Corinne Burton Memorial Trust 25 Years Exhibition

Art psychotherapists and their patients reflect on 25 years of accomplishments made possible by the Corinne Burton Memorial Trust in the field of cancer care. This exhibition and accompanying publication celebrates the incalculable contribution the Corinne Burton Memorial Trust has made to the practice of art psychotherapy with people affected by cancer, marking Sir Michael Burton’s and the Trustees’ 25 years of support for art psychotherapy at Goldsmiths. The exhibition features inspirational artwork and personal stories by past and present recipients of Corinne Burton Memorial Trust studentship as well as by Corinne Burton therapists, and their patients

Treadmill exercise activates subcortical neural networks and improves walking after a stroke

BACKGROUND AND PURPOSE: Stroke often impairs gait thereby reducing mobility and fitness and promoting chronic disability. Gait is a complex sensorimotor function controlled by integrated cortical, subcortical, and spinal networks. The mechanisms of gait recovery after stroke are not well understood. This study examines the hypothesis that progressive task-repetitive treadmill exercise (T-EX) improves fitness and gait function in subjects with chronic hemiparetic stroke by inducing adaptations in the brain (plasticity).METHODS: A randomized controlled trial determined the effects of 6-month T-EX (n=37) versus comparable duration stretching (CON, n=34) on walking, aerobic fitness and in a subset (n=15/17) on brain activation measured by functional MRI.RESULTS: T-EX significantly improved treadmill-walking velocity by 51% and cardiovascular fitness by 18% (11% and -3% for CON, respectively; P<0.05). T-EX but not CON affected brain activation during paretic, but not during nonparetic limb movement, showing 72% increased activation in posterior cerebellar lobe and 18% in midbrain (P<0.005). Exercise-mediated improvements in walking velocity correlated with increased activation in cerebellum and midbrain.CONCLUSIONS: T-EX improves walking, fitness and recruits cerebellum-midbrain circuits, likely reflecting neural network plasticity. This neural recruitment is associated with better walking. These findings demonstrate the effectiveness of T-EX rehabilitation in promoting gait recovery of stroke survivors with long-term mobility impairment and provide evidence of neuroplastic mechanisms that could lead to further refinements in these paradigms to improve functional outcomes

Consistent Practices for the Probability of Detection (POD) of Fracture Critical Metallic Components Project

NASA-STD-5009 requires that successful flaw detection by NDE methods be statistically qualified for use on fracture critical metallic components, but does not standardize practices. This task works towards standardizing calculations and record retention with a web-based tool, the NNWG POD Standards Library or NPSL. Test methods will also be standardized with an appropriately flexible appendix to -5009 identifying best practices. Additionally, this appendix will describe how specimens used to qualify NDE systems will be cataloged, stored and protected from corrosion, damage, or loss

"It's a can of worms": understanding primary care practitioners' behaviours in relation to HPV using the Theoretical Domains Framework

Background: The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention. ATHENS (A Trial of HPV Education and Support) aims to develop a theorybased intervention to support primary care practitioners in their HPV-related practice. This study, the first step in the intervention development process, aimed to: identify HPV-related clinical behaviours that the intervention will target; clarify general practitioners’ (GPs’) and practice nurses’ roles and responsibilities; and determine factors that potentially influence clinical behaviour. A secondary objective was to informally assess the utility of the Theoretical Domains Framework (TDF) in understanding clinical behaviours in an area with an evolving evidence-base. Methods: In-depth semi-structured telephone interviews were conducted with GPs and practice nurses. The topic guide, which contained open questions and HPV-related clinical scenarios, was developed through literature review and clinical experience. Interview transcripts were content-analysed using the TDF as the coding framework. Results: 19 GPs and 14 practice nurses were interviewed. The major HPV-related clinical behaviours were: initiating a discussion about HPV infection with female patients; offering/recommending HPV vaccination to appropriate patients; and answering patients’ questions about HPV testing. While the responsibility for taking smears was considered a female role, both male and female practitioners dealt with HPV-related issues. All 12 theoretical domains arose in relation to HPV infection; the domains judged to be most important were: knowledge, emotion, social influences, beliefs about capabilities and beliefs about consequences. Eleven domains emerged in relation to HPV vaccination, with beliefs about consequences, social influences, knowledge and environmental context and resources judged to be the most important. Nine domains were relevant to HPV testing, with knowledge and beliefs about capabilities judged to be the most important. Conclusions: The findings confirm the need for an intervention to support primary care practitioners around HPV and suggest it should target a range of theoretical domains. The TDF proved valuable in analysing qualitative data collected using a topic guide not specifically designed to capture TDF domains and understanding clinical behaviours in an area with an evolving evidence-base

The Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of acute leukemia.

Acute leukemia is a constellation of rapidly progressing diseases that affect a wide range of patients regardless of age or gender. Traditional treatment options for patients with acute leukemia include chemotherapy and hematopoietic cell transplantation. The advent of cancer immunotherapy has had a significant impact on acute leukemia treatment. Novel immunotherapeutic agents including antibody-drug conjugates, bispecific T cell engagers, and chimeric antigen receptor T cell therapies have efficacy and have recently been approved by the US Food and Drug Administration (FDA) for the treatment of patients with acute leukemia. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop a clinical practice guideline composed of consensus recommendations on immunotherapy for the treatment of acute lymphoblastic leukemia and acute myeloid leukemia

Freund's vaccine adjuvant promotes Her2/Neu breast cancer

<p>Abstract</p> <p>Background</p> <p>Inflammation has been linked to the etiology of many organ-specific cancers. Indirect evidence suggests a possible role for inflammation in breast cancer. We investigated whether the systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis in a rat model in which cancer is induced by the <it>neu </it>oncogene.</p> <p>Methods</p> <p>The effects of FA on hyperplastic mammary lesions and mammary carcinomas were determined in a <it>neu</it>-induced rat model. The inflammatory response to FA treatment was gauged by measuring acute phase serum haptoglobin. In addition, changes in cell proliferation and apoptosis following FA treatment were assessed.</p> <p>Results</p> <p>Rats receiving FA developed twice the number of mammary carcinomas as controls. Systemic inflammation following FA treatment is chronic, as shown by a doubling of the levels of the serum biomarker, haptoglobin, 15 days following initial treatment. We also show that this systemic inflammation is associated with the increased growth of hyperplastic mammary lesions. This increased growth results from a higher rate of cellular proliferation in the absence of changes in apoptosis.</p> <p>Conclusion</p> <p>Our data suggests that systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis. It will be important to determine whether adjuvants currently used in human vaccines also promote breast cancer.</p

Kinetics of M1 muscarinic receptor and G protein signaling to phospholipase C in living cells

G protein–coupled receptors (GPCRs) mediate responses to external stimuli in various cell types. Early events, such as the binding of ligand and G proteins to the receptor, nucleotide exchange (NX), and GTPase activity at the Gα subunit, are common for many different GPCRs. For Gq-coupled M1 muscarinic (acetylcholine) receptors (M1Rs), we recently measured time courses of intermediate steps in the signaling cascade using Förster resonance energy transfer (FRET). The expression of FRET probes changes the density of signaling molecules. To provide a full quantitative description of M1R signaling that includes a simulation of kinetics in native (tsA201) cells, we now determine the density of FRET probes and construct a kinetic model of M1R signaling through Gq to activation of phospholipase C (PLC). Downstream effects on the trace membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) and PIP2-dependent KCNQ2/3 current are considered in our companion paper in this issue (Falkenburger et al. 2010. J. Gen. Physiol. doi:10.1085/jgp.200910345). By calibrating their fluorescence intensity, we found that we selected transfected cells for our experiments with ∼3,000 fluorescently labeled receptors, G proteins, or PLC molecules per µm2 of plasma membrane. Endogenous levels are much lower, 1–40 per µm2. Our kinetic model reproduces the time courses and concentration–response relationships measured by FRET and explains observed delays. It predicts affinities and rate constants that align well with literature values. In native tsA201 cells, much of the delay between ligand binding and PLC activation reflects slow binding of G proteins to receptors. With M1R and Gβ FRET probes overexpressed, 10% of receptors have G proteins bound at rest, rising to 73% in the presence of agonist. In agreement with previous work, the model suggests that binding of PLC to Gαq greatly speeds up NX and GTPase activity, and that PLC is maintained in the active state by cycles of rapid GTP hydrolysis and NX on Gαq subunits bound to PLC

Anthoceros genomes illuminate the origin of land plants and the unique biology of hornworts

Hornworts comprise a bryophyte lineage that diverged from other extant land plants >400 million years ago and bears unique biological features, including a distinct sporophyte architecture, cyanobacterial symbiosis and a pyrenoid-based carbon-concentrating mechanism (CCM). Here, we provide three high-quality genomes of Anthoceros hornworts. Phylogenomic analyses place hornworts as a sister clade to liverworts plus mosses with high support. The Anthoceros genomes lack repeat-dense centromeres as well as whole-genome duplication, and contain a limited transcription factor repertoire. Several genes involved in angiosperm meristem and stomatal function are conserved in Anthoceros and upregulated during sporophyte development, suggesting possible homologies at the genetic level. We identified candidate genes involved in cyanobacterial symbiosis and found that LCIB, a Chlamydomonas CCM gene, is present in hornworts but absent in other plant lineages, implying a possible conserved role in CCM function. We anticipate that these hornwort genomes will serve as essential references for future hornwort research and comparative studies across land plants.</p

Asymptomatic Achilles tendon pathology is associated with a central fat distribution in men and a peripheral fat distribution in women: a cross sectional study of 298 individuals

<p>Abstract</p> <p>Background</p> <p>Adiposity is a modifiable factor that has been implicated in tendinopathy. As tendon pain reduces physical activity levels and can lead to weight gain, associations between tendon pathology and adiposity must be studied in individuals without tendon pain. Therefore, the purpose of this study was to determine whether fat distribution was associated with asymptomatic Achilles tendon pathology.</p> <p>Methods</p> <p>The Achilles tendons of 298 individuals were categorised as normal or pathological using diagnostic ultrasound. Fat distribution was determined using anthropometry (waist circumference, waist hip ratio [WHR]) and dual-energy x-ray absorptiometry.</p> <p>Results</p> <p>Asymptomatic Achilles tendon pathology was more evident in men (13%) than women (5%) (p = 0.007). Men with tendon pathology were older (50.9 ± 10.4, 36.3 ± 11.3, p < 0.001), had greater WHR (0.926 ± 0.091, 0.875 ± 0.065, p = 0.039), higher android/gynoid fat mass ratio (0.616 ± 0.186, 0.519 ± 0.142, p = 0.014) and higher upper-body/lower body fat mass ratio (2.346 ± 0.630, 2.022 ± 0.467, p = 0.013). Men older than 40 years with a waist circumference >83 cm had the greatest prevalence of tendon pathology (33%). Women with tendon pathology were older (47.4 ± 10.0, 36.0 ± 10.3, p = 0.008), had less total fat (17196 ± 3173 g, 21626 ± 7882 g, p = 0.009), trunk fat (7367 ± 1662 g, 10087 ± 4152 g, p = 0.003) and android fat (1117 ± 324 g, 1616 ± 811 g, p = 0.005). They had lower central/peripheral fat mass ratios (0.711 ± 0.321 g, 0.922 ± 0.194 g, p = 0.004) than women with normal tendons. Women with tendon pathology were more often menopausal (63%, 13%, p = 0.002).</p> <p>Conclusions</p> <p>Men with Achilles tendon pathology were older and had a central fat distribution. Women with tendon pathology were older and had a peripheral fat distribution. An interaction between age and waist circumference was observed among men.</p