Genomic analysis of spermatocytic tumors demonstrates recurrent molecular alterations in cases with malignant clinical behavior.

Spermatocytic tumor (ST) is a rare type of germ cell tumor that occurs exclusively in the postpubertal testis and typically affects elderly men. Most STs are benign, but rare cases exhibit aggressive clinical behavior, often in association with transition to sarcomatoid histology. Limited molecular analyses have been performed on STs; therefore, their genomic and epigenomic features remain incompletely described. Twenty-seven samples from 25 individual patients were analyzed with a combination of DNA sequencing panels, genomic methylation profiling, SNP array, isochromosome (12p) [i(12p)] FISH, and immunohistochemistry. The series included five metastasizing tumors (three with sarcomatoid transformation, one anaplastic, and one conventional) and 20 non-metastasizing tumors (14 anaplastic and six conventional). Anaplastic tumors comprised a monomorphic population of intermediate-sized neoplastic cells, as previously described. Multiomic analyses demonstrated that there were two genomic subgroups of STs: one with diploid genomes and hotspot RAS/RAF variants and the other with global ploidy shift and absence of recurrent mutations. Relative gain of chromosome 9 was a consistent finding in both subgroups. A comparison of metastasizing and non-metastasizing cases demonstrated that aggressive behavior was associated with the acquisition of pathogenic TP53 mutations and/or relative gains of 12p/i(12p). In cases with sarcomatoid transformation, TP53 mutations seem to underlie the transition to sarcomatoid histology. Genomic methylation analysis demonstrated that aggressive cases with gains of 12p cluster closer to pure seminomas than to STs without gains of 12p. In conclusion, STs include two genomic subgroups, characterized by global ploidy shifts without recurrent mutations and diploid genomes with RAS/RAF hotspot mutations, respectively. Biologic progression was associated with relative gains of 12p and TP53 mutations. The findings in STs with relative gains of 12p suggest that they may exhibit biologic characteristics akin to those seen in germ cell neoplasia in situ-related germ cell tumors rather than non-germ cell neoplasia in situ-derived STs. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Incidence of traffic light labelling on noncommunicable diseases: a roadmap for achieving sustainable development.

The production and diversity of the supply of food products has grown exponentially in recent decades, along with the increase in cardiovascular diseases associated with poor diet. Among the factors, one of the most important is the lack of information for the consumer when purchasing. The present work evaluates the impact of implementing the traffic light labelling of foods in reducing deaths due to Noncommunicable Diseases (NCD). Econometric techniques of two-way effects panel data from 21 Ecuadorian provinces taken from official sources for the analysis period 2010-2019. For Ecuador, a favourable impact was found in the reduction of the NCD mortality rate, especially in the last three years; in 2017, it was reduced by 0.129%, in 2018 by 0.305%, and in 2019 by 0.289%. An implication of economic policy is the advertising regulation of products that may affect health, strengthening surveillance and sanctioning companies that fail to comply with the regulation.

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.

The Economics of Tobacco Regulation: A Comprehensive Review.

Tobacco regulation has been a major component of health policy in the developed world since the UK Royal College of Physicians' and the US Surgeon General's reports in the 1960s. Such regulation, which has intensified in the past two decades, includes cigarette taxation, place-based smoking bans in areas ranging from bars and restaurants to workplaces, and regulations designed to make tobacco products less desirable. More recently, the availability of alternative products, most notably e-cigarettes, has increased dramatically, and these products are just starting to be regulated. Despite an extensive body of research on tobacco regulations, there remains substantial debate regarding their effectiveness, and ultimately, their impact on economic welfare. We provide the first comprehensive review of the state of research in the economics of tobacco regulation in two decades.

Fragment-based discovery of novel phenyltriazolyl derivatives as allosteric type-I1/2 ALK inhibitors with promising antitumor effects.

Based on the high-throughput screening hit BY-1, a series of phenyltriazolyl derivatives were developed. Satisfyingly, most compounds were detected moderate to excellent antitumor effects against Karpas299 and H2228 cells. Among them, 12k bearing 4­hydroxypiperidinyl group exhibited the optimal activities against tested cells with IC50 values of 51 nM and 175 nM, as well as promising inhibitory effects on ALKWT (3.7 nM) and ALKL1196M (6.8 nM). Unlike the conventional type-I ALK inhibitors, molecular models identified 12k as an allosteric type-I1/2 inhibitor by forming key interactions in both the ATP binding region and the hydrophobic back pocket of ALK. Intriguingly, 12k could dose-dependently induce apoptosis on H2228 cell and inhibit colony formation and tumor cell migration. Taken together, the rationalization of 12k may shed new light on the identification of novel allosteric type-I1/2 ALK inhibitors.

Design, synthesis and biological evaluation of 2-arylaminopyrimidine derivatives bearing 1,3,8-triazaspiro[4,5]decan-4-one or piperidine-3-carboxamide moiety as novel Type-I1/2 ALK inhibitors.

Aiming to develop novel Type-I1/2 inhibitors of ALK to overcome extensive resistance mutations, especially the L1196M mutation surrounding the ATP pocket, two series of 2-arylaminopyrimidine derivatives (11a-f and 22a-t) were designed based on scaffold hopping. The extensive structural elaboration discovered compound 22o which possessed excellent IC50 values of 0.06 and 0.23 µM against ALK-positive Karpas299 and H2228 cell lines, respectively. Meanwhile, 22o displayed encouraging inhibitory potency in the ALKWT (2.5 nM) and ALKL1196M (6.5 nM) enzymatic assays. Furthermore, the AO/EB and Hoechst 33258 assays illustrated 22o could induce cell apoptosis in a dose-dependent manner. Eventually, the molecular docking of 22o with ALK clearly presented the vital interactions within the active site, which was in accordance with Type-I1/2 inhibitor binding mode.

Does When You Die Depend on Where You Live? Evidence from Hurricane Katrina.

We follow Medicare cohorts to estimate Hurricane Katrina's long-run mortality effects on victims initially living in New Orleans. Including the initial shock, the hurricane improved eight-year survival by 2.07 percentage points. Migration to lower-mortality regions explains most of this survival increase. Those migrating to low-versus high-mortality regions look similar at baseline, but their subsequent mortality is 0.83-1.01 percentage points lower per percentage point reduction in local mortality, quantifying causal effects of place on mortality among this population. Migrants' mortality is also lower in destinations with healthier behaviors and higher incomes but is unrelated to local medical spending and quality.

Does Proximity to Fast Food Cause Childhood Obesity? Evidence from Public Housing.

We examine the causal link between proximity to fast food and the incidence of childhood obesity among low-income households in New York City. Using individual-level longitudinal data on students living in public housing linked to restaurant location data, we exploit the naturally occurring within-development variation in distance to fast food restaurants to estimate the impact of proximity on obesity. Since the assignment of households to specific buildings is based upon availability at the time of assignment to public housing, the distance between student residence and retail outlets-including fast food restaurants, wait-service restaurants, supermarkets, and corner stores-is plausibly random. Our credibly causal estimates suggest that childhood obesity increases with proximity to fast food, with larger effects for younger children who attend neighborhood schools.

Healthcare at the Beginning of Life and Child Survival: Evidence from a Cash Transfer Experiment in Nigeria.

Households in poor countries are encouraged (and sometimes coerced) to increase investments in formal health care services during pregnancy and childbirth. Is this good policy? The answer to a large extent depends on its effects on child welfare. We study the effects of a cash transfer program in Nigeria in which households were offered a payment of $14 conditioned on uptake of health services. We show that the transfer led to a large increase in uptake and a substantial increase in child survival driven by a decrease in in-utero child deaths. We present evidence suggesting that the key driver is prenatal health investments.

Cross-country experiences and lessons in nutraceutical health marketing in the United States, China, and India.

The distinction between food and drugs has blurred in recent years with a new - and novel - health paradigm representing a hybrid of "nutrition" and "pharmaceuticals." Nutraceuticals are formulated or processed to satisfy dietary requirements arising from physical or physiological conditions, and to treat certain diseases. This study examines the complex interface between the regulatory framework and nutraceutical marketing by drawing from the experiences of three leading global producers and markets: the United States, China, and India. It identifies opportunities in leveraging positive drivers of health marketing and the risks and challenges to market players, particularly in relation to product safety and effectiveness. Findings indicate that: 1) marketing incentives can stem from the regulatory framework; 2) regulation can yield adverse, albeit unintended, consequences on marketing activity; 3) containment or punishment of undesirable market behavior does not necessarily support the legitimate and desirable ends of health marketing; 4) uncommunicated differences between prescription nutraceutical products and nutraceutical supplements breed public confusion and misinformation, and encourage self-medication; and 5) health marketing may be effectively channeled to act as an agent of compliance and positive change. Practical implications and recommendations drawn from the comparative experiences of the three surveyed countries are addressed by way of conclusion.

CIGARETTE TAXES AND TEEN MARIJUANA USE.

The spillover effect of cigarette taxes on youth marijuana use has been the subject of intense public debate. Opponents of cigarette taxes warn that tax hikes will cause youths to substitute toward marijuana. On the other hand, public health experts often claim that because tobacco is a "gateway" drug, higher cigarette taxes will deter youth marijuana use. Using data from the National and State Youth Risk Behavior Surveys (YRBS) for the period 1991-2017, we explore the relationship between state excise taxes on cigarettes and teen marijuana use. In general, our results fail to support either of the above hypotheses. Rather, we find little evidence to suggest that teen marijuana use is sensitive to changes in the state cigarette tax. This null result holds for the sample period where cigarette taxes are observed to have the largest effect on teen cigarette use and across a number of demographic groups in the data. Finally, we find preliminary evidence that the recent adoption of state e-cigarette taxes is associated with a reduction in youth marijuana use.

The Mortality and Medical Costs of Air Pollution: Evidence from Changes in Wind Direction.

We estimate the causal effects of acute fine particulate matter exposure on mortality, health care use, and medical costs among the US elderly using Medicare data. We instrument for air pollution using changes in local wind direction and develop a new approach that uses machine learning to estimate the life-years lost due to pollution exposure. Finally, we characterize treatment effect heterogeneity using both life expectancy and generic machine learning inference. Both approaches find that mortality effects are concentrated in about 25 percent of the elderly population.

A Cost-Benefit Analysis of Hearing Aids, Including the Benefits of Reducing the Symptoms of Dementia.

We carried out a CBA of hearing aids (HAs) in which we estimated the direct utility benefits, and included the indirect utility benefits working through a reduction in dementia symptoms. The benefits methodology involved using QALYs as the outcome measure and then applying the price of a QALY to convert the outcome measure into monetary terms. The price of a QALY was derived from an age specific VSL estimate. The effects of HAs on utility were estimated from a fixed effects regression on a large national panel data set provided by NACC where we used a negative proxy for the QoL. We also used a fixed effects regression for the estimate of the indirect benefits involving HAs reducing dementia symptoms. We found that the total benefits, mainly coming from the direct benefits, were extremely large relative to the costs, with benefit-cost ratios over 30.

How Does Household Income Affect Child Personality Traits and Behaviors?

We examine the effects of a quasi-experimental unconditional household income transfer on child emotional and behavioral health and personality traits. Using longitudinal data, we find that there are large beneficial effects on children's emotional and behavioral health and personality traits during adolescence. We find evidence that these effects are most pronounced for children who start out with the lowest initial endowments. The income intervention also results in improvements in parental relationships which we interpret as a potential mechanism behind our findings.

The Effect of the Affordable Care Act Medicaid Expansions on Financial Wellbeing.

We examine the effect of the Medicaid expansions under the 2010 Patient Protection and Affordable Care Act (ACA) on consumer financial outcomes using data from a major credit reporting agency for a large, national sample of adults. We employ the synthetic control method to compare individuals living in states that expanded Medicaid to those that did not. We find that the Medicaid expansions significantly reduced the number of unpaid bills and the amount of debt sent to third-party collection agencies among those residing in zip codes with the highest share of low-income, uninsured individuals. Our estimates imply a reduction in collection balances of approximately $1,140 among those who gain Medicaid coverage due to the ACA. Our findings suggest that the ACA Medicaid expansions had important financial impacts beyond increasing health care use.

Marriage and Health: Selection, Protection, and Assortative Mating.

Using data from the Panel Study of Income Dynamics (PSID) and the Medical Expenditure Panel Survey (MEPS), we analyze the health gap between married and unmarried individuals of working-age. Controlling for observables, we find a gap that peaks at 10 percentage points at ages 55-59 years. The marriage health gap is similar for men and women. If we allow for unobserved heterogeneity in innate health (permanent and age-dependent), potentially correlated with timing and likelihood of marriage, we find that the effect of marriage on health disappears below age 40 years, while about 5 percentage points difference between married and unmarried individuals remains at older ages (55-59 years). This indicates that the observed gap is mainly driven by selection into marriage at younger ages, but there might be a protective effect of marriage at older ages. Exploring the mechanisms behind this result, we find that better innate health is associated with a higher probability of marriage and a lower probability of divorce, and there is strong assortative mating among couples by innate health. We also find that married individuals are more likely to have a healthier behavior compared to unmarried ones. Finally, we find that health insurance is critical for the beneficial effect of marriage.

Estimating the monetary benefits of medicare eligibility for reducing the symptoms of dementia.

We adopt a three-component method based on the idea of cost-saving for estimating the monetary benefits of Medicare eligibility for reducing dementia symptoms. The method involves Medicare eligibility lowering dementia symptoms, which reduces the need for dependent living, which in turn lowers caregiving costs. We use the Regression Discontinuity approach to establish a causal link between Medicare eligibility and dementia. The novel aspect of the study comes from using a quality-of-life proxy measure for the utility function to derive the marginal rate of substitution between dementia symptoms reduction and dependent living arrangements.

The value of a year's general education for reducing the symptoms of dementia.

We present a method for estimating the benefits of years of education for reducing dementia symptoms based on the cost savings that would accrue from continuing independent living rather than relying on formal or informal carers. Our method for estimating the benefits of education involves three steps: first taking a year of education and seeing how much this lowers dementia, second using this dementia reduction and estimating how much independent living is affected and third applying the change in caregiving costs associated with the independent living change. We apply our method for estimating education benefits to a National Alzheimer's Coordinating Center sample of 17,239 participants at 32 US Alzheimer's disease centres over the period September 2005 and May 2015.

A Dynamic Estimation of Obesity Using Nhanes Data: A Pseudo-Panel Approach.

In this analysis, we examine the effect of wages on obesity by constructing pseudo-panels to conduct a dynamic estimation of Grossman's human capital model. The results indicate that wages have an increasing effect on obesity status. After accounting for past health status, the protective effect of wages commonly disseminated in the literature reverses on obesity status. The results may also indicate possible asymmetric consumption behavior between foods/nutrients that improve diet quality versus those that degrade it. Individuals may be more keen to adhere to prophylactic diet strategies that abate consumption of unhealthy food/nutrients rather than measures which increase healthy nutrient consumption. Additionally, wages have an increasing effect on overall total calories consumed. These findings suggest that higher wage earners may focus their diet efforts on reducing consumption of specific nutrients but compensate by overconsuming other types of nutrients increasing overall calorie intake. Copyright © 2017 John Wiley & Sons, Ltd.

Household Financial Distress and Initial Endowments: Evidence from the 2008 Financial Crisis.

This paper studies in utero exposure to the 2008 financial crisis. Exploiting the sudden and unexpected collapse of the Icelandic economy, I find that first-trimester exposure to the crisis led to a sizable and significant reduction in birth weight, increased the probability of a low birth weight ( < 2500 g), and decreased the probability of a high birth weight ( > 4000 g). I also find evidence that the collapse reduced the sex ratio, indicating selection in utero due to maternal prenatal stress exposure. My results imply large welfare losses from financial distress that have hitherto been ignored - because children with worse health at birth can expect substantially lower lifetime earnings - and suggest that economic hardships may in general exacerbate income inequalities in the long run as low-income households are typically more exposed to financial distress. Copyright © 2016 John Wiley & Sons, Ltd.