Ascaris lumbricoides Infection and Its Relation to Environmental Factors in the Mbeya Region of Tanzania, a Cross-Sectional, Population-Based Study

Background: With one quarter of the world population infected, the intestinal nematode Ascaris lumbricoides is one of the most common infectious agents, especially in the tropics and sub-tropics. Infection is caused by oral intake of eggs and can cause respiratory and gastrointestinal problems. To identify high risk areas for intervention, it is necessary to understand the effects of climatic, environmental and socio-demographic conditions on A. lumbricoides infection. Methodology: Cross-sectional survey data of 6, 366 study participants in the Mbeya region of South-Western Tanzania were used to analyze associations between remotely sensed environmental data and A. lumbricoides infection. Non-linear associations were accounted for by using fractional polynomial regression, and socio-demographic and sanitary data were included as potential confounders. Principal Findings: The overall prevalence of A. lumbricoides infection was 6.8%. Our final multivariable model revealed a significant non-linear association between rainfall and A. lumbricoides infection with peak prevalences at 1740 mm of mean annual rainfall. Mean annual land surface temperature during the day was linearly modeled and negatively associated with A. lumbricoides infection (odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.78-0.97). Furthermore, age, which also showed a significant non-linear association (infection maximum at 7.7 years),socio-economic status (OR = 0.82, CI = 0.68-0.97),and latrine coverage around the house (OR = 0.80, CI = 0.67-0.96) remained in the final model. Conclusions: A. lumbricoides infection was associated with environmental, socio-demographic and sanitary factors both in uni-and multivariable analysis. Non-linear analysis with fractional polynomials can improve model fit, resulting in a better understanding of the relationship between environmental conditions and helminth infection, and more precise predictions of high prevalence areas. However, socio-demographic determinants and sanitary conditions should also be considered, especially when planning public health interventions on a smaller scale, such as the community level

Hookworm Infection and Environmental Factors in Mbeya Region, Tanzania: A Cross-sectional, Population-based study.

Hookworm disease is one of the most common infections and cause of a high disease burden in the tropics and subtropics. Remotely sensed ecological data and model-based geostatistics have been used recently to identify areas in need for hookworm control. Cross-sectional interview data and stool samples from 6,375 participants from nine different sites in Mbeya region, south-western Tanzania, were collected as part of a cohort study. Hookworm infection was assessed by microscopy of duplicate Kato-Katz thick smears from one stool sample from each participant. A geographic information system was used to obtain remotely sensed environmental data such as land surface temperature (LST), vegetation cover, rainfall, and elevation, and combine them with hookworm infection data and with socio-demographic and behavioral data. Uni- and multivariable logistic regression was performed on sites separately and on the pooled dataset. Univariable analyses yielded significant associations for all ecological variables. Five ecological variables stayed significant in the final multivariable model: population density (odds ratio (OR) = 0.68; 95% confidence interval (CI) = 0.63-0.73), mean annual vegetation density (OR = 0.11; 95% CI = 0.06-0.18), mean annual LST during the day (OR = 0.81; 95% CI = 0.75-0.88), mean annual LST during the night (OR = 1.54; 95% CI = 1.44-1.64), and latrine coverage in household surroundings (OR = 1.02; 95% CI = 1.01-1.04). Interaction terms revealed substantial differences in associations of hookworm infection with population density, mean annual enhanced vegetation index, and latrine coverage between the two sites with the highest prevalence of infection. This study supports previous findings that remotely sensed data such as vegetation indices, LST, and elevation are strongly associated with hookworm prevalence. However, the results indicate that the influence of environmental conditions can differ substantially within a relatively small geographic area. The use of large-scale associations as a predictive tool on smaller scales is therefore problematic and should be handled with care

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p

Implicit Reasons for Disclosure of the Use of Complementary Health Approaches (CHA): a Consumer Commitment Perspective

Background: Disclosure of the use of complementary health approaches (CHA) is an important yet understudied health behaviour with important implications for patient care. Yet research into disclosure of CHA has been atheoretical and neglected the role of health beliefs. Purpose: Using a consumer commitment model of CHA use as a guiding conceptual framework, the current study tests the hypotheses that perceived positive CHA outcomes (utilitarian values) and positive CHA beliefs (symbolic values) are associated with disclosure of CHA to conventional-care providers in a nationally representative US sample. Methods: From a sample of 33,594 with CHA use information from the 2012 National Health Interview Survey (NHIS), a subsample of 7,348 who used CHA within the past 12 months was analysed. The 2012 NHIS is a cross-sectional survey of the non-institutionalized US adult population, which includes the most recent nationally representative CHA use data. Results: The 63.2 % who disclosed CHA use were older, less educated, and had visited a health-care provider in the past year. Weighted logistic regression analyses controlling for demographic variables revealed that those who disclosed were more likely to report experiencing positive psychological (improved coping and well-being) and physical outcomes (better sleep, improved health) from CHA, and hold positive CHA-related beliefs. Conclusions: CHA users who perceive physical and psychological benefits from CHA use, and who hold positive attitudes towards CHA are more likely to disclose their CHA use. Findings support the relevance of a consumer commitment perspective for understanding CHA disclosure, and suggest CHA disclosure as an important proactive health behaviour that warrants further attention

“I’m not ready yet”: Intrapersonal and Interpersonal Processes Shaping the Adoption of Personal Emergency Response Systems Among Older Adults

The goal of this dissertation was to explore older adults’ perceptions of and experiences with quality of life technologies and the meanings they ascribe to a specific subset of quality of life technologies: personal emergency response systems (PERS). Specifically, the purpose was to analyze how older adults perceive the need for PERS and how they negotiate the uptake and use of PERS with themselves and with others.In collaboration with three community-based organizations in western Los Angeles, California, 18 persons (age 71-97 years) were interviewed. The sample was comprised of eight PERS subscribers and ten non-subscribers. The interviews were conducted using a semi- structured interview guide that included questions about perceptions of PERS prior to subscription and experiences with the use of PERS. Data collection and analyses were guided by constructivist grounded theory methodology. Analytic techniques included initial coding, focused coding, theoretical sampling, and memoing.The results are presented in a substantive theory that is grounded in the words and narratives of study participants. The theory situates participants’ pre-subscription experiences in the context of their efforts to counteract the impacts of aging. It is comprised of three processes: reclaiming control, protecting personhood, and walking the balance beam. Participants took action to reclaim control they had lost over their bodies due to aging-related changes. Interviewees also sought to protect their personhood from social forces that encroached on their sense of self. Participants appraised PERS with regards to the extent to which the technology could thwart or support these goals. In many cases, these appraisals stood in opposition to each other and participants’ repeatedly used phrases like “I’m not ready yet” to describe this conflict. Thiss internal conflict led participants to walk the balance beam, which entailed postponing their decision with regards to PERS while re-evaluating the meanings of PERS. Over time, participants edged closer to acquiring a PERS through imagined, vicarious, and actual experiences of emergency situations. Additionally, input from members of their social environment facilitated interviewees’ progression towards PERS.This research is the first to provide crucial insights into the decision-making process specifically prior to PERS subscription. Future research and interventions should conceptualize PERS adoption can be productively conceptualized as behavior change in future research and intervention, which should take into account older adults’ level of readiness to adopt a PERS

The Pantheon+ Analysis: Evaluating Peculiar Velocity Corrections in Cosmological Analyses with Nearby Type Ia Supernovae

Separating the components of redshift due to expansion and peculiar motion in the nearby universe ($z<0.1$) is critical for using Type Ia Supernovae (SNe Ia) to measure the Hubble constant ($H_0$) and the equation-of-state parameter of dark energy ($w$). Here, we study the two dominant 'motions' contributing to nearby peculiar velocities: large-scale, coherent-flow (CF) motions and small-scale motions due to gravitationally associated galaxies deemed to be in a galaxy group. We use a set of 584 low-$z$ SNe from the Pantheon+ sample, and evaluate the efficacy of corrections to these motions by measuring the improvement of SN distance residuals. We study multiple methods for modeling the large and small-scale motions and show that, while group assignments and CF corrections individually contribute to small improvements in Hubble residual scatter, the greatest improvement comes from the combination of the two (relative standard deviation of the Hubble residuals, Rel. SD, improves from 0.167 to 0.157 mag). We find the optimal flow corrections derived from various local density maps significantly reduce Hubble residuals while raising $H_0$ by $\sim0.4$ km s$^{-1}$ Mpc$^{-1}$ as compared to using CMB redshifts, disfavoring the hypothesis that unrecognized local structure could resolve the Hubble tension. We estimate that the systematic uncertainties in cosmological parameters after optimally correcting redshifts are 0.06-0.11 km s$^{-1}$ Mpc$^{-1}$ in $H_0$ and 0.02-0.03 in $w$ which are smaller than the statistical uncertainties for these measurements: 1.5 km s$^{-1}$ Mpc$^{-1}$ for $H_0$ and 0.04 for $w$

Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease.

Recently targeted disruption of Omi/HtrA2 has been found to cause neurodegeneration and a parkinsonian phenotype in mice. Using a candidate gene approach, we performed a mutation screening of the Omi/HtrA2 gene in German Parkinson's disease (PD) patients. In four patients, we identified a novel heterozygous G399S mutation, which was absent in healthy controls. Moreover, we identified a novel A141S polymorphism that was associated with PD (P<0.05). Both mutations resulted in defective activation of the protease activity of Omi/HtrA2. Immunohistochemistry and functional analysis in stably transfected cells revealed that S399 mutant Omi/HtrA2 and to a lesser extent, the risk allele of the A141S polymorphism induced mitochondrial dysfunction associated with altered mitochondrial morphology. Cells overexpressing S399 mutant Omi/HtrA2 were more susceptible to stress-induced cell death than wild-type. On the basis of functional genomics, our results provide a novel link between mitochondrial dysfunction and neurodegeneration in PD

Meeting the need for a discussion of unmet medical need

As Europe and the world continue to battle against COVID, the customary complacency of society over future threats is clearly on display. Just 30 months ago, such a massive disruption to global lives, livelihoods and quality of life seemed unimaginable. Some remedial European Union action is now emerging, and more is proposed, including in relation to tackling “unmet medical need” (UMN). This initiative—directing attention to the future of treating disease and contemplating incentives to stimulate research and development—is welcome in principle. But the current approach being considered by EU officials merits further discussion, because it may prove counter-productive, impeding rather than promoting innovation. This paper aims to feed into these ongoing policy discussions, and rather than presenting research in the classical sense, it discusses the key elements from a multistakeholder perspective. Its central concern is over the risk that the envisaged support will fail to generate valuable new treatments if the legislation is phrased in a rigidly linear manner that does not reflect the serpentine realities of the innovation process, or if the definition placed on unmet medical need is too restrictive. It cautions that such an approach presumes that “unmet need” can be precisely and comprehensively defined in advance on the basis of the past. It cautions that such an approach can reinforce the comfortable delusion that the future is totally predictable—the delusion that left the world as easy prey to COVID. Instead, the paper urges reflection on how the legislation that will shortly enter the pipeline can be phrased so as to allow for the flourishing of a culture capable of rapid adaptation to the unexpected