Whither Evidentialist Reliabilism?

Evidentialism and Reliabilism are two of the main contemporary theories of epistemic justification. Some authors have thought that the theories are not incompatible with each other, and that a hybrid theory which incorporates elements of both should be taken into account. More recently, other authors have argued that the resulting theory is well- placed to deal with fine-grained doxastic attitudes (credences). In this paper I review the reasons for adopting this kind of hybrid theory, paying attention to the case of credences and the notion of probability involved in their treatment. I argue that the notion of probability in question can only be an epistemic (or evidential) kind of probability. I conclude that the resulting theory will be incompatible with Reliabilism in one important respect: it cannot deliver on the reductivist promise of Reliabilism. I also argue that attention to the justification of basic beliefs reveals limitations in the Evidentialist framework as well. The theory that results from the right combination of Evidentialism and Reliabilism, therefore, is neither Evidentialist nor Reliabilist

The sixth data release of the Radial Velocity Experiment (RAVE). I. Survey description, spectra and radial velocities

The Radial Velocity Experiment (RAVE) is a magnitude-limited (9<I<12) spectroscopic survey of Galactic stars randomly selected in the southern hemisphere. The RAVE medium-resolution spectra (R~7500) cover the Ca-triplet region (8410-8795A). The 6th and final data release (DR6 or FDR) is based on 518387 observations of 451783 unique stars. RAVE observations were taken between 12 April 2003 and 4 April 2013. Here we present the genesis, setup and data reduction of RAVE as well as wavelength-calibrated and flux-normalized spectra and error spectra for all observations in RAVE DR6. Furthermore, we present derived spectral classification and radial velocities for the RAVE targets, complemented by cross matches with Gaia DR2 and other relevant catalogs. A comparison between internal error estimates, variances derived from stars with more than one observing epoch and a comparison with radial velocities of Gaia DR2 reveals consistently that 68% of the objects have a velocity accuracy better than 1.4 km/s, while 95% of the objects have radial velocities better than 4.0 km/s. Stellar atmospheric parameters, abundances and distances are presented in subsequent publication. The data can be accessed via the RAVE Web (http://rave-survey.org) or the Vizier database.Comment: 32 pages, 11 figures, accepted for publication to A

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The economic burden of sixteen measles outbreaks on United States public health departments in 2011.

BackgroundDespite vaccination efforts and documentation of elimination of indigenous measles in 2000, the United States (US) experienced a marked increase in imported cases and outbreaks of measles in 2011. Due to the high infectiousness and potential severity of measles, these outbreaks require a vigorous response from public health institutions. The effort and resources required to respond to these outbreaks are likely to impose a significant economic burden on these institutions.ObjectiveTo estimate the economic burden of measles outbreaks (defined as ≥ 3 epidemiologically linked cases) on the local and state public health institutions in the US in 2011.MethodsFrom the perspective of local and state public health institutions, we estimated personnel time and resources allocated to measles outbreak response in local and state public health departments, and estimated the corresponding costs associated with these outbreaks in the US in 2011. We used cost and resource utilization data from previous studies on measles outbreaks in the US and, relying on outbreak size classification based on a case-day index, we estimated costs incurred by local and state public health institutions.ResultsIn 2011, the US experienced 16 outbreaks with 107 confirmed cases. The average duration of an outbreak was 22 days (range: 5-68). The total estimated number of identified contacts to measles cases ranged from 8936 to 17,450, requiring from 42,635 to 83,133 personnel hours. Overall, the total economic burden on local and state public health institutions that dealt with measles outbreaks during 2011 ranged from an estimated $2.7 million to$5.3 million US dollars.ConclusionInvestigating and responding to measles outbreaks imposes a significant economic burden on local and state health institutions. Such impact is compounded by the duration of the outbreak and the number of potentially susceptible contacts

The economic burden of sixteen measles outbreaks on United States public health departments in 2011.

BackgroundDespite vaccination efforts and documentation of elimination of indigenous measles in 2000, the United States (US) experienced a marked increase in imported cases and outbreaks of measles in 2011. Due to the high infectiousness and potential severity of measles, these outbreaks require a vigorous response from public health institutions. The effort and resources required to respond to these outbreaks are likely to impose a significant economic burden on these institutions.ObjectiveTo estimate the economic burden of measles outbreaks (defined as ≥ 3 epidemiologically linked cases) on the local and state public health institutions in the US in 2011.MethodsFrom the perspective of local and state public health institutions, we estimated personnel time and resources allocated to measles outbreak response in local and state public health departments, and estimated the corresponding costs associated with these outbreaks in the US in 2011. We used cost and resource utilization data from previous studies on measles outbreaks in the US and, relying on outbreak size classification based on a case-day index, we estimated costs incurred by local and state public health institutions.ResultsIn 2011, the US experienced 16 outbreaks with 107 confirmed cases. The average duration of an outbreak was 22 days (range: 5-68). The total estimated number of identified contacts to measles cases ranged from 8936 to 17,450, requiring from 42,635 to 83,133 personnel hours. Overall, the total economic burden on local and state public health institutions that dealt with measles outbreaks during 2011 ranged from an estimated $2.7 million to$5.3 million US dollars.ConclusionInvestigating and responding to measles outbreaks imposes a significant economic burden on local and state health institutions. Such impact is compounded by the duration of the outbreak and the number of potentially susceptible contacts

Human-derived osteoblast-like cells and pericyte-like cells induce distinct metastatic phenotypes in primary breast cancer cells

Approximately 70% of advanced breast cancer patients will develop bone metastases, which accounts for ∼90% of cancer-related mortality. Breast cancer circulating tumor cells (CTCs) establish metastatic tumors in the bone after a close interaction with local bone marrow cells including pericytes and osteoblasts, both related to resident mesenchymal stem/stromal cells (BM-MSCs) progenitors. recapitulation of the critical cellular players of the bone microenvironment and infiltrating CTCs could provide new insights into their cross-talk during the metastatic cascade, helping in the development of novel therapeutic strategies. Human BM-MSCs were isolated and fractionated according to CD146 presence. CD146+ cells were utilized as pericyte-like cells (PLCs) given the high expression of the marker in perivascular cells, while CD146- cells were induced into an osteogenic phenotype generating osteoblast-like cells (OLCs). Transwell migration assays were performed to establish whether primary breast cancer cells (3384T) were attracted to OLC. Furthermore, proliferation of 3384T breast cancer cells was assessed in the presence of PLC- and OLC-derived conditioned media. Additionally, conditioned media cultures as well as transwell co-cultures of each OLCs and PLCs were performed with 3384T breast cancer cells for gene expression interrogation assessing their induced transcriptional changes with an emphasis on metastatic potential. PLC as well as their conditioned media increased motility and invasion potential of 3384T breast cancer cells, while OLC induced a dormant phenotype, downregulating invasiveness markers related with migration and proliferation. Altogether, these results indicate that PLC distinctively drive 3384T cancer cells to an invasive and migratory phenotype, while OLC induce a quiescence state, thus recapitulating the different phases of the bone metastatic process. These data show that phenotypic responses from metastasizing cancer cells are influenced by neighboring cells at the bone metastatic niche during the establishment of secondary metastatic tumors

Measles outbreak in a highly vaccinated population, San Diego, 2008: role of the intentionally undervaccinated.

OBJECTIVE: In January 2008, an intentionally unvaccinated 7-year-old boy who was unknowingly infected with measles returned from Switzerland, resulting in the largest outbreak in San Diego, California, since 1991. We investigated the outbreak with the objective of understanding the effect of intentional undervaccination on measles transmission and its potential threat to measles elimination. METHODS: We mapped vaccination-refusal rates according to school and school district, analyzed measles-transmission patterns, used discussion groups and network surveys to examine beliefs of parents who decline vaccination, and evaluated containment costs. RESULTS: The importation resulted in 839 exposed persons, 11 additional cases (all in unvaccinated children), and the hospitalization of an infant too young to be vaccinated. Two-dose vaccination coverage of 95%, absence of vaccine failure, and a vigorous outbreak response halted spread beyond the third generation, at a net public-sector cost of $10 376 per case. Although 75$775 per child. Substantial rates of intentional undervaccination occurred in public charter and private schools, as well as public schools in upper-socioeconomic areas. Vaccine refusal clustered geographically and the overall rate seemed to be rising. In discussion groups and survey responses, the majority of parents who declined vaccination for their children were concerned with vaccine adverse events. CONCLUSIONS: Despite high community vaccination coverage, measles outbreaks can occur among clusters of intentionally undervaccinated children, at major cost to public health agencies, medical systems, and families. Rising rates of intentional undervaccination can undermine measles elimination