A Systematic Review to Evaluate the Association between Clean Cooking Technologies and Time Use in Low- and Middle-Income Countries

Interventions implementing clean fuels to mitigate household air pollution in low- and middle-income countries have focused on environmental and health outcomes, but few have evaluated time savings. We performed a systematic review, searching for studies of clean fuel interventions that measured time use. A total of 868 manuscripts were identified that met the search criteria, but only 2 met the inclusion criteria. Both were cross-sectional and were conducted in rural India. The first surveyed the female head of household (141 using biogas and 58 using biomass) and reported 1.2 h saved per day collecting fuel and 0.7 h saved cooking, resulting in a combined 28.9 days saved over an entire year. The second surveyed the head of household (37 using biogas and 68 using biomass, 13% female) and reported 1.5 h saved per day collecting fuel, or 22.8 days saved over a year. Based on these time savings, we estimated that clean fuel use could result in a 3.8% or 4.7% increase in daily income, respectively, not including time or costs for fuel procurement. Clean fuel interventions could save users time and money. Few studies have evaluated this potential benefit, suggesting that prospective studies or randomized controlled trials are needed to adequately measure gains

Combining fish and benthic communities into multiple regimes reveals complex reef dynamics

Abstract Coral reefs worldwide face an uncertain future with many reefs reported to transition from being dominated by corals to macroalgae. However, given the complexity and diversity of the ecosystem, research on how regimes vary spatially and temporally is needed. Reef regimes are most often characterised by their benthic components; however, complex dynamics are associated with losses and gains in both fish and benthic assemblages. To capture this complexity, we synthesised 3,345 surveys from Hawai‘i to define reef regimes in terms of both fish and benthic assemblages. Model-based clustering revealed five distinct regimes that varied ecologically, and were spatially heterogeneous by island, depth and exposure. We identified a regime characteristic of a degraded state with low coral cover and fish biomass, one that had low coral but high fish biomass, as well as three other regimes that varied significantly in their ecology but were previously considered a single coral dominated regime. Analyses of time series data reflected complex system dynamics, with multiple transitions among regimes that were a function of both local and global stressors. Coupling fish and benthic communities into reef regimes to capture complex dynamics holds promise for monitoring reef change and guiding ecosystem-based management of coral reefs

Effects of Single and Integrated Water, Sanitation, Handwashing, and Nutrition Interventions on Child Soil-Transmitted Helminth and Giardia infections: A Cluster-Randomized Controlled Trial in Rural Kenya

Helminth and protozoan infections affect more than 1 billion children globally. Improving water quality, sanitation, handwashing, and nutrition could be more sustainable control strategies for parasite infections than mass drug administration, while providing other quality of life benefits

Using quantitative single molecule localization microscopy to optimize multivalent HER2-targeting ligands

IntroductionThe progression-free survival of patients with HER2-positive metastatic breast cancer is significantly extended by a combination of two monoclonal antibodies, trastuzumab and pertuzumab, which target independent epitopes of the extracellular domain of HER2. The improved efficacy of the combination over individual antibody therapies targeting HER2 is still being investigated, and several molecular mechanisms may be in play: the combination downregulates HER2, improves antibody-dependent cell mediated cytotoxicity, and/or affects the organization of surface-expressed antigens, which may attenuate downstream signaling.MethodsBy combining protein engineering and quantitative single molecule localization microscopy (qSMLM), here we both assessed and optimized clustering of HER2 in cultured breast cancer cells.ResultsWe detected marked changes to the cellular membrane organization of HER2 when cells were treated with therapeutic antibodies. When we compared untreated samples to four treatment scenarios, we observed the following HER2 membrane features: (1) the monovalent Fab domain of trastuzumab did not significantly affect HER2 clustering; (2) individual therapy with either trastuzumab or (3) pertuzumab produced significantly higher levels of HER2 clustering; (4) a combination of trastuzumab plus pertuzumab produced the highest level of HER2 clustering. To further enhance this last effect, we created multivalent ligands using meditope technology. Treatment with a tetravalent meditope ligand combined with meditope-enabled trastuzumab resulted in pronounced HER2 clustering. Moreover, compared to pertuzumab plus trastuzumab, at early time points this meditope-based combination was more effective at inhibiting epidermal growth factor (EGF) dependent activation of several downstream protein kinases.DiscussionCollectively, mAbs and multivalent ligands can efficiently alter the organization and activation of the HER2 receptors. We expect this approach could be used in the future to develop new therapeutics

Activating mutations of STAT5B and STAT3 in lymphomas derived from gamma delta-T or NK cells

Peer reviewe

Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR)

Bacterial populations co-ordinate gene expression collectively through quorum sensing (QS), a cell-to-cell communication mechanism employing diffusible signal molecules. The LysR-type transcriptional regulator (LTTR) protein PqsR (MvfR) is a key component of alkyl-quinolone (AQ)-dependent QS in Pseudomonas aeruginosa. PqsR is activated by 2-alkyl-4-quinolones including the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4(1H)-quinolone), its precursor 2-heptyl-4- hydroxyquinoline (HHQ) and their C9 congeners, 2-nonyl-3-hydroxy-4(1H)-quinolone (C9-PQS) and 2-nonyl-4-hydroxyquinoline (NHQ). These drive the autoinduction of AQ biosynthesis and the up-regulation of key virulence determinants as a function of bacterial population density. Consequently, PqsR constitutes a potential target for novel antibacterial agents which attenuate infection through the blockade of virulence. Here we present the crystal structures of the PqsR co-inducer binding domain (CBD) and a complex with the native agonist NHQ. We show that the structure of the PqsR CBD has an unusually large ligand-binding pocket in which a native AQ agonist is stabilized entirely by hydrophobic interactions. Through a ligand-based design strategy we synthesized and evaluated a series of 50 AQ and novel quinazolinone (QZN) analogues and measured the impact on AQ biosynthesis, virulence gene expression and biofilm development. The simple exchange of two isosteres (OH for NH2) switches a QZN agonist to an antagonist with a concomitant impact on the induction of bacterial virulence factor production. We also determined the complex crystal structure of a QZN antagonist bound to PqsR revealing a similar orientation in the ligand binding pocket to the native agonist NHQ. This structure represents the first description of an LTTR-antagonist complex. Overall these studies present novel insights into LTTR ligand binding and ligand-based drug design and provide a chemical scaffold for further anti-P. aeruginosa virulence drug development by targeting the AQ receptor PqsR

Effects of a household air pollution intervention using liquefied petroleum gas stoves, continuous fuel distribution and behavioural messaging on dietary and sodium intake of adult women in Puno, Peru: a randomised controlled trial

Abstract Objective: Household air pollution (HAP) is a widespread environmental exposure worldwide. While several cleaner fuel interventions have been implemented to reduce personal exposures to HAP, it is unclear if cooking with cleaner fuels also affects the choice of meals and dietary intake. Design: Individually randomised, open-label controlled trial of a HAP intervention. We aimed to determine the effect of a HAP intervention on dietary and Na intake. Intervention participants received a liquefied petroleum gas (LPG) stove, continuous fuel delivery and behavioural messaging during 1 year whereas control participants continued with usual cooking practices that involved the use of biomass-burning stoves. Dietary outcomes included energy, energy-adjusted macronutrients and Na intake at baseline, 6 months and 12 months post-randomisation using 24-h dietary recalls and 24-h urine. We used t-tests to estimate differences between arms in the post-randomisation period. Setting: Rural settings in Puno, Peru. Participants: One hundred women aged 25–64 years. Results: At baseline, control and intervention participants were similar in age (47·4 v. 49·5 years) and had similar daily energy (8894·3 kJ v. 8295·5 kJ), carbohydrate (370·8 g v. 373·3 g) and Na intake (4·9 g v. 4·8 g). One year after randomisation, we did not find differences in average energy intake (9292·4 kJ v. 8788·3 kJ; P = 0·22) or Na intake (4·5 g v. 4·6 g; P = 0·79) between control and intervention participants. Conclusions: Our HAP intervention consisting of an LPG stove, continuous fuel distribution and behavioural messaging did not affect dietary and Na intake in rural Peru

Fidelity and Adherence to a Liquefied Petroleum Gas Stove and Fuel Intervention during Gestation: The Multi-Country Household Air Pollution Intervention Network (HAPIN) Randomized Controlled Trial

BACKGROUND: Clean cookstove interventions can theoretically reduce exposure to household air pollution and benefit health, but this requires near-exclusive use of these types of stoves with the simultaneous disuse of traditional stoves. Previous cookstove trials have reported low adoption of new stoves and/or extensive continued traditional stove use. METHODS: The Household Air Pollution Intervention Network (HAPIN) trial randomized 3195 pregnant women in Guatemala, India, Peru, and Rwanda to either a liquefied petroleum gas (LPG) stove and fuel intervention (n = 1590) or to a control (n = 1605). The intervention consisted of an LPG stove and two initial cylinders of LPG, free fuel refills delivered to the home, and regular behavioral messaging. We assessed intervention fidelity (delivery of the intervention as intended) and adherence (intervention use) through to the end of gestation, as relevant to the first primary health outcome of the trial: infant birth weight. Fidelity and adherence were evaluated using stove and fuel delivery records, questionnaires, visual observations, and temperature-logging stove use monitors (SUMs). RESULTS: 1585 women received the intervention at a median (interquartile range) of 8.0 (5.0-15.0) days post-randomization and had a gestational age of 17.9 (15.4-20.6) weeks. Over 96% reported cooking exclusively with LPG at two follow-up visits during pregnancy. Less than 4% reported ever running out of LPG. Complete abandonment of traditional stove cooking was observed in over 67% of the intervention households. Of the intervention households, 31.4% removed their traditional stoves upon receipt of the intervention; among those who retained traditional stoves, the majority did not use them: traditional stove use was detected via SUMs on a median (interquartile range) of 0.0% (0.0%, 1.6%) of follow-up days (median follow-up = 134 days). CONCLUSIONS: The fidelity of the HAPIN intervention, as measured by stove installation, timely ongoing fuel deliveries, and behavioral reinforcement as needed, was high. Exclusive use of the intervention during pregnancy was also high

Designing a comprehensive behaviour change intervention to promote and monitor exclusive use of liquefied petroleum gas stoves for the Household Air Pollution Intervention Network (HAPIN) trial.

INTRODUCTION: Increasing use of cleaner fuels, such as liquefied petroleum gas (LPG), and abandonment of solid fuels is key to reducing household air pollution and realising potential health improvements in low-income countries. However, achieving exclusive LPG use in households unaccustomed to this type of fuel, used in combination with a new stove technology, requires substantial behaviour change. We conducted theory-grounded formative research to identify contextual factors influencing cooking fuel choice to guide the development of behavioural strategies for the Household Air Pollution Intervention Network (HAPIN) trial. The HAPIN trial will assess the impact of exclusive LPG use on air pollution exposure and health of pregnant women, older adult women, and infants under 1 year of age in Guatemala, India, Peru, and Rwanda. METHODS: Using the Capability, Opportunity, Motivation-Behaviour (COM-B) framework and Behaviour Change Wheel (BCW) to guide formative research, we conducted in-depth interviews, focus group discussions, observations, key informant interviews and pilot studies to identify key influencers of cooking behaviours in the four countries. We used these findings to develop behavioural strategies likely to achieve exclusive LPG use in the HAPIN trial. RESULTS: We identified nine potential influencers of exclusive LPG use, including perceived disadvantages of solid fuels, family preferences, cookware, traditional foods, non-food-related cooking, heating needs, LPG awareness, safety and cost and availability of fuel. Mapping formative findings onto the theoretical frameworks, behavioural strategies for achieving exclusive LPG use in each research site included free fuel deliveries, locally acceptable stoves and equipment, hands-on training and printed materials and videos emphasising relevant messages. In the HAPIN trial, we will monitor and reinforce exclusive LPG use through temperature data loggers, LPG fuel delivery tracking, in-home observations and behavioural reinforcement visits. CONCLUSION: Our formative research and behavioural strategies can inform the development, implementation, monitoring and evaluation of theory-informed strategies to promote exclusive LPG use in future stove programmes and research studies. TRIAL REGISTRATION NUMBER: NCT02944682, Pre-results