tbuckley/cabot-search huggingface dataset:
Planning and control of action as solutions to an independence of visual mechanisms
Authors: James G. Phillips, Thomas J. Triggs, James W. Meehan
Journal: Behavioral and Brain Sciences (2004)

Glover proposes a planning–control model for the parietal lobe that contrasts with previous formulations that suggest independent mechanisms for perception and action. The planning–control model potentially solves practical functional problems with a proposed independence of perception and action, and offers some new directions for a study of human performance.
Inhibition of p38α MAPK rescues cardiomyopathy induced by overexpressed β2-adrenergic receptor, but not β1-adrenergic receptor
Authors: Pallavi S. Peter, Jennifer E. Brady, Lin Yan, Wei Chen, Stefan Engelhardt, Yibin Wang, Junichi Sadoshima, Stephen F. Vatner, Dorothy E. Vatner
Journal: Journal of Clinical Investigation (2007)

We examined the role of p38α MAPK in mediating cardiomyopathy in mice overexpressing β1-adrenergic receptor (β1-AR) or β2-AR by mating them with dominant-negative p38α (DNp38α) MAPK mice. Both β1-AR and β2-AR Tg mice had enhanced LV ejection fraction (LVEF) as young adults and developed similar cardiomyopathy at 11–15 months, characterized by reduced LVEF, myocyte hypertrophy, fibrosis, and apoptosis. We inhibited p38α MAPK by mating β1-AR Tg and β2-AR Tg mice with DNp38α MAPK mice, which rescued the depressed LVEF and reduced apoptosis and fibrosis in bigenic β2-AR × DNp38α MAPK mice, but not bigenic β1-AR × DNp38α MAPK mice, and failed to reduce myocyte hypertrophy in either group. Gsα was increased in both β1-AR Tg and β2-AR Tg mice and was still present in bigenic β1-AR × DNp38α MAPK mice, but not bigenic β2-AR × DNp38α MAPK mice. This suggests that p38α MAPK is one critical downstream signal for the development of cardiomyopathy following chronic β2-AR stimulation, but other kinases may be more important in ameliorating the adverse effects of chronic β1-AR stimulation.
Plasma D-dimer concentration in patients with systemic sclerosis
Authors: I. Marie, J.-Y. Borg, M.-F. Hellot, H. Levesque
Journal: British Journal of Dermatology (2007)

It has been reported that increased plasma D-dimer is a reliable marker of systemic prothrombotic state in patients with cardiovascular diseases.To evaluate plasma D-dimer concentration in patients with systemic sclerosis (SSc) and healthy controls. We also investigated a possible relationship between the presence of a high plasma D-dimer concentration and clinical and biological parameters in patients with SSc.Measurements of plasma D-dimer concentration were performed in 69 consecutive patients with SSc and 69 age- and sex-matched controls. Clinical and biological findings were compared between patients with and without a high concentration of plasma D-dimer (i.e. >or=500 ng mL(-1)).Median plasma D-dimer concentrations appeared significantly increased in patients with SSc compared with control subjects (506 vs. 211 ng mL(-1); P<0.001). Furthermore, a high concentration of plasma D-dimer (>or=500 ng mL(-1)) was detected more frequently in patients with SSc than in healthy controls (47.8% vs. 4.5%; P<0.0001). Among vascular manifestations related to SSc, macrovascular impairment responsible for peripheral ischaemia was more frequent in patients with SSc with high levels of D-dimer (>or=500 ng mL(-1)), compared with those without (21% vs. 6%; P=0.05).The association between high levels of plasma D-dimer (>or=500 ng mL(-1)) and macrovascular involvement in patients with SSc is likely to be an innovative issue. We suggest that D-dimer levels may be a helpful additional test to identify patients with SSc at risk to develop thrombotic arterial complications (peripheral arterial disease, stroke and coronary event); such patients with high levels of plasma D-dimer (>or=500 ng mL(-1)) may require close monitoring of vascular parameters, including especially macrovascular impairment.
Accident departments can appoint more staff Helping GPs to provide better out of hours services Human rights will be emphasised at Istanbul meeting Maintaining Medical Excellence will impose new costs In brief
Authors: L. Beecham
Journal: BMJ (1996)

# Accident departments can appoint more staff {#article-title-2}

NHS trusts and health authorities are being allowed to appoint more staff grade doctors outside the agreed national ratio to consultants of 10% to ensure full cover in accident and emergency departments. In a letter to trust and authority chairmen the minister for health, Mr Gerald Malone, said that this would help those hospitals which might face difficulties in filling senior house officer (SHO) posts next month. These appointments will also free up sessions to allow the SHOs more time to take advantage of educational opportunities and improve the training element of the posts. SHOs will also be offered the opportunity of year long posts (instead of six months) linked to other inpatient specialties.

In a separate letter to chief executives of NHS trusts the medical director of the NHS Executive, Dr Graham Winyard, has recommended that hospitals review the work patterns in the accident and emergency departments. For example, patients with clear cut diagnoses or sent in by general practitioners could go direct to the appropriate team and patients could be seen directly by the relevant inpatient doctor and bypass the SHO.

Dr Winyard suggests that the working capacity of SHOs could be improved by providing dictaphones, secretarial support, reducing non-clinical and administrative tasks, and arranging for other appropriate staff to arrange discharge and follow up. As much as possible of the administrative workload of senior doctors should be transferred to non-medical staff.

The chief medical officer, Sir Kenneth Calman, is to review emergency care services outside hospital. This will focus on the organisation and delivery of services and the role of different professional staff including …
INCIDENCE OF DISEASE OF THE BLADDER IN WORKERS IN CERTAIN CHEMICALS
Authors: Thos. H. Wignall
Journal: BMJ (1929)

iMDJmJOUeXs 291 for this function.I have recently had uinder my care two patients with extreme and persistent conjugate deviation of headl and eves lasting foir weeks.In one case a large glioma almost completely excavating the left frontal lobe, but not involviing the cortex, was found.In the second case, in whlich the lesion was right-sided, the presence of complete Imeinianopia and astereogDoSis Witll imlarked lhemi- analgesia aind very little hemilplegia miiadle it certain that the lesion was in the posterior half of the hemisphere.I may, lhowi-ever, go so far as to say that conjugate devia- tioni, when persisting in the absenice of other localizing sign1s, may inidicate cither a frontal or a temporal location, but it will niot distinguish between the two, Tor Kolodny founid it well marked in 6 out of 38 cases of temoporal tumiour.Wh'lleni presenit it is of certain lateralizing value for tumnours in aniy part of the hemisplhere.It may be seen in. the fo-rmi of persistenit deviation to the con-tralater al side, or otf weakness and unwilliiagness in dleviationl to the ipsolateral side.Loss or (Ii/il .tition of the trunk reflexes may be of great laterali,/Min v alue, and is said to be valuable in frontal location.Buit I hold that it is much more characteristic of the tepll)oral tumour-, and I have several timies located a tempor-al tLunimour and had it successfully removed when this wla-, the only localizing signi prcsenlt.In one-half of Kolod'lav x temporal cases the trunik reflexes were com- pletely a.bsenlt on the conitr£alateral side.The presence of these rellexes hlas nio negating significanice.In botlh frontal an,d tP nimo;al tumours it is-probably a contiguous sign of pressurc511j )on tlhe pyramidal mechanism.Incotitolle?1ce is sometimes veryn marke(d in frontal tumours, even whlen the mielntal aberration is inconspicuous.I think I liave seen it more often in tempooral tumours.It was preseunt in 20 per cent. of Kolodny's cases of temporal tulou }'s.
IMPACT OF BETA-BLOCKER THERAPY AT DISCHARGE ON CLINICAL OUTCOMES IN PATIENTS WITH STEMI UNDERGOING PRIMARY PCI
Authors: Young Bin Song, Jeong Hoon Yang, Joo-Yong Hahn, Ki Hong Choi, Seung-Hyuk Choi, Jin-Ho Choi, Sang Hoon Lee, Myung-Ho Jeong, Dong-Joo Choi, Young-Jo Kim, Hyeon-Cheol Gwon
Journal: Journal of the American College of Cardiology (2013)
MHC class II genotype and the control of viremia in HIV-1–infected individuals on highly active antiretroviral therapy
Authors: Joel N. Blankson, Robert F. Siliciano
Journal: Journal of Clinical Investigation (2001)

HIV-1 infection sets up a complex dynamic equilibrium between viral replication and the HIV-1–specific immune response. In the absence of antiretroviral therapy, the high rate of viral replication, the associated depletion of CD4+ T cells, and the high mutation rate of the virus combine to eventually overwhelm the immune system. In certain cases, however, it appears that the immune system has the upper hand, and viral replication occurs at only very low levels. Two groups of individuals fall into this category: some long-term nonprogressors (LTNPs) who have either very low or undetectable levels of plasma virus (1–3), and patients who are treated with highly active antiretroviral therapy (HAART) shortly after seroconversion who subsequently discontinue therapy (4, 5).

Much recent effort has been directed toward studying the HIV-specific immune response of these subjects in the hope of finding clues that will be helpful in designing vaccines. Viral antigen-specific CD4+ and CD8+ T cells play an important role in HIV-specific immunity. The receptors on these cells recognize processed viral peptides that are presented by MHC molecules on the surfaces of antigen presenting cells. While considerable progress has been made regarding the mechanism by which responding T cells control viral replication, less is known about the role of the MHC genotype in patients who spontaneously control viremia.
GENETIC AND EPIGENETIC DEREGULATION ARE ASSOCIATED WITH THE ABERRANT EXPRESSION OF A STEM CELL RELATED HOX GENE SIGNATURE IN GLIOBLASTOMA
Authors: M. E. Hegi, S. Kurscheid, D. Sciuscio, I. Samarzija, R. Stupp, M. Delorenzi
Journal: Neuro-Oncology (2014)

BACKGROUND: (blind field). METHODS: Multidimensional molecular profiles of 70 gliobalstoma and 4 non-tumoral brain samples were obtained, comprising gene expression, DNA methylation, and gene copy number alterations. Validation datasets were downloaded from the public domain including The Cancer Genome Atlas (TCGA) Project. For 4 glioma-derived sphere lines marks for active and inactive chromatin were sought by ChIP-PCR. RESULTS: Prominent DNA methylation was observed in the HOXA gene cluster in glioblastoma and respective glioma-derived spheres, in contrast to non tumoral brain. High concordance of correlations between CpG methylation in the HOXA cluster and expression of the HOX-signature was observed with external datasets (RV 0.68 and 0.84). In search of the regulatory region explaining the overexpression of the HOX signature we identified a CpG island encompassing a promoter region in the HOXA locus with strong negative correlation of CpG methylation and expression. A model was constructed explaining the probability of HOX-high in glioblastoma by combining information on gene dosage and methylation at the CpGs identified. The model was successful validated in external datasets. Further experimental evidence supportive for the relevance of epigenetic modulation at this site came from concordance between the methylation status and the presence of marks for active or inactive chromatin, respectively, in HOX-high versus HOX-low sphere lines. CONCLUSIONS: The acquired overexpression of the stem-cell related HOX signature in glioblastoma is in accordance with aberrant de-repression of HOX genes mediated at least in part by increased gene dosage attenuated by DNA methylation. SECONDARY CATEGORY: Tumor Biology.
Antidepressant prescribing and suicide: Associations attribute possible causality inappropriately
Authors: B. M Draper
Journal: BMJ (2003)

EDITOR—Hall et al say that reductions in suicide rates in older people in Australia could be attributed to their increased exposure to antidepressants, in particular selective serotonin reuptake inhibitors.1 But the associations seem to attribute possible causality inappropriately.

According to the Australian Bureau of Statistics, suicide rates in …
A time to live or a time to die?: Summary of responses
Authors: Birte Twisselmann
Journal: BMJ (2004)

EDITOR—The personal view entitled “A time to live or a time to die?”—a reader's tale of how her dying husband has been kept alive by percutaneous endoscopic gastrostomy—sparked a small but impassioned debate on what one correspondent highlights as the right of patients and their families to influence medical treatment.1

Donald Couper, a general practitioner in Manchester, is surprised at the lack of commentary on a theme that must be familiar …
A technique for prolonged, continuous recording of blood pressure of unrestrained rats
Authors: R. J. LAFFAN, A. PETERSON, S. W. HITCH, C. JEUNELOT
Journal: Cardiovascular Research (1972)

A technique for long-term recording of direct arterial blood pressure from a colony of rats is described. A rotary fluid switch is used to sample pressures sequentially from the colony via a single transducer. A digital computer is used for reduction and analysis of the blood-pressure data.
SQUARE WAVES (BST) VERSUS SINE WAVES IN ELECTROCONVULSIVE THERAPY
Authors: SPENCER BAYLES, EWALD W. BUSSE, FRANKLIN G. EBAUGH
Journal: American Journal of Psychiatry (1950)

1. A report on our first year's experience with the Liberson-Offner Brief Stimulus technique for electroconvulsive therapy is presented in comparison with conventional sine wave technique. 2. Clinical study shows these methods to be equally effective in so far as observable improvement is concerned. 3. Electroencephalographic studies indicate the brief stimulus therapy method produces a significant reduction in post treatment electrocortical disturbance. The evidence at present does not permit a statement of the presence or absence of irreversible brain changes. 4. It is postulated that the electrocortical disturbance is of no favorable or adverse significance in the clinical course. The amount of confusion produced seems similarly to be of little or no clinical significance. 5. We have observed a greater incidence of fractures of the spine following treatment with brief stimulus therapy and conclude from this and from direct observation that the physical violence of the seizures is no different with either method. 6. As an incidental observation, it seems that electroconvulsive therapy is of value in the treatment of schizophrenics and that this value does not depend upon the presence of depression in the schizophrenic symptomatology. 7. Finally, we do not find any overwhelming evidence to indicate preference for either type of stimulator in clinical practice, although certain aspects of either method may be more or less objectionable in relation to the immediate feelings of given patients.
Abstract S1-7: Lack of Correlation between Gene Variants in Tamoxifen Metabolizing Enymes with Primary Endpoints in the ATAC Trial.
Authors: JM Rae, S Drury, DF Hayes, V Stearns, JN Thibert, BP Haynes, J Salter, S Pineda, J Cuzick, M. Dowsett
Journal: Cancer Research (2010)

Abstract Background. A number of studies have provided widely heterogeneous results for and against the hypothesis that genetic variants in drug metabolizing enzymes can influence patient response to tamoxifen. Most of these studies are confounded by relatively small numbers of patients, lack of comprehensive genotype information, lack of detailed clinical outcome data, and patient selection biases. The ATAC trial was a prospective randomized double-blind placebo-controlled trial designed to compare the adjuvant use of anastrozole versus tamoxifen for 5 years. The trial's detailed efficacy and safety data, long term (10-year) follow-up and high number of events make it an ideal setting for pharmacogenetic analyses. Here we report our initial findings testing for correlations with SNPs in CYP2D6 and UGT2B7, the primary enzymes responsible for the presumed activation and inactivation of tamoxifen, respectively, with clinical outcomes including any disease recurrence, distant recurrence, and overall survival. Methods: CYP2D6 genotype data for the 7 most common alleles were used to assign each patient a ‘score’ based on predicted allele activities from 0 (no activity) to 2 (high activity). Patients were also tested for the UGT2B7*2 variant, which has lower enzymatic activity and has been shown to correlate with higher serum endoxifen concentrations. All genotype determinations were made without knowledge of the patient's treatment assignment or outcomes. Results: Comprehensive CYP2D6 genotype data were obtained on 588 and 615 patients randomized to receive tamoxifen, and anastrozole, respectively. After median 10 years of follow-up, there were 115 recurrences in the tamoxifen cohort. We found no associations between any of the CYP2D6 scores and rates of recurrence in tamoxifen treated patients. A test for trend across CYP2D6 scores was not significant. In the anastrozole cohort, there were 92 recurrences, and there was no evidence of an association between CYP2D6 score with rates of recurrence. Likewise, there was no detectable association in either the tamoxifen or anastrozole group with UGT2B7 genotype alone or in combination with CYP2D6 score. Concomitant SSRI usage was recorded in these patients and is being assessed for possible impact on these results. Conclusion: These data from a large prospective clinical trial, with detailed outcome data and long-term follow-up do not support the hypothesis that patient with decreased CYP2D6 enzymatic activity receive less benefit from tamoxifen therapy compared to wild-type CYP2D6 patients. Variants in drug targets and estrogen signaling pathways may be the genetic basis for patient variability in anti-estrogen risk versus benefit profiles. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S1-7.
Comparison of serum and synovial fluid concentrations of beta 2-microglobulin and C reactive protein in relation to clinical disease activity and synovial inflammation in rheumatoid arthritis.
Authors: M.T Walters, F.K Stevenson, R Goswami, J.L Smith, M.I Cawley
Journal: Annals of the Rheumatic Diseases (1989)

beta 2-Microglobulin and C reactive protein (CPR) were measured in 33 and 57 matched pairs of serum and synovial fluid (SF) respectively, from patients with active rheumatoid arthritis (RA). Serum beta 2-microglobulin concentrations were higher than in normal controls and the SF concentration was higher than the serum concentration on 25 of 33 occasions (76%), suggesting a local production of beta 2-microglobulin within the synovial membrane. There was a correlation between serum and SF concentrations of beta 2-microglobulin (r = 0.50). Patients' serum CRP concentrations in 57 samples were higher than in normal controls and were greater than in the matched SFs on 49 of the 57 paired samples (86%). In 18 samples CRP was absent in the SF, suggesting a local consumption or binding within the synovial membrane. Twenty four patients with RA given either sodium aurothiomalate or D-penicillamine for six months showed highly significant clinical improvements accompanied by reductions in serum and SF immunoglobulin concentrations and knee joint suprapatellar pouch synovial membrane T lymphocyte infiltrates. In this group of patients serum CRP, but not beta 2-microglobulin, fell significantly, but there were no significant changes in SF beta 2-microglobulin or CRP. These data suggest that serum and SF beta 2-microglobulin concentrations are not a useful index for determining the therapeutic response to sodium aurothiomalate and D-penicillamine and that serum rather than SF CRP concentrations are more helpful. The persistent raised serum and SF concentrations of beta 2-microglobulin probably reflect synovial inflammatory infiltrates, which are still considerable despite apparent clinical remission.
Effect of sustained loading on the water content of intervertebral discs: implications for disc metabolism.
Authors: D.W McMillan, G Garbutt, M.A Adams
Journal: Annals of the Rheumatic Diseases (1996)

To examine regional changes in the fluid content of human intervertebral discs by comparing sagittal plane "profiles" of hydration before and after mechanical loading. Cadaveric lumbar intervertebral discs were loaded to simulate a typical day's loading in vivo. Ten motion segments were subjected to a 1500 N compressive load for a period of 6 h with the superior vertebrae inclined by 4-8 degrees to simulate a slightly flexed posture. Immediately after loading the discs were frozen at -80 degrees C. Subsequently they were cut into slices perpendicular to the sagittal midline of the disc, and each slice was weighed before and after freeze drying. This enabled a profile of fluid content across the disc to be constructed. Fluid loss due to loading was estimated by comparing the water content of each loaded disc with that of an adjacent unloaded disc from the same spine. After 6 h of creep loading, disc height approached, but did not quite reach, an equilibrium. The mean fluid loss from all discs was 18%. All regions except the outer 2 mm experienced a significant loss of fluid (P < 0.01). The posterior mid-annulus showed the greatest fluid loss (30%), while the nucleus lost 15%. A comparison with previously published work suggests that fluid exchange of this magnitude will have a considerable effect on disc cell metabolism and on metabolite transport.
VALUE OF ROENTGEN RAY IN DIAGNOSIS OF PULMONARY TUBERCULOSIS IN WAR TIME
Authors: LAWRASON BROWN
Journal: JAMA (1918)

The entire medical profession has for some months been deeply interested in the many problems connected with the war. Although later questioned, early reports of an alarming amount of tuberculosis in the French army among the men in the trenches, as well as those behind the lines, focused attention on this phase of the medical problem. The question of excluding the tuberculous from the army, especially from that part destined for overseas activity, has seemed to many to be most pressing at this time.  It is clearly evident to any one who has made even a cursory inquiry into the medical examinations of the national army that no army has ever been so well examined. My object is not to criticize but to attempt to show how, along one line, even greater efficiency might be obtained.  The early diagnosis of early pulmonary tuberculosis is always a difficult problem, and among
NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study
Authors: Vahid Asnafi, Agnès Buzyn, Sandrine Le Noir, Frédéric Baleydier, Arnauld Simon, Kheira Beldjord, Oumedaly Reman, Francis Witz, Thierry Fagot, Emmanuelle Tavernier, Pascal Turlure, Thibaut Leguay, Françoise Huguet, Jean-Paul Vernant, Francis Daniel, Marie-Christine Béné, Norbert Ifrah, Xavier Thomas, Hervé Dombret, Elizabeth Macintyre
Journal: Blood (2008)