We investigated how landscape features influence gene flow of black bears by testing the relative support for 36 alternative landscape resistance hypotheses, including isolation by distance (IBD) in ...each of 12 study areas in the north central U.S. Rocky Mountains. The study areas all contained the same basic elements, but differed in extent of forest fragmentation, altitude, variation in elevation and road coverage. In all but one of the study areas, isolation by landscape resistance was more supported than IBD suggesting gene flow is likely influenced by elevation, forest cover, and roads. However, the landscape features influencing gene flow varied among study areas. Using subsets of loci usually gave models with the very similar landscape features influencing gene flow as with all loci, suggesting the landscape features influencing gene flow were correctly identified. To test if the cause of the variability of supported landscape features in study areas resulted from landscape differences among study areas, we conducted a limiting factor analysis. We found that features were supported in landscape models only when the features were highly variable. This is perhaps not surprising but suggests an important cautionary note – that if landscape features are not found to influence gene flow, researchers should not automatically conclude that the features are unimportant to the species’ movement and gene flow. Failure to investigate multiple study areas that have a range of variability in landscape features could cause misleading inferences about which landscape features generally limit gene flow. This could lead to potentially erroneous identification of corridors and barriers if models are transferred between areas with different landscape characteristics.
The purpose of the present analysis was to use longitudinal data collected over 7 years (from 4 surveys) in the Residential Environments (RESIDE) Study (Perth, Australia, 2003-2012) to more carefully ...examine the relationship of neighborhood walkability and destination accessibility with walking for transportation that has been seen in many cross-sectional studies. We compared effect estimates from 3 types of logistic regression models: 2 that utilize all available data (a population marginal model and a subject-level mixed model) and a third subject-level conditional model that exclusively uses within-person longitudinal evidence. The results support the evidence that neighborhood walkability (especially land-use mix and street connectivity), local access to public transit stops, and variety in the types of local destinations are important determinants of walking for transportation. The similarity of subject-level effect estimates from logistic mixed models and those from conditional logistic models indicates that there is little or no bias from uncontrolled time-constant residential preference (self-selection) factors; however, confounding by uncontrolled time-varying factors, such as health status, remains a possibility. These findings provide policy makers and urban planners with further evidence that certain features of the built environment may be important in the design of neighborhoods to increase walking for transportation and meet the health needs of residents.
Elucidating genetic causes of cholestasis has proved to be important in understanding the physiology and pathophysiology of the liver. Here we show that protein-truncating mutations in the tight ...junction protein 2 gene (TJP2) cause failure of protein localization and disruption of tight-junction structure, leading to severe cholestatic liver disease. These findings contrast with those in the embryonic-lethal knockout mouse, highlighting differences in redundancy in junctional complexes between organs and species.
The study aimed to identify sources of campylobacter in 10 housed broiler flocks from three United Kingdom poultry companies. Samples from (i) the breeder flocks, which supplied the broilers, (ii) ...cleaned and disinfected houses prior to chick placement, (iii) the chickens, and (iv) the environments inside and outside the broiler houses during rearing were examined. Samples were collected at frequent intervals and examined for Campylobacter spp. Characterization of the isolates using multilocus sequence typing (MLST), serotyping, phage typing, and flaA restriction fragment length polymorphism typing was performed. Seven flocks became colonized during the growing period. Campylobacter spp. were detected in the environment surrounding the broiler house, prior to as well as during flock colonization, for six of these flocks. On two occasions, isolates detected in a puddle just prior to the birds being placed were indistinguishable from those colonizing the birds. Once flocks were colonized, indistinguishable strains of campylobacter were found in the feed and water and in the air of the broiler house. Campylobacter spp. were also detected in the air up to 30 m downstream of the broiler house, which raises the issue of the role of airborne transmission in the spread of campylobacter. At any time during rearing, broiler flocks were colonized by only one or two types determined by MLST but these changed, with some strains superseding others. In conclusion, the study provided strong evidence for the environment as a source of campylobacters colonizing housed broiler flocks. It also demonstrated colonization by successive campylobacter types determined by MLST during the life of a flock.
Acute coronary, cerebrovascular, and peripheral vascular events have common underlying arterial pathology, risk factors, and preventive treatments, but they are rarely studied concurrently. In the ...Oxford Vascular Study, we determined the comparative epidemiology of different acute vascular syndromes, their current burdens, and the potential effect of the ageing population on future rates.
We prospectively assessed all individuals presenting with an acute vascular event of any type in any arterial territory irrespective of age in a population of 91 106 in Oxfordshire, UK, in 2002–05.
2024 acute vascular events occurred in 1657 individuals: 918 (45%) cerebrovascular (618 stroke, 300 transient ischaemic attacks TIA); 856 (42%) coronary vascular (159 ST-elevation myocardial infarction, 316 non-ST-elevation myocardial infarction, 218 unstable angina, 163 sudden cardiac death); 188 (9%) peripheral vascular (43 aortic, 53 embolic visceral or limb ischaemia, 92 critical limb ischaemia); and 62 unclassifiable deaths. Relative incidence of cerebrovascular events compared with coronary events was 1·19 (95% CI 1·06–1·33) overall; 1·40 (1·23–1·59) for non-fatal events; and 1·21 (1·04–1·41) if TIA and unstable angina were further excluded. Event and incidence rates rose steeply with age in all arterial territories, with 735 (80%) cerebrovascular, 623 (73%) coronary, and 147 (78%) peripheral vascular events in 12 886 (14%) individuals aged 65 years or older; and 503 (54%), 402 (47%), and 105 (56%), respectively, in the 5919 (6%) aged 75 years or older. Although case-fatality rates increased with age, 736 (47%) of 1561 non-fatal events occurred at age 75 years or older.
The high rates of acute vascular events outside the coronary arterial territory and the steep rise in event rates with age in all territories have implications for prevention strategies, clinical trial design, and the targeting of funds for service provision and research.
•Pores/carbides in a SX superalloy have been evaluated by sub-μm resolution X-ray CT.•Evaluation of strain localisation in matrix and around pores/carbides using SEM-DIC.•Enhanced strain and denser ...dislocations around pores are captured by SEM-DIC and ECCI.•3D Image-based modelling of stress concentration around pores.•Link 3D features of pores to full field strain distribution to study crack initiation.
Pores and carbides inherited from SX superalloy manufacturing processes usually act as stress concentrators and are preferential sites for fatigue crack initiation. In this study, pore & carbide size, morphology and distribution in a SX superalloy MD2 has been evaluated by X-ray CT. Strain accumulation and fatigue cracking behaviour in MD2, particularly around the pores and carbides, has been investigated by ex-situ SEM-DIC at room temperature along with image-based modelling of the observed MD2 defect populations obtained through X-ray CT imaging. The deformation structures have also been examined by electron channelling contrast imaging under controlled diffraction conditions. The results indicate that the pores & carbides with complicated three-dimensional features are the dominant fatigue crack initiation sites. Deformation is concentrated within intense slip bands and an enhanced strain accumulation around pores is captured by SEM-DIC. Dislocation motion is mainly confined to the γ matrix channels with some dislocation shear cutting of γ′ precipitates also observed ahead of the crack tip. As the crack propagates, strain band density and dislocation density at the crack tip increases correspondingly. Image-based modelling using the observed defect populations in MD2 (micro)structure can effectively predict the stress concentrations and the resultant hot spot for subsequent fatigue crack initiation, which is consistent with the experimental observations.
The incidence of stroke is predicted to rise because of the rapidly ageing population. However, over the past two decades, findings of randomised trials have identified several interventions that are ...effective in prevention of stroke. Reliable data on time-trends in stroke incidence, major risk factors, and use of preventive treatments in an ageing population are required to ascertain whether implementation of preventive strategies can offset the predicted rise in stroke incidence. We aimed to obtain these data.
We ascertained changes in incidence of transient ischaemic attack and stroke, risk factors, and premorbid use of preventive treatments from 1981–84 (Oxford Community Stroke Project; OCSP) to 2002–04 (Oxford Vascular Study; OXVASC).
Of 476 patients with transient ischaemic attacks or strokes in OXVASC, 262 strokes and 93 transient ischaemic attacks were incident events. Despite more complete case-ascertainment than in OCSP, age-adjusted and sex-adjusted incidence of first-ever stroke fell by 29% (relative incidence 0·71, 95% CI 0·61–0·83, p=0·0002). Incidence declined by more than 50% for primary intracerebral haemorrhage (0·47, 0·27–0·83, p=0·01) but was unchanged for subarachnoid haemorrhage (0·83, 0·44–1·57, p=0·57). Thus, although 28% more incident strokes (366 vs 286) were expected in OXVASC due to demographic change alone (33% increase in those aged 75 or older), the observed number fell (262 vs 286). Major reductions were recorded in mortality rates for incident stroke (0.63, 0.44–0.90, p=0.02) and in incidence of disabling or fatal stroke (0·60, 0·50–0·73, p<0·0001), but no change was seen in case-fatality due to incident stroke (17·2% vs 17·8%; age and sex adjusted relative risk 0·85, 95% CI 0·57-1·28, p=0·45). Comparison of premorbid risk factors revealed substantial reductions in the proportion of smokers, mean total cholesterol, and mean systolic and diastolic blood pressures and major increases in premorbid treatment with antiplatelet, lipid-lowering, and blood pressure lowering drugs (all p<0.0001).
The age-specific incidence of major stroke in Oxfordshire has fallen by 40% over the past 20 years in association with increased use of preventive treatments and major reductions in premorbid risk factors.
Background & Aims Progressive familial intrahepatic cholestasis (PFIC) with normal serum levels of gamma-glutamyltranspeptidase can result from mutations in ATP8B1 (encoding familial intrahepatic ...cholestasis 1 FIC1) or ABCB11 (encoding bile salt export pump BSEP). We evaluated clinical and laboratory features of disease in patients diagnosed with PFIC, who carried mutations in ATP8B1 (FIC1 deficiency) or ABCB11 (BSEP deficiency). Our goal was to identify features that distinguish presentation and course of these two disorders, thus facilitating diagnosis and elucidating the differing consequences of ATP8B1 and ABCB11 mutations. Methods A retrospective multi-center study was conducted, using questionnaires and chart review. Available clinical and biochemical data from 145 PFIC patients with mutations in either ATP8B1 (61 “FIC1 patients”) or ABCB11 (84 “BSEP patients”) were evaluated. Results At presentation, serum aminotransferase and bile salt levels were higher in BSEP patients; serum alkaline phosphatase values were higher, and serum albumin values were lower, in FIC1 patients. Elevated white blood cell counts, and giant or multinucleate cells at liver biopsy, were more common in BSEP patients. BSEP patients more often had gallstones and portal hypertension. Diarrhea, pancreatic disease, rickets, pneumonia, abnormal sweat tests, hearing impairment, and poor growth were more common in FIC1 patients. Among BSEP patients, the course of disease was less rapidly progressive in patients bearing the D482G mutation. Conclusions Severe forms of FIC1 and BSEP deficiency differed. BSEP patients manifested more severe hepatobiliary disease, while FIC1 patients showed greater evidence of extrahepatic disease.