Ultrasound entropy may be a new non-invasive measure of pre-clinical vascular damage in young hypertensive patients

Background: The identification of pre-clinical microvascular damage in hypertension by non-invasive techniques has proved frustrating for clinicians. This proof of concept study investigated whether entropy, a novel summary measure for characterizing blood velocity waveforms, is altered in participants with hypertension and may therefore be useful in risk stratification.

Methods: Doppler ultrasound waveforms were obtained from the carotid and retrobulbar circulation in 42 participants with uncomplicated grade 1 hypertension (mean systolic/diastolic blood pressure (BP) 142/92 mmHg), and 26 healthy controls (mean systolic/diastolic BP 116/69 mmHg). Mean wavelet entropy was derived from flow-velocity data and compared with traditional haemodynamic measures of microvascular function, namely the resistive and pulsatility indices.

Results: Entropy, was significantly higher in control participants in the central retinal artery (CRA) (differential mean 0.11 (standard error 0.05 cms(-1)), CI 0.009 to 0.219, p 0.017) and ophthalmic artery (0.12 (0.05), CI 0.004 to 0.215, p 0.04). In comparison, the resistive index (0.12 (0.05), CI 0.005 to 0.226, p 0.029) and pulsatility index (0.96 (0.38), CI 0.19 to 1.72, p 0.015) showed significant differences between groups in the CRA alone. Regression analysis indicated that entropy was significantly influenced by age and systolic blood pressure (r values 0.4-0.6). None of the measures were significantly altered in the larger conduit vessel.

Conclusion: This is the first application of entropy to human blood velocity waveform analysis and shows that this new technique has the ability to discriminate health from early hypertensive disease, thereby promoting the early identification of cardiovascular disease in a young hypertensive population.

Molecular classification of non-invasive breast lesions for personalised therapy and chemoprevention

Breast cancer screening has led to a dramatic increase in the detection of pre-invasive breast lesions. While mastectomy is almost guaranteed to treat the disease, more conservative approaches could be as effective if patients can be stratified based on risk of co-existing or recurrent invasive disease.Here we use a range of biomarkers to interrogate and classify purely non-invasive lesions (PNL) and those with co-existing invasive breast cancer (CEIN). Apart from Ductal Carcinoma In Situ (DCIS), relative homogeneity is observed. DCIS contained a greater spread of molecular subtypes. Interestingly, high expression of p-mTOR was observed in all PNL with lower expression in DCIS and invasive carcinoma while the opposite expression pattern was observed for TOP2A.Comparing PNL with CEIN, we have identified p53 and Ki67 as predictors of CEIN with a combined PPV and NPV of 90.48% and 43.3% respectively. Furthermore, HER2 expression showed the best concordance between DCIS and its invasive counterpart.We propose that these biomarkers can be used to improve the management of patients with pre-invasive breast lesions following further validation and clinical trials. p53 and Ki67 could be used to stratify patients into low and high-risk groups for co-existing disease. Knowledge of expression of more actionable targets such as HER2 or TOP2A can be used to design chemoprevention or neo-adjuvant strategies. Increased knowledge of the molecular profile of pre-invasive lesions can only serve to enhance our understanding of the disease and, in the era of personalised medicine, bring us closer to improving breast cancer care.

Non-invasive ventilation for cystic fibrosis.

Non-invasive ventilation may be a means to temporarily reverse or slow the progression of respiratory failure in cystic fibrosis. To compare the effect of non-invasive ventilation versus no non-invasive ventilation in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. We searched the reference lists of each trial for additional publications possibly containing other trials.Most recent search: 22 February 2013. Randomised controlled trials comparing a form of pressure preset or volume preset non-invasive ventilation to no non-invasive ventilation in people with acute or chronic respiratory failure in cystic fibrosis. Three reviewers independently assessed trials for inclusion criteria and methodological quality, and extracted data. Fifteen trials were identified; seven trials met the inclusion criteria with a total of 106 participants. Six trials evaluated single treatment sessions and one evaluated a six-week intervention.Four trials (79 participants) evaluated non-invasive ventilation for airway clearance compared with an alternative chest physiotherapy method and showed that airway clearance may be easier with non-invasive ventilation and people with cystic fibrosis may prefer it. We were unable to find any evidence that NIV increases sputum expectoration, but it did improve some lung function parameters.Three trials (27 participants) evaluated non-invasive ventilation for overnight ventilatory support, measuring lung function, validated quality of life scores and nocturnal transcutaneous carbon dioxide. Due to the small numbers of participants and statistical issues, there were discrepancies in the results between the RevMan and the original trial analyses. No clear differences were found between non-invasive ventilation compared with oxygen or room air except for exercise performance, which significantly improved with non-invasive ventilation compared to room air over six weeks. Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with cystic fibrosis who have difficulty expectorating sputum. Non-invasive ventilation, used in addition to oxygen, may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. These benefits of non-invasive ventilation have largely been demonstrated in single treatment sessions with small numbers of participants. The impact of this therapy on pulmonary exacerbations and disease progression remain unclear. There is a need for long-term randomised controlled trials which are adequately powered to determine the clinical effects of non-invasive ventilation in cystic fibrosis airway clearance and exercise.

Non-invasive Ventilation of Patients with ARDS: Insights from the LUNG SAFE Study

Background: Non-invasive ventilation (NIV) is increasingly used in patients with Acute Respiratory Distress Syndrome (ARDS). Whether, during NIV, the categorization of ARDS severity based on the PaO2/FiO2 Berlin criteria is useful is unknown. The evidence supporting NIV use in patients with ARDS remains relatively sparse.

Methods: The Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study described the management of patients with ARDS. This sub-study examines the current practice of NIV use in ARDS, the utility of the PaO2/FiO2 ratio in classifying patients receiving NIV and the impact of NIV on outcome.

Results: Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severity based on PaO2/FiO2 ratio was associated with an increase in intensity of ventilatory support, NIV failure, and Intensive Care Unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1 % and 45.4%, respectively. NIV use was independently associated with increased ICU (HR 1.446; [1.159-1.805]), but not hospital mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a PaO2/FiO2 lower than 150 mmHg.

Conclusions: NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV appears to be associated with higher ICU mortality in patients with a PaO2/FiO2 lower than 150 mmHg.

Trial Registration: ClinicalTrials.gov NCT02010073

Exhaled breath temperature measurement and asthma control in children prescribed inhaled corticosteroids: A cross sectional study

BACKGROUND: Exhaled breath temperature (EBT) reflects airways (both eosinophilic and neutrophilic) inflammation in asthma and thus may aid the management of children with asthma that are treated with anti-inflammatory drugs. A new EBT monitor has become available that is cheap and easy to use and may be a suitable monitoring device for airways inflammation. Little is known about how EBT relates to asthma treatment decisions, disease control, lung function, or other non-invasive measures of airways inflammation, such as exhaled nitric oxide (ENO).

OBJECTIVE: To determine the relationships between EBT and asthma treatment decision, current control, pulmonary function, and ENO.

METHODS: Cross-sectional prospective study on 159 children aged 5-16 years attending a pediatric respiratory clinic. EBT was compared with the clinician's decision regarding treatment (decrease, no change, increase), asthma control assessment (controlled, partial, uncontrolled), level of current treatment (according to British Thoracic Society guideline, BTS step), ENO, and spirometry.

RESULTS: EBT measurement was feasible in the majority of children (25 of 159 could not perform the test) and correlated weakly with age (R = 0.33, P = <0.01). EBT did not differ significantly between the three clinician decision groups (P = 0.42), the three asthma control assessment groups (P = 0.9), or the current asthma treatment BTS step (P = 0.57).

CONCLUSIONS & CLINICAL IMPLICATIONS: EBT measurement was not related to measures of asthma control determined at the clinic. The routine intermittent monitoring of EBT in children prescribed inhaled corticosteroids who attend asthma clinics cannot be recommended for adjusting anti-inflammatory asthma therapy.

Real-time estimation of battery internal temperature based on a simplified thermoelectric model

Li-ion batteries have been widely used in the EVs, and the battery thermal management is a key but challenging part of the battery management system. For EV batteries, only the battery surface temperature can be measured in real-time. However, it is the battery internal temperature that directly affects the battery performance, and large temperature difference may exist between surface and internal temperatures, especially in high power demand applications. In this paper, an online battery internal temperature estimation method is proposed based on a novel simplified thermoelectric model. The battery thermal behaviour is first described by a simplified thermal model, and battery electrical behaviour by an electric model. Then, these two models are interrelated to capture the interactions between battery thermal and electrical behaviours, thus offer a comprehensive description of the battery behaviour that is useful for battery management. Finally, based on the developed model, the battery internal temperature is estimated using an extended Kalman filter. The experimental results confirm the efficacy of the proposed method, and it can be used for online internal temperature estimation which is a key indicator for better real-time battery thermal management.

Hybrid time dependent/independent solution for the He i line ratio temperature and density diagnostic for a thermal helium beam with applications in the scrape-off layer-edge regions in tokamaks

Spectroscopic studies of line emission intensities and ratios offer an attractive option in the\r\ndevelopment of non-invasive plasma diagnostics. Evaluating ratios of selected He I line\r\nemission profiles from the singlet and triplet neutral helium spin systems allows for simultaneous\r\nmeasurement of electron density (ne) and temperature (Te) profiles. Typically, this powerful\r\ndiagnostic tool is limited by the relatively long relaxation times of the 3S metastable term of helium\r\nthat populates the triplet spin system, and on which electron temperature sensitive lines are based.\r\nBy developing a time dependent analytical solution, we model the time evolution of the two spin\r\nsystems. We present a hybrid time dependent/independent line ratio solution that improves the\r\nrange of application of this diagnostic technique in the scrape-off layer (SOL) and edge plasma\r\nregions when comparing it against the current equilibrium line ratio helium model used at\r\nTEXTOR.

Real time monitoring of the polymerisation of PMMA bone cement using Raman spectroscopy

In this investigation Raman spectroscopy was shown to be a method that could be used to monitor the polymerisation of PMMA bone cement. Presently there is no objective method that orthopaedic surgeons can use to quantify the curing process of cement during surgery. Raman spectroscopy is a non-invasive, non-destructive technique that could offer such an option. Two commercially available bone cements (Palacos® R and SmartSet® HV) and different storage conditions (4 and 22°C) were used to validate the technique. Raman spectroscopy was found to be repeatable across all conditions with the completion of the polymerisation process particularly easy to establish. All tests were benchmarked against current temperature monitoring methods outlined in ISO and ASTM standards. There was found to be close agreement with the standard methods and the Raman spectroscopy used in this study.

Non-locality of two ultracold trapped atoms

We undertake a detailed analysis of the non-local properties of the fundamental problem of two trapped, distinguishable neutral atoms that interact with a short-range potential characterized by an s-wave scattering length. We show that this interaction generates continuous variable (CV) entanglement between the external degrees of freedom of the atoms and consider its behaviour as a function of both, the distance between the traps and the magnitude of the inter-particle scattering length. We first quantify the entanglement in the ground state of the system at zero temperature and then, adopting a phase-space approach, test the violation of the Clauser-Horn-Shimony-Holt inequality at zero and non-zero temperature and under the effects of general dissipative local environments.

Non-contact under-mattress sleep monitoring

Sleep quality and duration are increasingly recognised as being important prognostic parameters in the assessment of an individual's health. However, reliable non-invasive long-term monitoring of sleep in a non-clinical setting remains a challenging problem. This paper describes the validation of a novel under mattress pressure sensing sleep monitoring modality that can be seamlessly integrated into existing home environments and provides a pervasive and distributed solution for monitoring long-term changes in sleep patterns and sleep disorders in adults. 410 minutes of concomitant Under Mattress Bed Sensor (UMBS) and strain gauge data were analysed from eight healthy adults lying passively. In this analysis, customised respirations rate detection algorithms yielded a mean difference of −0.12 breaths per five minutes and a mean percentage error (MPE) of 0.16% when the sensor was placed beneath the mattress. 1,491 minutes of UMBS and video data were recorded simultaneously from four participants in order to assess the movement detection efficacy of customised UMBS algorithms. These algorithms yielded accuracies, sensitivities and specificities of over 90% when compared to a video-based movement detection gold standard. A reduced data set (267 minutes) of wrist actigraphy, the gold standard ambulatory sleep monitor, was recorded. The UMBS was shown to outperform the movement detection ability of wrist actigraphy and has the added advantage of not requiring active subject participation.

Automated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children: a cochrane systematic review and meta-analysis

IntroductionAutomated weaning systems may improve adaptation of mechanical support for a patient’s ventilatory needs and facilitate systematic and early recognition of their ability to breathe spontaneously and the potential for discontinuation of ventilation. Our objective was to compare mechanical ventilator weaning duration for critically ill adults and children when managed with automated systems versus non-automated strategies. Secondary objectives were to determine differences in duration of ventilation, intensive care unit (ICU) and hospital length of stay (LOS), mortality, and adverse events.MethodsElectronic databases were searched to 30 September 2013 without language restrictions. We also searched conference proceedings; trial registration websites; and article reference lists. Two authors independently extracted data and assessed risk of bias. We combined data using random-effects modelling.ResultsWe identified 21 eligible trials totalling 1,676 participants. Pooled data from 16 trials indicated that automated systems reduced the geometric mean weaning duration by 30% (95% confidence interval (CI) 13% to 45%), with substantial heterogeneity (I2 = 87%, P <0.00001). Reduced weaning duration was found with mixed or medical ICU populations (42%, 95% CI 10% to 63%) and Smartcare/PS™ (28%, 95% CI 7% to 49%) but not with surgical populations or using other systems. Automated systems reduced ventilation duration with no heterogeneity (10%, 95% CI 3% to 16%) and ICU LOS (8%, 95% CI 0% to 15%). There was no strong evidence of effect on mortality, hospital LOS, reintubation, self-extubation and non-invasive ventilation following extubation. Automated systems reduced prolonged mechanical ventilation and tracheostomy. Overall quality of evidence was high.ConclusionsAutomated systems may reduce weaning and ventilation duration and ICU stay. Due to substantial trial heterogeneity an adequately powered, high quality, multi-centre randomized controlled trial is needed.

Automated versus non-automated weaning for reducing the duration of mechanical ventilation in critically ill adults & children (Review)

Background Automated closed loop systems may improve adaptation of mechanical support for a patient's ventilatory needs and facilitate systematic and early recognition of their ability to breathe spontaneously and the potential for discontinuation of ventilation. This review was originally published in 2013 with an update published in 2014. Objectives The primary objective for this review was to compare the total duration of weaning from mechanical ventilation, defined as the time from study randomization to successful extubation (as defined by study authors), for critically ill ventilated patients managed with an automated weaning system versus no automated weaning system (usual care). Secondary objectives for this review were to determine differences in the duration of ventilation, intensive care unit (ICU) and hospital lengths of stay (LOS), mortality, and adverse events related to early or delayed extubation with the use of automated weaning systems compared to weaning in the absence of an automated weaning system. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8); MEDLINE (OvidSP) (1948 to September 2013); EMBASE (OvidSP) (1980 to September 2013); CINAHL (EBSCOhost) (1982 to September 2013); and the Latin American and Caribbean Health Sciences Literature (LILACS). Relevant published reviews were sought using the Database of Abstracts of Reviews of Effects (DARE) and the Health Technology Assessment Database (HTA Database). We also searched the Web of Science Proceedings; conference proceedings; trial registration websites; and reference lists of relevant articles. The original search was run in August 2011, with database auto-alerts up to August 2012. Selection criteria We included randomized controlled trials comparing automated closed loop ventilator applications to non-automated weaning strategies including non-protocolized usual care and protocolized weaning in patients over four weeks of age receiving invasive mechanical ventilation in an ICU. Data collection and analysis Two authors independently extracted study data and assessed risk of bias. We combined data in forest plots using random-effects modelling. Subgroup and sensitivity analyses were conducted according to a priori criteria. Main results We included 21 trials (19 adult, two paediatric) totaling 1676 participants (1628 adults, 48 children) in this updated review. Pooled data from 16 eligible trials reporting weaning duration indicated that automated closed loop systems reduced the geometric mean duration of weaning by 30% (95% confidence interval (CI) 13% to 45%), however heterogeneity was substantial (I2 = 87%, P < 0.00001). Reduced weaning duration was found with mixed or medical ICU populations (42%, 95% CI 10% to 63%) and Smartcare/PS™ (28%, 95% CI 7% to 49%) but not in surgical populations or using other systems. Automated closed loop systems reduced the duration of ventilation (10%, 95% CI 3% to 16%) and ICU LOS (8%, 95% CI 0% to 15%). There was no strong evidence of an effect on mortality rates, hospital LOS, reintubation rates, self-extubation and use of non-invasive ventilation following extubation. Prolonged mechanical ventilation > 21 days and tracheostomy were reduced in favour of automated systems (relative risk (RR) 0.51, 95% CI 0.27 to 0.95 and RR 0.67, 95% CI 0.50 to 0.90 respectively). Overall the quality of the evidence was high with the majority of trials rated as low risk. Authors' conclusions Automated closed loop systems may result in reduced duration of weaning, ventilation and ICU stay. Reductions are more likely to occur in mixed or medical ICU populations. Due to the lack of, or limited, evidence on automated systems other than Smartcare/PS™ and Adaptive Support Ventilation no conclusions can be drawn regarding their influence on these outcomes. Due to substantial heterogeneity in trials there is a need for an adequately powered, high quality, multi-centre randomized controlled trial in adults that excludes 'simple to wean' patients. There is a pressing need for further technological development and research in the paediatric population.

AURKA overexpression accompanies dysregulation of DNA-damage response genes in invasive urothelial cell carcinoma

Invasive urothelial cell carcinoma (UCC) is characterized by increased chromosomal instability and follows an aggressive clinical course in contrast to non-invasive disease. To identify molecular processes that confer and maintain an aggressive malignant phenotype, we used a high-throughput genome-wide approach to interrogate a cohort of high and low clinical risk UCC tumors. Differential expression analyses highlighted cohesive dysregulation of critical genes involved in the G(2)/M checkpoint in aggressive UCC. Hierarchical clustering based on DNA Damage Response (DDR) genes separated tumors according to a pre-defined clinical risk phenotype. Using array-comparative genomic hybridization, we confirmed that the DDR was disrupted in tumors displaying high genomic instability. We identified DNA copy number gains at 20q13.2-q13.3 (AURKA locus) and determined that overexpression of AURKA accompanied dysregulation of DDR genes in high risk tumors. We postulated that DDR-deficient UCC tumors are advantaged by a selective pressure for AURKA associated override of M phase barriers and confirmed this in an independent tissue microarray series. This mechanism that enables cancer cells to maintain an aggressive phenotype forms a rationale for targeting AURKA as a therapeutic strategy in advanced stage UCC.

Smartphone and GPS technology for freeroaming dog population surveillance -a methodological study (Studio metodologico sull’applicazione di smartphone e tecnologia GPS alla sorveglianza delle popolazioni di cani vaganti)

Free-roaming dogs (FRD) represent a potential threat to the quality of life in cities from an ecological, social and public health point of view. One of the most urgent concerns is the role of uncontrolled dogs as reservoirs of infectious diseases transmittable to humans and, above all, rabies. An estimate of the FRD population size and characteristics in a given area is the first step for any relevant intervention programme. Direct count methods are still prominent because of their non-invasive approach, information technologies can support such methods facilitating data collection and allowing for a more efficient data handling. This paper presents a new framework for data collection using a topological algorithm implemented as ArcScript in ESRI® ArcGIS software, which allows for a random selection of the sampling areas. It also supplies a mobile phone application for Android® operating system devices which integrates Global Positioning System (GPS) and Google Maps™. The potential of such a framework was tested in 2 Italian regions. Coupling technological and innovative solutions associated with common counting methods facilitate data collection and transcription. It also paves the way to future applications, which could support dog population management systems.

Network signatures based on gene pair expression ratios improve classification and the analysis of muscle-invasive urothelial cancer

Urothelial cancer (UC) is highly recurrent and can progress from non-invasive (NMIUC) to a more aggressive muscle-invasive (MIUC) subtype that invades the muscle tissue layer of the bladder. We present a proof of principle study that network-based features of gene pairs can be used to improve classifier performance and the functional analysis of urothelial cancer gene expression data. In the first step of our procedure each individual sample of a UC gene expression dataset is inflated by gene pair expression ratios that are defined based on a given network structure. In the second step an elastic net feature selection procedure for network-based signatures is applied to discriminate between NMIUC and MIUC samples. We performed a repeated random subsampling cross validation in three independent datasets. The network signatures were characterized by a functional enrichment analysis and studied for the enrichment of known cancer genes. We observed that the network-based gene signatures from meta collections of proteinprotein interaction (PPI) databases such as CPDB and the PPI databases HPRD and BioGrid improved the classification performance compared to single gene based signatures. The network based signatures that were derived from PPI databases showed a prominent enrichment of cancer genes (e.g., TP53, TRIM27 and HNRNPA2Bl). We provide a novel integrative approach for large-scale gene expression analysis for the identification and development of novel diagnostical targets in bladder cancer. Further, our method allowed to link cancer gene associations to network-based expression signatures that are not observed in gene-based expression signatures.