ≥ 3 concussions (SOR: B, based on a prospective cohort study and a small case-control study). There is a significant risk of bias in these studies because of their reliance on self-reported concussions, differing definitions of depression, and possible unmeasured confounders in the study designs, making a causative relationship between concussion and depression unclear.Jason W. Deck, MD; Thomas Kern, MD; LaMont Cavanagh, MD; Matthew Bartow, DO; Franklin T. Perkins III, MD (Department of Family and Community Medicine, OU-TU School of Community Medicine, University of Oklahoma Health Sciences Center, Tulsa); Toni Hoberecht, MA, MLIS, AHIP; Alyssa Migdalski, MLIS (Schusterman Library, University of Oklahoma-Tulsa