Resource allocation in public sector programmes: does the value of a life differ between governmental departments?

BACKGROUND: The value of a life is regularly monetised by government departments for informing resource allocation. Guidance documents indicate how economic evaluation should be conducted, often specifying precise values for different impacts. However, we find different values of life and health are used in analyses by departments within the same government despite commonality in desired outcomes. This creates potential inconsistencies in considering trade-offs within a broader public sector spending budget. We provide evidence to better inform the political process and to raise important issues in assessing the value of public expenditure across different sectors. METHODS: Our document analysis identifies thresholds, explicitly or implicitly, as observed in government-related publications in the following public sectors: health, social care, transport, and environment. We include both demand-side and supply-side thresholds, understood as societies' and governments' willingness to pay for health gains. We look at key countries that introduced formal economic evaluation processes early on and have impacted other countries' policy development: Australia, Canada, Japan, New Zealand, the Netherlands, and the United Kingdom. We also present a framework to consider how governments allocate resources across different public services. RESULTS: Our analysis supports that identifying and describing the Value of a Life from disparate public sector activities in a manner that facilitates comparison is theoretically meaningful. The optimal allocation of resources across sectors depends on the relative position of benefits across different attributes, weighted by the social value that society puts on them. The value of a Quality-Adjusted Life Year is generally used as a demand-side threshold by Departments of transport and environment. It exceeds those used in health, often by a large enough proportion to be a multiple thereof. Decisions made across departments are generally based on an unspecified rationing rule. CONCLUSIONS: Comparing government expenditure across different public sector departments, in terms of the value of each department outcome, is not only possible but also desirable. It is essential for an optimal resource allocation to identify the relevant social attributes and to quantify the value of these attributes for each department.

The benefits and costs of U.S. employer COVID-19 vaccine mandates.

In 2021, the Biden Administration issued mandates requiring COVID-19 vaccinations for U.S. federal employees and contractors and for some healthcare and private sector workers. These mandates have been challenged in court; some have been halted or delayed. However, their costs and benefits have not been rigorously appraised. This study helps fill that gap. We estimate the direct costs and health-related benefits that would have accrued if these vaccination requirements had been implemented as intended. Compared with the January 2022 vaccination rates, we find that the mandates could have led to 15 million additional vaccinated individuals, increasing the overall proportion of the fully vaccinated U.S. population from 64% to 68%. The associated net benefits depend on the subsequent evolution of the pandemic-information unavailable ex ante to analysts or policymakers. In scenarios involving the emergence of a novel, more transmissible variant, against which vaccination and previous infection offer moderate protection, the estimated net benefits are potentially large. They reach almost $20,000 per additional vaccinated individual, with more than 20,000 total deaths averted over the 6-month period assessed. In scenarios involving a fading pandemic, existing vaccination-acquired or infection-acquired immunity provides sufficient protection, and the mandates' benefits are unlikely to exceed their costs. Thus, mandates may be most useful when the consequences of inaction are catastrophic. However, we do not compare the effects of mandates with alternative policies for increasing vaccination rates or for promoting other protective measures, which may receive stronger public support and be less likely to be overturned by litigation.

All Optical Switching through Anistropic Gain of CsPbBr3 Single Crystal Microplatelet.

Perovskite micro/nanostructures have recently emerged as a highly attractive gain material for nanolasers. To explore their applications and further improve performance, it is essential to understand the optical gain and the anisotropic properties. Herein, we obtained high quality CsPbBr3 microplatelets (MP) with anisotropic orthorhombic phase. Optical gain of CsPbBr3 single crystal MP was investigated via microscale variable stripe-length measurement. A polarization-dependent optical gain was observed, and the gain along [002] was larger than that of [1-10]. The behavior was attributed to the lowest energy transition dipole moment of [002] induced by the smaller deviation of Br-Pb-Br bond from the perfect lattice. Along the [002] direction, we obtained the optical gain value up to 5077 cm-1, which is the record value ever reported. Moreover, all optical switching of lasing is realized by periodical polarized excitation. Our results provide new perceptions in the design of novel functional anisotropic devices based on perovskite micro/nanostructures.

The Beneficial Effect of Probiotics Supplementation on Penicillin-Induced Focal Seizure in Rats.

The focal epilepsy is a chronic neurological brain disorder which affects millions of people in the world. There is emerging evidence that changes in the gut microbiota may have effects on epileptic seizures. In the present study, we examined the effect of probiotics on penicillin-induced focal seizure model in rats. Male Wistar Albino rats (n: 21) were randomly divided into three groups: control (no medication), penicillin and penicillin + probiotic. Probiotic VSL#3 (12.86 bn living bacteria/kg/day) was given by gavage for 30 days. The seizures were induced by intracortical injection of penicillin G (500 IU) into the cortex. An ECoG recordings were made for 180 min after penicillin G application. The spike frequency and the amplitude were used to assess the severity of seizures. Tumor necrosis factor (TNF-α), nitric oxide (NO) and interleukin (IL-6) levels in the brain were studied biochemically. Our results indicated that probiotic supplementation improved focal seizures through increasing the latency (p < 0.001) and decreasing the spike frequency (p < 0.01) compared to the penicillin group. Penicillin-induced seizure in rats significantly enhanced TNF-α (p < 0.01), NO (p < 0.01) and IL-6 (p < 0.05) compared to the control. Probiotic supplementation significantly decreased IL-6 (p < 0.05), TNF-α (p < 0.01) and NO (p < 0.001) compared to the penicillin group. When the body weights were compared before and after the experiment, there was no difference between the control and penicillin groups, but it was observed that the body weight decreased after probiotic supplementation in the penicillin + probiotic group. Probiotic supplementation may have anti-seizure effect by reducing proinflammatory cytokine and NO levels in epileptic rat brain.

A proof of concept pilot trial of probiotics in symptomatic oral lichen planus (CABRIO).

OBJECTIVE: To preliminary evaluate the clinical effects of probiotics in individuals with symptomatic oral lichen planus and the possible mechanisms of action. SUBJECTS AND METHODS: A group of 30 individuals with symptomatic oral lichen planus were recruited in a randomised double-blind parallel group controlled (1:1) proof-of-concept pilot trial of probiotic VSL#3 vs placebo. Efficacy outcomes included changes in pain numeric rating scale, oral disease severity score and the chronic oral mucosal disease questionnaire. Adverse effects, home diary and withdrawals were assessed as feasibility outcomes. Mechanistic outcomes included changes in salivary and serum levels of CXCL10 and IFN-γ and in oral microbial composition. RESULTS: The probiotic VSL#3 was safe and well tolerated. We observed no statistically significant change in pain, disease activity, quality of life, serum/salivary CXCL10 or oral microbial composition with respect to placebo. Salivary IFN-γ levels demonstrate a trend for a reduced level in the active group (p = 0.082) after 30 days of probiotic consumption. CONCLUSIONS: The present proof-of-concept study provides some weak not convincing indication of biological and clinical effects of probiotic VSL#3 in individuals with painful oral lichen planus. Further research in this field is needed, with the current study providing useful information to the design of future clinical trials.

How Much Is a Human Life Worth? A Systematic Review.

OBJECTIVES: To systematically review studies eliciting monetary value of a statistical life (VSL) estimates within, and across, different sectors and other contexts; compare the reported estimates; and critically review the elicitation methods used. METHODS: In June 2019, we searched the following databases to identify methodological and empirical studies: Cochrane Library, Compendex, Embase, Environment Complete, Informit, ProQuest, PubMed, Scopus, and Web of Science. We used the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for reporting and a modified Consolidated Health Economic Evaluation Reporting Standards checklist to assess the quality of included studies. RESULTS: We identified 1455 studies, of which we included 120 in the systematic review. A stated-preference approach was used in 76 articles, with 51%, 41%, and 8% being contingent valuation studies, discrete-choice experiments, or both, respectively. A revealed-preference approach was used in 43 articles, of which 74% were based on compensating-wage differentials. The human capital approach was used in only 1 article. We assessed most publications (87%) as being of high quality. Estimates for VSL varied substantially by context (sector, developed/developing country, socio-economic status, etc), with the median of midpoint purchasing power parity-adjusted estimates of 2019 US$5.7 million ($6.8 million, $8.7 million, and $5.3 million for health, labor market, and transportation safety sectors, respectively). CONCLUSIONS: The large variation observed in published VSLs depends mainly on the context rather than the method used. We found higher median values for labor markets and developed countries. It is important that health economists and policymakers use context-specific VSL estimates. Methodological innovation and standardization are needed to maximize comparability of VSL estimates within, and across, sectors and methods.

Do the Benefits of COVID-19 Policies Exceed the Costs? Exploring Uncertainties in the Age-VSL Relationship.

Numerous analyses of the benefits and costs of COVID-19 policies have been completed quickly as the crisis has unfolded. The results often largely depend on the approach used to value mortality risk reductions, typically expressed as the value per statistical life (VSL). Many analyses rely on a population-average VSL estimate; some adjust VSL for life expectancy at the age of death. We explore the implications of theory and empirical studies, which suggest that the relationship between age and VSL is uncertain. We compare the effects of three approaches: (1) an invariant population-average VSL; (2) a constant value per statistical life-year (VSLY); and (3) a VSL that follows an inverse-U pattern, peaking in middle age. We find that when applied to the U.S. age distribution of COVID-19 deaths, these approaches result in average VSL estimates of $10.63 million, $4.47 million, and $8.31 million. We explore the extent to which applying these estimates alters the conclusions of frequently cited analyses of social distancing, finding that they significantly affect the findings. However, these analyses do not address other characteristics of COVID-19 deaths that may increase or decrease the VSL estimates. Examples include the health status and income level of those affected, the size of the risk change, and the extent to which the risk is dreaded, uncertain, involuntarily incurred, and outside of one's control. The effects of these characteristics and their correlation with age are uncertain; it is unclear whether they amplify or diminish the effects of age on VSL.

The price of precision: trade-offs between usability and validity in the World Health Organization Health Economic Assessment Tool for walking and cycling.

OBJECTIVES: The widely used World Health Organization (WHO) Health Economic Assessment Tool (HEAT) for walking and cycling quantifies health impacts in terms of premature deaths avoided or caused as a result of changes in active transport. This article attempts to assess the effect of incorporating 'life-years' as an impact measure to increase the precision of the model and assess the effect on the tool's usability. STUDY DESIGN: This article is a methods paper, using simulation to estimate the effect of a methodological change to the HEAT 4.2 physical activity module. METHODS: We use the widely used WHO HEAT for walking and cycling as a case study. HEAT currently quantifies health impacts in terms of premature deaths avoided or caused as a result of changes in active transport. We assess the effect of incorporating "duration of life gained" as an impact measure to increase the precision of the model without substantially affecting usability or increasing data requirements. RESULTS: Compared with the existing tool (HEAT version 4.2), which values premature deaths avoided, estimates derived by valuing life-years gained are more sensitive to the age of the population affected by an intervention, with results for older and younger age groups being markedly different between the two methods. This is likely to improve the precision of the tool, especially where it is applied to interventions that affect age groups differentially. The life-years method requires additional background data (obtained and used in this analysis) and minimal additional user inputs; however, this may also make the tool harder to explain to users. CONCLUSIONS: Methodological improvements in the precision of widely used tools, such as the HEAT, may also inadvertently reduce their practical usability. It is therefore important to consider the overall impact on the tool's value to stakeholders and explore ways of mitigating potential reductions in usability.

Effects of deployment of electric vehicles on air quality in the urban area of Turin (Italy).

This study aims to evaluate and quantify the environmental, health, and economic benefits due to the penetration of electric vehicles in the fleet composition by replacing conventional vehicles in an urban area. This study has been performed for the city of Turin, where road transport represents one of the main primary emission sources. Air pollution data were evaluated by ADMS-Roads, the flow traffic data used for simulation come from a real-time monitoring. Instead, statistics on mortality and hospitalizations due to cardiovascular and respiratory diseases were collected from the regional health information system and the National Health Institute and implemented in the BenMap software to evaluate the health and economic impacts. In both cases, two scenarios to evaluate the annual benefits of reducing PM10, PM2.5 and NO2 were used: reduction to the levels gained by the assumptions of 2025 and 2030 Scenario and the PM10, PM2.5 and NO2 concentrations were considered for evaluating short-term and long-term effects. The analysis performed doesn't include background pollution levels, i.e. the concentrations percentage reductions are only related to the local contribution, therefore derived from the contribution only of traffic source. The results show that fleet electrification has a potential benefit for concentrations reduction in comparison to the base Scenario, especially related to NO2, less for PM10 and PM2.5. Regarding 2025 Scenario (4 % (passenger car) and 5 % (light-duty vehicles) electric vehicles), reductions of 52 % of NO2, 35 % of PM10 and 49 % of PM2.5 are observed. Meanwhile, as regards 2030 Scenario reductions of 87 % of NO2, 36 % of PM10 and 50 % of PM2.5 are reached. Also, in terms of social costs a decrease of 47 % for the 2025 Scenario and 66 % for the 2030 Scenario in comparison to the base Scenario is arise.

If the Objective is Herd Immunity, on Whom Should it be Built?

Assuming that there is no other solution than herd immunity in front of the current pandemic, on which groups of citizens should we build this herd immunity? Given the fact that young people face a mortality rate which is at least a thousand times smaller than people aged 70 years and more, there is a simple rational to build it on these younger generations. The transfer of some mortality risk from the elderly to younger people raises difficult ethical issues. However, none of the familiar moral or operational guidelines (equality of rights, VSL, QALY, ...) that have been used in the Western world over the last century weights the value of young lives 1000 times or more than the lives of the elders. This suggests that Society could offer covid protection to the elders by recommending them to remain confined as long as this herd immunity has not been attained by the younger generations. This would be a potent demonstration of intergenerational solidarity towards the most vulnerable people in our community. The welfare gain of this age-specific deconfinement strategy is huge, as it can reduce the global death toll by more than 80% as compared to a strategy of non-targeted herd immunity.

Mechanisms of Probiotic VSL#3 in a Rat Model of Visceral Hypersensitivity Involves the Mast Cell-PAR2-TRPV1 Pathway.

BACKGROUND: Mast cells (MCs), PAR2 and TRPV1, play a key role in the regulation of visceral pain. Several studies have found that probiotics regulate visceral sensitivity. AIMS: The purpose of the current study was to explore the role of MC-PAR2-TRPV1 in VH and the mechanism of VSL#3 in a rat model of VH. METHODS: A total of 64 rats were randomly divided into eight groups: Control VH, VH + ketotifen, VH + FSLLRY-NH2, VH + SB366791, VH + VSL#3, VH + VSL#3 + capsaicin, and VH + VSL#3 + SLIGRL-NH2. The rat model of VH was induced by acetic acid enema and the partial limb restraint method. VH was assessed by the abdominal withdrawal reflex score. MCs in colonic tissue were detected by the toluidine blue staining assay. The expression of PAR2 and TRPV1 in DRGs (L6-S1) was measured by immunohistochemistry and Western blotting. RESULTS: The established VH was abolished by treatment with ketotifen, a mast cell stabilizer FSLLRY-NH2, a PAR2 antagonist SB366791 a TRPV1 antagonist, and probiotic VSL#3 in rats. The administration of ketotifen or probiotic VSL#3 caused a decrease in mast cell number in the colon and decreased PAR2 and TRPV1 expression in DRGs. Intrathecal injection of FSLLRY-NH2 or SB366791 caused decreased expression of PAR2 and/or TRPV1 in DRGs in VH rats. SLIGRL-NH2, a PAR2 agonist, and capsaicin, a TRPV1 agonist, blocked the effects of probiotic VSL#3. CONCLUSIONS: The probiotic VSL#3 decreases VH in rat model of VH. The mechanism may be related with the mast cell-PAR2-TRPV1 signaling pathway.

Dread and Risk Elimination Premium for the Value of a Statistical Life.

The value of a statistical life (VSL) is a widely used measure for the value of mortality risk reduction. As VSL should reflect preferences and attitudes to risk, there are reasons to believe that it varies depending on the type of risk involved. It has been argued that cancer should be considered a "dread disease," which supports the use of a "cancer premium." The objective of this study is to investigate the existence of a cancer premium (for pancreatic cancer and multiple myeloma) in relation to road traffic accidents, sudden cardiac arrest, and amyotrophic lateral sclerosis (ALS). Data were collected from 500 individuals in the Swedish general population of 50-74-year olds using a web-based questionnaire. Preferences were elicited using the contingent valuation method, and a split-sample design was applied to test scale sensitivity. VSL differs significantly between contexts, being highest for ALS and lowest for road traffic accidents. A premium (92-113%) for cancer was found in relation to road traffic accidents. The premium was higher for cancer with a shorter time from diagnosis to death. A premium was also found for sudden cardiac arrest (73%) and ALS (118%) in relation to road traffic accidents. Eliminating risk was associated with a premium of around 20%. This study provides additional evidence that there exist a dread premium and risk elimination premium. These factors should be considered when searching for an appropriate value for economic evaluation and health technology assessment.

Probiotics Upregulate Trefoil Factors and Downregulate Pepsinogen in the Mouse Stomach.

Probiotics are used in the management of some gastrointestinal diseases. However, little is known about their effects on normal gastric epithelial biology. The aim of this study was to explore how the probiotic mixture VSL#3 affects gastric cell lineages in mice with a special focus on protective and aggressive factors. Weight-matching littermate male mice (n = 14) were divided into treated and control pairs. The treated mice received VSL#3 (5 mg/day/mouse) by gastric gavage for 10 days. Control mice received only the vehicle. Food consumption and bodyweight were monitored. All mice were injected intraperitoneally with bromodeoxyuridine (120 mg/Kg bodyweight) two hours before sacrificed to label S-phase cells. Stomach tissues were processed for lectin- and immunohistochemical examination. ImageJ software was used to quantify immunolabeled gastric epithelial cells. Real-time quantitative polymerase chain reaction was used to provide relative changes in expression of gastric cell lineages specific genes. Results revealed that treated mice acquired (i) increased production of mucus, trefoil factor (TFF) 1 and TFF2, (ii) decreased production of pepsinogen, and (iii) increased ghrelin-secreting cells. No significant changes were observed in bodyweight, food consumption, cell proliferation, or parietal cells. Therefore, VSL#3 administration amplifies specific cell types specialized in the protection of the gastric epithelium.

[Effect of VSL#3 and S.Boulardii on intestinal microbiota in mice with acute colitis].

Objective: To investigate the effects of probiotics(VSL#3, S. Boulardii) on intestinal flora of mice with DDS-induced acute colitis. Methods: C57BL/6J mice were administered with 2.5% dextran sulfate sodium for 5 consecutive days to develop the acute colitis model except for the blank control group. Meantime,Mice were treated with drinking water (DSS model group),VSL#3 (1.5×10(9) CFU),or S.Boulardii(5×10(7) CFU) by gavage for 7 days respectively,and mice were sacrificed 2 days after the model of colitis was established. The fecal specimens before gavage (day 0),in the middle of experiment (day 4),and the end of gavage (day 7) and the intestinal mucosa after sacrifice were collected to analyze the differences between these four groups by 16s rDNA sequencing method. Results: Compared with the DSS model group, VSL#3 group showed a decrease in disease activity index (DAI) and histological scores, and there was no significant change in the S.Boulardii group. Fecal microbiota:in the middle of experiment,the alpha diversity of DSS model group,VSL#3 group and S.Boulardii group were lower than that of the blank control group(P=0.0135,P=0.0018,P=0.0151). After the end of gavage,the diversity of the VSL#3 group was lower than that of the blank control group(P=0.025), and the difference between any other two groups was not statistically significant. Mucosa-adherent microbiota:biodiversity of DSS model group,S.Boulardii group were lower than the blank control group(P=0.031,P=0.0437),while biodiversity of VSL#3 group was higher than DSS model group and S. Boulardii group(P=0.0394, P=0.0426). Compared with the blank control group, the DSS model group showed an increase in Bacteroides and a decrease in Lactobacillus. Abundance in the genus Turicibacter and Odoribacter increased in intestinal microbiota of mice with acute colitis, while VSL#3 inhibited them. Conclusions: VSL#3 alleviates inflammation in DSS-induced colitis of mice.Both VSL#3 and S.Boulardii can affect intestinal microbiota. Compared with healthy mice,mice with colitis showed a reduced diversity of microbiota both in feces and in intestinal mucosa. VSL#3 increases biodiversity of mucosal microbiota in mice with acute colitis,while it does not increase biodiversity of fecal microbiota. Genera such as Turicibacter and Odoribacter increase in mice with acute colitis, and these genera can be inhibited by VSL#3.

From Osteoimmunology to Osteomicrobiology: How the Microbiota and the Immune System Regulate Bone.

Osteomicrobiology refers to the role of microbiota in bone health and the mechanisms by which the microbiota regulates post-natal skeletal development, bone aging, and pathologic bone loss. Here, we review recent reports linking gut microbiota to changes in bone phenotype. A pro-inflammatory cytokine milieu drives bone resorption in conditions such as sex steroid hormone deficiency. The response of the immune system to activation by the microbiome results in increased circulating osteoclastogenic cytokines in a T cell-dependent mechanism. Additionally, gut microbiota affect bone homeostasis through nutrient absorption, mediation of the IGF-1 pathway, and short chain fatty acid and metabolic products. Manipulation of microbiota through prebiotics or probiotics reduces inflammatory cytokine production, leading to changes in bone density. One mechanism of probiotic action is through upregulating tight junction proteins, increasing the strength of the gut epithelial layer, and leading to less antigen presentation and less activation of intestinal immune cells. Thus, prebiotics or probiotics may represent a future therapeutic avenue for ameliorating the risk of postmenopausal bone loss in humans.

Effect of administration of a probiotic preparation on gut microbiota and immune response in healthy women in India: an open-label, single-arm pilot study.

BACKGROUND: Probiotics have been shown to be useful for the treatment of many disease conditions. These beneficial effects are believed to be mediated by change in the composition of gut microbiota and modulation of the host immune responses. However, the available data on the effect of probiotics on these parameters are quite limited. METHODS: We studied the composition of fecal microbiota, using 16S rRNA sequencing, and host immune responses in peripheral blood (plasma cytokine levels, T cell subsets and in vitro cytokine production after stimulation with anti-CD3/CD28 antibody or lipopolysaccharide) in a group of 14 healthy women at three time-points - before and after administration of a probiotic preparation (a capsule of VSL#3, each containing 112.5 billion freeze-dried bacterial cells belonging to 8 species, twice a day for 4 weeks), and 4-weeks after discontinuation of the probiotic administration. RESULTS: There was no change in the abundance of various bacterial taxa as well as in the alpha diversity of gut microbiota following administration of the probiotic, or following its discontinuation. Probiotic administration led to a reduction in the relative frequency of circulating Th17 cells, and in vitro production of cytokines in whole-blood cultures in response to lipopolysaccharide stimulation. However, it had no effect on the relative frequencies of Th1, Th2 and T regulatory cells among circulating peripheral blood mononuclear cells, on plasma cytokine levels and on in vitro production of cytokines by T cells. CONCLUSIONS: We found that VSL#3 administration did not lead to any changes in gut flora, but led to a reduction in the frequency of Th17 cells and in the production of pro-inflammatory cytokine on lipopolysaccharide stimulation. These findings suggest that the beneficial anti-inflammatory effect of this preparation in patients with autoimmune and allergic disorders may be related to reduced production of monocyte-derived cytokines rather than to changes in the composition of gut microbiota. TRIAL REGISTRATION: NCT03330678 , Date of registration 30th October 2017. Retrospectively registered.

Valuing deaths or years of life lost? Economic benefits of avoided mortality from early heat warning systems.

The study aims to explore the main drivers influencing the economic appraisal of heat warning systems by integrating epidemiological modelling and benefit-cost analysis. To shed insights on heat wave mortality valuation, we consider three valuation schemes: (i) a traditional one, where the value of a statistical life (VSL) is applied to both displaced and premature mortality; (ii) an intermediate one, with VSL applied for premature mortality and value of a life year (VOLY) for displaced mortality; and (iii) a conservative one, where both premature and displaced mortality are quantified in terms of loss of life expectancy, and then valued using the VOLY approach. When applying these three schemes to Madrid (Spain), we obtain a benefit-cost ratio varying from 12 to 3700. We find that the choice of the valuation scheme has the largest influence, whereas other parameters such as attributable risk, displaced mortality ratio, or the comprehensiveness and effectiveness of the heat warning system are less influential. The results raise the question of which is the most appropriate approach to value mortality in the context of heat waves, given that the lower bound estimate for the benefit-cost ratio (option iii using VOLY) is up to two orders of magnitude lower than the value based on the traditional VSL approach (option i). The choice of the valuation methodology has significant implications for public health authorities at the local and regional scale, which becomes highly relevant for locations where the application of the VOLY approach could lead to benefit-cost ratios significantly lower than 1. We propose that specific metrics for premature and displaced VOLYs should be developed for the context of heat waves. Until such values are available, we suggest testing the economic viability of heat warning systems under the three proposed valuation schemes (i-iii) and using values for VOLY commonly applied in air pollution as the health end points are similar. Lastly, periodical reassessment of heat alert plans should be performed by public health authorities to monitor their long-term viability and cost-effectiveness.

VSL#3 probiotic differently influences IEC-6 intestinal epithelial cell status and function.

The data here reported introduce the wound-healing assay as a tool for testing probiotics aimed at protecting gastrointestinal mucosal surfaces and to verify the consistency of their manufacturing. At the scope, we compared the in vitro effects of two multi-strain high concentration formulations both commercialized under the same brand VSL#3 but sourced from different production sites (USA and Italy) on a non-transformed small-intestinal epithelial cell line, IEC-6. The effects on cellular morphology, viability, migration, and H2 O2 -induced damage, were assessed before and after the treatment with both VSL#3 formulations. While the USA-sourced product ("USA-made") VSL#3 did not affect monolayer morphology and cellular density, the addition of bacteria from the Italy-derived product ("Italy-made") VSL#3 caused clear morphological cell damage and strongly reduced cellularity. The treatment with "USA-made" lysate led to a higher rate of wounded monolayer healing, while the addition of "Italy-made" bacterial lysate did not influence the closure rate as compared to untreated cells. While lysates from "USA-made" VSL#3 clearly enhanced the formation of elongated and aligned stress fibers, "Italy-made" lysates had not similar effect. "USA-made" lysate was able to cause a total inhibition of H2 O2 -induced cytotoxic effect whereas "Italy-made" VSL#3 lysate was unable to protect IEC-6 cells from H2 O2 -induced damage. ROS generation was also differently influenced, thus supporting the hypotesis of a protective action of "USA-made" VSL#3 lysates, as well as the idea that "Italy-made" formulation was unable to prevent significantly the H2 O2 -induced oxidative stress.

Suppression of colitis-associated carcinogenesis through modulation of IL-6/STAT3 pathway by balsalazide and VSL#3.

BACKGROUND AND AIM: Recent studies suggest that the anti-inflammatory agent balsalazide (BSZ) and probiotic agent VSL#3 have potential therapeutic benefits for the treatment of patients with inflammatory bowel disease. However, their effectiveness in preventing colitis-associated carcinogenesis (CAC) remains uncertain. The aim of the present study was to determine the chemopreventive effects of BSZ and VSL#3 in the murine azoxymethane (AOM)/dextran sodium sulfate (DSS) model. METHODS: C57B/L6J mice were randomly divided into four groups: CAC group, BSZ group, VSL#3 group, and BSZ + VSL#3 group. After 2 weeks, the AOM/DSS model was induced by AOM injection followed by two cycles of 2% DSS. RESULTS: During first and second cycles of DSS, the number of F4/80-positive macrophages was significantly lower in the drug-treated groups compared with the CAC group (P < 0.05). At the endpoint, the total numbers of tumors in the drug-treated groups were significantly low compared with the CAC group (P < 0.05), and the drug-treated groups had significantly lower F4/80-positive macrophages in the tumor stroma (P < 0.01). The protein production of macrophage inflammatory protein 1 beta, monocyte chemoattractant protein-1, interleukin (IL)-6, and IL-10 in the colon tissues decreased in concordance with the plasma concentrations of the cytokines (P < 0.05). The drug-treated groups revealed lower expression of p-STAT3 compared with the CAC group. In addition, BCL2 decreased, and BAX increased markedly in the BSZ + VSL#3 group. CONCLUSIONS: These results revealed that BSZ and VSL#3 have chemopreventive effects against CAC through IL-6/STAT3 suppression. BSZ and VSL#3 could be suitable options for chemoprevention of colorectal cancer.

Can property values capture changes in environmental health risks? Evidence from a stated preference study in Italy and the United Kingdom.

Hedonic models are a common nonmarket valuation technique, but, in practice, results can be affected by omitted variables and whether homebuyers respond to the assumed environmental measure. We undertake an alternative stated preference approach that circumvents these issues. We examine how homeowners in the United Kingdom and Italy value mortality risk reductions by asking them to choose among hypothetical variants of their home that differ in terms of mortality risks from air pollution and price. We find that Italian homeowners hold a value of a statistical life (VSL) of €6.4 million, but U.K. homeowners hold a much lower VSL (€2.1 million). This may be because respondents in the United Kingdom do not perceive air pollution where they live to be as threatening, and actually live in cities with relatively low air pollution. Italian homeowners value a reduction in the risk of dying from cancer more than from other causes, but U.K. respondents do not hold such a premium. Lastly, respondents who face higher baseline risks, due to greater air pollution where they live, hold a higher VSL, particularly in the United Kingdom. In both countries, the VSL is twice as large among individuals who perceive air pollution where they live as high.