Multivariate modeling to identify patterns in clinical data: the example of chest pain

<p>Abstract</p> <p>Background</p> <p>In chest pain, physicians are confronted with numerous interrelationships between symptoms and with evidence for or against classifying a patient into different diagnostic categories. The aim of our study was to find natural groups of patients on the basis of risk factors, history and clinical examination data which should then be validated with patients' final diagnoses.</p> <p>Methods</p> <p>We conducted a cross-sectional diagnostic study in 74 primary care practices to establish the validity of symptoms and findings for the diagnosis of coronary heart disease. A total of 1199 patients above age 35 presenting with chest pain were included in the study. General practitioners took a standardized history and performed a physical examination. They also recorded their preliminary diagnoses, investigations and management related to the patient's chest pain. We used multiple correspondence analysis (MCA) to examine associations on variable level, and multidimensional scaling (MDS), k-means and fuzzy cluster analyses to search for subgroups on patient level. We further used heatmaps to graphically illustrate the results.</p> <p>Results</p> <p>A multiple correspondence analysis supported our data collection strategy on variable level. Six factors emerged from this analysis: „chest wall syndrome“, „vital threat“, „stomach and bowel pain“, „angina pectoris“, „chest infection syndrome“, and „ self-limiting chest pain“. MDS, k-means and fuzzy cluster analysis on patient level were not able to find distinct groups. The resulting cluster solutions were not interpretable and had insufficient statistical quality criteria.</p> <p>Conclusions</p> <p>Chest pain is a heterogeneous clinical category with no coherent associations between signs and symptoms on patient level.</p

Long-term declines in ADLs, IADLs, and mobility among older Medicare beneficiaries

<p>Abstract</p> <p>Background</p> <p>Most prior studies have focused on short-term (≤ 2 years) functional declines. But those studies cannot address aging effects inasmuch as all participants have aged the same amount. Therefore, the authors studied the extent of long-term functional decline in older Medicare beneficiaries who were followed for varying time lengths, and the authors also identified the risk factors associated with those declines.</p> <p>Methods</p> <p>The analytic sample included 5,871 self- or proxy-respondents who had complete baseline and follow-up survey data that could be linked to their Medicare claims for 1993-2007. Functional status was assessed using activities of daily living (ADLs), instrumental ADLs (IADLs), and mobility limitations, with declines defined as the development of two of more new difficulties. Multiple logistic regression analysis was used to focus on the associations involving respondent status, health lifestyle, continuity of care, managed care status, health shocks, and terminal drop.</p> <p>Results</p> <p>The average amount of time between the first and final interviews was 8.0 years. Declines were observed for 36.6% on ADL abilities, 32.3% on IADL abilities, and 30.9% on mobility abilities. Functional decline was more likely to occur when proxy-reports were used, and the effects of baseline function on decline were reduced when proxy-reports were used. Engaging in vigorous physical activity consistently and substantially protected against functional decline, whereas obesity, cigarette smoking, and alcohol consumption were only associated with mobility declines. Post-baseline hospitalizations were the most robust predictors of functional decline, exhibiting a dose-response effect such that the greater the average annual number of hospital episodes, the greater the likelihood of functional status decline. Participants whose final interview preceded their death by one year or less had substantially greater odds of functional status decline.</p> <p>Conclusions</p> <p>Both the additive and interactive (with functional status) effects of respondent status should be taken into consideration whenever proxy-reports are used. Encouraging exercise could broadly reduce the risk of functional decline across all three outcomes, although interventions encouraging weight reduction and smoking cessation would only affect mobility declines. Reducing hospitalization and re-hospitalization rates could also broadly reduce the risk of functional decline across all three outcomes.</p

New microdeletion and microduplication syndromes: a comprehensive review

Several new microdeletion and microduplication syndromes are emerging as disorders that have been proven to cause multisystem pathologies frequently associated with intellectual disability (ID), multiple congenital anomalies (MCA), autistic spectrum disorders (ASD) and other phenotypic findings. In this paper, we review the “new” and emergent microdeletion and microduplication syndromes that have been described and recognized in recent years with the aim of summarizing their main characteristics and chromosomal regions involved. We decided to group them by genomic region and within these groupings have classified them into those that include ID, MCA, ASD or other findings. This review does not intend to be exhaustive but is rather a quick guide to help pediatricians, clinical geneticists, cytogeneticists and/or molecular geneticists

Corticotropin Releasing Factor-Induced CREB Activation in Striatal Neurons Occurs via a Novel Gβγ Signaling Pathway

The peptide corticotropin-releasing factor (CRF) was initially identified as a critical component of the stress response. CRF exerts its cellular effects by binding to one of two cognate G-protein coupled receptors (GPCRs), CRF receptor 1 (CRFR1) or 2 (CRFR2). While these GPCRs were originally characterized as being coupled to Gαs, leading to downstream activation of adenylyl cyclase (AC) and subsequent increases in cAMP, it has since become clear that CRFRs couple to and activate numerous other downstream signaling cascades. In addition, CRF signaling influences the activity of many diverse brain regions, affecting a variety of behaviors. One of these regions is the striatum, including the nucleus accumbens (NAc). CRF exerts profound effects on striatal-dependent behaviors such as drug addiction, pair-bonding, and natural reward. Recent data indicate that at least some of these behaviors regulated by CRF are mediated through CRF activation of the transcription factor CREB. Thus, we aimed to elucidate the signaling pathway by which CRF activates CREB in striatal neurons. Here we describe a novel neuronal signaling pathway whereby CRF leads to a rapid Gβγ- and MEK-dependent increase in CREB phosphorylation. These data are the first descriptions of CRF leading to activation of a Gβγ-dependent signaling pathway in neurons, as well as the first description of Gβγ activation leading to downstream CREB phosphorylation in any cellular system. Additionally, these data provide additional insight into the mechanisms by which CRF can regulate neuronal function

Observation of Gamma Rays from the Galactic Center with the MAGIC Telescope

Recently, the Galactic Center has been reported to be a source of very high energy (VHE) gamma-rays by the VERITAS, CANGAROO and HESS experiments. The energy spectra as measured by these experiments show substantial differences. In this Letter we present MAGIC observations of the Galactic Center, resulting in the detection of a differential gamma-ray flux consistent with a steady, hard-slope power law, described as dN/(dA dt dE) = (2.9+/-0.6)*10^{-12} (E/TeV)^{-2.2+/-0.2} cm^{-2}s^{-1}TeV^{-1}. The gamma-ray source is centered at (Ra, Dec)=(17h 45m 20s, -29deg 2'. This result confirms the previous measurements by the HESS experiment and indicates a steady source of TeV gamma-rays. We briefly describe the observational technique used, the procedure implemented for the data analysis, and discuss the results in the perspective of different models proposed for the acceleration of the VHE gamma-rays.Comment: ApJL submitte

Variable Very High Energy Gamma-ray Emission from the Microquasar LS I +61 303

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and laboratories for elucidating the physics of relativistic jets. Here we report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I +61 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, suggesting the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or the absorption processes.Comment: 11 pages with 4 figure

Variable Very High Energy Gamma-ray Emission from the Microquasar LS I +61 303

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and laboratories for elucidating the physics of relativistic jets. Here we report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I +61 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, suggesting the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or the absorption processes.Comment: 11 pages with 4 figure

The IceCube Neutrino Observatory - Contributions to ICRC 2017 Part VI: IceCube-Gen2, the Next Generation Neutrino Observatory

Papers on research & development towards IceCube-Gen2, the next generation neutrino observatory at South Pole, submitted to the 35th International Cosmic Ray Conference (ICRC 2017, Busan, South Korea) by the IceCube-Gen2 Collaboration