Acylcarnitine analysis is a useful test for identifying patients with inborn errors of mitochondrial fatty acid β-oxidation and certain organic acidemias. Plasma is routinely used in the diagnostic ...workup of symptomatic patients. Urine analysis of targeted acylcarnitine species may be helpful in the diagnosis of glutaric acidemia type I and other disorders in which polar acylcarnitine species accumulate. For newborn screening applications, dried blood spot acylcarnitine analysis can be performed as a multiplex assay with other analytes, including amino acids, succinylacetone, guanidinoacetate, creatine, and lysophosphatidylcholines. Tandem mass spectrometric methodology, established more than 30 years ago, remains a valid approach for acylcarnitine analysis. The method involves flow-injection analysis of esterified or underivatized acylcarnitines species and detection using a precursor-ion scan. Alternative methods utilize liquid chromatographic separation of isomeric and isobaric species and/or detection by selected reaction monitoring. These technical standards were developed as a resource for diagnostic laboratory practices in acylcarnitine analysis, interpretation, and reporting.
The Concept of the Police Miller, Eric J.
Criminal law and philosophy,
10/2023, Letnik:
17, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The organization of the modern police is a contingent social choice about how to engage in the process of governance when regulating public order on the street. The police are the agency authorized ...to act upon the state’s duty to govern in response to public emergencies. The duty to govern exists when there is some urgent social need that could be resolved by acting, and some person or institution has the resources and ability to do that act. The duty is impersonal: anybody with the relevant skill set is obligated to act to address the relevant need. Problems can arise, however, when too few individuals respond or too many compete to resolve the need. A core feature of governance, then, is to create publicly recognized institutions with special authority, resources, and abilities to address the demand for public services when someone needs to step in and do something to the exclusion of ordinary members of the public. Police agencies are further characterized by various powers and duties. These powers are normative powers to change the legal status of the people with whom the police interact, rather than physical powers to use some amount of violence to coerce individuals to comply with police demands. The core powers of the police include the powers to make authoritative determinations about how to respond to an emergency, to detain individuals, and to trespass upon their person or property, along with conjoined duties to govern, to protect, and to intervene at risk to themselves. The dominant approach attempts to distinguish the police from other institutions using the police ability to use violent to respond to public emergencies. On the governance based model of the police, however, the ability to use force is simply one of the resources available to the police, and does not mark them off as different from other public governance agencies.
The liquid–metal-cooling (LMC) directional-solidification process offers refinement of dendritic structure due to the increased cooling rate from enhanced heat extraction. However, under some ...conditions in the LMC process substantial lateral heat extraction occurs that leads to a change in dendrite morphology, resulting in grain nucleation or lateral growth – the formation of long secondary dendrite arms overgrowing favorably aligned primary dendrites. The conditions under which lateral growth occurs during solidification of alloys CMSX-486 and René-N4 have been studied experimentally and via solidification modeling. Solidification experiments have been conducted in a LMC furnace that utilizes liquid tin as the cooling medium and a floating ceramic baffle. A mold geometry was designed to evaluate a range of thermal conditions during solidification and assess the tendency for lateral growth. Correlations between dendritic structure, solidification-front curvature, solidification rate and thermal gradients have been analyzed. A criterion for predicting the onset of lateral growth based on the inclination of the solidification front at the casting surface is demonstrated.
The graph-based Cartesian genetic programming system has an unusual genotype representation with a number of advantageous properties. It has a form of redundancy whose role has received little ...attention in the published literature. The representation has genes that can be activated or deactivated by mutation operators during evolution. It has been demonstrated that this "junk" has a useful role and is very beneficial in evolutionary search. The results presented demonstrate the role of mutation and genotype length in the evolvability of the representation. It is found that the most evolvable representations occur when the genotype is extremely large and in which over 95% of the genes are inactive.
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•Genomic capture methods can resolve clades that lack decades of molecular marker development.•An enhanced bait setfor Hexacorallia recovers >2400 UCE/exon loci in stony ...corals.•Phylogenomics resolves coral relationships at deep and shallow time scales.•Well-supported clades in Acropora are not supported by macromorphological features.
Targeted enrichment of genomic DNA can profoundly increase the phylogenetic resolution of clades and inform taxonomy. Here, we redesign a custom bait set previously developed for the cnidarian class Anthozoa to more efficiently target and capture ultraconserved elements (UCEs) and exonic loci within the subclass Hexacorallia. We test this enhanced bait set (targeting 2476 loci) on 99 specimens of scleractinian corals spanning both the “complex” (Acroporidae, Agariciidae) and “robust” (Fungiidae) clades. Focused sampling in the staghorn corals (genus Acropora) highlights the ability of sequence capture to inform the taxonomy of a clade previously deficient in molecular resolution. A mean of 1850 (±298) loci were captured per taxon (955 UCEs, 894 exons), and a 75% complete concatenated alignment of 96 samples included 1792 loci (991 UCE, 801 exons) and ~1.87 million base pairs. Maximum likelihood and Bayesian analyses recovered robust molecular relationships and revealed that species-level relationships within the Acropora are incongruent with traditional morphological groupings. Both UCE and exon datasets delineated six well-supported clades within Acropora. The enhanced bait set will facilitate investigations of the evolutionary history of many important groups of reef corals, particularly where previous molecular marker development has been unsuccessful.
In this paper I offer a new characterisation of what makes a dispute merely verbal. This new characterisation builds on the framework initially outlined by Jenkins and additionally makes use of ...Stalnaker's notion of ‘common ground’. I argue that this ‘common ground account’ can better classify disputes as merely verbal, and can better explain cases of playing devil's advocate.
Impaired immune responses in the elderly lead to reduced vaccine efficacy and increased susceptibility to viral infections. Although several groups have documented age-dependent defects in adaptive ...immune priming, the deficits that occur prior to antigen encounter remain largely unexplored. Herein, we identify novel mechanisms for compromised adaptive immunity that occurs with aging in the context of infection with West Nile virus (WNV), an encephalitic flavivirus that preferentially causes disease in the elderly. An impaired IgM and IgG response and enhanced vulnerability to WNV infection during aging was linked to delayed germinal center formation in the draining lymph node (DLN). Adoptive transfer studies and two-photon intravital microscopy revealed a decreased trafficking capacity of donor naïve CD4+ T cells from old mice, which manifested as impaired T cell diapedesis at high endothelial venules and reduced cell motility within DLN prior to antigen encounter. Furthermore, leukocyte accumulation in the DLN within the first few days of WNV infection or antigen-adjuvant administration was diminished more generally in old mice and associated with a second aging-related defect in local cytokine and chemokine production. Thus, age-dependent cell-intrinsic and environmental defects in the DLN result in delayed immune cell recruitment and antigen recognition. These deficits compromise priming of early adaptive immune responses and likely contribute to the susceptibility of old animals to acute WNV infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Aims
To optimize per-vessel prediction of early coronary revascularization (ECR) within 90 days after fast single-photon emission computed tomography (SPECT) myocardial perfusion imaging ...(MPI) using machine learning (ML) and introduce a method for a patient-specific explanation of ML results in a clinical setting.
Methods and results
A total of 1980 patients with suspected coronary artery disease (CAD) underwent stress/rest 99mTc-sestamibi/tetrofosmin MPI with new-generation SPECT scanners were included. All patients had invasive coronary angiography within 6 months after SPECT MPI. ML utilized 18 clinical, 9 stress test, and 28 imaging variables to predict per-vessel and per-patient ECR with 10-fold cross-validation. Area under the receiver operator characteristics curve (AUC) of ML was compared with standard quantitative analysis total perfusion deficit (TPD) and expert interpretation. ECR was performed in 958 patients (48%). Per-vessel, the AUC of ECR prediction by ML (AUC 0.79, 95% confidence interval (CI) 0.77, 0.80) was higher than by regional stress TPD (0.71, 0.70, 0.73), combined-view stress TPD (AUC 0.71, 95% CI 0.69, 0.72), or ischaemic TPD (AUC 0.72, 95% CI 0.71, 0.74), all P < 0.001. Per-patient, the AUC of ECR prediction by ML (AUC 0.81, 95% CI 0.79, 0.83) was higher than that of stress TPD, combined-view TPD, and ischaemic TPD, all P < 0.001. ML also outperformed nuclear cardiologists’ expert interpretation of MPI for the prediction of early revascularization performance. A method to explain ML prediction for an individual patient was also developed.
Conclusion
In patients with suspected CAD, the prediction of ECR by ML outperformed automatic MPI quantitation by TPDs (per-vessel and per-patient) or nuclear cardiologists’ expert interpretation (per-patient).
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