bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation and Sensitivity Analysis of an Ocean Model Response to Hurricane Ivan
Authors: Halliwell G. R. , Shay L. K. , Brewster J. K. , Teague W. J.
Published: July 2010

An ocean model response to Hurricane Ivan (2004) over the northwest Caribbean Sea and Gulf of Mexico is evaluated to guide strategies for improving performance during strong forcing events in a region with energetic ocean features with the ultimate goal of improving coupled tropical cyclone forecasts. Based on prior experience, a control experiment is performed using quasi-optimal choices of initial ocean fields, atmospheric forcing fields, air–sea flux parameterizations, vertical mixing parameterizations, and both horizontal and vertical resolutions. Alternate experiments are conducted by altering one single model attribute and comparing the results to SST analyses and moored ADCP current measurements to quantify the sensitivity to that attribute and identify where to concentrate model improvement efforts. Atmospheric forcing that does not resolve the eye and eyewall of the storm (scales >10 km) substantially degrades the ocean response. Ordering other model attributes from greatest to least sensitivity, ocean model initialization with regard to the accuracy of upper-ocean temperature–salinity profiles along with accurate location of ocean currents and eddies is the most important factor for ensuring good ocean model performance. Ocean dynamics ranks second in this energetic ocean region because a one-dimensional ocean model fails to capture important physical processes that affect SST cooling. Wind stress drag coefficient parameterizations that yield values exceeding 2.5 × 10−3 at high wind speeds or that remain <2.0 × 10−3 over all wind speeds reduce the realism of wind-driven current profiles and have a large impact on both SST cooling and the heat flux from ocean to atmosphere. Turbulent heat flux drag coefficient parameterizations substantially impact the surface heat flux while having little impact on SST cooling, which is primarily controlled by entrainment at the mixed layer base. Vertical mixing parameterizations have a moderate impact on SST cooling but a comparatively larger impact on surface heat flux. The impacts of altering the horizontal and vertical resolutions are small, with horizontal resolution of ≈10 km and vertical resolution of ≈10 m in the mixed layer being adequate. Optimal choices of all attributes for simulating the ocean response to Ivan are identified.
A Non-Gaussian Ensemble Filter Update for Data Assimilation
Authors: Anderson Jeffrey L.
Published: July 2010

A deterministic square root ensemble Kalman filter and a stochastic perturbed observation ensemble Kalman filter are used for data assimilation in both linear and nonlinear single variable dynamical systems. For the linear system, the deterministic filter is simply a method for computing the Kalman filter and is optimal while the stochastic filter has suboptimal performance due to sampling error. For the nonlinear system, the deterministic filter has increasing error as ensemble size increases because all ensemble members but one become tightly clustered. In this case, the stochastic filter performs better for sufficiently large ensembles. A new method for computing ensemble increments in observation space is proposed that does not suffer from the pathological behavior of the deterministic filter while avoiding much of the sampling error of the stochastic filter. This filter uses the order statistics of the prior observation space ensemble to create an approximate continuous prior probability distribution in a fashion analogous to the use of rank histograms for ensemble forecast evaluation. This rank histogram filter can represent non-Gaussian observation space priors and posteriors and is shown to be competitive with existing filters for problems as large as global numerical weather prediction. The ability to represent non-Gaussian distributions is useful for a variety of applications such as convective-scale assimilation and assimilation of bounded quantities such as relative humidity.
William James’s “Sick-Minded Soul” and the AA Recovery Paradigm: Time for a Reappraisal
Authors: Bevacqua Tony , Hoffman Edward
Published: July 2010

This article focuses on William James’s influence on Alcoholics Anonymous (AA), which arose 25 years after his death to dominate alcoholism treatment ever since as a lay organization. With its early leaders admiringly referring to James as AA’s “cofounder,” AA and the numerous 12-step programs it has spawned have generally enjoyed a favorable reputation among humanistic psychologists. However, the authors regard this reputation as reflexive and largely undeserved, rather than critically generated. For essentially AA’s originators selected and promulgated one particular paradigm in James’s multiarrayed approach to alcoholism—the “self-surrender of the sick-minded soul”—to the exclusion of all others. In this paradigm, the addicted individual descends into a state of utter despair and then experiences an epiphany leading to self-transformation. However, James never regarded this state—which Maslow later called the “nadir-experience”—as the only means to addiction recovery, but rather advocated a diversity of paths, reflecting the variability of human personality. In celebrating this centennial year James’s enduring legacy, it is time for humanistic clinicians to take the lead in moving beyond AA’s outmoded, “one-size-fits-all” approach to addiction recovery.
The ‘New’ Industrial Relations and International Economic Crisis: Australia in 2009
Authors: Cooper Rae
Published: July 2010

While the sphere of industrial relations was overshadowed by the global financial crisis, 2009 was a year of immense change in the regulation of work and workplaces. Many provisions of the Rudd government’s Fair Work Act 2009, including the new collective bargaining regime, came into effect. Unions and employer organizations were preoccupied with the monumental process of award modernization throughout 2009. The AIRC has ceased to exist and it, along with a number of other regulatory bodies, has been subsumed into the new institution Fair Work Australia. The remaining key provisions of the Fair Work Act 2009, including the NES and modern awards, are effective on January 1 2010. This article analyses the early days of the operation of this ‘new’ Australian industrial relations.
Industrial Legislation in 2009
Authors: Sutherland Carolyn , Riley Joellen
Published: July 2010

In 2009, two major pieces of industrial legislation were enacted to give effect to the Labor Government’s commitment to replace Work Choices with laws for ‘Fair Work’. The Fair Work Act 2009 (Cth) promises to bring greater stability and simplicity to Australia’s workplace relations system. However, transitional rules in the Fair Work (Transitional Provisions and Consequential Amendments) Act 2009 (Cth) mean that it will be some time before participants in the system can enjoy these benefits. This review gives a brief account of both Acts before examining in more detail the enterprise bargaining rules which commenced operating in July under the supervision of a new institution, Fair Work Australia. We then consider two aspects of the Fair Work legislation which are most likely to provoke controversy when they commence operating in 2010, the adverse action and transfer of business provisions. We also look at the steps taken by federal and state governments to move towards a national system of workplace relations.
Major Tribunal Decisions in 2009
Authors: Catanzariti Joseph , Brown Simon
Published: July 2010

The year 2009 has seen significant change in Australian industrial relations, in particular, the repeal of the Workplace Relations Act 1996 and its replacement with Labor’s Fair Work Act 2009. From 1 July 2009, a new industrial tribunal, Fair Work Australia, replaced the Australian Industrial Relations Commission. The decisions issued by Fair Work Australia (FWA) since 1 July 2009 have put the provisions of the Fair Work Act into practice and perspective. This article focuses on those decisions which have dealt with enterprise bargaining and the agreement-making process under the Fair Work Act. Those cases demonstrate that the new agreement-making process is procedurally complex, and that FWA lacks discretion to approve enterprise agreements notwithstanding some procedural irregularity. FWA’s lack of discretion in determining whether an enterprise agreement has been ‘genuinely agreed to’ is inconsistent with the discretion reposed in FWA in other matters, including in determining whether an applicant for a protected action ballot order has been ‘genuinely trying to reach an agreement’.
Effects of Information Technology on Policy Decision-Making Processes
Authors: Myeong Seunghwan , Choi Younghoon
Published: July 2010

This study examined the effects of information technology (IT) on policy decision-making processes, especially in the stages of goal setting and choosing among policy alternatives. It used survey data collected in 1998 and 2005 from the metropolitan areas of Seoul and Busan in Korea. The survey results showed that there has been a positive change in the perception of the effects of IT on policy decision-making processes among government users. These changes could be made possible by strong leadership and e-government initiatives in central and metropolitan governments, not just due to the diffusion of technology and technologically capable staff members in organizations. The empirical results also showed that barriers to information sharing had increased in 2005 because of environmental changes, including requirement of authorization for providing information, complicated data management, and negative attitudes to information sharing. It suggests that city governments need to provide policy remedies for overcoming obstacles in information sharing in the areas of protection of privacy, network security, and official authorization processes for providing individual information. This study may contribute to the school of e-government and IT policy research as it helps decrease the gap between theory and practice.
Impact of Industry Incumbency and Product Newness on Pioneer Leadtime
Authors: Kim Namwoon , Min Sungwook
Published: July 2010

This study proposes a new theoretical frame to explain intermarket differences in the follow-up firm’s market entry that determines the pioneer’s monopoly period (i.e., pioneer leadtime). The authors note that firms’ new market entry is reflective of their entry capabilities as well as entry motivations. More specifically, they argue that industry incumbency of both the pioneer and follow-up firms and product newness of the market may influence the follow-up firms’ entry capabilities and motivations, creating variance in pioneer leadtime. Their empirical findings generally support the theoretical frame and complement the conventional entry-barrier perspective. For example, for really new products, pioneer leadtime is shorter when the follow-up entrant has experiences from similar industries than when it does not. For incrementally new products, pioneer leadtime is longer when the pioneer has experiences from similar industries than when it does not.
A Prospective Study of the Relationship between Lower Body Stiffness and Hamstring Injury in Professional Australian Rules Footballers
Authors: Watsford Mark L. , Murphy Aron J. , McLachlan Ken A. , Bryant Adam L. , Cameron Matt L. , Crossley Kay M. , Makdissi Michael
Published: July 2010

Background

Hamstring strains remain one of the most prevalent injuries in Australian Rules football. The authors prospectively examined the relationship between musculotendinous stiffness of the hamstring and leg stiffness with hamstring injury in professional Australian Rules footballers during the 2006 season.

Hypothesis

Higher hamstring stiffness and leg stiffness are related to noncontact, soft tissue hamstring injury risk in professional Australian Rules footballers.

Study Design

Case-control study; Level of evidence, 3.

Methods

Unilateral hamstring stiffness and leg stiffness were assessed in 136 professional footballers in the month before the commencement of the competitive season. This information was then investigated relative to players who suffered noncontact, soft tissue hamstring injuries during either matches or training throughout the season to identify whether preseason stiffness was related to injury occurrence.

Results

Fourteen tested players recorded acute, noncontact hamstring injuries, resulting in 3.3 ± 2.8 weeks of missed match play per injury. At preseason testing, the players who ended up sustaining a hamstring injury during the season recorded significantly higher mean hamstring stiffness (11%, P = .04) and leg stiffness (5%, P = .03). When considering the injured players, the leg stiffness of the involved limb was significantly higher than the noninjured players (P = .02), whereas hamstring stiffness was significantly higher on the noninvolved limb (P = .01). Further, those players who suffered a hamstring injury were significantly older than the noninjured players (P = .01).

Conclusion

It appears that a high bilateral hamstring stiffness and leg stiffness may be a determinant in the risk of sustaining a hamstring injury. Further, relatively lower hamstring stiffness in the involved limb of injured players appears to be associated with increased injury and may be related to a lack of strength. The information from stiffness assessment may allow medical staff to determine the hamstring risk status for individual players in team sports.
The Relationship between Forward Scapular Posture and Posterior Shoulder Tightness among Baseball Players
Authors: Laudner Kevin G. , Moline Mike T. , Meister Keith
Published: July 2010

Background

Excessive and untimely scapular dyskinesis during the throwing motion has been associated with several shoulder injuries. The scapula provides attachment for many soft tissue structures. Therefore, many have hypothesized that posterior shoulder tightness may alter proper scapular kinematics.

Hypothesis

As posterior shoulder tightness increases, so will forward scapular posture. Baseball players will have a significantly more forward scapular position of their dominant arm compared with their nondominant arm. The bilateral difference in forward scapular posture will be greater in pitchers than in position players, indicating pitchers have more forward scapular posture.

Study Design

Cross-sectional study; Level of evidence, 3.

Methods

Bilateral forward scapular posture, glenohumeral horizontal adduction, and rotational range of motion were measured among 20 professional baseball pitchers and 20 position players.

Results

A regression analysis showed a moderate to good negative relationship between glenohumeral horizontal adduction range of motion and forward scapular posture (r2 = .50, P = .001). T tests demonstrated that the dominant shoulders of both groups had significantly more forward scapular posture compared with nondominant shoulders (P < .004). There were no other significant relationships or differences found (r2 < .04, P > .15).

Conclusion

There was a moderate to good relationship between posterior shoulder tightness and forward scapular posture. Furthermore, baseball players had more forward scapular posture of the dominant arm than the nondominant arm. These results suggest that posterior shoulder tightness as evidenced by decreased glenohumeral adduction range of motion may be considered a partial predictor for excessive forward scapular posture and vice versa. Because of the association between this scapular dyskinesis and shoulder dysfunction, clinicians may find it advantageous to address these characteristics when examining and treating such athletes.
Bioabsorbable Fixation of Unstable Osteochondritis Dissecans Lesions
Authors: Millington Kendra L. , Shah Jay P. , Dahm Diane L. , Levy Bruce A. , Stuart Michael J.
Published: July 2010

Background

Osteochondritis dissecans lesions of the knee in adult patients frequently require surgical intervention. However, the ideal method of osteochondral fragment fixation remains uncertain.

Purpose

This study was undertaken to determine the clinical, functional, and radiographic outcomes of bioabsorbable fixation for unstable osteochondritis dissecans lesions involving the femoral condyles of the knee in skeletally mature patients.

Study Design

Case series; Level of evidence, 4.

Methods

Skeletally mature patients with an unstable osteochondritis dissecans lesion of the femoral condyle (Ewing and Voto stages II-IV) treated with bioabsorbable internal fixation and minimum 1-year follow-up were included in this retrospective study cohort. Pre- and postoperative radiographs were reviewed and postoperative Lysholm and International Knee Documentation Committee (IKDC) scores were documented.

Results

A total of 21 knees in 21 patients satisfied the inclusion criteria, and 3 patients were lost to follow-up. The remaining 18 patients were evaluated at a mean of 59 months after surgery (range, 12-154 months). The 14 male and 4 female patients had a mean age of 19 years at the time of surgery (range, 14-39 years). Ewing and Voto classification included 8 stage II lesions, 9 stage III lesions, and 1 stage IV lesion. Fragment fixation methods included bioabsorbable nails (11), pins (3), darts (2), screws (1), and combined screws and darts (1). Mean postoperative Lysholm and IKDC scores were 85 and 82, respectively. Fragment union occurred in 12 knees (67%); the remaining 6 knees (33%) required removal of the loose fragment. Of the 11 patients treated with bioabsorbable nails, 2 (18%) required reoperation for nail back-out.

Conclusion

The authors recommend caution when using bioabsorbable fixation for osteochondritis dissecans lesions in skeletally mature patients because of the low rate of clinical healing and high complication rate. Failure with unthreaded fixation devices may be caused by inadequate compression and not necessarily be related to bioabsorbability.
The Effect of a Holistic Program on Health-Promoting Behaviors in Hospital Registered Nurses
Authors: McElligott Deborah , Leask Capitulo Kathleen , Morris Diana Lynn , Click Elizabeth R.
Published: July 2010

Purpose: The purpose of the study was to examine the effect of a holistic program, the Collaborative Care Model (CCM) Program, and the development of a self-care plan on health-promoting behaviors in hospital nurses. Design: A quasi-experimental, pretest, posttest, repeated measure, comparison-group design was used. Method: The study was conducted in a large, academic medical center in the northeast. The experimental group included registered nurses (RNs) from units in one institution introduced to the CCM and development of a self-care plan in an 8-hour program. The control group received no intervention. Data were collected using the Health Promoting Lifestyle Profile II instrument (HPLP II); a 52-question Likert-type scale with six subscales examining health-promoting behaviors. Findings: Using repeated measures analysis of variance there was a significant increase ( p = .02) in the overall HPLP II mean, spirituality ( p = .04), interpersonal relations ( p = .04), and nutrition scores ( p = .04) of the experimental group as compared over time with the control group. Conclusions: The CCM plus the development of a self-care plan significantly increased overall health promoting behaviors, and spirituality, interpersonal relations, and nutrition scores in these RNs.
Lifelong Educational Practices and Resources in Enabling Health Literacy Among Older Adults
Authors: Wister Andrew V. , Malloy-Weir Leslie J. , Rootman Irving , Desjardins Richard
Published: July 2010

Objectives: The goal of this study is to examine the role of lifelong educational and learning practices and resources in enabling health literacy. Method: A subsample of older adults ( n = 2,979) derived from the 2003 seven country IALSS (Canadian survey) was used. An expanded Andersen-Newman model that included lifelong learning enabling factors was used to develop predictors of health literacy. Results: The formal education, lifelong and lifewide learning enabling factors exhibited the most robust associations with health literacy. These included education level; self-study in the form of reading manuals, reference books and journals; computer/Internet use, use of the library; leisure reading of books; reading letters, notes and e-mails; and volunteerism. Discussion: Findings are discussed in relation to the development and maintenance of health literacy over the life course. Programs and policies that encourage lifelong and lifewide educational resources and practices by older persons are needed.
Conflicting demands and the power of defensive routines in participatory action research
Authors: Jacobs Gaby
Published: July 2010

Participation has been of ongoing interest in the field of action research and the New Health Promotion movement, but it is not without tensions and problems. This article presents the challenge of containing the conflicting demands of personal empowerment, practical advancement and theory building in a community-based participatory action research project ‘Aspiring to Healthy Living in The Netherlands’. A Participatory Action Research (PAR) methodology was chosen because of its contribution to empowerment of the community of older people, which was one of the project goals. Besides that, the project aimed at the development of an intervention program for encouraging healthy living amongst older people in The Netherlands and contributing to the knowledge base on healthy living, by analyzing narratives from the participants. However, when time pressure rose, the empowerment goal started to collide with academic and practical aims, and the dialogue within the project team became obstructed leading to a return to the traditional routine of applied research and the accompanying power relationships, with implications for the learning in and about the project. This article starts with a short review of the literature on community participation in health research and the challenges of learning participatory action research, followed by a description of the PAR project and the process of participation, using the ladder of Pretty as a tool to highlight different levels of participation in different project stages. By using the theory of organizational learning developed by Argyris and Schön (Argyris, 1993; Argyris & Schön, 1978), insights will be provided into the attempts of a relatively inexperienced team to create a participatory and dialogic research project, and the problems in keeping reflection and learning going within a context of external pressure.
Preliminary evaluation of factors associated with premature trial closure and feasibility of accrual benchmarks in phase III oncology trials
Authors: Schroen Anneke T , Petroni Gina R , Hongkun Wang  , Gray Robert , Wang Xiaofei F , Cronin Walter , Sargent Daniel J , Benedetti Jacqueline , Wickerham Donald L , Djulbegovic Benjamin , Slingluff Craig L
Published: July 2010

Background A major challenge for randomized phase III oncology trials is the frequent low rates of patient enrollment, resulting in high rates of premature closure due to insufficient accrual.

Purpose We conducted a pilot study to determine the extent of trial closure due to poor accrual, feasibility of identifying trial factors associated with sufficient accrual, impact of redesign strategies on trial accrual, and accrual benchmarks designating high failure risk in the clinical trials cooperative group (CTCG) setting.

Methods A subset of phase III trials opened by five CTCGs between August 1991 and March 2004 was evaluated. Design elements, experimental agents, redesign strategies, and pretrial accrual assessment supporting accrual predictions were abstracted from CTCG documents. Percent actual/predicted accrual rate averaged per month was calculated. Trials were categorized as having sufficient or insufficient accrual based on reason for trial termination. Analyses included univariate and bivariate summaries to identify potential trial factors associated with accrual sufficiency.

Results Among 40 trials from one CTCG, 21 (52.5%) trials closed due to insufficient accrual. In 82 trials from five CTCGs, therapeutic trials accrued sufficiently more often than nontherapeutic trials (59% vs 27%, p = 0.05). Trials including pretrial accrual assessment more often achieved sufficient accrual than those without (67% vs 47%, p = 0.08). Fewer exclusion criteria, shorter consent forms, other CTCG participation, and trial design simplicity were not associated with achieving sufficient accrual. Trials accruing at a rate much lower than predicted (<35% actual/predicted accrual rate) were consistently closed due to insufficient accrual.

Limitations This trial subset under-represents certain experimental modalities. Data sources do not allow accounting for all factors potentially related to accrual success.

Conclusion Trial closure due to insufficient accrual is common. Certain trial design factors appear associated with attaining sufficient accrual. Defining accrual benchmarks for early trial termination or redesign is feasible, but better accrual prediction methods are critically needed. Future studies should focus on identifying trial factors that allow more accurate accrual predictions and strategies that can salvage open trials experiencing slow accrual. Clinical Trials 2010; 7: 312—321. http://ctj.sagepub.com
Statistical considerations in evaluating pharmacogenomics-based clinical effect for confirmatory trials
Authors: Wang Sue-Jane , O'Neill Robert T , Hung HM James
Published: July 2010

Background The current practice for seeking genomically favorable patients in randomized controlled clinical trials using genomic convenience samples.

Purpose To discuss the extent of imbalance, confounding, bias, design efficiency loss, type I error, and type II error that can occur in the evaluation of the convenience samples, particularly when they are small samples. To articulate statistical considerations for a reasonable sample size to minimize the chance of imbalance, and, to highlight the importance of replicating the subgroup finding in independent studies.

Methods Four case examples reflecting recent regulatory experiences are used to underscore the problems with convenience samples. Probability of imbalance for a pre-specified subgroup is provided to elucidate sample size needed to minimize the chance of imbalance. We use an example drug development to highlight the level of scientific rigor needed, with evidence replicated for a pre-specified subgroup claim.

Results The convenience samples evaluated ranged from 18% to 38% of the intent-to-treat samples with sample size ranging from 100 to 5000 patients per arm. The baseline imbalance can occur with probability higher than 25%. Mild to moderate multiple confounders yielding the same directional bias in favor of the treated group can make treatment group incomparable at baseline and result in a false positive conclusion that there is a treatment difference. Conversely, if the same directional bias favors the placebo group or there is loss in design efficiency, the type II error can increase substantially.

Limitations Pre-specification of a genomic subgroup hypothesis is useful only for some degree of type I error control.

Conclusion Complete ascertainment of genomic samples in a randomized controlled trial should be the first step to explore if a favorable genomic patient subgroup suggests a treatment effect when there is no clear prior knowledge and understanding about how the mechanism of a drug target affects the clinical outcome of interest. When stratified randomization based on genomic biomarker status cannot be implemented in designing a pharmacogenomics confirmatory clinical trial, if there is one genomic biomarker prognostic for clinical response, as a general rule of thumb, a sample size of at least 100 patients may be needed to be considered for the lower prevalence genomic subgroup to minimize the chance of an imbalance of 20% or more difference in the prevalence of the genomic marker. The sample size may need to be at least 150, 350, and 1350, respectively, if an imbalance of 15%, 10% and 5% difference is of concern. Clinical Trials 2010; 7: 525—536. http://ctj.sagepub.com
King among Kings: Understanding the Role and Responsibilities of the Department Chair in Higher Education
Authors: Berdrow Iris
Published: July 2010

The role and responsibilities of the chair of an academic department in higher education is considered from the perspective of both actor and agent, within the context of the institution being served and the department being represented. The intent of this article is to further research on the role of department chair by analyzing it in the context of the institution’s goals and expectations, the stakeholders affecting and affected by the department chair, and the chair’s own capabilities. A 360-degree exploration of the role, expectations and competencies of department chairs was carried out at a private business university in the Northeast area of the USA, including both business and liberal arts department chairs. The results led to new development programs for incoming chairs as well as better supports for current chairs. The design of this project allowed for both the study of the role of department chair and the improvement of support mechanisms to be effective in that role. The design, data and analysis are presented, along with descriptive models.
Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival
Authors: Silva J. , García V. , Zaballos Á. , Provencio M. , Lombardía L. , Almonacid L. , García J.M. , Domínguez G. , Peña C. , Diaz R. , Herrera M. , Varela A. , Bonilla F.
Published: July 2010

The identification of tumour biomarkers that detect the presence of disease using noninvasive diagnostic procedures is a key part of cancer research. We determined in plasma the vesicle-related microRNA (miRNA) expression profile of nonsmall cell lung cancer (NSCLC) and evaluate whether plasma miRNAs can be both discriminating (between patients and healthy controls) and prognostic markers.

365 human miRNAs were analysed by Taqman® low-density arrays (Applied Biosystems, Foster City, CA, USA) in the plasma from 28 NSCLC patients and 20 controls. Five selected miRNAs (let-7f, miR-20b, miR-30e-3p, miR-223 and miR-301) were validated independently by real-time PCR in plasma from 78 NSCLC and 48 controls and correlated with pathologic parameters and survival.

Levels of let-7f, miR-20b and miR-30e-3p were decreased in plasma vesicles of NSCLC patients. Moreover, levels of let-7f and miR-30e-3p distinguished between two groups of patients for stage of disease and therefore possibility of surgery. Plasma levels of miR-30e-3p and let-7f were associated with short disease-free survival and overall survival, respectively.

NSCLC patients and healthy controls differ in vesicle-related miRNAs in plasma. Levels of let-7f and miR-30e-3p in NSCLC patients are associated with poor outcome. Thus, plasma vesicle-related miRNAs obtained by noninvasive methods could serve as circulating tumour biomarkers of discriminating and prognostic value.
Bosentan does not improve pulmonary hypertension and lung remodeling in heart failure
Authors: Jiang B.H. , Tardif J-C. , Shi Y. , Dupuis J.
Published: July 2010

Pulmonary hypertension (PH) and right ventricular (RV) dysfunction associated with heart failure (HF) carry a poor prognosis. Although endothelin receptor antagonists (ERAs) demonstrated benefits in pulmonary arterial hypertension, their efficacy in PH associated with HF was not specifically evaluated.

2 weeks after myocardial infarction (MI) rats received bosentan (100 or 200 mg·kg−1·day−1) or no treatment for 3 weeks. PH, RV hypertrophy and function as well as lung remodeling and function were evaluated.

LV echocardiographic wall motion abnormality and function measured before treatment (2 weeks after MI) and after treatment (5 weeks after MI) were similar in MI control and MI treatment groups. HF induced PH and RV hypertrophy compared with sham: RV systolic pressure 39±5versus23±0.8 mmHg and RV/left ventricular+septum weight 52±7versus24±0.5% (all p<0.01). Bosentan did not significantly modify these parameters. In addition, bosentan did not improve depressed RV function measured by echocardiograph from the RV myocardial performance index and tricuspid annular plane systolic excursion. The respiratory pressure–volume relationship revealed that HF caused a restrictive lung syndrome with histological lung remodeling and fibrosis, also not improved by bosentan.

Dual ERA therapy with bosentan does not reduce PH, RV hypertrophy and lung remodeling and dysfunction associated with ischaemic HF.
Analysis of vkorc1 polymorphisms in Norway rats using the roof rat as outgroup
Authors: Díaz Juan C , Song Ying , Moore Anthony , Borchert Jeff N , Kohn Michael H
Published: July 2010

Background

Certain mutations in the vitamin K epoxide reductase subcomponent 1 gene (vkorc1) mediate rodent resistance to warfarin and other anticoagulants. Testing for resistance often involves analysis of the vkorc1. However, a genetic test for the roof rat (Rattus rattus) has yet to be developed. Moreover, an available roof rat vkorc1 sequence would enable species identification based on vkorc1 sequence and the evaluation of natural selection on particular vkorc1 polymorphisms in the Norway rat (R. norvegicus).

Results

We report the coding sequence, introns and 5' and 3' termini for the vkorc1 gene of roof rats (R. r. alexandrinus and R. r. frugivorus) from Uganda, Africa. Newly designed PCR primers now enable genetic testing of the roof rat and Norway rat. Only synonymous and noncoding polymorphisms were found in roof rats from Uganda. Both nominal subspecies of roof rats were indistinguishable from each other but were distinct from R. losea and R. flavipectus; however, the roof rat also shares at least three coding sequence polymorphisms with R. losea and R. flavipectus. Many of recently published vkorc1 synonymous and non-synonymous single nucleotide polymorphisms (SNPs) in Norway rats are likely SNPs from roof rats and/or other Rattus species. Tests applied to presumably genuine Norway rat vkorc1 SNPs are consistent with a role for selection in two populations carrying the derived Phe63Cys and Tyr139Cys mutations.

Conclusion

Geographic mapping of vkorc1 SNPs in roof rats should be facilitated by our report. Our assay should be applicable to most species of Rattus, which are intermediate in genetic distance from roof and Norway rats. Vkorc1-mediated resistance due to non-synonymous coding SNPs is not segregating in roof rats from Uganda. By using the roof rat sequence as a reference vkorc1, SNPs now can be assigned to the correct rat species with more confidence. Sampling designs and genotyping strategies employed so far have helped detect candidate mutations underlying vkorc1-mediated resistance, but generally provided unsuitable data to test for selection. We propose that our understanding of vkorc1-mediated evolution of resistance in rodents would benefit from the adoption of sampling and genotyping designs that enable tests for selection on vkorc1.
Does the core circadian clock in the moss Physcomitrella patens (Bryophyta) comprise a single loop?
Authors: Holm Karl , Källman Thomas , Gyllenstrand Niclas , Hedman Harald , Lagercrantz Ulf
Published: July 2010

Background

The endogenous circadian clock allows the organism to synchronize processes both to daily and seasonal changes. In plants, many metabolic processes such as photosynthesis, as well as photoperiodic responses, are under the control of a circadian clock. Comparative studies with the moss Physcomitrella patens provide the opportunity to study many aspects of land plant evolution. Here we present a comparative overview of clock-associated components and the circadian network in the moss P. patens.

Results

The moss P. patens has a set of conserved circadian core components that share genetic relationship and gene expression patterns with clock genes of vascular plants. These genes include Myb-like transcription factors PpCCA1a and PpCCA1b, pseudo-response regulators PpPRR1-4, and regulatory elements PpELF3, PpLUX and possibly PpELF4. However, the moss lacks homologs of AtTOC1, AtGI and the AtZTL-family of genes, which can be found in all vascular plants studied here. These three genes constitute essential components of two of the three integrated feed-back loops in the current model of the Arabidopsis circadian clock mechanism. Consequently, our results suggest instead a single loop circadian clock in the moss. Possibly as a result of this, temperature compensation of core clock gene expression appears to be decreased in P. patens.

Conclusions

This study is the first comparative overview of the circadian clock mechanism in a basal land plant, the moss P. patens. Our results indicate that the moss clock mechanism may represent an ancestral state in contrast to the more complex and partly duplicated structure of subsequent land plants. These findings may provide insights into the understanding of the evolution of circadian network topology.
Implication of genetic variants near SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, FTO, TCF2, KCNQ1, and WFS1 in Type 2 Diabetes in a Chinese population
Authors: Han Xueyao , Luo Yingying , Ren Qian , Zhang Xiuying , Wang Fang , Sun Xiuqin , Zhou Xianghai , Ji Linong
Published: July 2010

Background

Recently, several genome-wide and candidate gene association studies have identified many novel genetic loci for type 2 diabetes (T2D); among these genes, CDKAL1, IGF2BP2, SLC30A8, CDKN2A/B, HHEX, FTO, TCF2, KCNQ1, and WFS1 are the most important. We aimed to determine the effects of these genetic loci associated with T2D in the Chinese Han population of China.

Methods

Single-nucleotide polymorphisms (SNPs) in or near CDKAL1, IGF2BP2, SLC30A8, CDKN2A/B, HHEX, FTO, TCF2, KCNQ1, and WFS1 genes were genotyped in a case-control Chinese Han sample living in Beijing, China involving 1024 patients with T2D and 1005 control subjects.

Results

In Chinese Han, we replicated the associations between 7 genetic loci and T2D, with risk allele-specific odds ratios (ORs) as follows: 1.27 (95% CI, 1.11-1.45; p = 0.0008) for CDKAL1-rs10946398, 1.26 (95% CI, 1.08-1.47; p = 0.003) for IGF2BP2-rs4402960, 1.19 (95% CI, 1.04-1.37; p = 0.009) for SLC30A8-rs13266634, 1.22 (95% CI, 1.06-1.41; p = 0.005) for CDKN2A/B-rs10811661, 1.20 (95% CI, 1.01-1.42; p = 0.03) for HHEX-rs5015480, 1.37 (95% CI, 1.19-1.69; p = 1.0 × 10-4) for KCNQ1-rs2237892, and 1.24 (95% CI, 1.01-1.52; p = 0.046) for FTO-rs8050136 after adjustment for age, gender, and body mass index. Not only did an association between WFS1-rs6446482 and early-onset T2D exist in the subgroup analysis, but TCF2-rs7501939 and WFS1-rs6446482 were also confirmed to confer risk for T2D in this meta-analysis. Moreover, the relationship between FTO-rs8050136 and body mass index, together with the effect of CDKAL1-rs10946398 on beta cell function, was also observed in the control individuals.

Conclusions

Our findings support the important contribution of these genetic loci to susceptibility for T2D in the Chinese Han population in Beijing of China.
Serum vitamin D levels and survival of patients with colorectal cancer: Post-hoc analysis of a prospective cohort study
Authors: Mezawa Hidetoshi , Sugiura Tsutomu , Watanabe Michiaki , Norizoe Chihiro , Takahashi Daisuke , Shimojima Akira , Tamez Seryna , Tsutsumi Yusuke , Yanaga Katsuhiko , Urashima Mitsuyoshi
Published: July 2010

Background

Recently, serum 25-hydroxyvitamin D (25OHD) levels were shown to be associated with the survival of patients with colorectal cancer. However, 25OHD levels were measured a median of 6 years before diagnosis or were predicted levels. In this study, we directly measured serum 25OHD levels at surgery and examined the association with survival among patients with colorectal cancer.

Methods

We started a prospective cohort study to find prognostic factors in patients with colorectal cancer from 2003 to 2008 and stored serum samples and clinical data. As part of a post-hoc analysis, serum 25OHD levels were measured by radioimmunoassay. Association between overall survival and serum 25OHD levels were computed using the Cox proportional hazard model adjusted for month of serum sampling as well as age at diagnosis, gender, cancer stage, residual tumor after surgery, time period of surgery, location of tumor, adjuvant chemotherapy and number of lymph nodes with metastasis at surgery. Unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were determined.

Results

Serum 25OHD levels were measured in 257 patients. Only 3% had sufficient levels (30 ng/ml and greater). Based on month of blood sampling, an annual oscillation of 25OHD levels was seen, with levels being lower in spring and higher in late summer. Higher 25OHD levels were associated with better overall survival under multi-variate analysis (HR, 0.91: 95% CI, 0.84 to 0.99, P = 0.027).

Conclusions

These results suggest that higher 25OHD levels at surgery may be associated with a better survival rate of patients with colorectal cancer.
Molecular assays for the detection of prostate tumor derived nucleic acids in peripheral blood
Authors: Jost Matthias , Day John R , Slaughter Ryan , Koreckij Theodore D , Gonzales Deanna , Kinnunen Martin , Groskopf Jack , Rittenhouse Harry G , Vessella Robert L , Reynolds Mark A
Published: July 2010

Background

Prostate cancer is the second leading cause of cancer mortality in American men. Although serum PSA testing is widely used for early detection, more specific prognostic tests are needed to guide treatment decisions. Recently, the enumeration of circulating prostate epithelial cells has been shown to correlate with disease recurrence and metastasis following definitive treatment. The purpose of our study was to investigate an immunomagnetic fractionation procedure to enrich circulating prostate tumor cells (CTCs) from peripheral blood specimens, and to apply amplified molecular assays for the detection of prostate-specific markers (PSA, PCA3 and TMPRSS2:ERG gene fusion mRNAs).

Results

As few as five prostate cancer cells were detected per 5 mL of whole blood in model system experiments using anti-EpCAM magnetic particles alone or in combination with anti-PSMA magnetic particles. In our experiments, anti-EpCAM magnetic particles alone exhibited equivalent or better analytical performance with patient samples compared to a combination of anti-EpCAM + anti-PSMA magnetic particles. Up to 39% of men with advanced prostate cancer tested positive with one or more of the molecular assays tested, whereas control samples from men with benign prostate hyperplasia gave consistently negative results as expected. Interestingly, for the vast majority of men who tested positive for PSA mRNA following CTC enrichment, their matched plasma samples also tested positive, although CTC enrichment gave higher overall mRNA copy numbers.

Conclusion

CTCs were successfully enriched and detected in men with advanced prostate cancer using an immunomagnetic enrichment procedure coupled with amplified molecular assays for PSA, PCA3, and TMPRSS2:ERG gene fusion mRNAs. Our results indicate that men who test positive following CTC enrichment also exhibit higher detectable levels of non-cellular, circulating prostate-specific mRNAs.
Commonly applied positive end-expiratory pressures do not prevent functional residual capacity decline in the setting of intra-abdominal hypertension: a pig model
Authors: Regli Adrian , Hockings Lisen E , Musk Gabrielle C , Roberts Brigit , Noffsinger Bill , Singh Bhajan , van Heerden Peter V
Published: July 2010

Introduction

Intra-abdominal hypertension is common in critically ill patients and is associated with increased morbidity and mortality. The optimal ventilation strategy remains unclear in these patients. We examined the effect of positive end-expiratory pressures (PEEP) on functional residual capacity (FRC) and oxygen delivery in a pig model of intra-abdominal hypertension.

Methods

Thirteen adult pigs received standardised anaesthesia and ventilation. We randomised three levels of intra-abdominal pressure (3 mmHg (baseline), 18 mmHg, and 26 mmHg) and four commonly applied levels of PEEP (5, 8, 12 and 15 cmH2O). Intra-abdominal pressures were generated by inflating an intra-abdominal balloon. We measured intra-abdominal (bladder) pressure, functional residual capacity, cardiac output, haemoglobin and oxygen saturation, and calculated oxygen delivery.

Results

Raised intra-abdominal pressure decreased FRC but did not change cardiac output. PEEP increased FRC at baseline intra-abdominal pressure. The decline in FRC with raised intra-abdominal pressure was partly reversed by PEEP at 18 mmHg intra-abdominal pressure and not at all at 26 mmHg intra-abdominal pressure. PEEP significantly decreased cardiac output and oxygen delivery at baseline and at 26 mmHg intra-abdominal pressure but not at 18 mmHg intra-abdominal pressure.

Conclusions

In a pig model of intra-abdominal hypertension, PEEP up to 15 cmH2O did not prevent the FRC decline caused by intra-abdominal hypertension and was associated with reduced oxygen delivery as a consequence of reduced cardiac output. This implies that PEEP levels inferior to the corresponding intra-abdominal pressures cannot be recommended to prevent FRC decline in the setting of intra-abdominal hypertension.
Association of angiopoietin-like protein 3 with hepatic triglyceride lipase and lipoprotein lipase activities in human plasma
Authors: Nakajima K , Kobayashi J , Mabuchi H , Nakano T , Tokita Y , Nagamine T , Imamura S , Ai M , Otokozawa S , Schaefer E F
Published: July 2010

Background

The relationship between plasma angiopoietin-like protein 3 (ANGPTL3), and lipoprotein lipase (LPL) activity and hepatic triglyceride lipase (HTGL) activity has not been investigated in the metabolism of remnant lipoproteins (RLPs) and high-density lipoprotein (HDL) in human plasma.

Methods

ANGPTL3, LPL activity, HTGL activity, RLP-C and RLP-TG and small, dense LDL-cholesterol (sd LDL-C) were measured in 20 overweight and obese subjects in the fasting and postprandial states.

Results

Plasma TG, RLP-C, RLP-TG and sd LDL-C were inversely correlated with LPL activity both in the fasting and postprandial states, but not correlated with HTGL activity and ANGPTL3. However, plasma HDL-C was positively correlated with LPL activity both in the fasting and postprandial states, while inversely correlated with HTGL activity. ANGPTL3 was inversely correlated with HTGL activity both in the fasting and postprandial states, but not correlated with LPL activity.

Conclusion

HTGL plays a major role in HDL metabolism, but not RLP metabolism. These findings suggest that ANGPTL3 is strongly associated with the inhibition of HTGL activity and regulates HDL metabolism, but not associated with the inhibition of LPL activity for the metabolism of RLPs in human plasma.
On Cournot Equilibria in Electricity Transmission Networks
Authors: Downward A. , Zakeri G. , Philpottt A. B.
Published: July 2010

We consider electricity pool markets in radial transmission networks in which the lines have capacities. At each node there is a strategic generator injecting generation quantities into the pool. Prices are determined by a linear competitive fringe at each node (or equivalently a linear demand function) through a convex dispatch optimization. We derive a set of linear inequalities satisfied by the line capacities that gives necessary and sufficient conditions for the unconstrained one-shot Cournot equilibrium to remain an equilibrium in the constrained network. We discuss the extension of this model to general networks and to lines with transmission losses, and we conclude by discussing the application of this methodology to the New Zealand electricity transmission network.