Fixed Effect Estimation of Large T Panel Data Models

This article reviews recent advances in fixed effect estimation of panel data models for long panels, where the number of time periods is relatively large. We focus on semiparametric models with unobserved individual and time effects, where the distribution of the outcome variable conditional on covariates and unobserved effects is specified parametrically, while the distribution of the unobserved effects is left unrestricted. Compared to existing reviews on long panels (Arellano and Hahn 2007; a section in Arellano and Bonhomme 2011) we discuss models with both individual and time effects, split-panel Jackknife bias corrections, unbalanced panels, distribution and quantile effects, and other extensions. Understanding and correcting the incidental parameter bias caused by the estimation of many fixed effects is our main focus, and the unifying theme is that the order of this bias is given by the simple formula p/n for all models discussed, with p the number of estimated parameters and n the total sample size.Comment: 40 pages, 1 tabl

Effect of drug utilization reviews on the quality of in-hospital prescribing: a quasi-experimental study

BACKGROUND: Drug utilization review (DUR) programs are being conducted in Canadian hospitals with the aim of improving the appropriateness of prescriptions. However, there is little evidence of their effectiveness. The objective of this study was to assess the impact of both a retrospective and a concurrent DUR programs on the quality of in-hospital prescribing. METHODS: We conducted an interrupted time series quasi-experimental study. Using explicit criteria for quality of prescribing, the natural history of cisapride prescription was established retrospectively in three university-affiliated hospitals. A retrospective DUR was implemented in one of the hospitals, a concurrent DUR in another, whereas the third hospital served as a control. An archivist abstracted records of all patients who were prescribed cisapride during the observation period. The effect of DURs relative to the control hospital was determined by comparing estimated regression coefficients from the time series models and by testing the statistical significance using a 2-tailed Student's t test. RESULTS: The concurrent DUR program significantly improved the appropriateness of prescriptions for the indication for use whereas the retrospective DUR brought about no significant effect on the quality of prescribing. CONCLUSION: Results suggest a retrospective DUR approach may not be sufficient to improve the quality of prescribing. However, a concurrent DUR strategy, with direct feedback to prescribers seems effective and should be tested in other settings with other drugs

EZH2 Depletion Blocks the Proliferation of Colon Cancer Cells

The Enhancer of Zeste 2 (EZH2) protein has been reported to stimulate cell growth in some cancers and is therefore considered to represent an interesting new target for therapeutic intervention. Here, we investigated a possible role of EZH2 for the growth control of colon cancer cells. RNA interference (RNAi)-mediated intracellular EZH2 depletion led to cell cycle arrest of colon carcinoma cells at the G1/S transition. This was associated with a reduction of cell numbers upon transient transfection of synthetic EZH2-targeting siRNAs and with inhibition of their colony formation capacity upon stable expression of vector-borne siRNAs. We furthermore tested whether EZH2 may repress the growth-inhibitory p27 gene, as reported for pancreatic cancer. However, expression analyses of colon cancer cell lines and colon cancer biopsies did not reveal a consistent correlation between EZH2 and p27 levels. Moreover, EZH2 depletion did not re-induce p27 expression in colon cancer cells, indicating that p27 repression by EZH2 may be cell- or tissue-specific. Whole genome transcriptome analyses identified cellular genes affected by EZH2 depletion in colon cancer cell lines. They included several cancer-associated genes linked to cellular proliferation or invasion, such as Dag1, MageD1, SDC1, Timp2, and Tob1. In conclusion, our results demonstrate that EZH2 depletion blocks the growth of colon cancer cells. These findings might provide benefits for the treatment of colon cancer

Deciphering the intracellular metabolism of Listeria monocytogenes by mutant screening and modelling

Background: The human pathogen Listeria monocytogenes resides and proliferates within the cytoplasm of epithelial cells. While the virulence factors essentially contributing to this step of the infection cycle are well characterized, the set of listerial genes contributing to intracellular replication remains to be defined on a genome-wide level. Results: A comprehensive library of L. monocytogenes strain EGD knockout mutants was constructed upon insertion-duplication mutagenesis, and 1491 mutants were tested for their phenotypes in rich medium and in a Caco-2 cell culture assay. Following sequencing of the plasmid insertion site, 141 different genes required for invasion of and replication in Caco-2 cells were identified. Ten in-frame deletion mutants were constructed that confirmed the data. The genes with known functions are mainly involved in cellular processes including transport, in the intermediary metabolism of sugars, nucleotides and lipids, and in information pathways such as regulatory functions. No function could be ascribed to 18 genes, and a counterpart of eight genes is missing in the apathogenic species L. innocua. Mice infection studies revealed the in vivo requirement of IspE (Lmo0190) involved in mevalonate synthesis, and of the novel ABC transporter Lmo0135-0137 associated with cysteine transport. Based on the data of this genome-scale screening, an extreme pathway and elementary mode analysis was applied that demonstrates the critical role of glycerol and purine metabolism, of fucose utilization, and of the synthesis of glutathione, aspartate semialdehyde, serine and branched chain amino acids during intracellular replication of L. monocytogenes. Conclusion: The combination of a genetic screening and a modelling approach revealed that a series of transporters help L. monocytogenes to overcome a putative lack of nutrients within cells, and that a high metabolic flexibility contributes to the intracellular replication of this pathogen

From manned to unmanned aircraft: Adapting airborne particle size mapping methodologies to the characteristics of sUAS and SfM

Subaerial particle size data holds a wealth of valuable information for fluvial, coastal, glacial and other sedimentological applications. Recently, we have gained the opportunity to map and quantify surface particle sizes at the mesoscale using data derived from small unmanned aerial system (sUAS) imagery processed using structure from motion (SfM) photogrammetry. Typically, these sUAS-SfM approaches have been based on calibrating orthoimage texture or point cloud roughness with particle size. Variable levels of success are reported and a single, robust method capable of producing consistently accurate and precise results in a range of settings has remained elusive. In this paper, we develop an original method for mapping surface particle size with the specific constraints of sUAS and SfM in mind. This method uses the texture of single sUAS images, rather than orthoimages, calibrated with particle sizes normalised by individual image scale. We compare results against existing orthoimage texture and roughness approaches, and provide a quantitative investigation into the implications of the use of sUAS camera gimbals. Our results indicate that our novel single image method delivers an optimised particle size mapping performance for our study site, outperforming both other methods and delivering residual mean errors of 0.02mm (accuracy), standard deviation of residual errors of 6.90mm (precision) and maximum residual errors of 16.50mm. Accuracy values are more than two orders of magnitude worse when imagery is collected by a similar drone which is not equipped with a camera gimbal, demonstrating the importance of mechanical image stabilisation for particle size mapping using measures of image texture

Volunteer patients and small groups contribute to abdominal examination's success

Helen M Shields,1 Nielsen Q Fernandez-Becker,2 Sarah N Flier,2 Byron P Vaughn,2 Melissa H Tukey,2 Stephen R Pelletier,3 Douglas A Horst2 1Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, 2Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 3Center for Evaluation, Harvard Medical School, Boston, MA, USA Background: Prior to 2007, we taught the abdominal examination in a hospital based group to 40 students, at one hospital. We used volunteer patients, small groups, repetition, and required faculty development sessions. In 2007, our medical school changed its “Introduction to Physical Examination” session so that the entire class was to be taught in a geographically central session. Our hospital was selected to lead the abdominal examination portion of the session. Aim: Our aim was to answer three questions. First, could we quadruple the recruitment of volunteer patients, and faculty? Second, was it volunteer patients, small groups, repetition, or faculty training that was most valued by the students? Third, would volunteer patients and/or faculty agree to participate a second time? Methods: A total of 43-46 patients and 43-46 faculty were recruited and 43-46 examining rooms were obtained for each of the 5 years of this study. Teachers were required to attend a 1-hour faculty development session. The class of about 170 students was divided into 43–46 groups each year. The teacher demonstrated the abdominal examination and each student practiced the examination on another student. Each student then repeated the full abdominal examination on a volunteer patient. Results: Over the 5-year time period (2008–2012), the abdominal examination ranked first among all organ systems’ “Introductory Sessions”. The abdominal examination ratings had the best mean score (1.35) on a Likert scale where 1 is excellent and 5 is poor. The students gave the most positive spontaneous comments to having volunteer patients, with small groups coming in as the second most appreciated educational element. Conclusion: We successfully quadrupled the number of faculty, patients, and examining rooms and created a highly rated educational program as measured by anonymous student evaluations, patient and faculty participation, and the medical school’s selecting the abdominal examination methods as an “Advanced Examination” for the Pathways Curriculum. Keywords: abdominal examination, volunteer patients, small groups, repetition, faculty developmen