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    <title>DSpace Community:</title>
    <link>http://www.dspace.cam.ac.uk:80/handle/1810/221736</link>
    <description />
    <pubDate>Sat, 25 May 2013 20:17:03 GMT</pubDate>
    <dc:date>2013-05-25T20:17:03Z</dc:date>
    <item>
      <title>Risk assessment for osteoporotic fractures among men and women from a prospective population study: the EPIC-Norfolk study</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/243860</link>
      <description>Title: Risk assessment for osteoporotic fractures among men and women from a prospective population study: the EPIC-Norfolk study
Authors: Moayyeri, Alireza
Abstract: Osteoporotic fractures are a major and increasing clinical and public health concern internationally. Identification of individuals at high risk for fragility fractures may enable us to target preventive interventions more effectively. In this thesis, I aimed to evaluate novel risk factors for osteoporosis and develop a fracture risk assessment model among the middle-aged and older people. I used data from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, which is a large population-based prospective study started in 1993. About 25,000 men and women were assessed at baseline and about 15,000 of them returned for a second examination 4 years later. All participants are followed up to the present for clinical events including fractures. My work is in two parts. For the first part, I examined the risk of fracture associated with some novel or less well studied risk factors. These risk factors included change in height over time, respiratory function, physical activity and body fat mass. We found that men and women with annual height loss &gt;0.5 cm are at increased risk of hip and any fracture (relative risk=1.9 (95% CI 1.3-2.7) per cm/year height loss). One litre lower forced expiratory volume in 1 second (FEV1) was associated with a 2-fold risk of hip fracture in men and women. We also observed a non-linear association, independent of body mass index, between increasing body fat mass and lower fracture risk in women but not in men. I performed a systematic review and meta-analysis of studies evaluating the association between physical activity and hip fractures. Using a new validated questionnaire in EPIC-Norfolk, we observed varying relationships between physical activity in different domains of life and fracture risk in men and women. For the second part of the thesis, I developed a biostatistical model to calculate 10-year risk of developing a fracture among EPIC-Norfolk study participants. This model incorporates clinical and radiological assessments known to be associated with fractures and can be extended to other risk factors assessed in other prospective cohorts. This helps clinicians to achieve a better estimate of the prospective risk of fracture in their patients. I applied this model to compare the predictive value of two different clinical assessment methods for osteoporosis, namely dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS). We found that that the predictive power of QUS is comparable to, and independent of, predictive power of DXA. In summary, my studies have added to our knowledge about some novel and easy-to-use risk factors of osteoporosis and proposed a practical method to merge and utilise data from different risk factors for estimation of fracture risk in individuals.
Description: For appendices see hardbound copy deposited in the Manuscripts Reading Room, Cambridge University Library.</description>
      <pubDate>Tue, 06 Mar 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/243860</guid>
      <dc:date>2012-03-06T00:00:00Z</dc:date>
    </item>
    <item>
      <title>Perceived challenges to public health in Central and Eastern Europe: a qualitative analysis</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/243257</link>
      <description>Title: Perceived challenges to public health in Central and Eastern Europe: a qualitative analysis
Authors: Müller-Nordhorn, Jacqueline; Holmberg, Christine; Dokova, Klara G; Milevska-Kostova, Neda; Chicin, Gratiana; Ulrichs, Timo; Rechel, Bernd; Willich, Stefan N; Powles, John; Tinnemann, Peter
Abstract: AbstractBackgroundThere is a major gradient in burden of disease between Central and Eastern Europe compared to Western Europe. Many of the underlying causes and risk factors are amenable to public health interventions. The purpose of the study was to explore perceptions of public health experts from Central and Eastern European countries on public health challenges in their countries.MethodsWe invited 179 public health experts from Central and Eastern European countries to a 2-day workshop in Berlin, Germany. A total of 25 public health experts from 14 countries participated in May 2008. The workshop was structured into 8 sessions of 1.5 hours each, with the topic areas covering coronary heart disease, stroke, prevention, obesity, alcohol, tobacco, tuberculosis, and HIV/AIDS. The workshop was recorded and the proceedings transcribed verbatim. The transcripts were entered into atlas.ti for content analysis and coded according to the session headings. After analysis of the content of each session discussion, a re-coding of the discussions took place based on the themes that emerged from the analysis.ResultsThemes discussed recurred across disease entities and sessions. Major themes were the relationship between clinical medicine and public health, the need for public health funding, and the problems of proving the effectiveness of disease prevention. Areas for action identified included the need to engage with the public, to create a better scientific basis for public health interventions, to identify “best practices” of disease prevention, and to implement registries/surveillance instruments. The need for improved data collection was seen throughout all areas discussed, as was the need to harmonize data across countries.ConclusionsTo reduce the burden of disease across Europe, closer collaboration of countries across Europe seems important in order to learn from each other. A more credible scientific basis for effective public health interventions is urgently needed. The monitoring of health trends is crucial to evaluate the impact of public health programmes.
Description: RIGHTS : This article is licensed under the BioMed Central licence at  http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'.  In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work  - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.</description>
      <pubDate>Wed, 25 Apr 2012 23:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/243257</guid>
      <dc:date>2012-04-25T23:00:00Z</dc:date>
    </item>
    <item>
      <title>Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/243255</link>
      <description>Title: Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study
Authors: Ritte, Rebecca; Lukanova, Annekatrin; Berrino, Franco; Dossus, Laure; Tjønneland, Anne; Olsen, Anja; Overvad, Thure F; Overvad, Kim; Clavel-Chapelon, Françoise; Fournier, Agnès; Fagherazzi, Guy; Rohrmann, Sabine; Teucher, Birgit; Boeing, Heiner; Aleksandrova, Krasimira; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Sieri, Sabina; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Quirós, José R; Buckland, Genevieve; Sánchez, Maria-José; Amiano, Pilar; Chirlaque, María-Dolores; Ardanaz, Eva; Sund, Malin; Lenner, Per; Bueno-de-Mesquita, Bas; van Gils, Carla H; Peeters, Petra H M; Krum-Hansen, Sanda; Gram, Inger T; Lund, Eiliv; Khaw, Kay-Tee; Wareham, Nick; Allen, Naomi E; Key, Timothy J; Romieu, Isabelle; Rinaldi, Sabina; Siddiq, Afshan; Cox, David; Riboli, Elio; Kaaks, Rudolf
Abstract: Abstract Introduction Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. Methods Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. Results For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (P het = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. Conclusions An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors.
Description: RIGHTS : This article is licensed under the BioMed Central licence at  http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'.  In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work  - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.</description>
      <pubDate>Sun, 13 May 2012 23:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/243255</guid>
      <dc:date>2012-05-13T23:00:00Z</dc:date>
    </item>
    <item>
      <title>A genome-wide association study to identify genetic markers associated with endometrial cancer grade</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/242146</link>
      <description>Title: A genome-wide association study to identify genetic markers associated with endometrial cancer grade
Description: RIGHTS : This article is licensed under the BioMed Central licence at  http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'.  In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work  - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.</description>
      <pubDate>Wed, 11 Apr 2012 23:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/242146</guid>
      <dc:date>2012-04-11T23:00:00Z</dc:date>
    </item>
    <item>
      <title>Association of Tamoxifen use and reduced risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/242143</link>
      <description>Title: Association of Tamoxifen use and reduced risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers
Description: RIGHTS : This article is licensed under the BioMed Central licence at  http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'.  In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work  - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.</description>
      <pubDate>Wed, 11 Apr 2012 23:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/242143</guid>
      <dc:date>2012-04-11T23:00:00Z</dc:date>
    </item>
    <item>
      <title>Mid-term functional outcome after the internal fixation of distal radius fractures</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/241668</link>
      <description>Title: Mid-term functional outcome after the internal fixation of distal radius fractures
Authors: Phadnis, Joideep; Trompeter, Alex; Gallagher, Kieran; Bradshaw, Lucy; Elliott, David S; Newman, Kevin J
Abstract: Abstract Background Distal radius fracture is a common injury with a variety of operative and non-operative management options. There remains debate as to the optimal treatment for a given patient and fracture. Despite the popularity of volar locking plate fixation, there are few large cohort or long term follow up studies to justify this modality. Our aim was to report the functional outcome of a large number of patients at a significant follow up time after fixation of their distal radius with a volar locking plate. Methods 180 patients with 183 fractures and a mean age of 62.4 years were followed up retrospectively at a mean of 30 months (Standard deviation = 10.4). Functional assessment was performed using the Disabilities of the Arm, Shoulder and Hand (DASH) and modified MAYO wrist scores. Statistical analysis was performed to identify possible variables affecting outcome and radiographs were assessed to determine time to fracture union. Results The median DASH score was 2.3 and median MAYO score was 90 for the whole group. Overall, 133 patients (74%) had a good or excellent DASH and MAYO score. Statistical analysis showed that no specific variable including gender, age, fracture type, post-operative immobilisation or surgeon grade significantly affected outcome. Complications occurred in 27 patients (15%) and in 11 patients were major (6%). Conclusion This single centre large population series demonstrates good to excellent results in the majority of patients after volar locking plate fixation of the distal radius, with complication rates comparable to other non-operative and operative treatment modalities. On this basis we recommend this mode of fixation for distal radius fractures requiting operative intervention.
Description: RIGHTS : This article is licensed under the BioMed Central licence at  http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'.  In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work  - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.</description>
      <pubDate>Thu, 26 Jan 2012 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/241668</guid>
      <dc:date>2012-01-26T00:00:00Z</dc:date>
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    <item>
      <title>Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2.</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/241605</link>
      <description>Title: Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2.
Authors: Mulligan, Anna Marie; Couch, Fergus J; Barrowdale, Daniel; Domchek, Susan M; Eccles, Diana; Nevanlinna, Heli; Ramus, Susan J; Robson, Mark; Sherman, Mark; Spurdle, Amanda B; Wappenschmidt, Barbara; Antoniou, Antonis C; Family Registry, Breast Cancer; Embrace, .; Collaborators, GEMO Study; Hebon, .; Network, Ontario Cancer Genetics; Swe-brca, .; Cimba, .; Osorio, Ana; Munoz-Repeto, Ivan; Coupier, Isabelle; Duran, Mercedes; Godino, Javier; Pertesi, Maroulio; Benitez, Javier; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Cattaneo, Elisa; Bonanni, Bernardo; Lebrun, Marine; Viel, Alessandra; Pasini, Barbara; Papi, Laura; Ottini, Laura; Savarese, Antonella; Bernard, Loris; Radice, Paolo; Hamann, Ute; Verheus, Martijn; Meijers-Heijboer, Hanne EJ; Kientz, Caroline; Wijnen, Juul; Gomez Garcia, Encarna B; Nelen, Marcel R; Kets, C Marleen; Seynaeve, Caroline; Tilanus-Linthorst, Madeleine MA; van der Luijt, Rob B; van Os, Theo; Rookus, Matti; Frost, Debra; Longy, Michel; Jones, J Louise; Evans, D Gareth; Lalloo, Fiona; Eeles, Ros; Izatt, Louise; Adlard, Julian; Davidson, Rosemarie; Cook, Jackie; Donaldson, Alan; Dorkins, Huw; Sevenet, Nicolas; Gregory, Helen; Eason, Jacqueline; Houghton, Catherine; Barwell, Julian; Side, Lucy E; McCann, Emma; Murray, Alex; Peock, Susan; Godwin, Andrew; Schmutzler, Rita K; Stoppa-Lyonnet, Dominique; Rhiem, Kerstin; Engel, Christoph; Meindl, Alfons; Ruehl, Ina; Arnold, Norbert; Niederacher, Dieter; Sutter, Christian; Deissler, Helmut; Gadzicki, Dorothea; Kast, Karin; Isaacs, Claudine; Preisler-Adams, Sabine; Varon-Mateeva, Raymonda; Schoenbuchner, Ines; Fiebig, Britta; Heinritz, Wolfram; Schafer, Dieter; Gevensleben, Heidrun; Caux-Moncoutier, Virginie; Fassy-Colcombet, Marion; Cornelis, Francois; Caldes, Trinidad; Mazoyer, Sylvie; Leone, Melanie; Boutry-Kryza, Nadia; Hardouin, Agnes; Berthet, Pascaline; Muller, Daniele; Fricker, Jean-Pierre; Mortemousque, Isabelle; Pujol, Pascal; de al Hoya, Miguel; Heikkinen, Tuomas; Lee, Andrew; Aittomaki, Kristiina; Blanco, Ignacio; Lazaro, Conxi; Barkardottir, Rosa B; Soucy, Penny; Dumont, Martine; Simard, Jacques; Montagna, Marco; Tognazzo, Silvia; D'Andrea, Emma; McGuffog, Lesley; Fox, Stephen; Yan, Max; Rebbeck, Timothy R; Olopade, Olufunmilayo I; Weitzel, Jeffrey N; Lynch, Henry T; Ganz, Patricia A; Tomlinson, Gail E; Wang, Xianshu; Fredericksen, Zachary; Healey, Sue; Pankratz, Vernon S; Lindor, Noralane M; Szabo, Csila; Offit, Kenneth; Sakr, Rita; Gaudet, Mia; Bhatia, Jasmine; Kauff, Noah; Singer, Christian F; Tea, Muy-Kheng; Sinilnikova, Olga M; Gschwantler-Kaulich, Daphne; Fink-Retter, Anneliese; Mai, Phuong L; Greene, Mark H; Imyanitov, Evgeny; O'Malley, Frances P; Ozcelik, Hilmi; Glendon, Gordon; Toland, Amanda E; Gerdes, Anne-Marie; Janavicius, Ramunas; Thomassen, Mads; Kruse, Torben A; Birk Jensen, Uffe; Skytte, Anne-Bine; Caligo, Maria A; Soller, Maria; Henriksson, Karin; von Wachenfeldt, Anna; Arver, Brita; Stenmark-Askmalm, Marie; Hansen, Thomas V O; Karlsson, Per; Ding, Yuan Chun; Neuhausen, Susan L; Beattie, Mary; Pharoah, Paul D P; Moysich, Kirsten B; Nathanson, Katherine L; Karlan, Beth Y; Gross, Jenny; John, Esther M; Nielsen, Finn C; Daly, Mary B; Buys, Saundra M; Southey, Melissa C; Hopper, John L; Terry, Mary Beth; Chung, Wendy; Miron, Alexander F; Goldgar, David; Chenevix-Trench, Georgia; Easton, Douglas F; Ejlertsen, Bent; Andrulis, Irene L
Abstract: Abstract Introduction Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. Methods We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. Results The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 × 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. Conclusions The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers.
Description: RIGHTS : This article is licensed under the BioMed Central licence at  http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'.  In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work  - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.</description>
      <pubDate>Wed, 02 Nov 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/241605</guid>
      <dc:date>2011-11-02T00:00:00Z</dc:date>
    </item>
    <item>
      <title>Attitudes of medical students to medical leadership and management: a systematic review to inform curriculum development</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/241600</link>
      <description>Title: Attitudes of medical students to medical leadership and management: a systematic review to inform curriculum development
Authors: Abbas, Mark R; Quince, Thelma A; Wood, Diana F; Benson, John A
Abstract: Abstract Background There is a growing acknowledgement that doctors need to develop leadership and management competences to become more actively involved in the planning, delivery and transformation of patient services. We undertook a systematic review of what is known concerning the knowledge, skills and attitudes of medical students regarding leadership and management. Here we report the results pertaining to the attitudes of students to provide evidence to inform curriculum development in this developing field of medical education. Methods We searched major electronic databases and citation indexes within the disciplines of medicine, education, social science and management. We undertook hand searching of major journals, and reference and citation tracking. We accessed websites of UK medical institutions and contacted individuals working within the field. Results 26 studies were included. Most were conducted in the USA, using mainly quantitative methods. We used inductive analysis of the topics addressed by each study to identity five main content areas: Quality Improvement; Managed Care, Use of Resources and Costs; General Leadership and Management; Role of the Doctor, and Patient Safety. Students have positive attitudes to clinical practice guidelines, quality improvement techniques and multidisciplinary teamwork, but mixed attitudes to managed care, cost containment and medical error. Education interventions had variable effects on students' attitudes. Medical students perceive a need for leadership and management education but identified lack of curriculum time and disinterest in some activities as potential barriers to implementation. Conclusions The findings from our review may reflect the relatively little emphasis given to leadership and management in medical curricula. However, students recognise a need to develop leadership and management competences. Although further work needs to be undertaken, using rigorous methods, to identify the most effective and cost-effective curriculum innovations, this review offers the only currently available summary of work examining the attitudes of students to this important area of development for future doctors.
Description: RIGHTS : This article is licensed under the BioMed Central licence at  http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'.  In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work  - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.</description>
      <pubDate>Mon, 14 Nov 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/241600</guid>
      <dc:date>2011-11-14T00:00:00Z</dc:date>
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      <title>Talking about living and dying with the oldest old: public involvement in a study on end of life care in care homes.</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/241206</link>
      <description>Title: Talking about living and dying with the oldest old: public involvement in a study on end of life care in care homes.
Authors: Goodman, Claire; Mathie, Elspeth; Cowe, Marion; Mendoza, Alex; Westwood, Daphne; Munday, Diane; Wilson, Patricia M; Crang, Clare; Froggatt, Katherine; Iliffe, Steve; Manthorpe, Jill; Gage, Heather; Barclay, Stephen
Abstract: Abstract Background Public involvement in research on sensitive subjects, such as death and dying, can help to ensure that questions are framed to reflect the interests of their peers, develop a shared understanding of issues raised, and moderate the often unequal power relationship between researcher and participant. This paper describes the contribution and impact of older members of a Public Involvement in Research group (PIRg) to a study on living and dying in care homes. Methods A longitudinal study, with a mixed method approach, its aims were to capture key experiences, events and change over one year, of older people resident in participating care homes in the East of England. Residents were interviewed up to three times and their case notes were reviewed four times over the year. Interviews were semi structured, and recorded. Four members of a Public Involvement in Research group (PIRg) contributed to preliminary discussions about the research and three were involved with many of the subsequent stages of the research process including the facilitation of discussion groups with residents. Results There were three areas where the involvement of the Public Involvement in Research group (PIRg) positively influenced the study process. These were recruitment, governance and safeguarding, and in collaboration with the residents in the care homes, the discussion and interpretation of emergent findings. PIRg members were of similar age to the residents and their involvement provided different and often more reflective insights of the significance of the findings for the participants. There were examples where decision making about the range of PIRg participation was not always negotiable, and this raised issues about power relationships within the team. Nevertheless, PIRg members expressed personal benefit and satisfaction through participating in the research and a commitment to continue to support research with this older age group. Conclusions The contribution of the PIRg supported a successful recruitment process that exceeded response rates of other studies in care homes. It safeguarded residents during the conduct of research on a sensitive topic and helped in validating the interview data gathered by the researchers through the discussion groups facilitated by the PIRg. There were power differentials that persisted and affected PIRg participation. The study has showed the value of developing job descriptions and a more formal means of setting out respective expectations. Future research may wish to elicit the views of focal participants in such studies about the mediation of research by public involvement in research.
Description: RIGHTS : This article is licensed under the BioMed Central licence at  http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'.  In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work  - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.; RIGHTS : This article is licensed under the BioMed Central licence at  http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'.  In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work  - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.</description>
      <pubDate>Wed, 23 Nov 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/241206</guid>
      <dc:date>2011-11-23T00:00:00Z</dc:date>
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      <title>Caregivers' perceived adequacy of support in end-stage lung disease: results of a population survey</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/241097</link>
      <description>Title: Caregivers' perceived adequacy of support in end-stage lung disease: results of a population survey
Authors: Currow, David C; Farquhar, Morag; Ward, Alicia M; Crawford, Gregory B; Abernethy, Amy P
Abstract: Abstract Background End-stage lung disease (ESLD) is a frequent cause of death. What are the differences in the supports needed by caregivers of individuals with ESLD at end of life versus other life-limiting diagnoses? Methods The South Australian Health Omnibus is an annual, random, face-to-face, cross-sectional survey. In 2002, 2003 and 2005-2007, respondents were asked a range of questions about end-of-life care; there were approximately 3000 survey participants annually (participation rate 77.9%). Responses were standardised for the whole population. The families and friends who cared for someone with ESLD were the focus of this analysis. In addition to describing caring, respondents reported additional support that would have been helpful. Results Of 1504 deaths reported, 145 (9.6%) were due to ESLD. The ESLD cohort were older than those with other 'expected' causes of death (&gt; 65 years of age; 92.6% versus 70.6%; p &lt; 0.0001) and were less likely to access specialised palliative care services (38.4% versus 61.9%; p &lt; 0.0001). For those with ESLD, the mean caring period was significantly longer at 25 months (standard deviation (SD) 24) than for 'other diagnoses' (15 months; SD 18; p &lt; 0.0001). Domains where additional support would have been useful included physical care, information provision, and emotional and spiritual support. Conclusions Caregiver needs were similar regardless of the underlying diagnosis although access to palliative care specialist services occurred less often for ESLD patients. This was despite significantly longer periods of time for which care was provided.
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      <pubDate>Fri, 25 Nov 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/241097</guid>
      <dc:date>2011-11-25T00:00:00Z</dc:date>
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      <title>Factors associated with mosquito net use by individuals in households owning nets in Ethiopia</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/241072</link>
      <description>Title: Factors associated with mosquito net use by individuals in households owning nets in Ethiopia
Authors: Graves, Patricia M; Ngondi, Jeremiah M; Hwang, Jimee; Getachew, Asefaw; Gebre, Teshome; Mosher, Aryc W; Patterson, Amy E; Shargie, Estifanos B; Tadesse, Zerihun; Wolkon, Adam; Reithinger, Richard; Emerson, Paul M; Richards, Frank O Jr
Abstract: Abstract Background Ownership of insecticidal mosquito nets has dramatically increased in Ethiopia since 2006, but the proportion of persons with access to such nets who use them has declined. It is important to understand individual level net use factors in the context of the home to modify programmes so as to maximize net use. Methods Generalized linear latent and mixed models (GLLAMM) were used to investigate net use using individual level data from people living in net-owning households from two surveys in Ethiopia: baseline 2006 included 12,678 individuals from 2,468 households and a sub-sample of the Malaria Indicator Survey (MIS) in 2007 included 14,663 individuals from 3,353 households. Individual factors (age, sex, pregnancy); net factors (condition, age, net density); household factors (number of rooms [2006] or sleeping spaces [2007], IRS, women's knowledge and school attendance [2007 only], wealth, altitude); and cluster level factors (rural or urban) were investigated in univariate and multi-variable models for each survey. Results In 2006, increased net use was associated with: age 25-49 years (adjusted (a) OR = 1.4, 95% confidence interval (CI) 1.2-1.7) compared to children U5; female gender (aOR = 1.4; 95% CI 1.2-1.5); fewer nets with holes (Ptrend = 0.002); and increasing net density (Ptrend &lt; 0.001). Reduced net use was associated with: age 5-24 years (aOR = 0.2; 95% CI 0.2-0.3). In 2007, increased net use was associated with: female gender (aOR = 1.3; 95% CI 1.1-1.6); fewer nets with holes (aOR [all nets in HH good] = 1.6; 95% CI 1.2-2.1); increasing net density (Ptrend &lt; 0.001); increased women's malaria knowledge (Ptrend &lt; 0.001); and urban clusters (aOR = 2.5; 95% CI 1.5-4.1). Reduced net use was associated with: age 5-24 years (aOR = 0.3; 95% CI 0.2-0.4); number of sleeping spaces (aOR [per additional space] = 0.6, 95% CI 0.5-0.7); more old nets (aOR [all nets in HH older than 12 months] = 0.5; 95% CI 0.3-0.7); and increasing household altitude (Ptrend &lt; 0.001). Conclusion In both surveys, net use was more likely by women, if nets had fewer holes and were at higher net per person density within households. School-age children and young adults were much less likely to use a net. Increasing availability of nets within households (i.e. increasing net density), and improving net condition while focusing on education and promotion of net use, especially in school-age children and young adults in rural areas, are crucial areas for intervention to ensure maximum net use and consequent reduction of malaria transmission.
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      <pubDate>Tue, 13 Dec 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/241072</guid>
      <dc:date>2011-12-13T00:00:00Z</dc:date>
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      <title>Modelling multiple outcomes to improve the detection of causal mediation effects in complex intervention trials</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/240744</link>
      <description>Title: Modelling multiple outcomes to improve the detection of causal mediation effects in complex intervention trials
Description: RIGHTS : This article is licensed under the BioMed Central licence at  http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'.  In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work  - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.</description>
      <pubDate>Tue, 13 Dec 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/240744</guid>
      <dc:date>2011-12-13T00:00:00Z</dc:date>
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      <title>Recruiting patients with advanced malignant and non-malignant disease: lessons learned from a palliative care RCT</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/240743</link>
      <description>Title: Recruiting patients with advanced malignant and non-malignant disease: lessons learned from a palliative care RCT
Description: RIGHTS : This article is licensed under the BioMed Central licence at  http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'.  In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work  - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.</description>
      <pubDate>Tue, 13 Dec 2011 00:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/240743</guid>
      <dc:date>2011-12-13T00:00:00Z</dc:date>
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      <title>Stability of empathy among undergraduate medical students: A longitudinal study at one UK medical school.</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/240579</link>
      <description>Title: Stability of empathy among undergraduate medical students: A longitudinal study at one UK medical school.
Authors: Quince, Thelma A; Parker, Richard A; Wood, Diana F; Benson, John A
Abstract: Abstract Background Empathy is important to patient care. The prevailing view is that empathy declines during university medical education. The significance of that decline has been debated. This paper reports the findings in respect of two questions relating to university medical education: 1. Do men and women medical students differ in empathy? 2. Does empathy change amongst men and women over time? Methods The medical course at the University of Cambridge comprises two components: Core Science (Years 1-3) and Clinical (Years 4-6). Data were obtained from repeated questionnaire surveys of medical students from each component over a period of four years: 2007-2010. Participation in the study was voluntary. Empathy was measured using two subscales of the Interpersonal Reactivity Index: IRI-EC (affective empathy) and IRI-PT (cognitive empathy). We analysed data separately for men and women from the Core Science and Clinical components. We undertook missing value analyses using logistic regression separately, for each measure of empathy, to examine non-response bias. We used Student's t-tests to examine gender differences and linear mixed effects regression analyses to examine changes over time. To assess the influence of outliers, we repeated the linear mixed effects regression analyses having excluded them. Results Women displayed statistically significant higher mean scores than men for affective empathy in all 6 years of medical training and for cognitive empathy in 4 out of 6 years - Years 1 and 2 (Core Science component) and Years 4 and 5 (Clinical component). Amongst men, affective empathy declined slightly during both Core Science and Clinical components. Although statistically significant, both of these changes were extremely small. Cognitive empathy was unchanged during either component. Amongst women, neither affective empathy nor cognitive empathy changed during either component of the course. Analysis following removal of outliers showed a statistically significant slight increase in men's cognitive empathy during the Core Science component and slight decline in women's affective empathy during the Clinical component. Again, although statistically significant, these changes were extremely small and do not influence the study's overall conclusions. Conclusions Amongst medical students at the University of Cambridge, women are more empathetic than men (a generally observed phenomenon). Men's affective empathy declined slightly across the course overall, whilst women's affective empathy showed no change. Neither men nor women showed any change in cognitive empathy during the course. Although statistically significant, the size of such changes as occurred makes their practical significance questionable. Neither men nor women appear to become meaningfully less empathetic during their medical education at the University of Cambridge.
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      <pubDate>Mon, 24 Oct 2011 23:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/240579</guid>
      <dc:date>2011-10-24T23:00:00Z</dc:date>
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      <title>Protocol for the OUTREACH trial: a randomised trial comparing delivery of cancer systemic therapy in three different settings -patient's home, GP surgery and hospital day unit</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/240558</link>
      <description>Title: Protocol for the OUTREACH trial: a randomised trial comparing delivery of cancer systemic therapy in three different settings -patient's home, GP surgery and hospital day unit
Authors: Corrie, Pippa G; Moody, Margaret; Wood, Victoria; Bavister, Linda; Prevost, Toby; Parker, Richard A; Sabes-Figuera, Ramon; McCrone, Paul; Balsdon, Helen; McKinnon, Karen; O'Sullivan, Brendan; Tan, Ray S; Barclay, Steven IG
Abstract: Abstract Background The national Cancer Reform Strategy recommends delivering care closer to home whenever possible. Cancer drug treatment has traditionally been administered to patients in specialist hospital-based facilities. Technological developments mean that nowadays, most treatment can be delivered in the out-patient setting. Increasing demand, care quality improvements and patient choice have stimulated interest in delivering some treatment to patients in the community, however, formal evaluation of delivering cancer treatment in different community settings is lacking. This randomised trial compares delivery of cancer treatment in the hospital with delivery in two different community settings: the patient's home and general practice (GP) surgeries. Methods/design Patients due to receive a minimum 12 week course of standard intravenous cancer treatment at two hospitals in the Anglia Cancer Network are randomised on a 1:1:1 basis to receive treatment in the hospital day unit (control arm), or their own home, or their choice of one of three neighbouring GP surgeries. Overall patient care, treatment prescribing and clinical review is undertaken according to standard local practice. All treatment is dispensed by the local hospital pharmacy and treatment is delivered by the hospital chemotherapy nurses. At four time points during the 12 week study period, information is collected from patients, nursing staff, primary and secondary care teams to address the primary end point, patient-perceived benefits (using the emotional function domain of the EORTC QLQC30 patient questionnaire), as well as secondary end points: patient satisfaction, safety and health economics. Discussion The Outreach trial is the first randomised controlled trial conducted which compares delivery of out-patient based intravenous cancer treatment in two different community settings with standard hospital based treatment. Results of this study may better inform all key stakeholders regarding potential costs and benefits of transferring clinical services from hospital to the community. Trial registration number ISRCTN: ISRCTN66219681
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      <pubDate>Fri, 28 Oct 2011 23:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/240558</guid>
      <dc:date>2011-10-28T23:00:00Z</dc:date>
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      <title>Sedative load of medications prescribed for older people with dementia in care homes</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/239298</link>
      <description>Title: Sedative load of medications prescribed for older people with dementia in care homes
Authors: Parsons, Carole; Haydock, Jane; Mathie, Elspeth; Baron, Natasha; Machen, Ina; Stevenson, Elizabeth; Amador, Sarah; Goodman, Claire
Abstract: Abstract Background The objective of this study was to determine the sedative load and use of sedative and psychotropic medications among older people with dementia living in (residential) care homes. Methods Medication data were collected at baseline and at two further time-points for eligible residents of six care homes participating in the EVIDEM-End Of Life (EOL) study for whom medication administration records were available. Regular medications were classified using the Anatomical Therapeutic Chemical classification system and individual sedative loads were calculated using a previously published model. Results At baseline, medication administration records were reviewed for 115 residents; medication records were reviewed for 112 and 105 residents at time-points 2 and 3 respectively. Approximately one-third of residents were not taking any medications with sedative properties at each time-point, while a significant proportion of residents had a low sedative load score of 1 or 2 (54.8%, 59.0% and 57.1% at baseline and time-points 2 and 3 respectively). More than 10% of residents had a high sedative load score (≥ 3) at baseline (12.2%), and this increased to 14.3% at time-points 2 and 3. Approximately two-thirds of residents (66.9%) regularly used one or more psychotropic medication(s). Antidepressants, predominantly selective serotonin re-uptake inhibitors (SSRIs), were most frequently used, while antipsychotics, hypnotics and anxiolytics were less routinely administered. The prevalence of antipsychotic use among residents was 19.0%, lower than has been previously reported for nursing home residents. Throughout the duration of the study, administration of medications recognised as having prominent sedative adverse effects and/or containing sedative components outweighed the regular use of primary sedatives. Conclusions Sedative load scores were similar throughout the study period for residents with dementia in each of the care homes. Scores were lower than previously reported in studies conducted in long-term care wards which have on-site clinical support. Nevertheless, strategies to optimise drug therapy for care home residents with dementia which rely on clinicians external to the care home for support and medication review are required.
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      <pubDate>Thu, 29 Sep 2011 23:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/239298</guid>
      <dc:date>2011-09-29T23:00:00Z</dc:date>
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      <title>Gene- or region-based association study via kernel principal component analysis</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/238982</link>
      <description>Title: Gene- or region-based association study via kernel principal component analysis
Authors: Gao, Qingsong; He, Yungang; Yuan, Zhongshang; Zhao, Jinghua; Zhang, Bingbing; Xue, Fuzhong
Abstract: Abstract Background In genetic association study, especially in GWAS, gene- or region-based methods have been more popular to detect the association between multiple SNPs and diseases (or traits). Kernel principal component analysis combined with logistic regression test (KPCA-LRT) has been successfully used in classifying gene expression data. Nevertheless, the purpose of association study is to detect the correlation between genetic variations and disease rather than to classify the sample, and the genomic data is categorical rather than numerical. Recently, although the kernel-based logistic regression model in association study has been proposed by projecting the nonlinear original SNPs data into a linear feature space, it is still impacted by multicolinearity between the projections, which may lead to loss of power. We, therefore, proposed a KPCA-LRT model to avoid the multicolinearity. Results Simulation results showed that KPCA-LRT was always more powerful than principal component analysis combined with logistic regression test (PCA-LRT) at different sample sizes, different significant levels and different relative risks, especially at the genewide level (1E-5) and lower relative risks (RR = 1.2, 1.3). Application to the four gene regions of rheumatoid arthritis (RA) data from Genetic Analysis Workshop16 (GAW16) indicated that KPCA-LRT had better performance than single-locus test and PCA-LRT. Conclusions KPCA-LRT is a valid and powerful gene- or region-based method for the analysis of GWAS data set, especially under lower relative risks and lower significant levels.
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      <pubDate>Thu, 25 Aug 2011 23:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/238982</guid>
      <dc:date>2011-08-25T23:00:00Z</dc:date>
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      <title>The reliability of assigning individuals to cognitive states using the Mini Mental-State Examination: a population-based prospective cohort study.</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/238981</link>
      <description>Title: The reliability of assigning individuals to cognitive states using the Mini Mental-State Examination: a population-based prospective cohort study.
Authors: Marioni, Riccardo E; Chatfield, Mark; Brayne, Carol; Matthews, Fiona E; Ageing Study, Medical Research Council Cognitive Function and
Abstract: Abstract Background Previous investigations of test re-test reliability of the Mini-Mental State Examination (MMSE) have used correlations and statistics such as Cronbach's α to assess consistency. In practice, the MMSE is usually used to group individuals into cognitive states. The reliability of this grouping (state based approach) has not been fully explored. Methods MMSE data were collected on a subset of 2,275 older participants (≥ 65 years) from the population-based Medical Research Council Cognitive Function and Ageing Study. Two measurements taken approximately two months apart were used to investigate three state-based categorisations. Descriptive statistics were used to determine how many people remained in the same cognitive group or went up or down groups. Weighted logistic regression was used to identify predictive characteristics of those who moved group. Results The proportion of people who remained in the same MMSE group at screen and follow-up assessment ranged from 58% to 78%. The proportion of individuals who went up one or more groups was roughly equal to the proportion that went down one or more groups; most of the change occurred when measurements were close to the cut-points. There was no consistently significant predictor for changing cognitive group. Conclusion A state-based approach to analysing the reliability of the MMSE provided similar results to correlation analyses. State-based models of cognitive change or individual trajectory models using raw scores need multiple waves to help overcome natural variation in MMSE scores and to help identify true cognitive change.
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      <pubDate>Mon, 05 Sep 2011 23:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/238981</guid>
      <dc:date>2011-09-05T23:00:00Z</dc:date>
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    <item>
      <title>Exploring the link between MORF4L1 and risk of breast cancer</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/238301</link>
      <description>Title: Exploring the link between MORF4L1 and risk of breast cancer
Authors: Martrat, Griselda; Maxwell, Christopher A; Tominaga, Emiko; Porta, Montserrat; Bonifaci, Nuria; Gomez-Baldo, Laia; Bogliolo, Massimo; Lazaro, Conxi; Blanco, Ignacio; Brunet, Joan; Aguilar, Helena; Uhrhammer, Nancy; Torres, Diana; Caligo, Maria Adelaide; Godwin, Andrew K; Fernandez-Rodriguez, Juana; Imyanitov, Evgeny N; Janavicius, Ramunas; (gemo), Groupe Genetique et Cancer; Sinilnikova, Olga M; Stoppa-Lyonnet, Dominique; Davidson, Rosemarie; Mazoyer, Sylvie; Peyrat, Jean-Philippe; Verny-Pierre, Carole; Castera, Laurent; de Pauw, Antoine; Bignon, Yves-Jean; Vennin, Philippe; Fert Ferrer, Sandra; Collonge-Rame, Marie-Agnes; Mortemousque, Isabelle; Ramirez, Maria J; McGuffog, Lesley; Chenevix-Trench, Georgia; Pereira-Smith, Olivia M; Chu, Carol; Antoniou, Antonis C; Renwick, Anthony; Ceron, Julian; Tominaga, Kaoru; Surralles, Jordi; Pujana, Miguel Angel; Castella, Maria; Rahman, Nazneen; Kuhl, Julia; Neveling, Kornelia; Schindler, Detlev; Hernandez, Gonzalo; (embrace), Epidemiological Study of Familial Breast Cancers; Easton, Douglas F; Peock, Susan; Cook, Margaret; Oliver, Clare T; Frost, Debra; Blok, Marinus J; Platte, Radka; Ong, Kai-Ren; Evans, D Gareth; Lalloo, Fiona; Eeles, Rosalind; Izatt, Louise; Cook, Jackie; Douglas, Fiona; Hodgson, Shirley V; Brewer, Carole; Bernard, Loris; Morrison, Patrick J; Porteous, Mary; Peterlongo, Paolo; van Os, Theo A; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Roversi, Gaia; Barile, Monica; Viel, Alessandra; Radice, Paolo; Pasini, Barbara; Ottini, Laura; Putignano, Anna Laura; Savarese, Antonella; Healey, Sue; Spurdle, Amanda B; Chen, Xiaoqing; Beesley, Jonathan; (kConFab), Kathleen Cuningham Foundation Consortium for Research; Rookus, Matti A; Verhoef, Senno; Osorio, Ana; Tilanus-Linthorst, Madeleine A; Meijers-Heijboer, Hanne E J; Vreeswijk, Maaike P; Asperen, Christi J; Bodmer, Danielle; Ausems, Margreet G E M; Hogervorst, Frans B; (hebon), Hereditary Breast and Ovarian Cancer Research Group Netherlands; Goldgar, David E; Buys, Saundra; Laitman, Yael; John, Esther M; Miron, Alexander; Southey, Melissa C; Caldes, Trinidad; Daly, Mary B; (bcfr), Breast Cancer Family Registry; (swe-brca), Swedish Breast Cancer Study; Harbst, Katja; Borg, Ake; Rantala, Johanna; Milgrom, Roni; Barbany-Bustinza, Gisela; Ehrencrona, Hans; Stenmark-Askmalm, Marie; Kaufman, Bella; Friedman, Eitan; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy R; Johannsson, Oskar Thor; Couch, Fergus J; Wang, Xianshu; Seal, Sheila; Fredericksen, Zachary S; Benitez, Javier; Cuadras, Daniel; Moreno, Victor; Pientka, Friederike K; Depping, Reinhard; Bueren, Juan; Heikkinen, Tuomas; Nevanlinna, Heli; Hamann, Ute
Abstract: Abstract Introduction Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P trend = 0.45 and 0.05, P 2df = 0.51 and 0.14, respectively; and rs10519219, P trend = 0.92 and 0.72, P 2df = 0.76 and 0.07, respectively. Conclusions While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
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      <pubDate>Mon, 04 Apr 2011 23:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/238301</guid>
      <dc:date>2011-04-04T23:00:00Z</dc:date>
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    <item>
      <title>Antibiotic Consumption in Children Prior to Diagnosis of Asthma</title>
      <link>http://www.dspace.cam.ac.uk:80/handle/1810/238289</link>
      <description>Title: Antibiotic Consumption in Children Prior to Diagnosis of Asthma
Authors: Marra, Fawziah; Marra, Carlo A; Richardson, Kathryn J; Lynd, Larry D; Fitzgerald, J Mark
Abstract: AbstractBackgroundAsthma is difficult to diagnose in children and at times misdiagnosis of an infection can occur. However, little is known about the magnitude and patterns of antibiotic consumption in children with asthma relative to those without asthma.MethodsUsing population-based data, 128,872 children were identified with at least 6 years of follow-up. The adjusted rate-ratio (RR) of antibiotics dispensed to asthmatic as compared to non-asthmatic children was determined. ResultsAt age six, the RR of antibiotic consumption for asthmatics compared to non-asthmatics varied between, 1.66 to 2.32, depending on the year of asthma diagnosis. Of the 18,864 children with asthma at ages 2-8, 52% (n=9,841) had antibiotics dispensed in the 6 months prior to their index date of asthma diagnosis. The RR of antibiotic consumption in the 1 month prior to asthma diagnosis compared to 5 months prior was 1.66 (95% CI 1.60-1.71). The RR was lower in males compared to females (1.58 vs 1.77), and lower in those who received antibiotics in the first year of life relative to those that did not (1.60 vs. 1.76). ConclusionsThere is higher antibiotic consumption in children with asthma compared to those without asthma. The pattern of antibiotic use suggests that diagnosis guidelines are difficult to follow in young children leading to misdiagnosis and over treatment with antibiotics.
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      <pubDate>Mon, 30 May 2011 23:00:00 GMT</pubDate>
      <guid isPermaLink="false">http://www.dspace.cam.ac.uk:80/handle/1810/238289</guid>
      <dc:date>2011-05-30T23:00:00Z</dc:date>
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