Here we studied plasma metabolomic profiles as determinants of progression to end-stage renal disease (ESRD) in patients with type 2 diabetes (T2D). This nested case–control study evaluated 40 cases ...who progressed to ESRD during 8–12 years of follow-up and 40 controls who remained alive without ESRD from the Joslin Kidney Study cohort. Controls were matched with cases for baseline clinical characteristics, although controls had slightly higher eGFR and lower levels of urinary albumin excretion than cases. Plasma metabolites at baseline were measured by mass spectrometry–based global metabolomic profiling. Of the named metabolites in the library, 262 were detected in at least 80% of the study patients. The metabolomic platform recognized 78 metabolites previously reported to be elevated in ESRD (uremic solutes). Sixteen were already elevated in the baseline plasma of our cases years before ESRD developed. Other uremic solutes were either not different or not commonly detectable. Essential amino acids and their derivatives were significantly depleted in the cases, whereas certain amino acid–derived acylcarnitines were increased. All findings remained statistically significant after adjustment for differences between study groups in albumin excretion rate, eGFR, or HbA1c. Uremic solute differences were confirmed by quantitative measurements. Thus, abnormal plasma concentrations of putative uremic solutes and essential amino acids either contribute to progression to ESRD or are a manifestation of an early stage(s) of the disease process that leads to ESRD in T2D.
Invalid self-report and invalid performance occur with high base rates in attention deficit/hyperactivity disorder (ADHD; Harrison, 2006; Musso & Gouvier, 2014). Although much research has focused on ...the development and validation of symptom validity tests (SVTs) and performance validity tests (PVTs) for psychiatric and neurological presentations, less attention has been given to the use of SVTs and PVTs in ADHD evaluation. This introduction to the special section describes a series of studies examining the use of SVTs and PVTs in adult ADHD evaluation. We present the series of studies in the context of prior research on noncredible presentation and call for future research using improved research methods and with a focus on assessment issues specific to ADHD evaluation.
Public Significance Statement
This introduction to the special section focused on assessing the validity of presentation in attention deficit/hyperactivity disorder (ADHD) describes the growing research literature in this field. Emphasis is placed on the need to assess for both invalid self-report and invalid performance in ADHD evaluation and on presentation of the current state of the literature, as well as a call for continued and more rigorous research focused on unique issues in ADHD evaluation.
Brain-body interactions (BBIs) have been the focus of intense scrutiny since the inception of the scientific method, playing a foundational role in the earliest debates over the philosophy of ...science. Contemporary investigations of BBIs to elucidate the neural principles of motor control have benefited from advances in neuroimaging, device engineering, and signal processing. However, these studies generally suffer from two major limitations. First, they rely on interpretations of 'brain' activity that are behavioral in nature, rather than neuroanatomical or biophysical. Second, they employ methodological approaches that are inconsistent with a dynamical systems approach to neuromotor control. These limitations represent a fundamental challenge to the use of BBIs for answering basic and applied research questions in neuroimaging and neurorehabilitation. Thus, this review is written as a tutorial to address both limitations for those interested in studying BBIs through a dynamical systems lens. First, we outline current best practices for acquiring, interpreting, and cleaning scalp-measured electroencephalography (EEG) acquired during whole-body movement. Second, we discuss historical and current theories for modeling EEG and kinematic data as dynamical systems. Third, we provide worked examples from both canonical model systems and from empirical EEG and kinematic data collected from two subjects during an overground walking task.
(1) Background: Biomechanics during landing tasks, such as the kinematics and kinetics of the knee, are altered following anterior cruciate ligament (ACL) injury and reconstruction. These variables ...are recommended to assess prior to clearance for return to sport, but clinicians lack access to the current gold-standard laboratory-based assessment. Inertial sensors serve as a potential solution to provide a clinically feasible means to assess biomechanics and augment the return to sport testing. The purposes of this study were to (a) develop multi-sensor machine learning algorithms for predicting biomechanics and (b) quantify the accuracy of each algorithm. (2) Methods: 26 healthy young adults completed 8 trials of a double limb jump landing task. Peak vertical ground reaction force, peak knee flexion angle, peak knee extension moment, and peak sagittal knee power absorption were assessed using 3D motion capture and force plates. Shank- and thigh- mounted inertial sensors were used to collect data concurrently. Inertial data were submitted as inputs to single- and multiple- feature linear regressions to predict biomechanical variables in each limb. (3) Results: Multiple-feature models, particularly when an accelerometer and gyroscope were used together, were valid predictors of biomechanics (R2 = 0.68–0.94, normalized root mean square error = 4.6–10.2%). Single-feature models had decreased performance (R2 = 0.16–0.60, normalized root mean square error = 10.0–16.2%). (4) Conclusions: The combination of inertial sensors and machine learning provides a valid prediction of biomechanics during a double limb landing task. This is a feasible solution to assess biomechanics for both clinical and real-world settings outside the traditional biomechanics laboratory.
1 Department of Exercise and Movement Science, University of
Oregon, Eugene, Oregon 97403-1240; and 2 Department of
Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905
The ...mechanisms underlying the skin blood flow
(SkBF) response to local heating are complex and poorly understood. Our
goal was to examine the role of axon reflexes and nitric oxide (NO) in
the SkBF response to a local heating protocol. We performed 40 experiments following a standardized heating protocol with different
interventions, including blockade of the axon reflex (EMLA cream),
antebrachial nerve blockade (0.5% bupivacaine injection), and NO
synthase (NOS) inhibition ( 10 mM
N G -nitro- L -arginine methyl
ester; microdialysis). Appropriate controls were performed to verify
the efficacy of the various blocks. Values are expressed as a
percentage of maximal SkBF (SkBF max ; 50 mM sodium
nitroprusside). At the initiation of local heating, SkBF rose
to an initial peak, followed by a brief nadir, and a secondary, progressive rise to a plateau. Axon reflex block decreased the initial
peak from 75+3 to 32 ± 2% SkBF max ( P < 0.01 vs. control) but did not affect the plateau. NOS inhibition
before and throughout local heating reduced the initial peak from
75 ± 3 to 56 ± 3% SkBF max ( P < 0.01) and the plateau from 87 ± 4 to 40 ± 5%. NOS inhibition during axon reflex block did not further reduce the initial
SkBF peak compared with axon reflex block alone. Antebrachial nerve
block did not affect the local heating SkBF response. The primary
finding of these studies is that there are at least two independent
mechanisms contributing to the rise in SkBF during nonpainful local
heating: a fast-responding vasodilator system mediated by the axon
reflexes and a more slowly responding vasodilator system that relies on
local production of NO.
cutaneous vascular conductance; axon reflex; human; microvascular
dysfunction
Predicting vaccine effectiveness for mpox Berry, Matthew T; Khan, Shanchita R; Schlub, Timothy E ...
Nature communications,
05/2024, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was initially approved for mpox based on ...its reported immunogenicity (from phase I/II trials) and effectiveness in animal models, rather than evidence of clinical efficacy. However, no validated correlate of protection after vaccination has been identified. Here we performed a systematic search and meta-analysis of the available data to test whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. We observe a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, consistent with the existing assumption that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, we predict the durability of protection after vaccination and the impact of dose spacing. We find that delaying the second dose of MVA-BN vaccination will provide more durable protection and may be optimal in an outbreak with limited vaccine stock. Although further work is required to validate this correlate, this study provides a quantitative evidence-based approach for using antibody measurements to predict the effectiveness of mpox vaccination.
This study examined the unadjusted and adjusted prevalence estimates of depression and anxiety at the state level and examined the odds ratios of depression and anxiety for selected risk behaviors, ...obesity, and chronic diseases.
The 2006 Behavioral Risk Factor Surveillance Survey, a random-digit-dialed telephone survey, collected depression and anxiety data from 217,379 participants in 38 states, the District of Columbia, Puerto Rico, and the U.S. Virgin Islands. Current depressive symptoms were assessed with the standardized and validated eight-item Patient Health Questionnaire, and lifetime diagnosis of depression and anxiety was assessed by two additional questions (one question for each diagnosis).
The overall prevalence of current depressive symptoms was 8.7% (range by state and territory, 5.3%-13.7%); of a lifetime diagnosis of depression, 15.7% (range, 6.8%-21.3%); and of a lifetime diagnosis of anxiety, 11.3% (range, 5.4%-17.2%). After sociodemographic characteristics, adverse health behaviors, and chronic illnesses were adjusted for, cardiovascular disease, diabetes, asthma, smoking, and obesity were all significantly associated with current depressive symptoms, a lifetime diagnosis of anxiety, and a lifetime diagnosis of depression. Physically inactive adults were significantly more likely than those who were physically active to have current depressive symptoms or a lifetime diagnosis of depression, whereas those who drank heavily were significantly more likely than those who did not to have current depressive symptoms or a lifetime diagnosis of anxiety.
Depression and anxiety were strongly associated with common chronic medical disorders and adverse health behaviors. Examination of mental health should therefore be an integral component of overall health care.
Twenty-four studies utilizing the Wechsler Adult Intelligence Scale (WAIS) Digit Span subtest-either the Reliable Digit Span (RDS) or Age-Corrected Scaled Score (DS-ACSS) variant-for malingering ...detection were meta-analytically reviewed to evaluate their effectiveness in detecting malingered neurocognitive dysfunction. RDS and DS-ACSS effectively discriminated between honest responders and dissimulators, with average weighted effect sizes of 1.34 and 1.08, respectively. No significant differences were found between RDS and DS-ACSS. Similarly, no differences were found between the Digit Span subtest from the WAIS or Wechsler Memory Scale (WMS). Strong specificity and moderate sensitivity were observed, and optimal cutting scores are recommended.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
•MCNP, Serpent and OpenMC and DAGMC comparison for fusion neutronics application.•Validation of transport code physics through experimental and computational benchmarks.•Comparison of CSG and CAD ...based workflows.•Potentially more efficient workflows demonstrated for complex geometries.
The accurate and efficient mapping of the radiation environment in a nuclear fusion reactor requires the most advanced radiation transport tools. The Monte Carlo method has long been deployed to deal with the complexity of fusion relevant geometries, with MCNP the adopted industry standard code among the European and wider international community. However, reliance on a single code has driven explorations into alternatives to establish their capabilities and maturity for fusion analyses. These alternatives are being actively developed and increasingly adopted in some types of applied analysis by the user community. In this paper, we explore both experimental and computational benchmarks in order to examine the capabilities of Serpent, OpenMC as well as the framework for allowing CAD based particle transport, DAGMC, over a broad range of fusion relevant nuclear responses and geometries. This spans from more simple parametric models adopted in reactor scoping studies to the current ITER reference model which has been successfully translated to Monte Carlo codes other than MCNP using an open source utility, csg2csg. An assessment for both CSG and CAD based workflows has been conducted as well as a hybrid approach combining the two. The FNG HCPB, Cu and a subset of the FNS experiments were also converted to Serpent and OpenMC input files for comparison of calculation to available experimental data. Good agreement was observed across all codes for the determined tritium production rates and activation foil measurements. Potentially more efficient workflows for complex tokamak models are detailed. For a heterogeneous model of JET octant 1, an optimised CAD based model in Serpent is over 50% faster than the MCNP CSG equivalent model. In the case of the generated OpenMC model of ITER, an order of magnitude reduction in simulation time, including a model loading time of the order of minutes, is reported. Such validation and benchmarking activities should in the future be integrated as part of a testing suite for which a basic framework has been demonstrated here. To conclude, the current limitations and required development are outlined as well as identifying where each code may specialise for a particular application. Based on this future work relevant to both the developers and user community is briefly discussed.
Reduced- and low-fat cheeses are desired based on composition but often fall short on overall quality. One of the major problems with fat reduction in cheese is the development of a firm texture that ...does not break down during mastication, unlike that observed in full-fat cheeses. The objective of this investigation was to determine how the amount of fat affects the structure of Cheddar cheese from initial formation (2 wk) through 24 wk of aging. Cheeses were made with target fat contents of 3 to 33% (wt/wt) and moisture to protein ratios of 1.5:1. This allowed for comparisons based on relative amounts of fat and protein gel phases. Cheese microstructure was determined by confocal scanning laser microscopy combined with quantitative image analysis. Rheological analysis was used to determine changes in mechanical properties. Increasing fat content caused an increase in size of fat globules and a higher percentage of nonspherical globules. However, no changes in fat globules were observed with aging. Cheese rigidity (storage modulus) increased with fat content at 10°C, but differences attributable to fat were not apparent at 25°C. This was attributable to the storage modulus of fat approaching that of the protein gel; therefore, the amount of fat or gel phase did not have an effect on the cheese storage modulus. The rigidity of cheese decreased with storage and, because changes in the fat phase were not detected, it appeared to be attributable to changes in the gel network. It appeared that the diminished textural quality in low-fat Cheddar cheese is attributed to changes in the breakdown pattern during chewing, as altered by fat disrupting the cheese network.
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