tbuckley/cabot-search huggingface dataset:
ERYTHROID CELL MATURATION AND HEMOGLOBIN SYNTHESIS IN MEGALOBLASTIC ANEMIA*
Authors: David G. Nathan, Frank H. Gardner
Journal: Journal of Clinical Investigation (1962)

Recent observations of the rate of glycine uptake into heme and globin during normal red cell ma- turation in man have led to the conclusion that heme and globin may be synthesized independently during the development of the mature erythrocyte (1).Globin appears to be maximally synthesized at a primitive stage of erythrocyte development with a nearly linear decline of synthetic rate as the cell matures, whereas heme is maximally synthe- sized midway in maturation with less activity both early and late in red cell development.With such data available, it was of interest to evaluate heme and globin synthesis in megaloblastic anemias in an attempt to define not only relative rates of heme and globin synthesis, but also to examine the erythrocyte maturation time and the in vivo insertion of iron into protoporphyrin in such disorders.The data reported in this paper represent the experience of this laboratory in studies of four patients with pernicious anemia of varying severity.These results and their interpretation are compared with similar data, derived from the study of normal patients, which have been previously reported (1). MATERIALS AND METHODSSubjects.The laboratory data supporting the diagno- sis of pernicious anemia in the four patients are pre- sented in Table I.All four patients received diets and fluids as desired throughout the studies.Transfusion therapy of 400 ml of packed red cells was given to Pa- tient 3 during the two days preceding the study.Pa- tient 2 received 1,000 pug of vitamin B,, subcutaneously 1 hour before radioactive isotopes were administered.The patients received 1.5 g sodium benzoate by mouth each day for assay of urinary hippuric acid specific activity.
Interpreting Posterior Relative Risk Estimates in Disease-Mapping Studies
Authors: Sylvia Richardson, Andrew Thomson, Nicky Best, Paul Elliott
Journal: Environmental Health Perspectives (2004)

There is currently much interest in conducting spatial analyses of health outcomes at the small-area scale. This requires sophisticated statistical techniques, usually involving Bayesian models, to smooth the underlying risk estimates because the data are typically sparse. However, questions have been raised about the performance of these models for recovering the “true” risk surface, about the influence of the prior structure specified, and about the amount of smoothing of the risks that is actually performed. We describe a comprehensive simulation study designed to address these questions. Our results show that Bayesian disease-mapping models are essentially conservative, with high specificity even in situations with very sparse data but low sensitivity if the raised-risk areas have only a moderate (&lt; 2-fold) excess or are not based on substantial expected counts (&gt; 50 per area). Semiparametric spatial mixture models typically produce less smoothing than their conditional autoregressive counterpart when there is sufficient information in the data (moderate-size expected count and/or high true excess risk). Sensitivity may be improved by exploiting the whole posterior distribution to try to detect true raised-risk areas rather than just reporting and mapping the mean posterior relative risk. For the widely used conditional autoregressive model, we show that a decision rule based on computing the probability that the relative risk is above 1 with a cutoff between 70 and 80% gives a specific rule with reasonable sensitivity for a range of scenarios having moderate expected counts (~ 20) and excess risks (~1.5- to 2-fold). Larger (3-fold) excess risks are detected almost certainly using this rule, even when based on small expected counts, although the mean of the posterior distribution is typically smoothed to about half the true value.
Interval Training Normalizes Cardiomyocyte Function, Diastolic Ca <sup>2+</sup> Control, and SR Ca <sup>2+</sup> Release Synchronicity in a Mouse Model of Diabetic Cardiomyopathy
Authors: Tomas O. Stølen, Morten Andre Høydal, Ole Johan Kemi, Daniele Catalucci, Marcello Ceci, Ellen Aasum, Terje Larsen, Natale Rolim, Gianluigi Condorelli, Godfrey L. Smith, Ulrik Wisløff
Journal: Circulation Research (2009)

Rationale: In the present study we explored the mechanisms behind excitation–contraction (EC) coupling defects in cardiomyocytes from mice with type-2 diabetes (db/db). Objective: We determined whether 13 weeks of aerobic interval training could restore cardiomyocyte Ca 2+ cycling and EC coupling. Methods and Results: Reduced contractility in cardiomyocytes isolated from sedentary db/db was associated with increased diastolic sarcoplasmic reticulum (SR)-Ca 2+ leak, reduced synchrony of Ca 2+ release, reduced transverse (T)-tubule density, and lower peak systolic and diastolic Ca 2+ and caffeine-induced Ca 2+ release. Additionally, the rate of SR Ca 2+ ATPase–mediated Ca 2+ uptake during diastole was reduced, whereas a faster recovery from caffeine-induced Ca 2+ release indicated increased Na + /Ca 2+ -exchanger activity. The increased SR-Ca 2+ leak was attributed to increased Ca 2+ -calmodulin–dependent protein kinase (CaMKIIδ) phosphorylation, supported by the normalization of SR-Ca 2+ leak on inhibition of CaMKIIδ (AIP). Exercise training restored contractile function associated with restored SR Ca 2+ release synchronicity, T-tubule density, twitch Ca 2+ amplitude, SR Ca 2+ ATPase and Na + /Ca 2+ -exchanger activities, and SR-Ca 2+ leak. The latter was associated with reduced phosphorylation of cytosolic CaMKIIδ. Despite normal contractile function and Ca 2+ handling after the training period, phospholamban was hyperphosphorylated at Serine-16. Protein kinase A inhibition (H-89) in cardiomyocytes from the exercised db/db group abolished the differences in SR-Ca 2+ load when compared with the sedentary db/db mice. EC coupling changes were observed without changes in serum insulin or glucose levels, suggesting that the exercise training–induced effects are not via normalization of the diabetic condition. Conclusions: These data demonstrate that aerobic interval training almost completely restored the contractile function of the diabetic cardiomyocyte to levels close to sedentary wild type.
Evaluation of Memory Impairment in Aging Adult Survivors of Childhood Acute Lymphoblastic Leukemia Treated With Cranial Radiotherapy
Authors: Gregory T. Armstrong, Wilburn E. Reddick, Ronald C. Petersen, Aimee Santucci, Nan Zhang, Deokumar Srivastava, Robert J. Ogg, Claudia M. Hillenbrand, Noah Sabin, Matthew J. Krasin, Larry Kun, Ching-Hon Pui, Melissa M. Hudson, Leslie L. Robison, Kevin R. Krull
Journal: JNCI Journal of the National Cancer Institute (2013)

Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood cancer and may increase risk for mild cognitive impairment and dementia in adulthood. We performed a cross-sectional evaluation of survivors of childhood acute lymphoblastic leukemia (ALL) treated with 18 Gy (n = 127) or 24 Gy (n = 138) CRT. Impairment (age-adjusted score >1 standard deviation below expected mean, two-sided exact binomial test) on the Wechsler Memory Scale IV (WMS-IV) was measured. A subset of survivors (n = 85) completed structural and functional neuroimaging. Survivors who received 24 Gy, but not 18 Gy, CRT had impairment in immediate (impairment rate = 33.8%, 95% confidence interval [CI] = 25.9% to 42.4%; P < .001) and delayed memory (impairment rate = 30.2%, 95% CI = 22.6% to 38.6%; P < .001). The mean score for long-term narrative memory among survivors who received 24 Gy CRT was equivalent to that for individuals older than 69 years. Impaired immediate memory was associated with smaller right (P = .02) and left (P = .008) temporal lobe volumes, and impaired delayed memory was associated with thinner parietal and frontal cortices. Lower hippocampal volumes and increased functional magnetic resonance imaging activation were observed with memory impairment. Reduced cognitive status (Brief Cognitive Status Exam from the WMS-IV) was identified after 24 Gy (18.5%, 95% CI = 12.4% to 26.1%; P < .001), but not 18 Gy (8.7%, 95% CI = 4.4% to 15.0%; P = .11), CRT, suggesting a dose–response effect. Employment rates were equivalent (63.8% for 24 Gy CRT and 63.0% for 18 Gy CRT). Adult survivors who received 24 Gy CRT had reduced cognitive status and memory, with reduced integrity in neuroanatomical regions essential in memory formation, consistent with early onset mild cognitive impairment.
The Cell Biology of Phagocytosis
Authors: Ronald S. Flannagan, Valentin Jaumouillé, Sergio Grinstein
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Engulfment and destruction of invading microorganisms by phagocytosis are critical components of the innate immune response. In addition, phagocytosis is also required for the clearance of apoptotic bodies, an essential aspect of tissue homeostasis and remodeling. Here, we summarize the current knowledge of the cellular and molecular basis of phagosome formation and maturation. We discuss the manner in which phagocytosis is subverted by certain pathogens and consider congenital disorders that affect phagocyte function.
Allied respiratory professionals
Authors: B.G. Cooper, T. Troosters, G. Burge, D. Field, S.S. Hrafnkelsdottir, F. Pitta, J.K. Lloyd, I. Steenbuggen
Journal: European Respiratory Journal (2010)

In celebrating 20 years of the European Respiratory Society (ERS), we have to include, since 1992, the development of the Allied Respiratory Professionals' Assembly (Assembly 9). The Allied Respiratory Professionals' Assembly originated from the need of this growing group of healthcare providers to engage in the ERS as a visible group for its stakeholders (including patients, research bodies and regulators). Allied healthcare professionals also have specific needs in terms of the development of their field. Concerns in this field are both academic and “hands on”.

Unusually, Assembly 9 doesn't represent a specific scientific area in respiratory medicine, but covers clinical functions performed by healthcare professionals who are technologists/scientists, physiotherapists and nurses. Consequently, Assembly 9 has a lot of cross-affiliations with other Assemblies and Groups (table 1), and provides and supports a comprehensive raft of Symposia, Hot Topics, Postgraduate Courses and specialist sessions at the Annual ERS Congress. The Assembly, however, is also important in the “clinical reality” that allied healthcare professionals confront in their different fields during a typical day at work.

View this table:

Table 1– Key cross-affiliations with Assembly 9 

It is increasingly recognised that allied healthcare professionals play an important role in the diagnosis, treatment and care of patients with acute and chronic pulmonary diseases. High-quality measurement of pulmonary function plays an essential role in the diagnosis and follow-up of patients. It is one of the ERS' missions to harmonise and standardise these diagnostic tests. Similarly, nurses and physiotherapists face new challenges. Both groups increasingly participate in the education and self-management of patients in order encourage them to take more responsibility and control of their own condition. Nonpharmacological interventions, such as exercise training, typically applied by physiotherapists, have become evidence-based treatment, embedded in pulmonary rehabilitation. Breathing retraining in selected patient groups and mucocilliary clearance techniques are other areas of interest. Most allied …
Next-Generation Cancer Vaccine Approaches: Integrating Lessons Learned From Current Successes With Promising Biotechnologic Advances
Authors: Dung T. Le, Elizabeth M. Jaffee
Journal: Journal of the National Comprehensive Cancer Network (2013)

With the recent approval of sipuleucel-T for metastatic castration-resistant prostate cancer and ipilimumab for metastatic melanoma, there is increasing excitement in the field of cancer immunotherapy. A large number of clinical trials are currently testing various vaccine vectors in a diverse array of cancer types. Which of these strategies will ultimately prove successful has yet to be determined. However, a better understanding of the complex interplay of tumor-specific T cells and the challenges faced at the tumor microenvironment, advances in biotechnology, and lessons learned from prior successes and failures will likely lead to approvals of other therapeutic cancer vaccines.
Are Racial and Ethnic Minorities Less Willing to Participate in Health Research?
Authors: David Wendler, Raynard Kington, Jennifer Madans, Gretchen Van Wye, Heidi Christ-Schmidt, Laura A Pratt, Otis W Brawley, Cary P Gross, Ezekiel Emanuel
Journal: PLoS Medicine (2005)

Background It is widely claimed that racial and ethnic minorities, especially in the US, are less willing than non-minority individuals to participate in health research. Yet, there is a paucity of empirical data to substantiate this claim. Methods and Findings We performed a comprehensive literature search to identify all published health research studies that report consent rates by race or ethnicity. We found 20 health research studies that reported consent rates by race or ethnicity. These 20 studies reported the enrollment decisions of over 70,000 individuals for a broad range of research, from interviews to drug treatment to surgical trials. Eighteen of the twenty studies were single-site studies conducted exclusively in the US or multi-site studies where the majority of sites (i.e., at least 2/3) were in the US. Of the remaining two studies, the Concorde study was conducted at 74 sites in the United Kingdom, Ireland, and France, while the Delta study was conducted at 152 sites in Europe and 23 sites in Australia and New Zealand. For the three interview or non-intervention studies, African-Americans had a nonsignificantly lower overall consent rate than non-Hispanic whites (82.2% versus 83.5%; odds ratio [OR] = 0.92; 95% confidence interval [CI] 0.84–1.02). For these same three studies, Hispanics had a nonsignificantly higher overall consent rate than non-Hispanic whites (86.1% versus 83.5%; OR = 1.37; 95% CI 0.94–1.98). For the ten clinical intervention studies, African-Americans' overall consent rate was nonsignificantly higher than that of non-Hispanic whites (45.3% versus 41.8%; OR = 1.06; 95% CI 0.78–1.45). For these same ten studies, Hispanics had a statistically significant higher overall consent rate than non-Hispanic whites (55.9% versus 41.8%; OR = 1.33; 95% CI 1.08–1.65). For the seven surgery trials, which report all minority groups together, minorities as a group had a nonsignificantly higher overall consent rate than non-Hispanic whites (65.8% versus 47.8%; OR = 1.26; 95% CI 0.89–1.77). Given the preponderance of US sites, the vast majority of these individuals from minority groups were African-Americans or Hispanics from the US. Conclusions We found very small differences in the willingness of minorities, most of whom were African-Americans and Hispanics in the US, to participate in health research compared to non-Hispanic whites. These findings, based on the research enrollment decisions of over 70,000 individuals, the vast majority from the US, suggest that racial and ethnic minorities in the US are as willing as non-Hispanic whites to participate in health research. Hence, efforts to increase minority participation in health research should focus on ensuring access to health research for all groups, rather than changing minority attitudes.
A national study of medical care expenditures for respiratory conditions
Authors: E. Yelin, L. Trupin, M. Cisternas, M. Eisner, P. Katz, P. Blanc
Journal: European Respiratory Journal (2002)

This study was undertaken to estimate the magnitude of medical care expenditures among persons with respiratory conditions in the USA in 1996, and the increment in expenditures attributable to these conditions. The study data were derived from the 1996 Medical Expenditure Panel Survey, a national sample of 21,571 persons. Of the 21,571, 1,027 reported one or more respiratory condition. After weighting, the individuals may represent about 12.1 million persons in the USA. All medical care expenditures of these individuals were tabulated, stratified by comorbidity status, and then compared to those among persons with nonrespiratory conditions or with no conditions. Regression techniques were then used to estimate the increment of healthcare expenditures attributable to the respiratory conditions. From a national total of $45.3 billion, medical care expenditures averaged $3,753 among persons with respiratory conditions. Hospital stays comprised the largest component (45%). The per capita increment in total expenditures attributable to respiratory conditions ranged from $1,003–2,588, from a national total ranging from $12.1–31.3 billion. The total medical care expenditure of persons with respiratory conditions was estimated to be $45.3 billion, of which $12.1–31.3 billion represents an increment in expenditures associated with the conditions themselves.
Differential expression of biomarkers in lung adenocarcinoma: a comparative study between smokers and never-smokers
Authors: T. Dutu, S. Michiels, P. Fouret, F. Penault-Llorca, P. Validire, S. Benhamou, E. Taranchon, L. Morat, D. Grunenwald, T. Le Chevalier, L. Sabatier, J.-C. Soria
Journal: Annals of Oncology (2005)
Interferon Consensus Sequence Binding Protein–deficient Mice Display Impaired Resistance to Intracellular Infection Due to a Primary Defect in Interleukin 12 p40 Induction
Authors: Tanya Scharton-Kersten, Cristina Contursi, Atsuko Masumi, Alan Sher, Keiko Ozato
Journal: The Journal of Experimental Medicine (1997)

Mice lacking the transcription factor interferon consensus sequence binding protein (ICSBP), a member of the interferon regulatory factor family of transcription proteins, were infected with the intracellular protozoan, Toxoplasma gondii. ICSBP-deficient mice exhibited unchecked parasite replication in vivo and rapidly succumbed within 14 d after inoculation with an avirulent Toxoplasma strain. In contrast, few intracellular parasites were observed in wild-type littermates and these animals survived for at least 60 d after infection. Analysis of cytokine synthesis in vitro and in vivo revealed a major deficiency in the expression of both interferon (IFN)-γ and interleukin (IL)-12 p40 in the T. gondii exposed ICSBP−/− animals. In related experiments, macrophages from uninfected ICSBP−/− mice were shown to display a selective impairment in the mRNA expression of IL-12 p40 but not IL-1α, IL-1β, IL-1Ra, IL-6, IL-10, or TNF-α in response to live parasites, parasite antigen, lipopolysaccharide, or Staphylococcus aureus. This selective defect in IL-12 p40 production was observed regardless of whether the macrophages had been primed with IFN-γ. We hypothesize that the impaired synthesis of IL-12 p40 in ICSBP−/− animals is the primary lesion responsible for the loss in resistance to T. gondii because IFN-γ–induced parasite killing was unimpaired in vitro and, more importantly, administration of exogenous IL-12 in vivo significantly prolonged survival of the infected mice. Together these findings implicate ICSBP as a major transcription factor which directly or indirectly regulates IL-12 p40 gene activation and, as a consequence, IFN-γ–dependent host resistance.
Transforming Growth Factor-β1 to the Bone
Authors: Katrien Janssens, Peter ten Dijke, Sophie Janssens, Wim Van Hul
Journal: Endocrine Reviews (2005)

TGF-β1 is a ubiquitous growth factor that is implicated in the control of proliferation, migration, differentiation, and survival of many different cell types. It influences such diverse processes as embryogenesis, angiogenesis, inflammation, and wound healing. In skeletal tissue, TGF-β1 plays a major role in development and maintenance, affecting both cartilage and bone metabolism, the latter being the subject of this review. Because it affects both cells of the osteoblast and osteoclast lineage, TGF-β1 is one of the most important factors in the bone environment, helping to retain the balance between the dynamic processes of bone resorption and bone formation. Many seemingly contradictory reports have been published on the exact functioning of TGF-β1 in the bone milieu. This review provides an overall picture of the bone-specific actions of TGF-β1 and reconciles experimental discrepancies that have been reported for this multifunctional cytokine.
Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial
Authors: Shamir R Mehta, Jean-Francois Tanguay, John W Eikelboom, Sanjit S Jolly, Campbell D Joyner, Christopher B Granger, David P Faxon, Hans-Jurgen Rupprecht, Andrzej Budaj, Alvaro Avezum, Petr Widimsky, Philippe Gabriel Steg, Jean-Pierre Bassand, Gilles Montalescot, Carlos Macaya, Giuseppe Di Pasquale, Kari Niemela, Andrew E Ajani, Harvey D White, Susan Chrolavicius, Peggy Gao, Keith AA Fox, Salim Yusuf
Journal: The Lancet (2010)
Phase II Trial of Docetaxel, Cisplatin, Fluorouracil, and Leucovorin as Induction for Squamous Cell Carcinoma of the Head and Neck
Authors: A. D. Colevas, C. M. Norris, R. B. Tishler, M. P. Fried, H. I. Gomolin, P. Amrein, A. Nixon, C. Lamb, R. Costello, J. Barton, R. Read, S. Adak, M. R. Posner
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To evaluate the toxicity and efficacy of a 4-day regimen of docetaxel, cisplatin, fluorouracil, and leucovorin (TPFL4) in patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Thirty previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status of 2 or less were treated with TPFL4. Postchemotherapy support included prophylactic growth factors and antibiotics. Patients who achieved a complete response (CR) or partial response (PR) to three cycles of TPFL4 received definitive twice-daily radiation therapy. The primary end points were toxicity and response to TPFL4. RESULTS: Eighty-five cycles were administered to 30 patients. The major acute toxicities to TPFL4 were mucositis and nausea. One patient died of neutropenic sepsis during therapy. Additional major toxicities were neutropenia, anorexia, nephropathy, neuropathy, and diarrhea. Fourteen percent of all cycles were associated with hospitalization for toxicity. The overall clinical response rate to TPFL4 was 93%, with 63% CRs and 30% PRs. Primary tumor site clinical and pathologic response rates were 93% and 68%, respectively. CONCLUSION: TPFL4 has an acceptable toxicity profile in good-performance-status patients. Modification of the 5-day TPFL regimen (TPFL5: shorter chemotherapy infusion time, earlier intervention with growth factors and antibiotics) led to fewer episodes of febrile neutropenia and hospitalization. Response rates to TPFL justify further evaluation of combinations of these agents in the context of formal clinical trials.
Major health committee report falls victim to MPs' disagreement
Authors: A. O'Dowd
Journal: BMJ (2015)

MPs on the influential House of Commons Health Committee have taken the highly unusual step of not publishing a report from a major inquiry carried out late last year because they cannot agree on its conclusions, The BMJ has learnt.

The committee held its inquiry into public expenditure on health and social care from September to December last year. It involved submitted written evidence and five oral evidence sessions at which 19 witnesses from various organisations appeared to give information and opinions. However, the committee could not agree on a draft version of the report and have voted not to publish it before the general election in May.

An open letter has now been sent by the NHS Confederation, the body that represents most NHS organisations, and the …