Palliative radiotherapy:New prognostic factors for patients with bone metastasis

Purpose: Many cancer patients develop bone metastases, however the prognosis of overall survival differs. To provide an optimal treatment for these patients, especially towards the end of life, a reliable prediction of survival is needed. The goal of this study was to find new clinical factors in relation to overall survival. Materials and methods: Prospectively 22 clinical factors were collected from 734 patients. The Kaplan–Meier and Cox regression models were used. Results: Most patients were diagnosed with lung cancer (29%), followed by prostate (19.8%) and breast cancer (14.7%). Median overall survival was 6.4 months. Fourteen clinical factors showed significance in the univariate analyses. In the multivariate analyses 6 factors were found to be significant for the overall survival: Karnofsky performance status, primary tumor, gender, total organs affected, morphine use and systemic treatment options after radiotherapy. Conclusion: Morphine use and systemic treatment options after radiotherapy, Karnofsky performance status, primary tumor, gender and total organs affected are strong prediction factors on overall survival after palliative radiotherapy in patients with bone metastasis. These factors are easily applicable in the clinic.</p

Like Will to Like: Abundances of Closely Related Species Can Predict Susceptibility to Intestinal Colonization by Pathogenic and Commensal Bacteria

The intestinal ecosystem is formed by a complex, yet highly characteristic microbial community. The parameters defining whether this community permits invasion of a new bacterial species are unclear. In particular, inhibition of enteropathogen infection by the gut microbiota ( = colonization resistance) is poorly understood. To analyze the mechanisms of microbiota-mediated protection from Salmonella enterica induced enterocolitis, we used a mouse infection model and large scale high-throughput pyrosequencing. In contrast to conventional mice (CON), mice with a gut microbiota of low complexity (LCM) were highly susceptible to S. enterica induced colonization and enterocolitis. Colonization resistance was partially restored in LCM-animals by co-housing with conventional mice for 21 days (LCMcon21). 16S rRNA sequence analysis comparing LCM, LCMcon21 and CON gut microbiota revealed that gut microbiota complexity increased upon conventionalization and correlated with increased resistance to S. enterica infection. Comparative microbiota analysis of mice with varying degrees of colonization resistance allowed us to identify intestinal ecosystem characteristics associated with susceptibility to S. enterica infection. Moreover, this system enabled us to gain further insights into the general principles of gut ecosystem invasion by non-pathogenic, commensal bacteria. Mice harboring high commensal E. coli densities were more susceptible to S. enterica induced gut inflammation. Similarly, mice with high titers of Lactobacilli were more efficiently colonized by a commensal Lactobacillus reuteri RR strain after oral inoculation. Upon examination of 16S rRNA sequence data from 9 CON mice we found that closely related phylotypes generally display significantly correlated abundances (co-occurrence), more so than distantly related phylotypes. Thus, in essence, the presence of closely related species can increase the chance of invasion of newly incoming species into the gut ecosystem. We provide evidence that this principle might be of general validity for invasion of bacteria in preformed gut ecosystems. This might be of relevance for human enteropathogen infections as well as therapeutic use of probiotic commensal bacteria

Telling stories about European Union Health Law: The emergence of a new field of law

The ideational narrative power of law has now solidified, and continues to solidify, ‘European Union health law’, into an entity with a distinctive legal identity. EU health law was previously seen as either non-existent, or so broad as to be meaningless, or as existing only in relations between EU law and health (the ‘and’ approach), or as consisting of a body of barely or loosely connected policy domains (the ‘patchwork’ approach). The process of bringing EU health law into being is a process of narration. The ways in which EU health law is narrated (and continues to be narrated) involve three main groups of actors: the legislature, courts and the academy

Police performance measurement: an annotated bibliography

This study provides information to assist those involved in performance measurement in police organisations. The strategies used to identify the literature are described. Thematic sections cover; general overviews; methodological issues; performance management in other industries; national, international and cross-national studies; frameworks (e.g. Compstat; the Balanced Scorecard); criticisms (particularly unintended consequences); crime-specific measures; practitioner guides; performance evaluation of individual staff; police department plans and evaluations; annotated bibliographies in related areas, and; other literature. Our discussion offers two conclusions: the measures best aligned with performance are typically more expensive, while most operational data should only provide contextual information; the philosophy of open governance should be pursued to promote transparency, accountability and communication to improve police performance

Molecular networks of human muscle adaptation to exercise and age

Physical activity and molecular ageing presumably interact to precipitate musculoskeletal decline in humans with age. Herein, we have delineated molecular networks for these two major components of sarcopenic risk using multiple independent clinical cohorts. We generated genome-wide transcript profiles from individuals (n = 44) who then undertook 20 weeks of supervised resistance-exercise training (RET). Expectedly, our subjects exhibited a marked range of hypertrophic responses (3% to +28%), and when applying Ingenuity Pathway Analysis (IPA) up-stream analysis to ~580 genes that co-varied with gain in lean mass, we identified rapamycin (mTOR) signaling associating with growth (P = 1.4×10−30). Paradoxically, those displaying most hypertrophy exhibited an inhibited mTOR activation signature, including the striking down-regulation of 70 rRNAs. Differential analysis found networks mimicking developmental processes (activated all-trans-retinoic acid (ATRA, Z-score = 4.5; P = 6×10−13) and inhibited aryl-hydrocarbon receptor signaling (AhR, Z-score = −2.3; P = 3×10−7)) with RET. Intriguingly, as ATRA and AhR gene-sets were also a feature of endurance exercise training (EET), they appear to represent “generic” physical activity responsive gene-networks. For age, we found that differential gene-expression methods do not produce consistent molecular differences between young versus old individuals. Instead, utilizing two independent cohorts (n = 45 and n = 52), with a continuum of subject ages (18–78 y), the first reproducible set of age-related transcripts in human muscle was identified. This analysis identified ~500 genes highly enriched in post-transcriptional processes (P = 1×10−6) and with negligible links to the aforementioned generic exercise regulated gene-sets and some overlap with ribosomal genes. The RNA signatures from multiple compounds all targeting serotonin, DNA topoisomerase antagonism, and RXR activation were significantly related to the muscle age-related genes. Finally, a number of specific chromosomal loci, including 1q12 and 13q21, contributed by more than chance to the age-related gene list (P = 0.01–0.005), implying possible epigenetic events. We conclude that human muscle age-related molecular processes appear distinct from the processes regulated by those of physical activity

Research into the Health Benefits of Sprint Interval Training Should Focus on Protocols with Fewer and Shorter Sprints

Over the past decade, it has been convincingly shown that regularly performing repeated brief supramaximal cycle sprints (sprint interval training [SIT]) is associated with aerobic adaptations and health benefits similar to or greater than with moderate-intensity continuous training (MICT). SIT is often promoted as a time-efficient exercise strategy, but the most commonly studied SIT protocol (4–6 repeated 30-s Wingate sprints with 4 min recovery, here referred to as ‘classic’ SIT) takes up to approximately 30 min per session. Combined with high associated perceived exertion, this makes classic SIT unsuitable as an alternative/adjunct to current exercise recommendations involving MICT. However, there are no indications that the design of the classic SIT protocol has been based on considerations regarding the lowest number or shortest duration of sprints to optimise time efficiency while retaining the associated health benefits. In recent years, studies have shown that novel SIT protocols with both fewer and shorter sprints are efficacious at improving important risk factors of noncommunicable diseases in sedentary individuals, and provide health benefits that are no worse than those associated with classic SIT. These shorter/easier protocols have the potential to remove many of the common barriers to exercise in the general population. Thus, based on the evidence summarised in this current opinion paper, we propose that there is a need for a fundamental change in focus in SIT research in order to move away from further characterising the classic SIT protocol and towards establishing acceptable and effective protocols that involve minimal sprint durations and repetitions

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Risk Factors of Typhoid Infection in the Indonesian Archipelago.

BACKGROUND: Knowledge of risk factors and their relative importance in different settings is essential to develop effective health education material for the prevention of typhoid. In this study, we examine the effect of household level and individual behavioural risk factors on the risk of typhoid in three Indonesian islands (Sulawesi, Kalimantan and Papua) in the Eastern Indonesian archipelago encompassing rural, peri-urban and urban areas. METHODS: We enrolled 933 patients above 10 years of age in a health facility-based case-control study between June 2010 and June 2011. Individuals suspected of typhoid were tested using the typhoid IgM lateral flow assay for the serodiagnosis of typhoid fever followed by blood culture testing. Cases and controls were defined post-recruitment: cases were individuals with a culture or serology positive result (n = 449); controls were individuals negative to both serology and culture, with or without a diagnosis other than typhoid (n = 484). Logistic regression was used to examine the effect of household level and individual level behavioural risk factors and we calculated the population attributable fraction (PAF) of removing each risk significant independent behavioural risk factor. RESULTS: Washing hands at critical moments of the day and washing hands with soap were strong independent protective factors for typhoid (OR = 0.38 95% CI 0.25 to 0.58 for each unit increase in hand washing frequency score with values between 0 = Never and 3 = Always; OR = 3.16 95% CI = 2.09 to 4.79 comparing washing hands with soap sometimes/never vs. often). These effects were independent of levels of access to water and sanitation. Up to two thirds of cases could be prevented by compliance to these practices (hand washing PAF = 66.8 95% CI 61.4 to 71.5; use of soap PAF = 61.9 95%CI 56.7 to 66.5). Eating food out in food stalls or restaurant was an important risk factor (OR = 6.9 95%CI 4.41 to 10.8 for every unit increase in frequency score). CONCLUSIONS: Major gains could potentially be achieved in reducing the incidence of typhoid by ensuring adherence to adequate hand-washing practices alone. This confirms that there is a pivotal role for 'software' related interventions to encourage behavior change and create demand for goods and services, alongside development of water and sanitation infrastructure