Instability driven fragmentation of nanoscale fractal islands

Formation and evolution of fragmentation instabilities in fractal islands, obtained by deposition of silver clusters on graphite, are studied. The fragmentation dynamics and subsequent relaxation to the equilibrium shapes are controlled by the deposition conditions and cluster composition. Sharing common features with other materials' breakup phenomena, the fragmentation instability is governed by the length-to-width ratio of the fractal arms.Comment: 5 pages, 3 figures, Physical Review Letters in pres

Estimation of the Global Prevalence of Dementia in 2019 and Forecasted Prevalence in 2050: An Analysis for the Global Burden of Disease Study 2019

Background Given the projected trends in population ageing and population growth, the number of people with dementia is expected to increase. In addition, strong evidence has emerged supporting the importance of potentially modifiable risk factors for dementia. Characterising the distribution and magnitude of anticipated growth is crucial for public health planning and resource prioritisation. This study aimed to improve on previous forecasts of dementia prevalence by producing country-level estimates and incorporating information on selected risk factors. Methods We forecasted the prevalence of dementia attributable to the three dementia risk factors included in the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 (high body-mass index, high fasting plasma glucose, and smoking) from 2019 to 2050, using relative risks and forecasted risk factor prevalence to predict GBD risk-attributable prevalence in 2050 globally and by world region and country. Using linear regression models with education included as an additional predictor, we then forecasted the prevalence of dementia not attributable to GBD risks. To assess the relative contribution of future trends in GBD risk factors, education, population growth, and population ageing, we did a decomposition analysis. Findings We estimated that the number of people with dementia would increase from 57·4 (95% uncertainty interval 50·4–65·1) million cases globally in 2019 to 152·8 (130·8–175·9) million cases in 2050. Despite large increases in the projected number of people living with dementia, age-standardised both-sex prevalence remained stable between 2019 and 2050 (global percentage change of 0·1% [–7·5 to 10·8]). We estimated that there were more women with dementia than men with dementia globally in 2019 (female-to-male ratio of 1·69 [1·64–1·73]), and we expect this pattern to continue to 2050 (female-to-male ratio of 1·67 [1·52–1·85]). There was geographical heterogeneity in the projected increases across countries and regions, with the smallest percentage changes in the number of projected dementia cases in high-income Asia Pacific (53% [41–67]) and western Europe (74% [58–90]), and the largest in north Africa and the Middle East (367% [329–403]) and eastern sub-Saharan Africa (357% [323–395]). Projected increases in cases could largely be attributed to population growth and population ageing, although their relative importance varied by world region, with population growth contributing most to the increases in sub-Saharan Africa and population ageing contributing most to the increases in east Asia. Interpretation Growth in the number of individuals living with dementia underscores the need for public health planning efforts and policy to address the needs of this group. Country-level estimates can be used to inform national planning efforts and decisions. Multifaceted approaches, including scaling up interventions to address modifiable risk factors and investing in research on biological mechanisms, will be key in addressing the expected increases in the number of individuals affected by dementia

Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung

Population based absolute and relative survival to 1 year of people with diabetes following a myocardial infarction: A cohort study using hospital admissions data

<p>Abstract</p> <p>Background</p> <p>People with diabetes who experience an acute myocardial infarction (AMI) have a higher risk of death and recurrence of AMI. This study was commissioned by the Department for Transport to develop survival tables for people with diabetes following an AMI in order to inform vehicle licensing.</p> <p>Methods</p> <p>A cohort study using data obtained from national hospital admission datasets for England and Wales was carried out selecting all patients attending hospital with an MI for 2003-2006 (inclusion criteria: aged 30+ years, hospital admission for MI (defined using ICD 10 code I21-I22). STATA was used to create survival tables and factors associated with survival were examined using Cox regression.</p> <p>Results</p> <p>Of 157,142 people with an MI in England and Wales between 2003-2006, the relative risk of death or recurrence of MI for those with diabetes (n = 30,407) in the first 90 days was 1.3 (95%CI: 1.26-1.33) crude rates and 1.16 (95%CI: 1.1-1.2) when controlling for age, gender, heart failure and surgery for MI) compared with those without diabetes (n = 129,960). At 91-365 days post AMI the risk was 1.7 (95% CI 1.6-1.8) crude and 1.50 (95%CI: 1.4-1.6) adjusted. The relative risk of death or re-infarction was higher at younger ages for those with diabetes and directly after the AMI (Relative risk; RR: 62.1 for those with diabetes and 28.2 for those without diabetes aged 40-49 [compared with population risk]).</p> <p>Conclusions</p> <p>This is the first study to provide population based tables of age stratified risk of re-infarction or death for people with diabetes compared with those without diabetes. These tables can be used for giving advice to patients, developing a baseline to compare intervention studies or developing license or health insurance guidelines.</p

Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour

Although estimation of serum alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT), the clinical usefulness of this test is limited by a low specificity. However, there exist glycoforms of AFP which may be more specific for particular tumours. Previously, detailed analysis has been prevented by the low levels of AFP in human serum. We report here the application of fluorescence labelling, sequential exoglycosidase digestion, high-performance liquid chromatography and matrix-assisted laser desorption ionization in time-of-flight mass spectrometry, to determine the glycan structures of purified serum AFP from patients with HCC and NSGCT. Eleven major glycans were found, of which seven were N-linked, and four were O-linked, to the protein backbone. The structure of the N-linked glycans (all of bi-antennary complex-type with varying degrees of sialylation, fucosylation and galactosylation) were consistent with those previously reported. The O-linked glycans (three mucin O-GalNAc type glycans with variable degrees of sialylation, one O-HexNAc monosaccharide glycan) have not previously been reported. The finding of mucin O-GalNAc type glycans was supported by the prediction of potential O-GalNAc glycosylation sites on the protein backbone by analysis of the AFP structure by molecular modelling. With knowledge of these structures it may be possible to develop more specific assays for the detection of HCC and NSGCT. © 1999 Cancer Research Campaign © 1999 Cancer Research Campaig

Enhanced external counter pulsation in treatment of refractory angina pectoris: two year outcome and baseline factors associated with treatment failure

<p>Abstract</p> <p>Background</p> <p>Enhanced external counter pulsation (EECP) is a non-invasive treatment option for patients with refractory angina pectoris ineligible to further traditional treatment. The aim of this study was to evaluate the effect of EECP on patients at a Scandinavian medical centre and to investigate if outcome can be predicted by analysing baseline factors.</p> <p>Methods</p> <p>86 consecutive patients (70 male, 16 female) were treated with EECP and followed for two years post treatment. Canadian cardiovascular society (CCS) class was analysed, and medication and adverse clinical events were researched prior to EECP, at the end of the treatment, and at six, 12 and 24 months thereafter. Patients responding to therapy by improving at least one CCS class were compared with those who failed to respond. Any differences in background factors were recorded and analysed.</p> <p>Results</p> <p>79% of the patients responded to therapy by improving at least one CCS class. In general, the CCS class improved by one class after EECP treatment (3.05 before versus 2.14 after treatment). A total of 61.5% of the initial responders showed sustained improvement at the 12 month follow-up while 29% presented sustained improvement after 24 months. Treatment was most effective among patients suffering from CCS class III-IV angina pectoris, while patients suffering from CCS class II angina pectoris improved transiently but failed to show sustained improvement after the 12 month follow-up. Diabetes mellitus and calcium channel antagonists were more common among the non-responders (<it>p </it>< 0.05).</p> <p>Conclusion</p> <p>This study confirms the safety and efficiency of EECP as a treatment option for patients suffering from refractory angina pectoris. The therapy is most beneficial in patients suffering from severe angina (CCS III-IV) while sustained response to therapy could not be verified among patients suffering from CCS class II angina pectoris.</p

Applying Spatial Copula Additive Regression to Breast Cancer Screening Data

Breast cancer is associated with several risk factors. Although genetics is an important breast cancer risk factor, environmental and sociodemographic characteristics, that may differ across populations, are also factors to be taken into account when studying the disease. These factors, apart from having a role as direct agents in the risk of the disease, can also influence other variables that act as risk factors. The age at menarche and the reproductive lifespan are considered by the literature as breast cancer risk factors so that, there are several studies whose aim is to analyze the trend of age at menarche and menopause along generations. Also, it is believed that these two moments in a woman’s life can be affected by environmental, social status, and lifestyles of women. Using the information of 278,282 registries of women which entered in the breast cancer screening program in Central Portugal, we developed a bivariate copula model to quantify the effect a woman’s year of birth in the association between age at menarche and a woman’s reproductive lifespan, in addition to explore any possible effect of the geographic location in these variables and their association. For this analysis we employ Copula Generalized Additive Models for Location, Scale and Shape (CGAMLSS) models and the inference was carried out using the R package SemiParBIVProbit

Importance of heterogeneity in Porhyromonas gingivalis lipopolysaccharide lipid A in tissue specific inflammatory signaling

Lipopolysaccharide (LPS) of Porphyromonas gingivalis exists in at least two known forms, O-LPS and A-LPS. A-LPS shows heterogeneity in which two isoforms designated LPS1435/1449 and LPS1690 appear responsible for tissue specific immune signalingpathways activation and increased virulence. The modification of lipid A to tetra-acylated1435/1449 and/or penta-acylated1690 fatty acids indicates poor growth conditions and bioavailability of hemin. Hemin protects P. gingivalis from serum resistance and the lipid A serves as a site for its binding. The LPS1435/1449 and LPS1690 isoforms can produce opposite effects on the human Toll-like receptors (TLR) TLR 2 and TLR 4 activation. This enabless P. gingivalis to select the conditions for its entry, survival and that of its co-habiting species in the host, orchestrating its virulence to control innate immune pathway activation and biofilm dysbiosis. Thismini review describes a number of effects that LPS1435/1449 and LPS1690 can exert on the host tissues such as deregulation of the innate immune system, subversion of host cell autophagy, regulation of outer membrane vesicle production and adverse effects on pregnancy outcome. The ability to change its LPS1435/1449 and/or LPS1690 composition may enables P. gingivalis to paralyze local pro-inflammatory cytokine production, thereby gaining access to its primary location in periodontal tissue