The value of genomic relationship matrices to estimate levels of inbreeding.

BACKGROUND: Genomic relationship matrices are used to obtain genomic inbreeding coefficients. However, there are several methodologies to compute these matrices and there is still an unresolved debate on which one provides the best estimate of inbreeding. In this study, we investigated measures of inbreeding obtained from five genomic matrices, including the Nejati-Javaremi allelic relationship matrix (FNEJ), the Li and Horvitz matrix based on excess of homozygosity (FL&H), and the VanRaden (methods 1, FVR1, and 2, FVR2) and Yang (FYAN) genomic relationship matrices. We derived expectations for each inbreeding coefficient, assuming a single locus model, and used these expectations to explain the patterns of the coefficients that were computed from thousands of single nucleotide polymorphism genotypes in a population of Iberian pigs. RESULTS: Except for FNEJ, the evaluated measures of inbreeding do not match with the original definitions of inbreeding coefficient of Wright (correlation) or Malécot (probability). When inbreeding coefficients are interpreted as indicators of variability (heterozygosity) that was gained or lost relative to a base population, both FNEJ and FL&H led to sensible results but this was not the case for FVR1, FVR2 and FYAN. When variability has increased relative to the base, FVR1, FVR2 and FYAN can indicate that it decreased. In fact, based on FYAN, variability is not expected to increase. When variability has decreased, FVR1 and FVR2 can indicate that it has increased. Finally, these three coefficients can indicate that more variability than that present in the base population can be lost, which is also unreasonable. The patterns for these coefficients observed in the pig population were very different, following the derived expectations. As a consequence, the rate of inbreeding depression estimated based on these inbreeding coefficients differed not only in magnitude but also in sign. CONCLUSIONS: Genomic inbreeding coefficients obtained from the diagonal elements of genomic matrices can lead to inconsistent results in terms of gain and loss of genetic variability and inbreeding depression estimates, and thus to misleading interpretations. Although these matrices have proven to be very efficient in increasing the accuracy of genomic predictions, they do not always provide a useful measure of inbreeding.

Estimates of recent and historical effective population size in turbot, seabream, seabass and carp selective breeding programmes.

BACKGROUND: The high fecundity of fish species allows intense selection to be practised and therefore leads to fast genetic gains. Based on this, numerous selective breeding programmes have been started in Europe in the last decades, but in general, little is known about how the base populations of breeders have been built. Such knowledge is important because base populations can be created from very few individuals, which can lead to small effective population sizes and associated reductions in genetic variability. In this study, we used genomic information that was recently made available for turbot (Scophthalmus maximus), gilthead seabream (Sparus aurata), European seabass (Dicentrarchus labrax) and common carp (Cyprinus carpio) to obtain accurate estimates of the effective size for commercial populations. METHODS: Restriction-site associated DNA sequencing data were used to estimate current and historical effective population sizes. We used a novel method that considers the linkage disequilibrium spectrum for the whole range of genetic distances between all pairs of single nucleotide polymorphisms (SNPs), and thus accounts for potential fluctuations in population size over time. RESULTS: Our results show that the current effective population size for these populations is small (equal to or less than 50 fish), potentially putting the sustainability of the breeding programmes at risk. We have also detected important drops in effective population size about five to nine generations ago, most likely as a result of domestication and the start of selective breeding programmes for these species in Europe. CONCLUSIONS: Our findings highlight the need to broaden the genetic composition of the base populations from which selection programmes start, and suggest that measures designed to increase effective population size within all farmed populations analysed here should be implemented in order to manage genetic variability and ensure the sustainability of the breeding programmes.

Patients with rectal cancer are satisfied with in-hospital communication despite insufficient information regarding treatment alternatives and potential side-effects.

AIM: Patients with rectal cancer may undergo treatment such as surgery and (chemo)radiotherapy. Before treatment, patients are informed of different options and possible side-effects. The aim of the study was to evaluate the patients' experience of communication with healthcare personnel at time of diagnosis and after one year. METHOD: A total of 1085 patients from Denmark and Sweden were included. They answered a detailed questionnaire at diagnosis and at the one year follow-up. Clinical data were retrieved from national quality registries. RESULTS: Response rates were 87% at baseline and 74% at one year. Overall the patients were very satisfied with the communication with healthcare personnel. However, some patients reported insufficient information regarding treatment options and possible side-effects. Only 32% (335/1050) and 24% (248/1053), respectively, stated that they were informed about possible sexual and urinary dysfunction before treatment. CONCLUSIONS: Even though patients felt that they received insufficient information regarding side-effects on sexual and urinary function, they were generally satisfied with the communication with the healthcare personnel. Since overall satisfaction with the level of information was very high, it is unlikely that further information to patients with rectal cancer in the surgical and oncological settings will improve satisfaction with communication.

Correction to: Pretreatment quality of life in patients with rectal cancer is associated with intrusive thoughts and sense of coherence.

The original version of this article, unfortunately, contained errors.

Pretreatment quality of life in patients with rectal cancer is associated with intrusive thoughts and sense of coherence.

PURPOSE: Quality of life may predict survival. In addition to clinical variables, it may be influenced by psychological factors, some of which may be accessible for intervention. The primary objective of this study was to investigate the association of intrusive thoughts and the patients' sense of coherence with pretreatment quality of life in patients with newly diagnosed rectal cancer. METHODS: Patients were prospectively included in 16 hospitals in Sweden and Denmark. They answered an extensive questionnaire after receiving their treatment plan. Clinical data were retrieved from national quality registries for rectal cancer. RESULTS: Of 1248 included patients, a total of 1085 were evaluable. Pretreatment global health-related and overall quality of life was lower in patients planned for palliative compared with curative treatment (median 53 vs. 80 on the EuroQoL visual analogue scale, p < 0.001 and odds ratio 0.56, 95% confidence interval 0.36-0.88, respectively). Quality of life was associated with intrusive thoughts (odds ratio 0.33, 95% confidence interval 0.24-0.45) and sense of coherence (odds ratio 0.44, 95% confidence interval 0.37-0.52) irrespective of the treatment plan. CONCLUSIONS: Pretreatment quality of life was influenced by the intent of treatment as well as by intrusive thoughts and the patients' sense of coherence. Interventions could modify these psychological factors, and future studies should focus on initiatives to improve quality of life for this group of patients.

Self-reported wellbeing and body image after abdominoperineal excision for rectal cancer.

PURPOSE: Patients with low rectal cancer are often operated with an abdominoperineal excision (APE) rendering them a permanent stoma. The surgical procedure itself, the cancer diagnosis, and the permanent stoma might all affect quality of life. The aim of this study was to explore wellbeing and body image 3 years after APE in a population-based cohort of patients. METHODS: All patients with rectal cancer operated with an APE between 2007 and 2009 were identified using the Swedish ColoRectal Cancer Registry. A total of 545 patients answered a questionnaire 3 years after surgery. Two open-ended questions were analyzed with a mixed method design using both qualitative and quantitative content analysis. Main themes and sub-themes on wellbeing and body image were identified. RESULTS: Three main themes were identified: bodily limitations, mental suffering, and acceptance. Bodily limitations included other symptoms than stoma-related problems. A majority of patients expressed acceptance to their situation regardless of bodily limitations and mental suffering. However, 18 % did not describe any acceptance of their current situation. CONCLUSIONS: Most patients expressed acceptance reflecting wellbeing 3 years after APE for rectal cancer. There is, however, a subset of patients (18 %) who describe bodily limitations and mental suffering without acceptance and who require further support. Many aspects of the portrayed bodily limitations and mental suffering could be prevented or treated. TRIAL REGISTRATION: NCT01296984.

Stoma-related symptoms in patients operated for rectal cancer with abdominoperineal excision.

PURPOSE: The primary aim of this study was to characterize the frequency, severity, and distress of symptoms from the colostomy and colostomy acceptance in rectal cancer patients. The secondary aims were to study the symptomatic parastomal herniation, its relationship to stoma-related symptoms, and potential risk factors for the development of symptomatic parastomal herniation. METHODS: Data was collected from the Swedish Colorectal Cancer Registry and from surgical charts. Patients operated for rectal cancer with an abdominoperineal excision in Sweden between 2007 and 2009 and alive 3 years postoperatively were contacted (n = 852). Patients who consented to participate, had a colostomy constructed during the abdominoperineal excision, and who answered a questionnaire 3 years postoperative were included (n = 495). Answers were analyzed with emphasis on stoma-related symptoms and their intensity as well as the level of distress associated with the symptoms. RESULTS: Almost 90% of patients did not feel limited in their daily life by their colostomy. Patients with symptomatic parastomal hernia had a 53% higher risk of flatulence. Fifty-six patients developed symptomatic parastomal hernia (11%). The only risk factor associated with the development of symptomatic parastomal hernia was high body mass index (BMI). CONCLUSIONS: This study shows that most patients do not feel limited by their stoma 3 years after surgery for rectal cancer. Symptomatic parastomal hernia was associated with high BMI but not with the surgical technique.

Maintenance of genetic diversity in subdivided populations using genomic coancestry matrices.

For both undivided and subdivided populations, the consensus method to maintain genetic diversity is the Optimal Contribution (OC) method. For subdivided populations, this method determines the optimal contribution of each candidate to each subpopulation to maximize global genetic diversity (which implicitly optimizes migration between subpopulations) while balancing the relative levels of coancestry between and within subpopulations. Inbreeding can be controlled by increasing the weight given to within-subpopulation coancestry (λ). Here we extend the original OC method for subdivided populations that used pedigree-based coancestry matrices, to the use of more accurate genomic matrices. Global levels of genetic diversity, measured as expected heterozygosity and allelic diversity, their distributions within and between subpopulations, and the migration pattern between subpopulations, were evaluated via stochastic simulations. The temporal trajectory of allele frequencies was also investigated. The genomic matrices investigated were (i) the matrix based on deviations of the observed number of alleles shared by two individuals from the expected number under Hardy-Weinberg equilibrium; and (ii) a matrix based on a genomic relationship matrix. The matrix based on deviations led to higher global and within-subpopulation expected heterozygosities, lower inbreeding and similar allelic diversity than the second genomic and pedigree-based matrices when a relatively high weight was given to the within-subpopulation coancestries (λ ≥ 5). Under this scenario, allele frequencies moved only slightly away from the initial frequencies. Therefore, the recommended strategy is to use the former matrix in the OC methodology giving a high weight to the within-subpopulation coancestry.

Changes in Allele Frequencies When Different Genomic Coancestry Matrices Are Used for Maintaining Genetic Diversity.

A main objective in conservation programs is to maintain genetic variability. This can be achieved using the Optimal Contributions (OC) method that optimizes the contributions of candidates to the next generation by minimizing the global coancestry. However, it has been argued that maintaining allele frequencies is also important. Different genomic coancestry matrices can be used on OC and the choice of the matrix will have an impact not only on the genetic variability maintained, but also on the change in allele frequencies. The objective of this study was to evaluate, through stochastic simulations, the genetic variability maintained and the trajectory of allele frequencies when using two different genomic coancestry matrices in OC to minimize the loss of diversity: (i) the matrix based on deviations of the observed number of alleles shared between two individuals from the expected numbers under Hardy-Weinberg equilibrium (θLH); and (ii) the matrix based on VanRaden's genomic relationship matrix (θVR). The results indicate that the use of θLH resulted in a higher genetic variability than the use of θVR. However, the use of θVR maintained allele frequencies closer to those in the base population than the use of θLH.

Self-reported quality of life and functional outcome in patients with rectal cancer--QoLiRECT.

INTRODUCTION: The treatment of rectal cancer has improved, and survival rates today exceed those of colon cancer, but functional impairments and other adverse effects of treatment are common among patients. The impact of treatment on patients' quality of life (QoL) remains unclear. Many of the common QoL instruments are brief and not sufficiently detailed to provide a deeper understanding of the factors that determine QoL. The aim of this study was to explore patients' experiences and long-term QoL in an unselected cohort of patients with rectal cancer. METHODS: This is a prospective international multicentre study based on a comprehensive, validated questionnaire on functional impairments and QoL administered to an unselected population of 1,500 patients with rectal cancer at diagnosis and after one, two and five years. The clinical characteristics are retrieved from the national quality registers. A total of 14 hospitals in Sweden and Denmark are currently involved in the study. Inclusion is ongoing, and new including hospitals are welcome to join. Full accrual is expected within two years. CONCLUSION: This study will provide detailed knowledge about the challenges that patients face following diagnosis and treatment of rectal cancer. It will investigate the nature, severity and perceived significance of constraints and symptoms, as well as the impact of a variety of clinical and patient-related factors on QoL. The study will probably identify areas where changes in care routines may improve patients' QoL. FUNDING: This study was supported by the Swedish Research Council, grant number 2012-1768; the Swedish Cancer Society CAN 2010/593 and CAN 2013/500; the Swedish Society of Medicine; the Gothenburg Medical Society; the Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland; ALF grant 138751 and 136151, "Agreement concerning research and education of doctors"; Anna-Lisa and Bror Björnsson Foundation; Assar Gabrielsson Foundation; Mary von Sydow Foundation; Ruth and Richard Julin's Foundation and Lion's Cancer Research Foundation of Western Sweden. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01477229).

Parálisis del nervio abducens asociada a punción dural y a compresión neurovascular / Abducens nerve palsy associated with dural puncture and neurovascular compression

Presentamos el caso de un varón de 59 años, que cursa con un cuadro de parálisis del VI par craneal derecho, tras una cefalea postpunción dural, secundaria a una punción dural accidental durante una epidural. En la resonancia magnética, aparece un compromiso del espacio de la arteria basilar sobre la emergencia del VI par derecho. Posiblemente, esta variante anatómica vascular, lo haya predispuesto a una mayor vulnerabilidad del nervio abducens. La tracción del nervio, pudo producir una isquemia, convirtiendo a la hipotensión licuoral en el posible desencadenante de la parálisis. Con tratamiento conservador se recuperó completamente

We present the case of a 59 years old man, who is diagnosed with a right sixth cranial nerve palsy, after the development of a dural post-puncture headache, secondary to an accidental dural puncture during an epidural. In magnetic resonance imaging, a compromise of the basilar artery space appears on the emergence of the right sixth cranial nerve. Possibly, this vascular anatomical variant, predisposed him to a greater vulnerability of the abducens nerve. The traction of the nerve could cause a neural ischemia, so intracranial hypotension could be the trigger of the palsy. He recovered completely with conservative treatment

Propuesta de sistema para la atención integral al niño discapacitado por parálisis cerebral y a su familia / A system proposal for the integral care of the handicapped children with cerebral palsy and their family

Se realizó una investigación descriptiva, con carácter transversal, en el Policlínico Universitario “Santa Clara”, desde enero de 2006 hasta enero de 2010. Se desarrolló en dos etapas: de caracterización y de diseño, donde se creó un sistema para la atención integral al niño discapacitado y a su familia. La mayoría de estos niños fueron productos de una gestación de 41 semanas, partos distócicos, y al examen físico, el trastorno más frecuente fue en el tono muscular. En su mayoría, fueron niños sociables; casi todos los tutores dedicaban mucho tiempo a atender a su hijo, tenían edad promedio de 41 años y elevado nivel escolar. Sustituían al niño en muchas actividades, lo amaban y sentían preocupación por su futuro. Se concluye que la parálisis cerebral no puede prevenirse y que la atención integral es importante para los niños y sus tutores, por lo que se diseñó este sistema para lograrla.

A descriptive research of transversal type was carried out at the “Santa Clara” University Polyclinic from January, 2006 to January, 2010. It was divided into two stages: description stage and design stage, where it was created an integral care system of the handicapped children and their family. Most of the children were product of 41 weeks' gestation with dystocia, and the most frequent disorder found during the physical exam was in the muscular tone. Mostly of them were sociable children; almost all of the tutors spent much time caring them, the average age of tutors was 41 years and had high level of school education. They replaced children in many activities, loved them and felt worried for their future. We concluded that cerebral palsy can not be prevented, as well as, integral care is very important for children and tutors, that is why, it was designed this system in order to achieve it.

Hierarchical sampling of multiple strata: an innovative technique in exposure characterization.

Sampling of multiple strata, or hierarchical sampling of various exposure sources and activity areas, has been tested and is suggested as a method to sample (or to locate) areas with a high prevalence of elevated blood lead in children. Hierarchical sampling was devised to supplement traditional soil lead sampling of a single stratum, either residential or fixed point source, using a multistep strategy. Blood lead (n=1141) and soil lead (n=378) data collected under the USEPA/UCI Tijuana Lead Project (1996-1999) were analyzed to evaluate the usefulness of sampling soil lead from background sites, schools and parks, point sources, and residences. Results revealed that industrial emissions have been a contributing factor to soil lead contamination in Tijuana. At the regional level, point source soil lead was associated with mean blood lead levels and concurrent high background, and point source soil lead levels were predictive of a high percentage of subjects with blood lead equal to or greater than 10 micro g/dL (pe 10). Significant relationships were observed between mean blood lead level and fixed point source soil lead (r=0.93; P<0.05; R(2)=0.72 using a quadratic model) and between residential soil lead and fixed point source soil lead (r=0.90; P<0.05; R(2)=0.86 using a cubic model). This study suggests that point sources alone are not sufficient for predicting the relative risk of exposure to lead in the urban environment. These findings will be useful in defining regions for targeted or universal soil lead sampling by site type. Point sources have been observed to be predictive of mean blood lead at the regional level; however, this relationship alone was not sufficient to predict pe 10. It is concluded that when apparently undisturbed sites reveal high soil lead levels in addition to local point sources, dispersion of lead is widespread and will be associated with a high prevalence of elevated blood lead in children. Multiple strata sampling was shown to be useful in differentiating among sources by site-specific association to mean blood lead and the prevalence of elevated blood lead at the regional level.

Tijuana childhood lead risk assessment revisited: validating a GIS model with environmental data.

The objective of this research was to determine the spatial distributions of childhood lead poisoning and soil lead contamination in urban Tijuana. The Bocco-Sanchez model of point-source emissions was evaluated in terms of validity and reliability. We compared the model's predicted vulnerable populations with observed cases of childhood lead poisoning in Tijuana, identified fixed point sources in the field, and analyzed 76 soil samples from 14 sites. The soil lead results were compared to the blood lead analyses performed on Tijuana children whose blood lead levels were > or =10 microg/dL, who reported that they did not use lead-glazed ceramics for cooking or storing food (n = 63). Using GIS, predicted vs observed risk areas were assessed by examining spatial patterns, including the distribution of cases per designated risk area. Chi-square analysis of expected vs observed values did not differ significantly at the p = 0.02 level, showing that the model was strikingly accurate in predicting the distribution of subjects with elevated blood lead. Results reveal that while point sources are significant, other sources of lead exposure are also important. The relative public health risk from exposure to lead in an urban setting may be assessed by distinguishing among sources of exposure and associating concentrations to blood lead levels. The results represent an iterative approach in environmental health research by linking environmental and human biomarker lead concentrations and using these results to validate an environmental model of risk to lead exposure.

Developmental competence of prepubertal goat oocytes selected with brilliant cresyl blue and matured with cysteamine supplementation.

The aim of this study was to assess the effect of oocyte selection using the brilliant cresyl blue (BCB) test plus the addition of cysteamine to the in vitro maturation (IVM) medium to improve the in vitro embryo development of prepubertal goat oocytes. The oocytes were exposed to 26 microM BCB and classified according to their cytoplasm coloration: BCB+ (oocytes with blue cytoplasm) and BCB- (unstained oocytes). The oocytes were matured in a conventional IVM medium supplemented with cysteamine 100 microM. The control group consisted of oocytes not exposed to BCB and matured without cysteamine. The IVM-oocytes were inseminated and cultured in synthetic oviductal fluid (SOF) for 7 days. The normal fertilisation rate (oocytes showing 2 pronuclei and 1 sperm tail) of BCB+ oocytes (40%) was higher than those of BCB- (21%) and control oocytes (22%). The percentage of morulae plus blastocysts was higher (P < 0.05) in the BCB+ group than in the BCB- group (23.8 vs. 5.1%, respectively). In conclusion, the integration of the BCB test and the addition of cysteamine in the protocol of in vitro embryo production from prepubertal goat oocytes has improved the developmental rates of embryo development.