A cohort of 6,254 pregnancies surviving at least 20 weeks of gestation was identified through pregnancy testing and follow-up at three Kaiser Permanente medical offices in northern California in ...1981-82. Fetal death ratios per 1,000 live births were 12.1 for all fetal deaths versus 5.0 for the subset of fetal deaths reported to the California state registrar. Only fetal deaths resulting in overnight hospitalization of the mother were reported. Seventy-nine percent of fetal deaths over 28 completed weeks since the last menstrual period (LMP) were reported versus only 10 percent between 20 and 28 completed weeks since the LMP. Ninety-three percent of fetuses over 400 grams were reported. The unreported fetal deaths were mainly those perceived by attending physicians as spontaneous abortion, especially missed or incomplete spontaneous abortion. Physicians apparently preferred the label of spontaneous abortion over stillbirth or fetal death whenever fetal maturity could not be substantiated, regardless of prior estimates of the date of the LMP. Fetuses as large and developed as potentially viable infants were the most likely to be reported.
Venous thromboembolism (VTE), encompassing deep venous thrombosis (DVT) and pulmonary embolism (PE), causes postoperative morbidity and mortality in neurosurgical patients. The use of pharmacological ...prophylaxis for DVT prevention in the immediate postoperative period carries increased risk of intracranial hemorrhage, especially after skull base surgeries.
To investigate the impact of routine Doppler ultrasound monitoring in prevention and tiered management of VTE after skull base surgery.
We retrospectively analyzed a large cohort of consecutive adult patients who were prospectively and uniformly managed with routine monitoring by Doppler ultrasound for DVT after resection of a skull base tumor.
A total of 389 patients who underwent 459 surgeries for intracranial tumor resection were analyzed. Skull base meningioma was the most common pathology. Forty-four (9.59%) postoperative VTEs were detected: 9 (1.96%) with PE with or without DVT and 35 (7.63%) with DVT alone. Four cases of subsegmental PE were diagnosed without evidence of lower extremity DVT, possibly in the setting of peripherally inserted central catheters maintenance. One patient had a preoperative proximal DVT and underwent a prophylactic inferior vena cava filter but expired from PE after discharge. Prior history of VTE (risk ratio RR 5.13; 95% CI 2.76-7.18; P < .01), anesthesia duration (RR 1.14; 95% CI 1.03-1.27; P = .02), and blood transfusion (RR 1.95; 95% CI 1.01-3.37; P = .04) were associated with VTE development on multivariate analysis.
Routine postoperative venous ultrasound monitoring detects asymptomatic DVT guiding management. This is an alternative strategy to prescribing pharmacological VTE prophylaxis immediately after lengthy surgeries for intracranial tumors. Peripherally inserted central catheters were associated with subsegmental PE.
There is substantial variability among emergency departments (EDs) in their readiness to care for acutely ill and injured children, including US trauma centers. While high ED pediatric readiness is ...associated with improved in-hospital survival among children treated at trauma centers, the association between high ED readiness and long-term outcomes is unknown.
To evaluate the association between ED pediatric readiness and 1-year survival among injured children presenting to 146 trauma centers.
In this retrospective cohort study, injured children younger than 18 years who were residents of 8 states with admission, transfer to, or injury-related death at one of 146 participating trauma centers were included. Children cared for in and outside their state of residence were included. Subgroups included those with an Injury Severity Score (ISS) of 16 or more; any Abbreviated Injury Scale (AIS) score of 3 or more; head AIS score of 3 or more; and need for early critical resources. Data were collected from January 2012 to December 2017, with follow-up to December 2018. Data were analyzed from January to July 2021.
ED pediatric readiness for the initial ED, measured using the weighted Pediatric Readiness Score (wPRS; range, 0-100) from the 2013 National Pediatric Readiness Project assessment.
Time to death within 365 days.
Of 88 071 included children, 30 654 (34.8%) were female; 2114 (2.4%) were Asian, 16 730 (10.0%) were Black, and 49 496 (56.2%) were White; and the median (IQR) age was 11 (5-15) years. A total of 1974 (2.2%) died within 1 year of the initial ED visit, including 1768 (2.0%) during hospitalization and 206 (0.2%) following discharge. Subgroups included 12 752 (14.5%) with an ISS of 16 or more, 28 402 (32.2%) with any AIS score of 3 or more, 13 348 (15.2%) with a head AIS of 3 or more, and 9048 (10.3%) requiring early critical resources. Compared with EDs in the lowest wPRS quartile (32-69), children cared for in the highest wPRS quartile (95-100) had lower hazard of death to 1 year (adjusted hazard ratio aHR, 0.70; 95% CI, 0.56-0.88). Supplemental analyses removing early deaths had similar results (aHR, 0.75; 95% CI, 0.56-0.996). Findings were consistent across subgroups and multiple sensitivity analyses.
Children treated in high-readiness trauma center EDs after injury had a lower risk of death that persisted to 1 year. High ED readiness is independently associated with long-term survival among injured children.
We present a real-time supernova neutrino burst monitor at Super-Kamiokande (SK). Detecting supernova explosions by neutrinos in real time is crucial for giving a clear picture of the explosion ...mechanism. Since the neutrinos are expected to come earlier than light, a fast broadcasting of the detection may give astronomers a chance to make electromagnetic radiation observations of the explosions right at the onset. The role of the monitor includes a fast announcement of the neutrino burst detection to the world and a determination of the supernova direction. We present the online neutrino burst detection system and studies of the direction determination accuracy based on simulations at SK.
Tightly regulated Ca2+ homeostasis is a prerequisite for proper cardiac function. To dissect the regulatory network of cardiac Ca2+ handling, we performed a chemical suppressor screen on zebrafish ...tremblor embryos, which suffer from Ca2+ extrusion defects. Efsevin was identified based on its potent activity to restore coordinated contractions in tremblor. We show that efsevin binds to VDAC2, potentiates mitochondrial Ca2+ uptake and accelerates the transfer of Ca2+ from intracellular stores into mitochondria. In cardiomyocytes, efsevin restricts the temporal and spatial boundaries of Ca2+ sparks and thereby inhibits Ca2+ overload-induced erratic Ca2+ waves and irregular contractions. We further show that overexpression of VDAC2 recapitulates the suppressive effect of efsevin on tremblor embryos whereas VDAC2 deficiency attenuates efsevin's rescue effect and that VDAC2 functions synergistically with MCU to suppress cardiac fibrillation in tremblor. Together, these findings demonstrate a critical modulatory role for VDAC2-dependent mitochondrial Ca2+ uptake in the regulation of cardiac rhythmicity.
The heart is a large muscle that pumps blood around the body by maintaining a regular rhythm of contraction and relaxation. If the heart loses this regular rhythm it works less efficiently, which can lead to life-threatening conditions.
Regular heart rhythms are maintained by changes in the concentration of calcium ions in the cytoplasm of the heart muscle cells. These changes are synchronised so that the heart cells contract in a controlled manner. In each cell, a contraction begins when calcium ions from outside the cell enter the cytoplasm by passing through a channel protein in the membrane that surrounds the cell. This triggers the release of even more calcium ions into the cytoplasm from stores within the cell. For the cells to relax, the calcium ions must then be pumped out of the cytoplasm to lower the calcium ion concentration back to the original level.
Shimizu et al. studied a zebrafish mutant—called tremblor—that has irregular heart rhythms because its heart muscle cells are unable to efficiently remove calcium ions from the cytoplasm. Embryos of the tremblor mutant were treated with a wide variety of chemical compounds with the aim of finding some that could correct the heart defect.
A compound called efsevin restores regular heart rhythms in tremblor mutants. Efsevin binds to a pump protein called VDAC2, which is found in compartments called mitochondria within the cell. Although mitochondria are best known for their role in supplying energy for the cell, they also act as internal stores for calcium. By binding to VDAC2, efsevin increases the rate at which calcium ions are pumped from the cytoplasm into the mitochondria. This restores rhythmic calcium ion cycling in the cytoplasm and enables the heart muscle cells to develop regular rhythms of contraction and relaxation. Increasing the levels of VDAC2 or another similar calcium ion pump protein in the heart cells can also restore a regular heart rhythm.
Efsevin can also correct irregular heart rhythms in human and mouse heart muscle cells, therefore the new role for mitochondria in controlling heart rhythms found by Shimizu et al. appears to be shared in other animals. The experiments have also identified the VDAC family of proteins as potential new targets for drug therapies to treat people with irregular heart rhythms.
Besides the usual conductance plateaus at multiples of 2e(2)/h, quantum point contacts typically show an extra plateau at approximately 0.7(2e(2)/h), believed to arise from electron-electron ...interactions that prohibit the two spin channels from being simultaneously occupied. We present evidence that the disappearance of the 0.7 structure at very low temperature signals the formation of a Kondo-like correlated spin state. Evidence includes a zero-bias conductance peak that splits in a parallel field, scaling of conductance to a modified Kondo form, and consistency between peak width and the Kondo temperature.
Most global climate models parameterize separate cloud types using separate parameterizations. This approach has several disadvantages, including obscure interactions between parameterizations and ...inaccurate triggering of cumulus parameterizations. Alternatively, a unified cloud parameterization uses one equation set to represent all cloud types. Such cloud types include stratiform liquid and ice cloud, shallow convective cloud, and deep convective cloud. Vital to the success of a unified parameterization is a general interface between clouds and microphysics. One such interface involves drawing Monte Carlo samples of subgrid variability of temperature, water vapor, cloud liquid, and cloud ice, and feeding the sample points into a microphysics scheme. This study evaluates a unified cloud parameterization and a Monte Carlo microphysics interface that has been implemented in the Community Atmosphere Model (CAM) version 5.3. Model computational expense is estimated, and sensitivity to the number of subcolumns is investigated. Results describing the mean climate and tropical variability from global simulations are presented. The new model shows a degradation in precipitation skill but improvements in shortwave cloud forcing, liquid water path, long-wave cloud forcing, precipitable water, and tropical wave simulation.
Use of visual display terminals (VDTs) was examined in a case-control study of pregnancy outcome among 1,583 pregnant women who attended three Kaiser Permanente obstetrics and gynecology clinics in ...Northern California, 1981-1982. We found a significantly elevated risk of miscarriage for working women who reported using VDTs for more than 20 hr per week during the first trimester of pregnancy compared to other working women who reported not using VDTs (odds ratio 1.8, 95% CI: 1.2-2.8). This risk could not be explained by age, education, occupation, smoking, alcohol consumption, or other maternal characteristics. No significantly elevated risk for birth defects was found among working women although odds ratios were 1.4 for both moderate and high VDT exposure, compared with no exposure (95% CI: 0.7-2.7 and 0.7-2.9, respectively). One possible explanation for these findings is that women who had adverse pregnancy outcomes may have overreported their exposures to VDTs and/or women with normal births may have underreported theirs. The findings may also be due to unmeasured factors confounded with high VDT use such as poor ergonomic conditions or job-related stress. That VDTs themselves are hazardous to the pregnant operator remains a possibility. Our results underscore the need for large cohort studies of working women that will provide objective measures of VDT exposures, ergonomic factors, and stress.
Summary
New drugs therapies have revolutionized the treatment of hepatitis C virus (HCV) infection. The objectives of this study were to evaluate uptake and utilization of boceprevir and telaprevir ...in the Department of Veterans Affairs (VA). We evaluated whether therapies conformed to response‐guided protocols, whether they replaced standard interferon plus ribavirin treatment, and whether IL‐28B was used to guide treatment. We performed an administrative data‐based analysis of all patients receiving pharmacologic treatment for HCV in VA from October 2009 to July 2013. There were 12 737 new HCV prescriptions in VA during this time, with 5564 boceprevir or telaprevir prescriptions (44%) and 7173 prescriptions (56%) written for standard interferon plus ribavirin treatment. Prescriptions for the new treatments heavily favoured boceprevir vs telaprevir (83% vs 17%). Sixty‐two percent (62%) of boceprevir‐treated patients completed their minimum‐specified protocol, while 69.2% of telaprevir‐treated patients completed their minimum‐specified protocol. From October 2010 to July 2012, 4090 patients had an IL‐28B test; less than 16% of these tests guided subsequent HCV prescriptions. Uptake of boceprevir and telaprevir was rapid; the number of patients initiating treatment approximately doubled in the period after their introduction. While new prescriptions favor boceprevir or telaprevir over standard interferon plus ribavirin therapy, there appears to still be a strong role of interferon plus ribavirin in treating HCV patients. This work can inform our understanding of how other new effective HCV therapies will be used, their diffusion, and the timing of their diffusion in actual clinical practice.
PDF
