An Integrated Object Model and Method Framework for Subject-Centric e-Research Applications

A framework that integrates an object model, research methods (workflows), the capture of experimental data sets and the provenance of those data sets for subject-centric research is presented. The design of the Framework object model draws on and extends pre-existing object models in the public domain. In particular the Framework tracks the state and life cycle of a subject during an experimental method, provides for reusable subjects, primary, derived and recursive data sets of arbitrary content types, and defines a user-friendly and practical scheme for citably identifying information in a distributed environment. The Framework is currently used to manage neuroscience Magnetic Resonance and microscopy imaging data sets in both clinical and basic neuroscience research environments. The Framework facilitates multi-disciplinary and collaborative subject-based research, and extends earlier object models used in the research imaging domain. Whilst the Framework has been explicitly validated for neuroimaging research applications, it has broader application to other fields of subject-centric research

A cost-effective, community-based, mosquito-trapping scheme that captures spatial and temporal heterogeneities of malaria transmission in rural Zambia

Background Monitoring mosquito population dynamics is essential to guide selection and evaluation of malaria vector control interventions but is typically implemented by mobile, centrally-managed teams who can only visit a limited number of locations frequently enough to capture longitudinal trends. Community-based (CB) mosquito trapping schemes for parallel, continuous monitoring of multiple locations are therefore required that are practical, affordable, effective, and reliable. Methods A CB surveillance scheme, with a monthly sampling and reporting cycle for capturing malaria vectors, using Centers for Disease Control and Prevention light traps (LT) and Ifakara Tent Traps (ITT), were conducted by trained community health workers (CHW) in 14 clusters of households immediately surrounding health facilities in rural south-east Zambia. At the end of the study, a controlled quality assurance (QA) survey was conducted by a centrally supervised expert team using human landing catch (HLC), LT and ITT to evaluate accuracy of the CB trapping data. Active surveillance of malaria parasite infection rates amongst humans was conducted by CHWs in the same clusters to determine the epidemiological relevance of these CB entomological surveys. Results CB-LT and CB-ITT exhibited relative sampling efficiencies of 50 and 7%, respectively, compared with QA surveys using the same traps. However, cost per sampling night was lowest for CB-LT ($13.6), followed closely by CB-ITT ($18.0), both of which were far less expensive than any QA survey (HLC: $138, LT:$289, ITT: $269). Cost per specimen of Anopheles funestus captured was lowest for CB-LT ($5.3), followed by potentially hazardous QA-HLC ($10.5) and then CB-ITT ($28.0), all of which were far more cost-effective than QA-LT ($141) and QA-ITT ($168). Time-trends of malaria diagnostic positivity (DP) followed those of An. funestus density with a one-month lag and the wide range of mean DP across clusters was closely associated with mean densities of An. funestus caught by CB-LT (P < 0.001). Conclusions CB trapping schemes appear to be far more affordable, epidemiologically relevant and cost-effective than centrally supervised trapping schemes and may well be applicable to enhance intervention trials and even enable routine programmatic monitoring of vector population dynamics on unprecedented national scales

An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns.

ABSTRACT: BACKGROUND: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance. Methodology An intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. RESULTS: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153US$versus 187US$ per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373). Discussion and conclusion CB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly

Persistently high estimates of late night, indoor exposure to malaria vectors despite high coverage of insecticide treated nets

Background It has been speculated that widespread and sustained use of insecticide treated bed nets (ITNs) for over 10 years in Asembo, western Kenya, may have selected for changes in the location (indoor versus outdoor) and time (from late night to earlier in the evening) of biting of the predominant species of human malaria vectors (Anopheles funestus, Anopheles gambiae sensu stricto, and Anopheles arabiensis). Methods Mosquitoes were collected by human landing catches over a six week period in June and July, 2011, indoors and outdoors from 17 h to 07 h, in 75 villages in Asembo, western Kenya. Collections were separated by hour of the night, and mosquitoes were identified to species and tested for sporozoite infection with Plasmodium falciparum. A subset was dissected to determine parity. Human behavior (time going to bed and rising, time spent indoors and outdoors) was quantified by cross-sectional survey. Data from past studies of a similar design and in nearby settings, but conducted before the ITN scale up commenced in the early 2000s, were compared with those from the present study. Results Of 1,960 Anopheles mosquitoes collected in 2011, 1,267 (64.6%) were morphologically identified as An. funestus, 663 (33.8%) as An. gambiae sensu lato (An. gambiae s.s. and An. arabiensis combined), and 30 (1.5%) as other anophelines. Of the 663 An. gambiae s.l. collected, 385 were successfully tested by PCR among which 235 (61.0%) were identified as An. gambiae s.s. while 150 (39.0%) were identified as An. arabiensis. Compared with data collected before the scale-up of ITNs, daily entomological inoculation rates (EIRs) were consistently lower for An. gambiae s.l. (indoor EIR = 0.432 in 1985–1988, 0.458 in 1989–1990, 0.023 in 2011), and An. arabiensis specifically (indoor EIR = 0.532 in 1989–1990, 0.039 in 2009, 0.006 in 2011) but not An. funestus (indoor EIR = 0.029 in 1985–1988, 0.147 in 1989–1990, 0.010 in 2009 and 0.103 in 2011). Sporozoite rates were lowest in 2009 but rose again in 2011. Compared with data collected before the scale-up of ITNs, An. arabiensis and An. funestus were more likely to bite outdoors and/or early in the evening (p 90% of exposure of non-ITN users to mosquito bites occurring while people were indoors in all years. The proportion of bites occurring among non-ITN users while they were asleep was ≥90% for all species except for An. arabiensis. For this species, 97% of bites occurred while people were asleep in 1989–1990 while in 2009 and 2011, 80% and 84% of bites occurred while people were asleep for those not using ITNs. Assuming ITNs prevent a theoretical maximum of 93.7% of bites, it was estimated that 64-77% of bites would have occurred among persons using nets while they were asleep in 1989–1990, while 20-52% of bites would have occurred among persons using nets while they were asleep in 2009 and 2011. Conclusions This study found no evidence to support the contention that populations of Anopheles vectors of malaria in Asembo, western Kenya, are exhibiting departures from the well-known pattern of late night, indoor biting characteristic of these typically highly anthropophilic species. While outdoor, early evening transmission likely does occur in western Kenya, the majority of transmission still occurs indoors, late at night. Therefore, malaria control interventions such as ITNs that aim to reduce indoor biting by mosquitoes should continue to be prioritized

The epidemiology of residual Plasmodium falciparum malaria transmission and infection burden in an African city with high coverage of multiple vector control measures.

BACKGROUND In the Tanzanian city of Dar es Salaam, high coverage of long-lasting insecticidal nets (LLINs), larvicide application (LA) and mosquito-proofed housing, was complemented with improved access to artemisinin-based combination therapy and rapid diagnostic tests by the end of 2012. METHODS Three rounds of city-wide, cluster-sampled cross-sectional surveys of malaria parasite infection status, spanning 2010 to 2012, were complemented by two series of high-resolution, longitudinal surveys of vector density. RESULTS Larvicide application using a granule formulation of Bacillus thuringiensis var. israelensis (Bti) had no effect upon either vector density (P = 0.820) or infection prevalence (P = 0.325) when managed by a private-sector contractor. Infection prevalence rebounded back to 13.8 % in 2010, compared with <2 % at the end of a previous Bti LA evaluation in 2008. Following transition to management by the Ministry of Health and Social Welfare (MoHSW), LA consistently reduced vector densities, first using the same Bti granule in early 2011 [odds ratio (OR) (95 % confidence interval (CI)) = 0.31 (0.14, 0.71), P = 0.0053] and then a pre-diluted aqueous suspension formulation from mid 2011 onwards [OR (95 % CI) = 0.15 (0.07, 0.30), P ≪ 0.000001]. While LA by MoHSW with the granule formulation was associated with reduced infection prevalence [OR (95 % CI) = 0.26 (0.12, 0.56), P = 0.00040], subsequent liquid suspension use, following a mass distribution to achieve universal coverage of LLINs that reduced vector density [OR (95 % CI) = 0.72 (0.51, 1.01), P = 0.057] and prevalence [OR (95 % CI) = 0.80 (0.69, 0.91), P = 0.0013], was not associated with further prevalence reduction (P = 0.836). Sleeping inside houses with complete window screens only reduced infection risk [OR (95 % CI) = 0.71 (0.62, 0.82), P = 0.0000036] if the evenings and mornings were also spent indoors. Furthermore, infection risk was only associated with local vector density [OR (95 % CI) = 6.99 (1.12, 43.7) at one vector mosquito per trap per night, P = 0.037] among the minority (14 %) of households lacking screening. Despite attenuation of malaria transmission and immunity, 88 % of infected residents experienced no recent fever, only 0.4 % of these afebrile cases had been treated for malaria, and prevalence remained high (9.9 %) at the end of the study. CONCLUSIONS While existing vector control interventions have dramatically attenuated malaria transmission in Dar es Salaam, further scale-up and additional measures to protect against mosquito bites outdoors are desirable. Accelerated elimination of chronic human infections persisting at high prevalence will require active, population-wide campaigns with curative drugs

Correction to: Methods and indicators for measuring patterns of human exposure to malaria vectors

An amendment to this paper has been published and can be accessed via the original article

Modelling the impact of vector control interventions on Anopheles gambiae population dynamics

<p>Abstract</p> <p>Background</p> <p>Intensive anti-malaria campaigns targeting the <it>Anopheles </it>population have demonstrated substantial reductions in adult mosquito density. Understanding the population dynamics of <it>Anopheles </it>mosquitoes throughout their whole lifecycle is important to assess the likely impact of vector control interventions alone and in combination as well as to aid the design of novel interventions.</p> <p>Methods</p> <p>An ecological model of <it>Anopheles gambiae sensu lato </it>populations incorporating a rainfall-dependent carrying capacity and density-dependent regulation of mosquito larvae in breeding sites is developed. The model is fitted to adult mosquito catch and rainfall data from 8 villages in the Garki District of Nigeria (the 'Garki Project') using Bayesian Markov Chain Monte Carlo methods and prior estimates of parameters derived from the literature. The model is used to compare the impact of vector control interventions directed against adult mosquito stages - long-lasting insecticide treated nets (LLIN), indoor residual spraying (IRS) - and directed against aquatic mosquito stages, alone and in combination on adult mosquito density.</p> <p>Results</p> <p>A model in which density-dependent regulation occurs in the larval stages via a linear association between larval density and larval death rates provided a good fit to seasonal adult mosquito catches. The effective mosquito reproduction number in the presence of density-dependent regulation is dependent on seasonal rainfall patterns and peaks at the start of the rainy season. In addition to killing adult mosquitoes during the extrinsic incubation period, LLINs and IRS also result in less eggs being oviposited in breeding sites leading to further reductions in adult mosquito density. Combining interventions such as the application of larvicidal or pupacidal agents that target the aquatic stages of the mosquito lifecycle with LLINs or IRS can lead to substantial reductions in adult mosquito density.</p> <p>Conclusions</p> <p>Density-dependent regulation of anopheline larvae in breeding sites ensures robust, stable mosquito populations that can persist in the face of intensive vector control interventions. Selecting combinations of interventions that target different stages in the vector's lifecycle will result in maximum reductions in mosquito density.</p

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease