Atomistic Studies of Defect Nucleation during Nanoindentation of Au (001)

Atomistic studies are carried out to investigate the formation and evolution of defects during nanoindentation of a gold crystal. The results in this theoretical study complement the experimental investigations [J. D. Kiely and J. E. Houston, Phys. Rev. B, v57, 12588 (1998)] extremely well. The defects are produced by a three step mechanism involving nucleation, glide and reaction of Shockley partials on the {111} slip planes noncoplanar with the indented surface. We have observed that slip is in the directions along which the resolved shear stress has reached the critical value of approximately 2 GPa. The first yield occurs when the shear stresses reach this critical value on all the {111} planes involved in the formation of the defect. The phenomenon of strain hardening is observed due to the sessile stair-rods produced by the zipping of the partials. The dislocation locks produced during the second yield give rise to permanent deformation after retraction.Comment: 11 pages, 13 figures, submitted to Physical Review

Modeling the Subsurface Structure of Sunspots

While sunspots are easily observed at the solar surface, determining their subsurface structure is not trivial. There are two main hypotheses for the subsurface structure of sunspots: the monolithic model and the cluster model. Local helioseismology is the only means by which we can investigate subphotospheric structure. However, as current linear inversion techniques do not yet allow helioseismology to probe the internal structure with sufficient confidence to distinguish between the monolith and cluster models, the development of physically realistic sunspot models are a priority for helioseismologists. This is because they are not only important indicators of the variety of physical effects that may influence helioseismic inferences in active regions, but they also enable detailed assessments of the validity of helioseismic interpretations through numerical forward modeling. In this paper, we provide a critical review of the existing sunspot models and an overview of numerical methods employed to model wave propagation through model sunspots. We then carry out an helioseismic analysis of the sunspot in Active Region 9787 and address the serious inconsistencies uncovered by \citeauthor{gizonetal2009}~(\citeyear{gizonetal2009,gizonetal2009a}). We find that this sunspot is most probably associated with a shallow, positive wave-speed perturbation (unlike the traditional two-layer model) and that travel-time measurements are consistent with a horizontal outflow in the surrounding moat.Comment: 73 pages, 19 figures, accepted by Solar Physic

Lipid Formulations of Amphotericin B and Solid Organ Transplant Recipients with Central Nervous System Cryptococcosis

Immunogenetics and cellular immunology of bacterial infectious disease

Association between body mass index and obesity-related cancer risk in men and women with type 2 diabetes in primary care in the Netherlands: a cohort study (ZODIAC-56)

Contains fulltext : 190345.pdf (publisher's version ) (Open Access)OBJECTIVE: To investigate the relationship between body mass index (BMI) and obesity-related cancers in men and women with type 2 diabetes (T2D). DESIGN: Observational cohort study. SETTING: Primary care. PARTICIPANTS: A total of 52 044 patients with T2D who participated in the ZODIAC (Zwolle Outpatient Diabetes project Integrating Available Care) study between 1998 and 2012 was included (49% women). A dataset of these patients was linked to available information of the Netherlands Cancer Registry to obtain data on cancer incidents. PRIMARY OUTCOME MEASURES: Analyses were performed for the total group of obesity-related cancers and for non-sex-specific and sex-specific obesity-related cancers (in men: advanced prostate cancer, in women: ovarian, endometrial and postmenopausal breast cancer). RESULTS: The median follow-up period in all analyses was 3.1 (1.7-5.0) years in men and 3.1 (1.7-5.1) in women. During follow-up, 689 men and 914 women were diagnosed with an obesity-related cancer. In men, BMI was associated with a higher risk of the total group of obesity-related cancers and non-sex-specific obesity-related cancers (HR (per 5 kg/m(2) increase) 1.12 (95% CI 1.02 to 1.23) and HR 1.18 (95% CI 1.06 to 1.31)). No association was found with prostate cancer. In women, an association between BMI and all obesity-related cancers combined and sex-specific obesity-related cancers was present (HR 1.15 (95% CI 1.08 to 1.22) and HR 1.22 (95% CI 1.14 to 1.32)). No association with non-sex-specific cancers was found in women. CONCLUSIONS: BMI is associated with obesity-related cancers in men with T2D, except with advanced prostate cancer. The results of this study provide reason to reconsider the classification of advanced prostate cancer as an obesity-related cancer, at least in T2D. In women, BMI is associated with the total group of obesity-related cancers and with sex-specific obesity-related cancers

Persistent Coma in Strongyloides Hyperinfection Syndrome Associated With Persistently Increased Ivermectin Levels

Immunogenetics and cellular immunology of bacterial infectious disease

Sex differences in survival of patients with type 2 diabetes in primary care (ZODIAC-50)

OBJECTIVE: To investigate sex differences in survival of primary care treated patients with type 2 diabetes (T2D) in the Netherlands. SETTING: Primary care. PARTICIPANTS: A total of 1815 patients who participated in a prospective observational cohort study (Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC)) were included of which 56% was female. Inclusion took place in 1998, 1999 and 2001. Vital status was assessed in 2013. MAIN OUTCOME MEASURE: Relative survival of men and women with T2D. The relative survival rate was expressed as the ratio of observed survival of patients divided by the survival of the general population in the Netherlands with comparable age. RESULTS: After 14 years, 888 (49%) patients had died. The relative survival rate was 0.88 (0.81-0.94) for men and 0.82 (0.76-0.87) for women with T2D after 14 years (p value for difference between sexes=0.169). In patients without a history of cardiovascular diseases (CVD), the relative survival was 0.99 (0.94-1.05) in men and 0.92 (0.87-0.97) in women (p value for difference between sexes=0.046). CONCLUSIONS: The survival of men and women with T2D was 12% and 18% lower, respectively, after 14 years of follow-up compared with men and women in the general population. This corresponds to a decrease in median survival of 2.2 and 3.5 years in men and women, respectively. Only for patients with T2D without a history of CVD, a significantly lower relative survival in women compared with men with T2D was found

Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis

Item does not contain fulltextAims: Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium. Methods and results: We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1 217 986 participants followed up for a mean of 6.9 years. The average age was 55 +/- 16 years, average eGFR was 83 +/- 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 +/- 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26-1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts. Conclusions: Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria

Olympische Kämpfe, Carl Diem und Otto Peltzer

BackgroundThe usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach.MethodsWe meta-analysed individual-level data for 637?315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4·2–19·0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both.FindingsThe addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0·0139 [95% CI 0·0105–0·0174] for ACR and 0·0065 [0·0042–0·0088] for eGFR) and heart failure (0·0196 [0·0108–0·0284] and 0·0109 [0·0059–0·0159]) than for coronary disease (0·0048 [0·0029–0·0067] and 0·0036 [0·0019–0·0054]) and stroke (0·0105 [0·0058–0·0151] and 0·0036 [0·0004–0·0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0·0227 (0·0158–0·0296) after omission of eGFR and ACR compared with less than 0·007 for any single modifiable traditional predictor.InterpretationCreatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population.FundingUS National Kidney Foundation, National Institute of Diabetes and Digestive and Kidney Diseases