Showing papers by "University of Vermont published in 2007"

Top 10 algorithms in data mining

Abstract: This paper presents the top 10 data mining algorithms identified by the IEEE International Conference on Data Mining (ICDM) in December 2006: C4.5, k-Means, SVM, Apriori, EM, PageRank, AdaBoost, kNN, Naive Bayes, and CART. These top 10 algorithms are among the most influential data mining algorithms in the research community. With each algorithm, we provide a description of the algorithm, discuss the impact of the algorithm, and review current and further research on the algorithm. These 10 algorithms cover classification, clustering, statistical learning, association analysis, and link mining, which are all among the most important topics in data mining research and development.

Influentials, Networks, and Public Opinion Formation

Abstract: A central idea in marketing and diffusion research is that influentials—a minority of individuals who influence an exceptional number of their peers—are important to the formation of public opinion. Here we examine this idea, which we call the “influentials hypothesis,” using a series of computer simulations of interpersonal influence processes. Under most conditions that we consider, we find that large cascades of influence are driven not by influentials but by a critical mass of easily influenced individuals. Although our results do not exclude the possibility that influentials can be important, they suggest that the influentials hypothesis requires more careful specification and testing than it has received.

Robust dimensions of anxiety sensitivity: Development and initial validation of the anxiety sensitivity index-3

Abstract: Accumulating evidence suggests that anxiety sensitivity (fear of arousal-related sensations) plays an important role in many clinical conditions, particularly anxiety disorders. Research has increasingly focused on how the basic dimensions of anxiety sensitivity are related to various forms of psychopathology. Such work has been hampered because the original measure--the Anxiety Sensitivity Index (ASI)--was not designed to be multidimensional. Subsequently developed multidimensional measures have unstable factor structures or measure only a subset of the most widely replicated factors. Therefore, the authors developed, via factor analysis of responses from U.S. and Canadian nonclinical participants (n=2,361), an 18-item measure, the ASI-3, which assesses the 3 factors best replicated in previous research: Physical, Cognitive, and Social Concerns. Factorial validity of the ASI-3 was supported by confirmatory factor analyses of 6 replication samples, including nonclinical samples from the United States and Canada, France, Mexico, the Netherlands, and Spain (n=4,494) and a clinical sample from the United States and Canada (n=390). The ASI-3 displayed generally good performance on other indices of reliability and validity, along with evidence of improved psychometric properties over the original ASI.

Impaired fasting glucose and impaired glucose tolerance: implications for care.

Abstract: Type 2 diabetes is now epidemic. In the U.S., there has been a 61% increase in incidence between 1990 and 2001 (1). There are currently 1.5 million new cases per year, and the prevalence in 2005 was almost 21 million (2). The epidemic has affected developed and developing countries alike, and the worldwide prevalence of diabetes is projected to increase dramatically by 2025 (3). The increase in type 2 diabetes is related to lifestyle changes that have resulted in overweight, obesity, and decreased physical activity levels. These environmental changes, superimposed on genetic predisposition, increase insulin resistance, which, in concert with progressive β-cell failure, results in rising glycemia in the nondiabetic range. In addition to the risk for diabetes, insulin resistance and impaired insulin secretion are accompanied by a host of major cardiovascular disease (CVD) risk factors including hypertension and dyslipidemia. Further reduction in insulin secretion over time results in increasing glycemia and the development of diabetes, which in turn is associated with the development of microvascular and cardiovascular complications. The transition from the early metabolic abnormalities that precede diabetes, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), to diabetes may take many years; however, current estimates indicate that most individuals (perhaps up to 70%) with these pre-diabetic states eventually develop diabetes (4–10). During the pre-diabetic state, the risk of a CVD event is modestly increased (11–22). With the development of diabetes, however, there is a large increase in risk for CVD, as well as for long-term complications affecting the eyes, kidneys, and nervous system. The complications of diabetes, which are the cause of major morbidity and mortality, are related to its duration, chronic level of glycemia, and other risk factors. Although clinical trials have demonstrated the effectiveness of intensive glycemic and blood pressure control to …

General Tensor Discriminant Analysis and Gabor Features for Gait Recognition

Abstract: Traditional image representations are not suited to conventional classification methods such as the linear discriminant analysis (LDA) because of the undersample problem (USP): the dimensionality of the feature space is much higher than the number of training samples. Motivated by the successes of the two-dimensional LDA (2DLDA) for face recognition, we develop a general tensor discriminant analysis (GTDA) as a preprocessing step for LDA. The benefits of GTDA, compared with existing preprocessing methods such as the principal components analysis (PCA) and 2DLDA, include the following: 1) the USP is reduced in subsequent classification by, for example, LDA, 2) the discriminative information in the training tensors is preserved, and 3) GTDA provides stable recognition rates because the alternating projection optimization algorithm to obtain a solution of GTDA converges, whereas that of 2DLDA does not. We use human gait recognition to validate the proposed GTDA. The averaged gait images are utilized for gait representation. Given the popularity of Gabor-function-based image decompositions for image understanding and object recognition, we develop three different Gabor-function-based image representations: 1) GaborD is the sum of Gabor filter responses over directions, 2) GaborS is the sum of Gabor filter responses over scales, and 3) GaborSD is the sum of Gabor filter responses over scales and directions. The GaborD, GaborS, and GaborSD representations are applied to the problem of recognizing people from their averaged gait images. A large number of experiments were carried out to evaluate the effectiveness (recognition rate) of gait recognition based on first obtaining a Gabor, GaborD, GaborS, or GaborSD image representation, then using GDTA to extract features and, finally, using LDA for classification. The proposed methods achieved good performance for gait recognition based on image sequences from the University of South Florida (USF) HumanID Database. Experimental comparisons are made with nine state-of-the-art classification methods in gait recognition.

Mechanisms of Anterior Cruciate Ligament Injury in Basketball Video Analysis of 39 Cases

Abstract: Background: The mechanisms of anterior cruciate ligament injury in basketball are not well defined.Purpose: To describe the mechanisms of anterior cruciate ligament injury in basketball based on videos of injury situations.Study Design: Case series; Level of evidence, 4.Methods: Six international experts performed visual inspection analyses of 39 videos (17 male and 22 female players) of anterior cruciate ligament injury situations from high school, college, and professional basketball games. Two predefined time points were analyzed: initial ground contact and 50 milliseconds later. The analysts were asked to assess the playing situation, player behavior, and joint kinematics.Results: There was contact at the assumed time of injury in 11 of the 39 cases (5 male and 6 female players). Four of these cases were direct blows to the knee, all in men. Eleven of the 22 female cases were collisions, or the player was pushed by an opponent before the time of injury. The estimated time of injury, based on the group...

Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial

Abstract: Summary Background The goals of axillary-lymph-node dissection (ALND) are to maximise survival, provide regional control, and stage the patient. However, this technique has substantial side-effects. The purpose of the B-32 trial is to establish whether sentinel-lymph-node (SLN) resection can achieve the same therapeutic goals as conventional ALND but with decreased side-effects. The aim of this paper is to report the technical success and accuracy of SLN resection plus ALND versus SLN resection alone. Methods 5611 women with invasive breast cancer were randomly assigned to receive either SLN resection followed by immediate conventional ALND (n=2807; group 1) or SLN resection without ALND if SLNs were negative on intraoperative cytology and histological examination (n=2804; group 2) in the B-32 trial. Patients in group 2 underwent ALND if no SLNs were identified or if one or more SLNs were positive on intraoperative cytology or subsequent histological examination. Primary endpoints, including survival, regional control, and morbidity, will be reported later. Secondary endpoints are accuracy and technical success and are reported here. This trial is registered with the Clinical Trial registry, number NCT00003830. Findings Data for technical success were available for 5536 of 5611 patients; 75 declined protocol treatment, had no SLNs removed, or had no SLN resection done. SLNs were successfully removed in 97·2% of patients (5379 of 5536) in both groups combined. Identification of a preincision hot spot was associated with greater SLN removal (98·9% [5072 of 5128]). Only 1·4% (189 of 13171) of SLN specimens were outside of axillary levels I and II. 65·1% (8571 of 13 171) of SLN specimens were both radioactive and blue; a small percentage was identified by palpation only (3·9% [515 of 13 171]). The overall accuracy of SLN resection in patients in group 1 was 97·1% (2544 of 2619; 95% CI 96·4–97·7), with a false-negative rate of 9·8% (75 of 766; 95% CI 7·8–12·2). Differences in tumour location, type of biopsy, and number of SLNs removed significantly affected the false-negative rate. Allergic reactions related to blue dye occurred in 0·7% (37 of 5588) of patients with data on toxic effects. Interpretation The findings reported here indicate excellent balance in clinical patient characteristics between the two randomised groups and that the success of SLN resection was high. These findings are important because the B-32 trial is the only trial of sufficient size to provide definitive information related to the primary outcome measures of survival and regional control. Removal of more than one SLN and avoidance of excisional biopsy are important variables in reducing the false-negative rate.

Increased genetic variation and evolutionary potential drive the success of an invasive grass.

Abstract: Despite the increasing biological and economic impacts of invasive species, little is known about the evolutionary mechanisms that favor geographic range expansion and evolution of invasiveness in introduced species Here, we focus on the invasive wetland grass Phalaris arundinacea L and document the evolutionary consequences that resulted from multiple and uncontrolled introductions into North America of genetic material native to different European regions Continental-scale genetic variation occurring in reed canarygrass' European range has been reshuffled and recombined within North American introduced populations, giving rise to a number of novel genotypes This process alleviated genetic bottlenecks throughout reed canarygrass' introduced range, including in peripheral populations, where depletion of genetic diversity is expected and is observed in the native range Moreover, reed canarygrass had higher genetic diversity and heritable phenotypic variation in its invasive range relative to its native range The resulting high evolutionary potential of invasive populations allowed for rapid selection of genotypes with higher vegetative colonization ability and phenotypic plasticity Our results show that repeated introductions of a single species may inadvertently create harmful invaders with high adaptive potential Such invasive species may be able to evolve in response to changing climate, allowing them to have increasing impact on native communities and ecosystems in the future More generally, multiple immigration events may thus trigger future adaptation and geographic spread of a species population by preventing genetic bottlenecks and generating genetic novelties through recombination

Paradox lost: genetic diversity and the success of aquatic invasions

Abstract: There is mounting evidence that reduced genetic diversity in invasive populations is not as commonplace as expected. Recent studies indicate that high propagule vectors, such as ballast water and shellfish transplantations, and multiple introductions contribute to the elimination of founder effects in the majority of successful aquatic invasions. Multiple introductions, in particular, can promote range expansion of introduced populations through both genetic and demographic mechanisms. Closely related to vectors and corridors of introduction, propagule pressure can play an important role in determining the genetic outcome of introduction events. Even low-diversity introductions have numerous means of avoiding the negative impact of diversity loss. The interaction of high propagule vectors and multiple introductions reveal important patterns associated with invasion success and deserve closer scrutiny.

Abraxas and RAP80 Form a BRCA1 Protein Complex Required for the DNA Damage Response

Abstract: The BRCT repeats of the breast and ovarian cancer predisposition protein BRCA1 are essential for tumor suppression. Phosphopeptide affinity proteomic analysis identified a protein, Abraxas, that directly binds the BRCA1 BRCT repeats through a phospho-Ser-X-X-Phe motif. Abraxas binds BRCA1 to the mutual exclusion of BACH1 (BRCA1-associated C-terminal helicase) and CtIP (CtBP-interacting protein), forming a third type of BRCA1 complex. Abraxas recruits the ubiquitin-interacting motif (UIM)–containing protein RAP80 to BRCA1. Both Abraxas and RAP80 were required for DNA damage resistance, G2-M checkpoint control, and DNA repair. RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation, and the UIM domains alone were capable of foci formation. The RAP80-Abraxas complex may help recruit BRCA1 to DNA damage sites in part through recognition of ubiquitinated proteins.

Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial

Abstract: Summary Background Minocycline has anti-apoptotic and anti-inflammatory effects in vitro, and extends survival in mouse models of some neurological conditions. Several trials are planned or are in progress to assess whether minocycline slows human neurodegeneration. We aimed to test the efficacy of minocycline as a treatment for amyotrophic lateral sclerosis (ALS). Methods We did a multicentre, randomised placebo-controlled phase III trial. After a 4-month lead-in phase, 412 patients were randomly assigned to receive placebo or minocycline in escalating doses of up to 400 mg/day for 9 months. The primary outcome measure was the difference in rate of change in the revised ALS functional rating scale (ALSFRS-R). Secondary outcome measures were forced vital capacity (FVC), manual muscle testing (MMT), quality of life, survival, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00047723. Findings ALSFRS-R score deterioration was faster in the minocycline group than in the placebo group (−1·30 vs −1·04 units/month, 95% CI for difference −0·44 to −0·08; p=0·005). Patients on minocycline also had non-significant tendencies towards faster decline in FVC (−3·48 vs −3·01, −1·03 to 0·11; p=0·11) and MMT score (−0·30 vs −0·26, −0·08 to 0·01; p=0·11), and greater mortality during the 9-month treatment phase (hazard ratio=1·32, 95% CI 0·83 to 2·10; p=0·23) than did patients on placebo. Quality-of-life scores did not differ between the treatment groups. Non-serious gastrointestinal and neurological adverse events were more common in the minocycline group than in the placebo group, but these events were not significantly related to the decline in ALSFRS-R score. Interpretation Our finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS.

3-Year Follow-up of the NIMH MTA Study

Abstract: Objective: In the intent-to-treat analysis of the Multimodal Treatment Study of Children With ADHD (MTA), the effects of medication management (MedMgt), behavior therapy (Beh), their combination (Comb), and usual community care (CC) differed at 14 and 24 months due to superiority of treatments that used the MTA medication algorithm (Comb+MedMgt) over those that did not (Beh+CC). This report examines 36-month outcomes, 2 years after treatment by the study ended. Method: For primary outcome measures (attention-deficit/hyperactivity disorder [ADHD] and oppositional defiant disorder [ODD] symptoms, social skills, reading scores, impairment, and diagnostic status), mixed-effects regression models and orthogonal contrasts examined 36-month outcomes. Results: At 3 years, 485 of the original 579 subjects (83.8%) participated in the follow-up, now at ages 10 to 13 years, (mean 11.9 years). In contrast to the significant advantage of MedMgt+Comb over Beh+CC for ADHD symptoms at 14 and 24 months, treatment groups did not differ significantly on any measure at 36 months. The percentage of children taking medication >50% of the time changed between 14 and 36 months across the initial treatment groups: Beh significantly increased (14% to 45%), MedMed+Comb significantly decreased (91% to 71%), and CC remained constant (60%-62%). Regardless of their treatment use changes, all of the groups showed symptom improvement over baseline. Notably, initial symptom severity, sex (male), comorbidity, public assistance, and parental psychopathology (ADHD) did not moderate children's 36-month treatment responses, but these factors predicted worse outcomes over 36 months, regardless of original treatment assignment. Conclusions: By 36 months, the earlier advantage of having had 14 months of the medication algorithm was no longer apparent, possibly due to age-related decline in ADHD symptoms, changes in medication management intensity, starting or stopping medications altogether, or other factors not yet evaluated.

HER2 and Response to Paclitaxel in Node-Positive Breast Cancer

Abstract: BACKGROUND The status of human epidermal growth factor receptor type 2 (HER2) in breast-cancer cells predicts clinical outcomes in women who receive adjuvant anthracycline-based chemotherapy. We hypothesized that HER2 positivity predicts a benefit from adjuvant doxorubicin doses above standard levels, from the addition of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide, or from both. METHODS We randomly selected 1500 women from 3121 women with node-positive breast cancer who had been randomly assigned to receive doxorubicin (60, 75, or 90 mg per square meter of body-surface area) plus cyclophosphamide (600 mg per square meter) for four cycles, followed by four cycles of paclitaxel (175 mg per square meter) or observation. Tissue blocks from 1322 of these 1500 women were available. Immunohistochemical analyses of these tissue specimens for HER2 with the CB11 monoclonal antibody against HER2 or with a polyclonal-antibody assay kit and fluorescence in situ hybridization for HER2 amplification were performed. RESULTS No interaction was observed between HER2 positivity and doxorubicin doses above 60 mg per square meter. HER2 positivity was, however, associated with a significant benefit from paclitaxel. The interaction between HER2 positivity and the addition of paclitaxel to the treatment was associated with a hazard ratio for recurrence of 0.59 (P=0.01). Patients with a HER2-positive breast cancer benefited from paclitaxel, regardless of estrogen-receptor status, but paclitaxel did not benefit patients with HER2-negative, estrogen-receptor-positive cancers. CONCLUSIONS The expression or amplification, or both, of HER2 by a breast cancer is associated with a benefit from the addition of paclitaxel after adjuvant treatment with doxorubicin (<60 mg per square meter) plus cyclophosphamide in node-positive breast cancer, regardless of estrogen-receptor status. Patients with HER2-negative, estrogen-receptor-positive, node-positive breast cancer may gain little benefit from the administration of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide.

Anastomotic Leaks After Intestinal Anastomosis: It's Later Than You Think

Abstract: Anastomotic disruption is perhaps the most dreaded complication after intestinal surgery. Some leaks presents in a dramatic fashion early in the postoperative period, leaving little doubt about the diagnosis. However, many others present in a far more subtle fashion, often relatively late in the postoperative period, and can be difficult to distinguish from other postoperative infectious complications. It is this latter scenario where definitions are critical and retrospective analyses become rather suspect. In this light, it is not surprising that the reported incidence of anastomotic leakage varies so dramatically in the literature.1–7 The aim of this study was to use a rigorous, prospectively maintained complication database to more accurately define the incidence and presentation of anastomotic leakage after intestinal anastomosis.

Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome.

Abstract: Background Both prophylactic and early surfactant replacement therapy reduce mortality and pulmonary complications in ventilated infants with respiratory distress syndrome (RDS) compared with later selective surfactant administration. However, continued post-surfactant intubation and ventilation are risk factors for bronchopulmonary dysplasia (BPD). The purpose of this review was to compare outcomes between two strategies of surfactant administration in infants with RDS; prophylactic or early surfactant administration followed by prompt extubation, compared with later, selective use of surfactant followed by continued mechanical ventilation. Objectives To compare two treatment strategies in preterm infants with or at risk for RDS: early surfactant administration with brief mechanical ventilation (less than one hour) followed by extubation vs. later selective surfactant administration, continued mechanical ventilation, and extubation from low respiratory support. Two populations of infants receiving early surfactant were considered: spontaneously breathing infants with signs of RDS (who receive surfactant administration during evolution of RDS prior to requiring intubation for respiratory failure) and infants at high risk for RDS (who receive prophylactic surfactant administration within 15 minutes after birth). Search strategy Searches were made of the Oxford Database of Perinatal Trials, MEDLINE (1966 - December 2006), CINAHL (1982 to December Week 2, 2006), EMBASE (1980 - December 2006), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2006), Pediatric Research (1990 - 2006), abstracts, expert informants and hand searching. No language restrictions were applied. Selection criteria Randomized or quasi-randomized controlled clinical trials comparing early surfactant administration with planned brief mechanical ventilation (less than one hour) followed by extubation vs. selective surfactant administration continued mechanical ventilation, and extubation from low respiratory support. Data collection and analysis Data were sought regarding effects on the incidence of mechanical ventilation (ventilation continued or initiated beyond one hour after surfactant administration), incidence of bronchopulmonary dysplasia (BPD), chronic lung disease (CLD), mortality, duration of mechanical ventilation, duration of hospitalization, duration of oxygen therapy, duration of respiratory support (including CPAP and nasal cannula), number of patients receiving surfactant, number of surfactant doses administered per patient, incidence of air leak syndromes (pulmonary interstitial emphysema, pneumothorax), patent ductus arteriosus requiring treatment, pulmonary hemorrhage, and other complications of prematurity. Stratified analysis was performed according to inspired oxygen threshold for early intubation and surfactant administration in the treatment group: inspired oxygen within lower (FiO2 ≤ 0.45) or higher (FiO2 > 0.45) range at study entry. Treatment effect was expressed as relative risk (RR) and risk difference (RD) for categorical variables, and weighted mean difference (WMD) for continuous variables. Main results Six randomized controlled clinical trials met selection criteria and were included in this review. In these studies of infants with signs and symptoms of RDS, intubation and early surfactant therapy followed by extubation to nasal CPAP (NCPAP) compared with later selective surfactant administration was associated with a lower incidence of mechanical ventilation [typical RR 0.67, 95% CI 0.57, 0.79], air leak syndromes [typical RR 0.52, 95% CI 0.28, 0.96] and BPD [typical RR 0.51, 95% CI 0.26, 0.99]. A larger proportion of infants in the early surfactant group received surfactant than in the selective surfactant group [typical RR 1.62, 95% CI 1.41, 1.86]. The number of surfactant doses per patient was significantly greater among patients randomized to the early surfactant group [WMD 0.57 doses per patient, 95% CI 0.44, 0.69]. In stratified analysis by FIO2 at study entry, a lower threshold for treatment (FIO2 ≤ 0.45) resulted in lower incidence of airleak [typical RR 0.46 and 95% CI 0.23, 0.93] and BPD [typical RR 0.43, 95% CI 0.20, 0.92]. A higher treatment threshold (FIO2 > 0.45) at study entry was associated with a higher incidence of patent ductus arteriosus requiring treatment [typical RR 2.15, 95% CI 1.09, 4.13]. Authors' conclusions Early surfactant replacement therapy with extubation to NCPAP compared with later selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with less need mechanical ventilation, lower incidence of BPD and fewer air leak syndromes. A lower treatment threshold (FIO2 ≤ 0.45) confers greater advantage in reducing the incidences of airleak syndromes and BPD; moreover a higher treatment threshold (FIO2 at study > 0.45) was associated with increased risk of PDA. These data suggest that treatment with surfactant by transient intubation using a low treatment threshold (FIO2 ≤ 0.45) is preferable to later, selective surfactant therapy by transient intubation using a higher threshold for study entry (FIO2 > 0.45) or at the time of respiratory failure and initiation of mechanical ventilation. Plain Language Summary Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome Respiratory distress syndrome (RDS) is the single most important cause of illness and death in preterm infants. Common treatments for RDS include supplemental oxygen and nasal continuous positive airway pressure (NCPAP). For severe RDS, surfactant administration during mechanical ventilation is used. Although treating RDS with surfactant improves clinical outcomes, mechanical ventilation can cause lung injury in preterm infants with RDS and contribute to the development of chronic lung disease (oxygen requirements at 36 weeks) and bronchopulmonary dysplasia (requirement for supplementary oxygen at 28 days, BPD). An important question is whether giving early surfactant with planned brief mechanical ventilation followed by prompt extubation (to NCPAP) is better than selectively giving surfactant when RDS has worsened causing respiratory insufficiency necessitating mechanical ventilation. The review authors identified six randomized trials reported between 1994 and 2006 that met the selection criteria for this review. A strategy of early surfactant administration with extubation to NCPAP was associated with significant reductions in the need for mechanical ventilation, fewer air leak syndromes (such as pneumothorax) and lower incidence of BPD compared with a strategy of later selective surfactant administration and continued mechanical ventilation in infants with RDS. The findings suggest that a lower treatment threshold (oxygen requirement 0.45). An early surfactant therapy strategy results in a greater number of infants receiving surfactant and so more infants being exposed to the potential risks of intubation and surfactant administration. Although no complications of surfactant administration were reported in the studies reviewed, infants treated with an early surfactant therapy strategy tended to have a higher prevalence of patent ductus arteriosus (PDA). Two trials were terminated prior to achieving the targeted enrollment when the need for mechanical ventilation was found to be significantly different between groups at a scheduled interim analysis. Two other trials experienced slow enrollment leading to reduced numbers.

Functional properties and genomics of glucose transporters.

Abstract: Glucose is the major energy source for mammalian cells as well as an important substrate for protein and lipid synthesis. Mammalian cells take up glucose from extracellular fluid into the cell through two families of structurallyrelated glucose transporters. The facilitative glucose transporter family (solute carriers SLC2A, protein symbol GLUT) mediates a bidirectional and energy-independent process of glucose transport in most tissues and cells, while the NaM(+)/glucose cotransporter family (solute carriers SLC5A, protein symbol SGLT) mediates an active, Na(+)-linked transport process against an electrochemical gradient. The GLUT family consists of thirteen members (GLUT1-12 and HMIT). Phylogenetically, the members of the GLUT family are split into three classes based on protein similarities. Up to now, at least six members of the SGLT family have been cloned (SGLT1-6). In this review, we report both the genomic structure and function of each transporter as well as intra-species comparative genomic analysis of some of these transporters. The affinity for glucose and transport kinetics of each transporter differs and ranges from 0.2 to 17mM. The ability of each protein to transport alternative substrates also differs and includes substrates such as fructose and galactose. In addition, the tissue distribution pattern varies between species. There are different regulation mechanisms of these transporters. Characterization of transcriptional control of some of the gene promoters has been investigated and alternative promoter usage to generate different protein isoforms has been demonstrated. We also introduce some pathophysiological roles of these transporters in human.

Peer Functioning in Children With ADHD

Abstract: This article describes what is currently known about the peer relationships of children with attention-deficit/hyperactivity disorder (ADHD). This topic is addressed both from the perspective of how ADHD initially contributes to problematic relationships with peers, and also from the perspective of how peers' reactions to these problems may serve to maintain them. Given the limited improvement typically obtained in treatment studies that use peer report measures as outcomes with ADHD samples and the well-documented predictive validity of peer reports for later adjustment, the need for more intensive interventions and novel approaches to address the peer problems of children with ADHD is emphasized.

A critical review of self-perceptions and the positive illusory bias in children with ADHD.

Abstract: Despite significant functional problems in multiple domains, children with Attention-Deficit/Hyperactivity Disorder (ADHD) unexpectedly provide extremely positive reports of their own competence in comparison to other criteria reflecting actual competence. This counterintuitive phenomenon is known as the positive illusory bias (PIB). This article provides a comprehensive and critical review of the literature examining the self-perceptions of children with ADHD and the PIB. Specifically, we analyze methodological and statistical challenges associated with the investigation of the phenomenon, the theoretical basis for the PIB, and the effects of sample heterogeneity on self-perception patterns. We conclude by discussing the implications of this work and providing recommendations for advancing research in this area.

Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA).

Abstract: Background— The Multi-Ethnic Study of Atherosclerosis (MESA) provides an opportunity to study the association of traditional cardiovascular risk factors with the incidence and progression of coronary artery calcium (CAC) in a large community-based cohort with no evidence of clinical cardiovascular disease. Methods and Results— Follow-up CAC measurements were available for 5756 participants with an average of 2.4 years between scans. The incidence of newly detectable CAC averaged 6.6% per year. Incidence increased steadily across age, ranging from 12% in those >80 years of age. Median annual change in CAC for those with existing calcification at baseline was 14 Agatston units for women and 21 Agatston units for men. Most traditional cardiovascular risk factors were associated with both the risk of developing new incident coronary calcium and increases in existing calcification. These included age, male gender, white race/ethnicity, hypertension, body mass index, d...

Who needs environmental monitoring

Abstract: Environmental monitoring is often criticized as being unscientific, too expensive, and wasteful. While some monitoring studies do suffer from these problems, there are also many highly successful long-term monitoring programs that have provided important scientific advances and crucial information for environmental policy. Here, we discuss the characteristics of effective monitoring programs, and contend that monitoring should be considered a fundamental component of environmental science and policy. We urge scientists who develop monitoring programs to plan in advance to ensure high data quality, accessibility, and cost-effectiveness, and we urge government agencies and other funding institutions to make greater commitments to increasing the amount and long-term stability of funding for environmental monitoring programs.

Airway smooth muscle dynamics: A common pathway of airway obstruction in asthma

Abstract: Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma. As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. However, the precise role of ASM in the series of events leading to asthmatic symptoms is not clear. It is not certain whether, in asthma, there is a change in the intrinsic properties of ASM, a change in the structure and mechanical properties of the noncontractile components of the airway wall, or a change in the interdependence of the airway wall with the surrounding lung parenchyma. All these potential changes could result from acute or chronic airway inflammation and associated tissue repair and remodelling. Anti-inflammatory therapy, however, does not "cure" asthma, and airway hyperresponsiveness can persist in asthmatics, even in the absence of airway inflammation. This is perhaps because the therapy does not directly address a fundamental abnormality of asthma, that of exaggerated airway narrowing due to excessive shortening of ASM. In the present study, a central role for airway smooth muscle in the pathogenesis of airway hyperresponsiveness in asthma is explored.

Null model analysis of species nestedness patterns.

Abstract: Nestedness is a common biogeographic pattern in which small communities form proper subsets of large communities. However, the detection of nestedness in binary presence-absence matrices will be affected by both the metric used to quantify nestedness and the reference null distribution. In this study, we assessed the statistical performance of eight nestedness metrics and six null model algorithms. The metrics and algorithms were tested against a benchmark set of 200 random matrices and 200 nested matrices that were created by passive sampling. Many algorithms that have been used in nestedness studies are vulnerable to type I errors (falsely rejecting a true null hypothesis). The best-performing algorithm maintains fixed row and fixed column totals, but it is conservative and may not always detect nestedness when it is present. Among the eight indices, the popular matrix temperature metric did not have good statistical properties. Instead, the Brualdi and Sanderson discrepancy index and Cutler's index of unexpected presences performed best. When used with the fixed-fixed algorithm, these indices provide a conservative test for nestedness. Although previous studies have revealed a high frequency of nestedness, a reanalysis of 288 empirical matrices suggests that the true frequency of nested matrices is between 10% and 40%.

Founder and Recurrent CDH1 Mutations in Families With Hereditary Diffuse Gastric Cancer

Abstract: ContextHereditary diffuse gastric cancer is caused by germline mutations in the epithelial cadherin (CDH1) gene and is characterized by an increased risk for diffuse gastric cancer and lobular breast cancer.ObjectiveTo determine whether recurring germline CDH1 mutations occurred due to independent mutational events or common ancestry.Design, Setting, and PatientsThirty-eight families diagnosed clinically with hereditary diffuse gastric cancer were accrued between November 2004 and January 2006 and were analyzed for CDH1 mutations as part of an ongoing study at the British Columbia Cancer Agency. Twenty-six families had at least 2 gastric cancer cases with 1 case of diffuse gastric cancer in a person younger than 50 years; 12 families had either a single case of diffuse gastric cancer diagnosed in a person younger than 35 years or multiple cases of diffuse gastric cancer diagnosed in persons older than 50 years.Main Outcome MeasuresClassification of family members as carriers or noncarriers of CDH1 mutations. Haplotype analysis to assess recurring mutations for common ancestry was performed on 7 families from this study and 7 previously reported families with the same mutations.ResultsThirteen mutations (6 novel) were identified in 15 of the 38 families (40% detection rate). The 1137G>A splicing mutation and the 1901C>T (A634V) missense/splicing mutation occurred on common haplotypes in 2 families but on different haplotypes in a third family. The 2195G>A (R732Q) missense/splicing mutation occurred in 2 families on different haplotypes. The 2064-2065delTG mutation occurred on a common haplotype in 2 families. Two families from this study plus 2 additional families carrying the novel 2398delC mutation shared a common haplotype, suggesting a founder effect. All 4 families originate from the southeast coast of Newfoundland. Due to concentrations of lobular breast cancer cases, 2 branches of this family had been diagnosed as having hereditary breast cancer and were tested for BRCA mutations. Within these 4 families, the cumulative risk by age 75 years in mutation carriers for clinically detected gastric cancer was 40% (95% confidence interval [CI], 12%-91%) for males and 63% (95% CI, 19%-99%) for females and the risk for breast cancer in female mutation carriers was 52% (95% CI, 29%-94%).ConclusionsRecurrent CDH1 mutations in families with hereditary diffuse gastric cancer are due to both independent mutational events and common ancestry. The presence of a founder mutation from Newfoundland is strongly supported.Published online June 3, 2007 (doi:10.1001/jama.297.21.2360).