New Perspectives on Transforming States' Health and Human Services: Practical Commentaries on the First Year of the Work Support Strategies Initiative

Millions of low-income working families in America today are struggling to make ends meet. While working hard, often in low-wage jobs, many of these families are living close to the edge of hardship and have little or no resources to fall back on in case of emergencies. Public benefit programs can make a huge difference in the well-being of these working families, providing help with food, child care, and health insurance expenses. These programs help families address immediate needs and weather short-term crises, such as repairing a car needed to get to work or dealing with an unexpected health problem. They can make it possible for families to hold onto their jobs in these emergencies, stabilizing employment and keeping families from falling further into poverty. Yet many families that are eligible for public benefit programs do not participate. Although the recession and its aftermath led to unprecedented increases in receipt of nutrition assistance through the federal Supplemental Nutrition Assistance Program (SNAP), the latest data (from 2010) show that only 65 percent of the eligible working poor are participating. Similarly, of all children eligible for public health insurance coverage through Medicaid or the Children's Health Insurance Program, only 86 percent are participating. The participation rate for public health insurance for parents is only 66 percent. And, these participation rates vary widely across states.The Work Support Strategies, or WSS, Initiative is motivated by the value public benefit programs can provide to working families and the belief that the states and localities administering these programs can improve how eligible families access and retain these benefits. In the first year of the demonstration, nine states took on the challenge of streamlining, integrating, and improving the provision of work support benefits through their SNAP, Medicaid, and child care programs (and, in some states, additional programs such as heating assistance and cash welfare). While most states hope their efforts will also reduce burden on caseworkers and administrative costs in these systems, all are motivated to improve the lives of the families they serve

Modelling Costs of Interventional Pulmonary Embolism Treatment: Implications of US Trends for a European Healthcare System

BACKGROUND Catheter-directed treatment (CDT) of acute pulmonary embolism (PE) is entering a growth phase in Europe following a steady increase in the United States (US) in the past decade, but the potential economic impact on European healthcare systems remains unknown. METHODS AND RESULTS We built two statistical models for the monthly trend of proportion of CDT among patients with severe (intermediate- or high-risk) PE in the US. The conservative model was based on admission data from the National Inpatient Sample (NIS) 2016-2020, and the model reflecting increasing access to advanced treatment from the PERTTM national quality assurance database registry 2018-2021. By applying these models to the forecast of annual PE-related hospitalizations in Germany, we calculated the annual number of severe PE cases and the expected increase in CDT use for the period 2025-2030. The NIS-based model yielded a slow increase, reaching 3.1% (95% CI 3.0-3.2%) among all hospitalizations with PE in 2030; in the PERT-based model, increase would be steeper, reaching 8.7% (8.3-9.2%). Based on current reimbursement rates, we estimated an increase of annual costs for PE-related hospitalizations in Germany ranging from 15.3 to 49.8 million euros by 2030. This calculation does not account for potential cost savings, including those from reduced length of hospital stay. CONCLUSION Our approach and results, which may be adapted to other European healthcare systems, provide a benchmark for healthcare costs expected to result from CDT. Data from ongoing trials on clinical benefits and cost savings are needed to determine cost-effectiveness and inform reimbursement decisions

Enhancement of systemic and sputum granulocyte response to inhaled endotoxin in people with the GSTM1 null genotype

To determine if the GSTM1 null genotype is a risk factor for increased inflammatory response to inhaled endotoxin

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

KELT-16b: A Highly Irradiated, Ultra-short Period Hot Jupiter Nearing Tidal Disruption

We announce the discovery of KELT-16b, a highly irradiated, ultra-short period hot Jupiter transiting the relatively bright (V = 11.7) star TYC 2688-1839-1/KELT-16. A global analysis of the system shows KELT-16 to be an F7V star with K and . The planet is a relatively high-mass inflated gas giant with density g cm-3, surface gravity , and K. The best-fitting linear ephemeris is and day. KELT-16b joins WASP-18b, -19b, -43b, -103b, and HATS-18b as the only giant transiting planets with P \u3c 1 day. Its ultra-short period and high irradiation make it a benchmark target for atmospheric studies by the Hubble Space Telescope, Spitzer, and eventually the James Webb Space Telescope. For example, as a hotter, higher-mass analog of WASP-43b, KELT-16b may feature an atmospheric temperature-pressure inversion and day-to-night temperature swing extreme enough for TiO to rain out at the terminator. KELT-16b could also join WASP-43b in extending tests of the observed mass-metallicity relation of the solar system gas giants to higher masses. KELT-16b currently orbits at a mere ∼1.7 Roche radii from its host star, and could be tidally disrupted in as little as a few ×105 years (for a stellar tidal quality factor of ). Finally, the likely existence of a widely separated bound stellar companion in the KELT-16 system makes it possible that Kozai-Lidov (KL) oscillations played a role in driving KELT-16b inward to its current precarious orbit

Reporting of ethical approval and informed consent in clinical research published in leading nursing journals : a retrospective observational study

Background: Ethical considerations play a prominent role in the protection of human subjects in clinical research. To date the disclosure of ethical protection in clinical research published in the international nursing journals has not been explored. Our research objective was to investigate the reporting of ethical approval and informed consent in clinical research published in leading international nursing journals. Methods: This is a retrospective observational study. All clinical research published in the five leading international nursing journals from the SCI Journal Citation Reports between 2015 and 2017 were retrieved to evaluate for evidence of ethical review. Results: A total of 2041 citations have been identified from the contents of all the five leading nursing journals that were published between 2015 and 2017. Out of these, 1284 clinical studies have been included and text relating to ethical review has been extracted. From these, most of prospective clinical studies (87.5%) discussed informed consent. Only half of those (52.9%) reported that written informed consent had been obtained; few (3.6%) reported oral consent, and few (6.8%) used other methods such as online consent or completion and return of data collection (such as surveys) to denote assent. Notably, 36.2% of those did not describe the method used to obtain informed consent and merely described that “consent was obtained from participants or participants agreed to join in the research”. Furthermore, whilst most of clinical studies (93.7%) mentioned ethical approval; 92.5% of those stated the name of ethical committee and interestingly, only 37.1% of those mentioned the ethical approval reference. The rates of reporting ethical approval were different between different study type, country, and whether financial support was received (all P<0.05). Conclusion: The reporting of ethics in leading international nursing journals demonstrates progress, but improvement of the transparency and the standard of ethical reporting in nursing clinical research is required

The Origin and Evolution of Mutations in Acute Myeloid Leukemia

SummaryMost mutations in cancer genomes are thought to be acquired after the initiating event, which may cause genomic instability and drive clonal evolution. However, for acute myeloid leukemia (AML), normal karyotypes are common, and genomic instability is unusual. To better understand clonal evolution in AML, we sequenced the genomes of M3-AML samples with a known initiating event (PML-RARA) versus the genomes of normal karyotype M1-AML samples and the exomes of hematopoietic stem/progenitor cells (HSPCs) from healthy people. Collectively, the data suggest that most of the mutations found in AML genomes are actually random events that occurred in HSPCs before they acquired the initiating mutation; the mutational history of that cell is “captured” as the clone expands. In many cases, only one or two additional, cooperating mutations are needed to generate the malignant founding clone. Cells from the founding clone can acquire additional cooperating mutations, yielding subclones that can contribute to disease progression and/or relapse

Withaferin a-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species

Withaferin A (WA), a promising anticancer constituent of Ayurvedic medicinal plant Withania somnifera, inhibits growth of MDA-MB-231 and MCF-7 human breast cancer cells in culture and MDA-MB-231 xenografts in vivo in association with apoptosis induction, but the mechanism of cell death is not fully understood. We now demonstrate, for the first time, that WA-induced apoptosis is mediated by reactive oxygen species (ROS) production due to inhibition of mitochondrial respiration. WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). The HMEC was also resistant to WA-induced apoptosis. WA-mediated ROS production as well as apoptotic histone-associated DNA fragment release into the cytosol was significantly attenuated by ectopic expression of Cu,Zn-superoxide dismutase in both MDA-MB-231 and MCF-7 cells. ROS production resulting from WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity. Mitochondrial DNA-deficient Rho-0 variants of MDA-MB-231 and MCF-7 cells were resistant to WA-induced ROS production, collapse of mitochondrial membrane potential, and apoptosis compared with respective wild-type cells. WA treatment resulted in activation of Bax and Bak in MDA-MB-231 and MCF-7 cells, and SV40 immortalized embryonic fibroblasts derived from Bax and Bak double knockout mouse were significantly more resistant to WA-induced apoptosis compared with fibroblasts derived from wild-type mouse. In conclusion, the present study provides novel insight into the molecular circuitry of WA-induced apoptosis involving ROS production and activation of Bax/Bak. © 2011 Hahm et al

A Systematic Analysis of Cell Cycle Regulators in Yeast Reveals That Most Factors Act Independently of Cell Size to Control Initiation of Division

Upstream events that trigger initiation of cell division, at a point called START in yeast, determine the overall rates of cell proliferation. The identity and complete sequence of those events remain unknown. Previous studies relied mainly on cell size changes to identify systematically genes required for the timely completion of START. Here, we evaluated panels of non-essential single gene deletion strains for altered DNA content by flow cytometry. This analysis revealed that most gene deletions that altered cell cycle progression did not change cell size. Our results highlight a strong requirement for ribosomal biogenesis and protein synthesis for initiation of cell division. We also identified numerous factors that have not been previously implicated in cell cycle control mechanisms. We found that CBS, which catalyzes the synthesis of cystathionine from serine and homocysteine, advances START in two ways: by promoting cell growth, which requires CBS's catalytic activity, and by a separate function, which does not require CBS's catalytic activity. CBS defects cause disease in humans, and in animals CBS has vital, non-catalytic, unknown roles. Hence, our results may be relevant for human biology. Taken together, these findings significantly expand the range of factors required for the timely initiation of cell division. The systematic identification of non-essential regulators of cell division we describe will be a valuable resource for analysis of cell cycle progression in yeast and other organisms

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice