Predictive factors for skeletal complications in hormone-refractory prostate cancer patients with metastatic bone disease

Factors predictive of skeletal-related events (SREs) in bone metastatic prostate cancer patients with hormone-refractory disease were investigated. We evaluated the frequency of SREs in 200 hormone-refractory patients consecutively observed at our Institution and followed until death or the last follow-up. Baseline parameters were evaluated in univariate and multivariate analysis as potential predictive factors of SREs. Skeletal-related events were observed in 86 patients (43.0%), 10 of which (5.0%) occurred before the onset of hormone-refractory disease. In univariate analysis, patient performance status (P=0.002), disease extent (DE) in bone (P=0.0001), bone pain (P=0.0001), serum alkaline phosphatase (P=0.0001) and urinary N-telopeptide of type one collagen (P=0.0001) directly correlated with a greater risk to develop SREs, whereas Gleason score at diagnosis, serum PSA, Hb, serum albumin, serum calcium, types of bone lesions and duration of androgen deprivation therapy did not. Both DE in bone (hazard ratio (HR): 1.16, 95% confidence interval (CI): 1.07–1.25, P=0.000) and pain score (HR: 1.13, 95% CI: 1.06–1.20, P=0.000) were independent variables predicting for the onset of SREs in multivariate analysis. In patients with heavy tumour load in bone and great bone pain, the percentage of SREs was almost twice as high as (26 vs 52%, P<0.02) and occurred significantly earlier (P=0.000) than SREs in patients with limited DE in bone and low pain. Bone pain and DE in bone independently predict the occurrence of SREs in bone metastatic prostate cancer patients with hormone-refractory disease. These findings could help physicians in tailoring the skeletal follow-up most appropriate to individual patients and may prove useful for stratifying patients enrolled in bisphosphonate clinical trials

The TNFalpha gene relates to clinical phenotype in alpha-1-antitrypsin deficiency

<p>Abstract</p> <p>Background</p> <p>Genetic variation may underlie phenotypic variation in chronic obstructive pulmonary disease (COPD) in subjects with and without alpha 1 antitrypsin deficiency (AATD). Genotype specific sub-phenotypes are likely and may underlie the poor replication of previous genetic studies. This study investigated subjects with AATD to determine the relationship between specific phenotypes and <it>TNFα </it>polymorphisms.</p> <p>Methods</p> <p>424 unrelated subjects of the PiZZ genotype were assessed for history of chronic bronchitis, impairment of lung function and radiological presence of emphysema and bronchiectasis. A subset of subjects with 3 years consecutive lung function data was assessed for decline of lung function. Four single nucleotide polymorphisms (SNPs) tagging <it>TNFα </it>were genotyped using TaqMan^®genotyping technologies and compared between subjects affected by each phenotype and those unaffected. Plasma TNFα levels were measured in all PiZZ subjects.</p> <p>Results</p> <p>All SNPs were in Hardy-Weinberg equilibrium. A significant difference in rs361525 genotype (p = 0.01) and allele (p = 0.01) frequency was seen between subjects with and without chronic bronchitis, independent of the presence of other phenotypes. TNFα plasma level showed no phenotypic or genotypic associations.</p> <p>Conclusion</p> <p>Variation in <it>TNFα </it>is associated with chronic bronchitis in AATD.</p

PRegnancy Outcomes after a Maternity Intervention for Stressful EmotionS (PROMISES): study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>There is ample evidence from observational prospective studies that maternal depression or anxiety during pregnancy is a risk factor for adverse psychosocial outcomes in the offspring. However, to date no previous study has demonstrated that treatment of depressive or anxious symptoms in pregnancy actually could prevent psychosocial problems in children. Preventing psychosocial problems in children will eventually bring down the huge public health burden of mental disease. The main objective of this study is to assess the effects of cognitive behavioural therapy in pregnant women with symptoms of anxiety or depression on the child's development as well as behavioural and emotional problems. In addition, we aim to study its effects on the child's development, maternal mental health, and neonatal outcomes, as well as the cost-effectiveness of cognitive behavioural therapy relative to usual care.</p> <p>Methods/design</p> <p>We will include 300 women with at least moderate levels of anxiety or depression at the end of the first trimester of pregnancy. By including 300 women we will be able to demonstrate effect sizes of 0.35 or over on the total problems scale of the child behavioural checklist 1.5-5 with alpha 5% and power (1-beta) 80%.</p> <p>Women in the intervention arm are offered 10-14 individual cognitive behavioural therapy sessions, 6-10 sessions during pregnancy and 4-8 sessions after delivery (once a week). Women in the control group receive care as usual.</p> <p>Primary outcome is behavioural/emotional problems at 1.5 years of age as assessed by the total problems scale of the child behaviour checklist 1.5 - 5 years.</p> <p>Secondary outcomes will be mental, psychomotor and behavioural development of the child at age 18 months according to the Bayley scales, maternal anxiety and depression during pregnancy and postpartum, and neonatal outcomes such as birth weight, gestational age and Apgar score, health care consumption and general health status (economic evaluation).</p> <p>Trial Registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2242">NTR2242</a></p

A bacterial genome in transition - an exceptional enrichment of IS elements but lack of evidence for recent transposition in the symbiont Amoebophilus asiaticus

<p>Abstract</p> <p>Background</p> <p>Insertion sequence (IS) elements are important mediators of genome plasticity and are widespread among bacterial and archaeal genomes. The 1.88 Mbp genome of the obligate intracellular amoeba symbiont <it>Amoebophilus asiaticus </it>contains an unusually large number of transposase genes (n = 354; 23% of all genes).</p> <p>Results</p> <p>The transposase genes in the <it>A. asiaticus </it>genome can be assigned to 16 different IS elements termed ISCaa1 to ISCaa16, which are represented by 2 to 24 full-length copies, respectively. Despite this high IS element load, the <it>A. asiaticus </it>genome displays a GC skew pattern typical for most bacterial genomes, indicating that no major rearrangements have occurred recently. Additionally, the high sequence divergence of some IS elements, the high number of truncated IS element copies (n = 143), as well as the absence of direct repeats in most IS elements suggest that the IS elements of <it>A. asiaticus </it>are transpositionally inactive. Although we could show transcription of 13 IS elements, we did not find experimental evidence for transpositional activity, corroborating our results from sequence analyses. However, we detected contiguous transcripts between IS elements and their downstream genes at nine loci in the <it>A. asiaticus </it>genome, indicating that some IS elements influence the transcription of downstream genes, some of which might be important for host cell interaction.</p> <p>Conclusions</p> <p>Taken together, the IS elements in the <it>A. asiaticus </it>genome are currently in the process of degradation and largely represent reflections of the evolutionary past of <it>A. asiaticus </it>in which its genome was shaped by their activity.</p

Not Quite Right: Representations of Eastern Europeans in ECJ Discourse

Although the increasing responsiveness of the Court of Justice of the European Union (the ‘ECJ’) jurisprudence to western Member States’ concerns regarding Central and Eastern European (‘CEE’) nationals’ mobility has garnered academic attention, ECJ discourse has not been scrutinised for how it approaches the CEE region or CEE movers. Applying postcolonial theory, this article seeks to fill this gap and to explore whether there are any indications that ECJ discourse is in line with the historical western-centric inferiorisation of the CEE region. A critical discourse analysis of a set of ECJ judgments and corresponding Advocate General opinions pertaining to CEE nationals illustrates not only how the ECJ adopts numerous discursive strategies to maintain its authority, but also how it tends to prioritise values of the western Member States, while overlooking interests of CEE movers. Its one-sided approach is further reinforced by referring to irrelevant facts and negative assumptions to create an image of CEE nationals as socially and economically inferior to westerners, as not belonging to the proper EU polity and as not quite deserving of EU law’s protections. By silencing CEE nationals’ voices, while disregarding the background of east/west socio-economic and political power differentials and precariousness experienced by many CEE workers in the west, such racialising discourse normalises ethnicity- and class-based stereotypes. These findings also help to contextualise both EU and western policies targeting CEE movers and evidence of their unequal outcomes in the west, and are in line with today’s nuanced expressions of racisms. By illustrating the ECJ’s role in addressing values pertinent to mobile CEE individuals, this study facilitates a fuller appreciation of the ECJ’s power in shaping and reflecting western-centric EU identity and policies. Engaging with such issues will not only allow us to better appreciate—and question—the ECJ’s legitimacy, but might also facilitate a better understanding of power dynamics within the EU. This study also makes significant theoretical and methodological contributions. It expands (and complicates) the application of postcolonial theory to contemporary intra-EU processes, while illustrating the usefulness of applying critical discourse analysis to exploring differentiation, exclusion, subordination and power within legal language

Policing a Negotiated World: A Partial Test of Klinger’s Ecological Theory of Policing

The primary goal of the current study is to examine a portion of Klinger’s theory. Specifically, we test the influence of organizational and environmental contextual factors, guided by Klinger’s theory, on one measure of officer vigor. To date, few studies have taken this approach to examine Klinger’s theory. The study builds on prior research that has tested aspects of Klinger’s theory and adds new analytic strategies that prior studies have not used. The results of this study have implications for both theory and practice, and they add to the growing literature examining the influence of ecological and organization factors on police behavior