Behavioural, developmental and psychological characteristics in children with germline PTEN mutations:a carer report study

Background: PTEN is primarily known as a tumour suppressor gene. However, research describes higher rates of difficulties including intellectual disability and difficulties relating to autism spectrum conditions (ASCs) in people with germline PTEN mutations. Other psychological characteristics/experiences are less often reported and are explored in this study. Methods: The parents of 20 children with PTEN mutations completed an online survey exploring adaptive behaviour, ASC‐associated behaviours, anxiety, mood, hypermobility, behaviours that challenge, sensory experiences, quality of life and parental wellbeing. Published normative data and data from groups of individuals with other genetic neurodevelopmental conditions were used to contextualise findings. Results: Overall levels of adaptive behaviour were below the ‘typical’ range, and no marked relative differences were noted between domains. Higher levels of ASC‐related difficulties, including sensory experiences, were found in comparison with ‘typically developing’ children, with a possible peak in restrictive/repetitive behaviour; ASC and sensory processing atypicality also strongly correlated with reported joint hypermobility. A relative preservation of social motivation was noted. Anxiety levels were found to be elevated overall (and to relate to sensory processing and joint hypermobility), with the exception of social anxiety, which was comparable with normative data. Self‐injurious behaviour was common. Conclusions: Results suggest a wide range of possible difficulties in children with PTEN mutations, including elevated anxiety. Despite elevated ASC phenomenology, social motivation may remain relatively strong. Firm conclusions are restricted by a small sample size and potential recruitment bias, and future research is required to further explore the relationships between such characteristics

Maintaining Ecosystem Function by Restoring Forest Biodiversity – Reviewing Decision-Support Tools that link Biology, Hydrology and Geochemistry

Not all forest models are applicable to a meta-modelling approach. Hence, the objective of the research presented here was to identify and compare the available forest models already being used in research, and to evaluate their suitability for use as decision-support tools in designing successful restoration plans to bring forest biodiversity and function back to sites disturbed by industrial activities (mining in particular).This work was conducted with funding generously supplied by Total E&P Canada Ltd., Calgary, Alberta, Canada

Pleistocene landscape evolution in the Avon valley, southern Britain: optical dating of terrace formation and Palaeolithic archaeology

This paper presents the first comprehensive Optically Stimulated Luminescence dating programme from a sequence of Pleistocene river terraces in the Avon valley (Wiltshire-Hampshire-Dorset), southern Britain. These results offer the most complete chronometric framework for Pleistocene landscape evolution and Palaeolithic occupation in the Avon valley, allowing for the first time: (1) an assessment of the timing of terrace formation and landscape evolution, (2) the dating of hominin presence in the area, and (3) an investigation of the relationship between terrace formation and Quaternary climatic change. Analysis of 25 samples collected from terraces 10 and 7 to 4 show that the middle Avon terraces formed in response to the main Pleistocene climatic oscillations (Marine Isotope Stage (MIS) 10, 8, 6) and that fluvial mechanisms changed through time, resulting in three different types of terrace architecture. The highest and oldest deposits are compound terraces deposited during the Early Pleistocene before the Mid Pleistocene Transition. The middle reach of the valley is characterised by well-developed strath terraces overlain with thick fluvial deposits, reflecting the greater degree of incision in response to the increased amplitude of climate cycles in the Middle Pleistocene. The youngest deposits in the confined modern floodplain represent cut-and-fill terraces deposited after MIS5e. The results indicate that the two main Palaeolithic sites in the area, Milford Hill and Woodgreen, date to between at least MIS 10 and 8 with a pre-MIS 10 human occupation at a third main site at Bemerton. This is significant because the sites date to a period previously associated with a decline in hominin presence in Britain. The dating of the Avon valley terrace sequence highlights the complex nature of terrace formation during the Pleistocene and the need to critically reassess the chronological understanding of these fluvial archives in southern Britain. This research demonstrates that with a detailed and multidisciplinary approach shifts in hominin landscape use can be discovered, providing new information on hominin behavioural change during the Pleistocene

Remote conditioning or erythropoietin before surgery primes kidneys to clear ischemia-reperfusion-damaged cells: a renoprotective mechanism?

Acute kidney injury is common, serious with no specific treatment. Ischemia-reperfusion is a common cause of acute kidney injury (AKI). Clinical trials suggest that preoperative erythropoietin (EPO) or remote ischemic preconditioning may have a renoprotective effect. Using a porcine model of warm ischemia-reperfusion-induced AKI (40-min bilateral cross-clamping of renal arteries, 48-h reperfusion), we examined the renoprotective efficacy of EPO (1,000 iu/kg iv.) or remote ischemic preconditioning (3 cycles, 5-min inflation/deflation to 200 mmHg of a hindlimb sphygmomanometer cuff). Ischemia-reperfusion induced significant kidney injury at 24 and 48 h (χ(2), 1 degree of freedom, >10 for 6/7 histopathological features). At 2 h, a panel of biomarkers including plasma creatinine, neutrophil gelatinase-associated lipocalin, and IL-1β, and urinary albumin:creatinine could be used to predict histopathological injury. Ischemia-reperfusion increased cell proliferation and apoptosis in the renal cortex but, for pretreated groups, the apoptotic cells were predominantly intratubular rather than interstitial. At 48-h reperfusion, plasma IL-1β and the number of subcapsular cells in G2-M arrest were reduced after preoperative EPO, but not after remote ischemic preconditioning. These data suggest an intrarenal mechanism acting within cortical cells that may underpin a renoprotective function for preoperative EPO and, to a limited extent, remote ischemic preconditioning. Despite equivocal longer-term outcomes in clinical studies investigating EPO as a renoprotective agent in AKI, optimal clinical dosing and administration have not been established. Our data suggest further clinical studies on the potential renoprotective effect of EPO and remote ischemic preconditioning are justified