Assessing the cognitive contributors to violence:A pilot and feasibility study protocol

In recent years there has been considerable progress in the development, validation and use of violence risk assessments (VRA). Their predictive ability however remains modest and, due to the repetitive use of certain risk factors, collectively, they appear to have hit an allegorical ‘glass ceiling’. Further limiting VRA is the use of self-report, collateral information, and file reviews to assess clinical and risk-related factors, rather than validated performance measures. Correspondingly, converging findings from neuropsychology and neurobiology have underlined brain regions associated with violent behaviour and subsequent research has further demonstrated this through observational studies. Thus, it is hypothesised that VRA may benefit from the integration of behaviourally measured neuropsychological risk factors. The current study is a feasibility and pilot study with a prospective, observational approach and a retrospective component. It aims to investigate the feasibility of using a neuropsychological battery to aid in the identification of violence risk in an inpatient and community setting, and to pilot a neuropsychological battery of measures examining risk factors for violence identified through a meta-analysis and an international Delphi study. The primary outcomes of interest are violent incidents or offences recorded during the 6-month follow-up periods

Measurement of Hydrogen Peroxide Influx Into Cells: Preparation For Measurement Using On-Chip Microelectrode Array

Hydrogen peroxide (H2O2) is commonly known as a toxic reactive oxidative species (ROS) for cells. Recent studies have found evidence that H2O2 is also an important cellular signalling molecule. Quantifying cellular influx of H2O2 will contribute to researchers’ understanding of the role H2O2 plays in healthy cells and cells involved in the progression of cancers and degenerative diseases. This work utilizes an assay kit and fluorescence techniques to evaluate cell lines and conditions to create a model biological system for measuring cellular H2O2 consumption. Pancreatic beta cells (MIN6), astrocytes, and glioblastoma cells (GBM43 and GBAM1) were placed in 10 μM and 20 μM H2O2 solutions for up to 5 hours. The consumption of H2O2 was measured using an Amplex Red Hydrogen Peroxide/Peroxidase Assay Kit (Molecular Probes/Invitrogen). GBAM1 cells exposed to 20 μM H2O2 displayed the fastest rate of H2O2 consumption (4.8 ± 1.2 nmol H2O2/min/106 cells), followed by GBM43 cells (1.5±0.46), astrocytes (1.1±0.24), and MIN6 cells (0.29±0.075). Additionally, the rate of consumption increased with increases in H2O2 concentration. In the future, an on-chip micro-electrode array (MEA) will be used for real-time electrochemical experiments to measure influx of H2O2 by astrocytes and GBAM1 cells with spatio-temporal resolution that the current techniques lack. The results from the electrochemical experiments will be compared to results from the assay kit to determine the ability of the MEA to accurately measure H2O2 concentration and flux. The MEA can be extended to a wide variety of cellular environments for analysis of additional real-time biological events

Cellular Model of Hydrogen Peroxide Release: In Preparation for On-Chip Sensor Measurements

Hydrogen peroxide is traditionally associated with cellular damage; however, recent studies show that low levels of H2O2 are released by cells as part of normal intercellular communication. The mechanisms of hydrogen peroxide transport, uptake and release, and biological effects are not yet well known but have important implications for cancer, stem cells, and aging. Standard H2O2 assays cannot make spatially or temporally resolved quantitative measurements at a cellular scale. Previously we developed a microelectrode array (MEA) and calibration methods for quantifying H2O2 gradients in space and time. The sensor was validated using artificial H2O2 gradients at subsecond and micrometer scale resolutions. The present study begins cellular work on H2O2 release to identify a cellular model system for MEA sensor testing. The morphology and H2O2 release from U937 human monocytes were analyzed after stimulation with ionomycin (1.2 ug/mL) and/or phorbol 12-myristate 13-acetate (PMA). Monocytes were stimulated with PMA (10 ng/mL to 150 ng/mL) for six hours. Hydrogen peroxide release was quantified over time using a traditional amplex red flurometric assay method. Mouse pancreatic beta (MIN6) cells were also tested as a negative control. Monocytes stimulated with PMA alone produced, on average, three times more H2O2 than those stimulated with ionomycin or a combination. Monocytes without ionomycin released H2O2 at 18.34 pmol/min/106 cells at 25 ng/mL of PMA. Ten, 25, and 100 ng/mL of PMA produced H2O2 significantly faster than the non-stimulated control. No significant difference was seen between PMA concentrations when ionomycin was added. These results indicate that PMA stimulated human monocytes may serve as a good model system for cellular validation of the H2O2 MEAs. In the future, biofunctionalization of the electrodes for additional molecular specificity will allow for the expansion of the method to other analytes, giving the sensor potential use in non-traditional lab environments with the ability to perform multiple assays autonomously

Improving nursing care in a children’s hospital in rural India

Background: Nursing care quality in developing countries is an ongoing challenge leading to poor patient outcomes. The objective of this study is to evaluate changes in nursing performance providing routine cares following a training program in children’s hospital in Mota Fofalia, Gujarat, India. Methods: The main outcome measure was the proportion of newborns with vital signs and weights obtained by nursing staff before and after a training program. The training program consisted of an in-service reinforced by hands-on management of patient care for 2 weeks. Following the training, the nurses were observed for 2 months. Results: Observation of 138 newborn encounters demonstrated a 29.7% improvement in vital sign monitoring and 88.4% in weight monitoring from the 0% baseline. Conclusion: We observed a moderate improvement in measuring vital signs and a substantial improvement in measuring weights in newborns with the training intervention. For further improvement, continued training, and follow-up is indicated

Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis

OBJECTIVES: The study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF). METHODS: In an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments. Tortuosity evaluates the ratio of measured segmental length against direct end-to-end segmental length. Univariable linear regression analyses examined relationships between AirQuant variables, clinical variables, and lung function tests. Univariable and multivariable Cox proportional hazards models estimated mortality risk with the latter adjusted for patient age, gender, smoking status, antifibrotic use, CT usual interstitial pneumonia (UIP) pattern, and either forced vital capacity (FVC) or diffusion capacity of carbon monoxide (DLco) if obtained within 3 months of the CT. RESULTS: No significant collinearity existed between AirQuant variables and clinical or functional variables. On univariable Cox analyses, male gender, smoking history, no antifibrotic use, reduced DLco, reduced intersegmental tapering, and increased segmental tortuosity associated with increased risk of death. On multivariable Cox analyses (adjusted using FVC), intersegmental tapering (hazard ratio (HR) = 0.75, 95% CI = 0.66-0.85, p < 0.001) and segmental tortuosity (HR = 1.74, 95% CI = 1.22-2.47, p = 0.002) independently associated with mortality. Results were maintained with adjustment using DLco. CONCLUSIONS: AirQuant generated measures of intersegmental tapering and segmental tortuosity independently associate with mortality in IPF patients. Abnormalities in proximal airway generations, which are not typically considered to be abnormal in IPF, have prognostic value. CLINICAL RELEVANCE STATEMENT: Quantitative measurements of intersegmental tapering and segmental tortuosity, in proximal (second to sixth) generation airway segments, independently associate with mortality in IPF. Automated airway analysis can estimate disease severity, which in IPF is not restricted to the distal airway tree. KEY POINTS: • AirQuant generates measures of intersegmental tapering and segmental tortuosity. • Automated airway quantification associates with mortality in IPF independent of established measures of disease severity. • Automated airway analysis could be used to refine patient selection for therapeutic trials in IPF

Impact of radiographer immediate reporting of X-rays of the chest from general practice on the lung cancer pathway (radioX): a randomised controlled trial

The National Optimal Lung Cancer Pathway recommends rapid progression from abnormal chest X-rays (CXRs) to CT. The impact of the more rapid reporting on the whole pathway is unknown. The aim of this study was to determine the impact of immediate reporting of CXRs requested by primary care by radiographers on the time to diagnosis of lung cancer. METHOD: People referred for CXR from primary care to a single acute district general hospital in London attended sessions that were prerandomised to either immediate radiographer (IR) reporting or standard radiographer (SR) reporting within 24 hours. CXRs were subsequently reported by radiologists blind to the radiographer reports to test the reliability of the radiographer report. Radiographer and local radiologist discordant cases were reviewed by thoracic radiologists, blinded to reporter. RESULTS: 8682 CXRs were performed between 21 June 2017 and 4 August 2018, 4096 (47.2%) for IR and 4586 (52.8%) for SR. Lung cancer was diagnosed in 49, with 27 (55.1%) for IR. The median time from CXR to diagnosis of lung cancer for IR was 32 days (IQR 19, 70) compared with 63 days (IQR 29, 78) for SR (p=0.03).8258 CXRs (95.1%) were reported by both radiographers and local radiologists. In the 1361 (16.5%) with discordance, the reviewing thoracic radiologists were equally likely to agree with local radiologist and radiographer reports. CONCLUSIONS: Immediate reporting of CXRs from primary care reduces time to diagnosis of lung cancer by half, likely due to rapid progress to CT. Radiographer reports are comparable to local radiologist reports for accuracy. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN21818068. Registered on 20 June 2017

PROTEINCHALLENGE: Crowd sourcing in proteomics analysis and software development

AbstractIn large-scale proteomics studies there is a temptation, after months of experimental work, to plug resulting data into a convenient—if poorly implemented—set of tools, which may neither do the data justice nor help answer the scientific question. In this paper we have captured key concerns, including arguments for community-wide open source software development and “big data” compatible solutions for the future. For the meantime, we have laid out ten top tips for data processing. With these at hand, a first large-scale proteomics analysis hopefully becomes less daunting to navigate.However there is clearly a real need for robust tools, standard operating procedures and general acceptance of best practises. Thus we submit to the proteomics community a call for a community-wide open set of proteomics analysis challenges—PROTEINCHALLENGE—that directly target and compare data analysis workflows, with the aim of setting a community-driven gold standard for data handling, reporting and sharing. This article is part of a Special Issue entitled: New Horizons and Applications for Proteomics [EuPA 2012]

Sequential screening for lung cancer in a high-risk group: randomised controlled trial: LungSEARCH: a randomised controlled trial of Surveillance using sputum and imaging for the EARly detection of lung Cancer in a High-risk group.

BACKGROUND: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. METHODS: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). RESULTS: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. CONCLUSIONS: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening