Studies on resistance to mildew (Erysiphe graminis) and leaf blotch (Rhynchosporium secalis) in barley

A major consideration in the use of genetical resistance against infection of crop plants is the ability of the pathogen concerned to evolve genotypes with virulence to overcome such resistance. This applies particularly to oligogenic forms of resistance with major effects and it is Dossible that forms of partial resistance may be durable and have economic benefit. This study was concerned with the development of screening methods and identifying possible sources of partial resistance in barley to two fungal foliar pathogens, Evysiphe gvaminis f.sp. hovdei3 causal agent of mildew and Rhynahospovium seoalis causing leaf blotch.With respect to barley mildew, lines from Ethiopia, Turkey and Israel, as well as lines and cultivars from two European Barley Disease Nurseries, were found in preliminary work to exhibit a wide range of response when exposed to natural inocula of E. gvaminis. A screening procedure was adopted to favour the selection of virulences, from the pathogen population, for particular host genotypes and indicated those lines which gave consistently low disease levels. When these lines were tested in conjunction with commercial cultivars against known isolates of E. gvaminis with various virulence combinations, different patterns of resistance response were evidenced. Firstly, vertical resistance was associated with commercial cultivars but not lines; secondly, consistently high resistance was shown by some lines indicating resistance factors other than those apparently present in most existing commercial cultivars and thirdly, some lines consistently showed intermediate levels of horizontal resistance. In tests on commercial cultivars grouped according to their barley mildew resistance categories, both intra- and inter-group differences were recorded. Variations in group characteristics between years was attributable to changing virulence combinations in the pathogen population. Variations within groups were low and inconsistent between assessments: in some cases adult plant resistance may have been important. The reported tolerance of Proctor may be associated with delayed infection of emerging leaves and little necrosis resulting from infection. Microscopic assessments indicated that leaf position and plant age may influence fungal development, although there were no apparent qualitative differences in pathogen behaviour on cultivars evidencing varying degrees of partial resistance.Studies on R. secalis were hampered by difficulties in ensuring epidemic development in screening tests, although the development of a system, based on automatic misting equipment eventually overcame these and susceptible cultivars became rapidly infected. In glasshouse trials on a range of lines and cultivars, infection above a threshold level did not lead to increased impairment of leaf functioning: growth habit may be of some importance in determining cultivar susceptibility to this disease. It was demonstrated that lesion development and level of spore production for different cultivars may not be correlated, the level of spore production being epidemiologically significant in the field

General and specific components of depression and anxiety in an adolescent population.

BACKGROUND: Depressive and anxiety symptoms often co-occur resulting in a debate about common and distinct features of depression and anxiety. METHODS: An exploratory factor analysis (EFA) and a bifactor modelling approach were used to separate a general distress continuum from more specific sub-domains of depression and anxiety in an adolescent community sample (n = 1159, age 14). The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale were used. RESULTS: A three-factor confirmatory factor analysis is reported which identified a) mood and social-cognitive symptoms of depression, b) worrying symptoms, and c) somatic and information-processing symptoms as distinct yet closely related constructs. Subsequent bifactor modelling supported a general distress factor which accounted for the communality of the depression and anxiety items. Specific factors for hopelessness-suicidal thoughts and restlessness-fatigue indicated distinct psychopathological constructs which account for unique information over and above the general distress factor. The general distress factor and the hopelessness-suicidal factor were more severe in females but the restlessness-fatigue factor worse in males. Measurement precision of the general distress factor was higher and spanned a wider range of the population than any of the three first-order factors. CONCLUSIONS: The general distress factor provides the most reliable target for epidemiological analysis but specific factors may help to refine valid phenotype dimensions for aetiological research and assist in prognostic modelling of future psychiatric episodes.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Surface water management in humanitarian crises

This paper reports on the scoping stage of a practical toolkit being developed to support the application of surface water management practices in humanitarian contexts. The toolkit is predominately aimed at refugee and IDP camps for displaced people and aims to address the lack of suitable guidance in this area (Abbot et al. 2017). Effective surface water management will protect the health, dignity and wellbeing of communities in humanitarian crises. In developing the toolkit, the authors recognise the challenges posed in creating a document that can effectively support an audience with diverse interests and roles within humanitarian contexts. This will be a key focus for the next stage of the project

Cohort profile: mental health following extreme trauma in a northern Ugandan cohort of War-Affected Youth Study (The WAYS Study).

War experiences are associated with the risk of long-term mental health problems. The War-affected Youths (WAYS) Study comprises a cohort of 539 youths (61% female) aged between 18 to 25 (at baseline) randomly sampled from the population of war-affected youths in northern Uganda. The study aims to chart the trajectory of long-term mental health consequences of war and the roles of individual, family, and community contextual risk and protective factors in influencing the course of mental health using Social Ecology Model, thus, addressing both the individual and its social ecology. Knowledge of postwar contexts may inform policy and guide interventions on postwar psychosocial adjustment and reintegration in conflict-prone Great Lakes region of Africa (Rwanda, Burundi, DR Congo, Uganda, Central African Republic, and South Sudan). Two waves of data collection have been conducted and more data collection is planned. At baseline, information on demographic characteristics, pre-war experiences, psychosocial outcomes, coping, stigma/discrimination, family and community acceptance and relationship, family functioning, and post-war experiences were obtained. At follow-up, information on general health, gender-based violence, PTSD, social skills, trauma memory quality, rumination, self-esteem, and psychosocial outcomes were collected. Approval to access the data can be obtained on application to the Principal Investigator upon submission of a research proposal with ethical approval from the applicant's institution. This research is funded by Wellcome Trust and Gulu University.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Outcomes of conduct problems in adolescence: 40 year follow-up of national cohort

Objective To describe long term outcomes associated with externalising behaviour in adolescence, defined in this study as conduct problems reported by a teacher, in a population based sample

Profiles of family-focused adverse experiences through childhood and early adolescence: the ROOTS project a community investigation of adolescent mental health.

BACKGROUND: Adverse family experiences in early life are associated with subsequent psychopathology. This study adds to the growing body of work exploring the nature and associations between adverse experiences over the childhood years. METHODS: Primary carers of 1143 randomly recruited 14-year olds in Cambridgeshire and Suffolk, UK were interviewed using the Cambridge Early Experiences Interview (CAMEEI) to assess family-focused adversities. Adversities were recorded retrospectively in three time periods (early and later childhood and early adolescence). Latent Class Analysis (LCA) grouped individuals into adversity classes for each time period and longitudinally. Adolescents were interviewed to generate lifetime DSM-IV diagnoses using the K-SADS-PL. The associations between adversity class and diagnoses were explored. RESULTS: LCA generated a 4-class model for each time period and longitudinally. In early childhood 69% were allocated to a low adversity class; a moderate adversity class (19%) showed elevated rates of family loss, mild or moderate family discord, financial difficulties, maternal psychiatric illness and higher risk for paternal atypical parenting; a severe class (6%) experienced higher rates on all indicators and almost exclusively accounted for incidents of child abuse; a fourth class, characterised by atypical parenting from both parents, accounted for the remaining 7%. Class membership was fairly stable (~ 55%) over time with escape from any adversity by 14 years being uncommon. Compared to those in the low class, the odds ratio for reported psychopathology in adolescents in the severe class ranged from 8 for disruptive behaviour disorders through to 4.8 for depressions and 2.0 for anxiety disorders. Only in the low adversity class did significantly more females than males report psychopathology. CONCLUSIONS: Family adversities in the early years occur as multiple rather than single experiences. Although some children escape adversity, for many this negative family environment persists over the first 15 years of life. Different profiles of family risk may be associated with specific mental disorders in young people. Sex differences in psychopathologies may be most pronounced in those exposed to low levels of family adversities.This is the published version of the article. It was published in BMC Psychiatry by BioMed Central. The online version can be found here: http://www.biomedcentral.com/1471-244X/11/109

Sexual violence and general functioning among formerly abducted girls in Northern Uganda: the mediating roles of stigma and community relations--the WAYS study.

BACKGROUND: Although sexual violence in war is associated with long-term mental health problems, little is known about its association with general functioning and the factors that explain this association. This study aims to illuminate the path from sexual violence to poor functioning. The prevalence of sexual violence among formerly abducted girls in Northern Uganda was assessed as well as the extent to which stigma and community relations explain the association between sexual violence and general functioning. METHOD: In a cross-sectional analysis using data from the WAYS study (N = 210, baseline age 22.06, SD = 2.06, minimum-maximum 18-25), the extent of mediation of the association between sexual violence and general functioning was assessed in multiple regression models. RESULTS: Sexual violence was found to be associated with increased stigma, poor community relations, and poor general functioning. The association between sexual violence and general functioning was mediated by stigma and community relations. The bootstrap results indicated significant mediation by stigma of 47 % (95 % confidence interval [CI] 35 to 78 % and by community relations of 67 % (95 % CI: 52 to 78 %) in the association between sexual violence and general functioning. CONCLUSION: Thus, poor functioning among formerly abducted girls is largely mediated by stigma and poor community relations. However, due to the relatively small effect sizes of the associations, targeted interventions to prevent impaired functioning may have only modest benefits to the formerly abducted girls. Interventions to alleviate the toxic effects of sexual violence in formerly abducted girls would benefit from a holistic approach that targets stigma and poor relationships within communities

Threonine 149 Phosphorylation Enhances ΔFosB Transcriptional Activity to Control Psychomotor Responses to Cocaine

Stable changes in neuronal gene expression have been studied as mediators of addicted states. Of particular interest is the transcription factor ΔFosB, a truncated and stable FosB gene product whose expression in nucleus accumbens (NAc), a key reward region, is induced by chronic exposure to virtually all drugs of abuse and regulates their psychomotor and rewarding effects. Phosphorylation at Ser[superscript 27] contributes to ΔFosB's stability and accumulation following repeated exposure to drugs, and our recent work demonstrates that the protein kinase CaMKIIα phosphorylates ΔFosB at Ser[superscript 27] and regulates its stability in vivo. Here, we identify two additional sites on ΔFosB that are phosphorylated in vitro by CaMKIIα, Thr[superscript 149] and Thr[superscript 180], and demonstrate their regulation in vivo by chronic cocaine. We show that phosphomimetic mutation of Thr[superscript 149] (T149D) dramatically increases AP-1 transcriptional activity while alanine mutation does not affect transcriptional activity when compared with wild-type (WT) ΔFosB. Using in vivo viral-mediated gene transfer of ΔFosB-T149D or ΔFosB-T149A in mouse NAc, we determined that overexpression of ΔFosB-T149D in NAc leads to greater locomotor activity in response to an initial low dose of cocaine than does WT ΔFosB, while overexpression of ΔFosB-T149A does not produce the psychomotor sensitization to chronic low-dose cocaine seen after overexpression of WT ΔFosB and abrogates the sensitization seen in control animals at higher cocaine doses. We further demonstrate that mutation of Thr[superscript 149] does not affect the stability of ΔFosB overexpressed in mouse NAc, suggesting that the behavioral effects of these mutations are driven by their altered transcriptional properties

Outcomes of safety and effectiveness in a multicenter randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Whole-body hypothermia reduced the frequency of death or moderate/severe disabilities in neonates with hypoxic-ischemic encephalopathy in a randomized, controlled multicenter trial. OBJECTIVE: Our goal was to evaluate outcomes of safety and effectiveness of hypothermia in infants up to 18 to 22 months of age. DESIGN/METHODS: A priori outcomes were evaluated between hypothermia (n = 102) and control (n = 106) groups. RESULTS: Encephalopathy attributable to causes other than hypoxia-ischemia at birth was not noted. Inotropic support (hypothermia, 59% of infants; control, 56% of infants) was similar during the 72-hour study intervention period in both groups. Need for blood transfusions (hypothermia, 24%; control, 24%), platelet transfusions (hypothermia, 20%; control, 12%), and volume expanders (hypothermia, 54%; control, 49%) was similar in the 2 groups. Among infants with persistent pulmonary hypertension (hypothermia, 25%; control, 22%), nitric-oxide use (hypothermia, 68%; control, 57%) and placement on extracorporeal membrane oxygenation (hypothermia, 4%; control, 9%) was similar between the 2 groups. Non-central nervous system organ dysfunctions occurred with similar frequency in the hypothermia (74%) and control (73%) groups. Rehospitalization occurred among 27% of the infants in the hypothermia group and 42% of infants in the control group. At 18 months, the hypothermia group had 24 deaths, 19 severe disabilities, and 2 moderate disabilities, whereas the control group had 38 deaths, 25 severe disabilities, and 1 moderate disability. Growth parameters were similar between survivors. No adverse outcomes were noted among infants receiving hypothermia with transient reduction of temperature below a target of 33.5 degrees C at initiation of cooling. There was a trend in reduction of frequency of all outcomes in the hypothermia group compared with the control group in both moderate and severe encephalopathy categories. CONCLUSIONS: Although not powered to test these secondary outcomes, whole-body hypothermia in infants with encephalopathy was safe and was associated with a consistent trend for decreasing frequency of each of the components of disability

Digital endpoints in clinical trials: emerging themes from a multi-stakeholder Knowledge Exchange event

© The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, to view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Background: Digital technologies, such as wearable devices and smartphone applications (apps), can enable the decentralisation of clinical trials by measuring endpoints in people’s chosen locations rather than in traditional clinical settings. Digital endpoints can allow high-frequency and sensitive measurements of health outcomes compared to visit-based endpoints which provide an episodic snapshot of a person’s health. However, there are underexplored challenges in this emerging space that require interdisciplinary and cross-sector collaboration. A multi-stakeholder Knowledge Exchange event was organised to facilitate conversations across silos within this research ecosystem. Methods: A survey was sent to an initial list of stakeholders to identify potential discussion topics. Additional stakeholders were identified through iterative discussions on perspectives that needed representation. Co-design meetings with attendees were held to discuss the scope, format and ethos of the event. The event itself featured a cross-disciplinary selection of talks, a panel discussion, small-group discussions facilitated via a rolling seating plan and audience participation via Slido. A transcript was generated from the day, which, together with the output from Slido, provided a record of the day’s discussions. Finally, meetings were held following the event to identify the key challenges for digital endpoints which emerged and reflections and recommendations for dissemination. Results: Several challenges for digital endpoints were identified in the following areas: patient adherence and acceptability; algorithms and software for devices; design, analysis and conduct of clinical trials with digital endpoints; the environmental impact of digital endpoints; and the need for ongoing ethical support. Learnings taken for next generation events include the need to include additional stakeholder perspectives, such as those of funders and regulators, and the need for additional resources and facilitation to allow patient and public contributors to engage meaningfully during the event. Conclusions: The event emphasised the importance of consortium building and highlighted the critical role that collaborative, multi-disciplinary, and cross-sector efforts play in driving innovation in research design and strategic partnership building moving forward. This necessitates enhanced recognition by funders to support multi-stakeholder projects with patient involvement, standardised terminology, and the utilisation of open-source software.Peer reviewe