Adult triclabendazole-resistant Fasciola hepatica: morphological changes in the tegument and gut following in vivo treatment with artemether in the rat model

A study has been carried out to determine the morphological changes to the adult liver fluke, Fasciola hepatica after treatment in vivo with artemether. Rats were infected with the triclabendazole-resistant Sligo isolate of F. hepatica, dosed orally with artemether at a concentration of 200mg/kg and flukes recovered at 24, 48 and 72h post-treatment (p.t.). Surface changes were monitored by scanning electron microscopy and fine structural changes to the tegument and gut by transmission electron microscopy. Twenty-four hours p.t., the external surface showed minor disruption, in the form of mild swelling of the tegument. The tegumental syncytium and sub-tegumental tissues appeared relatively normal. Forty-eight and seventy-two hours p.t., disruption to the tegumental system increased, with isolated patches of surface blebbing and reduced production of secretory bodies by the tegumental cells being the main changes seen. The gastrodermal cells showed a relatively normal morphology 24h p.t. By 48h, large numbers of autophagic vacuoles and lipid droplets were present. Autophagy increased in magnitude by 72h p.t. and substantial disruption to the granular endoplasmic reticulum was observed. Results from this study show that flukes treated in vivo with artemether display progressive and time-dependent alterations to the tegument and gut. Disruption to the gut was consistently and substantially more severe than that to the tegument, suggesting that an oral route of uptake for this compound predominates. This is the first study providing ultrastructural information on the effect of an artemisinin compound against liver fluk

The normative underpinnings of population-level alcohol use: An individual-level simulation model

Background. By defining what is “normal,” appropriate, expected, and unacceptable, social norms shape human behavior. However, the individual-level mechanisms through which social norms impact population-level trends in health-relevant behaviors are not well understood. Aims. To test the ability of social norms mechanisms to predict changes in population-level drinking patterns. Method. An individual-level model was developed to simulate dynamic normative mechanisms and behavioral rules underlying drinking behavior over time. The model encompassed descriptive and injunctive drinking norms and their impact on frequency and quantity of alcohol use. A microsynthesis initialized in 1979 was used as a demographically representative synthetic U.S. population. Three experiments were performed in order to test the modelled normative mechanisms. Results. Overall, the experiments showed limited influence of normative interventions on population-level alcohol use. An increase in the desire to drink led to the most meaningful changes in the population’s drinking behavior. The findings of the experiments underline the importance of autonomy, that is, the degree to which an individual is susceptible to normative influence. Conclusion. The model was able to predict theoretically plausible changes in drinking patterns at the population level through the impact of social mechanisms. Future applications of the model could be used to plan norms interventions pertaining to alcohol use as well as other health behaviors

Commentary on Robinson et al. (2021): Evaluating theories of change for public health policies using computer model discovery methods

Recent developments in computer modelling—known as model discovery—could help to confirm the mechanisms underpinning Robinson and colleagues’ important early findings for the effectiveness of minimum unit pricing, and to test the complete theory of change underpinning this crucial evaluation

An integrated dual process simulation model of alcohol use behaviours in individuals, with application to US population-level consumption, 1984–2012

Introduction The Theory of Planned Behaviour (TPB) describes how attitudes, norms and perceived behavioural control guide health behaviour, including alcohol consumption. Dual Process Theories (DPT) suggest that alongside these reasoned pathways, behaviour is influenced by automatic processes that are determined by the frequency of engagement in the health behaviour in the past. We present a computational model integrating TPB and DPT to determine drinking decisions for simulated individuals. We explore whether this model can reproduce historical patterns in US population alcohol use and simulate a hypothetical scenario, “Dry January”, to demonstrate the utility of the model for appraising the impact of policy interventions on population alcohol use. Method Constructs from the TPB pathway were computed using equations from an existing individual-level dynamic simulation model of alcohol use. The DPT pathway was initialised by simulating individuals’ past drinking using data from a large US survey. Individuals in the model were from a US population microsimulation that accounts for births, deaths and migration (1984–2015). On each modelled day, for each individual, we calculated standard drinks consumed using the TPB or DPT pathway. In each year we computed total population alcohol use prevalence, frequency and quantity. The model was calibrated to alcohol use data from the Behavioral Risk Factor Surveillance System (1984–2004). Results The model was a good fit to prevalence and frequency but a poorer fit to quantity of alcohol consumption, particularly in males. Simulating Dry January in each year led to a small to moderate reduction in annual population drinking. Conclusion This study provides further evidence, at the whole population level, that a combination of reasoned and implicit processes are important for alcohol use. Alcohol misuse interventions should target both processes. The integrated TPB-DPT simulation model is a useful tool for estimating changes in alcohol consumption following hypothetical population interventions

Introducing CASCADEPOP: an open-source sociodemographic simulation platform for US health policy appraisal

Largescale individual-level and agent-based models are gaining importance in health policy appraisal and evaluation. Such models require the accurate depiction of the jurisdiction’s population over extended time periods to enable modeling of the development of non-communicable diseases under consideration of historical, sociodemographic developments. We developed CASCADEPOP to provide a readily available sociodemographic micro-synthesis and microsimulation platform for US populations. The micro-synthesis method used iterative proportional fitting to integrate data from the US Census, the American Community Survey, the Panel Study of Income Dynamics, Multiple Cause of Death Files, and several national surveys to produce a synthetic population aged 12 to 80 years on 01/01/1980 for five states (California, Minnesota, New York, Tennessee, and Texas) and the US. Characteristics include individuals’ age, sex, race/ethnicity, marital/employment/parental status, education, income and patterns of alcohol use as an exemplar health behavior. The microsimulation simulates individuals’ sociodemographic life trajectories over 35 years to 31/12/2015 accounting for population developments including births, deaths, and migration. Results comparing the 1980 micro-synthesis against observed data shows a successful depiction of state and US population characteristics and of drinking. Comparing the microsimulation over 30 years with Census data also showed the successful simulation of sociodemographic developments. The CASCADEPOP platform enables modelling of health behaviors across individuals’ life courses and at a population level. As it contains a large number of relevant sociodemographic characteristics it can be further developed by researchers to build US agent-based models and microsimulations to examine health behaviors, interventions, and policies

Genetically Determined Height and Risk of Non-hodgkin Lymphoma

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00\u20131.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01\u20131.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes