Stiffener debonding mechanisms in post-buckled CFRP aerospace panels

This paper describes the fractographic analysis of five CFRP post-buckled skin/stringer panels that were tested to failure in compression. The detailed damage mechanisms for skin/stiffener detachment in an undamaged panel were characterised and related to the stress conditions during post-buckling; in particular the sites of peak twist (at buckling nodes) and peak bending moments (at buckling anti-nodes). The initial event was intralaminar splitting of the +45 degrees plies adjacent to the skin/stiffener interface, induced by high twist at a nodeline. This was followed by mode II delamination, parallel to +/- 45 degrees plies and then lengthwise (0 degrees) shear along the stiffener centreline. The presence of defects or damage was found to influence this failure process, leading to a reduction in strength. This research provides an insight into the processes that control post-buckled performance of stiffened panels and suggests that 2D models and element tests do not capture the true physics of skin/stiffener detachment: a full 3D approach is required.

Post-slaughter changes in ATP metabolites, Reducing and phosphorylated sugars in chicken meat

The formation of ATP breakdown products in chicken M. pectoralis major post-slaughter is reported. The concentrations of metabolites were followed in chicken breast throughout the carcass processing post-slaughter and during chilled storage. The concentration of glucose remains similar throughout the period whilst that of glucose-6-phosphate decreases linearly. Glucose and glucose-6-phosphate concentrations were inversely related to the pHu of the breast meat throughout chilled storage. Rapid post-mortem glycolysis and high pHu values suggest the occurrence of stress at and pre-slaughter. Whilst ATP, ADP and AMP were rapidly broken down, the concentration of IMP rose rapidly and remained high. Concentrations of inosine, ribose and hypoxanthine increased gradually post-slaughter but an initial increase in ribose phosphate was not sustained. Most of the potential ribose present in chicken meat, believed to be important for flavor formation, remains bound in the form of inosine and IMP. There is evidence that additional breakdown pathways for ribose and ribose-5-phosphate may deplete the concentrations of these precursors.

TRP channels in vascular disorders

In recent years, research on the roles of TRP channels in vascular function and disease has undergone a rapid expansion from tens of reports published in the early 2000s to several hundreds of papers published to date. Multiple TRP subtypes are expressed in vascular smooth muscle cells and endothelial cells, where they form diverse non-selective cation channels permeable to Ca2+. These channels mediate Ca2+ entry following receptor stimulation, Ca2+ store depletion and mechanical stimulation of vascular myocytes and endothelial cells. The complex molecular composition and signalling pathways leading to the activation of various vascular TRP channels and the growing evidence for their involvement in various vascular disorders, including dysregulation of vascular tone and hypertension, impaired endothelium-dependent vasodilatation, increased endothelial permeability, occlusive vascular disease, vascular injury and oxidative stress, are summarised and discussed in this review.

Enquiring about traumatic experiences in bipolar disorder: A case note and self- report comparison

Objectives: This study examined: (i) the prevalence of lifetime trauma, childhood trauma and trauma related to civil unrest in a Bipolar Disorder sample, and (ii) the agreement between rates of disclosure of trauma in case notes and self-report questionnaires.

Methods: The case notes of sixty participants, recruited from a geographically well-defined mental health service in Northern Ireland, were examined for reports of experiences of lifetime, childhood and traumatic events related to civil conflict. The participants also completed self-report measures of trauma.

Results: Considerable differences were found between the prevalence of trauma as measured by self-report questionnaires and case notes reports. The prevalence of lifetime trauma as measured by the Trauma History Questionnaire was 61.7% (compared to case notes prevalence of 33.3%). The prevalence of moderate and severe levels of childhood trauma as measured by the Childhood Trauma Questionnaire was 65% (case notes 21.7%). Rates of trauma related to civil unrest were 35% (case notes 3.3%). Poor levels of agreement were found between all self-report trauma measures and case notes reports. Agreement on two categories of trauma (childhood emotional neglect and childhood physical neglect) reached statistical significance but kappa scores suggest this agreement was poor (kappa = .14. p<.05; kappa = .127, p<.05). © 2011 Elsevier B.V. All rights reserved.

Conclusions: It is probable that the increased rate of trauma disclosed in the self-report questionnaire arises because clinicians during initial assessment and subsequent treatment do not consistently enquire about trauma. The need for staff training is discussed. (C) 2011 Elsevier B.V. All rights reserved.

Effectiveness of Criminal Justice Liaison and Diversion Services for Offenders With Mental Disorders: A Review

Objective: The authors evaluated and synthesised the best-available evidence relating to the effectiveness of CJLD service models with respect to changes in mental health status and/or criminal recidivism.Methods: Research examining the effectiveness of CJLD services when compared to traditional Criminal Justice System (CJS) responses was reviewed and systematically appraised according to Campbell/Cochrane guidelines. Key outcomes included a reduction in offending and post-intervention changes in mental health. Results: Comprehensive searches of published and unpublished literature identified 6571 studies which varied considerably in terms of their methodological approach and overall quality. Ten studies met the inclusion criteria. The synthesised findings indicated that, when compared to traditional CJS outcomes, CJLD services appeared to be effective in terms of identifying MDOs and impacting positively on criminal justice and mental health outcomes.Conclusions: Although the evidence may be deemed to be moderate in terms of methodological rigour, overall, the findings suggest that CJLD services can be beneficial. The effectiveness of services depends upon the model of service delivery, the availability of community services and the engagement of MDOs.The successful implementation of CJLD services requires a clearer recognition of the importance of system of care principles.

Freeze-dried strawberry powder improves lipid profile and lipid peroxidation in women with metabolic syndrome:baseline and post intervention effects

Strawberry flavonoids are potent antioxidants and anti-inflammatory agents that have been shown to reduce cardiovascular disease risk factors in prospective cohort studies. Effects of strawberry supplementation on metabolic risk factors have not been studied in obese populations. We tested the hypothesis that freeze-dried strawberry powder (FSP) will lower fasting lipids and biomarkers of oxidative stress and inflammation at four weeks compared to baseline. We also tested the tolerability and safety of FSP in subjects with metabolic syndrome. FSP is a concentrated source of polyphenolic flavonoids, fiber and phytosterols.

Inhibition of Rho-kinase protects cerebral barrier from ischaemia-evoked injury through modulations of endothelial cell oxidative stress and tight junctions

Ischaemic strokes evoke blood-brain barrier (BBB) disruption and oedema formation through a series of mechanisms involving Rho-kinase activation. Using an animal model of human focal cerebral ischaemia, this study assessed and confirmed the therapeutic potential of Rho-kinase inhibition during the acute phase of stroke by displaying significantly improved functional outcome and reduced cerebral lesion and oedema volumes in fasudil- versus vehicle-treated animals. Analyses of ipsilateral and contralateral brain samples obtained from mice treated with vehicle or fasudil at the onset of reperfusion plus 4 h post-ischaemia or 4 h post-ischaemia alone revealed these benefits to be independent of changes in the activity and expressions of oxidative stress- and tight junction-related parameters. However, closer scrutiny of the same parameters in brain microvascular endothelial cells subjected to oxygen-glucose deprivation ± reperfusion revealed marked increases in prooxidant NADPH oxidase enzyme activity, superoxide anion release and in expressions of antioxidant enzyme catalase and tight junction protein claudin-5. Cotreatment of cells with Y-27632 prevented all of these changes and protected in vitro barrier integrity and function. These findings suggest that inhibition of Rho-kinase after acute ischaemic attacks improves cerebral integrity and function through regulation of endothelial cell oxidative stress and reorganization of intercellular junctions. Inhibition of Rho-kinase (ROCK) activity in a mouse model of human ischaemic stroke significantly improved functional outcome while reducing cerebral lesion and oedema volumes compared to vehicle-treated counterparts. Studies conducted with brain microvascular endothelial cells exposed to OGD ± R in the presence of Y-27632 revealed restoration of intercellular junctions and suppression of prooxidant NADPH oxidase activity as important factors in ROCK inhibition-mediated BBB protection.

The effects of Chronic Lycopene Supplementation on Exercise-Induced Oxidative Stress and Glucose Homeostasis.

Lycopene can exert antioxidant effects against peripheral and cellular oxidative stress and may be associated with reduced diabetic risk. Conversely, exercise-induced free radicals are thought to underpin many of the desirable whole-body adaptations following training and the use of antioxidants within the exercise model remains debatable. PURPOSE: To investigate the effect of lycopene supplementation on oxidative stress and glucose homeostasis following acute aerobic exercise. METHOD: Twenty-eight (n=28) apparently healthy male volunteers were recruited (age 24 ± 4 years; weight 78 ± 10 kg; height 178 ± 8 cm; 2max 40 ± 7 ml·kg-1 ·min-1 ) in a randomised, single blind, placebo-controlled study. Participants were required to attend the Laboratory on two occasions: prior to and following 6 weeks of supplementation of either 10mg lycopene (LG; n=15) or placebo (PG; n=13) followed by a bout of acute exercise for one hour at 65% 2max. Exogenous glucose oxidation was then measured on an isotope ratio mass spectrometer in a sub-group of participants (n=14) following exercise, by administration of a standard oral glucose tolerance test (OGTT; 75g glucose). Venous blood samples were drawn for measurement of oxidative stress parameters, plasma glucose and insulin. RESULTS: Plasma lycopene increased in LG only (0.01 ± 0.004 vs.0.02 ± 0.007 µmol/L; P <0.05) following supplementation and remained elevated post exercise compared to PG (0.01 ± 0.004 vs. 0.02 ± 0.009 µmol/L; P <0.05). There were no changes in other markers of oxidative stress (SOD, LOOHs, F2 ISP and Alkoxyl radical) either between or within the trials, (P >0.05, respectively). A main effect for an increase in insulin was observed two hours post OGTT in the sub-groups (Pooled data, P <0.05) but trends in the HOMA scores were evident with a 57% increase for LG (2.20 ± 1.84 vs. 5.14 ± 2.5; P >0.05) and an 11% decrease for PG (2.17 ± 1.06 vs. 1.94 ± 1.53; P >0.05). No change in plasma glucose was detected at any point, or after the OGTT (P >0.05). CONCLUSION: In healthy males, lycopene supplementation had no effect on post exercise levels of ROS or markers of lipid peroxidation, despite an increase in plasma lycopene. However, lycopene supplementation may affect post exercise insulin sensitivity in response to glucose consumption, but further parallel research is required.

Proposed role for COUP-TFII in regulating fetal Leydig cell steroidogenesis, perturbation of which leads to masculinization disorders in rodents

Reproductive disorders that are common/increasing in prevalence in human males may arise because of deficient androgen production/action during a fetal 'masculinization programming window'. We identify a potentially important role for Chicken Ovalbumin Upstream Promoter-Transcription Factor II (COUP-TFII) in Leydig cell (LC) steroidogenesis that may partly explain this. In rats, fetal LC size and intratesticular testosterone (ITT) increased ~3-fold between e15.5-e21.5 which associated with a progressive decrease in the percentage of LC expressing COUP-TFII. Exposure of fetuses to dibutyl phthalate (DBP), which induces masculinization disorders, dose-dependently prevented the age-related decrease in LC COUP-TFII expression and the normal increases in LC size and ITT. We show that nuclear COUP-TFII expression in fetal rat LC relates inversely to LC expression of steroidogenic factor-1 (SF-1)-dependent genes (StAR, Cyp11a1, Cyp17a1) with overlapping binding sites for SF-1 and COUP-TFII in their promoter regions, but does not affect an SF-1 dependent LC gene (3β-HSD) without overlapping sites. We also show that once COUP-TFII expression in LC has switched off, it is re-induced by DBP exposure, coincident with suppression of ITT. Furthermore, other treatments that reduce fetal ITT in rats (dexamethasone, diethylstilbestrol (DES)) also maintain/induce LC nuclear expression of COUP-TFII. In contrast to rats, in mice DBP neither causes persistence of fetal LC COUP-TFII nor reduces ITT, whereas DES-exposure of mice maintains COUP-TFII expression in fetal LC and decreases ITT, as in rats. These findings suggest that lifting of repression by COUP-TFII may be an important mechanism that promotes increased testosterone production by fetal LC to drive masculinization. As we also show an age-related decline in expression of COUP-TFII in human fetal LC, this mechanism may also be functional in humans, and its susceptibility to disruption by environmental chemicals, stress and pregnancy hormones could explain the origin of some human male reproductive disorders.

GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways

BACKGROUND: In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease.

METHODS: We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively.

RESULTS: Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples.

CONCLUSIONS: These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

Traumatic brain injury (TBI) in a prison population: a systematic review

Objective: To systematically explore the literature surrounding TBI in adult prison populations. Method: Twenty six studies spanning six countries were included. All studies were published in peer reviewed journals and sampled adults from general prison populations (aged 18+). Results: Only seven studies employed valid and reliable measures of TBI. The presence of TBI related problems such as aggression, depression, substance abuse, psychiatric disorders, and neurocognitive deficits were evident within prisoner samples.

Improved clonality assessment in germinal centre/post-germinal centre non-Hodgkin's lymphomas with high rates of somatic hypermutation.

BACKGROUND: PCR detects clonal rearrangements of the Ig gene in lymphoproliferative disorders. False negativity occurs in germinal centre/post-germinal centre lymphomas (GC/PGCLs) as they display a high rate of somatic hypermutation (SHM), which causes primer mismatching when detecting Ig rearrangements by PCR. AIMS: To investigate the degree of SHM in a group of GC/PGCLs and assess the rate of false negativity when using BIOMED-2 PCR when compared with previously published strategies. METHODS: DNA was isolated from snap-frozen tissue from 49 patients with GC/PGCL (23 diffuse large B cell lymphomas (DLBCLs), 26 follicular lymphomas (FLs)) and PCR-amplified for complete (VDJH), incomplete (DJH) and Ig kappa/lambda rearrangements using the BIOMED-2 protocols, and compared with previously published methods using consensus primers. Germinal centre phenotype was defined by immunohistochemistry based on CD10, Bcl-6 and MUM-1. RESULTS: Clonality detection by amplifying Ig rearrangements using BIOMED-2 family-specific primers was considerably higher than that found using consensus primers (74% DLBCL and 96% FL vs 69% DLBCL and 73% FL). Addition of BIOMED-2 DJH rearrangements increased detection of clonality by 22% in DLBCL. SHM was present in VDJH rearrangements from all patients with DLBCL (median (range) 5.7% (2.5-13.5)) and FL (median (range) 5.3% (2.3-11.9)) with a clonal rearrangement. CONCLUSIONS: Use of BIOMED-2 primers has significantly reduced the false negative rate associated with GC/PGCL when compared with consensus primers, and the inclusion of DJH rearrangements represents a potential complementary target for clonality assessment, as SHM is thought not to occur in these types of rearrangements.