Coordinated semi-adaptive closed-loop control for infusion of two interacting medications

This paper presents a coordinated and semi‐adaptive closed‐loop control approach to the infusion of 2 interacting medications. The proposed approach consists of an upper‐level coordination controller and a lower‐level semi‐adaptive controller. The coordination controller recursively adjusts the reference targets based on the estimated dose‐response relationship of a patient to ensure that they can be achieved by the patient. The semi‐adaptive controller drives the patient outputs to the reference targets while estimating the patient's dose‐response relationship online. In this way, the controller is resilient to unachievable caregiver‐specified reference targets and responsive to the medication needs of individual patients. To establish the proposed approach, we developed the following: (1) a linear two‐input–two‐output dose‐response model; (2) a two‐input–two‐output semi‐adaptive controller to regulate the patient outputs while adapting high‐sensitivity parameters in the patient model; and (3) a coordination controller to adjust the reference targets that reconcile caregiver inputs and medication use. The proposed approach was applied to an example scenario in which cardiac output and respiratory rate are regulated via infusion of propofol and remifentanil in an in silico simulation setting. The results show that the coordinated semi‐adaptive control could (1) track achievable reference targets with consistent transient and steady‐state performance and (2) resiliently adjust the unachievable reference targets to achievable ones

Spatial Connectivity and Drivers of Shark Habitat Use Within a Large Marine Protected Area in the Caribbean, The Bahamas Shark Sanctuary

Marine protected areas (MPAs) have emerged as potentially important conservation tools for the conservation of biodiversity and mitigation of climate impacts. Among MPAs, a large percentage has been created with the implicit goal of protecting shark populations, including 17 shark sanctuaries which fully protect sharks throughout their jurisdiction. The Commonwealth of the Bahamas represents a long-term MPA for sharks, following the banning of commercial longlining in 1993 and subsequent designation as a shark sanctuary in 2011. Little is known, however, about the longterm behavior and space use of sharks within this protected area, particularly among reef-associated sharks for which the sanctuary presumably offers the most benefit. We used acoustic telemetry to advance our understanding of the ecology of such sharks, namely Caribbean reef sharks (Carcharhinus perezi) and tiger sharks (Galeocerdo cuvier), over two discrete islands (New Providence and Great Exuma) varying in human activity level, over 2 years. We evaluated which factors influenced the likelihood of detection of individuals, analyzed patterns of movement and occurrence, and identified variability in habitat selection among species and regions, using a dataset of 23 Caribbean reef sharks and 15 tiger sharks which were passively monitored in two arrays with a combined total of 13 acoustic receivers. Caribbean reef sharks had lower detection probabilities than tiger sharks, and exhibited relatively low habitat connectivity and high residency, while tiger sharks demonstrated wider roaming behavior across much greater space. Tiger sharks were associated with shallow seagrass habitats where available, but frequently transited between and connected different habitat types. Our data support the notion that large MPAs afford greater degrees of protection for highly resident species such as Caribbean reef sharks, shark, acoustic telemetry, marine protected area, MPA, seagrass, coral reef, Bahamas, Caribbea

Felony Murder and Capital Punishment: an Examination of the Deterrence Question

A proper test of the deterrent effect of the death penalty must consider capital homicides. However, the criterion variable in most investigations has been total homicides—most of which bear no legal or theoretical relationship to capital punishment. To address this fundamental data problem, this investigation used Federal Bureau of Investigation data for 1976–1987 to examine the relationship between capital punishment and felony murder, the most common type of capital homicide. We conducted time series analyses of monthly felony murder rates, the frequency of executions, and the amount and type of television coverage of executions over the period. The analyses revealed occasional departures (for vehicle theft and narcotics killings) from the null hypotheses. However, on balance, and in line with the vast majority of capital punishment studies, this investigation found no consistent evidence that executions and the television coverage they receive are associated significantly with rates for total, index, or different types of felony murder

Cardiovascular Risk Factors Associated With Venous Thromboembolism.

IMPORTANCE: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). OBJECTIVE: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. DESIGN, SETTING, AND PARTICIPANTS: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. EXPOSURES: A panel of several established cardiovascular risk factors. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). RESULTS: Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. CONCLUSIONS AND RELEVANCE: Older age, smoking, and adiposity were consistently associated with higher VTE risk.This research has been conducted using the UK Biobank resource under Application Number 26865. This work was supported by underpinning grants from the UK Medical Research Council (grant G0800270), the British Heart Foundation (grant SP/09/002), the British Heart Foundation Cambridge Cardiovascular Centre of Excellence, UK National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council (grant 268834), the European Commission Framework Programme 7 (grant HEALTH-F2-2012-279233), and Health Data Research UK. Dr Danesh holds a British Heart Foundation Personal Chair and a National Institute for Health Research Senior Investigator Award

World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

BACKGROUND: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. METHODS: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. FINDINGS: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. INTERPRETATION: We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. FUNDING: World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Experimental Studies in Face Transplantation: Primate Model

In offering optimal reconstruction for severe facial disfigurement, the advent of human face transplantation constitutes a landmark achievement in medicine and stands as a historical testament to the creativity, intelligence, ingenuity, and boldness of the human species. Facial allotransplantation has been modeled in rodents, canines, swine, and lagomorphs. However, human and rodent immune systems are dissimilar to a degree that precludes translation of tolerance induction protocols to humans. Nonhuman primates have long been used as translational models of human immunology and transplant immunobiology due to recent evolutionary divergence and shared major histocompatibility complex (MHC) II polymorphisms. We have developed a reproducible heterotopic model of nonhuman primate facial CTA permissive of long-term rejection-free survival. The purpose of this chapter is to share our experience in the development and maturation of this model, from surgical technique and immunosuppressive strategies, to experimental results and future directions