Global mismatches between threat mapping research effort and the potential of threat abatement actions to reduce extinction risk.

Threat mapping is a necessary tool for identifying and abating direct threats to species in the ongoing extinction crisis. There are known gaps in the threat mapping literature for particular threats and geographic locations, and it remains unclear if the distribution of research effort is appropriately targeted relative to conservation need. We aimed to determine the drivers of threat mapping research effort and to quantify gaps that, if filled, could inform actions with the highest potential to reduce species' extinction risk. We used a negative binomial generalized linear model to analyze research effort as a function of threat abatement potential (quantified as the potential reduction in species extinction risk from abating threats), species richness, land area, and human pressure. The model showed that threat mapping research effort increased by 1.1 to 1.2 times per standardized unit change in threat abatement potential. However, species richness and land area were stronger predictors of research effort overall. The greatest areas of mismatch between research effort and threat abatement potential, receiving disproportionately low research effort, were related to the threats to species of agriculture, aquaculture, and biological resource use across the tropical regions of the Americas, Asia, and Madagascar. Conversely, the threat of linear infrastructure (e.g., roads and rails) across regions, the threat of biological resource use (e.g., hunting or collection) in sub-Saharan Africa, and overall threats in North America and Europe all received disproportionately high research effort. We discuss the range of methodological and sociopolitical factors that may be behind the overall trends and specific areas of mismatch we found. We urge a stronger emphasis on targeting research effort toward those threats and geographic locations where threat abatement activities could make the greatest contribution to reducing global species extinction risk.

Disparidades mundiales entre la investigación sobre el esfuerzo de mapeo de amenazas y la potencial amenaza de las acciones de abatimiento para reducir el riesgo de extinción Resumen El mapeo de amenazas es una herramienta necesaria para identificar y abatir las amenazas directas para las especies en la actual crisis de extinción. Existen vacíos conocidos en la literatura del mapeo de amenazas para amenazas particulares y ubicaciones geográficas, y todavía no está claro si la distribución de los esfuerzos de investigación está enfocada de forma apropiada en relación con las necesidades de conservación. Buscamos determinar los factores que influyen sobre el esfuerzo de investigación del mapeo de amenazas y cuantificar los vacíos que, si se cierran, podrían guiar las acciones con el potencial más alto para reducir el riesgo de extinción de las especies. Usamos un modelo binomial lineal negativo generalizado para analizar el esfuerzo de investigación como función del potencial de abatimiento de amenazas (cuantificado como la reducción potencial en el riesgo de extinción a partir del abatimiento de amenazas), la riqueza de especies, el área del suelo y la presión humana. El modelo mostró que el esfuerzo de investigación del mapeo de amenazas incrementó entre 1.1 y 1.2 veces por unidad estandarizada de cambio en el potencial de abatimiento de amenazas. Sin embargo, la riqueza de especies y el área del suelo fueron pronósticos más sólidos del esfuerzo de investigación generalizado. Las principales áreas de disparidad entre el esfuerzo de investigación y el potencial de abatimiento de amenazas, las cuales reciben un esfuerzo de investigación desproporcionalmente bajo, estuvieron relacionadas con las amenazas para las especies de agricultura, acuacultura y recursos biológicos que se usan en las regiones tropicales de América, Asia y Madagascar. Al contrario, la amenaza de la infraestructura lineal (p. ej.: carreteras y vías férreas) en las regiones, la amenaza del uso de recursos biológicos (p. ej.: caza o recolección) en la África subsahariana y las amenazas generales en América del Norte y en Europa recibieron un esfuerzo de investigación desproporcionalmente alto. Abordamos el rango de factores metodológicos y sociopolíticos que pueden estar detrás de las tendencias generales y las áreas específicas de disparidad que encontramos. Instamos a un mayor énfasis en el enfoque del esfuerzo de investigación hacia aquellas amenazas y ubicaciones geográficas en donde las actividades de abatimiento de amenazas podrían brindar una mayor contribución para reducir el riesgo mundial de extinción de especies.

Climate, human behaviour or environment: individual-based modelling of Campylobacter seasonality and strategies to reduce disease burden.

BACKGROUND: With over 800 million cases globally, campylobacteriosis is a major cause of food borne disease. In temperate climates incidence is highly seasonal but the underlying mechanisms are poorly understood, making human disease control difficult. We hypothesised that observed disease patterns reflect complex interactions between weather, patterns of human risk behaviour, immune status and level of food contamination. Only by understanding these can we find effective interventions. METHODS: We analysed trends in human Campylobacter cases in NE England from 2004 to 2009, investigating the associations between different risk factors and disease using time-series models. We then developed an individual-based (IB) model of risk behaviour, human immunological responses to infection and environmental contamination driven by weather and land use. We parameterised the IB model for NE England and compared outputs to observed numbers of reported cases each month in the population in 2004-2009. Finally, we used it to investigate different community level disease reduction strategies. RESULTS: Risk behaviours like countryside visits (t = 3.665, P < 0.001 and t = - 2.187, P = 0.029 for temperature and rainfall respectively), and consumption of barbecued food were strongly associated with weather, (t = 3.219, P = 0.002 and t = 2.015, P = 0.045 for weekly average temperature and average maximum temperature respectively) and also rain (t = 2.254, P = 0.02527). This suggests that the effect of weather was indirect, acting through changes in risk behaviour. The seasonal pattern of cases predicted by the IB model was significantly related to observed patterns (r = 0.72, P < 0.001) indicating that simulating risk behaviour could produce the observed seasonal patterns of cases. A vaccination strategy providing short-term immunity was more effective than educational interventions to modify human risk behaviour. Extending immunity to 1 year from 20 days reduced disease burden by an order of magnitude (from 2412-2414 to 203-309 cases per 50,000 person-years). CONCLUSIONS: This is the first interdisciplinary study to integrate environment, risk behaviour, socio-demographics and immunology to model Campylobacter infection, including pathways to mitigation. We conclude that vaccination is likely to be the best route for intervening against campylobacteriosis despite the technical problems associated with understanding both the underlying human immunology and genetic variation in the pathogen, and the likely cost of vaccine development.

Control of norovirus infection.

PURPOSE OF REVIEW: The purpose of the review is to provide an update on control measures for norovirus (NoV), which is the most commonly implicated pathogen in acute gastroenteritis and outbreaks, causing major disruption in nurseries, schools, hospitals and care homes. RECENT FINDINGS: Important developments include the discovery that virus particles, previously considered to be the infectious unit, also occur in clusters, which appear to be more virulent than individual virus particles; a working culture system using human stem-cell derived enteroids; promising results from early phase clinical trials of candidate NoV vaccines, which appear to be safe and immunogenic; chronic NoV affects patients with primary and secondary immune deficiencies. Although several treatments have been used none are supported by well designed clinical trials; infection control procedures are effective if properly implemented. SUMMARY: NoV remains an important cause of morbidity and mortality. Although there are exciting developments on the vaccine front, the mainstay of control remains good hand hygiene, adherence to infection control procedures and limiting contamination of food, water and the wider environment. Once vaccines are available there will be important decisions to be made about how best to implement them.

Increasing age and female gender are associated with early knee replacement following arthroscopy.

PURPOSE: Early knee replacement following arthroscopy may be perceived as a failure of the original treatment and thus a poor use of resources. Factors that may be associated with increased risk of early replacement were explored in this study. METHODS: All adult patients who underwent planned knee arthroscopy in a national cohort over a 6-month period in 2005 were extracted from the administrative hospital admissions database and linked to determine whether and when a knee replacement occurred on the same knee within the subsequent 5 years. A combination of survival analysis and mixed effect modelling was used to investigate risk factors for replacement. RESULTS: There were a total of 20,556 arthroscopies, of which 2,161 (10.6%) subsequently underwent knee replacement. For patients under 60 years, female gender (62.1% higher risk, p < 0.001) and increasing age (12.7% increased risk per increasing year of age, p < 0.001) were significant associations for requiring knee replacement, after risk adjusting. Of those aged ≥60, 12.7% (576) had undergone a replacement at 1 year following arthroscopy. Females (33% higher risk), increasing age (7.3% increased risk per increasing year of age, p < 0.001) and hypertension (1,600% higher risk, p < 0.001) were significant predictors. The risk associated with increased age was not proportional for the older age group, with risk declining as time passed from arthroscopy, indicating other factors were influencing progression to knee replacement. CONCLUSIONS: The predictors of early knee replacement following arthroscopy were female sex, age over 60 years and hypertension, irrespective of type of operation. This work may contribute to national recommendations regarding the provision of arthroscopy for patients over 60 years. LEVEL OF EVIDENCE: III.

Aetiology of paediatric pneumonia after the introduction of pneumococcal conjugate vaccine.

We describe the aetiology of community-acquired pneumonia in children before and after the introduction of the pneumococcal conjugate vaccination (PCV) programme in 2006. Prospective studies were conducted in 2001-2002 (pre-vaccine) and 2009-2011 (post-vaccine) of children aged 0-16 years with radiologically confirmed pneumonia seen in hospital. Investigations included culture, serology, immunofluorescence antibody and urine antigen testing, with an increased use of PCR assays and expanded panels of pathogens in the post-vaccine study. 241 and 160 children were enrolled in the pre- and post-vaccine studies, respectively (73% aged <5 years). Identification of a causative pathogen was higher post-vaccination (61%) than pre-vaccination (48.5%) (p=0.019). Rates of bacterial infections were not different between post- and pre-vaccine studies (17.5% versus 24%, p=0.258). Viral (31%) and mixed (12.5%) infections were found more often post-vaccination (19.5%, p=0.021) than pre-vaccination (5%, p=0.015). Rates of identified pneumococcal infections were comparable between pre- and post-vaccine studies (14.7% versus 17.4%, p=0.557). Diagnosis of pneumococcal infection post-vaccination improved when PCR was used compared to culture (21.6% versus 6%, p=0.0004). Serotypes included in PCV13 but not PCV7 were identified in 75% (18 out of 24) post-vaccination. Infection with nonvaccine pneumococcal serotypes continues to be a significant cause of pneumonia in children in the UK.

The relationships between adult juvenile idiopathic arthritis and employment.

OBJECTIVE: The chronicity of juvenile idiopathic arthritis (JIA) into adulthood and attendant potential disability may adversely influence educational attainment and the ability to secure and maintain gainful employment. We undertook this study to investigate the effects of patient- and disease-specific factors on education and employment outcomes in a group of adult patients with JIA. METHODS: We performed a cross-sectional study of 103 consecutive adults attending a JIA continuity clinic, and patients who consented completed questionnaires relating to educational achievement, employment status, and functional disability (the Health Assessment Questionnaire disability index [HAQ DI]), and, for those who were employed, the rheumatoid arthritis Work Instability Scale. We used the structural equation modeling technique to study key patient and disease variables for employment in adults with JIA. RESULTS: The median age of patients was 24 years (range 17-71 years) with median disease duration of 19 years (range 7-67 years). Functional disability (the mean HAQ DI score) was significantly lower in patients who were employed (P = 0.03) and in those with oligoarticular JIA (t = 2.29, P = 0.02). Educational achievement was not influenced by JIA subtype (F = 1.18, P = 0.33). Educational achievement measured by General Certificate of Secondary Education (GCSE) grades had a positive effect on the type of job achieved in later life (F = 11.63, P = 0.001), with greater success leading to more professional or managerial posts. In the complex structural equation model, job stability was influenced positively by educational achievement measured by GCSE grades and negatively by the HAQ DI score (t = 10.94, P = 6.36 × 10(-16) ). CONCLUSION: Educational attainment is key to successful employability and is influenced by functional disability rather than by JIA subtype. These findings have implications for choice of occupation and delivery of career advice to aid decision making by young people with JIA.

Elderly men with renal dysfunction are most at risk for poor outcome after neck of femur fractures.

BACKGROUND: both acute and chronic renal dysfunction (ARD and CRD) have been reported to influence outcomes after neck of femur fractures. We have examined the relationship between the length of stay, mortality and renal dysfunction using biomarkers. These included pre-operative (admission) serum concentrations of urea, creatinine and albumin, and estimated glomerular filtration rates (eGFR) derived from four- and six-variable Modification of Diet in Renal Disease (MDRD) study equations. METHODS: complete outcomes data for 566 patients and the patterns of variations in the biomarkers were analysed using generalised linear models. Cox-proportional hazard analyses investigated the association between kidney function (as assessed by the above-mentioned biochemical data) and post-operative length of stay and mortality. All patients were stratified for CRD according to their eGFR. RESULTS: serum urea and creatinine were significantly, positively correlated with age. After adjusting for age and sex, risk of mortality was positively related to six-variable eGFR and creatinine, and marginally so for urea. One-year mortality risk thus worsened with stages of CRD (1-4), increasing age and male gender. Risk of discharge from trauma ward, the length of stay in trauma ward and the overall length of stay were not related to urea and creatinine, but were negatively related to both four- and six-variable eGFR. CONCLUSIONS: the study has identified elderly renal-impaired males as the subgroup of patients most at risk for poor survival. This subgroup may require a more targeted approach to the management of their fluid and electrolyte homoeostasis to help improve their outcomes.

Association between respiratory prescribing, air pollution and deprivation, in primary health care.

BACKGROUND: We investigated the association between respiratory prescribing, air quality and deprivation in primary health care. Most previous studies have used data from secondary and tertiary care to quantify air pollution effects on exacerbations of asthma and chronic obstructive pulmonary disease (COPD). However, these outcomes capture patients who suffer from relatively severe symptoms. METHODS: This is a population-based ecological study. We analysed respiratory medication (salbutamol) prescribed monthly by 63 primary care practices, UK. Firstly, we captured the area-wide seasonal variation in prescribing. Then, using the area-wide variation in prescribing as an offset, we built a mixed-effects model to assess the remaining variation in relation to air quality and demographic variables. RESULTS: An increase of 10 µg/m(3) in ambient PM10 was associated with an increase of 1% (95% CI: 0.1-2%) in salbutamol prescribing. An increase of 1 SD in income and employment deprivation was associated with an increase of 20.5% (95% CI: 8.8-33.4%) and 14.7% (95% CI: 4.3-26.2%) in salbutamol prescribing rate, respectively. CONCLUSIONS: The study provides evidence that monthly respiratory prescribing in primary care is a useful indicator of the extent to which air pollution exacerbates asthma and COPD symptoms. Respiratory prescribing was higher on deprived populations.

Depression in Sjögren's syndrome mediates the relationship between pain, fatigue, sleepiness, and overall quality of life.

Objectives: Sjögren's syndrome (SS) includes many extra-glandular symptoms such as fatigue, pain, sleepiness and depression, which impact on quality of life (QoL). These symptoms also influence each other and could be linked by autonomic nervous system (ANS) dysregulation. Our aim was to model the role of putative predictive variables, including depression in the relationships between ANS function, fatigue, and QoL in SS. Methods: Cross-sectional analysis of self-reported data from the multicentre UK primary SS registry. The Composite Autonomic Symptom Scale (COMPASS) was used to assess autonomic function, the Hospital Anxiety and Depression Scale (HADS) to assess anxiety and depression and the EuroQol-5 Dimension (EQ-5D) to assess QoL. Validated scales were used for other clinical variables. Using multiple regression analysis and structural equation modelling (SEM), we investigated how the QoL of people with SS is impacted by the direct and indirect effects of fatigue, sleepiness, depression, symptom burden and ANS function, and their interactions. Results: Data was obtained for 1046 people with SS, 56% COMPASS completers. Symptoms of ANS dysregulation were common. Participants with ANS dysregulation had more severe depression, anxiety, dryness, fatigue, pain, sleepiness and QoL (P < 0.01 for all). Depression, anxiety, dryness, and pain were independent predictors of ANS function in the multiple regression model (P < 0.05 for all). ANS function could not be included in the SEM. The SEM model had good fit to the data (comparative fit index = 0.998) and showed that, in people with SS, depression mediates the effects of pain, fatigue and sleepiness on QoL. Conclusion: Our results show that diagnosing and treating depression in people with SS could have direct positive impact on QoL, and significantly ameliorate the impact of fatigue and pain.

Erratum: Author Correction: The influence of HLA genotype on the development of metal hypersensitivity following joint replacement.

[This corrects the article DOI: 10.1038/s43856-022-00137-0.].

The influence of HLA genotype on the development of metal hypersensitivity following joint replacement.

Background: Over five million joint replacements are performed across the world each year. Cobalt chrome (CoCr) components are used in most of these procedures. Some patients develop delayed-type hypersensitivity (DTH) responses to CoCr implants, resulting in tissue damage and revision surgery. DTH is unpredictable and genetic links have yet to be definitively established. Methods: At a single site, we carried out an initial investigation to identify HLA alleles associated with development of DTH following metal-on-metal hip arthroplasty. We then recruited patients from other centres to train and validate an algorithm incorporating patient age, gender, HLA genotype, and blood metal concentrations to predict the development of DTH. Accuracy of the modelling was assessed using performance metrics including time-dependent receiver operator curves. Results: Using next-generation sequencing, here we determine the HLA genotypes of 606 patients. 176 of these patients had experienced failure of their prostheses; the remaining 430 remain asymptomatic at a mean follow up of twelve years. We demonstrate that the development of DTH is associated with patient age, gender, the magnitude of metal exposure, and the presence of certain HLA class II alleles. We show that the predictive algorithm developed from this investigation performs to an accuracy suitable for clinical use, with weighted mean survival probability errors of 1.8% and 3.1% for pre-operative and post-operative models respectively. Conclusions: The development of DTH following joint replacement appears to be determined by the interaction between implant wear and a patient's genotype. The algorithm described in this paper may improve implant selection and help direct patient surveillance following surgery. Further consideration should be given towards understanding patient-specific responses to different biomaterials.

Bacillus Calmette-Guérin vaccination reduces the severity and progression of tuberculosis in badgers.

Control of bovine tuberculosis (TB) in cattle has proven particularly challenging where reservoirs of infection exist in wildlife populations. In Britain and Ireland, control is hampered by a reservoir of infection in Eurasian badgers (Meles meles). Badger culling has positive and negative effects on bovine TB in cattle and is difficult, costly and controversial. Here we show that Bacillus Calmette-Guérin (BCG) vaccination of captive badgers reduced the progression, severity and excretion of Mycobacterium bovis infection after experimental challenge. In a clinical field study, BCG vaccination of free-living badgers reduced the incidence of positive serological test results by 73.8 per cent. In common with other species, BCG did not appear to prevent infection of badgers subjected to experimental challenge, but did significantly reduce the overall disease burden. BCG vaccination of badgers could comprise an important component of a comprehensive programme of measures to control bovine TB in cattle.

Identifying the climatic drivers of honey bee disease in England and Wales.

Honey bee colony health has received considerable attention in recent years, with many studies highlighting multifactorial issues contributing to colony losses. Disease and weather are consistently highlighted as primary drivers of colony loss, yet little is understood about how they interact. Here, we combined disease records from government honey bee health inspections with meteorological data from the CEDA to identify how weather impacts EFB, AFB, CBP, varroosis, chalkbrood and sacbrood. Using R-INLA, we determined how different meteorological variables influenced disease prevalence and disease risk. Temperature caused an increase in the risk of both varroosis and sacbrood, but overall, the weather had a varying effect on the six honey bee diseases. The risk of disease was also spatially varied and was impacted by the meteorological variables. These results are an important step in identifying the impacts of climate change on honey bees and honey bee diseases.

Transmission routes of rare seasonal diseases: the case of norovirus infections.

Norovirus (NoV) is the most commonly recognized cause of acute gastroenteritis, with over a million cases globally per year. While usually self-limiting, NoV poses a substantial economic burden because it is highly contagious and there are multiple transmission routes. Infection occurs through inhalation of vomitus; faecal-oral spread; and food, water and environmental contamination. While the incidence of the disease is predictably seasonal, much less is known about the relative contribution of the various exposure pathways in causing disease. Additionally, asymptomatic excretion and viral shedding make forecasting disease burden difficult. We develop a novel stochastic dynamic network model to investigate the contributions of different transmission pathways in multiple coupled social networks representing schools, hospitals, care-homes and family households in a community setting. We analyse how the networks impact on transmission. We used ward-level demographic data from Northumberland, UK to create a simulation cohort. We compared the results with extant data on NoV cases from the IID2 study. Connectivity across the simulated cohort was high. Cases of NoV showed marked seasonality, peaking in early winter and declining through the summer. For the first time, we show that fomites and food appear to be the most important exposure routes in determining the population burden of disease. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'. This theme issue is linked with the earlier issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'.

Spatio-temporal models to determine association between Campylobacter cases and environment.

Background: Campylobacteriosis is a major cause of gastroenteritis in the UK, and although 70% of cases are associated with food sources, the remainder are probably associated with wider environmental exposure. Methods: In order to investigate wider environmental transmission, we conducted a spatio-temporal analysis of the association of human cases of Campylobacter in the Tyne catchment with weather, climate, hydrology and land use. A hydrological model was used to predict surface-water flow in the Tyne catchment over 5 years. We analysed associations between population-adjusted Campylobacter case rate and environmental factors hypothesized to be important in disease using a two-stage modelling framework. First, we investigated associations between temporal variation in case rate in relation to surface-water flow, temperature, evapotranspiration and rainfall, using linear mixed-effects models. Second, we used the random effects for the first model to quantify how spatial variation in static landscape features of soil and land use impacted on the likely differences between subcatchment associations of case rate with the temporal variables. Results: Population-adjusted Campylobacter case rates were associated with periods of high predicted surface-water flow, and during above average temperatures. Subcatchments with cattle on stagnogley soils, and to a lesser extent sheep plus cattle grazing, had higher Campylobacter case rates. Conclusions: Areas of stagnogley soils with mixed livestock grazing may be more vulnerable to both Campylobacter spread and exposure during periods of high rainfall, with resultant increased risk of human cases of the disease.

Trophic control of mesopredators in terrestrial ecosystems: top-down or bottom-up?

It has been argued that widespread extinctions of top predators have changed terrestrial ecosystem structures through mesopredator release, where increased abundances of medium-sized predators have detrimental effects on prey communities. This top-down concept has received much attention within conservation biology, but few studies have demonstrated the phenomenon. The concept has been criticized since alternative explanations involving bottom-up impacts from bioclimatic effects on ecosystem productivity and from anthropogenic habitat change are rarely considered. We analyse the response of a mesopredator (the red fox) to declines in top predators (wolf and Eurasian lynx) and agricultural expansion over 90 years in Sweden, taking bioclimatic effects into account. We show a top-down mesopredator release effect, but ecosystem productivity determined its strength. The impacts of agricultural activity were mediated by their effects on top predator populations. Thus, both top-down and bottom-up processes need to be understood for effective preservation of biodiversity in anthropogenically transformed ecosystems.

Murine scent mark microbial communities are genetically determined.

Scent marking in mice allows males to communicate information such as territory ownership, male competitive ability and current reproductive, nutritional, social and health status. It has been suggested that female mice eavesdrop on these olfactory cues, using them as a means of selecting mates with dissimilar major histocompatibility complex (MHC) genes, known as H2 in mice. The mechanisms underpinning MHC-dependent olfactory communication remain unresolved. Using congenic mouse strains and molecular methods we explore the involvement of the microbial communities, a known source of odourants, in scent marks to test the hypothesis that the microbial communities and hence the olfactory signals are genetically determined. Here we show that the indigenous microbial community of murine scent marks is genetically determined. Both background genotype and H2 haplotype influence the community structure of the scent mark flora, removing the possibility that community composition is solely orchestrated by the MHC. Qualitative and quantitative components of the bacterial community associated with MHC haplotype and background genotype were identified. The analyses confirm that the four groups of congenic mice tested are distinguishable on basis of the microbiology of their scent marks alone, strengthening the role of microorganisms in the development of MHC-dependent odours.

Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials.

Large randomized controlled trials (RCTs) in preterm infants offer unique opportunities for mechanistic evaluation of the risk factors leading to serious diseases, as well as the actions of interventions designed to prevent them. Necrotizing enterocolitis (NEC) a serious inflammatory gut condition and late-onset sepsis (LOS) are common feeding and nutrition-related problems that may cause death or serious long-term morbidity and are key outcomes in two current UK National Institutes for Health Research (NIHR) trials. Speed of increasing milk feeds trial (SIFT) randomized preterm infants to different rates of increases in milk feeds with a primary outcome of survival without disability at 2 years corrected age. Enteral lactoferrin in neonates (ELFIN) randomizes infants to supplemental enteral lactoferrin or placebo with a primary outcome of LOS. This is a protocol for the mechanisms affecting the gut of preterm infants in enteral feeding trials (MAGPIE) study and is funded by the UK NIHR Efficacy and Mechanistic Evaluation programme. MAGPIE will recruit ~480 preterm infants who were enrolled in SIFT or ELFIN. Participation in MAGPIE does not change the main trial protocols and uses non-invasive sampling of stool and urine, along with any residual resected gut tissue if infants required surgery. Trial interventions may involve effects on gut microbes, metabolites (e.g., short-chain fatty acids), and aspects of host immune function. Current hypotheses suggest that NEC and/or LOS are due to a dysregulated immune system in the context of gut dysbiosis, but mechanisms have not been systematically studied within large RCTs. Microbiomic analysis will use next-generation sequencing, and metabolites will be assessed by mass spectrometry to detect volatile organic and other compounds produced by microbes or the host. We will explore differences between disease cases and controls, as well as exploring the actions of trial interventions. Impacts of this research are multiple: translation of knowledge of mechanisms promoting gut health may explain outcomes or suggest alternate strategies to improve health. Results may identify new non-invasive diagnostic or monitoring techniques, preventative or treatment strategies for NEC or LOS, or provide data useful for risk stratification in future studies. Mechanistic evaluation might be especially informative where there are not clear effects on the primary outcome (ISRCTN 12554594).

Patterns of Coral-Reef Finfish Species Disappearances Inferred from Fishers' Knowledge in Global Epicentre of Marine Shorefish Diversity.

In the Philippines, very high fishing pressure coincides with the globally greatest number of shorefish species, yet no long-term fisheries data are available to explore species-level changes that may have occurred widely in the most species rich and vulnerable marine ecosystem, namely coral reefs. Through 2655 face-to-face interviews conducted between August 2012 and July 2014, we used fishers' recall of past catch rates of reef-associated finfish to infer species disappearances from catches in five marine key biodiversity areas (Lanuza Bay, Danajon Bank, Verde Island Passage, Polillo Islands and Honda Bay). We modeled temporal trends in perceived catch per unit effort (CPUE) based on fishers' reports of typical good days' catches using Generalized Linear Mixed Modelling. Fifty-nine different finfish disappeared from catches between the 1950s and 2014; 42 fish were identified to species level, two to genus, seven to family and eight to local name only. Five species occurring at all sites with the greatest number of fishers reporting zero catches were the green bumphead parrotfish (Bolbometopon muricatum), humphead wrasse (Cheilinus undulatus), African pompano (Alectis ciliaris), giant grouper (Epinephelus lanceolatus) and mangrove red snapper (Lutjanus argentimaculatus). Between the 1950s and 2014, the mean perceived CPUE of bumphead parrotfish declined by 88%, that of humphead wrasse by 82%, African pompano by 66%, giant grouper by 74% and mangrove red snapper by 64%. These declines were mainly associated with excess and uncontrolled fishing, fish life-history traits like maximum body size and socio-economic factors like access to market infrastructure and services, and overpopulation. The fishers' knowledge is indicative of extirpations where evidence for these losses was otherwise lacking. Our models provide information as basis for area-based conservation and regional resource management particularly for the more vulnerable, once common, large, yet wide-ranging reef finfish species.