Measurement of Inclusive Isolated Prompt Photon Production at √s = 7 TeV with the ATLAS Detector

Prompt photons at hadron colliders are useful probes of perturbative quantum chromodynamics (pQCD), and are also found in signatures of new physics. A precise measurement of prompt photon production is both a useful test of theoretical models as well as an important step towards understanding final states that contain energetic photons. This thesis presents a measurement of the inclusive isolated prompt photon production cross section in proton-proton collisions at a center-of-mass energy of √s = 7 TeV. The data are collected with the ATLAS detector at the Large Hadron Collider, and correspond to 35 pb-1 of integrated luminosity. The measurement is made in four photon pseudorapidity (η) regions: 0 ≤ η \u3c 0.6; 0.6 ≤ η \u3c 1.37; 1.52 ≤ η \u3c 1.81; and 1.81 ≤ η \u3c 2.37; and covers photon transverse energies (ET) in the range 15 GeV ≤ ET \u3c 400 GeV. Photon candidates are reconstructed and identified through the use of the ATLAS calorimeter and tracking systems. The residual background, primarily from neutral meson decays, is estimated using in-situ techniques based on observed distributions of the total transverse energy in a narrow cone around the photon candidate. The measurements are compared to predictions from next-to-leading order pQCD calculations, with good agreement for photon transverse energies greater than 25 GeV

The Influence of Deformation-Induced Residual Stresses on the Post-Forming Tensile Stress/Strain Behavior of Dual-Phase Steels

It was hypothesized that, in dual-phase (DP) steels, strain partitioning between ferrite and martensite during deformation results in a distribution of post-deformation residual stresses that, in turn, affects the subsequent strength, work hardening behavior and formability when the strain path is changed. The post-forming deformation-induced residual stress state was expected to depend upon the microstructure, the amount of strain and the prestrain path. The primary objective of this research program was to understand the influence of deformation-induced residual stresses on the post-forming tensile stress/strain behavior of DP steels. Three commercially produced sheet steels were considered in this analysis: 1) a DP steel with approximately 15 vol. % martensite, 2) a conventional high-strength, low-alloy (HSLA) steel, and 3) a conventional, ultra-low-carbon interstitial-free (IF) steel. Samples of each steel were subjected to various prestrain levels in various plane-stress forming modes, including uniaxial tension, plane strain and balanced biaxial stretching.Neutron diffraction experiments confirmed the presence of large post-forming deformation-induced residual stresses in the ferrite phase of the DP steel. The deformation-induced residual stress state varied systematically with the prestrain mode, where the principal residual stress components are proportional to the principal strain components of the prestrain mode, but opposite in sign. For the first time, and by direct experimental correlation, it was shown that deformation-induced residual stresses greatly affect the post-forming tensile stress/strain behavior of DP steels. As previously reported in the literature, the formability (residual tensile ductility) of the IF steel and the HSLA steel was adversely affected by strain path changes. The DP steel presents a formability advantage over the conventional IF and HSLA steels, and is expected to be particularly well suited for complex forming operations that involve abrupt strain path changes.Deformation-induced residual stresses were measured in the IF steel and the HSLA steel; however, the magnitudes of which are such that post-forming tensile stress/strain behavior was not significantly affected. Considering the vast differences in mechanical properties, microstructure, and composition, the IF steel and the HSLA steel showed remarkably similar post-forming tensile stress/strain behavior for all prestrain modes considered

Leydig Stem Cell Differentiation in the Prepubertal Hamster (\u3cem\u3eMesocricetus auratus\u3c/em\u3e)

Leydig cells in the testis are the primary source of androgens in the adult male mammal. Therefore, the process of Leydig cell differentiation during the prepubertal period is essential to establish the Leydig cell population in the adult. Little has been published regarding the factors that regulate the postnatal Leydig cell differentiation in hamsters. However, it has been observed in adult male hamsters that Leydig cells regress under reduced photoperiods, but recrudesce with re-exposure to normal photoperiods. In the present investigation, the effects of light, hypothyroidism, hyperthyroidism, and melatonin treatment on Leydig cell differentiation in the neonatal-prepubertal hamster are investigated. Six treatment groups of male Syrian Golden hamsters were used. Group I male hamsters were raised under regular light conditions (12hr: 12hr Light:Dark) and group II hamsters were raised under reduced light (23hr: 1hr Dark: Light). Hamsters in Groups III received triidothyronine (T3; 50 μg/ kg. bwt); lactating mothers were injected every four days from birth of pups to day 28, and were maintained under regular light conditions. Hamsters in Group IV were maintained under regular light regimes (12hr: 12hr) and were made hypothyroid by adding 0.1% propylthiouracil to drinking water of lactating mothers from birth to day 28. Hamsters in Group V were raised in dark (similar to Group II), but their mothers received T3 injections similar to those in Group III. Lactating mothers in Group VI received melatonin injections (15 milligrams/ kg. bwt) every other afternoon from birth to day 28. Following euthanasia at postnatal day 28, blood was collected from the heart, serum prepared and stored until assay for hormones: thyroxin (T4), and melatonin. One testis from each hamster in each group was fixed by whole body perfusion, processed and embedded in epon-aradite. Using 1-micron sections that were stained with Methylene Blue-Azure II, Leydig cell numbers per testis in the experimental groups were quantified by the disector method. Leydig cells were identified by their characteristic morphology and their location in the testis interstitium. The ipsilateral testis from each hamster in each group was incubated in media containing luteinizing hormone (100ng/ml) and used to determine testosterone and androstenedione secretory capacity per testis in vitro. There was a reduction in Leydig cell numbers per testis in D28 hamsters (Group II), D28T3 hamsters (Group V), L28PTU hamsters (Group IV), and L28M hamsters (Group VI) when compared to L28 hamsters (Group I) and L28T3 hamsters (Group III). Significantly increased testosterone secretory capacities were found in the hamster groups D28 (Group II) and L28T3 (Group III) when compared to L28 (Group I). There were significantly reduced testosterone secretory capacities in hamsters in L28PTU (Group IV), L28M (Group VI), and D28T3 (GroupV), compared to L28 (Group I).The majority of the groups were not significantly different in androstenedione secretory capacity per testis except there were significantly lower values in L28PTU (Group IV) and D28T3 (GroupV). L28 (Group I) hamsters had significantly higher serum thyroxin levels than hamsters in D28 (Group II), L28PTU (Group IV), L28M (Group VI). Serum melatonin levels were the lowest in L28 (Group I) hamsters and the highest in L28PTU (Group IV) hamsters. These findings demonstrate that increased levels of melatonin and decreased levels of thyroxin negatively regulate and decreased levels of melatonin and increased levels of thyroxin positively regulate Leydig cell differentiation in the prepubertal hamster testis. It is concluded that thyroid pineal interactions are important in regulating the process of postnatal Leydig cell differentiation in the perpubertal hamster testis

The Effects of 17- Beta Estradiol on G-Protein Inwardly Rectifying Potassium Channels (GIRKs) in Breast Cancer

Breast cancer is a leading cause of cancer death and in 2009, the American Cancer Society estimates that over 192,000 new cases of breast cancer will be diagnosed, and over 40,000 women will die from breast cancer. Estrogen (E2) is required for normal female development and reproduction, but long-term exposure is carcinogenic and considered a risk factor for breast cancer. Membrane ion channels are essential for cell proliferation and are suggested to have a role in cancer, especially potassium channels. In the present study, we investigate the effects of estrogen and the estrogen antagonist ICI182780 on G-protein inwardly rectifying potassium channels (GIRK) in estrogen responsive MCF-7 breast cancer cells. GIRK1 and GIRK2 specific channels are thought to play a major role in rapid channel activation. We found increases in GIRK1 and GIRK2 membrane protein levels in response to estrogen treatment, as well as increases in intracellular potassium concentrations and cellular proliferation. ICI182780 treatment increased GIRK1, GIRK2 and GIRK4 membrane protein levels but resulted in an initial decrease in intracellular potassium concentration and decreased cell proliferation. GIRK1 RNAi knockdown decreased estrogen receptor alpha protein levels and activation. In addition, estrogen treatment resulted in increased phosphorylation of specific members of GPCR and MAPK signaling pathways that have been shown to be responsive to GIRK1 knockdown. Using microarray analysis of nontreated and E2 treated MCF7 cells, we observed 489 differentially expressed genes (283 upregulated and 206 downregulated) that were comprised largely of transcription and cell cycle associated genes. This study identified several human cell cycle associated genes that are both responsive to E2 treatment and are functionally correlated with GIRKs. Five genes were selected for further analysis by real time PCR. Our data suggests that specific GIRK channel composition at the cell membrane may be stimulated by estrogen exposure or downstream targets of estrogen signaling and may contribute to increased cell proliferation in MCF-7 breast cancer cells. Taken together, these data add further support of GIRK involvement in cancer progression and identify some potential biological roles of GIRKs in cancer biology beyond the initilal findings of GIRK1 assciation in metastatic breast cancer

G-Protein Inwardly Rectifying Potassium Channel 1 (GIRK1) Knockdown Decreases Beta-Adrenergic, MAP Kinase and Akt Signaling in the MDA-MB-453 Breast Cancer Cell Line

Previous data from our laboratory have indicated that there is a functional link between the beta-adrenergic receptor signaling pathway and the G-protein inwardly rectifying potassium channel (GIRK1) in breast cancer cell lines and that these pathways are involved in growth regulation of these cells. To determine functionality, MDA-MB-453 breast cancer cells were stimulated with ethanol, known to open GIRK channels. Decreased GIRK1 protein levels were seen after treatment with 0.12% ethanol. In addition, serum-free media completely inhibited GIRK1 protein expression. This data indicates that there are functional GIRK channels in breast cancer cells and that these channels are involved in cellular signaling. In the present research, to further define the signaling pathways involved, we performed RNA interference (siRNA) studies. Three stealth siRNA constructs were made starting at bases 1104, 1315, and 1490 of the GIRK1 sequence. These constructs were transfected into MDA-MB-453 cells, and both RNA and protein were isolated. GIRK1, β2-adrenergic and 18S control levels were determined using real-time PCR 24 hours after transfection. All three constructs decreased GIRK1 mRNA levels. However, β2 mRNA levels were unchanged by the GIRK1 knockdown. GIRK1 protein levels were also reduced by the knockdown, and this knockdown led to decreases in beta-adrenergic, MAP kinase and Akt signaling

Preventive analgesia and novel strategies for the prevention of chronic post-surgical pain

Chronic post-surgical pain (CPSP) is a serious complication of major surgery that can impair a patient’s quality of life. The development of CPSP is a complex process which involves biologic, psychosocial, and environmental mechanisms that have yet to be fully understood. Currently perioperative pharmacologic interventions aim to suppress and prevent sensitization with the aim of reducing pain and analgesic requirement in acute as well as long-term pain . Despite the detrimental effects of CPSP on patients, the body of literature focused on treatment strategies to reduce CPSP remains limited and continues to be understudied. This article reviews the main pharmacologic candidates for the treatment of CPSP, discusses the future of preventive analgesia, and considers novel strategies to help treat acute postoperative pain and lessen the risk that it becomes chronic. In addition, this article highlights important areas of focus for clinical practice including: multimodal management of CPSP patients, psychological modifiers of the pain experience, and the development of a Transitional Pain Service specifically designed to manage patients at high risk of developing chronic post-surgical pain.HC is supported by a Merit Award (Department of Anaesthesia, University of Toronto) and the STAGE Training Program in Genetic Epidemiology (Canadian Institutes of Health Research, CIHR) and a grant by the Physicians Services Incorporated Foundation. JK is supported by a Canada Research Chair in Health Psychology. The authors of this manuscript have no conflicts of interest to declare

“Her Heart Matters”, Making Visible the Cardiac Pain Experiences of Women with Physical Disabilities and Heart Disease: A Qualitative Study

Background: Women with physical disabilities are faced with challenges in many aspects of life-education, work, income, relationships, as well as their general health. These women are at a greater risk of developing heart disease. This study aimed to explore the cardiac pain experiences of women with physical disabilities and heart disease within a Canadian healthcare context. Methods: In this qualitative study, 8 women with physical disabilities and heart disease from across Canada were interviewed. They were asked about their pre-, peri-, and post-diagnostic experiences in the Canadian healthcare system. Transcripts of the interviews were analyzed using a hermeneutic phenomenological approach inspired by Ricoeur. Results: Two main themes were uncovered in the analysis of the transcripts, as follows: (i) the diagnostic journey; and (ii) life with cardiac symptoms and a disability. The women indicated that they had experienced difficulties in utilizing the Canadian healthcare system prior to receiving a cardiac diagnosis, including long waitlists, expensive and unreliable transport, issues with accessibility, and dealing with providers’ attitudinal barriers regarding disability. Receiving a diagnosis was challenging due to poor relationships with healthcare providers; however, having a same-sex provider seemed essential to receiving adequate care. Self-managing a disability and heart disease had significant physical and psychological impact, which was lightened by financial and social supports, modified lifestyle choices, and self-advocacy. Conclusions: Women with physical disabilities are often forgotten in discussions encompassing equity and inclusion. The participants’ experiences offer insight into what changes are needed within the Canadian healthcare system in order to improve outcomes for these women.Contexte: Les femmes qui présentent une incapacité physique doivent composer avec des défis dans de nombreux aspects de leur vie, notamment en ce qui touche l’éducation, le travail, le revenu, les relations et la santé en général. Le risque de cardiopathie est plus important dans leur cas. Cette étude visait à examiner comment la douleur cardiaque est vécue par les femmes présentant une incapacité physique et une cardiopathie dans le contexte des soins de santé au Canada. Méthodologie: Dans le cadre de cette étude qualitative, huit femmes présentant une incapacité physique et une cardiopathie ont participé à des entrevues menées à l’échelle du Canada. Elles ont été interrogées sur leurs expériences au sein du système de santé canadien au cours des périodes précédant, entourant et suivant le diagnostic. Les transcriptions des entrevues ont été analysées en fonction d’une approche phénoménologique herméneutique inspirée par Ricœur. Résultats: Deux grands thèmes ressortent de l’analyse des transcriptions, à savoir : (i) le parcours diagnostique; (ii) la vie avec des symptômes cardiaques et une incapacité physique. Les femmes interrogées ont indiqué qu’elles avaient éprouvé des difficultés dans leur parcours au sein du système de santé canadien avant de recevoir un diagnostic en cardiologie, évoquant à cet égard les longues listes d’attente, les services de transport coûteux et peu fiables, les problèmes d’accessibilité et les obstacles liés à l’attitude des fournisseurs de soins vis-à-vis de l’incapacité physique. Le fait de recevoir un diagnostic a été éprouvant en raison de rapports difficiles avec les fournisseurs de soins de santé; cependant, le fait d’avoir un fournisseur de soins de sexe féminin semblait être une condition essentielle à une prestation de soins adéquate. L’autoprise en charge d’une incapacité physique et d’une cardiopathie a eu des répercussions physiques et psychologiques importantes qui ont pu être allégées par le soutien financier et social, des modifications des habitudes de vie et l’autonomie sociale. Conclusions: Les femmes qui présentent une incapacité physique sont souvent laissées pour compte dans les discussions portant sur l’équité et l’inclusion. Le vécu des participantes donne un aperçu des changements qui doivent être apportés au sein du système de santé canadien afin d’améliorer les résultats chez ces femmes.Funding was received from the Women’s Xchange 15K Challenge, Women’s College Hospital, Toronto, Ontario, Canada.publishedVersio

Radiographic Lucencies in the Medial Femoral Condyle of Thoroughbred Sale Yearlings: A Preliminary Investigation of the Effect on Race Records

Radiographic lucencies in the medial femoral condyle of Thoroughbred sale yearlings reduce the likelihood a horse will sell at auction and the price paid compared with unaffected horses in the same sale; however, no difference in racing results was found between affected and unaffected horses. Authors' addresses: Equine Medical Associates, 996 Nandino Boulevard, Lexington, KY 40511 (Whitman, Morehead, Prichard, Hance); and th

Examination of psychological risk factors for chronic pain following cardiac surgery: protocol for a prospective observational study

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: Approximately 400 000 Americans and 36 000 Canadians undergo cardiac surgery annually, and up to 56% will develop chronic postsurgical pain (CPSP). The primary aim of this study is to explore the association of pain-related beliefs and gender-based pain expectations on the development of CPSP. Secondary goals are to: (A) explore risk factors for poor functional status and patient-level cost of illness from a societal perspective up to 12 months following cardiac surgery; and (B) determine the impact of CPSP on quality-adjusted life years (QALYs) borne by cardiac surgery, in addition to the incremental cost for one additional QALY gained, among those who develop CPSP compared with those who do not. METHODS AND ANALYSES: In this prospective cohort study, 1250 adults undergoing cardiac surgery, including coronary artery bypass grafting and open-heart procedures, will be recruited over a 3-year period. Putative risk factors for CPSP will be captured prior to surgery, at postoperative day 3 (in hospital) and day 30 (at home). Outcome data will be collected via telephone interview at 6-month and 12-month follow-up. We will employ generalised estimating equations to model the primary (CPSP) and secondary outcomes (function and cost) while adjusting for prespecified model covariates. QALYs will be estimated by converting data from the Short Form-12 (version 2) to a utility score. ETHICS AND DISSEMINATION: This protocol has been approved by the responsible bodies at each of the hospital sites, and study enrolment began May 2015. We will disseminate our results through CardiacPain.Net, a web-based knowledge dissemination platform, presentation at international conferences and publications in scientific journals. TRIAL REGISTRATION NUMBER: NCT01842568

Stepped-wedge randomised trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation: Study protocol for a randomized controlled trial

BACKGROUND: Laparoscopic ventral mesh rectopexy (LVMR) is an established treatment for external full-thickness rectal prolapse. However, its clinical efficacy in patients with internal prolapse is uncertain due to the lack of high-quality evidence. METHODS: An individual level, stepped-wedge randomised trial has been designed to allow observer-blinded data comparisons between patients awaiting LVMR with those who have undergone surgery. Adults with symptomatic internal rectal prolapse, unresponsive to prior conservative management, will be eligible to participate. They will be randomised to three arms with different delays before surgery (0, 12 and 24 weeks). Efficacy outcome data will be collected at equally stepped time points (12, 24, 36 and 48 weeks). The primary objective is to determine clinical efficacy of LVMR compared to controls with reduction in the Patient Assessment of Constipation Quality of Life (PAC-QOL) at 24 weeks serving as the primary outcome. Secondary objectives are to determine: (1) the clinical effectiveness of LVMR to 48 weeks to a maximum of 72 weeks; (2) pre-operative determinants of outcome; (3) relevant health economics for LVMR; (4) qualitative evaluation of patient and health professional experience of LVMR and (5) 30-day morbidity and mortality rates. DISCUSSION: An individual-level, stepped-wedge, randomised trial serves the purpose of providing an untreated comparison for the active treatment group, while at the same time allowing the waiting-listed participants an opportunity to obtain the intervention at a later date. In keeping with the basic ethical tenets of this design, the average waiting time for LVMR (12 weeks) will be shorter than that for routine services (24 weeks)