tbuckley/cabot-search huggingface dataset:
The Doubly Conditioned Frequency Spectrum Does Not Distinguish between Ancient Population Structure and Hybridization
Authors: Anders Eriksson, Andrea Manica
Journal: Molecular Biology and Evolution (2014)

Distinguishing between hybridization and population structure in the ancestral species is a key challenge in our understanding of how permeable species boundaries are to gene flow. The doubly conditioned frequency spectrum (dcfs) has been argued to be a powerful metric to discriminate between these two explanations, and it was used to argue for hybridization between Neandertal and anatomically modern humans. The shape of the observed dcfs for these two species cannot be reproduced by a model that represents ancient population structure in Africa with two populations, while adding hybridization produces realistic shapes. In this letter, we show that this result is a consequence of the spatial coarseness of the demographic model and that a spatially structured stepping stone model can generate realistic dcfs without hybridization. This result highlights how inferences on hybridization between recently diverged species can be strongly affected by the choice of how population structure is represented in the underlying demographic model. We also conclude that the dcfs has limited power in distinguishing between the signals left by hybridization and ancient structure.
In vitro performance of three combinations of spacers and pressurized metered dose inhalers for treatment in children
Authors: E Berg, J Madsen, H Bisgaard
Journal: European Respiratory Journal (1998)

The performance of pressurized metered dose inhalers (pMDIs) and spacers in correct dose recommendations is important, but limited information on dose delivery and fine-particle dose from different combinations of spacers and pMDIs is available. In this study, three combinations of spacers and pMDIs were investigated: NebuChamber and AeroChamber with budesonide pMDI and Babyhaler with fluticasone propionate pMDI. Doses were withdrawn onto a filter either with a breathing simulator (dose to ventilator) or with constant flow (maximal dose). The fine-particle dose was assessed with a cascade impactor (Andersen Sampler). The effect of repeated use and cleaning of the spacers on the passive fallout of aerosol within the spacers was determined by evacuating the dose on a filter 2, 5, 10 and 30 s after actuating the spray. The drugs were quantified by liquid chromatography. The NebuChamber delivered the highest doses, both maximal dose and dose to ventilator. The recovered doses (means+/-SD) were 55+/-6% and 51+/-2%, respectively, of the delivered dose from the pMDI. The corresponding results for the Babyhaler were 41+/-7% and 24+/-4% and for the Aerochamber 27+/-3% and 17+/-3%. The passive fallout of aerosol, determined as half-life (t1/2) was around approximately 30 s for the NebuChamber, 9-15 s for the Babyhaler and approximately 10 s for the AeroChamber. The present study confirms that there are significant differences in dose output from different combinations of pressurized metered dose inhalers and spacers, with the NebuChamber giving the highest dose, both as delivered dose and in droplets &lt;4.7 microm. Interactions with the spacer material, dead space in the inspiratory line and entrainment of air during inhalation due to inefficient valve control could account for these differences.
Factors influencing change in baseline vitamin D level in mycobacterial infection
Authors: Gemma Hawthorne, Alice Turner, Heinke Kunst, Martin Dedicoat, David Thickett
Journal: European Respiratory Journal (2012)

Background 

Vitamin D may be an agent, of broad relevance in the treatment of infectious disease because of its immunomodulatory properties.

Methods 

In an ongoing open label observational trial, baseline bloods, vitamin D levels, sputum smear and culture results, radiological changes and TB score were recorded in patients with mycobacterial infection.

Each patient was supplemented with 100,000 units of cholecalciferol at 0, 8 and 16 weeks.

Results 

The mean age of patients recruited (n=42) was 36 years (M:F 27:15), with pulmonary disease (n=29) or extrapulmonary disease (n=13). There was a non-significant difference in vitamin D levels between the groups.

Pre supplementation median vitamin D levels were 11.9 nmol/l (mean 16.96 nmol/l, 92.9% with 25(OH)D3 levels <50nmol/l. At week 8 post supplementation levels had risen to median 44nmol/l (mean 43.9 nmol/l). There was a significant difference in vitamin D levels pre and post supplementation (p=0.00), with a significantly higher percentage rise in vitamin D levels in patients who were severely deficient (<20nmol/l) (p=0.01).

There was no correlation between vitamin D and DBP, antimicrobial product (LL37) levels or TB score at baseline measurement.

Conclusions 

Supplementation with 100 000 units of cholecalciferol does not result in sufficient levels (>50nmol/l) at 8 weeks in all patients with just 65% attaining levels >50nmol/l. However, there is a statistically significant rise in levels of vitamin D in those supplemented between week 0 and week 8.

Patients with mycobacterial infection with vitamin D deficiency may benefit from higher initial doses to obtain sufficiency.
Biomarkers to Help Guide Management of Patients with Pulmonary Nodules
Authors: Edward F. Patz, Michael J. Campa, Elizabeth B. Gottlin, Priscilla R. Trotter, James E. Herndon, Don Kafader, Russell P. Grant, Marcia Eisenberg
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Indeterminate pulmonary nodules are a common radiographic finding and require further evaluation because of the concern for lung cancer.We developed an algorithm to assign patients to a low- or high-risk category for lung cancer, based on a combination of serum biomarker levels and nodule size.For the serum biomarker assay, we determined levels of carcinoembryonic antigen, α1-antitrypsin, and squamous cell carcinoma antigen. Serum data and nodule size from a training set of 509 patients with (n = 298) and without (n = 211) lung cancer were subjected to classification and regression tree and logistic regression analyses. Multiple models were developed and tested in an independent, masked validation set for their ability to categorize patients with (n = 203) or without (n = 196) lung cancer as being low- or high-risk for lung cancer.In all models, a large percentage of individuals in the validation study with small nodules (<1 cm) were assigned to the low-risk group, and a large percentage of individuals with large nodules (≥3 cm) were assigned to the high-risk group. In the validation study, the classification and regression tree algorithm had overall sensitivity, specificity, and positive and negative predictive values for determining lung cancer of 88%, 82%, 84%, and 87%, respectively. The logistic regression model had overall sensitivity, specificity, and positive and negative predictive values of 80%, 89%, 89%, and 81%, respectively.Integration of biomarkers with lung nodule size has the potential to help guide the management of patients with indeterminate pulmonary nodules.
The potential shortcomings of measuring hyperactivated motility by computer-aided sperm analysis when sperm motion is multiphasic
Authors: A. A. Pacey, M. B. Ladbrook, C. L. R. Barratt, I. D. Cooke
Journal: Human Reproduction Update (1997)

This paper was written from the standpoint that computer-aided sperm analysis (CASA) instruments, which capture a 'snapshot' of sperm trajectories in order to generate their data, may provide a poor measure of hyperactivated motility in a sperm population where hyperactivation is multiphasic in nature. To illustrate this point, a series of theoretical sperm populations were constructed which varied subtly but significantly in the nature of the hyperactivated behaviour expressed by spermatozoa. The parameters which were manipulated were: (i) the number of hyperactivated phases exhibited within a given period of time; (ii) the duration of these phases; and (iii) proportion of spermatozoa within the population which exhibited hyperactivated phases. These populations were then subject to an analysis in which snapshots of sperm motion were examined to determine the percentage of hyperactivated spermatozoa for that population. The results indicated that whilst this snapshot approach to quantifying hyperactivation could provide a figure for the percentage of hyperactivated spermatozoa within the sample window, this often inaccurately described the underlying behaviour of the population. Since there is very likely to be a significant amount of biological information contained within the nature of multiphasic behaviour, this paper has argued that this aspect of snapshot analysis is one which requires serious consideration by CASA manufacturers and medical researchers.
Greater Loss of 5-HT<sub>2A</sub> Receptors in Midlife Than in Late Life
Authors: Yvette I. Sheline, Mark A. Mintun, Stephen M. Moerlein, Abraham Z. Snyder
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Earlier work has shown markedly lower density of serotonin 2A (5-HT2A) receptors in elderly subjects than in young healthy subjects. In this study the authors used positron emission tomography (PET) and [18F]altanserin, a ligand with high affinity for the 5-HT2A receptor, to examine the relationship between 5-HT2A receptor density and age in more detail. METHOD: The 22 subjects ranged in age from 21 to 69 years (mean=43.4, SD=13.3) and were healthy comparison subjects in a study of depression. Regions of interest were determined on magnetic resonance images and were transferred to coregistered PET data. The data were derived from dynamic PET scanning and arterial sampling with resulting plasma activity data corrected for labeled metabolites. Compartmental modeling was used to estimate the radioligand distribution volume. By comparing the distribution volume (DV) of different regions to the cerebellum distribution volume, DVratio–1, which is proportional to the binding potential, was calculated. RESULTS: The decrease in 5-HT2A binding was not linear but on average was approximately 17% per decade from age 20. The correlations between age and 5-HT2A DVratio–1 were significant for the global measure and for the medial gyrus rectus, anterior cingulate, posterior medial prefrontal cortex, hippocampus, and occipital cortex. Most of the falloff in receptor binding occurred up through midlife, and there was less decrease in late life. There were no decreases in regional brain volumes of corresponding magnitudes. CONCLUSIONS: 5-HT2A receptor binding decreases dramatically in a variety of brain regions up through midlife.
RNAi phenotype profiling of kinases identifies potential therapeutic targets in Ewing's sarcoma
Authors: Shilpi Arora, Irma M Gonzales, R Tanner Hagelstrom, Christian Beaudry, Ashish Choudhary, Chao Sima, Raoul Tibes, Spyro Mousses, David O Azorsa
Journal: Molecular Cancer (2010)

Abstract Background Ewing's sarcomas are aggressive musculoskeletal tumors occurring most frequently in the long and flat bones as a solitary lesion mostly during the teen-age years of life. With current treatments, significant number of patients relapse and survival is poor for those with metastatic disease. As part of novel target discovery in Ewing's sarcoma, we applied RNAi mediated phenotypic profiling to identify kinase targets involved in growth and survival of Ewing's sarcoma cells. Results Four Ewing's sarcoma cell lines TC-32, TC-71, SK-ES-1 and RD-ES were tested in high throughput-RNAi screens using a siRNA library targeting 572 kinases. Knockdown of 25 siRNAs reduced the growth of all four Ewing's sarcoma cell lines in replicate screens. Of these, 16 siRNA were specific and reduced proliferation of Ewing's sarcoma cells as compared to normal fibroblasts. Secondary validation and preliminary mechanistic studies highlighted the kinases STK10 and TNK2 as having important roles in growth and survival of Ewing's sarcoma cells. Furthermore, knockdown of STK10 and TNK2 by siRNA showed increased apoptosis. Conclusion In summary, RNAi-based phenotypic profiling proved to be a powerful gene target discovery strategy, leading to successful identification and validation of STK10 and TNK2 as two novel potential therapeutic targets for Ewing's sarcoma.
Ventricular aneurysms and ventricular arrhythmias complicating Coxsackie virus B1 myocarditis of Syrian golden hamsters
Authors: T. HOSHINO, A. MATSUMORI, C. KAWAI, J. IMAI
Journal: Cardiovascular Research (1984)

We inoculated Coxsackie virus B1 (CVB1) intraperitoneally into 36 2-week-old Syrian golden hamsters. Serial ECGs were recorded from 10 hamsters which survived the acute and electrocardiographically manifest myocarditis. In a mean 17.8 week (range 9 to 31 weeks) follow-up period, chronic ventricular premature contractions (VPC) followed the acute ECG changes in three of the animals. VPC were recorded in a uniform contour in a hamsters, which had a ventricular aneurysm and were of two kinds of contour in the other two hamsters, each of which had two ventricular aneurysms. No VPC was recorded from the other seven hamsters, which had no aneurysms in the heart. None of the inoculated animals died during the follow-up period, irrespective of the existence of ventricular aneurysm, after surviving the first 2 weeks post-infection. The results demonstrate a close relationship between chronic VPC of uniform contours following CVB1 myocarditis and the formation of ventricular aneurysms in Syrian golden hamsters. The hamsters were able to live for a considerably long period with the aneurysms. Ventricular aneurysms following CVB1 myocarditis in Syrian golden hamsters may be an experimental model of human ventricular aneurysms of unknown etiology.
Critical evaluation of computerised x ray planimetry for the measurement of lung volumes.
Authors: D P Spence, Y J Kelly, J Ahmed, P M Calverley, M G Pearson
Journal: Thorax (1995)

Computerised x-ray planimetry has been advocated as an alternative to body plethysmography and helium dilution for measuring static lung volumes. The accuracy and reproducibility of this method has been assessed in comparison with these standard methods.Plethysmographic and planimetric measurements of total lung capacity (TLC) and functional residual capacity (FRC) were made in 10 normal subjects and in 12 patients with chronic obstructive pulmonary disease (COPD), with additional helium dilution measurements in the latter 12 patients.Mean lung volumes (TLC and FRC) for groups of subjects measured by planimetry and by plethysmography were similar in both groups and larger than the helium dilution measurement in patients with COPD. Intraindividual agreement between planimetry and plethysmography was poor, however, with a wide confidence interval (-2.2 to +2.31). The planimeter did not measure reliably changes in volume from TLC to FRC in individuals.Mean lung volumes measured by planimetry in a group of patients probably reflect a regression to the mean of the computer algorithm rather than accurate TLC estimation. The technique is not yet robust enough to replace the established techniques of helium dilution or plethysmography.
Quality of Life of Long-Term Survivors of Breast Cancer and Lymphoma Treated With Standard-Dose Chemotherapy or Local Therapy
Authors: Tim A. Ahles, Andrew J. Saykin, Charlotte T. Furstenberg, Bernard Cole, Leila A. Mott, Linda Titus-Ernstoff, Karen Skalla, Marie Bakitas, Peter M. Silberfarb
Journal: Journal of Clinical Oncology (2005)

This study compared the quality of life (QOL) of long-term survivors of breast cancer and lymphoma who had been treated with standard-dose systemic chemotherapy or local therapy only.Long-term survivors (mean, 10.0 +/- 5.3 years after treatment) of breast cancer or lymphoma who had been treated with systemic chemotherapy (breast, n = 141, age = 57.0 +/- 10.1 years; lymphoma, n = 66, age = 55.8 +/- 13.5 years) or local therapy only (breast, n = 294, age = 65.8 +/- 9.1 years; lymphoma, n = 37, age = 50.4 +/- 12.8 years) were interviewed by phone using the Quality of Life-Cancer Survivors Tool.Multivariate analysis of covariance, controlling for sex, age, education, stage of disease, and time since last treatment, revealed that survivors who had been treated with systemic chemotherapy scored significantly lower on overall QOL compared with survivors treated with local therapy only (P = .04). Analysis of covariance on the subscale scores revealed that, compared with survivors who received local therapy, survivors treated with chemotherapy scored significantly lower on the Social subscale (P < .0001), but no differences emerged on the Psychological or Spiritual subscales. There was a statistically significant interaction between treatment and diagnosis (P = .01), as measured by the Physical subscale, indicating that lymphoma survivors treated with chemotherapy scored worse than all other groups.Important QOL differences emerged between the chemotherapy and local therapy groups, suggesting that long-term QOL may vary depending on the type of treatment and diagnosis.
Interleukin 10 treatment for rheumatoid arthritis
Authors: E W. St Clair
Journal: Annals of the Rheumatic Diseases (1999)

Interleukin (IL) 10 looms as a highly promising treatment for rheumatoid arthritis (RA) because of its capacity to inhibit cellular immunity and deactivate macrophages. In RA, activated CD4 T helper cells and macrophages are believed to be the primary driving force behind joint inflammation. Synovial macrophages play a critical part in stimulating synovial inflammation. They produce abundant quantities of pro-inflammatory cytokines such as IL1 and tumour necrosis factor (TNF) α. The body attempts to keep the inflammatory response in check by upregulating the synthesis of endogenous inhibitors such as IL1 receptor antagonist (ra), soluble TNF receptors (TNFR), and IL10. These inhibitors act in concert to dampen the inflammatory response. IL10 is relatively unique in its ability to downregulate the production of multiple pro-inflammatory cytokines, leading to the notion that IL10 would be an effective treatment for RA.

Monocytes and macrophages produce IL10 when they are activated with the bacterial endotoxin lipopolysaccharide (LPS). There is an initial burst of pro-inflammatory cytokines (TNFα, IL1, IL6, and GM-CSF) followed later by a rise in IL10 synthesis.1 LPS stimulated IL10 production requires both the synthesis of TNFα and IL1 as well as cognate interactions between monocytes and T cells.2 3 IL10 release from LPS stimulated monocytes may be increased by transforming growth factor (TGF) β, interferon (IFN) α, IFNβ,4-6 histamine7 and ligation of the Fcγ receptor I.8 On the other hand, LPS stimulated IL10 production may be inhibited by IL4, IFNγ,9 10 and ligation of CD23, the low affinity IgE receptor.11 IL10 and IL12 appear to be coordinately regulated in many of these experimental systems such that IL12 upregulates the synthesis of IL10 that controls the extent of the response.7 8 

T cells also produce IL10. This cytokine is a component of the overall T helper …
Effect of Leukotriene and Thromboxane Antagonist on Propranolol-induced Bronchoconstriction
Authors: MASAKI FUJIMURA, MIKI ABO, YUMIE KAMIO, SHIGEHARU MYOU, YOSHIHISA ISHIURA, TAKUMA HASHIMOTO, TAMOTSU MATSUDA
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

beta-adrenoreceptor blockers such as propranolol provoke bronchoconstriction only in asthmatic patients. Although cysteinyl leukotrienes (cLTs) and thromboxane A2 (TXA2) have been proposed to be involved in the pathophysiology of asthma, the role of these lipid mediators in propranolol-induced bronchoconstriction (PIB) has not been evaluated in asthmatics. This study was conducted to elucidate it. Nine patients with stable asthma, in whom a 20% or more decrease in FEV(1) occurred by inhalation of 20 mg/ml or less propranolol, participated in this study. A cLT antagonist, pranlukast (225 mg twice a day), a TXA2 antagonist, seratrodast (80 mg once a day), and placebo were orally given for 2 wk in a randomized and double-blinded manner. The provocative concentration of propranolol causing a 20% fall in FEV(1) (PC(20)) was determined on the last day of each 2-wk treatment. Pranlukast, but not seratrodast, tented to increase FEV(1) compared with placebo (2.14 +/- 0.29 versus 1.99 +/- 0.34 L, p = 0.0543). Pranlukast or seratrodast did not affect the PC(20) in comparison with placebo. We conclude that cLTs or TXA2 are not involved in PIB of asthmatics.
Hospice at home
Authors: J. Woyka
Journal: BMJ (1995)

On Friday 31 December 1993 my husband abandoned his car in heavy traffic and jogged the last three miles to his surgical outpatients session. He collided with a lamp post, fracturing two ribs and sustaining a moderately severe head injury, and was found by a hospital porter, wandering confused near the canal beside the hospital. It was the end of months of lurking anxiety about his health—extreme fatigue had been attributed either to his excessive workload or to our new addition to the family. Three short lived episodes of unilateral visual loss in the summer had not recurred, and although his ophthalmologist was concerned about the finding of optic vein hypertension, magnetic resonance imaging of the brain in September was entirely normal. More alarming were the strange attacks I had witnessed: a metallic taste in the mouth, sweating, terror, and collapse without loss of consciousness. Yet all measurements were normal: pulse the usual 45, blood pressure 130/80, BM sticks normal, reflexes brisk and equal. A general physician consulted in December could find no cause and diagnosed overwork, excessive exercise, and poor eating habits.

Temporary elation propelled me into Christmas preparations as I gratefully chose presents for my precious husband. But deep suspicion remained and lifestyle changes were not easy to make, so the call from the accident and emergency consultant telling me of Adrian's accident came as no great surprise. I was almost relieved. While I finished my surgery, Adrian's condition deteriorated and computed tomography was performed. Meeting …
Bronchioalveolar Lung Cancer: Screening and Overdiagnosis
Authors: Alain Braillon
Journal: Journal of Clinical Oncology (2014)

Thisis not trivial, as there are 110 cases of BAC (10.5% of lung cancersdiagnosed) in the computed tomography group (CT) versus 35(3.8%)intheradiographygroup.Second, NLCST was published in 2011 but coded histologicfeatures according to the WHO 2000 International Classiﬁcation ofDiseases for Oncology. The trial was neither updated for the 2004revision, nor for the more recent pathologic classiﬁcation of BACwhichnowexists.