Mortality Differences Between Traditional Medicare and Medicare Advantage: A Risk-Adjusted Assessment Using Claims Data.

Medicare Advantage (MA) has grown rapidly since the Affordable Care Act; nearly one-third of Medicare beneficiaries now choose MA. An assessment of the comparative value of the 2 options is confounded by an apparent selection bias favoring MA, as reflected in mortality differences. Previous assessments have been hampered by lack of access to claims diagnosis data for the MA population. An indirect comparison of mortality as an outcome variable was conducted by modeling mortality on a traditional fee-for-service (FFS) Medicare data set, applying the model to an MA data set, and then evaluating the ratio of actual-to-predicted mortality in the MA data set. The mortality model adjusted for clinical conditions and demographic factors. Model development considered the effect of potentially greater coding intensity in the MA population. Further analysis calculated ratios for subpopulations. Predicted, risk-adjusted mortality was lower in the MA population than in FFS Medicare. However, the ratio of actual-to-predicted mortality (0.80) suggested that the individuals in the MA data set were less likely to die than would be predicted had those individuals been enrolled in FFS Medicare. Differences between actual and predicted mortality were particularly pronounced in low income (dual eligibility), nonwhite race, high morbidity, and Health Maintenance Organization (HMO) subgroups. After controlling for baseline clinical risk as represented by claims diagnosis data, mortality differences favoring MA over FFS Medicare persisted, particularly in vulnerable subgroups and HMO plans. These findings suggest that differences in morbidity do not fully explain differences in mortality between the 2 programs

Vesicular stomatitis virus chimeras expressing the oropouche virus glycoproteins elicit protective immune responses in mice

Oropouche virus (OROV) infection of humans is associated with a debilitating febrile illness that can progress to meningitis or encephalitis. First isolated from a forest worker in Trinidad and Tobago in 1955, the arbovirus OROV has since been detected throughout the Amazon basin with an estimated 500,000 human infections over 60 years. Like other members of the famil

The miniJPAS survey quasar selection IV: Classification and redshift estimation with SQUEzE

We present a list of quasar candidates including photometric redshift estimates from the miniJPAS Data Release constructed using SQUEzE. This work is based on machine-learning classification of photometric data of quasar candidates using SQUEzE. It has the advantage that its classification procedure can be explained to some extent, making it less of a `black box' when compared with other classifiers. Another key advantage is that using user-defined metrics means the user has more control over the classification. While SQUEzE was designed for spectroscopic data, here we adapt it for multi-band photometric data, i.e. we treat multiple narrow-band filters as very low-resolution spectra. We train our models using specialized mocks from Queiroz et al. (2022). We estimate our redshift precision using the normalized median absolute deviation, $\sigma_{\rm NMAD}$ applied to our test sample. Our test sample returns an $f_1$ score (effectively the purity and completeness) of 0.49 for quasars down to magnitude $r=24.3$ with $z\geq2.1$ and 0.24 for quasars with $z<2.1$. For high-z quasars, this goes up to 0.9 for $r<21.0$. We present two catalogues of quasar candidates including redshift estimates: 301 from point-like sources and 1049 when also including extended sources. We discuss the impact of including extended sources in our predictions (they are not included in the mocks), as well as the impact of changing the noise model of the mocks. We also give an explanation of SQUEzE reasoning. Our estimates for the redshift precision using the test sample indicate a $\sigma_{NMAD}=0.92\%$ for the entire sample, reduced to 0.81\% for $r<22.5$ and 0.74\% for $r<21.3$. Spectroscopic follow-up of the candidates is required in order to confirm the validity of our findings.Comment: Accepted in A&A 24 pages, 24 figures, 7 table

Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver.

Whole-sporozoite (WSp) malaria vaccines induce protective immune responses in animal malaria models and in humans. A recent clinical trial with a WSp vaccine comprising genetically attenuated parasites (GAP) which arrest growth early in the liver (PfSPZ-GA1), showed that GAPs can be safely administered to humans and immunogenicity is comparable to radiation-attenuated PfSPZ Vaccine. GAPs that arrest late in the liver stage (LA-GAP) have potential for increased potency as shown in rodent malaria models. Here we describe the generation of four putative P. falciparum LA-GAPs, generated by CRISPR/Cas9-mediated gene deletion. One out of four gene-deletion mutants produced sporozoites in sufficient numbers for further preclinical evaluation. This mutant, PfΔmei2, lacking the mei2-like RNA gene, showed late liver growth arrest in human liver-chimeric mice with human erythrocytes, absence of unwanted genetic alterations and sensitivity to antimalarial drugs. These features of PfΔmei2 make it a promising vaccine candidate, supporting further clinical evaluation. PfΔmei2 (GA2) has passed regulatory approval for safety and efficacy testing in humans based on the findings reported in this study

Can we live in a self-tuning universe?

The self-tuning brane scenario is an attempt to solve the cosmological constant problem in the context of extra dimensions. Rather than making the vacuum energy small, this approach proceeds by removing the gravitational effect of vacuum energy on the expansion of the universe. Such behavior is only possible through changing the Friedmann equation of conventional cosmology, and we discuss difficulties in obtaining cosmological evolution compatible with observation in this context. Specific models considered include a bulk scalar field coupling to the brane via a conformal transformation of the brane metric, and via a rescaling of the brane volume element

Preferential Localization of Human Origins of DNA Replication at the 5′-Ends of Expressed Genes and at Evolutionarily Conserved DNA Sequences

Replication of mammalian genomes requires the activation of thousands of origins which are both spatially and temporally regulated by as yet unknown mechanisms. At the most fundamental level, our knowledge about the distribution pattern of origins in each of the chromosomes, among different cell types, and whether the physiological state of the cells alters this distribution is at present very limited.We have used standard λ-exonuclease resistant nascent DNA preparations in the size range of 0.7–1.5 kb obtained from the breast cancer cell line MCF–7 hybridized to a custom tiling array containing 50–60 nt probes evenly distributed among genic and non-genic regions covering about 1% of the human genome. A similar DNA preparation was used for high-throughput DNA sequencing. Array experiments were also performed with DNA obtained from BT-474 and H520 cell lines. By determining the sites showing nascent DNA enrichment, we have localized several thousand origins of DNA replication. Our major findings are: (a) both array and DNA sequencing assay methods produced essentially the same origin distribution profile; (b) origin distribution is largely conserved (>70%) in all cell lines tested; (c) origins are enriched at the 5′ends of expressed genes and at evolutionarily conserved intergenic sequences; and (d) ChIP on chip experiments in MCF-7 showed an enrichment of H3K4Me3 and RNA Polymerase II chromatin binding sites at origins of DNA replication.Our results suggest that the program for origin activation is largely conserved among different cell types. Also, our work supports recent studies connecting transcription initiation with replication, and in addition suggests that evolutionarily conserved intergenic sequences have the potential to participate in origin selection. Overall, our observations suggest that replication origin selection is a stochastic process significantly dependent upon local accessibility to replication factors

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease