A comparative integrated gene-based linkage and locus ordering by linkage disequilibrium map for the Pacific white shrimp, Litopenaeus vannamei

The Pacific whiteleg shrimp, Litopenaeus vannamei, is the most farmed aquaculture species worldwide with global production exceeding 3 million tonnes annually. Litopenaeus vannamei has been the focus of many selective breeding programs aiming to improve growth and disease resistance. However, these have been based primarily on phenotypic measurements and omit potential gains by integrating genetic selection into existing breeding programs. Such integration of genetic information has been hindered by the limited available genomic resources, background genetic parameters and knowledge on the genetic architecture of commercial traits for L. vannamei. This study describes the development of a comprehensive set of genomic gene-based resources including the identification and validation of 234,452 putative single nucleotide polymorphisms in-silico, of which 8,967 high value SNPs were incorporatedm into a commercially available Illumina Infinium ShrimpLD-24 v1.0 genotyping array. A framework genetic linkage map was constructed and combined with locus ordering by disequilibrium methodology to generate an integrated genetic map containing 4,817 SNPs, which spanned a total of 4552.5 cM and covered an estimated 98.12% of the genome. These gene-based genomic resources will not only be valuable for identifying regions underlying important L. vannamei traits, but also as a foundational resource in comparative and genome assembly activities

Amblyomma hebraeum is the predominant tick species on goats in the Mnisi Community Area of Mpumalanga Province South Africa and is co-infected with Ehrlichia ruminantium and Rickettsia africae

BACKGROUND : In sub-Saharan Africa, Amblyomma ticks are vectors of heartwater disease in domestic ruminants, caused by the rickettsial pathogen Ehrlichia ruminantium. Immature tick stages often bite humans, whereby they act as vectors of tick-bite fever caused by Rickettsia africae. Moreover, Amblyomma ticks cause damage to livestock due to their feeding behaviour. In South Africa, we studied the abundance of Amblyomma hebraeum ticks on goats of emerging farmers in Mpumalanga Province. A selected number of A. hebraeum nymphs and adult ticks was tested for co-infection with E. ruminantium and R. africae. METHODS : A total of 630 indigenous goats, belonging to farmers in the Mnisi Community area, were examined for ticks in 2013 and 2014. All ticks were identified, and a selected number was tested by PCR with reverse line blot hybridisation. RESULTS : In total, 13,132 ticks were collected from goats distributed over 17 different households. Amblyomma hebraeum was the predominant species, followed by R. microplus. Rhipicephalus appendiculatus, R. simus and R. zambeziensis were also identified. Amblyomma hebraeum was present throughout the year, with peak activity of adults in summer (November) and nymphs in winter (July). The ratio between adults and nymphs ranged from 1:2.7 in summer to 1:55.1 in winter. The mean prevalence of infection for E. ruminantium by PCR/RLB in adult ticks was 17.4% (31/178), whereas 15.7% (28/178) were infected with R. africae. In pooled nymphs, 28.4% were infected with E. ruminantium and 38.8% carried R. africae infection. Co-infections of E. ruminantium and R. africae in adult and pooled nymphal ticks were 3.9% (7/178) and 10% (14.9), respectively. Lameness of goats due to predilection of ticks for the interdigital space of their feet was observed in 89% of the households. CONCLUSIONS : Goats act as important alternative hosts for cattle ticks, which underscored the necessity to include goats in control programs. It is suggested to use acaricide-impregnated leg-bands as a sustainable method to kill ticks and prevent lameness in goats. The challenge of goats by considerable numbers of E. ruminantium-infected ticks is a major obstacle for upgrading the indigenous goat breeds. Humans may be at risk to contract tick-bite fever in this area.The Faculty of Veterinary Medicine of Utrecht University and the Faculty of Veterinary Science of the University of Pretoria.http://www.parasitesandvectors.comhj2020Veterinary Tropical Disease

Amblyomma hebraeum is the predominant tick species on goats in the Mnisi Community Area of Mpumalanga Province South Africa and is co-infected with Ehrlichia ruminantium and Rickettsia africae

BACKGROUND : In sub-Saharan Africa, Amblyomma ticks are vectors of heartwater disease in domestic ruminants, caused by the rickettsial pathogen Ehrlichia ruminantium. Immature tick stages often bite humans, whereby they act as vectors of tick-bite fever caused by Rickettsia africae. Moreover, Amblyomma ticks cause damage to livestock due to their feeding behaviour. In South Africa, we studied the abundance of Amblyomma hebraeum ticks on goats of emerging farmers in Mpumalanga Province. A selected number of A. hebraeum nymphs and adult ticks was tested for co-infection with E. ruminantium and R. africae. METHODS : A total of 630 indigenous goats, belonging to farmers in the Mnisi Community area, were examined for ticks in 2013 and 2014. All ticks were identified, and a selected number was tested by PCR with reverse line blot hybridisation. RESULTS : In total, 13,132 ticks were collected from goats distributed over 17 different households. Amblyomma hebraeum was the predominant species, followed by R. microplus. Rhipicephalus appendiculatus, R. simus and R. zambeziensis were also identified. Amblyomma hebraeum was present throughout the year, with peak activity of adults in summer (November) and nymphs in winter (July). The ratio between adults and nymphs ranged from 1:2.7 in summer to 1:55.1 in winter. The mean prevalence of infection for E. ruminantium by PCR/RLB in adult ticks was 17.4% (31/178), whereas 15.7% (28/178) were infected with R. africae. In pooled nymphs, 28.4% were infected with E. ruminantium and 38.8% carried R. africae infection. Co-infections of E. ruminantium and R. africae in adult and pooled nymphal ticks were 3.9% (7/178) and 10% (14.9), respectively. Lameness of goats due to predilection of ticks for the interdigital space of their feet was observed in 89% of the households. CONCLUSIONS : Goats act as important alternative hosts for cattle ticks, which underscored the necessity to include goats in control programs. It is suggested to use acaricide-impregnated leg-bands as a sustainable method to kill ticks and prevent lameness in goats. The challenge of goats by considerable numbers of E. ruminantium-infected ticks is a major obstacle for upgrading the indigenous goat breeds. Humans may be at risk to contract tick-bite fever in this area.The Faculty of Veterinary Medicine of Utrecht University and the Faculty of Veterinary Science of the University of Pretoria.http://www.parasitesandvectors.comhj2020Veterinary Tropical Disease

Palliative care implementation in long-term care facilities : European Association for Palliative Care white paper

Objectives: The number of older people dying in long-term care facilities (LTCFs) is increasing globally, but care quality may be variable. A framework was developed drawing on empirical research findings from the Palliative Care for Older People (PACE) study and a scoping review of literature on the implementation of palliative care interventions in LTCFs. The PACE study mapped palliative care in LTCFs in Europe, evaluated quality of end-of-life care and quality of dying in a cross-sectional study of deceased residents of LTCFs in 6 countries, and undertook a cluster-randomized control trial that evaluated the impact of the PACE Steps to Success intervention in 7 countries. Working with the European Association for Palliative Care, a white paper was written that outlined recommendations for the implementation of interventions to improve palliative and end-of-life care for all older adults with serious illness, regardless of diagnosis, living in LTCFs. The goal of the article is to present these key domains and recommendations. Design: Transparent expert consultation. Setting: International experts in LTCFs. Participants: Eighteen (of 20 invited) international experts from 15 countries participated in a 1-day face-to-face Transparent Expert Consultation (TEC) workshop in Bern, Switzerland, and 21 (of 28 invited) completed a follow-up online survey. Methods: The TEC study used (1) a face-to-face workshop to discuss a scoping review and initial recommendations and (2) an online survey. Results: Thirty recommendations about implementing palliative care for older people in LTCFs were refined during the TEC workshop and, of these, 20 were selected following the survey. These 20 recommendations cover domains at micro (within organizations), meso (across organizations), and macro (at national or regional) levels addressed in 3 phases: establishing conditions for action, embedding in everyday practice, and sustaining ongoing change. Conclusions and implications: We developed a framework of 20 recommendations to guide implementation of improvements in palliative care in LTCFs. (C) 2020 AMDA - The Society for Post-Acute and Long-Term Care Medicine

PORTEC-4a: International randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer

Background Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with highintermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients’ risk of recurrence based on molecular tumor characteristics. Primary objectives To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecularintegrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy Study hypothesis Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant t

Quantitative genotyping to estimate genetic contributions to pooled samples and genetic merit of the contributing entities

Genotyping required to track family membership in aquaculture breeding programs is reduced dramatically by estimating the contributions of different families to pooled samples of tissue. This approach is relevant to widely differing scenarios involving animals, plants, and microbes. For the family membership scenario, SNP markers are genotyped for the contributing families’ parents, and quantitatively genotyped to estimate allele frequencies within the mixed-family pooled tissue. Results are used to infer proportional contributions of the different families to the pool. Different computational strategies were tested for bias and sampling error. A correlation of 99% between estimated and true genetic contributions was achieved using 20 (50) randomly chosen SNPs at a standard error of allele frequency estimates of 0.01 (0.02). Optimal grouping of families and choice of markers further increases performance markedly. Trait means and distributions of families can be quite accurately estimated by tissue sampling across the range of trait values

Occurrence and timing of advance care planning in persons with dementia in general practice: Analysis of linked electronic health records and administrative data

Background: Advance care planning (ACP) is a process of communication in which patients and family caregivers discuss preferences for future care with the healthcare team. For persons with dementia, it is crucial to timely engage in ACP. Therefore, we study ACP in dementia using electronic health record data. This study aims to determine how often ACP conversations are recorded, analyze time from dementia diagnosis until the first recorded conversation and time from the first recorded conversation to death, and analyze which factors are associated with the timing of ACP. Methods: Electronic records of 15,493 persons with dementia in Dutch general practice between 2008 and 2016 were linked to national administrative databases. ACP conversations and indicators of health deficits to determine frailty were obtained from electronic records coded with the International Classification of Primary Care. Socio-demographic characteristics were derived from the national population registry managed by Statistics Netherlands. Date of death was derived from the Personal Records Database (2008–2018). Results: ACP was recorded as such as 22 (95% CI, 20–23) first conversations per 1,000 person-years of follow-up. The hazard ratio (HR) for the first conversation increased every year after dementia diagnosis, from 0.01 in the first year to 0.07 in the 7th and 8th year after diagnosis. Median time from a first conversation to death was 2.57 years (95% CI, 2.31–2.82). Migrant status [non-Western vs. Western (HR 0.31, 95% CI, 0.15–0.65)] was significantly associated with a longer time from dementia diagnosis to the first conversation. Being pre-frail (HR 2.06, 95% CI, 1.58–2.69) or frail (HR 1.40, 95% CI, 1.13–1.73) vs. non-frail was significantly associated with a shorter time from dementia diagnosis to the first ACP conversation. Conclusion: ACP conversations in Dutch general practice were rare for persons with dementia, or was rarely recorded as such. In particular among persons with a non-Western migration background and those who are non-frail, it started long after diagnosis. We advise further research into public health and practical strategies to engage persons with dementia with a non-Western migration background and non-frail persons early in the disease trajectory in ACP

MET expression during prostate cancer progression

Tyrosine-kinase inhibitors of the hepatocyte growth factor receptor MET are under investigation for the treatment of hormone-refractory prostate cancer (HRPC) metastasis. Analysis of MET protein expression and genetic alterations might contribute to therapeutic stratification of prostate cancer patients. Our objective was to investigate MET on protein, DNA and RNA level in clinical prostate cancer at various stages of progression. Expression of MET was analyzed in hormone-naive primary prostate cancers (N=481), lymph node (N=40) and bone (N=8) metastases, as well as HRPC (N=54) and bone metastases (N=15). MET protein expression was analyzed by immunohistochemistry (D1C2 C-terminal antibody). MET mRNA levels and MET DNA copy numbers were determined by in situ hybridization. None of the hormone-naive primary prostate cancer or lymph node metastases demonstrated MET protein or mRNA expression. In contrast, MET protein was expressed in 12/52 (23%) evaluable HRPC resections. RNA in situ demonstrated cytoplasmic signals in 14/54 (26%) of the HRPC patients, and was associated with MET protein expression (p=0.025, chi(2)), in absence of MET amplification or polysomy. MET protein expression was present in 7/8 (88%) hormone-naive and 10/15 (67%) HRPC bone metastases, without association of HRPC (p=0.37; chi(2)), with MET polysomy in 8/13 (61%) evaluable cases. In conclusion, MET was almost exclusively expressed in HRPC and prostate cancer bone metastasis, but was not related to MET amplification or polysomy. Evaluation of MET status could be relevant for therapeutic stratification of late stage prostate cancer

Occurrence and Timing of Advance Care Planning in Persons With Dementia in General Practice: Analysis of Linked Electronic Health Records and Administrative Data

Background: Advance care planning (ACP) is a process of communication in which patients and family caregivers discuss preferences for future care with the healthcare team. For persons with dementia, it is crucial to timely engage in ACP. Therefore, we study ACP in dementia using electronic health record data. This study aims to determine how often ACP conversations are recorded, analyze time from dementia diagnosis until the first recorded conversation and time from the first recorded conversation to death, and analyze which factors are associated with the timing of ACP. Methods: Electronic records of 15,493 persons with dementia in Dutch general practice between 2008 and 2016 were linked to national administrative databases. ACP conversations and indicators of health deficits to determine frailty were obtained from electronic records coded with the International Classification of Primary Care. Socio-demographic characteristics were derived from the national population registry managed by Statistics Netherlands. Date of death was derived from the Personal Records Database (2008–2018). Results: ACP was recorded as such as 22 (95% CI, 20–23) first conversations per 1,000 person-years of follow-up. The hazard ratio (HR) for the first conversation increased every year after dementia diagnosis, from 0.01 in the first year to 0.07 in the 7th and 8th year after diagnosis. Median time from a first conversation to death was 2.57 years (95% CI, 2.31–2.82). Migrant status [non-Western vs. Western (HR 0.31, 95% CI, 0.15–0.65)] was significantly associated with a longer time from dementia diagnosis to the first conversation. Being pre-frail (HR 2.06, 95% CI, 1.58–2.69) or frail (HR 1.40, 95% CI, 1.13–1.73) vs. non-frail was significantly associated with a shorter time from dementia diagnosis to the first ACP conversation. Conclusion: ACP conversations in Dutch general practice were rare for persons with dementia, or was rarely recorded as such. In particular among persons with a non-Western migration background and those who are non-frail, it started long after diagnosis. We advise further research into public health and practical strategies to engage persons with dementia with a non-Western migration background and non-frail persons early in the disease trajectory in ACP

The identification of a major sex QTL in the white-leg shrimp, Litopenaeus vannamei

The white-leg shrimp, Litopenaeus vannamei, is the most widely farmed shrimp species globally. In recent years, interest in developing selective breeding programs and identifying the mechanisms controlling sex determination in L. vannamei has increased in the hope that improvements can be made on productivity efficiency. L. vannamei exhibits sexual dimorphism whereby females grow faster and larger than males. The discovery of novel genes or regions involved in sex-determination within L. vannamei would allow farmers to exploit this natural sexual dimorphism to enhance productivity. This study utilised a revised genetic linkage map for L. vannamei (whereby linkage groups 42 and 44 were merged as LG42.44) to conduct QTL and GWAS analyses from 20 full-sib families to identify one major QTL across 20 mapping families. The QTL was identified on LG42.44 and had a 95% confidence interval of 0–12.7 cM across all families (428 progeny). This region explained from 79.4–100% of the phenotypic variation. Independent genome wide association studies (GWAS) across 1952 individuals identified 11 significant SNPs (in high linkage disequilibrium) located on LG42.44 (0–12.7 cM) with one SNP 5790_511 with an extreme -log10 (P-value) of 294. For SNP 5790_511, 93% of homozygous genotypes were males and 97.6% of heterozygous were females indicating relatively close proximity of this SNP to the sex-determination locus. The SNP heritability for the sex phenotype was 0.84 +-0.007 suggesting a strong genetic basis of sex determination. A previously described feminisation gene, Pvfem-1, characterised as being involved in male and female gonad differentiation, was annotated to LG16; however no significant associations or QTL for sex were identified at this region in this study. Even though no known sex-determination genes could be identified under the QTL region of LG42.44, the large proportion of phenotypic variance explained by the significantly associated markers underlying the QTL region is promising and highlights this region for further fine mapping and sex-determination gene discovery efforts