Exposure to viral and bacterial pathogens among Soay sheep (Ovis aries) of the St Kilda archipelago.

We assessed evidence of exposure to viruses and bacteria in an unmanaged and long-isolated population of Soay sheep (Ovis aries) inhabiting Hirta, in the St Kilda archipelago, 65 km west of Benbecula in the Outer Hebrides of Scotland. The sheep harbour many metazoan and protozoan parasites but their exposure to viral and bacterial pathogens is unknown. We tested for herpes viral DNA in leucocytes and found that 21 of 42 tested sheep were infected with ovine herpesvirus 2 (OHV-2). We also tested 750 plasma samples collected between 1997 and 2010 for evidence of exposure to seven other viral and bacterial agents common in domestic Scottish sheep. We found evidence of exposure to Leptospira spp., with overall seroprevalence of 6·5%. However, serological evidence indicated that the population had not been exposed to border disease, parainfluenza, maedi-visna, or orf viruses, nor to Chlamydia abortus. Some sheep tested positive for antibodies against Mycobacterium avium subsp. paratuberculosis (MAP) but, in the absence of retrospective faecal samples, the presence of this infection could not be confirmed. The roles of importation, the pathogen-host interaction, nematode co-infection and local transmission warrant future investigation, to elucidate the transmission ecology and fitness effects of the few viral and bacterial pathogens on Hirta.

Osteotomy around the knee: evolution, principles and results.

PURPOSE: This article summarises the history and evolution of osteotomy around the knee, examining the changes in principles, operative technique and results over three distinct periods: Historical (pre 1940), Modern Early Years (1940-2000) and Modern Later Years (2000-Present). We aim to place the technique in historical context and to demonstrate its evolution into a validated procedure with beneficial outcomes whose use can be justified for specific indications. MATERIALS AND METHODS: A thorough literature review was performed to identify the important steps in the development of osteotomy around the knee. RESULTS: The indications and surgical technique for knee osteotomy have never been standardised, and historically, the results were unpredictable and at times poor. These factors, combined with the success of knee arthroplasty from the 1980s onward, led to knee osteotomy being regarded as an irrelevant surgical option by many surgeons. Despite its fluctuating reputation, this article demonstrates the reasons for the enduring practice of osteotomy, not least because achieving the appropriate alignment is now recognised as the foundation step when planning any surgical intervention. CONCLUSIONS: With appropriate patient selection, accurate pre-operative planning, modern surgical fixation techniques and rapid rehabilitation, osteotomy around the knee is now an effective biological treatment for degenerative disease, deformity, knee instability and also as an adjunct to other complex joint surface and meniscal cartilage surgery. LEVEL OF EVIDENCE: V.

A tissue engineering strategy for the treatment of avascular necrosis of the femoral head.

BACKGROUND & PURPOSE: Skeletal stem cells (SSCs) and impaction bone grafting (IBG) can be combined to produce a mechanically stable living bone composite. This novel strategy has been translated to the treatment of avascular necrosis of the femoral head. Surgical technique, clinical follow-up and retrieval analysis data of this translational case series is presented. METHODS: SSCs and milled allograft were impacted into necrotic bone in five femoral heads of four patients. Cell viability was confirmed by parallel in vitro culture of the cell-graft constructs. Patient follow-up was by serial clinical and radiological examination. Tissue engineered bone was retrieved from two retrieved femoral heads and was analysed by histology, microcomputed tomography (µCT) and mechanical testing. RESULTS: Three patients remain asymptomatic at 22- to 44-month follow-up. One patient (both hips) required total hip replacement due to widespread residual necrosis. Retrieved tissue engineered bone demonstrated a mature trabecular micro-architecture histologically and on µCT. Bone density and axial compression strength were comparable to trabecular bone. CONCLUSIONS: Clinical follow-up shows this to be an effective new treatment for focal early stage avascular necrosis of the femoral head. Unique retrieval analysis of clinically translated tissue engineered bone has demonstrated regeneration of tissue that is both structurally and functionally analogous to normal trabecular bone.

Superspreading and the effect of individual variation on disease emergence.

Population-level analyses often use average quantities to describe heterogeneous systems, particularly when variation does not arise from identifiable groups. A prominent example, central to our current understanding of epidemic spread, is the basic reproductive number, R(0), which is defined as the mean number of infections caused by an infected individual in a susceptible population. Population estimates of R(0) can obscure considerable individual variation in infectiousness, as highlighted during the global emergence of severe acute respiratory syndrome (SARS) by numerous 'superspreading events' in which certain individuals infected unusually large numbers of secondary cases. For diseases transmitted by non-sexual direct contacts, such as SARS or smallpox, individual variation is difficult to measure empirically, and thus its importance for outbreak dynamics has been unclear. Here we present an integrated theoretical and statistical analysis of the influence of individual variation in infectiousness on disease emergence. Using contact tracing data from eight directly transmitted diseases, we show that the distribution of individual infectiousness around R(0) is often highly skewed. Model predictions accounting for this variation differ sharply from average-based approaches, with disease extinction more likely and outbreaks rarer but more explosive. Using these models, we explore implications for outbreak control, showing that individual-specific control measures outperform population-wide measures. Moreover, the dramatic improvements achieved through targeted control policies emphasize the need to identify predictive correlates of higher infectiousness. Our findings indicate that superspreading is a normal feature of disease spread, and to frame ongoing discussion we propose a rigorous definition for superspreading events and a method to predict their frequency.

Gender and acute myocardial infarction: is there a different response to thrombolysis?

OBJECTIVES: This study sought to 1) determine the effect of gender on early and late infarct-related artery patency and reocclusion after thrombolytic therapy for acute myocardial infarction; 2) examine the effect of gender on left ventricular function in response to injury/reperfusion; and 3) assess the independent contribution of gender to early (30-day) mortality after acute myocardial infarction. BACKGROUND: Women have a higher mortality rate than men after myocardial infarction. However, the effect of gender on infarct-related coronary artery patency and left ventricular response to injury/reperfusion have not been fully defined in the thrombolytic era. METHODS: Patency rates and global and regional left ventricular function were determined in patients at 90 min and 5 to 7 days after thrombolytic therapy for acute myocardial infarction. The effect of gender on infarct-related artery patency and left ventricular function was determined. Thirty-day mortality differences between women and men were compared. RESULTS: Women were significantly older and had more hypertension, diabetes, hypercholesterolemia, heart failure and shock. They were less likely to have had a previous myocardial infarction, history of smoking or previous bypass surgery. Ninety-minute patency rates (Thrombolysis in Myocardial Infarction [TIMI] flow grade 3) in women and men were 39% and 38%, respectively (p = 0.5). Reocclusion rates were 8.7% in women versus 5.1% in men (p = 0.14). Women had more recurrent ischemia than men (21.4% vs. 17.0%, respectively, p = 0.01). Ninety-minute ejection fraction and regional ventricular function were clinically similar in women and men with TIMI 2 or 3 flow (ejection fraction [mean +/- SD]: 63.4 +/- 6% vs. 59.4 +/- 0.7%, p = 0.02; number of chords: 21.4 +/- 0.9 vs. 21.0 +/- 1.9, p = 0.7; SD/chord: -2.4 +/- 08 vs. -2.4 +/- 0.2, p = 0.9, respectively). No clinically significant differences in left ventricular function were noted at 5- to 7-day follow-up. Women had a greater hyperkinetic response than men in the noninfarct zone (SD/chord: 2.4 +/- 0.2 vs. 1.7 +/- 0.1, p = 0.005). The 30-day mortality rate was 13.1% in women versus 4.8% in men (p < or = 0.0001). After adjustment for other clinical and angiographic variables, gender remained an independent determinant of 30-day mortality. CONCLUSIONS: Women do not differ significantly from men with regard to either early infarct-related artery patency rates or reocclusion after thrombolytic therapy or ventricular functional response to injury/reperfusion. Gender was an independent determinant of 30-day mortality after acute myocardial infarction.

Projected changes in mineral soil carbon of European croplands and grasslands, 1990-2080.

We present the most comprehensive pan-European assessment of future changes in cropland and grassland soil organic carbon (SOC) stocks to date, using a dedicated process-based SOC model and state-of-the-art databases of soil, climate change, land-use change and technology change. Soil carbon change was calculated using the Rothamsted carbon model on a European 10 × 10' grid using climate data from four global climate models implementing four Intergovernmental Panel on Climate Change (IPCC) emissions scenarios (SRES). Changes in net primary production (NPP) were calculated by the Lund-Potsdam-Jena model. Land-use change scenarios, interpreted from the narratives of the IPCC SRES story lines, were used to project changes in cropland and grassland areas. Projections for 1990-2080 are presented for mineral soil only. Climate effects (soil temperature and moisture) will tend to speed decomposition and cause soil carbon stocks to decrease, whereas increases in carbon input because of increasing NPP will slow the loss. Technological improvement may further increase carbon inputs to the soil. Changes in cropland and grassland areas will further affect the total soil carbon stock of European croplands and grasslands. While climate change will be a key driver of change in soil carbon over the 21st Century, changes in technology and land-use change are estimated to have very significant effects. When incorporating all factors, cropland and grassland soils show a small increase in soil carbon on a per area basis under future climate (1-7 t C ha-1 for cropland and 3-6 t C ha-1 for grassland), but when the greatly decreasing area of cropland and grassland are accounted for, total European cropland stocks decline in all scenarios, and grassland stocks decline in all but one scenario. Different trends are seen in different regions. For Europe (the EU25 plus Norway and Switzerland), the cropland SOC stock decreases from 11 Pg in 1990 by 4-6 Pg (39-54%) by 2080, and the grassland SOC stock increases from 6 Pg in 1990 to 1.5 Pg (25%) under the B1 scenario, but decreases to 1-3 Pg (20-44%) under the other scenarios. Uncertainty associated with the land-use and technology scenarios remains unquantified, but worst-case quantified uncertainties are 22.5% for croplands and 16% for grasslands, equivalent to potential errors of 2.5 and 1 Pg SOC, respectively. This is equivalent to 42-63% of the predicted SOC stock change for croplands and 33-100% of the predicted SOC stock change for grasslands. Implications for accounting for SOC changes under the Kyoto Protocol are discussed.

Five challenges in evolution and infectious diseases.

Evolution is a key aspect of the biology of many pathogens, driving processes ranging from immune escape to changes in virulence. Because evolution is inherently subject to feedbacks, and because pathogen evolution plays out at scales ranging from within-host to between-host and beyond, evolutionary questions provide special challenges to the modelling community. In this article, we provide an overview of five challenges in modelling the evolution of pathogens and their hosts, and point to areas for development, focussing in particular on the issue of linking theory and data.

Falling through the cracks: rehabilitation services for adults with learning disabilities.

The present study investigated the knowledge and perceptions of vocational rehabilitation (VR) of adults with learning disabilities (LD), as well as control variables which describe adults with LD and may have a bearing on access to VR services. This was accomplished by (1) determining the knowledge adults with LD had of their rights under federal rehabilitation regulations; (2) examining demographic control variables (e.g., sex, age, education level, hometown population, employment history, and income), which may have a bearing on the need for or access to VR services by adults with LD; and (3) examining experiences/perceptions of adults with LD regarding the VR application/eligibility process. A pretested questionnaire appeared in the January 1989 ACLD Newsbriefs. Findings indicate that while there was a group of respondents who were satisfied with the rehabilitation services they had received, there was also a large group of respondents who were either ineligible for rehabilitation services or dissatisfied with services they received. Generally, respondents' knowledge of VR was limited.

Continuing education needs assessment in dentistry: the SNAP system.

Needs assessment has become an integral step in planning for continuing education. This article describes a computer-based needs assessment system that has been used successfully in planning continuing dental education in South Carolina. The Statewide Needs Assessment Program (SNAP) provides a general purpose system for collecting and analyzing continuing education needs data for large populations. Needs assessment data from 489 practicing dentists in South Carolina are presented and analyzed.

Differences in perceptions of managerial roles by gender among southern business students.

Perception of the roles necessary for managerial success based on the 10 verbal descriptors of the Mintzberg roles were gathered from 128 business students at a southern U.S. university. The objective was to assess whether these 72 men and 56 women viewed the importance of the roles differently. Ratings were collected on the 10 roles for each of four different types of managers. The data were analyzed by one-way analysis of variance, chi-squared analysis, and Spearman rank-order correlation. No differences were observed in the perception of men and women in these roles or of their relative importance.

Tantalum trabecular metal - addition of human skeletal cells to enhance bone implant interface strength and clinical application.

The osteo-regenerative properties of allograft have recently been enhanced by addition of autogenous human bone marrow stromal cells (HBMSCs). Limitations in the use of allograft have prompted the investigation of tantalum trabecular metal (TTM) as a potential alternative. TTM is already in widespread orthopaedic use, although in applications where there is poor initial stability, or when TTM is used in conjunction with bone grafting, initial implant loading may need to be limited. The aim of this study was to evaluate the osteo-regenerative potential of TTM with HBMSCs, in direct comparison to human allograft and autograft. HBMSCs were cultured on blocks of TTM, allograft or autograft in basal and osteogenic media. Molecular profiling, confocal and scanning electron microscopy (SEM) and biochemical assays were used to characterize cell adherence, proliferation and phenotype. Mechanical testing was used to define the tensile characteristics of the constructs. HBMSCs displayed adherence and proliferation throughout TTM, evidenced by immunocytochemistry and SEM, with significant cellular ingrowth and matrix production through TTM. In contrast to cells cultured with allograft, cell proliferation assays showed significantly higher activity with TTM (p < 0.001), although molecular profiling confirmed no significant difference in expression of osteogenic genes. In contrast to acellular constructs, mechanical testing of cell-TTM constructs showed enhanced tensile characteristics, which compared favourably to cell-allograft constructs. These studies demonstrated the ability of TTM to support HBMSC growth and osteogenic differentiation comparable to allograft. Thus, TTM represents an alternative to allograft for osteo-regenerative strategies, extending its clinical applications as a substitute for allograft.

From bench to clinic and back: skeletal stem cells and impaction bone grafting for regeneration of bone defects.

Tissue engineering offers enormous potential for bone regeneration. Despite extensive in vitro and in vivo work, few strategies translate into clinical practice. This paper describes the combination of skeletal stem cells (SSCs) and impaction bone grafting (IBG) for the treatment of patients with bone defects associated with avascular necrosis of the femoral head. SSCs and milled allograft were impacted into necrotic bone in the femoral heads of four patients. Three patients remained asymptomatic at 22-44 month follow-up, but one patient has required total hip replacement (both hips). This has allowed retrieval of the femoral heads, which were analysed structurally and functionally by µCT, histology and mechanical testing. A central channel of impacted bone was found in the femoral heads, which displayed a mature trabecular micro-architecture. The impacted bone was denser than the surrounding trabecular bone, as strong in compression and with histological micro-architecture comparable to that of trabecular bone. Analysis of the retrieved femoral head samples has demonstrated that this tissue-engineering strategy regenerates bone that is both structurally and functionally analogous to normal trabecular bone. SSCs, together with IBG, have proved an effective treatment for avascular necrosis of the femoral head and offer significant potential for the broader spectrum of bone defects.

A comparison of polymer and polymer-hydroxyapatite composite tissue engineered scaffolds for use in bone regeneration. An in vitro and in vivo study.

Previous in vitro work demonstrated porous PLA and PLGA both had the mechanical strength and sustained the excellent skeletal stem cell (SSC) growth required of an osteogenic bonegraft substitute, for use in impaction bone grafting. The purpose of this investigation was to assess the effects of the addition of hydroxyapatite (HA) to the scaffolds before clinical translation. PLA, PLA+10% HA, PLGA, and PLGA+10% HA were milled and impacted into discs before undergoing a standardized shear test. Cellular compatibility analysis followed 14 days incubation with human skeletal stems cells (SSC). The best two performing polymers were taken forward for in vivo analysis. SSC seeded polymer discs were implanted subcutaneously in mice. All polymers had superior mechanical shear strength compared with allograft (p < 0.01). Excellent SSC survival was demonstrated on all polymers, but the PLA polymers showed enhanced osteoblastic activity (ALP assay p < 0.01) and collagen-1 formation. In vivo analysis was performed on PLA and PLA+10% HA. MicroCT analysis revealed increased bone formation on the PLA HA (p < 0.01), and excellent neo-vessel formation in both samples. Histology confirmed evidence of de novo bone formation. PLA HA showed both enhanced osteoinductive and osteogenic capacity. This polymer composite has been selected for scaled-up experimentation before clinical translation.

Force-sensitive detents improve user performance for linear selection tasks.

Haptic technology, providing force cues and creating a programmable interface, can assist users in more accurately using an interface. This paper investigates haptic assistance in combination with auditory feedback instead of visual feedback. A user test is carried out in which participants select fundamental frequencies from a continuous range to play brief musical melodies. Two control conditions are compared with two detent-based haptic assistance conditions. The detents gently guide the users toward locations of equal tempered fundamental frequencies. Results from the user test confirm improved accuracy brought about by the detents. It is further helpful to provide regulation of the strength of haptic assistance in real time, allowing the user to remain always in control. This concept motivated the force-sensitive detent condition, which enables the user to adjust the strength of the haptic assistance in real time by changing the downward force applied to the haptic device. The work implies that users of graphical user interfaces could similarly benefit from force-sensitive detents and more generally real-time regulation of the strength of haptic assistance.

Comparing methods for estimating R0 from the size distribution of subcritical transmission chains.

Many diseases exhibit subcritical transmission (i.e. 0

Translational hurdles for tissue engineering: an in vitro analysis of commonly used local anaesthetics on skeletal stem cell survival.

When transferring tissue regenerative strategies involving skeletal stem cells to human application, consideration needs to be given to factors that may affect the function of the cells that are transferred. Local anaesthetics are frequently used during surgical procedures, either administered directly into the operative site or infiltrated subcutaneously around the wound. The aim of this study was to investigate the effects of commonly used local anaesthetics on the morphology, function and survival of human adult skeletal stem cells. Cells from three patients who were undergoing elective hip replacement were harvested and incubated for two hours with 1% lidocaine, 0.5% levobupivacaine or 0.5% bupivacaine hydrochloride solutions. Viability was quantified using WST-1 and DNA assays. Viability and morphology were further characterised using CellTracker Green/Ethidium Homodimer-1 immunocytochemistry and function was assessed by an alkaline phosphatase assay. An additional group was cultured for a further seven days to allow potential recovery of the cells after removal of the local anaesthetic. A statistically significant and dose dependent reduction in cell viability and number was observed in the cell cultures exposed to all three local anaesthetics at concentrations of 25% and 50%, and this was maintained even following culture for a further seven days. This study indicates that certain local anaesthetic agents in widespread clinical use are deleterious to skeletal progenitor cells when studied in vitro; this might have relevance in clinical applications.

Supercritical CO2 fluid-foaming of polymers to increase porosity: a method to improve the mechanical and biocompatibility characteristics for use as a potential alternative to allografts in impaction bone grafting?

Disease transmission, availability and cost of allografts have resulted in significant efforts to find an alternative for use in impaction bone grafting (IBG). Recent studies identified two polymers with both structural strength and biocompatibility characteristics as potential replacements. The aim of this study was to assess whether increasing the polymer porosity further enhanced the mechanical and cellular compatibility characteristics for use as an osteogenic biomaterial alternative to allografts in IBG. Solid and porous poly(DL-lactide) (P(DL)LA) and poly(DL-lactide-co-glycolide) (P(DL)LGA) scaffolds were produced via melt processing and supercritical CO(2) foaming, and the differences characterized using scanning electron microscopy (SEM). Mechanical testing included milling and impaction, with comparisons made using a shear testing rig as well as a novel agitation test for cohesion. Cellular compatibility tests for cell number, viability, and osteogenic differentiation using WST-1 assays, fluorostaining, and ALP assays were determined following 14 day culture with skeletal stem cells. SEM showed excellent porosity throughout both of the supercritical-foam-produced polymer scaffolds, with pores between 50 and 200 µm. Shear testing showed that the porous polymers exceeded the shear strength of allograft controls (P<0.001). Agitation testing showed greater cohesion between the particles of the porous polymers (P<0.05). Cellular studies showed increased cell number, viability, and osteogenic differentiation on the porous polymers compared to solid block polymers (P<0.05). The use of supercritical CO(2) to generate porous polymeric biodegradable scaffolds significantly improves the cellular compatibility and cohesion observed compared to non-porous counterparts, without substantial loss of mechanical shear strength. These improved characteristics are critical for clinical translation as a potential osteogenic composite for use in IBG.