Advantages and Limitations of Commercially Available Electrocuting Grids for Studying Mosquito Behaviour.

Mosquito feeding behaviour plays a major role in determining malaria transmission intensity and the impact of specific prevention measures. Human Landing Catch (HLC) is currently the only method that can directly and consistently measure the biting rates of anthropophagic mosquitoes, both indoors and outdoors. However, this method exposes the participant to mosquito-borne pathogens, therefore new exposure-free methods are needed to replace it. Commercially available electrocuting grids (EGs) were evaluated as an alternative to HLC using a Latin Square experimental design in Dar es Salaam, Tanzania. Both HLC and EGs were used to estimate the proportion of human exposure to mosquitoes occurring indoors (πi), as well as its two underlying parameters: the proportion of mosquitoes caught indoors (Pi) and the proportion of mosquitoes caught between the first and last hour when most people are indoors (Pfl). HLC and EGs methods accounted for 69% and 31% of the total number of female mosquitoes caught respectively and both methods caught more mosquitoes outdoors than indoors. Results from the gold standard HLC suggest that An. gambiae s.s. in Dar es Salaam is neither exophagic nor endophagic (Pi ≈ 0.5), whereas An. arabiensis is exophagic (Pi < < 0.5). Both species prefer to feed after 10 pm when most people are indoors (Pfl > >0.5). EGs yielded estimates of Pi for An. gambiae s.s., An. arabiensis and An. coustani, that were approximately equivalent to those with HLC but significantly underestimated Pfl for An. gambiae s.s. and An. coustani. The relative sampling sensitivity of EGs declined over the course of the night (p ≤ 0.001) for all mosquito taxa except An. arabiensis. Commercial EGs sample human-seeking mosquitoes with high sensitivity both indoors and outdoors and accurately measure the propensity of Anopheles malaria vectors to bite indoors rather than outdoors. However, further modifications are needed to stabilize sampling sensitivity over a full nocturnal cycle so that they can be used to survey patterns of human exposure to mosquitoes

Development of the measure of ovarian symptoms and treatment concerns: aiming for optimal measurement of patient-reported symptom benefit with chemotherapy for symptomatic ovarian cancer

OBJECTIVE: The aim of this study was to determine the optimal patient-reported outcome measure (PROM) for assessing symptom benefit in trials of palliative chemotherapy for women with symptomatic ovarian cancer. METHODS: Candidate PROMs were EORTC QLQ-C30 plus ovarian-specific QLQ-OV28, Functional Assessment of Cancer Therapy-Ovarian (FACT-O), FACT Ovarian Symptom Index (FOSI), and gynecologic cancer-specific Symptom Representation Questionnaire. Predefined optimality criteria were inclusion of all symptoms necessary for the specified purpose, recall period covering typical length of palliative chemotherapy, numerical item rating scales, and all necessary symptoms included in a single symptom index. Qualitative and quantitative methods were applied to data from stage 1 of the Gynecologic Cancer Intergroup Symptom Benefit Study to determine the set of necessary symptoms and to objectively assess candidate PROMs against the optimality criteria. RESULTS: Ten necessary symptoms were identified: pain, fatigue, abdominal bloating/discomfort, sleep disturbance, bowel disturbance, nausea and vomiting, shortness of breath, poor appetite, urinary symptoms, and weight changes. Although QLQ-C30 and QLQ-OV28 together cover all these symptoms, they split them into numerous scales, dissipating potential symptom-benefit signal. Conversely, FACT-O does not cover all necessary symptoms and contains many other HRQoL-related items and treatment side effects, diluting potential symptom-benefit signal when summed into scales. Item response scales and composite scoring of all candidate PROMs were suboptimal to our specific purpose. We therefore developed a new PROM, the Measure of Ovarian Symptoms and Treatment (MOST) concerns, to provide optimal measurement for the specified purpose. CONCLUSIONS: This article documents the development of the MOST, a new PROM designed to assess patient-reported benefits and burden as end points in clinical trials of palliative chemotherapy for women with symptomatic ovarian cancer. The validity, reliability, and statistical efficiency of the MOST, relative to the best candidate scales of existing PROMs, will be assessed in the stage 2 of Gynecologic Cancer Intergroup Symptom Benefit Study

Comparison of the CDC Backpack aspirator and the Prokopack aspirator for sampling indoor- and outdoor-resting mosquitoes in southern Tanzania.

BACKGROUND\ud \ud Resting mosquitoes can easily be collected using an aspirating device. The most commonly used mechanical aspirator is the CDC Backpack aspirator. Recently, a simple, and low-cost aspirator called the Prokopack has been devised and proved to have comparable performance. The following study evaluates the Prokopack aspirator compared to the CDC backpack aspirator when sampling resting mosquitoes in rural Tanzania.\ud \ud METHODS\ud \ud Mosquitoes were sampled in- and outdoors of 48 typical rural African households using both aspirators. The aspirators were rotated between collectors and households in a randomized, Latin Square design. Outdoor collections were performed using artificial resting places (large barrel and car tyre), underneath the outdoor kitchen (kibanda) roof and from a drop-net. Data were analysed with generalized linear models.\ud \ud RESULTS\ud \ud The number of mosquitoes collected using the CDC Backpack and the Prokopack aspirator were not significantly different both in- and outdoors (indoors p = 0.735; large barrel p = 0.867; car tyre p = 0.418; kibanda p = 0.519). The Prokopack was superior for sampling of drop-nets due to its smaller size. The number mosquitoes collected per technician was more consistent when using the Prokopack aspirator. The Prokopack was more user-friendly: technicians preferred using the it over the CDC backpack aspirator as it weighs considerably less, retains its charge for longer and is easier to manoeuvre.\ud \ud CONCLUSIONS\ud \ud The Prokopack proved in the field to be more advantageous than the CDC Backpack aspirator. It can be self assembled using simple, low-cost and easily attainable materials. This device is a useful tool for researchers or vector-control surveillance programs operating in rural Africa, as it is far simpler and quicker than traditional means of sampling resting mosquitoes. Further longitudinal evaluations of the Prokopack aspirator versus the gold standard pyrethrum spray catch for indoor resting catches are recommended

Overcoming barriers to engaging socio-economically disadvantaged populations in CHD primary prevention: a qualitative study

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Preventative medicine has become increasingly important in efforts to reduce the burden of chronic disease in industrialised countries. However, interventions that fail to recruit socio-economically representative samples may widen existing health inequalities. This paper explores the barriers and facilitators to engaging a socio-economically disadvantaged (SED) population in primary prevention for coronary heart disease (CHD).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; The primary prevention element of Have a Heart Paisley (HaHP) offered risk screening to all eligible individuals. The programme employed two approaches to engaging with the community: a) a social marketing campaign and b) a community development project adopting primarily face-to-face canvassing. Individuals living in areas of SED were under-recruited via the social marketing approach, but successfully recruited via face-to-face canvassing. This paper reports on focus group discussions with participants, exploring their perceptions about and experiences of both approaches.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Various reasons were identified for low uptake of risk screening amongst individuals living in areas of high SED in response to the social marketing campaign and a number of ways in which the face-to-face canvassing approach overcame these barriers were identified. These have been categorised into four main themes: (1) processes of engagement; (2) issues of understanding; (3) design of the screening service and (4) the priority accorded to screening. The most immediate barriers to recruitment were the invitation letter, which often failed to reach its target, and the general distrust of postal correspondence. In contrast, participants were positive about the face-to-face canvassing approach. Participants expressed a lack of knowledge and understanding about CHD and their risk of developing it and felt there was a lack of clarity in the information provided in the mailing in terms of the process and value of screening. In contrast, direct face-to-face contact meant that outreach workers could explain what to expect. Participants felt that the procedure for uptake of screening was demanding and inflexible, but that the drop-in sessions employed by the community development project had a major impact on recruitment and retention.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; Socio-economically disadvantaged individuals can be hard-to-reach; engagement requires strategies tailored to the needs of the target population rather than a population-wide approach.&lt;/p&gt

Artificial intelligence in cancer imaging: Clinical challenges and applications

Judgement, as one of the core tenets of medicine, relies upon the integration of multilayered data with nuanced decision making. Cancer offers a unique context for medical decisions given not only its variegated forms with evolution of disease but also the need to take into account the individual condition of patients, their ability to receive treatment, and their responses to treatment. Challenges remain in the accurate detection, characterization, and monitoring of cancers despite improved technologies. Radiographic assessment of disease most commonly relies upon visual evaluations, the interpretations of which may be augmented by advanced computational analyses. In particular, artificial intelligence (AI) promises to make great strides in the qualitative interpretation of cancer imaging by expert clinicians, including volumetric delineation of tumors over time, extrapolation of the tumor genotype and biological course from its radiographic phenotype, prediction of clinical outcome, and assessment of the impact of disease and treatment on adjacent organs. AI may automate processes in the initial interpretation of images and shift the clinical workflow of radiographic detection, management decisions on whether or not to administer an intervention, and subsequent observation to a yet to be envisioned paradigm. Here, the authors review the current state of AI as applied to medical imaging of cancer and describe advances in 4 tumor types (lung, brain, breast, and prostate) to illustrate how common clinical problems are being addressed. Although most studies evaluating AI applications in oncology to date have not been vigorously validated for reproducibility and generalizability, the results do highlight increasingly concerted efforts in pushing AI technology to clinical use and to impact future directions in cancer care

Reduction of metastasis using a non-volatile buffer

The tumor microenvironment is acidic as a consequence of upregulated glycolysis and poor perfusion and this acidity, in turn, promotes invasion and metastasis. We have recently demonstrated that chronic consumption of sodium bicarbonate increased tumor pH and reduced spontaneous and experimental metastases. This occurred without affecting systemic pH, which was compensated. Additionally, these prior data did not rule out the possibility that bicarbonate was working though effects on carbonic anhydrase, and not as a buffer per se. Here, we present evidence that chronic ingestion of a non-volatile buffer, 2-imidazole-1-yl-3-ethoxycarbonylpropionic acid (IEPA) with a pKa of 6.9 also reduced metastasis in an experimental PC3M prostate cancer mouse model. Animals (n = 30) were injected with luciferase expressing PC3M prostate cancer cells either subcutaneously (s.c., n = 10) or intravenously (i.v., n = 20). Four days prior to inoculations, half of the animals for each experiment were provided drinking water containing 200 mM IEPA buffer. Animals were imaged weekly to follow metastasis, and these data showed that animals treated with IEPA had significantly fewer experimental lung metastasis compared to control groups (P < 0.04). Consistent with prior work, the pH of treated tumors was elevated compared to controls. IEPA is observable by in vivo magnetic resonance spectroscopy and this was used to measure the presence of IEPA in the bladder, confirming that it was orally available. The results of this study indicate that metastasis can be reduced by non-volatile buffers as well as bicarbonate and thus the effect appears to be due to pH buffering per se

Exploiting Anopheles responses to thermal, odour and visual stimuli to improve surveillance and control of malaria

Mosquito surveillance and control are at the heart of efforts to eliminate malaria, however, there remain significant gaps in our understanding of mosquito behaviour that impede innovation. We hypothesised that a combination of human-associated stimuli could be used to attract and kill malaria vectors more successfully than individual stimuli, and at least as well as a real human. To test this in the field, we quantified Anopheles responses to olfactory, visual and thermal stimuli in Burkina Faso using a simple adhesive trap. Traps baited with human odour plus high contrast visual stimuli caught more Anopheles than traps with odour alone, showing that despite their nocturnal habit, malaria vectors make use of visual cues in host-seeking. The best performing traps, however, combined odour and visual stimuli with a thermal signature in the range equivalent to human body temperature. When tested against a human landing catch during peak mosquito abundance, this “host decoy” trap caught nearly ten times the number of Anopheles mosquitoes caught by a human collector. Exploiting the behavioural responses of mosquitoes to the entire suite of host stimuli promises to revolutionise vector surveillance and provide new paradigms in disease control

Status of insecticide susceptibility in Anopheles arabiensis from Mwea rice irrigation scheme, Central Kenya

BACKGROUND: Control of the Anopheline mosquito vectors of malaria by use of insecticides has been shown to impact on both morbidity and mortality due to this disease. Evidence of insecticide resistance in different settings necessitates surveillance studies to allow prompt detection of resistance should it arise and thus enable its management. Possible resistance by Anopheles arabiensis mosquitoes from Mwea rice irrigation scheme in Central Kenya to insecticides in the four classes of insecticides approved by WHO for indoor residual spraying was investigated. METHODS: Susceptibility to DDT (an organochlorine), fenitrothion (an organophosphate), bendiocarb (a carbamate), lambdacyhalothrin and permethrin (both pyrethroids) was tested using standard WHO diagnostic bioassay kits. Bioassays were performed on non-blood fed mosquitoes one- to three-day old. Knockdown was recorded every 10 min and mortality 24 h post-exposure was noted. RESULTS: Mortality 24 h post-exposure was 100% for all insecticides except for lambdacyhalothrin, which averaged 99.46%. Knockdown rates at 10 min intervals were not significantly different between the Mwea population and the susceptible KISUMU strain of Anopheles gambiae sensu stricto control. The KDT(50 )and KDT(95 )values for the Mwea population were either lower than those for the control or higher by factors of no more than 2 for most comparisons and compared well with those of An. gambiae sensu lato categorized as susceptible in other studies. CONCLUSION: These results suggest that the Mwea population of An. arabiensis is susceptible to all the insecticides tested. This implies that vector control measures employing any of these insecticides would not be hampered by resistance

British container breeding mosquitoes: the impact of urbanisation and climate change on community composition and phenology

The proliferation of artificial container habitats in urban areas has benefitted urban adaptable mosquito species globally. In areas where mosquitoes transmit viruses and parasites, it can promote vector population productivity and fuel mosquito-borne disease outbreaks. In Britain, storage of water in garden water butts is increasing, potentially expanding mosquito larval habitats and influencing population dynamics and mosquito-human contact. Here we show that the community composition, abundance and phenology of mosquitoes breeding in experimental water butt containers were influenced by urbanisation. Mosquitoes in urban containers were less species-rich but present in significantly higher densities (100.4±21.3) per container than those in rural containers (77.7±15.1). Urban containers were dominated by Culex pipiens (a potential vector of West Nile Virus [WNV]) and appear to be increasingly exploited by Anopheles plumbeus (a human-biting potential WNV and malaria vector). Culex phenology was influenced by urban land use type, with peaks in larval abundances occurring earlier in urban than rural containers. Among other factors, this was associated with an urban heat island effect which raised urban air and water temperatures by 0.9°C and 1.2°C respectively. Further increases in domestic water storage, particularly in urban areas, in combination with climate changes will likely alter mosquito population dynamics in the UK