Gradual acquisition of immunity to severe malaria with increasing exposure

Previous analyses have suggested that immunity to non-cerebral severe malaria due to Plasmodium falciparum is acquired after only a few infections, whereas longitudinal studies show that some children experience multiple episodes of severe disease, suggesting that immunity may not be acquired so quickly. We fitted a mathematical model for the acquisition and loss of immunity to severe disease to the age distribution of severe malaria cases stratified by symptoms from a range of transmission settings in Tanzania, combined with data from several African countries on the age distribution and overall incidence of severe malaria. We found that immunity to severe disease was acquired more gradually with exposure than previously thought. The model also suggests that physiological changes, rather than exposure, may alter the symptoms of disease with increasing age, suggesting that a later age at infection would be associated with a higher proportion of cases presenting with cerebral malaria regardless of exposure. This has consequences for the expected pattern of severe disease as transmission changes. Careful monitoring of the decline in immunity associated with reduced transmission will therefore be needed to ensure rebound epidemics of severe and fatal malaria are avoided

Family and home correlates of children's physical activity in a multi-ethnic population: the cross-sectional Child Heart and Health Study in England (CHASE).

BACKGROUND: The influence of the family and home environment on childhood physical activity (PA) and whether this differs between ethnic groups remains uncertain. This paper investigates associations between family and home factors and childhood PA in a multi-ethnic population and explores whether associations differ between ethnic groups. METHODS: Cross-sectional study of 9-10 year-old schoolchildren, in which PA was objectively measured by Actigraph GT1 M accelerometers for ≤7 days to estimate average activity counts per minute (CPM). Information on 11 family and home environmental factors were collected from questionnaires. Associations between these factors and CPM were quantified using multi-level linear regression. Interactions with ethnicity were explored using likelihood ratio tests. RESULTS: 2071 children (mean ± SD age: 9.95 ± 0.38 years; 47.8% male) participated, including 25% white European, 28% black African-Caribbean, 24% South Asian, and 24% other ethnic origin. Family PA support and having a pet were associated with higher average CPM (adjusted mean difference: 6 (95%CI:1,10) and 13 (95%CI:3,23), respectively) while car ownership and having internet access at home were associated with lower average CPM (adjusted mean difference: -19 (95%CI:-30,-8) and -10 (95%CI:-19,0), respectively). These associations did not differ by ethnicity. Although the number of siblings showed no overall association with PA, there was some evidence of interaction with ethnicity (p for ethnicity interaction=0.04, 0.05 in a fully-adjusted model); a positive significant association with number of siblings was observed in white Europeans (per sibling CPM difference 10.3 (95% CI 1.7, 18.9)) and a positive non-significant association was observed in black African-Caribbeans (per sibling CPM difference: 3.5 (-4.2, 11.2)) while a negative, non-significant association was observed in South Asians (per sibling CPM difference -6.0 (-15.5, 3.4)). CONCLUSIONS: Some family and home environmental factors have modest associations with childhood PA and these are mostly similar across different ethnic groups. This suggests that targeting these factors in an intervention to promote PA would be relevant for children in different ethnic groups.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Critical Innovations in the UK Peer-to-Peer (P2P) and Equity Alternative Finance Markets for Small Firm Growth

© The Author(s) 2016. The final, definitive version of this paper has been published in The International Journal of Entrepreneurship and Innovation by Sage Publications Ltd. All rights reserved. It is available at: https://doi.org/10.1177/1465750316655906This paper examines the disruptive nature of financial innovations available to small firms by the growing range of online platforms that have emerged in the UK since the financial crisis. It is unveiled that finance provided to small firms via such mechanisms is not identical to more traditional sources and its adoption therefore cannot be said to be simply a question of direct substitution based, for example, on a price comparison. These offer a series of important advantages over more traditional sources of early-stage capital for entrepreneurs seeking funding. Service innovations around security, flexibility of terms, speed of access and transparency of pricing are as important as price considerations for many users, as are innovations made possible by the way these online markets are structured and in particular in the way these innovative structures allow important types of risk to be dispersed and mitigated.Peer reviewedFinal Accepted Versio

Practice nurse-led proactive care for chronic depression in primary care: a randomised controlled trial

Background: Management of long-term depression is a significant problem in primary care populations with considerable on-going morbidity, but few studies have focused on this group.AimsTo evaluate whether structured, nurse-led proactive care of patients with chronic depression in primary care improves outcomes. Method: Participants with chronic/recurrent major depression or dysthymia were recruited from 42 UK general practices and randomised to general practitioner (GP) treatment as usual or nurse intervention over 2 years (the ProCEED trial, trial registration: ISRCTN36610074). Results: In total 282 people received the intervention and there were 276 controls. At 24 months there was no significant improvement in Beck Depression Inventory (BDI-II) score or quality of life (Euroquol-EQ-VAS), but a significant improvement in functional impairment (Work and Social Activity Schedule, WSAS) of 2.5 (95% CI 0.6-4.3, P = 0.010) in the intervention group. The impact per practice-nurse intervention session was -0.37 (95% CI -0.68 to -0.07, P = 0.017) on the BDI-II score and -0.33 (95% CI -0.55 to -0.10, P = 0.004) on the WSAS score, indicating that attending all 10 intervention sessions could lead to a BDI-II score reduction of 3.7 points compared with controls. Conclusions: The intervention improved functioning in these patients, the majority of whom had complex long-term difficulties, but only had a significant impact on depressive symptoms in those engaging with the full intervention

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

Demography and disorders of German Shepherd Dogs under primary veterinarycare in the UK

The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompassTM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompassTM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported

Effects of water potential on spore germination and viability of Fusarium species

Germination of macroconidia and/or microconidia of 24 strains of Fusarium solani, F. chlamydosporum, F. culmorum, F. equiseti, F. verticillioides, F. sambucinum, F. oxysporum and F. proliferatum isolated from fluvial channels and sea beds of the south-eastern coast of Spain, and three control strains (F. oxysporum isolated from affected cultures) was studied in distilled water in response to a range of water potentials adjusted with NaCI. (0, -13.79, -41.79, -70.37, -99.56 and -144.54 bars). The vialibility (UFC/ml) of suspension was also tested in three time periods (0,24 and 48h). Conidia always germinated in distilled water. The pattern of conidial germination obseved of F. verticillioides, F. oxysporum, F. proliferatum, F. chlamydosporum and F. culmorum was similar. A great diminution of spore germination was found in -13.79 bars solutions. Spore germination percentage for F. solani isolates was maximal at 48 h. and -13.79 bars with 21.33% spore germination, 16% higher than germination in distilled water. F. equiseti shows the maximum germination percentage in -144.54 bars solution in 24 h time with 12.36% germination. These results did not agree with those obtained in the viability test where maximum germination was found in distilled water. The viability analysis showed the great capacity of F. verticilloides strains to form viable colonies, even in such extreme conditions as -144,54 bars after 24 h F. proliferatum colony formation was prevented in the range of -70.37 bars. These results show the clear affectation of water potential to conidia germination of Fusaria. The ability of certain species of Fusarium to develop a saprophytic life in the salt water of the Mediterraneam Sea could be certain. Successful germination, even under high salty media conditions, suggests taht Fusarium spp. could have a competitive advantage over other soil fungi in crops irrigated with saline water. In the specific case of F. solani, water potential of -13.79 bars affected germination positively. It could indicate that F. solani has an special physiological mechanism of survival in low water potential environments

Evaluation of alternative mosquito sampling methods for malaria vectors in Lowland South - East Zambia.

Sampling malaria vectors and measuring their biting density is of paramount importance for entomological surveys of malaria transmission. Human landing catch (HLC) has been traditionally regarded as a gold standard method for surveying human exposure to mosquito bites. However, due to the risk of human participant exposure to mosquito-borne parasites and viruses, a variety of alternative, exposure-free trapping methods were compared in lowland, south-east Zambia. Centres for Disease Control and Prevention miniature light trap (CDC-LT), Ifakara Tent Trap model C (ITT-C), resting boxes (RB) and window exit traps (WET) were all compared with HLC using a 3 × 3 Latin Squares design replicated in 4 blocks of 3 houses with long lasting insecticidal nets, half of which were also sprayed with a residual deltamethrin formulation, which was repeated for 10 rounds of 3 nights of rotation each during both the dry and wet seasons. The mean catches of HLC indoor, HLC outdoor, CDC-LT, ITT-C, WET, RB indoor and RB outdoor, were 1.687, 1.004, 3.267, 0.088, 0.004, 0.000 and 0.008 for Anopheles quadriannulatus Theobald respectively, and 7.287, 6.784, 10.958, 5.875, 0.296, 0.158 and 0.458, for An. funestus Giles, respectively. Indoor CDC-LT was more efficient in sampling An. quadriannulatus and An. funestus than HLC indoor (Relative rate [95% Confidence Interval] = 1.873 [1.653, 2.122] and 1.532 [1.441, 1.628], respectively, P < 0.001 for both). ITT-C was the only other alternative which had comparable sensitivity (RR = 0.821 [0.765, 0.881], P < 0.001), relative to HLC indoor other than CDC-LT for sampling An. funestus. While the two most sensitive exposure-free techniques primarily capture host-seeking mosquitoes, both have substantial disadvantages for routine community-based surveillance applications: the CDC-LT requires regular recharging of batteries while the bulkiness of ITT-C makes it difficult to move between sampling locations. RB placed indoors or outdoors and WET had consistently poor sensitivity so it may be useful to evaluate additional alternative methods, such as pyrethrum spray catches and back packer aspirators, for catching resting mosquitoes

Potential health impacts of heavy metals on HIV-infected population in USA.

Noninfectious comorbidities such as cardiovascular diseases have become increasingly prevalent and occur earlier in life in persons with HIV infection. Despite the emerging body of literature linking environmental exposures to chronic disease outcomes in the general population, the impacts of environmental exposures have received little attention in HIV-infected population. The aim of this study is to investigate whether individuals living with HIV have elevated prevalence of heavy metals compared to non-HIV infected individuals in United States. We used the National Health and Nutrition Examination Survey (NHANES) 2003-2010 to compare exposures to heavy metals including cadmium, lead, and total mercury in HIV infected and non-HIV infected subjects. In this cross-sectional study, we found that HIV-infected individuals had higher concentrations of all heavy metals than the non-HIV infected group. In a multivariate linear regression model, HIV status was significantly associated with increased blood cadmium (p=0.03) after adjusting for age, sex, race, education, poverty income ratio, and smoking. However, HIV status was not statistically associated with lead or mercury levels after adjusting for the same covariates. Our findings suggest that HIV-infected patients might be significantly more exposed to cadmium compared to non-HIV infected individuals which could contribute to higher prevalence of chronic diseases among HIV-infected subjects. Further research is warranted to identify sources of exposure and to understand more about specific health outcomes

Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity

TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations