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The global invasive meningococcal disease (IMD) landscape changed considerably during the COVID-19 pandemic, as evidenced by decreased incidence rates due to COVID-19 mitigation measures, such as limited social contact, physical distancing, mask wearing, and hand washing. Vaccination rates were also lower during the pandemic relative to pre-pandemic levels. Although policymakers may have shifted their focus away from IMD vaccination programs to COVID-19 vaccination programs, strong arguments support implementation and prioritization of IMD vaccination programs; IMD cases have increased in some countries and IMD rates may even have exceeded pre-pandemic levels. Additional concerns include increased susceptibility due to vaccination coverage gaps, increased incidence of other respiratory pathogens, immunity debt from lockdown restrictions, and increased IMD epidemiologic variability. The full range of benefits of widely available and effective meningococcal vaccines needs to be considered, especially in health technology assessments, where the broad benefits of these vaccines are neither accurately quantified nor captured in implementation policy decisions. Importantly, implementation of meningococcal vaccination programs in the current IMD climate also appeals to broader healthcare principles, including preparedness rather than reactive approaches, generally accepted benefit–risk approaches to vaccination, historical precedent, and the World Health Organization's goal of defeating meningitis by 2030. Countries should therefore act swiftly to bolster existing meningococcal vaccination strategies to provide broad coverage across age groups and serogroups given the recent increases in IMD incidence.

Micrometer- to submicrometer-scale indium-rich domains are preserved within sphalerite included in hornfels-hosted pyrrhotite from the Dulong polymetallic skarn, Yunnan, China. The nano-mineralogy of the ZnS-bearing blebs was investigated using scanning transmission electron microscopy on thinned foils extracted in situ from pyrrhotite. Indium incorporation in sphalerite occurs via the coupled substitution 2Zn2+↔ Cu++ In3+; the results thus allow insights into phase relationships in the system ZnS-CuInS2in which solubility limits are debated with respect to a cubic to tetragonal phase transition. The highest concentrations of In are measured in basket-weave domains from the smallest ZnS blebs or from un-patterned areas in coarser, irregular ZnS inclusions in pyrrhotite. Indium-rich domains contain 17–49 mol% CuInS2, whereas In-poor sphalerite contains <5 mol% CuInS2. Atomic-scale metal ordering observed in In-(Cu)-rich ZnS domains was modeled as mixed sites in a cubic structure with P4̅3msymmetry and empirical formula [(Cu,In,Zn)3(Zn0.5Fe0.5)]4S4. This sphalerite modification is distinct from the cubic-tetragonal phase transition reported elsewhere for analogous, synthetic phases with abundant planar defects. The Zn1.5Fe0.5CuInS4nanophase described here potentially represents a Fe-bearing polymorph of Zn2CuInS4, considered as an end-member in the sakuraiite solid-solution series. At ≤50 mol% CuInS2in the ZnS-CuInS2system, incorporation of In via coupled In+Cu substitution is promoted within a cubic ZnS phase with lower symmetry than sphalerite rather than into the spatially coexisting chalcopyrite of tetragonal symmetry. Solid-state diffusion accounts for phase re-equilibration resulting in the basket-weave textures typical of In-(Cu)-rich domains in the smallest blebs, whereas fluid percolation assists grain coarsening in the irregular inclusions. The results show evidence for the existence of a more complex phase transition than previously recognized from experimental studies, and, intriguingly, also to a potential eutectic in the system ZnS-CuInS2. Pyrrhotite-bearing hornfels in skarns may concentrate In and other critical metals hosted in sphalerite and related sulfides due to the efficient scavenging from fluid by these minerals and the subsequent preservation of those included phases by sealing within the pyrrhotite matrix.

AbstractObjectiveThe aims of this study were to evaluate health outcomes and the economic burden of hospitalized COVID-19 patients in the United States.MethodsHospitalized patients with a primary or secondary discharge diagnosis code for COVID-19 (ICD-10 code U07.1) from 1 April to 31 October 2020 were identified in the Premier Healthcare COVID-19 Database. Patient demographics, hospitalization characteristics, and concomitant medical conditions were assessed. Hospital length of stay (LOS), in-hospital mortality, hospital charges, and hospital costs were evaluated overall and stratified by age groups, insurance types, and 4 COVID-19 disease progression states based on intensive care unit (ICU) and invasive mechanical ventilation (IMV) usage.ResultsOf the 173,942 hospitalized COVID-19 patients, the median age was 63 years, 51.0% were male, and 48.5% were covered by Medicare. The most prevalent concomitant medical conditions were cardiovascular disease (73.5%), hypertension (64.8%), diabetes (40.7%), obesity (27.0%), and chronic kidney disease (24.2%). Approximately one-fifth (21.9%) of the hospitalized COVID-19 patients were admitted to the ICU and 16.9% received IMV; most patients (73.6%) did not require ICU admission or IMV, and 12.4% required both. The median hospital LOS was 5 days, in-hospital mortality was 13.6%, median hospital charges were $43,986, and median hospital costs were $12,046. Hospital LOS and in-hospital mortality increased with ICU and/or IMV usage and age; hospital charges and costs increased with ICU and/or IMV usage. Patients with both ICU and IMV usage had the longest median hospital LOS (15 days), highest in-hospital mortality (53.8%), and highest hospital charges ($198,394) and hospital costs ($54,402).LimitationsThis retrospective administrative database analysis relied on coding accuracy and a subset of admissions with validated/reconciled hospital costs.ConclusionsThis study summarizes the severe health outcomes and substantial hospital costs of hospitalized COVID-19 patients in the US. The findings support the urgent need for rapid implementation of effective interventions, including safe and efficacious vaccines.

To evaluate the expected impact of the Algeria national immunization program (NIP) and potential impact for a Tunisia NIP, this study assessed the public health and economic value of vaccination, through a cost-effectiveness analysis, for a PCV13 or PCV10 NIP, compared with no vaccination. A decision-analytic model was programmed in Microsoft Excel™ and adapted to evaluate the clinical and economic outcomes of PCV vaccination. Assuming a steady state, the model estimated invasive pneumococcal disease (IPD; bacteremia and meningitis), all-cause pneumonia (inpatient and outpatient), and all-cause otitis media cases as well as the associated costs from a payer perspective. The base case scenario assumed direct effects for both PCVs and indirect effects (against IPD) for PCV13 only. In Algeria, compared with no vaccination program, PCV13 would save 2177 lives and avoid nearly 349,000 cases of IPD, pneumonia, and AOM at a highly cost-effective value of $308 per QALY. In Tunisia, PCV13 would save 308 lives and avoid 1305 cases of IPD, 4833 cases of pneumonia, and 54,957 cases of AOM at a highly cost-effective value of $848 per QALY. PCV10 prevented 1224 deaths and 270,483 cases of disease in Algeria and prevented 172 deaths and 56,610 cases in Tunisia. PCV10 was cost-effective in both Algeria at $731/QALY and in Tunisia at $1366/QALY. The ongoing NIP in Algeria is projected to reduce the impact and economic toll of pneumococcal disease in Algeria. If an NIP were also introduced in Tunisia, a commensurate impact would be expected. PCV NIPs are highly cost-effective, highly impactful public health interventions. Pfizer.

•PCC and LG-134 had direct cytotoxicity in murine melanoma cell lines (IC50 values ranged from 0.19–1.8 µM).•PCC treatment induced apoptosis of tumor cells both in vitroand in vivo.•PCC treatment induced G0-G1 cell cycle arrest of melanoma cells.•PCC treatment caused complete regression of established melanoma tumors in all mice.•17β-hydroxywithanolides have the potential to improve melanoma therapeutic outcome.

Zusammenfassung: Die Auswirkungen von Humankapital und F&E auf die internationalen Handelsströme: Evidenz aus einem Modell mit mehreren Inputs und Outputs für die USA. - In diesem Aufsatz wird ein Modell mit mehreren Inputs und Outputs entwickelt, um den Au▾enhandelssektor der amerikanischen Volkswirtschaft zu untersuchen. Da es sowohl Humankapital als auch F&E auf der Produktionsseite einer offenen Volkswirtschaft modelliert, hat dieses Modell mehrere Vorteile gegenüber früheren Studien, die wie üblich einen Produktionsproze▾ mit nur zwei Inputs verwenden. Die empirischen Ergebnisse deuten darauf hin, da▾ Exportgüter humankapital- und Investitionsgüter forschungsintensiv sind. Au▾erdem ergibt sich, da▾ Erhöhungen des Humankapitals und der F&E-ausgaben zu einem Anstieg der Importe beitragen. Diese Ergebnisse haben weitreichende Implikationen für die Gestaltung sowohl der heimischen Industriepolitik als auch der internationalen Handelspolitik.