Incidence and treatment costs of severe bacterial infections among people who inject heroin: A cohort study in South London, England.

BACKGROUND: People who inject drugs often get bacterial infections. Few longitudinal studies have reported the incidence and treatment costs of these infections. METHODS: For a cohort of 2335 people who inject heroin entering treatment for drug dependence between 2006 and 2017 in London, England, we reported the rates of hospitalisation or death with primary causes of cutaneous abscess, cellulitis, phlebitis, septicaemia, osteomyelitis, septic arthritis, endocarditis, or necrotising fasciitis. We compared these rates to the general population. We also used NHS reference costs to calculate the cost of admissions. RESULTS: During a median of 8.0 years of follow-up, 24 % of patients (570/2335) had a severe bacterial infection, most commonly presenting with cutaneous abscesses or cellulitis. Bacterial infections accounted for 13 % of all hospital admissions. The rate was 73 per 1000 person-years (95 % CI 69-77); 50 times the general population, and the rate remained high throughout follow-up. The rate of severe bacterial infections for women was 1.50 (95 % CI 1.32-1.69) times the rate for men. The mean cost per admission was £4980, and we estimate that the annual cost of hospital treatment for people who inject heroin in London is £4.5 million. CONCLUSIONS: People who inject heroin have extreme and long-term risk of severe bacterial infections

Efficiently Reusing Natural Language Processing Models for Phenotype Identification in Free-text Electronic Medical Records: Methodological Study

Background: Many efforts have been put into the use of automated approaches, such as natural language processing (NLP), to mine or extract data from free-text medical records to construct comprehensive patient profiles for delivering better health-care. Reusing NLP models in new settings, however, remains cumbersome - requiring validation and/or retraining on new data iteratively to achieve convergent results. Objective: The aim of this work is to minimise the effort involved in reusing NLP models on free-text medical records. Methods: We formally define and analyse the model adaptation problem in phenotype identification tasks. We identify “duplicate waste” and “imbalance waste”, which collectively impede efficient model reuse. We propose a concept embedding based approach to minimise these sources of waste without the need for labelled data from new settings. Results: We conduct experiments on data from a large mental health registry to reuse NLP models in four phenotype identification tasks. The proposed approach can choose the best model for a new task, identifying up to 76% of phenotype mentions without the need for validation and model retraining, and with very good performance (93-97% accuracy). It can also provide guidance for validating and retraining the selected model for novel language patterns in new tasks, saving around 80% of the effort required in “blind” model-adaptation approaches. Conclusions: Adapting pre-trained NLP models for new tasks can be more efficient and effective if the language pattern landscapes of old settings and new settings can be made explicit and comparable. Our experiments show that the phenotype embedding approach is an effective way to model language patterns for phenotype identification tasks and that its use can guide efficient NLP model reuse

Sex-limited genome-wide linkage scan for body mass index in an unselected sample of 933 Australian twin families

Genes involved in pathways regulating body weight may operate differently in men and women. To determine whether sex-limited genes influence the obesity-related phenotype body mass index (BMI), we have conducted a general non-scalar sex-limited genome-wide linkage scan using variance components analysis in Mx (Neale, 2002). BMI measurements and genotypic data were available for 2053 Australian female and male adult twins and their siblings from 933 families. Clinical measures of BMI were available for 64.4% of these individuals, while only self-reported measures were available for the remaining participants. The mean age of participants was 39.0 years of age (SD 12.1 years). The use of a sex-limited linkage model identified areas on the genome where quantitative trait loci (QTL) effects differ between the sexes, particularly on chromosome 8 and 20, providing us with evidence that some of the genes responsible for BMI may have different effects in men and women. Our highest linkage peak was observed at 12q24 (-logp = 3.02), which was near the recommended threshold for suggestive linkage (-logp = 3.13). Previous studies have found evidence for a quantitative trait locus on 12q24 affecting BMI in a wide range of populations, and candidate genes for non-insulin-dependent diabetes mellitus, a consequence of obesity, have also been mapped to this region. We also identified many peaks near a -log p of 2 (threshold for replicating an existing finding) in many areas across the genome that are within regions previously identified by other studies, as well as in locations that harbor genes known to influence weight regulation

Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure

Identifying unmet clinical need in hypertrophic cardiomyopathy using national electronic health records

Introduction: To evaluate unmet clinical need in unselected hypertrophic cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent cardiovascular disease endpoints and safety endpoints relevant for trial design. Methods: Population based cohort (CALIBER, linked primary care, hospital and mortality records in England, period 1997–2010), all people diagnosed with HCM were identified and matched by age, sex and general practice with ten randomly selected people without HCM. Random-effects Poisson models were used to assess the associations between HCM and cardiovascular diseases and bleeding. Results: Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was found in 4 per 10,000. Forty-one percent of the 1,160 individuals with hypertrophic cardiomyopathy were women and the median age was 57 years. The median follow-up was 4.0 years. Compared to general population controls, people with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53, [95% confidence interval 12.67–43.72]), cardiac arrest or sudden cardiac death (6.33 [3.69–10.85]), heart failure (4.31, [3.30–5.62]), and atrial fibrillation (3.80 [3.04–4.75]). HCM was also associated with a higher incidence of myocardial infarction ([MI] 1.90 [1.27–2.84]) and coronary revascularisation (2.32 [1.46–3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite endpoint of cardiovascular death or heart failure, 8.4% for the composite of cardiovascular death, stroke or myocardial infarction, and 1.5% for major bleeding. Conclusions: Our study identified major unmet need in HCM and highlighted the importance of implementing improved cardiovascular prevention strategies to increase life-expectancy of the contemporary HCM population. They also show that national electronic health records provide an effective method for identifying outcomes and clinically relevant estimates of composite efficacy and safety endpoints essential for trial design in rare diseases

Measurements of daily energy intake and total energy expenditure in people with dementia in care homes: the use of wearable technology.

Objectives: To estimate daily total energy expenditure (TEE) using a physical activity monitor, combined with dietary assessment of energy intake to assess the relationship between daily energy expenditure and patterns of activity with energy intake in people with dementia living in care homes. Design and setting: A cross-sectional study in care homes in the UK. Participants: Twenty residents with confirmed dementia diagnosis were recruited from two care homes that specialised in dementia care. Measurements: A physical activity monitor (Sensewear TM Armband , Body Media, Pittsburgh, PA) was employed to objectively determine total energy expenditure, sleep duration and physical activity. The armband was placed around the left upper triceps for up to 7 days. Energy intake was determined by weighing all food and drink items over 4 days (3 weekdays and 1 weekend day) including measurements of food wastage. Results: The mean age was 78.7 (SD ± 11.8) years, Body Mass Index (BMI) 23.0 (SD ± 4.2) kg/m2 ; 50% were women. Energy intake (mean 7.4; SD ± 2.6) MJ/d) was correlated with TEE (mean 7.6; SD ± 1.8 MJ/d; r=0.49, p<0.05). Duration of sleeping ranged from 0.4-12.5 (mean 6.1) hrs/d and time spent lying down was 1.3-16.0 (8.3) hrs/d. On average residents spent 17.9 (6.3-23.4) hrs/d undertaking sedentary activity. TEE was correlated with BMI (r=0.52, p<0.05) and body weight (r=0.81, p<0.001) but inversely related to sleep duration (r=-0.59, p<0.01) and time lying down (r=-0.62, p<0.01). Multiple linear regression analysis revealed that after taking BMI, sleep duration and time spent lying down into account, TEE was no longer correlated with energy intake. Conclusions: The results show the extent to which body mass, variable activity and sleep patterns may be contributing to TEE and together with reduced energy intake, energy requirements were not satisfied. Thus wearable technology has the potential to offer real-time monitoring to provide appropriate nutrition management that is more person-centred to prevent weight loss in dementi

Daf-2 Signaling Modifies Mutant SOD1 Toxicity in C. elegans

The DAF-2 Insulin/IGF-1 signaling (IIS) pathway is a strong modifier of Caenorhabditis elegans longevity and healthspan. As aging is the greatest risk factor for developing neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), we were interested in determining if DAF-2 signaling modifies disease pathology in mutant superoxide dismutase 1 (SOD1) expressing C. elegans. Worms with pan-neuronal G85R SOD1 expression demonstrate significantly impaired locomotion as compared to WT SOD1 expressing controls and they develop insoluble SOD1 aggregates. Reductions in DAF-2 signaling, either through a hypomorphic allele or neuronally targeted RNAi, decreases the abundance of aggregated SOD1 and results in improved locomotion in a DAF-16 dependant manner. These results suggest that manipulation of the DAF-2 Insulin/IGF-1 signaling pathway may have therapeutic potential for the treatment of ALS

Electronic Cigarette Advertising Impacts Adversely on Smoking Behaviour Within a London Student Cohort: A Cross-Sectional Structured Survey.

INTRODUCTION: In contrast to tobacco smoking, electronic cigarette ("vaping") advertisement had been approved in the United Kingdom (UK) in January 2013. Currently, there are an estimated 3.2 million UK e-cigarette users. The impact of e-cigarette advertisement on tobacco use has not been studied in detail. We hypothesised that e-cigarette advertisement impacts on conventional smoking behaviour. METHODS: A cross-sectional structured survey assessed the impact of e-cigarette advertising on the perceived social acceptability of cigarette and e-cigarette smoking and on using either cigarettes or e-cigarettes (on a scale of 1 to 5/'not at all' to 'a lot'). The survey was administered between January to March 2015 to London university students, before and after viewing 5 UK adverts including a TV commercial. RESULTS: Data were collected from 106 participants (22 ± 2 years, 66% male), comprising cigarette smokers (32%), non-smokers (54%) and ex-smokers (14%). This included vapers (16%), non-vapers (77%) and ex-vapers (7%). After viewing the adverts, smokers (2.6 ± 1.0 vs. 3.8 ± 1.1, p = 0.001) and non-smokers (3.2 ± 0.7 vs. 3.7 ± 0.8, p = 0.007) felt smoking was more socially acceptable, compared to before viewing them. Participants were more likely to try both e-cigarettes (1.90 ± 1.03 to 3.09 ± 1.11, p < 0.001) and conventional cigarettes (1.73 ± 0.83 to 2.27 ± 1.13, p < 0.001) after viewing the adverts compared to before. Vapers were less likely to smoke both an e-cigarette, and a conventional cigarette after viewing the adverts. CONCLUSION: E-cigarette advertising encourages both e-cigarette and conventional cigarette use in young smokers and non-smokers. The adverts increase the social acceptability of smoking without regarding the importance of public health campaigns that champion smoking cessation

Inflammation Triggers Emergency Granulopoiesis through a Density-Dependent Feedback Mechanism

Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of “emergency” granulopoiesis that is dependent on C/EBPβ. Here, we show in mice that alum triggers emergency granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R neutralization impairs proliferative responses of hematopoietic stem and progenitor cells (HSPC) to alum, but also abrogates the acute mobilization of BM neutrophils, raising the possibility that HSPC responses to inflammation are an indirect result of the exhaustion of BM neutrophil stores. The induction of neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1, elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic responses indistinguishable from those induced by adjuvant. Notably, C/EBPβ, thought to be necessary for enhanced generative capacity of BM, is dispensable for increased proliferation of HSPC to alum or neutropenia, but plays a role in terminal neutrophil differentiation during granulopoietic recovery. We conclude that alum elicits a transient increase in G-CSF production via IL-1RI for the mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF for accelerated granulopoiesis

Juvenile Greylag Geese (Anser anser) Discriminate between Individual Siblings

Social species that maintain individualised relationships with certain others despite continuous changes in age, reproductive status and dominance rank between group members ought to be capable of individual recognition. Tests of “true” individual recognition, where an individual recognises unique features of another, are rare, however. Often kinship and/or familiarity suffice to explain dyadic interactions. The complex relationships within a greylag goose flock suggest that they should be able to recognise individuals irrespective of familiarity or kinship. We tested whether six-week-old hand-raised greylags can discriminate between two of their siblings. We developed a new experimental protocol, in which geese were trained to associate social siblings with geometrical symbols. Subsequently, focals were presented with two geometrical symbols in the presence of a sibling associated with one of the symbols. Significant choice of the geometrical symbol associated with the target present indicated that focals were able to distinguish between individual targets. Greylag goslings successfully learned this association-discrimination task, regardless of genetic relatedness or sex of the sibling targets. Social relationships within a goose flock thus may indeed be based on recognition of unique features of individual conspecifics