Negative energy balance hinders prosocial helping behavior.

The internal state of an animal, including homeostatic requirements, modulates its behavior. Negative energy balance stimulates hunger, thus promoting a range of actions aimed at obtaining food. While these survival actions are well established, the influence of the energy status on prosocial behavior remains unexplored. We developed a paradigm to assess helping behavior in which a free mouse was faced with a conspecific trapped in a restrainer. We measured the willingness of the free mouse to liberate the confined mouse under diverse metabolic conditions. Around 42% of ad libitum-fed mice exhibited a helping behavior, as evidenced by the reduction in the latencies to release the trapped cagemate. This behavior was independent of subsequent social contact reward and was associated with changes in corticosterone indicative of emotional contagion. This decision-making process was coupled with reduced blood glucose excursions and higher Adenosine triphosphate (ATP):Adenosine diphosphate (ADP) ratios in the forebrain of helper mice, suggesting that it was a highly energy-demanding process. Interestingly, chronic (food restriction and type 2 diabetes) and acute (chemogenetic activation of hunger-promoting AgRP neurons) situations mimicking organismal negative energy balance and enhanced appetite attenuated helping behavior toward a distressed conspecific. To investigate similar effects in humans, we estimated the influence of glycated hemoglobin (a surrogate of long-term glycemic control) on prosocial behavior (namely charity donation) using the Understanding Society dataset. Our results evidenced that organismal energy status markedly influences helping behavior and that hypothalamic AgRP neurons are at the interface of metabolism and prosocial behavior.

A nanobody activating metabotropic glutamate receptor 4 discriminates between homo- and heterodimers.

There is growing interest in developing biologics due to their high target selectivity. The G protein-coupled homo- and heterodimeric metabotropic glutamate (mGlu) receptors regulate many synapses and are promising targets for the treatment of numerous brain diseases. Although subtype-selective allosteric small molecules have been reported, their effects on the recently discovered heterodimeric receptors are often not known. Here, we describe a nanobody that specifically and fully activates homodimeric human mGlu4 receptors. Molecular modeling and mutagenesis studies revealed that the nanobody acts by stabilizing the closed active state of the glutamate binding domain by interacting with both lobes. In contrast, this nanobody does not activate the heterodimeric mGlu2-4 but acts as a pure positive allosteric modulator. These data further reveal how an antibody can fully activate a class C receptor and bring further evidence that nanobodies represent an alternative way to specifically control mGlu receptor subtypes.

The social value of a SARS-CoV-2 vaccine: Willingness to pay estimates from four western countries.

SARS-CoV-2 vaccines give rise to positive externalities on population health, society and the economy in addition to protecting the health of vaccinated individuals. Hence, the social value of such a vaccine exceeds its market value. This paper estimates the willingness to pay (WTP) for a hypothetical SARS-CoV-2 vaccine (or shadow prices), in four countries, namely the United States (US), the United Kingdom, Spain and Italy during the first wave of the pandemic when COVID-19 vaccines were in development but not yet approved. WTP estimates are elicited using a payment card method to avoid "yea saying" biases, and we study the effect of protest responses, sample selection bias, as well as the influence of trust in government and risk exposure when estimating the WTP. Our estimates suggest evidence of an average value of a hypothetical vaccine of 100-200 US dollars once adjusted for purchasing power parity. Estimates are robust to a number of checks.

Preterm birth and educational disadvantage: Heterogeneous effects.

Although preterm birth is the leading cause of perinatal morbidity and mortality in advanced economies, evidence about the consequences of prematurity in later life is limited. Using Swedish registers for cohorts born 1982-94 (N  =  1,087,750), we examine the effects of preterm birth on school grades at age 16 using sibling fixed effects models. We further examine how school grades are affected by degree of prematurity and the compensating roles of family socio-economic resources and characteristics of school districts. Our results show that the negative effects of preterm birth are observed mostly among children born extremely preterm (<28 weeks); children born moderately preterm (32-<37 weeks) suffer no ill effects. We do not find any evidence for a moderating effect of parental socio-economic resources. Children born extremely preterm and in the top decile of school districts achieve as good grades as children born at full term in an average school district.Supplementary material for this article is available at: http://dx.doi.org/10.1080/00324728.2022.2080247.

Light-Induced Activation of a Specific Type-5 Metabotropic Glutamate Receptor Antagonist in the Ventrobasal Thalamus Causes Analgesia in a Mouse Model of Breakthrough Cancer Pain.

Breakthrough cancer pain (BTcP) refers to a sudden and transient exacerbation of pain, which develops in patients treated with opioid analgesics. Fast-onset analgesia is required for the treatment of BTcP. Light-activated drugs offer a novel potential strategy for the rapid control of pain without the typical adverse effects of systemic analgesic drugs. mGlu5 metabotropic glutamate receptor antagonists display potent analgesic activity, and light-induced activation of one of these compounds (JF-NP-26) in the thalamus was found to induce analgesia in models of inflammatory and neuropathic pain. We used an established mouse model of BTcP based on the injection of cancer cells into the femur, followed, 16 days later, by systemic administration of morphine. BTcP was induced by injection of endothelin-1 (ET-1) into the tumor, 20 min after morphine administration. Mice were implanted with optic fibers delivering light in the visible spectrum (405 nm) in the thalamus or prelimbic cortex to locally activate systemically injected JF-NP-26. Light delivery in the thalamus caused rapid and substantial analgesia, and this effect was specific because light delivery in the prelimbic cortex did not relieve BTcP. This finding lays the groundwork for the use of optopharmacology in the treatment of BTcP.

Too Healthy to Fall Sick? Longevity Expectations and Protective Health Behaviours during the First Wave of COVID-19.

Longevity expectations (LE) are subjective assessments of future health status that can influence a number of individual health protective decisions. This is especially true during a pandemic such as COVID-19, as the risk of ill health depends more than ever on such protective decisions. This paper examines the causal effect of LE on some protective health behaviors and a number of decisions regarding forgoing health care using individual differences in LE. We use data from the Survey of Health Ageing and Retirement in Europe, and we draw on an instrumental variable strategy exploiting individual level information on parental age at death. Consistent with the too healthy to be sick hypothesis, we find that individuals, exhibiting higher expected longevity, are more likely to engage in protective behaviours, and are less likely to forgo medical treatment. We estimate that a one standard deviation increase in LE increases the probability to comply always with social distancing by 0.6%, to meet people less often by 0.4% and decreases the probability to forgo any medical treatment by 0.6%. Our estimates vary depending on supply side restrictions influencing the availability of health care, as well as individual characteristics such as their gender and the presence of pre-existing health conditions.

Measuring pure health inequality and mobility during a health insurance expansion: Evidence from Mexico.

The association of insurance expansions and the distribution of health status is still a matter we know little about. This paper draws upon new measures of pure (univariate) inequality and mobility which accommodate categorical data to understand how an expansion of public insurance may be related to both health inequality and mobility. These measures require a definition of individual's status that is either "downward looking" or "upward looking". Using data from the Mexican Family Life Survey, a nationally representative longitudinal survey, we find that the distribution of health has worsened in Mexico between 2002 and 2009, although the change is only consistent for an upward looking definition status. Together with the lack of mobility in self-reported health, we can thus conclude that Mexico has become more rigid over time despite the rapid public health expansion that took place over the 2000s decade. While further research on the potential drivers of health inequalities is needed, our findings suggest that insurance coverage alone may be not enough to reduce health disparities and promote health mobility. Indeed, health inequality and mobility likely depend on a myriad of factors beyond health care.

Innovation, aging, and health care: Unraveling "silver" from "red" herrings?

This perspective paper argues that a sustainable health system design encompasses identifying opportunities and incentives for innovation, alongside an analysis of its effect on expenditure. Although aging alone is not a powerful cost driver, the combined effect of costly innovation, personalized care, and the rise of chronic conditions is. We identify an increasing role of prevention, the reduction of the prevalence of chronic conditions, re-organisation of incentives in health care markerts, including a closer scrutiny of the appropriateness of new treatments.

'More than one red herring'? Heterogeneous effects of ageing on health care utilisation.

We study the effect of ageing, defined as an extra year of life, on health care utilisation. We disentangle the direct effect of ageing, from other alternative explanations such as the presence of comorbidities and endogenous time to death (TTD) that are argued to absorb the effect of ageing (so-called 'red herring' hypothesis). We exploit individual level end of life data from several European countries that record the use of medicine, outpatient and inpatient care and long-term care. Consistently with the 'red herring hypothesis', we find that corrected TTD estimates are significantly different from uncorrected ones, and their effect size exceeds that of an extra year of life, which in turn is moderated by individual comorbidities. Corrected estimates suggest an overall attenuated effect of ageing, which does not influence outpatient care utilisation. These results suggest the presence of 'more than one red herring' depending on the type of health care examined.

Careful in the Crisis? Determinants of Older People's Informal Care Receipt in Crisis-Struck European Countries.

Macroeconomic downturns can have an important impact on the receipt of informal and formal long-term care, because recessions increase the number of unemployed and affect net wealth. This paper investigates how the market for informal care changed during and after the Great Recession in Europe, with particular focus on the determinants of care receipt. We use data from the Survey of Health, Ageing and Retirement in Europe, which includes a rich set of variables covering waves before and after the Great Recession. We find evidence of an increase in the availability of informal care after the economic downturn when controlling for year and country fixed effects. This trend is mainly driven by changes in care provision of individuals not cohabiting with the care recipient. We also find evidence of several determinants of informal care receipt changing during the crisis - such as physical needs, personal wealth, and household structures. Copyright © 2016 John Wiley & Sons, Ltd.

Crowding out of long-term care insurance: evidence from European expectations data.

Long-term care (LTC) is the largest insurable risk that old-age individuals face in most western societies. However, the demand for LTC insurance is still ostensibly small in comparison with the financial risk. One explanation that has received limited support is that expectations of either 'public sector funding' and 'family support' crowd out individual incentives to seek insurance. This paper aims to investigate further the aforementioned motivational crowding-out hypothesis by developing a theoretical model and by drawing on an innovative empirical analysis of representative European survey data containing records on individual expectations of LTC funding sources (including private insurance, social insurance, and the family). The theoretical model predicts that, when informal care is treated as exogenously determined, expectations of both state support and informal care can potentially crowd out LTC insurance expectations, while this is not necessarily the case when informal care is endogenous to insurance, as happens when intra-family moral hazard is integrated in the insurance decision. We find evidence consistent with the presence of family crowding out but no robust evidence of public sector crowding out.

Financing long-term care: ex ante, ex post or both?

This paper attempts to examine the heterogeneity in the public financing of long-term care (LTC) and the wide-ranging instruments in place to finance LTC services. We distinguish and classify the institutional responses to the need for LTC financing as ex ante (occurring prior to when the need arises, such as insurance) and ex post (occurring after the need arises, such as public sector and family financing). Then, we examine country-specific data to ascertain whether the two types of financing are complements or substitutes. Finally, we examine exploratory cross-national data on public expenditure determinants, specifically economic, demographic and social determinants. We show that although both ex ante and ex post mechanisms exist in all countries with advanced industrial economies and despite the fact that instruments are different across countries, ex ante and ex post instruments are largely substitutes for each other. Expenditure estimates to date indicate that the public financing of LTC is highly sensitive to a country's income, ageing of the population and the availability of informal caregiving.

Tosvinyl and besvinyl as protecting groups of imides, azinones, nucleosides, sultams, and lactams. Catalytic conjugate additions to tosylacetylene.

The use of the 2-(4-methylphenylsulfonyl)ethenyl (tosvinyl, Tsv) group for the protection of the NH group of a series of imides, azinones (including AZT), inosines, and cyclic sulfonamides has been examined. The Tsv-protected derivatives are obtained in excellent yields by conjugate addition to tosylacetylene (ethynyl p-tolyl sulfone). The stereochemistry of the double bond can be controlled at will: with only 1 mol % of Et3N or with catalytic amounts of NaH, the Z stereoisomers are generated almost exclusively, while the E isomers are obtained using a stoichiometric amount of DMAP. Analogous phenylsulfonylvinyl-protected groups (with the besvinyl or Bsv group instead of Tsv) are obtained stereospecifically by reaction with (Z)- or (E)-bis(phenylsulfonyl)ethene. For lactams and oxazolidinones, this last method is much better. The Tsv and Bsv groups are stable in the presence of non-nucleophilic bases and to acids. They can be removed highly effectively via a conjugate addition-elimination mechanism using pyrrolidine or sodium dodecanethiolate as nucleophiles.

Cultural persistence and the 'herbal medicine paradox': Evidence from European data.

The use of herbal or traditional medicines has survived the proliferation of modern medicine. The phenomenon has been labeled as the 'herbal medicines paradox' (HMP). We study whether such HMP hypothesis can be explained by the persistence of attitudes across cultural boundaries. We undertake a secondary analysis of individual-level migration data to test the persistence of the use of herbal medicines in relation to norms in the person's country of birth (or home country). We study the association between attitudes towards herbal medicine treatments of both first (N = 3630) and second-generation (N = 1618) immigrants in 30 European countries, and the average attitudes of their sending country origins. We find robust evidence of an association that is stronger for the second-generation migrants. We document a stronger effect among maternal than paternal lineages, as well as significant heterogeneity based on migrants' country of origin. Our estimates are robust to different sample analysis. Our estimates are consistent with a cultural explanation for the HMP.

The labour market returns to sleep.

Despite the growing prevalence of insufficient sleep among individuals, we still know little about the labour market return to sleep. To address this gap, we use longitudinal data from Germany and leverage exogenous fluctuations in sleep duration caused by variations in time and local sunset times. Our findings reveal that a one-hour increase in weekly sleep is associated with a 1.6 percentage point rise in employment and a 3.4% increase in weekly earnings. Such effect on earnings stems from productivity improvements given that the number of working hours decreases with longer sleep duration. We also identify a key mechanism driving these effects, namely the enhanced mental well-being experienced by individuals who sleep longer hours.

Health inequality and health insurance coverage: The United States and China compared.

We study inequality in the distribution of self-assessed health (SAH) in the United States and China, two large countries that have expanded their insurance provisions in recent decades, but that lack universal coverage and differ in other social determinants of health. Using comparable health survey data from China and the United States, we compare health inequality trends throughout the period covering the public health insurance coverage expansions in the two countries. We find that whether SAH inequality is greater in the US or in China depends on the concept of status and the inequality-sensitivity parameter used; however, the regional pattern of SAH inequality is clearly associated with health-insurance coverage expansions in the US but not significant in China.

How to Use Quasi-Experimental Methods in Cardiovascular Research: A Review of Current Practice.

BACKGROUND: Quasi-experimental methods (QEMs) are a family of techniques used to estimate causal relationships when randomized controlled trials are unfeasible or unethical. They offer a powerful alternative to observational studies by introducing random assignment of individuals or groups into their design, thereby offering stronger means of establishing causation. The use of QEMs in cardiovascular research has not been systematically examined to determine steps toward improving and expanding their use. METHODS: We identified 4 main techniques using a systematic search strategy from 2016 to 2021: instrumental variable analysis, interrupted time series analysis, difference-in-differences analysis, and regression discontinuity designs. QEMs are examined as alternatives to randomized controlled trials and traditional observational studies; as more observational data becomes available to researchers, there are more opportunities to apply these techniques. Eligible articles were selected based on publication in high-ranked journals. The quality of eligible articles was appraised using the Joanna Briggs Institute checklist for quasi-experimental studies. RESULTS: Data from 380 studies were extracted based on our inclusion criteria. Forty-two of these studies were published in the top 10 medical or top 20 cardiovascular disease journals, and 25 studies were included after quality appraisal. The review identifies the main features and limitations associated with each technique, providing readers with practical guidance on how to apply these to their research. A graphical decision aid was developed to facilitate the routine use of QEMs. CONCLUSIONS: The use of QEMs in cardiovascular research published in contemporary, high-impact articles was examined. Findings are biased toward this segment of literature, which represents the latest developments in this growing area of cardiovascular research. The decision aid is a novel schematic that researchers can adopt into practice.

Nucleophile-catalyzed additions to activated triple bonds. Protection of lactams, imides, and nucleosides with MocVinyl and related groups.

Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations.

Not only a territorial matter: The electoral surge of VOX and the anti-libertarian reaction.

Although previous work has shown the complexity of motives behind the VOX vote, its emergence is often associated mainly with the Catalan conflict. Our analysis shows that VOX's first electoral success was marked importantly by preferences related to territorial conflict, but also by opposition to immigration, authoritarianism or ideology. The main contribution of the paper lies in demonstrating something that until now had not been empirically verified: the relevance of anti-feminist attitudes amongst the VOX electorate. This shows how, since its onset, these voters have not been so different from voters of other European radical right-wing parties, and how VOX has channelled into elections the reaction against different expressions of a more diverse and egalitarian society.

'Investing' in care for old age? An examination of long-term care expenditure dynamics and its spillovers.

We study the dynamic drivers of expenditure on long-term care (LTC) programmes, and more specifically, the effects of labour market participation of traditional unpaid caregivers (women aged 40 and older) on LTC spending, alongside the spillover effects of a rise in LTC expenditure on health care expenditures (HCE) and the economy (per capita GDP). Our estimates draw from a panel of more than a decade worth of expenditure data from a sample of OECD countries. We use a panel vector auto-regressive (panel-VAR) system that considers the dynamics between the dependent variables. We find that LTC expenditure increases with the rise of the labour market participation of the traditional unpaid caregiver (women over 40 years of age), and that such expenditures rise exerts large spillover effects on health spending and the economy. We find that a 1% increase in female labour participation gives rise to a 1.48% increase in LTC expenditure and a 0.88% reduction in HCE. The effect of LTC spending over HCE is mainly driven by a reduction in inpatient and medicine expenditures, exhibiting large country heterogeneity. Finally, we document significant spillover effects of LTC expenditures on per capita GDP. Supplementary Information: The online version contains supplementary material available at 10.1007/s00181-022-02246-0.