Aid In Interpretation Research Articles

Visible near-infrared spectroscopy as an aid for archaeological interpretation

We present a pilot study using visible near-infrared spectroscopy (vis-NIRS) to investigate ancient geochemical activity signals from an excavation of the Viking-Age Ribe Emporia, Denmark. Our aim is to study whether vis-NIRS is applicable to archaeological soil analysis and if it can provide additional insight into the use of space inside houses. Using 1059 bulk soil samples sampled in a 0.25 cm grid, we test if vis-NIRS is useful for predicting magnetic susceptibility and anthropogenic elements such as Ca, Cu, P and Sr. Furthermore, we test both portable X-ray fluorescence (pXRF), magnetic susceptibility and bulk chemistry (by inductively coupled plasma mass spectrometry, ICP-MS) as reference data for training the vis-NIRS models. Predictions were performed using a partial least squares (PLS) regression with a non-linear iterative partial least squares (NIPALS) algorithm, and the best cross-validation predictions for each element based on both portable pXRF and ICP-MS as well as predictions for magnetic susceptibility were analysed spatially using ordinary kriging. The spatial analysis showed reduced precision for all elements and magnetic susceptibility compared to reference maps. Additionally, the spectral predictions had difficulties in predicting the entire elemental and magnetic susceptibility range and especially struggled with the prediction of hotspot areas. Elemental predictions based on the two different reference datasets, collected with pXRF and ICP-MS, performed equally well. The more cost-efficient approach was pXRF for calibration data. Further development is needed for the application of vis-NIRS to be fully implemented together with geochemical tools as a regular part of archaeological soil analysis on site.

Evaluating single-cell cluster stability using the Jaccard similarity index.

One major goal of single-cell RNA sequencing (scRNAseq) experiments is to identify novel cell types. With increasingly large scRNAseq datasets, unsupervised clustering methods can now produce detailed catalogues of transcriptionally distinct groups of cells in a sample. However, the interpretation of these clusters is challenging for both technical and biological reasons. Popular clustering algorithms are sensitive to parameter choices, and can produce different clustering solutions with even small changes in the number of principal components used, the k nearest neighbor and the resolution parameters, among others. Here, we present a set of tools to evaluate cluster stability by subsampling, which can guide parameter choice and aid in biological interpretation. The R package scclusteval and the accompanying Snakemake workflow implement all steps of the pipeline: subsampling the cells, repeating the clustering with Seurat and estimation of cluster stability using the Jaccard similarity index and providing rich visualizations. R package scclusteval: https://github.com/crazyhottommy/scclusteval Snakemake workflow: https://github.com/crazyhottommy/pyflow_seuratv3_parameter Tutorial: https://crazyhottommy.github.io/EvaluateSingleCellClustering/.

The use of magnetic susceptibility and chemical analysis data for characterizing heavy metal contamination of topsoil in Denizli city, Turkey

Denizli is one of the most rapidly growing cities in Turkey having experienced fast urban and industrial development in the last decades, engendering a serious threat to the environment and the population health. Therefore, this study used the magnetic susceptibility method to evaluate the contamination degree of most parts of Denizli city. X-ray fluorescence (XRF) analysis was performed on samples chosen from different parts of the study area to identify the quantity and origins of the heavy metals present in the study area corresponding to the magnetic susceptibility measurements. Multivariate statistical analysis such as Cluster analysis (CA) and the principal component analysis (PCA) was performed for the best understanding of the relationship between heavy metal contamination, magnetic susceptibility measurements and XRF analysis results. The environmental status of the study area was evaluated by the aid of elaboration and interpretation of the contamination factor (CF), geoaccumulation index (Igeo), Enrichment factor (EF) and the pollution load index (PLI) which allowed the comparison between the different polluted parts of the study area. The results obtained as maximum values from the calculation of the contamination factor were found as follows: Fe (30.98), Cr (25.86), Ni (14.71), Zn (9.24), Cu (7.96), Pb (5.86). The mean values obtained for the implemented geoaccumulation index were found for each element as follow; Fe (4.39), Cr (4.12), Ni (3.29), Cu (2.44), Pb (2.01) Zn (2.62) while the enrichment factor's results were found as follow Fe (11.80), Cr (11.07), Ni (5.90), Cu (3.87), Pb (2.71) Zn (4). The average value of the pollution load index reflects the heavy pollution of the study area by reaching a value of 7.7. The contour maps plotted for the distribution of heavy metals concentration and magnetic susceptibility measurement showed similar pollution degrees in the city industrial zone and near the main highway (Antalya Highway), which passes through the city. This high heavy metal load gradually decreases toward the city borders. Furthermore, the content of heavy metal and the PLI are notably positively correlated with the magnetic susceptibility measurements. Overall, results testify to the effectiveness of the magnetic susceptibility method for applications in determining environmental contamination caused by heavy metals.

Inter-device reproducibility of transcutaneous bilirubin meters

BackgroundTranscutaneous bilirubinometry is a widely used screening method for neonatal hyperbilirubinemia. Deviation of the transcutaneous bilirubin concentration (TcB) from the total serum bilirubin concentration (TSB) is often ascribed to biological variation between patients, but variations between TcB meters may also have a role. This study aims to provide a systematic evaluation of the inter-device reproducibility of TcB meters.Materials and MethodsThirteen commercially available TcB meters (JM-105 and JM-103) were evaluated in vitro on phantoms that optically mimic neonatal skin. The mimicked TcB was varied within the clinical range (0.5–181.3 μmol/L).ResultsAbsolute differences between TcB meter outcomes increased with the measured TcB, from a difference of 5.0 μmol/L (TcB = 0.5 μmol/L phantom) up to 65.0 μmol/L (TcB = 181.3 μmol/L phantom).ConclusionThe inter-device reproducibility of the examined TcB meters is substantial and exceeds the specified accuracy of the device (±25.5 μmol/L), as well as the clinically used TcB safety margins (>50 µmol/L below phototherapy threshold). Healthcare providers should be well aware of this additional uncertainty in the TcB determination, especially when multiple TcB meters are employed in the same clinic. We strongly advise using a single TcB meter per patient to evaluate the TcB over time.ImpactKey message: The inter-device reproducibility of TcB meters is substantial and exceeds the clinically used TcB safety margins.What this study adds to existing literature: The inter-device reproducibility of transcutaneous bilirubin (TcB) meters has not been reported in the existing literature. This in vitro study systematically evaluates this inter-device reproducibility.Impact: This study aids in a better interpretation of the measured TcB value from a patient and is of particular importance during patient monitoring when using multiple TcB meters within the same clinical department. We strongly advise using a single TcB meter per patient to evaluate the TcB over time.

Evaluation of general practitioners' single-lead electrocardiogram interpretation skills: a case-vignette study.

BackgroundHandheld single-lead electrocardiograms (1L-ECG) present a welcome addition to the diagnostic arsenal of general practitioners (GPs). However, little is known about GPs’ 1L-ECG interpretation skills, and thus its reliability in real-world practice.ObjectiveTo determine the diagnostic accuracy of GPs in diagnosing atrial fibrillation or flutter (AF/Afl) based on 1L-ECGs, with and without the aid of automatic algorithm interpretation, as well as other relevant ECG abnormalities.MethodsWe invited 2239 Dutch GPs for an online case-vignette study. GPs were asked to interpret four 1L-ECGs, randomly drawn from a pool of 80 case-vignettes. These vignettes were obtained from a primary care study that used smartphone-operated 1L-ECG recordings using the AliveCor KardiaMobile. Interpretation of all 1L-ECGs by a panel of cardiologists was used as reference standard.ResultsA total of 457 (20.4%) GPs responded and interpreted a total of 1613 1L-ECGs. Sensitivity and specificity for AF/Afl (prevalence 13%) were 92.5% (95% CI: 82.5–97.0%) and 89.8% (95% CI: 85.5–92.9%), respectively. PPV and NPV for AF/Afl were 45.7% (95% CI: 22.4–70.9%) and 98.8% (95% CI: 97.1–99.5%), respectively. GP interpretation skills did not improve in case-vignettes where the outcome of automatic AF-detection algorithm was provided. In detecting any relevant ECG abnormality (prevalence 22%), sensitivity, specificity, PPV and NPV were 96.3% (95% CI: 92.8–98.2%), 68.8% (95% CI: 62.4–74.6%), 43.9% (95% CI: 27.7–61.5%) and 97.9% (95% CI: 94.9–99.1%), respectively.ConclusionsGPs can safely rule out cardiac arrhythmias with 1L-ECGs. However, whenever an abnormality is suspected, confirmation by an expert-reader is warranted.

Collaborative, Multidisciplinary Evaluation of Cancer Variants Through Virtual Molecular Tumor Boards Informs Local Clinical Practices.

PURPOSEThe cancer research community is constantly evolving to better understand tumor biology, disease etiology, risk stratification, and pathways to novel treatments. Yet the clinical cancer genomics field has been hindered by redundant efforts to meaningfully collect and interpret disparate data types from multiple high-throughput modalities and integrate into clinical care processes. Bespoke data models, knowledgebases, and one-off customized resources for data analysis often lack adequate governance and quality control needed for these resources to be clinical grade. Many informatics efforts focused on genomic interpretation resources for neoplasms are underway to support data collection, deposition, curation, harmonization, integration, and analytics to support case review and treatment planning.METHODSIn this review, we evaluate and summarize the landscape of available tools, resources, and evidence used in the evaluation of somatic and germline tumor variants within the context of molecular tumor boards.RESULTSMolecular tumor boards (MTBs) are collaborative efforts of multidisciplinary cancer experts equipped with genomic interpretation resources to aid in the delivery of accurate and timely clinical interpretations of complex genomic results for each patient, within an institution or hospital network. Virtual MTBs (VMTBs) provide an online forum for collaborative governance, provenance, and information sharing between experts outside a given hospital network with the potential to enhance MTB discussions. Knowledge sharing in VMTBs and communication with guideline-developing organizations can lead to progress evidenced by data harmonization across resources, crowd-sourced and expert-curated genomic assertions, and a more informed and explainable usage of artificial intelligence.CONCLUSIONAdvances in cancer genomics interpretation aid in better patient and disease classification, more streamlined identification of relevant literature, and a more thorough review of available treatments and predicted patient outcomes.

The Namibian Constitution, International Law and the Courts: a Critique

This article examines the Namibian position in relation to the domestic application of international law. Through an analysis of Article 144 as the primary Constitutional touchstone provision, the meaning and binding nature of international agreements is unpacked, in the process identifying how these sources become part of Namibian law. Moreover, the paper advances that Article 144’s phraseology renders both customary international law and general principles of law as sources of binding law in Namibia. A critique of the judicial application of international law, particularly by the Supreme Court, also reveals inconsistencies and errors. In addition to international law’s direct application, the paper identifies the parallel interpretative functionality of international law and enquires into the appropriate method for interpreting international law by domestic courts. The paper concludes by determining the relevance of soft law sources as deliberative, and potentially persuasive interpretative aids.

Experimental determination of the impact energy of horse kicks

Kicking is a natural behaviour of horses, but it can become problematic if stall components are hit and do not withstand the impact load. Injuries may occur due to material failure or hoof entrapment. In Germany, while the Animal Protection Law is intended to prevent such incidents, neither the law nor the corresponding interpretation aid indicates how this requirement should be fulfilled. This paper gives an overview of the methods of determining horse kick energy and presents results of own kick energy measurements. The outcome of a re-evaluation of literature data is presented and two attempts to roughly estimate the expected kick load are introduced. The developed measuring device consists of a steel-made framework, mechanical energy sensors, and an impact panel. Its verification was carried out by loading with impacts of defined energy applied by a pendulum impact machine. The measurement of kick energy was taken at a stud farm in the context of heat detection by observing the response of a mare to the presence of a stallion, whereby the kicks of the stallion were measured. With regard to the kick-resistance and entrapment-safety calculation, a representative value of 71 J was calculated and using a safety factor of 1.5 this gives a design value of 106 J. The presented results and the theoretical background of kick energy measurements described should in the future form the basis for the dimensioning of kick-resistant and entrapment-secure stall planks. • Theory background of horse kick energy determination. • Horse kick measurement applying specially designed dynamic energy sensors. • Kick energy determined to 106 J (design value) for stall plank dimensioning. • Result validation performed by application of various estimation approaches. • Kick-resistant and entrapment-safety stall plank dimensioning now possible.

The Unorthodox Relationship between the EU Charter of Fundamental Rights, the UN Convention on the Rights of Persons with Disabilities and Secondary Rights in the Court of Justice Case Law on Disability Discrimination

Court of Justice – Discrimination on the basis of disability – Article 21 and 26 of the Charter of Fundamental Rights – UN Convention on the Rights of Persons with Disabilities – Employment Equality Directive – Relationship between different sources of law protecting the right of persons with disabilities – Charter as interpretative aid – Charter as a parameter of validity – Scope of application of the Charter – Constitutionalisation of the UN Convention

Germline mutations in Brazilian pancreatic carcinoma patients.

e16749 Background: Pancreatic cancer has the prospect of becoming the second leading cause of cancer death by 2030. The NCCN Guidelines recommend genetic testing for all patients with pancreatic cancer, however, the spectrum of germline mutations has not been extensively evaluated because recent studies with genetic testing have explored only a limited number of genes and have focused predominantly on Caucasian populations. Therefore, our objective is to evaluate the frequency and spectrum of germline mutations in unselected patients with pancreatic cancer in a multiethnic population. Methods: Patients from Instituto do Câncer do Estado de São Paulo (Brazil) with histopathological diagnosis of non-endocrine pancreatic carcinoma were included, regardless of the family history of cancer. These patients answered a life habits and family history of cancer questionnaire and supplied blood for the Next Generation Sequencing (MiSeq platform) with the TruSight Hereditary Cancer panel (Illumina), which includes 115 cancer predisposing genes. Variant analysis was performed with the VarStation, a Brazilian tool that offers post-sequencing computational support and aid for clinical interpretation. Results: To the present moment, 77 patients were evaluated. The mean age of the patients was 62 years (27-83), among whom, 13% with young age (≤50 years) and 47 women (61%). Thirty-eight patients (49%) reported cases of cancer in first-degree relatives. Regarding risk factors, 41 patients (53%) reported smoking, 19 (25%) alcohol ingestion and 20 (26%) had obesity. Seven out of 77 patients presented pathogenic variants in ATM (n = 2) , CHEK2, FANCM (n = 2) or PALB2 (n = 2) genes. Two of these patients ( CHEK2 and FANCM) had early onset pancreatic cancer (≤45 years), both denied smoking habit and family history of cancer in 1st degree relatives. Two patients, who were ATM mutation carriers, reported 1st or 2nd degree relatives with cancer and are alive after 4 and 8 years of diagnosis. Conclusions: In this unselected group of pancreatic cancer patients, 15% were young, almost half reported first-degree relatives with cancer and 9% were carriers of pathogenic variants in genes related with the homologous recombination DNA repair.

INTERPRETING PARLIAMENTARY INACTION

AbstractThis article considers the interpretive significance of legislative inaction. Section I considers the nature of arguments based on legislative inaction. Section II explores the practical, conceptual and constitutional problems with trying to rely on legislative inaction as an interpretive aid. Section III concludes that attempts to draw inferences from legislative inaction alone are deeply flawed, but that inferences might legitimately be drawn from inaction if it forms part of the context against which the legislation is enacted. Even then, however, there are practical difficulties in determining what inferences to draw.

Do health claims add value to nutritional claims? Evidence from a close-to-real experiment on breakfast biscuits

Nutritional claims (NCs) and health claims (HCs) on food products have been introduced as interpretative aids to simplify the information provided on food labelling. However, HCs have been criticised for being unappealing and an information overload on food packages. We aimed to explore whether adding a HC to the associated NC is a good strategy or information overload in a close-to-real non-hypothetical choice experiment with real products and real payments. Consumers’ valuation of two NCs and HCs in breakfast biscuits is measured in two treatments. Treatment A communicates NCs and tests for the external ecological validity of the experiment, while treatment B communicates both, the NC and the associated HC. Results from the willingness to pay estimates showed that consumers are willing to pay premiums for the fat-related HC in addition to the NC while not for the claims related to the fibre content.

Continuous, complete and comparable NT-proBNP reference ranges in healthy children.

NT-proBNP is one of the most important biomarkers for the diagnosis and risk assessment of heart failure in adults. Age- and gender-independent reference intervals (RIs) have been reported. In contrast, RIs in children are strongly age-dependent, do not exist for all ages and reveal a right-skewed distribution. Accordingly, no common Z-score can be formed and a cross-age interpretive method, so far, is missing. Within the paper on hand, new evaluation techniques are applied to already published NT-proBNP study results and additionally to newly gained data. Upper limits (ULs), lower limits (LLs) and 50th percentiles are tested for power-like behavior as a function of age using linear regression analysis. Functions for continuous RIs are derived and reference limits are calculated on a per day basis. A corresponding Zlog formula is deduced and its usefulness is stated in two clinical examples. The power-like behavior of NT-proBNP concentration from birth to 18 years is demonstrated. With age in days t and measured NT-proBNP value x in pg/mL, an age-specific Zlog value may directly be calculated using the equation:ZlogNT-proBNP=log x+0.512⋅log t-3.4171.489+0.014⋅log t⋅3.92${\rm{Zlo}}{{\rm{g}}_{{\rm{NT - proBNP}}}} = {{\log \;x + 0.512 \cdot \log \;t - 3.417} \over {1.489 + 0.014 \cdot \log \;t}} \cdot 3.92$. Using formulas for UL and LL, continuous RIs from 0 to 18 years may be obtained. Continuity corresponds to physiological changes in the body much better than discrete RIs. With the advent of an NT-proBNP-specific Zlog value, a cross-age Z-score equivalent is providing an easy interpretation aid in everyday pediatric practice. This new approach allows to identify clinical worsening much better, sooner and more clearly than previous absolute values.

Development and validation of an interpretive guide for PROMIS scores

BackgroundAccurate score interpretation is required for the appropriate use of patient-reported outcome measures in clinical practice.ObjectiveTo create and evaluate figures (T-score Maps) to facilitate the interpretation of scores on Patient-Reported Outcome Measurement Information System (PROMIS) measures.MethodsFor 21 PROMIS® short forms, item-level information was used to predict the most probable responses to items for the range of possible scores on each short form. Predicted responses were then “mapped” graphically along the range of possible scores. In a previously conducted longitudinal study, 1594 adult participants with chronic conditions (e.g., multiple sclerosis) responded to four items each of a subset of these PROMIS short forms. Participants’ responses to these items were compared to those predicted by the T-score Maps. Difference scores were calculated between observed and predicted scores, and Spearman correlations were calculated.ResultsWe constructed T-score Maps for 21 PROMIS short forms for adults and pediatric self- and parent-proxy report. For the clinical population, participants’ actual responses were strongly correlated with their predicted responses (r = 0.762 to 0.950). The majority of predicted responses exactly matched observed responses (range 69.5% to 85.3%).ConclusionResults support the validity of the predicted responses used to construct T-score Maps. T-score Maps are ready to be tested as interpretation aids in a variety of applications.

Skin Friction Measurements of Transition in High Reynolds Number, Adverse Pressure Gradient Flow

Abstract A combined experimental and analytical modeling effort has been carried out to measure the skin friction response of the boundary layer in high Reynolds number adverse pressure gradient flow. The experiment was conducted in the United Technologies Research Center (UTRC) Acoustic Research Tunnel, an ultra-low freestream turbulence facility capable of laminar boundary layer research. Boundary layer computational fluid dynamics and stability modeling were used to provide pre-test predictions, as well as to aid in interpretation of measured results. Measurements were carried out at chord Reynolds numbers 2–3 × 106, with the model set at multiple incidence angles to establish a range of relevant leading edge pressure gradients. The combination of pressure gradient and flight Reynolds number testing on a thin airfoil has produced a unique data set relevant to propulsion system turbomachinery.

Role of Internal and External Aids in Statutory Interpretation: A Disquisition on Legitimateness of Jurisdictive Discretion

In view of the noticed sharp distinction between the meaning ascribed to the word “impeachment” in the United States of America and the meaning and use of the same in the Nigeria, certain questions have arisen of late, as to whether the legislature of each particular country is not entitled to give any meaning to any word used in the country`s constitution or statutes; whether lawmakers in a particular country or state, in determining the meaning to be ascribed to words used (or to be used) in the its constitution or other statute, are bound by the general meaning of such words in the “English dictionary” or under the US Constitution, and whether any a national statute is inferior or ineffective to another only because its language fails to comply with the form of legislative language adopted in that other jurisdiction. To this end, in an attempt to resolve these issues, this paper examines the question as to how far, beyond the actual word or language of a statute itself, is it permissible for courts, jurists, lawyers and non-lawyers alike to roam in their efforts at statutory interpretation. Put differently, what is the proper context in which one is permitted to interpret legislative directives or provisions? These questions are unavoidably intertwined with the more general question regarding the proper approach to statutory interpretation. Thus, the major issue sought to be resolved herein is as to which shall prevail, in situations of conflict between internal and external aids to statutory interpretation. Specifically, using the meaning of the word “impeachment” for illustration, where the definition given to “impeachment” under Nigerian Constitutional Law by the makers of Nigeria`s Constitution (internal aid) is found to be in conflict with the meaning of the same word as used either in standard English or Law dictionaries (external aid) or in other jurisdictions, such as in the United States' Constitution (external aid), how should we go about resolving the conflict?

Legal Principles, Constitutional Principles, and Judicial Review

Abstract Principles form part and parcel of our law and legal discourse, so much so that we seldom think of what they are and what they entail. For centuries they have been invoked daily to interpret and argue about the law. But when it comes to matters of constitutional law, principles are further called upon to perform a perennially controversial function: to help police the boundaries of state action. In most common law jurisdictions with a written constitution, this function of principles runs against the generally accepted view that the exercise of judicial review must ultimately be governed and restricted by the terms of the national constitution. This Article argues that the exercise of judicial review based on principles is not confined to that view, once the relationship between principles and the constitution is unpacked and recontextualized. While the English-language literature on principles over the past half-century has been dominated by a select group of Anglo-American scholars, there is a wealth of untapped insights from other parts of the world. One of the major contributions by continental legal theorists even predates the earliest modern Anglo-American writings on the subject by more than a decade. Overall, the law literature in common law and civil law systems reveals a significant degree of commonalities in the basic characters of principles despite the absence of initial evidence of transsystemic borrowings. The wider conceptual inquiry also displays a shift in the focus of the debate, from the protracted search for a clear-cut distinction between rules and principles towards a redefinition of principles’ relationship with “written” law, be it in the form of a civil code or a constitutional instrument. From this inquiry reemerge “unwritten” principles not deriving from codified or legislated law although they have been used to develop the law. Translated into the constitutional domain, these unwritten principles bear no logical connection with the terms of the constitution. Their main functions cover the entire spectrum from serving as interpretive aids to making law by filling gaps. The theoretical framework fits with an ongoing four-century-old narrative of the evolution of constitutional principles and judicial review across most common law-based systems. Constitutional principles are another area where Anglo-American law and legal discourse is less exceptional and more universal than what many assume. Throughout modern Western history, legal battles have been fought and ensuing developments have been made on the grounds of principles. Our law and jurisprudence remain based on them.

Knowledge map construction for question and answer archives

The rapid increase in the number of community-based question-and-answer services has built up large archives of questions and answers. These archives deliver a plethora of valuable knowledge to users who primarily browse to locate information. Question–answer pairs, which not only include knowledge content but also indicate knowledge needs, are a new form of information presentation. To facilitate browsing question and answer archives and alleviate information overload during the browsing process, this paper constructs a knowledge map for question and answer archives by exploiting question–answer pair characteristics to determine a more precise location of question–answer pairs. First, the questions and answers are modeled and then the knowledge map structure is completed. Questions and answers are the two main dimensions of this knowledge map, and their intersection comprises a cluster of corresponding question–answer pairs. The knowledge map can be widely and deeply extended to provide a comprehensive representation of the question and answer archive. When labeling the knowledge map to aid in interpretation and understanding, the key words are identified, and typical question–answer pair extraction methods are proposed. Finally, we conduct extensive experiments on a real dataset, and the results show that the proposed approach is feasible and performs well.

Thermotectonic History of the Kluane Ranges and Evolution of the Eastern Denali Fault Zone in Southwestern Yukon, Canada

AbstractExhumation and landscape evolution along strike‐slip fault systems reflect tectonic processes that accommodate and partition deformation in orogenic settings. We present 17 new apatite (U‐Th)/He (He), zircon He, apatite fission‐track (FT), and zircon FT dates from the eastern Denali fault zone (EDFZ) that bounds the Kluane Ranges in Yukon, Canada. The dates elucidate patterns of deformation along the EDFZ. Mean apatite He, apatite FT, zircon He, and zircon FT sample dates range within ~26–4, ~110–12, ~94–28, and ~137–83 Ma, respectively. A new zircon U‐Pb date of 113.9 ± 1.7 Ma (2σ) complements existing geochronology and aids in interpretation of low‐temperature thermochronometry data patterns. Samples ≤2 km southwest of the EDFZ trace yield the youngest thermochronometry dates. Multimethod thermochronometry, zircon He date‐effective U patterns, and thermal history modeling reveal rapid cooling ~95–75 Ma, slow cooling ~75–30 Ma, and renewed rapid cooling ~30 Ma to present. The magnitude of net surface uplift constrained by published paleobotanical data, exhumation, and total surface uplift from ~30 Ma to present are ~1, ~2–6, and ~1–7 km, respectively. Exhumation is highest closest to the EDFZ trace but substantially lower than reported for the central Denali fault zone. We infer exhumation and elevation changes associated with ~95–75 Ma terrane accretion and EDFZ activity, relief degradation from ~75–30 Ma, and ~30 Ma to present exhumation and surface uplift as a response to flat‐slab subduction and transpressional deformation. Integrated results reveal new constraints on landscape evolution within the Kluane Ranges directly tied to the EDFZ during the last ~100 Myr.

Determination and verification of reference interval limits in clinical chemistry. Recommendations for laboratories on behalf of the Working Group Guide Limits of the DGKL with respect to ISO Standard 15189 and the Guideline of the German Medical Association on Quality Assurance in Medical Laboratory Examinations (Rili-BAEK)

AbstractLaboratory measurement values require interpretative assistance e.g. so-called guide limits (GL), as an interpretative aid. Legal and normative requirements for medical laboratories do not provide specific information for their implementation and verification. A German Society for Clinical Chemistry and Laboratory Medicine (DGKL) Working Group GL (WG-GL) has, therefore, developed recommendations to support medical laboratories in the management of GL. A specific objective was to create a framework that mainly takes into account those aspects that can be realistically implemented by routine laboratories and that should improve the management of GL of frequently requested quantitative measurement procedures in clinical chemistry. Thus, the focus of these recommendations is on the distinction between reference interval limits and clinical decision limits as well as the determination and verification of reference interval limits. Indirect approaches are highlighted, as they enable routine laboratories with a broad analytical spectrum but limited resources to evaluate or to establish reference limits.