tbuckley/cabot-search huggingface dataset:
Assessment of the performance of electrocardiographic computer programs with the use of a reference data base.
Authors: J L Willems, P Arnaud, J H van Bemmel, P J Bourdillon, C Brohet, S Dalla Volta, J D Andersen, R Degani, B Denis, M Demeester
Journal: Circulation (1985)

To allow an exchange of measurements and criteria between different electrocardiographic (ECG) computer programs, an international cooperative project has been initiated aimed at standardization of computer-derived ECG measurements. To this end an ECG reference library of 250 ECGs with selected abnormalities was established and a comprehensive reviewing scheme was devised for the visual determination of the onsets and offsets of P, QRS, and T waves. This task was performed by a group of cardiologists on highly amplified, selected complexes from the library of ECGs. With use of a modified Delphi approach, individual outlying point estimates were eliminated in four successive rounds. In this way final referee estimates were obtained that proved to be highly reproducible and precise. This reference data base was used to study measurement results obtained with nine vectorcardiographic and 10 standard 12-lead ECG analysis programs. The medians of program determinations of P, QRS, and T wave onsets and offsets were close to the final referee estimates. However, an important variability could be demonstrated between measurements from individual programs and mean differences from the referee estimates amounted to 10 msec for QRS for certain programs. In addition, the variances of all programs with respect to the referee point estimates were variable. Some programs proved to be more accurate and stable when the data from high- vs low-noise recordings were analyzed. Average Q wave durations calculated from ECGs for which programs agreed on the presence of a Q or QS wave differed by more than 8 msec in several program-to-program comparisons. Such differences may have important consequences with respect to diagnostic performance. Various factors that might explain these differences have been determined. The present study demonstrates that to allow an exchange of results and diagnostic criteria between different ECG computer programs, definitions, minimum wave requirements, and measurement procedures urgently need to be standardized.
Genetic counselors: translating genomic science into clinical practice
Authors: Robin L. Bennett, Heather L. Hampel, Jessica B. Mandell, Joan H. Marks
Journal: Journal of Clinical Investigation (2003)

In a time of emerging genetic tests and technologies, genetic counselors are faced with the challenge of translating complex genomic data into information that will aid their client’s ability to learn about, understand, make, and cope with decisions relating to genetic diagnoses. The first of two companion articles in this issue examines the role of the genetic counselor, particularly in counseling individuals at risk for or diagnosed with breast cancer, in an era of high-tech health care and gene patents.
To Live—To Die
Authors: Thomas J. O'Donnell
Journal: JAMA (1974)

None would deny that death is more definitive than even a double-blind experiment; yet, while nearly equal amounts of ethical ink have been spilled about prolongation of life and about human experimentation, the question of consent has been exhaustively studied in relation to the latter, but seldom explored in the context of the former. While those of us who oppose positive euthanasia do so on the grounds that the physician should not kill, let us admit that there are some few who tend to see a bit of death-dealing as part of the physician's role; yet even most of these would add: "but only with the consent of the patient" (although to feel free to kill, but yet scruple about consent, might suggest an unusual priority of ethical values). It is not my purpose here to debate the moral aspects of so-called positive and negative euthanasia (a new terminology that
EFFICIENCY OF CHADS2 SCORING SYSTEM IN PREDICTION OF THROMBOEMBOLIC RISK: 10-YEAR SURVEY OF OVER 3000 STUDIES
Authors: Hirad Yarmohammadi, Tristan Klosterman, Brandon Varr, Bruce Lindsey, Andrew Zurick, Kevin Shrestha, Wai Hong Wilson Tang, Allan L. Klein
Journal: Journal of the American College of Cardiology (2010)
Fertility (update): summary of NICE guidance
Authors: E. Fields, J. Chard, D. James, T. Treasure
Journal: BMJ (2013)

Infertility affects about one in seven couples in the United Kingdom1 and can have a severe psychological impact.2 Since publication in 2004 of the original fertility guideline by the then National Institute for Clinical Excellence (NICE),3 more people are now having fertility treatment, which is increasingly successful.4 5 It is mandatory that this care is appropriate. This article summarises the recommendations relevant to general clinicians from the recent update of NICE's fertility guideline.6 NICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness. When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice. Evidence levels for the recommendations are given in italic in square brackets. ### Information on conception
Telephone-Based Self-management of Osteoarthritis
Authors: Kelli D. Allen, Eugene Z. Oddone, Cynthia J. Coffman, Santanu K. Datta, Karen A. Juntilla, Jennifer H. Lindquist, Tessa A. Walker, Morris Weinberger, Hayden B. Bosworth
Journal: Annals of Internal Medicine (2010)

Background: Osteoarthritis is a leading cause of pain and disability, and self-management behaviors for osteoarthritis are underutilized. Objective: To examine the effectiveness of a telephone-based self-management intervention for hip or knee osteoarthritis in a primary care setting. Design: Randomized clinical trial with equal assignment to osteoarthritis self-management, health education (attention control), and usual care control groups. (ClinicalTrials.gov registration number: NCT00288912) Setting: Primary care clinics in a Veterans Affairs Medical Center. Patients: 515 patients with symptomatic hip or knee osteoarthritis. Intervention: The osteoarthritis self-management intervention involved educational materials and 12 monthly telephone calls to support individualized goals and action plans. The health education intervention involved nonosteoarthritis educational materials and 12 monthly telephone calls related to general health screening topics. Measurements: The primary outcome was score on the Arthritis Impact Measurement Scales-2 pain subscale (range, 0 to 10). Pain was also assessed with a 10-cm visual analog scale. Measurements were collected at baseline and 12 months. Results: 461 participants (90%) completed the 12-month assessment. The mean Arthritis Impact Measurement Scales-2 pain score in the osteoarthritis self-management group was 0.4 point lower (95% CI, −0.8 to 0.1 point; P = 0.105) than in the usual care group and 0.6 point lower (CI, −1.0 to −0.2 point; P = 0.007) than in the health education group at 12 months. The mean visual analog scale pain score in the osteoarthritis self-management group was 1.1 points lower (CI, −1.6 to −0.6 point; P < 0.001) than in the usual care group and 1.0 point lower (CI, −1.5 to −0.5 point; P < 0.001) than in the health education group. Health care use did not differ across the groups. Limitation: The study was conducted at 1 Veterans Affairs Medical Center, and the sample consisted primarily of men. Conclusion: A telephone-based osteoarthritis self-management program produced moderate improvements in pain, particularly compared with a health education control group. Primary Funding Source: U.S. Department of Veterans Affairs Health Services Research and Development Service.
X-Linked Inhibitor of Apoptosis Protein (XIAP) Is a Nonredundant Modulator of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)- Mediated Apoptosis in Human Cancer Cells
Authors: Jordan M. Cummins, Manu Kohli, Carlo Rago, Kenneth W. Kinzler, Bert Vogelstein, Fred Bunz
Journal: Cancer Research (2004)

Abstract Although the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to play an important role in the immunosurveillance of neoplasia, apoptotic factors that modulate the sensitivity of cancer cells to TRAIL are poorly understood. The inhibitor of apoptosis proteins (IAPs) have generated considerable interest as potential targets for cancer therapy, but the lack of a phenotype in X-linked IAP (XIAP) knockout mice has generated speculation that IAP function may be redundant. Using gene targeting technology, we show that disruption of the gene encoding XIAP in human cancer cells did not interfere with basal proliferation, but caused a remarkable sensitivity to TRAIL. These results demonstrate that XIAP is a nonredundant modulator of TRAIL-mediated apoptosis and provide a rationale for XIAP as a therapeutic target.
CORONARY MICROVASCULAR DYSFUNCTION IN PRIMARY HYPERPARATHYROIDISM PATIENTS: A HINT FOR THEIR INCREASED CARDIOVASCULAR RISK
Authors: Elena Osto, Maria R Pellizzo, Francesco Fallo, Anna Maddalozzo, Nadia Sorgato, Roberta Montisci, Sabino Iliceto, Francesco Tona
Journal: Journal of the American College of Cardiology (2010)
A fast and sensitive method for measuring the integrity of siRNA-carrier complexes in full human serum
Authors: Kevin Buyens, Bart Lucas, Koen Raemdonck, Kevin Braeckmans, Jo Vercammen, Jelle Hendrix, Yves Engelborghs, Stefaan C. De Smedt, Niek N. Sanders
Journal: Journal of Controlled Release (2007)
Authors' reply to Mosholder and colleagues
Authors: C. Y. Lu, G. Simon, S. B. Soumerai
Journal: BMJ (2014)

We are glad that Mosholder and colleagues agree that psychotropic poisonings increased, not decreased, after the warnings and news reports.1 2 We believe that debate in this area is instructive for all those looking at nationwide health policies that cannot be studied using randomised controlled trials.3

As discussed in the online comments, Mosholder and colleagues mis-state our conclusion. We did not conclude that “antidepressant warnings discouraged appropriate pharmacotherapy for depression.” We stated repeatedly in the article and National Institute of Mental Health proposal that the most important intervention was the alarming worldwide publicity that exaggerated the FDA warnings. This was immediately accompanied by reductions in antidepressant use (as corroborated by Mosholder and colleagues’ older data), small increases in suicide attempts by psychotropic drug poisoning (possibly owing to undertreatment of mood …
Obatoclax Mesylate, a Pan–Bcl-2 Inhibitor, in Combination with Docetaxel in a Phase 1/2 Trial in Relapsed Non–Small-Cell Lung Cancer
Authors: Alberto Chiappori, Charles Williams, Donald W. Northfelt, John W. Adams, Shakun Malik, Martin J. Edelman, Peter Rosen, David A. Van Echo, Mark S. Berger, Eric B. Haura
Journal: Journal of Thoracic Oncology (2013)
Two thirds of Welsh district hospitals have higher than predicted mortality, figures show
Authors: S. Mayor
Journal: BMJ (2013)

Two thirds of district general hospitals in Wales have death rates that are higher than predicted by risk adjusted figures, show mortality data made public for the first time this week.1 2

Six of Wales’s seven local health boards published risk adjusted mortality index figures on their websites for individual hospitals as part of the Welsh government’s commitment to improving availability of information. The seventh board, Powys Teaching, doesn’t have any district general hospitals (those that provide acute and secondary or tertiary care).

The index …
Reduction of Cytosolic p27Kip1 Inhibits Cancer Cell Motility, Survival, and Tumorigenicity
Authors: Frederick Y. Wu, Shizhen Emily Wang, Melinda E. Sanders, Incheol Shin, Federico Rojo, Jose Baselga, Carlos L. Arteaga
Journal: Cancer Research (2006)

We generated a p27(Kip1) mutant (p27deltaNLS) that localized exclusively in cell cytosol. Expression of p27deltaNLS in MCF7 breast cancer cells down-regulated RhoA and increased motility, survival, and Akt levels without an effect on cell cycle distribution. RNA interference of p27 in U87 glioma cells, which express p27 predominantly in the cytoplasm, inhibited motility and survival. Conversely, knockdown of p27 in COS7 cells, with >95% nuclear p27 expression, accelerated proliferation but had no effect on motility or survival. U87 cells in which p27 had been eliminated by RNA interference exhibited lower Akt levels, shorter Akt turnover, and markedly impaired tumorigenicity in vivo. These xenografts were less invasive and exhibited increased apoptosis compared with p27-expressing tumors. Expression of cytosolic p27 in primary human breast carcinomas correlated linearly with Akt content as measured by immunohistochemistry. These data suggest that cytoplasmic p27 can exert oncogenic functions by modulating Akt stability, cell survival, and tumorigenicity.
Magnitude and Duration of the Effect of Sepsis on Survival
Authors: Andrew A. Quartin
Journal: JAMA (1997)

To determine the magnitude and duration of the effects of sepsis on survival.Cohort study.The 10 Department of Veterans Affairs Medical Centers of the Systemic Sepsis Cooperative Studies Group, which from 1983 to 1986 conducted the Department of Veterans Affairs Cooperative Study of Corticosteroids in Systemic Sepsis.The septic population consisted of 1505 patients with evaluable data from the screening log of the Cooperative Study of Corticosteroids in Systemic Sepsis. All 91830 nonpsychiatric, noninfected patients discharged from the participating medical centers between October 1, 1984, and September 30, 1985, were included in the control population.Death through 8 years after the index hospitalization.On the basis of a proportional hazards model constructed from the demographic and illness characteristics of the control population, the septic population was at significant risk of dying of nonseptic causes (26% predicted 1-year mortality). In the septic population, the daily risk of dying exceeded predictions from this model for 5 years, and the hazard rate rose with increasing severity of the septic episode throughout the first year (P<.05). Among 30-day survivors, sepsis reduced the remaining mean life span from a predicted 8.03 years to 4.08 years.Sepsis not only causes deaths acutely, but also increases the risk of death for up to 5 years after the septic episode even after comorbidities are accounted for. The risk of late death during the first year is associated with the severity of the septic episode.
Retention of skills by advanced trained ambulance staff: implications for monitoring and retraining.
Authors: G. Walters, E. Glucksman
Journal: BMJ (1989)

time of the operation but also because inpatient investigations and treatment are necessary.Revision operations take longer to perform than the equivalent primary procedure and are certainly more expensive in terms of the consumabie items used.Twenty five out of 36 of the exchange arthroplasties used cement impregnated with antibiotic, and 27 required non-standard implants.The cost of antibiotics was over 10 times that incurred with primary surgery because combined, often parenteral, treatment with expensive drugs was given for long periods.To reduce the costs to the patient and the NHS all efforts must ensure that a primary joint replacement is as successful as possible.We caution against short term economies, which may well produce considerable clinical and financial burdens in the long term.We thank Miss Margaret Richardson, principal pharmacist, and theatre sisters Margaret Douglas
Blocking the Protease-Activated Receptor 1-4 Heterodimer in Platelet-Mediated Thrombosis
Authors: Andrew J. Leger, Suzanne L. Jacques, Jehangir Badar, Nicole C. Kaneider, Claudia K. Derian, Patricia Andrade-Gordon, Lidija Covic, Athan Kuliopulos
Journal: Circulation (2006)

Thrombin is the most potent agonist of platelets and plays a critical role in the development of arterial thrombosis. Human platelets express dual thrombin receptors, protease-activated receptor (PAR) 1 and PAR4; however, there are no therapeutic strategies that effectively target both receptors.Platelet aggregation studies demonstrated that PAR4 activity is markedly enhanced by thrombin-PAR1 interactions. A combination of bivalirudin (hirulog) plus a novel PAR4 pepducin antagonist, P4pal-i1, effectively inhibited aggregation of human platelets to even high concentrations of thrombin and prevented occlusion of carotid arteries in guinea pigs. Likewise, combined inhibition of PAR1 and PAR4 with small-molecule antagonists and pepducins was effective against carotid artery occlusion. Coimmunoprecipitation and fluorescence resonance energy transfer studies revealed that PAR1 and PAR4 associate as a heterodimeric complex in human platelets and fibroblasts. PAR1-PAR4 cofactoring was shown by acceleration of thrombin cleavage and signaling of PAR4 on coexpression with PAR1.We show that PAR1 and PAR4 form a stable heterodimer that enables thrombin to act as a bivalent functional agonist. These studies suggest that targeting the PAR1-PAR4 complex may present a novel therapeutic opportunity to prevent arterial thrombosis.
Congenitally hypothyroid mice yield clues for man
Authors: Gail McBride
Journal: JAMA (1982)

What appears to be a good animal model for 80% of cases of human congenital hypothyroidism is being studied intensively at The Jackson Laboratory, Bar Harbor, Me, and a dozen or so other laboratories. Wesley Beamer, PhD, a staff scientist at The Jackson Laboratory, first discovered the mutation around the end of 1975 in a female laboratory mouse, although he first thought it was a deficiency of growth hormone. Further breeding of the mouse and its progeny led to the conclusion that the phenotype was due to an autosomal recessive gene. Eva Eicher, PhD, also of the laboratory, then mapped the gene to chromosome 12 in the mouse. (The gene or genes that may be related to some or all cases of human congenital hypothyroidism have not been mapped.) Thyroid glands in the affected (<i>hyt/hyt</i>) mice are of small size and very hypoplastic, similar to those in 80% of infants
THE TREATMENT OF DEPRESSION IN HOSPITALIZED PATIENTS BEFORE AND SINCE THE INTRODUCTION OF ANTIDEPRESSANT DRUGS
Authors: WILLIAM J. TURNER, FRANCIS J. O'NEILL, SIDNEY MERLIS
Journal: American Journal of Psychiatry (1962)

A study of the rates of admission, therapy and outcome of depressed patients at Central Islip State Hospital for the two years 1955 and 1960 is reported. A drop in the admission rate for the more severely psychotic depressions has been balanced by a rise in admission rate of reactive and neurotic depressions. The high value of EST in the severe depressions is again revealed by our data. There is evidence for high value of phenothiazines in the agitated and in the neurotic depressions. There has been surprisingly little use of the MAO inhibitors and of imipramine, despite the reported value of these drugs. The hopeful, protective and supportive attitude of admission services is in itself highly therapeutic. All in all, the present prognosis for a depressed patient admitted to hospital is highly favorable and constantly improving.
Eradication of non-Hodgkin lymphoma through the induction of tumor-specific T-cell immunity by CD20-Flex BiFP
Authors: Lei Zhao, Qin Tong, Weizhu Qian, Bohua Li, Dapeng Zhang, Tuo Fu, Shuyan Duan, Xueguang Zhang, Jian Zhao, Jianxin Dai, Hao Wang, Sheng Hou, Yajun Guo
Journal: Blood (2013)

Although monoclonal antibodies, including CD20 antibody rituximab, are standard therapeutics for several cancers, their efficacy remains variable and often modest. There is an urgent need to enhance the efficacy of the current generation of anticancer antibodies. Flt3 ligand, a soluble protein, has the ability to induce substantial expansion of dendritic cells (DCs). In this study, we constructed a bispecific immunoglobulin G-like bispecific fusion protein (BiFP) targeting both CD20 and Flt3 (CD20-Flex) by using CrossMab technology. We found that the BiFP exhibited stabilities that were comparable with the parental antibody rituximab and were able to bind to both targets with unaltered binding affinity. Notably, our data indicated that CD20-Flex BiFP could not only eliminate lymphoma temporarily but also potentiate tumor-specific T-cell immunity, which affords a long-lasting protection from tumor recurrence. The results showed that the expansion and infiltration of DCs into tumor tissues by CD20-Flex BiFP could be an effective way to generate protective immune responses against cancer, suggesting that the CD20-Flex BiFP could be a promising therapeutic agent against B-cell lymphomas.
CD4 and CD8 T-Lymphocyte Apoptosis Can Predict Radiation-Induced Late Toxicity: A Prospective Study in 399 Patients
Authors: Mahmut Ozsahin, Nigel E.A. Crompton, Sophie Gourgou, Andrew Kramar, Ling Li, YuQuan Shi, Wendy Jeanneret Sozzi, Abderrahim Zouhair, René O. Mirimanoff, David Azria
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Predicting late effects in patients treated with radiation therapy by assessing in vitro radiation-induced CD4 and CD8 T-lymphocyte apoptosis can be useful in individualizing treatment. Experimental Design: In a prospective study, 399 curatively irradiated patients were tested using a rapid assay where fresh blood samples were in vitro irradiated with 8 Gy X-rays. Lymphocytes were collected and prepared for flow cytometric analysis. Apoptosis was assessed by associated condensation of DNA. The incidences of late toxicities were compared for CD4 and CD8 T-lymphocyte apoptoses using receiver-operating characteristic curves and cumulative incidence. Results: No association was found between early toxicity and T-lymphocyte apoptosis. Grade 2 and 3 late toxicities were observed in 31% and 7% of patients, respectively. More radiation-induced T-lymphocyte apoptosis was significantly associated with less grade 2 and 3 late toxicity (Gray's test, P &amp;lt; 0.0001). CD8 (area under the curve = 0.83) was more sensitive and specific than CD4. No grade 3 late toxicity was observed for patients with CD4 and CD8 values greater than 15% and 24%, respectively. The 2-year cumulative incidence for grade 2 or 3 late toxicity was 70%, 32%, and 12% for patients with absolute change in CD8 T-lymphocyte apoptosis of ≤16, 16 to 24, and &amp;gt;24, respectively. Conclusions: Radiation-induced T-lymphocyte apoptosis can significantly predict differences in late toxicity between individuals. It could be used as a rapid screen for hypersensitive patients to radiotherapy. In future dose escalation studies, patients could be selected using the apoptosis assay.