tbuckley/cabot-search huggingface dataset:
Examining the Effects of Prevention Programs on the Incidence of New Cases of Mental Disorders: The Lack of Statistical Power
Authors: Pim Cuijpers
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: In the past few decades about 1,000 controlled studies have examined the effects of mental health prevention programs, but few studies have examined the effects of such programs on the incidence of new cases of mental disorders defined according to diagnostic criteria. A major reason why so few studies have examined this important question is that very large numbers of subjects are needed to provide sufficient statistical power for these studies. In this article this power problem is explored. METHOD: Power calculations are presented for studies examining universal prevention (aimed at the general population regardless of risk status), selective prevention (aimed at high-risk groups), and indicated prevention (aimed at subjects who have some symptoms of a disorder without meeting full diagnostic criteria). RESULTS: Studies examining universal prevention are hardly feasible, as the number of subjects required amounts to tens of thousands at least. Research examining selective prevention is more feasible, but the number of subjects needed for these studies is still very high. Studies of indicated prevention are possible. Three major studies of indicated prevention examining the effects on the incidence of new cases of mental disorders are described. CONCLUSIONS: There are several strategies for increasing statistical power in prevention studies: 1) focus on high-incidence groups (by concentrating on indicated prevention, by targeting high-risk groups with multiple risk factors, by targeting groups with multiple disorders), 2) strengthen the effects of prevention programs, and 3) make more efficient use of other trials through cumulative meta-analyses.
Non-steroidal anti-inflammatory drug use and risk of atrial fibrillation or flutter: population based case-control study
Authors: M. Schmidt, C. F. Christiansen, F. Mehnert, K. J. Rothman, H. T. Sorensen
Journal: BMJ (2011)

<b>Objectives</b> To examine the risk of atrial fibrillation or flutter associated with use of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclo-oxygenase (COX) 2 inhibitors. <b>Design</b> Population based case-control study using data from medical databases. <b>Setting</b> Northern Denmark (population 1.7 million). <b>Participants</b> 32 602 patients with a first inpatient or outpatient hospital diagnosis of atrial fibrillation or flutter between 1999 and 2008; 325 918 age matched and sex matched controls based on risk-set sampling. <b>Main outcome measures</b> Exposure to NSAID use at the time of admission (current use) or before (recent use). Current use was further classified as new use (first ever prescription redemption within 60 days before diagnosis date) or long term use. We used conditional logistic regression to compute odds ratios as unbiased estimates of the incidence rate ratios. <b>Results</b> 2925 cases (9%) and 21 871 controls (7%) were current users of either non-selective NSAIDs or COX 2 inhibitors. Compared with no use, the incidence rate ratio associating current drug use with atrial fibrillation or flutter was 1.33 (95% confidence interval 1.26 to 1.41) for non-selective NSAIDs and 1.50 (1.42 to 1.59) for COX 2 inhibitors. Adjustments for age, sex, and risk factors for atrial fibrillation or flutter reduced the incidence rate ratio to 1.17 (1.10 to 1.24) for non-selective NSAIDs and 1.27 (1.20 to 1.34) for COX 2 inhibitors. Among new users, the adjusted incidence rate ratio was 1.46 (1.33 to 1.62) for non-selective NSAIDs and 1.71 (1.56 to 1.88) for COX 2 inhibitors. Results for individual NSAIDs were similar. <b>Conclusions</b> Use of non-aspirin NSAIDs was associated with an increased risk of atrial fibrillation or flutter. Compared with non-users, the association was strongest for new users, with a 40-70% increase in relative risk (lowest for non-selective NSAIDs and highest for COX 2 inhibitors). Our study thus adds evidence that atrial fibrillation or flutter needs to be added to the cardiovascular risks to be considered when prescribing NSAIDs.
Activated hypoxia‐inducible factor‐1α pathway modulates early events in stretch‐induced skin neovascularization via stromal cell‐derived factor‐1 and vascular endothelial growth factor
Authors: Y.M. Liang, X.L. Huang, G. Chen, L.L. Sheng, Q.F. Li
Journal: British Journal of Dermatology (2014)

Tissue expansion promotes skin regeneration. These responses occur only early after mechanical load and are then replaced by apoptosis-related events during stress relaxation. The mechanism modulating this transient process remains unknown.To elucidate key phenomena that drive early regenerative events after tissue expansion.Intraoperative tissue expansion was performed on 25 patients undergoing facial reconstruction. Paired skin biopsies were obtained from an expanded and unexpanded site from each patient. Differentially expressed genes were inspected by microarray and bioinformatic analysis, and dissected by quantitative polymerase chain reaction, Western blot and immunostaining. Paired biopsies from another nine patients undergoing cyclical expansion for 3 months were also investigated.A total of 124 upregulated and 282 downregulated genes were identified. Among them, the biological terms of extracellular matrix organization and blood vessel growth were most significantly enriched, as shown by Gene Ontology analysis. GeneMANIA dissection demonstrated an interactive network highlighted by the canonical hypoxia-inducible factor-1α (HIF-1α) pathway with stromal cell-derived factor-1 (SDF-1) and vascular endothelial growth factor (VEGFA) being the hub genes. Levels of the HIF-1α protein and its targets SDF-1 and VEGFA were elevated in expanded skin, and CD31 and Ki67 expression increased, indicating augmented vascularity and cell proliferation. Trafficking of CD34(+) CD133(+) endothelial progenitor cells was enhanced in skin undergoing long-time cyclical expansion, a phenomenon that was usually modulated by the HIF-1α pathway.The HIF-1α pathway is quickly activated and modulates early events in stretch-induced skin neovascularization. The effect may be augmented through enhanced endothelial progenitor cells recruitment into the expanded skin.
A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep
Authors: Alex Clop, Fabienne Marcq, Haruko Takeda, Dimitri Pirottin, Xavier Tordoir, Bernard Bibé, Jacques Bouix, Florian Caiment, Jean-Michel Elsen, Francis Eychenne, Catherine Larzul, Elisabeth Laville, Françoise Meish, Dragan Milenkovic, James Tobin, Carole Charlier, Michel Georges
Journal: Nature Genetics (2006)
Patellofemoral osteoarthritis coexistent with tibiofemoral osteoarthritis in a meniscectomy population
Authors: M Englund
Journal: Annals of the Rheumatic Diseases (2005)

To evaluate the frequency of patellofemoral osteoarthritis and its relevance to symptoms and function in a meniscectomy population.317 patients with no cruciate ligament injury were evaluated (mean (SD) age, 54 (11) years). They had undergone meniscal resection 15 to 22 years earlier (follow up rate 70%). Standing tibiofemoral and skyline patellofemoral radiographs were graded according to the OARSI atlas. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was used to quantify symptoms and function. Controls were 68 unoperated subjects identified from national population records.Patellofemoral osteoarthritis (isolated or coexisting with tibiofemoral osteoarthritis) was present in 66 of 317 index knees (21%) and 21 of 263 unoperated contralateral knees (8%, p<0.001). In 57/66 (86%) of these index knees, tibiofemoral osteoarthritis was present (mixed osteoarthritis). In a model adjusted for age, sex, and body mass index, the odds ratio for patellofemoral osteoarthritis (alone or in combination with tibiofemoral osteoarthritis) was 2.6 (95% confidence interval, 1.1 to 6.6) after medial meniscectomy and 5.3 (1.9 to 15.0) after lateral meniscectomy, using controls as the reference. Individuals with a mixed knee osteoarthritis pattern had more symptoms, lower function in sports and recreation, and worse knee related quality of life than subjects with isolated tibiofemoral osteoarthritis.Mixed patellofemoral and tibiofemoral osteoarthritis is common in a meniscectomy population. Patellofemoral osteoarthritis is a contributing cause of knee symptoms and reduced knee related quality of life and is relevant to the management of knee complaints of this group of patients.
3-Year Suppression of HIV Viremia with Indinavir, Zidovudine, and Lamivudine
Authors: Roy M. Gulick, John W. Mellors, Diane Havlir, Joseph J. Eron, Anne Meibohm, Jon H. Condra, Fred T. Valentine, Deborah McMahon, Charles Gonzalez, Leslie Jonas, Emilio A. Emini, Jeffrey A. Chodakewitz, Robin Isaacs, Douglas D. Richman
Journal: Annals of Internal Medicine (2000)

Background: Antiretroviral regimens containing HIV protease inhibitors suppress viremia in HIV-infected patients, but the durability of this effect is not known. Objective: To describe the 3-year follow-up of patients randomly assigned to receive indinavir, zidovudine, and lamivudine in an ongoing clinical trial. Design: Open-label extension of a randomized, double-blind study. Setting: Four clinical research units. Patients: 33 HIV-infected, zidovudine-experienced patients with serum HIV RNA levels of at least 20 000 copies/mL and CD4 counts ranging from 50 to 400 cells/mm3. Intervention: Indinavir, zidovudine, and lamivudine. Measurements: Safety assessments, HIV RNA levels, CD4 cell counts, and genotypic analyses. Results: After 3 years of follow-up, 21 of 31 contributing patients (68% [95% CI, 49% to 83%]) had serum viral load levels less than 500 copies/mL. Twenty of 31 (65% [CI, 45% to 80%]) had levels less than 50 copies/mL. The median increase in CD4 count from baseline was 230 cells/mm3 (interquartile range, 150 to 316 cells/mm3). Nephrolithiasis occurred in 12 of 33 patients (36%). Conclusion: A three-drug regimen of indinavir, zidovudine, and lamivudine suppressed viremia in two thirds of patients for at least 3 years.
Cellular Mechanisms Underlying the Development of Catecholaminergic Ventricular Tachycardia
Authors: Gi-Byoung Nam, Alexander Burashnikov, Charles Antzelevitch
Journal: Circulation (2005)

Mutations in the ryanodine 2 receptor (RyR2) gene have been identified in patients with catecholaminergic polymorphic ventricular tachycardia. We examined the cellular basis for the ECG features and arrhythmia mechanisms using low-dose caffeine to mimic the defective calcium homeostasis encountered under these conditions.A transmural ECG and action potentials were recorded simultaneously from epicardial, M, and endocardial cells in arterially perfused canine ventricular wedge preparations. Caffeine alone produced no change (10 to 100 micromol/L) or a slight abbreviation (300 micromol/L) of the QT interval and no change in transmural dispersion of repolarization. Isoproterenol (100 nmol/L) alone induced sustained monomorphic ventricular tachycardia (VT) that originated in the epicardium in 3 of 14 wedge preparations. Isoproterenol in the presence of caffeine (100 to 300 micromol/L) induced epicardial VT in 9 of 16 wedge preparations. Delayed afterdepolarization-induced triggered beats that originated in the epicardium were associated with an increased Tpeak-Tend interval and transmural dispersion of repolarization. Bidirectional VT developed in 11 of 16 wedge preparations as a consequence of alternation in the origin of ectopic activity between endocardial, M, and epicardial regions. Single extrastimuli delivered during sustained epicardial VT induced a rapid polymorphic VT/ventricular fibrillation (VF) in 3 of 9 wedges. Spontaneous polymorphic VT was observed in 3 of 16 preparations. Propranolol (1.0 micromol/L) or verapamil (1.0 micromol/L) completely suppressed ectopic activity that arose from the epicardium and prevented induction of polymorphic VT.Our data suggest delayed afterdepolarization-induced extrasystolic activity serves to trigger catecholamine-induced VT/VF under conditions of defective calcium handling. Epicardial origin of the ectopic beats increases transmural dispersion of repolarization, thus providing the substrate for the development of reentrant tachyarrhythmias that underlie rapid polymorphic VT/VF.
Pre- and Postdiagnosis Physical Activity, Television Viewing, and Mortality Among Patients With Colorectal Cancer in the National Institutes of Health–AARP Diet and Health Study
Authors: Hannah Arem, Ruth M. Pfeiffer, Eric A. Engels, Catherine M. Alfano, Albert Hollenbeck, Yikyung Park, Charles E. Matthews
Journal: Journal of Clinical Oncology (2014)

Physical inactivity has been associated with higher mortality risk among survivors of colorectal cancer (CRC), but the independent effects of pre- versus postdiagnosis activity are unclear, and the association between watching television (TV) and mortality in survivors of CRC is previously undefined.We analyzed the associations between prediagnosis (n = 3,797) and postdiagnosis (n = 1,759) leisure time physical activity (LTPA) and TV watching and overall and disease-specific mortality among patients with CRC. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs, adjusting for known mortality risk factors.Comparing survivors of CRC reporting more than 7 hours per week (h/wk) of prediagnosis LTPA with those reporting no LTPA, we found a 20% lower risk of all-cause mortality (HR, 0.80; 95% CI, 0.68 to 0.95; P for trend = .021). Postdiagnosis LTPA of ≥ 7 h/wk, compared with none, was associated with a 31% lower all-cause mortality risk (HR, 0.69; 95% CI, 0.49 to 0.98; P for trend = .006), independent of prediagnosis activity. Compared with 0 to 2 TV hours per day (h/d) before diagnosis, those reporting ≥ 5 h/d of TV before diagnosis had a 22% increased all-cause mortality risk (HR, 1.22; 95% CI, 1.06 to 1.41; P trend = .002), and more postdiagnosis TV watching was associated with a nonsignificant 25% increase in all-cause mortality risk (HR, 1.25; 95% CI, 0.93 to 1.67; P for trend = .126).LTPA was inversely associated with all-cause mortality, whereas more TV watching was associated with increased mortality risk. For both LTPA and TV watching, postdiagnosis measures independently explained the association with mortality. Clinicians should promote both minimizing TV time and increasing physical activity for longevity among survivors of CRC, regardless of previous behaviors.
Tidal breathing parameters in the first week of life and subsequent cough and wheeze.
Authors: B. Yuksel, A. Greenough, F. Giffin, K. H. Nicolaides
Journal: Thorax (1996)

BACKGROUND: Assessment of tidal breathing parameters may be a useful method of predicting respiratory problems in early childhood. Low values of TPTEF/TE (the ratio of the proportion of time to reach peak tidal expiratory flow to total expiratory time) outside the neonatal period have been significantly related to respiratory tract illness with wheezing in boys in the first year of life. METHODS: TPTEF/TE measurements in the perinatal period were evaluated in nonsedated infants and the predictive value of this early measurement for subsequent respiratory morbidity during infancy was assessed. Flow during tidal breathing was measured while the infant slept quietly in a plethysmograph using a Fleisch pneumotachograph inserted into an infant face mask. Recruitment continued until traces from 60 infants with 10 consecutive flow curves without artefacts were obtained. In addition, plethysmographic measurements of airway resistance (Raw) and thoracic gas volume (TGV) were measured and specific conductance (sGaw) calculated. Parents recorded their infant9s cough and wheeze during the first 12 months of life. RESULTS: Sixty five measurements were made in 60 infants with a mean age of two days and gestational age of 40 weeks. Two observers separately calculated TPTEF/TE ratios on 25 traces randomly selected from the pool of 60. The mean difference between the two observers was -0.004 (limits of agreement 0.048 to -0.056). Thirteen infants became symptomatic (wheeze, with or without cough); their median TPTEF/TE ratio (0.349) was significantly lower than the rest of the cohort (median 0.412) and they also had significantly higher Raw and lower sGaw. The positive predictive value of a low TPTEF/TE ratio, however, was only 41%. CONCLUSIONS: These results suggest that the use of this test in the prediction of future respiratory disease in an individual is limited.
Ontogeny of the Human Complement System: In Vitro Biosynthesis of Individual Complement Components by Fetal Tissues
Authors: Harvey R. Colten
Journal: Journal of Clinical Investigation (1972)

The human fetal liver is capable of synthesizing the biologically active form of the second (C2) and fourth (C4) components of complement as early as 8 wk after conception, and the inhibitor of C1 (C1 INH) as early as 11 wk after conception. Biologically active C3 was produced in vitro by fetal liver obtained at 14 wk gestation. These conclusions were based on the observations that isolated fetal livers produced biologically active C2, C3, C4, and C1 INH, that this production was temperature dependent and reversibly inhibited by well-known inhibitors of protein synthesis, and that (14)C-labeled amino acids were incorporated into proteins immunochemically identical with these proteins. The data suggested that a large mononuclear cell was the cell type in the fetal liver that synthesized C2 and C4.
Gene Expression Profiling of Liposarcoma Identifies Distinct Biological Types/Subtypes and Potential Therapeutic Targets in Well-Differentiated and Dedifferentiated Liposarcoma
Authors: Samuel Singer, Nicholas D. Socci, Grazia Ambrosini, Elliot Sambol, Penelope Decarolis, Yuhsin Wu, Rachael O'Connor, Robert Maki, Agnes Viale, Chris Sander, Gary K. Schwartz, Cristina R. Antonescu
Journal: Cancer Research (2007)

Abstract Classification of liposarcoma into three biological types encompassing five subtypes, (a) well-differentiated/dedifferentiated, (b) myxoid/round cell, and (c) pleomorphic, based on morphologic features and cytogenetic aberrations, is widely accepted. However, diagnostic discordance remains even among expert sarcoma pathologists. We sought to develop a more systematic approach to liposarcoma classification based on gene expression analysis and to identify subtype-specific differentially expressed genes that may be involved in liposarcoma genesis/progression and serve as potential therapeutic targets. A classifier based on gene expression profiling was able to distinguish between liposarcoma subtypes, lipoma, and normal fat samples. A 142-gene predictor of tissue class was derived to automatically determine the class of an independent validation set of lipomatous samples and shows the feasibility of liposarcoma classification based entirely on gene expression monitoring. Differentially expressed genes for each liposarcoma subtype compared with normal fat were used to identify histology-specific candidate genes with an in-depth analysis of signaling pathways important to liposarcoma pathogenesis and progression in the well-differentiated/dedifferentiated subset. The activation of cell cycle and checkpoint pathways in well-differentiated/dedifferentiated liposarcoma provides several possible novel therapeutic strategies with MDM2 serving as a particularly promising target. We show that Nutlin-3a, an antagonist of MDM2, preferentially induces apoptosis and growth arrest in dedifferentiated liposarcoma cells compared with normal adipocytes. These results support the development of a clinical trial with MDM2 antagonists for liposarcoma subtypes which overexpress MDM2 and show the promise of using this expression dataset for new drug discovery in liposarcoma. [Cancer Res 2007;67(14):6626–36]
Hereditary Cerebellar Ataxy in Two Brothers
Authors: J. M. Clarke
Journal: BMJ (1902)

9--~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ of-urine were drawn off; there was dribbling incontinence.There was a large burn on the right buttock about 4 il. in diameter.Nervous system: Meatalvacuity and incoherence in speech.He slept well; the para- plegLa of lower limbs was almost complete.Over the lower dorsal area there was a difuse hyperaesthetic area, but nowhere was there any aboli- tion of sensation and handling his lower limbs caused much pain.His superflcial and deep reflexes were present but not exaggerated.He had drlbbling incontinence of urine and involuntaty evacuation of faeces.There was tenderness over the last lumbar and first sacral spines.The grip of both hands was very feeble, but no absolute paralysis.The left ipupil was larger than the right, but both responded to light and accom- modation.Respirations 2A, alight cough and tough mucous expectora- tion, expansion of chest fairly good and percussion clear, a few course r4fs over right lower lobe.Pulse 78, regular in time and force, tension fair, arteries contracted.The cardiac area is normal, apex beat diffuse.di fourth and fifth interspaces I in.internal to nipple line.Occasional doubling of both sounds but no murmur.Teeth bad tongue clean, no pain after food, stomach somewhat dilated, hepatic ana splenic dullness aormal, urine alkaline, specific gravity 0oi5, no albumen, blood, or sugar, chlorides excessive.His temperature, on admission 100.40, rose the fol- Qlowing day to 1030 F.He was placed in the prone position, had an icebag applied to the spine and was ordered urotropin and a milk diet.P-olgyress.-May 24th.During the last twenty-four hours 86 oz. of urine were drawn off.His pulse was small, firm, and vessels much contracted; extremities very cold.His temperature was 99.20 this morning, and rose to 3or.60 F. in the evening.Lumbar puncture was performed, and clear cerebro-spinal fluid drawn ofi.which on microscopical examination and on culture was found to contain staphylococei.1g Quininae sulphatis 36 gr., acidi hydrobromicl dil.3i, liq.trinitrini mxii, aq.ad.3vi.!ss every four hours.lEs Hydrarg.Subchlor.4g. ; to be taken at once.May .Isth.He had four involuntary motions; 78 oz. of urine drawn off to-day.Wemperature 99.20 and :oo.80 F. May x6th.To-day over the whole upper tobe of right lung the percussion note was impaired, breathing harsh and tubular.The sputum contained diplococci, but no tubercle bacilli; 107 Oz. of decomposing urine were drawn off.Temperature 98.40 and 99.60 F. May 17th.Patient had a good night, and feels much better to- day.The upper lobe of right lung is solid, expectoration thick muco- us and tinged with blood; 67oz. of foul ammoniacal urine drawn off;
Increased risk of infections and infection-related mortality in children undergoing haematopoietic stem cell transplantation compared to conventional anticancer therapy: a multicentre nationwide study
Authors: J. Styczynski, K. Czyzewski, M. Wysocki, O. Gryniewicz-Kwiatkowska, A. Kolodziejczyk-Gietka, M. Salamonowicz, L. Hutnik, O. Zajac-Spychala, A. Zaucha-Prazmo, L. Chelmecka-Wiktorczyk, K. Siewiera, J. Fraczkiewicz, Z. Malas, R. Tomaszewska, N. Irga-Jaworska, M. Plonowski, T. Ociepa, F. Pierlejewski, Z. Gamrot, A. Urbanek-Dadela, J. Gozdzik, W. Stolpa, B. Dembowska-Baginska, D. Perek, M. Matysiak, J. Wachowiak, J. Kowalczyk, W. Balwierz, K. Kalwak, A. Chybicka, W. Badowska, T. Szczepanski, E. Drozynska, M. Krawczuk-Rybak, T. Urasinski, W. Mlynarski, M. Woszczyk, G. Karolczyk, G. Sobol-Milejska, L. Gil
Journal: Clinical Microbiology and Infection (2015)