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[This corrects the article DOI: 10.1016/j.ekir.2018.01.002.].

Background The haemodynamic effects of a functioning haemodialysis arteriovenous fistula (AVF) can cause or exacerbate heart failure (HF). We investigated whether the presence of an AVF at the time of kidney transplant (KT) is associated with de novo HF. Methods This was an observational cohort study including adult patients who received a KT in the West of Scotland between 2010 and 2020. We evaluated the risk and associations of pretransplant factors with de novo HF, alone and as a composite cardiovascular (CV) outcome (including non-fatal myocardial infarction, non-fatal stroke, de novo HF and CV death). Multivariable proportional hazards regression and sensitivity analyses were used to identify independent correlates of the outcomes. Results Among 1330 included patients, the incident rate of de novo HF after transplantation was 58/1000 person-years [95% confidence interval (CI) 50–67] in AVF patients (n  = 716) compared with 33/1000 person-years (95% CI 27–41) in non-AVF patients (n  = 614). De novo HF was associated with the presence of an AVF [adjusted hazard ratio (aHR) 2.14 (95% CI 1.40–3.26)], duration of dialysis [aHR 1.03/year increase (95% CI 1.01–1.04)], age at transplant [aHR 1.03/year increase (95% CI 1.02–1.05)], female sex [aHR 1.93 (95% CI 1.40–2.65)] and pretransplant diabetes [aHR 2.43 (95% CI 1.48–4.01)]. The presence of an AVF was also associated with the composite CV outcome [aHR 1.91 (95% CI 1.31–2.78)]. Conclusions The presence of an AVF may be an underrecognized modifiable predictor of de novo HF posttransplantation. [ABSTRACT FROM AUTHOR]

Background Lymphocyte ratios reflect inflammation and have been associated with adverse outcomes in a range of diseases. We sought to determine any association between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and mortality in a haemodialysis cohort, including a coronavirus disease 2019 (COVID-19) infection subpopulation. Methods A retrospective analysis was performed of adults commencing hospital haemodialysis in the West of Scotland during 2010–21. NLR and PLR were calculated from routine samples around haemodialysis initiation. Kaplan–Meier and Cox proportional hazards analyses were used to assess mortality associations. Results In 1720 haemodialysis patients over a median of 21.9 (interquartile range 9.1–42.9) months, there were 840 all-cause deaths. NLR but not PLR was associated with all-cause mortality after multivariable adjustment [adjusted hazard ratio (aHR) for in participants with baseline NLR in quartile 4 (NLR ≥8.23) versus quartile 1 (NLR <3.12) 1.63, 95% confidence interval (CI) 1.32–2.00]. The association was stronger for cardiovascular death (NLR quartile 4 versus 1 aHR 3.06, 95% CI 1.53–6.09) than for non-cardiovascular death (NLR quartile 4 versus 1 aHR 1.85, 95% CI 1.34–2.56). In the COVID-19 subpopulation, both NLR and PLR at haemodialysis initiation were associated with risk of COVID-19-related death after adjustment for age and sex (NLR: aHR 4.69, 95% CI 1.48–14.92 and PLR: aHR 3.40, 95% CI 1.02–11.36; for highest vs lowest quartiles). Conclusions NLR is strongly associated with mortality in haemodialysis patients while the association between PLR and adverse outcomes is weaker. NLR is an inexpensive, readily available biomarker with potential utility in risk stratification of haemodialysis patients. [ABSTRACT FROM AUTHOR]

Abstract We analysed linkage disequilibrium (LD) in Australian Holstein-Friesian cattle by genotyping a sample of 45 bulls for 15 closely-spaced microsatellites on two regions of BTA6 reported to carry important QTL for dairy traits. The order and distance of markers were based on the USDA-MARC linkage map. Frequencies of haplotypes were estimated using the E-M approach and a more computationally-intensive Bayesian approach as implemented in PHASE. LD was then estimated using the Hedrick multiallelic extension of Lewontin normalised coefficient D'. Estimates of D' from the two approaches were in close agreement (r = 0.91). The mean estimates of D' for marker pairs with an inter-marker distance of less than 5 cM (n = 13) are 0.57 and 0.51, and for distances more than 20 cM (n = 44) are 0.29 and 0.17, estimated from the E-M and Bayesian approaches, respectively. The Malecot model was fitted for the exponential decline of LD with map distance between markers. The swept radii (the distance at which LD has declined to 1/e (~37%) of its initial value) are 11.6 and 13.7 cM for the above two methods, respectively. The Malecot model was also fitted using map distance in Mb from the bovine integrated map (bovine location database, bLDB) in addition to cM from the MARC map. Overall, the results indicate a high level of LD on chromosome 6 in Australian dairy cattle.

Abstract From an extensive review of public domain information on dairy cattle quantitative trait loci (QTL), we have prepared a draft online QTL map for dairy production traits. Most publications (45 out of 55 reviewed) reported QTL for the major milk production traits (milk, fat and protein yield, and fat and protein concentration (%)) and somatic cell score. Relatively few QTL studies have been reported for more complex traits such as mastitis, fertility and health. The collated QTL map shows some chromosomal regions with a high density of QTL, as well as a substantial number of QTL at single chromosomal locations. To extract the most information from these published records, a meta-analysis was conducted to obtain consensus on QTL location and allelic substitution effect of these QTL. This required modification and development of statistical methodologies. The meta-analysis indicated a number of consensus regions, the most striking being two distinct regions affecting milk yield on chromosome 6 at 49 cM and 87 cM explaining 4.2 and 3.6 percent of the genetic variance of milk yield, respectively. The first of these regions (near marker BM143) affects five separate milk production traits (protein yield, protein percent, fat yield, fat percent, as well as milk yield).

Abstract To date, most statistical developments in QTL detection methodology have been directed at continuous traits with an underlying normal distribution. This paper presents a method for QTL analysis of non-normal traits using a generalized linear mixed model approach. Development of this method has been motivated by a backcross experiment involving two inbred lines of mice that was conducted in order to locate a QTL for litter size. A Poisson regression form is used to model litter size, with allowances made for under- as well as over-dispersion, as suggested by the experimental data. In addition to fixed parity effects, random animal effects have also been included in the model. However, the method is not fully parametric as the model is specified only in terms of means, variances and covariances, and not as a full probability model. Consequently, a generalized estimating equations (GEE) approach is used to fit the model. For statistical inferences, permutation tests and bootstrap procedures are used. This method is illustrated with simulated as well as experimental mouse data. Overall, the method is found to be quite reliable, and with modification, can be used for QTL detection for a range of other non-normally distributed traits.

Analysis of data on 1000 Holstein-Friesian bulls genotyped for 15,036 single-nucleotide polymorphisms (SNPs) has enabled genomewide identification of haplotype blocks and tag SNPs. A final subset of 9195 SNPs in Hardy-Weinberg equilibrium and mapped on autosomes on the bovine sequence assembly (release Btau 3.1) was used in this study. The average intermarker spacing was 251.8 kb. The average minor allele frequency (MAF) was 0.29 (0.05-0.5). Following recent precedents in human HapMap studies, a haplotype block was defined where 95% of combinations of SNPs within a region are in very high linkage disequilibrium. A total of 727 haplotype blocks consisting of [greater than or equal to] 3 SNPs were identified. The average block length was 69.7 [+ or -] 7.7 kb, which is ~5-10 times larger than in humans. These blocks comprised a total of 2964 SNPs and covered 50,638 kb of the sequence map, which constitutes 2.18% of the length of all autosomes. A set of tag SNPs, which will be useful for further fine-mapping studies, has been identified. Overall, the results suggest that as many as 75,000-100,000 tag SNPs would be needed to track all important haplotype blocks in the bovine genome. This would require ~250,000 SNPs in the discovery phase.

We constructed a metric linkage disequilibrium (LD) map of bovine chromosome 6 (BTA6) on the basis of data from 220 SNPs genotyped on 433 Australian dairy bulls. This metric LD map has distances in LD units (LDUs) that are analogous to centimorgans in linkage maps. The LD map of BTA6 has a total length of 8.9 LDUs. Within the LD map, regions of high LD (represented as blocks) and regions of low LD (steps) are observed, when plotted against the integrated map in kilobases. At the most stringent block definition, namely a set of loci with zero LDU increase over the span of these markers, BTA6 comprises 40 blocks, accounting for 41% of the chromosome. At a slightly lower stringency of block definition (a set of loci covering a maximum of 0.2 LDUs on the LD map), up to 81% of BTA6 is spanned by 46 blocks and with 13 steps that are likely to reflect recombination hot spots. The mean swept radius (the distance over which LD is likely to be useful for mapping) is 13.3 Mb, confirming extensive LD in Holstein--Friesian dairy cattle, which makes such populations ideal for whole-genome association studies.

Breast cancer is a leading cause of death in women. The objective of the present study was to evaluate diagnostic utility of HER2/neu test and the association of premature termination of pregnancy with breast cancer. Two hundred breast cancer patients from INMOL hospital, Lahore (Pakistan) were interviewed on reproductive factors. HER2/neu levels were determined by ELISA from 52 patients and 37 age-matched control women. The results of survey study showed that “premature termination of pregnancy” emerges as a potential risk factor of breast cancer. Number of pregnancies has significant association with premature termination of pregnancies (P = 6 × 10–11). The regression coefficient for number of pregnancies is 0.220 ± 0.029= 1.25× i.e. a 25% increase for each additional pregnancy. There is a significant positive association between premature termination of pregnancies and number of children (P = 0.024): the regression coefficient is 0.108±0.048=1.11× i.e. 11% increase for each additional child. The analysis of Her2/neu showed that its levels were higher in younger patients (≤ 42 years) than in older patients (0.884 vs 0.614 units, P= 0.049). The ROC curve indicated that the optimal test (maximum Se + Sp) occurred at HER-2 Neu values of = 0.615, where Se= 0.73 and Sp= 0.49. The AUC value for this test was 0.57, with 1 being a perfect test, and 0.5 being equivalent to random allocation. In brief, premature termination of pregnancy/ miscarriage is a potential risk factor and HER2/neu cannot be used as a suitable diagnostic test. [ABSTRACT FROM AUTHOR]