Long-lasting insecticidal bed nets (LLINs) protect humans from malaria transmission and are fundamental to malaria control worldwide, but little is known of how mosquitoes interact with nets. ...Elucidating LLIN mode of action is essential to maintain or improve efficacy, an urgent need as emerging insecticide resistance threatens their future. Tracking multiple free-flying Anopheles gambiae responding to human-occupied bed nets in a novel large-scale system, we characterised key behaviours and events. Four behavioural modes with different levels of net contact were defined: swooping, visiting, bouncing and resting. Approximately 75% of all activity occurred at the bed net roof where multiple brief contacts were focussed above the occupant's torso. Total flight and net contact times were lower at LLINs than untreated nets but the essential character of the response was unaltered. LLINs did not repel mosquitoes but impacted rapidly: LLIN contact of less than 1 minute per mosquito during the first ten minutes reduced subsequent activity; after thirty minutes, activity at LLINs was negligible. Velocity measurements showed that mosquitoes detected nets, including unbaited untreated nets, prior to contact. This is the most complete characterisation of mosquito-LLIN interactions to date, and reveals many aspects of LLIN mode of action, important for developing the next generation of LLINs.
Understanding how mosquitoes respond to long lasting insecticide treated nets (LLINs) is fundamental to sustaining the effectiveness of this essential control tool. We report on studies with a ...tracking system to investigate behaviour of wild anophelines at an LLIN, in an experimental hut at a rural site in Mwanza, Tanzania.
Groups of adult female mosquitoes (n = 10 per replicate) reared from larvae of a local population, identified as predominantly (95%) Anopheles arabiensis, were released in the hut. An infrared video tracking system recorded flight and net contact activity over 1 h as the mosquitoes attempted to reach a supine human volunteer within a bed net (either a deltamethrin-treated LLIN or an untreated control net). A range of activities, including flight path, position in relation to the bed net and duration of net contact, were quantified and compared between treatments.
The total time that female An. arabiensis spent in flight around LLINs was significantly lower than at untreated nets F(1,10) = 9.26, p = 0.012, primarily due to a substantial reduction in the time mosquitoes spent in persistent 'bouncing' flight F(1,10) = 18.48, p = 0.002. Most activity occurred at the net roof but significantly less so with LLINs (56.8% of total) than untreated nets 85.0%; Χ
(15) = 234.69, p < 0.001. Activity levels at the bed net directly above the host torso were significantly higher with untreated nets (74.2%) than LLINs 38.4%; Χ
(15) = 33.54, p = 0.004. 'Visiting' and 'bouncing' rates were highest above the volunteer's chest in untreated nets (39.9 and 50.4%, respectively) and LLINs 29.9 and 42.4%; Χ
(13) = 89.91, p < 0.001; Χ
(9) = 45.73, p < 0.001. Highest resting rates were above the torso in untreated nets 77%; Χ
(9) = 63.12, p < 0.001, but in LLINs only 33.2% of resting occurred here Χ
(9) = 27.59, p = 0.001, with resting times spread between the short vertical side of the net adjacent to the volunteer's head (21.8%) and feet (16.2%). Duration of net contact by a single mosquito was estimated at 204-290 s on untreated nets and 46-82 s on LLINs. While latency to net contact was similar in both treatments, the reduction in activity over 60 min was significantly more rapid for LLINs F(1,10) = 6.81, p = 0.026, reiterating an 'attract and kill' rather than a repellent mode of action.
The study has demonstrated the potential for detailed investigations of behaviour of wild mosquito populations under field conditions. The results validate the findings of earlier laboratory studies on mosquito activity at LLINs, and reinforce the key role of multiple brief contacts at the net roof as the critical LLIN mode of action.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transmission of Plasmodium falciparum malaria parasites occurs when nocturnal Anopheles mosquito vectors feed on human blood. In Africa, where malaria burden is highest, bednets treated with ...pyrethroid insecticide were highly effective in preventing mosquito bites and reducing transmission, and essential to achieving unprecedented reductions in malaria until 2015 (ref.
). Since then, progress has stalled
, and with insecticidal bednets losing efficacy against pyrethroid-resistant Anopheles vectors
, methods that restore performance are urgently needed to eliminate any risk of malaria returning to the levels seen before their widespread use throughout sub-Saharan Africa
. Here, we show that the primary malaria vector Anopheles gambiae is targeted and killed by small insecticidal net barriers positioned above a standard bednet in a spatial region of high mosquito activity but zero contact with sleepers, opening the way for deploying many more insecticides on bednets than is currently possible. Tested against wild pyrethroid-resistant A. gambiae in Burkina Faso, pyrethroid bednets with organophosphate barriers achieved significantly higher killing rates than bednets alone. Treated barriers on untreated bednets were equally effective, without significant loss of personal protection. Mathematical modelling of transmission dynamics predicted reductions in clinical malaria incidence with barrier bednets that matched those of 'next-generation' nets recommended by the World Health Organization against resistant vectors. Mathematical models of mosquito-barrier interactions identified alternative barrier designs to increase performance. Barrier bednets that overcome insecticide resistance are feasible using existing insecticides and production technology, and early implementation of affordable vector control tools is a realistic prospect.
Abstract
Background
A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained ...dogs could distinguish between people infected with asymptomatic or mild symptoms, and uninfected individuals, and the impact of screening at ports-of-entry.
Methods
Odour samples were collected from adults, and SARS-CoV-2 infection status confirmed using RT-PCR. OSC sensors captured the volatile organic compound (VOC) profile of odour samples. Trained dogs were tested in a double-blind trial to determine their ability to detect differences in VOCs between infected and uninfected individuals, with sensitivity and specificity as the primary outcome. Mathematical modelling was used to investigate the impact of bio-detection dogs for screening.
Results
About, 3921 adults were enrolled in the study and odour samples collected from 1097 SARS-CoV-2 infected and 2031 uninfected individuals. OSC sensors were able to distinguish between SARS-CoV-2 infected individuals and uninfected, with sensitivity from 98% (95% CI 95–100) to 100% and specificity from 99% (95% CI 97–100) to 100%. Six dogs were able to distinguish between samples with sensitivity ranging from 82% (95% CI 76–87) to 94% (95% CI 89–98) and specificity ranging from 76% (95% CI 70–82) to 92% (95% CI 88–96). Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only.
Conclusions
People infected with SARS-CoV-2, with asymptomatic or mild symptoms, have a distinct odour that can be identified by sensors and trained dogs with a high degree of accuracy. Odour-based diagnostics using sensors and/or dogs may prove a rapid and effective tool for screening large numbers of people.
Trial Registration NCT04509713 (clinicaltrials.gov).
Midlife hypertension confers increased risk for cognitive impairment in late life. The sensitive period for risk exposure and extent that risk is mediated through amyloid or vascular-related ...mechanisms are poorly understood. We aimed to identify if, and when, blood pressure or change in blood pressure during adulthood were associated with late-life brain structure, pathology, and cognition.
Participants were from Insight 46, a neuroscience substudy of the ongoing longitudinal Medical Research Council National Survey of Health and Development, a birth cohort that initially comprised 5362 individuals born throughout mainland Britain in one week in 1946. Participants aged 69–71 years received T1 and FLAIR volumetric MRI, florbetapir amyloid-PET imaging, and cognitive assessment at University College London (London, UK); all participants were dementia-free. Blood pressure measurements had been collected at ages 36, 43, 53, 60–64, and 69 years. We also calculated blood pressure change variables between ages. Primary outcome measures were white matter hyperintensity volume (WMHV) quantified from multimodal MRI using an automated method, amyloid-β positivity or negativity using a standardised uptake value ratio approach, whole-brain and hippocampal volumes quantified from 3D-T1 MRI, and a composite cognitive score—the Preclinical Alzheimer Cognitive Composite (PACC). We investigated associations between blood pressure and blood pressure changes at and between 36, 43, 53, 60–64, and 69 years of age with WMHV using generalised linear models with a gamma distribution and log link function, amyloid-β status using logistic regression, whole-brain volume and hippocampal volumes using linear regression, and PACC score using linear regression, with adjustment for potential confounders.
Between May 28, 2015, and Jan 10, 2018, 502 individuals were assessed as part of Insight 46. 465 participants (238 51% men; mean age 70·7 years SD 0·7; 83 18% amyloid-β-positive) were included in imaging analyses. Higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) at age 53 years and greater increases in SBP and DBP between 43 and 53 years were positively associated with WMHV at 69–71 years of age (increase in mean WMHV per 10 mm Hg greater SBP 7%, 95% CI 1–14, p=0·024; increase in mean WMHV per 10 mm Hg greater DBP 15%, 4–27, p=0·0057; increase in mean WMHV per one SD change in SBP 15%, 3–29, p=0·012; increase in mean WMHV per 1 SD change in DBP 15%, 3–30, p=0·017). Higher DBP at 43 years of age was associated with smaller whole-brain volume at 69–71 years of age (−6·9 mL per 10 mm Hg greater DBP, −11·9 to −1·9, p=0·0068), as were greater increases in DBP between 36 and 43 years of age (−6·5 mL per 1 SD change, −11·1 to −1·9, p=0·0054). Greater increases in SBP between 36 and 43 years of age were associated with smaller hippocampal volumes at 69–71 years of age (−0·03 mL per 1 SD change, −0·06 to −0·001, p=0·043). Neither absolute blood pressure nor change in blood pressure predicted amyloid-β status or PACC score at 69–71 years of age.
High and increasing blood pressure from early adulthood into midlife seems to be associated with increased WMHV and smaller brain volumes at 69–71 years of age. We found no evidence that blood pressure affected cognition or cerebral amyloid-β load at this age. Blood pressure monitoring and interventions might need to start around 40 years of age to maximise late-life brain health.
Alzheimer's Research UK, Medical Research Council, Dementias Platform UK, Wellcome Trust, Brain Research UK, Wolfson Foundation, Weston Brain Institute, Avid Radiopharmaceuticals.
Objective
This study evaluated the effectiveness of an automated prompt in the electronic medical record (EMR) to increase screening rates for metabolic conditions and referrals to health education ...and to improve BMI percentile among children with obesity.
Methods
The intervention used an EMR reminder that provided a panel of lab orders (hemoglobin A1c, lipid panel, and alanine aminotransferase) during clinical encounters among pediatric patients ages 10 to 18 with BMI ≥ 95th percentile. Data on demographics, comorbid conditions, BMI, lab results, and health education referrals were analyzed. Cohorts during the year before (n = 3479) and after (n = 3439) workflow implementation were compared.
Results
The distribution of race/ethnicity among children with obesity was 56% Hispanic, 19% White, 11% Filipino, 4% Pacific Islander, 3% Black, and 1% East/South Asian. Orders for metabolic lab tests increased from 2% in the pre‐workflow period to 52% in the post‐workflow period (p < 0.0001). Completed screening rates improved from 1% to 27% (p < 0.0001). Health education referrals increased from 0.4% to 7% (p < 0.0001). We observed a mean change in BMI percentile of −0.13% (p = 0.06).
Conclusions
This study validates the use of an EMR‐based prompt to improve metabolic lab screening and health education referrals among children with obesity. During the limited period of follow‐up, we found no significant change in BMI percentile.
Adaptive evolution occurs when fitness covaries with genetic merit for a trait (or traits). The breeder's equation (BE), in both its univariate and multivariate forms, allows us to predict this ...process by combining estimates of selection on phenotype with estimates of genetic (co)variation. However, predictions are only valid if all factors causal for trait-fitness covariance are measured. Although this requirement will rarely (if ever) be met in practice, it can be avoided by applying Robertson's secondary theorem of selection (STS). The STS predicts evolution by directly estimating the genetic basis of trait-fitness covariation without any explicit model of selection. Here we apply the BE and STS to four morphological traits measured in Soay sheep (Ovis aries) from St. Kilda. Despite apparently positive selection on heritable size traits, sheep are not getting larger. However, although the BE predicts increasing size, the STS does not, which is a discrepancy that suggests unmeasured factors are upwardly biasing our estimates of selection on phenotype. We suggest this is likely to be a general issue, and that wider application of the STS could offer at least a partial resolution to the common discrepancy between naive expectations and observed trait dynamics in natural populations.
Partial cDNA and genomic clones of rat stem cell factor (SCF) have been isolated. Using probes based on the rat sequence, partial and full-length cDNA and genomic clones of human SCF have been ...isolated. Based on the primary structure of the 164 amino acid protein purified from BRL-3A cells, truncated forms of the rat and human proteins have been expressed in E. coli and mammalian cells and have been shown to possess biological activity. SCF is able to augment the proliferation of both myeloid and lymphoid hematopoietic progenitors in bone marrow cultures. SCF exhibits potent synergistic activities in conjunction with colony-stimulating factors, resulting in increased colony numbers and colony size.
Background:
Palliative care is an emerging scope of practice for paramedicine. The COVID-19 pandemic has highlighted the opportunity for emergency settings to deliver palliative and end-of-life care ...to patients wishing to avoid intensive life-sustaining treatment. However, a gap remains in understanding the scope and limitations of current ambulance services’ approach to palliative and end-of-life care.
Aim:
To examine the quality and content of existing Australian palliative paramedicine guidelines with a sample of guidelines from comparable Anglo-American ambulance services.
Design:
We appraised guideline quality using the AGREE II instrument and employed a collaborative qualitative approach to analyse the content of the guidelines.
Data sources:
Eight palliative care ambulance service clinical practice guidelines (five Australian; one New Zealand; one Canadian; one United Kingdom).
Results:
None of the guidelines were recommended by both appraisers for use based on the outcomes of all AGREE II evaluations. Scaled individual domain percentage scores varied across the guidelines: scope and purpose (8%–92%), stakeholder involvement (14%–53%), rigour of development (0%–20%), clarity of presentation (39%–92%), applicability (2%–38%) and editorial independence (0%–38%). Six themes were developed from the content analysis: (1) audience and approach; (2) communication is key; (3) assessing and managing symptoms; (4) looking beyond pharmaceuticals; (5) seeking support; and (6) care after death.
Conclusions:
It is important that ambulance services’ palliative and end-of-life care guidelines are evidence-based and fit for purpose. Future research should explore the experiences and perspectives of key palliative paramedicine stakeholders. Future guidelines should consider emerging evidence and be methodologically guided by AGREE II criteria.
Purpose To cross-validate T1-weighted oxygen-enhanced (OE) MRI measurements of tumor hypoxia with intrinsic susceptibility MRI measurements and to demonstrate the feasibility of translation of the ...technique for patients. Materials and Methods Preclinical studies in nine 786-0-R renal cell carcinoma (RCC) xenografts and prospective clinical studies in eight patients with RCC were performed. Longitudinal relaxation rate changes (∆R1) after 100% oxygen inhalation were quantified, reflecting the paramagnetic effect on tissue protons because of the presence of molecular oxygen. Native transverse relaxation rate (R2*) and oxygen-induced R2* change (∆R2*) were measured, reflecting presence of deoxygenated hemoglobin molecules. Median and voxel-wise values of ∆R1 were compared with values of R2* and ∆R2*. Tumor regions with dynamic contrast agent-enhanced MRI perfusion, refractory to signal change at OE MRI (referred to as perfused Oxy-R), were distinguished from perfused oxygen-enhancing (perfused Oxy-E) and nonperfused regions. R2* and ∆R2* values in each tumor subregion were compared by using one-way analysis of variance. Results Tumor-wise and voxel-wise ∆R1 and ∆R2* comparisons did not show correlative relationships. In xenografts, parcellation analysis revealed that perfused Oxy-R regions had faster native R2* (102.4 sec
vs 81.7 sec
) and greater negative ∆R2* (-22.9 sec
vs -5.4 sec
), compared with perfused Oxy-E and nonperfused subregions (all P < .001), respectively. Similar findings were present in human tumors (P < .001). Further, perfused Oxy-R helped identify tumor hypoxia, measured at pathologic analysis, in both xenografts (P = .002) and human tumors (P = .003). Conclusion Intrinsic susceptibility biomarkers provide cross validation of the OE MRI biomarker perfused Oxy-R. Consistent relationship to pathologic analyses was found in xenografts and human tumors, demonstrating biomarker translation. Published under a CC BY 4.0 license. Online supplemental material is available for this article.
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