Search

Introduction The paper describes and examines a novel methodology to co-define transport and mobility challenges and co-create solutions with residents of a socioeconomically disadvantaged area within Oxford in the UK. The co-creation methodology is examined in relation to the extent of participation, inclusivity, transparency, interactivity, scale, sustainability/continuity, replicability, potential for co-benefits. Methods A Citizen Mobility Community was established with local residents at the core, and including representatives from the local authority, and other stakeholders. The paper describes the main elements of the co-creation process applied to identify mobility challenges, identify solutions, endorse the mobility solutions, and develop the solutions into practical action. Setting The setting was the Eastern Arc of Oxford, the most socioeconomically deprived area in Oxford. Results A sequence of co-creation activities helped identify and understand the transport challenges in Barton in the Eastern Arc of Oxford. Challenges included the high cost of public transport, traffic congestion, particularly during morning peak times, and the lack of cross-connectivity and direct public transport routes to desirable locations including affordable supermarkets, train stations, workplaces, health services such as hospitals and other neighbourhoods. The co-creation methodology led to the development of three pilot interventions to address these challenges, namely face-to-face transport app training, a transport to supermarkets shuttle service, and an information campaign about concessionary bus passes. Analysis of the co-creation methodology found that the process achieved its aims of empowering citizens in decision making about addressing locally experienced transport challenges, and building social capital. Conclusions The co-creation enables communities in areas of socioeconomic disadvantage to identify their transport challenges, and to co-develop and co-design practical solutions. Co-creation to address local transport needs builds community empowerment, creates social capital and may contribute, through plausible causal pathways, to improved health and wellbeing in an area of socioeconomic disadvantage.

A systematic approach was developed to investigate the stability of gentamicin sulfate (GS) and GS/poly (lactic-co-glycolic acid) (PLGA) coatings on hydroxyapatite surfaces. The influence of environmental factors (light, humidity, oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry. GS coated rods were found to be stable across the range of environments assessed, with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition. In contrast, rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C, 75% relative humidity or exposure to light. The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect. Finally, liquid chromatography–mass spectrometry analysis revealed that known gentamines C1, C1a and C2 were the major degradants formed. Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities., Graphical abstract fx1, Highlights • Method developed for extraction and analysis of an antimicrobial coated orthopedic device. • Evaluated the effect of light, humidity, oxygen and heat on the storage stability of drug coatings. • Also evaluated the influence of γ-ray sterilization on the chemical composition of drug coatings.

Purpose Cold static storage (CSS) is the standard method for heart preservation during transplantation (HTx). However, CSS beyond 4 hours increases the risk of primary graft dysfunction (PGD). Hypothermic ex vivo perfusion (HEVP) of donor hearts allows oxygen delivery during preservation, and may facilitate extended donor preservation without increasing PGD risk. We compared post-HTx survival, systemic inflammation and cardiac function following donor heart preservation by CSS (2 hrs) versus HEVP (2 and 8 hrs). Methods Brain death was induced in donor sheep for 24 hrs. Donor hearts were preserved by a) CSS for 2 hrs (n=7), b) HEVP for 2 hrs (n=4), or c) HEVP for 8 hrs (n=4). Orthotopic HTx was performed in matched recipients. Recipients were weaned from cardiopulmonary bypass and monitored for 6 hrs. Recipient blood was collected and assayed for inflammatory cytokines and cardiac markers. Cardiac function was assessed by echocardiography. Results Six-hour survival was 71% following CSS, and 100% following 2 and 8 hrs HEVP, respectively. Recipients systemic interleukin-6 and 8 levels were reduced using HEVP vs CSS. Post-HTx haemodynamic function was no different between groups, but HEVP reduced the requirement for vasoactive support compared to CSS (2 hrs CSS: 1.57±0.7; 2 hrs HEVP: 0.35±0.09; 8 hrs HEVP: 0.35±0.05 mmHg−1). HEVP was associated with reduced post-HTx lactate (2 hrs CSS: 11.4±1.8; 2 hrs HEVP: 5.2±0.7; 8 hrs HEVP: 6.7±1.3 mmol/L), more stable base excess and physiological pH in blood. Post-HTx cardiac function was no different between groups. Cardiac troponin I levels were comparable between CSS vs. 8 hrs HEVP, but reduced with 2 hrs HEVP. Conclusion Preliminary data on donor heart preservation by HEVP shows promising outcomes in comparison to CSS. Heart preservation by HEVP can be extended up to 8 hours, without compromising post-HTx recipient survival. HEVP may assist in overcoming limitations in preservation time associated with HTx, without increasing PGD risk.

Purpose Brain death (BD) causes metabolic and energetic imbalances leading to cardiac dysfunction, and predisposes the donor heart to further injury following heart transplantation (HTx). The metabolic mechanisms required for myocardial energy production during BD and subsequent HTx are poorly understood. Our aim was to determine the myocardial metabolic profile and mitochondrial function following donor BD and HTx. Methods Donor BD in sheep was induced by inflation of a catheter placed through the skull (catheter placement, but no inflation for SHAM), followed by 24 hrs monitoring, and heart procurement (n=6/group, BD vs. SHAM). Additional donor hearts exposed to BD/SHAM were flushed with cold St Thomas cardioplegia, and stored via cold static storage (CSS) for ∼2 hrs. Following standard orthotopic HTx, recipients were weaned off bypass and monitored for ≤6 hrs prior to heart procurement (n=4/group, BD-Tx vs. Sh-Tx). Cardiac mitochondrial function was assessed using high resolution respirometry. Metabolic profiles were determined in hearts using metabolomics. Cardiac mitochondrial function was also determined in two sheep that underwent HTx following BD and 8 hr hypothermic ex vivo perfusion (HEVP) preservation. Results BD caused significant right ventricular (RV) mitochondrial uncoupling (vs. SHAM). HTx following CSS also impaired RV mitochondrial function, with these effects more pronounced in hearts exposed to both donor BD and HTx. Early findings show that HEVP improved cardiac mitochondrial function post-HTx (vs. CSS). Metabolically, BD increased myocardial amino-acid utilisation and accumulation of glucose metabolites. Post-HTx, particularly in those exposed to donor BD, there was a significant decrease in metabolites involved in mitochondrial respiration (eg. NAD, Acetyl-CoA) and accumulation of fatty acids and xanthine (purine breakdown). Conclusion BD appears to trigger cardiac mitochondrial uncoupling. This may be a protective mechanism against higher amino-acid utilisation and glucose accumulation, in order to maintain adequate mitochondrial function for cell survival. HTx following CSS, particularly from BD donors, induces significant mitochondrial dysfunction, which occurs in response to upstream metabolic impairments. Strategies that improve cardiac mitochondrial function or metabolism (eg. HEVP) may assist to improve HTx outcomes.

The investigation of neural substrates of autism spectrum disorder using neuroimaging has been the focus of recent literature. In addition, machine-learning approaches have also been used to extract relevant information from neuroimaging data. There are only few studies directly exploring the inter-regional structural relationships to identify and characterize neuropsychiatric disorders. In this study, we concentrate on addressing two issues: (i) a novel approach to extract individual subject features from inter-regional thickness correlations based on structural magnetic resonance imaging (MRI); (ii) using these features in a machine-learning framework to obtain individual subject prediction of a severity scores based on neurobiological criteria rather than behavioral information. In a sample of 82 autistic patients, we have shown that structural covariances among several brain regions are associated with the presence of the autistic symptoms. In addition, we also demonstrated that structural relationships from the left hemisphere are more relevant than the ones from the right. Finally, we identified several brain areas containing relevant information, such as frontal and temporal regions. This study provides evidence for the usefulness of this new tool to characterize neuropsychiatric disorders.

Preschool-aged children (M = 42.44 months-old, SD = 8.02) participated in a short-term longitudinal study investigating the effect of educational media exposure on social development (i.e., aggression and prosocial behavior) using multiple informants and methods. As predicted, educational media exposure significantly predicted increases in both observed and teacher reported relational aggression across time. Follow-up analyses showed that educational media exposure also significantly predicted increases in parent reported relational aggression across more than a two year period. Results replicate and extend prior research that has demonstrated links between educational media exposure and relational aggression, but not physical aggression, during early childhood.

A preventive intervention for reducing physical and relational aggression, peer victimization, and increasing prosocial behavior was developed for use in early childhood classrooms. Nine classrooms were randomly assigned to be intervention rooms ( N = 202 children) and nine classrooms were control rooms ( N = 201 children). Classroom was the unit of analysis and both observations and teacher-reports were obtained at pre and post-test. Focus groups were used to develop the initial program. The 6-week program consisted of developmentally appropriate puppet shows, active participatory sessions, passive concept activities and in vivo reinforcement periods. Preliminary findings suggest that the “Early Childhood Friendship Project” tended to reduce physical and relational aggression, as well as physical and relational victimization and tended to increase prosocial behavior more for intervention than control classrooms. Teachers and interventionists provided positive evaluations of the program and there is evidence for appropriate program implementation.

The homo-oxo-calix[3]arene-facilitated electrochemistry of dopamine at the polarised liquid|liquid interface is presented. Cyclic voltammetry indicated that the dopamine: homo-oxo-calix[3]arene complex formed at the interface between water and 1,2-dichloroethane had a 1:2 stoichiometry, which was confirmed by 1 H NMR titration. The electrochemically-determined association constants for the homo-oxo-calix[3]arene complexes with dopamine (log β 8.3), Na + (8.0) and K + (7.5) showed that the ionophore was more selective for dopamine over the two alkali metal cations than the dibenzo-18-crown-6 ionophore. Square wave voltammetry was employed for assessment of low concentration measurements, with a limit of detection of 3.8 μM dopamine achieved. These results show that oxo-calixarene-based ionophores are useful reagents for the detection of dopamine at the interface between two immiscible electrolyte solutions.

In December 2001, Canada's response to the international political climate was launched by the creation of the Chemical, Biological, Radiological/Nuclear Research & Technology Initiative (CRTI). The National Biological Dosimetry Response Plan (NBDRP), established through partnering the expertise of three federal departments and one university, was created in response to this initiative. The NBDRP objectives were to develop a network of laboratories with expertise to perform biological dosimetry by cytogenetics and to investigate new technologies that may be applicable in the development of the new biodosimetry program. Since the creation of the NBDRP, Canada has made significant progress in enhancing expertise and resources to be better prepared for radiological/nuclear events. Through participation in exercises, the existing capacities were tested and recommendations for improvements were made. This paper describes the results from two exercises. The first exercise was designed to test the culturing, analysis, and reporting procedures within a single laboratory, and the second exercise was intended to test the capacity of the NBDRP. Future exercises will further challenge the network resulting in an improved national response capability.

While biodosimetry is a valuable tool in radiation dose assessment, the dicentric assay, which is the most validated method to date, requires some degree of technical competence. Recently published ISO guidelines indicate the need for documenting competence and establishment of quality control programs. Inter-laboratory comparisons are required to document the ability to perform reproducible and accurate assessments. FOI and DRDC Ottawa have conducted an initial limited biodosimetry exercise inter-comparison for quality assurance purposes. The exercise involved blinded exchange of three previously prepared slides from each laboratory from samples that had been evaluated for each lab's dose–response curve. Approximately 100 cells from each slide were evaluated and aberration frequencies reported and compared to the expected frequencies. The limited number of cells evaluated for each sample could not permit statistically distinguishing a 20% difference in all the samples. However, the results indicated reasonable agreement in analyses for all samples for triage purposes. Comparison of aberration frequencies, rather than dose estimates, further illustrates consistent scoring criteria between the two laboratories. The exercise conducted by FOI and DRDC Ottawa provided an efficient means of documenting expertise. Such cooperation further establishes the international biodosimetry network and ensures our readiness for emergency response.

Participation of immunoglobulin E in immune-mediated glomerulonephritis. Renal biopsy specimens from 146 consecutive patients were studied by direct immunofluorescent tests for immunoglobulins G, M, A, D, E, third component of complement and fibrinogen; 46 of the patients had nephrotic syndrome. Glomerular-bound Ig was detected in glomeruli of 85 patients, and significant immunoglobulin E (IgE) in 22 of them. The granular glomerular deposits of six of the 22 patients comprised IgE as the dominant or codominant Ig class; in one patient it was the only Ig seen. In all other instances IgE was a relatively less obvious Ig component of glomerular deposits. No correlation was detected between serum IgE concentrations and glomerular IgE deposits. The six patients with notable IgE deposits had persistent disease clinically and generalized glomerular disease immunohistochemically; two of the six patients had rapidly progressive glomerulonephritis. Clinical data implicated the β-hemolytic streptococcus as etiologic agent in three of the six patients, and suggested it in another.

A pump-oxygenator and isolation-perfusion circuit were used to selectively elevate hepatic temperature in 33 dogs to either 37, 41, or 43°C. Temperatures were maintained for 10–30 min. Survival was 75% in 8 dogs after 37°C × 30 min, 40% in 10 dogs after 41°C × 30 min (not significant), 40% in 5 dogs after 43°C × 10 min (not significant), and 0% in 10 dogs after 43°C × 30 min ( P ⩽ 0.01). Animals subjected to 43°C × 30 min hepatic perfusion exhibited an increase in fatal intraoperative arrhythmias despite maintenance of relatively normal blood pressure, systemic temperature, blood gases, and electrolytes. Six animals (2 after 43°C × 10-min perfusion, 4 after 43°C × 30-min perfusion) developed a postoperative symptom complex of progressive obtundation, fever, oliguria, hypotension, and death. Blood cultures were negative. Laboratory values in some animals suggested hepatic necrosis and early hepatic and renal failure but did not completely explain the clinical picture observed. The most striking finding in hyperthermically perfused animals was a diffuse hepatocyte vacuolopathy which on serial liver biopsies in surviving animals progressed to ballooning degeneration then complete resolution. This study demonstrates that temperatures suitable for thermotherapy of hepatic malignancies have hepatotoxic effects which are both temperature and time dependent. Present studies attempt to modulate the toxicity of hepatic hyperthermia by use of perfusate additives.

During a two year period, 65 patients with Stage II non-seminomatous testis cancer were randomized to receive adjuvant chemotherapy and radiation. Of the 52 evaluable patients, 23 received radiation followed by chemotherapy (sequential), and 29 received the same chemotherapy as initial treatment, but had drug treatment temporarily interrupted for radiation (sandwich). The combined treatment was well tolerated, but did not eliminate recurrence. With regard to duration of survival and disease-free survival, no statistically significant difference could be found between the sequential and sandwich approaches.

Novobiocin (Cathomycin) is an antibiotic produced in nutrient media by Streptomyces spheroides . Physical characteristics of the amorphous acid form of novobiocin were studied. The amorphous acid is biologically active, but proved metastable in aqueous suspension, reverting on standing to a less soluble, inactive crystal line form. Several distinct steps were identified during the process of reversion; the rate of reversion was found to be temperature dependent. Methods for suppressing crystallization of the amorphous acid are discussed. The properties of amorphous calcium novobiocin in formulation of aqueous suspensions were studied.