Abiotic aerobic oxidation pathways of stibnite revealed by oxygen and sulfur isotope systematics of sulfate.

The environmental threat posed by stibnite is an important geoenvironmental issue of current concern. To better understand stibnite oxidation pathways, aerobic abiotic batch experiments were conducted in aqueous solution with varying δ18OH2O value at initial neutral pH for different lengths of time (15-300 days). The sulfate oxygen and sulfur isotope compositions as well as concentrations of sulfur and antimony species were determined. The sulfur isotope fractionation factor (Δ34SSO4-stibnite) values decreased from 0.8‰ to -2.1‰ during the first 90 days, and increased to 2.6‰ at the 180 days, indicating the dominated intermediate sulfur species such as S2O32-, S0, and H2S (g) involved in Sb2S3 oxidation processes. The incorporation of O into sulfate derived from O2 (∼100%) indicated that the dissociated O2 was only directly adsorbed on the stibnite-S sites in the initial stage (0-90 days). The proportion of O incorporation into sulfate from water (27%-52%) increased in the late stage (90-300 days), which suggested the oxidation mechanism changed to hydroxyl attack on stibnite-S sites promoted by nearby adsorbed O2 on stibnite-Sb sites. The exchange of oxygen between sulfite and water may also contributed to the increase of water derived O into SO42-. The new insight of stibnite oxidation pathway contributes to the understanding of sulfide oxidation mechanism and helps to interpret field data.

The Effects of Physician Vertical Integration on Referral Patterns, Patient Welfare, and Market Dynamics.

The growth of physician vertical integration raises concerns about distorted referral patterns, higher spending, and market foreclosure. Using 100% Medicare data, we combine reduced-form analysis with a discrete choice model to estimate the effects of physician vertical integration on patients' provider choices and welfare for two common "downstream" surgical procedures. Physician-hospital integration results in an approximately 10% increase in referrals to higher-priced facilities instead of lower-priced providers. Our counterfactual analysis implies that if all primary care physicians become integrated, total Medicare spending will increase by $315 million.

Resin acid δ13C and δ18O as indicators of intra-seasonal physiological and environmental variability.

Understanding the dynamics of δ13C and δ18O in modern resin is crucial for interpreting (sub)fossilized resin records and resin production dynamics. We measured the δ13C and δ18O offsets between resin acids and their precursor molecules in the top-canopy twigs and breast-height stems of mature Pinus sylvestris trees. We also investigated the physiological and environmental signals imprinted in resin δ13C and δ18O at an intra-seasonal scale. Resin δ13C was c. 2‰ lower than sucrose δ13C, in both twigs and stems, likely due to the loss of 13C-enriched C-1 atoms of pyruvate during isoprene formation and kinetic isotope effects during diterpene synthesis. Resin δ18O was c. 20‰ higher than xylem water δ18O and c. 20‰ lower than δ18O of water-soluble carbohydrates, possibly caused by discrimination against 18O during O2-based diterpene oxidation and 35%-50% oxygen atom exchange with water. Resin δ13C and δ18O recorded a strong signal of soil water potential; however, their overall capacity to infer intraseasonal environmental changes was limited by their temporal, within-tree and among-tree variations. Future studies should validate the potential isotope fractionation mechanisms associated with resin synthesis and explore the use of resin δ13C and δ18O as a long-term proxy for physiological and environmental changes.

Economic burden of respiratory syncytial virus in adults in Germany - a health claims analysis between 2015 and 2018.

AIMS: Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections (LRTI) in infants and adults. While the clinical burden was recently estimated in adults in Germany, little is known about the economic burden. To fill this gap, this study aimed to assess hospital and outpatient healthcare resource utilization (HRU) and costs of RSV infections in adults in Germany. METHODS: In this retrospective, observational study on nationwide, representative, anonymized claims data (2015-2018), we identified patients ≥18 years with ICD-10-GM-codes specific to RSV ("RSV-specific"). To increase sensitivity, patients with unspecified LRTIs (including unspecified bronchitis, bronchiolitis, bronchopneumonia, and pneumonia) during RSV seasons were also included as cases potentially caused by RSV ("RSV-possible"). RSV-related HRU (hospital days, ICU and ventilation treatment, drug dispensation) and direct costs were estimated per episode. Excess costs per episode and for follow-up periods were compared to a matched control cohort. All outcomes were reported per healthcare sector and stratified by age and risk groups as well as disease severity (ICU admission/ventilation). RESULTS: Direct inpatient and outpatient mean episode costs were 3,473€ and 82€, respectively, with substantially higher costs for severe cases requiring intensive care and/or ventilation (10,801€). Direct costs for RSV-specific cases were higher than for RSV-possible cases (inpatients: 6,247€ vs. 3,450€; outpatients: 127€ vs. 82€). Moreover, costs were significantly higher for RSV patients than for controls and increased over time (inpatients: 5,140€ per episode vs 10,093€ per year; outpatients: 46€ per quarter vs 114€ per year). LIMITATIONS: While the number of RSV-specific cases was low, inclusion of seasonal LRTI cases likely increased the sensitivity to detect RSV cases and allowed a better estimation of the total costs of RSV. CONCLUSIONS: The economic burden of RSV-LRTI in adults in Germany is substantial, persists long-term, and is particularly high in the elderly. This highlights the need for cost-effective prevention measures.

An evaluation of the best practices and barriers for the Nagasaki acute myocardial infarction secondary prevention clinical pathway.

AIMS: The Nagasaki Acute Myocardial Infarction Secondary Prevention Clinical Pathway (NASP), a guideline-based regional clinical pathway, was developed to manage low-density lipoprotein cholesterol levels for patients with acute myocardial infarction (AMI) in the Nagasaki prefecture in Japan. This study aimed to summarize the perceived best practices and barriers for the dissemination and operation of the NASP. METHODS: This exploratory sequential mixed methods study was developed around the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Focus group interviews were conducted with 24 physicians with experience treating AMI in alignment with the NASP at foundation hospitals. The identified themes and insights were integrated into the development of the questionnaire. The web-based, self-administered questionnaire with a cross-sectional study design was given to 62 physicians in the Nagasaki prefecture. Mixed-method data integration of the results from both study phases was conducted through meta-inferences made from the qualitative and quantitative data. RESULTS: The best practices included the development of multi-disciplinary operation teams at medical facilities in preparation for the implementation of the NASP, the simplification of the document preparation process, and the establishment of an additional medical fees policy for the utilization of the NASP instead of patient referral documents. Practices tailored to the type of medical institute such as instructing patients on the NASP regimen during index hospitalization for acute-care hospitals, and the development of NASP instructions and manuals for primary care hospitals/outpatient clinics were also recommended. In addition, barriers to the implementation of the NASP such as missed eligible AMI patients for the NASP and the inconsistent implementation to eligible AMI patients were identified. CONCLUSIONS: This study identified the perceived best practices and barriers for the NASP. This knowledge should be considered when expanding the NASP to other institutions across Japan.

The Effect of E-Cigarette Indoor Vaping Restrictions on Infant Mortality.

We estimate the effect of county-level e-cigarette indoor vaping restrictions (IVRs) on infant mortality using United States birth certificates from 2010 to 2015. We estimate difference-in-differences models and find that e-cigarette indoor vaping restrictions increased infant mortality by 0.39 infants per 1,000 live births (12.9%). These effects were disproportionately higher for infants born to younger mothers and in locations with higher baseline levels of prenatal smoking. Infant mortality increased by 34.1% between 100 days to 1 year after IVRs. Infant mortality due to infections and neoplasms were particularly elevated.

Healthcare resource utilization and costs associated with hepatitis A in the United States: a retrospective database analysis.

AIM: To investigate hepatitis A-related healthcare resource use and costs in the US. METHODS: The Merative Marketscan Commercial Claims and Encounters database was retrospectively analyzed for hepatitis A-related inpatient, outpatient, and emergency department (ED) claims from January 1, 2012 to December 31, 2018. We calculated the hepatitis A incidence proportion per 100,000 enrollees, healthcare resource utilization, and costs (in 2020 USD). Results were stratified by age, gender, and select comorbidities. RESULTS: The overall hepatitis A incidence proportion was 6.1 per 100,000 enrollees. Among individuals with ≥1 hepatitis A-related claim, the majority (92.6%) had ≥1 outpatient visit related to hepatitis A; 9.1% were hospitalized and 4.2% had ≥1 ED visit. The mean (standard deviation [SD]) length of hospital stay was 5.2 (8.1) days; the mean (SD) number of outpatient and ED visits were 1.3 (1.3) and 1.1 (0.6), respectively. The incidence proportion per 100,000 was higher among adults than children (7.5 vs. 1.5), individuals with HIV than those without (126.7 vs. 5.9), and individuals with chronic liver disease than those without (143.6 vs. 3.8). The total mean (SD)/median (interquartile range, IQR) per-patient cost for hepatitis A-related care was $2,520 ($10,899)/$156 ($74-$529) and the mean cost of hospitalization was 18.7 times higher than that of outpatient care ($17,373 vs. $928). LIMITATIONS: The study data included only a commercially insured population and may not be representative of all individuals. CONCLUSIONS: In conclusion, hepatitis A is associated with a substantial economic burden among privately insured individuals in the US.

Hepatitis A is an acute liver infection caused by the hepatitis A virus. In the US, safe and effective vaccines for hepatitis A have been available since 1996. Vaccination recommendations include children (all children aged 12­23 months and previously unvaccinated children aged 2­18 years old) and adults at risk of infection or severe disease (e.g. international travelers, men who have sex with men, persons experiencing homelessness, persons with chronic liver disease or persons with HIV infection). Since 2016, the US has experienced person-to-person outbreaks of hepatitis A, primarily affecting unvaccinated individuals who use drugs or are experiencing homelessness. To better understand the impact of hepatitis A in the US, we assessed healthcare resource use and costs in 15,435 patients with hepatitis A from 2012 to 2018 in the Merative Marketscan Commercial Claims and Encounters database. We found that slightly more than 6 per 100,000 enrollees had hepatitis A from 2012 to 2018 and the number of people treated for hepatitis A per 100,000 was highest for people living with HIV or with chronic liver disease. The majority (92.6%) of people reported at least an outpatient visit, 9.1% were hospitalized, and 4.2% had an emergency department visit. The average cost for hepatitis A-related care was $2,520 per patient and was 18.7 times higher for hospitalized patients ($17,373) than for patients treated in outpatient care ($928). Our results are limited by the generalizability of the dataset, which is a convenience sample of private insurance claims, and are therefore unlikely to capture groups at high-risk for hepatitis A, such as individuals experiencing homelessness. In conclusion, hepatitis A leads to considerable healthcare costs for privately insured individuals in the US.

Drinking Water Contaminant Concentrations and Birth Outcomes.

Previous research in the US has found negative health effects of contamination when it triggers regulatory violations. An important question is whether levels of contamination that do not trigger a health-based violation impact health. We study the impact of drinking water contamination in community water systems on birth outcomes using drinking water sampling results data in Pennsylvania. We focus on the effects of water contamination for births not exposed to regulatory violations. Our most rigorous specification employs mother fixed effects and finds changing from the 10th to the 90th percentile of water contamination (among births not exposed to regulatory violations) increases low birth weight by 12% and preterm birth by 17%.

Isotope-Based Techniques to Investigate Factors Influencing Water Use Efficiency in Pinus koraiensis Leaves during Plant Growth.

Plant water use efficiency (WUE) is a comprehensive physiological indicator of plant growth and ability to adapt to drought. However, research on the mechanisms controlling WUE during plant growth and development remains weak. Here, we studied Pinus koraiensis as a typical evergreen conifer species in Northeast China. After collecting 80 tree samples with varying diameters at breast height (DBH), we measured δ13C and δ18O as an indicator of WUE, leaf morphology (volume, dry weight, and total epidermal area), ecological stoichiometry (carbon, nitrogen, and phosphorus content), and abiotic factors (light environment, soil pH, soil water content, and soil nutrient content). Correlational analysis of these variables revealed distinct differences between smaller/younger and larger/older plants: (1) In plants with DBH less than 52 cm, δ13C was positively related to DBH, and δ18O was negatively related to DBH. Plants with DBH greater than 52 cm showed no relationship between δ13C and DBH, and δ18O was positively related to DBH. (2) In plants with DBH less than 52 cm, there was a negative correlation between δ13C and δ18O and between δ13C and leaf phosphorus content (LP), but a positive correlation between δ13C and DBH, leaf mass per area (LMA), and leaf density (LD). The slopes of DBH-δ13C, δ18O-δ13C, leaf nitrogen content (LN)-δ13C, and LMA-δ13C correlations were greater in smaller plants than large plants. (3) Structural equation modelling showed that in smaller plants, DBH had a direct positive effect on δ13C content and a direct negative effect on δ18O, and there was a direct positive effect of light environment on δ18O. In larger plants, there was a direct negative effect of light environment on δ13C and a direct positive effect of DBH on light environment, as well as a negative effect of soil nitrogen content on leaf nitrogen. In smaller plants, DBH was the most important factor influencing δ13C, followed by δ18O and soil moisture, with light and soil pH showing minimal influence. In larger plants, light environment influenced δ13C the most, followed by soil nitrogen content and soil moisture content, with leaf nitrogen and DBH contributing little. The results suggest that water use efficiency strategies of P. koraiensis vary according to growth stage, and the effects of abiotic factors and functional traits vary at different growth stages.

The indirect costs of vaccine-preventable cancer mortality in the Middle East and North Africa (MENA).

BACKGROUND: Infections are responsible for ∼13% of cancer cases worldwide, with human papillomavirus (HPV) and hepatitis B (HBV) among the infections associated with cancer for which vaccines are available. The aim of this study was to estimate the indirect cost of premature mortality related to cancers caused by HPV and HBV in Middle East and North Africa (MENA) countries. METHODS: The number of deaths and years of life lost (YLL) in 2019 from four HPV-related cancers: cervical cancer, oral cavity cancer, laryngeal cancer, and oropharynx cancer, as well as HBV-related liver cancer were sourced from the Institute for Health Metrics Evaluation (IHME) Global Burden of Disease database. HPV-attributable fractions were applied to deaths and YLL. The human capital approach was used to measure productivity loss, through value of YLL (VYLL), and estimated using gross domestic product per capita (World Bank; in USD). Seventeen countries in the MENA region were included. Four countries in the region were not included due to data availability. RESULTS: In 2019, there were 11,645 potentially vaccine-preventable cancer-related deaths across the MENA region. This resulted in an indirect cost of $1,688,821,605, with 76.1% of this accrued in the Middle East ($1,284,923,633). The number of deaths in the Middle East (5,986) were similar to Northern Africa (5,659) but YLL were higher in Northern Africa (179,425) compared to the Middle East (169,207). The highest indirect cost per death occurred in Qatar ($1,378,991), compared to $14,962 in Sudan. Oral cavity cancer had the highest VYLL per death ($186,084). CONCLUSIONS: There is a high burden of premature mortality and indirect costs of potentially vaccine-preventable cancer-related deaths in the MENA region. Improved vaccination program implementation, increased vaccine coverage of HPV and HBV vaccinations, and continued prioritization of public health measures, such as screening, could effectively reduce premature mortality and associated costs.

Tracing phosphorus sources in the river-lake system using the oxygen isotope of phosphate.

The biogeochemical cycling of phosphorus (P) in river-lake systems presents significant challenges in tracing P sources, highlighting the importance of effective traceability approaches for formulating targeted management measures to mitigate lake eutrophication. In this study, we used the oxygen isotope of phosphate (δ18Op) as a tracer in the river-lake systems, establishing a tracing pathway from potential end-members, through inflow rivers, and eventually to the lake. Taking Dianshan Lake and its main inflow rivers as the study area, we measured δ18Op values of potential end-members, including domestic sewage treatment plant effluents, industrial effluents from phosphorus-related enterprises (printing and dyeing, electroplating, plastics, etc.), and farmland soils. Notably, the industrial effluent signatures ranged from 13.1 ‰ to 21.0 ‰ with an average of 16.8 ‰ ± 3.2 ‰, enriching the δ18Op threshold database. Using the MixSIAR model, it was found that phosphorus in the Jishuigang River primarily originated from agricultural non-point sources and domestic sewage in the dry season, while the Qiandengpu River, with a higher proportion of urban area, had a greater influence from domestic sewage and industrial effluents. Moreover, significant differences were observed between δ18Op values at the lake entrances of the inflow rivers (13.7 ‰ ± 1.0 ‰) and in acid-soluble phosphate of the lake sediments (9.9 ‰ ± 1.0 ‰). Isotopic tracing revealed that phosphorus in the lake originated from both external inputs (80.6 %) and internal release (19.4 %) in the dry season. Alongside pollutant flux calculations based on the hydrological conditions and water quality of the inflow rivers, our findings indicated that phosphorus in Dianshan Lake was mainly attributed to agricultural non-point sources, domestic sewage and sediment release in the dry season. This study provided novel insights into the identification of pollution sources in the river-lake systems, with broad implications for pollution control and environmental protection.

Burden and indirect cost of vaccine-preventable cancer mortality in Europe.

BACKGROUND: The economic and mortality burden of cancer is high worldwide. In Europe, cancer was responsible for 1.3 million deaths in 2020 and incurred an estimated cost of €50 billion from premature mortality. Human papillomavirus (HPV) and hepatitis B virus (HBV) are among the leading causes of infection-related cancers despite the availability of effective vaccines against these infections. This analysis estimated the mortality and productivity loss of HBV- and HPV-associated cancers that could be preventable through vaccination across European regions. MATERIALS AND METHODS: Institute for Health Metrics Evaluation (IHME) data were used to estimate mortality, years of life lost (YLL), and the value of years of life lost (VYLL) from five HBV- and HPV-related cancers (oral cavity, oropharynx, larynx, cervical, and liver cancers) across 40 European countries in 2019. Preventable deaths and YLL were estimated based on fractions attributable to infections. Data from the World Bank on GDP per capita were used to estimate the VYLL. The robustness of these results was explored with sensitivity and scenario analyses. RESULTS: In 2019, 31,906 cancer deaths resulted in an economic burden of €18,521,614,725 due to productivity losses across Europe. HPV-related cervical cancer had the highest mortality (19,473 deaths) and economic burden (€10,706,253,185). HBV-related liver cancer and HPV-related larynx, oral cavity, and oropharynx cancers also had a substantial burden, particularly in males. Eastern Europe had the highest YLL (308,179; 39%) and Western Europe was responsible for the greatest VYLL (€8,281,306,504; 45%), although the highest VYLL per death was in Northern Europe (€923,638). HPV-related oropharynx cancer had the highest VYLL per death (€656,607). CONCLUSION: HPV- and HBV-related cancer deaths are associated with substantial mortality and productivity losses in Europe, which could be reduced by the continued prioritization and implementation of prophylactic public health measures including systematic awareness, vaccination, and screening efforts.

Cost-effectiveness analysis of budesonide/formoterol SMART therapy versus salmeterol/fluticasone plus as-needed SABA among patients ≥12 years with moderate asthma from the Chinese societal perspective.

OBJECTIVES: To evaluate the cost-effectiveness of budesonide/formoterol reliever and maintenance therapy compared with salmeterol/fluticasone plus salbutamol as reliever therapy for asthma patients ≥12 years from the societal perspective in China. METHODS: A Markov model was developed with three health states (non-exacerbation, exacerbation, and death) with a lifetime horizon. The exacerbation rates were obtained from a prospective cohort study conducted in Chinese asthma patients. Healthcare resources utilization data were estimated based on current clinical asthma management guidelines. Asthma-related mortality, cost input and utility values were derived from public database and literature. Model robustness was assessed with one-way sensitivity and probabilistic sensitivity analyses. RESULTS: Compared with salmeterol/fluticasone plus salbutamol, budesonide/formoterol reliever and maintenance therapy led to fewer exacerbation events (13.6 vs. 15.9) and 0.0077 quality-adjusted life years (QALY) gain at an additional cost of ¥196.38 over lifetime. The base case incremental cost-effectiveness ratio (ICER) was ¥25,409.98 per QALY gained. The variables that had most impact on the model output included drug costs and medication adherence. At a willingness-to-pay threshold of ¥257,094/QALY (3 times of gross domestic product per capita in China in 2022), the probability of budesonide/formoterol maintenance and reliever therapy being cost-effective versus salmeterol/fluticasone plus as-needed salbutamol was 83.00%. CONCLUSION: From the societal perspective, budesonide/formoterol reliever and maintenance therapy is likely to be a cost-effective option compared with salmeterol/fluticasone plus as-needed salbutamol for Chinese asthma patients ≥12 years.

A novel pretreatment method for analysis the oxygen isotopic compositions of inorganic phosphorus pools in freshwater sediment.

Identifying the sources and cycling of phosphorus (P) is particularly important for formulating effective P management strategies in inland water. The oxygen isotopic compositions of phosphate (δ18OP) are recognized as a promising tool to solve this problem. However, the application of δ18OP in freshwater sediment is currently constrained by multiple difficulties. In this study, we presented a novel pretreatment method for δ18OP analysis of sediment inorganic P pools. Our results showed that the new method has advantages of simple operation, less time-consuming, and high P recovery rates. Specifically, we replaced the traditional Mg-induced co-precipitation (MAGIC) method by introducing Zr-Oxides gels with high selective adsorption function for phosphate. This made subsequent processing simpler and reduced the time consumption to ∼10 days, and the range of P recovery rates were from 88 % to 104 %. Furthermore, we emphasized the necessity of vacuum roasting following lyophilized Ag3PO4 to eliminate residual oxygen-containing impurities (e.g., NO3-, Ag2O, and organic matter). Additionally, evidences from microscopy and spectroscopy confirmed that this method ultimately yielded high-purity Ag3PO4 with the Ag:P molar ratios of 3.35:1. Importantly, combining direct synthesis Ag3PO4 between KH2PO4 and AgNO3 with the Ag3PO4 obtained by the method revealed no stark oxygen isotopic fractionation of phosphate during the pretreatment processes. The newly established δ18OP pretreatment methods here can also be extended to broader studies of the biogeochemical cycling of P in aquatic ecosystems, potentially advancing the understanding of the global P cycle.

Assessing the fiscal consequences of novel and existing treatments for triple negative breast cancer in Switzerland by applying a government perspective framework.

BACKGROUND: Triple Negative Breast Cancer (TNBC) is an aggressive subtype of breast cancer that can impact patients' employment and workforce participation. This study estimates how the employment effects of TNBC impact government tax revenue and public benefits expenditure in Switzerland, representing the fiscal burden of disease (FBoD), and likely consequences of introducing new treatment options. METHODS: A four-state cohort model was used to calculate fiscal effects for two treatments: Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab monotherapy (P + C→P) and neoadjuvant chemotherapy alone (C). Lifetime present values of tax revenue, social benefit payments, and healthcare costs were calculated for the average population and those undergoing treatment to assess the FBoD. RESULTS: An average TNBC patient treated with C and P + C→P is expected to generate CHF128,999 and CHF97,008 less tax than the average population, respectively, and require increased social benefit payments. Compared to C, 75% of the incremental healthcare costs of P + C→P are estimated to be offset through tax revenue gains. CONCLUSIONS: This analysis demonstrates that 75% of the additional costs of a new TNBC treatment option can be offset by gains in tax revenue. Fiscal analysis can be a useful tool to complement existing methods for evaluating new treatments.

Productivity costs due to human papillomavirus-related cancer mortality in the United Kingdom.

BACKGROUND: Human papillomavirus (HPV) causes several cancers such as cervical cancer and some head and neck (oral cavity, pharynx, and larynx), vulval, vaginal, anal, and penile cancers. As HPV vaccination is available, there is potential to prevent these cancers attributed to HPV and consequently the burden associated with them. The aim of this analysis was to estimate the number of HPV-related cancer deaths and the productivity costs due to years of life lost (YLL) in the United Kingdom (UK). METHOD: A model was developed utilizing UK 2019 mortality data sourced from country-specific databases for England, Scotland, Wales, and Northern Ireland for the following HPV-related cancers: head and neck (ICD-10 C00-14 and C32), cervix uteri (C53), vaginal (C51), vulval (C52), anal (C21), and penile (C60). The proportion of deaths and years of life lost (YLL) due to HPV were estimated using HPV attributable fractions for each anatomic location from the published literature. Labor force participation, retirement ages, and mean annual earnings, discounted at 3.5% annually, were applied to YLL to calculate the present value of future lost productivity (PVFLP). RESULTS: A total of 1817 deaths due to HPV-related cancers were reported in the UK in 2019 resulting in 31,804 YLL. Restricting to only YLL that occurred prior to retirement age yielded a total YPLL of 11,765 and a total PVFLP of £187,764,978. CONCLUSIONS: There is a high disease burden in the UK for HPV-related cancers, with a large economic impact on the wider economy due to productivity losses. Implementing and reinforcing public health measures to maintain high HPV vaccination coverage in both males and females may further facilitate reduction of this burden.

Two common pitfalls in the analysis of water-stable isotopologues with cryogenic vacuum extraction and cavity ring-down spectroscopy.

Water stable isotopologue analysis is widely used to disentangle ecohydrological processes. Yet, there are increasing reports of measurement uncertainties for established and emerging methods, such as cryogenic vacuum extraction (CVE) or cavity ring-down spectroscopy (CRDS). With this study, we investigate two pitfalls, that potentially contribute to uncertainties in water-stable isotopologue research. To investigate fractionation sources in CVE, we extracted pure water of known isotopic composition with cotton, glass wool or without cover and compared the isotopologue results with non-extracted reference samples. To characterise the dependency of δ2H and δ18O on the water mixing ratio in CRDS, which is of high importance for in-situ applications with large natural variations in mixing ratios, we chose samples with a large range of isotopic compositions and determined δ2H and δ18O for different water mixing ratios with two CRDS analysers (Picarro, Inc.). Cotton wool had a strong fractionation effect on δ2H values, which increased with more 2H-enriched samples. δ2H and δ18O values showed a strong dependency on the water mixing ratio analysed with CRDS with differences of up to 34.5‰ (δ2H) and 3.9‰ (δ18O) for the same sample at different mixing ratios. CVE and CRDS, now routinely applied in water stable isotopologue research, come with pitfalls, namely fractionation effects of cover materials and water mixing ratio dependencies of δ2H and δ18O, which can lead to erroneous isotopologue results and thus, invalid conclusions about (ecohydrological) processes. These practical issues identified here should be reported and addressed adequately in water-stable isotopologue research.

Quantitative reconstruction of a single super rainstorm using daily resolved δ18O of land snail shells.

A "once-in-a-millennium" super rainstorm battered Zhengzhou, central China, from 07/17/2021 to 07/22/2021 (named "7.20" Zhengzhou rainstorm). It killed 398 people and caused billions of dollars in damage. A pressing question is whether rainstorms of this intensity can be effectively documented by geological archives to understand better their historical variabilities beyond the range of meteorological data. Here, four land snail shells were collected from Zhengzhou, and weekly to daily resolved snail shell δ18O records from June to September of 2021 were obtained by gas-source mass spectrometry and secondary ion mass spectrometry. The daily resolved records show a dramatic negative shift between 06/18/2021 and 09/18/2021, which has been attributed to the "7.20" Zhengzhou rainstorm. Moreover, the measured amplitude of this shift is consistent with the theoretical value estimated from the flux balance model and instrumental data for the "7.20" Zhengzhou rainstorm. Our results suggest that the ultra-high resolution δ18O of land snail shells have the potential to reconstruct local synoptic scale rainstorms quantitatively, and thus fossil snail shells in sedimentary strata can be valuable material for investigating the historical variability of local rainstorms under different climate backgrounds.

Global burden and economic impact of vaccine-preventable cancer mortality.

BACKGROUND: Infections are responsible for approximately 13% of cancer cases worldwide and many of these infections can be prevented by vaccination. Human papillomavirus (HPV) and hepatitis B virus (HBV) are among the most common infections that cause cancer deaths globally, despite effective prophylactic vaccines being available. This analysis aims to estimate the global burden and economic impact of vaccine-preventable cancer mortality across World Health Organization (WHO) regions. METHODS: The number of deaths and years of life lost (YLL) due to five different vaccine-preventable cancer forms (oral cavity, liver, laryngeal, cervical, and oropharyngeal cancer) in each of the WHO regions (African, Eastern Mediterranean, European, the Americas, South-East Asia Pacific, and Western Pacific) were obtained from the Institute for Health Metrics Evaluation global burden of disease dataset. Vaccine-preventable mortality was estimated considering the fraction attributable to infection, to estimate the number of deaths and YLL potentially preventable through vaccination. Data from the World Bank on GDP per capita were used to estimate the value of YLL (VYLL). The robustness of these results was explored with sensitivity analysis. Given that several Epstein-Barr virus (EBV) vaccines are in development, but not yet available, the impact of a potential vaccine for EBV was evaluated in a scenario analysis. RESULTS: In 2019, there were 465,740 potentially vaccine-preventable cancer deaths and 14,171,397 YLL across all WHO regions. The estimated economic impact due to this mortality was $106.3 billion globally. The sensitivity analysis calculated a range of 403,025-582,773 deaths and a range in productivity cost of $78.8-129.0 billion. In the scenario analysis EBV-related cancer mortality increased the global burden by 159,723 deaths and $32.4 billion. CONCLUSION: Overall, the findings from this analysis illustrate the high economic impact of premature cancer mortality that could be potentially preventable by vaccination which may assist decision-makers in allocating limited resources among competing priorities. Improved implementation and increased vaccination coverage of HPV and HBV should be prioritized to decrease this burden.

The indirect costs of human papillomavirus-related cancer in Central and Eastern Europe: years of life lost and productivity costs.

BACKGROUND: Human papilloma virus (HPV) is a common cause of several types of cancer, including head and neck (oral cavity, pharynx, oropharynx, hypopharynx, nasopharynx, and larynx), cervical, vulval, vaginal, anal, and penile cancers. As HPV vaccines are available, there is potential to prevent HPV-related disease burden and related costs. METHOD: A model was developed for nine Central Eastern European (CEE) countries (Bulgaria, Croatia, Czechia, Hungary, Poland, Romania, Serbia, Slovakia, Slovenia). This model considered cancer patients who died from 11 HPV-related cancers (oropharynx, oral cavity, nasopharynx, hypopharynx, pharynx, anal, larynx, vulval, vaginal, cervical, and penile) in 2019. Due to data limitations, Bulgaria only included four cancer types. The model estimated the number of HPV-related deaths and years of life lost (YLL) based on published HPV-attributable fractions. YLL was adjusted with labor force participation, retirement age and then multiplied by mean annual earnings, discounted at a 3% annual rate to calculate the present value of future lost productivity (PVFLP). RESULTS: In 2019, there were 6,832 deaths attributable to HPV cancers resulting in 107,846 YLL in the nine CEE countries. PVFLP related to HPV cancers was estimated to be €46 M in Romania, €37 M in Poland, €19 M in Hungary, €15 M in Czechia, €12 M in Croatia, €10 M in Serbia, €9 M in Slovakia, €7 M in Bulgaria and €4 M in Slovenia. CONCLUSIONS: There is a high disease burden of HPV-related cancer-related deaths in the CEE region, with a large economic impact to society due to substantial productivity losses. It is critical to implement and reinforce public health measures with the aim to reduce the incidence of HPV-related diseases, and the subsequent premature cancer deaths. Improving HPV screening and increasing vaccination programs, in both male and female populations, could help reduce this burden.