Data management for prospective research studies using SAS® software

<p>Abstract</p> <p>Background</p> <p>Maintaining data quality and integrity is important for research studies involving prospective data collection. Data must be entered, erroneous or missing data must be identified and corrected if possible, and an audit trail created.</p> <p>Methods</p> <p>Using as an example a large prospective study, the Missouri Lower Respiratory Infection (LRI) Project, we present an approach to data management predominantly using SAS software. The Missouri LRI Project was a prospective cohort study of nursing home residents who developed an LRI. Subjects were enrolled, data collected, and follow-ups occurred for over three years. Data were collected on twenty different forms. Forms were inspected visually and sent off-site for data entry. SAS software was used to read the entered data files, check for potential errors, apply corrections to data sets, and combine batches into analytic data sets. The data management procedures are described.</p> <p>Results</p> <p>Study data collection resulted in over 20,000 completed forms. Data management was successful, resulting in clean, internally consistent data sets for analysis. The amount of time required for data management was substantially underestimated.</p> <p>Conclusion</p> <p>Data management for prospective studies should be planned well in advance of data collection. An ongoing process with data entered and checked as they become available allows timely recovery of errors and missing data.</p

Assessment of burnout in veterinary medical students using the Maslach Burnout Inventory-Educational Survey: a survey during two semesters

BACKGROUND: Burnout among veterinary students can result from known stressors in the absence of a support system. The objectives of this study were to evaluate use of the Maslach Burnout Inventory-Educator Survey (MBI-ES) to assess burnout in veterinary students and evaluate the factors that predict the MBI-ES scores. METHODS: The MBI-ES was administered to first (Class of 2016) and second year (Class of 2015) veterinary medical students during the 2012-2013 academic year in the fall and spring semesters. Factor analysis and test reliability for the survey were determined. Mean scores for the subscales determining burnout namely emotional exhaustion (EE), depersonalization (DP) and lack of personal accomplishment (PA) were calculated for both classes in the 2 semesters. Multiple regression analysis was performed to evaluate other factors that predict the MBI-ES scores. RESULTS: A non-probability sampling method was implemented consisting of a voluntary sample of 170 and 123 students in the fall and spring semesters, respectively. Scores for EE, DP and PA were not different between the 2 classes within the same semester. Mean ± SD scores for EE, DP and PA for the fall semester were 22.9 ± 9.6, 5.0 ± 4.8 and 32.3 ± 6.7, respectively. Mean ± SD scores for EE, DP and PA the spring semester were 27.8 ± 10.7, 6.5 ± 6.1and 31.7 ± 6.8, respectively. The EE score was higher in spring compared to fall while DP and PA scores were not different between the 2 semesters. Living arrangements specifically as to whether or not a student lived with another veterinary medical students was the only variable significantly associated with the MBI-ES scores. Students in this study had moderate levels of burnout based on the MBI-ES scores. CONCLUSIONS: The MBI-ES was an acceptable instrument for assessing burnout in veterinary medical students. The EE scores were higher in the spring semester as compared to the fall semester. Thus students in the first and second years of veterinary school under the current curriculum experience the greatest levels of emotional exhaustion during the spring semester. This has administrative implications for the school, when considering the allocation and use of resources for student support systems during each semester

Conditionally Replicating Adenovirus Expressing TIMP2 Increases Survival in a Mouse Model of Disseminated Ovarian Cancer

Ovarian cancer remains difficult to treat mainly due to presentation of the disease at an advanced stage. Conditionally-replicating adenoviruses (CRAds) are promising anti-cancer agents that selectively kill the tumor cells. The present study evaluated the efficacy of a novel CRAd (Ad5/3-CXCR4-TIMP2) containing the CXCR4 promoter for selective viral replication in cancer cells together with TIMP2 as a therapeutic transgene, targeting the matrix metalloproteases (MMPs) in a murine orthotopic model of disseminated ovarian cancer. An orthotopic model of ovarian cancer was established in athymic nude mice by intraperitonal injection of the human ovarian cancer cell line, SKOV3-Luc, expressing luciferase. Upon confirmation of peritoneal dissemination of the cells by non-invasive imaging, mice were randomly divided into four treatment groups: PBS, Ad-ΔE1-TIMP2, Ad5/3-CXCR4, and Ad5/3-CXCR4-TIMP2. All mice were imaged weekly to monitor tumor growth and were sacrificed upon reaching any of the predefined endpoints, including high tumor burden and significant weight loss along with clinical evidence of pain and distress. Survival analysis was performed using the Log-rank test. The median survival for the PBS cohort was 33 days; for Ad-ΔE1-TIMP2, 39 days; for Ad5/3-CXCR4, 52.5 days; and for Ad5/3-CXCR4-TIMP2, 63 days. The TIMP2-armed CRAd delayed tumor growth and significantly increased survival when compared to the unarmed CRAd. This therapeutic effect was confirmed to be mediated through inhibition of MMP9. Results of the in vivo study support the translational potential of Ad5/3-CXCR4-TIMP2 for treatment of human patients with advanced ovarian cancer

Mediterranean-climate streams and rivers: geographically separated but ecologically comparable freshwater systems

Streams and rivers in mediterranean-climate regions (med-rivers in med-regions) are ecologically unique, with flow regimes reflecting precipitation patterns. Although timing of drying and flooding is predictable, seasonal and annual intensity of these events is not. Sequential flooding and drying, coupled with anthropogenic influences make these med-rivers among the most stressed riverine habitat worldwide. Med-rivers are hotspots for biodiversity in all med-regions. Species in med-rivers require different, often opposing adaptive mechanisms to survive drought and flood conditions or recover from them. Thus, metacommunities undergo seasonal differences, reflecting cycles of river fragmentation and connectivity, which also affect ecosystem functioning. River conservation and management is challenging, and trade-offs between environmental and human uses are complex, especially under future climate change scenarios. This overview of a Special Issue on med-rivers synthesizes information presented in 21 articles covering the five med-regions worldwide: Mediterranean Basin, coastal California, central Chile, Cape region of South Africa, and southwest and southern Australia. Research programs to increase basic knowledge in less-developed med-regions should be prioritized to achieve increased abilities to better manage med-rivers

Ice loss from the East Antarctic Ice Sheet during late Pleistocene interglacials

Understanding ice sheet behaviour in the geological past is essential for evaluating the role of the cryosphere in the climate system and for projecting rates and magnitudes of sea level rise in future warming scenarios1,2,3,4. Although both geological data5,6,7 and ice sheet models3,8 indicate that marine-based sectors of the East Antarctic Ice Sheet were unstable during Pliocene warm intervals, the ice sheet dynamics during late Pleistocene interglacial intervals are highly uncertain3,9,10. Here we provide evidence from marine sedimentological and geochemical records for ice margin retreat or thinning in the vicinity of the Wilkes Subglacial Basin of East Antarctica during warm late Pleistocene interglacial intervals. The most extreme changes in sediment provenance, recording changes in the locus of glacial erosion, occurred during marine isotope stages 5, 9, and 11, when Antarctic air temperatures11 were at least two degrees Celsius warmer than pre-industrial temperatures for 2,500 years or more. Hence, our study indicates a close link between extended Antarctic warmth and ice loss from the Wilkes Subglacial Basin, providing ice-proximal data to support a contribution to sea level from a reduced East Antarctic Ice Sheet during warm interglacial intervals. While the behaviour of other regions of the East Antarctic Ice Sheet remains to be assessed, it appears that modest future warming may be sufficient to cause ice loss from the Wilkes Subglacial Basin

Tetrahymena Metallothioneins Fall into Two Discrete Subfamilies

BACKGROUND: Metallothioneins are ubiquitous small, cysteine-rich, multifunctional proteins which can bind heavy metals. METHODOLOGY/PRINCIPAL FINDINGS: We report the results of phylogenetic and gene expression analyses that include two new Tetrahymena thermophila metallothionein genes (MTT3 and MTT5). Sequence alignments of all known Tetrahymena metallothioneins have allowed us to rationalize the structure of these proteins. We now formally subdivide the known metallothioneins from the ciliate genus Tetrahymena into two well defined subfamilies, 7a and 7b, based on phylogenetic analysis, on the pattern of clustering of Cys residues, and on the pattern of inducibility by the heavy metals Cd and Cu. Sequence alignment also reveals a remarkably regular, conserved and hierarchical modular structure of all five subfamily 7a MTs, which include MTT3 and MTT5. The former has three modules, while the latter has only two. Induction levels of the three T. thermophila genes were determined using quantitative real time RT-PCR. Various stressors (including heavy metals) brought about dramatically different fold-inductions for each gene; MTT5 showed the highest fold-induction. Conserved DNA motifs with potential regulatory significance were identified, in an unbiased way, upstream of the start codons of subfamily 7a MTs. EST evidence for alternative splicing in the 3′ UTR of the MTT5 mRNA with potential regulatory activity is reported. CONCLUSION/SIGNIFICANCE: The small number and remarkably regular structure of Tetrahymena MTs, coupled with the experimental tractability of this model organism for studies of in vivo function, make it an attractive system for the experimental dissection of the roles, structure/function relationships, regulation of gene expression, and adaptive evolution of these proteins, as well as for the development of biotechnological applications for the environmental monitoring of toxic substances

COMMON ENVELOPE EJECTION FOR A LUMINOUS RED NOVA IN M101

We present the results of optical, near-infrared, and mid-infrared observations of M101 OT2015-1 (PSN J14021678+ 5426205), a luminous red transient in the Pinwheel galaxy (M101), spanning a total of 16 years. The light curve showed two distinct peaks with absolute magnitudes M-r <= -12.4 and M-r similar or equal to -12, on 2014 November 11 and 2015 February 17, respectively. The spectral energy distributions during the second maximum show a cool outburst temperature of approximate to 3700 K and low expansion velocities (approximate to -300 km s(-1)) for the H I, Ca II, Ba II, and K I lines. From archival data spanning 15-8 years before the outburst, we find a single source consistent with the optically discovered transient, which we attribute to being the progenitor; it has properties consistent with being an F-type yellow supergiant with L similar to 8.7 x 10(4) L-circle dot, T-eff approximate to 7000. K, and an estimated mass of M1= 18 +/- 1 M-circle dot. This star has likely just finished the H-burning phase in the core, started expanding, and is now crossing the Hertzsprung gap. Based on the combination of observed properties, we argue that the progenitor is a binary system, with the more evolved system overfilling the Roche lobe. Comparison with binary evolution models suggests that the outburst was an extremely rare phenomenon, likely associated with the ejection of the common envelope of a massive star. The initial mass of the primary fills the gap between the merger candidates V838 Mon (5-10 M-circle dot) and NGC. 4490-OT. (30M(circle dot))

Common envelope ejection for a luminous red nova in M101

We present the results of optical, near-infrared, and mid-infrared observations of M101 OT2015-1 (PSN J14021678+5426205), a luminous red transient in the Pinwheel galaxy (M101), spanning a total of 16 years. The light curve showed two distinct peaks with absolute magnitudes $M_r$ $\leq$ -12.4 and $M_r$ $\simeq$ -12, on 2014 November 11 and 2015 February 17, respectively. The spectral energy distributions during the second maximum show a cool outburst temperature of $\approx$3700 K and low expansion velocities ($\approx$-300 km s$^{−1}$) for the H $\small \text{I}$, Ca $\small \text{II}$, Ba $\small \text{II}$, and K $\small \text{I}$ lines. From archival data spanning 15–8 years before the outburst, we find a single source consistent with the optically discovered transient, which we attribute to being the progenitor; it has properties consistent with being an F-type yellow supergiant with $L$ ~ 8.7 $\times$ 10$^4$ $L_\odot$, $T_{eff}$ $\approx$ 7000 K, and an estimated mass of M1 = 18 $\pm$ 1 $M_\odot$. This star has likely just finished the H-burning phase in the core, started expanding, and is now crossing the Hertzsprung gap. Based on the combination of observed properties, we argue that the progenitor is a binary system, with the more evolved system overfilling the Roche lobe. Comparison with binary evolution models suggests that the outburst was an extremely rare phenomenon, likely associated with the ejection of the common envelope of a massive star. The initial mass of the primary fills the gap between the merger candidates V838 Mon (5−10 $M_\odot$) and NGC 4490-OT (30 $M_\odot$).The research leading to these results has received funding from the European Union Seventh Framework Programme ([FP7/2007-2013] under grant agreement no. 264895. This work was partly supported by the European Union FP7 programme through ERC grant no. 320360. This work was supported, in whole or in part, by the European Science Foundation under the GREAT ESF RNP programme. This work was supported by the GROWTH project funded by the National Science Foundation under grant no. 1545949. LANL participation in iPTF was funded by the US Department of Energy as part of the Laboratory Directed Research and Development program. Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. Based on observations obtained with MegaPrime/MegaCam, a joint project of CFHT and CEA/IRFU, at the Canada–France–Hawaii Telescope (CFHT), which is operated by the National Research Council (NRC) of Canada, the Institut National des Science de l’Univers of the Centre National de la Recherche Scientifique (CNRS) of France, and the University of Hawaii. This work is based in part on data products produced at Terapix available at the Canadian Astronomy Data Centre as part of the Canada–France–Hawaii Telescope Legacy Survey, a collaborative project of NRC and CNRS. This paper makes use of data obtained from the Isaac Newton Group Archive, which is maintained as part of the CASU Astronomical Data Centre at the Institute of Astronomy, Cambridge. This work is partly based on observations obtained with the Nordic Optical Telescope, operated by the Nordic Optical Telescope Scientific Association at the Observatorio del Roque de los Muchachos, La Palma, Spain. This work is partly based on observations made with the William Hershell Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofsica de Canarias. The Gran Telescopio Canarias (GTC) operated on the island of La Palma at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias. This work is partly based on data from Copernico 1.82 m telescope operated by INAF Osservatorio Astronomico di Padova. NER, AP, GT, and MT are partially supported by the PRIN-INAF 2014 with the project “Transient universe: unveiling new types of stellar explosions with PESSTO.

Could lymphatic mapping and sentinel node biopsy provide oncological providence for local resectional techniques for colon cancer? A review of the literature

<p>Abstract</p> <p>Background</p> <p>Endoscopic resectional techniques for colon cancer are undermined by their inability to determine lymph node status. This limits their application to only those lesions at the most minimal risk of lymphatic dissemination whereas their technical capacity could allow intraluminal or even transluminal address of larger lesions. Sentinel node biopsy may theoretically address this breach although the variability of its reported results for this disease is worrisome.</p> <p>Methods</p> <p>Medline, EMBASE and Cochrane databases were interrogated back to 1999 to identify all publications concerning lymphatic mapping for colon cancer with reference cross-checking for completeness. All reports were examined from the perspective of in vivo technique accuracy selectively in early stage disease (i.e. lesions potentially within the technical capacity of endoscopic resection).</p> <p>Results</p> <p>Fifty-two studies detailing the experiences of 3390 patients were identified. Considerable variation in patient characteristics as well as in surgical and histological quality assurances were however evident among the studies identified. In addition, considerable contamination of the studies by inclusion of rectal cancer without subgroup separation was frequent. Indeed such is the heterogeneity of the publications to date, formal meta-analysis to pool patient cohorts in order to definitively ascertain technique accuracy in those with T1 and/or T2 cancer is not possible. Although lymphatic mapping in early stage neoplasia alone has rarely been specifically studied, those studies that included examination of false negative rates identified high T3/4 patient proportions and larger tumor size as being important confounders. Under selected circumstances however the technique seems to perform sufficiently reliably to allow it prompt consideration of its use to tailor operative extent.</p> <p>Conclusion</p> <p>The specific question of whether sentinel node biopsy can augment the oncological propriety for endoscopic resective techniques (including Natural Orifice Transluminal Endoscopic Surgery [NOTES]) cannot be definitively answered at present. Study heterogeneity may account for the variability evident in the results from different centers. Enhanced capacity (perhaps to the level necessary to consider selective avoidance of en bloc mesenteric resection) by its confinement to only early stage disease is plausible although not proven. Specific study of the technique in early stage tumors is clearly essential before proffering this approach.</p