Water, Sanitation and Hygiene (WASH) and environmental risk factors for soil-transmitted helminth intensity of infection in Timor-Leste, using real time PCR

Background: No investigations have been undertaken of risk factors for intensity of soil-transmitted helminth (STH) infection in Timor-Leste. This study provides the first analysis of risk factors for intensity of STH infection, as determined by quantitative PCR (qPCR), examining a broad range of water, sanitation and hygiene (WASH) and environmental factors, among communities in Manufahi District, Timor-Leste. Methods: A baseline cross-sectional survey of 18 communities was undertaken as part of a cluster randomised controlled trial, with additional identically-collected data from six other communities. qPCR was used to assess STH infection from stool samples, and questionnaires administered to collect WASH, demographic, and socioeconomic data. Environmental information was obtained from open-access sources and linked to infection outcomes. Mixed-effects multinomial logistic regression was undertaken to assess risk factors for intensity of Necator americanus and Ascaris infection. Results: 2152 participants provided stool and questionnaire information for this analysis. In adjusted models incorporating WASH, demographic and environmental variables, environmental variables were generally associated with infection intensity for both N. americanus and Ascaris spp. Precipitation (in centimetres) was associated with increased risk of moderate-intensity (adjusted relative risk [ARR] 6.1; 95% confidence interval [CI] 1.9–19.3) and heavy-intensity (ARR 6.6; 95% CI 3.1–14.1) N. americanus infection, as was sandy-loam soil around households (moderate-intensity ARR 2.1; 95% CI 1.0–4.3; heavy-intensity ARR 2.7; 95% CI 1.6–4.5; compared to no infection). For Ascaris, alkaline soil around the household was associated with reduced risk of moderate-intensity infection (ARR 0.21; 95% CI 0.09–0.51), and heavy-intensity infection (ARR 0.04; 95% CI 0.01–0.25). Few WASH risk factors were significant. Conclusion: In this high-prevalence setting, strong risk associations with environmental factors indicate that anthelmintic treatment alone will be insufficient to interrupt STH transmission, as conditions are favourable for ongoing environmental transmission. Integrated STH control strategies should be explored as a priorityACAC is an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellow (1058878), JSM is an Australian NHMRC Practitioner Fellow, and DJG is an Australian NHMRC Career Development Fellow. This work is funded by an NHMRC Partnership project in collaboration with WaterAid Australia. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Roundtable: Transcultural fan studies in practice: a conversation

At the end of 2018, a group of fan scholars led by Lori Morimoto journeyed to Japan for a fan studies field trip. The purpose was multifaceted: to speak at a symposium on transcultural popular culture; to bring together fans and fandom studies from both sides of the Pacific; and to augment their classrooms with practical experience. Eight participants share their experiences and reflect on what it means to be a transcultural fan scholar at the dawning of the 2020s

Water, Sanitation, and Hygiene (WASH): a critical component for sustainable soil-transmitted helminth and schistosomiasis control

Soil-transmitted helminths (STH) and schistosomes are parasites that affect the world’s poorest people, causing losses of up to 39 million and 70 million disability adjusted life years (DALYs) respectively. The World Health Organization (WHO) is at the forefront of developing policy for the control of STH and schistosomiasis, advocating for chemotherapy as the cornerstone of control, with the objective of reducing infection-associated morbidity. Global uptake of chemotherapy with albendazole or mebendazole for STH and praziquantel for schistosomiasis has significantly increased and remains the principal control strategy. It is cost-effective and reduces STH and schistosome infections in human hosts.SJC is funded by an Australian Postgraduate Award and a University of Queensland Advantage Scholarship, ACAC is an Australian National Health and Medical Research Council (NHMRC) Career Development Fellow (631619), RJSM is funded by a Post-doctoral Research Fellowship from the University of Queensland (41795457), JSM is an Australian National Health and Medical Research Council Practitioner Fellow, and DJG is an Australian Research Council (DECRA) Fellow. This work is funded by an NHMRC Partnership project in collaboration with WaterAid Australia

Pharmacokinetics, safety and tolerability of olaparib and temozolomide for recurrent glioblastoma: results of the phase I OPARATIC trial

Background: The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib potentiated radiation and temozolomide chemotherapy in pre-clinical glioblastoma models but brain penetration was poor. Clinically, PARP inhibitors exacerbate the hematological side-effects of temozolomide. The OPARATIC trial was conducted to measure penetration of recurrent glioblastoma by olaparib, and assess the safety and tolerability of its combination with temozolomide. Methods: Pre-clinical pharmacokinetic studies evaluated olaparib tissue distribution in rats and tumor-bearing mice. Adult patients with recurrent glioblastoma received various doses and schedules of olaparib and low-dose temozolomide in a 3+3 design. Suitable patients received olaparib prior to neurosurgical resection; olaparib concentrations in plasma, tumour core and tumour margin specimens were measured by mass spectrometry. A dose expansion cohort tested tolerability and efficacy of the recommended phase II dose (RP2D). Radiosensitizing effects of olaparib were measured by clonogenic survival in glioblastoma cell lines. Results: Olaparib was a substrate for multi-drug resistance protein-1 and showed no brain penetration in rats but was detected in orthotopic glioblastoma xenografts. Clinically, olaparib was detected in 71/71 tumor core specimens (27 patients, median 496nM) and 21/21 tumor margin specimens (9 patients, median 512.3nM). Olaparib exacerbated TMZ-related hematological toxicity, necessitating intermittent dosing. RP2D was olaparib 150mg (3 days/week) with TMZ 75mg/m2 daily for 42 days. Fourteen (36%) of 39 evaluable patients were progression-free at 6 months. Olaparib radiosensitized six glioblastoma cell lines at clinically relevant concentrations of 100 and 500 nM. Conclusions: Olaparib reliably penetrates recurrent glioblastoma at radiosensitizing concentrations, supporting further clinical development and highlighting the need for better pre-clinical models

East Bay Coalition for the Homeless: Branding Study and Marketing Strategy

There are a number of potential positioning strategies. The two which make the most sense for the EBCH are to “position the EBCH away from others in the category” and to “position the EBCH as unique.” These strategies have the advantage of setting the EBCH apart from the other organizations that address homelessness. Occupying its own “position” in the minds of potential and current donors is not only an effective communications/marketing strategy but also a less costly one because it avoids head-to-head competition and comparisons

Epidemiology of Streptococcus dysgalactiae subsp. equisimilis in Tropical Communities, Northern Australia

This subspecies is common in communities with high rates of streptococcal disease, and its epidemiology differs from that of Streptococcus pyogenes

Investigations into the association between soil-transmitted helminth infections, haemoglobin and child development indices in Manufahi District, Timor-Leste

Background: Timor-Leste has a high prevalence of soil-transmitted helminth (STH) infections. High proportions of the population have been reported as being anaemic, and extremely high proportions of children as stunted or wasted. There have been no published analyses of the contributions of STH to these morbidity outcomes in Timor-Leste. Methods: Using baseline cross-sectional data from 24 communities (18 communities enrolled in a cluster randomised controlled trial, and identically-collected data from six additional communities), analyses of the association between STH infections and community haemoglobin and child development indices were undertaken. Stool samples were assessed for STH using qPCR and participant haemoglobin, heights and weights were measured. Questionnaires were administered to collect demographic and socioeconomic data. Intensity of infection was categorised using correlational analysis between qPCR quantification cycle values and eggs per gram of faeces equivalents, with algorithms generated from seeding experiments. Mixed-effects logistic and multinomial regression were used to assess the association between STH infection intensity classes and anaemia, and child stunting, wasting and underweight. Results: Very high stunting (60%), underweight (60%), and wasting (20%) in children, but low anaemia prevalence (15%), were found in the study communities. STH were not significantly associated with morbidity outcomes. Male children and those in the poorest socioeconomic quintile were significantly more likely to be moderately and severely stunted. Male children were significantly more likely than female children to be severely underweight. Increasing age was also a risk factor for being underweight. Few risk factors emerged for wasting in these analyses. Conclusions: According to World Health Organization international reference standards, levels of child morbidity in this population constitute a public health emergency, although the international reference standards need to be critically evaluated for their applicability in Timor-Leste. Strategies to improve child development and morbidity outcomes, for example via nutrition and iron supplementation programmes, are recommended for these communities. Despite the apparent lack of an association from STH in driving anaemia, stunting, wasting and underweight, high endemicity suggests a need for STH control strategies.ACAC is an Australian National Health and Medical Research Council (NHMRC) Senior Research Fellow (1058878), JSM is an Australian NHMRC Practitioner Fellow, and DJG is an Australian NHMRC Career Development Fellow. This work is funded by an NHMRC Partnership project in collaboration with WaterAid Australia

Effectiveness of State and Federal Government Agreements with Major Credit Card and Shipping Companies to Block Illegal Internet Cigarette Sales

Most Internet vendors offer tax-free cigarettes making them cheaper than those sold at stores. This undermines the impact that higher prices have upon reducing consumption. Most Internet tobacco sales have violated taxation and youth access laws, which led to landmark voluntary agreements in 2005 with the major credit card companies and major private shippers to ban payment transactions and shipments for all Internet cigarette sales