Optimal Scheduling Using Branch and Bound with SPIN 4.0

The use of model checkers to solve discrete optimisation problems is appealing. A model checker can first be used to verify that the model of the problem is correct. Subsequently, the same model can be used to find an optimal solution for the problem. This paper describes how to apply the new PROMELA primitives of SPIN 4.0 to search effectively for the optimal solution. We show how Branch-and-Bound techniques can be added to the LTL property that is used to find the solution. The LTL property is dynamically changed during the verification. We also show how the syntactical reordering of statements and/or processes in the PROMELA model can improve the search even further. The techniques are illustrated using two running examples: the Travelling Salesman Problem and a job-shop scheduling problem

The reliability of inspiratory resistive load magnitude and detection testing

Objectives: To assess the test-retest reliability of inspiratory load detection and load magnitude perception tests in healthy volunteers. Design: Cohort of convenience. Setting: Respiratory physiology laboratory. Participants: Twenty healthy adults. Interventions: On two separate occasions participants performed tests of inspiratory loading. Participants breathed through custom made resistive tubing and were asked to indicate when they detected a different resistance during inspiration. In a second test participants rated the magnitude of presented inspiratory loads using the modified Borg score. Main Outcome Measures: Intra-class Correlation Coefficient (ICC2,1) values for repeated tests of inspiratory load detection threshold and load magnitude rating. Results: ICC2,1 values ranged from 0.657–0.786 for load detection testing and 0.739 to 0.969 for rating of load magnitude. Conclusions: The tests are simple and reliable measures of inspiratory load detection and magnitude rating. They can be used in future research to determine the effectiveness of interventions to reduce the effort of breathing in health and disease

Metal-polymer functionally graded materials for removing guided wave reflections at beam end boundaries

This paper investigates the potential of a metal-polymer functionally graded material (FGM) to remove beam end boundary wave reflections that produce complicated interference patterns in the response signals used for guided wave damage identification methodologies. The metal-polymer FGM matches the material properties to a metal beam for total wave transmission on one side and is continuously graded to a viscoelastic polymer on the other side. An Aluminium-Polycarbonate (Al-PC) FGM was fabricated and characterised using microscopy, hardness testing and through-transmission ultrasonics to verify the continuous gradient. Measurements of guided waves on an aluminium beam attached to the FGM on one end show reduction in boundary wave reflections that varies with wave frequency. A damaged aluminium beam attached with the FGM produced promising improvements in a damage identification system

Inspiratory muscle responses to sudden airway occlusion in chronic obstructive pulmonary disease

Brief airway occlusion produces a potent reflex inhibition of inspiratory muscles that is thought to protect against aspiration. Its duration is prolonged in asthma and obstructive sleep apnea. We assessed this inhibitory reflex (IR) in chronic obstructive pulmonary disease (COPD). Reflex responses to brief (250 ms) inspiratory occlusions were measured in 18 participants with moderate to severe COPD (age 73 ± 11 yr) and 17 healthy age-matched controls (age 72 ± 6 yr). We compared the incidence and properties of the IR between groups. Median eupneic preocclusion electromyographic activity was higher in the COPD group than controls (9.4 μV vs. 5.2 μV, P = 0.001). Incidence of the short-latency IR was higher in the COPD group compared with controls (15 participants vs. 7 participants, P = 0.010). IR duration for scalenes was similar for the COPD and control groups [73 ± 37 ms (means ± SD) and 90 ± 50 ms, respectively] as was the magnitude of inhibition. IRs in the diaphragm were not detected in the controls but were present in 9 participants of the COPD group (P = 0.001). The higher incidence of the IR in the COPD group than in the age-matched controls may reflect the increased inspiratory neural drive in the COPD group. This higher drive counteracts changes in chest wall and lung mechanics. However, when present, the reflex was similar in size and duration in the two groups. The relation between the IR in COPD and swallowing function could be assessed. NEW & NOTEWORTHY A potent short-latency reflex inhibition of inspiratory muscles produced by airway occlusion was tested in people with COPD and age-matched controls. The reflex was more prevalent in COPD, presumably due to an increased neural drive to breathe. When present, the reflex was similar in duration in the two groups, longer than historical data for younger control groups. The work reveals novel differences in reflex control of inspiratory muscles due to aging as well as COPD

Modulation of anabolic and catabolic responses via a porous polymer scaffold manufactured using thermally induced phase separation

We describe two studies encompassing the iterative refinement of a polymer-based rhBMP-2 delivery system for bone tissue engineering. Firstly, we compared the boneforming capacity of porous poly(D,L-lactic-co-glycolic acid) (PLGA) scaffolds produced by thermally induced phase separation (TIPS) with non-porous solvent cast poly(D,L-lactic acid) (PDLLA) used previously. Secondly, we examined the potential synergy between rhBMP-2 and local bisphosphonate in the PLGA scaffold system. In vivo ectopic bone formation studies were performed in C57BL6/J mice. Polymer scaffolds containing 0, 5, 10 or 20 μg rhBMP-2 were inserted into the dorsal musculature. At all rhBMP-2 doses, porous PLGA produced significantly higher bone volume (BV, mm) than the solid PDLLA scaffolds. Next, porous PLGA scaffolds containing 10μg rhBMP-2 ±0.2, or 2μg zoledronic acid (ZA) were inserted into the hind-limb musculature. Co-delivery of local 10μg rhBMP-2/2μg ZA significantly augmented bone formation compared with rhBMP-2 alone (400 % BV increase, p < 0.01). Hydroxyapatite microparticle (HAp) addition (2% w/w) to the 10μg rhBMP-2/0.2μg ZA group increased BV (200 %, p < 0.01). We propose that this was due to controlled ZA release of HAp-bound ZA. Consistent with this, elution analyses showed that HAp addition did not alter the rhBMP-2 elution, but delayed ZA release. Moreover, 2 % w/w HAp addition reduced the scaffold's compressive properties, but did not alter ease of surgical handling. In summary, our data show that refinement of the polymer selection and scaffold fabrication can enhance rhBMP-2 induced bone formation in our bone tissue engineering implant, and this can be further optimised by the local co-delivery of ZA/HAp

Optimal Scheduling Using Branch and Bound with SPIN 4.0

The use of model checkers to solve discrete optimisation problems is appealing. A model checker can first be used to verify that the model of the problem is correct. Subsequently, the same model can be used to find an optimal solution for the problem. This paper describes how the new Promela primitives of Spin 4.0 can be applied to search e#ectively for the optimal solution. We show how Branch-and-Bound techniques can be added to the LTL property that is used to find the solution. The LTL property is dynamically changed during the verification

Spatial control of bone formation using a porous polymer scaffold co-delivering anabolic RHBMP-2 and anti-resorptive agents

Current clinical delivery of recombinant human bone morphogenetic proteins (rhBMPs) utilises freeze-dried collagen. Despite effective new bone generation, rhBMP via collagen can be limited by significant complications due to inflammation and uncontrolled bone formation. This study aimed to produce an alternative rhBMP local delivery system to permit more controllable and superior rhBMP-induced bone formation. Cylindrical porous poly(lactic-co-glycolic acid) (PLGA) scaffolds were manufactured by thermally-induced phase separation. Scaffolds were encapsulated with anabolic rhBMP-2 (20 μg) ± anti-resorptive agents: zoledronic acid (5 μg ZA), ZA pre-adsorbed onto hydroxyapatite microparticles, (5 μg ZA/2 % HA) or IkappaB kinase (IKK) inhibitor (10 μg PS-1145). Scaffolds were inserted in a 6-mm critical-sized femoral defect in Wistar rats, and compared against rhBMP-2 via collagen. The regenerate region was examined at 6 weeks by 3D microCT and descriptive histology. MicroCT and histology revealed rhBMP-induced bone was more restricted in the PLGA scaffolds than collagen scaffolds (-92.3 % TV, p < 0.01). The regenerate formed by PLGA + rhBMP-2/ZA/HA showed comparable bone volume to rhBMP-2 via collagen, and bone mineral density was +9.1 % higher (p < 0.01). Local adjunct ZA/HA or PS-1145 significantly enhanced PLGA + rhBMP-induced bone formation by +78.2 % and +52.0 %, respectively (p ≤ 0.01). Mechanistically, MG-63 human osteoblast-like cells showed cellular invasion and proliferation within PLGA scaffolds. In conclusion, PLGA scaffolds enabled superior spatial control of rhBMP-induced bone formation over clinically-used collagen. The PLGA scaffold has the potential to avoid uncontrollable bone formation-related safety issues and to customise bone shape by scaffold design. Moreover, local treatment with anti-resorptive agents incorporated within the scaffold further augmented rhBMP-induced bone formation

Samen sterk: een groepsprogramma voor ouders van jongeren met een depressie

Health and Well-bein

Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a study protocol for a randomised controlled trial

© 2016 Lee et al. Background: Urinary tract infections [UTIs] are very common in people with Spinal Cord Injury [SCI]. UTIs are increasingly difficult and expensive to treat as the organisms that cause them become more antibiotic resistant. Among the SCI population, there is a high rate of multi-resistant organism [MRO] colonisation. Non-antibiotic prevention strategies are needed to prevent UTI without increasing resistance. Probiotics have been reported to be beneficial in preventing UTIs in post-menopausal women in several in vivo and in vitro studies. The main aim of this study is to determine whether probiotic therapy with combinations of Lactobacillus reuteri RC-14 + Lactobacillus rhamnosus GR-1 [RC14-GR1] and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 [LGG-BB12] are effective in preventing UTI in people with SCI compared to placebo. Method: This is a multi-site randomised double-blind double-dummy placebo-controlled factorial design study conducted in New South Wales, Australia. All participants have a neurogenic bladder as a result of spinal injury. Recruitment started in April 2011. Participants are randomised to one of four arms, designed for factorial analysis of LGG-BB12 and/or RC14-GR1 v Placebo. This involves 24 weeks of daily oral treatment with RC14-GR1 + LGG-BB12, RC14-GR1 + placebo, LGG-BB12 + placebo or two placebo capsules. Randomisation is stratified by bladder management type and inpatient status. Participants are assessed at baseline, three months and six months for Short Form Health Survey [SF-36], microbiological swabs of rectum, nose and groin; urine culture and urinary catheters for subjects with indwelling catheters. A bowel questionnaire is administered at baseline and three months to assess effect of probiotics on bowel function. The primary outcome is time from randomisation to occurrence of symptomatic UTI. The secondary outcomes are change of MRO status and bowel function, quality of life and cost-effectiveness of probiotics in persons with SCI. The primary outcome will be analysed using survival analysis of factorial groups, with Cox regression modelling to test the effect of each treatment while allowing for the other, assuming no interaction effect. Hazard ratios and Kaplan-Meier survival curves will be used to summarise results. Discussion: If these probiotics are shown to be effective in preventing UTI and MRO colonisation, they would be a very attractive alternative for UTI prophylaxis and for combating the increasing rate of antibiotic resistance after SCI. Trial registration: Australian New Zealand Clinical Trials Registry [ ACTRN 12610000512022 ]. Date of registration: 21 June 2010