Large Variations Research Articles

Comparative performance of pharmacogenetics-based warfarin dosing algorithms in Chinese population: use of a pharmacokinetic/pharmacodynamic model to explore dosing regimen through clinical trial simulation.

Warfarin has a narrow therapeutic window and large variability in dosing that are affected by clinical and genetic factors. To help guide the dosing of warfarin, the Clinical Pharmacogenetics Implementation Consortium has recommended the use of pharmacogenetic algorithms, such as the ones developed by the International Warfarin Pharmacogenetics Consortium (IWPC) and by Gage et al. when genotype information is available. In this study, simulations were performed in Chinese cohorts to explore how dosing differences between Western (by IWPC and Gage et al.) and Chinese algorithms (by Miao et al.) would mean in terms of anticoagulation effect in clinical trials. We first tried to replicate a published clinical trial comparing genotype-guided dosing to routine clinical dosing in Chinese patients. We then made simulations where Chinese cohorts received daily doses recommended by Gage, IWPC, and Miao algorithms. We found that in simulation conditions where dosing specifications were strictly followed, genotype-guided dosing by IWPC and Lenzini formulae was more likely to overshoot the upper limit of the therapeutic window by day 15, and thus may have a lower % time in therapeutic range (%TTR) than that of clinical dosing group. Also, in comparing Gage, IWPC, and Miao algorithms, we found that the Miao dosing cohort has the highest %TTR and the lowest risk of over-anticoagulation by day 28. In summary, our results confirmed that algorithms developed based on data from local patients may be more suitable for achieving therapeutic international normalized ratio window in Chinese population.

Eastern Tropical Pacific atmospheric and oceanic projected changes based on CMIP6 models

Atmosphere and ocean dynamics and their projections for the 21st century are assessed in the Eastern Tropical Pacific, using an ensemble of 17 models from the Coupled Model Intercomparison Project – CMIP6, under two radiative scenarios. Projections in the Panama Bight (PB) and Equatorial Pacific cold tongue (CT) are studied in more detail. In the 2071–2100 period and SSP5-8.5 scenario, referenced to the 1985–2014 period, air temperature (sea surface temperature) is expected to rise ∼3.5 °C (∼3 °C). Precipitation is projected to increase > 3 mm day−1 in the mean position of the Intertropical Convergence Zone, and decrease toward the north. A similar meridional pattern is projected in sea level atmospheric pressure and sea surface salinity (SSS) with negative anomalies toward the south. Large seasonal variations, which dominate the region, are projected to remain similar for the rest of the century. However, in January-April a weakening in the Panama wind jet and intensification of surface wind in the CT is expected, while in the June-November season, a weakening of the Choco wind jet will affect both sub-regions. Mean sea surface height (SSH) is expected to decrease, probably dominated by barotropic wind effects over SSS reduction effect on SSH. However, sterodynamic sea level (SDSL) is projected to rise (∼21 cm) driven by the global mean thermosteric contribution. For the end of the century, a mean sea level rise of ∼69 cm is estimated in the ETP, with SDSL being about half the barystatic contribution. These projections should be used with caution, as climate models have shown limitation reproducing atmospheric and ocean observations in the tropical Pacific Ocean during the last decades, due to large internal variability and systematic biases.

CMIP6 Models Underestimate Arctic Sea Ice Loss during the Early Twentieth-Century Warming, despite Simulating Large Low-Frequency Sea Ice Variability

Abstract The variability of Arctic sea ice extent (SIE) on interannual and multidecadal time scales is examined in 29 models with historical forcing participating in phase 6 of the Coupled Model Intercomparison Project (CMIP6) and in twentieth-century sea ice reconstructions. Results show that during the historical period with low external forcing (1850–1919), CMIP6 models display relatively good agreement in their representation of interannual sea ice variability (IVSIE) but exhibit pronounced intermodel spread in multidecadal sea ice variability (MVSIE), which is overestimated with respect to sea ice reconstructions and is dominated by model uncertainty in sea ice simulation in the subpolar North Atlantic. We find that this is associated with differences in models’ sensitivity to Northern Hemispheric sea surface temperatures (SSTs). Additionally, we show that while CMIP6 models are generally capable of simulating multidecadal changes in Arctic sea ice from the mid-twentieth century to present day, they tend to underestimate the observed sea ice decline during the early twentieth-century warming (ETCW; 1915–45). These results suggest the need for an improved characterization of the sea ice response to multidecadal climate variability in order to address the sources of model bias and reduce the uncertainty in future projections arising from intermodel spread. Significance Statement The credibility of Arctic sea ice predictions depends on whether climate models are capable of reproducing changes in the past climate, including patterns of sea ice variability which can mask or amplify the response to global warming. This study aims to better understand how latest-generation global climate models simulate interannual and multidecadal variability of Arctic sea ice relative to available observations. We find that models differ in their representation of multidecadal sea ice variability, which is overall larger than in observations. Additionally, models underestimate the sea ice decline during the period of observed warming between 1915 and 1945. Our results suggest that, to achieve better predictions of Arctic sea ice, the realism of low-frequency sea ice variability in models should be improved.

Sintering of different silica aerogels

This work reports on isothermal sintering experiments, conducted with silica aerogel samples in a broad density range (∼0.025–0.277 kg/m3) made by the same process by varying the solvent-to-sol ratio, as well as samples made by different formulations used by several aerogel manufacturers. The latter comparison is deficient in the literature. Low-density (<0.05 kg/m3) aerogels were found to be significantly more resilient to sintering, which is consistent with established sintering theories. Unexpectedly large variability in the susceptibility to sintering was observed in similar density (∼0.1 kg/m3) aerogels made by different formulations and by different producers. All material made by utilizing a CO2 solvent exchange step prior to supercritical drying exhibited effects attributable to residual original solvent in the micropores. This alludes to an incomplete solvent exchange process. The materials were examined in the context of devising a methodology for producing an ultra-pure silica aerogel, a substance free of organic constituents, intended to serve NASA life detection mission needs.

Process-Based Evaluation of Intraseasonal Oceanic Kelvin Waves in the Pacific Ocean in CMIP6 Models

Abstract Oceanic intraseasonal Kelvin waves (KWs) help modulate upper-ocean thermal characteristics, providing feedbacks to important coupled air–sea phenomena in the tropics. The recent availability of daily thermocline depth fields from several phase 6 of the Coupled Model Intercomparison Project (CMIP6) models makes it possible to evaluate the performance of KWs and identify potential sources of bias. Most models fail to simulate a realistic spatial distribution of KW variability. Models simulate a large variability of KWs in the western or eastern Pacific rather than in the central Pacific as observed. The modeled KWs propagate slowly (about 1.5 m s−1) compared to observations (about 2.5 m s−1). This slow propagation is also identified in wavenumber–frequency spectra for KWs and meridional KW structures, which is more consistent with a second baroclinic mode structure in models compared to the first baroclinic mode structure in observations. An analysis of the relative contributions of the vertical wavenumber and background ocean stability to KW phase speeds indicates that the high vertical wavenumber bias in models contributes most to the slow propagation, in which the higher-than-observed vertical wavenumbers imply the biased incorporation of higher baroclinic modes in the model KW structure. This finding is further supported by the results of vertical mode decomposition that incorporates background density profiles. These results indicate that a realistic representation of the KW vertical structure is essential to produce realistic KW propagations in models. Significance Statement Oceanic intraseasonal Kelvin waves (KWs) play a significant role in regulating the heat content and temperature of the ocean, which provides feedbacks to coupled ocean–atmosphere phenomena in the tropics such as El Niño–Southern Oscillation (ENSO). Consequently, identifying the biases in KWs and the potential sources of those biases in state-of-the-art models is essential to improve simulations of ENSO and its diversity and advance forecasts of weather extremes around the globe induced by ENSO. We find that KWs in the models propagate slower than observations, mainly due to biases in their vertical structure, with secondary effects due to biases in model ocean stability. These issues may be potential sources for current imperfect ENSO model simulations and predictions.

Intracerebral hemorrhage

Background: Compared to ischemic stroke, intracerebral hemorrhage (ICH) has higher mortality and more severe disability. Asian such as Chinese and Japanese and Mexican Americans, Latin Americans, African Americans, Native Americans have higher incidences than do white Americans. So, ICH is an important cerebrovascular disease in Asia. Summary: ICH accounts for approximately 10-20% of all strokes. The incidence of ICH is higher in low- and middle-income than high-income countries and is estimated 8-15% in western countries like USA, UK and Australia, and 18-24% in Japan, Taiwan and Korea. The ICH incidence increases exponentially with age, and old age especially over 80 years is a major predictor of mortality independent of ICH severity. Females are older at the onset of ICH and have higher clinical severity than males. Modifiable risk factors include blood pressure, smoking, alcohol consumption, lipid profiles, use of anticoagulants, antiplatelet agents and sympathomimetic drugs. Non-modifiable risk factors constitute old age, male gender, Asian ethnicity, cerebral amyloid angiopathy, cerebral microbleed, and chronic kidney disease. Blood pressure is the most important risk factor of ICH. Imaging markers may help predict ICH outcome, which include black hole sign, blend sign, iodine sign, island sign, leakage sign, satellite sign, spot sign, spot-tail sign, swirl sign, and hypodensities. ICH prognostic scoring system such as ICH scoring system and ICH grading scale scoring system in Chinese and Osaka prognostic score and Naples prognostic score has been used to predict ICH outcome. Early minimally invasive removal of ICH can be recommended for lobar ICH of 30–80 mL within 24 hours after onset. Decompressive craniectomy without clot evacuation might benefit ICH patients aged 18–75 years with 30–100 mL at basal ganglia or thalamus. However, clinical studies are needed to investigate the effect of surgery on patients with smaller or larger ICH, ICH in non-lobar locations, and for older patients or patients with preexisting disability. Surgical treatment is usually associated with neurological sequels if survived. For medical treatment, blood pressure lowering should be careful titrated to secure continuous smooth and sustained control and avoid peaks and large variability in systolic blood pressure. Stroke and cancer are the most common causes of death in Asian ICH patients, compared to stroke and cardiac disease in non-Asian patients. Key Messages: The incidence and outcome are different between Asian and non-Asian patients, and more clinical studies are needed to investigate the best management for Asian ICH patients.

Evidence for the acclimation of ecosystem photosynthesis to soil moisture.

Ecosystem gross primary productivity (GPP) is the largest carbon flux between the atmosphere and biosphere and is strongly influenced by soil moisture. However, the response and acclimation of GPP to soil moisture remain poorly understood, leading to large uncertainties in characterizing the impact of soil moisture on GPP in Earth system models. Here we analyze the GPP-soil moisture response curves at 143 sites from the global FLUXNET. We find that GPP at 108 sites exhibits hump-shaped response curves with increasing soil moisture, and an apparent optimum soil moisture ( , at which GPP reaches the maximum) exists widely with large variability among sites and biomes around the globe. Variation in is mostly explained by local water availability, with drier ecosystems having lower than wetter ecosystems, reflecting the water acclimation of . This acclimation is further supported by a field experiment that only manipulates water and keeps other factors constant, which shows a downward shift in after long-term water deficit, and thus a lower soil water requirement to maximize GPP. These results provide compelling evidence for the widespread and its acclimation, shedding new light on understanding and predicting carbon-climate feedbacks.

EEG Infrastructure Within the Veterans Administration: A Survey.

EEG is a vital tool in the diagnosis and management of neurologic conditions prevalent among veterans such as seizures, epilepsy, and brain injuries. This cross-sectional study aimed to assess the state of EEG infrastructure within the Veterans Administration (VA), focusing on availability, utilization, and the potential avenues to addressing gaps in infrastructure. This survey was distributed to 123 VA hospitals using the Research Electronic Data Capture (REDCap) platform, gathering data on EEG equipment, staffing, and service provision from June to December 2023. Of the 123 VA hospitals surveyed, 70 responded (56.9% response rate). Most respondents (88.6%) reported having EEG services, although only 38.7% offering continuous EEG (cEEG). Respondents reported having less EEG technologists, machines, and faculty readers than what they thought would be ideal. Significant correlations were found between the availability of resources (e.g., number of EEG machines) and service capabilities, including remote access and cEEG. The use of alternative EEG technologies such as rapid or quantitative EEG varied greatly. Interest in participating in the VA Tele-EEG program was reported by 59.4% of respondents. There is large variability in EEG infrastructure across the VA. Tele-EEG has the potential to maintain continuity of operations through challenges affecting staffing and to improve EEG service access, especially in resource-limited settings. Expanding access to quantitative, rapid, and tele-EEG services may enhance patient management and may be a potential avenue to explore as the VA continues to invest in and grow its capacity for treating neurologic conditions.

Hydrodynamic mechanisms of topographic evolution in straight sandy beach: a case study of Wanpingkou beach, China

Stricter controls on destructive human activities in recent years have improved the protection and management of sandy coasts in China. Marine-driven geomorphic changes have become the predominant process influencing future beach evolution. However, in the complex geomorphic conditions of mixed artificial and natural coastlines, the mechanisms and contributions of various marine-driven factors to beach changes remain unclear. Using methods of field observations and numerical simulations by FVCOM model, this study reveals the sedimentary dynamic mechanism of straight sandy beach in the southern Shandong Peninsula (Wanpingkou beach, WPK beach). From 2005 to 2016, the northern section of WPK Beach eroded at a rate of approximately 2-3 m/year, the middle section at about 0.5-1.5 m/year, and the southern section accrued at an average rate of about 1-2 m/year, demonstrating an overall pattern of “northern erosion and southern accretion.” During winter, the average grain size of beach sediments is about 0.5 mm with minimal variations, indicating an onshore transport trend; in summer, the average grain size is about 0.7 mm with larger variations, indicating an offshore transport trend. Offshore sediment transport correlates mainly with seasonal changes in wind direction, while alongshore sediment transport is influenced by tidal currents, wind-induced currents, and wave-induced currents. Wave-induced currents are the primary force in alongshore sediment transport with a velocity of 0.1-0.3 m/s toward southwest. Followed by tidal currents with a velocity of 0.05-0.1 m/s, and wind-induced currents with a velocity of 0-0.1 m/s, which have a relatively minor impact. Therefore, seasonal changes in beach morphology are primarily controlled by waves, while interannual variations is mainly influenced by a combination of wave-induced currents and tidal currents. With increasing efforts in beach maintenance and coastal ecological restoration in recent years, understanding the sedimentary dynamics of beaches remains of vital theoretical and practical value.

Abstract 4137518: The implications of polygenic versus phenotypic characterization of obesity for cardiovascular-kidney-metabolic health

Introduction: The overall amount and the distribution of body fat, proxied by body-mass index (BMI) and waist-to-hip ratio (WHR), are two important measures of obesity and have significant polygenic heritability. We aimed to investigate whether polygenic scores (PGS) for these traits have additional predictive utility, beyond phenotypic characterization of obesity, for cardiovascular-kidney-metabolic (CKM) health. Methods: We derived PGS for BMI (PGS BMI ) and WHR adjusted for BMI (PGS WHRadjBMI ) using PRS-CS-auto on summary statistics from ~700k individuals of European ancestry (EA) in the GIANT consortium and selecting ~1M common variants for each score. We conducted association analyses in the Atherosclerosis Risk in Communities study, a prospective cohort including 8,631 EA individuals with ascertainment of incident diabetes, hypertension, chronic kidney disease, atrial fibrillation, coronary heart disease, ischemic stroke, and heart failure. We used nested Cox models to measure the added predictive utility of PGS to BMI and WHR for incident CKM phenotypes. Results: The study cohort (age 54.4±5.7 years, 52.4% women, follow-up 24.5±7.6 years) had a baseline BMI of 26.4 kg/m 2 (median [IQR]; 21.6-29.6) and WHR of 0.94 (0.88-0.98). PGS BMI and PGS WHRadjBMI were associated with their phenotypes (partial R 2 ; BMI 0.11 and WHR 0.04, p &lt;0.001), although with a large phenotypic variability across the distribution of PGS (IQR for 1 st and 10 th deciles of PGS; BMI 19.6-28.3 and 22.6-35.9, WHR 0.79-1.03 and 0.87-1.05). Anthropometric measures of obesity were associated with a wider gradient of risk compared to PGS for obesity–most notable for diabetes and cardiovascular phenotypes (Table 1a). Addition of PGS BMI and PGS WHRadjBMI to BMI and WHR resulted in limited improvement in risk discrimination across incident CKM phenotypes (Table 1b). Conclusions: Observed anthropometric measures of obesity are sufficient, and for certain conditions far superior, to capture the risk of incident CKM phenotypes. These findings suggest PGS for adiposity traits likely have limited clinical utility to refine risk stratification for CKM syndrome among middle aged adults.

Variability and repeatability of spinal manipulation force-time characteristics in thoracic spinal manipulation on a manikin.

As part of multimodal therapy, spinal manipulation (SM) is a recommended and effective treatment for musculoskeletal pain. However, the underlying physiological mechanisms for pain relief are largely unknown. SM thrusts can be described and quantified using force-time characteristics (e.g. preload force, peak force, thrust speed, thrust duration, and thrust impulse). If these biomechanical parameters of SM are important for clinical outcomes, a large variability in the delivery of SM could lead to inconsistent responses and could thereby potentially mask a significant clinical effect. Our goal was to determine variability, and repeatability of thoracic spinal manipulation (SM) force-time profiles in a sample of Swiss chiropractors. All interventions were performed on a human analogue manikin. Participating chiropractors received three case scenarios with the following scenarios: 50-year-old male patient, 30-year-old male athlete, and a 70-year-old female patient, each presenting with uncomplicated musculoskeletal thoracic pain. Clinicians were asked to perform three consecutive thoracic SM thrusts for each of the scenarios and repeated the same interventions after 24-48h. Eighty-one chiropractors participated in the study, including 32 females (39.5%) with a mean age of 45.22 ± 12.96years. The variability in SM force-time characteristics between clinicians was substantial, with preload forces ranging from 4.50 to 450.25 N and peak forces ranging from 146.08 to 1285.17 N. Significant differences between case scenarios were observed for peak force (p < 0.0001), maximum thrust speed (p = 0.0002), and thrust impulse (p = 0.0004). Except for thrust duration, repeatability within and between sessions was fair to excellent (ICCs between 0.578 and 0.957). Substantial variability in application of SM was evident across clinicians and between case scenarios. Despite substantial clinician-dependent variability, the high repeatability of thoracic SM thrusts suggests a level of standardization in SM delivery, indicating that chiropractors might have 'their' individual force-time profile that they are capable to reproduce. Further research based on these findings should explore how to enhance the consistency, effectiveness, and safety of thoracic SM delivered clinically to humans.

Attentional network deficits in patients with migraine: behavioral and electrophysiological evidence.

Patients with migraine often experience not only headache pain but also cognitive dysfunction, particularly in attention, which is frequently overlooked in both diagnosis and treatment. The influence of these attentional deficits on the pain-related clinical characteristics of migraine remains poorly understood, and clarifying this relationship could improve care strategies. This study included 52 patients with migraine and 34 healthy controls. We employed the Attentional Network Test for Interactions and Vigilance-Executive and Arousal Components paradigm, combined with electroencephalography, to assess attentional deficits in patients with migraine, with an emphasis on phasic alerting, orienting, executive control, executive vigilance, and arousal vigilance. An extreme gradient boosting binary classifier was trained on features showing group differences to distinguish patients with migraine from healthy controls. Moreover, an extreme gradient boosting regression model was developed to predict clinical characteristics of patients with migraine using their attentional deficit features. For general performance, patients with migraine presented a larger inverse efficiency score, a higher prestimulus beta-band power spectral density and a lower gamma-band event-related synchronization at Cz electrode, and stronger high alpha-band activity at the primary visual cortex, compared to healthy controls. Although no behavior differences in three basic attentional networks were found, patients showed magnified N1 amplitude and prolonged latency of P2 for phasic alerting-trials as well as an increased orienting evoked-P1amplitude. For vigilance function, improvements in the hit rate of executive vigilance-trials were exhibited in controls but not in patients. Besides, patients with migraine exhibited longer reaction time as well as larger variability in arousal vigilance-trials than controls. The binary classifier developed by such attentional deficit features achieved an F1 score of 0.762 and an accuracy of 0.779 in distinguishing patients with migraine from healthy controls. Crucially,the predicted value available from the regression model involving attentional deficit features significantly correlated with the real value for the frequency of headache. Patients with migraine demonstrated significant attentional deficits, which can be used to differentiate migraine patients from healthy populations and to predict clinical characteristics. These findings highlight the need to address cognitive dysfunction, particularly attentional deficits, in the clinical management of migraine.

Dakar Niño under global warming investigated by a high-resolution regionally coupled model

Abstract. In this study, we investigated interannual variability in sea surface temperature (SST) along the northwestern African coast, focusing on strong Dakar Niño and Niña events and their potential alterations under the RCP8.5 emission scenario for global warming, using a high-resolution regional coupled model. Our model accurately reproduces the SST seasonal cycle along the northwestern African coast, including its interannual variability in terms of amplitude, timing, and the position of maximum variability. Comparing Dakar Niño variability between the 1980–2010 and 2069–2099 periods, we found that it intensifies under a warmer climate without changing its location and timing. The intensification is more pronounced during Dakar Niñas (cold SST events) than during Dakar Niños (warm SST events). In the future, SST variability will be correlated with ocean temperature and vertical motion at deeper layers. The increase in Dakar Niño variability can be explained by the larger variability in meridional wind stresses, which is likely to be amplified in the future by enhanced land–sea thermal contrast and associated sea-level-pressure anomalies extending from the Iberian Mediterranean area. A heat budget analysis of the mixed layer suggests that surface heat flux and horizontal-advection anomalies are comparably important for Dakar Niño and Niña events in the present climate. However, the future intensification of Dakar Niños and Niñas is likely to be driven by surface heat flux (latent heat flux and shortwave radiation). While horizontal- and vertical-advection anomalies also contribute to the intensification, their roles are secondary.

Snowmelt-mediated isotopic homogenization of shallow till soil

Abstract. The hydrological cycle of sub-arctic areas is dominated by the snowmelt event. An understanding of the mechanisms that control water fluxes during high-volume infiltration events in sub-arctic till soils is needed to assess how future changes in the timing and magnitude of snowmelt can affect soil water storage dynamics. We conducted a tracer experiment in which deuterated water was used to irrigate a plot on a forested hilltop in Lapland, tracked water fluxes of different mobility and monitored how the later snowmelt modifies the labelled soil water storage. We used lysimeters and destructive soil coring for soil water sampling and monitored and sampled the groundwater. Large spatiotemporal variability between the waters of different mobility was observed in the subsurface, while surface water flow during the tracer experiment was largely controlled by a fill-and-spill mechanism. Extensive soil saturation induced the flow of labelled water into the roots of nearby trees. We found that labelled water remained in deeper soil layers over the winter, but the snowmelt event gradually displaced all deuterated water and fully homogenized all water fluxes at the soil–vegetation interface. The conditions required for the full displacement of the old soil water occur only during a snowmelt with a persistently high groundwater table. We propose a conceptual model where infiltration into the soil and eventual soil water replenishment occur in three stages. First, unsaturated macropore flow is initiated via the surface microtopography and is directed towards the groundwater storage. The second stage is characterized by groundwater rise through the macropore network, subsequent pore water saturation and increased horizontal connectivity of macropores. Shallow subsurface lateral fluxes develop in more permeable shallow soil layers. In the third stage, which materializes during a long period with a high groundwater table and high hydrological connectivity within the soil, the soil water is replenished via enhanced matrix flow and pore water exchange with the macropore network.

Examining Whole Blood, Total and Free Plasma Tacrolimus in Elderly Kidney Transplant Recipients.

Therapeutic monitoring is routinely performed to ensure tacrolimus whole-blood concentrations fall within a predefined target. Despite this, patients still experience inefficacy and toxicity that could be related to variability in free (unbound) tacrolimus exposure. Therefore, the aim of this study was to compare tacrolimus-free plasma (Cu), total plasma (Cp), and whole-blood (Cwb) concentrations in adult kidney transplant recipients and to characterize tacrolimus disposition across different matrices. Twelve-hour concentration-time profiling was performed in 15 recipients, allowing simultaneous measurement of Cu, Cp, and Cwb. Pharmacokinetic parameters were estimated using noncompartmental analysis. The relationship between Cwb and Cp were examined using a capacity-limited binding model, incorporating the hematocrit fraction (fHCT) to estimate maximum binding concentration (Bmax) and dissociation constant (Kd). The relationship between Cp and Cu was evaluated using a linear binding model to estimate the nonspecific binding parameter (Nplasma). Nonlinear regression analysis was used to obtain estimates of Bmax, Kd, and Nplasma. A total of 195 paired Cwb, Cp, and Cu values were collected. The median ratios of Cwb:Cp, Cp:Cu, and Cwb:Cu were 9:1, 20:1, and 138:1, respectively. Variability in free plasma exposure was large; free trough values ranged from 8 to 51 ng/L and free area-under-the-concentration-time-curve values ranged from 424 to 7160 ng·h/L. Median (range) estimates of Bmax, Kd, and Nplasma were 90.4 µg/L (22.4-752.5 µg/L), 2.36 µg/L (0-69.2 µg/L), and 0.05 (0.035-0.085), respectively. The interindividual variability (CV%) in binding parameters was considerable (Bmax 117.2%; Nplasma 32.5%). Large variability was observed in tacrolimus-free plasma exposure and binding parameters. Future research to characterize the relationship between tacrolimus Cu and patient outcomes may be of benefit.

Do smaller P300 amplitudes in schizophrenia result from larger variability in temporal processing?

The P3b is a prominent event-related potential (ERP) with maximal amplitude between 250 ms and 500 ms after the onset of a rare target stimulus within a sequence of standard non-target stimuli (oddball paradigm). Several studies found reduced P3b amplitudes in patients with schizophrenia compared to neurotypicals. Our work and the literature suggest that temporal imprecision may play a large pathophysiological role in schizophrenia. Here, we investigated whether reduced P3b amplitudes result from reduced neural activity (power) or temporal imprecision (inter-trial phase coherence; ITC) in delta and theta bands, using two EEG datasets from different studies with different oddball paradigms (Study 1: 19 patients with schizophrenia and 17 matched controls, Study 2: 26 patients and 26 controls). Both studies revealed typical P3b ERP components with smaller amplitudes in patients. Reduced ITC in patients was found in the delta band, which correlated with P3b peak amplitudes for all participant groups (ρ = 0.58–0.89). In Study 1, we also found significant differences between patients and controls in ITC in the theta band, which also correlated with P3b peak amplitudes (patients’ ρ = 0.64, controls’ ρ = 0.54). This was not found in Study 2. The results indicate that P3b amplitude reduction in patients with schizophrenia is linked to a reduction in temporal precision of neural activity. These results expand the notion of imprecision in temporal processing at phenomenological, psychological, and neurological levels that have been related to disturbances of the sense of self. They confirm that temporal imprecision may be more important than the reduction of neural activity itself.

How to deal with the variability of peripheral nerve lesion patterns after inguinal herniotomy? A descriptive approach for a new terminology in clinical practice

BackgroundInguinal hernia is one of the most common visceral surgical conditions in industrialised countries. The aim of the present observational clinical study was to investigate the dermatome patterns after nerve injury following inguinal hernia surgery and to demonstrate the marked individual anatomical and topographical variability of peripheral nerves in the inguinal region. Methods220 patients were followed up for one year after inguinal herniotomy. Surgical treatment was performed either with tension-free mesh techniques or open according (Lichtenstein). ResultsOne year after inguinal herniotomy, 25 patients (11.4 %) reported postoperative symptoms. Of these, 15 patients showed evidence of a distinct nerve lesion. The results of the clinical neurological examination sometimes differed considerably from the subjective perceptions of the patients. In addition, a marked individual variability in the dermatomes of surgically lesioned nerves was found, with discrepancies to the classical and conventional dermatome data in textbooks. ConclusionsThis study has shown that it is hardly possible to assign a specific lesional inguinal dermatome to a specific nerve, as nerves show a large individual variability in their anatomical, topographical location and thus in their dermatome boundaries. Therefore, we propose a descriptive approach to the terminology of peripheral inguinal nerve lesions using common regional landmarks. This will avoid a potentially erroneous dermatome assignment to a certain nerve and facilitate the reproducibility of lesion descriptions between different observers, thus facilitating communication in clinical practice.

Beyond NT-proBNP: Circulating Protein Biomarkers for Atrial Fibrillation in Heart Failure and Cardiomyopathy

Atrial fibrillation (AF) is largely co-morbid with heart failure (HF), worsening prognosis in patients with ventricular dysfunction. Treating AF through ablation can improve outcomes and reduce the transition to end-stage HF, highlighting the importance of early recognition in patients with ventricular dysfunction. Circulating NT-proBNP is a well-known biomarker for AF in patients with ventricular dysfunction, however, large individual variability limits its predictive power and therefore utility. With the rise of high-throughput proteomics in the era of precision medicine, novel and stable biomarkers may be identified with the potential to improve risk stratification, detection, and management.

Validity and reliability of the short-form adolescent health promotion scale among adolescents and young adults in Ghana: methodological study

Background and aimAssessing health promotion among adolescents and young adults is vital to identify healthy and unhealthy behaviours as well as to evaluate health promotion interventions. However, there is no valid and reliable scale to assess health promotion among Ghanaians. For the first time, this study determined the validity and reliability of the original version of the Short‐Form Adolescent Health Promotion (AHP) scale among adolescents and young adults in Ghana.MethodThis cross-sectional methodological study included 617 adolescents and young adults within Kwame Nkrumah University of Science and Technology (KNUST) in Kumasi, Ghana. A well-structured questionnaire was used to collect sociodemographic data from study participants. The AHP-Scale was also used to collect data on participants health promoting behaviors. The scale’s validity was evaluated using Kaiser-Meyer-Olkin (KMO), Bartlett’s test of sphericity and Exploratory Factor Analysis (EFA), whilst the reliability was assessed using the Cronbach’s ɑ coefficient. Statistical analysis was performed using SPSS software version 26.ResultsThe KMO and the Bartlett’s test of sphericity were reported to be 0.899 and χ2 (276) = 6682.338 respectively, allowing for EFA with orthogonal rotation. The EFA revealed five factors covering 54.62% of the total variance. The factor loading order of the items did not exactly correspond to the order obtained in the original version of the scale’s validity analysis as the original scale had six factors. This six-factor loading scale was valid in regards to construct validity. The obtained factors included: life appreciation, exercise, stress management, nutrition, and social support. In this current study, Cronbach’s ɑ was calculated at 0.87 for the whole scale and between 0.71 and 0.92 for its subscales. Thus, indicating the current scale reliable.ConclusionThe six-factor loading scale of the Adolescent Health Promotion scale developed in the present study is acceptable for the validity and reliability assessment. However, the construct validity of this scale should be checked in other samples as it did not cover a large variance of the population. Large population wide studies are also needed to augment the current study findings with additional modifications for the adopted AHP scale.

Can Front-of-Pack Labeling Encourage Food Reformulation? A Cross-Sectional Study on Packaged Bread

Front-of-pack labeling (FOPL) may represent an important instrument for the food industry in the promotion of food product reformulation. The present cross-sectional study used salt reduction in packaged breads as a case study, aiming to investigate whether two different types of FOPL (i.e., Nutri-Score (NS) and NutrInform battery (NIB)) can capture food reformulation and thus be effective tools for encouraging reformulation. The Nutri-Score and NIB were calculated by consulting the nutritional declarations and ingredient lists of 527 packaged breads currently sold in Italy before and after applying three different theoretical reformulation strategies: (i) a 25% salt decrease from the current median salt content in bread; (ii) a reduction of up to 0.825 g/100 g of salt, corresponding to the sodium benchmark of 330 mg/100 g set by the World Health Organization (WHO); and (iii) the minimum salt reduction needed to improve the NS by one grade. The results show that only ~44% of breads had improved NSs when the sodium was lowered to reach the WHO benchmark or when salt was reduced by 25%, whereas large variability was observed in the minimum salt reduction needed to improve the NS. Regarding the NIB, the battery for salt improved when both strategies of reformulation were applied. FOPL is not always effective in capturing food reformulation in terms of salt reduction, possibly discouraging the efforts of food companies to improve the nutritional quality of foods.