Articles in the scientific literature and lay press over the past several years have implied that computed tomography (CT) may cause cancer and that physicians and patients must exercise caution in ...its use. Although there is broad agreement on the latter point--unnecessary medical tests of any type should always be avoided--there is considerable controversy surrounding the question of whether, or to what extent, CT scans can lead to future cancers. Although the doses used in CT are higher than those used in conventional radiographic examinations, they are still 10 to 100 times lower than the dose levels that have been reported to increase the risk of cancer. Despite the fact that at the low doses associated with a CT scan the risk either is too low to be convincingly demonstrated or does not exist, the magnitude of the concern among patients and some medical professionals that CT scans increase cancer risk remains unreasonably high. In this article, common questions about CT scanning and radiation are answered to provide physicians with accurate information on which to base their medical decisions and respond to patient questions.
Purpose To make recommendations regarding the use of bisphosphonates and other bone-modifying agents as adjuvant therapy for patients with breast cancer. Methods Cancer Care Ontario and ASCO convened ...a Working Group and Expert Panel to develop evidence-based recommendations informed by a systematic review of the literature. Results Adjuvant bisphosphonates were found to reduce bone recurrence and improve survival in postmenopausal patients with nonmetastatic breast cancer. In this guideline, postmenopausal includes patients with natural menopause or that induced by ovarian suppression or ablation. Absolute benefit is greater in patients who are at higher risk of recurrence, and almost all trials were conducted in patients who also received systemic therapy. Most studies evaluated zoledronic acid or clodronate, and data are extremely limited for other bisphosphonates. While denosumab was found to reduce fractures, long-term survival data are still required. Recommendations It is recommended that, if available, zoledronic acid (4 mg intravenously every 6 months) or clodronate (1,600 mg/d orally) be considered as adjuvant therapy for postmenopausal patients with breast cancer who are deemed candidates for adjuvant systemic therapy. Further research comparing different bone-modifying agents, doses, dosing intervals, and durations is required. Risk factors for osteonecrosis of the jaw and renal impairment should be assessed, and any pending dental or oral health problems should be dealt with prior to starting treatment. Data for adjuvant denosumab look promising but are currently insufficient to make any recommendation. Use of these agents to reduce fragility fractures in patients with low bone mineral density is beyond the scope of the guideline. Recommendations are not meant to restrict such use of bone-modifying agents in these situations. Additional information at www.asco.org/breast-cancer-adjuvant-bisphosphonates-guideline , www.asco.org/guidelineswiki , https://www.cancercareontario.ca/guidelines-advice/types-of-cancer/breast .
Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has ...been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high-performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to 're-invent the wheel' with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Data on the incidence and natural history of diverticulitis are largely hospital-based and exclude the majority of diverticulitis patients, who are treated in an outpatient setting for uncomplicated ...diverticulitis. We assessed temporal trends in the epidemiology of diverticulitis in the general population.
Through the Rochester Epidemiology Project we reviewed the records of all individuals with a diagnosis of diverticulitis from 1980 to 2007 in Olmsted County, Minnesota, USA.
In 1980-1989, the incidence of diverticulitis was 115/100,000 person-years, which increased to 188/100,000 in 2000-2007 (P<0.001). Incidence increased with age (P<0.001); however, the temporal increase was greater in younger people (P<0.001). Ten years after the index and second diverticulitis episodes, 22% and 55% had a recurrence, respectively. This recurrence rate was greater in younger people (hazard ratio (HR) per decade 0.63; 95% confidence interval (CI), 0.59-0.66) and women (HR 0.68; 95% CI, 0.58-0.80). Complications were seen in 12%; this rate did not change over time. Recurrent diverticulitis was associated with a decreased risk of complications (P<0.001). Age was associated with increased risk of local (odds ratio (OR) 1.27 per decade; 95% CI, 1.04-1.57) and systemic (OR 1.83; 95% CI, 1.20-2.80) complications. Survival after diverticulitis was lower in older people (P<0.001) and men (P<0.001) and worsened over time (P<0.001). The incidence of surgery for diverticulitis did not change from 1980 to 2007.
The incidence of diverticulitis has increased by 50% in 2000-2007 compared with 1990-1999, and more so in younger people. Complications are relatively uncommon. Recurrent diverticulitis is frequent but typically uncomplicated. Younger people with diverticulitis have less severe disease, more recurrence, and better survival.
The CCSM4 Land Simulation, 1850–2005 Lawrence, David M.; Oleson, Keith W.; Flanner, Mark G. ...
Journal of climate,
04/2012, Letnik:
25, Številka:
7
Journal Article
Recenzirano
Odprti dostop
This paper reviews developments for the Community Land Model, version 4 (CLM4), examines the land surface climate simulation of the Community Climate System Model, version 4 (CCSM4) compared to ...CCSM3, and assesses new earth system features of CLM4 within CCSM4. CLM4 incorporates a broad set of improvements including additions of a carbon–nitrogen (CN) biogeochemical model, an urban canyon model, and transient land cover and land use change, as well as revised soil and snow submodels.
Several aspects of the surface climate simulation are improved in CCSM4. Improvements in the simulation of soil water storage, evapotranspiration, surface albedo, and permafrost that are apparent in offline CLM4 simulations are generally retained in CCSM4. The global land air temperature bias is reduced and the annual cycle is improved in many locations, especially at high latitudes. The global land precipitation bias is larger in CCSM4 because of bigger wet biases in central and southern Africa and Australia.
New earth system capabilities are assessed. The present-day air temperature within urban areas is warmer than surrounding rural areas by 1°–2°C, which is comparable to or greater than the change in climate occurring over the last 130 years. The snow albedo feedback is more realistic and the radiative forcing of snow aerosol deposition is calculated as +0.083 W m−2for present day. The land carbon flux due to land use, wildfire, and net ecosystem production is a source of carbon to the atmosphere throughout most of the historical simulation. CCSM4 is increasingly suited for studies of the role of land processes in climate and climate change.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Fibrotic stricture is a common complication of Crohn's disease (CD) affecting approximately half of all patients. No specific anti‐fibrotic therapies are available; however, ...several therapies are currently under evaluation. Drug development for the indication of stricturing CD is hampered by a lack of standardised definitions, diagnostic modalities, clinical trial eligibility criteria, endpoints and treatment targets in stricturing CD.
Aim
To standardise definitions, diagnosis and treatment targets for anti‐fibrotic stricture therapies in Chron's disease.
Methods
An interdisciplinary expert panel consisting of 15 gastroenterologists and radiologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 109 candidate items derived from systematic review and expert opinion focusing on small intestinal strictures were anonymously rated as inappropriate, uncertain or appropriate. Survey results were discussed as a group before a second and third round of voting.
Results
Fibrotic strictures are defined by the combination of luminal narrowing, wall thickening and pre‐stenotic dilation. Definitions of anastomotic (at site of prior intestinal resection with anastomosis) and naïve small bowel strictures were similar; however, there was uncertainty regarding wall thickness in anastomotic strictures. Magnetic resonance imaging is considered the optimal technique to define fibrotic strictures and assess response to therapy. Symptomatic strictures are defined by abdominal distension, cramping, dietary restrictions, nausea, vomiting, abdominal pain and post‐prandial abdominal pain. Need for intervention (endoscopic balloon dilation or surgery) within 24‐48 weeks is considered the appropriate endpoint in pharmacological trials.
Conclusions
Consensus criteria for diagnosis and response to therapy in stricturing Crohn's disease should inform both clinical practice and trial design.
Background Controversy exists regarding the optimal management of incidentally discovered, small pancreatic neuroendocrine tumors (PNETs). Our aim was to review the outcomes of patients who underwent ...nonoperative and operative management. Methods We retrospectively reviewed patients with nonfunctioning PNETs at our institution from January 1, 2000 to June 30, 2011. Patients were included if the tumor was sporadic and <4 cm without radiographic evidence of local invasion or metastases. Results Nonoperative patients ( n = 77, median age, 67 years; range, 31–94) had a median tumor size of 1.0 cm (range, 0.3–3.2). Mean follow-up (F/U) was 45 months (max. 153 months). Median tumor size did not change throughout F/U; there was no disease progression or disease specific mortality. In the operative group ( n = 56, median age, 60 years; range, 27–82), median neoplasm size was 1.8 cm (range, 0.5–3.6). Mean F/U was 52 months (max. 138 months). A total of 46% of the operative patients had some type of complication, more than half due to a clinically significant pancreatic leak. No recurrence or disease specific mortality was seen in the operative group, including 5 patients with positive lymph nodes. Conclusion Small nonfunctioning PNETs usually exhibit minimal or no growth over many years. Nonoperative management may be advocated when serial imaging demonstrates minimal or no growth without suspicious features.
Our purpose was to detect pancreatic ductal adenocarcinoma (PDAC) at the prediagnostic stage (3–36 months before clinical diagnosis) using radiomics-based machine-learning (ML) models, and to compare ...performance against radiologists in a case-control study.
Volumetric pancreas segmentation was performed on prediagnostic computed tomography scans (CTs) (median interval between CT and PDAC diagnosis: 398 days) of 155 patients and an age-matched cohort of 265 subjects with normal pancreas. A total of 88 first-order and gray-level radiomic features were extracted and 34 features were selected through the least absolute shrinkage and selection operator–based feature selection method. The dataset was randomly divided into training (292 CTs: 110 prediagnostic and 182 controls) and test subsets (128 CTs: 45 prediagnostic and 83 controls). Four ML classifiers, k-nearest neighbor (KNN), support vector machine (SVM), random forest (RM), and extreme gradient boosting (XGBoost), were evaluated. Specificity of model with highest accuracy was further validated on an independent internal dataset (n = 176) and the public National Institutes of Health dataset (n = 80). Two radiologists (R4 and R5) independently evaluated the pancreas on a 5-point diagnostic scale.
Median (range) time between prediagnostic CTs of the test subset and PDAC diagnosis was 386 (97–1092) days. SVM had the highest sensitivity (mean; 95% confidence interval) (95.5; 85.5–100.0), specificity (90.3; 84.3–91.5), F1-score (89.5; 82.3–91.7), area under the curve (AUC) (0.98; 0.94–0.98), and accuracy (92.2%; 86.7–93.7) for classification of CTs into prediagnostic versus normal. All 3 other ML models, KNN, RF, and XGBoost, had comparable AUCs (0.95, 0.95, and 0.96, respectively). The high specificity of SVM was generalizable to both the independent internal (92.6%) and the National Institutes of Health dataset (96.2%). In contrast, interreader radiologist agreement was only fair (Cohen’s kappa 0.3) and their mean AUC (0.66; 0.46–0.86) was lower than each of the 4 ML models (AUCs: 0.95–0.98) (P < .001). Radiologists also recorded false positive indirect findings of PDAC in control subjects (n = 83) (7% R4, 18% R5).
Radiomics-based ML models can detect PDAC from normal pancreas when it is beyond human interrogation capability at a substantial lead time before clinical diagnosis. Prospective validation and integration of such models with complementary fluid-based biomarkers has the potential for PDAC detection at a stage when surgical cure is a possibility.
Display omitted
Artificial intelligence can detect pancreas cancer on computed tomography well before its detection by radiologists and before the onset of cancer symptoms when surgical cure is a possibility.
In epithelia, tricellular vertices are emerging as important sites for the regulation of epithelial integrity and function. Compared to bicellular contacts, however, much less is known. In ...particular, resident proteins at tricellular vertices were identified only at occluding junctions, with none known at adherens junctions (AJs). In a previous study, we discovered that in Drosophila embryos, the adhesion molecule Sidekick (Sdk), well-known in invertebrates and vertebrates for its role in the visual system, localises at tricellular vertices at the level of AJs. Here, we survey a wide range of Drosophila epithelia and establish that Sdk is a resident protein at tricellular AJs (tAJs), the first of its kind. Clonal analysis showed that two cells, rather than three cells, contributing Sdk are sufficient for tAJ localisation. Super-resolution imaging using structured illumination reveals that Sdk proteins form string-like structures at vertices. Postulating that Sdk may have a role in epithelia where AJs are actively remodelled, we analysed the phenotype of sdk null mutant embryos during Drosophila axis extension using quantitative methods. We find that apical cell shapes are abnormal in sdk mutants, suggesting a defect in tissue remodelling during convergence and extension. Moreover, adhesion at apical vertices is compromised in rearranging cells, with apical tears in the cortex forming and persisting throughout axis extension, especially at the centres of rosettes. Finally, we show that polarised cell intercalation is decreased in sdk mutants. Mathematical modelling of the cell behaviours supports the notion that the T1 transitions of polarised cell intercalation are delayed in sdk mutants, in particular in rosettes. We propose that this delay, in combination with a change in the mechanical properties of the converging and extending tissue, causes the abnormal apical cell shapes in sdk mutant embryos.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Using common datasets, to estimate and compare the diagnostic performance of image‐based denoising techniques or iterative reconstruction algorithms for the task of detecting hepatic ...metastases.
Methods
Datasets from contrast‐enhanced CT scans of the liver were provided to participants in an NIH‐, AAPM‐ and Mayo Clinic‐sponsored Low Dose CT Grand Challenge. Training data included full‐dose and quarter‐dose scans of the ACR CT accreditation phantom and 10 patient examinations; both images and projections were provided in the training data. Projection data were supplied in a vendor‐neutral standardized format (DICOM‐CT‐PD). Twenty quarter‐dose patient datasets were provided to each participant for testing the performance of their technique. Images were provided to sites intending to perform denoising in the image domain. Fully preprocessed projection data and statistical noise maps were provided to sites intending to perform iterative reconstruction. Upon return of the denoised or iteratively reconstructed quarter‐dose images, randomized, blinded evaluation of the cases was performed using a Latin Square study design by 11 senior radiology residents or fellows, who marked the locations of identified hepatic metastases. Markings were scored against reference locations of clinically or pathologically demonstrated metastases to determine a per‐lesion normalized score and a per‐case normalized score (a faculty abdominal radiologist established the reference location using clinical and pathological information). Scores increased for correct detections; scores decreased for missed or incorrect detections. The winner for the competition was the entry that produced the highest total score (mean of the per‐lesion and per‐case normalized score). Reader confidence was used to compute a Jackknife alternative free‐response receiver operating characteristic (JAFROC) figure of merit, which was used for breaking ties.
Results
103 participants from 90 sites and 26 countries registered to participate. Training data were shared with 77 sites that completed the data sharing agreements. Subsequently, 41 sites downloaded the 20 test cases, which included only the 25% dose data (CTDIvol = 3.0 ± 1.8 mGy, SSDE = 3.5 ± 1.3 mGy). 22 sites submitted results for evaluation. One site provided binary images and one site provided images with severe artifacts; cases from these sites were excluded from review and the participants removed from the challenge. The mean (range) per‐lesion and per‐case normalized scores were −24.2% (−75.8%, 3%) and 47% (10%, 70%), respectively. Compared to reader results for commercially reconstructed quarter‐dose images with no noise reduction, 11 of the 20 sites showed a numeric improvement in the mean JAFROC figure of merit. Notably two sites performed comparably to the reader results for full‐dose commercial images. The study was not designed for these comparisons, so wide confidence intervals surrounded these figures of merit and the results should be used only to motivate future testing.
Conclusion
Infrastructure and methodology were developed to rapidly estimate observer performance for liver metastasis detection in low‐dose CT examinations of the liver after either image‐based denoising or iterative reconstruction. The results demonstrated large differences in detection and classification performance between noise reduction methods, although the majority of methods provided some improvement in performance relative to the commercial quarter‐dose images with no noise reduction applied.
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