Age differences in the experience of cancer pain

The aim of this dissertation is to elucidate age-related patterns in the multidimensional experience of cancer pain. Chapter 1 presents a literature review of age-related patterns in cancer pain, outlines the methodological limitations of existing literature and highlights gaps in our knowledge. Chapter 2 presents the first psychometric analysis of the Short-Form McGill Pain Questionnaire-2 in older and younger people with cancer pain. The weight of the evidence suggests that this tool is valid for use in older and younger people with cancer pain. Chapter 3 presents an analysis of age-related patterns in the experience of cancer pain across the biopsychosocial spectrum. Pain intensity, qualities, and interference did not differ across age groups but older patients were somewhat less likely to be prescribed an opioid. Comorbidity was associated with greater pain for younger, but not older people, and chronic nonmalignant pain was associated with greater pain for older, but not younger people. An age-related pattern in the supportive context of cancer pain based on health status factors may also be present. There were no age differences in depressive symptoms, but intrusive thoughts were associated with greater pain for younger but not older patients, suggesting a unique adaptive advantage of prior experience with health limitations among older, but not younger patients. Chapter 4 presents a preliminary investigation of the role of pain three months after breast cancer surgery in the relationship between age and depressive symptoms. In women with moderate-to-severe pain, age was not associated with depressive symptoms but in women with mild or no pain, younger age was associated with greater depressive symptoms. However, in women with neuropathic pain, younger age was associated with greater depressive symptoms, but not in women without neuropathic pain. The impact of pain was not age-related. High preoperative pain expectations may be a risk factor for pain three months after breast cancer surgery, regardless of age. In Chapter 5, results are integrated and discussed along with implications for future research and treatment

In Situ Functionalized Polymers for siRNA Delivery

NOTICE:This is the peer-reviewed version of the following article:Juan M. Priegue, Daniel N. Crisan, José Martínez-Costas, Juan R. Granja, Francisco Fernandez-Trillo, and Javier Montenegro (2016),“In situ Functionalized Polymers for siRNA Delivery ; Angew. Chem. Int. Ed., 55, 7492–7495 [doi: 10.1002/anie.201601441]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for self-archivingA new method is reported herein for screening the biological activity of functional polymers across a consistent degree of polymerization and in situ, that is, under aqueous conditions and without purification/isolation of candidate polymers. In brief, the chemical functionality of a poly(acryloyl hydrazide) scaffold was activated under aqueous conditions using readily available aldehydes to obtain amphiphilic polymers. The transport activity of the resulting polymers can be evaluated in situ using model membranes and living cells without the need for tedious isolation and purification steps. This technology allowed the rapid identification of a supramolecular polymeric vector with excellent efficiency and reproducibility for the delivery of siRNA into human cells (HeLa-EGFP). The reported method constitutes a blueprint for the high-throughput screening and future discovery of new polymeric functional materials with important biological applicationsRoyal Society. Grant Number: IE130688 Spanish Ministry of Economy and Competitiveness. Grant Numbers: CTQ2014-59646-R, CTQ2013-43264-R, BFU2013-43513-R Birmingham Science City European Regional Development Fund Royal Society. Grant Number: RG140273 University of Birmingham MEC MINECO ERC. Grant Number: DYNAP-677786S

Health worker attrition at a rural district hospital in Rwanda: a need for improved placement and retention strategies

Introduction: The shortage and maldistribution of health care workers in sub-Saharan Africa is a major concern for rural health facilities. Rural areas have 63% of sub-Saharan Africa population but only 37% of its doctors. Although attrition of health care workers is implicated in the human resources for health crisis in the rural settings, few studies report attrition rates and risk factors for attrition in rural district hospitals in sub-Saharan Africa. Methods: We assessed attrition of health care workers at a Kirehe District Hospital in rural Rwanda. We included all hospital staff employed as of January 1, 2013 in this retrospective cohort study. We report the proportion of staff that left employment during 2013, and used a logistic regression to assess individual characteristics associated with attrition. Results: Of the 142 staff employed at Kirehe District Hospital at the start of 2013, 31.7% (n=45) of all staff and 81.8% (n=9) of doctors left employment in 2013. Being a doctor (OR=10.0, 95% CI: 1.9-52.1, p=0.006) and having up to two years of experience at the hospital (OR=5.3, 95% CI: 1.3-21.7, p=0.022) were associated with attrition. Conclusion: Kirehe District Hospital experienced high attrition rates in 2013, particularly among doctors. Opportunities for further training through Rwanda’s Human Resources for Health program in 2013 and a two-year compulsory service program for doctors that is not linked to interventions for rural retention may have driven these patterns. Efforts to link these programs with rural placement and retention strategies are recommended

Sequence analysis of call record data: exploring the role of different cost settings

Sequence analysis is widely used in life course research and more recently has been applied by survey methodologists to summarize complex call record data. However, summary variables derived in this way have proved ineffective for post-survey adjustments, owing to weak correlations with key survey variables. We reflect on the underlying optimal matching algorithm and test the sensitivity of the output to input parameters or ‘costs’, which must be specified by the analyst. The results illustrate the complex relationship between these costs and the output variables which summarize the call record data. Regardless of the choice of costs, there was a low correlation between the summary variables and the key survey variables, limiting the scope for bias reduction. The analysis is applied to call records from the Irish Longitudinal Study on Ageing, which is a nationally representative, face-to-face household surve

Sequence analysis of call record data: exploring the role of different cost settings

Sequence analysis is widely used in life course research and more recently has been applied by survey methodologists to summarize complex call record data. However, summary variables derived in this way have proved ineffective for post-survey adjustments, owing to weak correlations with key survey variables. We reflect on the underlying optimal matching algorithm and test the sensitivity of the output to input parameters or 'costs', which must be specified by the analyst. The results illustrate the complex relationship between these costs and the output variables which summarize the call record data. Regardless of the choice of costs, there was a low correlation between the summary variables and the key survey variables, limiting the scope for bias reduction. The analysis is applied to call records from the Irish Longitudinal Study on Ageing, which is a nationally representative, face-to-face household survey

Can we understand modern humans without considering pathogens?

Throughout our evolutionary history, humankind has always lived in contact with large numbers of pathogens. Some cultural traits, such as sedentarization and animal domestication, have considerably increased new parasitic contacts and epidemic transitions. Here, we review the various phenotypic traits that have been proposed to be affected by the highly parasitic human environment, including fertility, birth weight, fluctuating asymmetry, body odours, food recipes, sexual behaviour, pregnancy sickness, language, religion and intellectual quotient. We also discuss how such knowledge is important to understanding several aspects of the current problems faced by humanity in our changing world and to predicting the long-term consequences of parasite eradication policies on our health and well-being. The study of the evolutionary interactions between humans and parasites is a burgeoning and most promising field, as demonstrated by the recent increasing popularity of Darwinian medicine

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

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

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques