bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Patients' Gender on Informed Decision Making Regarding Total Knee Arthroplasty
Authors: Borkhoff Cornelia M. , Hawker Gillian A. , Kreder Hans J. , Glazier Richard H. , Mahomed Nizar N. , Wright James G. 
Published: February 2013

ObjectiveTo investigate the effect of patient gender on patient–physician communication in the process of recommendation for total knee arthroplasty (TKA).MethodsSeventy‐one physicians (38 family physicians and 33 orthopedic surgeons) in Ontario performed blinded assessments of 2 standardized patients (1 man and 1 woman) with moderate knee osteoarthritis and otherwise identical scenarios. Four surgeons did not consent to including their data. Standardized patients and accompanying mock family members recorded elements of informed decision making (IDM) as present/absent in the patient–physician discussion and rated the physicians' interpersonal skills.ResultsOverall, the completeness of IDM was low, but was lower still for the woman. Only 57% (38 of 67) and 15% (10 of 67) of physicians discussed the nature of the decision and elicited the patient's preference while consulting with the man and woman, respectively. Even after adjusting for physicians' recommendations regarding TKA, when interacting with the woman, physicians included fewer IDM elements (adjusted mean difference in IDM score 1.2 [95% confidence interval (95% CI) 0.6, 1.8]; P < 0.001) and had poorer interpersonal skills (adjusted mean difference 14.1 [95% CI 9.0, 19.2]; P < 0.001) compared with their consultation with the man.ConclusionPhysicians provided less medical information and less encouragement to participate in the decision to undergo TKA to a woman compared with a man, irrespective of their recommendation regarding TKA. Our findings suggest that in addition to directly influencing physicians' clinical decision making, gender bias may also influence physicians' interpersonal behavior.
Ambient Air Pollution Exposures and Risk of Rheumatoid Arthritis
Authors: Hart Jaime E. , Källberg Henrik , Laden Francine , Costenbader Karen H. , Yanosky Jeff D. , Klareskog Lars , Alfredsson Lars , Karlson Elizabeth W. 
Published: February 2013

ObjectiveEnvironmental factors may play a role in the development of rheumatoid arthritis (RA). We previously observed increased RA risk among women living closer to major roads (a source of air pollution). Herein, we examined whether long‐term exposures to specific air pollutants were associated with RA risk among women in the Nurses' Health Study (NHS).MethodsThe NHS is a large US cohort of female nurses followed up prospectively every 2 years since 1976. We studied 111,425 NHS participants with information on air pollution exposures as well as data concerning other lifestyle and behavioral exposures and disease outcomes. Outdoor levels of different size fractions of particulate matter (PM10 and PM2.5) and gaseous pollutants (SO2 and NO2) were predicted for all available residential addresses using monitoring data from the US Environmental Protection Agency. We examined the association of time‐varying exposures 6 and 10 years before each questionnaire cycle and cumulative average exposure with the risk of RA, seronegative (rheumatoid factor and anti–citrullinated peptide antibody negative) RA, and seropositive RA.ResultsOver the 3,019,424 person‐years of followup, 858 incident RA cases were validated by medical record review by 2 board‐certified rheumatologists. Overall, we found no evidence of increased risk of RA, seronegative RA, or seropositive RA with exposure to the different pollutants and little evidence of effect modification by socioeconomic status or smoking status, geographic region, or calendar period.ConclusionIn this group of socioeconomically advantaged middle‐aged and elderly women, adult exposures to air pollution were not associated with an increased RA risk.
Modest Association of Joint Hypermobility With Disabling and Limiting Musculoskeletal Pain: Results From a Large‐Scale General Population–Based Survey
Authors: Mulvey Matthew R. , Macfarlane Gary J. , Beasley Marcus , Symmons Deborah P. M. , Lovell Karina , Keeley Philip , Woby Steve , McBeth John 
Published: February 2013

ObjectiveTo determine the population prevalence of joint hypermobility (JH) and to test the hypothesis that JH would be associated with reporting musculoskeletal pain.MethodsWe conducted a cross‐sectional population survey in Aberdeen and Cheshire. A total of 45,949 questionnaires were mailed that assessed JH and the presence, distribution, duration, and severity of musculoskeletal pain. Based on their pain reports, participants were classified as having chronic widespread pain (CWP), some pain, or no pain. Multinominal logistic regression tested the relationship between JH and pain status. Associations were adjusted for age, sex, and other putative confounders. Participants with no pain were the referent category.ResultsA total of 12,853 participants (28.0%) returned a questionnaire with complete data; 2,354 participants (18.3%) were classified as hypermobile. A total of 2,094 participants (16.3%) had CWP, 5,801 participants (45.1%) had some pain, and 4,958 participants (38.6%) reported no pain. JH participants were significantly more likely to report CWP than non‐JH participants (18.5% versus 15.8%; P < 0.001). After adjusting for age and sex, hypermobile participants were 40% more likely to report the most severe CWP (relative risk ratio [RRR] 1.4, 95% confidence interval [95% CI] 1.1–1.7; P < 0.00). After further adjustments for employment status, smoking, alcohol, and physical activity, JH remained significantly associated with the most severe CWP (RRR 1.6, 95% CI 1.3–2.1; P < 0.000) and some pain (RRR 1.3, 95% CI 1.02–1.6; P = 0.03).ConclusionJH was associated with severe pain; however, this relationship was not specific to CWP. The relationship was relatively modest and may be explained by unmeasured confounding factors such as psychological distress.
Effect of Moderate to Vigorous Physical Activity on Long‐Term Clinical Outcomes and Pain Severity in Fibromyalgia
Authors: Kaleth Anthony S. , Saha Chandan K. , Jensen Mark P. , Slaven James E. , Ang Dennis C. 
Published: February 2013

ObjectiveTo evaluate the relationship between long‐term maintenance of moderate to vigorous physical activity (MVPA) and clinical outcomes in fibromyalgia (FM).MethodsPatients with FM (n = 170) received individualized exercise prescriptions and completed baseline and followup physical activity assessments using the Community Health Activities Model Program for Seniors questionnaire at weeks 12, 24, and 36. The primary outcome was the change in the Fibromyalgia Impact Questionnaire‐Physical Impairment (FIQ‐PI) score. The secondary outcomes included improvements in overall well‐being (FIQ total score), pain severity ratings, and depression.ResultsUsing a threshold increase in MVPA of ≥10 metabolic equivalent hours/week above usual activities, 27 subjects (15.9%) increased and sustained (SUS‐PA), 68 (40%) increased but then declined (UNSUS‐PA), and 75 (44.1%) did not achieve (LO‐PA) this benchmark. Compared to LO‐PA subjects, both SUS‐PA and UNSUS‐PA subjects reported greater improvement in FIQ‐PI (P < 0.01) and FIQ total score (P < 0.05). Additionally, the SUS‐PA group reported greater improvement in pain severity compared to the LO‐PA group (P < 0.05). However, there were no significant group differences between SUS‐PA and UNSUS‐PA for any primary or secondary outcome measure.ConclusionIncreased participation in MVPA for at least 12 weeks improved physical function and overall well‐being in patients with FM. Although sustained physical activity was not associated with greater clinical benefit compared with unsustained physical activity, these findings also suggest that performing greater volumes of physical activity is not associated with worsening pain in FM. Future research is needed to determine the relationship between sustained MVPA participation and subsequent improvement in patient outcomes.
Pregnancy Outcomes Among Patients With Vasculitis
Authors: Clowse Megan E. B. , Richeson Rachel L. , Pieper Carl , Merkel Peter A. ,   For The Vasculitis Clinical Research Consortium
Published: February 2013

ObjectivePregnancy outcomes of patients with vasculitis are unknown, but are of great concern to patients and physicians. Through an online survey, this study assessed pregnancy outcomes among patients with vasculitis.MethodsParticipants in the Vasculitis Clinical Research Consortium Patient Contact Registry were invited to respond to an anonymous, internet‐based survey that included questions about pregnancy outcomes, the timing of pregnancy relative to a diagnosis of vasculitis, and medication use.ResultsA total of 350 women and 113 men completed the survey. After a diagnosis of vasculitis, 74 pregnancies were reported by women and 18 conceptions were reported by men. The rate of pregnancy loss was higher among women who conceived after a diagnosis of vasculitis compared to those who conceived prior to diagnosis (33.8% versus 22.4%; P = 0.04). Among women, the rate of preterm births increased significantly for pregnancies conceived after a diagnosis of vasculitis relative to those conceived before diagnosis (23.3% versus 11.4%; P = 0.03). Only 18% of women reported worsening of vasculitis during pregnancy, but those who experienced increased vasculitis activity were more likely to deliver preterm. Exposure to cyclophosphamide or prednisone did not appear to impact pregnancy outcomes; however, the number of pregnancies among women taking these medications was small. Among the pregnancies conceived by men with vasculitis, the timing of diagnosis had no significant effect on the rate of pregnancy loss.ConclusionWomen who conceived after a diagnosis of vasculitis had a higher rate of pregnancy loss than those who conceived prior to diagnosis. Vasculitis did not worsen during the majority of pregnancies conceived after diagnosis.
Convergence and stability analysis of a digital automatic gain control
Authors: Mingyang Zhang , Zhugang Wang , Weiming Xiong 
Published: February 2013

SUMMARYThis paper is dedicated to the theoretical analysis of a digital automatic gain control (AGC), which feedbacks according to the desired output direct current (DC). First, we mathematically model the AGC, with the input signal interfered by AWGN. As it turns out, the loop model is a first‐order varying‐coefficient stochastic difference equation, and its solution consists of two parts, that is, the transient state and the steady state, which respectively explain the convergence and stability of the AGC. As is shown in the paper, the properties of convergence and stability of AGC are mutually contradictory, and both are determined by a key parameter in the loop, and the parameter is defined as the feedback sensitivity of the loop. The results of the paper are validated by numerical simulation, and they are of theoretical guide for practical digital AGC implementation on Application Specific Integrated Chips (ASICs) or Field Programmable Gate Arrays (FPGAs). Copyright © 2013 John Wiley & Sons, Ltd.
Anti–amyloid β autoantibodies in cerebral amyloid angiopathy–related inflammation: Implications for amyloid‐modifying therapies
Authors: Piazza Fabrizio , Greenberg Steven M. , Savoiardo Mario , Gardinetti Margherita , Chiapparini Luisa , Raicher Irina , Nitrini Ricardo , Sakaguchi Hideya , Brioschi Monica , Billo Giuseppe , Colombo Antonio , Lanzani Francesca , Piscosquito Giuseppe , Carriero Maria Rita , Giaccone Giorgio , Tagliavini Fabrizio , Ferrarese Carlo , DiFrancesco Jacopo C. 
Published: February 2013

ObjectiveCerebral amyloid angiopathy–related inflammation (CAA‐ri) is characterized by vasogenic edema and multiple cortical/subcortical microbleeds, sharing several aspects with the recently defined amyloid‐related imaging abnormalities (ARIA) reported in Alzheimer's disease (AD) passive immunization therapies. Herein, we investigated the role of anti–amyloid β (Aβ) autoantibodies in the acute and remission phases of CAA‐ri.MethodsWe used a novel ultrasensitive technique on patients from a retrospective multicenter case–control study, and evaluated the anti‐Aβ autoantibody concentration in the cerebrospinal fluid (CSF) of 10 CAA‐ri, 8 CAA, 14 multiple sclerosis, and 25 control subjects. Levels of soluble Aβ40, Aβ42, tau, P‐181 tau, and APOE genotype were also investigated.ResultsDuring the acute phase of CAA‐ri, anti‐Aβ autoantibodies were specifically increased and directly correlated with Aβ mobilization, together with augmented tau and P‐181 tau. Following clinical and radiological remission, autoantibodies progressively returned to control levels, and both soluble Aβ and axonal degeneration markers decreased in parallel.InterpretationOur data support the hypothesis that the pathogenesis of CAA‐ri may be mediated by a selective autoimmune reaction against cerebrovascular Aβ, directly related to autoantibody concentration and soluble Aβ. The CSF dosage of anti‐Aβ autoantibodies with the technique here described can thus be proposed as a valid alternative tool for the diagnosis of CAA‐ri. Moreover, given the similarities between ARIA developing spontaneously and those observed during immunization trials, anti‐Aβ autoantibodies can be considered as novel potential biomarkers in future amyloid‐modifying therapies for the treatment of AD and CAA. Ann Neurol 2013;73:449–458
Clinical correlates in an experimental model of repetitive mild brain injury
Authors: Mannix Rebekah , Meehan William P. , Mandeville Joseph , Grant Patricia E. , Gray Tory , Berglass Jacqueline , Zhang Jimmy , Bryant John , Rezaie Shervin , Chung Joon Yong , Peters Nicholas V. , Lee Christopher , Tien Lee W. , Kaplan David L. , Feany Mel , Whalen Michael 
Published: February 2013

ObjectiveAlthough there is growing awareness of the long‐term cognitive effects of repetitive mild traumatic brain injury (rmTBI; eg, sports concussions), whether repeated concussions cause long‐term cognitive deficits remains controversial. Moreover, whether cognitive deficits depend on increased amyloid β deposition and tau phosphorylation or are worsened by the apolipoprotein E4 allele remains unknown. Here, we use an experimental model of rmTBI to address these clinical controversies.MethodsA weight drop rmTBI model was used that results in cognitive deficits without loss of consciousness, seizures, or gross or microscopic evidence of brain damage. Cognitive function was assessed using a Morris water maze (MWM) paradigm. Immunostaining and enzyme‐linked immunosorbent assay (ELISA) were used to assess amyloid β deposition and tau hyperphosphorylation. Brain volume and white matter integrity were assessed by magnetic resonance imaging (MRI).ResultsMice subjected to rmTBI daily or weekly but not biweekly or monthly had persistent cognitive deficits as long as 1 year after injuries. Long‐term cognitive deficits were associated with increased astrocytosis but not tau phosphorylation or amyloid β (by ELISA); plaques or tangles (by immunohistochemistry); or brain volume loss or changes in white matter integrity (by MRI). APOE4 was not associated with worse MWM performance after rmTBI.InterpretationWithin the vulnerable time period between injuries, rmTBI produces long‐term cognitive deficits independent of increased amyloid β or tau phosphorylation. In this model, cognitive outcome is not influenced by APOE4 status. The data have implications for the long‐term mental health of athletes who suffer multiple concussions. Ann Neurol 2013;74:65–75
Nonconvulsive seizures after subarachnoid hemorrhage: Multimodal detection and outcomes
Authors: Claassen Jan , Perotte Adler , Albers David , Kleinberg Samantha , Schmidt J. Michael , Tu Bin , Badjatia Neeraj , Lantigua Hector , Hirsch Lawrence J. , Mayer Stephan A. , Connolly E. Sander , Hripcsak George 
Published: February 2013

ObjectiveSeizures have been implicated as a cause of secondary brain injury, but the systemic and cerebral physiologic effects of seizures after acute brain injury are poorly understood.MethodsWe analyzed intracortical electroencephalographic (EEG) and multimodality physiological recordings in 48 comatose subarachnoid hemorrhage patients to better characterize the physiological response to seizures after acute brain injury.ResultsIntracortical seizures were seen in 38% of patients, and 8% had surface seizures. Intracortical seizures were accompanied by elevated heart rate (p= 0.001), blood pressure (p< 0.001), and respiratory rate (p< 0.001). There were trends for rising cerebral perfusion pressure (p= 0.03) and intracranial pressure (p= 0.06) seen after seizure onset. Intracortical seizure–associated increases in global brain metabolism, partial brain tissue oxygenation, and regional cerebral blood flow (rCBF) did not reach significance, but a trend for a pronounced delayed rCBF rise was seen for surface seizures (p= 0.08). Functional outcome was very poor for patients with severe background attenuation without seizures and best for those without severe attenuation or seizures (77% vs 0% dead or severely disabled, respectively). Outcome was intermediate for those with seizures independent of the background EEG and worse for those with intracortical only seizures when compared to those with intracortical and scalp seizures (50% and 25% death or severe disability, respectively).InterpretationWe replicated in humans complex physiologic processes associated with seizures after acute brain injury previously described in laboratory experiments and illustrated differences such as the delayed increase in rCBF. These real world physiologic observations may permit more successful translation of laboratory research to the bedside. Ann Neurol 2013;74:53–64
Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR‐124 and reduced AMPA receptors
Authors: Dutta Ranjan , Chomyk Anthony M. , Chang Ansi , Ribaudo Michael V. , Deckard Sadie A. , Doud Mary K. , Edberg Dale D. , Bai Brian , Li Michael , Baranzini Sergio E. , Fox Robert J. , Staugaitis Susan M. , Macklin Wendy B. , Trapp Bruce D. 
Published: February 2013

ObjectiveHippocampal demyelination, a common feature of postmortem multiple sclerosis (MS) brains, reduces neuronal gene expression and is a likely contributor to the memory impairment that is found in >40% of individuals with MS. How demyelination alters neuronal gene expression is unknown.MethodsTo explore whether loss of hippocampal myelin alters expression of neuronal microRNAs (miRNAs), we compared miRNA profiles from myelinated and demyelinated hippocampi from postmortem MS brains and performed validation studies.ResultsA network‐based interaction analysis depicts a correlation between increased neuronal miRNAs and decreased neuronal genes identified in our previous study. The neuronal miRNA miR‐124 was increased in demyelinated MS hippocampi and targets mRNAs encoding 26 neuronal proteins that were decreased in demyelinated hippocampus, including the ionotrophic glutamate receptors AMPA2 and AMPA3. Hippocampal demyelination in mice also increased miR‐124, reduced expression of AMPA receptors, and decreased memory performance in water maze tests. Remyelination of the mouse hippocampus reversed these changes.InterpretationWe establish here that myelin alters neuronal gene expression and function by modulating the levels of the neuronal miRNA miR‐124. Inhibition of miR‐124 in hippocampal neurons may provide a therapeutic approach to improve memory performance in MS patients. Ann Neurol 2013;73:637–645
Improved outcomes with earlier surgery for intractable frontal lobe epilepsy
Authors: Simasathien Thitiwan , Vadera Sumeet , Najm Imad , Gupta Ajay , Bingaman William , Jehi Lara 
Published: February 2013

ObjectiveTo explore the prognostic implications of epilepsy duration and age at surgery for seizure outcomes after frontal lobe epilepsy (FLE) surgery.MethodsWe reviewed 158 patients who underwent FLE surgery from 1995 to 2010. The primary outcome was seizure freedom at last follow‐up (Engel class IA). Analyses employed Cox proportional and multiphase hazard modeling.ResultsThe mean age at surgery was 20.4 years, and mean epilepsy duration was 12.0 years. The estimated chance of seizure freedom was 66% (95% confidence interval [CI] = 62–68) at 1 postoperative year, 52% (95% CI = 48–56) at 2 years, and 44% (95% CI = 39–49) at 5 years and beyond. Seventy‐five percent of recurrences occurred within 6 postoperative months. Both younger age at surgery (<18 years) and shorter epilepsy duration (<5 years) correlated with better seizure outcomes on univariate analysis, but only epilepsy duration remained statistically significant after multivariate modeling. Independent poor prognostic indicators included left‐sided resections and acute postoperative seizures (APOSs; whole model log‐rank test p < 0.0001). APOSs were particularly predictive of early epilepsy recurrence, starting within 6 postoperative months (adjusted risk ratio [RR] = 4.42, p < 0.0001), whereas long epilepsy duration correlated with late recurrences (RR = 6.25, p < 0.0001). Worse outcomes were seen with longer epilepsy duration for duration cutoffs of 2, 5, and 10 years independently for adults and children, although statistical significance was only achieved in children (66% seizure free at 5 postoperative years if operated on within 5 years of epilepsy onset vs 31% if later; p = 0.01).InterpretationEarly resection may improve seizure outcomes of FLE surgery, particularly in children. Ann Neurol 2013;73:646–654
Pathological correlates of magnetic resonance imaging texture heterogeneity in multiple sclerosis
Authors: Zhang Yunyan , Moore G. R. Wayne , Laule Cornelia , Bjarnason Thorarin A. , Kozlowski Piotr , Traboulsee Anthony , Li David K. B. 
Published: February 2013

ObjectiveTo analyze the texture of T2‐weighted magnetic resonance imaging (MRI) of postmortem multiple sclerosis (MS) brain, and to determine whether and how MRI texture correlates with tissue pathology.MethodsTen brain samples from 3 subjects with MS were examined. Areas of complete, partial, or no loss of Luxol fast blue (myelin) and Bielschowsky (axons) staining were marked on histological images, and matched on corresponding MRI as lesions, diffusely abnormal white matter (DAWM), and normal‐appearing white matter (NAWM). The number of CD45+ cells (inflammation) was also counted. MRI texture was computed using polar Stockwell transform and compared to histology.ResultsThirty‐four lesions, 17 DAWM regions, and 36 NAWM regions were identified. After mixed effects modeling, MRI texture heterogeneity was greater in lesions than in DAWM (p < 0.001) and NAWM (p < 0.001), and was greater in DAWM than in NAWM (p < 0.001); the number of CD45+ cells was greater in both lesions (p < 0.001) and DAWM (p = 0.005) than in NAWM. In MRI, a gradient of texture heterogeneity was detected in lesions, with gradual tapering toward perilesional NAWM. Moreover, besides univariate correlation with histological markers, texture heterogeneity correlated independently with normalized myelin density (p < 0.01) when random effects were considered. Within sample, MRI texture correlated with myelin and axonal density in 7 of 10 samples (p < 0.01).InterpretationTexture analysis performed on routine clinical magnetic resonance images may be a potential measure of tissue integrity. Tissues with more severe myelin and axonal pathology are associated with greater texture heterogeneity. Ann Neurol 2013;74:91–99