Prospective observational study of point-of-care creatinine in trauma.

Background:Patients with trauma are at risk for renal dysfunction from hypovolemia or urological injury. In austere environments, creatinine values are not available to guide resuscitation. A new portable device, the Stat Sensor Point-of-care (POC) Whole Blood Creatinine Analyzer, provides accurate results in <30 s and requires minimal training. This device has not been evaluated in trauma despite the theoretical benefit it provides. The purpose of this study is to determine the clinical impact of the POC device in trauma. Methods:40 patients with trauma were enrolled in a prospective observational study. One drop of blood was used for creatinine determination on the Statsensor POC device. POC creatinine results were compared to the laboratory. Turnaround time (TAT) for POC and laboratory methods was calculated as well as time elapsed to CT scan if applicable. Results:Patients (n=40) were enrolled between December 2014 and March 2015. POC creatinine values were similar to laboratory methods with a mean bias of 0.075±0.27 (p=0.08). Mean analytical TATs for the POC measurements were significantly faster than the laboratory method (11.6±10.0 min vs 78.1±27.9 min, n=40, p<0.0001). Mean elapsed time before arrival at the CT scanner was 52.9±34.2 min. Conclusions:The POC device reported similar creatinine values to the laboratory and provided significantly faster results. POC creatinine testing is a promising development for trauma practice in austere environments and workup of a subset of stable patients with trauma. Further study is warranted to determine clinical impact, both in hospital-based trauma and austere environments

UAS for Public Safety: Active Threat Recognition

The Center for Homeland Defense and Security identified an increase of active threat events, such as mass shootings, annually since 1999. Literature suggests that 90% of shootings were over before law enforcement arrived at the scene and the first responder response was limited to “surround and contain” until Special Weapons and Tactics Teams (SWAT) arrived on the scene. Using Unmanned Aircraft Systems (UAS) to detect which individual was the threat and type of weapon used can provide useful information to increase the speed of the response for first-on-scene rather than waiting for SWAT if the type of weapon was known. A UAS equipped with a full spectrum sensor compared traditional red-green-blue (RGB) images to near-infrared (NIR) images in a simulated active threat scenario. A true positive rate (TPR) metric was used to measure the percentage of correctly-detected weapons consisting of either a knife, pistol, rifle, shotgun, or shovel at slant range distances of 25-, 50-, 75-, and 100-feet respectively. A convenience sample of 102 survey participants, recruited from constituents of the Airborne Public Safety Association (APSA) and DRONERESPONDERS was conducted to observe 48 randomly-presented images to determine which type of weapon was detected. The results suggest that survey participants could correctly detect weapons at a 12% greater rate with the NIR sensor than the RGB sensor; however, the pistol had the largest difference in TPR between NIR and RGB sensors. The pistol had an increased probability of detection by 33% when using the NIR sensor compared to an RGB sensor. Additionally, differences were also observed between slant range distances. The closest distance of 25 feet showed a 42% increase in participants’ ability to correctly determine the weapon type compared to the 100-foot slant range distance. Therefore, using a NIR sensor-equipped UAS at flying a maximum slant range distance of 50 feet may help a first-responder determine the type of weapon before SWAT arrives on the scene

Healthy living and cancer: evidence from UK Biobank.

CONTEXT: UK Biobank is a prospective study of half a million subjects, almost all aged 40-69 years, identified in 22 centres across the UK during 2006-2010. OBJECTIVE: A healthy lifestyle has been described as 'better than any pill, and no side effects [5]. We therefore examined the relationships between healthy behaviours: low alcohol intake, non-smoking, healthy BMI, physical activity and a healthy diet, and the risk of all cancers, colon, breast and prostate cancers in a large dataset. METHOD: Data on lifestyle behaviours were provided by 343,150 subjects, and height and weight were measured at recruitment. 14,285 subjects were diagnosed with cancer during a median of 5.1 years of follow-up. RESULTS: Compared with subjects who followed none or a single healthy behaviour, a healthy lifestyle based on all five behaviours was associated with a reduction of about one-third in incident cancer (hazard ratio [HR] 0.68; 95% confidence intervals [CI] 0.63-0.74). Colorectal cancer was reduced in subjects following the five behaviours by about one-quarter (HR 0.75; 95% CI 0.58-0.97), and breast cancer by about one-third (HR 0.65; 95% CI 0.52-0.83). The association between a healthy lifestyle and prostate cancer suggested a significant increase in risk, but this can be attributed to bias consequent on inequalities in the uptake of the prostate specific antigen screening test. CONCLUSIONS: Taken together with reported reductions in diabetes, vascular disease and dementia, it is clearly important that every effort is taken to promote healthy lifestyles throughout the population, and it is pointed out that cancer and other screening clinics afford 'teachable moments' for the promotion of a healthy lifestyle

Involvement of HTLV-I Tax and CREB in aneuploidy: a bioinformatics approach

BACKGROUND: Adult T-cell leukemia (ATL) is a complex and multifaceted disease associated with human T-cell leukemia virus type 1 (HTLV-I) infection. Tax, the viral oncoprotein, is considered a major contributor to cell cycle deregulation in HTLV-I transformed cells by either directly disrupting cellular factors (protein-protein interactions) or altering their transcription profile. Tax transactivates these cellular promoters by interacting with transcription factors such as CREB/ATF, NF-κB, and SRF. Therefore by examining which factors upregulate a particular set of promoters we may begin to understand how Tax orchestrates leukemia development. RESULTS: We observed that CTLL cells stably expressing wild-type Tax (CTLL/WT) exhibited aneuploidy as compared to a Tax clone deficient for CREB transactivation (CTLL/703). To better understand the contribution of Tax transactivation through the CREB/ATF pathway to the aneuploid phenotype, we performed microarray analysis comparing CTLL/WT to CTLL/703 cells. Promoter analysis of altered genes revealed that a subset of these genes contain CREB/ATF consensus sequences. While these genes had diverse functions, smaller subsets of genes were found to be involved in G2/M phase regulation, in particular kinetochore assembly. Furthermore, we confirmed the presence of CREB, Tax and RNA Polymerase II at the p97Vcp and Sgt1 promoters in vivo through chromatin immunoprecipitation in CTLL/WT cells. CONCLUSION: These results indicate that the development of aneuploidy in Tax-expressing cells may occur in response to an alteration in the transcription profile, in addition to direct protein interactions

Machine learning-based prediction of breast cancer growth rate in-vivo

BackgroundDetermining the rate of breast cancer (BC) growth in vivo, which can predict prognosis, has remained elusive despite its relevance for treatment, screening recommendations and medicolegal practice. We developed a model that predicts the rate of in vivo tumour growth using a unique study cohort of BC patients who had two serial mammograms wherein the tumour, visible in the diagnostic mammogram, was missed in the first screen.MethodsA serial mammography-derived in vivo growth rate (SM-INVIGOR) index was developed using tumour volumes from two serial mammograms and time interval between measurements. We then developed a machine learning-based surrogate model called Surr-INVIGOR using routinely assessed biomarkers to predict in vivo rate of tumour growth and extend the utility of this approach to a larger patient population. Surr-INVIGOR was validated using an independent cohort.ResultsSM-INVIGOR stratified discovery cohort patients into fast-growing versus slow-growing tumour subgroups, wherein patients with fast-growing tumours experienced poorer BC-specific survival. Our clinically relevant Surr-INVIGOR stratified tumours in the discovery cohort and was concordant with SM-INVIGOR. In the validation cohort, Surr-INVIGOR uncovered significant survival differences between patients with fast-growing and slow-growing tumours.ConclusionOur Surr-INVIGOR model predicts in vivo BC growth rate during the pre-diagnostic stage and offers several useful applications

Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia

Leukemia stem cells (LSCs) in individuals with chronic myelogenous leukemia (CML) (hereafter referred to as CML LSCs) are responsible for initiating and maintaining clonal hematopoiesis. These cells persist in the bone marrow (BM) despite effective inhibition of BCR–ABL kinase activity by tyrosine kinase inhibitors (TKIs). Here we show that although the microRNA (miRNA) miR-126 supported the quiescence, self-renewal and engraftment capacity of CML LSCs, miR-126 levels were lower in CML LSCs than in long-term hematopoietic stem cells (LT-HSCs) from healthy individuals. Downregulation of miR-126 levels in CML LSCs was due to phosphorylation of Sprouty-related EVH1-domain-containing 1 (SPRED1) by BCR–ABL, which led to inhibition of the RAN–exportin-5–RCC1 complex that mediates miRNA maturation. Endothelial cells (ECs) in the BM supply miR-126 to CML LSCs to support quiescence and leukemia growth, as shown using mouse models of CML in which Mir126a (encoding miR-126) was conditionally knocked out in ECs and/or LSCs. Inhibition of BCR–ABL by TKI treatment caused an undesired increase in endogenous miR-126 levels, which enhanced LSC quiescence and persistence. Mir126a knockout in LSCs and/or ECs, or treatment with a miR-126 inhibitor that targets miR-126 expression in both LSCs and ECs, enhanced the in vivo anti-leukemic effects of TKI treatment and strongly diminished LSC leukemia-initiating capacity, providing a new strategy for the elimination of LSCs in individuals with CML

Starting where I am: a grounded theory exploration of mindfulness as a facilitator of transition in living with a long-term condition

Aim: To explore how practising mindfulness affects people’s experiences of living with a long-term condition. Background: Increasing evidence suggests that mindfulness meditation-based interventions benefit people with long-term conditions, particularly in terms of psychological wellbeing. Most evidence however relates to short-term outcomes, and limited information exists about how people use mindfulness in the longer-term, and how this affects their experience of living with their condition. Design: A qualitative study using constructivist-informed grounded theory. Methods: Using interviews, diaries and focus groups, data were collected between 2011 and 2012 from participants and/or trainers of Breathworks’ mindfulness intervention. Phased recruitment enabled theoretical sampling, with data analysed concurrently using Charmaz’s two-stage coding strategy. Findings: The final sample comprised 41 adults with diverse physical and/or mental health conditions. Participants reported predominantly positive experiences, almost all identifying significant changes in thinking and behaviour. A core process of ‘Starting where I am’ was formulated, highlighting how people became more aware and accepting of their condition and thus able to self-care more effectively. The process was encapsulated in five themes: Getting a new perspective; Feeling equipped to cope; Doing life differently; Seeing a change; and Finding mindfulness difficult. Strong resonances were identified between participants’ experiences and the process of transition through which people come to terms with challenging life events. Conclusion: Mindfulness can be conceptualised as a facilitator of transition, enabling people to adapt to living with a long-term condition. Transition is associated with improved, self- directed self-management, which is significant to both people with long-term conditions and healthcare providers

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Durable, Self-Cleaning, Medical Fabric Coatings for Infectious Hazard Protection

There exists a socio-economical need to improve the safety of public health against infectious hazards. Global pandemics cause catastrophic physical, emotional, and economical costs. Similarly, healthcare associated infections (HAI) is a growing health concern that affects millions of people and costs US hospitals billions of dollars each year. In healthcare, hospitals hold immuno-compromised patients requiring the implementation of contamination mitigation measures. Healthcare professionals, patients, and visitors are exposed to high doses of infectious hazards such as human coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Personal protective equipment (PPE), from masks to clothing to gowns, are essential for protecting the general public, healthcare workers, patients and visitors from infectious hazards. However, PPE may become contaminated and inadvertently aid in the transmission of microorganisms that are commonly carried through bodily fluids. A fomite is any inanimate object that becomes contaminated and has the capability to transfer disease to a new host. PPE commonly become fomites that transmit infection. There is a need to improve the performance of PPE for fomite prevention. Self-cleaning surface coating treatments provide a solution to improve the safety of public health by reducing the risk of disease spread by fomites. PPE may undergo a surface coating treatment with a self-cleaning functionality to reduce the risk of infection transmission. Self-cleaning, medical surface coatings are a proactive strategy to improve public health safety by preventing surface contamination from human body fluid, bacteria, and viruses. Currently, there exists a gap in knowledge for incorporating functional materials into scalable and durable surface coatings to reduce the risk of infections caused by fomites. Current surface treatment strategies do not have long-lasting durability for practical use in medical settings. This research will overcome the current limiting factors for an effective medical coating: functionality of reducing the transmission of virus infection and the durability of that functionality