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INTRODUCTION: The understanding of the pathological events in Alzheimer's disease (AD) has advanced dramatically, but the successful translation from rodent models into efficient human therapies is still problematic. METHODS: To examine how tau pathology can develop in the primate brain, we injected 12 macaques with a dual tau mutation (P301L/S320F) into the entorhinal cortex (ERC). An investigation was performed using high‐resolution microscopy, magnetic resonance imaging (MRI), positron emission tomography (PET), and fluid biomarkers to determine the temporal progression of the pathology 3 and 6 months after the injection. RESULTS: Using quantitative microscopy targeting markers for neurodegeneration and neuroinflammation, as well as fluid and imaging biomarkers, we detailed the progression of misfolded tau spreading and the consequential inflammatory response induced by glial cells. DISCUSSION: By combining the analysis of several in vivo biomarkers with extensive brain microscopy analysis, we described the initial steps of misfolded tau spreading and neuroinflammation in a monkey model highly translatable to AD patients. Highlights: Dual tau mutation delivery in the entorhinal cortex induces progressive tau pathology in rhesus macaques.Exogenous human 4R‐tau coaptates monkey 3R‐tau during transneuronal spread, in a prion‐like manner.Neuroinflammatory response is coordinated by microglia and astrocytes in response to tau pathology, with microglia targeting early tau pathology, while astrocytes engaged later in the progression, coincident with neuronal death.Monthly collection of CSF and plasma revealed a profile of changes in several AD core biomarkers, reflective of neurodegeneration and neuroinflammation as early as 1 month after injection. [ABSTRACT FROM AUTHOR]

Control of multicomponent alloys during welding is challenging because it lacks a real‐time understanding of composition. The optical emissions of plasma formed during laser‐induced metal welding correlate with the composition of particles ejected from the melt pool. Plasma emissions observed in this study contain large iron, manganese, chrome, and copper signatures, which match the composition of emitted particles. Particles recovered closest to the melt pool exhibit a core–shell morphology that is composed of iron‐manganese‐chrome intermetallic cores within copper shells. Particles collected farther from the melt pool, do not share this core–shell morphology, though similar elemental compositions are observed. The correlation between plasma optical emissions and particle composition can be used to predict the composition of the melt pool, allowing for real‐time welding and sintering control. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is a devastating condition with no effective treatments, with promising findings in rodents failing to translate into successful therapies for patients. Methods: Targeting the vulnerable entorhinal cortex (ERC), rhesus monkeys received two injections of an adeno‐associated virus expressing a double tau mutation (AAV‐P301L/S320F) in the left hemisphere, and control AAV‐green fluorescent protein in the right ERC. Noninjected aged‐matched monkeys served as additional controls. Results: Within 3 months we observed evidence of misfolded tau propagation, similar to what is hypothesized to occur in humans. Viral delivery of human 4R‐tau also coaptates monkey 3R‐tau via permissive templating. Tau spreading is accompanied by robust neuroinflammatory response driven by TREM2+ microglia, with biomarkers of inflammation and neuronal loss in the cerebrospinal fluid and plasma. Discussion: These results highlight the initial stages of tau seeding and propagation in a primate model, a more powerful translational approach for the development of new therapies for AD. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated that intrastriatal injections of fibrillar α-synuclein in rodent brain induced a Parkinson's disease-like propagation of Lewy body pathology with significant nigrostriatal neurodegeneration. This study evaluated the pathological features when exogenous α-synuclein preformed fibrils were injected into the putamen of non-human primates. Eight cynomolgus monkeys received unilateral intraputamen injections of α-synuclein preformed fibrils and four monkeys received sham surgery. Monkeys were assessed with 123I-PE2I single-photon emission computerized tomography scans targeting the dopamine transprter at baseline, 3, 6, 9, 12, and 15 months. Imaging revealed a robust increase in dopamine transporter binding, an effect confirmed by port-mortem immunohistochemical analyses, suggesting that upregulation of dopamine transporter occurs as part of an early pathological process. Histochemistry and immunohistochemistry revealed that α-synuclein preformed fibrils injections into the putamen induced intraneuronal inclusions positive for phosphorylated α-synuclein in ipsilateral substantia nigra and adjacent to the injection site. α-Synuclein inclusions were thioflavin-S-positive suggesting that the inclusions induced by α-synuclein preformed fibrils exhibited pathological properties similar to amyloid-like Lewy body pathology in Parkinson's disease brains. The α-synuclein preformed fibrils resulted in Lewy pathology in the ipsilateral substantia nigra with significant reduction (-29.30%) of dopaminergic neurons as compared with controls. Nigral neurons with α-synuclein inclusions exhibited a phenotypic downregulation of the dopamine markers tyrosine hydroxylase and Nurr1. Taken together, our findings demonstrate that α-synuclein preformed fibrils induce a synucleinopathy in non-human primates with authentic Lewy pathology and nigrostriatal changes indicative of early Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Enhanced recovery programmes in total knee arthroplasty are well established. Post-operative knee swelling is common and impairs early post-operative function. The use of a short-stretch, inelastic compression bandage is hypothesised to reduce knee swelling and improve pain and early function. A study was designed to test feasibility with a view to informing a larger, future trial and to provide preliminary data. Methods/design: This is a randomised controlled feasibility study. Fifty consecutive patients selected for primary total knee arthroplasty will be enrolled in the trial. Patients with a BMI >35, latex allergy or neurological or peripheral vascular disease are excluded. Patients are randomised by distance randomisation to receive a compression bandage for 24 hours after surgery or a standard wool and crepe bandage. The bandages are applied by one of two consultant surgeons who have had training with their application. Knee swelling, range of motion and pain scores will be compared pre-operatively and at day 1, day 2 and at 6 weeks between groups. The Oxford knee score and EQ-5D health status will be compared pre-operatively and at 6 months between groups. Recruitment rates, retention rates, resource allocation, completeness of data collection, and tolerance and complications with the compression bandage are recorded. Descriptive statistics are used to calculate a standard deviation for post-operative knee swelling in the groups and to perform a power calculation incorporating anticipated patient retention rates to inform a future trial. Preliminary data will be analysed using the independent samples t-test for equal distributions and the Mann-Whitney U for unequal distributions with the significance denoted at P <0.05. Discussion: Enhanced recovery programmes have revolutionized the management of total knee arthroplasty. There is a paucity of clinical data regarding the efficacy of compression bandages. Large, randomised controlled trials are uncommon in orthopaedic surgery. The results of this study will provide feasibility and preliminary data prior to the construction of a larger, multicentre study. [ABSTRACT FROM AUTHOR]

Background: 187,000 hip and knee joint replacements are performed every year in the National Health Service (NHS). One of the commonest complications is surgical site infection (SSI), and this represents a significant burden in terms of patient morbidity, mortality and cost to health services around the world. The aim of this randomised controlled trial (RCT) is to determine if the addition of triclosan coated sutures to a standard regimen can reduce the rate of SSI after total knee replacement (TKR) and total hip replacement (THR). Methods: 2400 patients due to undergo a total hip or knee replacement are being recruited into this two-centre RCT. Participants are recruited before surgery and randomised to either standard care or intervention group. Participants, outcome assessors and statistician are blind to treatment allocation throughout the study. The intervention consists of triclosan coated sutures vs. standard non-coated sutures. The primary outcome is the Health protection Agency (HPA) defined superficial surgical site infection at 30 days. Secondary outcomes include HPA defined deep surgical site infection at 12 months, length of hospital stay, critical care stay, and payer costs. Discussion: To date there are no orthopaedic randomised controlled trials on this scale assessing the effectiveness of a surgical intervention, particularly those that can be translated across the surgical specialities. The results from this trial will inform evidence-based recommendations for suture selection in the management of patients undergoing total hip or knee replacement. If triclosan coated sutures are found to be an effective intervention, implementation into clinical practice could improve long-term outcomes for patients undergoing hip and knee replacement. [ABSTRACT FROM AUTHOR]

Background and purpose Enhanced Recovery (ER) is a well-established multidisciplinary strategy in lower limb arthroplasty and was introduced in our department in May 2008. This retrospective study reviews short-term outcomes in a consecutive unselected series of 3,000 procedures (the 'ER' group), and compares them to a numerically comparable cohort that had been operated on previously using a traditional protocol (the 'Trad' group). Methods Prospectively collected data on surgical endpoints (length of stay (LOS), return to theater (RTT), re-admission, and 30- and 90-day mortality) and medical complications (stroke, gastrointestinal bleeding, myocardial infarction, and pneumonia within 30 days; deep vein thrombosis and pulmonary embolism within 60 days) were compared. Results ER included 1,256 THR patients and 1,744 TKR patients (1,369 THRs and 1,631 TKRs in Trad). The median LOS in the ER group was reduced (3 days vs. 6 days; p = 0.01). Blood transfusion rate was also reduced (7.6% vs. 23%; p < 0.001), as was RTT rate (p = 0.05). The 30-day incidence of myocardial infarction declined (0.4% vs. 0.9%; p = 0.03) while that of stroke, gastrointestinal bleeding, pneumonia, deep vein thrombosis, and pulmonary embolism was not statistically significantly different. Mortality at 30 days and at 90 days was 0.1% and 0.5%, respectively, as compared to 0.5% and 0.8% using the traditional protocol (p = 0.03 and p = 0.1, respectively). Interpretation This is the largest study of ER arthroplasty, and provides safety data on a consecutive unselected series. The program has achieved a statistically significant reduction in LOS and in cardiac ischemic events for our patients, with a near-significant decrease in return to theater and in mortality rates. [ABSTRACT FROM AUTHOR]

Background and purpose Multimodal techniques can aid early rehabilitation and discharge of patients following primary joint replacement. We hypothesized that this not only reduces the economic burden of joint replacement by reducing length of stay, but also helps in reduction of early complications. Patients and methods We evaluated 4,500 consecutive unselected total hip replacements and total knee replacements regarding length of hospital stay, mortality, and perioperative complications. The first 3,000 underwent a traditional protocol while the other 1,500 underwent an enhanced recovery protocol involving behavioral, pharmacological, and procedural modifications. Results There was a reduction in 30-day death rate (0.5% to 0.1%, p == 0.02) and 90-day death rate (0.8% to 0.2%, p == 0.01). The median length of stay decreased from 6 days to 3 days (p < 0.001), resulting in a saving of 5,418 bed days. Requirement for blood transfusion was reduced (23% to 9.8%, p < 0.001). There was a trend of a reduced rate of 30-day myocardial infarction (0.8% to 0.5%. p == 0 .2) and stroke (0.5% to 0.2%, p == 0.2). The 60-day deep vein thrombosis figures (0.8% to 0.6%, p == 0.5) and pulmonary embolism figures (1.2% to 1.1%, p == 0.9) were similar. Re-admission rate remained unchanged during the period of the study (4.7% to 4.8%, p == 0.8). Interpretation This large observational study of unselected consecutive hip and knee arthroplasty patients shows a substantial reduction in death rate, reduced length of stay, and reduced transfusion requirements after the introduction of a multimodal enhanced recovery protocol. [ABSTRACT FROM AUTHOR]

The article examines the effects of indexing using the average wage index (AWI) on the disability benefits offered by the U.S. Social Security Administration (SSA). The discusses the hypothesis of economists David Autor and Mark Duggan holding that the use of the AWI, combined with a widening distribution of income, have resulted to a rise in replacement rates for low-earner disability beneficiaries. It offers an analysis of the potential impact of using alternative ways of indexing on benefits, replacement rates and programs solvency.

Abstract: Cement mantle voids remain controversial with respect to survival of total hip arthroplasty. Void evolution is poorly understood, and attempts at void manipulation can only be empirical. We induced voids in a cement model simulating the constraints of the proximal femur. Intravoid pressure and temperature were recorded throughout polymerization, and the initial and final void volumes were measured. Temperature-dependent peak intravoid pressures and void volume increases were observed. After solidification, subatmospheric intravoid pressures were observed. The magnitude of these observations could not be explained by the ideal gas law. Partial pressures of the void gas at peak pressures demonstrated a dominant effect of gaseous monomer, thereby suggesting that void growth is a pressure-driven phenomenon resulting from temperature-dependent evaporation of monomer into existing trapped air voids. [Copyright &y& Elsevier]

The Swedish hip register found an increased risk of early revision of vacuum-mixed cemented total hip replacements. The influence of cement mixing technique on the dynamic volume change in polymerising PMMA is not well understood and may be relevant to this observation. Applying Archimedes' principle, we have investigated the dynamic volume changes in polymerising cement and determined the influence of mixing technique. All specimens showed an overall volume reduction: handmixed 3.4% and vacuum-mixed 6.0%. Regression analysis of sectional porosity and volume reduction showed a highly significant relationship. Hand-mixed porous cement showed a transient volume increase before solidification. However, vacuum mixed cement showed a progressive volume reduction throughout polymerisation. Transient expansion of porous cement occurs at the critical time of micro-interlock formation, possibly improving fixation. Conversely, progressive volume reduction of vacuum-mixed cement throughout the formation of interlock may damage fixation. Stable fixation of vacuum-mixed cement may depend on additional techniques to offset the altered volumetric behaviour of vacuum-mixed cement. [ABSTRACT FROM AUTHOR]

Represents a preliminary investigation of factors influencing the decision of disabled-worker beneficiaries to look for employment and return to work. Impact of vocational rehabilitation (VR), work incentives and employer workplace accommodations on the decision to work, job search methods and types of jobs looked for; Reasons why beneficiaries look for work.