Systems genetics uncover new loci containing functional gene candidates in Mycobacterium tuberculosis-infected Diversity Outbred mice.

Mycobacterium tuberculosis, the bacillus that causes tuberculosis (TB), infects 2 billion people across the globe, and results in 8-9 million new TB cases and 1-1.5 million deaths each year. Most patients have no known genetic basis that predisposes them to disease. We investigated the complex genetic basis of pulmonary TB by modelling human genetic diversity with the Diversity Outbred mouse population. When infected with M. tuberculosis, one-third develop early onset, rapidly progressive, necrotizing granulomas and succumb within 60 days. The remaining develop non-necrotizing granulomas and survive longer than 60 days. Genetic mapping using clinical indicators of disease, granuloma histopathological features, and immune response traits identified five new loci on mouse chromosomes 1, 2, 4, 16 and three previously identified loci on chromosomes 3 and 17. Quantitative trait loci (QTLs) on chromosomes 1, 16, and 17, associated with multiple correlated traits and had similar patterns of allele effects, suggesting these QTLs contain important genetic regulators of responses to M. tuberculosis. To narrow the list of candidate genes in QTLs, we used a machine learning strategy that integrated gene expression signatures from lungs of M. tuberculosis-infected Diversity Outbred mice with gene interaction networks, generating functional scores. The scores were then used to rank candidates for each mapped trait in each locus, resulting in 11 candidates: Ncf2, Fam20b, S100a8, S100a9, Itgb5, Fstl1, Zbtb20, Ddr1, Ier3, Vegfa, and Zfp318. Importantly, all 11 candidates have roles in infection, inflammation, cell migration, extracellular matrix remodeling, or intracellular signaling. Further, all candidates contain single nucleotide polymorphisms (SNPs), and some but not all SNPs were predicted to have deleterious consequences on protein functions. Multiple methods were used for validation including (i) a statistical method that showed Diversity Outbred mice carrying PWH/PhJ alleles on chromosome 17 QTL have shorter survival; (ii) quantification of S100A8 protein levels, confirming predicted allele effects; and (iii) infection of C57BL/6 mice deficient for the S100a8 gene. Overall, this work demonstrates that systems genetics using Diversity Outbred mice can identify new (and known) QTLs and new functionally relevant gene candidates that may be major regulators of granuloma necrosis and acute inflammation in pulmonary TB.

3D printed porous PEEK created via fused filament fabrication for osteoconductive orthopaedic surfaces.

Due to its unique and advantageous material properties, polyetheretherketone (PEEK) is an attractive biomaterial for implantable devices. Though concerns exist regarding PEEK for orthopaedic implants due to its bioinertness, the creation of porous networks has shown promising results for interaction with surrounding tissue. In this study, we created porous PEEK via clinically-available fused filament fabrication (FFF, 3D printing) and assessed the pore structure morphology, mechanical properties, and biologic response. The designs of the porous structures were based on a simple rectilinear pattern as well as triply periodic minimal surfaces (TPMS), specifically gyroid and diamond types. The material characteristics, including porosity, yield strength, and roughness, were evaluated using µCT, static compression testing, and optical profilometry. The porous PEEK, along with 3D printed solid PEEK, was then seeded with MC3T3-E1 preosteoblast cells for evaluation of cell proliferation and alkaline phosphatase (ALP) activity. The samples were then imaged via scanning electron microscopy (SEM) to observe cell morphology. µCT imaging showed the porous networks to be open and interconnected, with porous sizes similar (p > 0.05) to the as-designed size of 600 µm. Average compressive properties ranged from 210 to 268 MPa for elastic modulus and 6.6-17.1 MPa for yield strength, with strength being greatest for TPMS constructs. SEM imaging revealed cells attaching to and bridging micro-topological features of the porous constructs, and cell activity was significantly greater for the porous PEEK compared to solid at multiple time points.

Incremental clinical and economic burden of suspected respiratory infections due to multi-drug-resistant Pseudomonas aeruginosa in the United States.

BACKGROUND: Multi-drug resistant (MDR) Pseudomonas aeruginosa can negatively affect patients and hospitals. AIM: To evaluate excess mortality and cost burden among patients hospitalized with suspected respiratory infections due to MDR P. aeruginosa vs patients with non-MDR P. aeruginosa in 78 United States (US) hospitals. METHODS: This study analyzed electronically captured microbiological and outcomes data of patients hospitalized with non-duplicate P. aeruginosa isolates from respiratory sources collected ≥3 days after admission to identify hospital-onset MDR or non-MDR P. aeruginosa per the Centers for Disease Control and Prevention definition. The risk of multi-drug resistance was estimated on mortality, length of stay (LOS), cost, operation gain/loss, and 30-day readmission. A sensitivity analysis was conducted utilizing a cohort with pharmacy data available. FINDINGS: Of 523 MDR and 1381 non-MDR P. aeruginosa cases, unadjusted mortality was 23.7% vs 18.0% and multi-variable-adjusted mortality was 20.0% (95% confidence interval (CI): 14.3-27.2%) vs 15.5% (95% CI: 11.2-20.9%; P=0.026), the average adjusted excess LOS was 6.7 days (P<0.001); excess cost per case was US$22,370 higher (P=0.002) and operational loss per case was US$10,661 (P=0.024) greater, and the multi-variable adjusted readmission rate was 16.2% (95% CI: 11.2-22.9%) vs 11.1% (95% CI: 7.8-15.6%; P=0.006). The sensitivity analysis yielded similar results. CONCLUSIONS: Compared with suspected infections due to non-MDR P. aeruginosa, patients with MDR P. aeruginosa had higher risk of mortality, readmission, and longer LOS, as well as US$20,000 incremental cost and >US$10,000 incremental net loss per case after controlling for patient and hospital characteristics.

Calf care personnel on dairy farms and their educational opportunities.

As dairy herd sizes become larger and the organization of the business more complex, targeting communication and education to enhance animal care becomes more difficult. The purpose of this study was to describe selected demographics of calf care employees on large (>500 animals) and small (<501 animals) dairy farms that raise their own calves. Two to 8 individuals per farm involved with calf care, including owners, veterinarians, and calf managers, feeders, and treaters, were interviewed in either English or Spanish. Interviews were conducted in person on 53 dairy farms located in Arizona, Idaho, New York, Oregon, and Washington State. The number of preweaned calves on the farm ranged from 9 to 1,500 (median = 93). A total of 224 individuals were interviewed across 8 job titles. As farm size increased, personnel structure became more complex. Farms with >100 preweaned calves were 15 times more likely to have a calf manager title compared with farms with ≤100 preweaned calves. Eight farms designated the same person as calf manager, treater, and feeder, all with ≤100 preweaned calves. Thirty-two (60%) of the farms had at least 1 full-time calf feeder. Almost 30% of owners and over 40% of veterinarians interviewed were over 50 yr of age, whereas over 40% of the calf managers, feeders, and treaters were under 30 yr of age. Seventy-three percent of feeders and 72% of treaters spoke Spanish at home. For languages in which interviewees were comfortable speaking, more than 30% of owners and 33% of veterinarians were comfortable communicating in Spanish. For calf care employees, 60% of calf managers, 42% of feeders, and 38% of treaters were bilingual (English and Spanish), but most (72%) preferred to be interviewed in Spanish. The level of education varied by job title for those interviewed, but most of the calf care team had high school or less education. However, some diversity was observed in educational background within job title with almost 38% of the calf managers having at least some college education. The majority of feeders (88%) and treaters (83%) reported being trained by another employee and 66 and 58%, respectively, had not received any continuing education in the previous year. With the amount of diversity seen on these farms, understanding employees' educational backgrounds, language, and generational differences may be valuable when developing training for new procedures for animal health or other aspects of animal care.

In vivo compatibility of Dynesys(®) spinal implants: a case series of five retrieved periprosthetic tissue samples and corresponding implants.

PURPOSE: To determine whether particulate debris is present in periprosthetic tissue from revised Dynesys(®) devices, and if present, elicits a biological tissue reaction. METHODS: Five Dynesys(®) dynamic stabilization systems consisting of pedicle screws (Ti alloy), polycarbonate-urethane (PCU) spacers and a polyethylene-terephthalate (PET) cord were explanted for pain and screw loosening after a mean of 2.86 years (1.9-5.3 years). Optical microscopy and scanning electron microscopy were used to evaluate wear, deformation and surface damage, and attenuated total reflectance Fourier transform infrared spectroscopy to assess surface chemical composition of the spacers. Periprosthetic tissue morphology and wear debris were determined using light microscopy, and PCU and PET wear debris by polarized light microscopy. RESULTS: All implants had surface damage on the PCU spacers consistent with scratches and plastic deformation; 3 of 5 exhibited abrasive wear zones. In addition to fraying of the outer fibers of the PET cords in five implants, one case also evidenced cord fracture. The pedicle screws were unremarkable. Patient periprosthetic tissues around the three implants with visible PCU damage contained wear debris and a corresponding macrophage infiltration. For the patient revised for cord fracture, the tissues also contained large wear particles (>10 µm) and giant cells. Tissues from the other two patients showed comparable morphologies consisting of dense fibrous tissue with no inflammation or wear debris. CONCLUSIONS: This is the first study to evaluate wear accumulation and local tissue responses for explanted Dynesys(®) devices. Polymer wear debris and an associated foreign-body macrophage response were observed in three of five cases.

Evaluation of carbon nanotubes and graphene as reinforcements for UHMWPE-based composites in arthroplastic applications: A review.

In this review we have evaluated the state of the art of CNT/UHMWPE and graphene/UHMWPE composites from four different points of view: mechanical properties, chemical stability, wear resistance and biocompatibility. The performance of these new carbonaceous composites allows us to conclude that these materials have overcome a first step on the way to developing into an alternative to the current HXLPEs used in orthopedic applications.

Factors influencing return to work after hip and knee replacement.

BACKGROUND: Return to employment is one of the key goals of joint replacement surgery in the working-age population. There is limited quantitative and qualitative research focusing on return to work after hip and knee replacement. It remains unclear why certain groups of patients are not able to achieve sufficient functional improvement to allow productive return to work while others can. Very little is known about the individual patient and employer perspectives in this regard. AIMS: To review current evidence for the factors influencing employment outcomes in patients undergoing hip and knee replacement. METHODS: Original articles and reviews in Medline, Embase and PsycINFO from 1987 to 2013 were included in the analysis. RESULTS: Age, patient motivation, employment before surgery and type of job were found to be important factors in determining return to work following hip and knee replacement. CONCLUSIONS: There is a need for further qualitative work on how and why these factors influence employment outcomes.

Advances in tribological testing of artificial joint biomaterials using multidirectional pin-on-disk testers.

The introduction of numerous formulations of Ultra-high molecular weight polyethylene (UHMWPE), which is widely used as a bearing material in orthopedic implants, necessitated screening of bearing couples to identify promising iterations for expensive joint simulations. Pin-on-disk (POD) testers capable of multidirectional sliding can correctly rank formulations of UHMWPE with respect to their predictive in vivo wear behavior. However, there are still uncertainties regarding POD test parameters for facilitating clinically relevant wear mechanisms of UHMWPE. Studies on the development of POD testing were briefly summarized. We systematically reviewed wear rate data of UHMWPE generated by POD testers. To determine if POD testing was capable of correctly ranking bearings and if test parameters outlined in ASTM F732 enabled differentiation between wear behavior of various formulations, mean wear rates of non-irradiated, conventional (25-50kGy) and highly crosslinked (≥90kGy) UHMWPE were grouped and compared. The mean wear rates of non-irradiated, conventional and highly crosslinked UHMWPEs were 7.03, 5.39 and 0.67mm(3)/MC. Based on studies that complied with the guidelines of ASTM F732, the mean wear rates of non-irradiated, conventional and highly crosslinked UHMWPEs were 0.32, 0.21 and 0.04mm(3)/km, respectively. In both sets of results, the mean wear rate of highly crosslinked UHMPWE was smaller than both conventional and non-irradiated UHMWPEs (p<0.05). Thus, POD testers can compare highly crosslinked and conventional UHMWPEs despite different test parameters. Narrowing the allowable range for standardized test parameters could improve sensitivity of multi-axial testers in correctly ranking materials.

In-vivo degradation of poly(carbonate-urethane) based spine implants.

Fourteen explanted Dynesys® spinal devices were analyzed for biostability and compared with a reference, never implanted, control. Both poly(carbonate-urethane) (PCU) spacers and polyethylene-terephthalate (PET) cords were analyzed. The effect of implantation was evaluated through the observation of physical alterations of the device surfaces, evaluation of the chemical degradation and fluids absorption on the devices and examination of the morphological and mechanical features. PCU spacers exhibited a variety of surface damage mechanisms, the most significant being abrasion and localized, microscopic surface cracks. Evidence of oxidation and chain scission were detected on PCU spacers ATR-FTIR. ATR-FTIR, DSC and hardness measurements also showed a slight heterogeneity in the composition of PCU. The extraction carried out on the PCU spacers revealed the presence of extractable polycarbonate segments. One spacer and all PET cords visually exhibited the presence of adherent biological material (proteins), confirmed by the ATR-FTIR results. GC/MS analyses of the extracts from PET cords revealed the presence of biological fluids residues, mainly cholesterol derivatives and fatty acids, probably trapped into the fiber network. No further chemical alterations were observed on the PET cords. Although the observed physical and chemical damage can be considered superficial, greater attention must be paid to the chemical degradation mechanisms of PCU and to the effect of byproducts on the body.

Evaluation of friction properties of hydrogels based on a biphasic cartilage model.

Characterizing hydrogels using a biphasic cartilage model, which can predict their behavior based on structural properties, such as permeability and aggregate modulus, may be useful for comparing active lubrication modes of cartilage and hydrogels for the design of articular cartilage implants. The effects of interstitial fluid pressurization, inherent matrix viscoelasticity and tension-compression nonlinearity on mechanical properties of the biphasic material were evaluated by linear biphasic (KLM), biphasic poroviscoelastic (BPVE) and linear biphasic with anisotropy cartilage models, respectively. The BPVE model yielded the lowest root mean square error and highest coefficient of determination when predicting confined and unconfined compression stress-relaxation response of hydrogels (n=15): 0.220±0.316MPa and 0.93±0.08; and 0.017±0.008MPa and 0.98±0.01 respectively. Since the differences in error between models were not statistically significant, the simplest model we considered, KLM model, was sufficient to predict the mechanical response of this family of hydrogels. The coefficient of friction (COF) of a hydrogel-ceramic articulation was measured at varying loads and pressures to explore the full range of lubrication behavior of hydrogel. Material parameters obtained by biphasic models correlated with COF. Based on the linear biphasic model, COF correlated positively with aggregate modulus (spearman's rho=0.5; p<0.001) and velocity (rho=0.3; p<0.001), and negatively with permeability (rho=-0.3; p<0.001) and load (rho=-0.6; p<0.001). Negative correlation of COF with load and positive correlation with velocity indicated that hydrogel-ceramic articulation was separated by a fluid film. These results together suggested that interstitial fluid pressurization was dominant in the viscoelasticity and lubrication properties of this biphasic material.

Life expectancy following diagnosis of a vertebral compression fracture.

SUMMARY: The life expectancy of vertebral compression fracture (VCF) patients was evaluated as a function of their treatment. Compared to non-operated patients, the kyphoplasty and vertebroplasty patient cohort had 115% and 44% greater adjusted life expectancy, respectively. Kyphoplasty patients had a 34% greater adjusted life expectancy than vertebroplasty patients. INTRODUCTION: Balloon kyphoplasty and vertebroplasty are minimally invasive procedures for the treatment of painful VCFs. This comparative effectiveness study characterized the life expectancy of VCF patients as a function of their treatment. METHODS: Life expectancy of VCF patients in the 100% U.S. Medicare dataset (2005-2008) was estimated using a parametric Weibull survival model (adjusted for comorbidities), and compared between operated and non-operated patients as well as between kyphoplasty and vertebroplasty patients. A total of 858,978 patients with a newly diagnosed VCF were identified, including 119,253 kyphoplasty patients (13.9%) and 63,693 vertebroplasty patients (7.4%). RESULTS: Adjusted life expectancy was 85% greater for operated than non-operated patients (p < 0.001; 95% confidence interval: 82-89%). Compared to non-operated patients, the kyphoplasty and vertebroplasty patient cohort had 115% (p < 0.001; 95% confidence interval: 111-119%) and 44% (p < 0.001; 95% confidence interval: 42-47%) greater adjusted life expectancy, respectively. Kyphoplasty patients had a 34% greater adjusted life expectancy than vertebroplasty patients (p < 0.001; 95% confidence interval: 31-36%). Across all gender-age groups, the median life expectancy predicted by the parametric Weibull model was 2.2-7.3 years greater for operated than non-operated patients. CONCLUSIONS: Statistically significant and substantial differences in life expectancy were observed between the treated and non-treated cohorts in the Medicare population. Among the treated cohorts, patients in the vertebroplasty group experienced less of a survival benefit than those who received kyphoplasty. The results will be a useful basis for future cost effectiveness studies of VCF treatments for the Medicare population.

Two-year cost comparison of vertebroplasty and kyphoplasty for the treatment of vertebral compression fractures: are initial surgical costs misleading?

UNLABELLED: The costs for treating kypho- and vertebroplasty patients were evaluated at up to 2 years postsurgery. There were no significant differences in adjusted costs in the first 9 months postsurgery, but kyphoplasty patients were associated with significantly lower adjusted treatment costs by 6.8-7.9% in the remaining periods through 2 years postsurgery. INTRODUCTION: Vertebral augmentation has been shown to be safe and effective for treating vertebral compression fractures. Comparative cost studies of initial treatment costs for kypho- and vertebroplasty have been mixed. The purpose of our study was to compare the costs for treating kypho- and vertebroplasty patients at up to 2 years postsurgery. METHODS: Vertebroplasty and kyphoplasty patients diagnosed with pathologic or closed lumbar/thoracic vertebral fractures were identified from the 5% sample of the Medicare dataset (2006-2009). The final study cohort with at least 2 years follow-up comprised of 1,609 vertebroplasty and 2,878 kyphoplasty patients. The cumulative treatment costs (adjusted to June 2011 US$) were determined from the payer perspective. Differences in costs and length of stay were assessed by generalized linear mixed model regression, adjusting for covariates. RESULTS: The average adjusted costs for vertebroplasty patients within the first quarter and the first 2 years postsurgery were $14,585 [95% confidence interval (CI), $14,109-15,078] and $44,496 (95% CI, $42,763-46,299), respectively. The corresponding average adjusted costs for kyphoplasty patients were $15,117 (95% CI, $14,752-15,491) and $41,339 (95% CI, $40,154-42,560). There were no significant differences in adjusted costs in the first 9 months postsurgery, but kyphoplasty patients were associated with significantly lower adjusted treatment costs by 6.8-7.9% in the remaining periods through 2 years postsurgery. CONCLUSION: Our present study addresses some of the limitations in previous comparative cost studies of vertebroplasty and kyphoplasty. The higher adjusted costs for vertebroplasty patients than kyphoplasty patients by 1 year following the surgery reflect greater utilization of medical resources.

Tribological evaluation of hydrogel articulations for joint arthroplasty applications.

Characterizing the wear behavior of hydrogel articulations is problematic and a standardized method has not yet been developed. The aims of this study were to evaluate the wear resistance of hydrogel-on-hydrogel articulations and to assess the suitability of a submerged measurement technique as a practical and non-destructive method in quantifying their wear rates. Five hydrogel bearings were tested for 5 million cycles using a pin-on-disk tester. As the test progressed, the coefficient of friction increased (Spearman's rho=0.76; p<0.001) while the surfaces of the pins were burnished (Spearman's rho=-0.31; p<0.001) and those of the disks got rougher (Spearman's rho=0.19; p<0.01). Environmental scanning electron microscopy analysis showed no evidence of gross wear and revealed similar surface morphology between contacting and non-contacting regions of specimens. These results support the finding of low wear, which were -1.4±8.3 and 6.6±35.3mm(3)/MC based on submerged and wet weights, respectively. Pins displayed higher wear than disks based on submerged weights. This was anticipated since surfaces of pins were constantly under load and cross-shear while only a portion of the disk in contact with the pin was loaded at a given time. Wet weights, on the other hand, indicated higher wear for disks than pins. In addition, submerged weights yielded a lower standard error of the mean in wear rates than wet weights, 3.7 and 14.6mm(3)/MC, respectively. These results indicated that submerged weights were more suitable than wet weights in quantifying wear of hydrogels in spite of unwanted effects of swelling.

Retrieval analysis of squeaking alumina ceramic-on-ceramic bearings.

This multicentre study analysed 12 alumina ceramic-on-ceramic components retrieved from squeaking total hip replacements after a mean of 23 months in situ (11 to 61). The rates and patterns of wear seen in these squeaking hips were compared with those seen in matched controls using retrieval data from 33 'silent' hip replacements with similar ceramic bearings. All 12 bearings showed evidence characteristic of edge-loading wear. The median rate of volumetric wear was 3.4 mm(3)/year for the acetabular component, 2.9 mm(3)/year on the femoral heads and 6.3 mm(3)/year for head and insert combined. This was up to 45 times greater than that of previously reported silent ceramic-on-ceramic retrievals. The rate of wear seen in ceramic components revised for squeaking hips appears to be much greater than in that seen in retrievals from 'silent' hips.

Nanomagnet logic: progress toward system-level integration.

Quoting the International Technology Roadmap for Semiconductors (ITRS) 2009 Emerging Research Devices section, 'Nanomagnetic logic (NML) has potential advantages relative to CMOS of being non-volatile, dense, low-power, and radiation-hard. Such magnetic elements are compatible with MRAM technology, which can provide input­output interfaces. Compatibility with MRAM also promises a natural integration of memory and logic. Nanomagnetic logic also appears to be scalable to the ultimate limit of using individual atomic spins.' This article reviews progress toward complete and reliable NML systems. More specifically, we (i) review experimental progress toward fundamental characteristics a device must possess if it is to be used in a digital system, (ii) consider how the NML design space may impact the system-level energy (especially when considering the clock needed to drive a computation), (iii) explain--using both the NML design space and a discussion of clocking as context­how reliable circuit operation may be achieved, (iv) highlight experimental efforts regarding CMOS friendly clock structures for NML systems, (v) explain how electrical I/O could be achieved, and (vi) conclude with a brief discussion of suitable architectures for this technology. Throughout the article, we attempt to identify important areas for future work.

[Utilization rates of lower extremity prostheses in Germany and Switzerland: A comparison of the years 2005-2008]. / Verwendungsraten von Prothesen der unteren Extremität in Deutschland und der Schweiz: Ein Vergleich der Jahre 2005-2008.

BACKGROUND: In the United States the use of total hip arthroplasty (THA) has substantially increased over the last decade. It is not known, however, if this trend can be applied to other countries as well. The aim of the current study was therefore a detailed comparison of hip, knee, and ankle arthroplasty utilization rates in Germany and Switzerland in the years 2005-2008 and a secondary comparison with the United States. PATIENTS AND METHODS: Based on datasets from the national statistical offices the number of inhabitants, gender and age distributions and the number of primary and revision surgeries were determined. These figures served for calculating primary, revision and overall surgical volumes, revision burden, primary and revision rates per 100,000 inhabitants, gender and age-specific primary and revision rates. A comparably smaller dataset was provided for the respective US analyses. RESULTS: In Germany, Switzerland and the US the number of implanted total and partial hip arthroplasties per 100,000 inhabitants rose from 235.8, 238.2 and 116.8 in 2005 to 254.7, 262.7 and 127.3 in 2008, respectively. For total and partial knee arthroplasty the rates were 156.3, 140.1 and 178.2 implantations in 2005 and 188.3, 176.8 and 213.6 in 2008, respectively. With 13.6% the revision burden in Germany was 3.6% higher than in Switzerland and accounted for 11.2% in the US. In 2008 it was 15.1% in Germany, was hence 4.6% higher than in Switzerland and remained stable at 11.2% in the US. For knee replacements the 2005 German revision burden was 11.1% which was 3.5% higher than in Switzerland and was 7.4% in the US. In 2008 it was 12.8% in Germany and 4.2% lower in Switzerland and in the US it accounted for 8.9%. In all three countries the revision burden for knee arthroplasty was constantly lower than for hip arthroplasty. CONCLUSION: In all three countries the primary rates for hip and knee replacements rose over the years but those for knee arthroplasty to a higher extent. The 2008 revision burden was highest in Germany for both types of arthroplasty. In Switzerland there was a transient revision burden decrease with a new increase from the year 2007 onwards. The US hip replacement utilization rates per 100,000 inhabitants were considerably lower than those in Germany and Switzerland and for knee replacements they were slightly higher.

Non-majority magnetic logic gates: a review of experiments and future prospects for 'shape-based' logic.

We discuss the experimental demonstration of non-majority, two-input, nanomagnet logic (NML) AND and OR gates. While gate designs still can incorporate the symmetric, rounded-rectangle magnets used in the three-input majority gate experiments by Imre (2006 Science 311 205-8), our new designs also leverage magnets with an edge that has a well-defined 'slant'. In rectangular and ellipsoid nanomagnets, the easy axis of the device coincides with its longer edge. For a magnet with a slanted edge, the easy and hard axes are 'tilted', and magnetic fields applied along the (geometrical) hard axis alone can set the easy axis magnetization state. This switching phenomenon can be employed to realize NML Boolean logic gates with both reduced footprints and critical path delays. Experimental demonstrations of two-input AND and OR gates are supported by corresponding micromagnetic simulations with temperature effects associated with a 300 K environment. Simulations suggest that the time evolution of experimentally demonstrated structures is correct, and that designs can also tolerate clock field misalignment. Additionally, simulations suggest that a slanted-edge 'compute magnet' can (i) be driven by two anti-ferromagnetically ordered lines of NML devices (for input) and (ii) drive an anti-ferromagnetically ordered line (for output). Both are essential if slanted-edge devices are to be used in NML circuits. We conclude with a discussion of extensibility and scaling prospects for shape-based computation with nanomagnets.

Accelerated aging, natural aging, and small punch testing of gamma-air sterilized polycarbonate urethane acetabular components.

The objectives of this study were three-fold: (1) to determine the applicability of the small punch test to characterize Bionate 80A polycarbonate urethane (PCU) acetabular implants; (2) to evaluate the susceptibility of PCU acetabular implants to exhibit degradation of mechanical behavior following gamma irradiation in air and accelerated aging; and (3) to compare the oxidation of gamma-air sterilized PCU following accelerated aging and 5 years of natural shelf aging. In addition to attenuated total reflectance-Fourier transform infrared spectroscopy, we also adapted a miniature specimen mechanical test, the small punch test, for the deformable PCU cups. Accelerated aging was performed using ASTM F2003, a standard test that represents a severe oxidative challenge. The results of this study suggest that the small punch test is sufficiently sensitive and reproducible to discriminate slight differences in the large-deformation mechanical behavior of Bionate 80A following accelerated aging. The gamma-air sterilized PCU had a reduction of 9% in ultimate load after aging. Five years of shelf aging had little effect on the mechanical properties of the PCU. Overall, our findings suggest that the Bionate 80A material has greater oxidative stability than ultra-high molecular weight polyethylene following gamma irradiation in air and exposure to a severe oxidative challenge.

The impact of chemokine receptor CX3CR1 deficiency during respiratory infections with Mycobacterium tuberculosis or Francisella tularensis.

Recruitment of immune cells to infection sites is a critical component of the host response to pathogens. This process is facilitated partly through interactions of chemokines with cognate receptors. Here, we examine the importance of fractalkine (CX3CL1) receptor, CX3CR1, which regulates function and trafficking of macrophages and dendritic cells, in the host's ability to control respiratory infections with Mycobacterium tuberculosis or Francisella tularensis. Following low-dose aerosol challenge with M. tuberculosis, CX3CR1(-/-) mice were no more susceptible to infection than wild-type C57BL/6 mice as measured by organ burden and survival time. Similarly, following inhalation of F. tularensis, CX3CR1(-/-) mice displayed similar organ burdens to wild-type mice. CX3CR1(-/-) mice had increased recruitment of monocytes and neutrophils in the lung; however, this did not result in increased abundance of infected monocytes or neutrophils. We conclude that CX3CR1-deficiency affects immune-cell recruitment; however, loss of CX3CR1 alone does not render the host more susceptible to M. tuberculosis or F. tularensis.

Essential education in communication skills and cultural sensitivities for global public health in an evolving veterinary world.

In the practise of veterinary medicine and global public health, communication skill is as critical as clinical reasoning and an extensive knowledge base. Effective communication skills and cross-cultural sensitivity are essential across the board for interdisciplinary, international, and local veterinary medicine. This paper offers an evidence-based, three-part framework for developing and sustaining curricula that enhance communication skills and cross-cultural sensitivity so that students are better prepared to practise veterinary medicine in an evolving world. These curricula may well also serve as a conduit for encouraging more veterinary graduates to choose global public health as a career path.