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1.  B cell sub-types following acute malaria and associations with clinical immunity 
Malaria Journal  2016;15:139.
Background
Repeated exposure to Plasmodium falciparum is associated with perturbations in B cell sub-set homeostasis, including expansion atypical memory B cells. However, B cell perturbations immediately following acute malaria infection have been poorly characterized, especially with regard to their relationship with immunity to malaria.
Methods
To better understand the kinetics of B cell sub-sets following malaria, the proportions of six B cell sub-sets were assessed at five time points following acute malaria in four to 5 years old children living in a high transmission region of Uganda. B cell sub-set kinetics were compared with measures of clinical immunity to malaria—lower parasite density at the time of malaria diagnosis and recent asymptomatic parasitaemia.
Results
Atypical memory B cell and transitional B cell proportions increased following malaria. In contrast, plasmablast proportions were highest at the time of malaria diagnosis and rapidly declined following treatment. Increased proportions of atypical memory B cells were associated with greater immunity to malaria, whereas increased proportions of transitional B cells were associated with evidence of less immunity to malaria.
Conclusions
These findings highlight the dynamic changes in multiple B cell sub-sets following acute, uncomplicated malaria, and how these sub-sets are associated with developing immunity to malaria.
doi:10.1186/s12936-016-1190-0
PMCID: PMC4778296  PMID: 26939776
Atypical memory B cells; Transitional B cells; Plasmablasts; Plasma cells Plasmodium falciparum; Malaria; Immunity
2.  An assessment of the barriers to accessing the Basic Package of Health Services (BPHS) in Afghanistan: was the BPHS a success? 
Afghanistan is one of the most fragile and conflict-affected countries in the world. It has experienced almost uninterrupted conflict for the last thirty years, with the present conflict now lasting over a decade. With no history of a functioning healthcare system, the creation of the Basic Package of Health Services (BPHS) in 2003 was a response to Afghanistan’s dire health needs following decades of war. Its objective was to provide a bare minimum of essential health services, which could be scaled up rapidly through contracting mechanisms with Non-Governmental Organisations (NGOs). The central thesis of this article is that, despite the good intentions of the BPHS, not enough has been done to overcome the barriers to accessing its services. This analysis, enabled through a review of the existing literature, identifies and categorises these barriers into the three access dimensions of: acceptability, affordability and availability. As each of these is explored individually, analysis will show the extent to which these barriers to access are a critical issue, consider the underlying reasons for their existence and evaluate the efforts to overcome these barriers. Understanding these barriers and the policies that have been implemented to address them is critical to the future of health system strengthening in Afghanistan.
doi:10.1186/s12992-016-0212-6
PMCID: PMC5111262  PMID: 27846910
Health system reconstruction; Fragile states; Health system policy; Aid effectiveness; Maternal health; Health system financing; Afghanistan
3.  Lumbar disc degeneration is associated with modic change and high paraspinal fat content – a 3.0T magnetic resonance imaging study 
Background
Degenerative disc disease of the lumbar spine is common, with severe disease increasing the risk for chronic low back pain. This cross-sectional study examined whether disc degeneration is representative of a ‘whole-organ’ pathology, by examining its association with bone (vertebral endplate) and soft tissue (paraspinal muscle fat) abnormalities.
Methods
Seventy-two community-based individuals unselected for low back pain, had Magnetic Resonance Imaging (MRI). Lumbosacral disc degeneration was determined via the Pfirrmann grading system, a validated method to assess the intervertebral disc, distinguishing the nucleus and annulus, the signal intensity and the height of the intervertebral disc. Modic change and high paraspinal muscle fat content was also measured from MRI.
Results
Severe disc degeneration was associated, or tended to be associated with type 2 Modic change from L2 to L5 (OR range 3.5 to 25.3, p ≤ 0.06). Moreover, severe disc degeneration at all intervertebral levels was associated with or tended to be associated with high fat content of the paraspinal muscles (OR range 3.7 to 14.3, p ≤ 0.09).
Conclusion
These data demonstrate that disc degeneration of the lumbar spine is commonly accompanied by Modic change and high fat content of paraspinal muscles, thus representing a ‘whole-organ’ pathology. Longitudinal studies are required to determine the temporal relationship between these structural abnormalities. Understanding this may have the potential to identify novel targets for the treatment and prevention of lumbosacral disc degeneration.
doi:10.1186/s12891-016-1297-z
PMCID: PMC5073831  PMID: 27765024
Lumbar; Intervertebral disc; Disc degeneration; Modic; Muscle; Fat
4.  Eradicating polio in Pakistan: an analysis of the challenges and solutions to this security and health issue 
Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988 the global incidence of poliomyelitis has fallen by nearly 99 %. From a situation where wild type poliovirus was endemic in 125 countries across five continents, transmission is now limited to regions of just three countries – Pakistan, Afghanistan and Nigeria. A sharp increase in Pakistan’s poliomyelitis cases in 2014 prompted the International Health Regulations Emergency Committee to declare the situation a ‘public health emergency of international concern’. Global polio eradication hinges on Pakistan’s ability to address the religious, political and socioeconomic barriers to immunisation; including discrepancies in vaccine coverage, a poor health infrastructure, and conflict in polio-endemic regions of the country. This analysis provides an overview of the GPEI, focusing on the historical and contemporary challenges facing Pakistan’s polio eradication programme and the impact of conflict and insecurity, and sheds light on strategies to combat vaccine hesitancy, engage local communities and build on recent progress towards polio eradication in Pakistan.
doi:10.1186/s12992-016-0195-3
PMCID: PMC5059991  PMID: 27729081
Polio; Pakistan; Conflict and health; Vaccine coverage; Socioeconomic factors; Global health
5.  ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016 
Dittrich, Christian | Kosty, Michael | Jezdic, Svetlana | Pyle, Doug | Berardi, Rossana | Bergh, Jonas | El-Saghir, Nagi | Lotz, Jean-Pierre | Österlund, Pia | Pavlidis, Nicholas | Purkalne, Gunta | Awada, Ahmad | Banerjee, Susana | Bhatia, Smita | Bogaerts, Jan | Buckner, Jan | Cardoso, Fatima | Casali, Paolo | Chu, Edward | Close, Julia Lee | Coiffier, Bertrand | Connolly, Roisin | Coupland, Sarah | De Petris, Luigi | De Santis, Maria | de Vries, Elisabeth G E | Dizon, Don S | Duff, Jennifer | Duska, Linda R | Eniu, Alexandru | Ernstoff, Marc | Felip, Enriqueta | Fey, Martin F | Gilbert, Jill | Girard, Nicolas | Glaudemans, Andor W J M | Gopalan, Priya K | Grothey, Axel | Hahn, Stephen M | Hanna, Diana | Herold, Christian | Herrstedt, Jørn | Homicsko, Krisztian | Jones, Dennie V | Jost, Lorenz | Keilholz, Ulrich | Khan, Saad | Kiss, Alexander | Köhne, Claus-Henning | Kunstfeld, Rainer | Lenz, Heinz-Josef | Lichtman, Stuart | Licitra, Lisa | Lion, Thomas | Litière, Saskia | Liu, Lifang | Loehrer, Patrick J | Markham, Merry Jennifer | Markman, Ben | Mayerhoefer, Marius | Meran, Johannes G | Michielin, Olivier | Moser, Elizabeth Charlotte | Mountzios, Giannis | Moynihan, Timothy | Nielsen, Torsten | Ohe, Yuichiro | Öberg, Kjell | Palumbo, Antonio | Peccatori, Fedro Alessandro | Pfeilstöcker, Michael | Raut, Chandrajit | Remick, Scot C | Robson, Mark | Rutkowski, Piotr | Salgado, Roberto | Schapira, Lidia | Schernhammer, Eva | Schlumberger, Martin | Schmoll, Hans-Joachim | Schnipper, Lowell | Sessa, Cristiana | Shapiro, Charles L | Steele, Julie | Sternberg, Cora N | Stiefel, Friedrich | Strasser, Florian | Stupp, Roger | Sullivan, Richard | Tabernero, Josep | Travado, Luzia | Verheij, Marcel | Voest, Emile | Vokes, Everett | Von Roenn, Jamie | Weber, Jeffrey S | Wildiers, Hans | Yarden, Yosef
ESMO Open  2016;1(5):e000097.
The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) thanks to contribution of 64 ESMO-appointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine apart from the revival of immunotherapy, requiring specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
doi:10.1136/esmoopen-2016-000097
PMCID: PMC5070299  PMID: 27843641
Global curriculum; clinical training; medical oncology; didactic principles; learning objectives
6.  European Non-Communicable Respiratory Disease Research, 2002-13: Bibliometric Study of Outputs and Funding 
PLoS ONE  2016;11(4):e0154197.
This study was conducted in order to map European research in chronic respiratory diseases (CRDs). It was intended to assist the European Commission and other research funders to identify gaps and overlaps in their portfolios, and to suggest ways in which they could improve the effectiveness of their support and increase the impact of the research on patient care and on the reduction of the incidence of the CRDs. Articles and reviews were identified in the Web of Science on research in six non-communicable respiratory diseases that were published in 2002–13 from 31 European countries. They represented only 0.8% of biomedical research output but these diseases accounted for 4.7% of the European disease burden, as measured by Disability-Adjusted Life Years (DALYs), so the sub-field is seriously under-researched. Europe is prominent in the sub-field and published 56% of the world total, with the UK the most productive and publishing more than France and Italy, the next two countries, combined. Asthma and Chronic Obstructive Pulmonary Disease (COPD) were the diseases with the most publications and the highest citation rates. They also received the most funding, with around two acknowledgments per paper (in 2009–13), whereas cystic fibrosis and emphysema averaged only one. Just over 37% of papers had no specific funding and depended on institutional support from universities and hospitals.
doi:10.1371/journal.pone.0154197
PMCID: PMC4844158  PMID: 27111670
7.  Observed and Predicted Risk of Breast Cancer Death in Randomized Trials on Breast Cancer Screening 
PLoS ONE  2016;11(4):e0154113.
Background
The role of breast screening in breast cancer mortality declines is debated. Screening impacts cancer mortality through decreasing the number of advanced cancers with poor diagnosis, while cancer treatment works through decreasing the case-fatality rate. Hence, reductions in cancer death rates thanks to screening should directly reflect reductions in advanced cancer rates. We verified whether in breast screening trials, the observed reductions in the risk of breast cancer death could be predicted from reductions of advanced breast cancer rates.
Patients and Methods
The Greater New York Health Insurance Plan trial (HIP) is the only breast screening trial that reported stage-specific cancer fatality for the screening and for the control group separately. The Swedish Two-County trial (TCT)) reported size-specific fatalities for cancer patients in both screening and control groups. We computed predicted numbers of breast cancer deaths, from which we calculated predicted relative risks (RR) and (95% confidence intervals). The Age trial in England performed its own calculations of predicted relative risk.
Results
The observed and predicted RR of breast cancer death were 0.72 (0.56–0.94) and 0.98 (0.77–1.24) in the HIP trial, and 0.79 (0.78–1.01) and 0.90 (0.80–1.01) in the Age trial. In the TCT, the observed RR was 0.73 (0.62–0.87), while the predicted RR was 0.89 (0.75–1.05) if overdiagnosis was assumed to be negligible and 0.83 (0.70–0.97) if extra cancers were excluded.
Conclusions
In breast screening trials, factors other than screening have contributed to reductions in the risk of breast cancer death most probably by reducing the fatality of advanced cancers in screening groups. These factors were the better management of breast cancer patients and the underreporting of breast cancer as the underlying cause of death. Breast screening trials should publish stage-specific fatalities observed in each group.
doi:10.1371/journal.pone.0154113
PMCID: PMC4839680  PMID: 27100174
9.  Modic changes in the lumbar spine and their association with body composition, fat distribution and intervertebral disc height – a 3.0 T-MRI study 
Background
Vertebral endplate (Modic) abnormalities are important structural lesions in the spine, but their association with body composition and fat distribution have not been examined. Moreover, no study has examined whether Modic change are related to other structural features of low back pain, such as reduced intervertebral disc height.
Methods
Seventy-two community-based individuals not selected for low back pain had lumbar vertebral Modic change and intervertebral disc height assessed from MRI. Dual energy x-ray absorptiometry measured body composition and fat distribution.
Results
The predominance of Modic change was type 2. Modic change was associated with an increased fat mass index (OR 1.20, 95 % CI 1.01 to 1.43), and tended to be associated with a reduced fat-free mass index (OR 0.62, 95 % CI 0.37 to 1.03, p = 0.07). While an increased percentage of gynoid fat was associated with a reduced risk (OR 0.62, 95 % CI 0.43 to 0.89), an increased percentage of android fat was associated with an increased risk of Modic change (OR 2.11, 95 % CI 1.18 to 3.76). Modic change was also associated with reduced intervertebral disc height at L2/3, L4/5 and L5/S1 (OR range 1.4 to 1.8; all p ≤ 0.03).
Conclusion
Modic type 2 change is associated with reduced intervertebral disc height and an increased fat mass index. Whereas gynoid fat distribution protected against Modic type 2 change, an android pattern increased the risk of this lesion. Modic type 2 change, which histologically represent fat replacement, might have a metabolic component to its aetiology.
doi:10.1186/s12891-016-0934-x
PMCID: PMC4759726  PMID: 26891686
Lumbar spine; Intervertebral disc; Modic; Fat mass; Fat free mass; Android; Gynoid; Height; Body composition; MRI; Adiposity
10.  Lung cancer researchers, 2008–2013: their sex and ethnicity 
Scientometrics  2015;106:105-117.
This paper describes the process by which almost all authors of papers in the Web of Science (WoS) can be characterised by their sex and ethnicity or national background, based on their names. These are compared with two large databases of surnames and given names to determine to which of some 160 different ethnic groups they are most likely to belong. Since 2008 the authors of WoS papers are tagged with their addresses, and many have their given names if they appear on the paper, so the workforce composition of each country can be determined. Conversely, the current location of members of particular ethnic groups can be found. This will show the extent of a country’s “brain drain”, if any. Key results are shown for one subject area, and inter alia it appears that the majority of researchers of Indian origin who are active in lung cancer research are working in the USA. But East Asians (Chinese, Japanese and Koreans) tend to stay in their country of birth.
doi:10.1007/s11192-015-1785-1
PMCID: PMC4709374  PMID: 26798161
Lung cancer; Onomastics; National origins; Sex
11.  Statistical analyses in Swedish randomised trials on mammography screening and in other randomised trials on cancer screening: a systematic review 
Objectives
We compared calculations of relative risks of cancer death in Swedish mammography trials and in other cancer screening trials.
Participants
Men and women from 30 to 74 years of age.
Setting
Randomised trials on cancer screening.
Design
For each trial, we identified the intervention period, when screening was offered to screening groups and not to control groups, and the post-intervention period, when screening (or absence of screening) was the same in screening and control groups. We then examined which cancer deaths had been used for the computation of relative risk of cancer death.
Main outcome measures
Relative risk of cancer death.
Results
In 17 non-breast screening trials, deaths due to cancers diagnosed during the intervention and post-intervention periods were used for relative risk calculations. In the five Swedish trials, relative risk calculations used deaths due to breast cancers found during intervention periods, but deaths due to breast cancer found at first screening of control groups were added to these groups. After reallocation of the added breast cancer deaths to post-intervention periods of control groups, relative risks of 0.86 (0.76; 0.97) were obtained for cancers found during intervention periods and 0.83 (0.71; 0.97) for cancers found during post-intervention periods, indicating constant reduction in the risk of breast cancer death during follow-up, irrespective of screening.
Conclusions
The use of unconventional statistical methods in Swedish trials has led to overestimation of risk reduction in breast cancer death attributable to mammography screening. The constant risk reduction observed in screening groups was probably due to the trial design that optimised awareness and medical management of women allocated to screening groups.
doi:10.1177/0141076815593403
PMCID: PMC4672251  PMID: 26152677
breast cancer; screening; randomised trials; statistical analyses
12.  Bone marrow lesions can be subtyped into groups with different clinical outcomes using two magnetic resonance imaging (MRI) sequences 
Introduction
Bone marrow lesions (BMLs) are features detected on MRI that are important in the pathogenesis of knee osteoarthritis. Since BMLs reflect heterogeneous pathologies this prospective cohort study examined whether BMLs detected using different MRI sequences are associated with distinct structural and clinical endpoints.
Methods
A total of 297 community-based adults without knee pain were examined to identify BMLs visualised using three-dimensional T1-weighted gradient-echo fat-suppressed (T1-weighted sequences) fat-suppressed and fat-saturated FSE T2-weighted MRI sequences (T2-weighted sequences) at baseline. Cartilage volume was measured at baseline and follow-up, while incident knee pain was assessed at follow-up, an average of 2.3 years later.
Results
At baseline, 46 BMLs were visualised in 39 participants. Of the 45 BMLs visualised on T2-weighted sequences, 34 (74 %) were also seen on T1-weighted sequences. One BML was seen on only T1-weighted sequences. Knees with BMLs visualised on both T1- and T2-weighted sequences had significantly higher medial tibial cartilage volume loss (45 mm3/annum, standard error of the mean (SEM) 14) than those with BMLs identified on only T2-weighted sequences (−13 mm3/annum SEM 19), after adjustment for age, gender and body mass index (p = 0.01). Incident knee pain was more likely in individuals with BMLs in the medial compartment visualised on both T1- and T2-weighted (eight participants, 53 %) compared to those with BMLs on only T2-weighted sequences (0 %) or no BMLs (76 participants, 31 %, p = 0.02).
Conclusions
BMLs present on both T1- and T2-weighted MRI sequences were associated with increased medial tibial cartilage loss and incident knee pain compared with those BMLs seen only on T2-weighted sequences. This suggests that combining different MRI sequences may provide more informative targets in the prevention and treatment of knee osteoarthritis.
doi:10.1186/s13075-015-0780-5
PMCID: PMC4584130  PMID: 26410822
Knee; Osteoarthritis; Bone marrow lesion; Pain
13.  FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure 
PLoS Pathogens  2015;11(5):e1004894.
Exposure to Plasmodium falciparum is associated with circulating “atypical” memory B cells (atMBCs), which appear similar to dysfunctional B cells found in HIV-infected individuals. Functional analysis of atMBCs has been limited, with one report suggesting these cells are not dysfunctional but produce protective antibodies. To better understand the function of malaria-associated atMBCs, we performed global transcriptome analysis of these cells, obtained from individuals living in an area of high malaria endemicity in Uganda. Comparison of gene expression data suggested down-modulation of B cell receptor signaling and apoptosis in atMBCs compared to classical MBCs. Additionally, in contrast to previous reports, we found upregulation of Fc receptor-like 5 (FCRL5), but not FCRL4, on atMBCs. Atypical MBCs were poor spontaneous producers of antibody ex vivo, and higher surface expression of FCRL5 defined a distinct subset of atMBCs compromised in its ability to produce antibody upon stimulation. Moreover, higher levels of P. falciparum exposure were associated with increased frequencies of FCRL5+ atMBCs. Together, our findings suggest that FCLR5+ identifies a functionally distinct, and perhaps dysfunctional, subset of MBCs in individuals exposed to P. falciparum.
Author Summary
A subset of “atypical” memory B cells found in individuals with high exposure to P. falciparum has been hypothesized to be dysfunctional, based on phenotypic similarities to analogous cells found in HIV-infected individuals. However, the functional capabilities of these cells have been poorly characterized in the setting of malaria exposure, and previous reports have been controversial regarding whether these cells produce antibody. In our study, we analyze the molecular programming of atypical memory B cells, find that they are dysfunctional in a manner similar to that observed in B cells from HIV-infected individuals, and present data that may reconcile previously conflicting studies. By delineating the transcriptional landscape of atMBCs and identifying expression of FCRL5 as a key marker of dysfunction, we provide a foundation for improving our understanding of the role of these cells in immunity to malaria.
doi:10.1371/journal.ppat.1004894
PMCID: PMC4438005  PMID: 25993340
14.  Physical inactivity is associated with narrower lumbar intervertebral discs, high fat content of paraspinal muscles and low back pain and disability 
Introduction
Although physical inactivity has been associated with numerous chronic musculoskeletal complaints, few studies have examined its associations with spinal structures. Moreover, previously reported associations between physical activity and low back pain are conflicting. This study examined the associations between physical inactivity and intervertebral disc height, paraspinal fat content and low back pain and disability.
Methods
Seventy-two community-based volunteers not selected for low back pain underwent magnetic resonance imaging (MRI) of their lumbosacral spine (L1 to S1) between 2011 and 2012. Physical activity was assessed between 2005 and 2008 by questionnaire, while low back pain and disability were assessed by the Chronic Pain Grade Scale at the time of MRI. Intervertebral disc height and cross-sectional area and fat content of multifidus and erector spinae were assessed from MRI.
Results
Lower physical activity levels were associated with a more narrow average intervertebral disc height (β −0.63 mm, 95% confidence interval (CI) −1.17 mm to −0.08 mm, P = 0.026) after adjusting for age, gender and body mass index (BMI). There were no significant associations between physical activity levels and the cross-sectional area of multifidus or erector spinae. Lower levels of physical activity were associated with an increased risk of high fat content in multifidus (odds ratio (OR) 2.7, 95% CI 1.1 to 6.7, P = 0.04) and high-intensity pain/disability (OR = 5.0, 95% CI 1.5 to 16.4, P = 0.008) after adjustment for age, gender and BMI.
Conclusions
Physical inactivity is associated with narrower intervertebral discs, high fat content of the multifidus and high-intensity low back pain and disability in a dose-dependent manner among community-based adults. Longitudinal studies will help to determine the cause and effect nature of these associations.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0629-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s13075-015-0629-y
PMCID: PMC4422596  PMID: 25947906
15.  The challenge of cancer in middle-income countries with an ageing population: Mexico as a case study 
ecancermedicalscience  2015;9:536.
Mexico is undergoing rapid population ageing as a result of its epidemiological transition. This study explores the interface between this rapid population ageing and the burden of cancer. The number of new cancer cases is expected to increase by nearly 75% by 2030 (107,000 additional cases per annum), with 60% of cases in the elderly (aged ≥ 65). A review of the literature was supplemented by a bibliometric analysis of Mexico’s cancer research output. Cancer incidence projections for selected sites were estimated with Globocan software. Data were obtained from recent national census, surveys, and cancer death registrations. The elderly, especially women and those living in rural areas, face high levels of poverty, have low rates of educational attainment, and many are not covered by health insurance schemes. Out of pocket payments and private health care usage remain high, despite the implementation of Seguro Popular that was designed to achieve financial protection for the lowest income groups. A number of cancers that predominate in elderly persons are not covered by the scheme and individuals face catastrophic expenditure in seeking treatment. There is limited research output in those cancer sites that have a high burden in the elderly Mexican population, especially research that focuses on outcomes. The elderly population in Mexico is vulnerable to the effects of the rising cancer burden and faces challenges in accessing high quality cancer care. Based on our evidence, we recommend that geriatric oncology should be an urgent public policy priority for Mexico.
doi:10.3332/ecancer.2015.536
PMCID: PMC4435755  PMID: 26015805
geriatric oncology; low middle-income country; demographic transition; ageing; cancer burden
16.  Bone geometry of the hip is associated with obesity and early structural damage – a 3.0 T magnetic resonance imaging study of community-based adults 
Introduction
The mechanism by which obesity increases the risk of hip osteoarthritis is unclear. One possibility may be by mediating abnormalities in bony geometry, which may in turn be associated with early structural abnormalities, such as cartilage defects and bone marrow lesions.
Methods
One hundred and forty one older adults with no diagnosed hip osteoarthritis had weight and body mass index measured between 1990 and 1994 and again in 2009 to 2010. Acetabular depth and lateral centre edge angle, both measures of acetabular over-coverage, as well as femoral head cartilage volume, cartilage defects and bone marrow lesions were assessed with 3.0 T magnetic resonance imaging performed in 2009 to 2010.
Results
Current body mass index, weight and weight gain were associated with increased acetabular depth and lateral centre edge angle (all P ≤ 0.01). For every 1 mm increase in acetabular depth, femoral head cartilage volume reduced by 59 mm3 (95% confidence interval (CI) 20 mm3 to 98 mm3, P < 0.01). Greater acetabular depth was associated with an increased risk of cartilage defects (odds ratio (OR) 1.22, 95% CI 1.03 to 1.44, P = 0.02) and bone marrow lesions (OR 1.29, 95% CI 1.01 to 1.64, P = 0.04) in the central region of the femoral head. Lateral centre edge angle was not associated with hip structure.
Conclusions
Obesity is associated with acetabular over-coverage. Increased acetabular depth, but not the lateral centre edge angle, is associated with reduced femoral head cartilage volume and an increased risk of cartilage defects and bone marrow lesions. Minimising any deepening of the acetabulum (for example, through weight management) might help to reduce the incidence of hip osteoarthritis.
doi:10.1186/s13075-015-0631-4
PMCID: PMC4440504  PMID: 25925369
17.  Occupational risk factors for hip osteoarthritis are associated with early hip structural abnormalities: a 3.0 T magnetic resonance imaging study of community-based adults 
Introduction
Occupational exposure to heavy lifting and stair climbing are associated with radiographic hip osteoarthritis (OA). This study examined whether these activities are associated with early structural hip joint changes in a community-based population.
Methods
In total, 198 community-based people with no history of hip disease, including OA, had 3.0 T-magnetic resonance imaging (MRI) to assess hip cartilage volume, defects and bone marrow lesions (BMLs). Recall of occupational exposure to heavy lifting and stair climbing aged 18 to 30 years and in the previous 10 years were collected. A persistence score was defined as exposure at neither time point (0), at one time point (1) or at both time points (2).
Results
Exposure to heavy lifting when aged 18 to 30 years was associated with BMLs of the central superolateral femoroacetabular region (odds ratio (OR) 3.9, 95% confidence interval (CI) 1.6 to 9.8, P <0.01), with persistence score associated with cartilage defects in the central superolateral region of the femoral head (OR 1.6, 95% CI 1.0 to 2.5, P = 0.04). Exposure to stair climbing aged 18 to 30 years and persistence score were associated with an increased risk of cartilage defects in the central superolateral femoral head and BMLs in the central superolateral and posterior femoroacetabular regions (OR range 2.1 to 3.2, all P ≤0.03).
Conclusions
Occupational exposure to heavy lifting and stair climbing are associated with hip structural abnormalities. If confirmed by longitudinal data, such associations may explain how occupational activities affect the hip joint and may identify new targets for the prevention of hip OA.
doi:10.1186/s13075-015-0535-3
PMCID: PMC4342869  PMID: 25627648
18.  A snapshot of cancer in Chile: analytical frameworks for developing a cancer policy 
Biological Research  2015;48(1):10.
Introduction
The South American country Chile now boasts a life expectancy of over 80 years. As a consequence, Chile now faces the increasing social and economic burden of cancer and must implement political policy to deliver equitable cancer care. Hindering the development of a national cancer policy is the lack of comprehensive analysis of cancer infrastructure and economic impact.
Objectives
Evaluate existing cancer policy, the extent of national investigation and the socio-economic impact of cancer to deliver guidelines for the framing of an equitable national cancer policy.
Methods
Burden, research and care-policy systems were assessed by triangulating objective system metrics – epidemiological, economic, etc. – with political and policy analysis. Analysis of the literature and governmental databases was performed. The oncology community was interviewed and surveyed.
Results
Chile utilizes 1% of its gross domestic product on cancer care and treatment. We estimate that the economic impact as measured in Disability Adjusted Life Years to be US$ 3.5 billion. Persistent inequalities still occur in cancer distribution and treatment. A high quality cancer research community is expanding, however, insufficient funding is directed towards disproportionally prevalent stomach, lung and gallbladder cancers.
Conclusions
Chile has a rapidly ageing population wherein 40% smoke, 67% are overweight and 18% abuse alcohol, and thus the corresponding burden of cancer will have a negative impact on an affordable health care system. We conclude that the Chilean government must develop a national cancer strategy, which the authors outline herein and believe is essential to permit equitable cancer care for the country.
doi:10.1186/0717-6287-48-10
PMCID: PMC4417314  PMID: 25761441
Chile; Cancer policy; Investigation; Research and development; Statistics; Gallbladder cancer; Stomach cancer; Developing country
19.  How Unique was Hurricane Sandy? Sedimentary Reconstructions of Extreme Flooding from New York Harbor 
Scientific Reports  2014;4:7366.
The magnitude of flooding in New York City by Hurricane Sandy is commonly believed to be extremely rare, with estimated return periods near or greater than 1000 years. However, the brevity of tide gauge records result in significant uncertainties when estimating the uniqueness of such an event. Here we compare resultant deposition by Hurricane Sandy to earlier storm-induced flood layers in order to extend records of flooding to the city beyond the instrumental dataset. Inversely modeled storm conditions from grain size trends show that a more compact yet more intense hurricane in 1821 CE probably resulted in a similar storm tide and a significantly larger storm surge. Our results indicate the occurrence of additional flood events like Hurricane Sandy in recent centuries, and highlight the inadequacies of the instrumental record in estimating current flood risk by such extreme events.
doi:10.1038/srep07366
PMCID: PMC4258685  PMID: 25482298
20.  How are we going to rebuild public health in Libya? 
doi:10.1258/jrsm.2011.110230
PMCID: PMC3241510  PMID: 22179288
21.  Structural changes of hip osteoarthritis using magnetic resonance imaging 
Introduction
Few data are available concerning structural changes at the hip observed by magnetic resonance imaging (MRI) in people with or without hip osteoarthritis (OA). The aim of this study was to compare cartilage volume and the presence of cartilage defects and bone marrow lesions (BMLs) in participants with and without diagnosed hip OA.
Methods
Femoral head cartilage volume was measured by MRI for 141 community-based persons with no diagnosed hip OA, and 19 with diagnosed hip OA. Cartilage defects and BMLs were regionally scored at the femoral head and acetabulum.
Results
Compared with those without diagnosed hip OA, people with diagnosed hip OA had less femoral head cartilage volume (1763 mm3 versus 3343 mm3; p <0.001) and more prevalent cartilage defects and BMLs (all p ≤0.05) at all sites other than the central inferomedial region of the femoral head. In those with no diagnosed hip OA, cartilage defects in the anterior and central superolateral region of the femoral head were associated with reduced femoral head cartilage volume (all p ≤0.02). Central superolateral BMLs at all sites were associated with reduced femoral head cartilage volume (all p ≤0.003), with a similar trend occurring when BMLs were located in the anterior region of the hip (all p ≤0.08).
Conclusions
Compared with community-based adults with no diagnosed hip OA, people with diagnosed hip OA have less femoral head cartilage volume and a higher prevalence of cartilage defects and BMLs. For people with no diagnosed hip OA, femoral head cartilage volume was reduced where cartilage defects and/or BMLs were present in the anterior and central superolateral regions of the hip joint. Cartilage defects and BMLs present in the anterior and central superolateral regions may represent early structural damage in the pathogenesis of hip OA.
doi:10.1186/s13075-014-0466-4
PMCID: PMC4212104  PMID: 25304036
22.  Association between obesity and magnetic resonance imaging defined patellar tendinopathy in community-based adults: a cross-sectional study 
Background
Patellar tendinopathy is a common cause of activity-related anterior knee pain. Evidence is conflicting as to whether obesity is a risk factor for this condition. The aim of this study was to determine the relationship between obesity and prevalence of magnetic resonance imaging (MRI) defined patellar tendinopathy in community-based adults.
Methods
297 participants aged 50–79 years with no history of knee pain or injury were recruited from an existing community-based cohort. Measures of obesity included measured weight and body mass index (BMI), self-reported weight at age of 18–21 years and heaviest lifetime weight. Fat-free mass and fat mass were measured using bioelectrical impedance. Participants underwent MRI of the dominant knee. Patellar tendinopathy was defined on both T1- and T2-weighted images.
Results
The prevalence of MRI defined patellar tendinopathy was 28.3%. Current weight (OR per kg = 1.04, 95% CI 1.01-1.06, P = 0.002), BMI (OR per kg/m2 = 1.10, 95% CI 1.04-1.17, P = 0.002), heaviest lifetime weight (OR per kg = 1.03, 95% CI 1.01-1.05, P = 0.007) and weight at age of 18–21 years (OR per kg = 1.03, 95% CI 1.00-1.07, P = 0.05) were all positively associated with the prevalence of patellar tendinopathy. Neither fat mass nor fat-free mass was associated with patellar tendinopathy.
Conclusion
MRI defined patellar tendinopathy is common in community-based adults and is associated with current and past history of obesity assessed by BMI or body weight, but not fat mass. The findings suggest a mechanical pathogenesis of patellar tendinopathy and patellar tendinopathy may be one mechanism for obesity related anterior knee pain.
doi:10.1186/1471-2474-15-266
PMCID: PMC4132193  PMID: 25098796
Obesity; Patellar tendinopathy; Body mass index; Weight; Fat mass; Magnetic resonance imaging
23.  “Nudge” in the clinical consultation – an acceptable form of medical paternalism? 
BMC Medical Ethics  2014;15:31.
Background
Libertarian paternalism is a concept derived from cognitive psychology and behavioural science. It is behind policies that frame information in such a way as to encourage individuals to make choices which are in their best interests, while maintaining their freedom of choice. Clinicians may view their clinical consultations as far removed from the realms of cognitive psychology but on closer examination there are a number of striking similarities.
Discussion
Evidence has shown that decision making is prone to bias and not necessarily rational or logical, particularly during ill health. Clinicians will usually have an opinion about what course of action represents the patient’s best interests and thus may “frame” information in a way which “nudges” patients into making choices which are considered likely to maximise their welfare. This may be viewed as interfering with patient autonomy and constitute medical paternalism and appear in direct opposition to the tenets of modern practice. However, we argue that clinicians have a responsibility to try and correct “reasoning failure” in patients. Some compromise between patient autonomy and medical paternalism is justified on these grounds and transparency of how these techniques may be used should be promoted.
Summary
Overall the extremes of autonomy and paternalism are not compatible in a responsive, responsible and moral health care environment, and thus some compromise of these values is unavoidable. Nudge techniques are widely used in policy making and we demonstrate how they can be applied in shared medical decision making. Whether or not this is ethically sound is a matter of continued debate but health care professionals cannot avoid the fact they are likely to be using nudge within clinical consultations. Acknowledgment of this will lead to greater self-awareness, reflection and provide further avenues for debate on the art and science of clinical communication.
doi:10.1186/1472-6939-15-31
PMCID: PMC4005908  PMID: 24742113
Nudge; Libertarian paternalism; Communication; Framing; Shared decision making; Medical consultation
24.  The media and cancer: education or entertainment? An ethnographic study of European cancer journalists 
ecancermedicalscience  2014;8:423.
The media plays a vital role in informing the public about new developments in cancer research and influencing cancer policy. This is no easy task, in view of the myriad of trials and wonder drugs that purport to be the ‘magic bullet’. However, misrepresentation can have profound consequences. In this qualitative study, we sought to understand the interaction between the media and cancer through the perspective of European science journalists by defining their attitudes towards current cancer research and challenges faced when reporting science news. A total of 67 respondents took part in this online survey, which was distributed by the European CanCer Organisation (ECCO) to all its media contacts between June and September 2013. Fifty-three per cent had over 20 years experience in reporting science news stories. The respondents utilised a number of media formats, including newsprint, online services, and radio.
Fifty per cent ranked public interest as the greatest influence on their selection of cancer research topics, followed by topicality. Respondents were conscious of being fed ambiguous and exaggerated results from trials by the research community. Sixty-five per cent of respondents would appreciate access to a forum of experts willing to provide comment on new research findings. Seventy per cent highlighted the importance of prompt responses from scientists and researchers during correspondence, and the need to have advance warning of new developments (49%). To conclude – coverage of cancer related issues and scientific advances require greater collaboration between the press and cancer healthcare community to provide both credibility and accountability for the health information disseminated. Key areas include a more precise definition of the research context and differentiation of absolute and relative risks, as well as individual and population risks and an informed discussion about the realities and limitations of cancer care and research.
doi:10.3332/ecancer.2014.423
PMCID: PMC3998657  PMID: 24834118
Cancer; health information; media; public reporting; research; trials
25.  A Catalyst for Change: The European Cancer Patient’s Bill of Rights 
The Oncologist  2014;19(3):217-224.
The European Cancer Concord is a unique patient-centered partnership that will act as a catalyst to achieve improved access to an optimal standard of cancer care and research for European citizens. In order to provide tangible benefits for European cancer patients, the partnership proposes the creation of a “European Cancer Patient’s Bill of Rights,” a patient charter that will underpin equitable access to an optimal standard of care for Europe’s citizens.
doi:10.1634/theoncologist.2013-0452
PMCID: PMC3958470  PMID: 24493667

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