Showing papers by "University of Louisville published in 2009"

Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).

Abstract: A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition and metabolism. The mission of SCCM is to secure the highest quality care for all critically ill and injured patients. Guideline Limitations: These A.S.P.E.N.−SCCM Clinical Guidelines are based on general conclusions of health professionals who, in developing such guidelines, have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy. However, practice guidelines are not intended as absolute requirements. The use of these practice guidelines does not in any way project or guarantee any specific benefit in outcome or survival. The judgment of the healthcare professional based on individual circumstances of the patient must always take precedence over the recommendations in these guidelines. The guidelines offer basic recommendations that are supported by review and analysis of the current literature, other national and international guidelines, and a blend of expert opinion and clinical practicality. The population of critically ill patients in an intensive care unit (ICU) is not homogeneous. Many of the studies on which the guidelines are based are limited by sample size, patient heterogeneity, variability in disease severity, lack of baseline nutritional status, and insufficient statistical power for analysis. Periodic Guideline Review and Update: This particular report is an update and expansion of guidelines published by A.S.P.E.N. and SCCM in 2009 (1). Governing bodies of both A.S.P.E.N. and SCCM have mandated that these guidelines be updated every three to five years. The database of randomized controlled trials (RCTs) that served as the platform for the analysis of the literature was assembled in a joint “harmonization process” with the Canadian Clinical Guidelines group. Once completed, each group operated separately in their interpretation of the studies and derivation of guideline recommendations (2). The current A.S.P.E.N. and SCCM guidelines included in this paper were derived from data obtained via literature searches by the authors through December 31, 2013. Although the committee was aware of landmark studies published after this date, these data were not included in this manuscript. The process by which the literature was evaluated necessitated a common end date for the search review. Adding a last-minute landmark trial would have introduced bias unless a formalized literature search was re-conducted for all sections of the manuscript. Target Patient Population for Guideline: The target of these guidelines is intended to be the adult (≥ 18 years) critically ill patient expected to require a length of stay (LOS) greater than 2 or 3 days in a medical ICU (MICU) or surgical ICU (SICU). The current guidelines were expanded to include a number of additional subsets of patients who met the above criteria, but were not included in the previous 2009 guidelines. Specific patient populations addressed by these expanded and updated guidelines include organ failure (pulmonary, renal, and liver), acute pancreatitis, surgical subsets (trauma, traumatic brain injury [TBI], open abdomen [OA], and burns), sepsis, postoperative major surgery, chronic critically ill, and critically ill obese. These guidelines are directed toward generalized patient populations but, like any other management strategy in the ICU, nutrition therapy should be tailored to the individual patient. Target Audience: The intended use of these guidelines is for all healthcare providers involved in nutrition therapy of the critically ill, primarily physicians, nurses, dietitians, and pharmacists. Methodology: The authors compiled clinical questions reflecting key management issues in nutrition therapy. A committee of multidisciplinary experts in clinical nutrition composed of physicians, nurses, pharmacists, and dietitians was jointly convened by the two societies.

The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs

Abstract: Invasion and metastasis of carcinomas is promoted by the activation of the embryonic 'epithelial to mesenchymal transition' (EMT) program, which triggers cellular mobility and subsequent dissemination of tumour cells. We recently showed that the EMT-activator ZEB1 (zinc finger E-box binding homeobox 1) is a crucial promoter of metastasis and demonstrated that ZEB1 inhibits expression of the microRNA-200 (miR-200) family, whose members are strong inducers of epithelial differentiation. Here, we report that ZEB1 not only promotes tumour cell dissemination, but is also necessary for the tumour-initiating capacity of pancreatic and colorectal cancer cells. We show that ZEB1 represses expression of stemness-inhibiting miR-203 and that candidate targets of miR-200 family members are also stem cell factors, such as Sox2 and Klf4. Moreover, miR-200c, miR-203 and miR-183 cooperate to suppress expression of stem cell factors in cancer cells and mouse embryonic stem (ES) cells, as demonstrated for the polycomb repressor Bmi1. We propose that ZEB1 links EMT-activation and stemness-maintenance by suppressing stemness-inhibiting microRNAs (miRNAs) and thereby is a promoter of mobile, migrating cancer stem cells. Thus, targeting the ZEB1-miR-200 feedback loop might form the basis of a promising treatment for fatal tumours, such as pancreatic cancer.

The international position on laparoscopic liver surgery: The Louisville Statement, 2008.

Abstract: Objective:To summarize the current world position on laparoscopic liver surgery.Summary Background Data:Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver re

Normalized Mutual Information Feature Selection

Abstract: A filter method of feature selection based on mutual information, called normalized mutual information feature selection (NMIFS), is presented. NMIFS is an enhancement over Battiti's MIFS, MIFS-U, and mRMR methods. The average normalized mutual information is proposed as a measure of redundancy among features. NMIFS outperformed MIFS, MIFS-U, and mRMR on several artificial and benchmark data sets without requiring a user-defined parameter. In addition, NMIFS is combined with a genetic algorithm to form a hybrid filter/wrapper method called GAMIFS. This includes an initialization procedure and a mutation operator based on NMIFS to speed up the convergence of the genetic algorithm. GAMIFS overcomes the limitations of incremental search algorithms that are unable to find dependencies between groups of features.

Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms

Abstract: A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.

Neuropathological assessment of Parkinson's disease: refining the diagnostic criteria.

Abstract: Summary To date, there have been few systematic attempts to provide a standard operating procedure for the neuropathological diagnosis of Parkinson's disease (PD). Pathological examination cannot classify the clinical syndrome with certainty; therefore, the neuropathological diagnosis is, at best, a probability statement. The neuropathological diagnosis of parkinsonism has become increasingly based on fundamental molecular underpinnings, with recognition that the genetics of parkinsonism is heterogeneous and includes disorders that are associated with and without Lewy bodies. The advent of α-synuclein immunohistochemistry has substantially improved the ability to identify Lewy pathology, particularly cortical Lewy bodies and smaller aggregates within processes and the neuropil. In this Review we discuss the diagnostic criteria for the neuropathological assessment of PD. These criteria are provisional and need to be validated through an iterative process that could help with their refinement. Additionally, we suggest future directions for neuropathology research on PD.

Ten Putative Contributors to the Obesity Epidemic

Abstract: The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines...

Differentiating neural responses to emotional pictures: evidence from temporal-spatial PCA.

Abstract: Consistent with the notion that emotional stimuli receive preferential attention and perceptual processing, many eventrelated potential (ERP) components appear sensitive to emotional stimuli. In an effort to differentiate components that are sensitive to emotional versus neutral stimuli, the current study utilized temporospatial principal components analysis to analyze ERPs from a large sample (N 5 82) while pleasant, neutral, and unpleasant images were passively viewed. Several factors sensitive to emotional stimuli were identifiedFcorresponding to the N1, early posterior negativity (EPN), and P3; multiple factors resembling the late positive potential (LPP) emerged. Results indicate that the N1 represents the earliest component modulated by emotional stimuli; the EPN and the LPP represent unique components; the scalp-recorded LPP appears to include a P3-like positivity as well as additional positivities at occipital and central recording sites.

Environmental toxicity, oxidative stress and apoptosis: ménage à trois.

Abstract: Apoptosis is an evolutionary conserved homeostatic process involved in distinct physiological processes including organ and tissue morphogenesis, development and senescence. Its deregulation is also known to participate in the etiology of several human diseases including cancer, neurodegenerative and autoimmune disorders. Environmental stressors (cytotoxic agents, pollutants or toxicants) are well known to induce apoptotic cell death and to contribute to a variety of pathological conditions. Oxidative stress seems to be the central element in the regulation of the apoptotic pathways triggered by environmental stressors. In this work, we review the established mechanisms by which oxidative stress and environmental stressors regulate the apoptotic machinery with the aim to underscore the relevance of apoptosis as a component in environmental toxicity and human disease progression.

Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial.

Abstract: Aims Comparison of intracoronary infusion of bone marrow (BM)-derived unselected mononuclear cells (UNSEL) and selected CD34+CXCR4+ cells (SEL) in patients with acute myocardial infarction (AMI) and reduced <40% left ventricular ejection fraction (LVEF). Methods and results Two hundred patients were randomized to intracoronary infusion of UNSEL ( n = 80) or SEL ( n = 80) BM cells or to the control (CTRL) group without BM cell treatment. Primary endpoint: change of LVEF and volumes measured by magnetic resonance imaging before and 6 months after the procedure. After 6 months, LVEF increased by 3% ( P = 0.01) in patients treated with UNSEL, 3% in patients receiving SEL ( P = 0.04) and remained unchanged in CTRL group ( P = 0.73). There were no significant differences in absolute changes of LVEF between the groups. Absolute changes of left ventricular end-systolic volume and left ventricular end-diastolic volume were not significantly different in all groups. Significant increase of LVEF was observed only in patients treated with BM cells who had baseline LVEF < median (37%). Baseline LVEF < median and time from the onset of symptoms to primary percutaneous coronary intervention ≥ median were predictors of LVEF improvement in patients receiving BM cells. There were no differences in major cardiovascular event (death, re-infarction, stroke, target vessel revascularization) between groups. Conclusion In patients with AMI and impaired LVEF, treatment with BM cells does not lead to a significant improvement of LVEF or volumes. There was however a trend in favour of cell therapy in patients with most severely impaired LVEF and longer delay between the symptoms and revascularization.

Effects of early family/parent training programs on antisocial behavior and delinquency

Abstract: Based on evidence that early antisocial behavior is a key risk factor for delinquency and crime throughout the life course, early family/parent training, among its many functions, has been advanced as an important intervention/prevention effort. There are several theories concerning why early family/parent training may cause a reduction in child behavior problems including antisocial behavior and delinquency (and have other ancillary benefits in non-crime domains over the life course). The prevention of behavior problems is one of the many objectives of early family/parent training, and it comprises the main focus of this review. Results indicate that early family/parent training is an effective intervention for reducing behavior problems among young children, and the weighted effect size was 0.35. The results from a series of analog to the analysis of variance (ANOVA) and weighted least squares regression models (with random effects) demonstrated that there were significant differences in the effect sizes of studies conducted in the USA versus those conducted in other countries and that studies that were based on samples smaller than 100 children had larger effect sizes. Sample size was also the strongest predictor of the variation in the effect sizes. Additional evidence indicated that early family/parent training was also effective in reducing delinquency and crime in later adolescence and adulthood. Overall, the findings lend support for the continued use of early family/parent training to prevent behavior problems. Future research should test the main theories of early family/parent training and detail more explicitly the causal mechanisms by which early family/parent training reduces delinquency and crime, and future evaluations should employ high quality designs with long-term follow-ups, including repeated measures of antisocial behavior, delinquency, and crime over the life course.

Altered regulation of metabolic pathways in human lung cancer discerned by 13C stable isotope-resolved metabolomics (SIRM)

Abstract: Background Metabolic perturbations arising from malignant transformation have not been systematically characterized in human lung cancers in situ. Stable isotope resolved metabolomic analysis (SIRM) enables functional analysis of gene dysregulations in lung cancer. To this purpose, metabolic changes were investigated by infusing uniformly labeled 13C-glucose into human lung cancer patients, followed by resection and processing of paired non-cancerous lung and non small cell carcinoma tissues. NMR and GC-MS were used for 13C-isotopomer-based metabolomic analysis of the extracts of tissues and blood plasma.

Estradiol downregulates miR-21 expression and increases miR-21 target gene expression in MCF-7 breast cancer cells.

Abstract: Select changes in microRNA (miRNA) expression correlate with estrogen receptor α (ERα) expression in breast tumors. miR-21 is higher in ERα positive than negative tumors, but no one has examined how estradiol (E2) regulates miR-21 in breast cancer cells. Here we report that E2 inhibits miR-21 expression in MCF-7 human breast cancer cells. The E2-induced reduction in miR-21 was inhibited by 4-hydroxytamoxifen (4-OHT), ICI 182 780 (Faslodex), and siRNA ERα indicating that the suppression is ERα-mediated. ERα and ERβ agonists PPT and DPN inhibited and 4-OHT increased miR-21 expression. E2 increased luciferase activity from reporters containing the miR-21 recognition elements from the 3′-UTRs of miR-21 target genes, corroborating that E2 represses miR-21 expression resulting in a loss of target gene suppression. The E2-mediated decrease in miR-21 correlated with increased protein expression of endogenous miR-21-targets Pdcd4, PTEN and Bcl-2. siRNA knockdown of ERα blocked the E2-induced increase in Pdcd4, PTEN and Bcl-2. Transfection of MCF-7 cells with antisense (AS) to miR-21 mimicked the E2-induced increase in Pdcd4, PTEN and Bcl-2. These results are the first to demonstrate that E2 represses the expression of an oncogenic miRNA, miR-21, by activating estrogen receptor in MCF-7 cells.

Do Workgroup Faultlines Help or Hurt? A Moderated Model of Faultlines, Team Identification, and Group Performance

Abstract: In this study we examine a moderated model of group faultlines, team identification, and group performance outcomes. We extend research on faultlines by showing how different faultline bases (social category and information-based faultlines) may have differential effects on the performance of groups. In addition to faultline strength (the extent of demographic alignment across members within a group), we examine the distance between faultline-based subgroups (e.g., two members of age 20 are closer in age to two members of an opposing subgroup of age 25 than of two members of age 50). We test our model using an archival field methodology and multiple-source data (qualitative and quantitative) from 76 workgroups in a Fortune 500 information-processing company. Our results revealed that groups with social category faultlines had low team discretionary awards. Faultline distance further exacerbated the negative effects of strength in groups with social category faultlines and produced similarly negative effects in groups with information-based faultlines. Team identification served as a moderator enhancing performance of groups with information-based faultlines.

Hybrid Tin Oxide Nanowires as Stable and High Capacity Anodes for Li-Ion Batteries

Abstract: In this report, we present a simple and generic concept involving metal nanoclusters supported on metal oxide nanowires as stable and high capacity anode materials for Li-ion batteries. Specifically, SnO(2) nanowires covered with Sn nanoclusters exhibited an exceptional capacity of >800 mAhg(-1) over hundred cycles with a low capacity fading of less than 1% per cycle. Post lithiation analyses after 100 cycles show little morphological degradation of the hybrid nanowires. The observed, enhanced stability with high capacity retention is explained with the following: (a) the spacing between Sn nanoclusters on SnO(2) nanowires allowed the volume expansion during Li alloying and dealloying; (b) high available surface area of Sn nanoclusters for Li alloying and dealloying; and (c) the presence of Sn nanoclusters on SnO(2) allowed reversible reaction between Sn and Li(2)O to produce both Sn and SnO phases.

Use of Cone Beam Computed Tomography in Endodontics

Abstract: Cone Beam Computed Tomography (CBCT) is a diagnostic imaging modality that provides high-quality, accurate three-dimensional (3D) representations of the osseous elements of the maxillofacial skeleton. CBCT systems are available that provide small field of view images at low dose with sufficient spatial resolution for applications in endodontic diagnosis, treatment guidance, and posttreatment evaluation. This article provides a literature review and pictorial demonstration of CBCT as an imaging adjunct for endodontics.

Fresh frozen plasma is independently associated with a higher risk of multiple organ failure and acute respiratory distress syndrome

Abstract: Background: Blood transfusion is known to be an independent risk factor for mortality, multiple organ failure (MOF), acute respiratory distress syndrome (ARDS), and nosocomial infection after injury. Less is known about the independent risks associated with plasma-rich transfusion components including fresh frozen plasma (FFP), platelets (PLTS), and cryoprecipitate (CRYO) after injury. We hypothesized that plasma-rich transfusion components would be independently associated with a lower risk of mortality but result in a greater risk of morbid complications. Methods: Data were obtained from a multicenter prospective cohort study evaluating clinical outcomes in bluntly injured adults with hemorrhagic shock. All patients required blood transfusion for enrollment. Patients with isolated traumatic brain injury and those not surviving beyond 48 hours were excluded. Cox proportional hazard regression models were used to estimate the outcome risks (per unit) associated with plasma-rich transfusion requirements during the initial 24 hours after injury after controlling for important confounders. Results: For the entire study population (n = 1,175), 65%, 41%, and 28% of patients received FFP, PLTS and CRYO, respectively. There was no association with plasma-rich transfusion components and mortality or nosocomial infection. For every unit given, FFP was independently associated with a 2.1 % and 2.5% increased risk of MOF and ARDS, respectively. CRYO was associated with a 4.4% decreased risk of MOF (per unit), and PLTS were not associated with any of the outcomes examined. When early deaths (within 48 hours) were included in the model, FFP was associated with a 2.9% decreased risk of mortality per unit transfused. Conclusions: In patients who survive their initial injury, FFP was independently associated with a greater risk of developing MOF and ARDS, whereas CRYO was associated with a lower risk of MOF. Further investigation into the mechanisms by which these plasma-rich component transfusions are associated with these effects are required.

Mathematics Teacher TPACK Standards and Development Model

Abstract: What knowledge is needed to teach mathematics with digital technologies? The overarching construct, called technology, pedagogy, and content knowledge (TPACK), has been proposed as the interconnection and intersection of technology, pedagogy, and content knowledge. Mathematics Teacher TPACK Standards offer guidelines for thinking about this construct. A Mathematics Teacher Development Model describes the development of TPACK toward meeting these standards. The standards and model provide structured detail to further the work of various groups. The proposals may guide teachers, researchers, teacher educators, professional development consultants, and school administrators in the development and evaluation of professional development activities, mathematics education programs, and school mathematics programs. Contemporary Issues in Technology and Teacher Education, 9(1) 5 In 1986 Lee Shulman launched a new way of thinking about the knowledge teachers need for teaching with a construct that he called pedagogical content knowledge (PCK). This new way of thinking about the knowledge teachers need for teaching called for the integration of content knowledge (the knowledge previously considered the primary knowledge for teachers) and pedagogical knowledge (the knowledge about teaching and learning). The intersection of these two knowledge bases, PCK, was described as the way of representing and formulating subject matter knowledge, the knowledge that makes the subject matter comprehensible to learners (Shulman, 1986, 1987; Wilson, Shulman, & Richert, 1987). More specifically, Shulman (1986) characterized a teacher’s PCK as knowledge of the most regularly taught topics in one’s subject area, the most useful forms of representation of those ideas, the most powerful analogies, illustrations, examples, explanations, and demonstrations ... including an understanding of what makes the learning of specific concepts easy or difficult: the concepts and preconceptions that students of different ages and backgrounds bring with them to the learning. ( p. 9) During those early discussions of the construction of knowledge growth in teaching, teacher preparation programs were challenged to determine how they might guide the development of this teacher knowledge. Some programs honed in on the development of six primary domains of knowledge essential for effective instruction: subject matter knowledge, pedagogical knowledge, knowledge of schools, knowledge of learners, and curricular knowledge, with PCK as the essence of the intersection of these five domains of knowledge (Niess, 2001). The relationship was viewed as a complex and integrated structure where no domain was totally distinct or separate from the other, with the relative amount of overlap and interaction among the domains constantly changing as preservice teachers made sense of and prioritized the multiple factors affecting student learning. Attention to PCK through research studies provided insight into the preparation of preservice mathematics teachers’ development of PCK (Ball, 1988; Civil, 1992; Grossman, 1991; McDiarmid, 1990; Simon & Brobeck, 1993; Simon & Mazza, 1993; Wilcox et al., 1990). Grossman’s (1989, 1990) research identified four central components of PCK to focus the description and understanding of the knowledge needing development in the preparation programs: (a) an overarching conception of what it means to teach a particular subject; (b) knowledge of instructional strategies and representations for teaching particular subject matter topics; (c) knowledge of students’ understandings, thinking, and learning in the subject area; (d) knowledge of curriculum and curriculum materials with learning subject matter (Borko & Purtnam, 1996). As this understanding of PCK evolved, modern digital technologies also began to be recognized as useful for teaching and learning. During the late 1970s and 1980s, the focus in mathematics education was on identifying places in mathematics instruction for inserting digital technology applications. A myriad of software programs afforded drill and practice in a variety of environments that were more entertaining than traditional paper-and-pencil worksheets for providing practice with computational skills. Graphing calculators offered capabilities for efficiently generating visuals of graphs useful for demonstrating mathematical ideas such as slope and y-intercept for linear functions and points of intersection for multiple functions. The primary vision for employing mathematical digital technologies was for demonstration and verification of ideas previously developed in the classroom. Calculators – from limited four-function calculators to scientific calculators – were Contemporary Issues in Technology and Teacher Education, 9(1) 6 restricted with the belief that these tools trivialized the mathematics rather than engaging students in learning mathematics. The lack of an in-depth integration of these technologies prompted Kaput’s (1992) lament that the “major limitations of computer use in the coming decades are likely to be less a result of technological limitations than a result of limited human imagination and the constraints of old habits and social structures” (p. 515). An examination of mathematics teachers’ PCK in the late 1980s and early 1990s revealed an overarching conception that teachers’ beliefs about how to teach mathematics generally were aligned with how they learned mathematics. Although a few teachers embraced the use of graphing calculators, spreadsheets, and software like Logo and Geometric Supposer, many did not. Mathematics teachers’ knowledge of instructional strategies and representations for teaching particular mathematical topics relegated the application of such digital technologies to demonstration, verification, and drill and practice. Their knowledge of students’ understandings, thinking, and learning in mathematics held to the importance of mastery of skills with paper and pencil prior to using modern digital technologies (Kastberg & Leatham, 2005; Walen, Williams, & Garner, 2003; Yoder, 2000). Furthermore, access to technology without necessary knowledge of related curriculum materials did not encourage teachers to incorporate the technology in their classroom instruction (Kastberg & Leatham, 2005). “In the absence of professional development on instructional technology and curriculum materials that integrate technology use into the lesson content, teachers are not particularly likely to embed technology-based or technology-rich activities into their courses” (Ferrini-Mundy & Breaux, 2008, p. 437438). Fast forward to 2008 to see that many mathematics teachers’ PCK lacks a solid and consistent integration of modern digital technologies in mathematics curriculum and instruction. Technologies, such as dynamic geometry tools or advanced graphing calculators with computer algebra systems (CAS), are primarily used for modeling and providing examples, where students imitate the actions and use the technologies for verification, demonstration, and drill and practice. In essence then, while digital technologies have evolved, strategies for their effective integration into the learning of mathematics have not evolved as rapidly. Mathematics TPACK: The Total Package for Teaching Mathematics As time shifted and digital technologies became more accessible and incorporated into citizens’ work and play, the International Society for Technology and Education (ISTE) challenged teachers to think about the technology skills and knowledge students would need in an increasingly technology savvy society. By the turn of the 21st century, the National Education Technology Standards for Students (NETS-S; ISTE, 2000) were released with the goal of supporting the evolution of effective use of appropriate technologies in school settings. ISTE recognized that these new standards called for different teacher knowledge than was currently operating in the schools. Within the following 2 years, the National Educational Technology Standards for Teachers (NETS-T; ISTE, 2002) were also released. Although embedded in a rapidly changing digital society, little real instructional change filtered into classrooms. Therefore, ISTE moved to shift the focus of the NETS-S from basic skills and knowledge needed to operate the technology to learning how to effectively use the technology; the NETS-S were updated in 2007. Subsequently, to assist Contemporary Issues in Technology and Teacher Education, 9(1) 7 teachers in responding to the call of learning environments supported by multiple technologies, a revision of the teacher standards was released in 2008. These standards effectively shifted the focus on digital technologies toward a concern about the curriculum and instructional uses of the digital tools and resources. Earle (2002) framed this shift most clearly: Integrating technology is not about technology – it is primarily about content and effective instructional practices. Technology involves the tools with which we deliver content and implement practices in better ways. Its focus must be on curriculum and learning. Integration is defined not by the amount or type of technology used, but by how and why it is used. (p. 8) Numerous researchers focused on the integration of technology, content, and pedagogy in much the same way that Shulman described PCK, to gain a broader perspective on the knowledge teachers need for teaching with technology. In essence, they defined technological pedagogical content knowledge (TPCK) as that body of knowledge teachers needed for teaching with and about technology in their assigned subject areas and grade levels. TPCK was presented as the interconnection and intersection of content, pedagogy (teaching and student learning), and technology (Margerum-Leys & Marx, 2002; Mishra & Koehler, 2006; Niess, 2005; Pierson, 2001). The idea of TPCK developed to the point that the American Association of Colleges of

Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells.

Abstract: Objective Repair of demyelinated axons in diseases such as multiple sclerosis requires activation of the myelination program in existing or newly recruited oligodendrocyte precursor cells (OPCs). The control of OPC differentiation and initiation of myelination during repair is poorly understood. In this study, we test the ability of anti–LINGO-1 reagents to promote myelination in vitro and remyelination in the rodent adult central nervous system in vivo. Methods The effects of LINGO-1 antagonists on the differentiation of OPCs and the promotion of myelination has been assayed using a combination of coculture and slice culture preparations. Using three different animal models of demyelination and remyelination, we morphologically and functionally assessed the effects of LINGO-1 antagonists on OPC differentiation and myelin repair. Results The data indicate that in vitro treatment with antagonists of LINGO-1 promote OPC differentiation and myelination, whereas in vivo remyelination is accelerated in lysophosphatidylcholine- or cuprizone-induced demyelination. This remyelination is associated with enhanced OPC differentiation and functional recovery of conduction velocities in demyelinated axons. Interpretation Our studies demonstrate that LINGO-1 antagonism promotes OPC differentiation and remyelination, and suggest LINGO-1 functions as an inhibitor of OPC differentiation to retard central nervous system remyelination. Ann Neurol 2009;65:304–315

Measurement of the gamma gamma* --> pi0 transition form factor

Abstract: We study the reaction e+e- --> e+e-pi0 and measure the gamma gamma* --> pi0 transition form factor in the momentum transfer range from 4 to 40 GeV^2. The analysis is based on 442 fb^-1 of integrated luminosity collected at PEP-II with the BABAR detector at e+e- center-of-mass energies near 10.6 GeV.

RankAggreg, an R package for weighted rank aggregation

Abstract: Researchers in the field of bioinformatics often face a challenge of combining several ordered lists in a proper and efficient manner. Rank aggregation techniques offer a general and flexible framework that allows one to objectively perform the necessary aggregation. With the rapid growth of high-throughput genomic and proteomic studies, the potential utility of rank aggregation in the context of meta-analysis becomes even more apparent. One of the major strengths of rank-based aggregation is the ability to combine lists coming from different sources and platforms, for example different microarray chips, which may or may not be directly comparable otherwise. The RankAggreg package provides two methods for combining the ordered lists: the Cross-Entropy method and the Genetic Algorithm. Two examples of rank aggregation using the package are given in the manuscript: one in the context of clustering based on gene expression, and the other one in the context of meta-analysis of prostate cancer microarray experiments. The two examples described in the manuscript clearly show the utility of the RankAggreg package in the current bioinformatics context where ordered lists are routinely produced as a result of modern high-throughput technologies.

Low thromboembolism and pump thrombosis with the HeartMate II left ventricular assist device: analysis of outpatient anti-coagulation.

Abstract: Background The HeartMate II (Thoratec, Pleasanton, CA) is an effective bridge to transplantation (BTT) but requires anti-coagulation with warfarin and aspirin. We evaluated the risk of thromboembolism and hemorrhage related to the degree of anti-coagulation as reflected by the international normalized ratio (INR). Methods INRs were measured monthly for 6 months in all discharged HeartMate II BTT patients and at an event. Each INR was assigned to ranges of INRs. Adverse events analyzed were ischemic and hemorrhagic stroke, pump thrombosis, and bleeding requiring surgery or transfusion. Events were correlated to the INR during the event and at the start of the month. Results In 331 patients discharged on support, 10 had thrombotic events (9 ischemic strokes, 3 pump thromboses), and 58 had hemorrhagic events (7 strokes, 4 hemorrhages requiring surgery, and 102 requiring transfusions). The median INR was 2.1 at discharge and 1.90 at 6 months. Although the incidence of stroke was low, 40% of ischemic strokes occurred in patients with INRs 3.0. The highest incidence of bleeding was at INRs > 2.5. Conclusions The rate of thromboembolism during long-term outpatient support with the HeartMate II is low. The low number of thrombotic events appears to be offset by a greater number of hemorrhagic events. An appropriate target INR is 1.5 to 2.5 in addition to aspirin therapy. In patients having recurrent episodes of bleeding, the risk of lowering the target INR appears to be small.