Instrumental Variable Estimation of the Causal Effect of Hunger Early in Life on Health Later in Life

Numerous studies have evaluated the effect of nutrition early in life on health much later in life by comparing individuals born during a famine to others. Nutritional intake is typically unobserved and endogenous, whereas famines arguably provide exogenous variation in the provision of nutrition. However, living through a famine early in life does not necessarily imply a lack of nutrition during that age interval, and vice versa, and in this sense the observed difference at most provides a qualitative assessment of the average causal effect of a nutritional shortage, which is the parameter of interest. In this paper we estimate this average causal effect on health outcomes later in life, by applying instrumental variable estimation, using data with self-reported periods of hunger earlier in life, with famines as instruments. The data contain samples from European countries and include birth cohorts exposed to various famines in the 20th century. We use two-sample IV estimation to deal with imperfect recollection of conditions at very early stages of life. The estimated average causal effects often exceed famine effects by a factor three.2SLS, obesity, high blood pressure, height, developmental origins, ageing, famine, nutrition, two-sample IV

Instrumental Variable Estimation of the Causal Effect of Hunger Early in Life on Health Later in Life

Numerous studies have evaluated the effect of nutrition early in life on health much later in life by comparing individuals born during a famine to others. Nutritional intake is typically unobserved and endogenous, whereas famines arguably provide exogenous variation in the provision of nutrition. However, living through a famine early in life does not necessarily imply a lack of nutrition during that age interval, and vice versa, and in this sense the observed difference at most provides a qualitative assessment of the average causal effect of a nutritional shortage, which is the parameter of interest. In this paper we estimate this average causal effect on health outcomes later in life, by applying instrumental variable estimation, using data with self-reported periods of hunger earlier in life, with famines as instruments. The data contain samples from European countries and include birth cohorts exposed to various famines in the 20th century. We use two-sample IV estimation to deal with imperfect recollection of conditions at very early stages of life. The estimated average causal effects often exceed famine effects by a factor three

Peptides identify multiple hotspots within the ligand binding domain of the TNF receptor 2

BACKGROUND: Hotspots are defined as the minimal functional domains involved in protein:protein interactions and sufficient to induce a biological response. RESULTS: Here we describe the use of complex and high diversity phage display libraries to isolate peptides (called Hotspot Ligands or HSPLs) which sub-divide the ligand binding domain of the tumor necrosis factor receptor 2 (TNFR2; p75) into multiple hotspots. We have shown that these libraries could generate HSPLs which not only subdivide hotspots on protein and non-protein targets but act as agonists or antagonists. Using this approach, we generated peptides which were specific for human TNFR2, could be competed by the natural ligands, TNFα and TNFβ and induced an unexpected biological response in a TNFR2-specific manner. CONCLUSIONS: To our knowledge, this is the first report describing the dissection of the TNFR2 into biologically active hotspots with the concomitant identification of a novel and unexpected biological activity

Maintaining (locus of) control? : Assessing the impact of locus of control on education decisions and wages

This paper establishes that individuals with an internal locus of control, i.e., who believe that reinforcement in life comes from their own actions instead of being determined by luck or destiny, earn higher wages. However, this positive effect only translates into labor income via the channel of education. Factor structure models are implemented on an augmented data set coming from two different samples. By so doing, we are able to correct for potential biases that arise due to reverse causality and spurious correlation, and to investigate the impact of premarket locus of control on later outcomes

Patterns of alcohol consumption among individuals with alcohol use disorder during the COVID-19 pandemic and lockdowns in Germany

Objective: To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms. Design, setting, and participants: This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021). Main outcomes and measures: Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates. Results: Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year's Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = -5.45; 95% CI, -8.00 to -2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = -11.10; 95% CI, -13.63 to -8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = -6.14; 95% CI, -9.96 to -2.31; P = .002) and in participants with severe AUD (β = -6.26; 95% CI, -10.18 to -2.34; P = .002). Conclusions and relevance: This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals

African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat

The African trypanosome, Trypanosoma brucei spp., is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity. The parasite elicits robust antibody-mediated immune responses to its Variant Surface Glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and “switching” to antigenically distinct VSGs. This persistent immune evasion has been ascribed exclusively to amino acid variance on the VSG surface presented by a conserved underlying protein architecture. We establish here that this model does not account for the scope of VSG structural and biochemical diversity. The 1.4Å resolution crystal structure of variant VSG3 manifests heretofore unappreciated divergence in the tertiary fold and oligomeric state. The structure also reveals an O linked carbohydrate on the top surface of VSG3, a modification previously unknown in African trypanosomes. Mass spectrometric analysis indicates that this O -glycosylation site is heterogeneously occupied in VSG3 by 0 to 3 hexose residues and is also present in other VSGs. We demonstrate that this O -glycosylation increases parasite virulence by impairing the generation of protective immunity. These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino acid sequence to include surface posttranslational modifications with immunomodulatory impact