Design of the Physical exercise during Adjuvant Chemotherapy Effectiveness Study (PACES):A randomized controlled trial to evaluate effectiveness and cost-effectiveness of physical exercise in improving physical fitness and reducing fatigue

<p>Abstract</p> <p>Background</p> <p>Cancer chemotherapy is frequently associated with a decline in general physical condition, exercise tolerance, and muscle strength and with an increase in fatigue. While accumulating evidence suggests that physical activity and exercise interventions during chemotherapy treatment may contribute to maintaining cardiorespiratory fitness and strength, the results of studies conducted to date have not been consistent. Additional research is needed to determine the optimal intensity of exercise training programs in general and in particular the relative effectiveness of supervised, outpatient (hospital- or physical therapy practice-based) versus home-based programs.</p> <p>Methods</p> <p>This multicenter, prospective, randomized trial will evaluate the effectiveness of a low to moderate intensity, home-based, self-management physical activity program, and a high intensity, structured, supervised exercise program, in maintaining or enhancing physical fitness (cardiorespiratory fitness and muscle strength), in minimizing fatigue and in enhancing the health-related quality of life (HRQoL). Patients receiving adjuvant chemotherapy for breast or colon cancer (n = 360) are being recruited from twelve hospitals in the Netherlands, and randomly allocated to one of the two treatment groups or to a 'usual care' control group. Performance-based and self-reported outcomes are assessed at baseline, at the end of chemotherapy and at six month follow-up.</p> <p>Discussion</p> <p>This large, multicenter, randomized clinical trial will provide additional empirical evidence regarding the effectiveness of physical exercise during adjuvant chemotherapy in enhancing physical fitness, minimizing fatigue, and maintaining or enhancing patients' quality of life. If demonstrated to be effective, exercise intervention programs will be a welcome addition to the standard program of care offered to patients with cancer receiving chemotherapy.</p> <p>Trial registration</p> <p>This study is registered at the Netherlands Trial Register (NTR 2159)</p

A longitudinal study of muscle strength and function in patients with cancer cachexia

Purpose Patients with cancer frequently experience an involuntary loss of weight (in particular loss of muscle mass), defined as cachexia, with profound implications for independence and quality of life. The rate at which such patients’ physical performance declines has not been well established. The aim of this study was to determine the change in muscle strength and function over 8 weeks in patients with already established cancer cachexia, to help inform the design and duration of physical activity interventions applicable to this patient group. Methods Patients with thoracic and gastrointestinal cancer, with unintentional weight loss of >5% in 6 months or BMI < 20 plus 2% weight loss were included. Physical and functional assessments (baseline, 4 weeks, 8 weeks) included: isometric quadriceps and hamstring strength, handgrip, standing balance, 10m walk time and timed up and go. Results Fifty patients (32 male), mean ±SD age 65 ±10 years and BMI 24.9 ±4.3kg/m2 were recruited. Thoracic cancer patients had lower muscle strength and function (p0.05). Baseline variables did not differentiate between completers and non-completers (p>0.05). Conclusions More than a third of patients with established cancer cachexia in our study were stable over 8 weeks, suggesting a subgroup who may benefit from targeted interventions of reasonable duration. Better understanding the physical performance parameters which characterize and differentiate these patients has important clinical implications for cancer multidisciplinary team practice

What helps or hinders the transformation from a major tertiary center to a major trauma center? Identifying barriers and enablers using the Theoretical Domains Framework

BACKGROUND: Major Trauma Centers (MTCs), as part of a trauma system, improve survival and functional outcomes from injury. Developing such centers from current teaching hospitals is likely to generate diverse beliefs amongst staff. These may act as barriers or enablers. Prior identification of these may make the service development process more efficient. The importance of applying theory to systematically identify barriers and enablers to changing clinical practice in emergency medicine has been emphasized. This study systematically explored theory-based barriers and enablers towards implementing the transformation of a tertiary hospital into a MTC. Our goal was to demonstrate the use of a replicable method to identify targets that could be addressed to achieve a successful transformation from an organization evolved to provide a particular type of clinical care into a clinical system with different demands, requirements and expectations. METHODS: The Theoretical Domains Framework (TDF) is a tool designed to elicit and analyze beliefs affecting behavior. Semi-structured interviews based around the TDF were conducted in a major tertiary hospital in Scotland due to become a MTC with a purposive sample of major stakeholders including clinicians and nurses from specialties involved in trauma care, clinical managers and administration. Belief statements were identified through qualitative analysis, and assessed for importance according to prevalence, discordance and evidence base. RESULTS AND DISCUSSION: 1728 utterances were recorded and coded into 91 belief statements. 58 were classified as important barriers/enablers. There were major concerns about resource demands, with optimism conditional on these being met. Distracting priorities abound within the Emergency Department. Better communication is needed. Staff motivation is high and they should be engaged in skills development and developing performance improvement processes. CONCLUSIONS: This study presents a systematic and replicable method of identifying theory-based barriers and enablers towards complex service development. It identifies multiple barriers/enablers that may serve as a basis for developing an implementation intervention to enhance the development of MTCs. This method can be used to address similar challenges in developing specialist centers or implementing clinical practice change in emergency care across both developing and developed countries

Anthrax Toxins Inhibit Neutrophil Signaling Pathways in Brain Endothelium and Contribute to the Pathogenesis of Meningitis

Anthrax meningitis is the main neurological complication of systemic infection with Bacillus anthracis approaching 100% mortality. The presence of bacilli in brain autopsies indicates that vegetative bacteria are able to breach the blood-brain barrier (BBB). The BBB represents not only a physical barrier but has been shown to play an active role in initiating a specific innate immune response that recruits neutrophils to the site of infection. Currently, the basic pathogenic mechanisms by which B. anthracis penetrates the BBB and causes anthrax meningitis are poorly understood.Using an in vitro BBB model, we show for the first time that B. anthracis efficiently invades human brain microvascular endothelial cells (hBMEC), the single cell layer that comprises the BBB. Furthermore, transcriptional profiling of hBMEC during infection with B. anthracis revealed downregulation of 270 (87%) genes, specifically key neutrophil chemoattractants IL-8, CXCL1 (Gro alpha) and CXCL2 (Gro beta), thereby strongly contrasting hBMEC responses observed with other meningeal pathogens. Further studies using specific anthrax toxin-mutants, quantitative RT-PCR, ELISA and in vivo assays indicated that anthrax toxins actively suppress chemokine production and neutrophil recruitment during infection, allowing unrestricted proliferation and dissemination of the bacteria. Finally, mice challenged with B. anthracis Sterne, but not the toxin-deficient strain, developed meningitis.These results suggest a significant role for anthrax toxins in thwarting the BBB innate defense response promoting penetration of bacteria into the central nervous system. Furthermore, establishment of a mouse model for anthrax meningitis will aid in our understanding of disease pathogenesis and development of more effective treatment strategies

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Factors Associated with Hepatitis B Testing Among Vietnamese Americans

Chronic hepatitis B and hepatitis B-associated liver cancer is a major health disparity among Vietnamese Americans, who have a chronic hepatitis B prevalence rate of 7–14% and an incidence rate for liver cancer six times that of non-Latino whites. Describe factors associated with hepatitis B testing among Vietnamese Americans. A population-based telephone survey conducted in 2007–2008. Vietnamese Americans age 18–64 and living in the Northern California and Washington, DC areas (N = 1,704). Variables included self-reports of sociodemographics, health care factors, and hepatitis B-related behaviors, knowledge, beliefs, and communication with others. The main outcome variable was self-reported receipt of hepatitis B testing. The cooperation rate was 63.1% and the response rate was 27.4%. Only 62% of respondents reported having received a hepatitis B test and 26%, hepatitis B vaccination. Only 54% knew that hepatitis B could be transmitted by sexual intercourse. In multivariable analyses, factors negatively associated with testing included: age 30–49 years, US residence for &gt;10 years, less Vietnamese fluency, lower income, and believing that hepatitis B can be deadly. Factors positively associated with testing included: Northern California residence, having had hepatitis B vaccination, having discussed hepatitis B with family/friends, and employer requested testing. Physician recommendation of hepatitis B testing (OR 4.46, 95% CI 3.36, 5.93) and respondent's request for hepatitis B testing (OR 8.37, 95% CI 5.95, 11.78) were strongly associated with test receipt. Self-reports of hepatitis B testing among Vietnamese Americans remain unacceptably low. Physician recommendation and patient request were the factors most strongly associated with test receipt. A comprehensive effort is needed to promote hepatitis B testing in this population, including culturally-targeted community outreach, increased access to testing, and physician education

The influence of refuge sharing on social behaviour in the lizard Tiliqua rugosa

Refuge sharing by otherwise solitary individuals during periods of inactivity is an integral part of social behaviour and has been suggested to be the precursor to more complex social behaviour. We compared social association patterns of active versus inactive sheltering individuals in the social Australian sleepy lizard, Tiliqua rugosa, to empirically test the hypothesis that refuge sharing facilitates social associations while individuals are active. We fitted 18 neighbouring lizards with Global Positioning System (GPS) recorders to continuously monitor social associations among all individuals, based on location records taken every 10 min for 3 months. Based on these spatial data, we constructed three weighted, undirected social networks. Two networks were based on empirical association data (one for active and one for inactive lizards in their refuges), and a third null model network was based on hypothetical random refuge sharing. We found patterns opposite to the predictions of our hypothesis. Most importantly, association strength was higher in active than in inactive sheltering lizards. That is, individual lizards were more likely to associate with other lizards while active than while inactive and in shelters. Thus, refuge sharing did not lead to increased frequencies of social associations while lizards were active, and we did not find any evidence that refuge sharing was a precursor to sleepy lizard social behaviour. Our study of an unusually social reptile provides both quantitative data on the relationship between refuge sharing and social associations during periods of activity and further insights into the evolution of social behaviour in vertebrates

The embryo as moral work object: PGD/IVF staff views and experiences

Copyright @ 2008 the authors. This article is available in accordance with the Creative Commons Deed, Attribution 2.5, see http://creativecommons.org/licenses/by-nc-nd/2.5/deed.en_CA.We report on one aspect of a study that explored the views and experiences of practitioners and scientists on social, ethical and clinical dilemmas encountered when working in the field of preimplantation genetic diagnosis (PGD) for serious genetic disorders. The study produced an ethnography based on observation, interviews and ethics discussion groups with staff from two PGD/IVF Units in the UK. We focus here on staff perceptions of work with embryos that entails disposing of ‘affected’ or ‘spare’ embryos or using them for research. A variety of views were expressed on the ‘embryo question’ in contrast to polarised media debates. We argue that the prevailing policy acceptance of destroying affected embryos, and allowing research on embryos up to 14 days leaves some staff with rarely reported, ambivalent feelings. Staff views are under-researched in this area and we focus on how they may reconcile their personal moral views with the ethical framework in their field. Staff construct embryos in a variety of ways as ‘moral work objects’. This allows them to shift attention between micro-level and overarching institutional work goals, building on Casper's concept of ‘work objects’ and focusing on negotiation of the social order in a morally contested field.The Wellcome Trust Biomedical Ethics Programme, who funded the projects‘Facilitating choice, framing choice: the experience of staff working in pre-implantation genetic diagnosis’ (no: 074935), and ‘Ethical Frameworks for Embryo Donation:the views and practices of IVF/PGD staff’ (no: 081414)