bluuebunny/crossref_metadata_2025 huggingface dataset:
Variance Estimation for Generalized Entropy and Atkinson Inequality Indices: the Complex Survey Data Case*
Authors: Biewen Martin , Jenkins Stephen P.
Published: May 2006

We derive the sampling variances of generalized entropy and Atkinson indices when estimated from complex survey data, and show how they can be calculated straightforwardly using widely available software. We also show that, when the same approach is used to derive variance formulae for the independent and identically distributed case, it leads to estimators that are simpler than those proposed before. Both cases are illustrated with a comparison of income inequality in Britain and Germany.
Racial Profiling Versus Community
Authors: LIPPERT‐RASMUSSEN KASPER
Published: May 2006

abstract  A police technique known as racial profiling draws on statistical beliefs about crime rates in racial groups. Supposing that such beliefs are true, and that racial profiling is effective in fighting crime, is such profiling morally justified? Recently, Risse and Zeckhauser have explored the racial profiling of African‐Americans and argued that justification is forthcoming from a utilitarian as well as deontological point of view. Drawing on criticisms made by G. A. Cohen of the incentives argument for inequality, I argue that, assuming that crime rates between different racial groups would converge in the absence of racial discrimination and unjust inequality, racial profiling is comprehensively unjustified. I also explain that, because Risse and Zeckhauser simply compare the status quo with an outcome that differs from it only in respect of the practice of racial profiling, they fail to show that such profiling is non‐comprehensively justified. And, exploring the problem from the point of view of a deontological concern for fairness, I identify a number of situations in which it would be non‐comprehensively unjustified to implement racial profiling (as well as some in which it might be non‐comprehensively unjustified not to implement racial profiling).
A Living Will Clause for Supporters of Animal Experimentation
Authors: SZTYBEL DAVID
Published: May 2006

abstract  Many people assume that invasive research on animals is justified because of its supposed benefits and because of the supposed mental inferiority of animals. However probably most people would be unwilling to sign a living will which consigns themselves to live biomed‐ical experimentation if they ever, through misfortune, end up with a mental capacity equivalent to a laboratory animal. The benefits would be greater by far for medical science if living will signatories were to be used, and also the mental superiority boast would no longer apply. Ultimately, it is argued that invasive biomedical experiments would be unacceptable in a democratic society whose members are philosophically self‐consistent.
Character evolution in the orbital region of the Afrotheria
Authors: Cox P. G.
Published: May 2006

The orbit or eye socket is a highly plastic area of the mammalian skull. There is significant variation within and between the different mammalian orders in the size and position of the bones and foramina that contribute to this region. For this reason, orbital characters are often used in attempts to determine the relationships of the various mammalian groups. This study describes the orbital region of the Afrotheria, the proposed group of endemic African mammals that comprises the paenungulates (elephants, manatees and dugongs, and hyraxes), elephant‐shrews, aardvarks, golden moles and tenrecs. Evolution within the Afrotherian orbit is then explored by scoring 19 orbital characters in each Afrotherian genus, and plotting the character state changes on to previously existing phylogenies of the Afrotheria. These phylogenies were all produced from recent molecular work. It was found that there is a great deal of variation in the orbital region within the Afrotheria, most notably in the size of the lacrimal and its contacts with other bones, the appearance of the palatine in the orbit and the structure of the zygomatic arch. Overall, orbital characters strongly supported an elephant‐hyrax clade over the more traditional grouping of elephants and sirenians (Tethytheria) within the paenungulates. There was also support for a monophyletic Tenrecoidea (a clade of tenrecs plus golden moles). Additionally, it was shown that there is a great deal of variation in the orbital region among the genera of the Tenrecidae and the Macroscelididae.
Continuous dyeing and false‐twist texturing of polyamide 6 yarns
Authors: Nazi M , Mojtahedi M R M , Malek R M A , Mazaheri F M
Published: May 2006

The present study was conducted to investigate the possibility of continuous dyeing and texturing of polyamide 6 yarns. To achieve this goal, a false‐twist texturing machine was modified with impregnation and drying zones. Dye fixation and texturing were carried out using a heater temperature of 170 °C and contact time of 1.2–1.8 s at a texturing speed in the range of 34–51 m/min. The appropriate temperature of the drying zone was found to be 400 ± 2 °C. Furthermore, a suitable dyeing formulation with selective disperse dyes was determined to achieve high colour strength and fastness. The results showed that the crimp properties of the continuously dyed and textured yarns were similar to normally textured yarns. However, the tensile properties of the continuously dyed and textured yarns were worse than those of the normally textured ones. It seems that, according to the results obtained from this laboratory‐modified texturing machine, it is possible to design a pilot plant and then an industrial machine.
A theoretical approach to characterising setups in batch fabric dyeing operations
Authors: Cho Eunkyoung G , Thoney Kristin A , Krauss Jeffrey D
Published: May 2006

Traditionally, most of the research published on dyeing has been on achievements in optimising the mechanical and chemical technology associated with the physical dyeing process. However, relatively little research is available in the area of scheduling dyeing operations. This could be due to a lack of information available about dyeing setups. In this study, a theoretical approach to structuring machine‐cleaning setups in batch fabric dyeing operations based on the CIELAB L*C*h colour space and the tolerance of the human visual system is presented. This will permit more research on the detailed scheduling of dyeing operations that could ultimately help dyeing facilities to better meet the needs of their customers in terms of improving on‐time delivery.
Youth Justice in New Zealand: Restorative Justice in Practice?
Authors: Maxwell Gabrielle , Morris Allison
Published: May 2006

The Children, Young Persons, and Their Families Act 1989 put in place new objects, principles, and procedures for youth justice in New Zealand. Both the philosophy underpinning this system and the use of family group conferences exemplify a restorative justice approach that has now been adopted in many other countries. This article describes these changes and presents some of the results of recently published research that examines the extent to which young offenders have been diverted from courts and custody, held accountable for their actions, and had their wellbeing enhanced. It suggests that the New Zealand youth justice system has achieved many but not all of its goals, and that there are still aspects where improvement is possible.
Family First: The Development of an Evidence‐Based Family Intervention for Increasing Participation in Psychiatric Clinical Care and Research in Depressed African American Adolescents
Authors: BRELAND‐NOBLE ALFIEE M. , BELL CARL , NICOLAS GUERDA
Published: May 2006

Researchers have documented health disparities for African American and other youth of color in the area of mental health. In accordance with calls for the development of innovative methods for use in reducing these disparities, the purpose of this article is to describe the development of an evidence‐based intervention targeting the use of psychiatric clinical care by African American families.The authors summarize current research in the areas of perceived and demonstrated bias in the provision of mental health services, the significance of the problem of low African American participation in psychiatric clinical research and care, and evidence‐based approaches to conducting family‐oriented research to address adolescent mental illness in this population. This discussion is followed by a description of the development of an intervention to improve familial treatment engagement and plans to test the intervention. The article is provided as a foundation for carefully defined plans to address the unmet mental health needs of depressed African American adolescents within a culturally relevant familial context.
The Family Check‐Up: A Pilot Study of a Brief Intervention to Improve Family Functioning in Adults
Authors: UEBELACKER LISA A. , HECHT JACKI , MILLER IVAN W.
Published: May 2006

Many barriers exist for families seeking appropriate treatment for family problems. In an effort to minimize some of these barriers, we developed the Family Check‐Up, a brief two‐session family intervention. The Family Check‐Up is based on the Drinker's Check‐Up and consists of assessment, feedback, discussion, and goal setting. The purpose of the intervention is to help families identify and become motivated to make needed changes in any aspect of their family functioning. We conducted an open pilot trial of the Family Check‐Up with 32 families. Our data suggest that the Family Check‐Up (1) is sought out by the target audience, namely those with family problems; (2) is sought out by people with elevated depression symptoms or a history of treatment for depression or anxiety; (3) is feasible to conduct; (4) is acceptable to families; and (5) may be associated with changes in family functioning and depression symptoms over time. These results suggest that further research, particularly a randomized clinical trial, is warranted.
High Thermal Conductivity Aluminum Nitride Substrates Prepared by Aqueous Tape Casting
Authors: Luo Xiaojun , Li Jun , Zhang Baolin , Li Wenlan , Zhuang Hanrui
Published: May 2006

High thermal conductivity aluminum nitride (AlN) substrates were prepared by aqueous tape casting. The characteristics of surface‐treated AlN powder were studied in aqueous ball‐milling media. The oxygen content of AlN powder with the dispersant was lower than that of AlN powder without the dispersant at the same ball‐milling time. The isoelectric points of the surface‐treated AlN with and without a dispersant were, respectively, at pH∼3.35 and pH∼3.90. The atmosphere had considerable effects on organic additive burnout of aqueous AlN green sheets. The composition of grain boundaries changed with increasing holding time at 1850°C. A translucent AlN substrate with a uniform microstructure and a thermal conductivity of 263 W·(m·K)−1 was obtained by pressureless sintering at 1850°C for 6 h in a nitrogen atmosphere.
Human cancers and the FHIT gene
Authors: AGRAWAL Suraksha , MOORCHUNG Nikhil , PRIYA Padma , KAPOOR VK
Published: May 2006

The FHIT gene is a relatively newly discovered tumor suppressor gene, which is located on the chromosome 3p14.2. The gene encompasses the FRA3B fragile site. The gene has been implicated in the pathogenesis of various carcinomas, particularly cancers of the stomach and oral squamous cell carcinomas. The protein encoded by the gene bears a significant homology to a group of proteins that have a histidine triad motif, designated HIT proteins. The function of the protein remains essentially unknown. Loss of heterozygosity and microsatellite instability are responsible for FHIT gene alterations. A mutation in a gene will invariably give abnormal transcripts and contribute to the pathogenesis of cancer. A better understanding of FHIT mutations will also help us to understand the pathogenesis of the multistep process of carcinogenesis. Therapeutic potentials of Fhit can also be explored. Replacement of FHIT cDNA in human cancer cell lines has resulted in the suppression of tumor growth. This opens the possibility of therapeutic potentials using recombinant vectors carrying the FHIT gene.
Oxidation of fugitive methane in ground water linked to bacterial sulfate reduction
Authors: Van Stempvoort Dale , Maathuis Harm , Jaworski Ed , Mayer Bernhard , Rich Kathleen
Published: May 2006

When fugitive methane migrates upward along boreholes of oil and gas wells, it may migrate into shallow ground water or pass through overlying soil to the atmosphere. Prior to this study, there was little information on the fate of fugitive methane that migrates into ground water. In a field study near Lloydminster, Alberta, Canada, we found hydrogeochemical evidence that fugitive methane from an oil well migrated into a shallow aquifer but has been attenuated by dissimilatory bacterial sulfate reduction at low temperature (∼5°C) under anaerobic conditions. Evidence includes spatial and temporal trends in concentrations of methane and sulfate in ground water and associated trends in concentrations of bicarbonate and sulfide. Within 10 m of the oil well, sulfate concentrations were low, and sulfate was enriched in both 34S and 18O. Sulfate concentrations had a strong positive correlation with δ13C values of bicarbonate, and sulfide was depleted in 34S compared to sulfate. These data indicate that bacterial sulfate reduction occurred near the production well. Near the oil well, elevated concentrations of bicarbonate were observed, and the bicarbonate was depleted in 13C. Modeling indicates that the main source of this excess 13C‐depleted bicarbonate is oxidized methane. In concert with the sulfate concentration and isotope data, these results support an interpretation that in situ bacterial oxidation of methane has occurred, linked to bacterial sulfate reduction. Bacterial sulfate reduction may play a major role in bioattenuation of fugitive natural gas in ground water in western Canada.
Epac-mediated Ca2+ mobilization and exocytosis in inner medullary collecting duct
Authors: Yip Kay-Pong
Published: May 2006

PKA has traditionally been thought as the binding protein of cAMP for mediating arginine vasopressin (AVP)-regulated osmotic water permeability in kidney collecting duct. It is now known that cAMP also exerts its effects via Epac (exchange protein directly activated by cAMP) and that intracellular Ca2+ mobilization is necessary for AVP-induced apical exocytosis in inner medullary collecting duct (IMCD). The role of Epac as an effector of cAMP action in addition to PKA was investigated using confocal fluorescence microscopy in perfused IMCD. PKA inhibitors (1 μM H-89 or 10 μM KT-5720) at concentrations known to inhibit aquaporin-2 (AQP2) phosphorylation did not prevent AVP-induced Ca2+ mobilization and oscillations. Epac-selective cAMP agonist (8-pCPT-2′- O-Me-cAMP) mimicked AVP in triggering Ca2+ mobilization and oscillations, which was blocked by ryanodine but not by Rp-cAMP (a competitive antagonist of cAMP binding to PKA). 8-pCPT-2′- O-Me-cAMP also triggered apical exocytosis in the presence of a PKA inhibitor. Immunolocalization of AQP2 in perfused IMCD demonstrated that 8-pCPT-2′- O-Me-cAMP induces apical targeting of AQP2 and that AQP2 is abundant in junctional regions of basolateral membrane. Immunofluorescence study also confirmed the presence of Epac (isoform I) in IMCD. These results indicate that activation of Epac by an exogenous cAMP analog triggers intracellular Ca2+ mobilization and apical exocytotic insertion of AQP2 in IMCD.
The Annular Response to Tropical Pacific SST Forcing
Authors: Li Shuanglin , Hoerling Martin P. , Peng Shiling , Weickmann Klaus M.
Published: May 2006

The leading pattern of Northern Hemisphere winter height variability exhibits an annular structure, one related to tropical west Pacific heating. To explore whether this pattern can be excited by tropical Pacific SST variations, an atmospheric general circulation model coupled to a slab mixed layer ocean is employed. Ensemble experiments with an idealized SST anomaly centered at different longitudes on the equator are conducted. The results reveal two different response patterns—a hemispheric pattern projecting on the annular mode and a meridionally arched pattern confined to the Pacific–North American sector, induced by the SST anomaly in the west and the east Pacific, respectively. Extratropical air–sea coupling enhances the annular component of response to the tropical west Pacific SST anomalies.

A diagnosis based on linear dynamical models suggests that the two responses are primarily maintained by transient eddy forcing. In both cases, the model transient eddy forcing response has a maximum near the exit of the Pacific jet, but with a different meridional position relative to the upper-level jet. The emergence of an annular response is found to be very sensitive to whether transient eddy forcing anomalies occur within the axis of the jet core. For forcing within the jet core, energy propagates poleward and downstream, inducing an annular response. For forcing away from the jet core, energy propagates equatorward and downstream, inducing a trapped regional response. The selection of an annular versus a regionally confined tropospheric response is thus postulated to depend on how the storm tracks respond. Tropical west Pacific SST forcing is particularly effective in exciting the required storm-track response from which a hemisphere-wide teleconnection structure emerges.
Composite Analysis of Winter Cyclones in a GCM: Influence on Climatological Humidity
Authors: Bauer Mike , Del Genio Anthony D.
Published: May 2006

The role of midlatitude baroclinic cyclones in maintaining the extratropical winter distribution of water vapor in an operational global climate model is investigated. A cyclone identification and tracking algorithm is used to compare the frequency of occurrence, propagation characteristics, and composite structure of 10 winters of storms in the Goddard Institute for Space Studies general circulation model (GCM) and in two reanalysis products. Cyclones are the major dynamical source of water vapor over the extratropical oceans in the reanalyses. The GCM produces fewer, generally weaker, and slower-moving cyclones than the reanalyses and is especially deficient in storms associated with secondary cyclogenesis. Composite fields show that GCM cyclones are shallower and drier aloft than those in the reanalyses and that their vertical structure is less tilted in the frontal region because of the GCM’s weaker ageostrophic circulation. This is consistent with the GCM’s underprediction of midlatitude cirrus. The GCM deficiencies do not appear to be primarily due to parameterization errors; the model is too dry despite producing less storm precipitation than is present in the reanalyses and in an experimental satellite precipitation dataset, and the weakness and shallow structure of GCM cyclones is already present at storm onset. These shortcomings may be common to most climate GCMs that do not resolve the mesoscale structure of frontal zones, and this may account for some universal problems in climate GCM midlatitude cloud properties.
Centered Composite Analysis of Variations Associated with the Madden–Julian Oscillation
Authors: Weare Bryan C.
Published: May 2006

Centered composite analysis is described and applied to gain a better understanding of the initial phases of the Madden–Julian oscillation (MJO). Centered composite analysis identifies the dates and central locations of key events. The elements of the composite means are centered on these central locations before averages are calculated. In this way much of the spatial fuzziness, which is inherent in traditional composite analysis, is removed. The results for the MJO, based on MJO-filtered outgoing longwave radiation for the reference data and 40-yr ECMWF Re-Analysis (ERA-40) and NCEP–NCAR reanalysis products for the composites, show highly significant composites of unfiltered data for not only zero lag, but also lags back to 20 days before the target events. These composites identify propagating patterns of surface pressure, upper- and lower-troposphere zonal winds, surface temperature, and 850-hPa specific humidity associated with MJO convective events in the Indian Ocean. The propagation characteristics of important features, especially surface pressure, differ substantially for MJO convective anomalies centered over the Indian or western Pacific Oceans. This suggests that distinctly different mechanisms may be dominant in these two regions, and that many earlier analyses may be mixing properties of the two.
Conserved genes in a path from commensalism to pathogenicity: comparative phylogenetic profiles of Staphylococcus epidermidis RP62A and ATCC12228
Authors: Wei Wu , Cao ZhiWei , Zhu Yu-Li , Wang XiaoJing , Ding GuoHui , Xu Hao , Jia PeiLin , Qu Di , Danchin Antoine , Li YiXue
Published: May 2006

Background

Staphylococcus epidermidis, long regarded as an innocuous commensal bacterium of the human skin, is the most frequent cause of nosocomial infections associated with implanted medical devices. This conditional pathogen provides a model of choice to study genome landmarks correlated with the transition between commensalism and pathogenicity. Traditional investigations stress differences in gene content. We focused on conserved genes that have accumulated small mutation differences during the transition.

Results

A comparison of strain ATCC12228, a non-biofilm forming, non-infection associated strain and strain RP62A, a methicillin-resistant biofilm clinical isolate, revealed consistent variation, mostly single-nucleotide polymorphisms (SNPs), in orthologous genes in addition to the previously investigated global changes in gene clusters. This polymorphism, scattered throughout the genome, may reveal genes that contribute to adaptation of the bacteria to different environmental stimuli, allowing them to shift from commensalism to pathogenicity. SNPs were detected in 931 pairs of orthologs with identical gene length, accounting for approximately 45% of the total pairs of orthologs. Assuming that non-synonymous mutations would mark recent evolution, and hence be associated to the onset of the pathogenic process, analysis of ratios of non-synonymous SNPs vs synonymous SNPs suggested hypotheses about possible pathogenicity determinants. The N/S ratios for virulence factors and surface proteins differed significantly from that of average SNPs. Of those gene pairs, 40 showed a disproportionate distribution of dN vs dS. Among those, the presence of the gene encoding methionine sulfoxide reductase suggested a possible involvement of reactive oxygen species. This led us to uncover that the infection associated strain was significantly more resistant to hydrogen peroxide and paraquat than the environmental strain. Some 16 genes of the list were of unknown function. We could suggest however that they were likely to belong to surface proteins or considered in priority as important for pathogenicity.

Conclusion

Our study proposed a novel approach to identify genes involved in pathogenic processes and provided some insight about the molecular mechanisms leading a commensal inhabitant to become an invasive pathogen.
Interval estimation and optimal design for the within-subject coefficient of variation for continuous and binary variables
Authors: Shoukri Mohamed M , Elkum Nasser , Walter Stephen D
Published: May 2006

Background

In this paper we propose the use of the within-subject coefficient of variation as an index of a measurement's reliability. For continuous variables and based on its maximum likelihood estimation we derive a variance-stabilizing transformation and discuss confidence interval construction within the framework of a one-way random effects model. We investigate sample size requirements for the within-subject coefficient of variation for continuous and binary variables.

Methods

We investigate the validity of the approximate normal confidence interval by Monte Carlo simulations. In designing a reliability study, a crucial issue is the balance between the number of subjects to be recruited and the number of repeated measurements per subject. We discuss efficiency of estimation and cost considerations for the optimal allocation of the sample resources. The approach is illustrated by an example on Magnetic Resonance Imaging (MRI). We also discuss the issue of sample size estimation for dichotomous responses with two examples.

Results

For the continuous variable we found that the variance stabilizing transformation improves the asymptotic coverage probabilities on the within-subject coefficient of variation for the continuous variable. The maximum like estimation and sample size estimation based on pre-specified width of confidence interval are novel contribution to the literature for the binary variable.

Conclusion

Using the sample size formulas, we hope to help clinical epidemiologists and practicing statisticians to efficiently design reliability studies using the within-subject coefficient of variation, whether the variable of interest is continuous or binary.
Weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) as first-line chemotherapy for elderly patients with advanced gastric cancer: results of a phase II trial
Authors: Santini D , Graziano F , Catalano V , Di Seri M , Testa E , Baldelli AM , Giordani P , La Cesa A , Spalletta B , Vincenzi B , Russo A , Caraglia M , Virzi V , Cascinu S , Tonini G
Published: May 2006

Background

Elderly patients have been often excluded from or underrepresented in the study populations of combination chemotherapy trials. The primary end point of this study was to determine the response rate and the toxicity of the weekly oxaliplatin, 5-fluorouracil and folinic acid (OXALF) regimen in elderly patients with advanced gastric cancer. The secondary objective was to measure the time to disease progression and the survival time.

Methods

Chemotherapy-naive patients with advanced gastric cancer aged 70 or older were considered eligible for study entry. Patients received weekly oxaliplatin 40 mg/m2, fluorouracil 500 mg/m2 and folinic acid 250 mg/m2. All drugs were given intravenously on a day-1 schedule.

Results

A total of 42 elderly patients were enrolled. Median age was 73 years and all patients had metastatic disease. The response rate according to RECIST criteria was 45.2% (95% CIs: 30%–56%) with two complete responses, 17 partial responses, 13 stable diseases and 10 progressions, for an overall tumor rate control of 76.2% (32 patients). Toxicity was generally mild and only three patients discontinued treatment because of treatment related adverse events. The most common treatment-related grade 3/4 adverse events were fatigue (7.1%), diarrhoea (4.8%), mucositis (2.4%), neurotoxicity (2.4%) and neutropenia (4.8%). The median response duration was 5.3 months (95% CIs: 2.13 – 7.34), the median time to disease progression was 5.0 months (95% CIs: 3.75 – 6.25) and the median survival time was 9.0 months (95% CIs: 6.18 – 11.82).

Conclusion

OXALF represents an active and well-tolerated treatment modality for elderly patients with locally advanced and metastatic gastric cancer.
Reliability of case definitions for public health surveillance assessed by Round-Robin test methodology
Authors: Krause Gérard , Brodhun Bonita , Altmann Doris , Claus Hermann , Benzler Justus
Published: May 2006

Background

Case definitions have been recognized to be important elements of public health surveillance systems. They are to assure comparability and consistency of surveillance data and have crucial impact on the sensitivity and the positive predictive value of a surveillance system. The reliability of case definitions has rarely been investigated systematically.

Methods

We conducted a Round-Robin test by asking all 425 local health departments (LHD) and the 16 state health departments (SHD) in Germany to classify a selection of 68 case examples using case definitions. By multivariate analysis we investigated factors linked to classification agreement with a gold standard, which was defined by an expert panel.

Results

A total of 7870 classifications were done by 396 LHD (93%) and all SHD. Reporting sensitivity was 90.0%, positive predictive value 76.6%. Polio case examples had the lowest reporting precision, salmonellosis case examples the highest (OR = 0.008; CI: 0.005–0.013). Case definitions with a check-list format of clinical criteria resulted in higher reporting precision than case definitions with a narrative description (OR = 3.08; CI: 2.47–3.83). Reporting precision was higher among SHD compared to LHD (OR = 1.52; CI: 1.14–2.02).

Conclusion

Our findings led to a systematic revision of the German case definitions and build the basis for general recommendations for the creation of case definitions. These include, among others, that testable yes/no criteria in a check-list format is likely to improve reliability, and that software used for data transmission should be designed in strict accordance with the case definitions. The findings of this study are largely applicable to case definitions in many other countries or international networks as they share the same structural and editorial characteristics of the case definitions evaluated in this study before their revision.
The contribution of general practice based research to the development of national policy: case studies from Ireland and Australia
Authors: Pirkis JE , Blashki GA , Murphy AW , Hickie IB , Ciechomski L
Published: May 2006

Background

This paper aims to describe the influence of general practice based research on the development of two specific policy initiatives, namely the Heartwatch Programme in Ireland and the Better Outcomes in Mental Health Care (BOiMHC) program in Australia. A case study approach was used to explore the extent to which relevant general practice based research shaped these initiatives.

Results

In both case studies, a range of factors beyond general practice based research shaped the initiative in question, including political will, the involvement of stakeholders (including key opinion leaders), and the historical context. Nonetheless, the research played an important role, and was not merely put to 'symbolic use' to support a position that had already been reached independently. Rather, both case studies provide examples of 'instrumental use': in the case of Heartwatch, the research was considered early in the piece; in the case of the BOiMHC program, it had a specific impact on the detail of the components of the initiative.

Conclusion

General practice based research can influence policy-making and planning processes by strengthening the foundation of evidence upon which they draw. This influence will not occur in a vacuum, however, and general practice researchers can maximise the likelihood of their work being 'picked up' in policy if they consider the principles underpinning knowledge transfer.
The Inferelator: an algorithm for learning parsimonious regulatory networks from systems-biology data sets de novo
Authors: Bonneau Richard , Reiss David J , Shannon Paul , Facciotti Marc , Hood Leroy , Baliga Nitin S , Thorsson Vesteinn
Published: May 2006

We present a method (the Inferelator) for deriving genome-wide transcriptional regulatory interactions, and apply the method to predict a large portion of the regulatory network of the archaeon Halobacterium NRC-1. The Inferelator uses regression and variable selection to identify transcriptional influences on genes based on the integration of genome annotation and expression data. The learned network successfully predicted Halobacterium's global expression under novel perturbations with predictive power similar to that seen over training data. Several specific regulatory predictions were experimentally tested and verified.
Adult Height in Patients with Permanent Growth Hormone Deficiency with and without Multiple Pituitary Hormone Deficiencies
Authors: Maghnie Mohamad , Ambrosini Linda , Cappa Marco , Pozzobon Gabriella , Ghizzoni Lucia , Ubertini Maria Grazia , di Iorgi Natascia , Tinelli Carmine , Pilia Sabrina , Chiumello Giuseppe , Lorini Renata , Loche Sandro
Published: May 2006

Context: It has been reported that patients with multiple pituitary hormone deficiencies (MPHDs) achieve a greater final height, compared with patients with isolated GH deficiency (IGHD). However, the outcome of patients with permanent GH deficiency (GHD) has not yet been reported.

Objectives: The objectives of the study were to evaluate and compare adult height data and the effect of spontaneous or induced puberty after long-term treatment with GH in young adults with either permanent IGHD or MPHD.

Design and Setting: This was a retrospective multicenter study conducted in university research hospitals and a tertiary referral endocrine unit.

Patients and Methods: Thirty-nine patients with IGHD (26 males, 13 females) and 49 with MPHD (31 males, 18 females), diagnosed at a median age of 7.7 and 6.9 yr, respectively, were reevaluated for GH secretion after adult height achievement (median age 17.6 and 19.8 yr). The diagnosis of permanent GHD was based on peak GH levels less than 3 μg/liter after an insulin tolerance test or peak GH levels less than 5 μg/liter after two different tests. Fifteen subjects had idiopathic GHD and seventy-three had magnetic resonance imaging evidence of congenital hypothalamic-pituitary abnormalities. Height sd score (SDS) was analyzed at diagnosis, the onset of puberty (either spontaneous or induced), and the time of GH withdrawal.

Results: The subjects with IGHD entered puberty at a median age of 12.6 yr (females) and 13.4 yr (males). Puberty was induced at a median age of 13.5 and 14.0 yr, respectively, in males and females with MPHD. Median height SDS at the beginning of puberty was similar in the IGHD and MPHD subjects. Total pubertal height gain was similar between patients with IGHD or MPHD. Median adult height was also not significantly different between IGHD and MPHD patients (males, 168.5 vs. 170.3 cm; females, 160.0 vs. 157.3 cm). The adult height SDS of the IGHD subjects was positively correlated with height at the time of diagnosis and with total pubertal height gain. Conversely, the adult height SDS of the MPHD subjects was positively correlated with both the duration of GH treatment and height SDS at the time of GHD diagnosis.

Conclusions: Adult height in patients with permanent IGHD and spontaneous puberty is similar to adult height in patients with MPHD and induced puberty.
The Diagnosis of Ectopic Focal Hyperinsulinism of Infancy with [18F]-Dopa Positron Emission Tomography
Authors: Hussain Khalid , Seppänen Marko , Näntö-Salonen Kirsti , Adzick N. Scott , Stanley Charles A. , Thornton Paul , Minn Heikki
Published: May 2006

Background: Congenital hyperinsulinism (CHI) is a cause of severe hypoglycemia in the neonatal and infancy period. Histologically, there are two subtypes with diffuse and focal disease. The preoperative differentiation of these two forms is very important because the surgical management is radically different. The focal form of the disease can be cured if the focal lesion can be localized accurately and completely resected with surgery.

Aim: We report the case of a child who underwent three pancreatectomies with a choledochoduodenostomy and a cholecystectomy but continued to have severe hyperinsulinemic hypoglycemia.

Methods/Results: Radiological investigations including imaging with 18fluoro-l-Dopa positron emission tomography scan showed a clear focus of increased 18F-fluoro-l-Dopa uptake in the vicinity of the former head of the pancreas. On the magnetic resonance imaging scan, this focal uptake appeared to localize adjacent or next to duodenum (in the wall or cavity of the duodenum).

Conclusions: This unique case highlights the importance of correctly localizing and completely resecting the focal lesion in patients with CHI. 18Fluoro-l-Dopa positron emission tomography scan can identify ectopic focal lesions in patients with CHI.
Outcomes of pharmaceutical care intervention to hypertensive patients in a Nigerian community pharmacy
Authors: Oparah Azuka C , Adje David U , Enato Ehijie F O
Published: May 2006

Objective

To describe pharmaceutical care interventions provided to hypertensive patients in a Nigerian community pharmacy setting, and to assess the impact of the practice on selected patient outcomes.

Method

A non-randomised, single-site study was conducted using community-dwelling patients with hypertension. A pharmaceutical care intervention, which consisted mainly of verbal counselling, provision of an information leaflet, and subsequent monitoring with reinforcement, was provided. Parameters assessed at baseline and end of investigation included blood pressure control, body mass index determination, level of medication adherence, patient knowledge of the disease, and patient satisfaction.

Key findings

Forty-two (42) patients were recruited and 36 completed the study, 26 (73%) were males, and 33 (92%) were married. Twenty (20, 58%) had post-secondary education. About three-quarters (27, 81%) were either overweight or obese (BMI >25). There was a significant difference between mean systolic blood pressure at baseline (187.67 ± 29.46 mmHg) and at the end of the study (137.22 ± 21.65 mmHg), P< 0.0001. Changes in mean diastolic blood pressure at baseline (117.56 ± 21.65) and end of study (89 ± 17.23), were also significant (P< 0.0001). Some 27 (75%) reached systolic blood pressure goals while 25 (69%) attained diastolic blood pressure goals. Prior to the pharmaceutical care intervention, 27 (75%) were not aware that salt intake was a risk factor in hypertension, and a similar proportion thought that hypertension was curable. The pharmaceutical care intervention produced a significantly higher patient-reported satisfaction rating than baseline: 3.48 ± 0.83 (49%) versus 3.92 ± 0.62 (74%); t = 2.548; P=0.013 and 3.30 ± 0.72 (41%) versus 4.27 ± 0.56 (87%); t= 6.381, P< 0.0001 on the subscales respectively.

Conclusion

Pharmaceutical care provided to hypertensive patients in a Nigerian community pharmacy setting improved blood pressure control and overall patient satisfaction with pharmaceutical services.
Cholesterol contributes to the organization of tetraspanin-enriched microdomains and to CD81-dependent infection by malaria sporozoites
Authors: Silvie Olivier , Charrin Stéphanie , Billard Martine , Franetich Jean-François , Clark Krista L. , van Gemert Geert-Jan , Sauerwein Robert W. , Dautry François , Boucheix Claude , Mazier Dominique , Rubinstein Eric
Published: May 2006

Tetraspanins constitute a family of widely expressed integral membrane proteins that associate extensively with one another and with other membrane proteins to form specific membrane microdomains distinct from conventional lipid rafts. So far, because of the lack of appropriate tools, the functionality of these microdomains has remained largely unknown. Here, using a new monoclonal antibody that only binds to the tetraspanin CD81 associated with other tetraspanins, we show that membrane cholesterol contributes to the organization of tetraspanin microdomains on the surface of live cells. Furthermore, our data demonstrate involvement of host membrane cholesterol during infection by Plasmodium yoelii and Plasmodium falciparum sporozoites, which both depend on host CD81 expression for invasion, but not during CD81-independent infection by Plasmodium berghei sporozoites. Our results unravel a functional link between CD81 and cholesterol during infection by malaria parasites, and illustrate that tetraspanin microdomains constitute a novel type of membrane microdomains that could be used by pathogens for infection.
Elimination of plasma membrane phosphatidylinositol (4,5)-bisphosphate is required for exocytosis from mast cells
Authors: Hammond Gerald R. V. , Dove Stephen K. , Nicol Alastair , Pinxteren Jef A. , Zicha Daniel , Schiavo Giampietro
Published: May 2006

The inositol lipid phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P2] is involved in a myriad of cellular processes, including the regulation of exocytosis and endocytosis. In this paper, we address the role of PtdIns(4,5)P2 in compound exocytosis from rat peritoneal mast cells. This process involves granule-plasma membrane fusion as well as homotypic granule membrane fusion and occurs without any immediate compensatory endocytosis. Using a novel quantitative immunofluorescence technique, we report that plasma membrane PtdIns(4,5)P2 becomes transiently depleted upon activation of exocytosis, and is not detected on the membranes of fusing granules. Depletion is caused by phospholipase C activity, and is mandatory for exocytosis. Although phospholipase C is required for Ca2+ release from internal stores, the majority of the requirement for PtdIns(4,5)P2 hydrolysis occurs downstream of Ca2+ signalling - as shown in permeabilised cells, where the inositol (1,4,5)-trisphosphate-Ca2+ pathway is bypassed. Neither generation of the PtdIns(4,5)P2 metabolite, diacylglycerol (DAG) or simple removal and/or sequestration of PtdIns(4,5)P2 are sufficient for exocytosis to occur. However, treatment of permeabilised cells with DAG induces a small potentiation of exocytosis, indicating that it may be required. We propose that a cycle of PtdIns(4,5)P2 synthesis and breakdown is crucial for exocytosis to occur in mast cells, and may have a more general role in all professional secretory cells.
Benzenetellurinic Mixed Anhydrides as Mild Oxidizing Agents
Authors: Fukumoto Takahiro , Matsuki Toshiaki , Hu Nan Xing , Aso Yoshio , Otsubo Tetsuo , Ogura Fumio
Published: May 2006

Three benzenetellurinic mixed anhydrides, i.e., benzenetellurinyl acetate, trifluoroacetate, and trifluoromethanesulfonate, have been found to be mild oxidizing agents for various substrates such as thiol, phosphine, acyloin, α-hydroxy ester, catechol, hydroquinone, thiourea, and thioamide. The reactions towards the last two substrates are highly chemoselective, depending on both the reagent and substrate.
N-Tosyltriarylbismuthimines. Synthesis and Reactions with Some Electrophiles
Authors: Suzuki Hitomi , Nakaya Chie , Matano Yoshihiro , Ogawa Takuji
Published: May 2006

N-Tosyltriarylbismuthimines were prepared by the reaction of triarylbismuthines with chloramine-T and their properties were characterized. These bismuthimines reacted with aromatic aldehydes, acid chlorides, and isocyanates to form N-arylidenetosylamides, N-aroyltosylamides, and N-aryl-N′-tosylureas, respectively. In the presence of copper catalyst, they readily decomposed into N-aryl- and N,N-diaryltosylamides, tosylamide, and triarylbismuthine.
Double Germylation of Unsaturated Carbon Compounds with Digermanes in the Presence of Palladium and Platinum Catalysts
Authors: Hayashi Teruyuki , Yamashita Hiroshi , Sakakura Toshiyasu , Uchimaru Yuko , Tanaka Masato
Published: May 2006

Double germylation of acetylenes, isoprene, and ethylene with 1,2-dichloro-1,1,2,2-tetramethyldigermane proceeds in the presence of palladium- and platinum-phosphorus ligand complexes to afford α,ω-bis(chlorodimethylgermyl) compounds in moderate to good yields.
A Placebo Controlled, Double-Blind Study of Mecamylamine Treatment for Cocaine Dependence in Patients Enrolled in an Opiate Replacement Program
Authors: Reid Malcolm S. , Angrist Burt , O'Leary Siobhan , Stone Jennifer , Schwartz Marion , Rotrosen John , Baker Sherryl A. , Robinson James , Leiderman Deborah , Montgomery Ann , Elkashef Ahmed , Majewska Dorota
Published: May 2006

A placebo controlled, double-blind trial of mecamylamine treatment of cocaine dependence was performed in methadone or LAAM maintained subjects who met DSM-IV criteria for cocaine dependence. After an eight-week placebo run-in screening period, 35 subjects were randomly assigned to receive either mecamylamine (6 mg/day) or placebo transdermal patches for a 16-week treatment period. Outcome measures included quantitative urine benzoylecognine (BE) levels, self-report of cocaine use, cocaine craving, global impression scores, mood, retention, and safety. Mecamylamine was well tolerated, and study retention did not differ by treatment group. Evidence for cocaine use, based on urine BE levels and cocaine abstinence rates, did not differ by treatment group. Self reported cocaine use, cocainecraving, and global impression scores showed moderate improvement in both groups, with a significantly greater reduction in cocaine craving (p < 0.05) and self-rated severity of cocaine dependence (p < 0.05) in the placebo group. This pilot study does not support theeffectiveness of mecamylamine for the treatment of cocaine dependence in methadone or LAAM maintained patients.
State-Dependent AMPA Receptor Trafficking in the Mammalian Retina
Authors: Xia Yingqiu , Carroll Reed C. , Nawy Scott
Published: May 2006

The rapid cycling of AMPA receptors (AMPARs) at the membrane maintains synaptic transmission at a number of CNS synapses and may play a role in several forms of synaptic plasticity. It is unclear, however, how prevalent the trafficking of AMPARs is in the CNS, particularly at synapses not known to exhibit activity-dependent plasticity. Because trafficking is regulated by basal synaptic activity, a question also remains as to how receptor trafficking is modulated at synapses subject to different patterns of synaptic activation. We have investigated whether trafficking of AMPARs occurs in retinal neurons, which are subject to tonic glutamate release. We find two distinct states of AMPAR trafficking in ON ganglion cells. Light adaptation serves to stabilize AMPARs in a noncycling mode. However, dark adaptation for as little as 8 h triggers a switch to a second state of trafficking characterized by rapid cycling. We provide evidence that the activation of AMPARs is critical for switching between cycling and noncycling states. The induction of cycling further appears to be modulated by changes in the function of glutamate receptor 2/3-interacting proteins. Our results suggest that there is a strong link between synaptic activity and AMPAR trafficking in retinal neurons. These results further suggest the existence of a previously unknown form of activity-dependent plasticity in the retina that may be regulated in the course of a normal light/dark cycle.
Distinct Subtypes of Somatostatin-Containing Neocortical Interneurons Revealed in Transgenic Mice
Authors: Ma Yunyong , Hu Hang , Berrebi Albert S. , Mathers Peter H. , Agmon Ariel
Published: May 2006

GABA-releasing inhibitory interneurons in the cerebral cortex can be classified by their neurochemical content, firing patterns, or axonal targets, to name the most common criteria, but whether classifications using different criteria converge on the same neuronal subtypes, and how many such subtypes exist, is a matter of much current interest and considerable debate. To address these issues, we generated transgenic mice expressing green fluorescent protein (GFP) under control of the GAD67 promoter. In two of these lines, named X94 and X98, GFP expression in the barrel cortex was restricted to subsets of somatostatin-containing (SOM+) GABAergic interneurons, similar to the previously reported “GIN” line (Oliva et al., 2000), but the laminar distributions of GFP-expressing (GFP+) cell bodies in the X94, X98, and GIN lines were distinct and nearly complementary. We compared neurochemical content and axonal distribution patterns of GFP+ neurons among the three lines and analyzed in detail electrophysiological properties in a dataset of 150 neurons recorded in whole-cell, current-clamp mode. By all criteria, there was nearly perfect segregation of X94 and X98 GFP+ neurons, whereas GIN GFP+ neurons exhibited intermediate properties. In the X98 line, GFP expression was found in infragranular, calbindin-containing, layer 1-targeting (“Martinotti”) cells that had a propensity to fire low-threshold calcium spikes, whereas X94 GFP+ cells were stuttering interneurons with quasi fast-spiking properties, residing in and targeting the thalamo-recipient neocortical layers. We conclude that much of the variability previously attributed to neocortical SOM+ interneurons can be accounted for by their natural grouping into distinct subtypes.