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Biomedical subjects

John Rose

Publications and source records attributed to John Rose.

At least 19 recordsLinked to original sources

Dynamic mechanical studies of hydrolytic degradation in isotropic and oriented Maxon B.

Hydrolytic degradation studies have been undertaken on Maxon B, a bioresorbable block copolymer of polyglycolic acid (PGA) and polytrimethylene carbonate (TMC). Isotropic and oriented samples were studied by dynamic mechanical measurements over a wide range of temperatures. In addition to mechanical tests, water content and mass loss were also determined on the degraded samples. At early stages of degradation water content was the dominant factor and plasticisation lead to reductions in the glass transition temperatures of the PGA and TMC components. Orientation was shown to give significant improvements in the mechanical properties, including overall increases in modulus and an increase in the glass transition temperature of the PGA component, which is important for the behaviour at body temperature (37 degrees C). Oriented samples also showed significantly less reduction in mechanical properties on degradation. Simple one-dimensional Takayanagi models were used to provide useful insight into the understanding of the mechanical behaviour.

Biocompatible Materials↗

IM interferon beta-1a delays definite multiple sclerosis 5 years after a first demyelinating event.

BACKGROUND: The Controlled High Risk Subjects Avonex Multiple Sclerosis Prevention Study (CHAMPS) showed that IM interferon beta-1a (IFNbeta-1a) significantly slows the rate of development of clinically definite multiple sclerosis (CDMS) over 2 years in high-risk patients who experience a first clinical demyelinating event. This report highlights the primary results of a 5-year, open-label extension of CHAMPS (the Controlled High Risk Avonex Multiple Sclerosis Prevention Study in Ongoing Neurologic Surveillance [CHAMPIONS Study]). OBJECTIVE: To determine if the benefits of IFNbeta-1a observed in CHAMPS are sustained for up to 5 years. METHODS: CHAMPS patients at participating CHAMPIONS sites were enrolled in the study. All patients were offered, but not required to take, IFNbeta-1a 30 microg IM once weekly for up to 5 years (from CHAMPS randomization). Patients who received placebo in CHAMPS were considered the delayed treatment (DT) group, and patients who received IFNbeta-1a in CHAMPS were considered the immediate treatment (IT) group. The primary outcome measure was the rate of development of CDMS. Additional outcomes included disease state classification at 5 years, annualized relapse rates, disability level at 5 years (Expanded Disability Status Scale), and MRI measures at 5 years. RESULTS: Fifty-three percent (203/383) of patients enrolled in CHAMPIONS (n = 100, IT group; n = 103, DT group) and 64% (32/50) of CHAMPS study sites participated in CHAMPIONS. The median time to initiation of IFNbeta-1a therapy in the DT group was 29 months. The cumulative probability of development of CDMS was significantly lower in the IT group compared with the DT group (5-year incidence 36 +/- 9 vs 49 +/- 10%; p = 0.03). Multivariate analysis suggested that the only factors independently associated with an increased rate of development of CDMS were randomization to the DT group and younger age at onset of neurologic symptoms. Few patients in either group developed major disability within 5 years. CONCLUSIONS: These results support the use of IM interferon beta-1a after a first clinical demyelinating event and indicate that there may be modest beneficial effects of immediate treatment compared with delayed initiation of treatment.

Adjuvants, Immunologic↗

Comparison of the hydrolytic degradation and deformation properties of a PLLA-lauric acid based family of biomaterials.

Addition of lauric acid to PLLA results in a significantly increased rate of hydrolytic degradation, with the time-to-loss of tensile strength directly related to the concentration of lauric acid. In this study, the hydrolytic degradation profiles of four materials were studied: amorphous PLLA, amorphous PLLA containing 1.8 wt % lauric acid, amorphous PLLA containing 4.5 wt % lauric acid, and pre-crystallized PLLA containing 1.8 wt % lauric acid. Hydrolytic degradation was monitored through mass profiles, molecular weight profiles, crystallinity and the development of mechanical properties and deformation mechanisms (through simultaneous small-angle X-ray scattering and tensile testing), and a "phase diagram" of properties suggested. The key factor in determining the development of properties was found to be the time at which crystallization occurred in relation to the loss of molecular weight, with the two factors most affecting this being the lauric acid content and the pre-degradation annealing treatment.

Biocompatible Materials↗

The offence process of sex offenders with intellectual disabilities: a qualitative study.

There have been few attempts to build a model of sexual offending for men with intellectual disabilities and hence clarify appropriate intervention. This study examines any commonalities that characterize the offence process of such men. Using a grounded theory approach, qualitative interviews with sex offenders with intellectual disabilities are analyzed to generate a model of the offence process. Data from qualitative interviews with clinicians is used to triangulate offender participants' data. The subsequent model highlights the importance of individual's attitudes and beliefs and the impact that they have at all stages of the offence process. It raises issues concerning the variation in the process that is seen within and between offences. Additionally, it identifies a marked lack of awareness of any "decency insult" in these offenders, an inability to empathize with society's view of sex offending. A clear implication is that thorough assessment and formulation are likely to be the key to successful and appropriate intervention.

Adult↗

Attitudes of direct care staff towards external professionals, team climate and psychological wellbeing: a pilot study.

Relationships with external professionals may be an important factor in the psychological wellbeing of care staff. A questionnaire to measure team climate and staff wellbeing was developed, tested and revised. Seventy-two direct care staff completed the revised questionnaire, which had acceptable levels of internal consistency. Significant correlations were found between care staff attitudes towards professionals and levels of team climate and psychological wellbeing. The pattern of relationships was explored by path analysis. Further work is needed on the reliability and validity of the questionnaire. There is a clear association between attitudes to professionals and team climate and between some aspects of climate and psychological wellbeing. Professionals should adopt collaborative ways of working based on problem-solving approaches with staff teams, with the aim of delivering improved quality of care to residents.

Adult↗

Identifying and assessing depression in prelingually deaf people: a literature review.

IDENTIFYING AND ASSESSING DEPRESSION is essential to ensuring access to appropriate treatment and services. Unfortunately, limited literature exists on identifying and assessing depression in prelingually deaf people. In a literature review, the authors critically examined relevant published studies. The earliest reported information on depression in deaf people was found in historical studies that descriptively evaluated specialist psychiatric services for deaf people. These studies did not accurately reflect the prevalence of depression; reasons for this are discussed. Issues regarding assessment of depression in deaf people, such as communication, use of interpreters, and use of standardized assessments, are examined. Studies that have attempted to overcome these challenges are reviewed, including studies using modified versions of written questionnaires designed for hearing people and studies in which standardized questionnaires were translated and administered in sign. Advantages and disadvantages of different methods are highlighted; recommendations for future research are made.

Activities of Daily Living↗

Use of the profunda femoris to facilitate closure of an antegrade puncture with the StarClose device after proximal SFA angioplasty.

PURPOSE: To report a novel technique for safely closing antegrade common femoral artery (CFA) punctures using the StarClose device after proximal superficial femoral artery (SFA) angioplasty. TECHNIQUE: The vessel locator of the StarClose device should not be deployed within a recently dilated vessel, so after proximal SFA angioplasty, the sheath is withdrawn into the CFA. A second guidewire is inserted into the profunda femoris artery followed by insertion of the StarClose sheath. The vessel locator is deployed in the profunda main stem and withdrawn into the CFA until resistance is felt, indicating apposition to the luminal aspect of the vessel wall. The device is subsequently deployed according to the manufacturer's instructions. CONCLUSION: Use of profunda femoris artery allows safe closure of the CFA using the StarClose device following antegrade puncture for proximal SFA angioplasty.

Alloys↗

SGXPro: a parallel workflow engine enabling optimization of program performance and automation of structure determination.

SGXPro consists of four components. (i) A parallel workflow engine that was designed to automatically manage communication between the different processes and build systematic searches of algorithm/program/parameter space to generate the best possible result for a given data set. This is performed by offering the user a palette of programs and techniques commonly used in X-ray structure determination in an environment that lets the user choose programs in a mix-and-match manner, without worrying about inter-program communication and file formats, during the structure-determination process. The current SGXPro program palette includes 3DSCALE, SHELXD, ISAS, SOLVE/RESOLVE, DM, SOLOMON, DMMULTI, BLAST, AMoRe, EPMR, XTALVIEW, ARP/wARP and MAID. (ii) A client/server architecture that allows the user to utilize the best computing facility available. (iii) Plug-in-and-play design, which allows easily integration of new programs into the system. (iv) User-friendly interface.

Crystallography, X-Ray↗

The effect of crystallinity on the deformation mechanism and bulk mechanical properties of PLLA.

Poly (l-lactide) is a widely studied biomaterial, currently approved for use in a range of medical devices, however, most in vitro studies have so far focussed upon either the bulk properties during degradation and/or deformation, or on the microstructure of the unloaded material during degradation. This study aimed to combine these approaches through the technique of simultaneous small-angle X-ray scattering and tensile testing at various stages of degradation up to 8 months, on material with a range of induced microstructures. Results showed that the amorphous material deformed by crazing in the dry, wet and degraded states, however, the mechanism by which the craze developed changed significantly on hydration. Despite this difference, there was little change in the bulk mechanical properties. Crystalline materials deformed through crystal-mediated deformation, with contributions from both cavitation and fibrillated shear, but surprisingly, differences in the length scales within the spherulitic structure caused by annealing at different temperatures had very little effect on the mechanism of deformation, though differences were seen in the bulk properties. Furthermore, hydration had little effect on the crystalline materials, though degradation over 8 months resulted in loss of mechanical properties for samples produced at higher annealing temperatures. In conclusion, the introduction of crystallinity had a huge effect on both bulk and microscopic properties of PLLA, but the spherulitic structure of the crystalline material affected the bulk properties significantly more than it did the micromechanism of deformation.

Absorbable Implants↗

All three Ca2+-binding loops of photoproteins bind calcium ions: the crystal structures of calcium-loaded apo-aequorin and apo-obelin.

The crystal structures of calcium-loaded apo-aequorin and apo-obelin have been determined at resolutions 1.7A and 2.2 A, respectively. A calcium ion is observed in each of the three EF-hand loops that have the canonical calcium-binding sequence, and each is coordinated in the characteristic pentagonal bipyramidal configuration. The calcium-loaded apo-protein retain the same compact scaffold and overall fold as the unreacted photoproteins containing the bound substrate, 2-hyroperoxycoelenterazine, and also the same as the Ca2+-discharged obelin bound with product, coleneteramide. Nevertheless, there are easily discerned shifts in both helix and loop regions, and the shifts are not the same between the two proteins. It is suggested that these photoproteins to sense Ca2+ concentration transients and to produce their bioluminescence response on the millisecond timescale. A mechanism of intrastructural transmission of the calcium signal is proposed.

Aequorin↗

Radiofrequency ablation of recurrent cholangiocarcinoma after orthotopic liver transplantation -- a case report.

AIM: To report the use of radiofrequency ablation in the treatment of recurrent cholangiocarcinoma in the transplanted liver. METHODS: A lady who underwent orthotopic liver transplantation (OLT) for intrahepatic cholangiocarcinoma recurrence of tumour 13 mo after transplantation inspite of adjuvant chemotherapy. Her recurrent tumour was treated with radiofrequency ablation. RESULTS: She survived for 18 mo following the recurrence of her tumour. CONCLUSION: Radiofrequency ablation can be used safely in the transplanted liver to treat recurrent tumour.

Bile Duct Neoplasms↗

Protein production and crystallization at SECSG -- an overview.

Using a high degree of automation, the Southeast Collaboratory for Structural Genomics (SECSG) has developed high throughput pipelines for protein production, and crystallization using a two-tiered approach. Primary, or tier-1, protein production focuses on producing proteins for members of large Pfam families that lack a representative structure in the Protein Data Bank. Target genomes are Pyrococcus furiosus and Caenorhabditis elegans. Selected human proteins are also under study. Tier-2 protein production, or target rescue, focuses on those tier-1 proteins, which either fail to crystallize or give poorly diffracting crystals. This two tier approach is more efficient since it allows the primary protein production groups to focus on the production of new targets while the tier-2 efforts focus on providing additional sample for further studies and modified protein for structure determination. Both efforts feed the SECSG high throughput crystallization pipeline, which is capable of screening over 40 proteins per week. Details of the various pipelines in use by the SECSG for protein production and crystallization, as well as some examples of target rescue are described.

Animals↗

Salvaging Pyrococcus furiosus protein targets at SECSG.

Proteins derived from the coding regions of Pyrococcus furiosus are targets for three-dimensional X-ray and NMR structure determination by the Southeast Collaboratory for Structural Genomics (SECSG). Of the 2,200 open reading frames (ORFs) in this organism, 220 protein targets were cloned and expressed in a high-throughput (HT) recombinant system for crystallographic studies. However, only 96 of the expressed proteins could be crystallized and, of these, only 15 have led to structures. To address this issue, SECSG has recently developed a two-tier approach to protein production and crystallization. In this approach, tier-1 efforts are focused on producing protein for new Pfu(italics?) targets using a high-throughput approach. Tier-2 protein production efforts support tier-1 activities by (1) producing additional protein for further crystallization trials, (2) producing modified protein (further purification, methylation, tag removal, selenium labeling, etc) as required and (3) serving as a salvaging pathway for failed tier-1 proteins. In a recent study using this two-tiered approach, nine structures were determined from a set of 50 Pfu proteins, which failed to produce crystals suitable for X-ray diffraction analysis. These results validate this approach and suggest that it has application to other HT crystal structure determination applications.

Archaeal Proteins↗

A degradation study of PLLA containing lauric acid.

Addition of lauric acid to poly (L-lactide) (PLLA) has resulted in a new family of enhanced degradation biomaterials. Presented is PLLA4.5 (PLLA containing 4.5 wt% lauric acid), the fastest degrading of the family. Degradation was studied via mass changes, gel-permeation chromatography, wide- and small-angle X-ray scattering (WAXS and SAXS), simultaneous SAXS and tensile testing, and visual observation. The undegraded PLLA4.5 deformed by crazing, recognisable from the characteristic shape of the SAXS pattern. As water up-take and degradation proceeded, samples crystallised, decreasing the SAXS long period, until by 4 days the deformation mechanism had become that of crystal-mediated deformation. This resulted in a 'peanut-lemon'-shaped SAXS pattern, interpreted in terms of cavitation and fibrillated shear. Further degradation up to 12 days resulted in the same deformation mechanism at different sample displacements, with samples failing earlier during tensile testing until a ductile-brittle transition occurred. At 30-40 days water up-take and mass-loss increased significantly and global whitening of samples occurred, while the crystallinity and long period stabilised. Complete degradation had not occurred by the end of the study at 73 days. Through an understanding of how the changes in morphology during degradation affect the micromechanisms of deformation, it may be possible to design microstructures to give a tailored evolution of mechanical response in the body.

Absorbable Implants↗

Complications and bail-out situations during AAA endovascular repair.

The endovascular stent-graft is now a universally accepted treatment for abdominal aortic aneurysms but remains nonetheless experimental. There are generic aspects of endograft insertion as well as device specific deployment issues. There are a number of potential procedural complications, related to vascular access and to the deployment sequence. The common technical problems are described and, where possible, the endovascular solutions are outlined.

Aortic Aneurysm, Abdominal↗

Randomized, controlled clinical trial of point-of-care limited ultrasonography assistance of central venous cannulation: the Third Sonography Outcomes Assessment Program (SOAP-3) Trial.

CONTEXT: A 2001 Agency for Healthcare Research and Quality Evidence Report on patient safety addressed point-of-care limited ultrasonography guidance for central venous cannulation and strongly recommended real-time, dynamic guidance for all central cannulas. However, on the basis of one limited study, the report dismissed static assistance, a "quick look" with ultrasound to confirm vein location before preparing the sterile field, as unhelpful. OBJECTIVE: The objective of this trial was to compare the overall success rate of central cannula placement with use of dynamic ultrasound (D), static ultrasound (S), and anatomical landmarks (LM). DESIGN AND SETTING: A concealed, randomized, controlled, clinical trial conducted from September 2003 to February 2004 in a U.S. urban teaching hospital. PATIENTS: Two-hundred one patients undergoing internal jugular vein central venous cannulation. INTERVENTIONS: Patients were randomly assigned to three groups: 60 to D, 72 to S, and 69 to LM. An iLook25 SonoSite was used for all imaging. MEASUREMENTS AND MAIN RESULTS: Cannulation success, first-attempt success, and number of attempts were noted. Other measures were vein size and clarity of LM. Results, controlled for pretest difficulty assessment, are stated as odds improvement (95% confidence interval) over LM for D and S. D had an odds 53.5 (6.6-440) times higher for success than LM. S had an odds 3 (1.3-7) times higher for success than LM. The unadjusted success rates were 98%, 82%, and 64% for D, S, and LM. For first-attempt success, D had an odds 5.8 (2.7-13) times higher for first success than LM, and S had an odds 3.4 (1.6-7.2) times higher for first success than LM. The unadjusted first-attempt success rates were 62%, 50%, and 23% for D, S, and LM. CONCLUSIONS: Ultrasound assistance was superior to LM techniques. D outperformed S but may require more training and personnel. All central cannula placement should be conducted with ultrasound assistance. The 2001 Agency for Healthcare Research and Quality Evidence Report dismissing static assistance was incorrect.

Aged↗

Factors affecting the likelihood that people with intellectual disabilities will gain employment.

The study aimed to identify factors that may affect the likelihood that people with intellectual disabilities will find employment through a supported employment agency. A retrospective analysis of the files of the last 200 individuals to use such an agency was carried out. Variables were identified that may influence outcome, such as demographic factors, job preferences and identified support needs. A specific rating of staff assessed client motivation was developed from written comments made by staff. Staff assessed motivation after two weeks on the scheme was found to be the only significant predictor of employment outcome. Motivation levels decreased for all groups of participants while at the agency, irrespective of work outcome. This study highlights that a greater emphasis on motivation within employment agencies may increase the chances of people with intellectual disability finding work.

Adult↗