OPENING KEYNOTE ADDRESS: Using Data to Understand Cultural Destruction

Brian I. Daniels, Ph.D, Penn Cultural Heritage Center, University of Pennsylvania Museum. Why is cultural heritage targeted in conflict? Under what circumstances? By whom? Today, due in part to the recent notorious instances of cultural destruction in the Middle East and North Africa, there is perhaps more attention among the broader scientific community than ever before about the phenomenon of cultural loss. At the same time, there are many significant data and analytical gaps. Little social science literature about cultural destruction exists and many critical questions—and avenues of research—are, as of yet, unstudied. A primary reason for this lack of attention is the absence of event-level data about cultural destruction that can test theories about this kind of violence. This presentation discusses some of the data needs that exist in order to develop a more robust understanding about cultural destruction and the problems and prospects for future analysis

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

The assessment of the quality of reporting of meta-analyses in diagnostic research: a systematic review

<p>Abstract</p> <p>Background</p> <p>Over the last decade there have been a number of guidelines published, aimed at improving the quality of reporting in published studies and reviews. In systematic reviews this may be measured by their compliance with the PRISMA statement. This review aims to evaluate the quality of reporting in published meta-analyses of diagnostic tests, using the PRISMA statement and establish whether there has been a measurable improvement over time.</p> <p>Methods</p> <p>Eight databases were searched for reviews published prior to 31^stDecember 2008. Studies were selected if they evaluated a diagnostic test, measured performance, searched two or more databases, stated the search terms and inclusion criteria, and used a statistical method to summarise a test's performance. Data were extracted on the review characteristics and items of the PRISMA statement. To measure the change in the quality of reporting over time, PRISMA items for two periods of equal duration were compared.</p> <p>Results</p> <p>Compliance with the PRISMA statement was generally poor: none of the reviews completely adhered to all 27 checklist items. Of the 236 meta-analyses included following selection: only 2(1%) reported the study protocol; 59(25%) reported the searches used; 76(32%) reported the results of a risk of bias assessment; and 82(35%) reported the abstract as a structured summary. Only 11 studies were published before 2000. Thus, the impact of QUOROM on the quality of reporting was not evaluated. However, the periods 2001-2004 and 2005-2008 (covering 93% of studies) were compared using relative risks (RR). There was an increase in the proportion of reviews reporting on five PRISMA items: eligibility criteria (RR 1.13, 95% CI 1.00 - 1.27); risk of bias across studies (methods) (RR 1.81, 95% CI 1.34 - 2.44); study selection results (RR 1.48, 95% CI 1.05 - 2.09); results of individual studies (RR 1.37, 95% CI 1.09 - 1.72); risk of bias across studies (results) (RR 1.65, 95% CI 1.20 - 2.25).</p> <p>Conclusion</p> <p>Although there has been an improvement in the quality of meta-analyses in diagnostic research, there are still many deficiencies in the reporting which future reviewers need to address if readers are to trust the validity of the reported findings.</p

A comparative thematic review of vocational leadership literature from the USA, Great Britain and Australia

Vocational education and its leadership is an important sphere of economic activity worldwide and is being impacted by several trends including: the increasing significance and centrality of skills development in today’s economies; economic trends associated with globalisation (internationalisation of education and emergence of global labour markets); and demographic trends resulting in ageing populations and workforces. Leadership in vocational education contexts is crucial to the economic success of this sector. The aim of this paper is to provide a comparative thematic review of the research and literature on leadership in vocational education between the USA, Great Britain and Australia posed by the research question, ‘What are the key leadership issues facing vocational education and training sectors in the USA, Great Britain and Australia?’ This study contributes to the research and literature by identifying key impact factors for vocational education leadership in these nations over the last 13 years. Results from the comparative review established the following three key issues: a concern over equity and diversity; the importance of change management; and leadership skills and their development. Although leadership competencies are the subject of some debate there appears to be a broad consensus that leaders are developed not only by formal courses, but more importantly by on-the-job experiential learning. The future development of leaders within vocational education is discussed in relation to the implications for policy and practice, and suggestions for future research are provided

Candidate Glutamatergic Neurons in the Visual System of Drosophila

The visual system of Drosophila contains approximately 60,000 neurons that are organized in parallel, retinotopically arranged columns. A large number of these neurons have been characterized in great anatomical detail. However, studies providing direct evidence for synaptic signaling and the neurotransmitter used by individual neurons are relatively sparse. Here we present a first layout of neurons in the Drosophila visual system that likely release glutamate as their major neurotransmitter. We identified 33 different types of neurons of the lamina, medulla, lobula and lobula plate. Based on the previous Golgi-staining analysis, the identified neurons are further classified into 16 major subgroups representing lamina monopolar (L), transmedullary (Tm), transmedullary Y (TmY), Y, medulla intrinsic (Mi, Mt, Pm, Dm, Mi Am), bushy T (T), translobula plate (Tlp), lobula intrinsic (Lcn, Lt, Li), lobula plate tangential (LPTCs) and lobula plate intrinsic (LPi) cell types. In addition, we found 11 cell types that were not described by the previous Golgi analysis. This classification of candidate glutamatergic neurons fosters the future neurogenetic dissection of information processing in circuits of the fly visual system

Brown Planthopper (N. lugens Stal) Feeding Behaviour on Rice Germplasm as an Indicator of Resistance

BACKGROUND: The brown planthopper (BPH) Nilaparvata lugens (Stal) is a serious pest of rice in Asia. Development of novel control strategies can be facilitated by comparison of BPH feeding behaviour on varieties exhibiting natural genetic variation, and then elucidation of the underlying mechanisms of resistance. METHODOLOGY/PRINCIPAL FINDINGS: BPH feeding behaviour was compared on 12 rice varieties over a 12 h period using the electrical penetration graph (EPG) and honeydew clocks. Seven feeding behaviours (waveforms) were identified and could be classified into two phases. The first phase involved patterns of sieve element location including non penetration (NP), pathway (N1+N2+N3), xylem (N5) [21] and two new feeding waveforms, derailed stylet mechanics (N6) and cell penetration (N7). The second feeding phase consisted of salivation into the sieve element (N4-a) and sieve element sap ingestion (N4-b). Production of honeydew drops correlated with N4-b waveform patterns providing independent confirmation of this feeding behaviour. CONCLUSIONS/SIGNIFICANCE: Overall variation in feeding behaviour was highly correlated with previously published field resistance or susceptibility of the different rice varieties: BPH produced lower numbers of honeydew drops and had a shorter period of phloem feeding on resistant rice varieties, but there was no significant difference in the time to the first salivation (N4-b). These qualitative differences in behaviour suggest that resistance is caused by differences in sustained phloem ingestion, not by phloem location. Cluster analysis of the feeding and honeydew data split the 12 rice varieties into three groups: susceptible, moderately resistant and highly resistant. The screening methods that we have described uncover novel aspects of the resistance mechanism (or mechanisms) of rice to BPH and will in combination with molecular approaches allow identification and development of new control strategies

Can computerized clinical decision support systems improve practitioners' diagnostic test ordering behavior? A decision-maker-researcher partnership systematic review

<p>Abstract</p> <p>Background</p> <p>Underuse and overuse of diagnostic tests have important implications for health outcomes and costs. Decision support technology purports to optimize the use of diagnostic tests in clinical practice. The objective of this review was to assess whether computerized clinical decision support systems (CCDSSs) are effective at improving ordering of tests for diagnosis, monitoring of disease, or monitoring of treatment. The outcome of interest was effect on the diagnostic test-ordering behavior of practitioners.</p> <p>Methods</p> <p>We conducted a decision-maker-researcher partnership systematic review. We searched MEDLINE, EMBASE, Ovid's EBM Reviews database, Inspec, and reference lists for eligible articles published up to January 2010. We included randomized controlled trials comparing the use of CCDSSs to usual practice or non-CCDSS controls in clinical care settings. Trials were eligible if at least one component of the CCDSS gave suggestions for ordering or performing a diagnostic procedure. We considered studies 'positive' if they showed a statistically significant improvement in at least 50% of test ordering outcomes.</p> <p>Results</p> <p>Thirty-five studies were identified, with significantly higher methodological quality in those published after the year 2000 (<it>p </it>= 0.002). Thirty-three trials reported evaluable data on diagnostic test ordering, and 55% (18/33) of CCDSSs improved testing behavior overall, including 83% (5/6) for diagnosis, 63% (5/8) for treatment monitoring, 35% (6/17) for disease monitoring, and 100% (3/3) for other purposes. Four of the systems explicitly attempted to reduce test ordering rates and all succeeded. Factors of particular interest to decision makers include costs, user satisfaction, and impact on workflow but were rarely investigated or reported.</p> <p>Conclusions</p> <p>Some CCDSSs can modify practitioner test-ordering behavior. To better inform development and implementation efforts, studies should describe in more detail potentially important factors such as system design, user interface, local context, implementation strategy, and evaluate impact on user satisfaction and workflow, costs, and unintended consequences.</p

Justify your alpha

Benjamin et al. proposed changing the conventional “statistical significance” threshold (i.e.,the alpha level) from p ≤ .05 to p ≤ .005 for all novel claims with relatively low prior odds. They provided two arguments for why lowering the significance threshold would “immediately improve the reproducibility of scientific research.” First, a p-value near .05provides weak evidence for the alternative hypothesis. Second, under certain assumptions, an alpha of .05 leads to high false positive report probabilities (FPRP2 ; the probability that a significant finding is a false positive

The NANOGrav 11-year Data Set: High-precision Timing of 45 Millisecond Pulsars

We present high-precision timing data over time spans of up to 11 years for 45 millisecond pulsars observed as part of the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) project, aimed at detecting and characterizing low-frequency gravitational waves. The pulsars were observed with the Arecibo Observatory and/or the Green Bank Telescope at frequencies ranging from 327 MHz to 2.3 GHz. Most pulsars were observed with approximately monthly cadence, and six high-timing-precision pulsars were observed weekly. All were observed at widely separated frequencies at each observing epoch in order to fit for time-variable dispersion delays. We describe our methods for data processing, time-of-arrival (TOA) calculation, and the implementation of a new, automated method for removing outlier TOAs. We fit a timing model for each pulsar that includes spin, astrometric, and (for binary pulsars) orbital parameters; time-variable dispersion delays; and parameters that quantify pulse-profile evolution with frequency. The timing solutions provide three new parallax measurements, two new Shapiro delay measurements, and two new measurements of significant orbital-period variations. We fit models that characterize sources of noise for each pulsar. We find that 11 pulsars show significant red noise, with generally smaller spectral indices than typically measured for non-recycled pulsars, possibly suggesting a different origin. A companion paper uses these data to constrain the strength of the gravitational-wave background