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  • 1
    Article
    Article
    Bone creep and short and long term subsidence after cemented stem total hip arthroplasty (THA) (2013)
    Details
    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
    DOI: 10.1016/j.jbiomech.2012.12.010
    URL: View record in ScienceDirect (Access to full text may be restricted)
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  • 2
    Article
    Article
    Effective stakeholder participation in setting research priorities using a Global Evidence Mapping approach (2013)
    Details
    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
    DOI: 10.1016/j.jclinepi.2012.04.002
    URL: View record in ScienceDirect (Access to full text may be restricted)
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  • 3
    Article
    Article
    Criterion Validation Testing of Clinical Metrology Instruments for Measuring Degenerative Joint Disease Associated Mobility Impairment in Cats (2015)
    Details
    Language: English
    In: PLoS ONE, 01 January 2015, Vol.10(7), p.e0131839
    Description: Degenerative joint disease and associated pain are common in cats, particularly in older cats. There is a need for treatment options, however evaluation of putative therapies is limited by a lack of suitable, validated outcome measures that can be used in the target population of client owned cats. The objectives of this study were to evaluate low-dose daily meloxicam for the treatment of pain associated with degenerative joint disease in cats, and further validate two clinical metrology instruments, the Feline Musculoskeletal Pain Index (FMPI) and the Client Specific Outcome Measures (CSOM).Sixty-six client owned cats with degenerative joint disease and owner-reported impairments in mobility were screened and enrolled into a double-masked, placebo-controlled, randomized clinical trial. Following a run-in baseline period, cats were given either placebo or meloxicam for 21 days, then in a masked washout, cats were all given placebo for 21 days. Subsequently, cats were given the opposite treatment, placebo or meloxicam, for 21 days. Cats wore activity monitors throughout the study, owners completed clinical metrology instruments following each period.Activity counts were increased in cats during treatment with daily meloxicam (p〈0.0001) compared to baseline. The FMPI results and activity count data offer concurrent validation for the FMPI, though the relationship between baseline activity counts and FMPI scores at baseline was poor (R2=0.034). The CSOM did not show responsiveness for improvement in this study, and the relationship between baseline activity counts and CSOM scores at baseline was similarly poor (R2=0.042).Refinements to the FMPI, including abbreviation of the instrument and scoring as percent of possible score are recommended. This study offered further validation of the FMPI as a clinical metrology instrument for use in detecting therapeutic efficacy in cats with degenerative joint disease.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
    DOI: 10.1371/journal.pone.0131839
    URL: View full text in DOAJ
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  • 4
    Article
    Article
    Saccade-Related Modulations of Neuronal Excitability Support Synchrony of Visually Elicited Spikes (2011)
    Details
    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
    DOI: 10.1093/cercor/bhr020
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  • 5
    Article
    Article
    Paternal RNA contributions in the Caenorhabditis elegans zygote (2014)
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    In: EMBO Journal, 18 August 2014, Vol.33(16), pp.1740-1750
    Description: Development of the early embryo is thought to be mainly driven by maternal gene products and post‐transcriptional gene regulation. Here, we used metabolic labeling to show that can be transferred by sperm into the oocyte upon fertilization. To identify genes with paternal expression in the embryo, we performed crosses of males and females from divergent strains. RNA sequencing of s and small s in the 1‐cell hybrid embryo revealed that about one hundred sixty paternal s are reproducibly expressed in the embryo and that about half of all assayed endogenous sis and pis are also of paternal origin. Together, our results suggest an unexplored paternal contribution to early development. This paper establishes significant paternal contributions in zygotes, a result with major bearings on their potential functional relevance. Metabolic labeling of males shows that male RNA is transferred into the oocyte upon fertilization. We performed a cross of hybrid strains and sequenced RNA from the 1‐cell‐fertilized embryo. Computational analyses of these data allow to quantify maternal and paternal RNA in the fertilized embryo. We discover numerous mRNAs and different classes of non‐coding RNAs of paternal origin in the fertilized embryo. This paper establishes significant paternal contributions in zygotes, a result with major bearings on their potential functional relevance.
    Keywords: Embryogenesis ; Epigenetic Inheritance ; Paternal ; Transgenerational Inheritance
    ISSN: 0261-4189
    E-ISSN: 1460-2075
    DOI: 10.15252/embj.201488117
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  • 6
    Article
    Article
    The Impact of Environmental and Genetic Factors on Neonatal Late-Onset Sepsis (2011)
    Details
    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
    DOI: 10.1016/j.jpeds.2010.07.060
    URL: View record in ScienceDirect (Access to full text may be restricted)
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  • 7
    Article
    Article
    Impact of Macrophage Inflammatory Protein-1α Deficiency on Atherosclerotic Lesion Formation, Hepatic Steatosis, and Adipose Tissue Expansion (CCL3 Deficiency in LDLR−/− Mice) (2012)
    Details
    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
    DOI: 10.1371/journal.pone.0031508
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  • 8
    Article
    Article
    Prevention and self-management interventions are top priorities for osteoarthritis systematic reviews (2013)
    Details
    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
    DOI: 10.1016/j.jclinepi.2012.06.017
    URL: View record in ScienceDirect (Access to full text may be restricted)
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  • 9
    Article
    Article
    Does Additional Head Trauma Affect the Long-term Outcome After Upper Extremity Trauma in Multiple Traumatized Patients: Is There an Additional Effect of Traumatic Brain Injury? (2013)
    Details
    In: Clinical Orthopaedics and Related Research, 2013, Vol.471(9), pp.2899-2905
    Description: BACKGROUND: Musculoskeletal injuries are common in patients with multiple trauma resulting in pain, functional deficits, and disability. Traumatic brain injuries (TBIs) are common in severely injured patients potentially resulting in neurological impairment and permanent disability that would add to that from the musculoskeletal injuries. However, it is unclear to what degree the combination affects impairment. QUESTIONS/PURPOSES: We therefore asked whether added upper extremity injuries or TBI worsened the functional, psychological, and vocational status in multiple trauma patients. METHODS: We retrospectively reviewed 281 patients with multiple trauma: 229 with upper extremity injuries but without TBI (Group I), 32 with concomitant upper extremity injuries and TBI (Group II), and 20 with TBI but no upper extremity injuries (Group III). We assessed patients with the Glasgow Outcome Score (GOS), Hannover Score for Polytrauma Outcome, SF-12 (Physical Component Summary Score and Mental Component Summary Score), medical aid requirements, need of psychological support, and vocational living circumstances. The minimum followup was 10 years (median, 17.5 years; range, 10-28 years). RESULTS: Additional TBI in multiple trauma patients led to reduced function (GOS: Group I: 4.9 ± 0.2, Group II: 4.5 ± 0.7, Group III: 4.5 ± 0.8) resulting in vocational restrictions (job change: Group I: 74%, Group II: 91%, Group III: 90%). The combination of upper extremity and TBIs did not result in worse long-term scores compared with TBI alone. CONCLUSIONS: Rehabilitation and social reintegration in multiple trauma patients with TBI requires particular emphasis to minimize disability and vocational isolation. Musculoskeletal injuries should not be neglected to ensure the maximum extremity function given the impaired cognitive functions after TBI. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
    Keywords: Brain Injuries -- Patient Outcomes;
    ISSN: 0009-921X
    E-ISSN: 15281132
    DOI: 10.1007/s11999-013-3031-6
    URL: View record at Wolters Kluwer Health Ovid Technologies
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  • 10
    Article
    Article
    Prevalence and Clinical Relevance of Radiographic Signs of Impingement in Metal-on-Metal Hybrid Hip Resurfacing (2011)
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    In: The Journal of Bone & Joint Surgery, 2011, Vol.93(16), pp.1519-1526
    Description: BACKGROUND:: Implant-related impingement has been reported following metal-on-metal hip resurfacing, and reactive osseous patterns associated with implant-bone impingement have been identified. The purpose of this study was to determine the prevalence and clinical implications of radiographic signs of femoral neck-acetabular cup impingement following metal-on-metal hip resurfacing. METHODS:: Serial anteroposterior and lateral radiographs made five to 12.9 years postoperatively were available for ninety-one of the first 100 metal-on-metal hip resurfacing procedures (in eighty-nine patients) performed by the senior author. These radiographs were reviewed by a single independent observer, who was blinded to the clinical results. Radiographic signs of impingement were assessed and were correlated with clinical outcomes. RESULTS:: Twenty hips (in eighteen patients) had at least one of two reactive osseous signs: a solitary exostosis (six hips, 7%) and an erosive “divot-type” deformity (twenty hips, 22%). Each radiographic sign occurred predominantly at the superior aspect of the femoral neck just distal to the femoral component. None of the patients with such an impingement sign reported any symptoms or discomfort during examination of the range of hip motion. These patients had a greater mean postoperative University of California Los Angeles activity score and a greater mean range of hip motion than the patients without an impingement sign. Based on the numbers available, there was no association between component size, abduction angle and anteversion angle of the socket, femoral stem-femoral shaft angle, or femoral component-femoral neck ratio and the occurrence of repetitive impingement signs on radiographs. CONCLUSIONS:: The reactive osseous features identified in this study should facilitate the radiographic assessment of impingement in other patients following hip resurfacing arthroplasty. Longer-term follow-up is needed to determine whether radiographic signs of impingement are of prognostic consequence. LEVEL OF EVIDENCE:: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.
    Keywords: Adolescent–Methods ; Adult–Diagnostic Imaging ; Aged–Epidemiology ; Arthroplasty, Replacement, Hip–Etiology ; Female–Diagnostic Imaging ; Femoracetabular Impingement–Surgery ; Hip–Diagnostic Imaging ; Hip Joint–Surgery ; Hip Prosthesis–Adverse Effects ; Humans–Adverse Effects ; Male–Adverse Effects ; Middle Aged–Adverse Effects ; Prevalence–Adverse Effects ; Radiography–Adverse Effects ; Range of Motion, Articular–Adverse Effects ; Abridged;
    ISSN: 0021-9355
    E-ISSN: 15351386
    DOI: 10.2106/JBJS.I.01723
    URL: View record at Wolters Kluwer Health Ovid Technologies
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