Temporal progression of tau pathology and neuroinflammation in a rhesus monkey model of Alzheimer's disease.

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.

A novel tau-based rhesus monkey model of Alzheimer's pathogenesis.

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.

Intrastriatal alpha-synuclein fibrils in monkeys: spreading, imaging and neuropathological changes.

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.

Radiofrequency Microdebridement Versus Surgical Decompression for Achilles Tendinosis: A Randomized Controlled Trial.

Achilles tendinosis is primarily managed nonoperatively with activity modification and physiotherapy, although surgery can be required. This has classically involved surgical decompression of the Achilles tendon, although the use of radiofrequency microdebridement has been suggested as a novel minimally invasive alternative. We present a randomized controlled trial comparing radiofrequency microdebridement using the Topaz® microdebrider wand and traditional surgical decompression. All patients with Achilles tendinosis referred to a single surgeon and meeting the inclusion criteria were invited to participate in our single-blinded, randomized controlled study. The Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire and the visual analog scale were used as measures at baseline and 6 months postoperatively. From 2009 to 2014, 16 patients were randomized to traditional decompression treatment and 20 to Topaz® treatment. All surgical procedures were performed as day-case procedures with the patient under general anesthetic by a single surgeon. No significant differences were found between the groups in demographic data. At 6 months after intervention, both groups demonstrated an improvement in the Victorian Institute of Sports Assessment-Achilles and visual analog scale scores compared with baseline, with no difference found between treatment modalities at 6 months. The Topaz® microdebrider resulted in variable outcomes after surgery and is not without complications. Regarding the patient-reported outcome measures, Topaz® conferred no additional benefit compared with traditional surgical decompression and we have stopped using Topaz® in our treatment of Achilles tendinosis.

The effect of triclosan coated sutures on rate of surgical site infection after hip and knee replacement: a protocol for a double-blind randomised controlled trial.

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. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 17807356.

Reduced short-term complications and mortality following Enhanced Recovery primary hip and knee arthroplasty: results from 6,000 consecutive procedures.

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.

Which measure should be used to assess the patient's functional outcome after distal radius fracture?

The Disability of the Arm, Shoulder and Hand (DASH) and the Patient-Rated Wrist Evaluation (PRWE) scores appear most frequently in the literature when assessing functional outcome after distal radius fracture. We aimed to evaluate if the two questionnaires correlate. We reviewed 258 cases of adults who sustained a distal radius fracture over a one year period. At mean follow-up of 17 months the disability of the arm, shoulder and hand (DASH) and the patient-rated wrist evaluation (PRWE) scores were recorded. The outcome scores for each group were not statistically different (DASH p = 0.86, PRWE p = 0.80). The results of both questionnaires correlated strongly (Spearman's coefficient = 0.90). As the DASH score is potentially influenced by concomitant upper limb problems we suggest that the specific patient rated wrist evaluation (PRWE) be the sole instrument for assessing the functional outcome of distal radius fractures. This will reduce questionnaire fatigue and standardise the literature.

An open database of computed bulk ternary transition metal dichalcogenides.

We present a dataset of structural relaxations of bulk ternary transition metal dichalcogenides (TMDs) computed via plane-wave density functional theory (DFT). We examined combinations of up to two chalcogenides with seven transition metals from groups 4-6 in octahedral (1T) or trigonal prismatic (2H) coordination. The full dataset consists of 672 unique stoichiometries, with a total of 50,337 individual configurations generated during structural relaxation. Our motivations for building this dataset are (1) to develop a training set for the generation of machine and deep learning models and (2) to obtain structural minima over a range of stoichiometries to support future electronic analyses. We provide the dataset as individual VASP xml files as well as all configurations encountered during relaxations collated into an ASE database with the corresponding total energy and atomic forces. In this report, we discuss the dataset in more detail and highlight interesting structural and electronic features of the relaxed structures.

Reoperation and revision rates at ten years after 1,312 cemented Thompson's hemiarthroplasties : any need to change to a different implant?

AIMS: Despite multiple trials and case series on hip hemiarthroplasty designs, guidance is still lacking on which implant to use. One particularly deficient area is long-term outcomes. We present over 1,000 consecutive cemented Thompson's hemiarthroplasties over a ten-year period, recording all accessible patient and implant outcomes. METHODS: Patient identifiers for a consecutive cohort treated between 1 January 2003 and 31 December 2011 were linked to radiographs, surgical notes, clinic letters, and mortality data from a national dataset. This allowed charting of their postoperative course, complications, readmissions, returns to theatre, revisions, and deaths. We also identified all postoperative attendances at the Emergency and Outpatient Departments, and recorded any subsequent skeletal injuries. RESULTS: In total, 1,312 Thompson's hemiarthroplasties were analyzed (mean age at surgery 82.8 years); 125 complications were recorded, necessitating 82 returns to theatre. These included 14 patients undergoing aspiration or manipulation under anaesthesia, 68 reoperations (5.2%) for debridement and implant retention (n = 12), haematoma evacuation (n = 2), open reduction for dislocation (n = 1), fixation of periprosthetic fracture (n = 5), and 48 revised stems (3.7%), for infection (n = 13), dislocation (n = 12), aseptic loosening (n = 9), persistent pain (n = 6), periprosthetic fracture (n = 4), acetabular erosion (n = 3), and metastatic bone disease (n = 1). Their status at ten years is summarized as follows: 1,180 (89.9%) dead without revision, 34 (2.6%) dead having had revision, 84 (6.6%) alive with the stem unrevised, and 14 (1.1%) alive having had revision. Cumulative implant survivorship was 90.3% at ten years; patient survivorship was 7.4%. CONCLUSION: The Thompson's stem demonstrates very low rates of complications requiring reoperation and revision, up to ten years after the index procedure. Fewer than one in ten patients live for ten years after fracture. This study supports the use of a cemented Thompson's implant as a cost-effective option for frail hip fracture patients.Cite this article: Bone Jt Open 2022;3(9):710-715.

Enhanced recovery program for hip and knee replacement reduces death rate.

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.

Do orthopaedic surgeons practice what they preach?

Good medical practice predicates a contemporary knowledge of the literature. The British edition of the Journal of Bone and Joint Surgery (JBJS [Br]) is considered one of the leading orthopaedic journals. While seeking guidance on proposed changes to departmental policy, discussion with some high-profile units raised concerns regarding the implementation of their published clinical recommendations. We intended to contact the publishing departments, to establish their routine practice with respect to the topic on which they have written. We reviewed all articles published in JBJS (Br) between January 2005 and December 2006. Target papers were those that recommended a change in practice. The originating department was contacted by telephone and communication sought from an individual not directly involved in the publication, but on whom the change in practice would impact. Seventy-nine papers; representing the work of 87 separate hospitals from 22 different countries, were identified. We found that published articles were being followed in 56% of cases, 42% were not. Our study demonstrates that a large proportion of institutions making clinical recommendations are not practising them. Have we exposed a fundamental flaw in the publication of clinical research? In conclusion, we do practice what we preach… sometimes.

Latex-free gloves: safer for whom?

Increasing latex hypersensitivity among patients and health care workers has prompted the development of latex-free surgical gloves. Latex-free gloves must perform equally as the existing latex standard. We analyzed perforation rates in a clinical trial comparing latex and a latex-free alternative during primary hip and knee arthroplasty. The overall latex glove perforation rate was 8.4% compared with 21.6% for the latex-free alternative (chi(2) P < .001). The operation perforation rate for latex gloves was 34.4% compared with 80% for latex-free gloves (chi(2) P < .001). We suggest that the latex-free glove tested cannot provide a reliable barrier between the surgeon and the patient. As such, we question the safety of these gloves and the standards sets by the regulators.

Short-stretch inelastic compression bandage in knee swelling following total knee arthroplasty study (STICKS): study protocol for a randomised controlled feasibility study.

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. TRIAL REGISTRATION: The study was registered with Current Controlled Trials ( ISRCTN86903140 ) on 30 May 2013.

Pulmonary embolism following ankle fractures treated without an operation - an analysis using National Health Service data.

The majority of ankle fractures are stable and can be treated without an operation, most commonly with cast immobilisation. Based on concerns regarding the risk of a venous thromboembolic event (VTE) while immobilised, there is currently debate as to whether these patients should receive VTE prophylaxis for the duration of treatment. Rates of pulmonary embolism (PE) in this patient group are unknown. This retrospective cohort study was designed to identify patients treated without an operation for ankle fracture and determine the occurrence of PE and inpatient mortality within 90 days of injury using the English National Health Service administrative databases. Logistic regression models were used to assess the influence of age, gender and Charlson co-morbidity score on these outcomes. We identified 14777 adult patients over a 54-month period (April 2007-September 2011) that met our linkage and inclusion criteria (isolated, unilateral closed ankle fracture that did not require hospitalisation). Mean age was 46.4 years (range 18-99) and the majority had a Charlson 0 score (97.7%). There were 32 (0.22%) PEs within 90 days of the fracture (including in one patient who subsequently died). After adjustment, Charlson score of ≥1 was associated with a greater risk of PE (Odds ratio = 11.97, p < 0.001) compared to Charlson 0. Risk for these patients was 2.08%. In total, fifteen patients (0.11%) died in hospital within 90 days. Pulmonary embolism is rare following ankle fractures treated without an operation. Patients with multiple co-morbidities are at a higher risk. Based on this evidence, an ankle fracture treated without an operation does not appear to be an indication for routine VTE prophylaxis.

Femoral artery rupture during total hip arthroplasty.

Vascular injuries are an uncommon but significant complication of total hip arthroplasty. We present a case of femoral artery rupture through an atherosclerotic plaque during primary total hip arthroplasty and a review of the published literature. The early recognition and prompt treatment of this complication can reduce the mortality and morbidity associated with this injury.

Cemented versus cementless hemiarthroplasty for intracapsular neck of femur fracture--a comparison of 60,848 matched patients using national data.

National guidelines recommend cemented hemiarthroplasty for intracapsular fractured neck of femur (NOF), based on evidence of less pain, better mobility and lower costs. We aimed to compare complications following cemented and cementless implants, using the national hospital episode statistics (HES) database in England. Dislocation, revision, return to theatre and medical complications were extracted for all patients with NOF fracture who underwent hemiarthroplasty between January 2005 and December 2008. To make a 'like for like' comparison all 30,424 patients with a cementless implant were matched to 30,424 cemented implants (from a total of 42,838) in terms of age, sex and Charlson co-morbidity score. In the cementless group, 18-month revision (1.62% versus 0.57% (OR 2.90, p<0.001)), 4-year revision (2.45% versus 1.11% (OR 2.28, p<0.001)) and 30-day chest infection (8.14% versus 7.23% (OR 1.14, p=0.028)) were significantly higher. Four-year dislocation rate was higher in cemented implants (0.60% versus 0.26% (OR 0.45, p<0.001)). No significant differences were seen in return to theatre or other medical complications. In this national analysis of matched patients mid-term revision and perioperative chest infection was significantly higher in the cementless group. This supports the published evidence and national guidelines recommending cement fixation of hemiarthroplasty.

Cemented hemiarthroplasty or hip replacement for intracapsular neck of femur fracture? A comparison of 7732 matched patients using national data.

BACKGROUND: The treatment of choice for intracapsular neck of femur (NOF) fractures in younger, more active patients remains unknown. Some surgeons advocate total hip replacement (THR). AIM: This study aimed to compare complications following THR and hemiarthroplasty using the Hospital Episode Statistics (HES) database in England. METHOD: Dislocation and revision rates were extracted for all patients with NOF fracture who underwent either cemented hemiarthroplasty or cemented THR between January 2005 and December 2008. To make a 'like for like' comparison all 3866 THR patients were matched to 3866 hemiarthroplasty patients (from a total of 41,343) in terms of age, sex and Charlson score. RESULTS AND CONCLUSION: Eighteen-month dislocation was significantly higher in the THR group (2.4% vs. 0.5%, odds ratio (OR) 3.90 (2.99-5.05), p<0.001). This difference was sustained at the 4-year stage (2.9% vs. 0.9%, OR 3.18 (1.58-6.94), p=0.001) in a subset of patients with longer follow-up. There was no significant difference in revision rate up to 4 years (1.8% vs. 2.1%, OR 0.85 (0.46-1.55), p=0.666). In this national analysis of matched patients short- and medium-term dislocation rates following THR were significantly higher than following cemented hemiarthroplasty, without any difference in revision rates at 4 years. The low risk of dislocation may be acceptable in order to experience the apparent functional benefits of THR.

Wound complications following rivaroxaban administration: a multicenter comparison with low-molecular-weight heparins for thromboprophylaxis in lower limb arthroplasty.

BACKGROUND: The oral anticoagulant rivaroxaban is recommended for venous thromboembolic prophylaxis following lower limb arthroplasty. Concerns regarding high rates of wound complications following its use have prompted this multicenter comparison with low-molecular-weight heparins. METHODS: English hospital trusts that replaced a low-molecular-weight heparin with rivaroxaban for thromboprophylaxis in lower limb arthroplasty during 2009 were identified. Prospectively collected national data for these units were analyzed to determine the thirty-day rates of wound complications and major bleeding (cerebrovascular event or gastrointestinal hemorrhage) and the ninety-day rates of symptomatic deep venous thrombosis (proximal or distal), symptomatic pulmonary embolism, and all-cause inpatient mortality before and after the change to rivaroxaban. A total of 2762 patients prescribed rivaroxaban following knee or hip arthroplasty were compared with 10,361 patients prescribed a low- molecular weight heparin. Data were analyzed with use of odds ratios (ORs). RESULTS: There were significantly fewer wound complications in the low-molecular-weight heparin group (2.81% compared with 3.85%; OR = 0.72, 95% confidence interval [CI] = 0.58 to 0.90; p = 0.005). There were no significant differences between the low-molecular-weight heparin and rivaroxaban groups in the rates of pulmonary embolism (0.55% compared with 0.36%; OR = 1.52, 95% CI = 0.78 to 2.98), major bleeding (OR = 0.73, 95% CI = 0.48 to 1.12), or all-cause mortality (OR = 0.93, 95% CI = 0.46 to 1.89). There were significantly more symptomatic deep venous thromboses in the low-molecular-weight heparin group (0.91% compared with 0.36%; OR = 2.51, 95% CI = 1.31 to 4.84; p = 0.004). CONCLUSIONS: The rivaroxaban group had a higher wound complication rate and a lower deep venous thrombosis rate; there were no differences in symptomatic pulmonary embolism or all-cause mortality. Longer follow-up is needed to assess any potential relationship between wound complications and joint stiffness, latent infection, and limb consequences of deep venous thrombosis.

Climate change, dermatology and ecosystem services; trends and trade-offs.

Climate change is one of the defining issues for human well-being in the 21st century. As several dermatological diseases have a high sensitivity to climate and ecologic change, dermatologists will have an increasingly important role in public health affairs. The International Society of Dermatology's (ISD) establishment of a task force to track the impact of climate change on the incidence of dermatologic conditions is an example of scientific monitoring critical to future interdisciplinary adaptation and decision making to improve human well-being.

Dynamic void behavior in polymerizing polymethyl methacrylate cement.

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.