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.
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.
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.
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).
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.
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.
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.
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.
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.
Obesity; Patellar tendinopathy; Body mass index; Weight; Fat mass; Magnetic resonance imaging
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.
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.
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.
Nudge; Libertarian paternalism; Communication; Framing; Shared decision making; Medical consultation
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.
Cancer; health information; media; public reporting; research; trials
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.
This study aimed to critically appraise translational research models for suitability in performance assessment of cancer centers. Process models, such as the Process Marker Model and Lean and Six Sigma applications, seem to be suitable for performance assessment of cancer centers. However, they must be thoroughly tested in practice.
Translational research is a complex cumulative process that takes time. However, the operating environment for cancer centers engaged in translational research is now financially insecure. Centers are challenged to improve results and reduce time from discovery to practice innovations. Performance assessment can identify improvement areas that will help reduce translational delays. Currently, no standard method exists to identify models for use in performance assessment. This study aimed to critically appraise translational research models for suitability in performance assessment of cancer centers.
We conducted a systematic review to identify models and developed a set of criteria based on scientometrics, complex adaptive systems, research and development processes, and strategic evaluation. Models were assessed for linkage between research and care components, new knowledge, systems integration, performance assessment, and review of other models.
Twelve models were identified; six described phases/components for translational research in different blocks (T models) and six described the process of translational research (process models). Both models view translational research as an accumulation of new knowledge. However, process models more clearly address systems integration, link research and care components, and were developed for evaluating and improving the performance of translational research. T models are more likely to review other models.
Process models seem to be more suitable for performance assessment of cancer centers than T models. The most suitable process models (the Process Marker Model and Lean and Six Sigma applications) must be thoroughly tested in practice.
Translational medical research; Models; Performance assessment; Cancer centers; Performance improvement
Cancer is predicted to be an increasingly important cause of morbidity and mortality in Bangladesh in the next few decades. The estimated incidence of 12.7 million new cancer cases will rise to 21.4 million by 2030. More than two-thirds of the total expenditure on health is through out-of-pocket payments. According to the Bangladesh Bureau of Statistics, cancer is the sixth leading cause of death. International Agency for Research on Cancer has estimated cancer-related death rates in Bangladesh to be 7.5% in 2005 and 13% in 2030. The two leading causes are in males are lung and oral cancer and in females are breast cancer and cervical cancer. Bangladesh is now in severe shortage of radiation therapy machines, hospital bed, trained oncologists, medical radiation physicists and technologists. Bangladesh having different cancers associated with smoking and smokeless tobacco use, Human papilloma virus infection, Hepatitis B and C infection, Helicobacter Pylori infection, arsenic contaminated groundwater, availability of chemical carcinogens mainly formalin treated fruits, fish and vegetables at open market, tannery waste contaminated with chromium (which is used for poultry feed and fish feed preparation). A World Health Organization study revealed the annual cost of illnesses in Bangladesh attributable to tobacco usage is US$ 500 million and the total annual benefit from the tobacco sector is US$ 305 million as tax revenue. Bangladesh has developed a National Cancer Control Strategy and Action Plan with the aim of delivering a universal, quality-based and timely service. Cancer prevention through tobacco control, health promotion and vaccination program, cancer early detection program for oral cavity, breast and cervix has initiated. Cancer detection and diagnostic facilities will be made available at medical colleges and district- hospitals and establish a referral chain. National capacity development, more cancer research will allow Bangladesh to deal effectively and efficiently with the cancer problems through evidence-based decision making.
cancer control; Bangladesh
Streptococcus mutans is considered a major causative of tooth decay due to it’s ability to rapidly metabolize carbohydrates such as sucrose. One prominent excreted end product of sucrose metabolism is lactic acid. Lactic acid causes a decrease in the pH of the oral environment with subsequent demineralization of the tooth enamel. Biologically relevant bacteria-induced enamel demineralization was studied.
Optical profiling was used to measure tooth enamel decay with vertical resolution under one nanometer and lateral features with optical resolution as a result of S. mutans biofilm exposure. Comparison measurements were made using AFM.
After 72 hr of biofilm exposure the enamel displayed an 8-fold increase in the observed roughness average, (Ra), as calculated over the entire measured array. Similarly, the average root mean square (RMS) roughness, RRMS, of the enamel before and after biofilm exposure for 3 days displayed a 7-fold increase. Further, the direct effect of chemically induced enamel demineralization using biologically relevant organic acids was shown. Optical profiles of the enamel surface after addition of a 30% lactic acid solution showed a significant alteration in the surface topography with a corresponding increase in respective surface roughness statistics. Similar measurements with 10% citric acid over seconds and minutes give insight into the demineralization process by providing quantitative measures for erosion rates: comparing surface height and roughness as metrics.
The strengths of optical profilometry as an analytical tool for understanding and analyzing biologically relevant processes such as biofilm induced tooth enamel demineralization were demonstrated.
enamel erosion; optical profilometry; biofilm; Streptococcus mutans; enamel demineralization; citric acid; lactic acid; AFM
Although obesity is widely accepted as a risk factor for knee osteoarthritis, whether weight per se or the specific components of body composition are the major determinants of properties of articular knee cartilage is unclear.
To examine associations between anthropometric and body composition measures and knee cartilage properties in healthy adults.
297 healthy adults with no clinical knee osteoarthritis were recruited from an existing community‐based cohort. Anthropometric measures and body composition, including fat‐free mass and fat mass assessed using bioelectrical impedance analysis, were measured at baseline (1990–4) and current follow‐up (2003–4). Tibial cartilage volume and tibiofemoral cartilage defects were assessed using MRI at follow‐up.
After adjustment for potential confounders, baseline and current fat‐free mass, independent of fat mass, were positively associated with tibial cartilage volume (all p<0.001). Increased fat‐free mass over the time period was positively associated with tibial cartilage volume (p<0.001). Current fat mass was negatively associated with tibial cartilage volume (p = 0.004). Baseline and current fat mass were weakly associated with increased tibiofemoral cartilage defects (p = 0.06 and p = 0.07, respectively), independent of fat‐free mass.
The findings suggest a beneficial effect of fat‐free mass, but a deleterious effect of fat mass, on knee cartilage properties in healthy adults. This suggests that weight‐loss programmes aimed at reducing fat mass but maintaining muscle mass may be important in preventing the onset and/or progression of knee osteoarthritis.
fat‐free mass; fat mass; cartilage; cartilage defects; osteoarthritis
To examine the relationship between development or resolution of bone marrow lesions (BMLs) and knee cartilage properties in a 2 year prospective study of asymptomatic middle-aged adults.
271 adults recruited from the Melbourne Collaborative Cohort Study, underwent a magnetic resonance imaging scan (MRI) of their dominant knee at baseline and again approximately 2 years later. Cartilage volume, cartilage defects and BMLs were determined at both time points.
Among 234 subjects free of BMLs at baseline, 33 developed BMLs over 2 years. The incidence of BMLs was associated with progression of tibiofemoral cartilage defects (OR 2.63 (95% CI 0.93, 7.44), P = 0.07 for medial compartment; OR 3.13 (95% CI 1.01, 9.68), P = 0.048 for lateral compartment). Among 37 subjects with BMLs at baseline, 17 resolved. Resolution of BMLs was associated with reduced annual loss of medial tibial cartilage volume (regression coefficient -35.9 (95%CI -65, -6.82), P = 0.02) and a trend for reduced progression of medial tibiofemoral cartilage defects (OR 0.2 (95% CI 0.04, 1.09), P = 0.06).
In this cohort study of asymptomatic middle-aged adults the development of new BMLs was associated with progressive knee cartilage pathology while resolution of BMLs prevalent at baseline was associated with reduced progression of cartilage pathology. Further work examining the relationship between changes and BML and cartilage may provide another important target for the prevention of knee osteoarthritis.
Fatty acids have been implicated in osteoarthritis (OA), yet the mechanism by which fatty acids affect knee structure and consequently the risk of knee OA has not been fully elucidated. Higher intakes of fatty acids have been shown to be associated with the risk of bone marrow lesions (BMLs) in a healthy population. The aim of this study was to examine the association between fatty acid consumption and the incidence of BMLs in healthy middle-aged adults without clinical knee OA.
Two hundred ninety-seven middle-aged adults without clinical knee OA underwent magnetic resonance imaging (MRI) of their dominant knee at baseline. BMLs were assessed. Of the 251 participants with no BMLs in their knee at baseline, 230 underwent MRI of the same knee approximately 2 years later. Intakes of fatty acids were estimated from a food frequency questionnaire.
Increased consumption of saturated fatty acids was associated with an increased incidence of BMLs over 2 years after adjusting for energy intake, age, gender, and body mass index (odds ratio of 2.56 for each standard deviation increase in dietary intake, 95% confidence interval 1.03 to 6.37, P = 0.04). Intake of monounsaturated or polyunsaturated fatty acids was not significantly associated with the incidence of BMLs.
Increased fatty acid consumption may increase the risk of developing BMLs. As subchondral bone is important in maintaining joint integrity and the development of OA, this study suggests that dietary modification of fatty acid intake may be one strategy in the prevention of knee OA which warrants further investigation.
Epidemiological and pedigree studies suggest that lung cancer results from the combined effects of age, smoking, impaired lung function and genetic factors. In a case control association study of healthy smokers and lung cancer cases, we identified genetic markers associated with either susceptibility or protection to lung cancer.
We screened 157 candidate single nucleotide polymorphisms (SNP) in a discovery cohort of 439 subjects (200 controls and 239 lung cancer cases) and identified 30 SNPs associated with either the healthy smokers (protective) or lung cancer (susceptibility) phenotype. After genotyping this 30 SNP panel in a validation cohort of 491 subjects (248 controls and 207 lung cancers) and, using the same protective and susceptibility genotypes from our discovery cohort, a 20 SNP panel was selected based on replication of SNP associations in the validation cohort. Following multivariate logistic regression analyses, including the selected SNPs from runs 1 and 2, we found age and family history of lung cancer to be significantly and independently associated with lung cancer. Numeric scores were assigned to both the SNP and demographic data, and combined to form a simple algorithm of risk.
Significant differences in the distribution of the lung cancer susceptibility score was found between normal controls and lung cancer cases, which remained after accounting for differences in lung function. Validation in other case-control and prospective cohorts are underway to further define the potential clinical utility of this model.
Immunologic tolerance to endogenous antigens reduces antitumor responses. Gp70 is an endogenous tumor-associated antigen (TAA) of the BALB/c-derived colon carcinoma CT26. We found that expression of gp70 mRNA is detectable in tissues of mice 8 months of age and older. We showed that expression of gp70 establishes immunologic tolerance and affects antitumor immunity in a similarly age-dependent manner using gp70-deficient mice. We found that tumors grew in all gp70-sufficient mice, while approximately half of gp70-deficient mice controlled tumor growth with endogenous T cell responses. Protection in gp70-deficient mice correlated with more robust gp70-specific CTL responses, and increased numbers and avidity of responding antigen-specific T cells after vaccination. We conclude that immunosurveillance may decline with age due to increased or de novo peripheral expression of endogenous TAAs.
Tumor-associated antigen; immunologic tolerance; immunosurveillance
Magnetic resonance imaging (MRI) is increasingly used to examine joints for research purposes. It may detect both suspected and unsuspected abnormalities. This raises both clinical and ethical issues, especially when incidental abnormalities are detected. The prevalence of incidental, potentially clinically significant abnormalities identified by MRI and their clinical significance in a population undergoing knee MRI in research studies are unknown.
We examined the prevalence of such lesions in healthy asymptomatic adults and those with symptomatic knee osteoarthritis (OA) undergoing knee MRI with limited sequences for the purpose of research. The MRI findings in 601 asymptomatic subjects and 132 with knee OA who underwent at least one limited knee MRI scan for cartilage volume measurement were examined by an MRI radiologist for the presence of potentially clinically significant abnormalities.
These were present in 2.3% of healthy and 2.3% of OA subjects. All required further investigation to exclude non-benign disease, including four with bone marrow expansion (0.7%), requiring further investigation and management. A single potentially life-threatening lesion, a myeloma lesion, was identified in a subject with symptomatic knee OA on their second MRI scan in a longitudinal study.
As musculoskeletal MRI is increasingly used clinically and for research purposes, the potential for detecting unsuspected abnormalities that require further investigation should be recognized. Incorporating a system to detect these, to characterize unexpected findings, and to facilitate appropriate medical follow-up when designing studies using this technology should be considered ethical research practice.
The aim of the present study is to examine the effect of dietary antioxidants on knee structure in a cohort of healthy, middle-aged subjects with no clinical knee osteoarthritis.
Two hundred and ninety-three healthy adults (mean age = 58.0 years, standard deviation = 5.5) without knee pain or knee injury were selected from an existing community-based cohort. The intake of antioxidant vitamins and food sources by these individuals was estimated from a food frequency questionnaire at baseline. The cartilage volume, bone area, cartilage defects and bone marrow lesions were assessed approximately 10 years later using magnetic resonance imaging.
In multivariate analyses, higher vitamin C intake was associated with a reduced risk of bone marrow lesions (odds ratio = 0.50, 95% confidence interval (CI) = 0.29–0.87, P = 0.01) and with a reduction in the tibial plateau bone area (β = -35.5, 95% CI = -68.8 to -2.3, P = 0.04). There was an inverse association between fruit intake and the tibial plateau bone area (β = -27.8, 95% CI = -54.9 to -0.7, P = 0.04) and between fruit intake and the risk of bone marrow lesions (odds ratio = 0.72, 95% CI = 0.52–0.99, P = 0.05). Neither fruit intake nor vitamin C intake was significantly associated with the cartilage volume or cartilage defects. Lutein and zeaxanthin intake was associated with a decreased risk of cartilage defects (odds ratio = 0.71, 95% CI = 0.51–0.99, P = 0.04), and vitamin E intake tended to be positively associated with the tibial plateau bone area (β = 33.7, 95% CI = -3.1 to 70.4, P = 0.07) only after adjusting for vitamin C intake. The β-cryptoxanthin intake was inversely associated with the tibial plateau bone area after adjusting for vitamin E intake (β = -33.2, 95% CI = -63.1 to -3.4, P = 0.03). Intake of vegetables and other carotenoids was not significantly associated with cartilage or bone measures.
The present study suggests a beneficial effect of fruit consumption and vitamin C intake as they are associated with a reduction in bone size and the number of bone marrow lesions, both of which are important in the pathogenesis of knee osteoarthritis. While our findings need to be confirmed by longitudinal studies, they highlight the potential of the diet to modify the risk of osteoarthritis.
Oral biofilms are multispecies communities, and in their nascent stages of development, numerous bacterial species engage in interspecies interactions. Better insight into the spatial relationship between different species and how species diversity increases over time can guide our understanding of the role of interspecies interactions in the development of the biofilms. Quantum dots (QD) are semiconductor nanocrystals and have emerged as a promising tool for labeling and detection of bacteria. We sought to apply QD-based primary immunofluorescence for labeling of bacterial cells with in vitro and in vivo biofilms and to compare this approach with the fluorophore-based primary immunofluorescence approach we have used previously. To investigate QD-based primary immunofluorescence as the means to detect distinct targets with single-cell resolution, we conjugated polyclonal and monoclonal antibodies to the QD surface. We also conducted simultaneous QD conjugate-based and fluorophore conjugate-based immunofluorescence and showed that these conjugates were complementary tools in immunofluorescence applications. Planktonic and biofilm cells were labeled effectively by considering two factors: the final nanomolar concentration of QD conjugate and the amount of antibody conjugated to the QD, which we define as the degree of labeling. These advances in the application of QD-based immunofluorescence for the study of biofilms in vitro and in vivo will help to define bacterial community architecture and to facilitate investigations of interactions between bacterial species in these communities.
The European Cancer Research Funding Survey found inadequate public funding of cancer research, say Sullivan and Eckhouse.