A complex receptor locus confers responsiveness to necrosis and ethylene-inducing like peptides in Brassica napus.

Brassica crops are susceptible to diseases which can be mitigated by breeding for resistance. MAMPs (microbe-associated molecular patterns) are conserved molecules of pathogens that elicit host defences known as pattern-triggered immunity (PTI). Necrosis and Ethylene-inducing peptide 1-like proteins (NLPs) are MAMPs found in a wide range of phytopathogens. We studied the response to BcNEP2, a representative NLP from Botrytis cinerea, and showed that it contributes to disease resistance in Brassica napus. To map regions conferring NLP response, we used the production of reactive oxygen species (ROS) induced during PTI across a population of diverse B. napus accessions for associative transcriptomics (AT), and bulk segregant analysis (BSA) on DNA pools created from a cross of NLP-responsive and non-responsive lines. In silico mapping with AT identified two peaks for NLP responsiveness on chromosomes A04 and C05 whereas the BSA identified one peak on A04. BSA delimited the region for NLP-responsiveness to 3 Mbp, containing ~245 genes on the Darmor-bzh reference genome and four co-segregating KASP markers were identified. The same pipeline with the ZS11 genome confirmed the highest-associated region on chromosome A04. Comparative BLAST analysis revealed unannotated clusters of receptor-like protein (RLP) homologues on ZS11 chromosome A04. However, no specific RLP homologue conferring NLP response could be identified. Our results also suggest that BR-SIGNALLING KINASE1 may be involved with modulating the NLP response. Overall, we demonstrate that responsiveness to NLP contributes to disease resistance in B. napus and define the associated genomic location. These results can have practical application in crop improvement.

Project EPIC (Empowering People to Independence in COPD): Study protocol for a hybrid effectiveness-implementation pilot randomized controlled trial of telephonic, geriatrics-palliative care nurse-coaching in older adults with COPD and their family caregivers.

BACKGROUND: EPIC (Empowering People to Independence in COPD) is a geriatric-palliative care telephonic, nurse coach intervention informed by Baltes' Theory of Successful Aging and adapted from the ENABLE (Educate, Nurture, Advise, Before Life Ends) intervention. EPIC, focused on improving independence, mobility, well-being, and COPD symptoms, has undergone formative and summative evaluation for adults with COPD. METHODS: The primary study aim is to assess the refined EPIC intervention's feasibility and acceptability via a pilot hybrid effectiveness-implementation randomized control trial in community-dwelling older adults with moderate to severe COPD and their family caregivers. The secondary aim is to explore the impact of EPIC on patient and caregiver outcomes. Older adults with COPD and their family caregivers (target N = 60 dyads) will be randomized to EPIC (intervention) or usual COPD care (control). EPIC includes six patient and four family caregiver weekly, telephone-based nurse coach sessions using a manualized curriculum (Charting Your Course), plus three monthly follow-up calls. Feasibility will be measured as completion of EPIC intervention and trial components (e.g., recruitment, retention, data collection). Acceptability will be evaluated using satisfaction surveys and post-study feedback interviews. A blinded data collector will assess exploratory outcomes (e.g., Life-Space mobility, quality of life, caregiver burden, emotional symptoms, loneliness, cognitive impairment, functional status, healthcare utilization) at baseline, 12, and 24 weeks. DISCUSSION: This intervention fills a gap in addressing the geriatrics and palliative care needs and equity for adults with COPD and their family caregivers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05040386.

Pathogen lifestyle determines host genetic signature of quantitative disease resistance loci in oilseed rape (Brassica napus).

KEY MESSAGE: Using associative transcriptomics, our study identifies genes conferring resistance to four diverse fungal pathogens in crops, emphasizing key genetic determinants of multi-pathogen resistance. Crops are affected by several pathogens, but these are rarely studied in parallel to identify common and unique genetic factors controlling diseases. Broad-spectrum quantitative disease resistance (QDR) is desirable for crop breeding as it confers resistance to several pathogen species. Here, we use associative transcriptomics (AT) to identify candidate gene loci associated with Brassica napus constitutive QDR to four contrasting fungal pathogens: Alternaria brassicicola, Botrytis cinerea, Pyrenopeziza brassicae, and Verticillium longisporum. We did not identify any shared loci associated with broad-spectrum QDR to fungal pathogens with contrasting lifestyles. Instead, we observed QDR dependent on the lifestyle of the pathogen-hemibiotrophic and necrotrophic pathogens had distinct QDR responses and associated loci, including some loci associated with early immunity. Furthermore, we identify a genomic deletion associated with resistance to V. longisporum and potentially broad-spectrum QDR. This is the first time AT has been used for several pathosystems simultaneously to identify host genetic loci involved in broad-spectrum QDR. We highlight constitutive expressed candidate loci for broad-spectrum QDR with no antagonistic effects on susceptibility to the other pathogens studies as candidates for crop breeding. In conclusion, this study represents an advancement in our understanding of broad-spectrum QDR in B. napus and is a significant resource for the scientific community.

A transcriptomic time-series reveals differing trajectories during pre-floral development in the apex and leaf in winter and spring varieties of Brassica napus.

Oilseed rape (Brassica napus) is an important global oil crop, with spring and winter varieties grown commercially. To understand the transcriptomic differences between these varieties, we collected transcriptomes from apex and leaf tissue from a spring variety, Westar, and a winter variety, Tapidor, before, during, and after vernalisation treatment, until the plants flowered. Large transcriptomic differences were noted in both varieties during the vernalisation treatment because of temperature and day length changes. Transcriptomic alignment revealed that the apex transcriptome reflects developmental state, whereas the leaf transcriptome is more closely aligned to the age of the plant. Similar numbers of copies of genes were expressed in both varieties during the time series, although key flowering time genes exhibited expression pattern differences. BnaFLC copies on A2 and A10 are the best candidates for the increased vernalisation requirement of Tapidor. Other BnaFLC copies show tissue-dependent reactivation of expression post-cold, with these dynamics suggesting some copies have retained or acquired a perennial nature. BnaSOC1 genes, also related to the vernalisation pathway, have expression profiles which suggest tissue subfunctionalisation. This understanding may help to breed varieties with more consistent or robust vernalisation responses, of special importance due to the milder winters resulting from climate change.

The impact of an integrated early palliative care telehealth intervention on the quality of life of heart failure patients: a randomized controlled feasibility study.

BACKGROUND: While palliative care for patients with heart failure has gained global attention, in Iran most palliative care interventions have focused only on cancer patients. The purpose of this study is to determine the feasibility and acceptability of a telehealth palliative care intervention to improve the quality of life in patients with heart failure in Iran. METHODS: This single-site, pilot randomized controlled trial of a telehealth palliative care intervention versus usual care was conducted on patients with New York Heart Association class II/III heart failure recruited from a heart failure clinic in Iran. Under the supervision of a nurse interventionist, intervention participants received 6 weekly educational webinars and concurrent WhatsApp® group activities, with 6 weeks of follow-up. Feasibility was assessed by measuring recruitment, attrition, and questionnaire completion rates; acceptability was assessed via telephone interviews asking about satisfaction and attitudes. Secondary outcomes measured at baseline and 6 weeks included quality of life (PKCCQ and FACIT-Pal-14), anxiety and depression (HADS), and emergency department visits. RESULTS: We recruited and randomized 50 patients (mean age 47.5 years, 60% men). Among those approached for consent, 66% of patients agreed to participate and total study attrition was 10%. Also 68% of patients successfully completed at least 4 out of the 6 webinar sessions. Acceptability: 78% of patient participants expressed willingness to participate in the present study again or recommend other patients to participate. There was a trend towards improvement in anxiety and depression scores in the intervention group though the study was not powered to detect a statistical difference. CONCLUSION: This nurse-led, early telehealth-palliative care intervention demonstrated evidence of feasibility, acceptability, and potential improvement on quality of life in patients with heart failure in Iran. TRIAL REGISTRATION: The study was registered at the Iranian Registry of Clinical Trials (IRCT) at 14 November, 2021, and can be found on the Iranian Registry of Clinical Trials Platform. IRCT registration number: IRCT20100725004443N29.

Restricted life-space mobility impacts physical but not mental quality of life in older cancer survivors.

BACKGROUND: Older cancer survivors often value quality of life (QOL) over survival. Life-space mobility (LSM), defined as the individual's spatial geographic mobility range, is an important QOL indicator in older adults with chronic illnesses; however, this relationship is unexplored in older cancer survivors. METHODS: We examined the longitudinal associations and causal relationships between LSM and QOL in 153 older cancer survivors (≥65 years) from the University of Alabama at Birmingham (UAB) Study of Aging. LSM was assessed using the UAB Life-Space Assessment-Composite score (LSA-C), and QOL was assessed by the SF-12 Mental Component Score (MCS12) and Physical Component Score (PCS12) at 0 (study entry), 6, 18, 36, 54, and 72 months. We examined the causal relationship between LSM and QOL using a cross-lagged panel model (CLPM). RESULTS: The cohort (n = 153) was 76 years old on average and predominantly White (58%), female (58%), and married (55%). Longitudinal analyses found LSM decreased over time (p < 0.0001), and this decrease was associated with decreased QOL (PCS12, p < 0.0001, MCS12, p < 0.0001). In the CLPM causal analysis, lower LSM resulted in worse PCS12 (p < 0.001), but not worse MSC12. CONCLUSIONS: Restricted LSM resulted in worse physical QOL over 72 months in a sample of 153 older cancer survivors. Developing and evaluating interventions to preserve greater LSM could be a promising approach to improving QOL.

Exploring the health-related decision-making experiences of people with chronic kidney disease and their caregivers: A qualitative study.

BACKGROUND: This study aimed to explore the decision-making experience of patients with chronic kidney disease (CKD) and their caregivers. METHODS: This was a qualitative descriptive study of the decision-making experiences of individuals with stage 3-end-stage CKD and their family caregivers. One-on-one, semistructured interviews were conducted using a guide developed and approved by a community advisory group. Data were analyzed using thematic analysis. RESULTS: Three themes were identified: (1) decisions triggered by declining health and broad in scope, (2) challenges to decision-making and (3) factors influencing decision-making. Participants' experiences with health-related decision-making demonstrated that decisions were triggered when health declined. Yet, decisions that impact disease progression were being made in stage 3. Decision-making was made difficult due to lack of information, complex co-morbidities, and poor resource utilization. However, the structure and nature of the medical appointment, supportive caregivers, and resources served to remove challenges. CONCLUSION: Decision-support interventions must train patients and caregivers to be empowered participants in answer-seeking behaviours upstream of advanced illness. PUBLIC CONTRIBUTIONS: This work was conducted in full collaboration with a community advisory board consisting of patients with CKD, caregivers and clinicians. These members are noted in the acknowledgement section, and those who worked with the team to develop the interview guide, study protocols, and manuscript preparation are included as authors. As part of their role, advisory members met monthly, providing input on recruitment, study progress, inclusion of diverse voices and added relevance to study findings.

Effectiveness of a comprehensive tele-empowerment programme on self-care behaviours, uncertainty and readmission of patients with heart failure: protocol for a randomised controlled trial.

INTRODUCTION: Heart failure (HF) as a long-term clinical syndrome is associated with inadequate self-care behaviours, a feeling of uncertainty and frequent hospitalisation. In recent years, empowerment has evolved for improving chronic disease management. Nevertheless, there is a lack of studies investigating remote care interventions such as a tele-empowerment programme in patients with HF. Therefore, this protocol proposes a randomised controlled trial which aims to evaluate the effectiveness of a comprehensive tele-empowerment programme on self-care behaviours, uncertainty and readmission in patients with HF. METHODS AND ANALYSIS: The study is a double-arm and parallel-group randomised controlled trial in which a 10-week intervention, including 6 weeks of a comprehensive tele-empowerment programme and 4 weeks of follow-up, will be compared with usual care. A total of 96 eligible patients with HF will be recruited and randomly assigned to the intervention or control group. The patients in the intervention group will join virtual groups and receive the five-step tele-empowerment programme through the internet. The primary outcomes include self-care behaviours and uncertainty which will be measured with valid instruments at baseline and 10th week. The secondary outcome is the number of patients' hospital readmissions and will be assessed at the end of the study. Descriptive statistics will be used to describe variables. According to the types of variables, appropriate statistical tests including two-sample t-tests, Χ2, analysis of covariance or linear regression will be performed. In addition, standardised intervention effect sizes will be calculated for each outcome. ETHICS AND DISSEMINATION: The trial has been approved by the Research Ethics Committee of School of Nursing and Midwifery & Rehabilitation at Tehran University of Medical Sciences. In this study, written consent will be obtained from all participants. The results will be presented to representative groups and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: Iranian Registry of Clinical Trials (IRCT20100725004443N30).

Decision support training for advanced cancer family caregivers: Study protocol for the CASCADE factorial trial.

BACKGROUND: Patients with advanced cancer face numerous decisions when diagnosed and often receive decision support from family caregivers. The CASCADE (CAre Supporters Coached to be Adept DEcision partners) factorial trial intervention aims to train caregivers in skills to provide effective decision support to patients and identify most effective intervention components. METHODS: This is a 2-site, single-blind, 24 factorial trial to test components of the CASCADE decision support training intervention for family caregivers of patients with newly-diagnosed advanced cancer delivered by specially-trained, telehealth, palliative care lay coaches over 24 weeks. Family caregivers (target N = 352) are randomly assigned to one of 16 combinations of four components with two levels each: 1) psychoeducation on effective decision partnering principles (1 vs. 3 sessions); 2) decision support communication training (1 session vs. none); 3) Ottawa Decision Guide training (1 session vs. none) and 4) monthly follow-up (1 call vs. calls for 24 weeks). The primary outcome is patient-reported decisional conflict at 24 weeks. Secondary outcomes include patient distress, healthcare utilization, caregiver distress, and quality of life. Mediators and moderators (e.g., sociodemographics, decision self-efficacy, social support) will be explored between intervention components and outcomes. Results will be used to build two versions of CASCADE: one with only effective components (d ≥ 0.30) and another optimized for scalability and cost. DISCUSSION: This protocol describes the first factorial trial, informed by the multiphase optimization strategy, of a palliative care decision-support intervention for advanced cancer family caregivers and will address the field's need to identify effective components that support serious illness decision-making. TRIAL REGISTRATION: NCT04803604.

Evaluation of cardiovascular and cerebrovascular control mechanisms in postural orthostatic tachycardia syndrome via conditional transfer entropy: the impact of the respiratory signal type.

Objective.Closed loop cardiovascular (CV) and cerebrovascular (CBV) variability interactions are assessed via transfer entropy (TE) from systolic arterial pressure (SAP) to heart period (HP) and vice versa and from mean arterial pressure (MAP) to mean cerebral blood velocity (MCBv) and vice versa. This analysis is exploited to assess the efficiency of baroreflex and cerebral autoregulation. This study aims at characterizing CV and CBV controls in postural orthostatic tachycardiac syndrome (POTS) subjects experiencing exaggerated sympathetic response during orthostatic challenge via unconditional TE and TE conditioned on respiratory activity (R).Approach.In 18 healthy controls (age: 28 ± 13 yrs; 5 males, 13 females) and 15 POTS individuals (age: 29 ± 11 yrs; 3 males, 12 females) we acquired beat-to-beat variability of HP, SAP, MAP and MCBv and twoRsignals, namely respiratory chest movement (RCM) and capnogram (CAP). Recordings were made at sitting rest and during active standing (STAND). TE was computed via vector autoregressive approach.Main results.We found that: (i) when assessing CV interactions, the increase of the TE from SAP to HP during STAND, indicating baroreflex activation, is detected solely when conditioning on RCM; (ii) when assessing CBV interactions, the impact ofRon the TE computation is negligible; (iii) POTS shows baroreflex impairment during STAND; (iv) POTS exhibits a normal CBV response to STAND.Significance.TE is useful for detecting the impairment of specific regulatory mechanisms in POTS. Moreover, using differentRsignals highlights the sensitivity of CV and CBV controls to specificRaspects.

How Values Are Discussed, Reflected Upon, and Acted On by Patients and Family Caregivers in the Context of Heart Failure: A Scoping Review.

PURPOSE: Values are critical to how individuals make decisions and cope, yet the values of heart failure (HF) patients and their family caregivers (FCGs) remain understudied. We sought to report the state of the science on how values are discussed, reflected upon, and acted on by patients with HF, their FCGs, or both related to health-related decision making and coping. METHOD: A scoping review was conducted of empirical studies using the following keywords: "heart failure," "values," "decision-making," and "coping." PubMed, PsycINFO, and Scopus were searched from inception to June 2022 in English. Included articles reported values as a key finding (outcome/theme) in their abstract. RESULTS: Of 448 articles screened for eligibility, 16 met the inclusion criteria. Twelve articles reported findings addressing patient values, 3 addressed patient and FCG values, and 1 addressed FCG values. Values were reported to influence patient self-care behaviors and left ventricular assist device (LVAD) implantation decisions, although their prioritization varied across time and contexts. When prioritized values conflicted with recommended self-care activities, some patients modified their approach to achieving the value. Others modified or abandoned tasks in favor of the value and accompanying goals. Low motivation and alignment between unhealthy behaviors and values often led to nonadherent decisions. Five of 8 articles focusing on cardiac devices reported patient survival as the most prioritized value during implantation decisions. FCG values were rarely reported or evaluated separately from patient values. Patients leveraged several coping strategies, although the processes through which values affected coping was not described. CONCLUSIONS: Prioritized values influenced HF-related decisions, including self-care and LVAD implantation. While several articles reported on coping and values, none described processes through which values affect coping, which highlights a research gap. HIGHLIGHTS: Family caregiver values were rarely reported or evaluated separately from patient values, highlighting a gap in the literature.

The feasibility and acceptability of an early tele-palliative care intervention to improve quality of life in heart failure patients in Iran: A protocol for a randomized controlled trial.

Background: Heart failure (HF) has become a global health problem that has affected the quality of life of millions of people. One approach to improving patients' quality of life (QoL) with chronic diseases such as HF is palliative care. In Iran, the bulk of palliative care research is directed to patients with cancer, with the primary focus on the physical aspect rather than the psychosocial and spiritual aspects of palliative care. To address this gap, this study aims to determine the feasibility and acceptability of this early tele-palliative care intervention to improve quality of life in heart failure patients in Iran. Methods: The early tele-palliative care versus usual care study is designed as a single-centre, randomised, feasibility trial of 50 patients with heart failure aged 18 to 65 and clinician-determined New York Heart Association class II/III or American College of Cardiology stage B/C HF, recruited in Imam Khomeini Hospital Complex, Tehran, Iran. This intervention contains 6 weekly educational webinars and concurrent WhatsApp® group activities. Program feasibility and acceptability will be assessed by measuring the recruitment, attrition, and questionnaire completion rates; satisfaction and attitudes about the intervention will be measured via a telephone-based interviews. Secondary outcomes of Qol, mood status and number of emergency department visits will be measured with validated instruments. Participants in both groups will be followed up for 6 weeks, and the measures will be re-administered. Appropriate statistical tests will be used to analyse the data. Conclusion: This is the first early tele-palliative care intervention designed for heart failure patients in Iran. The intervention has been developed by a multidisciplinary team of academic and clinical professionals with patient stakeholder input to create a rigorous and culturally responsive approach for palliative care delivery for heart failure patients in Iran. Trial registration: IRCT registration number - IRCT20100725004443N29.

Novel gene loci associated with susceptibility or cryptic quantitative resistance to Pyrenopeziza brassicae in Brassica napus.

KEY MESSAGE: Quantitative disease resistance (QDR) controls the association of the light leaf spot pathogen with Brassica napus; four QDR loci that were in linkage disequilibrium and eight gene expression markers were identified. Quantitative disease resistance (QDR) can provide durable control of pathogens in crops in contrast to resistance (R) gene-mediated resistance which can break down due to pathogen evolution. QDR is therefore a desirable trait in crop improvement, but little is known about the causative genes, and so it is difficult to incorporate into breeding programmes. Light leaf spot, caused by Pyrenopeziza brassicae, is an important disease of oilseed rape (canola, Brassica napus). To identify new QDR gene loci, we used a high-throughput screening pathosystem with P. brassicae on 195 lines of B. napus combined with an association transcriptomics platform. We show that all resistance against P. brassicae was associated with QDR and not R gene-mediated. We used genome-wide association analysis with an improved B. napus population structure to reveal four gene loci significantly (P = 0.0001) associated with QDR in regions showing linkage disequilibrium. On chromosome A09, enhanced resistance was associated with heterozygosity for a cytochrome P450 gene co-localising with a previously described locus for seed glucosinolate content. In addition, eight significant gene expression markers with a false discovery rate of 0.001 were associated with QDR against P. brassicae. For seven of these, expression was positively correlated with resistance, whereas for one, a HXXXD-type acyl-transferase, negative correlation indicated a potential susceptibility gene. The study identifies novel QDR loci for susceptibility and resistance, including novel cryptic QDR genes associated with heterozygosity, that will inform future crop improvement.

Project EPIC (Early Palliative Care In COPD): A Formative and Summative Evaluation of the EPIC Telehealth Intervention.

CONTEXT: Early, concurrent palliative care interventions in chronic obstructive pulmonary disease (COPD) are limited. Project EPIC (Early Palliative Care In COPD) is a multiphase mixed methods study working to fill this gap. OBJECTIVES: To conduct a formative and summative evaluation of EPIC, a telephonic nurse coach-led early palliative care intervention for COPD adapted from the ENABLE© intervention in cancer. METHODS: Phase I Formative Evaluation: Patients with moderate-to-very-severe COPD, family caregivers, and pulmonary and palliative care clinicians rated the acceptability and feasibility of EPIC (≥4 out of five on a Likert-scale survey). Phase II Summative Evaluation: Patients and family caregivers in Phase I participated in a pilot of the three month EPIC prototype to evaluate intervention and data collection feasibility (≥70% completion) and to seek qualitative feedback. RESULTS: Phase I Formative Evaluation: Patients (n=10), family caregivers (n=10), pulmonary clinicians (n=6), and palliative care clinicians (n=6) found EPIC acceptable and feasible to support adaptation, while priority early palliative care needs in COPD from our prior research mapped well to the EPIC prototype. Phase II Summative Evaluation: Patients (n=5; ages 49-72, 40% moderate COPD, 40% Black) and their family caregivers (n=5; ages 51-73, 40% Black) completed 100% of EPIC prototype components, including weekly telephone sessions, a one month follow-up call, Advance Directive, palliative care clinic attendance, and 95% of monthly phone data collection sessions. Feedback from participants about EPIC was all positive. CONCLUSION: EPIC was acceptable and feasible in patients with COPD and their family caregivers. Larger feasibility and effectiveness trials are warranted.

African American Recruitment in Early Heart Failure Palliative Care Trials: Outcomes and Comparison With the ENABLE CHF-PC Randomized Trial.

BACKGROUND: Palliative care trial recruitment of African Americans (AAs) is a formidable research challenge. OBJECTIVES: Examine AA clinical trial recruitment and enrollment in a palliative care randomized controlled trial (RCT) for heart failure (HF) patients and compare patient baseline characteristics to other HF palliative care RCTs. METHODS: This is a descriptive analysis the ENABLE CHF-PC (Educate, Nurture, Advise, Before Life Ends: Comprehensive Heartcare for Patients and Caregivers) RCT using bivariate statistics to compare racial and patient characteristics and differences through recruitment stages. We then compared the baseline sample characteristics among three palliative HF trials. RESULTS: Of 785 patients screened, 566 eligible patients with NYHA classification III-IV were approached; 461 were enrolled and 415 randomized (AA = 226). African Americans were more likely to consent than Caucasians (55%; P FDR = .001), were younger (62.7 + 8; P FDR = .03), had a lower ejection fraction (39.1 + 15.4; PFDR = .03), were more likely to be single (P FDR = .001), and lack an advanced directive (16.4%; P FDR < .001). AAs reported higher goal setting (3.3 + 1.3; P FDR = .007), care coordination (2.8 + 1.3; P FDR = .001) and used more "denial" coping strategies (0.8 + 1; P FDR = .001). Compared to two recent HF RCTs, the ENABLE CHF-PC sample had a higher proportion of AAs and higher baseline KCCQ clinical summary scores. CONCLUSION: ENABLE CHF-PC has the highest reported recruitment rate and proportion of AAs in a palliative clinical trial to date. Community-based recruitment partnerships, recruiter training, ongoing communication with recruiters and clinician co-investigators, and recruiter racial concordance likely contributed to successful recruitment of AAs. These important insights provide guidance for design of future HF palliative RCTs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02505425.

Natural history and outcomes of patients with liver cirrhosis complicated by hepatic hydrothorax.

BACKGROUND: Hepatic hydrothorax (HH) is an uncommon and difficult-to-manage complication of cirrhosis with limited treatment options. AIM: To define the clinical outcomes of patients presenting with HH managed with current standards-of-care and to identify factors associated with mortality. METHODS: Cirrhotic patients with HH presenting to 3 tertiary centres from 2010 to 2018 were retrospectively identified. HH was defined as pleural effusion in the absence of cardiopulmonary disease. The primary outcomes were overall and transplant-free survival at 12-mo after the index admission. Cox proportional hazards analysis was used to determine factors associated with the primary outcomes. RESULTS: Overall, 84 patients were included (mean age, 58 years) with a mean model for end-stage liver disease score of 29. Management with diuretics alone achieved long-term resolution of HH in only 12% patients. At least one thoracocentesis was performed in 73.8% patients, transjugular intrahepatic portosystemic shunt insertion in 11.9% patients and 33% patients received liver transplantation within 12-mo of index admission. Overall patient survival and transplant-free survival at 12 mo were 68% and 41% respectively. At multivariable analysis, current smoking [hazard ratio (HR) = 8.65, 95% confidence interval (CI): 3.43-21.9, P < 0.001) and acute kidney injury (AKI) (HR = 2.91, 95%CI: 1.21-6.97, P = 0.017) were associated with a significantly increased risk of mortality. CONCLUSION: Cirrhotic patients with HH are a challenging population with a poor 12-mo survival despite current treatments. Current smoking and episodes of AKI are potential modifiable factors affecting survival. HH is often refractory of diuretic therapy and transplant assessment should be considered in all cases.

Winter warming post floral initiation delays flowering via bud dormancy activation and affects yield in a winter annual crop.

Winter annual life history is conferred by the requirement for vernalization to promote the floral transition and control the timing of flowering. Here we show using winter oilseed rape that flowering time is controlled by inflorescence bud dormancy in addition to vernalization. Winter warming treatments given to plants in the laboratory and field increase flower bud abscisic acid levels and delay flowering in spring. We show that the promotive effect of chilling reproductive tissues on flowering time is associated with the activity of two FLC genes specifically silenced in response to winter temperatures in developing inflorescences, coupled with activation of a BRANCHED1-dependent bud dormancy transcriptional module. We show that adequate winter chilling is required for normal inflorescence development and high yields in addition to the control of flowering time. Because warming during winter flower development is associated with yield losses at the landscape scale, our work suggests that bud dormancy activation may be important for effects of climate change on winter arable crop yields.

The Project ENABLE Cornerstone randomized controlled trial: study protocol for a lay navigator-led, early palliative care coaching intervention for African American and rural-dwelling advanced cancer family caregivers.

BACKGROUND: Family caregivers play a vital, yet stressful role in managing the healthcare needs and optimizing the quality of life of patients with advanced cancer, from the time they are newly diagnosed until end of life. While early telehealth palliative care has been found to effectively support family caregivers, little work has focused on historically under-resourced populations, particularly African American and rural-dwelling individuals. To address this need, we developed and are currently testing Project ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone, a lay navigator-led, early palliative care coaching intervention for family caregivers of African American and rural-dwelling patients with newly diagnosed advanced cancer. METHODS: This is a 2-site, single-blind, hybrid type I implementation-effectiveness trial of the Cornerstone intervention versus usual care. Cornerstone is a multicomponent intervention based on Pearlin's Stress-Health Process Model where African American and/or rural-dwelling family caregivers of patients with newly diagnosed advanced cancer (target sample size = 294 dyads) are paired with a lay navigator coach and receive a series of six, brief 20-60-min telehealth sessions focused on stress management and coping, caregiving skills, getting help, self-care, and preparing for the future/advance care planning. Subsequent to core sessions, caregivers receive monthly follow-up indefinitely until the patient's death. Caregiver and patient outcomes are collected at baseline and every 12 weeks until the patient's death (primary outcome: caregiver distress at 24 weeks; secondary outcomes: caregiver: quality of life and burden; patient: distress, quality of life, and healthcare utilization). Implementation costs and the intervention cost effectiveness are also being evaluated. DISCUSSION: Should this intervention demonstrate efficacy, it would yield an implementation-ready model of early palliative care support for under-resourced family caregivers. A key design principle that has centrally informed the Cornerstone intervention is that every caregiving situation is unique and each caregiver faces distinct challenges that cannot be addressed using a one-size-fits all approach. Hence, Cornerstone employs culturally savvy lay navigator coaches who are trained to establish a strong, therapeutic alliance with participants and tailor their coaching to a diverse range of individual circumstances. TRIAL REGISTRATION: ClinicalTrials.gov NCT04318886 . Registered on 20 March, 2020.

Quantitative Trait Locus Mapping for Resistance Against Pyrenopeziza brassicae Derived From a Brassica napus Secondary Gene Pool.

Use of host resistance is the most economical and environmentally safe way to control light leaf spot disease of oilseed rape (Brassica napus). The causal organism of light leaf spot, Pyrenopeziza brassicae, is one of the most economically damaging pathogens of oilseed rape in the United Kingdom and it is considered to have a high potential to evolve due to its mixed reproduction system and airborne ascospores. This necessitates diverse sources of host resistance, which are inadequate at present to minimize yield losses caused by this disease. To address this, we screened a doubled haploid (DH) population of oilseed rape, derived from a secondary gene pool (ancestral genomes) of B. napus for the introgression of resistance against P. brassicae. DH lines were phenotyped using controlled-environment and glasshouse experiments with P. brassicae populations obtained from three different geographic locations in the United Kingdom. Selected DH lines with different levels of resistance were further studied in a controlled-environment experiment using both visual (scanning electron microscope - SEM) and molecular (quantitative PCR) assessment methods to understand the mode/s of host resistance. There was a clear phenotypic variation for resistance against P. brassicae in this DH population. Quantitative trait locus (QTL) analysis identified four QTLs with moderate to large effects, which were located on linkage groups C1, C6, and C9. Of these, the QTL on the linkage group C1 appeared to have a major effect on limiting P. brassicae asexual sporulation. Study of the sub-cuticular growth phase of P. brassicae using qPCR and SEM showed that the pathogen was able to infect and colonise both resistant and susceptible Q DH lines and control B. napus cultivars. However, the rate of increase of pathogen biomass was significantly smaller in resistant lines, suggesting that the resistance segregating in this DH population limits colonisation/sporulation by the pathogen rather than eliminating the pathogen. Resistance QTLs identified in this study provide a useful resource for breeding cultivar resistance for effective control of light leaf spot and form a starting point for functional identification of the genes controlling resistance against P. brassicae that can contribute to our knowledge on mechanisms of partial resistance of crops against pathogens.