Computerized clinical decision support systems, or CDSS, represent a paradigm shift in healthcare today. CDSS are used to augment clinicians in their complex decision-making processes. Since their ...first use in the 1980s, CDSS have seen a rapid evolution. They are now commonly administered through electronic medical records and other computerized clinical workflows, which has been facilitated by increasing global adoption of electronic medical records with advanced capabilities. Despite these advances, there remain unknowns regarding the effect CDSS have on the providers who use them, patient outcomes, and costs. There have been numerous published examples in the past decade(s) of CDSS success stories, but notable setbacks have also shown us that CDSS are not without risks. In this paper, we provide a state-of-the-art overview on the use of clinical decision support systems in medicine, including the different types, current use cases with proven efficacy, common pitfalls, and potential harms. We conclude with evidence-based recommendations for minimizing risk in CDSS design, implementation, evaluation, and maintenance.
Next-generation sequencing technologies have enabled a dramatic expansion of clinical genetic testing both for inherited conditions and diseases such as cancer. Accurate variant calling in NGS data ...is a critical step upon which virtually all downstream analysis and interpretation processes rely. Just as NGS technologies have evolved considerably over the past 10 years, so too have the software tools and approaches for detecting sequence variants in clinical samples. In this review, I discuss the current best practices for variant calling in clinical sequencing studies, with a particular emphasis on trio sequencing for inherited disorders and somatic mutation detection in cancer patients. I describe the relative strengths and weaknesses of panel, exome, and whole-genome sequencing for variant detection. Recommended tools and strategies for calling variants of different classes are also provided, along with guidance on variant review, validation, and benchmarking to ensure optimal performance. Although NGS technologies are continually evolving, and new capabilities (such as long-read single-molecule sequencing) are emerging, the "best practice" principles in this review should be relevant to clinical variant calling in the long term.
Purpose
To determine the incidence of and risk factors for adverse cardiac events during catecholamine vasopressor therapy in surgical intensive care unit patients with cardiovascular failure.
...Methods
The occurrence of any of seven predefined adverse cardiac events (prolonged elevated heart rate, tachyarrhythmia, myocardial cell damage, acute cardiac arrest or death, pulmonary hypertension-induced right heart dysfunction, reduction of systemic blood flow) was prospectively recorded during catecholamine vasopressor therapy lasting at least 12 h.
Results
Fifty-four of 112 study patients developed a total of 114 adverse cardiac events, an incidence of 48.2 % (95 % CI, 38.8–57.6 %). New-onset tachyarrhythmia (49.1 %), prolonged elevated heart rate (23.7 %), and myocardial cell damage (17.5 %) occurred most frequently. Aside from chronic liver diseases, factors independently associated with the occurrence of adverse cardiac events included need for renal replacement therapy, disease severity (assessed by the Simplified Acute Physiology Score II), number of catecholamine vasopressors (OR, 1.73; 95 % CI, 1.08–2.77;
p
= 0.02) and duration of catecholamine vasopressor therapy (OR, 1.01; 95 % CI, 1–1.01;
p
= 0.002). Patients developing adverse cardiac events were on catecholamine vasopressors (
p
< 0.001) and mechanical ventilation (
p
< 0.001) for longer and had longer intensive care unit stays (
p
< 0.001) and greater mortality (25.9 vs. 1.7 %;
p
< 0.001) than patients who did not.
Conclusions
Adverse cardiac events occurred in 48.2 % of surgical intensive care unit patients with cardiovascular failure and were related to morbidity and mortality. The extent and duration of catecholamine vasopressor therapy were independently associated with and may contribute to the pathogenesis of adverse cardiac events.
L’intérêt récemment suscité par le rôle des pandémies et des épidémies dans l’histoire a mis en lumière les tourments de la malaria dans le monde antique. Aucune étude n’a néanmoins produit jusqu’à ...maintenant de modèle spatial quant au risque de malaria dans l’antiquité. En outre, la menace de la malaria pour les voyageurs de l’antiquité eux-mêmes et le danger que ces derniers représentaient pour autrui n’ont jamais fait l’objet d’études sérieuses. Pour combler ces lacunes concernant l’application à certains problèmes historiques, l’auteur construit et déploie un modèle du risque de malaria dans le monde romain pour évaluer le risque auquel étaient exposés les voyageurs circulant sur les voies romaines. Le projet est pluridisciplinaire à dessein, puisqu’il met à contribution les ressources techniques des SIG dans l’exercice d’évaluation des sources documentaires textuelles nuancées en vue de la reconstruction historique.
ANOSIM, PERMANOVA, and the Mantel test are all resemblance-based permutation methods widely used in ecology. Here, we report the results of the first simulation study, to our knowledge, specifically ...designed to examine the effects of heterogeneity of multivariate dispersions on the rejection rates of these tests and on a classical MANOVA test (Pillai's trace). Increasing differences in dispersion among groups were simulated under scenarios of changing sample sizes, correlation structures, error distributions, numbers of variables, and numbers of groups for balanced and unbalanced one-way designs. The power of these tests to detect environmental impacts or natural large-scale biogeographic gradients was also compared empirically under simulations based on parameters derived from real ecological data sets.
Overall, ANOSIM and the Mantel test were very sensitive to heterogeneity in dispersions, with ANOSIM generally being more sensitive than the Mantel test. In contrast, PERMANOVA and Pillai's trace were largely unaffected by heterogeneity for balanced designs. PERMANOVA was also unaffected by differences in correlation structure, unlike Pillai's trace. For unbalanced designs, however, all of the tests were (1) too liberal when the smaller group had greater dispersion and (2) overly conservative when the larger group had greater dispersion, especially ANOSIM and the Mantel test. For simulations based on real ecological data sets, PERMANOVA was generally, but not always, more powerful than the others to detect changes in community structure, and the Mantel test was usually more powerful than ANOSIM. Both the error distributions and the resemblance measure affected results concerning power.
Differences in the underlying construction of these test statistics result in important differences in the nature of the null hypothesis they are testing, their sensitivity to heterogeneity, and their power to detect important changes in ecological communities. For balanced designs, PERMANOVA and PERMDISP can be used to rigorously identify location vs. dispersion effects, respectively, in the space of the chosen resemblance measure. ANOSIM and the Mantel test can be used as more "omnibus" tests, being sensitive to differences in location, dispersion or correlation structure among groups. Unfortunately, none of the tests (PERMANOVA, Mantel, or ANOSIM) behaved reliably for unbalanced designs in the face of heterogeneity.
Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications but does not restore full health. HIV-infected adults have excess ...risk of cardiovascular, liver, kidney, bone, and neurologic diseases. Many markers of inflammation are elevated in HIV disease and strongly predictive of the risk of morbidity and mortality. A conceptual model has emerged to explain this syndrome of diseases where HIV-mediated destruction of gut mucosa leads to local and systemic inflammation. Translocated microbial products then pass through the liver, contributing to hepatic damage, impaired microbial clearance, and impaired protein synthesis. Chronic activation of monocytes and altered liver protein synthesis subsequently contribute to a hypercoagulable state. The combined effect of systemic inflammation and excess clotting on tissue function leads to end-organ disease. Multiple therapeutic interventions designed to reverse these pathways are now being tested in the clinic. It is likely that knowledge gained on how inflammation affects health in HIV disease could have implications for our understanding of other chronic inflammatory diseases and the biology of aging.
The decay of a surface plasmon, a collective electron oscillation at the surface of a metal, can generate hot charge carriers that may be transferred to an adjacent semiconductor. This ...plasmon-induced charge transfer process can be used to enhance photocatalysis, to create photodetectors, or to drive selective photochemistry. However, the charge transfer efficiency in many fabricated devices remains too low for practical applications, typically <1%. In this Perspective, I discuss critical aspects of designing plasmonic systems for improved performance and highlight important findings for maximizing the transfer efficiency. In particular, I draw attention to the article by Ma and Gao in this issue of ACS Nano that describes using real-time time-dependent density functional theory to give a detailed and informative look at the charge transfer dynamics at a TiO2–Ag nanocluster interface.
The route to certainty on the degree and nature of the immunity required for protection will require evidence from formal proofs using approaches such as titrated transfers of antibodies and T ...lymphocytes to define protection in non-human primate models, as used, for example, in studies of Ebola virus.9 A study of survivors of SARS showed that about 90% had functional, virus-neutralising antibodies and around 50% had strong T-lymphocyte responses.10 These observations bolster confidence in a simple view that most survivors of severe COVID-19 would be expected to have protective antibodies. There are more than 100 candidate COVID-19 vaccines in development, with a handful in, or soon to be in, phase 1 trials to assess safety and immunogenicity.4 Candidate vaccines encompass diverse platforms that differ in the potency with which immunity is stimulated, the specific arsenal of immune mediators mobilised, the number of required boosts, durability of protection, and tractability of production and supply chains.3,4 Safety evaluation of candidate COVID-19 vaccines will need to be of the highest rigour. Some features of the immune response induced by infection, such as high concentrations of tumour necrosis factor and interleukin 6, which could be elicited by some candidate vaccines, have been identified as biomarkers of severe outcome.19 Researchers should be commended for decades of iterative efforts, bringing us to a point where there are many candidate vaccines in development against a novel virus first sequenced in January, 2020.
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