tbuckley/cabot-search huggingface dataset:
Sports injuries and illnesses in the 2009 FINA World Championships (Aquatics)
Authors: Margo Mountjoy, Astrid Junge, Juan Manuel Alonso, Lars Engebretsen, Ioan Dragan, David Gerrard, Mohamed Kouidri, Eide Luebs, Farhad Moradi Shahpar, Jiri Dvorak
Journal: British Journal of Sports Medicine (2010)

Analysis of injury and illness prevalence in elite sport provides the basis for the development of prevention programmes.To analyse the frequency and characteristics of injuries and illnesses occurring during the 13th Federation Internationale de Natation (FINA) World Championships 2009.Prospective recording of newly incurred injuries and illnesses.The 13th FINA World Championships hosted 2592 athletes from 172 countries in the disciplines of swimming, diving, synchronised swimming water polo and open water swimming. All team physicians or physiotherapists were asked to complete daily a standardised reporting form for all newly incurred injuries and illnesses for their teams. To cover teams without medical staff, the physicians of the Local Organizing Committee also submitted daily report forms.171 injuries were reported resulting in an incidence of 66.0 per 1000 registered athletes. The most affected body parts were the shoulder (n=25; 14.6%), and head (n=21; 12.3%). Half of the injuries occurred during training. The most common cause of injury was overuse (n=61; 37.5%). 184 illnesses were reported resulting in an incidence of 71.0 per 1000 registered athletes. The respiratory tract was most commonly affected (n=91; 50.3%) and the most frequently classified cause was infection (n=81; 49.2%). The incidence of injuries and illnesses varied substantially among the five disciplines, with the highest incidence of injury in diving and the lowest in swimming.As the risk of injury varied with the discipline, preventive measures should be discipline specific and focused on minimising the potential for overuse. As most of the illnesses were caused by infection of the respiratory and gastrointestinal tract, preventive interventions should focus on eliminating common modes of transmission.
Surrogate or conventional light chains are required for membrane immunoglobulin mu to activate the precursor B cell transition.
Authors: F Papavasiliou, M Jankovic, M C Nussenzweig
Journal: The Journal of Experimental Medicine (1996)

To examine the role of light chains in early B cell development we combined RAG-1 and lambda 5 mutations to produce mice that expressed neither conventional nor surrogate light chains (RAG-1-/-, lambda 5-/-). Unique heavy and light chain genes were then introduced into the double and single mutant backgrounds. Membrane immunoglobulin (Ig)mu (mIg mu) associated with Ig alpha-Ig beta but was unable to activate the pre-B cell transition in RAG-1-/-lambda 5-/- mice. Either lambda 5 or kappa light chains were sufficient to complement this deficiency. Therefore light chains are absolutely required for a functional Ig signaling module in early B cell development. Our data provide direct evidence for the existence of two pathways for induction of early B cell development: one which is activated through surrogate light chains and mIg mu, and an alternative pathway which uses conventional light chains and mIg mu.
THE PLASTIC HUMAN BRAIN CORTEX
Authors: Alvaro Pascual-Leone, Amir Amedi, Felipe Fregni, Lotfi B. Merabet
Journal: Annual Review of Neuroscience (2005)

Plasticity is an intrinsic property of the human brain and represents evolution's invention to enable the nervous system to escape the restrictions of its own genome and thus adapt to environmental pressures, physiologic changes, and experiences. Dynamic shifts in the strength of preexisting connections across distributed neural networks, changes in task-related cortico-cortical and cortico-subcortical coherence and modifications of the mapping between behavior and neural activity take place in response to changes in afferent input or efferent demand. Such rapid, ongoing changes may be followed by the establishment of new connections through dendritic growth and arborization. However, they harbor the danger that the evolving pattern of neural activation may in itself lead to abnormal behavior. Plasticity is the mechanism for development and learning, as much as a cause of pathology. The challenge we face is to learn enough about the mechanisms of plasticity to modulate them to achieve the best behavioral outcome for a given subject.
Paradigm Shifts in Atherosclerotic Renovascular Disease
Authors: Stephen C. Textor, Lilach O. Lerman
Journal: Journal of the American Society of Nephrology (2015)

Results of recent clinical trials and experimental studies indicate that whereas atherosclerotic renovascular disease can accelerate both systemic hypertension and tissue injury in the poststenotic kidney, restoring vessel patency alone is insufficient to recover kidney function for most subjects. Kidney injury in atherosclerotic renovascular disease reflects complex interactions among vascular rarefication, oxidative stress injury, and recruitment of inflammatory cellular elements that ultimately produce fibrosis. Classic paradigms for simply restoring blood flow are shifting to implementation of therapy targeting mitochondria and cell-based functions to allow regeneration of vascular, glomerular, and tubular structures sufficient to recover, or at least stabilize, renal function. These developments offer exciting possibilities of repair and regeneration of kidney tissue that may limit progressive CKD in atherosclerotic renovascular disease and may apply to other conditions in which inflammatory injury is a major common pathway.
eThrombosis: the 21st Century variant of venous thromboembolism associated with immobility
Authors: R. Beasley, N. Raymond, S. Hill, M. Nowitz, R. Hughes
Journal: European Respiratory Journal (2003)

The association between immobility with prolonged sitting and venous thromboembolism has been recognised for > 60 yrs, most recently with long distance air travel. The case of a 32-yr-old male, in whom immobility associated with sitting for long periods at a computer represented the major provoking risk factor for his life-threatening venous thromboembolism, is presented. The authors propose the term "eThrombosis" to describe this 21st Century variant of venous thromboembolism associated with immobility from prolonged sitting. In view of the widespread use of computers in relation to work, recreation and personal communication, the potential burden of eThrombosis may be considerable.
Nephroprotection by Theophylline in Patients with Cisplatin Chemotherapy
Authors: Peter Benoehr, Patricia Krueth, Carsten Bokemeyer, Almut Grenz, Hartmut Osswald, Jorg T. Hartmann
Journal: Journal of the American Society of Nephrology (2004)

The aim of the present study was to assess the possible prevention of cisplatin-induced impairment of GFR by theophylline in patients with various malignancies. The trial design was parallel, randomized, single blinded, and placebo controlled. Patients received cisplatin at a dosage of 50 mg/m(2) either combined with etoposide, ifosfamide, and epirubicin or with paclitaxel and 5-fluorouracil/folinic acid with the usual precautions, including a standard hydration scheme before application of cisplatin in both arms. In the control arm, placebo was administered; in the verum arm, patients received theophylline in a loading dose of 4 mg/kg intravenously over 30 min before cisplatin, followed by 0.4 mg/kg per min over a minimum of 6 h, and then 350 mg three times daily orally for 4 consecutive days after completion of chemotherapy. GFR of each patient was assessed by renal clearance of inulin within 3 d before and at day 5 after cisplatin chemotherapy. Despite usual precautions, patients in the placebo group had a 21% decrease (range, 11 to 31%) of inulin clearance after a single cycle of cisplatin-containing chemotherapy (92.9 +/- 3.4 versus 71.8 +/- 3.5 ml/min; P < 0.01). Patients who received theophylline had no deterioration of GFR (91.5 +/- 3.7 versus 90.0 +/- 3.8 ml/min; P > 0.05). No adverse effects have been observed during theophylline application. Conventional precautions such as hydration and osmotic diuresis cannot prevent a significant decrease of GFR after a single cycle of cisplatin-containing chemotherapy. The prophylactic application of theophylline as an intravenous loading dose and oral maintenance regimen may preserve kidney function in terms of GFR.
TAK1 in brain endothelial cells mediates fever and lethargy
Authors: Dirk A. Ridder, Ming-Fei Lang, Sergei Salinin, Jan-Peter Röderer, Marcel Struss, Christiane Maser-Gluth, Markus Schwaninger
Journal: The Journal of Experimental Medicine (2011)

Systemic inflammation affects the brain, resulting in fever, anorexia, lethargy, and activation of the hypothalamus–pituitary–adrenal axis. How peripheral inflammatory signals reach the brain is still a matter of debate. One possibility is that, in response to inflammatory stimuli, brain endothelial cells in proximity to the thermoregulatory centers produce cyclooxygenase 2 (COX-2) and release prostaglandin E2, causing fever and sickness behavior. We show that expression of the MAP kinase kinase kinase TAK1 in brain endothelial cells is needed for interleukin 1β (IL-1β)–induced COX-2 production. Exploiting the selective expression of the thyroxine transporter Slco1c1 in brain endothelial cells, we generated a mouse line allowing inducible deletion of Tak1 specifically in brain endothelium. Mice lacking the Tak1 gene in brain endothelial cells showed a blunted fever response and reduced lethargy upon intravenous injection of the endogenous pyrogen IL-1β. In conclusion, we demonstrate that TAK1 in brain endothelial cells induces COX-2, most likely by activating p38 MAPK and c-Jun, and is necessary for fever and sickness behavior.
Major conceptual change required to improve lung cancer: see a respiratory physician
Authors: J.K. Field, C. Brambilla
Journal: European Respiratory Journal (2003)

In this issue of the European Respiratory Journal , Ferguson et al. 1 have provided valuable evidence of the importance of patients with a diagnosis of lung cancer seeing a respiratory physician (RP). Their data support the concept that patients who have had the fortune of seeing an RP benefit. The authors are careful to indicate that the patients who did not see an RP were generally older and had more extensive disease. However, even after correcting for this factor, a significant advantage was observed for those who were seen by an RP. Their findings support the national guidelines and it is clear that patients seeing an RP are more likely to be managed by a multidisciplinary team and receive active treatment. However, there is no information available to associate this with a better quality of survival.

Unfortunately, in the UK there has been little change in the 5-yr survival figures for lung cancer …
Statistical Methods for Analyzing Sequentially Randomized Trials
Authors: O. Bembom, M. J. van der Laan
Journal: JNCI Journal of the National Cancer Institute (2007)

In this issue of the Journal, Thall et al. present the results of a clinical trial that makes use of sequential randomization, a novel trial design that allows the investigator to study adaptive treatment strategies. Our aim is to complement this groundbreaking work by reviewing the current state of the art of statistical methods available for such analyses. Using the data collected by Thall et al. as an example, we focus on two different approaches for estimating the success rates of different adaptive treatment strategies of interest. By emphasizing the intuitive appeal and straightforward implementation of these methods and illustrating the striking findings to which these methods can lead, we hope to convince the reader that this novel trial design provides a rich source of information that is made readily accessible through current analytical approaches.
Pharmacologic and anti‐IgE treatment of allergic rhinitis ARIA update (in collaboration with GA<sup>2</sup>LEN)
Authors: J. Bousquet, P. Van Cauwenberge, N. Aït Khaled, C. Bachert, C. E. Baena‐Cagnani, J. Bouchard, C. Bunnag, G. W. Canonica, K.‐H. Carlsen, Y.‐Z. Chen, A. A. Cruz, A. Custovic, P. Demoly, R. Dubakiene, S. Durham, W. Fokkens, P. Howarth, J. Kemp, M. L. Kowalski, V. Kvedariene, B. Lipworth, R. Lockey, V. Lund, S. Mavale‐Manuel, E. O. Meltzer, J. Mullol, R. Naclerio, K. Nekam, K. Ohta, N. Papadopoulos, G. Passalacqua, R. Pawankar, T. Popov, P. Potter, D. Price, G. Scadding, F. E. R. Simons, V. Spicak, E. Valovirta, D.‐Y. Wang, B. Yawn, O. Yusuf
Journal: Allergy (2006)

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence‐based and step‐wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti‐IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non‐nasal symptoms are presented as these will be discussed in a separate document.
Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study
Authors: S.F. Slovin, C.S. Higano, O. Hamid, S. Tejwani, A. Harzstark, J.J. Alumkal, H.I. Scher, K. Chin, P. Gagnier, M.B. McHenry, T.M. Beer
Journal: Annals of Oncology (2013)
Hyponatremia Predicts Right Heart Failure and Poor Survival in Pulmonary Arterial Hypertension
Authors: Paul R. Forfia, Stephen C. Mathai, Micah R. Fisher, Traci Housten-Harris, Anna R. Hemnes, Hunter C. Champion, Reda E. Girgis, Paul M. Hassoun
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Hyponatremia is associated with decompensated heart failure and poor prognosis in patients with left ventricular systolic dysfunction.We sought to determine if hyponatremia is associated with right heart failure and worse prognosis in patients with pulmonary arterial hypertension (PAH).We prospectively followed 40 patients with PAH and examined the relationship between serum sodium and right heart function as well as survival.Subjects with hyponatremia (Na < or = 136 mEq/L) were more symptomatic (11/13 World Health Organization [WHO] class III/IV vs. 12/27 WHO class III/IV; P = 0.02), had more peripheral edema (69 vs. 26%; P = 0.009), and had higher hospitalization rates (85 vs. 41%; P = 0.009) than normonatremic subjects. Hyponatremic subjects had higher right atrial pressure (14 +/- 6 vs. 9 +/- 3 mm Hg; P < 0.001), lower stroke volume index (21 +/- 7 vs. 32 +/- 10 ml/m(2); P < 0.01), larger right ventricular:left ventricular area ratio (1.8 +/- 0.4 vs. 1.3 +/- 0.4; P < 0.001), and lower tricuspid annular plane systolic excursion (1.4 +/- 0.3 vs. 2.0 +/- 0.6 cm; P = 0.001), despite similar mean pulmonary artery pressure (49 +/- 10 vs. 47 +/- 12 mm Hg; P = 0.60). The 1- and 2-year survival estimates were 93% (95% confidence interval [CI], 73-98%) and 85% (95% CI, 65-94%), and 38% (95% CI, 14-63%) and 15% (95% CI, 2-39%) for normonatremic and hyponatremic subjects, respectively (log-rank chi(2) = 25.19, P < 0.001). The unadjusted risk of death (hazard ratio) in hyponatremic compared with normonatremic subjects was 10.16 (95% CI, 3.42-30.10, P < 0.001). Hyponatremia predicted outcome after adjusting for WHO class, diuretic use, as well as right atrial pressure and cardiac index.Hyponatremia is strongly associated with right heart failure and poor survival in PAH.
Regulation of herpes simplex virus γ134.5 expression and oncolysis of diffuse liver metastases by Myb34.5
Authors: Hideo Nakamura, Hideki Kasuya, John T. Mullen, Sam S. Yoon, Timothy M. Pawlik, Soundararajalu Chandrasekhar, James M. Donahue, E. Antonio Chiocca, Richard Y. Chung, Kenneth K. Tanabe
Journal: Journal of Clinical Investigation (2002)

Myb34.5 is a herpes simplex virus 1 (HSV-1) mutant deleted in the gene for ribonucleotide reductase (ICP6). It also carries a version of γ134.5 (a viral gene product that promotes the dephosphorylation of eIF-2α) that is under control of the E2F-responsive cellular B-myb promoter, rather than of its endogenous promoter. Myb34.5 replication in tumor cells results in their destruction (oncolysis). γ134.5 expression by HSV-1 subverts an important cell defense mechanism against viral replication by preventing shutoff of protein synthesis after viral infection. Infection of colon carcinoma cells with Myb34.5 results in greater eIF-2α dephosphorylation and viral replication compared with infection with HSV-1 mutants completely defective in γ134.5 expression. In contrast, infection of normal hepatocytes with Myb34.5 results in low levels of eIF-2α dephosphorylation and viral replication that are similar to those observed with HSV-1 mutants completely defective in γ134.5 and ICP6. When administered intravascularly into mice with diffuse liver metastases, Myb34.5 has greater antineoplastic activity than HSV-1 mutants with completely defective γ134.5 expression and more restricted biodistribution compared with HSV-1 mutants with wild-type γ134.5 expression. Myb34.5 displays reduced virulence and toxicity compared to HSV-1 mutants with wild-type γ134.5 expression. Portal venous administration of Myb34.5 significantly reduces liver tumor burden in and prolongs the life of mice with diffuse liver metastases. Preexisting Ab's to HSV-1 do not reduce the antitumor efficacy of Myb34.5 in vivo.
Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1
Authors: Victor-F. Mautner, Florence A. Asuagbor, Eva Dombi, Carsten Fünsterer, Lan Kluwe, Ralf Wenzel, Brigitte C. Widemann, Jan M. Friedman
Journal: Neuro-Oncology (2008)

People with neurofibromatosis 1 (NF1) have multiple benign neurofibromas and a 10% lifetime risk of developing malignant peripheral nerve sheath tumors (MPNSTs). Most MPNSTs develop from benign plexiform neurofibromas, so the burden of benign tumors may be a risk factor for developing MPNST. We studied 13 NF1 patients with MPNSTs and 26 age- and sex-matched controls (NF1 patients who did not have MPNSTs) with detailed clinical examinations and whole-body MRI to characterize their body burden of internal benign neurofibromas. Internal plexiform neurofibromas were identified in 22 (56%) of the 39 NF1 patients studied. All six of the NF1 patients with MPNSTs under 30 years of age had neurofibromas visualized on whole-body MRI, compared to only 3 of 11 matched NF1 controls under age 30 (p < 0.05). Both the median number of plexiform neurofibromas (p < 0.05) and the median neurofibroma volume (p < 0.01) on whole-body MRI were significantly greater among MPNST patients younger than 30 years of age than among controls. No significant differences in whole-body MRI findings were observed between NF1 patients with MPNSTs and controls who were 30 years of age or older. Whole-body MRI of NF1 patients allows assessment of the burden of internal neurofibromas, most of which are not apparent on physical examination. Whole-body imaging of young NF1 patients may allow those at highest risk for developing MPNST to be identified early in life. Close surveillance of these high-risk patients may permit earlier diagnosis and more effective treatment of MPNSTs that develop.
Validity of final examinations in undergraduate medical training
Authors: C. van der Vleuten
Journal: BMJ (2000)

Most medical schools, particularly those in the United Kingdom, have a final examination at the end of undergraduate medical training. Although the format of these examinations has been changed recently by the introduction of newer types of assessment such as objective structured clinical examinations, medical educators are still questioning their validity and worth. I believe that there is a strong case for better continuous assessment during undergraduate training and less reliance on final examinations.

#### Summary points

Even with modern forms of assessment, final examinations are of questionable reliability and validity

They are of limited educational value to students because there is little opportunity for feedback and correction

The effort spent on running final examinations would be better invested in improved continuous assessment during training

Continuous assessment through “clinical work samples” is a promising new method of assessing medical students

The final examination has at least two functions—an accountability or selective function and an educational one. First and foremost, the final exam should provide a guarantee to society that the training programme delivers competent doctors. It should be able to identify any students who are unfit to practise, so that they can be prevented from doing harm, and to license competent students who are ready for further practice and training. With regard to the educational function, proponents claim that the requirement to sit a comprehensive examination at the end of training means that students revise and recapitulate what they have learned throughout the course, a process which leads to a more integrated understanding of the knowledge and skills they have acquired. Let me examine these functions in greater detail.

The outcome of the final examination should predict whether a student will be competent. The process should prevent false negative results and, in particular, false positive ones. In other words, the final examination should …
Clinical significance of brain natriuretic peptide in primary pulmonary hypertension
Authors: Hanno H. Leuchte, Michael Holzapfel, Rainer A. Baumgartner, Isabelle Ding, Claus Neurohr, Michael Vogeser, Tilman Kolbe, Martin Schwaiblmair, Jürgen Behr
Journal: Journal of the American College of Cardiology (2004)
Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder: observational follow-up study
Authors: Jari Tiihonen, Kristian Walhbeck, Jouko Lönnqvist, Timo Klaukka, John P A Ioannidis, Jan Volavka, Jari Haukka
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To study the association between prescribed antipsychotic drugs and outcome in schizophrenia or schizoaffective disorder in the community. <b>Design</b> Prospective cohort study using national central registers. <b>Setting</b> Community care in Finland. <b>Participants</b> Nationwide cohort of 2230 consecutive adults hospitalised in Finland for the first time because of schizophrenia or schizoaffective disorder, January 1995 to December 2001. <b>Main outcome measures</b> Rates of discontinuation of drugs (all causes), rates of rehospitalisation, and mortality associated with monotherapy with the 10 most commonly used antipsychotic drugs. Multivariate models and propensity score methods were used to adjust estimates of effectiveness. <b>Results</b> Initial use of clozapine (adjusted relative risk 0.17, 95% confidence interval 0.10 to 0.29), perphenazine depot (0.24, 0.13 to 0.47), and olanzapine (0.35, 0.18 to 0.71) were associated with the lowest rates of discontinuation for any reason when compared with oral haloperidol. During an average follow-up of 3.6 years, 4640 cases of rehospitalisation were recorded. Current use of perphenazine depot (0.32, 0.22 to 0.49), olanzapine (0.54, 0.41 to 0.71), and clozapine (0.64, 0.48 to 0.85) were associated with the lowest risk of rehospitalisation. Use of haloperidol was associated with a poor outcome among women. Mortality was markedly raised in patients not taking antipsychotics (12.3, 6.0 to 24.1) and the risk of suicide was high (37.4, 5.1 to 276). <b>Conclusions</b> The effectiveness of first and second generation antipsychotics varies greatly in the community. Patients treated with perphenazine depot, clozapine, or olanzapine have a substantially lower risk of rehospitalisation or discontinuation (for any reason) of their initial treatment than do patients treated with haloperidol. Excess mortality is seen mostly in patients not using antipsychotic drugs.