Statistical learning techniques applied to epidemiology: a simulated case-control comparison study with logistic regression

<p>Abstract</p> <p>Background</p> <p>When investigating covariate interactions and group associations with standard regression analyses, the relationship between the response variable and exposure may be difficult to characterize. When the relationship is nonlinear, linear modeling techniques do not capture the nonlinear information content. Statistical learning (SL) techniques with kernels are capable of addressing nonlinear problems without making parametric assumptions. However, these techniques do not produce findings relevant for epidemiologic interpretations. A simulated case-control study was used to contrast the information embedding characteristics and separation boundaries produced by a specific SL technique with logistic regression (LR) modeling representing a parametric approach. The SL technique was comprised of a kernel mapping in combination with a perceptron neural network. Because the LR model has an important epidemiologic interpretation, the SL method was modified to produce the analogous interpretation and generate odds ratios for comparison.</p> <p>Results</p> <p>The SL approach is capable of generating odds ratios for main effects and risk factor interactions that better capture nonlinear relationships between exposure variables and outcome in comparison with LR.</p> <p>Conclusions</p> <p>The integration of SL methods in epidemiology may improve both the understanding and interpretation of complex exposure/disease relationships.</p

An Institutional Peri-operative Intravenous Insulin Infusion Algorithm: Evaluation and Recommendations

The purpose of this retrospective medical record analysis was to examine our non-cardiac surgery insulin algorithm for efficacy, safety and provider adherence. The sample included 132 hyperglycemic patients (standard group) that were placed on intravenous insulin infusions. Nineteen patients using insulin pumps at home that had been converted for surgery to intravenous infusions were separately studied. Efficacy, safety and adherence definitions were developed and data was extrapolated to address the research purpose.  Captured data did not reflect any incidences of blood glucose (BG) measurements &lt;50 mg/dl; two BG were however &lt;70 mg/dl in the standard group. In the standard group, 73% of patients achieved BG of 100-179 mg/dl and an 85% mean proportion of subsequent time within range (MPST) through the remaining peri-operative period. Algorithm adherence metrics were 54-58%. Lower time-weighted average BG (190 vs 206 mg/dl; p=.03) was achieved where providers adhered to the intravenous insulin maintenance table &gt;67% of the time. In insulin pump patients, MPST was 81% after conversion to intravenous infusions. Increased algorithm adherence was associated with improved peri-operative glycemic control. In insulin pump patients, successful conversion was attributed to glycemic nurse practitioner collaboration and algorithm reference. Algorithm modifications are proposed to increase adherence and safety.      

Application of multiple statistical tests to enhance mass spectrometry-based biomarker discovery

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry-based biomarker discovery has long been hampered by the difficulty in reconciling lists of discriminatory peaks identified by different laboratories for the same diseases studied. We describe a multi-statistical analysis procedure that combines several independent computational methods. This approach capitalizes on the strengths of each to analyze the same high-resolution mass spectral data set to discover consensus differential mass peaks that should be robust biomarkers for distinguishing between disease states.</p> <p>Results</p> <p>The proposed methodology was applied to a pilot narcolepsy study using logistic regression, hierarchical clustering, t-test, and CART. Consensus, differential mass peaks with high predictive power were identified across three of the four statistical platforms. Based on the diagnostic accuracy measures investigated, the performance of the consensus-peak model was a compromise between logistic regression and CART, which produced better models than hierarchical clustering and t-test. However, consensus peaks confer a higher level of confidence in their ability to distinguish between disease states since they do not represent peaks that are a result of biases to a particular statistical algorithm. Instead, they were selected as differential across differing data distribution assumptions, demonstrating their true discriminatory potential.</p> <p>Conclusion</p> <p>The methodology described here is applicable to any high-resolution MALDI mass spectrometry-derived data set with minimal mass drift which is essential for peak-to-peak comparison studies. Four statistical approaches with differing data distribution assumptions were applied to the same raw data set to obtain consensus peaks that were found to be statistically differential between the two groups compared. These consensus peaks demonstrated high diagnostic accuracy when used to form a predictive model as evaluated by receiver operating characteristics curve analysis. They should demonstrate a higher discriminatory ability as they are not biased to a particular algorithm. Thus, they are prime candidates for downstream identification and validation efforts.</p

Unwanted incidents during transition of geriatric patients from hospital to home: a prospective observational study

<p>Abstract</p> <p>Background</p> <p>Geriatric patients recently discharged from hospital experience increased chance of unplanned readmissions and admission to nursing homes. Several studies have shown that medication-related discrepancies are common. Few studies report unwanted incidents by other factors than medications. In 2002 an ambulatory team (AT) was established within the Department of Geriatrics, St. Olavs University Hospital HF, Trondheim, Norway. The AT monitored the transition of the patients from hospital to home and four weeks after discharge in order to reveal unwanted incidents.</p> <p>The aim of the present study was to describe unwanted incidents registered by the AT among patients discharged from a geriatric evaluation and management unit (GEMU) by character, frequency and stage in the transitional process. Only unwanted incidents with a severity making contact with the primary health care (PHC) necessary were registered.</p> <p>Methods</p> <p>A prospective observational study with patients treated in the GEMU and followed by the AT was performed. Current practice included comprehensive geriatric assessment and management including discharge planning in the GEMU and collaboration with the primary health care on appointments on assistance to be provided after discharge from hospital. Unwanted incidents severe enough to induce contact with the primary health care were registered during the transitional phase and after discharge.</p> <p>Results</p> <p>118 patients (65% female), with mean age 83.2 ± 6.4 years participated. Median Barthel Index at discharge was 18 (interquartile range 16-19) and median Mini Mental Status Examination 24 (interquartile range 21-26). A total of 146 unwanted incidents were registered in 70 (59%) of the patients. Most frequent were unwanted incidents related to drug prescription regime (32%), exchange of information in and between the GEMU and the primary health care (25%) and service or help provided from the PHC (17%).</p> <p>Conclusions</p> <p>Despite a seemingly well-organised system for transition of patients from the GEMU to their homes, one or more unwanted incidents occurred in most patients during discharge or four weeks post discharge. The study has revealed areas of importance for improving transitional care of geriatric patients.</p

Polyclonal rabbit anti-murine plasmacytoma cell globulins induce myeloma cells apoptosis and inhibit tumour growth in mice

Multiple myelomas (MMs) are etiologically heterogeneous and there are limited treatment options; indeed, current monoclonal antibody therapies have had limited success, so more effective antibodies are urgently needed. Polyclonal antibodies are a possible alternative because they target multiple antigens simultaneously. In this study, we produced polyclonal rabbit anti-murine plasmacytoma cell immunoglobulin (PAb) by immunizing rabbits with the murine plasmacytoma cell line MPC-11. The isolated PAb bound to plasma surface antigens in several MM cell lines, inhibited their proliferation as revealed by MTT assay, and induce apoptosis as indicated by flow cytometry, microscopic observation of apoptotic changes in morphology, and DNA fragmentation on agarose gels. The cytotoxicity of PAb on MPC-11 cell lines was both dose-dependent and time-dependent; PAb exerted a 50% inhibitory effect on MPC-11 cell viability at a concentration of 200 µg/ml in 48 h. Flow cytometry demonstrated that PAb treatment significantly increased the number of apoptotic cells (48.1%) compared with control IgG (8.3%). Apoptosis triggered by PAb was confirmed by activation of caspase-3, -8, and -9. Serial intravenous or intraperitoneal injections of PAb inhibited tumour growth and prolonged survival in mice bearing murine plasmacytoma, while TUNEL assay demonstrated that PAb induced statistically significant apoptosis (P < 0.05) compared to control treatments. We conclude that PAb is an effective agent for in vitro and in vivo induction of apoptosis in multiple myeloma and that exploratory clinical trials may be warranted

Local flexibility in feeding behaviour and contrasting microhabitat use of an omnivore across latitudes

As the environment is getting warmer and species are redistributed, consumers can be forced to adjust their interactions with available prey, and this could have cascading effects within food webs. To better understand the capacity for foraging flexibility, our study aimed to determine the diet variability of an ectotherm omnivore inhabiting kelp forests, the sea urchin Echinus esculentus, along its entire latitudinal distribution in the northeast Atlantic. Using a combination of gut content and stable isotope analyses, we determined the diet and trophic position of sea urchins at sites in Portugal (42° N), France (49° N), southern Norway (63° N), and northern Norway (70° N), and related these results to the local abundance and distribution of putative food items. With mean estimated trophic levels ranging from 2.4 to 4.6, omnivory and diet varied substantially within and between sites but not across latitudes. Diet composition generally reflected prey availability within epiphyte or understorey assemblages, with local affinities demonstrating that the sea urchin adjusts its foraging to match the small-scale distribution of food items. A net “preference” for epiphytic food sources was found in northern Norway, where understorey food was limited compared to other regions. We conclude that diet change may occur in response to food source redistribution at multiple spatial scales (microhabitats, sites, regions). Across these scales, the way that key consumers alter their foraging in response to food availability can have important implication for food web dynamics and ecosystem functions along current and future environmental gradients

Shear wave velocity prediction using seismic attributes and well log data

Formation’s properties can be estimated indirectly using joint analysis of compressional and shear wave velocities. Shear wave data isnot usually acquired during well logging, which is most likely for costsaving purposes. Even if shear data is available, the logging programs provide only sparsely sampled one-dimensional measurements: this informationis inadequate to estimate reservoir rock properties. Thus, if the shear wave data can be obtained using seismic methods, the results can be used across the field to estimate reservoir properties. The aim of this paper is to use seismic attributes for prediction of shear wave velocity in a field located in southern part of Iran. Independent component analysis(ICA) was used to select the most relevant attributes to shear velocity data. Considering the nonlinear relationship between seismic attributes and shear wave velocity, multi-layer feed forward neural network was used for prediction of shear wave velocity and promising results were presented

Nestin-GFP Transgene Reveals Neural Precursor Cells in Adult Skeletal Muscle

Background: Therapy for neural lesions or degenerative diseases relies mainly on finding transplantable active precursor cells. Identifying them in peripheral tissues accessible for biopsy, outside the central nervous system, would circumvent the serious immunological and ethical concerns impeding cell therapy. Methodology/Principal Findings: In this study, we isolated neural progenitor cells in cultured adult skeletal muscle from transgenic mice in which nestin regulatory elements control GFP expression. These cells also expressed the early neural marker Tuj1 and light and heavy neurofilament but not S100b, indicating that they express typical neural but not Schwann cell markers. GFP+/Tuj1+ cells were also negative for the endothelial and pericyte markers CD31 and a-smooth muscle actin, respectively. We established their a) functional response to glutamate in patch-clamp recordings; b) interstitial mesenchymal origin; c) replicative capacity; and d) the environment necessary for their survival after fluorescenceactivated cell sorting. Conclusions/Significance: We propose that the decline in nestin-GFP expression in muscle progenitor cells and its persistence in neural precursor cells in muscle cultures provide an invaluable tool for isolating a population of predifferentiated neural cells with therapeutic potential

Clonal Characterization of Rat Muscle Satellite Cells: Proliferation, Metabolism and Differentiation Define an Intrinsic Heterogeneity

Satellite cells (SCs) represent a distinct lineage of myogenic progenitors responsible for the postnatal growth, repair and maintenance of skeletal muscle. Distinguished on the basis of their unique position in mature skeletal muscle, SCs were considered unipotent stem cells with the ability of generating a unique specialized phenotype. Subsequently, it was demonstrated in mice that opposite differentiation towards osteogenic and adipogenic pathways was also possible. Even though the pool of SCs is accepted as the major, and possibly the only, source of myonuclei in postnatal muscle, it is likely that SCs are not all multipotent stem cells and evidences for diversities within the myogenic compartment have been described both in vitro and in vivo. Here, by isolating single fibers from rat flexor digitorum brevis (FDB) muscle we were able to identify and clonally characterize two main subpopulations of SCs: the low proliferative clones (LPC) present in major proportion (∼75%) and the high proliferative clones (HPC), present instead in minor amount (∼25%). LPC spontaneously generate myotubes whilst HPC differentiate into adipocytes even though they may skip the adipogenic program if co-cultured with LPC. LPC and HPC differ also for mitochondrial membrane potential (ΔΨm), ATP balance and Reactive Oxygen Species (ROS) generation underlying diversities in metabolism that precede differentiation. Notably, SCs heterogeneity is retained in vivo. SCs may therefore be comprised of two distinct, though not irreversibly committed, populations of cells distinguishable for prominent differences in basal biological features such as proliferation, metabolism and differentiation. By these means, novel insights on SCs heterogeneity are provided and evidences for biological readouts potentially relevant for diagnostic purposes described