Tropospheric ozone (O3) is potentially associated with cardiovascular disease risk and premature death. Results from long-term epidemiological studies on O3 are scarce and inconclusive.
In this ...study, we examined associations between chronic ambient O3 exposure and all-cause and cause-specific mortality in a large cohort of U.S. adults.
Cancer Prevention Study II participants were enrolled in 1982. A total of 669,046 participants were analyzed, among whom 237,201 deaths occurred through 2004. We obtained estimates of O3 concentrations at the participant's residence from a hierarchical Bayesian space-time model. Estimates of fine particulate matter (particulate matter with an aerodynamic diameter of up to 2.5 μm PM2.5) and NO2 concentrations were obtained from land use regression. Cox proportional hazards regression models were used to examine mortality associations adjusted for individual- and ecological-level covariates.
In single-pollutant models, we observed significant positive associations between O3, PM2.5, and NO2 concentrations and all-cause and cause-specific mortality. In two-pollutant models adjusted for PM2.5, significant positive associations remained between O3 and all-cause (hazard ratio HR per 10 ppb, 1.02; 95% confidence interval CI, 1.01-1.04), circulatory (HR, 1.03; 95% CI, 1.01-1.05), and respiratory mortality (HR, 1.12; 95% CI, 1.08-1.16) that were unchanged with further adjustment for NO2. We also observed positive mortality associations with both PM2.5 (both near source and regional) and NO2 in multipollutant models.
Findings derived from this large-scale prospective study suggest that long-term ambient O3 contributes to risk of respiratory and circulatory mortality. Substantial health and environmental benefits may be achieved by implementing further measures aimed at controlling O3 concentrations.
Identifying the prime drivers of the twentieth-century multidecadal variability in the Atlantic Ocean is crucial for predicting how the Atlantic will evolve in the coming decades and the resulting ...broad impacts on weather and precipitation patterns around the globe. Recently, Booth et al. showed that the Hadley Centre Global Environmental Model, version 2, Earth system configuration (HadGEM2-ES) closely reproduces the observed multidecadal variations of area-averaged North Atlantic sea surface temperature in the twentieth century. The multidecadal variations simulated in HadGEM2-ES are primarily driven by aerosol indirect effects that modify net surface shortwave radiation. On the basis of these results, Booth et al. concluded that aerosols are a prime driver of twentieth-century North Atlantic climate variability. However, here it is shown that there are major discrepancies between the HadGEM2-ES simulations and observations in the North Atlantic upper-ocean heat content, in the spatial pattern of multidecadal SST changes within and outside the North Atlantic, and in the subpolar North Atlantic sea surface salinity. These discrepancies may be strongly influenced by, and indeed in large part caused by, aerosol effects. It is also shown that the aerosol effects simulated in HadGEM2-ES cannot account for the observed anticorrelation between detrended multidecadal surface and subsurface temperature variations in the tropical North Atlantic. These discrepancies cast considerable doubt on the claim that aerosol forcing drives the bulk of this multidecadal variability.
We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). The LSST design is driven by four main science themes: probing dark energy and ...dark matter, taking an inventory of the solar system, exploring the transient optical sky, and mapping the Milky Way. LSST will be a large, wide-field ground-based system designed to obtain repeated images covering the sky visible from Cerro Pachón in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg2 field of view, a 3.2-gigapixel camera, and six filters (ugrizy) covering the wavelength range 320-1050 nm. The project is in the construction phase and will begin regular survey operations by 2022. About 90% of the observing time will be devoted to a deep-wide-fast survey mode that will uniformly observe a 18,000 deg2 region about 800 times (summed over all six bands) during the anticipated 10 yr of operations and will yield a co-added map to r ∼ 27.5. These data will result in databases including about 32 trillion observations of 20 billion galaxies and a similar number of stars, and they will serve the majority of the primary science programs. The remaining 10% of the observing time will be allocated to special projects such as Very Deep and Very Fast time domain surveys, whose details are currently under discussion. We illustrate how the LSST science drivers led to these choices of system parameters, and we describe the expected data products and their characteristics.
Bundled Payments for Care Improvement (BPCI) is a voluntary initiative of the Centers for Medicare & Medicaid Services to test the effect of holding an entity accountable for all services provided ...during an episode of care on episode payments and quality of care.
To evaluate whether BPCI was associated with a greater reduction in Medicare payments without loss of quality of care for lower extremity joint (primarily hip and knee) replacement episodes initiated in BPCI-participating hospitals that are accountable for total episode payments (for the hospitalization and Medicare-covered services during the 90 days after discharge).
A difference-in-differences approach estimated the differential change in outcomes for Medicare fee-for-service beneficiaries who had a lower extremity joint replacement at a BPCI-participating hospital between the baseline (October 2011 through September 2012) and intervention (October 2013 through June 2015) periods and beneficiaries with the same surgical procedure at matched comparison hospitals.
Lower extremity joint replacement at a BPCI-participating hospital.
Standardized Medicare-allowed payments (Medicare payments), utilization, and quality (unplanned readmissions, emergency department visits, and mortality) during hospitalization and the 90-day postdischarge period.
There were 29 441 lower extremity joint replacement episodes in the baseline period and 31 700 in the intervention period (mean SD age, 74.1 8.89 years; 65.2% women) at 176 BPCI-participating hospitals, compared with 29 440 episodes in the baseline period (768 hospitals) and 31 696 episodes in the intervention period (841 hospitals) (mean SD age, 74.1 8.92 years; 64.9% women) at matched comparison hospitals. The BPCI mean Medicare episode payments were $30 551 (95% CI, $30 201 to $30 901) in the baseline period and declined by $3286 to $27 265 (95% CI, $26 838 to $27 692) in the intervention period. The comparison mean Medicare episode payments were $30 057 (95% CI, $29 765 to $30 350) in the baseline period and declined by $2119 to $27 938 (95% CI, $27 639 to $28 237). The mean Medicare episode payments declined by an estimated $1166 more (95% CI, -$1634 to -$699; P < .001) for BPCI episodes than for comparison episodes, primarily due to reduced use of institutional postacute care. There were no statistical differences in the claims-based quality measures, which included 30-day unplanned readmissions (-0.1%; 95% CI, -0.6% to 0.4%), 90-day unplanned readmissions (-0.4%; 95% CI, -1.1% to 0.3%), 30-day emergency department visits (-0.1%; 95% CI, -0.7% to 0.5%), 90-day emergency department visits (0.2%; 95% CI, -0.6% to 1.0%), 30-day postdischarge mortality (-0.1%; 95% CI, -0.3% to 0.2%), and 90-day postdischarge mortality (-0.0%; 95% CI, -0.3% to 0.3%).
In the first 21 months of the BPCI initiative, Medicare payments declined more for lower extremity joint replacement episodes provided in BPCI-participating hospitals than for those provided in comparison hospitals, without a significant change in quality outcomes. Further studies are needed to assess longer-term follow-up as well as patterns for other types of clinical care.
Background Video-assisted thoracic surgical (VATS) lobectomies and wedge resections result in less morbidity and shorter length of stay than resections via thoracotomy. The impact of robot-assisted ...thoracic surgical (RATS) lobectomy on clinical and economic outcomes has not been examined. This study compared hospital costs and clinical outcomes for VATS lobectomies and wedge resections versus RATS. Methods Using the Premier hospital database, patients aged ≥18 years with a record of thoracoscopic lobectomy, segmental resection, or excision of a lesion or tissue from the lung between 2009 and 2011 were identified. Procedures using robotic technology were identified if 1 of 2 conditions were met: (1) a robotic International Classification of Diseases, Ninth Revision procedure code or (2) the text fields in the hospital record indicated that the robot was used. Using a propensity score and based on severity and comorbidities, certain demographics and hospital characteristics were matched. The association between VATS or RATS and adverse events, hospital costs, surgery time, and length of stay was examined. Results Of 15,502 patient records analyzed, 96% (n = 14,837) were performed without robotic assistance. Using robotic assistance was associated with higher average hospital costs per patient. The average cost of inpatient procedures with RATS was $25,040.70 versus $20,476.60 for VATS ( P = .0001) for lobectomies and $19,592.40 versus $16,600.10 ( P = .0001) for wedge resections, respectively. Inpatient operating times were longer for RATS lobectomy than VATS lobectomy (4.49 hours vs 4.23 hours; P = .0959) and wedge resection (3.26 vs 2.86 hours; P = .0003). Length of stay was similar with no differences in adverse events. Conclusions RATS lobectomy and wedge resection seem to have higher hospital costs and longer operating times, without any differences in adverse events.
A highly protective vaccine will greatly facilitate achieving and sustaining malaria elimination. Understanding mechanisms of antibody-mediated immunity is crucial for developing vaccines with high ...efficacy. Here, we identify key roles in humoral immunity for Fcγ-receptor (FcγR) interactions and opsonic phagocytosis of sporozoites. We identify a major role for neutrophils in mediating phagocytic clearance of sporozoites in peripheral blood, whereas monocytes contribute a minor role. Antibodies also promote natural killer cell activity. Mechanistically, antibody interactions with FcγRIII appear essential, with FcγRIIa also required for maximum activity. All regions of the circumsporozoite protein are targets of functional antibodies against sporozoites, and N-terminal antibodies have more activity in some assays. Functional antibodies are slowly acquired following natural exposure to malaria, being present among some exposed adults, but uncommon among children. Our findings reveal targets and mechanisms of immunity that could be exploited in vaccine design to maximize efficacy.
Cities around the world are facing an ever-increasing variety of challenges that seem to make more sustainable urban futures elusive. Many of these challenges are being driven by, and exacerbated by, ...increases in urban populations and climate change. Novel solutions are needed today if our cities are to have any hope of more sustainable and resilient futures. Because most of the environmental impacts of any project are manifest at the point of design, we posit that this is where a real difference in urban development can be made. To this end, we present a transformative model that merges urban design and ecology into an inclusive, creative, knowledge-to-action process. This design-ecology nexus-an ecology for cities-will redefine both the process and its products. In this paper we: (1) summarize the relationships among design, infrastructure, and urban development, emphasizing the importance of joining the three to achieve urban climate resilience and enhance sustainability; (2) discuss how urban ecology can move from an ecology of cities to an ecology for cities based on a knowledge-to-action agenda; (3) detail our model for a transformational urban design-ecology nexus, and; (4) demonstrate the efficacy of our model with several case studies.
The neocortex is disproportionately expanded in human compared with mouse
, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed ...of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth
. Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues. We demonstrate a strong correspondence between morphological, physiological and transcriptomic phenotypes of five human glutamatergic supragranular neuron types. These were enriched in but not restricted to layers, with one type varying continuously in all phenotypes across layers 2 and 3. The deep portion of layer 3 contained highly distinctive cell types, two of which express a neurofilament protein that labels long-range projection neurons in primates that are selectively depleted in Alzheimer's disease
. Together, these results demonstrate the explanatory power of transcriptomic cell-type classification, provide a structural underpinning for increased complexity of cortical function in humans, and implicate discrete transcriptomic neuron types as selectively vulnerable in disease.
Since its discovery in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been estimated to be responsible for at least 769.3 million infections and over 6.95 million ...deaths. Despite significant global vaccination efforts, there are limited therapies that are considered safe and effective for use in the management of COVID-19 during pregnancy despite the common knowledge that pregnant patients have a much higher risk of adverse outcomes. A bioactive compound found in broccoli sprout—sulforaphane—is a potent inducer of phase-II detoxification enzymes promoting a series of potentially beneficial effects notably as an antioxidant, anti-inflammatory, and anti-viral. A pilot, double-blinded, placebo-controlled randomised trial is to be conducted in Melbourne, Australia, across both public and private hospital sectors. We will assess a commercially available broccoli sprout extract in pregnant women between 20+0 and 36+0 weeks gestation with SARS-CoV-2 infection to investigate (i) the duration of COVID-19 associated symptoms, (ii) maternal and neonatal outcomes, and (iii) biomarkers of infection and inflammation. We plan to enrol 60 outpatient women with COVID-19 irrespective of vaccination status diagnosed by PCR swab or RAT (rapid antigen test) within five days and randomised to 14 days of oral broccoli sprout extract (42 mg of sulforaphane daily) or identical microcrystalline cellulose placebo. The primary outcome of this pilot trial will be to assess the feasibility of conducting a larger trial investigating the duration (days) of COVID-19-associated symptoms using a broccoli sprout supplement for COVID-19-affected pregnancies. Pregnant patients remain an at-risk group for severe disease following infection with SARS-CoV-2 and currently unclear consequences for the offspring. Therefore, this study will assess feasibility of using a broccoli sprout supplement, whilst providing important safety data for the use of sulforaphane in pregnancy.
To characterize health care utilization and costs associated with care after diagnosis of Kawasaki disease including adherence to guidelines for echocardiograms.
We analyzed children hospitalized for ...Kawasaki disease using 2015-2017 national Truven MarketScan commercial claims data. The mean 90-day prehospitalization utilization and costs were quantified and compared with the 90 days posthospitalization via Wilcoxon 2-sample test. Adherence to echocardiogram guidelines was examined using multivariable logistic regression to identify factors associated with adherence.
The mean total payments 90 days prior to hospitalization ($2090; n = 360) were significantly lower than those after discharge ($3778), though out of pocket costs were higher ($400 vs $270) (P < .0001). There was an increase in office visits, medical procedures, and echocardiograms after discharge. A majority of health care utilization before hospitalization occurred in the 7 days immediately prior to the date of admission; 51% obtained an echocardiogram within the first 2 weeks, and 14% were completely adherent with recommendations. Children with greater utilization prior to admission were more likely to adhere to American Heart Association guidelines for follow-up echocardiograms (OR 1.03, 95% CI 1.01-1.06).
Outpatient health care expenditure nearly doubles after Kawasaki disease hospital discharge when compared with prehospitalization, suggesting the financial ramifications of this diagnosis persist beyond costs incurred during hospitalization. A significant portion of patients do not receive guideline recommended follow-up echocardiograms. This issue should be explored in more detail given the morbidity and mortality associated with this diagnosis.
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