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  • Medicine  (144)
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  • 1
    Language: English
    In: Journal of Biomechanics, 15 March 2013, Vol.46(5), pp.949-955
    Description: Stem–cement and cement–bone interfacial failures as well as cement fractures have been noted in cemented total hip arthroplasty (THA) as the cause of aseptic loosening. Attempts to reduce the risk of femoral component loosening include improving the stem–cement interface by various coatings, using a textured or porous coated stem surfaces or by using a tapered stem having a highly-polished surface. The latter approach, often referred to as “force-closed” femoral stem design, would theoretically result in stem stabilization subsequent to debonding and ‘taper-lock’. Previous work using three-dimensional finite element analysis has shown a state of stress at the stem–cement interface indicative of ‘taper-lock’ for the debonded stem and indicated that stem–cement interface friction and bone cement creep played a significant role in the magnitudes of stresses and subsidence of the stem. However, the previous analysis did not include the viscoelastic properties of bone, which has been hypothesized to permit additional expansion of the bone canal and allow additional stem subsidence ( ). The goal of this study was to investigate the effect of bone viscoelastic behavior on stem subsidence using a 3D finite element analysis. It was hypothesized that the viscoelastic behavior of bone in the hoop direction would allow expansion of the bone reducing the constraint on bone over time and permit additional stem subsidence, which may account for the discrepancies between predicted and clinical subsidence measurements. Analyses were conducted using physiological loads, ‘average peak loads’ and ‘high peak loads’ for ‘normal patient’ and ‘active patient’ ( ) from which short and long term subsidence was predicted. Results indicated that bone creep does contribute to higher stem subsidence initially and after 10 years of simulated loading. However, it was concluded that the “constraint” upon the cement mantle is not mitigated enough to result in stem subsidence equivalent to that observed clinically.
    Keywords: Cemented Total Hip Arthroplasty ; Cortical Bone Creep ; Bone Cement Creep ; Stem Subsidence ; Stem–Cement Interface Failure ; Medicine ; Engineering ; Anatomy & Physiology
    ISSN: 0021-9290
    E-ISSN: 1873-2380
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  • 2
    Language: English
    In: Journal of Clinical Epidemiology, May 2013, Vol.66(5), pp.496-502.e2
    Description: We present a multistep process for identifying priority research areas in rehabilitation and long-term care of traumatic brain-injured (TBI) patients. In particular, we aimed to (1) identify which stakeholders should be involved; (2) identify what methods are appropriate; (3) examine different criteria for the generation of research priority areas; and (4) test the feasibility of linkage and exchange among researchers, decision makers, and other potential users of the research. Potential research questions were identified and developed using an initial scoping meeting and preliminary literature search, followed by a facilitated mapping workshop and an online survey. Identified research questions were then prioritized against specific criteria (clinical importance, novelty, and controversy). Existing evidence was then mapped to the high-priority questions using usual processes for search, screening, and selection. A broad range of stakeholders were then brought together at a forum to identify priority research themes for future research investment. Using clinical and research leaders, smaller targeted planning workshops prioritized specific research projects for each of the identified themes. Twenty-six specific questions about TBI rehabilitation were generated, 14 of which were high priority. No one method identified all high-priority questions. Methods that relied solely on the views of clinicians and researchers identified fewer high-priority questions compared with methods that used broader stakeholder engagement. Evidence maps of these high-priority questions yielded a number of evidence gaps. Priority questions and evidence maps were then used to inform a research forum, which identified 12 priority themes for future research. Our research demonstrates the value of a multistep and multimethod process involving many different types of stakeholders for prioritizing research to improve the rehabilitation outcomes of people who have suffered TBI. Enhancing stakeholder representation can be augmented using a combination of methods and a process of linkage and exchange. This process can inform decisions about prioritization of research areas.
    Keywords: Prioritization ; Traumatic Brain Injury ; Research Funding ; Evidence Mapping ; Research Gaps ; Rehabilitation ; Medicine
    ISSN: 0895-4356
    E-ISSN: 1878-5921
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  • 3
    In: Cerebral Cortex, 2011, Vol. 21(11), pp.2482-2497
    Description: During natural vision, primates perform frequent saccadic eye movements, allowing only a narrow time window for processing the visual information at each location. Individual neurons may contribute only with a few spikes to the visual processing during each fixation, suggesting precise spike timing as a relevant mechanism for information processing. We recently found in V1 of monkeys freely viewing natural images, that fixation-related spike synchronization occurs at the early phase of the rate response after fixation-onset, suggesting a specific role of the first response spikes in V1. Here, we show that there are strong local field potential (LFP) modulations locked to the onset of saccades, which continue into the successive fixation periods. Visually induced spikes, in particular the first spikes after the onset of a fixation, are locked to a specific epoch of the LFP modulation. We suggest that the modulation of neural excitability, which is reflected by the saccade-related LFP changes, serves as a corollary signal enabling precise timing of spikes in V1 and thereby providing a mechanism for spike synchronization.
    Keywords: Free Viewing ; Local Field Potential ; Phase Locking ; Primary Visual Cortex ; Spike Synchrony
    ISSN: 1047-3211
    E-ISSN: 1460-2199
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  • 4
    Language: English
    In: The Journal of Pediatrics, February 2011, Vol.158(2), pp.234-238.e1
    Description: To assess the genetic contribution to late-onset sepsis in twins in the newborn intensive care unit. A retrospective cohort analysis of twins born from 1994 to 2009 was performed on data collected from the newborn intensive care units at Yale University and the University of Connecticut. Sepsis concordance rates were compared between monozygotic and dizygotic twins. Mixed-effects logistic regression analysis was performed to determine the impact of selected nongenetic factors on late-onset sepsis. The influence of additive genetic and common and residual environmental effects were analyzed and quantified. One hundred seventy monozygotic and 665 dizygotic twin pairs were analyzed, and sepsis identified in 8.9%. Mean gestational age and birth weight of the cohort was 31.1 weeks and 1637 grams, respectively. Mixed-effects logistic regression determined birth weight (regression coefficient, −0.001; 95% CI, −0.003 to 0.000; = .028), respiratory distress syndrome (regression coefficient, 1.769; 95% CI, 0.943 to 2.596; 〈 .001), and duration of total parenteral nutrition (regression coefficient, 0.041; 95% CI, 0.017 to 0.064; 〈 .001) as significant nongenetic factors. Further analysis determined 49.0% ( = .002) of the variance in liability to late-onset sepsis was due to genetic factors alone, and 51.0% ( = .001) the result of residual environmental factors. Our data support significant genetic susceptibility to late-onset sepsis in the newborn intensive care unit population.
    Keywords: Medicine
    ISSN: 0022-3476
    E-ISSN: 1097-6833
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  • 5
    Language: English
    In: PLoS ONE, 2012, Vol.7(2), p.e31508
    Description: Macrophage inflammatory protein-1α (CCL3) plays a well-known role in infectious and viral diseases; however, its contribution to atherosclerotic lesion formation and lipid metabolism has not been determined. Low density lipoprotein receptor deficient (LDLR −/− ) mice were transplanted with bone marrow from CCL3 −/− or C57BL/6 wild type donors. After 6 and 12 weeks on western diet (WD), recipients of CCL3 −/− marrow demonstrated lower plasma cholesterol and triglyceride concentrations compared to recipients of C57BL/6 marrow. Atherosclerotic lesion area was significantly lower in female CCL3 −/− recipients after 6 weeks and in male CCL3 −/− recipients after 12 weeks of WD feeding ( P 〈0.05). Surprisingly, male CCL3 −/− recipients had a 50% decrease in adipose tissue mass after WD-feeding, and plasma insulin, and leptin levels were also significantly lower. These results were specific to CCL3, as LDLR −/− recipients of monocyte chemoattractant protein −/− (CCL2) marrow were not protected from the metabolic consequences of high fat feeding. Despite these improvements in LDLR −/− recipients of CCL3 −/− marrow in the bone marrow transplantation (BMT) model, double knockout mice, globally deficient in both proteins, did not have decreased body weight, plasma lipids, or atherosclerosis compared with LDLR −/− controls. Finally, there were no differences in myeloid progenitors or leukocyte populations, indicating that changes in body weight and plasma lipids in CCL3 −/− recipients was not due to differences in hematopoiesis. Taken together, these data implicate a role for CCL3 in lipid metabolism in hyperlipidemic mice following hematopoietic reconstitution.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Diabetes And Endocrinology
    E-ISSN: 1932-6203
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  • 6
    Language: English
    In: Journal of Clinical Epidemiology, May 2013, Vol.66(5), pp.503-510.e4
    Description: To identify high-priority research questions for osteoarthritis systematic reviews with consideration of health equity and the social determinants of health (SDH). We consulted with experts and conducted a literature search to identify a priority-setting method that could be adapted to address the health equity and SDH. We selected the Global Evidence Mapping priority-setting method, and through consultations and consensus, we adapted the method to meet our objectives. This involves developing an evidence map of the existing systematic reviews on osteoarthritis; conducting one face-to-face workshop with patients and another one with clinicians, researchers, and patients; and conducting an online survey of patients to rank the top 10 research questions. We piloted the adapted method with the Cochrane Musculoskeletal Review Group to set research priorities for osteoarthritis. Our focus was on systematic reviews: we identified 34 high-priority research questions for osteoarthritis systematic reviews. Prevention and self-management interventions, mainly diet and exercise, are top priorities for osteoarthritis systematic reviews. Evaluation against our predefined objectives showed that this method did prioritize SDH (50% of the research questions considered SDH). There were marked gaps: no high-priority topics were identified for access to care until patients had advanced disease–lifestyle changes once the disease was diagnosed. This method was felt feasible if conducted annually. We confirmed the utility of an adapted priority-setting method that is feasible and considers SDH. Further testing of this method is needed to assess whether considerations of health equity are prioritized and involve disadvantaged groups of the population.
    Keywords: Priority Setting ; Health Equity ; Osteoarthritis ; Social Determinants of Health ; Systematic Reviews ; Methods ; Methodology ; Research Priorities ; Medicine
    ISSN: 0895-4356
    E-ISSN: 1878-5921
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  • 7
    In: Circulation, 2012, Vol.125(18), pp.e640-e644
    Description: A 68-year-old white man presented for work-up of recurring atypical resting chest pain in the setting of known coronary artery disease. ECG and chest x-ray on admission can be viewed in Figures 1 and 2. Two years previously, invasive angiography was performed because of unstable angina revealing dilative coronary sclerosis of all coronaries with a proximal right coronary artery stenosis, which was treated with percutaneous intervention by another cardiologist at that time (Figure 3 and online-only Data Supplement Movies I–III). Figure 1. Twelve-lead ECG on admission demonstrating left-axis deviation, ectopic beats, and nonsignificant ST-segment abnormalities. Figure 2. Chest x-ray on admission revealing a normal-size heart, aspects of pulmonary emphysema, and small amounts of fluid in the right costophrenic angle. Figure 3. First invasive coronary angiography of the left (LCA) ( A ) and the right (RCA) ( B ) coronary arteries performed by another cardiologist 2 years previously. Note the proximal RCA stenosis (white arrows) in the setting of diffuse dilative coronary sclerosis ( C ), which was treated by percutaneous intervention. To evaluate possible progress of coronary artery disease, adenosine stress first-pass perfusion cardiovascular magnetic resonance (CMR) using a 1.5T Magnetom Aera (Siemens Healthcare, Erlangen, Germany) was performed. However, no myocardial ischemia could be detected by CMR in …
    Keywords: Medicine ; Anatomy & Physiology;
    ISSN: 0009-7322
    E-ISSN: 15244539
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  • 8
    Language: English
    In: Seminars in Perinatology, December 2015, Vol.39(8), pp.568-573
    Description: Gene–environment interactions likely account for some degree of the variance in response rates that are clinically observed with antenatal corticosteroids, breast milk prophylaxis, surfactant administration, early recognition and treatment of sepsis, utility of non-invasive ventilation, and judicious exposure to supplemental oxygen. While these therapies and practice guidelines have significantly decreased overall neonatal mortality in the NICU, they have not made a marked impact on the frequency and severity of conditions such as bronchopulmonary dysplasia (BPD), necrotizing enterocolitis, and periventricular leukomalacia. One possible explanation is that genetic factors in the neonate modulate response to external intervention or preventative agents, culminating in variable levels of injury and different degrees of resolution and repair. Gene–environment explanations are supported by the observed heritability of BPD in twin studies, but they do not differentiate the interactions between neonate and offending toxin or pathogen, from interactions between neonate and intervention or therapeutic agent. Likely, both kinds of interactions are important in determining outcome.
    Keywords: Twin Studies ; Premature Newborn ; Rds ; IVH ; Bpd ; PDA ; NEC ; Rop ; Neonatal Sepsis ; Apnea of Prematurity ; Medicine
    ISSN: 0146-0005
    E-ISSN: 1558-075X
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  • 9
    Language: English
    In: Journal of the American College of Cardiology, 01 May 2012, Vol.59(18), pp.1604-1615
    Description: This study sought to evaluate the long-term mortality in patients with viral myocarditis, and to establish the prognostic value of various clinical, functional, and cardiovascular magnetic resonance (CMR) parameters. Long-term mortality of viral myocarditis, as well as potential risk factors for poor clinical outcome, are widely unknown. A total of 222 consecutive patients with biopsy-proven viral myocarditis and CMR were enrolled. A total of 203 patients were available for clinical follow-up, and 77 patients underwent additional follow-up CMR. The median follow-up was 4.7 years. Primary endpoints were all-cause mortality and cardiac mortality. We found a relevant long-term mortality in myocarditis patients (19.2% all cause, 15% cardiac, and 9.9% sudden cardiac death [SCD]). The presence of late gadolinium enhancement (LGE) yields a hazard ratio of 8.4 for all-cause mortality and 12.8 for cardiac mortality, independent of clinical symptoms. This is superior to parameters like left ventricular (LV) ejection fraction, LV end-diastolic volume, or New York Heart Association (NYHA) functional class, yielding hazard ratios between 1.0 and 3.2 for all-cause mortality and between 1.0 and 2.2 for cardiac mortality. No patient without LGE experienced SCD, even if the LV was enlarged and impaired. When focusing on the subgroup undergoing follow-up CMR, we found an initial NYHA functional class 〉I as the best independent predictor for incomplete recovery (p = 0.03). Among our population with a wide range of clinical symptoms, biopsy-proven viral myocarditis is associated with a long-term mortality of up to 19.2% in 4.7 years. In addition, the presence of LGE is the best independent predictor of all-cause mortality and of cardiac mortality. Furthermore, initial presentation with heart failure may be a good predictor of incomplete long-term recovery.
    Keywords: Cardiovascular Magnetic Resonance ; Mortality ; Myocarditis ; Prognosis ; Medicine
    ISSN: 0735-1097
    E-ISSN: 1558-3597
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  • 10
    Language: English
    In: Journal of Clinical Neuroscience, 2011, Vol.18(2), pp.197-202
    Description: The Quality of Life after Brain Injury (QOLIBRI) is a new international instrument for assessing quality of life after traumatic brain injury (TBI). We report first use and validation. Patients previously admitted with TBI to the Royal Melbourne Hospital, Melbourne, Australia, were randomly sampled ( = 66, 61% response rate) and administered the QOLIBRI. Fifty-five re-completed it at 2-week follow-up. QOLIBRI scales (with two exceptions) met standard criteria for internal consistency, homogeneity and test–re-test reliability. Correlations with the Assessment of Quality of Life, Short Form-36 version 2 and the Satisfaction with Life Scale were moderate. The QOLIBRI was sensitive to the Glasgow Outcome Scale – Extended scores, Hospital Anxiety and Depression scale, and measures of social isolation (Friendship Scale). There was evidence that further refinement may improve the QOLIBRI. The QOLIBRI should be considered as an outcome measure by clinicians and researchers conducting treatment trials, rehabilitation studies or epidemiological surveys into the treatment or sequelae of trauma.
    Keywords: Clinical Trials ; Evaluation ; Participant Reported Outcome ; Quality of Life ; Qolibri ; Traumatic Brain Injury ; Medicine
    ISSN: 0967-5868
    E-ISSN: 1532-2653
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