A structural variant at ASIP associated with the darkness of hair coat is found in multiple zebu cattle populations.

A structural variant (SV) in the agouti signaling protein gene (ASIP), namely ASIP-SV1, has been found to strongly correlate with the darkness of hair coat in specific regions of the body of bulls from the zebu (Bos indicus) Nellore breed. Here we visually analyzed the whole-genome sequence of zebu and taurine (Bos taurus) cattle to elucidate the extent of spread of ASIP-SV1 in different cattle populations. Of 216 sequences analyzed, 63 zebu (45.9%) and five taurine (6.3%) animals had at least one copy of ASIP-SV1. Four of the taurine animals presenting the SV were Romagnola cattle, a breed with history of zebu introgression. The remaining taurine animal was a Simmental, a breed frequently used in crossbreeding. These data provide evidence that ASIP-SV1 is commonly found in zebu populations, in addition to taurine animals with zebu admixture.

Genomic predictions combining SNP markers and copy number variations in Nellore cattle.

BACKGROUND: Due to the advancement in high throughput technology, single nucleotide polymorphism (SNP) is routinely being incorporated along with phenotypic information into genetic evaluation. However, this approach often cannot achieve high accuracy for some complex traits. It is possible that SNP markers are not sufficient to predict these traits due to the missing heritability caused by other genetic variations such as microsatellite and copy number variation (CNV), which have been shown to affect disease and complex traits in humans and other species. RESULTS: In this study, CNVs were included in a SNP based genomic selection framework. A Nellore cattle dataset consisting of 2230 animals genotyped on BovineHD SNP array was used, and 9 weight and carcass traits were analyzed. A total of six models were implemented and compared based on their prediction accuracy. For comparison, three models including only SNPs were implemented: 1) BayesA model, 2) Bayesian mixture model (BayesB), and 3) a GBLUP model without polygenic effects. The other three models incorporating both SNP and CNV included 4) a Bayesian model similar to BayesA (BayesA+CNV), 5) a Bayesian mixture model (BayesB+CNV), and 6) GBLUP with CNVs modeled as a covariable (GBLUP+CNV). Prediction accuracies were assessed based on Pearson's correlation between de-regressed EBVs (dEBVs) and direct genomic values (DGVs) in the validation dataset. For BayesA, BayesB and GBLUP, accuracy ranged from 0.12 to 0.62 across the nine traits. A minimal increase in prediction accuracy for some traits was noticed when including CNVs in the model (BayesA+CNV, BayesB+CNV, GBLUP+CNV). CONCLUSIONS: This study presents the first genomic prediction study integrating CNVs and SNPs in livestock. Combining CNV and SNP marker information proved to be beneficial for genomic prediction of some traits in Nellore cattle.

Twenty-year follow-up of a familial case of PTH1R-associated primary failure of tooth eruption.

INTRODUCTION: Nonsyndromic primary failure of eruption (PFE) is a rare autosomal dominant disorder of dental eruption with no obvious dental or soft tissue interference. The purposes of this study were to genetically and clinically characterize a family with many members affected by PFE and to describe the natural evolution of the disorder. METHODS: Three generations of a family with 18 members, 10 of them clinically affected by PFE, were evaluated periodically during 20 years of clinical follow-up. PFE was observed in varying degrees of severity in both sexes. Clinical presentation became more severe in adulthood. One patient had spontaneous reeruption of 2 posterior teeth. Cervical root resorptions were observed in 3 members. Genetic analysis showed a deleterious heterozygous mutation in intron 9 of the PTH1R gene (c.639-2A>G) and diagnosed an additional affected member. CONCLUSIONS: The long-term follow-up of PFE cases in this family permitted the following observations: (1) the onset occurred from the preemergence to the postemergence phases, (2) PFE appeared to be closely related to ankylosis, (3) affected teeth maintained the eruptive potential even in adulthood, (4) the earlier the onset the more severe the open bite, and (5) cervical root resorptions occurred in 3 affected members.

Genome-wide CNV analysis reveals variants associated with growth traits in Bos indicus.

BACKGROUND: Apart from single nucleotide polymorphism (SNP), copy number variation (CNV) is another important type of genetic variation, which may affect growth traits and play key roles for the production of beef cattle. To date, no genome-wide association study (GWAS) for CNV and body traits in beef cattle has been reported, so the present study aimed to investigate this type of association in one of the most important cattle subspecies: Bos indicus (Nellore breed). RESULTS: We have used intensity data from over 700,000 SNP probes across the bovine genome to detect common CNVs in a sample of 2230 Nellore cattle, and performed GWAS between the detected CNVs and nine growth traits. After filtering for frequency and length, a total of 231 CNVs ranging from 894 bp to 4,855,088 bp were kept and tested as predictors for each growth trait using linear regression analysis with principal components correction. There were 49 significant associations identified among 17 CNVs and seven body traits after false discovery rate correction (P < 0.05). Among the 17 CNVs, three were significant or marginally significant for all the traits. We have compared the locations of associated CNVs with quantitative trait locus and the RefGene database, and found two sets of 9 CNVs overlapping with either known QTLs or genes, respectively. The gene overlapping with CNV100, KCNJ12, is a functional candidate for muscle development and plays critical roles in muscling traits. CONCLUSION: This study presents the first CNV-based GWAS of growth traits using high density SNP microarray data in cattle. We detected 17 CNVs significantly associated with seven growth traits and one of them (CNV100) may be involved in growth traits through KCNJ12.

Copy number variation of individual cattle genomes using next-generation sequencing.

Copy number variations (CNVs) affect a wide range of phenotypic traits; however, CNVs in or near segmental duplication regions are often intractable. Using a read depth approach based on next-generation sequencing, we examined genome-wide copy number differences among five taurine (three Angus, one Holstein, and one Hereford) and one indicine (Nelore) cattle. Within mapped chromosomal sequence, we identified 1265 CNV regions comprising ~55.6-Mbp sequence--476 of which (~38%) have not previously been reported. We validated this sequence-based CNV call set with array comparative genomic hybridization (aCGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH), achieving a validation rate of 82% and a false positive rate of 8%. We further estimated absolute copy numbers for genomic segments and annotated genes in each individual. Surveys of the top 25 most variable genes revealed that the Nelore individual had the lowest copy numbers in 13 cases (~52%, χ(2) test; P-value <0.05). In contrast, genes related to pathogen- and parasite-resistance, such as CATHL4 and ULBP17, were highly duplicated in the Nelore individual relative to the taurine cattle, while genes involved in lipid transport and metabolism, including APOL3 and FABP2, were highly duplicated in the beef breeds. These CNV regions also harbor genes like BPIFA2A (BSP30A) and WC1, suggesting that some CNVs may be associated with breed-specific differences in adaptation, health, and production traits. By providing the first individualized cattle CNV and segmental duplication maps and genome-wide gene copy number estimates, we enable future CNV studies into highly duplicated regions in the cattle genome.

Evidence of Bos javanicus x Bos indicus hybridization and major QTLs for birth weight in Indonesian Peranakan Ongole cattle.

BACKGROUND: Peranakan Ongole (PO) is a major Indonesian Bos indicus breed that derives from animals imported from India in the late 19(th) century. Early imports were followed by hybridization with the Bos javanicus subspecies of cattle. Here, we used genomic data to partition the ancestry components of PO cattle and map loci implicated in birth weight. RESULTS: We found that B. javanicus contributes about 6-7% to the average breed composition of PO cattle. Only two nearly fixed B. javanicus haplotypes were identified, suggesting that most of the B. javanicus variants are segregating under drift or by the action of balancing selection. The zebu component of the PO genome was estimated to derive from at least two distinct ancestral pools. Additionally, well-known loci underlying body size in other beef cattle breeds, such as the PLAG1 region on chromosome 14, were found to also affect birth weight in PO cattle. CONCLUSIONS: This study is the first attempt to characterize PO at the genome level, and contributes evidence of successful, stabilized B. indicus x B. javanicus hybridization. Additionally, previously described loci implicated in body size in worldwide beef cattle breeds also affect birth weight in PO cattle.

Revisiting AFLP fingerprinting for an unbiased assessment of genetic structure and differentiation of taurine and zebu cattle.

BACKGROUND: Descendants from the extinct aurochs (Bos primigenius), taurine (Bos taurus) and zebu cattle (Bos indicus) were domesticated 10,000 years ago in Southwestern and Southern Asia, respectively, and colonized the world undergoing complex events of admixture and selection. Molecular data, in particular genome-wide single nucleotide polymorphism (SNP) markers, can complement historic and archaeological records to elucidate these past events. However, SNP ascertainment in cattle has been optimized for taurine breeds, imposing limitations to the study of diversity in zebu cattle. As amplified fragment length polymorphism (AFLP) markers are discovered and genotyped as the samples are assayed, this type of marker is free of ascertainment bias. In order to obtain unbiased assessments of genetic differentiation and structure in taurine and zebu cattle, we analyzed a dataset of 135 AFLP markers in 1,593 samples from 13 zebu and 58 taurine breeds, representing nine continental areas. RESULTS: We found a geographical pattern of expected heterozygosity in European taurine breeds decreasing with the distance from the domestication centre, arguing against a large-scale introgression from European or African aurochs. Zebu cattle were found to be at least as diverse as taurine cattle. Western African zebu cattle were found to have diverged more from Indian zebu than South American zebu. Model-based clustering and ancestry informative markers analyses suggested that this is due to taurine introgression. Although a large part of South American zebu cattle also descend from taurine cows, we did not detect significant levels of taurine ancestry in these breeds, probably because of systematic backcrossing with zebu bulls. Furthermore, limited zebu introgression was found in Podolian taurine breeds in Italy. CONCLUSIONS: The assessment of cattle diversity reported here contributes an unbiased global view to genetic differentiation and structure of taurine and zebu cattle populations, which is essential for an effective conservation of the bovine genetic resources.

Assessing signatures of selection through variation in linkage disequilibrium between taurine and indicine cattle.

BACKGROUND: Signatures of selection are regions in the genome that have been preferentially increased in frequency and fixed in a population because of their functional importance in specific processes. These regions can be detected because of their lower genetic variability and specific regional linkage disequilibrium (LD) patterns. METHODS: By comparing the differences in regional LD variation between dairy and beef cattle types, and between indicine and taurine subspecies, we aim at finding signatures of selection for production and adaptation in cattle breeds. The VarLD method was applied to compare the LD variation in the autosomal genome between breeds, including Angus and Brown Swiss, representing taurine breeds, and Nelore and Gir, representing indicine breeds. Genomic regions containing the top 0.01 and 0.1 percentile of signals were characterized using the UMD3.1 Bos taurus genome assembly to identify genes in those regions and compared with previously reported selection signatures and regions with copy number variation. RESULTS: For all comparisons, the top 0.01 and 0.1 percentile included 26 and 165 signals and 17 and 125 genes, respectively, including TECRL, BT.23182 or FPPS, CAST, MYOM1, UVRAG and DNAJA1. CONCLUSIONS: The VarLD method is a powerful tool to identify differences in linkage disequilibrium between cattle populations and putative signatures of selection with potential adaptive and productive importance.

Accuracy of genotype imputation in Nelore cattle.

BACKGROUND: Genotype imputation from low-density (LD) to high-density single nucleotide polymorphism (SNP) chips is an important step before applying genomic selection, since denser chips tend to provide more reliable genomic predictions. Imputation methods rely partially on linkage disequilibrium between markers to infer unobserved genotypes. Bos indicus cattle (e.g. Nelore breed) are characterized, in general, by lower levels of linkage disequilibrium between genetic markers at short distances, compared to taurine breeds. Thus, it is important to evaluate the accuracy of imputation to better define which imputation method and chip are most appropriate for genomic applications in indicine breeds. METHODS: Accuracy of genotype imputation in Nelore cattle was evaluated using different LD chips, imputation software and sets of animals. Twelve commercial and customized LD chips with densities ranging from 7 K to 75 K were tested. Customized LD chips were virtually designed taking into account minor allele frequency, linkage disequilibrium and distance between markers. Software programs FImpute and BEAGLE were applied to impute genotypes. From 995 bulls and 1247 cows that were genotyped with the Illumina® BovineHD chip (HD), 793 sires composed the reference set, and the remaining 202 younger sires and all the cows composed two separate validation sets for which genotypes were masked except for the SNPs of the LD chip that were to be tested. RESULTS: Imputation accuracy increased with the SNP density of the LD chip. However, the gain in accuracy with LD chips with more than 15 K SNPs was relatively small because accuracy was already high at this density. Commercial and customized LD chips with equivalent densities presented similar results. FImpute outperformed BEAGLE for all LD chips and validation sets. Regardless of the imputation software used, accuracy tended to increase as the relatedness between imputed and reference animals increased, especially for the 7 K chip. CONCLUSIONS: If the Illumina® BovineHD is considered as the target chip for genomic applications in the Nelore breed, cost-effectiveness can be improved by genotyping part of the animals with a chip containing around 15 K useful SNPs and imputing their high-density missing genotypes with FImpute.

Investigation of the genetic diversity of domestic Capra hircus breeds reared within an early goat domestication area in Iran.

BACKGROUND: Iran is an area of particular interest for investigating goat diversity. Archaeological remains indicate early goat domestication (about 10,000 years ago) in the Iranian Zagros Mountains as well as in the high Euphrates valley and southeastern Anatolia. In addition, mitochondrial DNA data of domestic goats and wild ancestors (C. aegagrusor bezoar) suggest a pre-domestication management of wild populations in southern Zagros and central Iranian Plateau. In this study genetic diversity was assessed in seven Iranian native goat breeds, namely Markhoz, Najdi, Taleshi, Khalkhali, Naini, native Abadeh and Turki-Ghashghaei. A total of 317 animals were characterized using 14 microsatellite loci. Two Pakistani goat populations, Pahari and Teddy, were genotyped for comparison. RESULTS: Iranian goats possess a remarkable genetic diversity (average expected heterozygosity of 0.671 across loci, 10.7 alleles per locus) mainly accounted for by the within-breed component (GST = 5.9%). Positive and highly significant FIS values in the Naini, Turki-Ghashghaei, Abadeh and Markhoz breeds indicate some level of inbreeding in these populations. Multivariate analyses cluster Iranian goats into northern, central and western groups, with the western breeds relatively distinct from the others. Pakistani breeds show some relationship with Iranian populations, even if their position is not consistent across analyses. Gene flow was higher within regions (west, north, central) compared to between regions but particularly low between the western and the other two regions, probably due to the isolating topography of the Zagros mountain range. The Turki-Ghashghaei, Najdi and Abadeh breeds are reared in geographic areas where mtDNA provided evidence of early domestication. These breeds are highly variable, located on basal short branches in the neighbor-joining tree, close to the origin of the principal component analysis plot and, although highly admixed, they are quite distinct from those reared on the western side of the Zagros mountain range. CONCLUSIONS: These observations call for further investigation of the nuclear DNA diversity of these breeds within a much wider geographic context to confirm or re-discuss the current hypothesis (based on maternal lineage data) of an almost exclusive contribution of the eastern Anatolian bezoar to the domestic goat gene pool.

Accuracy of genomic predictions in Bos indicus (Nellore) cattle.

BACKGROUND: Nellore cattle play an important role in beef production in tropical systems and there is great interest in determining if genomic selection can contribute to accelerate genetic improvement of production and fertility in this breed. We present the first results of the implementation of genomic prediction in a Bos indicus (Nellore) population. METHODS: Influential bulls were genotyped with the Illumina Bovine HD chip in order to assess genomic predictive ability for weight and carcass traits, gestation length, scrotal circumference and two selection indices. 685 samples and 320 238 single nucleotide polymorphisms (SNPs) were used in the analyses. A forward-prediction scheme was adopted to predict the genomic breeding values (DGV). In the training step, the estimated breeding values (EBV) of bulls were deregressed (dEBV) and used as pseudo-phenotypes to estimate marker effects using four methods: genomic BLUP with or without a residual polygenic effect (GBLUP20 and GBLUP0, respectively), a mixture model (Bayes C) and Bayesian LASSO (BLASSO). Empirical accuracies of the resulting genomic predictions were assessed based on the correlation between DGV and dEBV for the testing group. RESULTS: Accuracies of genomic predictions ranged from 0.17 (navel at weaning) to 0.74 (finishing precocity). Across traits, Bayesian regression models (Bayes C and BLASSO) were more accurate than GBLUP. The average empirical accuracies were 0.39 (GBLUP0), 0.40 (GBLUP20) and 0.44 (Bayes C and BLASSO). Bayes C and BLASSO tended to produce deflated predictions (i.e. slope of the regression of dEBV on DGV greater than 1). Further analyses suggested that higher-than-expected accuracies were observed for traits for which EBV means differed significantly between two breeding subgroups that were identified in a principal component analysis based on genomic relationships. CONCLUSIONS: Bayesian regression models are of interest for future applications of genomic selection in this population, but further improvements are needed to reduce deflation of their predictions. Recurrent updates of the training population would be required to enable accurate prediction of the genetic merit of young animals. The technical feasibility of applying genomic prediction in a Bos indicus (Nellore) population was demonstrated. Further research is needed to permit cost-effective selection decisions using genomic information.

A confirmatory factor analysis of the "Autoconcepto Forma 5" questionnaire in young adults from Spain and Chile.

The aim of this work is to examine the pentafactorial validity of the AF5 Self-Concept Questionnaire in Spanish and Chilean young adults. From the responses of a total of 4,383 young adults aged 17 to 22 years (1,918 Spanish, 44%, and 2,465 Chilean, 56%) it was analyzed the reliability of the instrument, the compared validity of the 5 oblique factor model proposed by the authors versus the unifactorial and the orthogonal alternative models, and was studied the invariance of one Chilean sample. The results of confirmatory factor analyses supported the authors' pentafactorial model. The multi-group factorial invariance showed that Chilean sample of the AF5 does not change neither the Spanish factor weights, nor the variances and covariances of the factors, or the error variances of items. Finally, the internal consistency of the five scales was good in the samples of both countries.

Methylome Patterns of Cattle Adaptation to Heat Stress.

Heat stress has a detrimental impact on cattle health, welfare and productivity by affecting gene expression, metabolism and immune response, but little is known on the epigenetic mechanisms mediating the effect of temperature at the cellular and organism level. In this study, we investigated genome-wide DNA methylation in blood samples collected from 5 bulls of the heat stress resilient Nellore breed and 5 bulls of the Angus that are more heat stress susceptible, exposed to the sun and high temperature-high humidity during the summer season of the Brazilian South-East region. The methylomes were analyzed during and after the exposure by Reduced Representation Bisulfite Sequencing, which provided genome-wide single-base resolution methylation profiles. Significant methylation changes between stressful and recovery periods were observed in 819 genes. Among these, 351 were only seen in Angus, 366 were specific to Nellore, and 102 showed significant changes in methylation patterns in both breeds. KEGG and Gene Ontology (GO) enrichment analyses showed that responses were breed-specific. Interestingly, in Nellore significant genes and pathways were mainly involved in stress responses and cellular defense and were under methylated during heat stress, whereas in Angus the response was less focused. These preliminary results suggest that heat challenge induces changes in methylation patterns in specific loci, which should be further scrutinized to assess their role in heat tolerance.

Growth Rate and Acceleration Analysis of the COVID-19 Pandemic Reveals the Effect of Public Health Measures in Real Time.

Background: Ending the COVID-19 pandemic is arguably one of the most prominent challenges in recent human history. Following closely the growth dynamics of the disease is one of the pillars toward achieving that goal. Objective: We aimed at developing a simple framework to facilitate the analysis of the growth rate (cases/day) and growth acceleration (cases/day2) of COVID-19 cases in real-time. Methods: The framework was built using the Moving Regression (MR) technique and a Hidden Markov Model (HMM). The dynamics of the pandemic was initially modeled via combinations of four different growth stages: lagging (beginning of the outbreak), exponential (rapid growth), deceleration (growth decay), and stationary (near zero growth). A fifth growth behavior, namely linear growth (constant growth above zero), was further introduced to add more flexibility to the framework. An R Shiny application was developed, which can be accessed at https://theguarani.com.br/ or downloaded from https://github.com/adamtaiti/SARS-CoV-2. The framework was applied to data from the European Center for Disease Prevention and Control (ECDC), which comprised 3,722,128 cases reported worldwide as of May 8th 2020. Results: We found that the impact of public health measures on the prevalence of COVID-19 could be perceived in seemingly real-time by monitoring growth acceleration curves. Restriction to human mobility produced detectable decline in growth acceleration within 1 week, deceleration within ~2 weeks and near-stationary growth within ~6 weeks. Countries exhibiting different permutations of the five growth stages indicated that the evolution of COVID-19 prevalence is more complex and dynamic than previously appreciated. Conclusions: These results corroborate that mass social isolation is a highly effective measure against the dissemination of SARS-CoV-2, as previously suggested. Apart from the analysis of prevalence partitioned by country, the proposed framework is easily applicable to city, state, region and arbitrary territory data, serving as an asset to monitor the local behavior of COVID-19 cases.

Single-Nucleotide Polymorphism Variations Associated With Specific Genes Putatively Identified Enhanced Genetic Predisposition for 305-Day Milk Yield in the Girolando Crossbreed.

Milk production phenotypes are the main focus of genetic selection in dairy herds, and although there are many genes identified as related to the biology of these traits in pure breeds, little is known about crossbreed animals. This study aimed to identify potential genes associated with the 305-day milk yield in 337 crossbreed Gir × Holstein (Girolando) animals. Milk production records were genotyped for 45,613 single-nucleotide polymorphisms (SNPs). This dataset was used for a genome-wide association study (GWAS) using the 305-day milk yield adjusted for the fixed effects of herd and year and linear and quadratic effects of age at calving (in days) and calving factor averaged per animal. Genes within the significant SNPs were retrieved from the Bos taurus ARS-UCD1.2 assembly (bosTau9) for gene ontology analysis. In summary, the GWAS identified 52 SNPs associated [p ≤ 10-4, false discovery rate (FDR) = 8.77%] with milk production, including NUB1 and SLC24A2, which were previously described as related to milk production traits in cattle. The results suggest that SNPs associated mainly with NUB1 and SLC24A2 could be useful to understand milk production in Girolando and used as predictive markers for selecting genetic predisposition for milk yield in Girolando.

Targeted nucleotide exchange in bovine myostatin gene.

The myostatin gene, known as Growth Differentiation Factor 8 (GDF8), located at chromosome 2 (BTA2) in cattle, is specifically expressed during embryo development and in the adult skeletal muscle. Molecular analysis of this gene reveals the presence of three exons and two introns. Several cattle breeds, such as Piedmontese, Belgian Blue, Blond'Aquitaine, among others, show polymorphisms in this gene, which are directly related to double muscling phenotype. Piedmontese cattle shows a nucleotide transition G --> A (G938A) at exon 3, resulting in the substitution of cysteine to tyrosine, leading to a protein structure change, which determines myostatin inactivation and consequent muscular hypertrophy. The objective of this work was to implant the polymorphism G938A, naturally existent in Piedmontese breed, into in vitro propagated foetal myoblasts, from Nellore cattle. Single strand DNA (ssDNA) oligonucleotides were used to direct the same nucleotidic transition (G938A) to exon 3. Two transfection protocols (cationic lipid solution and electroporation) were tested and, 48 hours after transfection, RNA and DNA were extracted from myoblasts. Reverse transcription and polymerase chain reaction (PCR) were performed, using primers flanking the mutation region. The PCR products were cloned and analyzed by DNA sequencing, and it was possible to detect the nucleotidic CT transition at position 938, in the electroporated myoblasts. The existence of a positive signal in the transfection indicates that ssDNA oligonucleotides can be used to introduce this point mutation in specific functional gene sites.

Internalization of values and self-esteem among Brazilian teenagers from authoritative, indulgent, authoritarian, and neglectful homes.

The relation between parenting styles and adolescent outcomes was analyzed in a sample of 1,198 15-18-year-old Brazilians. The adolescents were classified into 1 of 4 groups (Authoritative, Authoritarian, Indulgent, and Neglectful) on the basis of their own ratings of their parents on two dimensions: Acceptance/ Involvement and Strictness/Imposition. The adolescents were then contrasted along two different outcomes: (1) priority given to Schwartz Self-transcendence and Conservation values, and (2) level of Self-esteem (appraised in 5 domains: Academic, Social, Emotional, Family, and Physical). Results showed that Authoritative and Indulgent parenting is associated with the highest internalization of Self-Transcendence and Conservation values of teenagers, whereas Authoritarian parenting is associated with the lowest. On the other hand, adolescents with Indulgent parents have equal or higher levels of Self-esteem than adolescents with Authoritative parents, while adolescents raised in Authoritarian and Neglectful homes have the lowest scores in Self-Esteem.

[Design and power analysis: n and confidence intervals of means]. / Diseño y análisis de la potencia: n y los intervalos de confianza de las medias.

In this study, we analyzed the validity of the conventional 80% power. The minimal sample size and power needed to guarantee non-overlapping (1-alpha)% confidence intervals for population means were calculated. Several simulations indicate that the minimal power for two means (m = 2) to have non-overlapping CIs is .80, for (1-alpha) set to 95%. The minimal power becomes .86 for 99% CIs and .75 for 90% CIs. When multiple means are considered, the required minimal power increases considerably. This increase is even higher when the population means do not increase monotonically. Therefore, the often adopted criterion of a minimal power equal to .80 is not always adequate. Hence, to guarantee that the limits of the CIs do not overlap, most situations require a direct calculation of the minimum number of observations that should enter in a study.

[Lethality analysis in patients with tuberculosis diagnosis in a high complexity hospital in Cali, Colombia]. / Análisis de letalidad en pacientes con diagnóstico de tuberculosis en un centro de alta complejidad en Cali, Colombia.

Background In 2016 tuberculosis (TB) was considered the ninth leading cause of death worldwide and the leading cause of a single infectious agent, with approximately 1.6 million deaths worldwide and a lethality of 15%. Over 95% of cases and deaths are in developing countries like Colombia. AIM: To describe the sociodemographic and clinical characteristics of patients who died during TB treatment in a high complexity hospital in Cali, Colombia. METHODS: We conducted an analytic retrospective cohort during 2007-2016 in Fundación Valle del Lili. We included patients with TB diagnosis, who died during TB treatment. RESULTS: From 787 patients with TB, 69 died (8.8%). Fifty nine percent were male, the average of age was 51.9 years. There was diagnosis delay in 51% of the patients and 74% presented pulmonary TB. Sixty four percent 64 died in the first 30 days of the TB diagnosis and 61% of the deaths were attributable to TB. Twenty five percent of patients had TB/HIV coinfection. Elderly patients (> 65 years old) were associated with death in the first 30 days of TB diagnosis (p < 0,001). DISCUSSION: The lethality found in this study was higher than expected (8.8%), the majority of patients had serious comorbidities. Elderly patients were associated with early death. The main pathophysiological mechanism of death was septic shock caused by severe tuberculous pneumonia.