Ethnic and socio-economic differences in the prevalence of wheeze, severe wheeze, asthma, eczema and medication usage at 4 years of age: Findings from the Born in Bradford birth cohort.

Asthma, wheeze and eczema are common in early childhood and cause considerable morbidity. Generally rates of these conditions are higher in high income compared to low income countries. Rates in developed nations are generally higher than in less developed countries. After migration to Western countries, differences in risks of developing these conditions may between migrant and non-migrant may diminish. A convenience sample of 1648 children of White British, Pakistani or Other ethnicity aged between 4 and 5 years were recruited from the main Born in Bradford cohort. Children's parents or guardians were asked to report on a range of potential risk factors and their associations with wheeze, asthma and eczema. Relationships between ethnicity and disease outcomes were examined using logistic regression after adjustment for other relevant risk factors and confounders. Ethnic differences in doctor diagnosed asthma were evident, with children of other ethnic Origin being less likely and children of Pakistani origin more likely to have a diagnosis than White British or other origin children, although after adjustment for other risk factors this difference only remained significant for the Other Ethnic group. Ethnic differences were not observed in other outcomes including wheeze in the past 12 months, severe wheeze and taking medications for breathing problems. In UK born children, traditional risk factors such as gender, family history, socio-economic status and child's medical history may be stronger risk factors than ethnicity or familial migration patterns

Developing Prediction Equations and a Mobile Phone Application to Identify Infants at Risk of Obesity

Background: Advancements in knowledge of obesity aetiology and mobile phone technology have created the opportunity to develop an electronic tool to predict an infant’s risk of childhood obesity. The study aims were to develop and validate equations for the prediction of childhood obesity and integrate them into a mobile phone application (App). Methods and Findings: Anthropometry and childhood obesity risk data were obtained for 1868 UK-born White or South Asian infants in the Born in Bradford cohort. Logistic regression was used to develop prediction equations (at 6±1.5, 9±1.5 and 12±1.5 months) for risk of childhood obesity (BMI at 2 years >91st centile and weight gain from 0–2 years >1 centile band) incorporating sex, birth weight, and weight gain as predictors. The discrimination accuracy of the equations was assessed by the area under the curve (AUC); internal validity by comparing area under the curve to those obtained in bootstrapped samples; and external validity by applying the equations to an external sample. An App was built to incorporate six final equations (two at each age, one of which included maternal BMI). The equations had good discrimination (AUCs 86–91%), with the addition of maternal BMI marginally improving prediction. The AUCs in the bootstrapped and external validation samples were similar to those obtained in the development sample. The App is user-friendly, requires a minimum amount of information, and provides a risk assessment of low, medium, or high accompanied by advice and website links to government recommendations. Conclusions: Prediction equations for risk of childhood obesity have been developed and incorporated into a novel App, thereby providing proof of concept that childhood obesity prediction research can be integrated with advancements in technology

β-Catenin is a pH sensor with decreased stability at higher intracellular pH.

β-Catenin functions as an adherens junction protein for cell-cell adhesion and as a signaling protein. β-catenin function is dependent on its stability, which is regulated by protein-protein interactions that stabilize β-catenin or target it for proteasome-mediated degradation. In this study, we show that β-catenin stability is regulated by intracellular pH (pHi) dynamics, with decreased stability at higher pHi in both mammalian cells and Drosophila melanogaster β-Catenin degradation requires phosphorylation of N-terminal residues for recognition by the E3 ligase β-TrCP. While β-catenin phosphorylation was pH independent, higher pHi induced increased β-TrCP binding and decreased β-catenin stability. An evolutionarily conserved histidine in β-catenin (found in the β-TrCP DSGIHS destruction motif) is required for pH-dependent binding to β-TrCP. Expressing a cancer-associated H36R-β-catenin mutant in the Drosophila eye was sufficient to induce Wnt signaling and produced pronounced tumors not seen with other oncogenic β-catenin alleles. We identify pHi dynamics as a previously unrecognized regulator of β-catenin stability, functioning in coincidence with phosphorylation

Influence of muscle mass in the assessment of lower limb strength in COPD: validation of the prediction equation

Absence of established reference values limits application of quadriceps maximal voluntary contraction (QMVC) measurement. The impact of muscle mass inclusion in predictions is unclear. Prediction equations encompassing gender, age and size with (FFM+) and without (FFM−), derived in healthy adults (n=175), are presented and compared in two COPD cohorts recruited from primary care (COPD-PC, n=112) and a complex care COPD clinic (COPD-CC, n=189). Explained variance was comparable between the prediction models (R2: FFM+: 0.59, FFM−: 0.60) as were per cent predictions in COPD-PC (88.8%, 88.3%). However, fat-free mass inclusion reduced the prevalence of weakness in COPD, particularly in COPD-CC where 11.9% fewer were deemed weak

The influence of muscle mass in the assessment of lower limb strength in COPD [Abstract]

The influence of muscle mass in the assessment of lower limb strength in COPD [Abstract

The Social and Political Dimensions of the Ebola Response: Global Inequality, Climate Change, and Infectious Disease

The 2014 Ebola crisis has highlighted public-health vulnerabilities in Liberia, Sierra Leone, and Guinea – countries ravaged by extreme poverty, deforestation and mining-related disruption of livelihoods and ecosystems, and bloody civil wars in the cases of Liberia and Sierra Leone. Ebola’s emergence and impact are grounded in the legacy of colonialism and its creation of enduring inequalities within African nations and globally, via neoliberalism and the Washington Consensus. Recent experiences with new and emerging diseases such as SARS and various strains of HN influenzas have demonstrated the effectiveness of a coordinated local and global public health and education-oriented response to contain epidemics. To what extent is international assistance to fight Ebola strengthening local public health and medical capacity in a sustainable way, so that other emerging disease threats, which are accelerating with climate change, may be met successfully? This chapter considers the wide-ranging socio-political, medical, legal and environmental factors that have contributed to the rapid spread of Ebola, with particular emphasis on the politics of the global and public health response and the role of gender, social inequality, colonialism and racism as they relate to the mobilization and establishment of the public health infrastructure required to combat Ebola and other emerging diseases in times of climate change

Government responses and COVID-19 deaths : global evidence across multiple pandemic waves

We provide an assessment of the impact of government closure and containment measures on deaths from COVID-19 across sequential waves of the COVID-19 pandemic globally. Daily data was collected on a range of containment and closure policies for 186 countries from January 1, 2020 until March 11th , 2021. These data were combined into an aggregate stringency index (SI) score for each country on each day (range: 0-100). Countries were divided into successive waves via a mathematical algorithm to identify peaks and troughs of disease. Within our period of analysis, 63 countries experienced at least one wave, 40 countries experienced two waves, and 10 countries saw three waves, as defined by our approach. Within each wave, regression was used to assess the relationship between the strength of government stringency and subsequent deaths related to COVID-19 with a number of controls for time and country-specific demographic, health system, and economic characteristics. Across the full period of our analysis and 113 countries, an increase of 10 points on the SI was linked to 6 percentage points (P < 0.001, 95% CI = [5%, 7%]) lower average daily deaths. In the first wave, in countries that ultimately experiences 3 waves of the pandemic to date, ten additional points on the SI resulted in lower average daily deaths by 21 percentage points (P<.001, 95% CI = [8%, 16%]). This effect was sustained in the third wave with reductions in deaths of 28 percentage points (P<.001, 95% CI = [13%, 21%]). Moreover, interaction effects show that government policies were effective in reducing deaths in all waves in all groups of countries. These findings highlight the enduring importance of non-pharmaceutical responses to COVID-19 over time

Palaeo-dust records: a window to understanding past environments

Dust entrainment, transport over vast distances and subsequent deposition is a fundamental part of the Earth system. Yet the role and importance of dust has been underappreciated, due largely to challenges associated with recognising dust in the landscape and interpreting its depositional history. Despite these challenges, interest in dust is growing. Technical advances in remote sensing and modelling have improved understanding of dust sources and production, while advances in sedimentology, mineralogy and geochemistry (in particular) have allowed dust to be more easily distinguished within sedimentary deposits. This has facilitated the reconstruction of records of dust emissions through time. A key advance in our understanding of dust has occurred following the development of methods to geochemically provenance (fingerprint) dust to its source region. This ability has provided new information on dust transport pathways, as well as the reach and impact of dust. It has also expanded our understanding of the processes driving dust emissions over decadal to millennial timescales through linking dust deposits directly to source area conditions. Dust provenance studies have shown that dust emission, transport and deposition are highly sensitive to variability in climate. They also imply that dust emissions are not simply a function of the degree of aridity in source areas, but respond to a more complex array of conditions, including sediment availability. As well as recording natural variability, dust records are also shown to sensitively track the impact of human activity. This is reflected by both changing dust emission rates and changing dust chemistry. Specific examples of how dust responds to, and records change, are provided with our work on dust emissions from Australia, the most arid inhabited continent and the largest dust source in the Southern Hemisphere. These case studies show that Australian dust emissions reflect hydro-climate variability, with reorganisation of Australian dust source areas occurring during the mid to late Holocene. Dust emissions are shown to sensitively map the structure of the Last Glacial Maximum in Australia, demonstrating that this period was associated with enhanced, but also variable dust emissions, driven by changing sources area conditions. Finally we show how dust emissions have responded to the arrival of Europeans and the associated onset of broad-scale agriculture across the Australian continent

Nutrient stress alters the glycosylation status of LGR5 resulting in reduced protein stability and membrane localisation in colorectal tumour cells: implications for targeting cancer stem cells

BACKGROUND LGR5 is an important marker of intestinal stem cells and performs its vital functions at the cell membrane. Despite the importance of LGR5 to both normal and cancer stem cell biology, it is not known how microenvironmental stress affects the expression and subcellular distribution of the protein. METHODS Nutrient stress was induced through glucose starvation. Glycosylation status was assessed using endoglycosidase or tunicamycin treatment. Flow cytometry and confocal microscopy were used to assess subcellular distribution of LGR5. RESULTS Glucose deprivation altered the glycosylation status of LGR5 resulting in reduced protein stability and cell surface expression. Furthermore, inhibiting LGR5 glycosylation resulted in depleted surface expression and reduced localisation in the cis-Golgi network. CONCLUSIONS Nutrient stress within a tumour microenvironment has the capacity to alter LGR5 protein stability and membrane localisation through modulation of LGR5 glycosylation status. As LGR5 surface localisation is required for enhanced Wnt signalling, this is the first report to show a mechanism by which the microenvironment could affect LGR5 function