Mapping trends in insecticide resistance phenotypes in African malaria vectors

Mitigating the threat of insecticide resistance in African malaria vector populations requires comprehensive information about where resistance occurs, to what degree, and how this has changed over time. Estimating these trends is complicated by the sparse, heterogeneous distribution of observations of resistance phenotypes in field populations. We use 6,423 observations of the prevalence of resistance to the most important vector control insecticides to inform a Bayesian geostatistical ensemble modelling approach, generating fine-scale predictive maps of resistance phenotypes in mosquitoes from the Anopheles gambiae complex across Africa. Our models are informed by a suite of 111 predictor variables describing potential drivers of selection for resistance. Our maps show alarming increases in the prevalence of resistance to pyrethroids and DDT across sub-Saharan Africa from 2005 to 2017, with mean mortality following insecticide exposure declining from almost 100% to less than 30% in some areas, as well as substantial spatial variation in resistance trends

Indoor residual spraying for malaria control in sub-Saharan Africa 1997 to 2017: an adjusted retrospective analysis

Indoor residual spraying (IRS) is a key tool for controlling and eliminating malaria by targeting vectors. To support the development of effective intervention strategies it is important to understand the impact of vector control tools on malaria incidence and on the spread of insecticide resistance. In 2006, the World Health Organization (WHO) stated that countries should report on coverage and impact of IRS, yet IRS coverage data are still sparse and unspecific. Here, the subnational coverage of IRS across sub‑Saharan Africa for the four main insecticide classes from 1997 to 2017 were estimated

Study protocol : Minimum effective low dose: anti-human thymocyte globulin (MELD-ATG): phase II, dose ranging, efficacy study of antithymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes

Introduction Type 1 diabetes (T1D) is a chronic autoimmune disease, characterised by progressive destruction of the insulin-producing beta cells of the pancreas. One immunosuppressive agent that has recently shown promise in the treatment of new-onset T1D subjects aged 12-45 years is antithymocyte globulin (ATG), Thymoglobuline, encouraging further exploration in lower age groups. Methods and analysis Minimal effective low dose (MELD)-ATG is a phase 2, multicentre, randomised, double-blind, placebo-controlled, multiarm parallel-group trial in participants 5-25 years diagnosed with T1D within 3-9 weeks of planned treatment day 1. A total of 114 participants will be recruited sequentially into seven different cohorts with the first cohort of 30 participants being randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg and 0.1 mg/kg ATG total dose in a 1:1:1:1:1 allocation ratio. The next six cohorts of 12-15 participants will be randomised to placebo, 2.5 mg/kg, and one or two selected middle ATG total doses in a 1:1:1:1 or 1:1:1 allocation ratio, as dependent on the number of middle doses, given intravenously over two consecutive days. The primary objective will be to determine the changes in stimulated C-peptide response over the first 2 hours of a mixed meal tolerance test at 12 months for 2.5 mg/kg ATG arm vs the placebo. Conditional on finding a significant difference at 2.5 mg/kg, a minimally effective dose will be sought. Secondary objectives include the determination of the effects of a particular ATG treatment dose on (1) stimulated C-peptide, (2) glycated haemoglobin, (3) daily insulin dose, (4) time in range by intermittent continuous glucose monitoring measures, (5) fasting and stimulated dry blood spot (DBS) C-peptide measurements. Ethics and dissemination MELD-ATG received first regulatory and ethical approvals in Belgium in September 2020 and from the German and UK regulators as of February 2021. The publication policy is set in the INNODIA (An innovative approach towards understanding and arresting Type 1 diabetes consortium) grant agreement (www.innodia.eu).Peer reviewe

Clinimetric evaluation of active range of motion measures in patients with non-specific neck pain: a systematic review

The study is to provide a critical analysis of the research literature on clinimetric properties of instruments that can be used in daily practice to measure active cervical range of motion (ACROM) in patients with non-specific neck pain. A computerized literature search was performed in Medline, Cinahl and Embase from 1982 to January 2007. Two reviewers independently assessed the clinimetric properties of identified instruments using a criteria list. The search identified a total of 33 studies, investigating three different types of measurement instruments to determine ACROM. These instruments were: (1) different types of goniometers/inclinometers, (2) visual estimation, and (3) tape measurements. Intra- and inter-observer reliability was demonstrated for the cervical range of motion instrument (CROM), Cybex electronic digital instrument (EDI-320) and a single inclinometer. The presence of agreement was assessed for the EDI-320 and a single inclinometer. The CROM received a positive rating for construct validity. When clinical acceptability is taken into account both the CROM and the single inclinometer can be considered appropriate instruments for measuring the active range of motion in patients with non-specific neck pain in daily practice. Reliability is the aspect most frequently evaluated. Agreement, validity and responsiveness are documented less frequently

INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes

Background The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of phase 2 clinical trials. Methods In this context, we have developed a Master Protocol, based on the “backbone” of the INNODIA natural history study, which we believe could improve the delivery of phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in individuals with newly diagnosed type 1 diabetes. Although many IMPs have demonstrated potential efficacy in phase 2 studies, few subsequent phase 3 studies have confirmed these benefits. Currently, phase 2 drug development for this indication is limited by poor evaluation of drug dosage and lack of mechanistic data to understand variable responses to the IMPs. Identification of biomarkers which might permit more robust stratification of participants at baseline has been slow. Discussion The Master Protocol provides (1) standardised assessment of efficacy and safety, (2) comparable collection of mechanistic data, (3) the opportunity to include adaptive designs and the use of shared control groups in the evaluation of combination therapies, and (4) benefits of greater understanding of endpoint variation to ensure more robust sample size calculations and future baseline stratification using existing and novel biomarkers

Does labelling a food as 'light' vs. 'filling' influence intake and sensory-specific satiation?

Although several studies have investigated the influence of nutrition labelling on food intake, the effect of labels indicating a food's satiating power on food intake and sensory-specific satiation (SSS) is poorly understood. We investigated whether providing information about the satiating power of a meal affects intake and SSS. Participants (19 men and 18 women) consumed the same test meal of pasta salad ad libitum on two occasions, once described as 'light' and once as 'filling'. SSS was determined as the change in liking of the flavor and desire to eat the test meal before and after consumption, compared to seven uneaten foods. As hypothesized, intake increased by a mean (±SD) of 31 ± 59 g and 42 ± 81 kcal when the meal was labelled 'light' as opposed to 'filling' (p < 0.01). After eating, ratings for both liking and desire to eat decreased significantly more for the test meal than for the uneaten control foods (p < 0.001), demonstrating SSS. These relative changes in liking and desire to eat did not differ between the label conditions, despite differences in intake. Furthermore, accounting for amount consumed, the magnitude of SSS did not differ between the label conditions, which suggests that it did not explain the effect of the labels on intake. This study shows that labels indicating the satiating power of a meal can affect intake, warranting caution in the use of such labels on products intended to reduce intake

Does labelling a food as 'light' vs. 'filling' influence intake and sensory-specific satiation?

Although several studies have investigated the influence of nutrition labelling on food intake, the effect of labels indicating a food's satiating power on food intake and sensory-specific satiation (SSS) is poorly understood. We investigated whether providing information about the satiating power of a meal affects intake and SSS. Participants (19 men and 18 women) consumed the same test meal of pasta salad ad libitum on two occasions, once described as 'light' and once as 'filling'. SSS was determined as the change in liking of the flavor and desire to eat the test meal before and after consumption, compared to seven uneaten foods. As hypothesized, intake increased by a mean (±SD) of 31 ± 59 g and 42 ± 81 kcal when the meal was labelled 'light' as opposed to 'filling' (p < 0.01). After eating, ratings for both liking and desire to eat decreased significantly more for the test meal than for the uneaten control foods (p < 0.001), demonstrating SSS. These relative changes in liking and desire to eat did not differ between the label conditions, despite differences in intake. Furthermore, accounting for amount consumed, the magnitude of SSS did not differ between the label conditions, which suggests that it did not explain the effect of the labels on intake. This study shows that labels indicating the satiating power of a meal can affect intake, warranting caution in the use of such labels on products intended to reduce intake

Child-reported vegetable neophobia is associated with risk avoidance for distaste in children aged 4-15 years

Children who are food neophobic and/or picky eaters often refuse intake of especially fruits and vegetables, thereby narrowing their dietary variety and impairing the quality of their food intake. In this preregistered study, we investigated whether picky eating and food neophobia are related to bitter taste sensitivity (PROP taster status) and risk avoidance for distaste. A total of 367 children (201 girls; M age = 8.7 years, range: 4-15 years) participated in the study. They completed the vegetable neophobia subscale of the fruit and vegetable neophobia instrument (FVNI). A caregiver completed the child food rejection scale (CFRS), a parent-report measure of food neophobia and picky eating. Children's bitter taste sensitivity was measured with a PROP (6-n-propylthiouracil) taste strip, and the children completed a modified Children's Gambling Task (Candy Gambling Game) to measure risk avoidance for distaste. In this task, children could select cards from a risky deck (chance of winning two tasty cherry-flavoured jelly beans, but also the risk of getting a distasteful soap-flavoured jelly bean) or a safe deck (chance of winning one tasty jelly bean or no jelly bean). The results show that picky eating and food neophobia (either parent- or self-reported) are not related to PROP taster status. However, children who self-reported higher levels of vegetable neophobia showed less risky choice behaviour in the Candy Gambling Game, although this relationship was not found with parent-reported food neophobia. We conclude that risk avoidance for distaste, but not taste function, is associated with children's self-reported food rejection tendencies. To broaden the food repertoire of children high in food neophobia, it might be useful to reduce the perceived risk of distaste, when introducing a novel food or meal