tbuckley/cabot-search huggingface dataset:
Armies
Authors: Mary E Black
Journal: BMJ (2007)

I have mixed feelings about armies. In 1970s Belfast, we Catholic children welcomed British soldiers as our saviours till the tide of opinion changed and we were told to ignore them as they passed by on street patrols. In fake military-style justice thousands of young people had brutal punishment beatings from Northern Irish paramilitaries—a big number for a small country. In the Royal Victoria Hospital I patched up a young father, shot through the spine by an 18 year old from an impoverished housing estate in Glasgow; given an army uniform and a gun he had simply lost it one afternoon.

I grew up near Long Kesh, a dark and secretive place where the innocent, the politically motivated, and the murderous were interned for years without trial and where the prison authorities used the “five techniques” of wall-standing, hooding, subjection to white noise, and deprivation of food and drink. Now, the internet, global news coverage, and documentary films shine light on Guantanamo Bay, follow the British Navy personnel taken prisoner by Iran this year, and show us the rape and murder by US soldiers of a 14 year girl in Iraq. Armies and their workings are more familiar. We can have virtual seats on the world's international front lines, and we can choose to watch, to engage . . . or not.

It was a member of the French Foreign Legion, an abscondee from Belfast, who would let me into the UN compound in Bosnia after curfew. It was the British soldiers in UNPROFOR (the United Nations Protection Force) who would “commission” items for my UN medical evacuation unit in Sarajevo. Decent, practical men all, but I never did ask them what their units had done while serving in Northern Ireland. For armies make me nervous. Armies put people into structures where the individual can be sacrificed for the greater good, where violence can be central to the mission.

Time moves on. Long Kesh may become an International Centre for Conflict Transformation, a national sports centre, and residential and commercial units. I teach with British Army colleagues on planning and logistics in complex emergencies, as they do both so well. In Belgrade, I bring my children each year to Anzac day, Remembrance Sunday, and the French equivalent, bearing the framed photograph of my grandfather in his British Army medical officer uniform, a gas survivor from the trenches in the first world war. We talk about my aunt, a member of the Women's Royal Naval Service in the second world war. We wear poppies and lay flowers on the graves of those brave, scared, and lonely soldiers who died far away from home. Soldiers who had mothers with mixed feelings.

And my prayer? May I never have to watch my children march off to war. May my children do anything else to save the world but pull a trigger.
Abstract #3696: AZD8330 (ARRY-424704): Preclinical evaluation of a potent, selective MEK 1/2 inhibitor currently in phase I trials
Authors: Eli Wallace, Joseph Lyssikatos, James Blake, Allison Marlow, Julie Greschuk, Tammie Yeh, Michele Callejo, Vivienne Marsh, Gregory Poch, Jennifer Otten, Gary Hingorani, Shannon Winski, Deborah Anderson, Patrice Lee, James Winkler, Kevin Koch, Barry Davies, Darren Jones, Armelle Logie, Nicola Curtis, Christine Chresta, Paul Smith, David Robinson
Journal: Cancer Research (2009)

The dual-specificity kinases MEK 1/2 play key roles in tumorgenesis by activating the serine/threonine kinases ERK 1/2. These kinases play critical roles in cellular proliferation, differentiation, apoptosis, migration, and invasion. As such, inhibition of MEK 1/2 is an attractive mechanism for anti-cancer therapy and several small molecule inhibitors have entered human clinical trials, including AZD6244 (ARRY-142886). We have discovered AZD8330 (ARRY-424704), a novel, selective, highly efficacious, uncompetitive MEK 1/2 inhibitor with superior drug-like properties. In cell-free kinase assays, AZD8330 inhibits MEK with an IC50 of 7 nM, and has no inhibitory activity against over 200 other kinases at concentrations up to 10 \#956;M. AZD8330 demonstrates sub-nano molar potency in mechanistic (pERK) and low to sub-nano-molar potency in functional (proliferation) assays in MEK inhibitor sensitive cell lines. In a Calu-6 rat xenograft PK/PD model a single, 1.25 mg/kg oral dose of AZD8330 inhibits ERK phosphorylation by > 90% for between 4 and 8 hours. In pharmacokinetic studies, the high permeability, low predicted hepatic Cl and solubility of AZD8330 translates to high %F and long plasma half-life in rat and dog , 63 and 77% and 10 and 11 hours, respectively following oral administration. The pharmacodynamic and pharmacokinetic properties of AZD8330 result in impressive efficacy at low doses in rodent models of cancer. Doses as low as 0.4 mg/kg once daily are sufficient for > 80% tumour growth inhibition in the Calu-6 nude rat xenograft model. Comparison of once and twice daily dosing schedules indicate similar efficacy for both. In multiple-dose toxicity studies, oral dosing of AZD8330 has an acceptable overall safety profile in the rat and the dog. AZD8330 is currently in Phase I clinical trials for the treatment of cancer.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3696.
Identifying HIV care continuum gaps with verbal autopsy
Authors: Isaac I Bogoch, Mireille Gomes, Laura Fuente-Soro, Rosauro Varo, Denise Naniche, Charfudin Sacoor, Raquel González, Nico Nagelkerke, Quique Bassat, Prabhat Jha
Journal: The Lancet HIV (2018)
malERA: An updated research agenda for diagnostics, drugs, vaccines, and vector control in malaria elimination and eradication
Journal: PLoS Medicine (2017)

Since the turn of the century, a remarkable expansion has been achieved in the range and effectiveness of products and strategies available to prevent, treat, and control malaria, including advances in diagnostics, drugs, vaccines, and vector control. These advances have once again put malaria elimination on the agenda. However, it is clear that even with the means available today, malaria control and elimination pose a formidable challenge in many settings. Thus, currently available resources must be used more effectively, and new products and approaches likely to achieve these goals must be developed. This paper considers tools (both those available and others that may be required) to achieve and maintain malaria elimination. New diagnostics are needed to direct treatment and detect transmission potential; new drugs and vaccines to overcome existing resistance and protect against clinical and severe disease, as well as block transmission and prevent relapses; and new vector control measures to overcome insecticide resistance and more powerfully interrupt transmission. It is also essential that strategies for combining new and existing approaches are developed for different settings to maximise their longevity and effectiveness in areas with continuing transmission and receptivity. For areas where local elimination has been recently achieved, understanding which measures are needed to maintain elimination is necessary to prevent rebound and the reestablishment of transmission. This becomes increasingly important as more countries move towards elimination.
Oral Medications to Treat Toenail Fungal Infection
Authors: Sanne Kreijkamp-Kaspers, Kate L. Hawke, Mieke L. van Driel
Journal: JAMA (2018)

<h3>Clinical Question</h3> Which oral antifungal medication is associated with the highest clinical (ie, normal appearance of the toenail) and mycological (negative culture, microscopy, or both) cure rates vs placebo or other antifungals when used to treat fungal infections? <h3>Bottom Line</h3> Both terbinafine and azole-based medications were associated with higher clinical and mycological cure rates compared with placebo (high-quality evidence). Azoles were associated with lower cure rates than terbinafine when compared directly.
Gaze patterns hold key to unlocking successful search strategies and increasing polyp detection rate in colonoscopy
Authors: Mariam Lami, Harsimrat Singh, James Dilley, Hajra Ashraf, Matthew Edmondon, Felipe Orihuela-Espina, Jonathan Hoare, Ara Darzi, Mikael Sodergren
Journal: Endoscopy (2018)

The adenoma detection rate (ADR) is an important quality indicator in colonoscopy. The aim of this study was to evaluate the changes in visual gaze patterns (VGPs) with increasing polyp detection rate (PDR), a surrogate marker of ADR.18 endoscopists participated in the study. VGPs were measured using eye-tracking technology during the withdrawal phase of colonoscopy. VGPs were characterized using two analyses - screen and anatomy. Eye-tracking parameters were used to characterize performance, which was further substantiated using hidden Markov model (HMM) analysis.Subjects with higher PDRs spent more time viewing the outer ring of the 3 × 3 grid for both analyses (screen-based: r = 0.56, P = 0.02; anatomy: r = 0.62, P < 0.01). Fixation distribution to the "bottom U" of the screen in screen-based analysis was positively correlated with PDR (r = 0.62, P = 0.01). HMM demarcated the VGPs into three PDR groups.This study defined distinct VGPs that are associated with expert behavior. These data may allow introduction of visual gaze training within structured training programs, and have implications for adoption in higher-level assessment.
Higher rates of molecular response to Peg-IFNa in JAK2V617F vs. CALR mutant MPN patients are due to JAK1-mediated STAT1 activation and autoregulation
Authors: Julia Czech, Sabrina Cordua, Barbora Weinbergerova, Lijuan Han, Claudia Schubert, Tim H. Brümmendorf, Jiri Mayer, Zdenek Racil, Blanka Kubesova, Trine Alma Knudsen, Anders Sørensen, Morten Holmstrøm, Lasse Kjær, Vibe Skov, Thomas Stauffer Larsen, Hans Carl Hasselbalch, Nicolas Chatain, Steffen Koschmieder
Journal: Blood (2017)
Union vows to support NHS staff who refuse to act as “border guards”
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The medical union Doctors in Unite has vowed to support health workers who refuse to check migrant patients’ eligibility for NHS care before treating them, and who may face disciplinary action for doing so.

The pledge came in a motion passed at the union’s annual conference on 20 January, which put on record its opposition to the government’s policy of charging migrants and overseas visitors for NHS care.

The group—which is part of the Unite union—noted “the progressive tightening” of the rules regarding eligibility …
Serlopitant for the treatment of chronic pruritus: Results of a randomized, multicenter, placebo-controlled phase 2 clinical trial
Authors: Gil Yosipovitch, Sonja Ständer, Matthew B. Kerby, James W. Larrick, Andrew J. Perlman, Edward F. Schnipper, Xiaoming Zhang, Jean Y. Tang, Thomas Luger, Martin Steinhoff
Journal: Journal of the American Academy of Dermatology (2018)

BackgroundThe substance P/neurokinin 1 receptor pathway is critical in chronic pruritus; anecdotal evidence suggests that antagonism of this pathway can reduce chronic itch.ObjectiveTo assess the safety and efficacy of the substance P/neurokinin 1 receptor antagonist serlopitant in treating chronic pruritus.MethodsEligible patients with severe chronic pruritus who were refractory to antihistamines or topical steroids were randomized to serlopitant, 0.25, 1, or 5 mg, or to placebo, administered once daily for 6 weeks as monotherapy or with midpotency steroids and emollients. The primary efficacy end point was percentage change in visual analog scale pruritus score from baseline.ResultsSerlopitant treatment resulted in a dose-dependent decrease in pruritus. The mean percentage decreases from baseline visual analog scale pruritus scores were statistically significantly larger with the 1- and 5-mg doses of serlopitant (P = .022 and P = .013, respectively) than with placebo at week 6. No significant safety or tolerability differences were detected among the groups.LimitationsThe sample size was insufficient for subgroup analyses of the efficacy of serlopitant for chronic pruritus on the basis of underlying conditions.ConclusionsSerlopitant, 1 mg and 5 mg daily, was associated with a statistically significant reduction in chronic pruritus and was well tolerated (NCT01951274).
Population impact of lung cancer screening in the United States: Projections from a microsimulation model
Authors: Steven D. Criss, Deirdre F. Sheehan, Lauren Palazzo, Chung Yin Kong
Journal: PLoS Medicine (2018)

Background Previous simulation studies estimating the impacts of lung cancer screening have ignored the changes in smoking prevalence over time in the United States. Our primary rationale was to perform, to our knowledge, the first simulation study that estimates the health outcomes of lung cancer screening with explicit modeling of smoking trends for the whole US population. Methods/Findings Utilizing a well-validated microsimulation model, we estimated the benefits and harms of an annual low-dose computed tomography screening scenario with a realistic screening adherence rate versus a no-screening scenario for the US population from 2016–2030. The Centers for Medicare and Medicaid Services (CMS) eligibility criteria were applied: age 55–77 years at time of screening, history of at least 30 pack-years of smoking, and current smoker or former smoker with fewer than 15 years since quitting. In the screened population, cumulative mortality reduction was projected to reach 16.98% (95% CI 16.90%–17.07%). Cumulative mortality reduction was estimated to be 3.52% (95% CI 3.50%–3.53%) for the overall study population, with annual mortality reduction peaking at 4.38% (95% CI 4.36%–4.41%) in 2021 and falling to 3.53% (95% CI 3.50%–3.56%) by 2030. Lung cancer screening would save a projected 148,484 life-years (95% CI 147,429–149,540) across the total population through 2030. There were estimated to be 9,054 (95% CI 9,011–9,098) overdiagnosed cases among the 252,429 (95% CI 251,208–253,649) screen-detected lung cancer diagnoses, yielding an overdiagnosis rate of 3.59%. The limitations of our study are that we do not explicitly model race or socioeconomic status and our model was calibrated to data from studies performed in academic centers, both of which may impact the generalizability of our results. We also exclusively model the effects of the CMS guidelines for lung cancer screening and not any other screening strategies. Conclusions The mortality reduction and life-years gained estimated by this study are lower than those of single birth cohort studies. Single cohort studies neglect the changing dynamics of smoking behavior across generations, whereas this study reflects the trend of decreasing smoking prevalence since the 1960s. Maximum benefit could be derived from lung cancer screening through 2021; in later years, mortality reduction due to screening will decline. If a comprehensive screening program is not implemented in the near future, the opportunity to achieve these benefits will have passed.
Abstract 10756: Chronic Kidney Disease in Long-term Survivors After Fontan Palliation
Authors: Sheena Sharma, Rebecca L Ruebner, Susan L Furth, Kathryn M Dodds, Jack Rychik, David J Goldberg
Journal: Circulation (2015)

Background: The Fontan operation is a palliative procedure for children with congenital single ventricle heart disease. With advances in prenatal diagnosis and surgical techniques, more children are surviving into adulthood with unique cardiovascular physiology. Little is currently known about long-term kidney function in these patients. Hypothesis: We hypothesize that long-term survivors after Fontan palliation will have a higher prevalence of chronic kidney disease (CKD) compared to healthy controls. Methods: We performed a retrospective cohort study of subjects evaluated through the Single Ventricle Survivorship Program (SVSP) at the Children’s Hospital of Philadelphia between July 1, 2010 and December 5, 2014 and healthy children similar in sex and age. The primary outcome was CKD, defined as eGFR &lt;90 ml/min/1.73m2 calculated with age-appropriate estimating equations using creatinine and cystatin C. Secondary outcomes included proteinuria and hyperparathyroidism. Results: The Fontan cohort included 68 subjects with mean age of 13.9 years (SD 5.8) at SVSP visit who were 11.2 years (SD 5.7) from Fontan operation. The healthy cohort included 70 patients with mean age of 15.9 years (SD 3.9). Mean eGFR was 102.6 versus 101.9ml/min/1.73m2 (p=0.89) in pediatric Fontan versus healthy subjects using the complete CKiD equation, and 128.5 versus 129.7ml/min/1.73m2 (p=0.56) in adult Fontan versus healthy subjects using the CKD-EPI creatinine and cystatin formula. 10% of Fontan subjects had an eGFR&lt;90 ml/min/1.73m2. Mean intact parathyroid hormone level was higher at 68.0pg/mL (SD 35.4) in the Fontan group compared to 26.0pg/mL (SD 13.6) in the healthy group. Proteinuria was found within 34% of the Fontan group compared to 4.6% within the control group. Conclusion: We found that 10% of subjects have eGFR &lt;90ml/min/1.73m2 after Fontan palliation which would indicate CKD if this remained persistent over time. Although the majority of the cohort had normal kidney function by eGFR, we found a higher proportion with proteinuria and increased parathyroid hormone levels which may indicate early kidney disease. Future studies will focus on evaluating changes in kidney function over time in long-term survivors after Fontan palliation.
Abstract 222: North American Kawasaki Disease Registry - Advancing Clinical Research Through Collaboration
Authors: Brian W McCrindle
Journal: Circulation (2015)

Background: Clinical research in children with Kawasaki disease (KD), particularly those with coronary artery aneurysms (CAA), is challenging due to the limited number of patients available at any single institution. This has resulted in imperfect evidence for optimal management and considerable practice variation. Methods: The North American Kawasaki Disease Registry (NAKDR) was started in July 2013 to determine the prevalence, patient-level and pharmacological risk factors for outcomes of CAA after KD. The NAKDR enrolls KD patients diagnosed from 1999-2013 with CAA (defined as any segment with a z-score &gt;2.5). The NAKDR and its internet-based data entry portal are maintained at The Hospital for Sick Children in Toronto. Local ethics approvals and bilateral data sharing agreements are necessary for participation. Participation in the NAKDR is currently unfunded and voluntary. In September 2014, a survey on the future of the NAKDR was sent to all participating centers (response rate: 54%). Results: 45 sites have been invited, of which 37 (82%) agreed to participate. As of September 2014, 20 sites are actively submitting data; 17 are still being initiated; 706 cases have been submitted. The majority (90%) of members indicated that they wished to continue enrolling newly diagnosed patients and continue follow-up on patients already enrolled. Members were split (45% for, 55% against) as to whether the NAKDR should be expanded to include all KD patients, regardless of CAA status. Finally, while most NAKDR members (60%) indicated that site reimbursement was not an absolute condition for future participation, most members suggested that potential funding sources should be sought to expand/facilitate activities. At term, the NAKDR is expected to comprise ~1,400 patients and, if moving forward, add ~120 new KD patients with CAA per year. Conclusions: The NAKDR is an important tool for clinical research in children with CAAs after KD, and its success represents broad support from clinicians. The next step will be to formalize the NAKDR leadership structure, create standard operating procedures, and pursue prospective studies and funding.
Preliminary results from TOPAZ-III, a phase 3b study evaluating the efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin in naive or experienced adults in Brazil with HCV genotype 1 infection and advanced fibrosis/cirrhosis
Authors: Mario G. Pessoa, José Valdez Madruga Ramalho, Katia Alves, Daniel E. Cohen, Estevao Portela Nunes, Hugo Cheinquer, Carlos E. Brandão-Mello, Maria Cássia Jacintho Mendes-Côrrea, Maria Lucia G. Ferraz, Sara Lari, Li Lui, Rakesh Tripathi, Tami Pilot-Matias, Nancy Schulman, Ana de Lourdes Candolo Martinelli
Journal: Hepatology (2016)
Targeting HER2 by Combination Therapies
Authors: Ana Ruiz-Saenz, Mark M. Moasser
Journal: Journal of Clinical Oncology (2018)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor–Positive Metastatic Breast Cancer: ALTERNATIVE. December 15, 2017 ARTICLE CITATION DOI: 10.1200/JCO.2017.77.1899 Journal of Clinical Oncology - published online before print January 30, 2018 PMID: 29381433 Targeting HER2 by Combination Therapies Ana Ruiz-SaenzxAna Ruiz-SaenzSearch for articles by this author and Mark M. MoasserxMark M. MoasserSearch for articles by this author Show More Ana Ruiz-Saenz, University of California at San Francisco, San Francisco, CA; and Mark M. Moasser, University of California at San Francisco, San Francisco, CA https://doi.org/10.1200/JCO.2017.77.1899 First Page Full Text PDF Figures and Tables © 2018 by American Society of Clinical Oncology Companion Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor–Positive Metastatic Breast Cancer: ALTERNATIVE
Acute pancreatitis: ascaris in the pancreatic duct
Authors: Naveed Khan, Chuncheng Wu, Bing Hu
Journal: Endoscopy (2018)

A 36-year-old woman was admitted to our department with epigastric radiating pain, nausea, vomiting, fever, tachycardia, and sweating. The pain radiated to the back and had worsened. The sclera showed mild icterus. Laboratory test results showed elevated levels of total bilirubin (38 mmol/L), serum amylase, lipase, and white blood cells. Computed tomography scan showed an enlarged pancreatic head and a dilated pancreatic duct. A diagnosis of acute biliary pancreatitis was considered, although the cause of the dilated pancreatic duct was not clear. The Ranson’s prognosis scale was 4, and therefore we performed endoscopic retrograde cholangiopancreatography (ERCP).