Showing papers by "University of Sydney published in 2008"
University of Sydney1, Icahn School of Medicine at Mount Sinai2, University of Paris3, The Heart Research Institute4, University of Oxford5, University of Queensland6, Utrecht University7, Université de Montréal8, University of Melbourne9, University of Sheffield10, Aarhus University11, St Mary's Hospital12, University of Auckland13, University of Leicester14, The George Institute for Global Health15, Radboud University Nijmegen16
TL;DR: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21%relative reduction in nephropathy.
Abstract: BACKGROUND: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. METHODS: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately. RESULTS: After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001). CONCLUSIONS: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)
6,477 citations
Radboud University Nijmegen1, National Institutes of Health2, Stanford University3, University of California, Los Angeles4, University of Lausanne5, University of Alabama6, University of Paris7, University of Michigan8, University of Texas Health Science Center at San Antonio9, University of Strasbourg10, University of Manchester11, University College London12, Oregon Health & Science University13, Complutense University of Madrid14, University of Aberdeen15, Duke University16, Charité17, University at Buffalo18, Wayne State University19, University of Sydney20, University of Genoa21, University of Florida22, University of Pennsylvania23
TL;DR: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
Abstract: BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
4,389 citations
TL;DR: Telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema and a increased risk of hypotensive symptoms.
Abstract: Background In patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting–enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes. Methods After a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. Results Mean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P<0.001) and angioedema (0.1% vs. 0.3%, P = 0.01) and a higher rate of hypotensive symptoms (2.6% vs. 1.7%, P<0.001); the rate of syncope was the same in the two groups (0.2%). In the combination-therapy group, the primary outcome occurred in 1386 patients (16.3%; relative risk, 0.99; 95% CI, 0.92 to 1.07); as compared with the ramipril group, there was an increased risk of hypotensive symptoms (4.8% vs. 1.7%, P<0.001), syncope (0.3% vs. 0.2%, P = 0.03), and renal dysfunction (13.5% vs. 10.2%, P<0.001). Conclusions Telmisartan was equivalent to ramipril in patients with vascular disease or highrisk diabetes and was associated with less angioedema. The combination of the two drugs was associated with more adverse events without an increase in benefit. (ClinicalTrials.gov number, NCT00153101.)
3,262 citations
TL;DR: In this paper, the authors explore the nature of value co-creation in the context of service-dominant (S-D) logic and develop a conceptual framework for understanding and managing value cocreation.
Abstract: Central to service-dominant (S-D) logic is the proposition that the customer becomes a co-creator of value. This emphasizes the development of customer–supplier relationships through interaction and dialog. However, research to date suggests relatively little is known about how customers engage in the co-creation of value. In this article, the authors: explore the nature of value co-creation in the context of S-D logic; develop a conceptual framework for understanding and managing value co-creation; and utilize field-based research to illustrate practical application of the framework. This process-based framework provides a structure for customer involvement that takes account of key foundational propositions of S-D logic and places the customer explicitly at the same level of importance as the company as co-creators of value. Synthesis of diverse concepts from research on services, customer value and relationship marketing into a new process-based framework for co-creation provide new insights into managing the process of value co-creation.
3,114 citations
TL;DR: It is proposed that a more measured and disinterested approach is now required to investigate ‘digital natives’ and their implications for education and it is argued that rather than being empirical and theoretically informed, the debate can be likened to an academic form of a ‘moral panic’.
Abstract: The idea that a new generation of students is entering the education system has excited recent attention among educators and education commentators. Termed ‘digital natives’ or the ‘Net generation’, these young people are said to have been immersed in technology all their lives, imbuing them with sophisticated technical skills and learning preferences for which traditional education is unprepared. Grand claims are being made about the nature of this generational change and about the urgent necessity for educational reform in response. A sense of impending crisis pervades this debate. However, the actual situation is far from clear. In this paper, the authors draw on the fields of education and sociology to analyse the digital natives debate. The paper presents and questions the main claims made about digital natives and analyses the nature of the debate itself. We argue that rather than being empirically and theoretically informed, the debate can be likened to an academic form of a ‘moral panic’. We propose that a more measured and disinterested approach is now required to investigate ‘digital natives’ and their implications for education.
2,711 citations
TL;DR: The evidence suggests a pathophysiological link between TDP-43 and ALS, and neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases.
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder characterized pathologically by ubiquitinated TAR DNA binding protein (TDP-43) inclusions. The function of TDP-43 in the nervous system is uncertain, and a mechanistic role in neurodegeneration remains speculative. We identified neighboring mutations in a highly conserved region of TARDBP in sporadic and familial ALS cases. TARDBPM337V segregated with disease within one kindred and a genome-wide scan confirmed that linkage was restricted to chromosome 1p36, which contains the TARDBP locus. Mutant forms of TDP-43 fragmented in vitro more readily than wild type and, in vivo, caused neural apoptosis and developmental delay in the chick embryo. Our evidence suggests a pathophysiological link between TDP-43 and ALS.
2,425 citations
TL;DR: The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva).
Abstract: The LHCb experiment is dedicated to precision measurements of CP violation and rare decays of B hadrons at the Large Hadron Collider (LHC) at CERN (Geneva). The initial configuration and expected performance of the detector and associated systems, as established by test beam measurements and simulation studies, is described.
2,286 citations
TL;DR: The paper concludes that both conceptualizations are important and are helping to stimulate a more sophisticated understanding of the process of health communication in both clinical and community settings, as well as highlighting factors impacting on its effectiveness.
2,082 citations
TL;DR: Most of the mechanistic studies of fatigue are on isolated animal tissues, and another major challenge is to use the knowledge generated in these studies to identify the mechanisms of fatigue in intact animals and particularly in human diseases.
Abstract: Repeated, intense use of muscles leads to a decline in performance known as muscle fatigue. Many muscle properties change during fatigue including the action potential, extracellular and intracellular ions, and many intracellular metabolites. A range of mechanisms have been identified that contribute to the decline of performance. The traditional explanation, accumulation of intracellular lactate and hydrogen ions causing impaired function of the contractile proteins, is probably of limited importance in mammals. Alternative explanations that will be considered are the effects of ionic changes on the action potential, failure of SR Ca2+ release by various mechanisms, and the effects of reactive oxygen species. Many different activities lead to fatigue, and an important challenge is to identify the various mechanisms that contribute under different circumstances. Most of the mechanistic studies of fatigue are on isolated animal tissues, and another major challenge is to use the knowledge generated in these studies to identify the mechanisms of fatigue in intact animals and particularly in human diseases.
2,054 citations
TL;DR: In this article, the authors present a digital model of the age, spreading rate, and asymmetry at each grid node by linear interpolation between adjacent seafloor isochrons in the direction of spreading.
Abstract: We present four companion digital models of the age, age uncertainty, spreading rates, and spreading asymmetries of the world's ocean basins as geographic and Mercator grids with 2 arc min resolution. The grids include data from all the major ocean basins as well as detailed reconstructions of back-arc basins. The age, spreading rate, and asymmetry at each grid node are determined by linear interpolation between adjacent seafloor isochrons in the direction of spreading. Ages for ocean floor between the oldest identified magnetic anomalies and continental crust are interpolated by geological estimates of the ages of passive continental margin segments. The age uncertainties for grid cells coinciding with marine magnetic anomaly identifications, observed or rotated to their conjugate ridge flanks, are based on the difference between gridded age and observed age. The uncertainties are also a function of the distance of a given grid cell to the nearest age observation and the proximity to fracture zones or other age discontinuities. Asymmetries in crustal accretion appear to be frequently related to asthenospheric flow from mantle plumes to spreading ridges, resulting in ridge jumps toward hot spots. We also use the new age grid to compute global residual basement depth grids from the difference between observed oceanic basement depth and predicted depth using three alternative age-depth relationships. The new set of grids helps to investigate prominent negative depth anomalies, which may be alternatively related to subducted slab material descending in the mantle or to asthenospheric flow. A combination of our digital grids and the associated relative and absolute plate motion model with seismic tomography and mantle convection model outputs represents a valuable set of tools to investigate geodynamic problems.
1,731 citations
TL;DR: In this article, the authors systematically tabulate published and unpublished sources of reliable glycemic index (GI) values to improve the quality and quantity of GI data available for research and clinical practice.
Abstract: OBJECTIVE —To systematically tabulate published and unpublished sources of reliable glycemic index (GI) values. RESEARCH DESIGN AND METHODS —A literature search identified 205 articles published between 1981 and 2007. Unpublished data were also included where the data quality could be verified. The data were separated into two lists: the first representing more precise data derived from testing healthy subjects and the second primarily from individuals with impaired glucose metabolism. RESULTS —The tables, which are available in the online-only appendix, list the GI of over 2,480 individual food items. Dairy products, legumes, and fruits were found to have a low GI. Breads, breakfast cereals, and rice, including whole grain, were available in both high and low GI versions. The correlation coefficient for 20 staple foods tested in both healthy and diabetic subjects was r = 0.94 ( P CONCLUSIONS —These tables improve the quality and quantity of GI data available for research and clinical practice.
National Institutes of Health1, Harvard University2, New York Medical College3, University of Michigan4, University of Sydney5, Johns Hopkins University6, University of California, San Diego7, Hospital for Special Surgery8, University of Texas Health Science Center at San Antonio9, GlaxoSmithKline10, Carlos III Health Institute11, Pennington Biomedical Research Center12, University of Washington13
TL;DR: It is found that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife.
TL;DR: In the Sydney Myopia Study as discussed by the authors, the authors assessed the relationship of near, mid-working distance, and outdoor activities with prevalence of myopia in school-aged children and found that higher levels of outdoor activity (sport and leisure activities) were associated with more hyperopic refractions and lower myopia prevalence in the 12-year-old students.
TL;DR: In this paper, the authors performed a meta-analysis of published literature to determine which simple index of overweight and obesity is the best discriminator of cardiovascular risk factors, including hypertension, type-2 diabetes, and dyslipidemia.
TL;DR: Low-GI and/or low-GL diets are independently associated with a reduced risk of certain chronic diseases and the hypothesis that higher postprandial glycemia is a universal mechanism for disease progression is supported.
TL;DR: It is argued that elaborating principled and informed models is a prerequisite for grounding empirical neuroscience in a cogent theoretical framework, commensurate with the achievements in the physical sciences.
Abstract: The cortex is a complex system, characterized by its dynamics and architecture, which underlie many functions such as action, perception, learning, language, and cognition Its structural architecture has been studied for more than a hundred years; however, its dynamics have been addressed much less thoroughly In this paper, we review and integrate, in a unifying framework, a variety of computational approaches that have been used to characterize the dynamics of the cortex, as evidenced at different levels of measurement Computational models at different space-time scales help us understand the fundamental mechanisms that underpin neural processes and relate these processes to neuroscience data Modeling at the single neuron level is necessary because this is the level at which information is exchanged between the computing elements of the brain; the neurons Mesoscopic models tell us how neural elements interact to yield emergent behavior at the level of microcolumns and cortical columns Macroscopic models can inform us about whole brain dynamics and interactions between large-scale neural systems such as cortical regions, the thalamus, and brain stem Each level of description relates uniquely to neuroscience data, from single-unit recordings, through local field potentials to functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), and magnetoencephalogram (MEG) Models of the cortex can establish which types of large-scale neuronal networks can perform computations and characterize their emergent properties Mean-field and related formulations of dynamics also play an essential and complementary role as forward models that can be inverted given empirical data This makes dynamic models critical in integrating theory and experiments We argue that elaborating principled and informed models is a prerequisite for grounding empirical neuroscience in a cogent theoretical framework, commensurate with the achievements in the physical sciences
TL;DR: This review confirms previous research demonstrating that FOBT screening reduces the risk of CRC mortality and indicates that there is no difference in all-cause mortality between the screened and nonscreened populations.
TL;DR: The use of recent techniques in nutrition research to quantify the detailed relationship between diet, nutrient intake, lifespan, and reproduction in Drosophila melanogaster indicates a role for both direct costs of reproduction and other deleterious consequences of ingesting high levels of protein.
Abstract: Modest dietary restriction (DR) prolongs life in a wide range of organisms, spanning single-celled yeast to mammals. Here, we report the use of recent techniques in nutrition research to quantify the detailed relationship between diet, nutrient intake, lifespan, and reproduction in Drosophila melanogaster. Caloric restriction (CR) was not responsible for extending lifespan in our experimental flies. Response surfaces for lifespan and fecundity were maximized at different protein–carbohydrate intakes, with longevity highest at a protein-to-carbohydrate ratio of 1:16 and egg-laying rate maximized at 1:2. Lifetime egg production, the measure closest to fitness, was maximized at an intermediate P:C ratio of 1:4. Flies offered a choice of complementary foods regulated intake to maximize lifetime egg production. The results indicate a role for both direct costs of reproduction and other deleterious consequences of ingesting high levels of protein. We unite a body of apparently conflicting work within a common framework and provide a platform for studying aging in all organisms.
St George's, University of London1, University of Sydney2, University of California, San Diego3, University of Iceland4, Karolinska Institutet5, University of Amsterdam6, University of Saskatchewan7, National Institute for Health and Welfare8, University of Helsinki9, Thomas Jefferson University10, University of Southampton11, Norwegian University of Science and Technology12, Crozer-Keystone Health System13, University College London14, University of Bristol15, University of London16, Dokkyo Medical University17, Harvard University18, University of Eastern Finland19, Providence Sacred Heart Medical Center and Children's Hospital20
TL;DR: In most populations studied, birth weight was inversely related to type 2 diabetes risk, and the shape of the birth weight-type 2 diabetes association was strongly graded, particularly at birth weights of 3 kg or less.
Abstract: Context Low birth weight is implicated as a risk factor for type 2 diabetes. However, the strength, consistency, independence, and shape of the association have not been systematically examined. Objective To conduct a quantitative systematic review examining published evidence on the association of birth weight and type 2 diabetes in adults. Data Sources and Study Selection Relevant studies published by June 2008 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1950), and Web of Science (from 1980), with a combination of text words and Medical Subject Headings. Studies with either quantitative or qualitative estimates of the association between birth weight and type 2 diabetes were included. Data Extraction Estimates of association (odds ratio [OR] per kilogram of increase in birth weight) were obtained from authors or from published reports in models that allowed the effects of adjustment (for body mass index and socioeconomic status) and the effects of exclusion (for macrosomia and maternal diabetes) to be examined. Estimates were pooled using random-effects models, allowing for the possibility that true associations differed between populations. Data Synthesis Of 327 reports identified, 31 were found to be relevant. Data were obtained from 30 of these reports (31 populations; 6090 diabetes cases; 152 084 individuals). Inverse birth weight–type 2 diabetes associations were observed in 23 populations (9 of which were statistically significant) and positive associations were found in 8 (2 of which were statistically significant). Appreciable heterogeneity between populations (I 2 = 66%; 95% confidence interval [CI], 51%-77%) was largely explained by positive associations in 2 native North American populations with high prevalences of maternal diabetes and in 1 other population of young adults. In the remaining 28 populations, the pooled OR of type 2 diabetes, adjusted for age and sex, was 0.75 (95% CI, 0.70-0.81) per kilogram. The shape of the birth weight–type 2 diabetes association was strongly graded, particularly at birth weights of 3 kg or less. Adjustment for current body mass index slightly strengthened the association (OR, 0.76 [95% CI, 0.70-0.82] before adjustment and 0.70 [95% CI, 0.65-0.76] after adjustment). Adjustment for socioeconomic status did not materially affect the association (OR, 0.77 [95% CI, 0.70-0.84] before adjustment and 0.78 [95% CI, 0.72-0.84] after adjustment). There was no strong evidence of publication or small study bias. Conclusion In most populations studied, birth weight was inversely related to type 2 diabetes risk.
TL;DR: This review has attempted to examine catabolism/remodeling in fractures in a systematic fashion by examining the cellular participants in soft callus remodeling and in particular the role of the osteoclast in endochondral ossification.
TL;DR: The most significant features can be summarized in an acronym: AEIOU (asymptomatic/lack of tenderness, expanding rapidly, immune suppression, older than 50 years, and ultraviolet-exposed site on a person with fair skin) and 89% of primary MCCs had 3 or more of these findings.
Abstract: Background Merkel cell carcinoma (MCC) is an aggressive skin cancer with a mortality of 33%. Advanced disease at diagnosis is a poor prognostic factor, suggesting that earlier detection may improve outcome. No systematic analysis has been published to define the clinical features that are characteristic of MCC. Objective We sought to define the clinical characteristics present at diagnosis to identify features that may aid clinicians in recognizing MCC. Methods We conducted a cohort study of 195 patients given the diagnosis of MCC between 1980 and 2007. Data were collected prospectively in the majority of cases, and medical records were reviewed. Results An important finding was that 88% of MCCs were asymptomatic (nontender) despite rapid growth in the prior 3 months (63% of lesions) and being red or pink (56%). A majority of MCC lesions (56%) were presumed at biopsy to be benign, with a cyst/acneiform lesion being the single most common diagnosis (32%) given. The median delay from lesion appearance to biopsy was 3 months (range 1-54 months), and median tumor diameter was 1.8 cm. Similar to earlier studies, 81% of primary MCCs occurred on ultraviolet-exposed sites, and our cohort was elderly (90% >50 years), predominantly white (98%), and often profoundly immune suppressed (7.8%). An additional novel finding was that chronic lymphocytic leukemia was more than 30-fold overrepresented among patients with MCC. Limitations The study was limited to patients seen at a tertiary care center. Complete clinical data could not be obtained on all patients. This study could not assess the specificity of the clinical characteristics of MCC. Conclusions To our knowledge, this study is the first to define clinical features that may serve as clues in the diagnosis of MCC. The most significant features can be summarized in an acronym: AEIOU ( a symptomatic/lack of tenderness, e xpanding rapidly, i mmune suppression, o lder than 50 years, and u ltraviolet-exposed site on a person with fair skin). In our series, 89% of primary MCCs had 3 or more of these findings. Although MCC is uncommon, when present in combination, these features may indicate a concerning process that would warrant biopsy. In particular, a lesion that is red and expanding rapidly yet asymptomatic should be of concern.
TL;DR: A valid and reliable scale for the assessment of the methodological quality of physical therapy trials needs to be developed after it was found that the Jadad Scale presented the best validity and reliability evidence; however, its validity forPhysical therapy trials has not been supported.
Abstract: Background and Purpose: The methodological quality of randomized controlled trials (RCTs) is commonly evaluated in order to assess the risk of biased estimates of treatment effects. The purpose of this systematic review was to identify scales used to evaluate the methodological quality of RCTs in health care research and summarize the content, construction, development, and psychometric properties of these scales.
Methods: Extensive electronic database searches, along with a manual search, were performed.
Results: One hundred five relevant studies were identified. They accounted for 21 scales and their modifications. The majority of scales had not been rigorously developed or tested for validity and reliability. The Jadad Scale presented the best validity and reliability evidence; however, its validity for physical therapy trials has not been supported.
Discussion and Conclusion: Many scales are used to evaluate the methodological quality of RCTs, but most of these scales have not been adequately developed and have not been adequately tested for validity and reliability. A valid and reliable scale for the assessment of the methodological quality of physical therapy trials needs to be developed.
TL;DR: There is a need to reduce FP MRI detection in detection of multifocal and/or multicentric cancer not identified on conventional imaging, however there is not enough evidence to determine the clinical value of detecting additional disease which changes surgical treatment in women with apparently localized breast cancer.
Abstract: Purpose We review the evidence on magnetic resonance imaging (MRI) in staging the affected breast to determine its accuracy and impact on treatment. Methods Systematic review and meta-analysis of the accuracy of MRI in detection of multifocal (MF) and/or multicentric (MC) cancer not identified on conventional imaging. We estimated summary receiver operating characteristic curves, positive predictive value (PPV), true-positive (TP) to false positive (FP) ratio, and examined their variability according to quality criteria. Pooled estimates of the proportion of women whose surgery was altered were calculated. Results Data from 19 studies showed MRI detects additional disease in 16% of women with breast cancer (N = 2,610). MRI incremental accuracy differed according to the reference standard (RS; P = .016) decreasing from 99% to 86% as the quality of the RS increased. Summary PPV was 66% (95% CI, 52% to 77%) and TP:FP ratio was 1.91 (95% CI, 1.09 to 3.34). Conversion from wide local excision (WLE) to mastecto...
TL;DR: Dermoscopy is a noninvasive technique that enables the clinician to perform direct microscopic examination of diagnostic features, not seen by the naked eye, in pigmented skin lesions.
Abstract: Summary
Background Dermoscopy is a noninvasive technique that enables the clinician to perform direct microscopic examination of diagnostic features, not seen by the naked eye, in pigmented skin lesions. Diagnostic accuracy of dermoscopy has previously been assessed in meta-analyses including studies performed in experimental and clinical settings.
Objectives To assess the diagnostic accuracy of dermoscopy for the diagnosis of melanoma compared with naked eye examination by performing a meta-analysis exclusively on studies performed in a clinical setting.
Methods We searched for publications from 1987 to January 2008 and found nine eligible studies. The selected studies compare diagnostic accuracy of dermoscopy with naked eye examination using a valid reference test on consecutive patients with a defined clinical presentation, performed in a clinical setting. Hierarchical summary receiver operator curve analysis was used to estimate the relative diagnostic accuracy for clinical examination with, and without, the use of dermoscopy.
Results We found the relative diagnostic odds ratio for melanoma, for dermoscopy compared with naked eye examination, to be 15·6 [95% confidence interval (CI) 2·9–83·7, P = 0·016]; removal of two outlier studies changed this to 9·0 (95% CI 1·5–54·6, P = 0·03).
Conclusions Dermoscopy is more accurate than naked eye examination for the diagnosis of cutaneous melanoma in suspicious skin lesions when performed in the clinical setting.
Washington University in St. Louis1, Australian National University2, University of Oxford3, University of Adelaide4, University of Sydney5, Pennsylvania State University6, Wellcome Trust Sanger Institute7, University of Cambridge8, University of Oviedo9, University of Washington10, Walter and Eliza Hall Institute of Medical Research11, Weizmann Institute of Science12, Institute for Systems Biology13, University of Melbourne14, Hudson Institute of Medical Research15, Louisiana State University16, University of Canterbury17, University of Münster18, Howard Hughes Medical Institute19, Monash University20, West Virginia University21, New York University22, Institut national de la recherche agronomique23, Iowa State University24, Broad Institute25
TL;DR: It is found that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypUS biology.
Abstract: We present a draft genome sequence of the platypus, Ornithorhynchus anatinus This monotreme exhibits a fascinating combination of reptilian and mammalian characters For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles Analysis of the first monotreme genome aligned these features with genetic innovations We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation
TL;DR: This review summarizes what has been learned about the roles of these proteins from transgenic mice and invertebrate species such as flies and worms and suggests an early, preclinical diagnosis of AD and FTD could be within reach.
Abstract: Insoluble protein aggregates have been linked to Alzheimer's disease (AD) and frontotemporal dementia (FTD). Recent work in transgenic mice has shed light on the role of these aggregates by identifying soluble oligomeric species that may interfere with essential cellular mechanisms at an early disease stage. This review summarizes what we have learned about the roles of these proteins from transgenic mice and invertebrate species such as flies and worms. Proteomic and transcriptomic analyses of tissue from these animal models have identified new molecules with crucial roles in disease. Moreover, transgenic animals have been instrumental in defining drug targets and designing novel therapeutic strategies. With advanced imaging techniques that can be used in both humans and mice an early, preclinical diagnosis of AD and FTD could be within reach.
TL;DR: A mantle convection model is used to suggest that New Jersey subsided by 105 to 180 meters in the past 70 million years because of North America's westward passage over the subducted Farallon plate, which reconciles New Jersey margin–based sea-level estimates with ocean basin reconstructions.
Abstract: Earth9s long-term sea-level history is characterized by widespread continental flooding in the Cretaceous period (∼145 to 65 million years ago), followed by gradual regression of inland seas. However, published estimates of the Late Cretaceous sea-level high differ by half an order of magnitude, from ∼40 to ∼250 meters above the present level. The low estimate is based on the stratigraphy of the New Jersey margin. By assimilating marine geophysical data into reconstructions of ancient ocean basins, we model a Late Cretaceous sea level that is 170 (85 to 270) meters higher than it is today. We use a mantle convection model to suggest that New Jersey subsided by 105 to 180 meters in the past 70 million years because of North America9s westward passage over the subducted Farallon plate. This mechanism reconciles New Jersey margin–based sea-level estimates with ocean basin reconstructions.
TL;DR: In this article, the authors analyze four different reference frames (paleomagnetic, African fixed hot spot, African moving hot spot and global moving hot spots) and develop a unifying approach for connecting a hot spot track system and a paleomagnetic absolute plate reference system into a hybrid model for the time period from the assembly of Pangea (∼320 Ma) to the present.
Abstract: [1] Plate tectonics constitutes our primary framework for understanding how the Earth works over geological timescales. High-resolution mapping of relative plate motions based on marine geophysical data has followed the discovery of geomagnetic reversals, mid-ocean ridges, transform faults, and seafloor spreading, cementing the plate tectonic paradigm. However, so-called “absolute plate motions,” describing how the fragments of the outer shell of the Earth have moved relative to a reference system such as the Earth's mantle, are still poorly understood. Accurate absolute plate motion models are essential surface boundary conditions for mantle convection models as well as for understanding past ocean circulation and climate as continent-ocean distributions change with time. A fundamental problem with deciphering absolute plate motions is that the Earth's rotation axis and the averaged magnetic dipole axis are not necessarily fixed to the mantle reference system. Absolute plate motion models based on volcanic hot spot tracks are largely confined to the last 130 Ma and ideally would require knowledge about the motions within the convecting mantle. In contrast, models based on paleomagnetic data reflect plate motion relative to the magnetic dipole axis for most of Earth's history but cannot provide paleolongitudes because of the axial symmetry of the Earth's magnetic dipole field. We analyze four different reference frames (paleomagnetic, African fixed hot spot, African moving hot spot, and global moving hot spot), discuss their uncertainties, and develop a unifying approach for connecting a hot spot track system and a paleomagnetic absolute plate reference system into a “hybrid” model for the time period from the assembly of Pangea (∼320 Ma) to the present. For the last 100 Ma we use a moving hot spot reference frame that takes mantle convection into account, and we connect this to a pre–100 Ma global paleomagnetic frame adjusted 5° in longitude to smooth the reference frame transition. Using plate driving force arguments and the mapping of reconstructed large igneous provinces to core–mantle boundary topography, we argue that continental paleolongitudes can be constrained with reasonable confidence.
TL;DR: In this article, a qualitative interpretive study on secondary school teachers' professional identities and emotional experiences is presented, which examines the reasons behind the marginalisation of discourses of emotionality and discusses the lived experiences of three teachers.
TL;DR: In this article, the basic principles for the evaluation of design efficiency in discrete choice modelling with a focus on efficiency of WTP estimates from the multinomial logit model are reviewed under the realistic assumption that researchers can plausibly define a prior belief on the range of values for the utility coefficients.
Abstract: We review the basic principles for the evaluation of design efficiency in discrete choice modelling with a focus on efficiency of WTP estimates from the multinomial logit model. The discussion is developed under the realistic assumption that researchers can plausibly define a prior belief on the range of values for the utility coefficients. D-, A-, B-, S- and C-errors are compared as measures of design performance in applied studies and their rationale is discussed. An empirical example based on the generation and comparison of fifteen separate designs from a common set of assumptions illustrates the relevant considerations to the context of non-market valuation, with particular emphasis placed on C-efficiency. Conclusions are drawn for the practice of reporting in non-market valuation and for future work on design research.