A Bayesian modelling framework to quantify multiple sources of spatial variation for disease mapping.

Spatial connectivity is an important consideration when modelling infectious disease data across a geographical region. Connectivity can arise for many reasons, including shared characteristics between regions and human or vector movement. Bayesian hierarchical models include structured random effects to account for spatial connectivity. However, conventional approaches require the spatial structure to be fully defined prior to model fitting. By applying penalized smoothing splines to coordinates, we create two-dimensional smooth surfaces describing the spatial structure of the data while making minimal assumptions about the structure. The result is a non-stationary surface which is setting specific. These surfaces can be incorporated into a hierarchical modelling framework and interpreted similarly to traditional random effects. Through simulation studies, we show that the splines can be applied to any symmetric continuous connectivity measure, including measures of human movement, and that the models can be extended to explore multiple sources of spatial structure in the data. Using Bayesian inference and simulation, the relative contribution of each spatial structure can be computed and used to generate hypotheses about the drivers of disease. These models were found to perform at least as well as existing modelling frameworks, while allowing for future extensions and multiple sources of spatial connectivity.

Interaction between xylanase and a proton pump inhibitor on broiler chicken performance and gut function.

Three hundred thirty-six Ross 308 male broiler chicks were used in a 21-d study to explore performance and gut function when treated with a proton pump inhibitor (PPI; 0 or 89 mg/kg) in a 2 × 2 factorial arrangement with a xylanase (Xyl; 0 or 0.1 g/kg) to determine if the beneficial activity of arabinoxylan (AX) depolymerisation, through arabinoxylo-oligosaccharides (AXOS) production, starts in the upper gastrointestinal tract. Treatment with the PPI started from d 14, and by d 21 animal performance had deteriorated (P < 0.001). An interaction was observed between PPI and Xyl for feed conversion ratio (FCR) (P < 0.05), whereby the combination reduced the negative effect of PPI on FCR. Application of PPI raised digesta pH in the gizzard and caecum (P < 0.05), increased protein concentrations in the lower gut (P < 0.05) and reduced intake of digestible nutrients (P < 0.05). Caecal concentrations of indole, p-cresol, ammonia and the ratio of total volatile fatty acid (VFA) to butyric acid were increased with PPI (P < 0.05), indicating enhanced protein fermentation. Xylanase activity in the digesta were greatest in the caeca, especially when Xyl was supplemented (P < 0.001). The concentration of total soluble AX was greater in the gizzard and ileal digesta with Xyl supplementation (P < 0.05), supporting the depolymerisation action of xylanase even under acidic conditions. These data suggest xylanase may function in the gizzard even though pH is not optimal for activity and emphasises the importance of chlorohydric acid secretions in ensuring overall optimum gut function. AX depolymerisation benefits animal performance although it is still unknown how the AXOS produced with xylanase supplementation in the upper gastrointestinal tract influence the microbial populations and overall gut functionality.

The impact of climate suitability, urbanisation, and connectivity on the expansion of dengue in 21st century Brazil.

Dengue is hyperendemic in Brazil, with outbreaks affecting all regions. Previous studies identified geographical barriers to dengue transmission in Brazil, beyond which certain areas, such as South Brazil and the Amazon rainforest, were relatively protected from outbreaks. Recent data shows these barriers are being eroded. In this study, we explore the drivers of this expansion and identify the current limits to the dengue transmission zone. We used a spatio-temporal additive model to explore the associations between dengue outbreaks and temperature suitability, urbanisation, and connectivity to the Brazilian urban network. The model was applied to a binary outbreak indicator, assuming the official threshold value of 300 cases per 100,000 residents, for Brazil's municipalities between 2001 and 2020. We found a nonlinear relationship between higher levels of connectivity to the Brazilian urban network and the odds of an outbreak, with lower odds in metropoles compared to regional capitals. The number of months per year with suitable temperature conditions for Aedes mosquitoes was positively associated with the dengue outbreak occurrence. Temperature suitability explained most interannual and spatial variation in South Brazil, confirming this geographical barrier is influenced by lower seasonal temperatures. Municipalities that had experienced an outbreak previously had double the odds of subsequent outbreaks. We identified geographical barriers to dengue transmission in South Brazil, western Amazon, and along the northern coast of Brazil. Although a southern barrier still exists, it has shifted south, and the Amazon no longer has a clear boundary. Few areas of Brazil remain protected from dengue outbreaks. Communities living on the edge of previous barriers are particularly susceptible to future outbreaks as they lack immunity. Control strategies should target regions at risk of future outbreaks as well as those currently within the dengue transmission zone.

Application of Creep Feed and Phytase Super-Dosing as Tools to Support Digestive Adaption and Feed Efficiency in Piglets at Weaning.

A total of 64 piglets were used in a 35-day study to evaluate whether creep feeding piglets on the sow or super-dosing phytase to piglets post-weaning can be used as a tool to reduce stress and support adaption to weaning. Treatments consisted of creep or no creep feed being offered pre-weaning and with or without phytase supplementation at 2000 FTU/kg post-weaning. Blood samples were collected from eight piglets per treatment on days 0 (weaning), 7 and 21 post-weaning to determine plasma cortisol and myo-inositol concentrations. Four piglets per treatment (n = 16) were administered Heidelberg pH capsules 1 week prior to weaning, on the day of weaning, as well as 7 days and 21 days post-weaning, with readings monitored over a 3 h period. In the first week post-weaning, creep-fed piglets had higher daily gains (0.23 vs. 0.14 kg/d, p < 0.05) and a lower feed conversion ratio (FCR, 0.99 vs. 1.35, p < 0.01), compared to non-creep-fed pigs. At 21 days post-weaning, irrespective of creep feed, phytase supplementation reduced FCR (1.10 vs. 1.18, p = 0.05) of piglets. Average real-time stomach pH was lower in creep-fed piglets at 1 week prior to weaning (pH 3.2 vs. 4.6, p < 0.001) and on day of weaning (pH 3.1 vs. 3.7, p < 0.01). Following weaning, phytase reduced average stomach pH of piglets at days 7 (pH 2.6 vs. 3.3, p < 0.001) and 21 (pH 2.2 vs. 2.6, p < 0.01). Both cortisol and myo-inositol concentrations in plasma decreased with age; however, cortisol levels were unaffected by either treatment. Plasma myo-inositol concentrations were higher in creep-fed piglets at day of weaning (p < 0.05) and with phytase super-dosing on day 21 (p < 0.001). These findings demonstrate that both creep feeding and phytase super-dosing are useful practices to encourage better adaption to weaning and support piglet performance. This response was not related to reduced stress in piglets, as determined by cortisol levels, but instead appears to relate to improved gastric conditions for digestion, phytate degradation and myo-inositol provision in piglets.

Spatial connectivity in mosquito-borne disease models: a systematic review of methods and assumptions.

Spatial connectivity plays an important role in mosquito-borne disease transmission. Connectivity can arise for many reasons, including shared environments, vector ecology and human movement. This systematic review synthesizes the spatial methods used to model mosquito-borne diseases, their spatial connectivity assumptions and the data used to inform spatial model components. We identified 248 papers eligible for inclusion. Most used statistical models (84.2%), although mechanistic are increasingly used. We identified 17 spatial models which used one of four methods (spatial covariates, local regression, random effects/fields and movement matrices). Over 80% of studies assumed that connectivity was distance-based despite this approach ignoring distant connections and potentially oversimplifying the process of transmission. Studies were more likely to assume connectivity was driven by human movement if the disease was transmitted by an Aedes mosquito. Connectivity arising from human movement was more commonly assumed in studies using a mechanistic model, likely influenced by a lack of statistical models able to account for these connections. Although models have been increasing in complexity, it is important to select the most appropriate, parsimonious model available based on the research question, disease transmission process, the spatial scale and availability of data, and the way spatial connectivity is assumed to occur.

Combined effects of hydrometeorological hazards and urbanisation on dengue risk in Brazil: a spatiotemporal modelling study.

BACKGROUND: Temperature and rainfall patterns are known to influence seasonal patterns of dengue transmission. However, the effect of severe drought and extremely wet conditions on the timing and intensity of dengue epidemics is poorly understood. In this study, we aimed to quantify the non-linear and delayed effects of extreme hydrometeorological hazards on dengue risk by level of urbanisation in Brazil using a spatiotemporal model. METHODS: We combined distributed lag non-linear models with a spatiotemporal Bayesian hierarchical model framework to determine the exposure-lag-response association between the relative risk (RR) of dengue and a drought severity index. We fit the model to monthly dengue case data for the 558 microregions of Brazil between January, 2001, and January, 2019, accounting for unobserved confounding factors, spatial autocorrelation, seasonality, and interannual variability. We assessed the variation in RR by level of urbanisation through an interaction between the drought severity index and urbanisation. We also assessed the effect of hydrometeorological hazards on dengue risk in areas with a high frequency of water supply shortages. FINDINGS: The dataset included 12 895 293 dengue cases reported between 2001 and 2019 in Brazil. Overall, the risk of dengue increased between 0-3 months after extremely wet conditions (maximum RR at 1 month lag 1·56 [95% CI 1·41-1·73]) and 3-5 months after drought conditions (maximum RR at 4 months lag 1·43 [1·22-1·67]). Including a linear interaction between the drought severity index and level of urbanisation improved the model fit and showed the risk of dengue was higher in more rural areas than highly urbanised areas during extremely wet conditions (maximum RR 1·77 [1·32-2·37] at 0 months lag vs maximum RR 1·58 [1·39-1·81] at 2 months lag), but higher in highly urbanised areas than rural areas after extreme drought (maximum RR 1·60 [1·33-1·92] vs 1·15 [1·08-1·22], both at 4 months lag). We also found the dengue risk following extreme drought was higher in areas that had a higher frequency of water supply shortages. INTERPRETATION: Wet conditions and extreme drought can increase the risk of dengue with different delays. The risk associated with extremely wet conditions was higher in more rural areas and the risk associated with extreme drought was exacerbated in highly urbanised areas, which have water shortages and intermittent water supply during droughts. These findings have implications for targeting mosquito control activities in poorly serviced urban areas, not only during the wet and warm season, but also during drought periods. FUNDING: Royal Society, Medical Research Council, Wellcome Trust, National Institutes of Health, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, and Conselho Nacional de Desenvolvimento Científico e Tecnológico. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Prevention of Morbidity in Sickle Cell Disease (POMS2a)-overnight auto-adjusting continuous positive airway pressure compared with nocturnal oxygen therapy: a randomised crossover pilot study examining patient preference and safety in adults and children.

DESIGN: This randomised crossover trial compared nocturnal auto-adjusting continuous positive airway pressure (APAP) and nocturnal oxygen therapy (NOT) in adults and children with sickle cell anaemia, with patient acceptability as the primary outcome. Secondary outcomes included pulmonary physiology (adults), safety, and daily pain during interventions and washout documented using tablet technology. METHODS: Inclusion criteria were age > 8 years and the ability to use an iPad to collect daily pain data. Trial participation was 4 weeks; week 1 involved baseline data collection and week 3 was a washout between interventions, which were administered for 7 days each during weeks 2 and 4 in a randomised order. Qualitative interviews were transcribed verbatim and analysed for content using a funnelling technique, starting generally and then gaining more detailed information on the experience of both interventions. Safety data included routine haematology and median pain days between each period. Missing pain day values were replaced using multiple imputation. RESULTS: Ten adults (three female, median age 30.2 years, range 18-51.5 years) and eleven children (five female, median age 12 years, range 8.7-16.9 years) enrolled. Nine adults and seven children completed interviews. Qualitative data revealed that the APAP machine was smaller, easier to handle, and less noisy. Of 16 participants, 10 preferred APAP (62.5%, 95% confidence interval (CI) 38.6-81.5%). Haemoglobin decreased from baseline on APAP and NOT (mean difference -3.2 g/L (95% CI -6.0 to -0.2 g/L) and -2.5 g/L (95% CI -4.6 to 0.3 g/L), respectively), but there was no significant difference between interventions (NOT versus APAP, 1.1 (-1.2 to 3.6)). Pulmonary function changed little. Compared with baseline, there were significant decreases in the median number of pain days (1.58 for APAP and 1.71 for NOT) but no significant difference comparing washout with baseline. After adjustment for carry-over and period effects, there was a non-significant median difference of 0.143 (95% CI -0.116 to 0.401) days additional pain with APAP compared with NOT. CONCLUSION: In view of the point estimate of patient preference for APAP, and no difference in haematology or pulmonary function or evidence that pain was worse during or in washout after APAP, it was decided to proceed with a Phase II trial of 6 months APAP versus standard care with further safety monitoring for bone marrow suppression and pain. TRIAL REGISTRATION: ISRCTN46078697 . Registered on 18 July 2014.

Influence of fibre and betaine on development of the gastrointestinal tract of broilers between hatch and 14 d of age.

An experiment was designed to determine the influence of fibre and betaine on the development of the intestine, liver and pancreas of broilers from hatch to 14 d of age. A total of 250-day-old Cobb 500 male broilers were allocated to 16 cages with 15 broilers each. Treatments were arranged in a 2 × 4 factorial design, consisting of 2 feed formulations (low and high fibre diets) and 4 levels of betaine (0, 1, 3 or 5 kg/t). At hatch, 10 birds in total were euthanised, and samples of the liver, pancreas, yolk sac and intestine were collected for reference of the analysed parameters before the start of the trial. On d 4, 9 and 14, 5 birds per cage (10 birds per treatment) were selected, euthanised and treated as the same as the birds at hatch. Villus height and width and crypt depth were determined on the duodenum samples, and absorptive area was calculated. The number of enterocytes in mitosis at the villus was determined by a positive reaction to antibody for Ki67 protein, and fused villus was evaluated visually. The relative weight of the yolk sac reduced (P < 0.05) as birds aged while the intestine and liver reached a maximum (P < 0.05) at around d 4 and the pancreas at d 9. Birds fed the high fibre diet had greater feed intake, lower relative weight of the pancreas and higher villus (P < 0.05) than birds fed the low fibre diet. Villus width increased (P < 0.05) at 4 d of age, and this was associated with fused villus. Betaine inclusion reduced (P < 0.05) villus width, increased (P < 0.05) villus size and absorptive area, and reduced (P < 0.05) the number of enterocytes with positive reaction for the antibody Ki-67. Betaine inclusion reduced the width and increased the absorptive area and the villus height of the duodenum of birds up to 14 d of age. The higher fibre diet increased feed intake and villus height, yet reduced pancreas relative weight, while not affecting body weight gain. This response was possibly due to a dilution effect of the fibre, reducing nutrient absorption and consequently stimulating villus growth to improve absorption rates.

Review on docosahexaenoic acid in poultry and swine nutrition: Consequence of enriched animal products on performance and health characteristics.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are linked to a variety of health benefits against human disorders and disease. However, the typical western diet is generally low in n-3 PUFA and high in n-6 PUFA, suggesting that the recommended intake of these essential fatty acids is seldom achieved. Therefore, dietary enrichment of animal meat and eggs with n-3 PUFA could help increase consumption of these fatty acids. Fish oils and microalgae (MA) are rich sources of long chain n-3 PUFA, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Feeding these marine products has been shown to increase DHA content of tissues and yolk, however, this may also lead to an increased requirement for anti-oxidants to prevent oxidative deterioration and associated negative sensory attributes. Nonetheless, increased DHA has been linked to promising results in animal growth, fertility, immunity and bone strength in both pigs and poultry. These findings suggest that feeding DHA-rich ingredients to mono-gastric can enrich human diets as well as providing additional benefits to the animal.

Phytase as an alleviator of high-temperature stress in broilers fed adequate and low dietary calcium.

This study aimed to investigate the effect of phytase and dietary Ca level on performance, phytate (inositol hexa-phosphate, IP6) concentration, and anti-oxidant enzyme activity in broilers exposed to cycling high environmental temperatures. A total of 2,970 day-old Cobb 400 male broilers were randomly allocated among 6 treatments, with 15 replicate pens, and 33 birds per pen. Corn-soy diets low in available phosphorus (avP, 0.15% matrix applied) were fed in 2 phases; starter (0 to 21 d) and grower (22 to 42 d). Diets were factorially arranged by 2 × 3, with adequate (0.90% starter, 0.80% grower) or low (0.60% starter, 0.50% grower) dietary Ca and phytase (0, 500, or 3,000 phytase units (FTU)/kg). Temperature was not regulated, but followed environmental changes determined by the summer season in India; 22 to 39°C in the morning and 23 to 40°C at night. At 42 d of age, supplementing either dose of phytase increased (P < 0.001) weight gain (+128 g) and feed intake (+194 g) of birds, while only 3,000 FTU/kg phytase lowered (P < 0.01) feed conversion ratio (FCR) compared to the control. Birds fed low Ca diets had poorer (P < 0.01) weight gain (-33 g) and FCR (+0.04) than birds fed adequate Ca levels, suggesting that Ca was limiting in these diets. Phytase and low dietary Ca reduced the concentration of IP esters in the gastrointestinal tract of broilers. Lower IP6, IP5, IP4, and IP3 concentrations and increased myo-inositol provision was positively correlated to anti-oxidant enzyme activity in tissues. These results indicate that phytase can be used to alleviate the negative performance traits accredited to broilers under high temperature stress, potentially by reducing the anti-nutritive effect of IP6 and improving anti-oxidant status of birds. However, caution should be taken when reducing dietary Ca levels as improvements in IP6 degradation and anti-oxidant status cannot overcome the constraints on growth by diets that do not meet the Ca requirements.

Effect of phytase superdosing, myo-inositol and available phosphorus concentrations on performance and bone mineralisation in broilers.

A total of 2,376 one-day-old Ross broiler chickens were used to investigate the effect of myo-inositol (MYO) and phytase supplementation on performance and bone mineralization variables in broilers fed diets formulated to have varying concentrations of available phosphorus (P). The trial was designed as a 2 × 2 × 3 factorial; with and without phytase superdosing (0 or 1,500 FTU/kg), MYO (0 or 3 g/kg), and dietary P (low, moderate or high). At 21 d, dietary phytase and MYO had no consistent benefit on bone mineralization variables. Bone ash reduced by 4.7% from the medium to low P diet (P < 0.01), with no effect of phytase supplementation. Superdosing improved bone P content by 6% in birds fed the low P diet, signifying an interaction between dietary P concentrations and phytase (P < 0.05). Dietary MYO addition resulted in a numerical reduction in bone ash and a significant reduction in bone strength (P < 0.05). At 42 d, the beneficial effect of phytase superdosing on feed intake and body weight gain was evident in the low P diet. Superdosing reduced feed conversion rate (FCR) at all P levels (P < 0.05), although this effect was more pronounced on the low P diet, suggesting that sufficient P being released from the phytase itself to re-phosphorylate MYO and hence improve FCR. The significant improvement in FCR was greater with superdosing than with MYO alone, and the combination led to no further improvement in FCR compared with superdosing alone, signifying a phytase and MYO interaction (P < 0.05). From these results, it can be estimated that MYO is providing around 30% to 35% of the total response to superdosing.