tbuckley/cabot-search huggingface dataset:
The European consensus on ulcerative colitis: new horizons?
Authors: E. F Stange, S. P L Travis
Journal: Gut (2008)

A European consensus on anything is not easy to achieve, and inflammatory bowel disease (IBD) is no exception. The European Crohn’s and Colitis Organisation (ECCO), has now published the Consensus on the management of ulcerative colitis1–3 to complement the highly successful Crohn’s disease Consensus, which became the most downloaded papers from Gut in 2007.4–6 A further European Consensus on opportunistic infections and IBD, to be published during 2008 and an update of the Crohn’s Consensus presented at the United European Gastroenterology Week (UEGW) in Vienna, are the product of a formal process, and hence the capital C in Consensus.

The limits of evidence-based medicine are such that guidelines appear most necessary where evidence is limited. The Consensus process endeavours to quantify opinion through a detailed preparatory phase, with systematic literature searches on selected topics, questionnaires on areas of controversy and grading of evidence according to the Oxford Centre for Evidence Based Medicine, from the optimal 1a (systematic review with homogeneity of randomised controlled trials) to the lowest level 5 (expert opinion, even including our own).1 4 Based on the evidence levels, recommendations are graded from A (consistent level 1 studies) to D (level 5 evidence). Preliminary statements are then drafted by working parties, discussed and modified at a plenary meeting of experts (72 from the then 22 countries of ECCO in the ulcerative colitis Consensus). Consent has to prevail over dissent and evidence over eminence: habemus consensus, formally defined as >80% agreement, a majority vote for 50–80% agreement and no consensus for <50% accord. The statements, forged as if from molten metal at the plenary session, provide the framework for the guideline. The supporting text is then written by the working parties to place statements in the necessary context and collated into the …
Prevalence estimates for primary brain tumors in the United States by behavior and major histology groups
Authors: Faith G. Davis, Varant Kupelian, Sally Freels, Bridget McCarthy, Tanya Surawicz
Journal: Neuro-Oncology (2001)

Prevalence rates are used to supplement descriptions of disease and are unavailable for all primary brain tumors in the United States.Data from two population-based tumor registries were obtained from the Central Brain Tumor Registry of the United States and used to compute age-speci c incidence rates (1985-1994) and survival curves for further use in a statistical model to estimate prevalence rates.Prevalence rates were then used to estimate the number of individuals living with a brain tumor diagnosis in the U.S. population for the year 2000.The overall incidence rate in these regions is 13.8 per 100,000 with 2-, 5-, and 10-year survival rates of 58%, 49%, and 38%, respectively.The prevalence rate for all primary brain tumors is 130.8 per 100,000 with approximately 350,000 individuals estimated to be living with this diagnosis in the United States in 2000.The prevalence rate for malignant tumors, 29.5 per 100,000, is similar to previous reports.The prevalence rate for benign tumors, 97.5 per 100,000, is new.Unlike incidence data, the proportion (and expected number) of existing benign tumors (75%, 267,000) is considerably greater than that for malignant tumors (23%, 81,000), re ecting the better prognosis of benign tumors diagnosed in individuals younger than 60 years old.These data underscore the impact of primary brain tumors in the U.S. health care system and emphasize the need for quality-of-life considerations, particularly for those long-term survivors of benign tumors.
Prevailing Role of Contact Guidance in Intrastromal T-cell Trapping in Human Pancreatic Cancer
Authors: Natalie Hartmann, Nathalia A. Giese, Thomas Giese, Isabel Poschke, Rienk Offringa, Jens Werner, Eduard Ryschich
Journal: Clinical Cancer Research (2014)

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive collagen-rich stroma. T cells that infiltrate pancreatic cancers frequently become trapped in the stroma and do not contact tumor cells. Here, we aimed to analyze how chemokines and extracellular matrix (ECM) collagen interact in mediating T-cell infiltration in PDAC.T-cell distribution and ECM structure within tumors were analyzed. Chemokine concentrations in human PDAC were compared with the levels of immune cell infiltration. We assessed the influences of selected chemokines and collagen on directed and random T-cell movement using in vitro migration systems.PDAC overproduced several T-cell-active chemokines, but their levels were not correlated with intratumoral T-cell infiltration. In the absence of collagen, directed migration of activated T cells was induced by chemokines. Interestingly, collagen itself promoted high migratory activity of T cells, but completely abolished chemokine-guided movement. This effect was not altered by a β1-integrin blocking antibody. Activated T cells actively migrated in low-density collagen matrices, but migration was inhibited in dense collagen. Accordingly, T cells were heterogeneously distributed in the pancreatic cancer stroma, with the majority residing in areas of low-density collagen far from tumor clusters.The excessive desmoplasia in PDAC promotes T-cell migration by contact guidance, which abrogates tumor cell-directed movement. Furthermore, dense collagen networks represent a physical barrier, additionally rearranging T-cell distribution to favor tumor stroma. These mechanisms are mainly responsible for intrastromal T-cell trapping in pancreatic cancer and may hinder the development of T-cell-based immunotherapies.
Incidences, Treatments, Outcomes, and Sex Effect on Survival in Patients With End-Stage Renal Disease by Diabetes Status in Australia and New Zealand (1991–2005)
Authors: Emmanuel Villar, Sean Haw Chang, Stephen Peter McDonald
Journal: Diabetes Care (2007)

We aimed to update the epidemiology of type 1 and type 2 diabetic patients among the incident end-stage renal disease (ESRD) population in Australia and New Zealand (ANZ) and to determine whether outcome is worse for diabetic women, as described in the general population.All resident adults of ANZ who began renal replacement therapy (RRT) from 1 April 1991 to 31 December 2005 were included using data from the ANZ Dialysis and Transplant Registry. Incidence rates, RRT, and survival were analyzed. Risk factors for death were assessed using Cox regression.The study included 1,284 type 1 diabetic (4.5%), 8,560 type 2 diabetic (30.0%), and 18,704 nondiabetic (65.5%) patients. The incidence rate of ESRD with type 2 diabetes increased markedly over time (+10.2% annually, P < 0.0001). In patients aged <70 years, rates of renal transplantation in type 1 diabetic, type 2 diabetic, and nondiabetic patients were 41.8, 6.5 (P < 0.0001 vs. other patients), and 40.9% (P = 0.56 vs. type 1 diabetic patients), respectively. Compared with nondiabetic patients, the adjusted hazard ratio (HR) for death was 1.64 (P < 0.0001) in type 1 diabetes and 1.13 (P < 0.0001) in type 2 diabetes. Survival rates per 5-year period improved by 6% in type 1 diabetic patients (P = 0.36), by 9% in type 2 diabetic patients (P < 0.0001), and by 5% in nondiabetic patients (P = 0.001). In type 2 diabetic patients aged >or=60 years, the adjusted HR for death in women versus men was 1.19 (P = 0.0003).The incidence of ESRD with type 2 diabetes increased markedly. Despite high access to renal transplants, type 1 diabetic patients had a poor prognosis after starting RRT. Survival improved significantly in type 2 diabetic patients during the study period. Older type 2 diabetic women had a worse prognosis than older type 2 diabetic men.
Hyposecretion of fluid from tracheal submucosal glands of CFTR-deficient pigs
Authors: Nam Soo Joo, Hyung-Ju Cho, Monal Khansaheb, Jeffrey J. Wine
Journal: Journal of Clinical Investigation (2010)

Cystic fibrosis (CF) results from mutations that disrupt CF transmembrane conductance regulator (CFTR), an anion channel found mainly in apical membranes of epithelial cells. CF leads to chronic infection of the airways with normally innocuous bacteria and fungi. Hypotheses to explain the pathophysiology of CF airways have been difficult to test because mouse models of CF do not develop human-like airway disease. The recent production of pigs lacking CFTR and pigs expressing the most common CF-causing CFTR mutant, DeltaF508, provide another model that might help clarify the pathophysiology of CF airway disease. Here, we studied individual submucosal glands from 1-day-old piglets in situ in explanted tracheas, using optical methods to monitor mucus secretion rates from multiple glands in parallel. Secretion rates from control piglets (WT and CFTR+/-) and piglets with CF-like disease (CFTR-/- and CFTR-/DeltaF508) were measured under 5 conditions: unstimulated (to determine basal secretion), stimulated with forskolin, stimulated with carbachol, stimulated with substance P, and, as a test for synergy, stimulated with forskolin and a low concentration of carbachol. Glands from piglets with CF-like disease responded qualitatively to all agonists like glands from human patients with CF, producing virtually no fluid in response to stimulation with forskolin and substantially less in response to all other agonists except carbachol. These data are a step toward determining whether gland secretory defects contribute to CF airway disease.
Safety and Feasibility of Catheter-Based Local Intracoronary Vascular Endothelial Growth Factor Gene Transfer in the Prevention of Postangioplasty and In-Stent Restenosis and in the Treatment of Chronic Myocardial Ischemia
Authors: Marja Hedman, Juha Hartikainen, Mikko Syvänne, Joachim Stjernvall, Antti Hedman, Antti Kivelä, Esko Vanninen, Hanna Mussalo, Esa Kauppila, Sakari Simula, Outi Närvänen, Arto Rantala, Keijo Peuhkurinen, Markku S. Nieminen, Markku Laakso, Seppo Ylä-Herttuala
Journal: Circulation (2003)

Catheter-based intracoronary vascular endothelial growth factor (VEGF) gene transfer is a potential treatment for coronary heart disease. However, only limited data are available about local VEGF gene transfer given during angioplasty (PTCA) and stenting.Patients with coronary heart disease (n=103; Canadian Cardiovascular Society class II to III; mean age, 58+/-6 years) were recruited in this randomized, placebo-controlled, double-blind phase II study. PTCA was performed with standard methods, followed by gene transfer with a perfusion-infusion catheter. Ninety percent of the patients were given stents; 37 patients received VEGF adenovirus (VEGF-Adv, 2x10(10) pfu), 28 patients received VEGF plasmid liposome (VEGF-P/L; 2000 microg of DNA with 2000 microL of DOTMA:DOPE [1:1 wt/wt]), and 38 control patients received Ringer's lactate. Follow-up time was 6 months. Gene transfer to coronary arteries was feasible and well tolerated. The overall clinical restenosis rate was 6%. In quantitative coronary angiography analysis, the minimal lumen diameter and percent of diameter stenosis did not significantly differ between the study groups. However, myocardial perfusion showed a significant improvement in the VEGF-Adv-treated patients after the 6-month follow-up. Some inflammatory responses were transiently present in the VEGF-Adv group, but no increases were detected in the incidences of serious adverse events in any of the study groups.Gene transfer with VEGF-Adv or VEGF-P/L during PTCA and stenting shows that (1) intracoronary gene transfer can be performed safely (no major gene transfer-related adverse effects were detected), (2) no differences in clinical restenosis rate or minimal lumen diameter were present after the 6-month follow-up, and (3) a significant increase was detected in myocardial perfusion in the VEGF-Adv-treated patients.
The frame/content model and syntactic evolution
Authors: Andrew Carstairs-McCarthy
Journal: Behavioral and Brain Sciences (1998)

The frame/content theory suggests that chewing was tinkered into speaking. A simple extrapolation of this approach suggests that syllable structure may have been tinkered into syntax. That would explain the widely noted parallels between sentence structure and syllable structure, and also the otherwise mysterious pervasiveness of the grammatical distinction between sentences and noun phrases.
Sternocostoclavicular hyperostosis presenting with thoracic sinus formation.
Authors: G. E. Wilson, C. C. Evans
Journal: Thorax (1996)

Sternocostoclavicular hyperostosis (SCCH) is a condition which is well described in the Japanese literature but is rare in Western Europe. It is characterised by pain and swelling in the upper anterior part of the chest, which tends to be progressive. A patient is described with bilateral chronic discharging sinuses over the anterior ends of the clavicles in whom the diagnosis appeared to be one of SCCH.
Sowing the seeds of doubt: a narrative review on metacognitive training in schizophrenia
Authors: Steffen Moritz, Christina Andreou, Brooke C. Schneider, Charlotte E. Wittekind, Mahesh Menon, Ryan P. Balzan, Todd S. Woodward
Journal: Clinical Psychology Review (2014)

The present article provides a narrative review of empirical studies on metacognitive training in psychosis (MCT). MCT represents an amalgam of cognitive-behavioral therapy (CBT), cognitive remediation (CRT) and psychoeducation. The intervention is available in either a group (MCT) or an individualized (MCT+) format. By sowing the seeds of doubt in a playful and entertaining fashion, the program targets positive symptoms, particularly delusions. It aims to raise patients' awareness for common cognitive traps or biases (e.g., jumping to conclusions, overconfidence in errors, bias against disconfirmatory evidence) that are implicated in the formation and maintenance of psychosis. The majority of studies confirm that MCT meets its core aim, the reduction of delusions. Problems (e.g., potential allegiance effects) and knowledge gaps (i.e., outcome predictors) are highlighted. The preliminary data suggest that the individual MCT format is especially effective in addressing symptoms, cognitive biases and insight. We conclude that MCT appears to be a worthwhile complement to pharmacotherapy.
Prognostic significance of TRAIL death receptors in Middle Eastern colorectal carcinomas and their correlation to oncogenic KRAS alterations
Authors: Prashant Bavi, Sarita E Prabhakaran, Jehad Abubaker, Zeeshan Qadri, Thara George, Nasser Al-Sanea, Alaa Abduljabbar, Luai H Ashari, Samar Alhomoud, Fouad Al-Dayel, Azhar R Hussain, Shahab Uddin, Khawla S Al-Kuraya
Journal: Molecular Cancer (2010)

Abstract Background Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumour necrosis factor cytokine family that induces apoptosis upon binding to its death domain containing receptors, TRAIL receptor 1 (DR4) and TRAIL receptor 2 (DR5). Expression of TRAIL receptors is higher in colorectal carcinoma (CRC) as compared to normal colorectal mucosa and targeted therapy with TRAIL leads to preferential killing of tumor cells sparing normal cells. Methods We investigated the expression of TRAIL and its receptors in a tissue microarray cohort of 448 Middle Eastern CRC. We also studied the correlation between TRAIL receptors and various clinico-pathological features including key molecular alterations and overall survival. Results CRC subset with TRAIL-R1 expression was associated with a less aggressive phenotype characterized by early stage (p = 0.0251) and a histology subtype of adenocarcinomas (p = 0.0355). Similarly CRC subset with TRAIL-R2 expression was associated with a well-differentiated tumors (p &lt; 0.0001), histology subtype of adenocarcinomas (p = 0.0010) and tumors in left colon (p = 0.0009). Over expression of pro apoptotic markers: p27 KIP1 and KRAS4A isoforms was significantly higher in CRC subset with TRAIL-R1 and TRAIL-R2 expression; TRAIL-R1 expression was also associated with cleaved caspase-3(p = 0.0011). Interestingly, TRAIL-R2 expression was associated with a microsatellite stable (MS--S/L) phenotype (p = 0.0003) and with absence of KRAS mutations (p = 0.0481). Conclusion TRAIL-R1 expression was an independent prognostic marker for better survival in all CRC samples and even in the CRC group that received adjuvant therapy. The biological effects of TRAIL in CRC models, its enhancement of chemosensitivity towards standard chemotherapeutic agents and the effect of endogenous TRAIL receptor levels on survival make TRAIL an extremely attractive therapeutic target.
Inability to get up after falling, subsequent time on floor, and summoning help: prospective cohort study in people over 90
Authors: J. Fleming, C. Brayne
Journal: BMJ (2008)

<b>Objectives</b> To describe the incidence and extent of lying on the floor for a long time after being unable to get up from a fall among people aged over 90; to explore their use of call alarm systems in these circumstances. <b>Design</b> 1 year follow-up of participants in a prospective cohort study of ageing, using fall calendars, phone calls, and visits. <b>Setting</b> Participants’ usual place of residence (own homes or care homes), mostly in Cambridge. <b>Participants</b> 90 women and 20 men aged over 90 (n=110), surviving participants of the Cambridge City over-75s Cohort, a population based sample. <b>Main outcome measures</b> Inability to get up without help, lying on floor for a long time after falling, associated factors; availability and use of call alarm systems; participants’ views on using call alarms to summon help if needed after falling. <b>Results</b> In one year’s intensive follow-up, 54% (144/265) of fall reports described the participant as being found on the floor and 82% (217/265) of falls occurred when the person was alone. Of the 60% who fell, 80% (53/66) were unable to get up after at least one fall and 30% (20/66) had lain on the floor for an hour or more. Difficulty in getting up was consistently associated with age, reported mobility, and severe cognitive impairment. Cognition was the only characteristic that predicted lying on the floor for a long time. Lying on the floor for a long time was strongly associated with serious injuries, admission to hospital, and subsequent moves into long term care. Call alarms were widely available but were not used in most cases of falls that led to lying on the floor for a long time. Comments from older people and carers showed the complexity of issues around the use of call alarms, including perceptions of irrelevance, concerns about independence, and practical difficulties. <b>Conclusions</b> Lying on the floor for a long time after falling is more common among the “oldest old” than previously thought and is associated with serious consequences. Factors indicating higher risk and comments from participants suggest practical implications. People need training in strategies to get up from the floor. Work is needed on access and activation issues for design of call alarms and information for their effective use. Care providers need better understanding of the perceptions of older people to provide acceptable support services.
Angiogenesis in Endocrine Tumors
Authors: Helen E. Turner, Adrian L. Harris, Shlomo Melmed, John A. H. Wass
Journal: Endocrine Reviews (2003)

Abstract Angiogenesis is the process of new blood vessel development from preexisting vasculature. Although vascular endothelium is usually quiescent in the adult, active angiogenesis has been shown to be an important process for new vessel formation, tumor growth, progression, and spread. The angiogenic phenotype depends on the balance of proangiogenic growth factors such as vascular endothelial growth factor (VEGF) and inhibitors, as well as interactions with the extracellular matrix, allowing for endothelial migration. Endocrine glands are typically vascular organs, and their blood supply is essential for normal function and tight control of hormone feedback loops. In addition to metabolic factors such as hypoxia, the process of angiogenesis is also regulated by hormonal changes such as increased estrogen, IGF-I, and TSH levels. By measuring microvascular density, differences in angiogenesis have been related to differences in tumor behavior, and similar techniques have been applied to both benign and malignant endocrine tumors with the aim of identification of tumors that subsequently behave in an aggressive fashion. In contrast to other tumor types, pituitary tumors are less vascular than normal pituitary tissue, although the mechanism for this observation is not known. A relationship between angiogenesis and tumor size, tumor invasiveness, and aggressiveness has been shown in some pituitary tumor types, but not in others. There are few reports on the role of microvascular density or angiogenic factors in adrenal tumors. The mechanism of the vascular tumors, which include adrenomedullary tumors, found in patients with Von Hippel Lindau disease has been well characterized, and clinical trials of antiangiogenic therapy are currently being performed in patients with Von Hippel Lindau disease. Thyroid tumors are more vascular than normal thyroid tissue, and there is a clear correlation between increased VEGF expression and more aggressive thyroid tumor behavior and metastasis. Although parathyroid tissue induces angiogenesis when autotransplanted and PTH regulates both VEGF and MMP expression, there are few studies of angiogenesis and angiogenic factors in parathyroid tumors. An understanding of the balance of angiogenesis in these vascular tumors and mechanisms of vascular control may assist in therapeutic decisions and allow appropriately targeted treatment.
Pulmonary function and maximal transrespiratory pressures in ankylosing spondylitis.
Authors: D Vanderschueren, M Decramer, P Van den Daele, J Dequeker
Journal: Annals of the Rheumatic Diseases (1989)

Clinical measurements and pulmonary functions, including maximal transrespiratory pressures, were studied in 30 patients (age 43 (SD 10) years) with ankylosing spondylitis. Vital capacity (VC) was slightly reduced to 79 (16)% and forced expiratory volume in one second (FEV1) was similarly reduced to 82 (20)% such that the average FEV1/VC ratio was 77.8 (6.65). Total lung capacity was slightly reduced to 85 (13)%. Transfer factor of the lung for carbon monoxide (TLCO) averaged 88 (17)% and TLCO per unit lung volume was 114 (26)%. Reductions in lung volumes correlated well with clinical measurements. Both maximal expiratory pressures (PEmax) and inspiratory pressures (PImax) were clearly reduced to 56 (17)% and 76 (28)% respectively. This suggests that spirometrically determined volumes were better preserved than respiratory muscle strength in ankylosing spondylitis. It is speculated that the reduction in respiratory muscle strength may be due to intercostal muscle atrophy.