The Hierarchical Age-Period-Cohort model: Why does it find the results that it finds?

It is claimed the hierarchical-age–period–cohort (HAPC) model solves the age–period–cohort (APC) identification problem. However, this is debateable; simulations show situations where the model produces incorrect results, countered by proponents of the model arguing those simulations are not relevant to real-life scenarios. This paper moves beyond questioning whether the HAPC model works, to why it produces the results it does. We argue HAPC estimates are the result not of the distinctive substantive APC processes occurring in the dataset, but are primarily an artefact of the data structure—that is, the way the data has been collected. Were the data collected differently, the results produced would be different. This is illustrated both with simulations and real data, the latter by taking a variety of samples from the National Health Interview Survey (NHIS) data used by Reither et al. (Soc Sci Med 69(10):1439–1448, 2009) in their HAPC study of obesity. When a sample based on a small range of cohorts is taken, such that the period range is much greater than the cohort range, the results produced are very different to those produced when cohort groups span a much wider range than periods, as is structurally the case with repeated cross-sectional data. The paper also addresses the latest defence of the HAPC model by its proponents (Reither et al. in Soc Sci Med 145:125–128, 2015a). The results lend further support to the view that the HAPC model is not able to accurately discern APC effects, and should be used with caution when there appear to be period or cohort near-linear trends

Principal component analysis of socioeconomic factors and their association with malaria in children from the Ashanti Region, Ghana

<p>Abstract</p> <p>Background</p> <p>The socioeconomic and sociodemographic situation are important components for the design and assessment of malaria control measures. In malaria endemic areas, however, valid classification of socioeconomic factors is difficult due to the lack of standardized tax and income data. The objective of this study was to quantify household socioeconomic levels using principal component analyses (PCA) to a set of indicator variables and to use a classification scheme for the multivariate analysis of children < 15 years of age presented with and without malaria to an outpatient department of a rural hospital.</p> <p>Methods</p> <p>In total, 1,496 children presenting to the hospital were examined for malaria parasites and interviewed with a standardized questionnaire. The information of eleven indicators of the family's housing situation was reduced by PCA to a socioeconomic score, which was then classified into three socioeconomic status (poor, average and rich). Their influence on the malaria occurrence was analysed together with malaria risk co-factors, such as sex, parent's educational and ethnic background, number of children living in a household, applied malaria protection measures, place of residence and age of the child and the mother.</p> <p>Results</p> <p>The multivariate regression analysis demonstrated that the proportion of children with malaria decreased with increasing socioeconomic status as classified by PCA (p < 0.05). Other independent factors for malaria risk were the use of malaria protection measures (p < 0.05), the place of residence (p < 0.05), and the age of the child (p < 0.05).</p> <p>Conclusions</p> <p>The socioeconomic situation is significantly associated with malaria even in holoendemic rural areas where economic differences are not much pronounced. Valid classification of the socioeconomic level is crucial to be considered as confounder in intervention trials and in the planning of malaria control measures.</p

Different Modes of Retrovirus Restriction by Human APOBEC3A and APOBEC3G In Vivo

The apolipoprotein B editing complex 3 (A3) cytidine deaminases are among the most highly evolutionarily selected retroviral restriction factors, both in terms of gene copy number and sequence diversity. Primate genomes encode seven A3 genes, and while A3F and 3G are widely recognized as important in the restriction of HIV, the role of the other genes, particularly A3A, is not as clear. Indeed, since human cells can express multiple A3 genes, and because of the lack of an experimentally tractable model, it is difficult to dissect the individual contribution of each gene to virus restriction in vivo. To overcome this problem, we generated human A3A and A3G transgenic mice on a mouse A3 knockout background. Using these mice, we demonstrate that both A3A and A3G restrict infection by murine retroviruses but by different mechanisms: A3G was packaged into virions and caused extensive deamination of the retrovirus genomes while A3A was not packaged and instead restricted infection when expressed in target cells. Additionally, we show that a murine leukemia virus engineered to express HIV Vif overcame the A3G-mediated restriction, thereby creating a novel model for studying the interaction between these proteins. We have thus developed an in vivo system for understanding how human A3 proteins use different modes of restriction, as well as a means for testing therapies that disrupt HIV Vif-A3G interactions.United States. Public Health Service (Grant R01-AI-085015)United States. Public Health Service (Grant T32-CA115299 )United States. Public Health Service (Grant F32-AI100512

Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: user acceptability

<p>Abstract</p> <p>Background</p> <p>Malaria in pregnancy is associated with increased risks of maternal and foetal complications. Currently, intermittent preventive treatment (IPT) of malaria during pregnancy with sulphadoxine-pyrimethamine (SP) is recommended by the WHO as part of a package of interventions also including insecticide-treated nets and effective case management. However, with increasing resistance to SP, the effectiveness of SP-IPT has been questioned. A randomized controlled trial (RCT) to investigate the relative efficacy of an alternative strategy of intermittent screening and treatment (IST), which involves a rapid diagnostic test for malaria at scheduled ANC visits and treatment of women only if positive, versus SP-IPT has been conducted in Ashanti region, Ghana. This paper reports on a complementary study investigating the acceptability of the different strategies to women enrolled in the trial.</p> <p>Methods</p> <p>Data were collected through twelve focus group discussions with women selected at random from the different arms of the RCT, exploring their experiences and perceptions about antenatal care and their involvement in the trial. Content analysis was used to identify relevant themes to structure the results.</p> <p>Results</p> <p>Five main themes emerged from participants' experiences of ANC and the RCT that would influence their acceptability of malaria prevention strategies during pregnancy: health benefits; drugs received; tests received; other services received; and health worker attitude. Their own health and that of their baby were strong motivations for attending ANC, and reported favourably as an outcome of being in the RCT. Women were not always clear on the biomedical function of drugs or blood tests but generally accepted them due to strong trust in the health staff. Home visits by staff and free ITNs as part of the trial were appreciated. Politeness and patience of health staff was a very strong positive factor.</p> <p>Conclusions</p> <p>Overall, both intermittent screening and treatment and intermittent preventive treatment appeared equally acceptable to pregnant women as strategies for the control of malaria in pregnancy. The women were more concerned about quality of services received, in particular the polite and patient attitude of health staff, and positive health implications for themselves and their babies than about the nature of the intervention.</p

Predictive Value of Fever and Palmar Pallor for P. falciparum Parasitaemia in Children from an Endemic Area

INTRODUCTION: Although the incidence of Plasmodium falciparum malaria in some parts of sub-Saharan Africa is reported to decline and other conditions, causing similar symptoms as clinical malaria are gaining in relevance, presumptive anti-malarial treatment is still common. This study traced for age-dependent signs and symptoms predictive for P. falciparum parasitaemia. METHODS: In total, 5447 visits of 3641 patients between 2-60 months of age who attended an outpatient department (OPD) of a rural hospital in the Ashanti Region, Ghana, were analysed. All Children were examined by a paediatrician and a full blood count and thick smear were done. A Classification and Regression Tree (CART) model was used to generate a clinical decision tree to predict malarial parasitaemia a7nd predictive values of all symptoms were calculated. RESULTS: Malarial parasitaemia was detected in children between 2-12 months and between 12-60 months of age with a prevalence of 13.8% and 30.6%, respectively. The CART-model revealed age-dependent differences in the ability of the variables to predict parasitaemia. While palmar pallor was the most important symptom in children between 2-12 months, a report of fever and an elevated body temperature of ≥37.5°C gained in relevance in children between 12-60 months. The variable palmar pallor was significantly (p<0.001) associated with lower haemoglobin levels in children of all ages. Compared to the Integrated Management of Childhood Illness (IMCI) algorithm the CART-model had much lower sensitivities, but higher specificities and positive predictive values for a malarial parasitaemia. CONCLUSIONS: Use of age-derived algorithms increases the specificity of the prediction for P. falciparum parasitaemia. The predictive value of palmar pallor should be underlined in health worker training. Due to a lack of sensitivity neither the best algorithm nor palmar pallor as a single sign are eligible for decision-making and cannot replace presumptive treatment or laboratory diagnosis

Spatial Analysis of Land Cover Determinants of Malaria Incidence in the Ashanti Region, Ghana

Malaria belongs to the infectious diseases with the highest morbidity and mortality worldwide. As a vector-borne disease malaria distribution is strongly influenced by environmental factors. The aim of this study was to investigate the association between malaria risk and different land cover classes by using high-resolution multispectral Ikonos images and Poisson regression analyses. The association of malaria incidence with land cover around 12 villages in the Ashanti Region, Ghana, was assessed in 1,988 children <15 years of age. The median malaria incidence was 85.7 per 1,000 inhabitants and year (range 28.4–272.7). Swampy areas and banana/plantain production in the proximity of villages were strong predictors of a high malaria incidence. An increase of 10% of swampy area coverage in the 2 km radius around a village led to a 43% higher incidence (relative risk [RR] = 1.43, p<0.001). Each 10% increase of area with banana/plantain production around a village tripled the risk for malaria (RR = 3.25, p<0.001). An increase in forested area of 10% was associated with a 47% decrease of malaria incidence (RR = 0.53, p = 0.029)

Overexpression of the Mitochondrial T3 Receptor p43 Induces a Shift in Skeletal Muscle Fiber Types

In previous studies, we have characterized a new hormonal pathway involving a mitochondrial T3 receptor (p43) acting as a mitochondrial transcription factor and consequently stimulating mitochondrial activity and mitochondrial biogenesis. We have established the involvement of this T3 pathway in the regulation of in vitro myoblast differentiation.We have generated mice overexpressing p43 under control of the human α-skeletal actin promoter. In agreement with the previous characterization of this promoter, northern-blot and western-blot experiments confirmed that after birth p43 was specifically overexpressed in skeletal muscle. As expected from in vitro studies, in 2-month old mice, p43 overexpression increased mitochondrial genes expression and mitochondrial biogenesis as attested by the increase of mitochondrial mass and mt-DNA copy number. In addition, transgenic mice had a body temperature 0.8°C higher than control ones and displayed lower plasma triiodothyronine levels. Skeletal muscles of transgenic mice were redder than wild-type animals suggesting an increased oxidative metabolism. In line with this observation, in gastrocnemius, we recorded a strong increase in cytochrome oxidase activity and in mitochondrial respiration. Moreover, we observed that p43 drives the formation of oxidative fibers: in soleus muscle, where MyHC IIa fibers were partly replaced by type I fibers; in gastrocnemius muscle, we found an increase in MyHC IIa and IIx expression associated with a reduction in the number of glycolytic fibers type IIb. In addition, we found that PGC-1α and PPARδ, two major regulators of muscle phenotype were up regulated in p43 transgenic mice suggesting that these proteins could be downstream targets of mitochondrial activity. These data indicate that the direct mitochondrial T3 pathway is deeply involved in the acquisition of contractile and metabolic features of muscle fibers in particular by regulating PGC-1α and PPARδ

APOBEC3G and APOBEC3F Require an Endogenous Cofactor to Block HIV-1 Replication

APOBEC3G (A3G)/APOBEC3F (A3F) are two members of APOBEC3 cytidine deaminase subfamily. Although they potently inhibit the replication of vif-deficient HIV-1, this mechanism is still poorly understood. Initially, A3G/A3F were thought to catalyze C-to-U transitions on the minus-strand viral cDNAs during reverse transcription to disrupt the viral life cycle. Recently, it was found more likely that A3G/A3F directly interrupts viral reverse transcription or integration. In addition, A3G/A3F are both found in the high-molecular-mass complex in immortalized cell lines, where they interact with a number of different cellular proteins. However, there has been no evidence to prove that these interactions are required for A3G/A3F function. Here, we studied A3G/A3F-restricted HIV-1 replication in six different human T cell lines by infecting them with wild-type or vif-deficient HIV-1. Interestingly, in a CEM-derived cell line CEM-T4, which expresses high levels of A3G/A3F proteins, the vif-deficient virus replicated as equally well as the wild-type virus, suggesting that these endogenous antiretroviral genes lost anti-HIV activities. It was confirmed that these A3G/A3F genes do not contain any mutation and are functionally normal. Consistently, overexpression of exogenous A3G/A3F in CEM-T4 cells still failed to restore their anti-HIV activities. However, this activity could be restored if CEM-T4 cells were fused to 293T cells to form heterokaryons. These results demonstrate that CEM-T4 cells lack a cellular cofactor, which is critical for A3G/A3F anti-HIV activity. We propose that a further study of this novel factor will provide another strategy for a complete understanding of the A3G/A3F antiretroviral mechanism

Women in (Dis)placement: The Field of Studies on Migrations, Social Remittances, Care and Gender in Chile

This article presents current perspectives on the gender approach to the study of migration in Chile between 1990 and 2018, contextualizing it in light of international debates in the social sciences. We will discuss how the feminization and the growth of Latin American migrations have given rise to a prolific field of research, as exemplified by studies conducted in central and northern Chile. We will show how the concepts of social remittances and caregiving permeate the Chilean debate on migrant women. We conclude with reflections on topics and perspectives to be incorporated into the Chilean research agenda on gender and migration.Se presenta un estado del arte sobre el enfoque de género en los estudios de la migración en Chile entre 1990 y 2018, contextualizándolo a la luz de debates internacionales de las ciencias sociales. Abordaremos cómo la feminización y el incremento de las migraciones latinoamericanas inauguran un prolijo campo de investigaciones, articulado a través de estudios desarrollados en el centro y en el norte de Chile. Señalaremos cómo los conceptos de remesas sociales y cuidados permean el debate chileno sobre las mujeres migrantes. Finalizamos con reflexiones sobre temas y perspectivas a ser incorporados en la agenda chilena de investigaciones sobre género y migración.The authors would like to thank the Chilean National Commission for Scientific and Technological Research (CONICYT) for funding the study that led to this article through Fondecyt Regular Project number 1160683: “Ser Mujer Mayor en Santiago. Organización social de los cuidados, feminización del envejecimiento y desigualdades acumuladas” (“Being an older woman in Santiago. Social organization of care, feminization of ageing and accumulated inequalities”), led by Herminia Gonzálvez Torralbo and Fondecyt Regular Project number 1190056: “The Boundaries of Gender Violence: Migrant Women’s Experiences in South American Border Territories” led by Menara Lube Guizardi