tbuckley/cabot-search huggingface dataset:
Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study
Authors: Leigh F. Johnson, Margaret T. May, Rob E. Dorrington, Morna Cornell, Andrew Boulle, Matthias Egger, Mary-Ann Davies
Journal: PLoS Medicine (2017)

Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART.Model estimates of mortality rates in ART patients were obtained from the International Epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration. The model was calibrated to HIV prevalence data (1997-2013) and mortality data from the South African vital registration system (1997-2014), using a Bayesian approach. In the 1985-2014 period, 2.70 million adult HIV-related deaths occurred in South Africa. Adult HIV deaths peaked at 231,000 per annum in 2006 and declined to 95,000 in 2014, a reduction of 74.7% (95% CI: 73.3%-76.1%) compared to the scenario without ART. However, HIV mortality in 2014 was estimated to be 69% (95% CI: 46%-97%) higher in 2014 (161,000) if the model was calibrated only to HIV prevalence data. In the 2000-2014 period, the South African ART programme is estimated to have reduced the cumulative number of HIV deaths in adults by 1.72 million (95% CI: 1.58 million-1.84 million) and to have saved 6.15 million life years in adults (95% CI: 5.52 million-6.69 million). This compares with a potential saving of 8.80 million (95% CI: 7.90 million-9.59 million) life years that might have been achieved if South Africa had moved swiftly to implement WHO guidelines (2004-2013) and had achieved high levels of ART uptake in HIV-diagnosed individuals from 2004 onwards. The model is limited by its reliance on all-cause mortality data, given the lack of reliable cause-of-death reporting, and also does not allow for changes over time in tuberculosis control programmes and ART effectiveness.ART has had a dramatic impact on adult mortality in South Africa, but delays in the rollout of ART, especially in the early stages of the ART programme, have contributed to substantial loss of life. This is the first study to our knowledge to calibrate a model of ART impact to population-level recorded death data in Africa; models that are not calibrated to population-level death data may overestimate HIV-related mortality.
Ecological validity, embodiment, and killjoy explanations in developmental psychology
Authors: Shane Zappettini
Journal: Behavioral and Brain Sciences (2017)

Abstract Keven &amp; Akins (K&amp;A) present a compelling alternative to the case for neonatal orofacial imitation, offered by Meltzoff and Moore. However, they provide little concerning what lessons their proposal has to offer developmental psychology more generally. I suggest three candidates and elaborate on how they raise outstanding methodological and philosophical questions for the approach taken in the target article.
Firefighter Skin Cancer and Sun Protection Practices
Authors: Kevin J. Moore, Alberto J. Caban-Martinez, Robert S. Kirsner, Natasha Schaefer-Solle, David J. Lee, Tulay Koru-Sengul, Erin N. Kobetz
Journal: JAMA Dermatology (2017)

psoriasis. 3-5Crude point estimates did not suggest an increased HZ risk in systemically treated patients with psoriasis, and we found no significant differences in HZ risk among those exposed to biologic vs nonbiologic therapy after adjusting for age and sex.Limitations.limitations of the study include lack of data on disease severity and potentially limited generalizability to other healthcare settings.Conclusions | Among a cohort of patients with moderate-tosevere psoriasis who were treated with a systemic agent on cohort entry, we found no significant differences in HZ risk at time of HZ diagnosis among those treated with systemic therapy vs no systemic therapy, and among systemically treated patients, among those treated with biologics versus no biologic agents.Our results are similar to those of a recently published retrospective cohort study 4 that found no significant association between biologics as single agents and adjusted HZ risk in patients with psoriasis.We previously reported an increased risk of bacterial skin and soft tissue infections among those treated with biologics compared with those treated with nonbiologics in this cohort. 6Biologics block the activity of cytokines such as TNF-α, which plays a role in protecting against bacterial infections and inhibiting reactivation of latent viruses.Incident rates of HZ were increased in systemically treated patients with psoriasis as compared with the general population.However, we found no significant differences in HZ risk among those exposed to biologic vs nonbiologic therapy after adjusting for age and sex.Our results suggest that among systemically treated psoriasis patients, biologics may preferentially inhibit immune mechanisms specific for bacterial defense while sparing cell-mediated immune responses specific for maintaining VZV latency.
44 Conscious sedation in ERCP : the uncomfortable truth
Authors: S Palaniappan, P Maheswari, A Monged, C Moran, V Parihar, B Hall, S Patchett, F Murray, D Cheriyan
Journal: Gut (2017)

Background  Compared with standard endoscopy, Endoscopic Retrograde Cholangio-Pancreatography(ERCP) is an uncomfortable, complex procedure that typically requires higher doses of sedative and analgesic medication. Our unit, like many throughout Ireland and the UK, performs the vast majority of ERCPs under conscious sedation. Challenges with appropriate sedation levels and patient compliance during ERCP are common.  Aim  To evaluate patient comfort (1-4) and sedation score (1–5) with conscious sedation using a scoring system based on the modified Gloucester score.  Method  We prospectively evaluated consecutive ERCPs performed under conscious sedation over a three-month period in a single, tertiary referral centre.  Results  121 patients were evaluated. The median age was 73, and 60/121 (49.6%) were female. 46 patients (38%) were ≥75 years. 62 patients (51%) had a comfort score of ≤2, and 59 (49%) had a comfort score of ≥3. One patient required reversal of sedation due to respiratory compromise. Median doses of medication were: midazolam (4.27 mg), diazepam (7.5 mg), fentanyl (84 mcg), and pethidine (35.7 mg). 7 patients received more than one benzodiazepines, 7 with more than one opiates and 6 with all four medications.  Conclusions  There are limited data to define what is acceptable sedation practice for ERCP. The RCPI have recently recommended that>80% of colonoscopies should have a comfort score of 1 or 2. Though there are no validated comfort scores for ERCP, our data demonstrate that many patients undergoing ERCP with conscious sedation are subjected to an experience that would be considered unacceptable in general endoscopy.
FDG-PET/CT Guided Biopsy in Angiosarcoma of Bone
Authors: Antonella Matti, Andrea Farolfi, Tommaso Frisoni, Stefano Fanti, Cristina Nanni
Journal: Clinical Nuclear Medicine (2017)

Abstract Primary angiosarcoma of the bone (PAB) is a particularly rare and aggressive form of malignancy in the spectrum of vascular tumours, and it accounts for less than 1% of sarcomas. This case of PAB, diagnosed thanks to FDG-PET/CT guided biopsy, is a paradigm of how powerful are clinical informations that can be derived by a 18 F-FDG PET/CT, in view of negative or inconclusive imaging of conventional radiology, starting from the metabolic characterization of an equivocal finding, the possibility to drive the biopsy towards the most active site, the accurate total body staging, the stratification of prognosis and early therapy assessment.
Accelerating Discovery of Functional Mutant Alleles in Cancer
Authors: Matthew T. Chang, Tripti Shrestha Bhattarai, Alison M. Schram, Craig M. Bielski, Mark T.A. Donoghue, Philip Jonsson, Debyani Chakravarty, Sarah Phillips, Cyriac Kandoth, Alexander Penson, Alexander Gorelick, Tambudzai Shamu, Swati Patel, Christopher Harris, JianJiong Gao, Selcuk Onur Sumer, Ritika Kundra, Pedram Razavi, Bob T. Li, Dalicia N. Reales, Nicholas D. Socci, Gowtham Jayakumaran, Ahmet Zehir, Ryma Benayed, Maria E. Arcila, Sarat Chandarlapaty, Marc Ladanyi, Nikolaus Schultz, José Baselga, Michael F. Berger, Neal Rosen, David B. Solit, David M. Hyman, Barry S. Taylor
Journal: Cancer Discovery (2017)

Abstract Most mutations in cancer are rare, which complicates the identification of therapeutically significant mutations and thus limits the clinical impact of genomic profiling in patients with cancer. Here, we analyzed 24,592 cancers including 10,336 prospectively sequenced patients with advanced disease to identify mutant residues arising more frequently than expected in the absence of selection. We identified 1,165 statistically significant hotspot mutations of which 80% arose in 1 in 1,000 or fewer patients. Of 55 recurrent in-frame indels, we validated that novel AKT1 duplications induced pathway hyperactivation and conferred AKT inhibitor sensitivity. Cancer genes exhibit different rates of hotspot discovery with increasing sample size, with few approaching saturation. Consequently, 26% of all hotspots in therapeutically actionable oncogenes were novel. Upon matching a subset of affected patients directly to molecularly targeted therapy, we observed radiographic and clinical responses. Population-scale mutant allele discovery illustrates how the identification of driver mutations in cancer is far from complete. Significance: Our systematic computational, experimental, and clinical analysis of hotspot mutations in approximately 25,000 human cancers demonstrates that the long right tail of biologically and therapeutically significant mutant alleles is still incompletely characterized. Sharing prospective genomic data will accelerate hotspot identification, thereby expanding the reach of precision oncology in patients with cancer. Cancer Discov; 8(2); 174–83. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 127
A Cure for Hemophilia within Reach
Authors: H Marijke van den Berg
Journal: New England Journal of Medicine (2017)

Severe hemophilia has changed from a debilitating disease to a condition that is compatible with normal life, provided that patients receive a diagnosis early and also receive prophylactic therapy.1 The disease burden is now related largely to the demanding infusions and the development of alloantibodies that can neutralize the effect of exogenously administered clotting factors (so-called inhibitors). Products with an extended half-life have reduced the burden of treatment. In patients with hemophilia B, therapeutic levels can be obtained with infusions every 2 weeks.2 Yet, the high costs of lifelong prophylactic therapy and the continuous bleeding risk that is due to . . .
Government must create foundation training places for 1500 new medical students, says BMA
Authors: Abi Rimmer
Journal: BMJ (2017)

The government must ensure that there are enough foundation training places to accommodate 1500 new medical students, the BMA has said.

In 2016 the health secretary Jeremy Hunt announced that an extra 1500 doctors would be trained in England from September 2018.1

So far, 500 new medical school places have been allocated to existing medical schools. Universities were able to bid for the remaining 1000 places in a process which closed on 23 November. However, the government has not made any …
Meditation effects on physical, psychological, and symptom distress in an outpatient integrative medicine clinic.
Authors: Alejandro Chaoul, Gabriel Lopez, Richard T. Lee, Jane Williams, Qi Wei, Amica D Onyemeh Sea, Amy Spelman, Kathrin Milbury, M. Kay Garcia, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2014)

e20675 Background: Mind-body practices help cancer patients manage psychological distress and control symptoms such as pain, nausea, and sleep disturbances. However, the effects of a single meditation session on self-reported symptoms, including physical, psychological and symptom distress in an outpatient setting, are largely unknown. Methods: All patients receiving an individual meditation consultation (60 minute initial visits, and 30 minutes follow-up visits) at our Integrative Medicine Center outpatient clinic from May 2011 through December 2013, were asked to complete a modified Edmonton Symptom Assessment Scale (ESAS; scale from 0-10, where 10 is most severe). Data were analyzed examining the pre- and post-meditation scores using paired t-tests. Results: Our analysis included 81 meditation visits for 121 participants (mean 1.2 visits/person) over 32 months. The ESAS revealed a significant reduction from pre- to post-meditation session in physical, psychological, and symptom distress component scores (-7.85; -4.6; and -12.4, respectively; all p’s <0.0001). The greatest mean reductions for individual symptoms were for: Anxiety [-1.9], Fatigue [-1.9], Distress [-1.8], Well Being [-1.6]; Sleep [-1.5]; and Pain [-1.0]; all changes reaching statistically (all p’s <0.0001) and clinically significant thresholds (decrease in symptom score ≥1). Conclusions: A single meditation session resulted in acute relief of self-reported symptoms, as well as physical, psychological and symptom distress subscores in patients. Further research with a larger sample size and appropriate control groups is needed to better understand the symptoms that meditation can help control and the frequency of self-practice outside of the clinic to help maintain the long-term benefits.
Abstract #1456: A genomic and transcriptional analysis of HPV-infected oropharyngeal head and neck squamous cell carcinoma.
Authors: Alain Jung, Régine Millon, Joseph Abecassis, Jenny Briolat, Christine Clavel, David Rickman, Aurélien De Reynies, Emilie Thomas, Bohdan Wasylyk
Journal: Cancer Research (2009)

The infection by High Risk Human Papillomavirus (HR-HPV) is linked to the onset and development of about 25% of head and neck squamous cell carcinoma (HNSCC) and defines a distinct clinical subpopulation, whose molecular features are loosely defined. In order to get more insights in the molecular bases of HPV-driven head and neck carcinogenesis, we have performed a statistical as well as a transcriptomic and genomic analysis of infected and non-infected HNSCC by using an Affymetrix GeneChip® and Comparative Genomic Hybridation (CGH) approach. A supervised differential gene expression analysis using SAM approach resulted in a total of 645 up- and down-regulated genes in HPV-positive samples. Results from the microarray experiments were validated in vivo by quantitative real-time RT-PCR. We performed an unsupervised Statistical Analysis of Microarray (SAM) comparing 30 HPV-negative to 8 HPV-positive lesions from the oropharynx, 5/8 infected HNSCC were recovered in the same tumor cluster, suggesting that HPV-driven carcinogenesis correlates with a specific deregulated gene expression pattern. The analysis of the CGH data showed that HPV-positive oropharyngeal lesions did not display the genomic aberrations that are classically found in oral lesions (loss of the 3p and 9p regions, amplification of the 11q13 locus). However, the loss of the 16q chromosomic regions was found to be a HPV-specific genetic event. Strikingly, genes clustered in the 16q22-24 locus displayed a decreased expression in HPV-infected HNSCC. Among them, the locus encoding the Amyloid \#946; Precursor Protein Binding Protein 1 (APPBP1) showed a low mRNA expression specifically in HPV RNA+ HNSCC. APPBP1 is the regulatory subunit of the Uba3-APPBP1 complex, which is an E1 Ubiquitine-like conjugating enzyme involved in p53 transcriptional activity inhibition via p53 NEDDylation. The loss of the APPBP1 function would result in a higher p53 activity and participate to the increased radiosensitivity of HPV-infected HNSCC. APPBP1 is therefore an interesting candidate to predict the tumor response to radiation therapy.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1456.
GPR55 regulates intraepithelial lymphocyte migration dynamics and susceptibility to intestinal damage
Authors: Hayakazu Sumida, Erick Lu, Hsin Chen, Qiyun Yang, Ken Mackie, Jason G. Cyster
Journal: Science Immunology (2017)

Intraepithelial lymphocytes (IELs) of the small intestine are intimately associated with the epithelial cells. Yet, the factors controlling their migration and interaction dynamics are poorly understood. We demonstrate that GPR55, a receptor that mediates migration inhibition in response to lysophosphatidylinositol (LPI), negatively regulates T cell receptor γδ (TCRγδ) IEL accumulation in the small intestine. Intravital imaging studies show that GPR55-deficient IELs migrate faster and interact more extensively with epithelial cells. GPR55 also negatively regulates T cell homing to the small intestine and γδT cell egress from Peyer's patches. GPR55 deficiency or short-term antagonist treatment protects from nonsteroidal anti-inflammatory drug-induced increases in intestinal permeability. These findings identify a migration-inhibitory receptor that restrains IEL-epithelial cell cross-talk and show that antagonism of this receptor can protect from intestinal barrier dysfunction.
Abstract IA1: Progress in scaling up cervical cancer prevention in health services of developing countries
Authors: Rengaswamy Sankaranarayanan
Journal: Cancer Research (2017)

Abstract Cervical cancer is a major threat to women's health accounting for 528,000 new cases and 266,000 deaths annually around 2012, of which 85% occurred in low- and middle-income (LMICs). Substantial declines in cervical cancer incidence and mortality rates can be achieved by integrating HPV vaccination and cervical screening in public health services in LMICs. Since 2007, HPV vaccination has been introduced in national immunization programs in 73 countries, of which 33 are LMICs; in addition it has been introduced in pilot programs in another 17 countries, mostly in sub-Saharan Africa. It is particularly impressive that 7 out of 8 girls have access to HPV vaccination in Latin Region. So far, more than 270 million doses have been administered globally with excellent safety profile and high acceptance, despite the negative publicity surrounding HPV vaccination. The falling vaccine prices, possibility of new vaccines from China and India and the currently recommended two-dose schedule will make HPV vaccination more feasible. Screening is yet to be widely implemented in many LMICs and many of these countries lack the health care infrastructure and resources to introduce efficient screening programs. Screening has been sub-optimally performing in some LMICs for lack of adequate coverage, follow-up and quality assurance. A number of countries have introduced visual inspection (VIA) screening in their health services as opportunistic or pilot programs. HPV testing is the most effective cervical screening tool and HPV negative women are at very low risk for cervical cancer. Currently Mexico and Argentina have introduced HPV screening. The eventual availability of a simple, affordable, faster and accurate HPV tests will facilitate wider HPV screening in LMICs. Planned investments to implement HPV vaccination of single year cohorts of 9-13 year old girls and at least a single HPV screening of women between 30-59 will save many precious lives in developing countries. Citation Format: Rengaswamy Sankaranarayanan. Progress in scaling up cervical cancer prevention in health services of developing countries [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA1.
Association Between Physicians’ Experiences With Members of Their Social Network and Efforts to Reduce Breast Cancer Screening
Authors: Craig Evan Pollack, Archana Radhakrishnan, Andrew M. Parker, Xinwei Chen, Kala Visvanathan, Sarah A. Nowak
Journal: JAMA Internal Medicine (2017)

Table 2 examines the relationship between the level of evidence and class of the recommendations.A median of 10% specified both level of evidence A and class I; 6%, level B and class I, and 8% level C and class I.The RA guideline had the highest percentage (16%) of such strong class I recommendations based on weak C evidence.The combination class II and level C evidence was the most common at a median of 30% across guidelines and comprised 50% of the RA recommendations.Discussion | Our findings suggest the evidence supporting ACR recommendations is limited, with more than 50% and occasionally 2 of every 3 recommendations classified as level C, that is, based on experts, standards of care, case reports or series.Of the 35 class I recommendations, only 17 were supported by level A evidence.Our analysis reflects the different methodologies used in the ACR guidelines at 1 time point.Most recently, the ACR applies GRADE to evaluate the study design and the quality of the evidence. 2 The ACR recommendations overall remain mostly expert-based but are comparable with guidelines in other subspecialties. [3]4][5] The findings underline the need to enhance the evidence level.Although RCT evidence level A for all clinical questions is infeasible, in this era of "big data," the creation of registries, (eg, ACR's RISE 6 and federal real-world data initiatives) should increase opportunities to build a learning health care system.Such a system would identify heterogeneity and gaps in care practices and outcomes, which would help set research priorities that would enhance the quality of rheumatology care and increase appropriate use and patient-centered clinical outcomes while minimizing unwarranted practice variation.
A non-cardiac cause of bilateral leg swelling
Authors: Daniel R Stevenson, Hasnain Hashim, Mohammed Salman, Maria Mouyis
Journal: BMJ (2017)

A 65 year old man described swelling in both legs, which had worsened over six weeks. He also reported vague abdominal discomfort and tiredness. Examination of the lower limbs revealed pitting oedema bilaterally up to the groin, but no erythema, tenderness, or warmth. The patient was otherwise systemically well with normal heart sounds and a clear chest examination. There were no palpable masses in the abdomen or lymphadenopathy. Blood tests were unremarkable other than a normocytic anaemia (haemoglobin 95 g/L; normal range 130-180), C reactive protein of 33.0 mg/L (normal range 0-5.0) and a raised IgG4 level (3.55 g/L; normal range 0.08-1.4). No deep vein thrombosis was found on Doppler ultrasound. The patient had computed tomography of his abdomen and pelvis, which showed retroperitoneal fibrosis (fig 1). A unifying diagnosis was made of retroperitoneal fibrosis secondary to IgG4 related disease.



Fig 1 
Cross sectional and coronal views of computed tomography of the abdomen and pelvis. The arrowhead shows a mass encasing the aorta, suggesting a diagnosis of retroperitoneal fibrosis





### 1. What typical features should lead to consideration of retroperitoneal fibrosis as a diagnosis?

#### Short answer

The onset of retroperitoneal fibrosis is insidious and most commonly presents with poorly localised abdominal and lumbar pain, fatigue, and weight loss. Routine investigations find increased acute phase reactants, and acute kidney injury if ureteral obstruction is present.

#### Discussion

Retroperitoneal fibrosis is a rare condition of inflammation and fibrosis in the infrarenal periaortic and iliac vessel.1 It is difficult to diagnose because it is rare …
Isolated myelosarcoma is characterized by recurrent NFE2 mutations and concurrent preleukemic clones in the bone marrow
Authors: Vladimir Lazarevic, Christina Orsmark-Pietras, Henrik Lilljebjörn, Louise Pettersson, Marianne Rissler, Anna Lübking, Mats Ehinger, Gunnar Juliusson, Thoas Fioretos
Journal: Blood (2017)