Quantum Criticality at the Origin of Life

Why life persists at the edge of chaos is a question at the very heart of evolution. Here we show that molecules taking part in biochemical processes from small molecules to proteins are critical quantum mechanically. Electronic Hamiltonians of biomolecules are tuned exactly to the critical point of the metal-insulator transition separating the Anderson localized insulator phase from the conducting disordered metal phase. Using tools from Random Matrix Theory we confirm that the energy level statistics of these biomolecules show the universal transitional distribution of the metal-insulator critical point and the wave functions are multifractals in accordance with the theory of Anderson transitions. The findings point to the existence of a universal mechanism of charge transport in living matter. The revealed bio-conductor material is neither a metal nor an insulator but a new quantum critical material which can exist only in highly evolved systems and has unique material properties.Comment: 10 pages, 4 figure

Preclinical models of myocardial infarction: from mechanism to translation

Approximately 7 million people are affected by acute myocardial infarction (MI) each year, and despite significant therapeutic and diagnostic advancements, MI remains a leading cause of mortality worldwide. Pre-clinical animal models have significantly advanced our understanding of MI and enable the development of therapeutic strategies to combat this debilitating disease. Notably, some drugs currently used to treat MI and heart failure (HF) in patients had initially been studied in pre-clinical animal models. Despite this, pre-clinical models are limited in their ability to fully recapitulate the complexity of MI in humans. The pre-clinical model must be carefully selected to maximise the translational potential of experimental findings. This review describes current experimental models of MI and considers how they have been used to understand drug mechanisms of action (MOA) and support translational medicine development

CALIPSO Satellite Lidar Identification Of Elevated Dust Over Australia Compared With Air Quality Model PM60 Forecasts

Global measurements of the vertical distribution of clouds and aerosols have been recorded by the lidar on board the CALIPSO (Cloud Aerosol Lidar Infrared Pathfinder Satellite Observations) satellite since June 2006. Such extensive, height-resolved measurements provide a rare and valuable opportunity for developing, testing and validating various atmospheric models, including global climate, numerical weather prediction, chemical transport and air quality models. Here we report on the initial results of an investigation into the performance of the Australian Air Quality Forecast System (AAQFS) model in forecasting the distribution of elevated dust over the Australian region. The model forecasts of PM60 dust distribution are compared with the CALIPSO lidar Vertical Feature Mask (VFM) data product. The VFM classifies contiguous atmospheric regions of enhanced backscatter as either cloud or aerosols. Aerosols are further classified into six subtypes. By comparing forecast PM60 concentration profiles to the spatial distribution of dust reported in the CALIPSO VFM, we can assess the model s ability to predict the occurrence and the vertical and horizontal extents of dust events within the study area

Wearable activity technology and action-planning (WATAAP) to promote physical activity in cancer survivors: Randomised controlled trial protocol

Background/Objective: Colorectal and gynecologic cancer survivors are at cardiovascular risk due to comorbidities and sedentary behaviour, warranting a feasible intervention to increase physical activity. The Health Action Process Approach (HAPA) is a promising theoretical frame-work for health behaviour change, and wearable physical activity trackers offer a novel means of self-monitoring physical activity for cancer survivors. Method: Sixty-eight survivors of colorectal and gynecologic cancer will be randomised into 12- week intervention and control groups. Intervention group participants will receive: a Fitbit AltaTM to monitor physical activity, HAPA-based group sessions, booklet, and support phone-call. Participants in the control group will only receive the HAPA-based booklet. Physical activity (using accelerometers), blood pressure, BMI, and HAPA constructs will be assessed at baseline, 12-weeks (post-intervention) and 24-weeks (follow-up). Data analysis will use the Group x Time interaction from a General Linear Mixed Model analysis. Conclusions: Physical activity interventions that are acceptable and have robust theoretical underpinnings show promise for improving the health of cancer survivors

Low-loss slot waveguides with silicon (111) surfaces realized using anisotropic wet etching

We demonstrate low-loss slot waveguides on silicon-on-insulator (SOI) platform. Waveguides oriented along the (11-2) direction on the Si (110) plane were first fabricated by a standard e-beam lithography and dry etching process. A TMAH based anisotropic wet etching technique was then used to remove any residual side wall roughness. Using this fabrication technique propagation loss as low as 3.7dB/cm was realized in silicon slot waveguide for wavelengths near 1550nm. We also realized low propagation loss of 1dB/cm for silicon strip waveguides

Heart failure with preserved ejection fraction (HFpEF) pathophysiology study (IDENTIFY-HF): does increased arterial stiffness associate with HFpEF, in addition to ageing and vascular effects of comorbidities? Rationale and design

Aims: There has been a paradigm shift proposing that comorbidities are a major contributor towards the heart failure with preserved ejection fraction (HFpEF) syndrome. Furthermore, HFpEF patients have abnormal macrovascular and microvascular function, which may significantly contribute towards altered ventricular-vascular coupling in these patients. The IDENTIFY-HF study will investigate whether gradually increased arterial stiffness (in addition to ageing) as a result of increasing common comorbidities, such as hypertension and diabetes, is associated with HFpEF. Methods and analysis: In our observational study, arterial compliance and microvascular function will be assessed in five groups (Groups A to E) of age, sex and body mass index matched subjects (age ≥70 years in all groups): Group A; normal healthy volunteers without major comorbidities such as hypertension and diabetes mellitus (control). Group B; patients with hypertension without diabetes mellitus or heart failure (HF). Group C; patients with hypertension and diabetes mellitus without HF. Group D; patients with HFpEF. Group E; patients with heart failure and reduced ejection fraction (parallel group). Vascular function and arterial compliance will be assessed using pulse wave velocity, as the primary outcome measure. Further outcome measures include cutaneous laser Doppler flowmetry as a measure of endothelial function, transthoracic echocardiography and exercise tolerance measures. Biomarkers include NT-proBNP, high-sensitivity troponin T, as well as serum galectin-3 as a marker of fibrosis. Ethics and dissemination: The study was approved by the regional research ethics committee (REC), West Midland and Black Country 17/WM/0039, UK, and permission to conduct the study in the hospital was also obtained from the RDI, UHCW NHS Trust. The results will be published in peer-reviewed journals and presented in local, national and international medical society meetings. Trial registration number: NCT0318683

The direct medical costs of epilepsy in children and young people: a population-based study of health resource utilisation

We described the health resource utilisation (HRU) and associated direct medical costs of managing epilepsy in children and young people (CYP) using population-level data from the United Kingdom. The study cohort were CYP born between 1988 and 2004 who were newly diagnosed with epilepsy and identified using a nationally representative primary care database from the United Kingdom. Reference unit costs were applied to each element of HRU to calculate annual direct medical costs per child. We assessed whether HRU and costs differed by time from diagnosis, age, sex and socioeconomic deprivation. Of 798 CYP newly diagnosed with epilepsy, 56% were male and the mean age at diagnosis was 5.6 years. The highest burden of HRU was in the first year following diagnosis with a mean annual cost of £930 (95% confidence interval (CI) £839–1022) per child in this first year. This decreased to £461 (95%CI 368–551) in the second year which remained fairly constant each subsequent year (£413 (95% CI 282–540) in the 8th year). The highest contribution to the annual medical costs was from inpatient hospital admissions followed by the costs of AEDs. Mean annual medical costs were significantly higher in children under 6 years of age compared with older children (p < 0.01), but were similar across socioeconomic groups (p = 0.62). The direct medical costs of HRU in CYP with epilepsy are higher in the first year after diagnosis compared to subsequent years, reflecting HRU related to the diagnostic process in the first year. Medical costs did not vary substantially by sex or socioeconomic deprivation indicating a similar level of consultation and care across these groups

Central Role of IL-23 and IL-17 Producing Eosinophils as Immunomodulatory Effector Cells in Acute Pulmonary Aspergillosis and Allergic Asthma

Aspergillus fumigatus causes invasive pulmonary disease in immunocompromised hosts and allergic asthma in atopic individuals. We studied the contribution of lung eosinophils to these fungal diseases. By in vivo intracellular cytokine staining and confocal microscopy, we observed that eosinophils act as local sources of IL-23 and IL-17. Remarkably, mice lacking eosinophils had a \u3e95% reduction in the percentage of lung IL-23p19+ cells as well as markedly reduced IL-23 heterodimer in lung lavage fluid. Eosinophils killed A. fumigatus conidia in vivo. Eosinopenic mice had higher mortality rates, decreased recruitment of inflammatory monocytes, and decreased expansion of lung macrophages after challenge with conidia. All of these functions underscore a potential protective role for eosinophils in acute aspergillosis. Given the postulated role for IL-17 in asthma pathogenesis, we assessed whether eosinophils could act as sources of IL-23 and IL-17 in models where mice were sensitized to either A. fumigatus antigens or ovalbumin (OVA). We found IL-23p19+ IL-17AF+ eosinophils in both allergic models. Moreover, close to 95% of IL-23p19+ cells and \u3e90% of IL-17AF+ cells were identified as eosinophils. These data establish a new paradigm in acute and allergic aspergillosis whereby eosinophils act not only as effector cells but also as immunomodulatory cells driving the IL-23/IL-17 axis and contributing to inflammatory cell recruitment

Racial Disparities in Emergency General Surgery: Do Differences in Outcomes Persist Among Universally Insured Military Patients?

Research Objective: Described as one of the most serious health problems affecting the nation, racial disparities are estimated to account for \u3e83,000 deaths, \u3e$57 billion per year. They have been identified in multiple surgical settings, including differences in outcomes by race among emergency general surgery(EGS) patients. As many minority patients are uninsured, increasing access to care is thought to be a viable solution to mitigate inequities. The objectives of this study were to determine whether racial disparities in 30/90/180day outcomes exist within a universally-insured population of military/civilian-dependent EGS patients and whether differences in outcomes differentially persist in care received at military-vs-civilian hospitals and among sponsors who are enlisted-service members-vs-officers. It also considered longer-term outcomes of care. Study Design: Risk-adjusted survival analyses using Cox proportional-hazards models assessed race-based differences in mortality, major morbidity, and readmission from index-hospital admission (discharge for readmission) through 30/90/180days. Models accounted for hospital clustering and possible biases associated with missing race (reweighted-estimating equations). Sub-analyses considered effects restricted to operative interventions, stratified by 24 EGS-diagnostic categories defined by the American Association for the Surgery of Trauma(AAST), and effect modification related to rank (SES-proxy: officers-vs-enlisted-sponsors) and military-vs-civilian-hospital care. Population Studied: Five years of national TRICARE Prime/Prime-plus data, which provides insurance to active/reserve/retired members of the US Armed Services and dependents, were queried for adults (≥18y) with primary EGS conditions, defined by the AAST. Patients who did not have an index admission between 01/01/2006-01/07/2010 (minimum 180days follow-up) or who were not continuously enrolled in TRICARE for 180days were excluded. Non-surviving patients were retained while they survived. Principal Findings: A total of 101,011 patients were included: 73.5% White, 14.5% Black, 4.4% Asian, 7.7% other. Risk-adjusted analyses reported equivalent-or-better mortality and readmission outcomes among minority patients at 30/90/180days—even when restricted to civilian hospitals where studies suggest that EGS disparities are found. Readmissions within military hospitals were lower among minority patients. Major morbidity was higher among Black versus White patients (HR[95%CI]): 30day-1.23[1.13-1.35], 90day-1.18[1.09-1.28], 180day-1.15[1.07-1.24]—a finding driven by appendiceal disorders (HR:1.69-1.70). No other diagnostic category-based HR was significant. When considered by rank, significant effects were isolated to enlisted-service members. However, given the relatively small number of patients who were (dependents of) officers, it is difficult to determine whether rank-based findings are a result of social determinants or influenced by the limited number of minority patients. Conclusions: The first of its kind to examine racial disparities in longer-term outcomes of EGS care, this longitudinal analysis of military patients demonstrated apparent mitigation of racial disparities within a universally-insured health system when compared to the overall US health system. Efforts to explain findings based on consideration of care provided in military-vs-civilian hospitals, among specific EGS-diagnostic categories, and based on sponsor rank revealed modification of the association between race and outcomes to some extent for all three. Implications for Policy or Practice: The contrast between results for universally-insured military/civilian-dependent patients and reported disparities among all US civilian patients merits consideration. The data speak to the importance of insurance-coverage in the development of disparities interventions nationwide and will help to inform policy within the DoD