Increasing morphological disparity and decreasing optimality for jaw speed and strength during the radiation of jawed vertebrates.

The Siluro-Devonian adaptive radiation of jawed vertebrates, which underpins almost all living vertebrate biodiversity, is characterized by the evolutionary innovation of the lower jaw. Multiple lines of evidence have suggested that the jaw evolved from a rostral gill arch, but when the jaw took on a feeding function remains unclear. We quantified the variety of form in the earliest jaws in the fossil record from which we generated a theoretical morphospace that we then tested for functional optimality. By drawing comparisons with the real jaw data and reconstructed jaw morphologies from phylogenetically inferred ancestors, our results show that the earliest jaw shapes were optimized for fast closure and stress resistance, inferring a predatory feeding function. Jaw shapes became less optimal for these functions during the later radiation of jawed vertebrates. Thus, the evolution of jaw morphology has continually explored previously unoccupied morphospace and accumulated disparity through time, laying the foundation for diverse feeding strategies and the success of jawed vertebrates.

Receiving care according to national heart failure guidelines is associated with lower total costs: an observational study in Region Halland, Sweden.

AIMS: Patients with heart failure (HF) have high costs, morbidity, and mortality, but it is not known if appropriate pharmacotherapy (AP), defined as compliance with international evidence-based guidelines, is associated with improved costs and outcomes. The purpose of this study was to evaluate HF patients' health care utilization, cost and outcomes in Region Halland (RH), Sweden, and if AP was associated with lower costs. METHODS AND RESULTS: A total of 5987 residents of RH in 2016 carried HF diagnoses. Costs were assigned to all health care utilization (inpatient, outpatient, emergency department, primary health care, and medications) using a Patient Encounter Costing methodology. Care of HF patients cost €58.6 M, (€9790/patient) representing 8.7% of RH's total visit expenses and 14.9% of inpatient care (IPC) expenses. Inpatient care represented 57.2% of this expenditure, totalling €33.5 M (€5601/patient). Receiving AP was associated with significantly lower costs, by €1130 per patient (P < 0.001, 95% confidence interval 574-1687). Comorbidities such as renal failure, diabetes, chronic obstructive pulmonary disease, and cancer were significantly associated with higher costs. CONCLUSION: Heart failure patients are heavy users of health care, particularly IPC. Receiving AP is associated with lower costs even adjusting for comorbidities, although causality cannot be proven from an observational study. There may be an opportunity to decrease overall costs and improve outcomes by improving prescribing patterns and associated high-quality care.

Development of a Clinical Prediction Model for In-hospital Mortality from the South African Cohort of the African Surgical Outcomes Study.

BACKGROUND: Data on the factors that influence mortality after surgery in South Africa are scarce, and neither these data nor data on risk-adjusted in-hospital mortality after surgery are routinely collected. Predictors related to the context or setting of surgical care delivery may also provide insight into variation in practice. Variation must be addressed when planning for improvement of risk-adjusted outcomes. Our objective was to identify the factors predicting in-hospital mortality after surgery in South Africa from available data. METHODS: A multivariable logistic regression model was developed to identify predictors of 30-day in-hospital mortality in surgical patients in South Africa. Data from the South African contribution to the African Surgical Outcomes Study were used and included 3800 cases from 51 hospitals. A forward stepwise regression technique was then employed to select for possible predictors prior to model specification. Model performance was evaluated by assessing calibration and discrimination. The South African Surgical Outcomes Study cohort was used to validate the model. RESULTS: Variables found to predict 30-day in-hospital mortality were age, American Society of Anesthesiologists Physical Status category, urgent or emergent surgery, major surgery, and gastrointestinal-, head and neck-, thoracic- and neurosurgery. The area under the receiver operating curve or c-statistic was 0.859 (95% confidence interval: 0.827-0.892) for the full model. Calibration, as assessed using a calibration plot, was acceptable. Performance was similar in the validation cohort as compared to the derivation cohort. CONCLUSION: The prediction model did not include factors that can explain how the context of care influences post-operative mortality in South Africa. It does, however, provide a basis for reporting risk-adjusted perioperative mortality rate in the future, and identifies the types of surgery to be prioritised in quality improvement projects at a local or national level.

Clinical lactation studies and the role of pharmacokinetic modeling and simulation in predicting drug exposures in breastfed infants.

The relative lack of information on medication use during breastfeeding is an ongoing problem for health professionals and mothers alike. Most nursing mothers are prescribed some form of medication, yet some mothers either discontinue breastfeeding or avoid medications entirely. Although regulatory authorities have proposed a framework for clinical lactation studies, data on drug passage into breastmilk are often lacking. Model-based approaches can potentially be used to estimate the passage of drugs into milk, predict exposures in breastfed infants, and identify drugs that need clinical lactation studies. When a human study is called for, measurement of the drug concentration in milk are often adequate to characterize safety. Data from these studies can be leveraged to further refine pharmacokinetic models with subsequent Monte Carlo simulations to estimate the spread of exposure values. Both clinical lactation studies and model-based approaches have some limitations and pitfalls which are discussed.

Herbivorous dinosaur jaw disparity and its relationship to extrinsic evolutionary drivers.

Morphological responses of nonmammalian herbivores to external ecological drivers have not been quantified over extended timescales. Herbivorous nonavian dinosaurs are an ideal group to test for such responses, because they dominated terrestrial ecosystems for more than 155 Myr and included the largest herbivores that ever existed. The radiation of dinosaurs was punctuated by several ecologically important events, including extinctions at the Triassic/Jurassic (Tr/J) and Jurassic/Cretaceous (J/K) boundaries, the decline of cycadophytes, and the origin of angiosperms, all of which may have had profound consequences for herbivore communities. Here we present the first analysis of morphological and biomechanical disparity for sauropodomorph and ornithischian dinosaurs in order to investigate patterns of jaw shape and function through time. We find that morphological and biomechanical mandibular disparity are decoupled: mandibular shape disparity follows taxonomic diversity, with a steady increase through the Mesozoic. By contrast, biomechanical disparity builds to a peak in the Late Jurassic that corresponds to increased functional variation among sauropods. The reduction in biomechanical disparity following this peak coincides with the J/K extinction, the associated loss of sauropod and stegosaur diversity, and the decline of cycadophytes. We find no specific correspondence between biomechanical disparity and the proliferation of angiosperms. Continual ecological and functional replacement of pre-existing taxa accounts for disparity patterns through much of the Cretaceous, with the exception of several unique groups, such as psittacosaurids that are never replaced in their biomechanical or morphological profiles.

World Health Assembly Resolution 60.22 and its importance as a health care policy tool for improving emergency care access and availability globally.

The recent adoption of World Health Assembly Resolution 60.22, titled "Health Systems: Emergency Care Systems," has established an important health care policy tool for improving emergency care access and availability globally. The resolution highlights the role that strengthened emergency care systems can play in reducing the increasing burden of disease from acute illness and injury in populations across the socioeconomic spectrum and calls on governments and the World Health Organization to take specific and concrete actions to make this happen. This resolution constitutes recognition by the World Health Assembly of the growing public health role of emergency care systems and is the highest level of international attention ever devoted to emergency care systems worldwide. Emergency care systems for secondary prevention of acute illnesses and injury remain inadequately developed in many low- and middle-income countries, despite evidence that basic strategies for improving emergency care systems can reduce preventable mortality and morbidity and can in many cases also be cost-effective. Emergency care providers and their professional organizations have used their comprehensive expertise to strengthen emergency care systems worldwide through the development of tools for emergency medicine education, systems assessment, quality improvement, and evidence-based clinical practice. World Health Assembly 60.22 represents a unique opportunity for emergency care providers and other advocates for improved emergency care to engage with national and local health care officials and policymakers, as well as with the World Health Organization, and leverage the expertise within the international emergency medicine community to make substantial improvements in emergency care delivery in places where it is most needed.

Design and quality of ICF-compatible data items for national disability support services.

PURPOSE: To examine the structure, distribution and interrelationships of International Classification of Functioning, Disability and Health (ICF)-compatible items in Australia's national data collection about disability support services. METHOD: Rasch analyses were carried out on 93,000 records relating to people aged 15 to 64 years, receiving disability support services in Australia in 2003. The range of disabilities and services received was diverse. 'Support needs', in all nine life areas based on the ICF Activities and Participation domains, are recorded in the national data collection in one of the following three categories: 'needs no help/supervision in this life area'; 'sometimes needs help/supervision'; or 'always needs help/supervision or unable to do activity'. RESULTS: The results of the analysis demonstrate the value of the 'support needs' questions. The three categories of need for support were distinct and widely separated; the ICF domains were also found to be distinct. The results also showed that 'support needs' in one subset of ICF Activities and Participation domains could not be used to predict values in another subset. CONCLUSIONS: The two-dimensional question about 'support needs' offers promise as a general data capture tool for indicating 'extent' of disability. Caution should be exercised in the omission of any ICF Activities and Participation life areas for measurement in diverse populations.

Core curricular elements for fellowship training in international emergency medicine.

OBJECTIVES: The objective was to describe the common educational goals, curricular elements, and methods of evaluation used in international emergency medicine (IEM) fellowship training programs currently. IEM fellowship programs have been developed to provide formal training for emergency physicians (EPs) interested in pursuing careers in IEM. Those fellowships are variable in scope, objectives, and duration. Previously published articles have suggested a general curriculum structure for IEM fellowships. METHODS: A search of MEDLINE, EMBASE, and CINAHL databases from 1950 to June 2008 was performed, combining the terms international, emergency medicine, and fellowship. Online curricula and descriptive materials from IEM fellowships listed by the Society for Academic Emergency Medicine (SAEM) were reviewed. Knowledge and skill areas common to multiple programs were organized in discrete categories. IEM fellowship directors were contacted for input and feedback. RESULTS: Eight articles on IEM fellowships were identified. Two articles described a general structure for fellowship curriculum. Sixteen of 20 IEM fellowship programs had descriptive materials posted online. These information sources, plus input from seven fellowship program directors, yielded the following seven discrete knowledge and skill areas: 1) emergency medicine systems development, 2) humanitarian relief, 3) disaster management, 4) public health, 5) travel and field medicine, 6) program administration, and 7) academic skills. CONCLUSIONS: While IEM fellowships vary with regard to objectives and structure, this article presents an overview of the current focus of IEM fellowship training curricula that could serve as a resource for IEM curriculum development at individual institutions.

Hidden Fermi liquid; the moral: a good effective low-energy theory is worth all of Monte Carlo with Las Vegas thrown in.

We present a formalism for dealing directly with the effects of the Gutzwiller projection implicit in the t-J model which is widely believed to underlie the phenomenology of the high-T(c) cuprates. We suggest that a true Bardeen-Cooper-Schrieffer condensation from a Fermi liquid state takes place, but in the unphysical space prior to projection. At low doping, however, instead of a hidden Fermi liquid one gets a 'hidden' non-superconducting resonating valence bond state which develops hole pockets upon doping. The theory which results upon projection does not follow conventional rules of diagram theory and in fact in the normal state is a Z = 0 non-Fermi liquid. Anomalous properties of the 'strange metal' normal state are predicted and compared against experimental findings.

International emergency medicine fellowships.

The active interchange of intellectual ideas in the quest to improve healthcare globally will likely be best served by active interchange among physicians around the world. Subspecialty fellowship training programs for United States and foreign graduates will provide a focused path to development of a global network of physicians dedicated to the delivery of high-quality emergency health services.

Evidence-based assessment of pregnancy outcome after sumatriptan exposure.

OBJECTIVE: Assessment of best available evidence for tolerability of sumatriptan after inadvertent exposure during pregnancy. BACKGROUND: Migraine's demography suggests that inadvertent exposure to acute therapies is likely during the earliest undiagnosed stages of pregnancy. The tolerability of such therapies under these conditions is not amenable to clinical trial for ethical reasons. In the United States, sumatriptan is currently labeled pregnancy category C (ie, not recommended for use during pregnancy unless the potential benefit justifies the potential risk to the fetus). METHODS: Three types of adverse events were studied: spontaneous abortion, fetal abnormality, and obstetric complications. Traditional evidence-based criteria were used to assess a search-protocol product of four clinical studies and two case reports. RESULTS: The single positive finding ("preterm delivery" without low birth weight) was in the smallest study; this study was retrospective and the finding was externally inconsistent with the other three larger studies, all of which were prospective. No study followed children for more than 4 years, which is the period needed to identify the maximum number of congenital anomalies. Rigorous teratological technique was generally not employed. Post hoc power calculations were used to provide parameters of the hazard detectable by these studies in aggregate. CONCLUSIONS: Pregnancy categories B and C both seem feasible for sumatriptan. Within the limits of the examined studies, there is no evidence for any specific effect of sumatriptan on pregnancy outcome. Patients inadvertently exposed to sumatriptan during an early stage of pregnancy should be reassured by these data.