tbuckley/cabot-search huggingface dataset:
Letter from Haiti: Fighting for survival
Authors: C Chelala
Journal: BMJ (1994)

Children dressed as soldiers on Afnica 's Day ofthe Child take care of them, that is the recipe," he says."The attendance should be voluntary.Never lock them upthat is the biggest mistake you can make.Don't force the children to stay.They will run away, but eventually they come back because they receive food and are given attention-things they crave and cannot get elsewhere.This process of demobilisation is also an adventure for them.After a while they will trust you-that is what it is all about.Give them love, care for them, listen to their story, no matter how horrible it is, and gradually you will see them change.After half a year you will see them play.That is the aim: that they become children again, enjoying football."They come in as criminals, ready to fight, they fight with everything available-bottles, chairs.They are very aggressive; self mutilation is common.They know how to kill."The priest looks me deep in the eyes and speaks softly: "They know perfectly well how to decapitate somebody-the back side first."He does not explain the reason for this approach, and as a doctor I'm too embarrassed to ask.The priest tells me of a child who is deaf from launching rocket propelled grenades from his shoulder and of 8 year old children who take a gun apart while you have a cup of coffee.'We trace the parents through our Catholic network, and I'm proud to say that the first 100 children recovered well.We plan to follow them up for three years.We will pay for schooling and teach them a trade."I'm impressed with his story and believe that he has hit the right approach.Education and employment are the important issues.The lack of them has caused a decline beyond repair in Sierra Leone.In the airport I'm body searched by a child.Officially the children take the role of an adult only on this day, but many children in Sierra Leone have no youth at all.By the time I board the plane I have already worked out a plan to offer support for the displaced people in the camps.I also have ideas for giving aid to child soldiers that we could use in other countries.It was a tiring but useful trip.
GMC promises more compassionate approach to doctors under investigation
Authors: Clare Dyer
Journal: BMJ (2015)

Letters from the General Medical Council to doctors facing investigation will use more “sensitive” language from early next year and will lay more emphasis on the support services available to them, after a report into a series of suicides by doctors undergoing fitness to practise investigations.

The report in December 2014 looked at the 28 cases from 2005 to 2013 in which doctors had killed themselves during an investigation by the regulator, and it made a number of recommendations for reform.1 Of these suicides, four happened in 2012 and a further nine in 2013.

The review by Sarndrah Horsfall, an independent consultant and former chief executive of the National Patient Safety …
Regulation of Starch Stores by a Ca2+-Dependent Protein Kinase Is Essential for Viable Cyst Development in Toxoplasma gondii
Authors: Alessandro D. Uboldi, James M. McCoy, Martin Blume, Motti Gerlic, David J.P. Ferguson, Laura F. Dagley, Cherie T. Beahan, David I. Stapleton, Paul R. Gooley, Antony Bacic, Seth L. Masters, Andrew I. Webb, Malcolm J. McConville, Christopher J. Tonkin
Journal: Cell Host & Microbe (2015)
Impact of Ipsilateral Blood Draws, Injections, Blood Pressure Measurements, and Air Travel on the Risk of Lymphedema for Patients Treated for Breast Cancer
Authors: Chantal M. Ferguson, Meyha N. Swaroop, Nora Horick, Melissa N. Skolny, Cynthia L. Miller, Lauren S. Jammallo, Cheryl Brunelle, Jean A. O’Toole, Laura Salama, Michelle C. Specht, Alphonse G. Taghian
Journal: Journal of Clinical Oncology (2015)

Purpose The goal of this study was to investigate the association between blood draws, injections, blood pressure readings, trauma, cellulitis in the at-risk arm, and air travel and increases in arm volume in a cohort of patients treated for breast cancer and screened for lymphedema. Patients and Methods Between 2005 and 2014, patients undergoing treatment of breast cancer at our institution were screened prospectively for lymphedema. Bilateral arm volume measurements were performed preoperatively and postoperatively using a Perometer. At each measurement, patients reported the number of blood draws, injections, blood pressure measurements, trauma to the at-risk arm(s), and number of flights taken since their last measurement. Arm volume was quantified using the relative volume change and weight-adjusted change formulas. Linear random effects models were used to assess the association between relative arm volume (as a continuous variable) and nontreatment risk factors, as well as clinical characteristics. Results In 3,041 measurements, there was no significant association between relative volume change or weight-adjusted change increase and undergoing one or more blood draws (P = .62), injections (P = .77), number of flights (one or two [P = .77] and three or more [P = .91] v none), or duration of flights (1 to 12 hours [P = .43] and 12 hours or more [P = .54] v none). By multivariate analysis, factors significantly associated with increases in arm volume included body mass index ≥ 25 (P = .0236), axillary lymph node dissection (P &lt; .001), regional lymph node irradiation (P = .0364), and cellulitis (P &lt; .001). Conclusion This study suggests that although cellulitis increases risk of lymphedema, ipsilateral blood draws, injections, blood pressure readings, and air travel may not be associated with arm volume increases. The results may help to educate clinicians and patients on posttreatment risk, prevention, and management of lymphedema.
Using venous blood gas analysis in the assessment of COPD exacerbations: a prospective cohort study
Authors: Tricia M McKeever, Glenn Hearson, Gemma Housley, Catherine Reynolds, William Kinnear, Tim W Harrison, Anne-Maree Kelly, Dominick E Shaw
Journal: Thorax (2015)

<h3>Introduction</h3> Identifying acute hypercapnic respiratory failure is crucial in the initial management of acute exacerbations of COPD. Guidelines recommend obtaining arterial blood samples but these are more difficult to obtain than venous. We assessed whether blood gas values derived from venous blood could replace arterial at initial assessment. <h3>Methods</h3> Patients requiring hospital treatment for an exacerbation of COPD had paired arterial and venous samples taken. Bland–Altman analyses were performed to assess agreement between arterial and venous pH, CO<sub>2</sub> and . The relationship between SpO<sub>2</sub> and SaO<sub>2</sub> was assessed. The number of attempts and pain scores for each sample were measured. <h3>Results</h3> 234 patients were studied. There was good agreement between arterial and venous measures of pH and (mean difference 0.03 and −0.04, limits of agreement −0.05 to 0.11 and −2.90 to 2.82, respectively), and between SaO<sub>2</sub> and SpO<sub>2</sub> (in patients with an SpO<sub>2</sub> of &gt;80%). Arterial sampling required more attempts and was more painful than venous (mean pain score 4 (IQR 2–5) and 1 (IQR 0–2), respectively, p&lt;0.001). <h3>Conclusions</h3> Arterial sampling is more difficult and more painful than venous sampling. There is good agreement between pH and values derived from venous and arterial blood, and between pulse oximetry and arterial blood gas oxygen saturations. These agreements could allow the initial assessment of COPD exacerbations to be based on venous blood gas analysis and pulse oximetry, simplifying the care pathway and improving the patient experience.
Confounding and Simpson's paradox
Authors: C R Charig
Journal: BMJ (1995)

considered, it was unnecessary as the areas of ulceration healed completely after resolution of the infection.I agree that cutaneous radionecrosis and osteonecrosis often require excision and the use of myocutaneous flaps.These and other complications of radiotherapy are covered in a subsequent article in the ABC series.Reconstruction of the breast and its complications are also being covered separately.The point of the illustration was to show a good example of cellulitis after surgery and radiotherapy.This cellulitis needs to be controlled by antibiotics before other measures are con- sidered.In this respect I do not believe that the illustration was misleading or inappropriate.
Abstract 20055: The αvβ3 Integrin Positron Emission Tomography Radiotracer 18F-Fluciclatide is a Marker of Remodeling Following Myocardial Infarction
Authors: William S Jenkins, Alexander Vesey, Anoushka Neale, Vickers Anna, Catriona Moles, Christophe Lucatelli, Alison Fletcher, Saeed Mirsadee, Edwin J Van Beek, James H Rudd, Marc R Dweck, David E Newby
Journal: Circulation (2015)

Introduction: The integrin receptor αvβ3 is upregulated by vascular endothelial cells, macrophages and myofibroblasts during cardiac interstitial remodeling. We evaluated the role for the novel αvβ3 radiotracer 18F-fluciclatide in the non-invasive assessment of repair post-myocardial infarction. Methods: We performed combined PET/CT and CT-coronary angiography (CTCA) imaging of the heart following intravenous administration of 18F-fluciclatide (230mBq) in 21 patients 12±4 days after acute ST-elevation myocardial infarction, 7 stable patients with occlusion of a major coronary vessel for &gt;6months, and 9 healthy volunteers. ECG-gated PET data was acquired over 30 minutes, 40 minutes after ligand injection. Subjects also underwent Cardiac MRI (CMR) with assessment of late gadolinium enhancement and T1 mapping. PET data was fused with the CTCA and re-orientated into the left ventricular short-axis plane. The infarct site was identified through co-registration with CMR and delineated using regions of interest and a 16-segment approach. PET values, corrected for blood activity, were expressed as a mean tissue-to-background ratio. Myocardial extracellular volume (ECV) in a 16-segment model was quantified on CMR using T1 mapping pre-and post-gadolinium administration. Results: 18F-fluciclatide uptake correlated with cardiac ECV (r=0.37(0.29-0.45),p&lt;0.001), and was increased in sites of acute myocardial infarction when compared to regions of remote myocardium (1.32±0.23 vs 0.85±0.17; p&lt;0.001), sites of established infarction in subjects with a chronically occluded coronary vessel (1.32±0.23 vs 0.70±0.14; p&lt;0.001), and when matched with regions in control subjects (0.94±0.23 vs 0.67±0.09; p=0.003). Conclusions: 18F-Fluciclatide uptake localises to sites of acute myocardial infarction and correlates with extracellular volume on CMR. This holds great potential in the non-invasive quantification of active myocardial remodeling.
Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers
Authors: Brett A. Clementz, John A. Sweeney, Jordan P. Hamm, Elena I. Ivleva, Lauren E. Ethridge, Godfrey D. Pearlson, Matcheri S. Keshavan, Carol A. Tamminga
Journal: American Journal of Psychiatry (2015)

Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations.
MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data
Authors: Greg Finak, Andrew McDavid, Masanao Yajima, Jingyuan Deng, Vivian Gersuk, Alex K. Shalek, Chloe K. Slichter, Hannah W. Miller, M. Juliana McElrath, Martin Prlic, Peter S. Linsley, Raphael Gottardo
Journal: Genome biology (2015)

Single-cell transcriptomics reveals gene expression heterogeneity but suffers from stochastic dropout and characteristic bimodal expression distributions in which expression is either strongly non-zero or non-detectable. We propose a two-part, generalized linear model for such bimodal data that parameterizes both of these features. We argue that the cellular detection rate, the fraction of genes expressed in a cell, should be adjusted for as a source of nuisance variation. Our model provides gene set enrichment analysis tailored to single-cell data. It provides insights into how networks of co-expressed genes evolve across an experimental treatment. MAST is available at https://github.com/RGLab/MAST .
The N17 domain mitigates nuclear toxicity in a novel zebrafish Huntington’s disease model
Authors: Matthew B. Veldman, Yesenia Rios-Galdamez, Xiao-Hong Lu, Xiaofeng Gu, Wei Qin, Song Li, X. William Yang, Shuo Lin
Journal: Molecular Neurodegeneration (2015)

Although the genetic cause for Huntington's disease (HD) has been known for over 20 years, the mechanisms that cause the neurotoxicity and behavioral symptoms of this disease are not well understood. One hypothesis is that N-terminal fragments of the HTT protein are the causative agents in HD and that peptide sequences adjacent to the poly-glutamine (Q) repeats modify its toxicity. Here we test the function of the N-terminal 17 amino acids (N17) in the context of the exon 1 fragment of HTT in a novel, inducible zebrafish model of HD. Deletion of N17 coupled with 97Q expansion (mHTT-ΔN17-exon1) resulted in a robust, rapidly progressing movement deficit, while fish with intact N17 and 97Q expansion (mHTT-exon1) have more delayed-onset movement deficits with slower progression. The level of mHTT-ΔN17-exon1 protein was significantly higher than mHTT-exon1, although the mRNA level of each transgene was marginally different, suggesting that N17 may regulate HTT protein stability in vivo. In addition, cell lineage specific induction of the mHTT-ΔN17-exon1 transgene in neurons was sufficient to recapitulate the consequences of ubiquitous transgene expression. Within neurons, accelerated nuclear accumulation of the toxic HTT fragment was observed in mHTT-ΔN17-exon1 fish, demonstrating that N17 also plays an important role in sub-cellular localization in vivo. We have developed a novel, inducible zebrafish model of HD. These animals exhibit a progressive movement deficit reminiscent of that seen in other animal models and human patients. Deletion of the N17 terminal amino acids of the huntingtin fragment results in an accelerated HD-like phenotype that may be due to enhanced protein stability and nuclear accumulation of HTT. These transgenic lines will provide a valuable new tool to study mechanisms of HD at the behavioral, cellular, and molecular levels. Future experiments will be focused on identifying genetic modifiers, mechanisms and therapeutics that alleviate polyQ aggregation in the nucleus of neurons.
Heparan sulfate mimetic PG545-mediated antilymphoma effects require TLR9-dependent NK cell activation
Authors: Todd V. Brennan, Liwen Lin, Joshua D. Brandstadter, Victoria R. Rendell, Keith Dredge, Xiaopei Huang, Yiping Yang
Journal: Journal of Clinical Investigation (2015)

Heparan sulfate (HS) is an essential component of the extracellular matrix (ECM), which serves as a barrier to tumor invasion and metastasis. Heparanase promotes tumor growth by cleaving HS chains of proteoglycan and releasing HS-bound angiogenic growth factors and facilitates tumor invasion and metastasis by degrading the ECM. HS mimetics, such as PG545, have been developed as antitumor agents and are designed to suppress angiogenesis and metastasis by inhibiting heparanase and competing for the HS-binding domain of angiogenic growth factors. However, how PG545 exerts its antitumor effect remains incompletely defined. Here, using murine models of lymphoma, we determined that the antitumor effects of PG545 are critically dependent on NK cell activation and that NK cell activation by PG545 requires TLR9. We demonstrate that PG545 does not activate TLR9 directly but instead enhances TLR9 activation through the elevation of the TLR9 ligand CpG in DCs. Specifically, PG545 treatment resulted in CpG accumulation in the lysosomal compartment of DCs, leading to enhanced production of IL-12, which is essential for PG545-mediated NK cell activation. Overall, these results reveal that PG545 activates NK cells and that this activation is critical for the antitumor effect of PG545. Moreover, our findings may have important implications for improving NK cell–based antitumor therapies.
Releasing the Brake on Oncolytic Viral Therapy
Authors: Clare Y. Slaney, Phillip K. Darcy
Journal: Clinical Cancer Research (2015)

Oncolytic virus that selectively targets and eradicates tumor cells and immune checkpoint blockade that unleashes host antitumor immune responses show synergistic effects against cancer. This combination holds great promise for future treatment of a broad range of cancers in patients. Clin Cancer Res; 21(24); 5417-9. ©2015 AACR.See related article by Rojas et al., p. 5543.
Chronic Rhinosinusitis: More Than Just “Asthma of the Upper Airway”
Authors: Larry Borish
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Chronic Rhinosinusitis: More Than Just "Asthma of the Upper Airway"Traditionally, rhinosinusitis (RS) was divided into three distinct conditions according to duration, with chronic RS (CRS) defined as disease present for longer than 12 weeks.In addition, whereas acute and subacute sinusitis were defined as infectious processes driven by pyogenic organisms such as Streptococcus, Haemophilus, and Moraxella, CRS was contrasted by the presence of anaerobic, gram-negative, and Staphylococcus infections.Although more
Moderate versus aggressive chemotherapy of nodular lymphocytic poorly differentiated lymphoma.
Authors: E Z Ezdinli, J R Anderson, F Melvin, J H Glick, T E Davis, M J O'Connell
Journal: Journal of Clinical Oncology (1985)

One hundred twenty-eight patients with purely nodular lymphocytic poorly differentiated lymphoma (NLPDL) without any prior therapy, entered on Eastern Cooperative Oncology Group protocol EST 2474, were analyzed for response, progression-free and overall survival. The restaged complete response rates with cyclophosphamide-prednisone (CP) (moderate regimen) of 54% compared favorably with those of the more intensive regimens; cyclophosphamide, vincristine, procarbazine and prednisone (COPP) (56%) and BCNU, cyclophosphamide, vincristine, and prednisone (BCVP) (53%). The toxicity of the regimens decreased from BCVP to COPP to CP. The median survival rate for the entire group was 7.8 years. Estimated progression-free survival at five years by regimen was COPP, 57%; BCVP, 26%; CP, 22% (P = .02). No other prognostic parameter significantly affected progression-free survival. In spite of the better progression-free survival of COPP-treated patients, the overall survival rates with the different induction regimens were similar. Maintenance therapy for patients in complete response at the end of induction therapy with periodic BCVP reinduction did not significantly affect the disease-free or overall survival. Cyclophosphamide-prednisone is a minimally toxic regimen effective in the treatment of NLPDL, but COPP, in view of its acceptable toxicity in this patient population and apparent superiority in providing a longer disease-free state, deserves further testing.
Comparative Effectiveness of CRT-D Versus Defibrillator Alone in HF Patients With Moderate-to-Severe Chronic Kidney Disease
Authors: Daniel J. Friedman, Jagmeet P. Singh, Jeptha P. Curtis, W.H. Wilson Tang, Haikun Bao, Erica S. Spatz, Adrian F. Hernandez, Uptal D. Patel, Sana M. Al-Khatib
Journal: Journal of the American College of Cardiology (2015)
Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection
Authors: Gregory T. Everson, William J. Towner, Mitchell N. Davis, David L. Wyles, Ronald G. Nahass, Paul J. Thuluvath, Kyle Etzkorn, Federico Hinestrosa, Myron Tong, Mordechai Rabinovitz, John McNally, Diana M. Brainard, Lingling Han, Brian Doehle, John G. McHutchison, Timothy Morgan, Raymond T. Chung, Tram T. Tran
Journal: Annals of Internal Medicine (2015)

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed. Objective: To assess the safety and efficacy of sofosbuvir with velpatasvir in patients infected with HCV genotypes 1 to 6. Design: Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01858766) Setting: 48 U.S. sites. Patients: 377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks. Measurements: Sustained virologic response at 12 weeks (SVR12). Results: In part A, SVR12 rates were 96% (26 of 27) with velpatasvir, 25 mg, and 100% (28 of 28) with velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with velpatasvir, 25 mg, and 95% (21 of 22) with velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In part B, for genotype 1, SVR12 rates were 87% (26 of 30) with velpatasvir, 25 mg; 83% (25 of 30) with velpatasvir, 25 mg, plus ribavirin; 90% (26 of 29) with velpatasvir, 100 mg; and 81% (25 of 31) with velpatasvir, 100 mg, plus ribavirin. For genotype 2, SVR12 rates were 77% (20 of 26) with velpatasvir, 25 mg; 88% (22 of 25) with velpatasvir, 25 mg, plus ribavirin; 88% (23 of 26) with velpatasvir, 100 mg; and 88% (23 of 26) with velpatasvir, 100 mg, plus ribavirin. Adverse events included fatigue (21%), headache (20%), and nausea (12%). One patient committed suicide. Limitation: The study was open-label, no inferential statistics were planned, and sample sizes were small. Conclusion: Twelve weeks of sofosbuvir, 400 mg, and velpatasvir, 100 mg, was well-tolerated and resulted in high SVR in patients infected with HCV genotypes 1 to 6. Primary Funding Source: Gilead Sciences.