tbuckley/cabot-search huggingface dataset:
Modification of Heat-Related Mortality in an Elderly Urban Population by Vegetation (Urban Green) and Proximity to Water (Urban Blue): Evidence from Lisbon, Portugal
Authors: Katrin Burkart, Fred Meier, Alexandra Schneider, Susanne Breitner, Paulo Canário, Maria João Alcoforado, Dieter Scherer, Wilfried Endlicher
Journal: Environmental Health Perspectives (2015)

Urban populations are highly vulnerable to the adverse effects of heat, with heat-related mortality showing intra-urban variations that are likely due to differences in urban characteristics and socioeconomic status.We investigated the influence of urban green and urban blue, that is, urban vegetation and water bodies, on heat-related excess mortality in the elderly > 65 years old in Lisbon, Portugal, between 1998 and 2008.We used remotely sensed data and geographic information to determine the amount of urban vegetation and the distance to bodies of water (the Atlantic Ocean and the Tagus Estuary). Poisson generalized additive models were fitted, allowing for the interaction between equivalent temperature [universal thermal climate index (UTCI)] and quartiles of urban greenness [classified using the Normalized Difference Vegetation Index (NDVI)] and proximity to water (≤ 4 km vs. > 4 km), while adjusting for potential confounders.The association between mortality and a 1°C increase in UTCI above the 99th percentile (24.8°C) was stronger for areas in the lowest NDVI quartile (14.7% higher; 95% CI: 1.9, 17.5%) than for areas in the highest quartile (3.0%; 95% CI: 2.0, 4.0%). In areas > 4 km from water, a 1°C increase in UTCI above the 99th percentile was associated with a 7.1% increase in mortality (95% CI: 6.2, 8.1%), whereas in areas ≤ 4 km from water, the estimated increase in mortality was only 2.1% (95% CI: 1.2, 3.0%).Urban green and blue appeared to have a mitigating effect on heat-related mortality in the elderly population in Lisbon. Increasing the amount of vegetation may be a good strategy to counteract the adverse effects of heat in urban areas. Our findings also suggest potential benefits of urban blue that may be present several kilometers from a body of water.Burkart K, Meier F, Schneider A, Breitner S, Canário P, Alcoforado MJ, Scherer D, Endlicher W. 2016. Modification of heat-related mortality in an elderly urban population by vegetation (urban green) and proximity to water (urban blue): evidence from Lisbon, Portugal. Environ Health Perspect 124:927-934; http://dx.doi.org/10.1289/ehp.1409529.
USF1 deficiency activates brown adipose tissue and improves cardiometabolic health
Authors: Pirkka-Pekka Laurila, Jarkko Soronen, Sander Kooijman, Saara Forsström, Mariëtte R. Boon, Ida Surakka, Essi Kaiharju, Claudia P. Coomans, Sjoerd A. A. Van Den Berg, Anu Autio, Antti-Pekka Sarin, Johannes Kettunen, Emmi Tikkanen, Tuula Manninen, Jari Metso, Reija Silvennoinen, Krista Merikanto, Maija Ruuth, Julia Perttilä, Anne Mäkelä, Ayaka Isomi, Anita M. Tuomainen, Anna Tikka, Usama Abo Ramadan, Ilkka Seppälä, Terho Lehtimäki, Johan Eriksson, Aki Havulinna, Antti Jula, Pekka J. Karhunen, Veikko Salomaa, Markus Perola, Christian Ehnholm, Miriam Lee-Rueckert, Miranda Van Eck, Anne Roivainen, Marja-Riitta Taskinen, Leena Peltonen, Eero Mervaala, Anu Jalanko, Esa Hohtola, Vesa M. Olkkonen, Samuli Ripatti, Petri T. Kovanen, Patrick C. N. Rensen, Anu Suomalainen, Matti Jauhiainen
Journal: Science Translational Medicine (2016)

Deficiency of USF1 protects against obesity, insulin resistance, and cardiovascular disease in mice and humans, and induces brown adipose tissue to burn triglycerides and glucose.
Acute lymphoblastic leukemia of childhood: identification of two distinct regions of deletion on the short arm of chromosome 12 in the region of TEL and KIP1
Authors: S Takeuchi, CR Bartram, CW Miller, A Reiter, T Seriu, M Zimmerann, M Schrappe, N Mori, J Slater, I Miyoshi, HP Koeffler
Journal: Blood (1996)
Resource Burden During the 2014 Enterovirus D68 Respiratory Disease Outbreak at Children’s Hospital Colorado
Authors: Kevin Messacar, Stephen M. M. Hawkins, Joyce Baker, Kelly Pearce, Suhong Tong, Samuel R. Dominguez, Sarah Parker
Journal: JAMA Pediatrics (2016)

saturation group.It is known that SGA infants have higher mortality and worse outcomes compared with AGA infants of the same gestation. 35][6] These reports mirror our finding of bronchopulmonary dysplasia as a leading mortality cause in the SGA cohort.We view these analyses as hypothesis generating.These results must be confirmed in other oxygen targetting studies.An important opportunity to do this is in the planned Neonatal Oxygenation Prospective Meta-analysis, which includes data from 4800 infants with a prespecified analysis by growth status.We speculate that SGA infants may experience hypoxia in utero that destabilizes respiratory control or affects pulmonary vascular resistance, increasing vulnerability to lower saturation targets.
Abstract 17261: Inhibition of Fibrinolysis Attenuates Influenza A-induced Lung Injury
Authors: Luisa Morales-Nebreda, Mesut Eren, Saul Soberanes, Recep Nigdelioglu, Micah Rogel, Monica Chi, Takugo Cho, Robert Hamanaka, Douglas E Vaughan, GR Scott Budinger, Gokhan M Mutlu
Journal: Circulation (2014)

Rationale: Influenza A virus (IAV) is the leading cause of death from an infectious cause and ranks 8th in the list of attributable annual mortality in the United States. Currently available antiviral treatments are limited and may become ineffective as resistant strains emerge. The coexistence of hemostatic alterations with inflammatory responses to viral infections support the idea that common molecular mechanisms contribute to the regulation of these systems. Previous studies demonstrated that IAV induces the activation of both coagulation and fibrinolytic pathways, and that the impairment of the latter is mainly attributable to high levels of plasminogen activator inhibitor type I (PAI-1), the major inhibitor of tissue-type plasminogen activator (t-PA). Interferon-α (IFN-α) plays a key role in the control of viral replication and overall shaping of the immune response. We sought to determine whether PAI-1, plays a role in the immune response and morbidity and mortality associated with IAV infection. Methods: Wild-type (C57BL/6J), PAI-1-/-, t-PA-/- and PAI-1 stab (transgenic mice expressing an active form of human PAI-1) mice were treated intratracheally with IAV (A/WSN/33 [H1N1] 500 pfu/mouse in 50μl PBS). We assessed the levels of IFN-α in bronchoalveolar lavage fluid (BALF) on day 2 and 4, and influenza A-induced morbidity (weight loss) and mortality. Results: Compared with wild-type mice, PAI-1-/- mice had increased IAV-induced morbidity and mortality. In contrast, both PAI-1 stab and t-PA-/- mice had improved survival. In wild-type mice, IAV induced a significant elevation IFN-α levels in BALF. PAI-1 stab mice had a 2-fold increase, while PAI-1-/-mice had a 69% reduction in IFN-α levels in BALF compared to wild-type mice. Conclusions: Inhibition of fibrinolysis by means of genetic overexpression of PAI-1 or deletion of t-PA augments the antiviral response and attenuates the morbidity and mortality associated with IAV infection. These results suggest an important functional role for PAI-1 and fibrinolysis in the pathogenesis of influenza A infection. Modulation of the fibrinolytic pathway or PAI-1 may potentially be useful as a target for novel therapeutics in the management of IAV-induced lung injury.
Cyclosporine-induced renal dysfunction
Authors: W M Bennett, D C Houghton, W C Buss
Journal: Journal of the American Society of Nephrology (1991)

The main adverse reaction to the immunosuppressive drug cyclosporine is dose-dependent renal dysfunction. Although renal vasoconstriction without major tubular dysfunction is usually noted, recent studies have demonstrated an inhibition of renal cortical microsomal protein synthesis. Sprague-Dawley rats and appropriate pair-fed controls were given cyclosporine orally in doses of 5, 10, 25, and 50 mg/kg/day for periods up to 10 days. A dose-dependent decline in glomerular filtration rate and effective renal plasma flow was maximal by day 3 and did not worsen despite continued dosing. Microsomal protein synthesis as measured by [3H]leucine incorporation was also depressed in a dose-dependent fashion; however, inhibition did not reach the nadir until day 4, 1 day after renal dysfunction was established. When cyclosporine was discontinued, microsomal protein synthesis was normalized by 4 days after drug withdrawal; in contrast, the return of glomerular filtration rate and effective renal plasma flow to normal required 8 days after drug discontinuation. Tubular function as measured by fractional excretion of lithium, enzymuria, and urinary osmolality was well maintained despite the depression of renal hemodynamics. There was no evidence of tubular necrosis by light or electron microscopy. Although cyclosporine produces reductions in renal microsomal protein synthesis, measured by "run-off" translation assays, these effects appear unlikely to be the direct cause of acute renal dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)
Psychometric properties of the Itch Numeric Rating Scale in patients with moderate‐to‐severe plaque psoriasis
Authors: A.B. Kimball, A.N. Naegeli, E. Edson‐Heredia, C.‐Y. Lin, C. Gaich, E. Nikaï, K. Wyrwich, G. Yosipovitch
Journal: British Journal of Dermatology (2016)

Itching is a profoundly distressing symptom for many patients with psoriasis, but it has not been rigorously studied using validated tools for this condition. This study investigated the psychometric properties of the Itch Numeric Rating Scale (Itch NRS), a single‐item patient‐reported outcome (PRO) measuring the worst itching severity due to psoriasis in the past 24 h. Using disease‐specific clinician‐rated and PRO data from one phase II and three phase III randomized clinical studies of subjects with moderate‐to‐severe plaque psoriasis, the Itch NRS was evaluated for test–retest reliability, construct validity and responsiveness. A responder definition was explored using anchor‐ and distribution‐based methods. Test–retest reliability analyses supported the reproducibility of the measure (intraclass correlation coefficient range 0·71–0·74). To support the construct validity of the Itch NRS, large cross‐sectional correlations with the Dermatology Life Quality Index (DLQI) Symptoms and Feelings domain (r ≥ 0·60 at baseline and r ≥ 0·80 at week 12) supported a priori hypotheses, while large correlations (r ≥ 0·71) between changes in Itch NRS scores and changes in DLQI Symptoms and Feelings domain scores from baseline to week 12 established responsiveness. A 4‐point change was optimal for demonstrating a level of clinically meaningful improvement in itch severity after 12 weeks of treatment, which corresponds with marked clinical improvements in plaque psoriasis. The Itch NRS demonstrated sufficient reliability, validity and responsiveness, and appropriate interpretation standards for evaluating change over time in itch severity among patients with moderate‐to‐severe plaque psoriasis when validated using clinical trial data for this condition.
Phase II study of oxaliplatin, capecitabine, and cetuximab in advanced hepatocellular carcinoma
Authors: B. H. O’Neil, S. A. Bernard, R. M. Goldberg, D. T. Moore, R. Garcia, C. Marroquin, M. A. Morse, L. Woods, H. K. Sanoff
Journal: Journal of Clinical Oncology (2008)

4604 Background: Hepatocellular carcinomas (HCC) are known to express EGFR, and a ph II study of erlotinib suggested clinical activity of EGFR inhibition. Combinations with EGFR and chemotherapies have been synergistic in a number of settings. We therefore studied the efficacy of capecitabine (cape), oxaliplatin (ox) plus cetuximab (ctx) in patients with advanced HCC. Methods: Patients had advanced/unresectable HCC by tissue dx or AFP>1,000. Prior chemoembolization was allowed, but no prior systemic therapy. EGFR testing was not required for entry. Patients were treated with cape 850 mg/m2 bid for 14 days, ox 130 mg/m2 iv q3wks and ctx 400 mg/m2 on day one followed by 250 mg/m2 weekly. A toxicity evaluation was performed after 10 patients were enrolled and doses continued at initial levels throughout the trial. Tumor evaluations were performed q 6 weeks. No particular Childs class was required, but bilirubin had to be < 3, and adequate hematologic and renal parameters were required. Results: 24 of 25 planned pts have completed at least one cycle of therapy. 20 pts are evaluable for response. 2/20 (10%, 95% CI: 1%,-33%) had PR, 13(65%) SD and 5(25%) PD. The most frequent Grade 3 and 4 toxicities have included hyperbilirubinemia (n=8, 35%), fatigue (n = 7, 30%), hypomagnesemia (n = 6, 26%), diarrhea (n = 5, 22%), and hypocalcemia (n = 5, 22%). Three patients died within the first 30 days of treatment, one due to toxicity and 2 due to rapid disease progression. Median TTP is 4.3 mos (95% CI 2.3, 5.0). Conclusions: The combination of capecitabine, oxaliplating and cetuximab is tolerable for most patients, although diarrhea and electrolyte abnormalities are more pronounced in this population than in other patient populations and led to death in one patient. The combination is associated with a modest rate of radiographic response, but a high rate of stable disease and a promising TTP. Updated TTP and preliminary OS data will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, sanofi-aventis sanofi-aventis
Phase II study of temsirolimus in children with high-grade glioma, neuroblastoma, and rhabdomyosarcoma.
Authors: B. Geoerger, M. W. Kieran, S. Grupp, S. Blaney, D. Perek, J. Clancy, M. Krygowski, J. Boni, A. Berkenblit, S. L. Spunt
Journal: Journal of Clinical Oncology (2010)

9541 Background: Temsirolimus (TEMSR), an mTOR inhibitor, prolongs survival in adults with advanced renal cell carcinoma. In part 1 of a phase I/II study of TEMSR in children with advanced solid tumors, 75mg/m2 was determined to be the MTD (Spunt et al. ASPHO 2007). Part 2 of the study explored the safety and efficacy of 75mg/m2 TEMSR in children with neuroblastoma, high grade glioma or rhabdoymyosarcoma. Methods: Part 2 of this open-label study enrolled patients (pts) with a confirmed diagnosis of recurrent/refractory neuroblastoma, high-grade glioma, or rhabdomyosarcoma, with measurable disease. TEMSR 75 mg/m2 was given intravenously once weekly until disease progression or intolerance. Primary efficacy endpoint was objective response (OR; complete response + partial response [PR]) within first 12 weeks. If fewer than 2 ORs occurred after 12 evaluable pts (those who received ≥3 TEMSR doses) were enrolled in one of each tumor types, then enrollment in that tumor type would be stopped for lack of efficacy. Population pharmacokinetics were evaluated. Results: Fifty-two pts were enrolled (17 glioma, 19 neuroblastoma, 16 rhabdomyosarcoma), 35 (67%) male, median age 8 yr (range 1-21 yr). At 12 weeks, 2 pts had PR (1 neuroblastoma, 1 rhabdomyosarcoma). Eleven pts achieved stable disease ≥12 weeks (5 neuroblastoma and 6 glioma). Two pts with neuroblastoma remain on treatment >2 years. Most common treatment-related adverse events were thrombocytopenia (56% pts), asthenia (38%), fever (33%), cough (31%), and pain (31%), most grade 1 or 2. Eleven pts required ≥1 dose delay; 16 required ≥1 dose reduction due to adverse events, most commonly thrombocytopenia (67%). Conclusions: Temsirolimus 75 mg/m2 was well tolerated in pediatric pts with solid tumors and the safety profile was comparable among the treatment groups. As per the trial design, the OR rate failed to meet the threshold level set for study continuation and efficacy. Nevertheless, observed OR and prolonged stable disease in neuroblastoma, rhabdomyosarcoma, and supratentorial and pontine glioma merits further evaluation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer
Epithelial Pten controls acute lung injury and fibrosis by regulating intercellular junctional integrity and EMT
Authors: Shigehisa Yanagi, Kahori Miyoshi, Hironobu Tsubouchi, Nobuhiro Matsumoto, Masamitsu Nakazato
Journal: European Respiratory Journal (2012)

Injury to alveolar epithelial cells (AECs) and its repair process are integral to the pathogenesis of acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF). Disruption of AECs integrity and its reconstitution are crucial for ALI progression. In addition, myofibroblasts, key effector cells in IPF, partially originate from AECs through epithelial-mesenchymal transition (EMT). However, the regulation mechanisms of AECs integrity remains unclear. We explored the role of epithelial Pten in lung injury by generating a postnatally, and lung epithelium-specifically Pten-null (SOPten) mouse strain. Sixty percent of SOPten mice died of hypoxia, whereas all control mice survived after bleomycin insult. SOPten mice demonstrated aggravated ALI and lung fibrosis with enhanced disruptions of intercellular junctional complexes of AECs and degradation of basement membranes. Epithelial-derived myofibroblasts were increased in epithelium-specific Pten-deficient mice. Lungs of bleomycin-treated SOPten mice showed increased pAkt, pS6K, Snail and MMP expressions, and decreased claudin-4, E-cadherin, and laminin-beta1 expressions. Systemic Akt inactivation definitively saved SOPten mice through amelioration of ALI and aberrant EMT. Finally, we detected reduction of PTEN expression and hyperactivation of AKT in the AECs of human IPF lung. Our results indicate the pivotal role of EMT process for the progression of ALI and lung fibrosis. They also highlight epithelial Pten as an essential gatekeeper controlling ALI and lung fibrosis by modulating intercellular junctional integrity and EMT, and the Pten/PI3K/Akt pathway as a potential therapeutic target in these intractable diseases.
Inhibition of Lymphocyte-Mediated Cytotoxicity (51Cr-Release) by Antisera Preabsorbed With Various Cells2
Authors: Fujiro Sendo, Tadao Aoki, Charles K. Buafo
Journal: JNCI Journal of the National Cancer Institute (1974)

Immunologic specificities of lymphocytemediated cytotoxicity (LMC) were studied with the use of the in vitro 51Cr-releasing method. When compared with inhibition of LMC by unlabeled cells or by antiserumpretreated cells, inhibition of LMC by antisera preabsorbed with test cells was more sensitive and specific in detecting minor antigenic differences. The inhibitory effects of antiserum-pretreated cells were unexpectedly strong, showing very weak blocking effects of antiserum on unlabeled inhibiting cells. Cell-free antigens alone or cellfree antigen-antibody complexes did not inhibit LMC within the system used, while cell-free antigens neutralized the inhibiting activity of antiserum.
Reprogramming SynchroMed pumps: unanticipated inaccuracy.
Authors: W J Hrushesky
Journal: Journal of Clinical Oncology (1991)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1991.9.6.1089 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2033422 Reprogramming SynchroMed pumps: unanticipated inaccuracy. W J HrusheskyxW J HrusheskySearch for articles by this author https://doi.org/10.1200/JCO.1991.9.6.1089 PDF "Reprogramming SynchroMed pumps: unanticipated inaccuracy.." Journal of Clinical Oncology, 9(6), pp. 1089–1090© 1991 by American Society of Clinical Oncology
Production and Characterization of Tumor-Degenerating Factor
Authors: A Tanaka, H Matsuoka, H Uemura, Y Kakui, T Imanishi, H Nishino, J Imanishi
Journal: JNCI Journal of the National Cancer Institute (1985)

Degenerative changes of human tumor cells or continuous cell lines occur when they are cocultured with human embryonic fibroblasts. The present study confirmed that the degenerative changes of the target cells were due to a factor secreted from the human fibroblast culture, because the culture supernatant of human fibroblast caused the same degenerative changes as those induced by the coculture. This factor was termed “tumor-degenerating factor” (TDF). TDF was produced in the fibroblast culture as early as the 1st day and increased gradually up to the 8th day. TDF induced the degenerative changes in human KB cells, HeLa cells, FL cells, and PLC/PRF/5 cells but not in human WiDr cells or in fibroblasts. Also, it did not induce the degenerative changes in various murine cells, bovine cells, rabbit cells, or monkey cells, suggesting that TDF has species specificity. Furthermore, human leukocyte interferon enhanced the activity of TDF. TDF with the specific activity of 2.9 U/mg protein was purified by several chromatographies. At a final recovery rate of 14.6%, the specific activity was increased to 9.010 U/mg protein. Its molecular weight was estimated about 26,500–30,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. TDF was relatively stable to heat treatment.
Inheritance of Cellular Resistance to the Antitumor Agent ICRF 159 in Somatic Cell Hybrids
Authors: D H Edgar, A M Creighton
Journal: JNCI Journal of the National Cancer Institute (1982)

Two independently derived sublines of Syrian hamster BHK 21 S cells that demonstrate resistance to the antitumor agent ICRF 159 (NSC-129943) were fused to sensitive cells in both intraspecific and interspecific crosses, and the responses of the resultant hybrids to the drug were determined. In intraspecific hybrids from crosses involving either of the sublines, resistance to ICRF 159 was expressed codominantly ith the hybrid response being halfway between the parental responses. In interspecific hybrids from crosses with sensitive mouse cells, resistance was also expressed but to a lesser extent than in the intraspecific hybrids. However, subsequent passaging of an interspecific hybrid resulted in an increase in the degree of resistance, which appeared to be accompanied by a loss of telocentric mouse chromosomes. The results suggested that resistance in these lines was due to an alteration in the cellular target involved in the response to ICRF 159.
When mental capacity becomes an issue in medical practice
Authors: Chris Danbury
Journal: BMJ (2016)

Consider mediation before going to court

The courts developed the concept of mental capacity over a long period before it was codified in the Mental Capacity Act 2005 (England and Wales). It relates to a person’s ability to make a decision. In medicine, that decision is usually whether to consent, or refuse to consent, to a treatment.

The act starts by saying: “A person must be assumed to have capacity unless it is established that he lacks capacity.” It then sets out the necessary tests to establish capacity. A person must be able to understand the information relevant to the decision, to retain that information, to use or weigh that information as part of the process of making the decision, or to communicate his decision (whether by talking, using sign language, or any other means).

The latest edition of the BMA/Law Society’s Assessment of Mental …