Two common questions asked in archaeological investigations are: where did a particular culture come from, and which living cultures is it related to? In this book, Robert A. Cook brings a ...theoretically and methodologically holistic perspective to his study on the origins and continuity of Native American villages in the North American Midcontinent. He shows that to affiliate archaeological remains with descendant communities fully we need to unaffiliate some of our well-established archaeological constructs. Cook demonstrates how and why Native American villages formed and responded to events such as migration, environment and agricultural developments. He focuses on the big picture of cultural relatedness over broad regions and the amount of social detail that can be gleaned from archaeological and biological data, as well as oral histories.
Anomaly detection is a problem with applications for a wide variety of domains; it involves the identification of novel or unexpected observations or sequences within the data being captured. The ...majority of current anomaly detection methods are highly specific to the individual use case, requiring expert knowledge of the method as well as the situation to which it is being applied. The Internet of Things (IoT) as a rapidly expanding field offers many opportunities for this type of data analysis to be implemented, however, due to the nature of the IoT, this may be difficult. This review provides a background on the challenges which may be encountered when applying anomaly detection techniques to IoT data, with examples of applications for the IoT anomaly detection taken from the literature. We discuss a range of approaches that have been developed across a variety of domains, not limited to IoT due to the relative novelty of this application. Finally, we summarize the current challenges being faced in the anomaly detection domain with a view to identifying potential research opportunities for the future.
Friedreich's ataxia is the most common inherited ataxia.
Literature search using PubMed with keywords Friedreich's ataxia together with published papers known to the authors.
The last decade has seen ...important advances in our understanding of the pathogenesis of disease. In particular, the genetic and epigenetic mechanisms underlying the disease now offer promising novel therapeutic targets.
The search for effective disease-modifying agents continues. It remains to be determined whether the most effective approach to treatment lies with increasing frataxin protein levels or addressing the metabolic consequences of the disease, for example with antioxidants.
Management of Freidreich's ataxia is currently focussed on symptomatic management, delivered by the multidisciplinary team. Phase II clinical trials in agents that address the abberrant silencing of the frataxin gene need to be translated into large placebo-controlled Phase III trials to help establish their therapeutic potential.
Objective
To succinctly summarise five contemporary theories about motivation to learn, articulate key intersections and distinctions among these theories, and identify important considerations for ...future research.
Results
Motivation has been defined as the process whereby goal‐directed activities are initiated and sustained. In expectancy‐value theory, motivation is a function of the expectation of success and perceived value. Attribution theory focuses on the causal attributions learners create to explain the results of an activity, and classifies these in terms of their locus, stability and controllability. Social‐ cognitive theory emphasises self‐efficacy as the primary driver of motivated action, and also identifies cues that influence future self‐efficacy and support self‐regulated learning. Goal orientation theory suggests that learners tend to engage in tasks with concerns about mastering the content (mastery goal, arising from a ‘growth’ mindset regarding intelligence and learning) or about doing better than others or avoiding failure (performance goals, arising from a ‘fixed’ mindset). Finally, self‐determination theory proposes that optimal performance results from actions motivated by intrinsic interests or by extrinsic values that have become integrated and internalised. Satisfying basic psychosocial needs of autonomy, competence and relatedness promotes such motivation. Looking across all five theories, we note recurrent themes of competence, value, attributions, and interactions between individuals and the learning context.
Conclusions
To avoid conceptual confusion, and perhaps more importantly to maximise the theory‐building potential of their work, researchers must be careful (and precise) in how they define, operationalise and measure different motivational constructs. We suggest that motivation research continue to build theory and extend it to health professions domains, identify key outcomes and outcome measures, and test practical educational applications of the principles thus derived.
Discuss ideas arising from the article at www.mededuc.com discuss.
Abstract Dilated cardiomyopathy (DCM) is best understood as the final common response of myocardium to diverse genetic and environmental insults. A rigorous work-up can exclude alternative causes of ...left ventricular (LV) dilation and dysfunction, identify etiologies that may respond to specific treatments, and guide family screening. A significant proportion of DCM cases have an underlying genetic or inflammatory basis. Measurement of LV size and ejection fraction remain central to diagnosis, risk stratification, and treatment, but other aspects of cardiac remodeling inform prognosis and carry therapeutic implications. Assessment of myocardial fibrosis predicts both risk of sudden cardiac death and likelihood of LV functional recovery, and has significant potential to guide patient selection for cardioverter-defibrillator implantation. Detailed mitral valve assessment is likely to assume increasing importance with the emergence of percutaneous interventions for functional mitral regurgitation. Detection of pre-clinical DCM could substantially reduce morbidity and mortality by allowing early instigation of cardioprotective therapy.
Cardiac fibrosis is central to the pathology of heart failure, particularly heart failure with preserved ejection fraction (HFpEF). Irrespective of the underlying profibrotic condition (e.g. ageing, ...diabetes, hypertension), maladaptive cardiac fibrosis is defined by the transformation of resident fibroblasts to matrix‐secreting myofibroblasts. Numerous profibrotic factors have been identified at the molecular level (e.g. TGFβ, IL11, AngII), which activate gene expression programs for myofibroblast activation. A number of existing HF therapies indirectly target fibrotic pathways; however, despite multiple clinical trials in HFpEF, a specific clinically effective antifibrotic therapy remains elusive. Therapeutic inhibition of TGFβ, the master‐regulator of fibrosis, has unfortunately proven toxic and ineffective in clinical trials to date, and new approaches are needed. In this review, we discuss the pathophysiology and clinical implications of interstitial fibrosis in HFpEF. We provide an overview of trials targeting fibrosis in HFpEF to date and discuss the promise of potential new therapeutic approaches and targets in the context of underlying molecular mechanisms.
This review discusses recent advances in novel therapeutic approaches against cardiac fibrosis in heart failure with preserved ejection fraction and their underlying molecular mechanisms.
Azine‐containing biaryls are ubiquitous scaffolds in many areas of chemistry, and efficient methods for their synthesis are continually desired. Pyridine rings are prominent amongst these motifs. ...Transition‐metal‐catalysed cross‐coupling reactions have been widely used for their synthesis and functionalisation as they often provide a swift and tuneable route to related biaryl scaffolds. However, 2‐pyridine organometallics are capricious coupling partners and 2‐pyridyl boron reagents in particular are notorious for their instability and poor reactivity in Suzuki–Miyaura cross‐coupling reactions. The synthesis of pyridine‐containing biaryls is therefore limited, and methods for the formation of unsymmetrical 2,2′‐bis‐pyridines are scarce. This Review focuses on the methods developed for the challenging coupling of 2‐pyridine nucleophiles with (hetero)aryl electrophiles, and ranges from traditional cross‐coupling processes to alternative nucleophilic reagents and novel main group approaches.
This Review focuses on methods developed as solutions for the challenging coupling of 2‐pyridyl nucleophiles with (hetero)aryl electrophiles. The topic encompasses traditional cross‐coupling processes, modifications to the Suzuki–Miyaura coupling, as well as alternative nucleophilic reagents and recent developments in C−H activation.
In recent decades, hundreds of glaciers draining the Antarctic Peninsula (63° to 70°S) have undergone systematic and progressive change. These changes are widely attributed to rapid increases in ...regional surface air temperature, but it is now clear that this cannot be the sole driver. Here, we identify a strong correspondence between mid-depth ocean temperatures and glacier-front changes along the ∼1000-kilometer western coastline. In the south, glaciers that terminate in warm Circumpolar Deep Water have undergone considerable retreat, whereas those in the far northwest, which terminate in cooler waters, have not. Furthermore, a mid-ocean warming since the 1990s in the south is coincident with widespread acceleration of glacier retreat. We conclude that changes in ocean-induced melting are the primary cause of retreat for glaciers in this region.
Context
Assessment is central to medical education and the validation of assessments is vital to their use. Earlier validity frameworks suffer from a multiplicity of types of validity or failure to ...prioritise among sources of validity evidence. Kane's framework addresses both concerns by emphasising key inferences as the assessment progresses from a single observation to a final decision. Evidence evaluating these inferences is planned and presented as a validity argument.
Objectives
We aim to offer a practical introduction to the key concepts of Kane's framework that educators will find accessible and applicable to a wide range of assessment tools and activities.
Results
All assessments are ultimately intended to facilitate a defensible decision about the person being assessed. Validation is the process of collecting and interpreting evidence to support that decision. Rigorous validation involves articulating the claims and assumptions associated with the proposed decision (the interpretation/use argument), empirically testing these assumptions, and organising evidence into a coherent validity argument. Kane identifies four inferences in the validity argument: Scoring (translating an observation into one or more scores); Generalisation (using the scores as a reflection of performance in a test setting); Extrapolation (using the scores as a reflection of real‐world performance), and Implications (applying the scores to inform a decision or action). Evidence should be collected to support each of these inferences and should focus on the most questionable assumptions in the chain of inference. Key assumptions (and needed evidence) vary depending on the assessment's intended use or associated decision. Kane's framework applies to quantitative and qualitative assessments, and to individual tests and programmes of assessment.
Conclusions
Validation focuses on evaluating the key claims, assumptions and inferences that link assessment scores with their intended interpretations and uses. The Implications and associated decisions are the most important inferences in the validity argument.
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Socioeconomic disparities in diet quality are well established. This study tested the hypothesis that such disparities are mediated, in part, by diet cost.
The Seattle Obesity Study (S.O.S) was a ...cross-sectional study based on a representative sample of 1266 adults of King County, WA, conducted in 2008-09. Demographic and socioeconomic variables were obtained through telephone survey. Income and education were used as indicators of socioeconomic position. Dietary intake data were obtained using a food frequency questionnaire (FFQ). Diet cost was calculated based on retail prices for FFQ component foods. Energy density (KJ/g) and mean adequacy ratio (MAR) were used as two indices of overall diet quality.
Higher income and education were each associated with lower energy density and higher MAR scores, adjusting for covariates. Higher income and education were also associated with higher energy adjusted diet cost. Higher quality diets were in turn associated with higher diet costs. All these associations were significant (P<0.0001). In formal mediation analyses, diet cost significantly mediated the pathway between income and diet quality measures, adjusting for covariates (P<0.05 each). Further, income-diet cost-diet quality pathway was found to be moderated by education level.
The social gradient in diet quality may be explained by diet cost. Strategies to improve diet quality among lower socioeconomic strata may need to take food prices and diet cost along with nutrition education into account.
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