Analysis and design optimization of an integrated micropump-micromixer operated for bio-MEMS applications

This paper was presented at the 4th Micro and Nano Flows Conference (MNF2014), which was held at University College, London, UK. The conference was organised by Brunel University and supported by the Italian Union of Thermofluiddynamics, IPEM, the Process Intensification Network, the Institution of Mechanical Engineers, the Heat Transfer Society, HEXAG - the Heat Exchange Action Group, and the Energy Institute, ASME Press, LCN London Centre for Nanotechnology, UCL University College London, UCL Engineering, the International NanoScience Community, www.nanopaprika.eu.A generic microfluidic system composed by two single chamber valveless micropumps connected to a simple T-type channel intersection is examined numerically. The characteristics of a feasible valveless micropump have been used in the design, where efficient mixing is produced due to the pulsating flow generated by the micropumps. The advantages of using time pulsing inlet flows for enhancing mixing in channels have been harnessed through the activation of intrinsic characteristics of the pumps required to achieve the periodic flows. A parametric study is carried out on this microfluidic system using Computational Fluids Dynamics (CFD)on a design space defined by a Design-of-Experiments (DOE) technique. The frequency f and the phase difference f of the periodic fluid velocities (operation parameters) and the angle q formed by the inlet channels at the intersection (geometric parameter) are used as design parameters, whereas mixing quality, pressure drop and maximum shear strain rate in the channel are the performance parameters. The study identifies design features for which the pressure drop and shear strain are reduced whereas the mixing quality is increased. The proposed microfluidic system achieves high mixing quality with performance parameters that enable manipulation of biological fluids in microchannels

Novel associations of bile acid diarrhoea with fatty liver disease and gallstones: a cohort retrospective analysis.

Background Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea with a population prevalence of primary BAD around 1%. Previous studies have identified associations with low levels of the ileal hormone fibroblast growth factor 19 (FGF19), obesity and hypertriglyceridaemia. The aim of this study was to identify further associations of BAD. Methods A cohort of patients with chronic diarrhoea who underwent 75selenohomocholic acid taurate (SeHCAT) testing for BAD was further analysed retrospectively. Additional clinical details available from the electronic patient record, including imaging, colonoscopy, chemistry and histopathology reports were used to calculate the prevalence of fatty liver disease, gallstones, colonic neoplasia and microscopic colitis, which was compared for BAD, the primary BAD subset and control patients with diarrhoea. Findings Of 578 patients, 303 (52%) had BAD, defined as a SeHCAT 7d retention value 31 ng/mL with imaging showing fatty liver (p40 IU/L. In 176 subjects with gallbladder imaging, 27% had gallstones, 7% had a prior cholecystectomy and 34% either of these. The median SeHCAT values were lower in those with gallstones (3.8%, p<0.0001), or gallstones/cholecystectomy (7.2%, p<0.001), compared with normal gallbladder imaging (14%). Overall, BAD had an OR of 2.0 for gallstones/cholecystectomy (p<0.05). BAD was not significantly associated with colonic adenoma/carcinoma or with microscopic colitis. Interpretation The diagnosis of BAD is associated with fatty liver disease and with gallstones. The reasons for these associations require further investigation into potential metabolic causes

Magnetic Resonance Imaging in a Patient with a Dual Chamber Pacemaker

Having a pacemaker has been seen an absolute contraindication to having an MRI scan. This has become increasingly difficult in clinical practice as insertion of pacemakers and implantable cardiac defibrillators is at an all time high. Here we outline a case where a 71-year-old male patient with a permanent pacemaker needed to have an MRI scan to ascertain the aetiology of his condition and help guide further management. Given this clinical dilemma, an emergency clinical ethics consultation was arranged. As a result the patient underwent an MRI scan safely under controlled conditions with a consultant cardiologist and radiologist present. The results of the MRI scan were then able to tailor further treatment. This case highlights that in certain conditions an MRI can be performed in patients with permanent pacemakers and outlines the role of clinical ethics committees in complex medical decision making

Development of a Risk Prediction Model for New Episodes of Atrial Fibrillation in Medical-Surgical Critically Ill Patients Using the AmsterdamUMCdb

The occurrence of atrial fibrillation (AF) represents clinical deterioration in acutely unwell patients and leads to increased morbidity and mortality. Prediction of the development of AF allows early intervention. Using the AmsterdamUMCdb, clinically relevant variables from patients admitted in sinus rhythm were extracted over the full duration of the ICU stay or until the first recorded AF episode occurred. Multiple logistic regression was performed to identify risk factors for AF. Input variables were automatically selected by a sequential forward search algorithm using cross-validation. We developed three different models: For the overall cohort, for ventilated patients and non-ventilated patients. 16,144 out of 23,106 admissions met the inclusion criteria. 2,374 (12.8%) patients had at least one AF episode during their ICU stay. Univariate analysis revealed that a higher percentage of AF patients were older than 70 years (60% versus 32%) and died in ICU (23.1% versus 7.1%) compared to non-AF patients. Multivariate analysis revealed age to be the dominant risk factor for developing AF with doubling of age leading to a 10-fold increased risk. Our logistic regression models showed excellent performance with AUC.ROC & 0.82 and & 0.91 in ventilated and non-ventilated cohorts, respectively. Increasing age was the dominant risk factor for the development of AF in both ventilated and non-ventilated critically ill patients. In non-ventilated patients, risk for development of AF was significantly higher than in ventilated patients. Further research is warranted to identify the role of ventilatory settings on risk for AF in critical illness and to optimise predictive models

Lactate signalling regulates fungal β-glucan masking and immune evasion

AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPostprin

Socioeconomic deprivation and mortality after emergency laparotomy: an observational epidemiological study

Background: Socioeconomic circumstances can influence access to healthcare, the standard of care provided, and a variety of outcomes. This study aimed to determine the association between crude and risk-adjusted 30-day mortality and socioeconomic group after emergency laparotomy, measure differences in meeting relevant perioperative standards of care, and investigate whether variation in hospital structure or process could explain any difference in mortality between socioeconomic groups. / Methods: This was an observational study of 58 790 patients, with data prospectively collected for the National Emergency Laparotomy Audit in 178 National Health Service hospitals in England between December 1, 2013 and November 31, 2016, linked with national administrative databases. The socioeconomic group was determined according to the Index of Multiple Deprivation quintile of each patient's usual place of residence. / Results: Overall, the crude 30-day mortality was 10.3%, with differences between the most-deprived (11.2%) and least-deprived (9.8%) quintiles (P<0.001). The more-deprived patients were more likely to have multiple comorbidities, were more acutely unwell at the time of surgery, and required a more-urgent surgery. After risk adjustment, the patients in the most-deprived quintile were at significantly higher risk of death compared with all other quintiles (adjusted odds ratio [95% confidence interval]: Q1 [most deprived]: reference; Q2: 0.83 [0.76–0.92]; Q3: 0.84 [0.76–0.92]; Q4: 0.87 [0.79–0.96]; Q5 [least deprived]: 0.77 [0.70–0.86]). We found no evidence that differences in hospital-level structure or patient-level performance in standards of care explained this association. / Conclusions: More-deprived patients have higher crude and risk-adjusted 30-day mortality after emergency laparotomy, but this is not explained by differences in the standards of care recorded within the National Emergency Laparotomy Audit

Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas

Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI). Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas

Tradable Pollution Permits and the Regulatory Game

This paper analyzes polluters\u27 incentives to move from a traditional command and control (CAC) environmental regulatory regime to a tradable permits (TPP) regime. Existing work in environmental economics does not model how firms contest and bargain over actual regulatory implementation in CAC regimes, and therefore fail to compare TPP regimes with any CAC regime that is actually observed. This paper models CAC environmental regulation as a bargaining game over pollution entitlements. Using a reduced form model of the regulatory contest, it shows that CAC regulatory bargaining likely generates a regulatory status quo under which firms with the highest compliance costs bargain for the smallest pollution reductions, or even no reduction at all. As for a tradable permits regime, it is shown that all firms are better off under such a regime than they would be under an idealized CAC regime that set and enforced a uniform pollution standard, but permit sellers (low compliance cost firms) may actually be better off under a TPP regime with relaxed aggregate pollution levels. Most importantly, because high cost firms (or facilities) are the most weakly regulated in the equilibrium under negotiated or bargained CAC regimes, they may be net losers in a proposed move to a TPP regime. When equilibrium costs under a TPP regime are compared with equilibrium costs under a status quo CAC regime, several otherwise paradoxical aspects of firm attitudes toward TPP type reforms can be explained. In particular, the otherwise paradoxical pattern of allowances awarded under Phase II of the 1990 Clean Air Act\u27s acid rain program, a pattern tending to favor (in Phase II) cleaner, newer generating units, is explained by the fact that under the status quo regime, a kind of bargained CAC, it was the newer cleaner units that were regulated, and which therefore had higher marginal control costs than did the largely unregulated older, plants. As a normative matter, the analysis here implies that the proper baseline for evaluating TPP regimes such as those contained in the Bush Administration\u27s recent Clear Skies initiative is not idealized, but nonexistent CAC regulatory outcomes, but rather the outcomes that have resulted from the bargaining game set up by CAC laws and regulations