So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Guidelines summarize and evaluate available evidence with the aim of assisting health professionals in proposing the best management strategies for an individual patient with a given condition. Guidelines and their recommendations should facilitate decision making of health professionals in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.

/pdf/2019-esc-guidelines-for-the-diagnosis-and-management-of-4aacwvv1mo.pdf

2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European respiratory society (ERS)

Early goal-directed therapy in the treatment of severe sepsis and septic shock

The global endemic of cardiovascular diseases calls for improved risk assessment and treatment. Here, we describe an association between myocardial infarction (MI) and a common sequence variant on chromosome 9p21. This study included a total of 4587 cases and 12,767 controls. The identified variant, adjacent to the tumor suppressor genes CDKN2A and CDKN2B, was associated with the disease with high significance. Approximately 21% of individuals in the population are homozygous for this variant, and their estimated risk of suffering myocardial infarction is 1.64 times as great as that of noncarriers. The corresponding risk is 2.02 times as great for early-onset cases. The population attributable risk is 21% for MI in general and 31% for early-onset cases.

https://science.sciencemag.org/content/sci/316/5830/1491.full.pdf

A Common Variant on Chromosome 9p21 Affects the Risk of Myocardial Infarction

. Zdravkovic S, Wienke A, Pedersen NL,Marenberg ME, Yashin AI, de Faire U (KarolinskaInstitutet, Stockholm, Sweden; Max-Planck Institutefor Demographic Research, Rostock, Germany;University of Pennsylvania School of Medicine,Philadelphia, PA, USA). Heritability of death fromcoronary heart disease: a 36-year follow-up of20 966 Swedish twins. J Intern Med 2002; 252:247–254.Objective. The aim of the present study was toevaluate and distinguish between environmentaland genetic effects for death from coronary heartdisease (CHD) as well as to determine whether theimportance of genetic inﬂuences is changing withage.Design. A cohort study with a follow-up time of36 years.Subjects. The cohort drawn for the present studyincludes 20 966 twins born in Sweden between1886 and 1925 where both twins within a pair stilllived within the country in 1961.Methods. Concordances and correlated c-frailtymodel were used to assess and distinguish betweengenetic and environmental inﬂuences as well as toevaluate age-related changes in genetic inﬂuences.Results. A total number of 4007 CHD-deaths (2208males, and 1799 females) was observed. The prob-ability of dying from CHD given that one’s twinpartner already has died from CHD decreased withincreasing age, particularly amongst males. Thegenetic variation in susceptibility to death from CHDwas moderately large, and decreased slightly acrosstime, particularly amongst males. The heritabilitywas 0.57 (95% CI, 0.45–0.69) amongst male twins,and 0.38 (0.26–0.50) amongst female twins.Conclusions. The genetic contribution to the vari-ation in CHD-mortality was moderate both infemales and males. Furthermore, although geneticeffects appeared to be greater at younger ages ofdeath, our ﬁndings clearly suggest that genetic fac-tors are in operation throughout the entire life span.Keywords: concordance, Coronary heart disease,frailty, heritability, twinsAbbreviations: CHD, coronary heart disease; AIC,Akaike information criterion.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2796.2002.01029.x

Heritability of death from coronary heart disease: a 36‐year follow‐up of 20 966 Swedish twins

Introduction Goals and outline Examples Survival Analysis Basic concepts in survival analysis Censoring and truncation Parametric models Estimation of survival and hazard functions Regression models Identifiability problems Univariate Frailty Models The concept of univariate frailty Discrete frailty model Gamma frailty model Log-normal frailty model Inverse Gaussian frailty model Positive stable frailty model PVF frailty model Compound Poisson frailty model Quadratic hazard frailty model Levy-type frailty models Log-t frailty model Univariate frailty cure models Missing covariates in proportional hazard models Shared Frailty Models Marginal versus frailty model The concept of shared frailty Shared gamma frailty model Shared log-normal frailty model Shared positive stable frailty model Shared compound Poisson/PVF frailty model Shared frailty models more general Dependence measures Limitations of the shared frailty model Correlated Frailty Models The concept of correlated frailty Correlated gamma frailty model Correlated log-normal frailty model MCMC methods for the correlated log-normal frailty model Correlated compound Poisson frailty model Correlated quadratic hazard frailty model Other correlated frailty models Bivariate frailty cure models Comparison of different estimation strategies Dependent competing risks in frailty models Copula Models Shared gamma frailty copula Correlated gamma frailty copula General correlated frailty copula Cross-ratio function Different Aspects of Frailty Modeling Dependence and interaction between frailty and observed covariates Cox model with general Gaussian random effects Nested frailty models Recurrent event time data Tests for heterogeneity Log-rank test in frailty models Time-dependent frailty models Identifiability of frailty models Applications of frailty models Software for frailty models Appendix References Index

/pdf/frailty-models-in-survival-analysis-260ntqn9sj.pdf

Frailty Models in Survival Analysis

// Alexey Surov 1, * , Hans Jonas Meyer 1, * and Andreas Wienke 2, * 1 Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany 2 Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany * All authors contributed equally for this work Correspondence to: Alexey Surov, email: Alexey.Surov@medizin.uni-leipzig.de Keywords: DWI, MRI, ADC, cellularity, tumor Received: March 31, 2017      Accepted: April 27, 2017      Published: May 10, 2017 ABSTRACT The purpose of this meta-analysis was to provide clinical evidence regarding relationship between ADC and cellularity in different tumors based on large patient data. Medline library was screened for associations between ADC and cell count in different tumors up to September 2016. Only publications in English were extracted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) was used for the research. Overall, 39 publications with 1530 patients were included into the analysis. The following data were extracted from the literature: authors, year of publication, number of patients, tumor type, and correlation coefficients. The pooled correlation coefficient for all studies was ρ = -0.56 (95 % CI = [−0.62; −0.50]),. Correlation coefficients ranged from ρ =−0.25 (95 % CI = [−0.63; 0.12]) in lymphoma to ρ=−0.66 (95 % CI = [−0.85; −0.47]) in glioma. Other coefficients were as follows: ovarian cancer, ρ = −0.64 (95% CI = [−0.76; −0.52]); lung cancer, ρ = −0.63 (95 % CI = [−0.78; −0.48]); uterine cervical cancer, ρ = −0.57 (95 % CI = [−0.80; −0.34]); prostatic cancer, ρ = −0.56 (95 % CI = [−0.69; −0.42]); renal cell carcinoma, ρ = −0.53 (95 % CI = [−0.93; −0.13]); head and neck squamous cell carcinoma, ρ = −0.53 (95 % CI = [-0.74; −0.32]); breast cancer, ρ = −0.48 (95 % CI = [−0.74; −0.23]); and meningioma, ρ = -0.45 (95 % CI = [−0.73; −0.17]).

/pdf/correlation-between-apparent-diffusion-coefficient-adc-and-2wl1ljfpss.pdf

Correlation between apparent diffusion coefficient (ADC) and cellularity is different in several tumors: a meta-analysis.

Background: Intravascular embolization of device fragments is a rare but potentially serious complication Method: A systematic search of the PubMed and MEDLINE databases for all articles pertaining to central catheter related embolization published in English between 1985 and 2007 was made Results: A total of 215 cases of intravenous catheter embolization were identified There were 143 totally implanted venous devices (TIVD) or port catheters and 72 percutaneous venous catheters (PVC) Sites of catheter fragments following embolization were the superior vena cava or peripheral veins (154%), the right atrium (276%), right ventricle (22%), and pulmonary arteries (35%) Clinical signs of catheter embolization included catheter malfunction (563%), arrhythmia (13%), pulmonary symptoms (47%), and septic syndromes (18%), but 242% of cases were asymptomatic The causes of intravascular catheter embolization were pinch-off syndrome (409%), catheter injury during explantation (177%), catheter disconnecti

Intravascular Embolization of Venous Catheter—Causes, Clinical Signs, and Management: A Systematic Review

Objectives: The purpose of this study was to determine the prevalence, clinical signs and radiological features of breast lymphoma. Methods: This is a retrospective review of 36 patients with breast lymphoma (22 primary and14secondary).35 patientswere femaleand1 wasmale; theirmedian agewas65years (range 24–88 years). In all patients, the diagnosis was confirmed histopathologically. Results: The prevalence of breast lymphoma was 1.6% of all identified cases with non-Hodgkin lymphoma and 0.5% of cases with breast cancer. B-cell lymphoma was found in 94% and T-cell lymphoma in 6%. 96 lesions were identified (2.7 per patient). The mean size was 15.8i8.3mm. The number of intramammary lesions was higher in secondary than in primary lymphoma. The size of the identified intramammary lesions was larger in primary than in secondary lymphoma. Clinically, 86% of the patients presented with solitary or multiple breast lumps. In 14%, breast involvement was diagnosed incidentally during staging examinations. Conclusion: On mammography, intramammary masses were the most commonly seen (27 patients, 82%). Architectural distortion occurred in three patients (9%). In three patients (9%), no abnormalities were found on mammography. On ultrasound, the identified lesions were homogeneously hypoechoic or heterogeneously mixed hypo- to hyperechoic. On MRI, the morphology of the lesions was variable. After intravenous administration of contrast medium, a marked inhomogeneous contrast enhancement was seen in most cases. On CT, most lesions presented as circumscribed round or oval masses with moderate or high enhancement.

https://www.birpublications.org/doi/pdfplus/10.1259/bjr/78413721

Andreas Wienke

Papers

Heritability of death from coronary heart disease: a 36‐year follow‐up of 20 966 Swedish twins

Frailty Models in Survival Analysis

Correlation between apparent diffusion coefficient (ADC) and cellularity is different in several tumors: a meta-analysis.

Intravascular Embolization of Venous Catheter—Causes, Clinical Signs, and Management: A Systematic Review

Primary and secondary breast lymphoma: prevalence, clinical signs and radiological features.