tbuckley/cabot-search huggingface dataset:
Abstract P116: Physical Fitness in Early Adulthood: A Modifiable Risk Factor for Neurological and Psychiatric Diseases
Authors: Jenny Nyberg, David Åberg, Waern Margda, Anders Wallin, Kjell Torén, Michael Nilsson, Maria A Åberg, Georg Kuhn
Journal: Circulation (2016)

Low cardiovascular fitness in mid- and late life represents a risk factor for several neurological diseases. However, the respective effect of aerobic cardiovascular and muscle fitness in early adulthood is largely unknown. Therefore, we analyzed these in young men with regard to long-term risk serious depression, bipolar disorders, stroke and dementia. We performed population-based longitudinal cohort studies of Swedish male conscripts registered in 1968-2005 for mandatory military service (approx. 1,800,000 subjects), representing about 95 % of all Swedish males at age 18 during this time period. Data on cardiovascular fitness (determined by the cycle ergometric test), muscle strength (isometric contraction) and cognitive performance (IQ tests) were subdivided into low, medium, high fitness groups. Over a 40-year follow-up, risk of serious depression, bipolar disorder, stroke and dementia were calculated with Cox proportional hazards models controlling for potential confounders. To identify cases, we used the International Classification of Diseases (ICD) 8-10 in the Hospital Discharge Register and the Cause of Death Register. Depression. Adjusted hazard ratios (HRs) with confidence interval (CI) show significant relationships between fitness and severe depression for low compared to high fitness: HR (CI) 1.80 (1.64-1.99) for cardiovascular fitness and 1.43 (1.32-1.55) for muscle strength. Bipolar disorders exhibited a lower, yet significant association with cardiovascular fitness and muscle strength (adjusted hazard ratios (HRs) with confidence interval (CI): 1.35 (1.12-1.63) and 1.22 (1.05-1.42), respectively. Stroke. Adjusted HRs show inverse relationships between fitness and stroke for low compared to high fitness HR (CI) 1.70 (1.50-1.93) for cardiovascular fitness and 1.39 (1.27-1.53) for muscle strength. All three stroke types (subarachnoidal hemorrhage, intracerebral hemorrhage and ischemic stroke displayed similar associations. There were stronger associations for fatal stroke. Dementia. Low compared to high cardiovascular fitness was significantly associated with an increased risk for diagnosis of dementia before age 60: HR (CI) 2.49 (1.87-3.32). Mild cognitive impairment (MCI) showed an even greater association: HR (CI) 3.57 (2.23-5.74). The combination of low cardiovascular fitness and poor cognitive performance in early adulthood was associated with a &gt;8-fold increase in the risk of early-onset MCI and a &gt;7-fold increased risk of early-onset dementia. In summary, this study sheds light on physical fitness as an early-life risk factor for psychiatric and neurological conditions, and underlines the potential for lifestyle modification to reduce the risk of late-life CNS impairments.
Association Between Trauma Center Type and Mortality Among Injured Adolescent Patients
Authors: Rachel B. Webman, Elizabeth A. Carter, Sushil Mittal, Jichaun Wang, Chethan Sathya, Avery B. Nathens, Michael L. Nance, David Madigan, Randall S. Burd
Journal: JAMA Pediatrics (2016)

<h3>Importance</h3> Although data obtained from regional trauma systems demonstrate improved outcomes for children treated at pediatric trauma centers (PTCs) compared with those treated at adult trauma centers (ATCs), differences in mortality have not been consistently observed for adolescents. Because trauma is the leading cause of death and acquired disability among adolescents, it is important to better define differences in outcomes among injured adolescents by using national data. <h3>Objectives</h3> To use a national data set to compare mortality of injured adolescents treated at ATCs, PTCs, or mixed trauma centers (MTCs) that treat both pediatric and adult trauma patients and to determine the final discharge disposition of survivors at different center types. <h3>Design, Setting, and Participants</h3> Data from level I and II trauma centers participating in the 2010 National Trauma Data Bank (January 1 to December 31, 2010) were used to create multilevel models accounting for center-specific effects to evaluate the association of center characteristics (PTC, ATC, or MTC) on mortality among patients aged 15 to 19 years who were treated for a blunt or penetrating injury. The models controlled for sex; mechanism of injury (blunt vs penetrating); injuries sustained, based on the Abbreviated Injury Scale scores (post-dot values &lt;3 or ≥3 by body region); initial systolic blood pressure; and Glasgow Coma Scale scores. Missing data were managed using multiple imputation, accounting for multilevel data structure. Data analysis was conducted from January 15, 2013, to March 15, 2016. <h3>Exposures</h3> Type of trauma center. <h3>Main Outcomes and Measures</h3> Mortality at each center type. <h3>Results</h3> Among 29 613 injured adolescents (mean [SD] age, 17.3 [1.4] years; 72.7% male), most were treated at ATCs (20 402 [68.9%]), with the remainder at MTCs (7572 [25.6%]) or PTCs (1639 [5.5%]). Adolescents treated at PTCs were more likely to be injured by a blunt than penetrating injury mechanism (91.4%) compared with those treated at ATCs (80.4%) or MTCs (84.6%). Mortality was higher among adolescents treated at ATCs and MTCs than those treated at PTCs (3.2% and 3.5% vs 0.4%;<i>P</i> &lt; .001). The adjusted odds of mortality were higher at ATCs (odds ratio, 4.19; 95% CI, 1.30-13.51) and MTCs (odds ratio, 6.68; 95% CI, 2.03-21.99) compared with PTCs but was not different between level I and II centers (odds ratio, 0.76; 95% CI, 0.59-0.99). <h3>Conclusion and Relevance</h3> Mortality among injured adolescents was lower among those treated at PTCs, compared with those treated at ATCs and MTCs. Defining resource and patient features that account for these observed differences is needed to optimize adolescent outcomes after injury.
Trends in Survival after In-Hospital Cardiac Arrest
Authors: Gagan Kumar, Rahul Nanchal
Journal: New England Journal of Medicine (2013)

BACKGROUND-Despite numerous advances in resuscitation care in recent years, it remains unknown whether survival and neurological function after in-hospital cardiac arrest has improved over time. METHODS-We identified all adults with an index in-hospital cardiac arrest at 374 hospitals in the Get With The Guidelines-Resuscitation registry between 2000 and 2009.Using multivariable regression, we examined temporal trends in risk-adjusted rates of survival to discharge.Additional analyses explored whether trends: (1) were due to improved survival during the acute resuscitation or post-resuscitation care and (2) occurred at the expense of greater neurological disability among survivors.RESULTS-Among 84,625 hospitalized patients with cardiac arrest, 67,135 (79.3%) had an initial rhythm of asystole or pulseless electrical activity while 17,490 (20.7%) had ventricular fibrillation or pulseless ventricular tachycardia.The proportion of cardiac arrests due to asystole or pulseless electrical activity increased over time (P for trend <0.001).Risk-adjusted rates of survival to discharge in the overall cohort increased from 13.7% in 2000 to 22.4% in 2009 (adjusted rate-ratio per 1-year: 1.04, 95% CI [1.02-1.05];P for trend <0.001).Survival improvement was similar in both rhythm groups and largely due to improved survival from the acute resuscitation (risk-adjusted rates: 42.7% in 2000, 54.1% in 2009; adjusted rate-ratio per 1-year: 1.03, 95% CI [1.02-1.04];P for trend <0.001).Importantly, rates of neurological disability among survivors decreased over time (risk-adjusted rates: 32.9% in 2000, 28.1% in 2009; P for trend=0.02).CONCLUSIONS-Both survival and neurological outcomes after in-hospital cardiac arrest have improved over the past decade.
Need-for-treatment criteria for involuntary civil commitment: impact in practice
Authors: R D Miller
Journal: American Journal of Psychiatry (1992)

There has been considerable discussion in the literature on the differences between criteria for involuntary commitment that are based on dangerousness and criteria based on need for treatment. A number of states have adopted clinical criteria, and other state legislatures are actively considering them. Some libertarians argue that dangerousness is constitutionally required if a person is to undergo the loss of liberty involved in commitment. Citing widely publicized data from the state of Washington, they predict that a return to clinical criteria would result in a deluge of inappropriate commitments. Some clinicians counter that use of clinical criteria would result in selection of a much more appropriate clinical population and point to research indicating that strict observation of the need-for-treatment provisions of the APA model commitment statute would actually decrease the number of commitments. The author examines state hospital admission and census data from eight states that added need-for-treatment criteria to their commitment codes between 1975 and 1990 and argues that the data indicate that there is little reason to believe that such changes would result in the deluge of admissions predicted by the critics.
Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma
Authors: Michael J. McGeachie, Katherine P. Yates, Xiaobo Zhou, Feng Guo, Alice L. Sternberg, Mark L. Van Natta, Robert A. Wise, Stanley J. Szefler, Sunita Sharma, Alvin T. Kho, Michael H. Cho, Damien C. Croteau-Chonka, Peter J. Castaldi, Gaurav Jain, Amartya Sanyal, Ye Zhan, Bryan R. Lajoie, Job Dekker, John Stamatoyannopoulos, Ronina A. Covar, Robert S. Zeiger, N. Franklin Adkinson, Paul V. Williams, H. William Kelly, Hartmut Grasemann, Judith M. Vonk, Gerard H. Koppelman, Dirkje S. Postma, Benjamin A. Raby, Isaac Houston, Quan Lu, Anne L. Fuhlbrigge, Kelan G. Tantisira, Edwin K. Silverman, James Tonascia, Robert C. Strunk, Scott T. Weiss
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease.Objectives: To determine the genetic underpinnings of lung function patterns in subjects with childhood asthma.Methods: We performed a genome-wide association study of 581 non-Hispanic white individuals with asthma that were previously classified by patterns of lung function growth and decline (normal growth, normal growth with early decline, reduced growth, and reduced growth with early decline). The strongest association was also measured in two additional cohorts: a small asthma cohort and a large chronic obstructive pulmonary disease metaanalysis cohort. Interaction between the genomic region encompassing the most strongly associated single-nucleotide polymorphism and nearby genes was assessed by two chromosome conformation capture assays.Measurements and Main Results: An intergenic single-nucleotide polymorphism (rs4445257) on chromosome 8 was strongly associated with the normal growth with early decline pattern compared with all other pattern groups (P = 6.7 × 10−9; odds ratio, 2.8; 95% confidence interval, 2.0–4.0); replication analysis suggested this variant had opposite effects in normal growth with early decline and reduced growth with early decline pattern groups. Chromosome conformation capture experiments indicated a chromatin interaction between rs4445257 and the promoter of the distal CSMD3 gene.Conclusions: Early decline in lung function after normal growth is associated with a genetic polymorphism that may also protect against early decline in reduced growth groups.Clinical trial registered with www.clinicaltrials.gov (NCT00000575).
Anaemia in rheumatoid arthritis.
Authors: K S Deep, H Singh
Journal: BMJ (1969)

Leading ArticlesBRITSHf 659both this and the virus discovered at Salisbury had identical appearances under the electron microscope.Moreover, many of their features had never been seen before in a virus recovered from man, but they were indistinguishable from the viruses causing mouse hepatitis6 and avian infectious bronchitis.7 -I A further stage in the story was provided by K. McIntosh and his co-workers, who used both organ culture and electron microscopy to study the properties of six more viruses and successfully adapted two of them to suckling mice.2 13 "They compared these and other viruses by comple-
Predictive value of the antiangiogenic VEGF splice variant expression for bevacizumab efficacy in the phase III trial of bevacizumab and FOLFOX4 versus FOLFOX4 in previously treated patients with advanced colorectal cancer (ECOG E3200T2).
Authors: David O. Bates, Paul J. Catalano, Kirsty E. Symonds, Alexander H. R. Varey, Pramila Ramani, Peter James O'Dwyer, Bruce J. Giantonio, Neal J. Meropol, Al Bowen Benson, Steven J. Harper
Journal: Journal of Clinical Oncology (2012)

545 Background: Treatment of metastatic colorectal cancer (CRC) with bevacizumab (anti-VEGF) in combination with chemotherapy increases survival in a proportion of patients, but it is not possible a priori to predict which patients will receive benefit. The VEGF-A gene is alternatively spliced into two families by alternative splice site usage in exon 8. The pro-angiogenic (e.g. VEGF 165 ) isoforms are generated by proximal splice site selection, and the anti-angiogenic (e.g. VEGF 165 b) by distal splice site selection. The relative levels of the isoforms vary in CRC. VEGF 165 b over-expression in mice inhibits bevacizumab treatment.We tested the hypothesis that survival would be better in patients with low VEGF 165 b levels on bevacizumab than placebo. Methods: To determine whether survival was better in patietns with low VEGF 165 b when treated with FOLFOX4+bevacizumab (Arm A) than FOLFOX4 + placebo (Arm B), 108 coded patient samples from the E3200 trial of FOLFOX4±bevacizumab (NCT NCT00897754 ) were successfully stained for VEGF-A 165 b and scored in well differentiated tissue relative to normal tissue blind to outcome. The VEGF 165 b expression relative to normal tissue was calculated. 108 cases were analysed for VEGF 165 b/Normal, 48 in arm A, 60 in Arm B. Results: Adjusted Cox Binary analysis of VEGF 165 b/Normal comparing staining ratio in bevacizumab versus placebo treated patients demonstrated significantly better survival for the less than median ratios (HR=0.28, p=0.0031, median progression free survival, 8.4 versus 5.1 months in placebo), whereas in the higher than median VEGF 165 b/Normal group there was no effect of bevacizumab (HR=0.96, median PFS, 11.9 compared with 11.0months). Results held after adjustment for other clinical and demographic features in proportional hazards regression modelling. Conclusions: In conclusion, these results indicate that low VEGF 165 b levels in well-differentiated tumours may predict response to bevacizumab.
Four-year minimum follow-up of ongoing patients (pts) with chronic-phase chronic myeloid leukemia (CP-CML) in a phase 1 trial of ponatinib (PON).
Authors: Moshe Talpaz, Jorge E. Cortes, Hagop M. Kantarjian, Neil P. Shah, Dale L. Bixby, Ian Flinn, Thomas J O'Hare, Simin Hu, Victor M. Rivera, Timothy Piers Clackson, Maureen G Conlan, Frank G. Haluska, Brian J. Druker, Michael W.N. Deininger, Michael J. Mauro
Journal: Journal of Clinical Oncology (2015)

7047 Background: PON, an approved oral tyrosine kinase inhibitor (TKI), has potent activity against native BCR-ABL and resistant mutants, including T315I. A phase 1 trial evaluated PON safety and antileukemic activity; this analysis includes 4-year minimum follow-up of ongoing pts, the longest follow-up of PON-treated pts to date. Methods: Pts (N = 81) with resistant/refractory hematologic malignancies received PON (2–60 mg qd) in this ongoing, open-label, dose-escalation trial (NCT00660920; enrollment 2008–2010; data cutoff, 26 Sept 2014). The median follow-up for 43 CP-CML pts was 49.9 (1.7–69.9) mo; minimum follow-up for 22 ongoing CP-CML pts was 50.2 mo. Results: Data are reported for CP-CML pts. Median age was 55 years; time since diagnosis 6.6 years. 60% of pts had received ≥ 3 TKIs; 63% had BCR-ABL mutations (28% T315I). At time of analysis, 51% remained on study. Most common reasons for discontinuation: adverse events (AEs) 26%; progression 9%. By intention-to-treat analysis: major cytogenetic response (MCyR) was 72%; complete cytogenetic response (CCyR), 65%; major molecular response (MMR), 56%; MR4, 42%; and MR4.5, 28%; responses are durable (Table). Median durations of MCyR, CCyR, and MMR were not reached. Of 22 ongoing pts at data cutoff, 18 (82%) were in CCyR; 17 (77%) had MMR or better (MMR n = 6; MR4 n = 1; MR4.5 n = 10). Most common treatment-emergent AEs were rash 65%, fatigue 60%, abdominal pain 58%, headache 58%, and arthralgia 53%. Arterial occlusive event (AE/serious AE) rates were 40%/30%, including cardiovascular (30%/21%), cerebrovascular (9%/7%), and peripheral vascular (14%/9%); venous thromboembolic event rates were 5%/0%. Conclusions: These data represent the longest follow-up with PON. With 4-year minimum follow-up for ongoing pts, PON continues to provide benefit to ongoing CP-CML pts with prior TKI failure. Risks and benefits should be evaluated when using PON. Clinical trial information: NCT00660920.Stability of Response in CP-CML Pts Treated With PON. Responders, n Lost Response, na Maintain Response at 4 Years, % (95% CI)b MCyR 31 8 68 (44–84) CCyR 28 8 70 (48–84) MMR 25 11 52 (30–70) aFailed to meet criteria for response at any single time point after initial response bKaplan-Meier estimate
Word Gap Redux
Authors: Meredith L. Rowe, Barry Zuckerman
Journal: JAMA Pediatrics (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Dental abscesses have increased most among poorer people
Authors: David R Moles
Journal: BMJ (2008)

Thomas et al analysed aggregate data on drainage of abscess of alveolus of tooth from the hospital episode statistics (HES) website.1 I analysed the individual episode records for the same procedure (OPCS4.2 code F16.1), using data obtained as an extract from HES from 1 April 1997 to 30 March 2006. Using individual episode data permits a greater degree of resolution, particularly when combined with other relevant …
NHS hits target on reducing carbon emissions
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

The NHS reduced its carbon emissions by 11% from 2007 to 2015, exceeding the 10% target set in 2009, although it is unlikely to meet long term goals on climate change if the pace of change does not improve.

In 2008 the Climate Change Act set a target for the United Kingdom to reduce its carbon emissions by 80% from 1990 levels by 2050.1

The latest report on progress from the NHS’s Sustainable Development Unit showed that …
Abstract 397: Generation of Raf1 Mutant and Crispr-cas9 Corrected Isogenic iPSC-derived Cardiomyocytes to Model Hypertrophic Cardiomyopathy in Noonan Syndrome
Authors: Fabrice Jaffré, Gang Wang, Amy Roberts, William Pu, Andreas Hahn, Maria Kontaridis
Journal: Circulation Research (2015)

Background: Hypertrophic cardiomyopathy (HCM) is a major cause of death in infants and children. Noonan Syndrome (NS), an autosomal dominant RASopathy disorder, is characterized by multiple defects, including short stature, facial dysmorphia, and congenital heart defects that include HCM. RASopathies are caused by germ-line mutations that affect the canonical RAS-MAPK pathway. Indeed, 95% of NS patients with a mutation in Raf1 , a gene that plays an integral role in this signaling cascade, exhibit HCM. However, the molecular mechanisms that elicit HCM in these patients remain poorly understood. Objective: To generate human NS Raf1 induced-pluripotent stem cells (iPSCs), correct the mutation by genome editing and subsequently differentiate isogenic iPSC lines into cardiomyocytes to characterize the molecular and genetic basis of HCM in NS patients. Results: We generated iPSCs from skin fibroblasts obtained from a NS pediatric patient with a single point mutation in the Raf1 gene. Using electroporation of four episomal vectors containing the Yamanaka factors, we obtained several iPSC clones with normal karyotypes and strong expression of pluripotent markers (Nanog, Oct4, Lin28, Sox2) as detected by RT-qPCR and immunofluorescence. We next corrected the mutation in the NS Raf1 iPSCs using genome editing CRISPR-Cas9 nickase technology. Correction of the Raf1 mutation was determined at the clonal level by PCR followed by Restriction Fragment Length Polymorphism and confirmed by Sanger sequencing. In addition, by inducing a Cas9 nickase-dependent frame shift mutation we also generated an isogenic iPSC line where Raf1 gene was knockout (KO), as demonstrated at the RNA level by RT-qPCR and at the protein level by Western Blot. We next differentiated these multiple iPSC lines (mutant, corrected and KO) into isogenic beating cardiomyocytes, with more &gt;98% of the cells positive for specific cardiomyocyte markers (α-actinin and cardiac TroponinT). Conclusion: We have successfully generated human NS Raf1 isogenic iPSC lines and corresponding cardiomyocytes. Currently, we are in progress of characterizing these cardiac cells to determine the molecular basis of NS-dependent HCM. Ultimately, our work should reveal new targets to treat HCM in NS patients.
A third of British describe NHS funding crisis as “severe”
Authors: Helen Mooney
Journal: BMJ (2016)

Over 90% of the UK public recognise that the NHS has a funding problem, but few agree on how to solve the crisis.

The latest British Social Attitudes survey of 3000 people, conducted by NatCen Social Research, also showed a marked increase in the number of people identifying the funding crisis as “severe”—32% described it as such, up from 19% in 2014.1

However, despite the public’s near unanimity in its view of the funding problem, there is less consensus on how to deal with …