Health-seeking behaviour, diagnostics and transmission dynamics in the control of visceral leishmaniasis in the Indian subcontinent

Countries in the Indian subcontinent have committed to reducing the incidence of kala-azar, a clinical manifestation of visceral leishmaniasis, to below 1 in 10,000 by 2020. We address the role of timing of use and accuracy of diagnostics in kala-azar control and elimination. We use empirical data on health-seeking behaviour and health-system performance from the Indian state of Bihar, Bangladesh and Nepal to parameterize a mathematical model. Diagnosis of cases is key to case management, control and surveillance. Treatment of cases prevents onward transmission, and we show that the differences in time to diagnosis in these three settings explain the observed differences in incidence. Shortening the time from health-care seeking to diagnosis is likely to lead to dramatic reductions in incidence in Bihar, bringing the incidence down to the levels seen in Bangladesh and Nepal. The results emphasize the importance of maintaining population and health-system awareness, particularly as transmission and disease incidence decline. We explore the possibility of diagnosing patients before the onset of clinical kala-azar (before 14 days fever), and show that this could have a marked impact on incidence, even for a moderately sensitive test. However, limited specificity (that results in false positives) is a major barrier to such a strategy. Diagnostic tests of high specificity used at an early stage of active infection, even if sensitivity is only moderate, could have a key role in the control of kala-azar, and prevent its resurgence when paired with the passive health-care system and tests of high sensitivity, such as the test for rK39 antibody response

Prevalence of iron deficiency in 62,685 women of seven race/ethnicity groups: The HEIRS Study.

BackgroundFew cross-sectional studies report iron deficiency (ID) prevalence in women of different race/ethnicity and ages in US or Canada.Materials and methodsWe evaluated screening observations on women who participated between 2001-2003 in a cross-sectional, primary care-based sample of adults ages ≥25 y whose observations were complete: race/ethnicity; age; transferrin saturation; serum ferritin; and HFE p.C282Y and p.H63D alleles. We defined ID using a stringent criterion: combined transferrin saturation <10% and serum ferritin <33.7 pmol/L (<15 μg/L). We compared ID prevalence in women of different race/ethnicity subgrouped by age and determined associations of p.C282Y and p.H63D to ID overall, and to ID in women ages 25-44 y with or without self-reported pregnancy.ResultsThese 62,685 women included 27,079 whites, 17,272 blacks, 8,566 Hispanics, 7,615 Asians, 449 Pacific Islanders, 441 Native Americans, and 1,263 participants of other race/ethnicity. Proportions of women with ID were higher in Hispanics and blacks than whites and Asians. Prevalence of ID was significantly greater in women ages 25-54 y of all race/ethnicity groups than women ages ≥55 y of corresponding race/ethnicity. In women ages ≥55 y, ID prevalence did not differ significantly across race/ethnicity. p.C282Y and p.H63D prevalence did not differ significantly in women with or without ID, regardless of race/ethnicity, age subgroup, or pregnancy.ConclusionsID prevalence was greater in Hispanic and black than white and Asian women ages 25-54 y. p.C282Y and p.H63D prevalence did not differ significantly in women with or without ID, regardless of race/ethnicity, age subgroup, or pregnancy

Transcription factor ATF4 directs basal and stress-induced gene expression in the unfolded protein response and cholesterol metabolism in the liver

Disturbances in protein folding and membrane compositions in the endoplasmic reticulum (ER) elicit the unfolded protein response (UPR). Each of three UPR sensory proteins-PERK (PEK/EIF2AK3), IRE1, and ATF6-is activated by ER stress. PERK phosphorylation of eIF2 represses global protein synthesis, lowering influx of nascent polypeptides into the stressed ER, coincident with preferential translation of ATF4 (CREB2). In cultured cells, ATF4 induces transcriptional expression of genes directed by the PERK arm of the UPR, including genes involved in amino acid metabolism, resistance to oxidative stress, and the proapoptotic transcription factor CHOP (GADD153/DDIT3). In this study, we characterize whole-body and tissue-specific ATF4-knockout mice and show in liver exposed to ER stress that ATF4 is not required for CHOP expression, but instead ATF6 is a primary inducer. RNA-Seq analysis indicates that ATF4 is responsible for a small portion of the PERK-dependent UPR genes and reveals a requirement for expression of ATF4 for expression of genes involved in oxidative stress response basally and cholesterol metabolism both basally and under stress. Consistent with this pattern of gene expression, loss of ATF4 resulted in enhanced oxidative damage, and increased free cholesterol in liver under stress accompanied by lowered cholesterol in sera

Dataset associated with "Seeking congruity for agentic women: a longitudinal examination of college women's persistence in STEM"

Those interested in using these data are encouraged to contact Dr. Paul Hernandez ([email protected]) and Dr. Emily Fischer ([email protected]) for more information. Data Contacts: Paul R. Hernandez (primary), [email protected], 979-464-9229 Emily V. Fischer, [email protected], 970-491-8587.Survey data were collected via the online Qualtrics survey system twice yearly in the fall and spring semesters from fall 2015 through spring 2019. This repository contains the data file associated with all surveys utilized in the analyses presented in this research article.Format of Data Files: Data files are in .csv format. Files can be opened by most software (e.g., Notepad, WordPad, Excel) – anything that can read a comma delimited ASCII text file. Here, the file name is "Dataset." In addition, a codebook accompanies the data file. The codebook contains the variable names, variable labels, and value labels for all variables contained within the "Dataset.csv" file.An abundance of literature has examined barriers to women's equal representation in science, technology, engineering, and math (STEM) fields, with many studies showing that STEM fields are not perceived to afford communal goals, a key component of women's interest in future careers. Using Goal Congruity Theory as a framework, we tested the longitudinal impact of perceptions of STEM career goal affordances, communal and agentic goals, and their congruity on persistence in science from the second through fourth years of college among women in STEM majors. We found that women's intent to persist in science were highest in fall of their second year, that persistence intentions exhibited a sharp decline, and that eventually leveled off by their fourth year of college. This pattern was moderated by perceptions of agentic affordances in STEM, such that women with higher perceptions of agentic affordances experienced smaller declines. Similar to prior research, we found that higher perceptions of communal goal affordances in STEM consistently predicted higher persistence intentions. Finally, we found an agentic goal-affordance congruity interaction, such that higher perceptions of agentic affordances in STEM predicted higher persistence intentions; however, the positive relationship was stronger for women with higher agentic goals. We conclude that because STEM fields are stereotyped as affording agentic goals, women who identify interest in a STEM major during their first year of college may be drawn to these fields for this reason, and may benefit from perceptions that STEM affords both communal and agentic goals.Funding for this work was provided by the National Science Foundation through grant number DUE- 1431795, DUE-1431823, and DUE-1460229

Detecting Schistosoma mansoni infections among pre-school-aged children in southern Ghana: a diagnostic comparison of urine-CCA, real-time PCR and Kato-Katz assays

Background In Ghana, pre-school-aged children (PSAC) are at risk of intestinal schistosomiasis and are living in need of praziquantel treatment. To better assess the infection burden within this vulnerable demographic group, we have provided a comparative assessment of the prevalence of Schistosoma mansoni in pre-school-aged children by urine circulating cathodic antigen (CCA) dipsticks, real-time PCR Taqman® faecal assays and Kato-Katz coproscopy. Methods In all, 190 pre-school-aged children were sampled from three endemic communities (viz. Tomefa, Torgahkope/Adakope, and Manheam) around Weija dam, Southern Ghana. Fresh stool and urine samples were collected from all participants for diagnosis. Results Among all the three communities, the urine-CCA assay recorded the highest prevalence values of 90.5% (95% CI 80.4–96.4), 87.9% (95% CI 76.7–95), and 81.2% (95% CI 69.9–89.6) in Tomefa, Torgahkope/Adakope, and Manheam respectively. Prevalence by real-time PCR was 50% (95% CI 35.5–64.5), 8% (95% CI 2.2–19.2) and 16.7% (95% CI 8.3–28.5), while by Kato-Katz was 55.6% (95% CI 42.5–68.1), 8.6% (95% CI 2.9–19) and 11.6% (95% CI 5.1–21.6) respectively. Children aged 1 year and over were found to be positive with the urine-CCA assay; by the ages of 3–4, over 50% were urine-CCA patent. The sensitivity and specificity of the POC-CCA dipsticks, when compared against the combined results of Kato-Katz/TaqMan results was found to be 84.1% (95% CI = 72.7–92.1) and 12.9% (95% CI = 6.6–22) respectively. Conclusions We propose that the urine-CCA dipstick may be a useful rapid diagnostic tool to estimate the prevalence of intestinal schistosomiasis in PSAC, particularly in rapid identification of at-risk areas. However, our assessment has shown that it possible to record false positives when compared to combined Kato-Katz and qPCR results. To guide PSAC praziquantel treatment needs, we propose the urine CCA assay should be included in routine surveillance of intestinal schistosomiasis alongside other diagnostics such as Kato-Katz and urine filtration

Macroalgal biorefinery concepts for the circular bioeconomy: A review on biotechnological developments and future perspectives

The imminent need for transition to a circular bioeconomy, based on the valorisation of renewable biomass feedstocks, will ameliorate global challenges induced by climate change, environmental pollution and population growth. A reduced reliance on depleting fossil fuel resources and ensured production of eco-friendly and cost-effective bioproducts and biofuels, requires the development of sustainable biorefinery processes, with many utilising macroalgae as feedstock, showing promising and viable prospects. Nonetheless, macroalgal biorefinery research is still in its infancy compared to lignocellulosic biorefineries that utilise terrestrial plants. This article presents a review on the latest scientific literature associated with the development and status of macroalgal biorefineries, and how bioproducts generated from these bioprocesses have contributed towards the bioeconomy. The fundamental need to understand how the unique biochemical composition of macroalgae fit within a biorefinery concept are explained, alongside discussion of the novel biotechnologies that have been applied. In order to comprehend the increasing significance of this exciting field, the review will also provide insight, for the first time, on the current global funding and intellectual property landscape related to macroalgae and their implementation across the entire biorefinery concept. Imperative areas for further research and development, to bridge the gap between fundamental bioscience in the laboratory and the successful application of compatible biotechnologies at a commercial scale, to boost the macroalgae industry are also covered

Role modeling is a viable retention strategy for undergraduate women in the geosciences

Gender diversity leads to better science; however, a number of science, technology, engineering, and mathematics (STEM) disciplines, including many geoscience subdisciplines, show a persistent gender gap. PROmoting Geo- science Research, Education, and SuccesS (PROGRESS) is a theory-driven role modeling and mentoring program aimed at supporting undergraduate women interested in geoscience-related degree and career pathways. This study is unique because it is being conducted in a long-term applied setting, rather than as a laboratory exercise. We compare female STEM majors in PROGRESS to a matched control group (N = 380) using a longitudinal prospec- tive multisite quasi-experimental design. College women in PROGRESS par- ticipated in a mentoring and role-modeling weekend workshop with follow- up support, while women in the control group participated in neither the workshop nor the follow-up support. PROGRESS members identified more female STEM career role models than controls (60% versus 42%, respectively), suggesting that deliberate interventions can develop the networks of under- graduate women. Undergraduate women that participate in PROGRESS have higher rates of persistence in geoscience-related majors (95% versus 73%), although the rates of switching into a geoscience-related major did not differ across groups. More strikingly, we also find that the persistence of undergrad- uate women in geoscience-related majors is related to the number of female STEM career role models they identify, as their odds of persisting approxi- mately doubles for each role model they identify. We conclude that our ability to retain undergraduate women in the geosciences will depend, in part, on helping them to identify same-gender career role models. Further, the suc- cess of PROGRESS points to steps universities and departments can take to sustain their students’ interest and persistence, such as hosting interactive panels with diverse female scientists to promote the attainability and social relevance of geoscience careers

Using Seroprevalence and Immunisation Coverage Data to Estimate the Global Burden of Congenital Rubella Syndrome, 1996-2010: A Systematic Review.

BACKGROUND: The burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries. METHODS: We reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000-2010 for each country, region and globally. RESULTS: The estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4-61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46-195) in the Western Pacific, excluding China, to 116 (95% CI: 56-235) and 121 (95% CI: 31-238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000-80,000) and SE Asia (49,000, 95% CI: 11,000-97,000). In 2010, 105,000 (95% CI: 54,000-158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000-169,000) in 1996. CONCLUSIONS: Whilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination

Obesity challenges the hepatoprotective function of the integrated stress response to asparaginase exposure in mice

Obesity increases risk for liver toxicity by the anti-leukemic agent asparaginase, but the mechanism is unknown. Asparaginase activates the integrated stress response (ISR) via sensing amino acid depletion by the eukaryotic initiation factor 2 (eIF2) kinase GCN2. The goal of this work was to discern the impact of obesity, alone versus alongside genetic disruption of the ISR, on mechanisms of liver protection during chronic asparaginase exposure in mice. Following diet-induced obesity, biochemical analysis of livers revealed that asparaginase provoked hepatic steatosis that coincided with activation of another eIF2 kinase PKR-like endoplasmic reticulum kinase (PERK), a major ISR transducer to ER stress. Genetic loss of Gcn2 intensified hepatic PERK activation to asparaginase, yet surprisingly, mRNA levels of key ISR gene targets such as Atf5 and Trib3 failed to increase. Instead, mechanistic target of rapamycin complex 1 (mTORC1) signal transduction was unleashed, and this coincided with liver dysfunction reflected by a failure to maintain hydrogen sulfide production or apolipoprotein B100 (ApoB100) expression. In contrast, obese mice lacking hepatic activating transcription factor 4 (Atf4) showed an exaggerated ISR and greater loss of endogenous hydrogen sulfide but normal inhibition of mTORC1 and maintenance of ApoB100 during asparaginase exposure. In both genetic mouse models, expression and phosphorylation of Sestrin2, an ATF4 gene target, was increased by asparaginase, suggesting mTORC1 inhibition during asparaginase exposure is not driven via eIF2-ATF4-Sestrin2. In conclusion, obesity promotes a maladaptive ISR during asparaginase exposure. GCN2 functions to repress mTORC1 activity and maintain ApoB100 protein levels independently of Atf4 expression, whereas hydrogen sulfide production is promoted via GCN2-ATF4 pathway

Infectious disease and health systems modelling for local decision making to control neglected tropical diseases

Most neglected tropical diseases (NTDs) have complex life cycles and are challenging to control. The “2020 goals” of control and elimination as a public health programme for a number of NTDs are the subject of significant international efforts and investments. Beyond 2020 there will be a drive to maintain these gains and to push for true local elimination of transmission. However, these diseases are affected by variations in vectors, human demography, access to water and sanitation, access to interventions and local health systems. We therefore argue that there will be a need to develop local quantitative expertise to support elimination efforts. If available now, quantitative analyses would provide updated estimates of the burden of disease, assist in the design of locally appropriate control programmes, estimate the effectiveness of current interventions and support ‘real-time’ updates to local operations. Such quantitative tools are increasingly available at an international scale for NTDs, but are rarely tailored to local scenarios. Localised expertise not only provides an opportunity for more relevant analyses, but also has a greater chance of developing positive feedback between data collection and analysis by demonstrating the value of data. This is essential as rational program design relies on good quality data collection. It is also likely that if such infrastructure is provided for NTDs there will be an additional impact on the health system more broadly. Locally tailored quantitative analyses can help achieve sustainable and effective control of NTDs, but also underpin the development of local health care systems