Compact spectroscopy of keV to MeV X-rays from a laser wakefield accelerator.

We reconstruct spectra of secondary X-rays from a tunable 250-350 MeV laser wakefield electron accelerator from single-shot X-ray depth-energy measurements in a compact (7.5 × 7.5 × 15 cm), modular X-ray calorimeter made of alternating layers of absorbing materials and imaging plates. X-rays range from few-keV betatron to few-MeV inverse Compton to > 100 MeV bremsstrahlung emission, and are characterized both individually and in mixtures. Geant4 simulations of energy deposition of single-energy X-rays in the stack generate an energy-vs-depth response matrix for a given stack configuration. An iterative reconstruction algorithm based on analytic models of betatron, inverse Compton and bremsstrahlung photon energy distributions then unfolds X-ray spectra, typically within a minute. We discuss uncertainties, limitations and extensions of both measurement and reconstruction methods.

Coherent Optical Signatures of Electron Microbunching in Laser-Driven Plasma Accelerators.

We report observations of coherent optical transition radiation interferometry (COTRI) patterns generated by microbunched ∼200-MeV electrons as they emerge from a laser-driven plasma accelerator. The divergence of the microbunched portion of electrons, deduced by comparison to a COTRI model, is ∼9× smaller than the ∼3 mrad ensemble beam divergence, while the radius of the microbunched beam, obtained from COTR images on the same shot, is <3 µm. The combined results show that the microbunched distribution has estimated transverse normalized emittance ∼0.4 mm mrad.

Effectiveness of Workplace Interventions in Return-to-Work for Musculoskeletal, Pain-Related and Mental Health Conditions: An Update of the Evidence and Messages for Practitioners.

Purpose The objective of this systematic review was to synthesize evidence on the effectiveness of workplace-based return-to-work (RTW) interventions and work disability management (DM) interventions that assist workers with musculoskeletal (MSK) and pain-related conditions and mental health (MH) conditions with RTW. Methods We followed a systematic review process developed by the Institute for Work & Health and an adapted best evidence synthesis that ranked evidence as strong, moderate, limited, or insufficient. Results Seven electronic databases were searched from January 1990 until April 2015, yielding 8898 non-duplicate references. Evidence from 36 medium and high quality studies were synthesized on 12 different intervention categories across three broad domains: health-focused, service coordination, and work modification interventions. There was strong evidence that duration away from work from both MSK or pain-related conditions and MH conditions were significantly reduced by multi-domain interventions encompassing at least two of the three domains. There was moderate evidence that these multi-domain interventions had a positive impact on cost outcomes. There was strong evidence that cognitive behavioural therapy interventions that do not also include workplace modifications or service coordination components are not effective in helping workers with MH conditions in RTW. Evidence for the effectiveness of other single-domain interventions was mixed, with some studies reporting positive effects and others reporting no effects on lost time and work functioning. Conclusions While there is substantial research literature focused on RTW, there are only a small number of quality workplace-based RTW intervention studies that involve workers with MSK or pain-related conditions and MH conditions. We recommend implementing multi-domain interventions (i.e. with healthcare provision, service coordination, and work accommodation components) to help reduce lost time for MSK or pain-related conditions and MH conditions. Practitioners should also consider implementing these programs to help improve work functioning and reduce costs associated with work disability.

Developing a tool to assess the quality of socio-demographic data in community health centres.

OBJECTIVE: The objectives of this study are to 1) create a quality assessment tool for socio-demographic data aligned with the needs of Community Health Centres (CHCs) and based on the data quality framework of the Canadian Institute for Health Information (CIHI), and 2) test the feasibility of the tool in CHCs. METHODS: The tool was developed based on both theoretical and practical knowledge. A review of the literature was performed to identify data quality frameworks and dimensions that could be employed. In addition, informal discussions with Community Health Centres staff members holding various positions were conducted and a team of subject matter experts was established. This approach supported the alignment between the tool (i.e., the indicators developed, the rating scale, and weighting system) and the setting for which it has been designed. The tool was pilot tested in five CHCs across Ontario. RESULTS: The decision to focus on socio-demographic data was based on findings from the discussions with staff members. The team established nine principles for the development of the tool, including the use of computer software, whenever possible, to query the data and ensure consistency of the measurement. Data quality scores ranged from 45 to 74 on a scale of 0 (lowest quality) to 100 (highest data quality), with one CHC that was not able to run all of the queries. The feedback from staff was positive and supports the feasibility of the tool as an application of the CIHI data quality framework in a local setting. CONCLUSION: Pilot test results demonstrate the feasibility of the tool and an applicability of the CIHI framework as a basis for developing tools for data quality assessment in health care organizations.

Effects of serum deprivation on the mechanical properties of adherent vascular smooth muscle cells.

Vascular smooth muscle cell (VSMC) function plays a key role in regulating the development and progression of vascular lesions. Among the more significant phenomena that occur during the development of these lesions is the phenotypic switching of VSMCs from a contractile to a synthetic state. A better understanding of the concurrent changes to VSMC mechanical properties that occur with phenotypic shifts can help to elucidate the role of VSMC mechanics in the development of vascular diseases. In the current study, the mechanical properties of adherent cultured rat aortic VSMCs were assessed by atomic force microscopy. Serum starvation was used to induce a phenotypic shift in vitro. It was concluded that serum starvation led to a statistically significant increase in apparent elastic modulus after 5 days, as well as a statistically significant decrease in hysteresis after culture for 3 days. If this trend of VSMC mechanical properties changing concurrently with phenotypic shifts were to hold true in vivo, such changes could affect the processes of mechanotransduction and/or arterial mechanical properties, thereby contributing to the progression of vascular disease.

Increased total knee arthroplasty ultra-high molecular weight polyethylene wear using a clinically relevant hyaluronic acid simulator lubricant.

In this study, osteoarthritic and periprosthetic synovial fluid samples were rheologically and biochemically compared to develop a hyaluronic acid (HA) supplemented bovine serum (BS) lubricant that mimicked the properties of human joint synovial fluid. The effect of this BS + HA lubricant (50 per cent bovine calf serum + 1.5 g/l HA) on the wear rate of ultra-high molecular weight polyethylene (UHMWPE) during a total knee replacement wear test was then investigated. In conjunction with biochemical similarities, the rheological analysis showed that the BS + HA lubricant viscosity was not statistically different to aspirated total knee arthroplasty (TKA) revision joint fluid viscosity over a range of physiologic shear rates. Gravimetric results at 5 million wear testing cycles showed that the BS + HA lubricant produced an average of 6.88 times more UHMWPE wear than 50 per cent bovine serum lubricant alone. The BS + HA lubricated CoCr femoral component surfaces revealed pitting and surface roughening that was not observed using standard bovine serum only lubricants, but that was similar to the metallic surface corrosion observed on in vivo CoCr femoral component retrievals. These findings support the hypothesis that the addition of HA to simulator lubricant is capable of producing CoCr femoral component surface damage similar to that observed in vivo.

Effect of lubricant composition on the fatigue properties of ultra-high molecular weight polyethylene for total knee replacement.

Ultrahigh molecular weight polyethylene (UHMWPE) fatigue is a critical factor affecting the longevity of total knee replacement (TKR) bearings. With the increased need for laboratory studies to mimic near in vivo conditions for accurate characterization of material performance, the present study investigated the role of hyaluronic acid (HA) in testing lubricant on the crack growth response of UHMWPE. It was hypothesized that the change in lubricant viscosity as a result of HA would affect the fatigue life of the polymer. A fracture mechanics approach as per ASTM E 647 was adopted for this study. Surface micrograph and surface chemistry analyses were employed to study the micromechanisms of fatigue failure and protein adsorption of the specimen surfaces. Rheological analysis indicated that the addition of HA to diluted bovine serum increased testing lubricant viscosity. HA concentrations of 2.22, 0.55, and 1.5 g/l closely matched the viscosity ranges reported for osteoarthritis, rheumatoid arthritic diseased joint fluid, and periprosthetic fluids respectively. Results showed that the addition of HA to standard diluted bovine serum lubricants, in concentrations similar to that of periprosthetic fluid, delayed crack initiation and crack growth during fatigue testing.

Biocompatibility of supercritical CO2-treated titanium implants in a rat model.

Supercritical phase CO2 is a promising method for sterilizing implantable devices and tissue grafts. The goal of this study is to evaluate the biocompatibility of titanium implants sterilized by supercritical phase CO2 in a rat subcutaneous implantation model. At 5 weeks post implantation titanium implants sterilized by supercritical phase CO2 produce a soft tissue reaction that is comparable to other methods of sterilization (steam autoclave, ultraviolet light radiation, ethylene oxide gas, and radio-frequency glow-discharge), as indicated by the thickness and density of the foreign body capsule, although there were some differences on the capillary density. Overall the soft tissue response to the implants was similar among all methods of sterilization, indicating supercritical phase CO2 treatment did not compromise the biocompatibility of the titanium implant.

High pressure reveals that the stability of interdimeric contacts in the R- and T-state of HbA is influenced by allosteric effectors: Insights from computational simulations.

The molecular details of the mechanism of action of allosteric effectors on hemoglobin oxygen affinity are not clearly understood. The global allostery model proposed by Yonetani et al. suggests that the binding of allosteric effectors can take place both in the R and T states and that they influence oxygen affinity through inducing global tertiary changes in the subunits. Recently published high pressure studies yielded dissociation constants at atmospheric pressure that showed a stabilizing effect of heterotropic allosteric effectors on the dimer interface in the R state, and a more pronounced destabilizing effect in a T state model. In the present work, we report on computational modeling used to interpret the high pressure experimental data. We show structural changes in the hemoglobin interdimeric interfaces, indicative of a global tertiary structural change induced by the binding of allosteric effectors. We also show that the number of water molecules bound at the interface is significantly influenced by binding effectors in the T state in accordance with the experimental data. Our results suggest that the binding of effectors at definite sites leads to tertiary changes that propagate to the interfaces and results in overall structural re-organizations.

Effects of sterilization on implant mechanical property and biocompatibility.

This article concisely reviews the effects of sterilization on the mechanical properties and surface chemistries of implantable biomaterials. This article also summarizes the biological effects of the sterilization-related changes in the implant. Because there are so many different types of implant materials currently in use (including metals, polymers, and diverse biological materials), the response of tissue to these different materials varies dramatically. This review further discusses the effects of sterilization on in vivo and in vitro tissue response specifically to implantable metals and polyethylene, with the possibility of future biocompatibility testing of the implants sterilized with supercritical phase carbon dioxide sterilization.

Nanoindentation properties of compression-moulded ultra-high molecular weight polyethylene.

This paper investigates the elastic modulus and hardness of untreated and treated compression-moulded ultra-high molecular weight polyethylene (UHMWPE) tibial inserts of a total knee replacement (TKR) prosthesis. Investigations were carried out at a nanoscale using a Nanoindenter at penetration depths of 100,250 and 500 nm. The nanomechanical properties of surface and subsurface layers of the compression-moulded tibial inserts were studied using the untreated UHMWPE. The nanomechanical properties of intermediate and core layers of the compression-moulded tibial insert were studied using the cryoultrasectioned and etched UHMWPE treated samples. The cryoultrasectioning temperature (-150 degrees C) of the samples was below the glass transition temperature, Tg (-122 +/- 2 degrees C ), of UHMWPE. The measurement of the mechanical response of crystalline regions within the nanostructure of UHMWPE was accomplished by removing the amorphous regions using a time-varying permanganic-etching technique. The percentage crystallinity of UHMWPE was measured using differential scanning calorimetry (DSC) and the Tg of UHMWPE was determined by dynamic mechanical analysis (DMA). Atomic force microscopy (AFM) was used to assess the effect of surface preparation on the samples average surface roughness, Ra. In this study, it was demonstrated that the untreated UHMWPE samples had a significantly lower (p < 0.0001) elastic modulus and hardness relative to treated UHMWPE cryoultrasectioned and etched samples at all penetration depths. No significant difference (p > 0.05) in elastic modulus and hardness between the cryoultrasectioned and etched samples was observed. These results suggest that the surface nanomechanical response of an UHMWPE insert in a total joint replacement (TJR) prosthesis is significantly lower compared with the bulk of the material. Additionally, it was concluded that the nanomechanical response of material with higher percentage crystallinity (67 per cent) was predominantly determined by the crystalline regions within the semi-crystalline UHMWPE nanostructure.

In vitro strain-induced endothelial cell dysfunction determined by DNA synthesis.

Rapid re-endothelialization following balloon angioplasty can reduce restenosis by inhibiting smooth muscle cell migration and proliferation. However, formation of a neointima following angioplasty can be inhibited due to endothelial cell dysfunction and denudation. The purpose of this study was to evaluate mechanical tensile stress as a cause of endothelial cell dysfunction. The Flexercell strain unit was utilized to generate both short-term cyclic and static tensile strain on cultured bovine aortic endothelial cells (BAECs). Before analysis of this loading on BAECs, strain behaviour of the Flexercell system and DNA assay conditions were optimized. This paper demonstrates that, when compared with unloaded controls, 4-h cyclic loading at 4 per cent elongation and 0.1 Hz, and static loading at 4 per cent elongation cause a 44 and 70 per cent decrease in DNA synthesis respectively. In a companion paper, it is demonstrated that low DNA synthesis levels in mechanically loaded cells can be increased by incubation with Ap4A and/or NO donors.

P1,P4-diadenosine 5'-tetraphosphate induced DNA synthesis in mechanically injured cultured endothelial cells.

Rapid re-endothelialization following balloon angioplasty can reduce restenosis by inhibiting smooth muscle cell migration and proliferation. However, formation of a neointima layer following angioplasty can be inhibited due to endothelial cell dysfunction and denudation. In a companion paper, it has been illustrated that mechanical loading causes a decrease in DNA synthesis in bovine aortic endothelial cells (BAECs) thus rendering them dysfunctional. The purpose of this study was to overcome BAEC dysfunction by incubation with pharmacological agents to increase DNA synthesis. Previous studies demonstrated that the adenosine dinucleotides Ap4A and Ap2A induced nitric oxide (NO) production from BAEC while Ap3A, Ap5A and Ap6A did not. This paper demonstrates that Ap4A and Ap2A induce a 1.46- and 1.16-fold increase in DNA synthesis in mechanically stressed BAECs respectively, while Ap3A, Ap5A and Ap6A do not. Additionally, NOC-18, a slow NO release NO donor, significantly increases DNA synthesis in mechanically stressed BAECs without affecting unloaded cells. These results are consistent with NO inducing DNA synthesis in mechanically stressed BAECs.

Effect of stair descent loading on ultra-high molecular weight polyethylene wear in a force-controlled knee simulator.

A loading protocol approximating forces, torques and motions at the knee during stair descent was developed from previously published data for input into a force-controlled knee simulator. A set of total knee replacements (TKRs) was subjected to standard walking cycles and stair descent cycles at a ratio of 70: 1 for 5 million cycles. Another set of implants with similar articular geometry and the same ultra-high molecular weight polyethylene (UHMWPE) resin (GUR 415), sterilization and packaging was tested with standard walking cycles only. Implant kinematics, gravimetric wear and surface roughness of the UHMWPE inserts were analysed for both sets of implants. Contact stresses were calculated for both loading protocols using a Hertzian line contact model. Significantly greater weight loss (p < 0.05) and more severe surface damage of UHMWPE inserts resulted with the walking + stair descent loading protocol compared to walking cycles only. Anterior-posterior (AP) tibiofemoral contact point displacements were lower during stair descent than walking, but not significantly different (p = 0.05). Contact stresses were significantly higher during stair descent than walking, owing to higher axial loads and the smaller radius of curvature of the femoral components at higher flexion angles. High contact stresses on UHMWPE components are likely to accelerate the fatigue of the material, resulting in more severe wear, similar to what is observed in retrieved implants. Thus the inclusion of loading protocols for activities of daily living in addition to walking is warranted for more realistic in vitro testing of TKRs.

Effects of the sample preparation temperature on the nanostructure of compression moulded ultrahigh molecular weight polyethylene.

In this study, the effects of the sample sectioning temperature on the surface nanostructure and mechanical response of compression moulded ultrahigh molecular weight polyethylene (UHMWPE) at a nanometer scale (nanomechanical properties) have been characterized. The primary focus of this work was to determine if the sample sectioning temperature significantly changed the nanostructure of UHMWPE, while the secondary focus was to characterize the effect on the mechanical response due to the changes in the sectioned surface nanostructure. The goals of this study were: (a) to investigate the potential possibility of creating surface artefacts by the sample preparation technique by sectioning at different temperatures relative to the published range of glass transition temperatures, Tg, for PE (-12, -80 and -25 degrees C); (b) to determine the possibility of molecular orientation induced by plastic deformation of the UHMWPE sample during the process of sample preparation; (c) to measure the relative difference in nanomechanical properties owing to evolution of different nanostructures as a function of sample sectioning temperature. Field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM) and nanoindentation were used to demonstrate that the sectioning temperature caused a change in nanostructure of the compression moulded UHMWPE sectioned surface, explaining the change in mechanical response to indentation at a nanoscale. In this study, it was demonstrated that significant plastic deformation occurs when a shear stress is applied between the glass or diamond blade and the UHMWPE during sample preparation under ambient conditions at a temperature of 22 degrees C. These results also suggest that an optimum sample sectioning temperature should definitely be below the measured Tg of the polymer.

Effects of in vitro wear of machined and molded UHMWPE tibial inserts on TKR kinematics.

The effect of manufacturing process on the wear and mechanical performance of a total knee replacement (TKR) design was investigated with the use of a force-controlled knee joint simulator. Ultra-high molecular weight polyethylene (UHMWPE) tibial inserts processed by direct compression molding from 1900H resin were compared to UHMWPE tibial inserts machined from a compression-molded sheet of GUR 1050. Both sets of components had the same posterior-cruciate-retaining geometry, and were identically aligned with cobalt-chromium-molybdenum alloy femoral components. Wear tests were conducted at a frequency of 1 Hz for 4 million cycles with the use of a standard walking cycle pattern. Implant kinematics, including anterior-posterior (AP) displacement and internal-external (IE) rotation in response to applied loads were monitored. Gravimetric wear, surface roughness, and surface morphology were used to characterize the wear process of the UHMWPE inserts. Results showed that the molded UHMWPE inserts exhibited less gravimetric wear over time than the machined inserts of the same design. Both the machined and molded components exhibited scratching, pitting, and burnishing over their wear areas. The AP displacement distance per cycle of the molded tibial inserts decreased over the course of testing, resulting in a shorter total testing displacement for this group compared to machined tibial inserts. Although AP displacement distance per cycle for machined tibial inserts did not change significantly over the course of testing, their position relative to the femoral components shifted posteriorly over time, resulting in an elongated wear track.

Phospholipid composition of articular cartilage boundary lubricant.

The mechanism of lubrication in normal human joints depends on loading and velocity conditions. Boundary lubrication, a mechanism in which layers of molecules separate opposing surfaces, occurs under severe loading. This study was aimed at characterizing the phospholipid composition of the adsorbed molecular layer on the surface of normal cartilage that performs as a boundary lubricant. The different types of phospholipid adsorbed onto the surface of cartilage were isolated by extraction and identified by chromatography on silica gel paper and mass spectroscopy. The main phospholipid classes identified were quantified by a phosphate assay. Gas chromatography and electrospray ionization mass spectrometry were used to further characterize the fatty acyl chains in each major phospholipid component and to identify the molecular species present. Phosphatidylcholine (41%), phosphatidylethanolamine (27%) and sphingomyelin (32%) were the major components of the lipid layer on the normal cartilage surface. For each lipid type, a mixture of fatty acids was detected, with a higher percentage of unsaturated species compared to saturated species. The most abundant fatty acid observed with all three lipid types was oleic acid (C18:1). Additional work to further quantify the molecular species using electrospray ionization mass spectrometry is recommended.

Aromatic substrate specificity of horseradish peroxidase C studied by a combined fluorescence line narrowing/energy minimization approach: the effect of localized side-chain reorganization.

Horseradish peroxidase C binds a wide variety of small H-donor compounds such as benzohydroxamic acid (BHA) and 2-naphthohydroxamic acid (NHA). In this work, we use the Mg(II)-mesoporphyrin prosthetic group derivative as a spectroscopic probe of the active site and of the interaction with the substrates. We report on high-resolution fluorescence line-narrowed spectra which show that the effects of substrate binding on the electronic transitions are similar for both substrates and present data on the normal vibrational modes that are active in the vibronic spectra. Analysis of the vibrational frequencies shows that the Mg(II) ion is 5-coordinate in all cases, thus ruling out a solvent water as sixth ligand. The frequency shifts observed as a result of substrate binding are also indicative of a more rigid prosthetic group upon substrate binding. We present models for MgMP-HRP and its complexes with both substrates and compare the resulting structures on the basis of a modeling approach combining energy minimization to finite difference Poisson--Boltzmann calculations which partitions the various relative protein contributions to substrate binding. We show that the electrostatic potential of the prosthetic group is modified by the binding event. Analysis of the unbound and bound energy-minimized structures shows that the enzyme modulates substrate binding by subtle charge reorganization in the vicinity of the catalytic site and that this rearrangement is not attributable to significant secondary structure conformational changes but to side-chain reorganization.

The carbohydrate and caloric content of concomitant medications for children with epilepsy on the ketogenic diet.

BACKGROUND: The ketogenic diet for children with refractory epilepsy requires a strict control of the amount of ingested carbohydrates. This can be altered by medication prescribed for the epileptic syndrome or for intercurrent illnesses. The goal of this paper is to compile the carbohydrate and caloric content of commonly used medications in this population. METHODS: We compiled a list of frequently used medications with the help of Canadian manufacturers and the Compendium of Pharmaceuticals and Specialties. We also tested a worst case scenario calculation based on the weight of the tablet. RESULTS: We list the carbohydrate and caloric content of 790 medications studied. Our worst case scenario gives an over-estimate in all cases, making adjustments based on this calculation in an emergency setting safe. CONCLUSION: We propose this list as a tool for physicians, dietitians, nurses and pharmacists. The list can easily be adjusted, based on local practices and reviewed periodically.