Outcomes of the "BRCA Quality Improvement Dissemination Program": An initiative to improve patient receipt of cancer genetics services at five health systems.

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC). METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, chi-squared/Fisher's exact test, and logistic regression. RESULTS: For patients with OC, improvement was observed in the rate of referral (from 70% to 79%), GC (from 44% to 61%), GT (from 54% to 62%) and decreased time from diagnosis to GC and GT. For patients with TNBC, increased rates of referral (from 90% to 92%), GC (from 68% to 72%) and GT (81% to 86%) were observed. Effective interventions streamlined GC scheduling and standardized referral processes. CONCLUSION: A multi-year QII increased patient referral and uptake of recommended genetics services across five unique community-based oncology care settings.

Genetic analysis of global faba bean diversity, agronomic traits and selection signatures.

KEY MESSAGE: We identified marker-trait associations for key faba bean agronomic traits and genomic signatures of selection within a global germplasm collection. Faba bean (Vicia faba L.) is a high-protein grain legume crop with great potential for sustainable protein production. However, little is known about the genetics underlying trait diversity. In this study, we used 21,345 high-quality SNP markers to genetically characterize 2678 faba bean genotypes. We performed genome-wide association studies of key agronomic traits using a seven-parent-MAGIC population and detected 238 significant marker-trait associations linked to 12 traits of agronomic importance. Sixty-five of these were stable across multiple environments. Using a non-redundant diversity panel of 685 accessions from 52 countries, we identified three subpopulations differentiated by geographical origin and 33 genomic regions subjected to strong diversifying selection between subpopulations. We found that SNP markers associated with the differentiation of northern and southern accessions explained a significant proportion of agronomic trait variance in the seven-parent-MAGIC population, suggesting that some of these traits were targets of selection during breeding. Our findings point to genomic regions associated with important agronomic traits and selection, facilitating faba bean genomics-based breeding.

The giant diploid faba genome unlocks variation in a global protein crop.

Increasing the proportion of locally produced plant protein in currently meat-rich diets could substantially reduce greenhouse gas emissions and loss of biodiversity1. However, plant protein production is hampered by the lack of a cool-season legume equivalent to soybean in agronomic value2. Faba bean (Vicia faba L.) has a high yield potential and is well suited for cultivation in temperate regions, but genomic resources are scarce. Here, we report a high-quality chromosome-scale assembly of the faba bean genome and show that it has expanded to a massive 13 Gb in size through an imbalance between the rates of amplification and elimination of retrotransposons and satellite repeats. Genes and recombination events are evenly dispersed across chromosomes and the gene space is remarkably compact considering the genome size, although with substantial copy number variation driven by tandem duplication. Demonstrating practical application of the genome sequence, we develop a targeted genotyping assay and use high-resolution genome-wide association analysis to dissect the genetic basis of seed size and hilum colour. The resources presented constitute a genomics-based breeding platform for faba bean, enabling breeders and geneticists to accelerate the improvement of sustainable protein production across the Mediterranean, subtropical and northern temperate agroecological zones.

Diagnostic considerations in a 16-year-old girl with multiple personalities.

This case report describes a 16-year-old patient, who presented with multiple personalities. A diagnosis of dissociative identity disorder (DID) was considered, but rejected, based on the patient's presenting psychopathology and a lack of confidence in the current scientific literature describing the diagnosis. DID is a rare diagnosis in Danish clinical practice and there is much dissent concerning its validity.

Richter's transformation in patients with chronic lymphocytic leukaemia: a Nationwide Epidemiological Study.

Richter's transformation (RT) refers to the development of an aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL). Approximately, 2-10% of patients with CLL develop RT, most often as diffuse large B-cell lymphoma. To assess the incidence of RT, we examined risk factors for RT and death among patients with RT in a nationwide CLL cohort (from 2008 to 2016). Among 3772 patients, 113 had biopsy-proven RT. With a median follow-up of 4.3 years, the 5-year cumulative incidence of RT was 2.8%. Advanced Binet stage (B/C) (p<.001), unmutated IGHV (p<.001), and del(17p) (p<.001) were independently associated with risk of developing RT. Half of the patients with RT (49%) were treatment-naïve prior to transformation and demonstrated longer survival after RT compared to patients previously treated for CLL (6.1 vs. 2.8 years, p=.03). Whether this finding could be explained by a higher proportion of clonally unrelated RT among treatment-naïve patients, remain to be addressed.

Breeding for dual-purpose wheat varieties using marker-trait associations for biomass yield and quality traits.

KEY MESSAGE: This study demonstrates that an active breeding nursery with rotation can be used to identify marker-trait associations for biomass yield and quality parameters that are important for biorefinery purposes. Wheat straw is a valuable feedstock for bioethanol production, but due to the recalcitrant nature of lignocellulose, its efficient use in biorefineries is limited by its low digestibility and difficult conversion of structural carbohydrates into free sugars. A genome-wide association study (GWAS) was conducted to search for significant SNP markers that could be used in a breeding programme to improve the value of wheat straw in a biorefinery setting. As part of a 3-year breeding programme (2013-2016), 190 winter wheat lines were phenotyped for traits that affect the yield and quality of the harvested biomass. These traits included straw yield, plant height, lodging at three growth stages and Septoria tritici blotch (STB) susceptibility. Release of glucose, xylose and arabinose was determined after hydrothermal pretreatment and enzymatic hydrolysis of the straw. The lines were genotyped using 15 K SNP markers and 5552 SNP markers could be used after filtering. Heritability for all traits ranged from 0.02 to 0.74. GWASs were conducted using CMLM, SUPER and FarmCPU algorithms, to analyse which algorithm could detect the highest number of marker-trait associations (MTAs). Comparable tendencies were obtained from CMLM and FarmCPU, but FarmCPU produced the most significant results. MTAs were obtained for lodging, harvest index, plant height, STB, glucose, xylose and arabinose at a significance level of p < 9.01 × 10-6. MTAs in chromosome 6A were observed for glucose, xylose and arabinose, and could be of importance for increasing sugar release for bioethanol production.

Relationship between Fusarium Head Blight, Kernel Damage, Concentration of Fusarium Biomass, and Fusarium Toxins in Grain of Winter Wheat Inoculated with Fusarium culmorum.

Winter wheat lines were evaluated for their reaction to Fusarium head blight (FHB) after inoculation with Fusarium culmorum in two field experiments. A mixture of two F. culmorum chemotypes was applied (3ADON-deoxynivalenol producing, NIV-nivalenol producing). Different types of resistance were evaluated, including head infection, kernel damage, Fusarium biomass content and trichothecenes B (deoxynivalenol (DON), and nivalenol (NIV)) accumulation in grain. The aim of the study was to find relationships between different types of resistance. Head infection (FHB index) and Fusarium damaged kernels (FDK) were visually scored. Fusarium biomass was analysed using real-time PCR. Trichothecenes B accumulation was analysed using gas chromatography. Wheat lines differ in their reaction to inoculation for all parameters describing FHB resistance. We found a wide variability of FHB indexes, FDK, and Fusarium biomass content. Both toxins were present. DON content was about 60% higher than NIV and variability of this proportion between lines was observed. Significant correlation was found between head infection symptoms and FDK. Head infection was correlated with F. culmorum biomass and NIV concentration in grain. No correlation was found between the FHB index and DON concentration. Similarly, FDK was not correlated with DON content, but it was with NIV content; however, the coefficients were higher than for the FHB index. Fusarium biomass amount was positively correlated with both toxins as well as with the FHB index and FDK. Environmental conditions significantly influenced the DON/NIV ratio in grain. In locations where less F. culmorum biomass was detected, the DON amount was higher than NIV, while in locations where more F. culmorum biomass was observed, NIV prevailed over DON.

Venous thromboembolism in chronic lymphocytic leukemia: a Danish nationwide cohort study.

Venous thromboembolism (VTE) is associated with inferior survival in cancer patients. The risk of VTE and its effect on survival in chronic lymphocytic leukemia (CLL) patients remains unclear. The present study investigated the impact of patient-related factors, CLL prognostic markers, and CLL treatment on the risk of VTE and assessed overall survival relative to VTE. All patients in the Danish National CLL Registry (2008-2015) were followed from the date of CLL diagnosis to death, VTE, emigration, or administrative censoring. Hazard ratios (HRs) were estimated using Cox models, and second primary cancers and anticoagulation treatment were included as time-varying exposures. During a median follow-up of 2.6 years, 92 VTEs occurred among 3609 CLL patients, corresponding to a total incidence rate of 8.2 VTEs per 1000 person-years (95% confidence interval [CI], 6.7-10.1). A history of VTE or second primary cancer was associated with HRs of VTE of 5.09 (95% CI, 2.82-9.17) and 3.72 (95% CI, 2.15-6.34), respectively, while ß2-microglobulin >4 mg/L, unmutated immunoglobulin HV and unfavorable cytogenetics had lower HRs. CLL patients with VTE had marginally higher mortality, which was most pronounced among patients <60 years of age (HR, 7.74; 95% CI, 2.12-28.29). Our findings suggest that markers of unfavorable CLL prognosis contribute to an increased risk of VTE; however, previous VTE or a second primary cancer is more strongly associated with the risk of VTE than any CLL-specific marker. Focusing attention on this preventable complication may improve survival in young CLL patients.

The Danish National Chronic Lymphocytic Leukemia Registry.

AIM: In 2008, the Danish National Chronic Lymphocytic Leukemia Registry was founded within the Danish National Hematology Database. The primary aim of the registry is to assure quality of diagnosis and care of patients with chronic lymphocytic leukemia (CLL) in Denmark. Secondarily, to evaluate adherence to national guidelines and to provide source data for research purposes. STUDY POPULATION: All patients diagnosed with CLL in Denmark from 2008 onward are included in the registry. Patients are followed in one of nine hematology centers. All centers participate in the registry and are all obliged to collect data. MAIN VARIABLES: Predefined data are collected at the time of diagnosis, and follow-up at the time of significant events: treatment, progression, transplantation, and death. Parameters included in the International Workshop on Chronic Lymphocytic Leukaemia criteria for diagnosis, and for decision on treatment initiation as well as characteristics included in the CLL International Prognostic Index are collected. DESCRIPTIVE DATA: To ensure full coverage of Danish CLL patients in the registry, both continuous queries in case of missing data, and cross-referencing with the Danish National Patient Registry are performed. Data from the registry are published in an annual report summarizing the collected data, the overall survival for yearly cohorts, and the degree of data coverage. Per year approximately 450 new patients with CLL are registered in the registry, cumulative as of July 1, 2015, 3,082 patients have been registered. CONCLUSION: The Danish National CLL Registry is based within the Danish National Hematology Database. The registry covers a cohort of all patients diagnosed with CLL in Denmark since 2008. It forms the basis for quality assessment of CLL treatment in Denmark and offers a unique opportunity for population-based research.

Real-time PCR for quantification of eleven individual Fusarium species in cereals.

Contamination of cereals with Fusarium species is one of the major sources of mycotoxins in food and feed. Quantification of biomass of Fusarium species is essential to understand the interactions of individual species in disease development. In this study quantitative real-time PCR assays based on the elongation factor 1 alpha (EF1alpha) gene for the 11 Fusarium species F. graminearum, F. culmorum, F. poae, F. langsethiae, F. sporotrichioides, F. equiseti, F. tricinctum, F. avenaceum, F. verticillioides, F. subglutinans and F. proliferatum were developed and tested on 24 wheat and 24 maize field samples. The assays were found to be specific and sensitive. Generally, the results from the quantitative real-time PCR assays corresponded well with mycotoxin data of the field samples.

Genetic diversity in the yellow head nidovirus complex.

Penaeus monodon shrimp collected from across the Indo-Pacific region during 1997-2004 were screened for the presence of yellow head-related viruses. Phylogenetic analyses of amplified ORF1b gene segments identified at least six distinct genetic lineages (genotypes). Genotype 1 (YHV) was detected only in shrimp with yellow head disease. Genotype 2 (GAV) was detected in diseased shrimp with the less severe condition described as mid-crop mortality syndrome and in healthy shrimp from Australia, Thailand and Vietnam. Other genotypes occurred commonly in healthy shrimp. Sequence comparisons of structural protein genes (ORF2 and ORF3), intergenic regions (IGRs) and the long 3'-UTR supported the delineation of genotypes and identified both conserved and variant structural features. In putative transcription regulating sequences (TRSs) encompassing the sub-genomic mRNA 5'-termini, a core motif (5'-GUCAAUUACAAC-3') is absolutely conserved. A small (83 nt) open reading frame (ORF4) in the 3'-UTR of GAV is variously truncated in all other genotypes and a TRS-like element preceding ORF4 is invariably corrupted by a A>G/U substitution in the central core motif (5'-UU(G/U)CAAC-3'). The data support previous evidence that ORF4 is a non-functional gene under construction or deconstruction. The 3'-UTRs also contain predicted 3'-terminal hairpin-loop structures that are preserved in all genotypes by compensatory nucleotide substitutions, suggesting a role in polymerase recognition for minus-strand RNA synthesis.

The enantioselective synthesis of elecanacin through an intramolecular naphthoquinone-vinyl ether photochemical cycloaddition.

Elecanacin, an unusual cyclobuta-fused naphthalene-1,4-dione derivative isolated from the bulbs of Eleutherine Americana Merr. et Heyne (Iridaceae) has been obtained, together with its epimer isoelecanacin, by a 2 + 2 cycloaddition resulting from irradiation of 5-methoxy-2-(2-vinyloxypropyl)naphthalene-1,4-dione. The synthesis of enantiopure elecanacin starting with (R)-propylene oxide has established the absolute configuration of the natural product and has revealed that the sample isolated from the bulbs possessed an enantiomeric excess of only 14%.

Biomechanical analysis of rollator walking.

BACKGROUND: The rollator is a very popular walking aid. However, knowledge about how a rollator affects the walking patterns is limited. Thus, the purpose of the study was to investigate the biomechanical effects of walking with and without a rollator on the walking pattern in healthy subjects. METHODS: The walking pattern during walking with and without rollator was analyzed using a three-dimensional inverse dynamics method. Sagittal joint dynamics and kinematics of the ankle, knee and hip were calculated. In addition, hip joint dynamics and kinematics in the frontal plane were calculated. Seven healthy women participated in the study. RESULTS: The hip was more flexed while the knee and ankle joints were less flexed/dorsiflexed during rollator walking. The ROM of the ankle and knee joints was reduced during rollator-walking. Rollator-walking caused a reduction in the knee extensor moment by 50% when compared to normal walking. The ankle plantarflexor and hip abductor moments were smaller when walking with a rollator. In contrast, the angular impulse of the hip extensors was significantly increased during rollator-walking. CONCLUSION: Walking with a rollator unloaded the ankle and especially the knee extensors, increased the hip flexion and thus the contribution of hip extensors to produce movement. Thus, rollator walking did not result in an overall unloading of the muscles and joints of the lower extremities. However, the long-term effect of rollator walking is unknown and further investigation in this field is needed.

Taura syndrome virus (TSV) in Thailand and its relationship to TSV in China and the Americas.

The cultivation of exotic Penaeus vannamei in Thailand began on a very limited scale in the late 1990s, but a Thai government ban on the cultivation of P. monodon in freshwater areas in 2000 led many Thai shrimp farmers to shift to cultivation of P. vannamei. Alarmed by the possibility of Taura syndrome virus (TSV) introduction, the Thai Department of Fisheries required that imported stocks of P. vannamei be certified free of TSV by RT-PCR (Reverse Trasciption Polymerase Chain Reaction) testing. During the interval of allowed importation, over 150,000 broodstock shrimp were imported, 67% of these from China and Taiwan. Despite the safeguards, TSV outbreaks occurred and we confirmed the first outbreak by RT-PCR in early 2003. This resulted in a governmental ban on all shrimp broodstock imports from February 2003, but TSV outbreaks have continued, possibly due to original introductions or to the continued illegal importation of stocks. To determine the origin of the TSV in Thailand, the viral coat protein gene VP1 was amplified by RT-PCR from several shrimp specimens found positive for TSV by RT-PCR from January to November 2003. These included 7 samples from P. vannamei disease outbreaks in Thailand, 3 other non-diseased shrimp samples from Thailand and Burma and 6 samples including P. vannamei and P. japonicus from China. Comparison revealed that the Thai, Burmese and Chinese TSV types formed a clade distinct from a clade of TSV types from the Americas.

Impact of the Pathways food service intervention on breakfast served in American-Indian schools.

BACKGROUND: Pathways was a multisite, multicomponent obesity prevention intervention for American-Indian schoolchildren. The goal of the school breakfast and lunch component was to reduce fat content of school meals to 30% or fewer calories from fat without compromising dietary quality. METHODS: An intensive 3-year intervention was implemented with school food service staff. Five consecutive days of school breakfast menu and recipe information was collected at 20 control and 19 intervention schools at four time intervals. Data were analyzed at nutrient and (in final year) food levels. RESULTS: Average total fat decreased in intervention schools from 16.0 grams at baseline to 13.6 grams by end of study, compared with 16.6 and 16.7 grams at baseline and final measurement in control schools (P<0.030). Percentage of calories from saturated fat were also significantly reduced from 12.0 to 8.9%, compared with 12.1 to 10.6% in control schools (P<0.014). There were no significant differences in total energy or other nutrients by treatment condition across four time points. Food-level data revealed a consistent pattern of more lower-fat items served in intervention schools compared to control schools. CONCLUSIONS: Pathways was successful in achieving its overall goal of reducing dietary fat in meals served for school breakfasts.

Comparison of penaeid shrimp and insect parvoviruses suggests that viral transfers may occur between two distantly related arthropod groups.

The DNA and putative amino acid sequences of representative insect and shrimp parvoviruses (subfamily Densovirinae) were analyzed using computer programs. Shrimp viruses included hepatopancreatic parvovirus (HPV) of Penaeus monodon (HPVmon) and P. chinensis (HPVchin), spawner-isolated mortality virus from P. monodon (SMVmon) and infectious hypodermal and hematopoietic necrosis virus (IHHNV) from P. vannamei. Insect viruses included Aedes aegypti densovirus (AaeDNV), Aedes albopictus densovirus (AalDNV), Junonia coenia densovirus (JcDNV), Galleria mellonella densovirus (GmDNV), Bombyx mori densovirus 5 (BmDNV), Diatraea saccharalis densovirus (DsDNV) and Periplaneta fuliginosa densovirus (PfDNV). Virion size for all these viruses ranged between 18 and 30 nm diameter and ssDNA genome length was between 4 and 6 kb. Using BLAST or Clustal W with the sequence fragments available, no significant DNA homology was found except for 77% DNA identity between HPVmon and HPVchin. However, phylogenetic trees constructed by comparing DNA genome sequences for putative viral polypeptides, capsid proteins and nonstructural proteins placed the parvoviruses into two Clades: Clade 1 with SMVmon, PfDNV, DsDNV, GmDNV, JcDNV, and BmDNV; and Clade 2 with HPVmon, HPVchin, IHHNV, AalDNV and AaeDNV. The four shrimp parvoviruses fell into two different clades that grouped with different insect parvoviruses.

Prisoners of progress or hostages to fortune?

The new reproductive technologies, especially in vitro fertilization (IVF), have extended the possibilities of assisted reproduction to the benefit of the childless couples. At the same time these technologies and their added techniques, however, have fragmented reproduction and exposed the human egg to intervention yet unknown.... These possibilities have legal as well as ethical implications. The challenge is to obtain all the advantages of the reproduction revolution and avoid the disadvantages: to avoid becoming prisoners of progress, but to control the development and guide it in the directions we want. One of the problems is trying to foresee unwarranted consequences. Another is to agree upon which consequences are unwarranted and how they are best avoided or minimized. Although the questions that arise with respect to law, medicine and bioethics are similar all over the world, there are differences of a philosophical, economic, social, political, religious and even geographical nature which are not easily bridged. It is apparent, though, that core approaches are desirable. This article is an attempt to explore the ways in which these determinants have been manipulated in two European [Great Britain, Denmark] legal systems. We are interested in the ways in which those legal systems have been customized to provide temporary answers and marshalling points for regulating reproduction and we seek to make some observations on the ways in which laws, customs and values have been manipulated to produce pictures of the family and the way in which we want -- literally and figuratively -- to conceive of it in the 21st century.