Treatment Outcome of Alcoholics with and without Cocaine Disorders

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65587/1/j.1530-0277.1994.tb00939.x.pd

The Science Case for ALMA Band 2 and Band 2+3

We discuss the science drivers for ALMA Band 2 which spans the frequency range from 67 to 90 GHz. The key science in this frequency range are the study of the deuterated molecules in cold, dense, quiescent gas and the study of redshifted emission from galaxies in CO and other species. However, Band 2 has a range of other applications which are also presented. The science enabled by a single receiver system which would combine ALMA Bands 2 and 3 covering the frequency range 67 to 116 GHz, as well as the possible doubling of the IF bandwidth of ALMA to 16 GHz, are also considered

Hirsch Index and Truth Survival in Clinical Research

BACKGROUND: Factors associated with the survival of truth of clinical conclusions in the medical literature are unknown. We hypothesized that publications with a first author having a higher Hirsch' index value (h-I), which quantifies and predicts an individual's scientific research output, should have a longer half-life. METHODS AND RESULTS: 474 original articles concerning cirrhosis or hepatitis published from 1945 to 1999 were selected. The survivals of the main conclusions were updated in 2009. The truth survival was assessed by time-dependent methods (Kaplan Meier method and Cox). A conclusion was considered to be true, obsolete or false when three or more observers out of the six stated it to be so. 284 out of 474 conclusions (60%) were still considered true, 90 (19%) were considered obsolete and 100 (21%) false. The median of the h-I was=24 (range 1-85). Authors with true conclusions had significantly higher h-I (median=28) than those with obsolete (h-I=19; P=0.002) or false conclusions (h-I=19; P=0.01). The factors associated (P<0.0001) with h-I were: scientific life (h-I=33 for>30 years vs. 16 for<30 years), -methodological quality score (h-I=36 for high vs. 20 for low scores), and -positive predictive value combining power, ratio of true to not-true relationships and bias (h-I=33 for high vs. 20 for low values). In multivariate analysis, the risk ratio of h-I was 1.003 (95%CI, 0.994-1.011), and was not significant (P=0.56). In a subgroup restricted to 111 articles with a negative conclusion, we observed a significant independent prognostic value of h-I (risk ratio=1.033; 95%CI, 1.008-1.059; P=0.009). Using an extrapolation of h-I at the time of article publication there was a significant and independent prognostic value of baseline h-I (risk ratio=0.027; P=0.0001). CONCLUSIONS: The present study failed to clearly demonstrate that the h-index of authors was a prognostic factor for truth survival. However the h-index was associated with true conclusions, methodological quality of trials and positive predictive values

Predicting the Impact of Climate Change on Threatened Species in UK Waters

Global climate change is affecting the distribution of marine species and is thought to represent a threat to biodiversity. Previous studies project expansion of species range for some species and local extinction elsewhere under climate change. Such range shifts raise concern for species whose long-term persistence is already threatened by other human disturbances such as fishing. However, few studies have attempted to assess the effects of future climate change on threatened vertebrate marine species using a multi-model approach. There has also been a recent surge of interest in climate change impacts on protected areas. This study applies three species distribution models and two sets of climate model projections to explore the potential impacts of climate change on marine species by 2050. A set of species in the North Sea, including seven threatened and ten major commercial species were used as a case study. Changes in habitat suitability in selected candidate protected areas around the UK under future climatic scenarios were assessed for these species. Moreover, change in the degree of overlap between commercial and threatened species ranges was calculated as a proxy of the potential threat posed by overfishing through bycatch. The ensemble projections suggest northward shifts in species at an average rate of 27 km per decade, resulting in small average changes in range overlap between threatened and commercially exploited species. Furthermore, the adverse consequences of climate change on the habitat suitability of protected areas were projected to be small. Although the models show large variation in the predicted consequences of climate change, the multi-model approach helps identify the potential risk of increased exposure to human stressors of critically endangered species such as common skate (Dipturus batis) and angelshark (Squatina squatina)

Aromatase expression is increased in BRCA1 mutation carriers

<p>Abstract</p> <p>Background</p> <p>Until recently, the molecular mechanisms explaining increased incidence of ovarian and breast cancers in carriers of <it>BRCA1 </it>gene mutations had not been clearly understood. Of significance is the finding that BRCA1 negatively regulates aromatase expression <it>in vitro</it>. Our objective was to characterise aromatase gene <it>(CYP19A1) </it>and its promoter expression in breast adipose and ovarian tissue in <it>BRCA1 </it>mutation carriers and unaffected controls.</p> <p>Methods</p> <p>We measured aromatase transcripts, total and promoter-specific (PII, PI.3, PI.4) in prophylactic oophorectomy or mastectomy, therapeutic mastectomy, ovarian and breast tissue from unaffected women.</p> <p>Results</p> <p>We demonstrate that the lack of functional BRCA1 protein correlates to higher aromatase levels in 85% of <it>BRCA1 </it>mutation carriers. This increase is mediated by aberrant transcriptional regulation of aromatase; in breast adipose by increases in promoter II/I.3 and I.4-specific transcripts; and in the ovary with elevation in promoter I.3 and II-specific transcripts.</p> <p>Conclusion</p> <p>Understanding the link between BRCA1 and aromatase is significant in terms of understanding why carcinogenesis is restricted to estrogen-producing tissues in <it>BRCA1 </it>mutation carriers.</p

The Science Case for ALMA Band 2 and Band 2+3

We discuss the science drivers for ALMA Band 2 which spans the frequency range from 67 to 90 GHz. The key science in this frequency range are the study of the deuterated molecules in cold, dense, quiescent gas and the study of redshifted emission from galaxies in CO and other species. However, Band 2 has a range of other applications which are also presented. The science enabled by a single receiver system which would combine ALMA Bands 2 and 3 covering the frequency range 67 to 116 GHz, as well as the possible doubling of the IF bandwidth of ALMA to 16 GHz, are also considered

p68/DdX5 supports β-Catenin &amp; RNAP II during androgen receptor mediated transcription in prostate cancer

The DEAD box RNA helicase p68 (Ddx5) is an important androgen receptor (AR) transcriptional co-activator in prostate cancer (PCa) and is over-expressed in late stage disease. β-Catenin is a multifunctional protein with important structural and signalling functions which is up-regulated in PCa and similar to p68, interacts with the AR to co-activate expression of AR target genes. Importantly, p68 forms complexes with nuclear β-Catenin and promotes gene transcription in colon cancer indicating a functional interplay between these two proteins in cancer progression. In this study, we explore the relationship of p68 and β-Catenin in PCa to assess their potential co-operation in AR-dependent gene expression, which may be of importance in the development of castrate resistant prostate cancer (CRPCa). We use immunoprecipitation to demonstrate a novel interaction between p68 and β-Catenin in the nucleus of PCa cells, which is androgen dependent in LNCaP cells but androgen independent in a hormone refractory derivative of the same cell line (representative of the CRPCa disease type). Enhanced AR activity is seen in androgen-dependent luciferase reporter assays upon transient co-transfection of p68 and β-Catenin as an additive effect, and p68-depleted Chromatin-Immunoprecipitation (ChIP) showed a decrease in the recruitment of the AR and β-Catenin to androgen responsive promoter regions. In addition, we found p68 immunoprecipitated with the processive and non-processive form of RNA polymerase II (RNAP II) and show p68 recruited to elongating regions of the AR mediated PSA gene, suggesting a role for p68 in facilitating RNAP II transcription of AR mediated genes. These results suggest p68 is important in facilitating β-Catenin and AR transcriptional activity in PCa cells

Detection of viral respiratory pathogens in mild and severe acute respiratory infections in Singapore.

To investigate the performance of laboratory methods and clinical case definitions in detecting the viral pathogens for acute respiratory infections (ARIs) from a prospective community cohort and hospital inpatients, nasopharyngeal swabs from cohort members reporting ARIs (community-ARI) and inpatients admitted with ARIs (inpatient-ARI) were tested by Singleplex Real Time-Polymerase Chain Reaction (SRT-PCR), multiplex RT-PCR (MRT-PCR) and pathogen-chip system (PathChip) between April 2012 and December 2013. Community-ARI and inpatient-ARI was also combined with mild and severe cases of influenza from a historical prospective study as mild-ARI and severe-ARI respectively to evaluate the performance of clinical case definitions. We analysed 130 community-ARI and 140 inpatient-ARI episodes (5 inpatient-ARI excluded because multiple pathogens were detected), involving 138 and 207 samples respectively. Detection by PCR declined with days post-onset for influenza virus; decrease was faster for community-ARI than for inpatient-ARI. No such patterns were observed for non-influenza respiratory virus infections. PathChip added substantially to viruses detected for community-ARI only. Clinical case definitions discriminated influenza from other mild-ARI but performed poorly for severe-ARI and for older participants. Rational strategies for diagnosis and surveillance of influenza and other respiratory virus must acknowledge the differences between ARIs presenting in community and hospital settings

Woodland Recovery after Suppression of Deer: Cascade effects for Small Mammals, Wood Mice (Apodemus sylvaticus) and Bank Voles (Myodes glareolus)

Over the past century, increases in both density and distribution of deer species in the Northern Hemisphere have resulted in major changes in ground flora and undergrowth vegetation of woodland habitats, and consequentially the animal communities that inhabit them. In this study, we tested whether recovery in the vegetative habitat of a woodland due to effective deer management (from a peak of 0.4–1.5 to <0.17 deer per ha) had translated to the small mammal community as an example of a higher order cascade effect. We compared deer-free exclosures with neighboring open woodland using capture-mark-recapture (CMR) methods to see if the significant difference in bank vole (Myodes glareolus) and wood mouse (Apodemus sylvaticus) numbers between these environments from 2001–2003 persisted in 2010. Using the multi-state Robust Design method in program MARK we found survival and abundance of both voles and mice to be equivalent between the open woodland and the experimental exclosures with no differences in various metrics of population structure (age structure, sex composition, reproductive activity) and individual fitness (weight), although the vole population showed variation both locally and temporally. This suggests that the vegetative habitat - having passed some threshold of complexity due to lowered deer density - has allowed recovery of the small mammal community, although patch dynamics associated with vegetation complexity still remain. We conclude that the response of small mammal communities to environmental disturbance such as intense browsing pressure can be rapidly reversed once the disturbing agent has been removed and the vegetative habitat is allowed to increase in density and complexity, although we encourage caution, as a source/sink dynamic may emerge between old growth patches and the recently disturbed habitat under harsh conditions