From climate change to GM foods, we are increasingly confronted with complex, interconnected social and environmental problems that span disciplines, knowledge bases and value systems. This book ...offers a transdisciplinary, open approach for those working towards resolving these 'wicked' problems and highlights the crucial role of this 'transdisciplinary imagination' in addressing the shift to sustainable futures.
Tackling Wicked Problems provides readers with a framework and practical examples that will guide the design and conduct of their own open-ended enquiries. In this approach, academic disciplines are combined with personal, local and strategic understanding and researchers are required to recognise multiple knowledge cultures, accept the inevitability of uncertainty, and clarify their own and others' ethical positions. The authors then comment on fifteen practical examples of how researchers have engaged with the opportunities and challenges of conducting transdisciplinary inquiries.
The book gives those who are grappling with complex problems innovative methods of inquiry that will allow them to work collaboratively towards long-term solutions.
We present a framework for interpreting the carbon isotopic composition of sedimentary rocks, which in turn requires a fundamental reinterpretation of the carbon cycle and redox budgets over Earth's ...history. We propose that authigenic carbonate, produced in sediment pore fluids during early diagenesis, has played a major role in the carbon cycle in the past. This sink constitutes a minor component of the carbon isotope mass balance under the modern, high levels of atmospheric oxygen but was much larger in times of low atmospheric O 2 or widespread marine anoxia. Waxing and waning of a global authigenic carbonate sink helps to explain extreme carbon isotope variations in the Proterozoic, Paleozoic, and Triassic.
A large stable isotope dataset from East and Central Africa from ca. 30 regional collection sites that range from forest to grassland shows that most extant East and Central African large herbivore ...taxa have diets dominated by C₄ grazing or C₃ browsing. Comparison with the fossil record shows that faunal assemblages fromca.4.1–2.35 Ma in the Turkana Basin had a greater diversity of C₃–C₄ mixed feeding taxa than is presently found in modern East and Central African environments. In contrast, the period from 2.35 to 1.0 Ma had more C₄-grazing taxa, especially nonruminant C₄-grazing taxa, than are found in modern environments in East and Central Africa. Many nonbovid C₄ grazers became extinct in Africa, notably the suidNotochoerus,the hipparion equidEurygnathohippus,the giraffidSivatherium,and the elephantidElephas.Other important nonruminant C₄-grazing taxa switched to browsing, including suids in the lineageKolpochoerus-Hylochoerusand the elephantLoxodonta.Many modern herbivore taxa in Africa have diets that differ significantly from their fossil relatives. Elephants and tragelaphin bovids are two groups often used for paleoecological insight, yet their fossil diets were very different from their modern closest relatives; therefore, their taxonomic presence in a fossil assemblage does not indicate they had a similar ecological function in the past as they do at present. Overall, we find ecological assemblages of C₃-browsing, C₃–C₄-mixed feeding, and C₄-grazing taxa in the Turkana Basin fossil record that are different from any modern ecosystem in East or Central Africa.
The current acute kidney injury (AKI) risk prediction model for patients undergoing percutaneous coronary intervention (PCI) from the American College of Cardiology (ACC) National Cardiovascular Data ...Registry (NCDR) employed regression techniques. This study aimed to evaluate whether models using machine learning techniques could significantly improve AKI risk prediction after PCI.
We used the same cohort and candidate variables used to develop the current NCDR CathPCI Registry AKI model, including 947,091 patients who underwent PCI procedures between June 1, 2009, and June 30, 2011. The mean age of these patients was 64.8 years, and 32.8% were women, with a total of 69,826 (7.4%) AKI events. We replicated the current AKI model as the baseline model and compared it with a series of new models. Temporal validation was performed using data from 970,869 patients undergoing PCIs between July 1, 2016, and March 31, 2017, with a mean age of 65.7 years; 31.9% were women, and 72,954 (7.5%) had AKI events. Each model was derived by implementing one of two strategies for preprocessing candidate variables (preselecting and transforming candidate variables or using all candidate variables in their original forms), one of three variable-selection methods (stepwise backward selection, lasso regularization, or permutation-based selection), and one of two methods to model the relationship between variables and outcome (logistic regression or gradient descent boosting). The cohort was divided into different training (70%) and test (30%) sets using 100 different random splits, and the performance of the models was evaluated internally in the test sets. The best model, according to the internal evaluation, was derived by using all available candidate variables in their original form, permutation-based variable selection, and gradient descent boosting. Compared with the baseline model that uses 11 variables, the best model used 13 variables and achieved a significantly better area under the receiver operating characteristic curve (AUC) of 0.752 (95% confidence interval CI 0.749-0.754) versus 0.711 (95% CI 0.708-0.714), a significantly better Brier score of 0.0617 (95% CI 0.0615-0.0618) versus 0.0636 (95% CI 0.0634-0.0638), and a better calibration slope of observed versus predicted rate of 1.008 (95% CI 0.988-1.028) versus 1.036 (95% CI 1.015-1.056). The best model also had a significantly wider predictive range (25.3% versus 21.6%, p < 0.001) and was more accurate in stratifying AKI risk for patients. Evaluated on a more contemporary CathPCI cohort (July 1, 2015-March 31, 2017), the best model consistently achieved significantly better performance than the baseline model in AUC (0.785 versus 0.753), Brier score (0.0610 versus 0.0627), calibration slope (1.003 versus 1.062), and predictive range (29.4% versus 26.2%). The current study does not address implementation for risk calculation at the point of care, and potential challenges include the availability and accessibility of the predictors.
Machine learning techniques and data-driven approaches resulted in improved prediction of AKI risk after PCI. The results support the potential of these techniques for improving risk prediction models and identification of patients who may benefit from risk-mitigation strategies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
On February 28, 2020, public health officials in the Seattle area were informed of a Covid-19 infection at a long-term care facility. An investigation identified 167 infected persons associated with ...the facility, including residents, health care personnel, and visitors; more than a third of the 101 residents identified died.
Before publication of the original version of this report in 1987, practitioners of bone histomorphometry communicated with each other in a variety of arcane languages, which in general were ...unintelligible to those outside the field. The need for standardization of nomenclature had been recognized for many years, super((1)) during which there had been much talk but no action. To satisfy this need, B Lawrence Riggs (ASBMR President, 1985 to 1986) asked A Michael Parfitt to convene an ASBMR committee to develop a new and unified system of terminology, suitable for adoption by the Journal of Bone and Mineral Research (JBMR) as part of its Instructions to Authors. The resulting recommendations were published in 1987 super((2)) and were quickly adopted not only by JBMR but also by all respected journals in the bone field. The recommendations improved markedly the ability of histomorphometrists to communicate with each other and with nonhistomorphometrists, leading to a broader understanding and appreciation of histomorphometric data.
Knowing when the geodynamo started is important for understanding the evolution of the core, the atmosphere, and life on Earth. We report full-vector paleointensity measurements of Archean to Hadean ...zircons bearing magnetic inclusions from the Jack Hills conglomerate (Western Australia) to reconstruct the early geodynamo history. Data from zircons between 3.3 billion and 4.2 billion years old record magnetic fields varying between 1.0 and 0.12 times recent equatorial field strengths. A Hadean geomagnetic field requires a core-mantle heat flow exceeding the adiabatic value and is suggestive of plate tectonics and/or advective magmatic heat transport. The existence of a terrestrial magnetic field before the Late Heavy Bombardment is supported by terrestrial nitrogen isotopic evidence and implies that early atmospheric evolution on both Earth and Mars was regulated by dynamo behavior.
In light of major advances in immunoglobulin light chain (AL) amyloidosis, we evaluated the trends in presentation, management, and outcome among 1551 newly diagnosed AL amyloidosis patients seen in ...our institution from 2000 to 2014. As compared with the 2 intervals 2000-2004 and 2005-2009, patients diagnosed in 2010-2014 were less likely to have >2 involved organs. Utilization of autologous stem cell transplant (ASCT) was similar across all periods, about one-third of patients, but there was an increase in the use of pre-ASCT bortezomib induction and of unattenuated melphalan conditioning in 2010-2014 compared with earlier periods. Non-ASCT first-line regimen changed with 65% of patients in 2010-2014 received bortezomib-based therapy, 79% of patients in 2005-2009 received melphalan-dexamethasone, and 64% of patients in 2000-2004 received melphalan-prednisone. The rate of better than very good partial response (VGPR) was higher in more recent periods (66% vs 58% vs 51%; P = .001), a change largely driven by improved VGPR rates in the non-ASCT population. Overall survival (OS) has improved, with inflection points for improvement differing for the ASCT and non-ASCT groups. In the ASCT population, the greatest gains were after 2010 (4-year OS, 91% compared with 73% and 65%). In the non-ASCT group, greatest gains were after 2005 (4-year OS, 38%, 32%, and 16%). Fewer patients died within 6 months of diagnosis in the 2 later periods (24% vs 25% vs 37%; P < .001). Overall, outcomes among patients with AL amyloidosis have improved with earlier diagnosis, higher rates of VGPR, lower early mortality, and improved OS.
•Significant improvement in outcome is a reality for newly diagnosed AL amyloidosis in the past decade.•Six-month mortality among transplant ineligible patients has declined since 2005.
Previous preclinical and clinical data suggest that the immune system influences prognosis and response to chemotherapy (CT); however, clinical relevance has yet to be established in breast cancer ...(BC). We hypothesized that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic CT-in this case, anthracycline-only CT-in selected BC subtypes.
We investigated the relationship between quantity and location of lymphocytic infiltrate at diagnosis with clinical outcome in 2009 node-positive BC samples from the BIG 02-98 adjuvant phase III trial comparing anthracycline-only CT (doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil CMF or doxorubicin plus cyclophosphamide followed by CMF) versus CT combining doxorubicin and docetaxel (doxorubicin plus docetaxel followed by CMF or doxorubicin followed by docetaxel followed by CMF). Readings were independently performed by two pathologists. Disease-free survival (DFS), overall survival (OS), and interaction with type of CT associations were studied. Median follow-up was 8 years.
There was no significant prognostic association in the global nor estrogen receptor (ER) -positive/human epidermal growth factor receptor 2 (HER2) -negative population. However, each 10% increase in intratumoral and stromal lymphocytic infiltrations was associated with 17% and 15% reduced risk of relapse (adjusted P = .1 and P = .025), respectively, and 27% and 17% reduced risk of death in ER-negative/HER2-negative BC regardless of CT type (adjusted P = .035 and P = .023), respectively. In HER2-positive BC, there was a significant interaction between increasing stromal lymphocytic infiltration (10% increments) and benefit with anthracycline-only CT (DFS, interaction P = .042; OS, P = .018).
In node-positive, ER-negative/HER2-negative BC, increasing lymphocytic infiltration was associated with excellent prognosis. Further validation of the clinical utility of tumor-infiltrating lymphocytes in this context is warranted. Our data also support the evaluation of immunotherapeutic approaches in selected BC subtypes.
Abstract Objectives Existing practice guidelines for osteoarthritis (OA) analyze the evidence behind each proposed treatment but do not prioritize the interventions in a given sequence. The objective ...was to develop a treatment algorithm recommendation that is easier to interpret for the prescribing physician based on the available evidence and that is applicable in Europe and internationally. The knee was used as the model OA joint. Methods ESCEO assembled a task force of 13 international experts (rheumatologists, clinical epidemiologists, and clinical scientists). Existing guidelines were reviewed; all interventions listed and recent evidence were retrieved using established databases. A first schematic flow chart with treatment prioritization was discussed in a 1-day meeting and shaped to the treatment algorithm. Fine-tuning occurred by electronic communication and three consultation rounds until consensus. Results Basic principles consist of the need for a combined pharmacological and non-pharmacological treatment with a core set of initial measures, including information access/education, weight loss if overweight, and an appropriate exercise program. Four multimodal steps are then established. Step 1 consists of background therapy, either non-pharmacological (referral to a physical therapist for re-alignment treatment if needed and sequential introduction of further physical interventions initially and at any time thereafter) or pharmacological. The latter consists of chronic Symptomatic Slow-Acting Drugs for OA (e.g., prescription glucosamine sulfate and/or chondroitin sulfate) with paracetamol at-need; topical NSAIDs are added in the still symptomatic patient. Step 2 consists of the advanced pharmacological management in the persistent symptomatic patient and is centered on the use of oral COX-2 selective or non-selective NSAIDs, chosen based on concomitant risk factors, with intra-articular corticosteroids or hyaluronate for further symptom relief if insufficient. In Step 3, the last pharmacological attempts before surgery are represented by weak opioids and other central analgesics. Finally, Step 4 consists of end-stage disease management and surgery, with classical opioids as a difficult-to-manage alternative when surgery is contraindicated. Conclusions The proposed treatment algorithm may represent a new framework for the development of future guidelines for the management of OA, more easily accessible to physicians.
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