Analyzing program termination and complexity automatically with AProVE

In this system description, we present the tool AProVE for automatic termination and complexity proofs of Java, C, Haskell, Prolog, and rewrite systems. In addition to classical term rewrite systems (TRSs), AProVE also supports rewrite systems containing built-in integers (int-TRSs). To analyze programs in high-level languages, AProVE automatically converts them to (int-)TRSs. Then, a wide range of techniques is employed to prove termination and to infer complexity bounds for the resulting rewrite systems. The generated proofs can be exported to check their correctness using automatic certifiers. To use AProVE in software construction, we present a corresponding plug-in for the popular Eclipse software development environment

Correlation between case mix index and antibiotic use in hospitals

BACKGROUND: To compare the quantitative antibiotic use between hospitals or hospital units and to explore differences, adjustment for severity of illness of hospitalized patients is essential. The case mix index (CMI) is an economic surrogate marker (i.e. the total cost weights of all inpatients per a defined time period divided by the number of admissions) to describe the average patients' morbidity of individual hospitals. We aimed to investigate the correlation between CMI and hospital antibiotic use. METHODS: We used weighted linear regression analysis to evaluate the correlation between in-hospital antibiotic use in 2006 and CMI of 18 departments of the tertiary care University Hospital Zurich and of 10 primary and 2 secondary acute care hospitals in the Canton of Zurich in Switzerland. RESULTS: Antibiotic use varied substantially between different departments of the university hospital [defined daily doses (DDD)/100 bed-days, 68.04; range, 20.97-323.37] and between primary and secondary care hospitals (range of DDD/100 bed-days, 15.45-57.05). Antibiotic use of university hospital departments and the different hospitals, respectively, correlated with CMI when calculated in DDD/100 bed-days [coefficient of determination (R(2)), 0.57 (P = 0.0002) and 0.46 (P = 0.0065)], as well as when calculated in DDD/100 admissions [R(2), 0.48 (P = 0.0008) and 0.85 (P < 0.0001), respectively]. CONCLUSIONS: Antibiotic use correlated with CMI across various specialties of a university hospital and across different acute care hospitals. For benchmarking antibiotic use within and across hospitals, adjustment for CMI may be a useful tool in order to take into account the differences in hospital category and patients' morbidities

Recasting the theory of mosquito-borne pathogen transmission dynamics and control

Mosquito-borne diseases pose some of the greatest challenges in public health, especially in tropical and sub-tropical regions of theworld. Efforts to control these diseases have been underpinned by a theoretical framework developed for malaria by Ross and Macdonald, including models, metrics for measuring transmission, and theory of control that identifies key vulnerabilities in the transmission cycle. That framework, especially Macdonald’s formula for R0 and its entomological derivative, vectorial capacity, are nowused to study dynamics and design interventions for many mosquito-borne diseases. A systematic review of 388 models published between 1970 and 2010 found that the vast majority adopted the Ross–Macdonald assumption of homogeneous transmission in a well-mixed population. Studies comparing models and data question these assumptions and point to the capacity to model heterogeneous, focal transmission as the most important but relatively unexplored component in current theory. Fine-scale heterogeneity causes transmission dynamics to be nonlinear, and poses problems for modeling, epidemiology and measurement. Novel mathematical approaches show how heterogeneity arises from the biology and the landscape on which the processes of mosquito biting and pathogen transmission unfold. Emerging theory focuses attention on the ecological and social context formosquito blood feeding, themovement of both hosts and mosquitoes, and the relevant spatial scales for measuring transmission and for modeling dynamics and control

Papio Baboon species indicative alu elements

The genus of Papio (baboon) has six recognized species separated into Northern and Southern clades, each comprised of three species distributed across the African continent. Geographic origin and phenotypic variants such as coat color and body size have commonly been used to identify different species. The existence of multiple hybrid zones, both ancient and current, have complicated efforts to characterize the phylogeny of Papio baboons. More recently, mitochondrial DNA (mtDNA) and Y-chromosome genetic markers have been utilized for species identification with particular focus on the hybrid zones. Alu elements accumulate in a random manner and are a novel source of identical by descent variation with known ancestral states for inferring population genetic and phylogenetic relationships. As part of the Baboon Genome Analysis Consortium, we assembled an Alu insertion polymorphism database of nearly 500 Papio-lineage specific insertions representing all six species and performed population structure and phylogenetic analyses. In this study, we have selected a subset of 48 species indicative Alu insertions and demonstrate their utility as genetic systems for the identification of baboon species within Papio. Individual elements from the panel are easy to genotype and can be used in a hierarchical fashion based on the original level of uncertainty. This Alu-48 panel should serve as a valuable tool during the maintenance of pedigree records in captive populations and assist in the forensic identification of fossils and potential hybrids in the wild

Analysis of lineage-specific Alu subfamilies in the genome of the olive baboon, Papio anubis

Background: Alu elements are primate-specific retroposons that mobilize using the enzymatic machinery of L1 s. The recently completed baboon genome project found that the mobilization rate of Alu elements is higher than in the genome of any other primate studied thus far. However, the Alu subfamily structure present in and specific to baboons had not been examined yet. Results: Here we report 129 Alu subfamilies that are propagating in the genome of the olive baboon, with 127 of these subfamilies being new and specific to the baboon lineage. We analyzed 233 Alu insertions in the genome of the olive baboon using locus specific polymerase chain reaction assays, covering 113 of the 129 subfamilies. The allele frequency data from these insertions show that none of the nine groups of subfamilies are nearing fixation in the lineage. Conclusions: Many subfamilies of Alu elements are actively mobilizing throughout the baboon lineage, with most being specific to the baboon lineage

The comparative genomics and complex population history of Papio baboons

Recent studies suggest that closely related species can accumulate substantial genetic and phenotypic differences despite ongoing gene flow, thus challenging traditional ideas regarding the genetics of speciation. Baboons (genus Papio) are Old World monkeys consisting of six readily distinguishable species. Baboon species hybridize in the wild, and prior data imply a complex history of differentiation and introgression. We produced a reference genome assembly for the olive baboon (Papio anubis) and whole-genome sequence data for all six extant species. We document multiple episodes of admixture and introgression during the radiation of Papio baboons, thus demonstrating their value as a model of complex evolutionary divergence, hybridization, and reticulation. These results help inform our understanding of similar cases, including modern humans, Neanderthals, Denisovans, and other ancient hominins

Pragmatic solutions to reduce the global burden of stroke: a World Stroke Organization–Lancet Neurology Commission

Stroke is the second leading cause of death worldwide. The burden of disability after a stroke is also large, and is increasing at a faster pace in low-income and middle-income countries than in high-income countries. Alarmingly, the incidence of stroke is increasing in young and middle-aged people (ie, age &lt;55 years) globally. Should these trends continue, Sustainable Development Goal 3.4 (reducing the burden of stroke as part of the general target to reduce the burden of non-communicable diseases by a third by 2030) will not be met. In this Commission, we forecast the burden of stroke from 2020 to 2050. We project that stroke mortality will increase by 50%—from 6·6 million (95% uncertainty interval [UI] 6·0 million–7·1 million) in 2020, to 9·7 million (8·0 million–11·6 million) in 2050—with disability-adjusted life-years (DALYs) growing over the same period from 144·8 million (133·9 million–156·9 million) in 2020, to 189·3 million (161·8 million–224·9 million) in 2050. These projections prompted us to do a situational analysis across the four pillars of the stroke quadrangle: surveillance, prevention, acute care, and rehabilitation. We have also identified the barriers to, and facilitators for, the achievement of these four pillars. Disability-adjusted life-years (DALYs) The sum of the years of life lost as a result of premature mortality from a disease and the years lived with a disability associated with prevalent cases of the disease in a population. One DALY represents the loss of the equivalent of one year of full health On the basis of our assessment, we have identified and prioritised several recommendations. For each of the four pillars (surveillance, prevention, acute care, and rehabilitation), we propose pragmatic solutions for the implementation of evidence-based interventions to reduce the global burden of stroke. The estimated direct (ie, treatment and rehabilitation) and indirect (considering productivity loss) costs of stroke globally are in excess of US$891 billion annually. The pragmatic solutions we put forwards for urgent implementation should help to mitigate these losses, reduce the global burden of stroke, and contribute to achievement of Sustainable Development Goal 3.4, the WHO Intersectoral Global Action Plan on epilepsy and other neurological disorders (2022–2031), and the WHO Global Action Plan for prevention and control of non-communicable diseases. Reduction of the global burden of stroke, particularly in low-income and middle-income countries, by implementing primary and secondary stroke prevention strategies and evidence-based acute care and rehabilitation services is urgently required. Measures to facilitate this goal include: the establishment of a framework to monitor and assess the burden of stroke (and its risk factors) and stroke services at a national level; the implementation of integrated population-level and individual-level prevention strategies for people at any increased risk of cerebrovascular disease, with emphasis on early detection and control of hypertension; planning and delivery of acute stroke care services, including the establishment of stroke units with access to reperfusion therapies for ischaemic stroke and workforce training and capacity building (and monitoring of quality indicators for these services nationally, regionally, and globally); the promotion of interdisciplinary stroke care services, training for caregivers, and capacity building for community health workers and other health-care providers working in stroke rehabilitation; and the creation of a stroke advocacy and implementation ecosystem that includes all relevant communities, organisations, and stakeholders