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University students who are placed on academic warning are often required to enroll in a course or program to support their return to good academic standing. This case study investigated the major issues that contributed to first-year students' academic struggles and how their participation in the Learning Contract course, guided by Appreciative Advising, addressed their needs and supported their development. Implications for advising practice are discussed.

Engineering works greatly influence the lateral channel migration (LCM) of meandering rivers. We aimed to characterise the spatiotemporal characteristics of LCM during the last 174 years of the almost freely meandering Upper Rába (Hungary) and to identify units with distinctive LCM histories. The studied Rába's reach has been regulated just at some points. Due to the free meandering, its length varied between 119 and 133 km. The most intensive length increase (+291 m/y) took place between 2005 and 2008, and by the end of the process , the sinuosity had reached its historical maximum (SI 2018 = 1.93). The mean LCM was 3.3 m/y (1844-2018). The periods with intensive channel migration (max: 24-27 m/y) were followed by periods with low migration rates. Based on local channel morphology and LCM rates, 14 units were identified. The highest LCM rate was measured in the freely migrating units (R5: 5.8 m/y; R3: 4.4 m/y and R6 4.0 m/y).

Abstract Background It is accepted that a woman's lifetime risk of developing breast cancer after menopause is reduced by early full term pregnancy and multiparity. This phenomenon is thought to be associated with the development and differentiation of the breast during pregnancy. Methods In order to understand the underlying molecular mechanisms of pregnancy induced breast cancer protection, we profiled and compared the transcriptomes of normal breast tissue biopsies from 71 parous (P) and 42 nulliparous (NP) healthy postmenopausal women using Affymetrix Human Genome U133 Plus 2.0 arrays. To validate the results, we performed real time PCR and immunohistochemistry. Results We identified 305 differentially expressed probesets (208 distinct genes). Of these, 267 probesets were up- and 38 down-regulated in parous breast samples; bioinformatics analysis using gene ontology enrichment revealed that up-regulated genes in the parous breast represented biological processes involving differentiation and development, anchoring of epithelial cells to the basement membrane, hemidesmosome and cell-substrate junction assembly, mRNA and RNA metabolic processes and RNA splicing machinery. The down-regulated genes represented biological processes that comprised cell proliferation, regulation of IGF-like growth factor receptor signaling, somatic stem cell maintenance, muscle cell differentiation and apoptosis. Conclusions This study suggests that the differentiation of the breast imprints a genomic signature that is centered in the mRNA processing reactome. These findings indicate that pregnancy may induce a safeguard mechanism at post-transcriptional level that maintains the fidelity of the transcriptional process.

Abstract Background Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs) and height, body mass index (BMI) and hormone replacement therapy (HRT). Methods We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case–control study. Totally 2884 invasive breast cancer cases and 4508 controls were analysed in the study. Genotypes were determined using Mass spectrometry-Maldi-TOF and phenotypic variables were derived from measurements and/or questionnaires. Odds Ratios and 95% confidence intervals were calculated using unconditional logistic regression with the inclusion of an interaction term in the logistic regression model. Results One SNP (rs851987 in ESR1) tended to interact with height, with an increasingly protective effect of the major allele in taller women (p = 0.007) and rs13281615 (on 8q24) tended to confer risk only in non users of HRT (p-for interaction = 0.03). There were no significant interactions after correction for multiple testing. Conclusions We conclude that much larger sample sets would be necessary to demonstrate interactions between low-risk genetic polymorphisms and the phenotypic variables height, BMI and HRT on the risk for breast cancer. However the present hypothesis-generating study has identified tendencies that would be of interest to evaluate for gene-environment interactions in independent materials.

Abstract Background Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers. Methods The quantitative methylation analysis was performed using the SEQUENOM’s EpiTYPER™ assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results The quantitative DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for the APC, BIN1, BMP6, BRCA1, CST6, ESR-b, P16, PTEN and TIMP3 promoter regions (PAPC, BMP6, BRCA1 and P16 displayed higher methylation proportion in the matched lymph node metastasis than that found in the normal tissue (PBMP6, BRCA1 and P16 have a role in prevention of neoplasm metastasis. Conclusions The results of the present study showed methylation heterogeneity between primary tumors and metastatic lesion. The contribution of aberrant methylation alterations of BMP6, BRCA1 and P16 genes in lymph node metastasis might provide a further clue to establish useful biomarkers for screening metastasis.

Abstract Background The single nucleotide polymorphism rs7566605, located in the promoter of the INSIG2 gene, has been the subject of a strong scientific effort aimed to elucidate its possible association with body mass index (BMI). The first report showing that rs7566605 could be associated with body fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC). Methods we tested in a large-scale association study (3,973 women, including 1,269 invasive BC cases and 2,194 controls), nested within the EPIC cohort, the involvement of rs7566605 as predictor of BMI and BC risk. Results and Conclusions In this study we were not able to find any statistically significant association between this SNP and BMI, nor did we find any significant association between the SNP and an increased risk of breast cancer overall and by subgroups of age, or menopausal status.

Abstract Background Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3). Methods We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms (SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition (EPIC), Multiethnic Cohort (MEC), Nurses' Health Study (NHS), and Women's Health Study (WHS). Circulating levels of sex steroids (androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects. Results Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels. Conclusion Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.

Abstract Background Dysregulation of apoptosis, specifically overexpression of soluble Fas (sFas), has been proposed to play a role in the development of ovarian cancer. The main objective of the present study was to evaluate serum sFas as a potential biomarker of ovarian cancer risk. Methods The association between serum sFas levels and the risk of ovarian cancer was examined in a case-control study nested within three prospective cohorts in New York (USA), Umeå (Sweden), and Milan (Italy). Case subjects were 138 women with primary invasive epithelial ovarian cancer diagnosed between 2 months and 13.2 years after the initial blood donation. Control subjects were 263 women who were free of cancer, and matched the case on cohort, menopausal status, age, and enrollment date. Serum sFas levels were determined using a quantitative sandwich enzyme immunoassay. Results Serum sFas levels were similar in women subsequently diagnosed with ovarian cancer (median, 6.5 ng/mL; range, 4.4 – 10.2) and in controls (median, 6.8 ng/mL; range, 4.5 – 10.1). Statistically significant trends of increasing serum sFas with age were observed among cases (r = 0.39, p < 0.0001) and controls (r = 0.42, p < 0.0001). Compared to women in the lowest third, women in the highest third of serum sFas were not at increased risk of ovarian cancer after adjustment for potential confounders (odd ratio (OR), 0.87; 95% confidence interval (CI), 0.42 – 1.82). Conclusion The results suggest that serum sFas may not be a suitable marker for identification of women at increased risk of ovarian cancer.

Sound analysis is an important field of research for improving precision livestock farming systems. If the information carried by livestock sounds is interpreted correctly, it could be used to improve management and welfare assessment in this field. Therefore, we hypothesized that the nasal vocalization of a mother cow could have a calming effect on conspecifics. The nasal vocalization in our study was recorded from a mother cow (not part of the test herd) while it was licking its day-old calf. The raw sound was analyzed, cleaned from noises, and the most representative vocalization was lengthened to two minutes. Thirty cows having calves were randomly selected from eighty Hungarian grey cattle cows. Two test days were selected, one week apart; the weather circumstances in both days were similar. The herd was collected in a paddock, and the test site (a restraining crate with a headlock) was 21 m away from them. The cows from the herd were gently moved to the restraining crate, and, after the installation of the headlock, Polar® heart rate monitors were fixed on the animals. The recording of the RR intervals was carried out for two minutes. On day one of the test, the processed nasal sound was played to every second cow during the heart rate monitoring. When the sound ended, the heart rate monitor was removed. On test day two, the sound and no sound treatments were switched among the participating cows. At the end of the measurement, the headlock was opened, letting the animals out voluntarily, and a flight test was performed along a 5 m distance. The time needed to pass the 5 m length was measured with a stopwatch and divided by the distance. The RR intervals were analyzed with the Kubios HRV Standard (ver. 3.5.0) software. The following data were recorded for the entire measurement: average and maximum heart rate; SD1 and SD2; pNN50; VLF, LF, and HF. The quasi-periodic signal detected in the sound analyses can hardly be heard, even when it is enhanced to the maximum. This can be considered a vibration probably caused by the basis of articulation, such as a vibration of the tongue, for example. The SD2/SD1 ratio (0.97 vs. 1.07 for the animals having no sound and sound played, respectively, p = 0.0110) and the flight speed (0.92 vs. 1.08 s/m for the animals having no sound and sound played, respectively, p = 0.0409) indicate that the sound treatment had a calming effect on the restrained cows. The day of the test did not influence any of the measured parameters; therefore, no effect of the routine was observed. The yes–no sequence of the sound treatment significantly reduced the pNN50 and flight speed values, suggesting a somewhat more positive association with the headlock and the effectiveness of the processed nasal sound. In conclusion, we have demonstrated that, by means of sound analyses, not only information about individuals and the herd can be gathered but that, with proper processing, the sound obtained can be used to improve animal welfare.

BackgroundB-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms.MethodsWe investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts.ResultsOur analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection.ConclusionsThis is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.

Analysis of the implementation of the Jordan Compact offers three key lessons: governmental approval is important but not sufficient, the incorporation of critical voices is crucial, and meeting numeric targets is not the same as achieving underlying goals.

There is great interest in developing an adequate partial factor format for the assessment of existing structures, and in particular bridges, that should be able to take various aspects into account linked to the fact that the structure already exists. As the structure is existing, additional information related to material parameters, loading conditions, local structural defects, etc. can be accounted for. In addition, the degree of conservatism needs to be well balanced to avoid unnecessary investment of resources in replacement or retrofitting. This contribution considers the experience gained in recent years in parallel with some ongoing standardisation work in relation to Eurocodes and the next edition of the fib Model Code for new and existing concrete structures. The current state of the art of partial factors for the assessment of existing structures is explored and the differences are assessed based on a comparison between (i) the use of recommended fixed partial factors as provided in many national and international codes, (ii) adjusted (flexible) partial factors derived for the individual case under consideration, and (ii) reliability-based verification. In order to assess the adequacy of proposals and identify some differences, the available partial factor formats are applied to two case studies of reinforced concrete bridges and they are critically assessed. [ABSTRACT FROM AUTHOR]

• For the first time student responses to science questions from the Swedish PISA 2006 Main Study and the PISA 2015 Field Trial have been used in order to investigate differences in boys’ and girls’ written responses. Students’ correct and incorrect answers to the science questions are studied with respect to response length, the number of everyday words used, and the inclusion of nouns and long words in the responses. The results reveal that girls give longer and denser correct responses to most of the questions, compared to boys. The difference in response length cannot be explained by girls’ excessive use of the most common Swedish words, since boys and girls use the same proportion of these words. For incorrect answers the only difference between boys and girls is in the response length, since girls give longer answers than boys.

Objectives. To examine the relationship between “traditional Sami” dietary pattern and mortality in a general northern Swedish population. Study design . Population-based cohort study. Methods. We examined 77,319 subjects from the Västerbotten Intervention Program (VIP) cohort. A traditional Sami diet score was constructed by adding 1 point for intake above the median level of red meat, fatty fish, total fat, berries and boiled coffee, and 1 point for intake below the median of vegetables, bread and fibre. Hazard ratios (HR) for mortality were calculated by Cox regression. Results. Increasing traditional Sami diet scores were associated with slightly elevated all-cause mortality in men [Multivariate HR per 1-point increase in score 1.04 (95% CI 1.01–1.07), p=0.018], but not for women [Multivariate HR 1.03 (95% CI 0.99–1.07), p=0.130]. This increased risk was approximately equally attributable to cardiovascular disease and cancer, though somewhat more apparent for cardiovascular disease mortality in men free from diabetes, hypertension and obesity at baseline [Multivariate HR 1.10 (95% CI 1.01–1.20), p=0.023]. Conclusions. A weak increased all-cause mortality was observed in men with higher traditional Sami diet scores. However, due to the complexity in defining a “traditional Sami” diet, and the limitations of our questionnaire for this purpose, the study should be considered exploratory, a first attempt to relate a “traditional Sami” dietary pattern to health endpoints. Further investigation of cohorts with more detailed information on dietary and lifestyle items relevant for traditional Sami culture is warranted.

Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH)D concentration in GWAS were also associated with plasma 25(OH)D in our study (p-trend

Genome-wide association studies (GWASs) may help to understand the effects of genetic polymorphisms on breast cancer (BC) progression and survival. However, they give only a focused view, which cannot capture the tremendous complexity of this disease. Therefore, we investigated data from a previously conducted GWAS on BC survival for enriched pathways by different enrichment analysis tools using the two main annotation databases Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The goal was to identify the functional categories (GO terms and KEGG pathways) that are consistently overrepresented in a statistically significant way in the list of genes generated from the single nucleotide polymorphism (SNP) data. The SNPs with allelic p-value cut-offs 0.005 and 0.01 were annotated to the genes by excluding or including a 20 kb up-and down-stream sequence of the genes and analyzed by six different tools. We identified eleven consistently enriched categories, the most significant ones relating to cell adhesion and calcium ion binding. Moreover, we investigated the similarity between our GWAS and the enrichment analyses of twelve published gene expression signatures for breast cancer prognosis. Five of them were commonly used and commercially available, five were based on different aspects of metastasis formation and two were developed from meta-analyses of published prognostic signatures. This comparison revealed similarities between our GWAS data and the general and the specific brain metastasis gene signatures as well as the Oncotype DX signature. As metastasis formation is a strong indicator of a patient's prognosis, this result reflects the survival aspect of the conducted GWAS and supports cell adhesion and calcium signaling as important pathways in cancer progression.