A knowledge broker facilitated intervention to improve the use of standardized assessment tools by physical therapists: A cluster randomized trial.

OBJECTIVE: To compare two methods of knowledge broker support to improve standardized assessment use. DESIGN: Two-site cluster randomized trial. SETTING: Acute rehabilitation hospital. PARTICIPANTS: 18 physical therapists. INTERVENTION: A 10-month intervention was collaboratively designed with an external knowledge broker and physical therapists to compare full and partial implementation support. The knowledge broker provided education and strategies for implementation to the fully supported group and recommended strategies to the partially supported group that they self-implemented. MEASUREMENT: Chart audit data documenting frequency of use was extracted at four timepoints. Ten focus groups were conducted to describe factors that influenced use. Focus group data were coded using the Consolidated Framework for Implementation Research and rated as barriers and facilitators for standardized assessment use. RESULTS: For the fully supported group, standardized assessment use at initial examination increased from 0% to 58.3% at month 2 and decreased to 17.6% and 11.8% at months 4 and 8-10. For the partially supported group, standardized assessment use increased from 0% to 46% and 50% at month 2 and 4 and decreased to 2.8% at months 8-10. For both groups, early use was seen multiple facilitators. At month 10, barriers included organizational changes that impacted intervention fit. In addition, the fully supported group didn't value the selected standardized assessment and the partially supported group lacked space. CONCLUSIONS: Knowledge broker support improved both groups standardized assessment use early on, but it was not sustained. The amount of support could not be isolated as factors that influenced use varied by groups.

Templated Assembly of Pore-forming Peptides in Lipid Membranes.

Pore-forming peptides are of interest due to their antimicrobial activity and ability to form gateways through lipid membranes. Chemical modification of these peptides makes it possible to arrange several peptide monomers into well-defined pore-forming structures using various templating strategies. These templated super-structures can exert antimicrobial activity at significantly lower total peptide concentration than their untemplated equivalents. In addition, the chemical moieties used for templating may be functionalized to interact specifically with targeted membranes such as those of pathogens or cancer cells. A range of molecular templates has been explored, including dimerization of pore-forming monomers, their covalent attachment to cyclodextrin, porphyrin or fullerene scaffolds as well as attachment of amino acid linkers or nucleic acid constructs to generate assemblies of 4 to 26 peptides or proteins. Compared to free peptide monomers, templated pore assemblies showed increased membrane affinity, prolonged open-state lifetimes of the pores and more frequent pore formation due to higher local concentration. These constructs are useful model systems for biophysical studies to understand porin and ion channel proteins and their mechanisms of insertion into lipid membranes. Recently designed DNA-templates are expanding the usefulness of templated pore assemblies beyond applications of cell killing and may include targeted drug delivery and accelerate the emerging field of single-molecule detection and characterization of biomolecules by nanopore-based resistive pulse sensing.

Escaping the Ashby limit for mechanical damping/stiffness trade-off using a constrained high internal friction interfacial layer.

The development of new materials with reduced noise and vibration levels is an active area of research due to concerns in various aspects of environmental noise pollution and its effects on health. Excessive vibrations also reduce the service live of the structures and limit the fields of their utilization. In oscillations, the viscoelastic moduli of a material are complex and it is their loss part - the product of the stiffness part and loss tangent - that is commonly viewed as a figure of merit in noise and vibration damping applications. The stiffness modulus and loss tangent are usually mutually exclusive properties so it is a technological challenge to develop materials that simultaneously combine high stiffness and high loss. Here we achieve this rare balance of properties by filling a solid polymer matrix with rigid inorganic spheres coated by a sub-micron layer of a viscoelastic material with a high level of internal friction. We demonstrate that this combination can be experimentally realised and that the analytically predicted behaviour is closely reproduced, thereby escaping the often termed 'Ashby' limit for mechanical stiffness/damping trade-off and offering a new route for manufacturing advanced composite structures with markedly reduced noise and vibration levels.

Modelling of loading, stress relaxation and stress recovery in a shape memory polymer.

A multi-element constitutive model for a lactide-based shape memory polymer has been developed that represents loading to large tensile deformations, stress relaxation and stress recovery at 60, 65 and 70°C. The model consists of parallel Maxwell arms each comprising neo-Hookean and Eyring elements. Guiu-Pratt analysis of the stress relaxation curves yields Eyring parameters. When these parameters are used to define the Eyring process in a single Maxwell arm, the resulting model yields at too low a stress, but gives good predictions for longer times. Stress dip tests show a very stiff response on unloading by a small strain decrement. This would create an unrealistically high stress on loading to large strain if it were modelled by an elastic element. Instead it is modelled by an Eyring process operating via a flow rule that introduces strain hardening after yield. When this process is incorporated into a second parallel Maxwell arm, there results a model that fully represents both stress relaxation and stress dip tests at 60°C. At higher temperatures a third arm is required for valid predictions.

NMR T1 relaxation time measurements and calculations with translational and rotational components for liquid electrolytes containing LiBF4 and propylene carbonate.

Longitudinal relaxation (T1) measurements of (19)F, (7)Li, and (1)H in propylene carbonate/LiBF4 liquid electrolytes are reported. Comparison of T1 values with those for the transverse relaxation time (T2) confirm that the measurements are in the high temperature (low correlation time) limit of the T1 minimum. Using data from pulsed field gradient measurements of self-diffusion coefficients and measurements of solution viscosity measured elsewhere, it is concluded that although in general there are contributions to T1 from both translational and rotational motions. For the lithium ions, this is mainly translational, and for the fluorine ions mainly rotational.

Bowel cancer screening is safe, detects earlier stage cancer and adenomas in 50% of cases: experience of the prevalent round of screening from two first wave centres in the North East of England.

OBJECTIVE: The NHS Bowel Cancer Screening Programme (BCSP) began roll-out in 2006 aiming to reduce cancer mortality through detection at an earlier stage. We report results from the prevalent round of screening at two first wave centres and compare with the UK pilot study. DESIGN: This is a service evaluation study. Data were collected prospectively for all individuals undergoing faecal occult blood testing (FOBt) and colonoscopy including: uptake and outcomes of FOBt, colonoscopic performance, findings, histological data and complications. Continuous data were compared using a two-tailed test of two proportions. SETTING: The South of Tyne and Tees Bowel Cancer Screening centres. PATIENTS: Participants of the BCSP. MAIN OUTCOME MEASURES: 1) Colonoscopy Quality Assurance and 2) Cancer stage shift. RESULTS: 195,772 individuals were invited to participate. Uptake was 54% and FOBt positivity 1.7%. 1524 underwent colonoscopy with caecal intubation in 1485 (97%). 180 (12%) cancers were detected. Dukes stages were: 76 (42%) A; 47 (26%) B; 47 (26%) C; 8 (4%) D and 2 (1%) unknown. This demonstrates a significantly earlier stage at diagnosis compared with data from 2867 non-screening detected cancers (p<0.001). Adenomas were detected in 758 (50%). One perforation occurred (0.07%) and two intermediate bleeds requiring transfusion only (0.12%). Both caecal intubation and adenoma detection were significantly higher than in the UK pilot study (p<0.001). CONCLUSIONS: The prevalent round of screening demonstrates a high adenoma and cancer detection rate and significantly earlier stage at diagnosis. Complications were few providing reassurance regarding safety. Efforts are required to improve uptake.

The wear and fracture behaviour of ultra high molecular weight polyethylene subjected to gamma-irradiation in an atmosphere of acetylene.

The wear and mechanical properties of GUR 1020 (Perplas IMP 2000-2) Ultra High Molecular Weight Polyethylene (UHMWPE) subjected to gamma-irradiation in an atmosphere of acetylene, were evaluated for a range of processing conditions of irradiation, annealing and ageing. The results were compared with those obtained for the virgin UHMWPE material and material processed using conventional gamma-irradiation in nitrogen. Cross-linking produced by irradiation in acetylene, followed by subsequent annealing was found to be significantly more effective in improving the mechanical and wear properties of UHMWPE compared to when the material was irradiated in nitrogen. Gel fraction analysis on its own, while being able to detect the degree of cross-linking, was found to be insufficient in determining the effectiveness of the cross-links and the resulting mechanical properties of the UHMWPE material. The results suggest that gamma-irradiation in an atmosphere of acetylene may provide significant advantages over conventional UHMWPE processing and irradiation cross-linking techniques.

Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress.

H2AX, a member of the histone H2A family, is rapidly phosphorylated in response to ionizing radiation. This phosphorylation, at an evolutionary conserved C-terminal phosphatidylinositol 3-OH-kinase-related kinase (PI3KK) motif, is thought to be critical for recognition and repair of DNA double strand breaks. Here we report that inhibition of DNA replication by hydroxyurea or ultraviolet irradiation also induces phosphorylation and foci formation of H2AX. These phospho-H2AX foci colocalize with proliferating cell nuclear antigen (PCNA), BRCA1, and 53BP1 at the arrested replication fork in S phase cells. This response is ATR-dependent but does not require ATM or Hus1. Our findings suggest that, in addition to its role in the recognition and repair of double strand breaks, H2AX also participates in the surveillance of DNA replication.

Threonine 68 of Chk2 is phosphorylated at sites of DNA strand breaks.

The protein kinase Chk2 has been implicated in signaling DNA damage to cell cycle checkpoints. In response to ionizing radiation, Chk2 becomes rapidly phosphorylated at threonine 68 by ataxia-telangiectasia mutated (ATM). Here we show that the Thr(68)-phosphorylated form of Chk2 forms distinct nuclear foci in response to ionizing radiation. Only this activated form of Chk2 localizes at sites of DNA strand breaks. The kinase activity of Chk2 and the number of Chk2 foci formed depend on the severity of DNA damage and gradually decline correlating with the predicted value of slowly re-joining double strand breaks. These results suggest that Chk2 is regulated at the sites of DNA strand breaks in response to ionizing radiation.

The effect of molecular orientation and acetylene-enhanced crosslinking on the wear of UHMWPE in total artificial joints.

This paper investigates the benefits of combining roll-drawing and acetylene-enhanced crosslinking to alter the mechanical properties of the ultra high molecular weight polyethylene (UHMWPE) used in total hip and knee replacements, with the aim of improving its resistance to wear. UHMWPE was processed via crosslinking, roll-drawing and a combination of crosslinking and roll-drawing and subjected to gel content analysis, tensile tests, X-ray diffraction and wear tests using different types of motion and smooth and rough counterfaces. Purely roll-drawn materials with length and width draw ratios of lambda l x lambda w = 1.3 x 1.0 and lambda1 x lambdaw = 1.6 x 0.9 respectively, were found to have lower wear factors in a unidirectional motion test with a rough counterface when compared to the virgin material. The crosslinked roll-drawn material, with length and width draw ratios of lambda1 x lambdaw = 1.6 x 0.9, was seen to possess five crosslinks per initial number average molecule. This crosslinked and roll-drawn material showed 5.5 times less wear than the virgin material in a multidirectional motion test with a smooth counterface and 1.4 times more wear than the virgin material in a unidirectional motion test with a rough counterface. Hence this study supports previous work by the authors that acetylene-enhanced crosslinked materials may show benefits for a total hip replacement, but only where the femoral head remains smooth. The improvements in wear with the roll-drawn material in unidirectional tests were smaller, but may prove to have some benefits in the knee.

Androgen threshold to activate copulation differs in male rats prenatally exposed to alcohol, stress, or both factors.

Few male rats prenatally exposed to a combination of alcohol and stress copulate spontaneously. This study determined adult sensitivity to testosterone (T) in males prenatally exposed to alcohol, to stress, or to both factors. Sexually naive males were tested with receptive females following castration and implantation of 20-, 30-, or 45-mm Silastic T-filled capsules. Serum T levels provided by these implants were measured. The behavior shown by males exposed only to prenatal alcohol did not differ from untreated control animals at any T dosage. Prenatal stress alone diminished the copulatory potential below control levels only when the intermediate T dosage was provided. Few males exposed to both alcohol and stress copulated under the lowest or the intermediate dose of adult T replacement, but most ejaculated normally when the largest capsule was implanted. The threshold to the sexual behavior-activating-properties of adult T exposure was moderately raised by prenatal stress but was severely affected when prenatal stress was combined with alcohol. We conclude that a diminished sensitivity to androgen in adulthood underlies some copulatory deficits resulting from treatments that alter fetal T levels. Such deficits may be concealed when behavior is evaluated in gonadally intact animals.

Multiple radon entry modeling in a house with a cellar.

Combining a computational fluid dynamics (CFD) model and a multi-zonal model, a study was carried out on radon entry through the complex substructure of a house with a cellar. The uniqueness of the radon entry problem in this type of house was due to the involvement of two radon entry routes to two chambers: the cellar and the living area of the house. Soil gas carrying radon was driven through the two routes by two coupled disturbance pressures in the chambers. The effects of temperature differences were considered as another driving force for the radon entry. Examined in this study were the effects of the geometry of the substructure, air permeability of the soil, air-tightness of the cellar shell, and cellar ventilation on radon entry to both the cellar and the living area. The ground floor covering on top of the soil outside a cellar wall increased radon entry through this wall by about 68%, as radon built up to a very high level under the covering. The effect of cellar ventilation was found as follows: the cellar ventilation created a layer of airflow in the soil under the ground floor; the flow passed over a crack in the ground floor, the entry route to the living area, diluting the radon in the area. Hence, the soil gas entering the living area carried less radon. Cellar ventilation seems more effective in reducing radon entry to the living area in a more permeable soil and leaky cellar shell; a moderate cellar ventilation condition achieved 77% reduction in radon entry to the area. When permeability of these two materials was lower and soil radon content remained the same, the chances of radon entry was also lower; hence, the indoor radon level was lower and no radon control was needed. When such soil contains high radon concentration, other mitigation measures must be sought.

Fetal alcohol exposure blocks full masculinization of the dorsolateral nucleus in rat spinal cord.

Male rats prenatally exposed to a combination of stress and ethanol show severely impaired ejaculatory patterns. This study examined two sexually dimorphic nuclei in the lumbar spinal cord implicated in the control of male copulatory reflexes in rats whose mothers were exposed to alcohol, to stress, or to both treatments during pregnancy. Alcohol exposure led to a marked decrease (22%) in the number of motor neurons in the dorsolateral nucleus (DLN) of the adult male offspring, but no significant change in cell count was detectable in the sexually dimorphic nucleus of the bulbocavernosus (SNB). The combination of alcohol and stress did not enhance the effect on the DLN above that produced by alcohol alone. Somal sizes in the DLN and SNB were not altered by any of the treatment conditions. Alcohol exposure probably leads to incomplete masculinization of the DLN in male rats by decreasing testicular steroidogenesis during the fetal stage(s) when sexual differentiation is ongoing in that CNS structure.

Comparative wear under four different tribological conditions of acetylene enhanced cross-linked ultra high molecular weight polyethylene.

In this study, the wear of ultra high molecular weight polyethylene (UHMWPE) (Grade RCH 1000) crosslinked by gamma irradiation in acetylene was compared to virgin (non-irradiated) UHMWPE using four different wear configurations: (i) unidirectional motion with a smooth counterface, (ii) multidirectional motion with a smooth counterface, (iii) unidirectional motion with a rough counterface and (iv) multidirectional motion with a rough counterface.

A case study on radon remedial measures in a family dwelling.

Field testing and computer modeling were used to study substructure ventilation, as a measure of controlling indoor radon in a house with a cellar. This is a common type of single family dwellings in areas of North England where radon is a problem. Testing carried out in the occupied house found that natural ventilation was not sufficient and both extract and supply ventilation were effective. Extract ventilation produced larger concentration reduction than supply at small air change rates. The house was also modeled by using a computer multi-zone air and pollutant movement simulation package. The simulated results were in good agreement with those measured for a wide range of conditions.

Prenatal alcohol and stress interact to attenuate ejaculatory behavior, but not serum testosterone or LH in adult male rats.

Restraint stress reduced blood alcohol levels in pregnant rats given a liquid alcohol diet. The male offspring prenatally exposed to both stress and alcohol failed to ejaculate spontaneously, although they copulated normally following exogenous testosterone (T) administration. Males prenatally exposed only to alcohol or only to stress showed no behavioral deficits. Adult serum T and luteinizing hormone levels were normal in both of the fetal alcohol exposed male groups. It appears that the androgen threshold for ejaculatory behavior is elevated in males prenatally exposed to alcohol plus stress and cannot be realized with normal testosterone titers, but it can be attained with exogenous hormone administration. Presumably the alcohol and stress combination interfered with ontogenetic patterns of T needed to fully masculinize the fetal nervous system.

Critical periods of sensitivity of sexually dimorphic spinal nuclei to prenatal testosterone exposure in female rats.

Male rats normally have more neurons than do females in two nuclei of the lumbar spinal cord, the spinal nucleus of the bulbocavernosus (SNB) and the dorsolateral nucleus (DLN). Female rats exposed to testosterone propionate (TP) on the 2 days of gestation (Days 18 and 19) when males normally experience a surge in plasma testosterone showed a maximal increase in both SNB and DLN neuronal number. TP exposure just prior to, or following, Days 18 and 19 led to smaller increments. Administration of a small (5 microg) dose of TP after birth, while having no effect by itself, synergized with prenatal TP to enhance the number of SNB neurons. DLN neurons were less responsive to postnatal TP. The somal and nuclear size of SNB, but not DLN, neurons was increased by perinatal TP. Paradoxically, the number of DLN neurons with large somas (1358 microm2 or larger) was reduced by perinatal TP, a finding congruent with a previous report that females and feminized males have more of these large DLN neurons than control males. Our data suggest an exquisite sensitivity of the developing spinal nuclei to the timing of hormonal surges normally found in fetal males. Exposure to androgens during a brief prenatal period is needed to assure responsiveness to the low amounts of androgen circulating during neonatal ontogeny, when the process of sexual differentiation is completed.