tbuckley/cabot-search huggingface dataset:
Representation of basic kinds: Not a case of evolutionary internalization of <i>universal </i>regularities
Authors: Dennis Lomas
Journal: Behavioral and Brain Sciences (2001)

Shepard claims that “evolutionary internalization of universal regularities in the world” takes place. His position is interesting and seems plausible with regard to “default” motion detection and aspects of colour constancy which he addresses. However, his claim is not convincing with regard to object recognition. [Shepard]
In search of control variables: A systems approach
Authors: G. J. Dalenoort
Journal: Behavioral and Brain Sciences (1997)

Motor processes cannot be modeled by a single (unified) model. Instead, a number of models at different levels of description are needed. The concepts of control and control variable only make sense at the functional level. A clear distinction must be made between external models and internal models. General Systems Theory provides the framework for a proper treatment of these issues.
Feasibility of 10-Day Use of a Continuous Glucose-Monitoring System in Adults With Type 1 Diabetes
Authors: Satish K. Garg, Mary K. Voelmle, Peter Gottlieb
Journal: Diabetes Care (2008)

OBJECTIVE—The purpose of this pilot study was to evaluate the feasibility of 10-day use of a transcutaneous, real-time, continuous glucose-monitoring (CGM) system. All previous reports using different CGM systems were for 3-, 5-, or 7-day use. RESEARCH DESIGN AND METHODS—On day 1, subjects received the CGM device (SEVEN System) and underwent training on proper use. Subjects returned to the clinic on days 2, 7, and 10 for in-clinic sessions. On days 2 and 7, half the subjects performed fingersticks every 15 min and the other half had Yellow Springs Instruments (YSI) samples drawn every 15 min. On day 10, all subjects participated in an 8-h in-clinic session with YSI and fingerstick testing. RESULTS—The median absolute relative difference for CGM versus YSI was 12.6, 11.3, and 14.5% on days 2, 7, and 10, respectively (P = 0.63). CGM performed better on day 10 when compared with self-monitoring of blood glucose as compared with YSI. CONCLUSIONS—This is the first study to document 10-day use of a 7-day CGM system.
Phase III, Randomized, Placebo-Controlled Study of Docetaxel in Combination With Zibotentan in Patients With Metastatic Castration-Resistant Prostate Cancer
Authors: Karim Fizazi, Celestia S. Higano, Joel B. Nelson, Martin Gleave, Kurt Miller, Thomas Morris, Faith E. Nathan, Stuart McIntosh, Kristine Pemberton, Judd W. Moul
Journal: Journal of Clinical Oncology (2013)

PURPOSE As part of the ENTHUSE (Endothelin A Use) program, the efficacy and safety of zibotentan (ZD4054), an oral specific endothelin A receptor antagonist, has been investigated in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS In this randomized, double-blind, placebo-controlled, phase III study, patients received intravenous docetaxel 75 mg/m(2) on day 1 of 21-day cycles plus oral zibotentan 10 mg or placebo once daily. The primary end point was overall survival (OS). Secondary end points included time to pain and prostate-specific antigen (PSA) progression, pain and PSA response, progression-free survival, health-related quality of life, and safety. Results A total of 1,052 patients received study treatment (docetaxel-zibotentan, n = 524; docetaxel-placebo, n = 528). At the time of data cutoff, there had been 277 and 280 deaths, respectively. There was no difference in OS for patients receiving docetaxel-zibotentan compared with those receiving docetaxel-placebo (hazard ratio, 1.00; 95% CI, 0.84 to 1.18; P = .963). No significant differences were observed on secondary end points, including time to pain progression (median 9.3 v 10.0 months, respectively) or pain response (odds ratio, 0.84; 95% CI, 0.61 to 1.16; P = .283). The median time to death was 20.0 and 19.2 months for the zibotentan and placebo groups, respectively. The most commonly reported adverse events in zibotentan-treated patients were peripheral edema (52.7%), diarrhea (35.4%), alopecia (33.9%), and nausea (33.3%). CONCLUSION Docetaxel plus zibotentan 10 mg/d did not result in a significant improvement in OS compared with docetaxel plus placebo in patients with metastatic CRPC.
Rate of coronary vascularization during embryonic chicken development is influenced by the rate of myocardial growth
Authors: R Tomanek
Journal: Cardiovascular Research (1999)

We tested the hypothesis that the degree of coronary microvessel formation in the embryonic heart is regulated by the magnitude of myocardial growth.The outflow tract of Hamburger-Hamilton stage 21 chicken hearts (prior to the onset of coronary vasculogenesis) was constricted in ovo with a loop of 10-0-nylon suture, and the hearts were studied at stages 29 and 36.At stage 29 ventricular mass was 64% greater in the pressure-overloaded than in the hearts of sham-operated controls, but vascular volume density and numerical density, determined by electron microscopic morphometry, were identical. As demonstrated by histological morphometric evaluation, the compact region of the left ventricle at stage 29 was 43% thicker than the shams. However, by stage 36 heart mass, thickness of the compact region, and overall wall thickness (demonstrated by scanning electron microscopy) were significantly less than in the sham group of this stage, but vascular volume density was virtually identical in the two groups. Formation of the two main coronary arteries was clearly impeded in the banded hearts, i.e., the coronaries were stunted in their development or failed to completely form coronary ostia.Vascular growth is proportional to myocardial growth in the embryonic, overloaded heart, but the persistence of the pressure overload results in a failure of or severe limitations in coronary artery development. These data support the hypothesis that vascular growth during this period of development is regulated, at least in part, by the rate and magnitude of myocardial growth.
The influence of a high negative control on the interpretation of QuantiFERON Gold in Tube (QFN) results
Authors: William Ricketts, Graham Bothamley
Journal: European Respiratory Journal (2011)

Introduction: The QFN result is a composite of a nil control, a mitogen positive control and a test sample (TB Ag) utilising ESAT-6, CFP-10 and TB 7.7 antigens. The result is defined as TB Ag minus nil control (positive >0.35 IU/ml). A strongly positive nil control (>8 IU/ml) or failure of the positive control are defined as indeterminate results. We were concerned that high values obtained after antigen stimulation might be significant.  Method: All patients tested by QFT-GIT between 31/3/10 and 28/1/11 (n=651) had the raw data from their test reviewed. Clinical diagnosis was examined in all those with a TB Ag result >0.35 IU/ml with a nil control high enough to bring the net result to   Results: There were 39 (6%) instances of a net negative result despite a response to antigen, including four cases of active TB (4.7% of TB cases). Nil control results ranged from 0.1-3.07 IU/ml, with TB Ag levels up to 1.52 IU/ml.  Eight with a negative mitogen response included two cases of active TB, one of whom also had HIV. No cases were defined as indeterminate by virtue of a strongly positive negative control.  Conclusion: Reporting of a net result without a breakdown leaves clinicians vulnerable to missing cases of active TB. Sarcoidosis, Crohn9s disease and bronchiectasis, all diseases associated with polyclonal B cell activation, also appear to show spontaneous interferon-gamma release.
100 CIGARETTE SMOKING EXACERBATES NON-ALCOHOLIC STEATOHEPATITIS IN OBESE RATS
Authors: L. Azzalini, L.N. Ramalho, E. Ferrer, M. Moreno, R. Casamitjana, J. Colmenero, M. Dominguez, V. Peinado, A. Barbera, V. Arroyo, J. Caballeria, P. Gines, R. Bataller
Journal: Journal of Hepatology (2008)
B-RAF kinase drives developmental axon growth and promotes axon regeneration in the injured mature CNS
Authors: Kevin J. O’Donovan, Kaijie Ma, Hengchang Guo, Chen Wang, Fang Sun, Seung Baek Han, Hyukmin Kim, Jamie K. Wong, Jean Charron, Hongyan Zou, Young-Jin Son, Zhigang He, Jian Zhong
Journal: The Journal of Experimental Medicine (2014)

Activation of intrinsic growth programs that promote developmental axon growth may also facilitate axon regeneration in injured adult neurons. Here, we demonstrate that conditional activation of B-RAF kinase alone in mouse embryonic neurons is sufficient to drive the growth of long-range peripheral sensory axon projections in vivo in the absence of upstream neurotrophin signaling. We further show that activated B-RAF signaling enables robust regenerative growth of sensory axons into the spinal cord after a dorsal root crush as well as substantial axon regrowth in the crush-lesioned optic nerve. Finally, the combination of B-RAF gain-of-function and PTEN loss-of-function promotes optic nerve axon extension beyond what would be predicted for a simple additive effect. We conclude that cell-intrinsic RAF signaling is a crucial pathway promoting developmental and regenerative axon growth in the peripheral and central nervous systems.
Potential Mechanism for the Effects of Dexamethasone on Growth of Androgen-Independent Prostate Cancer
Authors: K. Nishimura, N. Nonomura, E. Satoh, Y. Harada, M. Nakayama, T. Tokizane, T. Fukui, Y. Ono, H. Inoue, M. Shin, Y. Tsujimoto, H. Takayama, K. Aozasa, A. Okuyama
Journal: JNCI Journal of the National Cancer Institute (2001)

Dexamethasone, a synthetic glucocorticoid, has clinical benefit in patients with hormone-refractory prostate cancer (HRPC), but the mechanisms responsible for its effects are unknown. The nuclear factor-kappaB (NF-kappaB)-dependent cytokine interleukin (IL) 6 (IL-6) is thought to stimulate growth of HRPC. Because dexamethasone interferes with NF-kappaB activation, we determined whether dexamethasone inhibits prostate cancer growth by working through the glucocorticoid receptor (GR) to interfere with NF-kappaB-IL-6 pathway.Three human prostate cancer cell lines (DU145, PC-3, and LNCaP) were assessed for GR expression and responsiveness to dexamethasone. Levels of GR, NF-kappaB, and the cytoplasmic NF-kappB inhibitor IkappaBalpha were determined by western blotting and of IL-6 by enzyme immunoassay. The subcellular localization of NF-kappaB was analyzed by immunofluorescence. The effects of dexamethasone (thrice weekly injections of 1 microg/mouse) on DU145 xenografts in nude and severe combined immunodeficient (SCID) mice were evaluated. GR expression in human prostate cancers was assessed by immunohistochemistry. All statistical tests were two-sided.Dexamethasone dose dependently decreased GR levels and inhibited the growth of DU145 and PC-3 but not LNCaP cells (DU145 cells, P< .001; PC-3 cells, P = .009). Dexamethasone increased IkappaBalpha protein levels and the cytosolic accumulation of NF-kappaB in DU145 cells and decreased secreted IL-6 levels to 37 pg/mL (95% confidence interval [CI] = 33 pg/mL to 41 pg/mL), compared with 164 pg/mL (95% CI = 162 pg/mL to 166 pg/mL) secreted by ethanol-treated control cells. Dexamethasone inhibited the growth of DU145 xenografts in nude (P = .006) and SCID (P = .026) mice without affecting GR levels. Eight of 16 human prostate cancers expressed GR at high levels (>or=30% GR-positive cells).Dexamethasone inhibited the growth of GR-positive cancers, possibly through the disruption of the NF-kappaB-IL-6 pathway.
Inactivation of lysosomal proteases by oxidized low density lipoprotein is partially responsible for its poor degradation by mouse peritoneal macrophages.
Authors: G Hoppe, J O'Neil, H F Hoff
Journal: Journal of Clinical Investigation (1994)

Deficient processing of apo B in oxidized LDL (ox-LDL) by macrophage lysosomal proteases has been documented and attributed to modifications in apo B. We have investigated whether direct inactivation of lysosomal proteases by ox-LDL could also be responsible for this deficient degradation. When mouse peritoneal macrophages (MPM) were preincubated for 21 h at 37 degrees C with ox-LDL, LDL, or vortex-aggregated LDL, only ox-LDL inhibited the subsequent degradation of 125I-labeled forms of the above lipoproteins. Uptake of labeled lipoproteins was not appreciably affected by preincubation with ox-LDL, suggesting that the inhibition was at the level of lysosomal degradation. Thiol protease activity of cell extracts at pH 4.0, was reduced in MPM preincubated with ox-LDL relative to cells preincubated with LDL or medium alone. Extracts from untreated MPM, or mixtures of cathepsin B and D, showed a reduced ability to degrade 125I-LDL at pH 4.5 and reduced cathepsin B activity, after incubation with ox-LDL relative to incubation with LDL. Thus, the reduced degradation of lipoproteins in MPM pretreated with ox-LDL could be due to direct inactivation of the lysosomal protease, cathepsin B.
Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C
Authors: Yasuhiro Asahina, Namiki Izumi, Nobuyuki Enomoto, Masakatsu Uchihara, Masayuki Kurosaki, Yuko Onuki, Yuki Nishimura, Ken Ueda, Kaoru Tsuchiya, Hiroyuki Nakanishi, Takatoshi Kitamura, Shozo Miyake
Journal: Journal of Hepatology (2005)
Characteristics of sputum smear-positive tuberculosis patients with and without HIV infection in a hospital in Zimbabwe
Authors: OD Schoch, HL Rieder
Journal: European Respiratory Journal (1996)

Human immunodeficiency virus (HIV) infection has a large impact on tuberculosis in Africa. In this study, the prevalence of HIV infection in a population of hospitalized tuberculosis patients in Zimbabwe was determined and demographic characteristics, clinical signs and symptoms, as well as radiographic appearance were compared in tuberculosis patients with and without HIV infection. During a 5 month observation period, information on tuberculosis patients referred to Driefontein Tuberculosis Sanatorium, Mvuma, Zimbabwe was collected, computerized and analysed with commercially available software. Of 467 patients admitted, 255 were sputum smear positive for acid-fast bacilli. Of 196 patients with complete information, 127 (65%) were HIV-seropositive. When compared to the 69 HIV-seronegative patients, HIV-infected patients were not different in age, gender, the period of delay between the onset of symptoms and diagnosis, radiographic appearance, history of previous antituberculosis treatment and symptoms and signs reported, with the exception of herpes zoster and other sexually-transmitted disease. The prevalence of HIV infection in our population of tuberculosis patients was large. However, since demographic and clinical characteristics are remarkably similar in tuberculosis patients with and without HIV infection, case-finding activities need not be altered in the wake of the HIV epidemic.During April-September 1992, demographic, clinical, and bacteriological information was collected on all 467 tuberculosis (TB) patients aged 15 years and older admitted to the Driefontein Tuberculosis Sanatorium serving people from the Midlands and Masvingo provinces in Zimbabwe. 255 people had at least one sputum smear positive for acid-fast bacilli. Researchers retained 196 of these for analysis and compared demographic characteristics, clinical signs and symptoms, and radiographic appearance in TB patients with and without HIV infection. 127 (65%) people tested positive for HIV. HIV-infected TB patients were not significantly different compared to HIV-negative TB patients in age, gender, the period of delay between the onset of symptoms and diagnosis (about 2 months for both groups), radiographic appearance, history of previous anti-TB treatment, and symptoms and signs reported. They were more likely than HIV-negative TB patients to have a history of sexually transmitted diseases (adjusted odds ratio = 3.4; p = 0.01) and herpes zoster infection (9 vs. 0 patients). These findings suggest that health workers need not change case finding activities in the wake of the HIV epidemic. In conclusion, the most cost-effective intervention continues to be identification and curative treatment of sputum smear-positive TB patients irrespective of their HIV status.
ABC of computing. Computers in high dependency units.
Authors: A J Asbury, K Lush, C I Franks
Journal: BMJ (1983)

Blood pressure I'Revew on day 20 Artefact -?*~Inotropic drug ?)lNew nurse".In many hospitals the most severely ill patients are cared for together in specialist areas-for example, in postsurgical, intensive care, and coronary care units-to simplify management and provide a high ratio of staff to patients.These patients usually need extensive monitoring and the necessary equipment generates a large volume of data.Computers are increasingly used in high dependency units to make these data available and useful to the staff, but unfortunately it is difficult to predict their best application.New methods need to be critically examined, and the views of the people who will have to use the system should be taken into account.It is perfectly possible to implement a computer system for the sake of doing so yet remain unaware that the real benefits may be small.The applications can be divided into off line, on line, and feedback control.Offline applications are simple computer systems where epidemiological information is collected to help in directing and refining management policies.The information is entered into the computer in batches, sometimes even when the patient has left the unit, and the results of the analysis form the basis of local mortality reports.This technique allows the high dependency unit to be managed on the basis of facts rather than opinions and is an excellent form of internal audit.One important feature of information from an high dependency unit is that it includes a wide range of different types of information, from that relating to states, such as being conscious or unconscious, to measurements such as blood pressures which are on a continuous scale.Off line applications
Active surveillance for rheumatic heart disease in endemic regions: a systematic review and meta-analysis of prevalence among children and adolescents
Authors: Martina Rothenbühler, Crochan J O'Sullivan, Stefan Stortecky, Giulio G Stefanini, Ernest Spitzer, Janne Estill, Nikesh R Shrestha, Olivia Keiser, Peter Jüni, Thomas Pilgrim
Journal: The Lancet Global Health (2014)

BackgroundRheumatic heart disease accounts for up to 250 000 premature deaths every year worldwide and can be regarded as a physical manifestation of poverty and social inequality. We aimed to estimate the prevalence of rheumatic heart disease in endemic countries as assessed by different screening modalities and as a function of age.MethodsWe searched Medline, Embase, the Latin American and Caribbean System on Health Sciences Information, African Journals Online, and the Cochrane Database of Systematic Reviews for population-based studies published between Jan 1, 1993, and June 30, 2014, that reported on prevalence of rheumatic heart disease among children and adolescents (≥5 years to <18 years). We assessed prevalence of clinically silent and clinically manifest rheumatic heart disease in random effects meta-analyses according to screening modality and geographical region. We assessed the association between social inequality and rheumatic heart disease with the Gini coefficient. We used Poisson regression to analyse the effect of age on prevalence of rheumatic heart disease and estimated the incidence of rheumatic heart disease from prevalence data.FindingsWe included 37 populations in the systematic review and meta-analysis. The pooled prevalence of rheumatic heart disease detected by cardiac auscultation was 2·9 per 1000 people (95% CI 1·7–5·0) and by echocardiography it was 12·9 per 1000 people (8·9–18·6), with substantial heterogeneity between individual reports for both screening modalities (I2=99·0% and 94·9%, respectively). We noted an association between social inequality expressed by the Gini coefficient and prevalence of rheumatic heart disease (p=0·0002). The prevalence of clinically silent rheumatic heart disease (21·1 per 1000 people, 95% CI 14·1–31·4) was about seven to eight times higher than that of clinically manifest disease (2·7 per 1000 people, 1·6–4·4). Prevalence progressively increased with advancing age, from 4·7 per 1000 people (95% CI 0·0–11·2) at age 5 years to 21·0 per 1000 people (6·8–35·1) at 16 years. The estimated incidence was 1·6 per 1000 people (0·8–2·3) and remained constant across age categories (range 2·5, 95% CI 1·3–3·7 in 5-year-old children to 1·7, 0·0–5·1 in 15-year-old adolescents). We noted no sex-related differences in prevalence (p=0·829).InterpretationWe found a high prevalence of rheumatic heart disease in endemic countries. Although a reduction in social inequalities represents the cornerstone of community-based prevention, the importance of early detection of silent rheumatic heart disease remains to be further assessed.FundingUBS Optimus Foundation.
V(D)j Recombination Becomes Accessible
Authors: Michael S. Krangel
Journal: The Journal of Experimental Medicine (2001)

The diverse antigen receptor repertoires of B and T lymphocytes are generated by somatic rearrangement of Ig and TCR V, D, and J gene segments during lymphocyte development. A basic mechanistic understanding of V(D)J recombination reaction is now at hand. The process is initiated by recombinase proteins recombination activating gene (RAG)-1 and RAG-2, which bind to recombination signal sequences (RSSs) that flank Ig and TCR gene segments, recruit a pair of RSSs into a synaptic complex, and generate double strand breaks (DSBs) between the RSSs and coding segments. The reaction is then completed with the additional participation of DSB repair proteins, which help to process and rejoin the coding and signal end molecules to generate coding joints and signal joints, respectively. V(D)J recombination at the various Ig and TCR loci is highly regulated during lymphocyte development, with lineage- and developmental stage‐specific rearrangement events distinguishing individual loci, and even individual gene segments within loci. It has long been appreciated that this developmental regulation cannot be accounted for by the expression of either RAG or DNA repair proteins. It has been noted that transcription of unrearranged gene segments (germline transcription) parallels their developmental activation for V(D)J recombination. Yancopoulos and Alt interpreted this transcriptional activity to reflect a permis
Immunotherapy coming of age: What will it take to make it standard of care for glioblastoma?
Authors: A. B. Heimberger, J. H. Sampson
Journal: Neuro-Oncology (2010)

With the recent approval by the FDA of an immunotherapy for prostate cancer and another positive immunotherapy trial in melanoma, immunotherapy may finally be coming of age. So what will it take for it to become part of the standard treatment for glioblastoma? To put this question into perspective, we summarize critical background information in neuro-immunology, address immunotherapy clinical trial design, and discuss a number of extrinsic factors that will impact the development of immunotherapy in neuro-oncology.