Genomic landscapes and clonality of de novo AML

No abstract available

Genetic profiling in acute myeloid leukemia

No abstract available

Unique co-operative landcare venture in the Avon catchment

The Avon catchment is bustling with landcare activity generated by a unique co-operative venture between farmers, the Department of Agriculture, the National Soil Conservation Program and Alcoa of Australia Ltd. The Avon Catchment Landcare Program was initiated by the Department of Agriculture and Alcoa, in support of the national Decade ofLandcare. The program provides financial, human and technical resources to undertake catchment and farm planning and demonstrations of rehabilitation techniques that tackle soil and water degradation problems. We know that without specially planned landcare programs and substantial changes in land management, land degradation will continue and further losses of agricultural production will follo

Oxidative stress and haemolytic anaemia in dogs and cats: a comparative approach

Oxidative stress contributes to haemolytic anaemia in many species including dogs and cats, as well as in humans. Red cells are exposed to a continual oxidant challenge, both endogenously from within the red cells themselves and also exogenously from other tissues, and from ingested or administered oxidants. When the oxidative challenge exceeds the antioxidant provisions of the red cell, damage occurs in the form of lipid and protein peroxidation, cytoskeletal crosslinking, oxidation of haemoglobin to methaemolglobin, and precipitation of denatured sulphhaemoglobin as Heinz bodies. These deleterious sequelae produce fragile red cells with reduced lifespan, and result in poorer oxygen delivery to tissues, intravascular haemolysis, anaemia, haemoglobinuria and jaundice. A number of features increase the risk of oxidant damage in dogs and cats. Thus dog red cells have low levels of the antioxidant enzyme catalase. Cat haemoglobin has at least four times as many readily oxidizable thiol residues compared to most species, whilst their hepatic capacity for glucuronidation is much reduced, which can result in greater accumulation of oxidants. Like humans, both species may also be exposed to excess oxidants from systemic diseases such as diabetes mellitus, hepatic lipidosis, hypophosphataemia and neoplasias. Iatrogenic oxidants include drugs such as acetaminophen and other non-steroidal anti-inflammatory compounds. Ingested toxins include heavy metals, particularly important in dogs with their increased propensity for scavenging. Ingestion of feeds containing products from Allium species of plants has also long been associated with red cell oxidative damage and Heinz body formation in both dogs and cats. Though less common than in humans, there are occasional congenital enzyme deficiencies which reduce the enzymatic oxidant defence of the red cells in these species. Treatment usually relies on removal of the oxidant challenge or support against the resulting anaemia. Specific antioxidants currently lack efficacy but analogy with human medicine suggests that a range possible antioxidants may be potentially beneficial.Non

The effect of the antisickling compound GBT1118 on the permeability of red blood cells from patients with sickle cell anemia.

Sickle cell anemia (SCA) is one of the commonest severe inherited disorders. Nevertheless, effective treatments remain inadequate and novel ones are avidly sought. A promising advance has been the design of novel compounds which react with hemoglobin S (HbS) to increase oxygen (O2 ) affinity and reduce sickling. One of these, voxelotor (GBT440), is currently in advanced clinical trials. A structural analogue, GBT1118, was investigated in the current work. As RBC dehydration is important in pathogenesis of SCA, the effect of GBT1118 on RBC cation permeability was also studied. Activities of Psickle , the Gardos channel and the KCl cotransporter (KCC) were all reduced. Gardos channel and KCC activities were also inhibited in RBCs treated with Ca2+ ionophore or the thiol reagent N-ethylmaleimide, indicative of direct effects on these two transport systems. Consistent with its action on RBC membrane transporters, GBT1118 significantly increased RBC hydration. RBC hemolysis was reduced in a nonelectrolyte lysis assay. Further to its direct effects on O2 affinity, GBT1118 was therefore found to reduce RBC shrinkage and fragility. Findings reveal important effects of GBT1118 on protecting sickle cells and suggest that this is approach may represent a useful therapy for amelioration of the clinical complications of SCA.Sultanate of Oman His Majesty Sultan Qaboos's 1000 grants British Heart Foundatio

Compassionate faces: Evidence for distinctive facial expressions associated with specific prosocial motivations

Compassion is a complex cognitive, emotional and behavioural process that has important real-world consequences for the self and others. Considering this, it is important to understand how compassion is communicated. The current research investigated the expression and perception of compassion via the face. We generated exemplar images of two compassionate facial expressions induced from two mental imagery tasks with different compassionate motivations (Study 1). Our kind- and empathic compassion faces were perceived differently and the empathic-compassion expression was perceived as best depicting the general definition of compassion (Study 2). Our two composite faces differed in their perceived happiness, kindness, sadness, fear and concern, which speak to their underling motivation and emotional resonance. Finally, both faces were accurately discriminated when presented along a compassion continuum (Study 3). Our results demonstrate two perceptually and functionally distinct facial expressions of compassion, with potentially different consequences for the suffering of others.CRB, PG, JAK and CJF were supported (MR/J009210/1) by the UK Medical Research Council (https://mrc.ukri.org/). JSL was supported by a grant (PP00P1_163758/1) from the Swiss National Science Foundation (www.snf.ch). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Allocentric spatial memory performance predicts intrusive memory severity in posttraumatic stress disorder

BACKGROUND: Posttraumatic stress disorder (PTSD) is characterised by distressing trauma-related memories. According to the dual representation theory, intrusive memories arise from strengthened egocentric encoding and a poor contextual encoding, with spatial context requiring allocentric processing. Contextualization of mental imagery is proposed to be formed hierarchically through the ventral visual stream (VVS) to the hippocampal formation. Here, we tested this notion by investigating whether neuronal aberrations in structures of the VVS or in the hippocampus, as well as allocentric memory performance are associated with intrusive memory severity. METHODS: The sample comprised 33 women with PTSD due to childhood trauma. Allocentric memory performance was measured with the virtual Town Square Task and T1-weighted images acquired on a 3T Siemens Scanner. Intrusive memories were evoked by presenting an audio script describing parts of their trauma (script-driven imagery). RESULTS: Using hierarchical linear regression analysis, we found a significant association between lower intrusive memory severity and higher allocentric spatial memory, controlling for age, working memory, and general visuospatial ability. No significant association was found between cortical thickness of VVS structures, hippocampal volume and intrusive memory severity. Post hoc exploratory analyses revealed a negative correlation between years since index trauma and left hippocampal volume. LIMITATIONS: Our results are based on correlational analyses, causality cannot be inferred. CONCLUSION: This study supports the dual representation theory, which emphasizes the role of allocentric spatial memory for the contextualization of mental imagery in PTSD. Clinical implications are discussed

Levels of depression in transgender people and its predictors: Results of a large matched control study with transgender people accessing clinical services

Background Depression is a serious disorder which significantly impacts wellbeing and quality of life. Studies exploring mental wellbeing in the transgender population are mostly limited by small, non-homogenous samples and lack of matched controls. This study aimed to address these limitations and explore depression rates in a large sample of transgender people, compared with matched controls from the general population, as well as factors predicting depression in those taking cross-sex hormone treatment (CHT) compared to those not. Methods Transgender individuals (n=913) completed a measure of depression, measures which predict psychopathology (self-esteem, victimization, social support, interpersonal problems), and information regarding CHT use. Participants were matched by age and experienced gender with adults from the general population who had completed the measure of depression. Results Individuals were categorized as having no, possible or probable depressive disorder. Transgender individuals not on CHT had a nearly four-fold increased risk of probable depressive disorder, compared to controls. Older age, lower self-esteem, poorer interpersonal function and less social support predicted depressive disorder. Use of CHT was associated with less depression. Limitations Participants were attending a national gender identity service and therefore represent only a sub-group of transgender people. Due to the cross-sectional design, longitudinal research is required to fully confirm the finding that CHT use reduces depression. Conclusion This study confirms that non-treated transgender individuals have an increased risk of a depressive disorder. Interventions offered alongside gender affirming treatment to develop interpersonal skills, increase self-esteem and improve social support may reduce depression and prepare individuals for a more successful transition

Effects of study design and allocation on participant behaviour-ESDA: study protocol for a randomized controlled trial

Background: What study participants think about the nature of a study has been hypothesised to affect subsequent behaviour and to potentially bias study findings. In this trial we examine the impact of awareness of study design and allocation on participant drinking behaviour. Methods/Design: A three-arm parallel group randomised controlled trial design will be used. All recruitment, screening, randomisation, and follow-up will be conducted on-line among university students. Participants who indicate a hazardous level of alcohol consumption will be randomly assigned to one of three groups. Group A will be informed their drinking will be assessed at baseline and again in one month (as in a cohort study design). Group B will be told the study is an intervention trial and they are in the control group. Group C will be told the study is an intervention trial and they are in the intervention group. All will receive exactly the same brief educational material to read. After one month, alcohol intake for the past 4 weeks will be assessed. Discussion: The experimental manipulations address subtle and previously unexplored ways in which participant behaviour may be unwittingly influenced by standard practice in trials. Given the necessity of relying on self-reported outcome, it will not be possible to distinguish true behaviour change from reporting artefact. This does not matter in the present study, as any effects of awareness of study design or allocation involve bias that is not well understood. There has been little research on awareness effects, and our outcomes will provide an indication of the possible value of further studies of this type and inform hypothesis generation

Characterising the geomorphological and physicochemical effects of water injection dredging on estuarine systems

Dredging is a globally important aquatic system management activity, used for navigation improvement, contamination removal, aggregate production and/or flood risk mitigation. Despite widespread application, understanding of the environmental effects of some dredging types remains limited. Field campaigns in 2016 and 2017 in the River Parrett estuary, UK, therefore investigated the geomorphic and physicochemical effects of Water Injection Dredging (WID), a poorly studied hydrodynamic dredging technology. WID, applied to restore channel capacity for the maintenance of flood water conveyance in the tidal River Parrett, influenced surface elevations but not grain-size characteristics of dredged bed sediments. Topographic alterations due to the 2016 WID operation were short-lived, lasting less than 10 months, although benefits of the 2017 WID operation, in terms of volumetric change, outlasted the ≈ 12-month study period. Dredging had a significant impact on water physicochemistry (pH, dissolved oxygen, total suspended solids and turbidity) when comparing pre- and during- dredging conditions within the dredge reach, although time-series analysis found dredging effects were comparable in magnitude to tidal effects for some parameters. WID is typically targeted at the thalweg and not the banks, rendering the geomorphic signature of the method different to those of other, often more invasive dredging technologies (e.g. mechanical dredging methods). Further, thalweg not bankside dredging may have potential positive ecological implications, particularly where the majority of biomass is located within the channel margins, as in the tidal River Parrett. Collectively, data suggest WID can be an effective method for sediment dispersal within tidal systems although regular application may be required to maintain cross sectional areas, particularly where management precedes periods of low flows and/or high rates of sediment accumulation. In future, more work is required to better understand both the physical and ecological implications of WID as a flood risk management tool in estuaries and rivers