Transitioning from electrodialysis to reverse electrodialysis stack design for energy generation from high concentration salinity gradients.

In this study, stack design for high concentration gradient reverse electrodialysis operating in recycle is addressed. High concentration gradients introduce complex transport phenomena, which are exacerbated when recycling feeds; a strategy employed to improve system level energy efficiency. This unique challenge indicates that membrane properties and spacer thickness requirements may differ considerably from reverse electrodialysis for lower concentration gradients (e.g. seawater/river water), drawing closer parallels to electrodialysis stack design. Consequently, commercially available electrodialysis and reverse electrodialysis stack design was first compared for power generation from high concentration gradients. Higher gross power densities were identified for the reverse electrodialysis stack, due to the use of thinner membranes characterised by a higher permselectivity, which improved current. However, energy efficiency of the electrodialysis stack was twice that recorded for the reverse electrodialysis stack at low current densities, which was attributed to: (i) an increased residence time provided by the larger intermembrane distance, and (ii) reduced exergy losses of the electrodialysis membranes, which provided comparatively lower water permeance. Further in-depth investigation into membrane properties and spacer thickness identified that membranes characterised by an intermediate water permeability and ohmic resistance provided the highest power density and energy efficiency (Neosepta ACS/CMS), while wider intermembrane distances up to 0.3 mm improved energy efficiency. This study confirms that reverse electrodialysis stacks for high concentration gradients in recycle therefore demand design more comparable to electrodialysis stacks to drive energy efficiency, but when selecting membrane properties, the trade-off with permselectivity must also be considered to ensure economic viability.

Scale-up of reverse electrodialysis for energy generation from high concentration salinity gradients.

Whilst reverse electrodialysis (RED) has been extensively characterised for saline gradient energy from seawater/river water (0.5 M/0.02 M), less is known about RED stack design for high concentration salinity gradients (4 M/0.02 M), important to closed loop applications (e.g. thermal-to-electrical, energy storage). This study therefore focuses on the scale-up of RED stacks for high concentration salinity gradients. Higher velocities were required to attain a maximum Open Circuit Voltage (OCV) for 4 M/0.02 M, which gives a measure of the electrochemical potential of the cell. The experimental OCV was also much below the theoretical OCV, due to the greater boundary layer resistance observed, which is distinct from 0.5 M/0.02 M. However, negative net power density (net produced electrical power divided by total membrane area) was demonstrated with 0.5 M/0.02 M for larger stacks using shorter residence times (three stack sizes tested: 10 × 10cm, 10 × 20cm and 10 × 40cm). In contrast, the highest net power density was observed at the shortest residence time for the 4 M/0.02 M concentration gradient, as the increased ionic flux compensated for the pressure drop. Whilst comparable net power densities were determined for the 10 × 10cm and 10 × 40cm stacks using the 4 M/0.02 M concentration gradient, the osmotic and ionic transport mechanisms are distinct. Increasing cell pair number improved maximum current density. This subsequently increased power density, due to the reduction in boundary layer resistance, and may therefore be used to improve thermodynamic efficiency and power density from RED for high concentrations. Although comparable power densities may be achieved for small and large stacks, large stacks maybe preferred for high concentration salinity gradients due to the comparative benefit in thermodynamic efficiency in single pass. The greater current achieved by large stacks may also be complemented by an increase in cell pair number and current density optimisation to increase power density and reduce exergy losses.

Managing power dissipation in closed-loop reverse electrodialysis to maximise energy recovery during thermal-to-electric conversion.

Whilst the efficiency of reverse electrodialysis (RED) for thermal-to-electrical conversion has been theoretically demonstrated for low-grade waste heat, the specific configuration and salinity required to manage power generation has been less well described. This study demonstrates that operating RED by recycling feed solutions provides the most suitable configuration for energy recovery from a fixed solution volume, providing a minimum unitary cost for energy production. For a fixed membrane area, recycling feeds achieves energy efficiency seven times higher than single pass (conventional operation), and with an improved power density. However, ionic transport, water flux and concentration polarisation introduce complex temporal effects when concentrated brines are recirculated, that are not ordinarily encountered in single pass systems. Regeneration of the concentration gradient at around 80% energy dissipation was deemed most economically pragmatic, due to the increased resistance to mass transport beyond this threshold. However, this leads to significant exergy destruction that could be improved by interventions to better control ionic build up in the dilute feed. Further improvements to energy efficiency were fostered through optimising current density for each brine concentration independently. Whilst energy efficiency was greatest at lower brine concentrations, the work produced from a fixed volume of feed solution was greatest at higher saline concentrations. Since the thermal-to-electrical conversion proposed is governed by volumetric heat utilisation (distillation to reset the concentration gradient), higher brine concentrations are therefore recommended to improve total system efficiency. Importantly, this study provides new evidence for the configuration and boundary conditions required to realise RED as a practical solution for application to sources of low-grade waste heat in industry.

Injury prevalence across sports: a descriptive analysis on a representative sample of the Danish population.

BACKGROUND: Physical activity plays an important role in public health, owing to a range of health-related benefits that it provides. Sports-related injuries are known to be an important barrier to continued physical activity. Still, the prevalence of injuries on a general population level has not yet been explored in a descriptive epidemiological investigation. The purpose of the questionnaire-based study, therefore, was to describe the prevalence of injury in a representative sample of the Danish population. METHODS: Two samples of 10,000 adults (> 15 years) and 6500 children and adolescents (7-15 years) were invited to respond to a web-based questionnaire. Of these, 3498 adults (35.0%) and 3221 children (49.6%) responded successfully. The definition of sports injury was time-loss and medical attention-based, inhibiting participants from sports activity for at least 7 days, and/or involved contact with a healthcare professional, respectively. RESULTS: Amongst adults, 642 (18.4% [95%CI: 17.1%; 19.6%]) reported to have had an injury within the past 12 months. Males reported significantly more injuries than females (difference in prevalence proportion: 9.2%-points [95%CI: 6.7%-points; 11.8%-points]). The prevalence of injuries was greatest in running (ninj = 198), football (ninj = 94) and strength training (ninj = 89). Amongst children, 621 (19.3% [95%CI: 17.9%; 20.6%]) had been injured. No difference in injury prevalence proportion existed between boys and girls. The prevalence of injuries was greatest in football (ninj = 235), handball (ninj = 86) and gymnastics (ninj = 66). CONCLUSIONS: Sports injuries seem to be very frequent in Denmark, since a total of 18.4% of the adults and 19.3% of the children reported having had one or more injuries within the past 12 months, equal to either time lost with physical activity and/or contact to the health care system.

From control to causation: Validating a 'complex systems model' of running-related injury development and prevention.

INTRODUCTION: There is a need for an ecological and complex systems approach for better understanding the development and prevention of running-related injury (RRI). In a previous article, we proposed a prototype model of the Australian recreational distance running system which was based on the Systems Theoretic Accident Mapping and Processes (STAMP) method. That model included the influence of political, organisational, managerial, and sociocultural determinants alongside individual-level factors in relation to RRI development. The purpose of this study was to validate that prototype model by drawing on the expertise of both systems thinking and distance running experts. MATERIALS AND METHODS: This study used a modified Delphi technique involving a series of online surveys (December 2016- March 2017). The initial survey was divided into four sections containing a total of seven questions pertaining to different features associated with the prototype model. Consensus in opinion about the validity of the prototype model was reached when the number of experts who agreed or disagreed with survey statement was ≥75% of the total number of respondents. RESULTS: A total of two Delphi rounds was needed to validate the prototype model. Out of a total of 51 experts who were initially contacted, 50.9% (n = 26) completed the first round of the Delphi, and 92.3% (n = 24) of those in the first round participated in the second. Most of the 24 full participants considered themselves to be a running expert (66.7%), and approximately a third indicated their expertise as a systems thinker (33.3%). After the second round, 91.7% of the experts agreed that the prototype model was a valid description of the Australian distance running system. CONCLUSION: This is the first study to formally examine the development and prevention of RRI from an ecological and complex systems perspective. The validated model of the Australian distance running system facilitates theoretical advancement in terms of identifying practical system-wide opportunities for the implementation of sustainable RRI prevention interventions. This 'big picture' perspective represents the first step required when thinking about the range of contributory causal factors that affect other system elements, as well as runners' behaviours in relation to RRI risk.

A framework for the etiology of running-related injuries.

The etiology of running-related injury is important to consider as the effectiveness of a given running-related injury prevention intervention is dependent on whether etiologic factors are readily modifiable and consistent with a biologically plausible causal mechanism. Therefore, the purpose of the present article was to present an evidence-informed conceptual framework outlining the multifactorial nature of running-related injury etiology. In the framework, four mutually exclusive parts are presented: (a) Structure-specific capacity when entering a running session; (b) structure-specific cumulative load per running session; (c) reduction in the structure-specific capacity during a running session; and (d) exceeding the structure-specific capacity. The framework can then be used to inform the design of future running-related injury prevention studies, including the formation of research questions and hypotheses, as well as the monitoring of participation-related and non-participation-related exposures. In addition, future research applications should focus on addressing how changes in one or more exposures influence the risk of running-related injury. This necessitates the investigation of how different factors affect the structure-specific load and/or the load capacity, and the dose-response relationship between running participation and injury risk. Ultimately, this direction allows researchers to move beyond traditional risk factor identification to produce research findings that are not only reliably reported in terms of the observed cause-effect association, but also translatable in practice.

Stimulated Raman scattering microscopy: an emerging tool for drug discovery.

Optical microscopy techniques have emerged as a cornerstone of biomedical research, capable of probing the cellular functions of a vast range of substrates, whilst being minimally invasive to the cells or tissues of interest. Incorporating biological imaging into the early stages of the drug discovery process can provide invaluable information about drug activity within complex disease models. Spontaneous Raman spectroscopy has been widely used as a platform for the study of cells and their components based on chemical composition; but slow acquisition rates, poor resolution and a lack of sensitivity have hampered further development. A new generation of stimulated Raman techniques is emerging which allows the imaging of cells, tissues and organisms at faster acquisition speeds, and with greater resolution and sensitivity than previously possible. This review focuses on the development of stimulated Raman scattering (SRS), and covers the use of bioorthogonal tags to enhance sample detection, and recent applications of both spontaneous Raman and SRS as novel imaging platforms to facilitate the drug discovery process.

The value of MRI undertaken immediately after reduction of the hip as a predictor of long-term acetabular dysplasia.

Our aim was to determine whether abnormalities noted on MRI immediately after reduction for developmental dysplasia of the hip could predict the persistance of dysplasia and aid surgical planning. Scans of 13 hips in which acetabular dysplasia had resolved by the age of four years were compared with those of five which had required pelvic osteotomy for persisting dysplasia. The scans were analysed by two consultant musculoskeletal radiologists who were blinded to the outcome in each child. The postreduction scans highlighted a number of anatomical abnormalities secondary to developmental dysplasia of the hip, but statistical analysis showed that none were predictive of persisting acetabular dysplasia in the older child, suggesting that the factors which determine the long-term outcome were not visible on these images.

MRI features of posterior ankle impingement syndrome in ballet dancers: a review of 25 cases.

AIM: To describe the magnetic resonance imaging (MRI) features of posterior ankle impingement syndrome (PAIS) in classical ballet dancers. MATERIALS AND METHODS: A retrospective review was undertaken of 25 MRI examinations of the ankle performed on 23 ballet dancers over a 26-month period. Images were examined for the presence of osseous and soft-tissue anatomical variants at the posterior ankle and imaging signs of PAIS. All patients presented with symptoms and signs suggestive of PAIS including posterior ankle pain, swelling and stiffness during plantar flexion. RESULTS: Anatomical variants predisposing to PAIS including as os trigonum and tuberosity arising from the superior calcaneum were clearly depicted. The most common imaging feature of PAIS in our series was high T2 signal posterior to the talocalcaneal joint indicating synovitis (n = 25). Thickening of the posterior capsule (n = 13) and tenosynovitis of flexor hallucis longus (n = 17) were also common. An os trigonum was an infrequent finding (n = 7). Bone marrow oedema, commonly in the posterior talus (n = 10) or in a patchy distribution (n = 10) was often noted. CONCLUSION: MRI is a useful diagnostic tool in PAIS, and in the present series, clearly demonstrates the anatomical variants and range of osseous and soft-tissue abnormalities associated with this condition. Prospective studies are needed to understand the significance and importance of individual MRI findings in producing the symptoms of PAIS.

Randomized multicenter trial of natalizumab in acute MS relapses: clinical and MRI effects.

BACKGROUND: Relapses in multiple sclerosis (MS) can cause significant neurologic disability. Natalizumab (Antegren) is a humanized anti-alpha4-integrin antibody that inhibits the trafficking of leukocytes across endothelium by blocking binding of alpha4beta1-integrin to vascular cell adhesion molecule-1. OBJECTIVE: To assess the effects of a single dose of IV natalizumab administered soon after the onset of MS relapses. METHODS: In this randomized, double-blind, multicenter trial, the effects of a single dose of IV natalizumab administered soon after the onset of MS relapses were assessed. MS patients (n = 180) in acute relapse were randomly assigned to receive a single dose of natalizumab 1 or 3 mg/kg or placebo and were followed for 14 weeks. RESULTS: There was no difference in Expanded Disability Status Scale (EDSS) score change over time between treatment and placebo groups. In all three groups, approximately half of patients showed EDSS improvement after 2 weeks, rising to 67% by 8 weeks. EDSS improved by a mean value of 0.8 point at week 1, 1.2 points at week 4, and 1.6 points at week 8 in the natalizumab group compared with EDSS improvement of 1.0 point at week 1, 1.6 points at week 4, and 1.6 points at week 8 in the placebo group. A significant decrease in Gd-enhancing lesion volume was seen in both active treatment groups at weeks 1 and 3 compared with placebo. CONCLUSIONS: A single dose of IV natalizumab did not hasten clinical recovery after relapse, although a significant decrease in Gd-enhancing lesion volume was observed at 1 and 3 weeks after treatment. These MRI findings are consistent with prior studies of natalizumab and support its further investigation as an agent for the treatment of MS.

Pictorial review: MRI features of foot and ankle injuries in ballet dancers.

Foot and ankle pain is common in ballet dancers. Although clinical examination often points to the underlying cause, imaging is often necessary to confirm the diagnosis and thus ensure appropriate future management. Factors predisposing to the increased incidence of injuries in this population include the classical position in which ballet dancers stand, which is on the tips of the toes in the en pointe position or on the balls of the feet in the demi-pointe position. Furthermore, the repetitious nature of ballet and the long hours spent rehearsing cause over-use injuries. The causes of foot and ankle pain can be thought of in four different groups: the impingement syndromes; tendon abnormalities; osseous pathology; and ligament abnormalities. These will be discussed and illustrated.

Expression of Escherichia coli B nitroreductase in established human tumor xenografts in mice results in potent antitumoral and bystander effects upon systemic administration of the prodrug CB1954.

Expression of the Escherichia coli enzyme nitroreductase (NTR) in mammalian cells enables them to activate the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954), leading to interstrand DNA cross-linking and apoptosis in both proliferating and quiescent cells. In the work reported here, we used human hepatocellular carcinoma and squamous carcinoma cell lines constitutively expressing NTR to demonstrate that the ntr/CB1954 system results in potent, long-lasting antitumoral effects in mice. We also demonstrate that this enzyme/prodrug combination results in antitumoral effects in vivo when only a minority of tumor cells express the enzyme, using either cells constitutively expressing NTR or ntr gene delivery in situ.

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with type A-resistant cervical dystonia (CD). BACKGROUND: Local intramuscular injections of BoNT are an effective therapy for CD. After repeated use, some patients become resistant to therapy. BoNT/B, effective in type A toxin-responsive patients, is proposed as an alternative therapy for type A-resistant patients. METHODS: The authors performed a 16-week, double-blind, placebo-controlled trial of BoNT/B in type A-resistant patients with CD. After resistance to therapy was confirmed with the frontalis-type A test, placebo or 10,000 U BoNT/B was administered in a single session into two to four clinically involved muscles. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was the primary efficacy measurement. TWSTRS-Total, three visual analog scales (Patient Global Assessment of Change, Principal Investigator Global Assessment of Change, Patient Analog Pain Assessment), and adverse events were assessed at baseline and weeks 2, 4, 8, 12, and 16. RESULTS: A total of 77 patients participated (38 placebo, 39 active). Improvements in severity, disability, and pain were documented in the BoNT/B-treated group. TWSTRS-Total scores were improved in the BoNT/B-treated group at weeks 4 (p = 0.0001), 8 (p = 0.0002), and 12 (p = 0.0129). All three visual analog scales demonstrated improvements at week 4 (p < 0.0001, 0.0001, and 0.001). A Kaplan-Meier analysis supported a duration of effect of 12 to 16 weeks in the active group. Dry mouth and dysphagia were self-limited adverse effects, reported more commonly in the BoNT/B group. CONCLUSIONS: Botulinum toxin type B (BoNT/B) (NeuroBloc) is safe and efficacious for the management of patients with type A-resistant cervical dystonia with an estimated duration of treatment effect of 12 to 16 weeks.

Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia.

OBJECTIVE: To determine the safety and efficacy of botulinum toxin type B (BoNT/B) in patients with cervical dystonia (CD). BACKGROUND: BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD. METHODS: The authors performed a 16-week, randomized, multicenter, double-blind, placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A. Placebo, or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinically in CD. The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure. Clinical assessments and adverse events were recorded for treatment day 1 and at weeks 2, 4, 8, 12, and 16. RESULTS: A total of 109 patients were enrolled randomly across all three treatment groups. The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 (placebo), 9.3 (5,000 U), and 11.7 (10,000 U). For the prospectively defined primary contrast (10,000 U versus placebo), highly significant differences were noted for the primary (TWSTRS-Total, baseline to week 4, p = 0.0004) and supportive secondary (Patient Global Assessment, baseline to week 4, p = 0.0001) outcome measures. Improvement in pain, disability, and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients. Overall, improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose. The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses. CONCLUSION: Botulinum toxin type B (NeuroBloc) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia.

A safety and pharmacokinetic study of intravenous natalizumab in patients with MS.

A phase 1, randomized, placebo-controlled, five-level dose escalation safety and tolerability and pharmacokinetic study of a single IV dose of natalizumab was performed. Doses of 0.03 to 3.0 mg/kg natalizumab or placebo were studied in 28 stable relapsing-remitting or secondary-progressive MS. All doses were safe and well tolerated in MS. Serum concentrations of natalizumab are detectable for 3 to 8 weeks after a single 1- or 3-mg/kg IV dose and justify controlled efficacy studies.

Targeting of microdiscs in white cells to tibial abscesses in rabbits.

The ability to deliver drugs to specific foci of infection is a sought-after goal. One solution is to use microparticles as drug carriers. This approach is limited by detection of microparticles by the reticuloendothelial system (RES). In order to reduce RES uptake of such particles, we investigated the possibility of "hiding" microparticles within white cells prior to targeting them to experimental tibial abscesses. We used radioactive silicone microdiscs, supplied by the Royal Signals & Radar Establishment. Twelve rabbits with abscesses in the right tibia were used: six control animals received radioactive opsonised microdiscs intravenously, and six animals received the same dose of microdiscs following incubation of the microdiscs with white cells. Each animal's liver, spleen, lungs, and both tibiae were removed, weighed, and homogenised. Radioactivity counts were obtained from each tissue, and the ratio of counts per gram of tissue for the right/left tibiae was calculated for the two groups of animals. The ratio of counts in the control group was 1.66 (+/- 0.57 SD), and the mean ratio of counts from the rabbits who had microdisc incubated with white cells was 3.32 (+/- 0.52 SD). This difference was statistically significant at p = 0.02 (Mann-Whitney U test).

Intestinal ischaemia associated with phaeochromocytoma.

The present case report describes a patient with an adrenal phaeochromocytoma who presented with infarction of the small intestine. The clinical features, diagnosis and treatment of this case are described. Despite excision of the tumour and necrotic intestine, this patient died in the postoperative period from overwhelming sepsis and multi-organ failure. Special reference is made to the delayed effects of established intestinal ischaemia on immune function and it is suggested that this was major contributory factor to the fatal outcome in the present case. The onset of gastro-intestinal symptoms in patients with phaeochromocytoma should suggest the possibility of imminent gut ischaemia and indicate the necessity for prompt excision of the tumour.

Baclofen in the elderly stroke patient its side-effects and pharmacokinetics.

A double blind crossover trial of baclofen against placebo in elderly stroke patients was discontinued because the drug produced an unacceptably high level of drowsiness. In a subsequent study baclofen 10 mg was given orally to 12 elderly stroke patients, and drug concentrations measured from a series of plasma samples. A group of healthy subjects given the same dose in a previous study were used as controls. Elderly patients took longer to achieve peak plasma baclofen concentrations, but healthy controls had higher peak values and eliminated the drug more rapidly; areas under the curve were similar in the two groups. Simulations based on mean data suggest that increased drowsiness in the elderly was probably not due to changes in the drug's pharmacokinetic behaviour.