SummaryBackgroundResults of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.MethodsFOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.FindingsBetween Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.InterpretationFluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.FundingUK Stroke Association and NIHR Health Technology Assessment Programme.

Excessive tourist traffic concentration in cities of high tourist attractiveness often leads to overtourism, manifested, among others, by overcrowding in appealing areas and means of transport, rising prices, or degradation of natural and cultural resources. The effects of an excessive number of tourists include an unfavourable change in the local community's attitude towards tourists. The paper determines the extent and forms of overtourism symptoms in Wrocław, Poland. The research allowed for the identification of negative and positive effects of tourist traffic in Wrocław as perceived by three groups of respondents: experts, Wrocław residents: key experts from the scientific, administrative, planning, and business communities; people directly involved in tourist services; and students of tourism. The crucial part was direct research, conducted in November 2019 with a questionnaire technique. The results confirm symptoms of overtourism in Wrocław, but the threat is not significant. The article shows specific potential overtourism threat factors; the respondents' opinions did not significantly differ between the groups. The presented findings and conclusions may be useful in developing the tourism policy of this and other cities, especially regarding sustainable development of tourism and the potential threat imposed by overtourism. The methodology may be used in similar comparative studies in other cities.

BackgroundThe aim of this study was to estimate haplotype effects and then to predict breeding values using linear models. The haplotype based analysis enables avoidance of loosing information due to linkage disequilibrium between single markers. There are also less explanatory variables in the linear model which makes the estimation more reliable.MethodsDifferent methods and criteria for marker and haplotype selection were considered. First, markers with MAF lower than 5% where excluded from the data set. Then, SNPs in complete linkage disequilibrium where selected. Next step was to construct haplotypes and to estimate their frequencies basing on selected SNPs. The haplotypes with a frequency lower than 1% were not considered in further analysis. Chosen haplotypes were used as the explanatory variables in the linear models for breeding values prediction. Linear models with fixed and random haplotype effects as well as animal model were tested.ResultsThe number of markers was limited to 1206, 1189, 1249, 1288 and 1167 for chromosome 1, 2, 3, 4 and 5, respectively due to MAF criterion. In total 409 subsets of SNPs with r2=1 were found. 1476 haplotypes with different lengths were inferred. The frequencies of 817 haplotypes were higher than 1% - 184 for the first chromosome, 172 for the second, 131 for the third, 146 for the forth and 184 haplotypes for the fifth chromosome. The haplotype effects estimated using random models were comparable and more precise in prediction for individuals with unknown phenotypes. A few haplotypes with large effects were found when their effects were defined as fixed in the linear model . The correlations of the predicted breeding values with true breeding values were not that high. This could be brought about by selection criteria imposed on the genotype data which led to substantial reduction of number of markers.ConclusionsAlthough not many markers were considered in the study, the results obtained show that the implemented approach can be considered as quite promising. The haplotype approach let to avoid high dimensional models as compared with single SNPs models.

This paper demonstrates the influence of artificial selection on morphometric traits in the red fox [Vulpes vulpes (Linnaeus, 1758)]. Measurements and two proportion coefficients were analysed in 132 wild and 199 farm red foxes. The two groups differed significantly (P ≤ 0.05) on all but one of the measurements. Eight out of 11 measurements were significantly greater in the farm fox population, while only tail length, ear height, and length of the right hind limb were greater in the population of wild foxes. The opposite trend was observed when analysing variation in the measurements -the farm foxes were characterized by a greater variability only in the case of body weight, body length, and breadth of chest. When analysing the sexual dimorphism index in different sex and population groups, in almost all analysed traits, the greatest differences occurred between farm males and wild females. All of the traits examined in this study are important for survival of wild foxes. However, because importance of some traits was reduced during domestication and selective breeding (farm foxes do not have to fight for survival), the genetic relationship between them may have weakened. Other possible causes of morphological differences between the studied groups of red foxes are discussed as well.Key words: morphometrics, farm red fox, wild red fox, Vulpes vulpes.Résumé : Cet article démontre l'influence de la sélection artificielle sur les caractéristiques morphométriques du renard roux [Vulpes vulpes (Linnaeus, 1758)]. Des mesures ainsi que deux coefficients de proportion ont été analysés chez 132 renards roux sauvages et 199 renards roux d'élevage. Les deux groupes différaient de façon significative (P ≤ 0,05) sur toutes les mesures sauf une. Huit des 11 mesures étaient significativement plus élevées dans la population de renards d'élevage, tandis que seulement la longueur de queue, la hauteur des oreilles et la longueur de la patte droite arrière étaient plus élevées dans la population de renards sauvages. Une tendance inverse a été observée lorsqu'il y a eu analyse de la variation dans les mesures -les renards d'élevage se caractérisaient par une plus grande variabilité seulement dans le cas du poids corporel, de la longueur du corps et de la largeur de poitrine. Lors de l'analyse de l'indice de dimorphisme sexuel parmi les différents groupes sexe et population, dans la plupart des caractéristiques analysées, les plus grandes différences se retrouvent entre les mâles d'élevage et les femelles sauvages. Toutes les caractéristiques examinées lors de cette étude sont importantes pour la survie des renards sauvages. Par contre, puisque l'importance de certaines caractéristiques est diminuée pendant la domestication et l'élevage sélectif (les renards d'élevage ne sont pas obligés de se battre pour leur survie), la relation génétique entre eux pourrait avoir faibli. D'autres causes possibles des différences morphologiques entre les groupes de renards roux étudiés sont aussi discutées. [Traduit par la Rédaction] Mots-...

The aim of this study was to predict the genomic breeding value (DGV) of production, selected conformation and reproductive traits, and somatic cell score of dairy cattle in Poland using high-frequency marker haplotypes. The dataset consisted of phenotypic, genotypic, and pedigree data of 1216 Polish Holstein-Friesian bulls. The genotypic data consisted of 54,000 single-nucleotide polymorphisms (SNPs). The data were divided into two subsets: a test dataset ( n = 1064) and a validation dataset ( n = 152). Genotypic data were selected using three criteria: the percentage of missing genotypes, minor allele frequency, and linkage disequilibrium. The purpose of the data selection was to identify blocks of SNPs that were then used for the construction of haplotypes. Only haplotypes with a frequency higher than 25% were selected. DGV was predicted using four variants of a linear model with random haplotype effects and deregressed breeding values as the response variables. The accuracy of genomic prediction was checked by comparing DGVs with estimated breeding values (EBVs) using two methods: Pearson’s correlations and the regression of EBV on DGV. The use of high-frequency haplotypes showed a tendency to underestimate DGVs. None of the models tested was clearly superior with regard to the traits studied. DGVs of production and conformation traits as well as somatic cell score (medium or high heritability traits) were more accurate than those estimated for fertility traits (low heritability traits).

The skulls of 165 red foxes (75 wild and 90 farm-bred individuals) collected in Poland in the years 2012-2014 were measured, analysed, and compared to further investigate the effect of ancestry and selective breeding on craniometrical variation between wild and farm red fox populations. Univariate comparisons of skull measurements (19 cranial traits), as well as four craniometric indices, revealed significant differences among vast majority of the studied measurements. Principal component analyses and two-dimensional plots showed almost complete separation of the two studied populations of the red fox, as well as clear separation of sexes between populations and within the farm population. This may suggest that the selective forces (artificial vs. natural selection) acting upon cranial morphology of the red fox vary between wild and farm populations. Furthermore, the second important factor which cannot be ignored when considering morphological differences between wild and farm foxes is the origin of compared populations (the Eurasian wild red fox population vs. the red foxes of North American origina founder population of farm foxes). Thus, the ancestry of the farm foxes is discussed as well. Résumé : Les crânes de 165 renards roux (75 sauvages et 90 d'élevage) collectés en Pologne dans les années 2012 à 2014 ont été mesurés, analysés et comparés pour étudier davantage les effets d'ascendance et de reproduction sélective sur les variations craniométriques entre les populations de renards roux sauvages et d'élevage. Les comparaisons unidimensionnelles des mesures de crânes (19 caractéristiques crâniennes) ainsi que quatre indices craniométriques ont révélé des différences significatives dans la vaste majorité des mesures étudiées. Des analyses en composantes principales et des graphiques en deux dimensions montraient une séparation presque complète des deux populations étudiées de renard roux ainsi qu'une séparation nette des sexes entre les populations, et à l'intérieure de la population d'élevage. Ceci pourrait suggérer que les forces de sélection (sélection artificielle c. naturelle) qui agissent sur la morphologie du crâne des renards roux varient entre les populations sauvages et d'élevage. De plus, le deuxième facteur important qui ne peut pas être ignoré lors de la considération des différences morphologiques entre les renards sauvages et d'élevage est l'origine des populations comparées (la population eurasienne de renards roux sauvages c. les renards roux d'origine nord-américaineune population fondatrice des renards d'élevage). Donc, l'ascendance des renards d'élevage est discutée aussi. [Traduit par la Rédaction]Mots-clés : craniométrie, renard roux d'élevage, renard roux sauvage, Vulpes vulpes.

Polymorphism of 30 canine-derived microsatellites was studied in a group of 200 red foxes kept on 2 Polish farms. 22 out of 30 microsatellites were selected to study association between marker genotypes and body weight (BW), body length (BL), body circumference (BC), tail length (TL), ear height (EH), length of the right front limb (FRLL), length of the right rear limb (RRLL), length of the right front foot (FRFL) and length of the right rear foot (RRFL). A total of 112 alleles and 243 genotypes were found at 22 autosomal microsatellite loci. Three monomorphic loci deemed as uninformative were excluded from the study. The association between marker genotypes and the studied traits was analysed using general linear model (GLM) procedure and least squares means (LSM). Linkage disequilibrium (LD) was estimated to assess non-random association between microsatellite loci. Out of 19 microsatellites studied four markers showed no association with the studied traits, three markers had a significant effect on one trait, and another three markers had significant effect on two traits. Among ten microsatellites with significant effect on four economically important traits (BW, BL, BC, TL) four were associated with two characters: marker FH2613 with BW and BC, marker FH2097withBL and BC, marker ZUBECA6 with BW and BC, whereas marker REN75M10 was associated with BL and TL. The strongest LD (r2 ranged from 0.15 to 0.33) was estimated between nine loci with significant effect on economically important traits (BW, BL, BC, TL).

The aim of this work is to analyse the proliferation of tumour cells in the treatment gapduring the radiotherapy for head neck cancer.Material and Methods: The clinical material is based on records of head and neck patients treated by radiotherapyalone in our institution. The effect of radiotherapy was assumed to be described by a linearquadratic model. The patient data were fitted directly to the radiobiological model and theparameters were estimated using maximum-likelihood procedures.Results: According to our model results of treatment were significantly correlated with Normalised Total Dose of radiation, the tumour progression (according to TNM), the overall treatment time and the gap duration. The laryngeal cancers had better prognosis then cancers of oroand nasopharynx. When the treatment time is prolonged without treatment interruptions 0.36 Gylday is lost due to the repopulation of tumour cells. During the treatment gap proliferation is faster and 0.67 Gylday is lost.Conclusion: Proliferation of tumour cells is faster during the treatment gap then during the days with irradiation.