Prognostic variables and scores identifying the last year of life in COPD: a systematic review protocol

Introduction People living with advanced chronic obstructive pulmonary disease (COPD) suffer from significant morbidity, reduced quality of life and high mortality, and are likely to benefit from many aspects of a palliative care approach. Prognostic estimates are a meaningful part of decision-making and better evidence for such estimates would facilitate advance care planning. We aim to provide quality evidence on known prognostic variables and scores which predict a prognosis in COPD of <12 months for use in the community. Methods and analysis We will conduct a systematic review of randomised or quasi-randomised controlled trials, prospective and retrospective longitudinal cohort and case–control studies on prognostic variables, multivariate scores or models for COPD. The search will cover the period up to April 2016. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with data extraction using fields from the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) checklist for multivariate models, and study quality will be assessed using a modified version of the Quality In Prognosis Studies (QUIPS) tool. Ethics and dissemination The results will be disseminated through peer-reviewed publications and national and international conference presentations

Power distance orientation alleviates the beneficial effects of empowering leadership on actors' work engagement via negative affect and sleep quality

Although many studies have explored the benefits of empowering leadership for followers, the beneficial effect of such behavior for actors who demonstrate empowering leadership has been overlooked. Applying conservation of resources theory, we propose and test a model that determines why and when empowering leadership benefits actors. We use an experience sampling survey to examine the effect of empowering leadership on actors’ daily work engagement. In particular, we focus on the moderating role of power distance orientation and the mediating roles of negative affect and sleep quality, which operate sequentially. The results based on responses from 160 supervisors in two Chinese organizations indicated that empowering leadership in the morning was negatively related to negative affect in the afternoon and positively related to sleep quality at night and next-day work engagement. The strength of this beneficial effect was moderated by power distance orientation, such that supervisors with a high degree of power distance orientation obtained fewer benefits from empowering leadership than those with a low degree of power distance orientation. The theoretical and practical implications of these findings for the leadership, affect, sleep, power distance, and conservation of resources literatures are discussed

Phosphorylation of the androgen receptor is associated with reduced survival in hormonerefractory prostate cancer patients

Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed to investigate the expression and phosphorylation status of Akt and AR in matched hormone-sensitive and -refractory prostate cancer tumours from 68 patients. In the hormone-refractory tissue, only phosphorylated AR (pAR) was associated with shorter time to death from relapse (&lt;i&gt;P&lt;/i&gt;=0.003). However, when an increase in expression in the transition from hormone-sensitive to -refractory prostate cancer was investigated, an increase in expression of PI3K was associated with decreased time to biochemical relapse (&lt;i&gt;P&lt;/i&gt;=0.014), and an increase in expression of pAkt&lt;sup&gt;473&lt;/sup&gt; and pAR&lt;sup&gt;210&lt;/sup&gt; were associated with decreased disease-specific survival (&lt;i&gt;P&lt;/i&gt;=0.0019 and 0.0015, respectively). Protein expression of pAkt&lt;sup&gt;473&lt;/sup&gt; and pAR&lt;sup&gt;210&lt;/sup&gt; also strongly correlated (&lt;i&gt;P&lt;/i&gt;&#60;0.001, c.c.=0.711) in the hormone-refractory prostate tumours. These results provide evidence using clinical specimens, that upregulation of the PI3K/Akt pathway is associated with phosphorylation of the AR during development of HRPC, suggesting that this pathway could be a potential therapeutic target

Mice have a transcribed L-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene

BACKGROUND: There are three pathways of L-threonine catabolism. The enzyme L-threonine aldolase (TA) has been shown to catalyse the conversion of L-threonine to yield glycine and acetaldehyde in bacteria, fungi and plants. Low levels of TA enzymatic activity have been found in vertebrates. It has been suggested that any detectable activity is due to serine hydroxymethyltransferase and that mammals lack a genuine threonine aldolase. RESULTS: The 7-exon murine L-threonine aldolase gene (GLY1) is located on chromosome 11, spanning 5.6 kb. The cDNA encodes a 400-residue protein. The protein has 81% similarity with the bacterium Thermotoga maritima TA. Almost all known functional residues are conserved between the two proteins including Lys242 that forms a Schiff-base with the cofactor, pyridoxal-5'-phosphate. The human TA gene is located at 17q25. It contains two single nucleotide deletions, in exons 4 and 7, which cause frame-shifts and a premature in-frame stop codon towards the carboxy-terminal. Expression of human TA mRNA was undetectable by RT-PCR. In mice, TA mRNA was found at low levels in a range of adult tissues, being highest in prostate, heart and liver. In contrast, serine/threonine dehydratase, another enzyme that catabolises L-threonine, is expressed very highly only in the liver. Serine dehydratase-like 1, also was most abundant in the liver. In whole mouse embryos TA mRNA expression was low prior to E-15 increasing more than four-fold by E-17. CONCLUSION: Mice, the western-clawed frog and the zebrafish have transcribed threonine aldolase/GLY1 genes, but the human homolog is a non-transcribed pseudogene. Serine dehydratase-like 1 is a putative L-threonine catabolising enzyme

Coordination of opposing sex-specific and core muscle groups regulates male tail posture during Caenorhabditis elegans male mating behavior

Background To survive and reproduce, animals must be able to modify their motor behavior in response to changes in the environment. We studied a complex behavior of Caenorhabditis elegans, male mating behavior, which provided a model for understanding motor behaviors at the genetic, molecular as well as circuit level. C. elegans male mating behavior consists of a series of six sub-steps: response to contact, backing, turning, vulva location, spicule insertion, and sperm transfer. The male tail contains most of the sensory structures required for mating, in addition to the copulatory structures, and thus to carry out the steps of mating behavior, the male must keep his tail in contact with the hermaphrodite. However, because the hermaphrodite does not play an active role in mating and continues moving, the male must modify his tail posture to maintain contact. We provide a better understanding of the molecular and neuro-muscular pathways that regulate male tail posture during mating. Results Genetic and laser ablation analysis, in conjunction with behavioral assays were used to determine neurotransmitters, receptors, neurons and muscles required for the regulation of male tail posture. We showed that proper male tail posture is maintained by the coordinated activity of opposing muscle groups that curl the tail ventrally and dorsally. Specifically, acetylcholine regulates both ventral and dorsal curling of the male tail, partially through anthelmintic levamisole-sensitive, nicotinic receptor subunits. Male-specific muscles are required for acetylcholine-driven ventral curling of the male tail but dorsal curling requires the dorsal body wall muscles shared by males and hermaphrodites. Gamma-aminobutyric acid activity is required for both dorsal and ventral acetylcholine-induced curling of the male tail and an inhibitory gamma-aminobutyric acid receptor, UNC-49, prevents over-curling of the male tail during mating, suggesting that cross-inhibition of muscle groups helps maintain proper tail posture. Conclusion Our results demonstrated that coordination of opposing sex-specific and core muscle groups, through the activity of multiple neurotransmitters, is required for regulation of male tail posture during mating. We have provided a simple model for regulation of male tail posture that provides a foundation for studies of how genes, molecular pathways, and neural circuits contribute to sensory regulation of this motor behavior

An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability

Carbon stock growth in a forest stand: the power of age

BACKGROUND: Understanding the relationship between the age of a forest stand and its biomass is essential for managing the forest component of the global carbon cycle. Since biomass increases with stand age, postponing harvesting to the age of biological maturity may result in the formation of a large carbon sink. This article quantifies the carbon sequestration capacity of forests by suggesting a default rule to link carbon stock and stand age. RESULTS: The age dependence of forest biomass is shown to be a power-law monomial where the power of age is theoretically estimated to be 4/5. This theoretical estimate is close to the known empirical estimate; therefore, it provides a scientific basis for a quick and transparent assessment of the benefits of postponing the harvest, suggesting that the annual magnitude of the sink induced by delayed harvest lies in the range of 1–2% of the baseline carbon stock. CONCLUSION: The results of this study imply that forest age could be used as an easily understood and scientifically sound measure of the progress in complying with national targets on the protection and enhancement of forest carbon sinks

Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China

In a cohort of 29 584 residents of Linxian, China, followed from 1985 to 2001, we conducted a case–cohort study of the magnitude of the association of Helicobacter pylori seropositivity with cancer risk in a random sample of 300 oesophageal squamous cell carcinomas, 600 gastric cardia adenocarcinomas, all 363 diagnosed gastric non-cardia adenocarcinomas, and a random sample of the entire cohort (N=1050). Baseline serum was evaluated for IgG antibodies to whole-cell and CagA H. pylori antigens by enzyme-linked immunosorbent assay. Risks of both gastric cardia and non-cardia cancers were increased in individuals exposed to H. pylori (Hazard ratios (HRs) and 95% confidence intervals=1.64; 1.26–2.14, and 1.60; 1.15–2.21, respectively), whereas risk of oesophageal squamous cell cancer was not affected (1.17; 0.88–1.57). For both cardia and non-cardia cancers, HRs were higher in younger individuals. With longer time between serum collection to cancer diagnosis, associations became stronger for cardia cancers but weaker for non-cardia cancers. CagA positivity did not modify these associations. The associations between H. pylori exposure and gastric cardia and non-cardia adenocarcinoma development were equally strong, in contrast to Western countries, perhaps due to the absence of Barrett's oesophagus and oesophageal adenocarcinomas in Linxian, making all cardia tumours of gastric origin, rather than a mixture of gastric and oesophageal malignancies