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Shared patient–clinician decision-making is central to choosing between medical treatments. Decision support tools can have an important role to play in these decisions. We developed a decision support tool for deciding between nonsurgical treatment and surgical total knee replacement for patients with severe knee osteoarthritis. The tool aims to provide likely outcomes of alternative treatments based on predictive models using patient-specific characteristics. To make those models relevant to patients with knee osteoarthritis and their clinicians, we involved patients, family members, patient advocates, clinicians, and researchers as stakeholders in creating the models.
Stakeholders were recruited through local arthritis research, advocacy, and clinical organizations. After being provided with brief methodological education sessions, stakeholder views were solicited through quarterly patient or clinician stakeholder panel meetings and incorporated into all aspects of the project.
Participating in each aspect of the research from determining the outcomes of interest to providing input on the design of the user interface displaying outcome predications, 86% (12/14) of stakeholders remained engaged throughout the project. Stakeholder engagement ensured that the prediction models that form the basis of the Knee Osteoarthritis Mathematical Equipoise Tool and its user interface were relevant for patient–clinician shared decision-making.
Methodological research has the opportunity to benefit from stakeholder engagement by ensuring that the perspectives of those most impacted by the results are involved in study design and conduct. While additional planning and investments in maintaining stakeholder knowledge and trust may be needed, they are offset by the valuable insights gained.
To enhance enrollment into randomized clinical trials (RCTs), we proposed electronic health record-based clinical decision support for patient–clinician shared decision-making about care and RCT enrollment, based on “mathematical equipoise.”
As an example, we created the Knee Osteoarthritis Mathematical Equipoise Tool (KOMET) to determine the presence of patient-specific equipoise between treatments for the choice between total knee replacement (TKR) and nonsurgical treatment of advanced knee osteoarthritis.
With input from patients and clinicians about important pain and physical function treatment outcomes, we created a database from non-RCT sources of knee osteoarthritis outcomes. We then developed multivariable linear regression models that predict 1-year individual-patient knee pain and physical function outcomes for TKR and for nonsurgical treatment. These predictions allowed detecting mathematical equipoise between these two options for patients eligible for TKR. Decision support software was developed to graphically illustrate, for a given patient, the degree of overlap of pain and functional outcomes between the treatments and was pilot tested for usability, responsiveness, and as support for shared decision-making.
The KOMET predictive regression model for knee pain had four patient-specific variables, and an r2 value of 0.32, and the model for physical functioning included six patient-specific variables, and an r2 of 0.34. These models were incorporated into prototype KOMET decision support software and pilot tested in clinics, and were generally well received.
Use of predictive models and mathematical equipoise may help discern patient-specific equipoise to support shared decision-making for selecting between alternative treatments and considering enrollment into an RCT.
Risk adjustment is needed to fairly compare central-line–associated bloodstream infection (CLABSI) rates between hospitals. Until 2017, the Centers for Disease Control and Prevention (CDC) methodology adjusted CLABSI rates only by type of intensive care unit (ICU). The 2017 CDC models also adjust for hospital size and medical school affiliation. We hypothesized that risk adjustment would be improved by including patient demographics and comorbidities from electronically available hospital discharge codes.
Using a cohort design across 22 hospitals, we analyzed data from ICU patients admitted between January 2012 and December 2013. Demographics and International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) discharge codes were obtained for each patient, and CLABSIs were identified by trained infection preventionists. Models adjusting only for ICU type and for ICU type plus patient case mix were built and compared using discrimination and standardized infection ratio (SIR). Hospitals were ranked by SIR for each model to examine and compare the changes in rank.
Overall, 85,849 ICU patients were analyzed and 162 (0.2%) developed CLABSI. The significant variables added to the ICU model were coagulopathy, paralysis, renal failure, malnutrition, and age. The C statistics were 0.55 (95% CI, 0.51–0.59) for the ICU-type model and 0.64 (95% CI, 0.60–0.69) for the ICU-type plus patient case-mix model. When the hospitals were ranked by adjusted SIRs, 10 hospitals (45%) changed rank when comorbidity was added to the ICU-type model.
Our risk-adjustment model for CLABSI using electronically available comorbidities demonstrated better discrimination than did the CDC model. The CDC should strongly consider comorbidity-based risk adjustment to more accurately compare CLABSI rates across hospitals.
British general incorporation law granted companies an extraordinary degree of contractual freedom. It provided companies with a default set of articles of association, but incorporators were free to reject any or all of the provisions and write their own rules instead. We study the uses to which incorporators put this flexibility by examining the articles of association filed by three random samples of companies from the late nineteenth and early twentieth centuries, as well as by a sample of companies whose securities traded publicly. Contrary to the literature, we find that most companies, regardless of size or whether their securities traded on the market, wrote articles that shifted power from shareholders to directors. We find, moreover, that there was little pressure from the government, shareholders, or the market to adopt more shareholder-friendly governance rules.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
The montane inselbergs of northern Mozambique have been comparatively little-studied, yet recent surveys have shown they have a rich biodiversity with numerous endemic species. Here we present the main findings from a series of scientific expeditions to one of these inselbergs, Mt Mabu, and discuss the conservation implications. Comprehensive species lists of plants, birds, mammals and butterflies are presented. The most significant result was the discovery of a c. 7,880 ha block of undisturbed rainforest, most of it at medium altitude (900–1,400 m), a forest type that is not well represented elsewhere. It is possibly the largest continuous block of this forest type in southern Africa. To date, 10 new species (plants, mammals, reptiles and butterflies) have been confirmed from Mt Mabu, even though sampling effort for most taxonomic groups has been low. The species assemblages indicate a relatively long period of isolation and many species found are at the southern limit of their range. Conservationists are now faced with the challenge of how best to protect Mt Mabu and similar mountains in northern Mozambique, and various ways that this could be done are discussed.
Compositional analyses were undertaken to evaluate the hypothesis that Shivwits Ware pottery found in southern Nevada was not produced in that area but, instead, manufactured on the Shivwits Plateau. The evidence supports this hypothesis and indicates that large quantities of Shivwits Ware jars moved through a distribution system linking the upland areas of the western Arizona Strip with the lowlands of southeastern Nevada. This long-distance movement of utilitarian pottery is unusual for precontact North America, in that it occurred in the apparent absence of any centralized distribution mechanisms and between what would have been small, kin-based communities. The nature and the causes for the development of this distribution system are discussed.
In 1999, I was a young postdoc moving to Syracuse University to work on LIGO, which had been a dream of mine since I was first introduced to gravitational wave detection as an undergraduate in Kip Thorne's class at Caltech. I had done my PhD in gravitational wave detection, but using the older technology of resonant masses rather than LIGO's laser inteferometry. I was concerned that my background would not prove appropriate. I soon found a common issue, thermal noise, that I was able to focus on. Beyond just a good fit for me, thermal noise was actually a topic in flux within LIGO at the time. A talented young theorist at Caltech named Yuri Levin had just shown that the optical coatings on the LIGO mirrors could well contribute much more thermal noise than anyone had anticipated. What was missing were realistic numbers to plug into Yuri's formulas to see just how big of an impact coating thermal noise might have. This became one of my principal roles in LIGO, as part of a group of experimentalists interested in this question at Stanford, Glasgow, as well as Syracuse and other collaborating institutions.
Since then, we in LIGO have found that coating thermal noise is a very important limit to sensitivity, and we have engaged in over a decade of theoretical, experimental, and modeling work to better understand and reduce it.
Thermal noise from optical coatings is a growing area of concern and overcoming limits to the sensitivity of high precision measurements by thermal noise is one of the greatest challenges faced by experimental physicists. In this timely book, internationally renowned scientists and engineers examine our current theoretical and experimental understanding. Beginning with the theory of thermal noise in mirrors and substrates, subsequent chapters discuss the technology of depositing coatings and state-of-the-art dielectric coating techniques used in precision measurement. Applications and remedies for noise reduction are also covered. Individual chapters are dedicated to specific fields where coating thermal noise is a particular concern, including the areas of quantum optics/optomechanics, gravitational wave detection, precision timing, high-precision laser stabilisation via optical cavities and cavity quantum electrodynamics. While providing full mathematical detail, the text avoids field-specific jargon, making it a valuable resource for readers with varied backgrounds in modern optics.
This article identifies ways to overcome impediments to restoring natural features on developed shores where human-use functions are the dominant driving forces. Suggestions are made for (1) incorporating natural features and natural dynamism into beach nourishment projects; (2) addressing constraints in size and space; (3) reducing the impact of human actions and elements in the landscape; (4) integrating endangered species programmes; (5) overcoming impediments to implementing restoration projects; (6) conducting post-construction evaluations and actions; (7) obtaining public support; and (8) addressing regulatory issues. Beach nourishment projects can better mimic natural landforms, while protecting infrastructure and habitat, creating space for dunes, and providing sediment for dune building. Dunes can have more value as habitat if sub-environments representative of natural gradients are accommodated. Greater human effort will be required to maintain both dynamic and stable zones for habitat, and these zones may be restricted to smaller scales. Controls can be placed on human actions, such as raking the beach, driving on the beach, walking through the dune, emplacing more structures than necessary and introducing exotic vegetation for landscaping. Regulatory restrictions that now prevent environmentally friendly actions can be eased, and adaptive management and education programmes can be implemented.
We report on novel liquid crystals with extremely large flexoelectric coefficients in a range of ultra-fast photonic modes, namely 1) the uniform lying helix, that leads to in-plain switching, birefringence phase devices with 100 μs switching times at low fields, i.e.2-5 V/μm, and analogue or grey scale capability, 2) the uniform standing helix, using planar surface alignment and in-plane fields, with sub ms response times and optical contrasts in excess of 5000:1 with a perfect optically isotropic or black “off state”, 3) the wide temperature range blue phase that leads to field controlled reflective color, 4) chiral nematic optical reflectors electric field tunable over a wide wavelength range and 5) high slope efficiency, wide wavelength range tunable narrow linewidth microscopic liquid crystal lasers.