Liver Transplantation in Adults

Human liver transplantation has been possible since 1967. We report our experience in 32 adult patients who received liver transplants at the University of Pittsburgh over a 16‐month period. Survival data, method utilized for patient selection, costs, and morbidity of the procedure are discussed. Copyright © 1982 American Association for the Study of Liver Disease

Remote Visual Inspection of Steam Turbines

Case Stud

BASEBALL PITCHING BIOMECHANICS AFTER SURGERY

Baseball pitchers with and without histories of elbow or shoulder surgery were tested with a 240 Hz automated 3D motion capture system. No differences were found between pitchers with history of UCL reconstruction and matched controls. Pitchers tested shortly after returning from UCL repair demonstrated reduced elbow extension, elbow velocity, and shoulder velocity compared to a control group, but it is unknown whether these few kinematic differences resolve with time. Pitchers with a history of SLAP repair produced less shoulder horizontal abduction, shoulder external rotation, and forward trunk tilt than matched controls. The Thoracic Outlet Syndrome case report demonstrated significantly more shoulder abduction after surgery. Thus the ability to return to normal pitching biomechanics after injury depends upon the type of surgery

Longitudinal biomarkers in amyotrophic lateral sclerosis

OBJECTIVE: To investigate neurodegenerative and inflammatory biomarkers in people with amyotrophic lateral sclerosis (PALS), evaluate their predictive value for ALS progression rates, and assess their utility as pharmacodynamic biomarkers for monitoring treatment effects. METHODS: De-identified, longitudinal plasma, and cerebrospinal fluid (CSF) samples from PALS (n = 108; 85 with samples from \u3e /=2 visits) and controls without neurological disease (n = 41) were obtained from the Northeast ALS Consortium (NEALS) Biofluid Repository. Seventeen of 108 PALS had familial ALS, of whom 10 had C9orf72 mutations. Additional healthy control CSF samples (n = 35) were obtained from multiple sources. We stratified PALS into fast- and slow-progression subgroups using the ALS Functional Rating Scale-Revised change rate. We compared cytokines/chemokines and neurofilament (NF) levels between PALS and controls, among progression subgroups, and in those with C9orf72 mutations. RESULTS: We found significant elevations of cytokines, including MCP-1, IL-18, and neurofilaments (NFs), indicators of neurodegeneration, in PALS versus controls. Among PALS, these cytokines and NFs were significantly higher in fast-progression and C9orf72 mutation subgroups versus slow progressors. Analyte levels were generally stable over time, a key feature for monitoring treatment effects. We demonstrated that CSF/plasma neurofilament light chain (NFL) levels may predict disease progression, and stratification by NFL levels can enrich for more homogeneous patient groups. INTERPRETATION: Longitudinal stability of cytokines and NFs in PALS support their use for monitoring responses to immunomodulatory and neuroprotective treatments. NFs also have prognostic value for fast-progression patients and may be used to select similar patient subsets in clinical trials

Radical-containing ultrafine particulate matter initiates epithelial-to-mesenchymal transitions in airway epithelial cells

Environmentally persistent free radicals (EPFRs) in combustion generated particulate matter (PM) are capable of inducing pulmonary pathologies and contributing to the development of environmental asthma. In vivo exposure of infant rats to EPFRs demonstrates their ability to induce airway hyperresponsiveness to methacholine, a hallmark of asthma. However, the mechanisms by which combustion-derived EPFRs elicit in vivo responses remain elusive. In this study, we used a chemically defined EPFR consisting of approximately 0.2 μm amorphrous silica containing 3% cupric oxide with the organic pollutant 1,2-dichlorobenzene (DCB-230). DCB-230 possesses similar radical content to urban-collected EPFRs but offers several advantages, including lack of contaminants and chemical uniformity. DCB-230 was readily taken up by BEAS-2B and at high doses (200 μg/cm2) caused substantial necrosis. At low doses (20 μg/cm2), DCB-230 particles caused lysosomal membrane permeabilization, oxidative stress, and lipid peroxidation within 24 hours of exposure. During this period, BEAS-2B underwent epithelial-to-mesenchymal transition (EMT), including loss of epithelial cell morphology, decreased E-cadherin expression, and increased α-smooth muscle actin (α-SMA) and collagen I production. Similar results were observed in neonatal air-liquid interface culture (i.e., disruption of epithelial integrity and EMT). Acute exposure of infant mice to DCB-230 resulted in EMT, as confirmed by lineage tracing studies and evidenced by coexpression of epithelial E-cadherin and mesenchymal α-SMA proteins in airway cells and increased SNAI1 expression in the lungs. EMT in neonatal mouse lungs after EPFR exposure may provide an explanation for epidemiological evidence supporting PM exposure and increased risk of asthma. Copyright © 2013 by the American Thoracic Society

Clinical map document based on XML (cMDX): document architecture with mapping feature for reporting and analysing prostate cancer in radical prostatectomy specimens

<p>Abstract</p> <p>Background</p> <p>The pathology report of radical prostatectomy specimens plays an important role in clinical decisions and the prognostic evaluation in Prostate Cancer (PCa). The anatomical schema is a helpful tool to document PCa extension for clinical and research purposes. To achieve electronic documentation and analysis, an appropriate documentation model for anatomical schemas is needed. For this purpose we developed cMDX.</p> <p>Methods</p> <p>The document architecture of cMDX was designed according to Open Packaging Conventions by separating the whole data into template data and patient data. Analogue custom XML elements were considered to harmonize the graphical representation (e.g. tumour extension) with the textual data (e.g. histological patterns). The graphical documentation was based on the four-layer visualization model that forms the interaction between different custom XML elements. Sensible personal data were encrypted with a 256-bit cryptographic algorithm to avoid misuse. In order to assess the clinical value, we retrospectively analysed the tumour extension in 255 patients after radical prostatectomy.</p> <p>Results</p> <p>The pathology report with cMDX can represent pathological findings of the prostate in schematic styles. Such reports can be integrated into the hospital information system. "cMDX" documents can be converted into different data formats like text, graphics and PDF. Supplementary tools like cMDX Editor and an analyser tool were implemented. The graphical analysis of 255 prostatectomy specimens showed that PCa were mostly localized in the peripheral zone (Mean: 73% ± 25). 54% of PCa showed a multifocal growth pattern.</p> <p>Conclusions</p> <p>cMDX can be used for routine histopathological reporting of radical prostatectomy specimens and provide data for scientific analysis.</p

A prognostic tool to identify adolescents at high risk of becoming daily smokers

<p>Abstract</p> <p>Background</p> <p>The American Academy of Pediatrics advocates that pediatricians should be involved in tobacco counseling and has developed guidelines for counseling. We present a prognostic tool for use by health care practitioners in both clinical and non-clinical settings, to identify adolescents at risk of becoming daily smokers.</p> <p>Methods</p> <p>Data were drawn from the Nicotine Dependence in Teens (NDIT) Study, a prospective investigation of 1293 adolescents, initially aged 12-13 years, recruited in 10 secondary schools in Montreal, Canada in 1999. Questionnaires were administered every three months for five years. The prognostic tool was developed using estimated coefficients from multivariable logistic models. Model overfitting was corrected using bootstrap cross-validation. Goodness-of-fit and predictive ability of the models were assessed by R², the c-statistic, and the Hosmer-Lemeshow test.</p> <p>Results</p> <p>The 1-year and 2-year probability of initiating daily smoking was a joint function of seven individual characteristics: age; ever smoked; ever felt like you needed a cigarette; parent(s) smoke; sibling(s) smoke; friend(s) smoke; and ever drank alcohol. The models were characterized by reasonably good fit and predictive ability. They were transformed into user-friendly tables such that the risk of daily smoking can be easily computed by summing points for responses to each item. The prognostic tool is also available on-line at <url>http://episerve.chumontreal.qc.ca/calculation_risk/daily-risk/daily_smokingadd.php</url>.</p> <p>Conclusions</p> <p>The prognostic tool to identify youth at high risk of daily smoking may eventually be an important component of a comprehensive tobacco control system.</p

The Health Informatics Trial Enhancement Project (HITE): Using routinely collected primary care data to identify potential participants for a depression trial

<p>Abstract</p> <p>Background</p> <p>Recruitment to clinical trials can be challenging. We identified anonymous potential participants to an existing pragmatic randomised controlled depression trial to assess the feasibility of using routinely collected data to identify potential trial participants. We discuss the strengths and limitations of this approach, assess its potential value, report challenges and ethical issues encountered.</p> <p>Methods</p> <p>Swansea University's Health Information Research Unit's Secure Anonymised Information Linkage (SAIL) database of routinely collected health records was interrogated, using Structured Query Language (SQL). Read codes were used to create an algorithm of inclusion/exclusion criteria with which to identify suitable anonymous participants. Two independent clinicians rated the eligibility of the potential participants' identified. Inter-rater reliability was assessed using the kappa statistic and inter-class correlation.</p> <p>Results</p> <p>The study population (N = 37263) comprised all adults registered at five general practices in Swansea UK. Using the algorithm 867 anonymous potential participants were identified. The sensitivity and specificity results > 0.9 suggested a high degree of accuracy from the algorithm. The inter-rater reliability results indicated strong agreement between the confirming raters. The Intra Class Correlation Coefficient (Cronbach's Alpha) > 0.9, suggested excellent agreement and Kappa coefficient > 0.8; almost perfect agreement.</p> <p>Conclusions</p> <p>This proof of concept study showed that routinely collected primary care data can be used to identify potential participants for a pragmatic randomised controlled trial of folate augmentation of antidepressant therapy for the treatment of depression. Further work will be needed to assess generalisability to other conditions and settings and the inclusion of this approach to support Electronic Enhanced Recruitment (EER).</p

A tool for examining the role of the zinc finger myelin transcription factor 1 (Myt1) in neural development: Myt1 knock-in mice

The Myt1 family of transcription factors is unique among the many classes of zinc finger proteins in how the zinc-stabilized fingers contact the DNA helix. To examine the function of Myt1 in the developing nervous system, we generated mice in which Myt1 expression was replaced by an enhanced Green Fluorescent Protein fused to a Codon-improved Cre recombinase as a protein reporter. Myt1 knock-in mice die at birth, apparently due to improper innervation of their lungs. Elimination of Myt1 did not significantly affect the number or distribution of neural precursor cells that normally express Myt1 in the embryonic spinal cord. Nor was the general pattern of differentiated neurons altered in the embryonic spinal cord. The Myt1 knock-in mice should provide an important tool for identifying the in vivo targets of Myt1 action and unraveling the role of this structurally distinct zinc finger protein in neural development

New Strategies for Combining Mindfulness with Integrative Cognitive Behavioral Therapy for the Treatment of Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) severely impacts social functioning, distress levels, and utilization of medical care compared with that of other major psychiatric disorders. Neither pharmacological nor psychotherapy interventions have adequately controlled cardinal symptoms of GAD: pervasive excessive anxiety and uncontrollable worry. Research has established cognitive behavioral therapy (CBT) as the most effective psychotherapy for controlling GAD; however, outcomes remain at only 50% reduction, with high relapse rates. Mindfulness has been integrated with CBT to treat people suffering from numerous psychiatric disorders, with mindfulness based stress reduction (MBSR) being the most researched. Preliminary evidence supports MBSR’s potential for controlling GAD symptoms and key researchers suggest mindfulness practices possess key elements for treating GAD. Classical mindfulness (CM) differs significantly from MBSR and possesses unique potentials for directly targeting process and state GAD symptoms inadequately treated by CBT. This article introduces the theory and practice of CM, its differences from MBSR, and a critical review of MBSR and CBT treatments for GAD. CM strategies designed to complement CBT targeting cardinal GAD symptoms are outlined with a case study illustrating its use