Reachability in Biochemical Dynamical Systems by Quantitative Discrete Approximation (extended abstract)

In this paper, a novel computational technique for finite discrete approximation of continuous dynamical systems suitable for a significant class of biochemical dynamical systems is introduced. The method is parameterized in order to affect the imposed level of approximation provided that with increasing parameter value the approximation converges to the original continuous system. By employing this approximation technique, we present algorithms solving the reachability problem for biochemical dynamical systems. The presented method and algorithms are evaluated on several exemplary biological models and on a real case study.Comment: In Proceedings CompMod 2011, arXiv:1109.104

Urgent Need to Strengthen the Chain of Survival in the United Arab Emirates; a Letter to the Editor

Further to our recently published findings, we have completed the analysis of our second year of prehospital data collection for the same service. We wish to expedite the availability of this data to clinicians, researchers and policy makers in the region.Our 2015/2016 out-of-hospital cardiac arrest (OHCA) data displayed the following demographic results: 514 OHCA resuscitation attempts were attended by national ambulance (NA) emergency medical services (EMS) in the Northern Emirates region (75% male). Male patients continued on average to be younger than female ones (50 vs. 61 years), and the median age of OHCA cases in the United Arab Emirates remains well below that of cases in Western countries (52 years, interquartile range: 38; 69).Over half of these cases occurred at a home residence, with the next most common location being a street or highway. A total of 282 (54.5%) incidents were witnessed by a bystander, 43 (8.3%) events by NA crew, and 189 (36.7%) incidents were not witnessed. Bystander cardiopulmonary resuscitation (CPR) was attempted in 135 (28.6%) of non-EMS-witnessed cases (n=471). A bystander or public access defibrillator was applied in only five cases (1%) and no shocks were delivered by bystanders in any case. A total of 34 (6.6%) patients had a return of spontaneous circulation in the pre-hospital setting, over twice the rate demonstrated in the first year of our study. Survival to discharge data has been collected for the first time by our hospital partners, and the publication of these results in the near future will contribute greatly to our understanding of the OHCA issue in the region.The increase in the number of OHCA responses by NA crew is notable in our findings. This may be attributable to several reasons, including greater public awareness of EMS capabilities, and improved access to EMS via the dedicated 998 emergency number and the NA mobile application. This trend is to be welcomed, as implementation of the chain of survival increases the odds for survival. However, similar to our previous findings, a large number of the cases that were witnessed still had a significant time lapse before EMS was activated.A chain is only as strong as its weakest link. As such, increasing public awareness of the need for early EMS activation, improving bystander CPR rates, and increasing the availability of public access defibrillators still remain significant challenges in implementing the chain of survival in full to address this public health issue in the United Arab Emirates

Implementation of an ST-Segment Elevation Myocardial Infraction Bypass Protocol in the Northern United Arab Emirates

Objective: The aim was to evaluate the translation of an ST-segment elevation myocardial infraction (STEMI) bypass protocol to the outcomes of patients with acute coronary syndrome in the Emirate of Ras al-Khaimah in the United Arab Emirates (UAE). Methods: A prospective cohort study was conducted, which included all patients who had a prehospital 12-lead electrocardiogram (ECG) performed by ambulance crews. Analysis of those who were identified as having STEMI and who subsequently underwent percutaneous coronary intervention (PCI) was performed. Results: A total of 152 patients had a 12-lead ECG performed during the pilot study period (February 24, 2016-August 31, 2016) with 118 included for analysis. Mean patient age was 52 years. There were 87 male (74%) and 31 female (26%) patients. Twenty-nine patients suffered a STEMI, and data were available for 11 who underwent PCI. There was no mortality, and no major adverse cardiac events were reported. The median door-to-balloon (D2B) time was 73 min (range 48-124), and 81% of patients had a D2B time \u3c90 min. Discharge data were available for six patients: All were discharged home with no impediments to rehabilitation. Conclusion: This pilot study has demonstrated agreement with the existing literature surrounding prehospital ECG and PCI activation in an unstudied STEMI population and in a novel clinical setting. It has demonstrated a D2B time of \u3c90 min in over 80% of STEMI patients, and a faster mean D2B time than self-presentations (mean 77 min vs. 113 min), with no associated mortality or major adverse cardiac events

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Identification of Serotype in Culture Negative Pneumococcal Meningitis Using Sequential Multiplex PCR: Implication for Surveillance and Vaccine Design

BACKGROUND: PCR-based serotyping of Streptococcus pneumoniae has been proposed as a simpler approach than conventional methods, but has not been applied to strains in Asia where serotypes are diverse and different from other part of the world. Furthermore, PCR has not been used to determine serotype distribution in culture-negative meningitis cases. METHODOLOGY: Thirty six serotype-specific primers, 7 newly designed and 29 previously published, were arranged in 7 multiplex PCR sets, each in new hierarchies designed for overall serotype distribution in Bangladesh, and specifically for meningitis and non-meningitis isolates. Culture-negative CSF specimens were then tested directly for serotype-specific sequences using the meningitis-specific set of primers. PCR-based serotyping of 367 strains of 56 known serotypes showed 100% concordance with quellung reaction test. The first 7 multiplex reactions revealed the serotype of 40% of all, and 31% and 48% non-meningitis and meningitis isolates, respectively. By redesigning the multiplex scheme specifically for non-meningitis or meningitis, the quellung reaction of 43% and 48% of respective isolates could be identified. Direct examination of 127 culture-negative CSF specimens, using the meningitis-specific set of primers, yielded serotype for 51 additional cases. CONCLUSIONS: This PCR approach, could improve ascertainment of pneumococcal serotype distributions, especially for meningitis in settings with high prior use of antibiotics

Are vaccination programmes delivered by lay health workers cost-effective? A systematic review

<p>Abstract</p> <p>Background</p> <p>A recently updated Cochrane systematic review on the effects of lay or community health workers (LHWs) in primary and community health care concluded that LHW interventions could lead to promising benefits in the promotion of childhood vaccination uptake. However, understanding of the costs and cost-effectiveness of involving LHWs in vaccination programmes remains poor. This paper reviews the costs and cost-effectiveness of vaccination programme interventions involving LHWs.</p> <p>Methods</p> <p>Articles were retrieved if the title, keywords or abstract included terms related to 'lay health workers', 'vaccination' and 'economics'. Reference lists of studies assessed for inclusion were also searched and attempts were made to contact authors of all studies included in the Cochrane review. Studies were included after assessing eligibility of the full-text article. The included studies were then reviewed against a set of background and technical characteristics.</p> <p>Results</p> <p>Of the 2616 records identified, only three studies fully met the inclusion criteria, while an additional 11 were retained as they included some cost data. Methodologically, the studies were strong but did not adequately address affordability and sustainability and were also highly heterogeneous in terms of settings and LHW outcomes, limiting their comparability. There were insufficient data to allow any conclusions to be drawn regarding the cost-effectiveness of LHW interventions to promote vaccination uptake. Studies focused largely on health outcomes and did illustrate to some extent how the institutional characteristics of communities, such as governance and sources of financial support, influence sustainability.</p> <p>Conclusion</p> <p>The included studies suggest that conventional economic evaluations, particularly cost-effectiveness analyses, generally focus too narrowly on health outcomes, especially in the context of vaccination promotion and delivery at the primary health care level by LHWs. Further studies on the costs and cost-effectiveness of vaccination programmes involving LHWs should be conducted, and these studies should adopt a broader and more holistic approach.</p

Simulation of structural phenomena in mixed-particle fluidized beds

A statistical mechanical simulation was developed and used to predict the macroscopic and microscopic behavior of fluidized beds. In particular, the model was used to study structural phenomena in liquid fluidized beds that contain a distribution of particle sizes and/or densities. Bed structural phenomena, such as density-based and size-based segregation, classification, expansion, inversion, and solids dispersion have all been successfully simulated. Experimental data for the segregation of glass beads of different sizes and different densities agree well with predictions made from the simulation (without adjustable parameters). Classification and dispersion simulations also show good agreement with experimental data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34232/1/690440304_ftp.pd

Psychoactive Pharmaceuticals Induce Fish Gene Expression Profiles Associated with Human Idiopathic Autism

Idiopathic autism, caused by genetic susceptibility interacting with unknown environmental triggers, has increased dramatically in the past 25 years. Identifying environmental triggers has been difficult due to poorly understood pathophysiology and subjective definitions of autism. The use of antidepressants by pregnant women has been associated with autism. These and other unmetabolized psychoactive pharmaceuticals (UPPs) have also been found in drinking water from surface sources, providing another possible exposure route and raising questions about human health consequences. Here, we examined gene expression patterns of fathead minnows treated with a mixture of three psychoactive pharmaceuticals (fluoxetine, venlafaxine & carbamazepine) in dosages intended to be similar to the highest observed conservative estimates of environmental concentrations. We conducted microarray experiments examining brain tissue of fish exposed to individual pharmaceuticals and a mixture of all three. We used gene-class analysis to test for enrichment of gene sets involved with ten human neurological disorders. Only sets associated with idiopathic autism were unambiguously enriched. We found that UPPs induce autism-like gene expression patterns in fish. Our findings suggest a new potential trigger for idiopathic autism in genetically susceptible individuals involving an overlooked source of environmental contamination

A Genome-Wide Association Study Identifies Susceptibility Variants for Type 2 Diabetes in Han Chinese

To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54×10−10; odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36–1.82), and serine racemase (SRR) (P = 3.06×10−9; OR = 1.28; 95% CI = 1.18–1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65×10−10; OR = 1.29, 95% CI = 1.19–1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations

Development and validation of self-reported line drawings of the modified Beighton score for the assessment of generalised joint hypermobility

Background: The impracticalities and comparative expense of carrying out a clinical assessment is an obstacle in many large epidemiological studies. The purpose of this study was to develop and validate a series of electronic self-reported line drawing instruments based on the modified Beighton scoring system for the assessment of selfreported generalised joint hypermobility.Methods: Five sets of line drawings were created to depict the 9-point Beighton score criteria. Each instrument consisted of an explanatory question whereby participants were asked to select the line drawing which best represented their joints. Fifty participants completed the self-report online instrument on two occasions, before attending a clinical assessment. A blinded expert clinical observer then assessed participants’ on two occasions,using a standardised goniometry measurement protocol. Validity of the instrument was assessed by participant observeragreement and reliability by participant repeatability and observer repeatability using unweighted Cohen’s kappa (k). Validity and reliability were assessed for each item in the self-reported instrument separately, and for the sum of the total scores. An aggregate score for generalised joint hypermobility was determined based on a Beighton score of 4 or more out of 9.Results: Observer-repeatability between the two clinical assessments demonstrated perfect agreement (k 1.00; 95%CI 1.00, 1.00). Self-reported participant-repeatability was lower but it was still excellent (k 0.91; 95% CI 0.74, 1.00). Theparticipant-observer agreement was excellent (k 0.96; 95% CI 0.87, 1.00). Validity was excellent for the self-report instrument, with a good sensitivity of 0.87 (95% CI 0.81, 0.91) and excellent specificity of 0.99 (95% CI 0.98, 1.00).Conclusions: The self-reported instrument provides a valid and reliable assessment of the presence of generalisedjoint hypermobility and may have practical use in epidemiological studie