tbuckley/cabot-search huggingface dataset:
O2.02 * ROLE OF AN INTEGRATED IMAGING FOR TARGET VOLUME DEFINITION AND RADIOTHERAPY PLANNING IN PATIENTS WITH DIAGNOSED HIGH GRADE GLIOMA
Authors: P. Navarria, F. Pessina, S. Tomatis, P. Mancosu, A. Ascolese, E. Lopci, A. Bizzi, E. Clerici, L. Bello, M. Scorsetti
Journal: Neuro-Oncology (2014)

PURPOSE: To evaluate the impact of FLAIR/MRI and 11C-MET PET for high grade glioma (HGG) tumor volume delineation on radiotherapy (RT) planning. End point is local and systemic toxicity, local control and patients survival. METHODS AND MATERIALS: Patients with diagnosis of HGG underwent CT scan, MRI and 11CMET-PET for RT planning were included. Surgery, concomitant chemo-radiotherapy and adjuvant chemotherapy (CT) were performed in all patients. Clinical Target Volume was delineated on enhanced T1-MRI (CTV1) and on FLAIR-MRI images (CTV2) that were compared between them. Planning Target Volume (PTV1 and PTV2) was generated enlarging CTV1 and CTV2 of 20 mm and 10 mm respectively; also Biological Target Volume (BTV) was delineated. Plans were optimized using volumetric modulated arc therapy (VMAT). Response and toxicity were recorded. RESULTS: From November 2011 to June 2013, 69 patients were evaluated. MET-PET uptake was visible in all cases after surgery. In 50% of patients part of BTV was outside of the PTV1 up to 32 mm, while in all cases BTV was inside of the PTV2. No severe toxicities were recorded. Recurrence in the same site of treatment occurred in 38/69 (55%) patients at a median time of 13 months (range 5-14 months) all in field. With a median observation time of 16 months (range 6-21 months) 57 patients (84%) are alive and 11 (16%) dead. DFS and OS at 1 and 2 years were 63 % and 33%, 87% and 82% respectively. Extent of resection (EOR) and MGMT promoter methilation significantly affected survival (p< 0.01). CONCLUSION: Our data suggest that target volume definition using FLAIR-MRI is more adequate for target definition compared with enhanced T1MRI. This approach allows a better target coverage and increased normal brain sparing. Besides, uptake 11C-METPET could help to identify microscopic residual risk areas that should need higher radiation therapy doses.
Ventilator-associated pneumonia
Authors: M. Tweed
Journal: European Respiratory Journal (2001)

Ventilator-associated pneumoniaTo the Editor: recent task force report is a welcome review of the situation regarding ventilator associated pneumonia (VAP) [1].In the prevention of VAP section a number of nonpharmacological measures, including posture were discussed.However there was no mention of rotational therapy [2-9].Admittedly, these publications are variously limited by: selected patient diagnoses, extensive exclusion criteria, various definitions of outcomes (including VAP), lack of controls and small numbers.There is no trial that has produced statistically and clinically significant results that can be generalized to the majority of patients.How successful this treatment is in a wide variety of patients and how it compares with other treatment strategies, alone or in combination, needs to be studied.This subject deserves further research and should be included in the "What should be investigated" section.
Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and function
Authors: Lalit Kumar, Janet Chou, Christina S.K. Yee, Arturo Borzutzky, Elisabeth H. Vollmann, Ulrich H. von Andrian, Shin-Young Park, Georg Hollander, John P. Manis, P. Luigi Poliani, Raif S. Geha
Journal: The Journal of Experimental Medicine (2014)

Lrrc8a is a ubiquitously expressed gene that encodes a leucine-rich repeat (LRR)–containing protein detected at higher levels on the surface of thymocytes than on other immune cells. We generated Lrrc8a−/− mice to investigate the role of LRRC8A in lymphocyte development and function. Lrrc8a−/− mice had increased prenatal and postnatal mortality, growth retardation, and multiple tissue abnormalities. Lrrc8a−/− mice displayed a modest block in B cell development but intact intrinsic B cell function. In contrast, both Lrrc8a−/− mice and Lrrc8a−/−→Rag2−/− bone marrow chimeras exhibited a severe cell-intrinsic block in early thymic development, with decreased proliferation and increased apoptosis of thymocytes, and impaired peripheral T cell function. Thymic epithelial cells expressed an LRRC8A ligand that was critical for double-negative to double-positive thymocyte differentiation and survival in vitro. LRRC8A constitutively associated with the GRB2–GAB2 complex and lymphocyte-specific protein tyrosine kinase (LCK) in thymocytes. LRRC8A ligation activated AKT via the LCK–ZAP–70–GAB2–PI3K pathway, and AKT phosphorylation was markedly reduced in the thymus of Lrrc8a−/− mice. These findings reveal an essential role for LRRC8A in T cell development, survival, and function.
Effect of physician specialty on outcomes in diabetic ketoacidosis.
Authors: C S Levetan, M D Passaro, K A Jablonski, R E Ratner
Journal: Diabetes Care (1999)

OBJECTIVE: More than 100,000 people are hospitalized annually in the U.S. with diabetic ketoacidosis (DKA). Outcome differences have not been examined for these patients based on whether their primary care provider is a generalist or a diabetes specialist. The objective of this study was to investigate hospital charges and hospital length of stay (LOS) for patients with DKA according to the specialty of their primary care provider. RESEARCH DESIGN AND METHODS: We investigated all patients with a primary diagnosis of DKA during a 3.5-year period (n = 260) in a large urban teaching hospital. Hospital charges and LOS were studied regarding the specialty of the primary care provider. Demographic factors, severity of illness, laboratory data, and readmission rates were compared. RESULTS: Patients cared for by generalists and endocrinologists had a similar case mix and severity of DKA. The age-adjusted mean LOS for patients of generalists was 4.9 days (95% CI 4.5-5.4), and the mean LOS for patients of endocrinologists was 3.3 days (2.6-4.2) (P &amp;lt; 0.0043). Mean hospital charges differed (P &amp;lt; 0.0001) with an age- and sex-adjusted mean for patients of endocrinologists of $5,463 ($4,179-7,141) and a mean for patients of generalists of $10,109 ($9,151-11,166). The additional charges incurred by generalists were due in part to patients undergoing more procedures. No differences in diabetes-related complications occurred during admission, but the endocrinologist-treated group had a lower readmission rate for DKA during the study period than the generalist-treated group (2 vs. 6%, respectively) (P = 0.03). CONCLUSIONS: Endocrinologists provide more cost-effective care than generalists do when serving as primary care providers for patients hospitalized with DKA.
Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: clinical activity and molecular response (GORTEC 2008-02)
Authors: S. Schmitz, M.-C. Kaminsky-Forrett, S. Henry, S. Zanetta, L. Geoffrois, E. Bompas, A. Moxhon, L. Mignion, J. Guigay, L. Knoops, M. Hamoir, J.-P. Machiels
Journal: Annals of Oncology (2012)
Assessment of dermal water by high-frequency ultrasound: comparative studies with nuclear magnetic resonance
Authors: M. GNIADECKA, B. QUISTORFF
Journal: British Journal of Dermatology (1996)

Although a principal constituent of human skin, cutaneous water is difficult to study, and little is known about water behaviour in physiological and pathological conditions of the skin. It has been proposed recently that changes in dermal echogenicity measured by high-frequency ultrasonography reflect changes in dermal water content. To validate skin ultrasonography for assessment of dermal water changes we have studied the relationship between dermal echogenicity and skin water content determined by nuclear magnetic resonance technique. Twenty MHz ultrasound scanning of the dorsal and ventral forearm skin was performed in 59 healthy volunteers (age 18-65) and dermal echogenicity was determined by counting low echogenic pixels (LEPs) in skin images. 1H magnetic resonance spectra were obtained from the same regions and the ratio of areas under the water- and fat-specific peaks (W/F) were calculated to measure a relative water content. Acute dermal oedema (histamine weal) was studied in the same way in 40 individuals. Baseline dermal echogenicity correlated significantly with W/F, both in the ventral (r = 0.47) and dorsal (r = 0.57) forearm. Intradermal application of histamine caused a development of intradermal oedema which could be visualized by nuclear magnetic resonance imaging. In a corresponding ultrasound image oedema was seen as a low-echogenic area. The proportional increases in LEPs and W/F after histamine application were correlated, but the elevation in LEPs was 25-48% (95% confidence intervals) higher than that for W/F. These results suggest that high-frequency ultrasonography is a sensitive method for assessment of changes in dermal hydration. This technique may find important applications in comparative and non-invasive evaluations of dermal water in physiological conditions and in skin pathologies associated with oedema formation.
Death to Carbohydrate Counting?
Authors: Nichola J. Davis, Judith Wylie-Rosett
Journal: Diabetes Care (2008)

Insulin therapy is an effective strategy for achieving glycemic control in patients with type 2 diabetes. Although often neglected, it is important to use an appropriate diet strategy to complement the insulin. Furthermore, a basic tenet of such therapy is that insulin dosage and administration should be appropriate to balance diet and physical activity in order to maintain normoglycemia.

In this issue of Diabetes Car e, Bergenstal et al. (1) evaluated two strategies for determining the appropriate dosage of mealtime bolus insulin. A simple algorithm that adjusted bolus insulin dose based on weekly average of premeal glucose was compared with an algorithm based on mealtime carbohydrate counting. The authors demonstrated the equivalence of both the simple strategy and the more elaborate carbohydrate-counting strategy in achieving glycemic control; almost one-half the participants in both groups achieved an A1C <6.5%. Can patients with type 2 diabetes treated with basal:bolus insulin succeed without adding the complexity of carbohydrate counting?

Carbohydrate counting has been around since the 1920s and became integral in managing patients with type 1 diabetes after the landmark findings of the Diabetes Control and Complications …
Neutralisation of Dkk-1 protects from systemic bone loss during inflammation and reduces sclerostin expression
Authors: Gisela Ruiz Heiland, Karin Zwerina, Wolfgang Baum, Trayana Kireva, Jörg H Distler, Mario Grisanti, Frank Asuncion, Xiadong Li, Michael Ominsky, William Richards, Georg Schett, Jochen Zwerina
Journal: Annals of the Rheumatic Diseases (2010)

Introduction Inflammation is a major risk factor for systemic bone loss. Proinflammatory cytokines like tumour necrosis factor (TNF) affect bone homeostasis and induce bone loss. It was hypothesised that impaired bone formation is a key component in inflammatory bone loss and that Dkk-1, a Wnt antagonist, is a strong inhibitor of osteoblast-mediated bone formation.TNF transgenic (hTNFtg) mice were treated with neutralising antibodies against TNF, Dkk-1 or a combination of both agents. Systemic bone architecture was analysed by bone histomorphometry. The expression of β-catenin, osteoprotegerin and osteocalcin was analysed. In vitro, primary osteoblasts were stimulated with TNF and analysed for their metabolic activity and expression of Dkk-1 and sclerostin. Sclerostin expression and osteocyte death upon Dkk-1 blockade were analysed in vivo.Neutralisation of Dkk-1 completely protected hTNFtg mice from inflammatory bone loss by preventing TNF-mediated impaired osteoblast function and enhanced osteoclast activity. These findings were accompanied by enhanced skeletal expression of β-catenin, osteocalcin and osteoprotegerin. In vitro, TNF rapidly increased Dkk-1 expression in primary osteoblasts and effectively blocked osteoblast differentiation. Moreover, blockade of Dkk-1 not only rescued impaired osteoblastogenesis but also neutralised TNF-mediated sclerostin expression in fully differentiated osteoblasts in vitro and in vivo.These findings indicate that low bone formation and expression of Dkk-1 trigger inflammatory bone loss. Dkk-1 blocks osteoblast differentiation, induces sclerostin expression and leads to osteocyte death. Inhibition of Dkk-1 may thus be considered as a potent strategy to protect bone from inflammatory damage.
Perinatal programming of the kidney: is bigger always better?
Authors: Michiel F. Schreuder
Journal: Kidney International (2011)

To the Editor: Escribano et al.1.Escribano J. Luque V. Ferre N. et al.Increased protein intake augments kidney volume and function in healthy infants.Kidney Int. 2011; 79: 783-790Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar recently described that a high-protein formula was associated with higher kidney volumes in infants. Whether this has an effect on long-term kidney and cardiovascular parameters (the programming effect) remains to be determined. However, I feel that such long-term effects may even turn out to be undesirable. Low nephron numbers have been associated with a higher blood pressure in the long run,2.Keller G. Zimmer G. Mall G. et al.Nephron number in patients with primary hypertension.N Engl J Med. 2003; 348: 101-108Crossref PubMed Scopus (894) Google Scholar caused by glomerular hyperfiltration.3.Brenner B.M. Lawler E.V. Mackenzie H.S. The hyperfiltration theory: a paradigm shift in nephrology.Kidney Int. 1996; 49: 1774-1777Abstract Full Text PDF PubMed Scopus (662) Google Scholar Renal size is often used as a marker for nephron endowment, although many studies show no association between nephron number and renal size.2.Keller G. Zimmer G. Mall G. et al.Nephron number in patients with primary hypertension.N Engl J Med. 2003; 348: 101-108Crossref PubMed Scopus (894) Google Scholar In addition, nephron formation has ceased before term birth, which indicates that effects of postnatal interventions, such as a high-protein diet, will not lead to a higher nephron number: the size increase is merely due to hypertrophy. Glomerular hyperfiltration has been shown to be more detrimental when starting early in life. For instance, a congenital solitary functioning kidney leads to signs of glomerular hyperfiltration and injury in 32% of children at the mean age of 8.4 years,4.Westland R. Schreuder M.F. Bokenkamp A. et al.Renal injury in children with a solitary functioning kidney—the KIMONO study.Nephrol Dial Transplant. 2011; 26: 1533-1541Crossref PubMed Scopus (107) Google Scholar exceeding the risks of donor nephrectomy. In addition, animal studies have shown that preventing hyperfiltration during a short period before adulthood leads to a long-lasting lower blood pressure.5.Nakaya H. Sasamura H. Hayashi M. et al.Temporary treatment of prepubescent rats with angiotensin inhibitors suppresses the development of hypertensive nephrosclerosis.J Am Soc Nephrol. 2001; 12: 659-666PubMed Google Scholar As the higher-protein formula did lead to a significant higher renal workload,1.Escribano J. Luque V. Ferre N. et al.Increased protein intake augments kidney volume and function in healthy infants.Kidney Int. 2011; 79: 783-790Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar this may start the vicious circle of glomerular hyperfiltration. It remains to be determined whether this hypertrophy persists and what the impact is on later blood pressure, but this may be unfavorable.
Chaotic itinerancy is a key to mental diversity
Authors: Ichiro Tsuda
Journal: Behavioral and Brain Sciences (2004)

Kampis proposes the study of chaotic itinerancy, pointing out its significance in domains of cognitive science and philosophy. He has discovered in the concept of chaotic itinerancy the possibility for a new dynamical approach that elucidates mental states with a physical basis. This approach may therefore provide the means to go beyond the connectionist approach. In accordance with his theory, I here highlight three issues regarding chaotic itinerancy: transitory dynamics, diversity, and self-modifying system.
Detection and Prognostic Significance of Optic Disc Hemorrhages during the Ocular Hypertension Treatment Study
Authors: Donald L. Budenz, Douglas R. Anderson, William J. Feuer, Julia A. Beiser, Joyce Schiffman, Richard K. Parrish, Jody R. Piltz-Seymour, Mae O. Gordon, Michael A. Kass
Journal: Ophthalmology (2006)
Use of statins is associated with a lower prevalence of generalised osteoarthritis
Authors: A M Valdes, W Zhang, K Muir, R A Maciewicz, S Doherty, M Doherty
Journal: Annals of the Rheumatic Diseases (2013)

Recent reports, from The Netherlands1 and the UK,2 suggest that statins have a modifying role in osteoarthritis (OA) using different outcome definitions, specifically radiographic OA in the Rotterdam cohort and general practitioner diagnosis from a national database in the UK study. On the other hand, a large longitudinal study from the USA found that statin use was not associated with improvements in knee pain, function or structural progression over a 4-year period.3 A separate US longitudinal study in elderly women found that statin use may be associated with an increased risk of developing incident radiographic hip OA.4 The discrepancies between published studies on statins and OA may be due to methodological factors as has been discussed elsewhere.5

Studies of generalised OA suggest the potential role of systemic processes in disease pathogenesis.6 It …
Attenuation of isocapnic hyperpnoea-induced guinea-pig bronchoconstriction by chronic hypoxia
Authors: YL Lai, CW Lin, LC Lai
Journal: European Respiratory Journal (1998)

Chronic hypoxia has been shown to augment the production of antioxidants in rat lungs and to reduce airway hyperreactivity in patients with asthma. This study investigated indirectly whether this increase in antioxidants occurs in guinea-pig lungs and whether the increased antioxidants affect hyperpnoea-induced bronchoconstriction (HIB). Guinea-pigs were divided into four groups: control (n=8); chronic hypoxia (n=7); capsaicin pretreatment (n=7); and capsaicin pretreatment plus chronic hypoxia (n=8). Control animals were not treated. Animals in the hypoxia group were intermittently exposed to an ambient pressure of 380 mmHg for 7 days. A five day pretreatment of capsaicin was used to deplete tachykinins. In the last group, animals were pretreated with capsaicin, followed by a seven day hypoxic exposure. On the day of the study, airway function was examined in the anaesthetized and paralysed animal. Fifteen minutes of hyperpnoea caused marked decreases in the maximal expiratory flow rate at 15% vital capacity, forced expiratory volume in one second, and dynamic respiratory compliance, indicating HIB. This HIB and plasma substance P levels were significantly attenuated by chronic hypoxia, capsaicin pretreatment, and capsaicin pretreatment plus chronic hypoxia. Furthermore, chronic hypoxia attenuated airway constriction induced by xanthine-xanthine oxidase. The results suggest that chronic hypoxia attenuates hyperpnoea-induced bronchoconstriction via a decrease in the oxygen radical-mediated release of tachykinins.
Residency Selection: Making a Match
Authors: Hobart W. Walling
Journal: JAMA (2001)

THE OPPORTUNITY TO GAIN exposure to the various fields of medicine en route to selecting a specialty.Each spring, the residency match process lights a fire under senior medical students.Interviewing applicants and residencies evaluate and rank each other prior to final placement by the National Residency Matching Program (NRMP).At many schools, the culminating event is a Match Day ceremony, where seniors gather to learn whether their efforts have merited entry into their program of choice.The agony and ecstasy of medical school crystallize into a single moment as the seal is broken on the envelope holding each graduate's match outcome.The result is met with elation and relief for many, disappointment for some.Most feel satisfaction at advancing closer to a career, perhaps mingled with regret at leaving other options behind.Even amid the jubilation, an undercurrent of anticipation and trepidation is palpable at the prospect of assuming real responsibilities.In 2001, 93.7% of graduating allopathic US medical students matched into residency, accounting for 73.8% of the 18354 positions filled by the NRMP. 1 An additional 4215 positions were filled by US osteopathic applicants, US international medical graduates (IMGs) and non-US IMGs.Overall, available positions in primary and specialty care both showed an 89% fill rate, although entry into primary care was down 3.6% compared to 2000. 1 Residency training is a relatively new development in medical education. 2 In the early 1900s, medical school was considered adequate preparation for general practice.Expansion of information by the 1920s necessitated a "rounding out" year of internship.Specialty training (a privilege reserved for only the most promising candidates) was also launched around this time.Required to live on hospital grounds, these intrepid and typically unpaid souls were aptly dubbed "residents."Although much of their time was spent caring for patients, resident physicians also languished in laboratory and custodial work.The process could take many years, advancement was arbitrary, and attrition was high.Some physicians eschewed this pathway and sought specialty training abroad; others proclaimed themselves specialists after brief, unregulated study.The quality of postgraduate education varied widely.The lack of standardization was addressed in the 1930s with the establishment of many specialty boards.By the 1950s, residents exceeded medical students in number and specialist physicians exceeded generalists.A match plan (similar to today's) was established in 1951.Further refinements included salaries for residents and relaxation of rules pertaining to personal life.The 1970s saw merging of internship and residency as well as proliferation of subspecialty and fellowship training.Electronic application was recently introduced.How will the residency selection process continue to evolve?jms060601f1scan
Dietary Energy Density Is Associated With Obesity and the Metabolic Syndrome in U.S. Adults
Authors: Jason A. Mendoza, Adam Drewnowski, Dimitri A. Christakis
Journal: Diabetes Care (2007)

Rising obesity rates have been linked to the consumption of energy-dense diets. We examined whether dietary energy density was associated with obesity and related disorders including insulin resistance and the metabolic syndrome.We conducted a cross-sectional study using nationally representative data of U.S. adults > or =20 years of age from the 1999-2002 National Health and Nutrition Examination Survey (n = 9,688). Dietary energy density was calculated based on foods only. We used a series of multivariate linear regression models to determine the independent association between dietary energy density, obesity measures (BMI [in kilograms per meters squared] and waist circumference [in centimeters]), glycemia, or insulinemia. We used multivariate Poisson regression models to determine the independent association between dietary energy density and the metabolic syndrome as defined by the National Cholesterol and Education Program (Adult Treatment Panel III).Dietary energy density was independently and significantly associated with higher BMI in women (beta = 0.44 [95% CI 0.14-0.73]) and trended toward a significant association in men (beta = 0.37 [-0.007 to 0.74], P = 0.054). Dietary energy density was associated with higher waist circumference in women (beta = 1.11 [0.42-1.80]) and men (beta = 1.33 [0.46-2.19]). Dietary energy density was also independently associated with elevated fasting insulin (beta = 0.65 [0.18-1.12]) and the metabolic syndrome (prevalence ratio = 1.10 [95% CI 1.03-1.17]).Dietary energy density is an independent predictor of obesity, elevated fasting insulin levels, and the metabolic syndrome in U.S. adults. Intervention studies to reduce dietary energy density are warranted.