Timing Of Events Research Articles

Atrial fibrillation and prediabetes: Interplay between left atrium and systemic diseases

Atrial fibrillation (AF) is associated with multiple other comorbidities, i.e. multimorbidity. Prediabetes is one of the multiple comorbidities observed in patients with AF, whereby these two disease entities share the same pathophysiological mechanisms, namely oxidative stress and inflammation. Although prediabetes is reported to have a negative impact on major adverse cardiac or cerebrovascular events in hospitalized AF patients, information about the interactions between prediabetes and AF remains inconsistent. A more in-depth exploration of pathophysiology and more comprehensive prospective clinical studies of AF and diabetes would provide a thorough understanding of the timing of events and further treatment strategies. Deeper investigations are needed to clarify the interactions and causal relationships between AF and prediabetes.

The Impact of Geomagnetic Storms on the Ionospheric Critical Frequency in the Northern and Southern Mid-Latitude Hemisphere Regions

In this work, the impact of different geomagnetic storm events on the plasma-sphere layer (ionosphere layer) over the northern and southern hemisphere regions was investigated during solar cycle 23. To grasp the influence of geomagnetic storms on the behavior and variation of the critical frequency parameter of the F2 ionospheric layer (foF2), five geomagnetic storms (classified as great, severe, and strong), with Disturbance storm time (Dst) values <-100 nT were chosen. Four stations located in different mid-latitude regions in northern and southern hemispheres were designated, the northern stations are: Millstone Hill (42.6° N, 288.50° W) and Rome (41.90° N, 12.50° E) and the southern stations are: Port Stanley (-51.60° S, 302.10° W) and Grahamstown (-33.30° S, 26.50° E). The findings of this study showed that during events of 16 July 2000 and 24 August 2005, the negative storms cause a noticeable reduction in the values of the foF2 parameter at the northern hemisphere stations compared to those at the southern hemisphere. These outcomes are consistent with the results of the examining the variation of D(foF2) and the electron density depletion during the tested event times at all stations except in Rome, where minor enhancements in foF2 value were observed during the August 24 2005 storm. During equinox storm events occurring on March 31 and November 6 2001, a noticeable negative impact of storms was observed across all stations. However, at Millstone Hill and Port Stanley stations, the results showed a slight positive storm impact during the October 21, 2001event.

Multi-stage tectonic record of the Central Sakarya Terrane Basement (NW Turkey): Implications for the Paleozoic evolution of Rheic Ocean and northern Gondwanan margin

In northwestern Turkey, within the Central Sakarya Terrane, the Söğüt Metamorphics is one of the Variscan tectonic units preserved as a pre-Jurassic basement assemblage of the Sakarya Composite Terrane (SCT). It consists of para- and orthogneisses that host bands, lenses, boudins, and tectonic slices of amphibolites, and are altogether intruded by the Sarıcakaya Granitoid. The characterization and timing of the precursor magmatic events for the protoliths of this assemblage and the timing and conditions of metamorphism have been the topics of a long-lasting debate. Here we present new geochemical and geochronological data from the Söğüt orthogneisses, amphibolites, and the crosscutting Sarıcakaya Granitoid to provide further understanding of the geodynamic evolution of the SCT Basement and the larger-scale tectonic events that controlled its formation. Available geological and geochronological data indicate that the generation of the orthogneiss protoliths began in the Late Cambrian (ca. 485 Ma) and continued until the middle Silurian (ca. 430 Ma), accompanied by the subduction of the Iapetus Ocean and its progressive roll-back beneath northern Gondwana. The slab roll-back caused mantle-upwelling and Ordovician (ca. 465 Ma) continental rift-related mafic magmatism, eventually leading to the opening of the Rheic Ocean. Prior to the Variscan orogeny, a short-lived episode of middle Carboniferous (ca. 336−328 Ma) intra-oceanic arc magmatism occurred within the Rheic Ocean north of the SCT. Accretion of all this material and continuous subduction beneath the SCT led to a two-stage metamorphism during the late Carboniferous (ca. 326−324 Ma and ca. 318 Ma) and synchronous generation of granitic (ca. 327−324) and dioritic (ca. 319−317 Ma) rocks of the Sarıcakaya Granitoid during the Variscan orogeny, terminating the life cycle of the Rheic Ocean.

Joint Modeling of Longitudinal and Survival Data

In medical studies, time-to-event outcomes such as time to death or relapse of a disease are routinely recorded along with longitudinal data that are observed intermittently during the follow-up period. For various reasons, marginal approaches to model the event time, corresponding to separate approaches for survival data/longitudinal data, tend to induce bias and lose efficiency. Instead, a joint modeling approach that brings the two types of data together can reduce or eliminate the bias and yield a more efficient estimation procedure. A well-established avenue for joint modeling is the joint likelihood approach that often produces semiparametric efficient estimators for the finite-dimensional parameter vectors in both models. Through a transformation survival model with an unspecified baseline hazard function, this review introduces joint modeling that accommodates both baseline covariates and time-varying covariates. The focus is on the major challenges faced by joint modeling and how they can be overcome. A review of available software implementations and a brief discussion of future directions of the field are also included.

Balancing the Interactions: Assessing Antiplatelet and Antiretroviral Therapy Drug-Drug Interactions in People Living with HIV.

The clinical effect of drug-drug interactions (DDIs) between antiplatelets and antiretrovirals (ART) on bleeding, thrombosis, and other major adverse cardiovascular events (MACE) is unknown. The objective of this retrospective study was to assess the incidence of DDI at P2Y12 inhibitor (P2Y12inh) initiation and the effect of DDI on patient outcomes. Adult people living with human immunodeficiency virus (PLWH; HIV) receiving ART newly initiated on an oral P2Y12inh were included. The primary outcome was the incidence of DDI between ART and P2Y12inh at P2Y12inh initiation. Secondary outcomes included bleeding events, MACE, and switches in P2Y12inh. There were 149 PLWH included, of these, 119 (80%) were initiated on clopidogrel, 23 (15%) on ticagrelor, and 7 (5%) on prasugrel. 93 PLWH (60%) had a DDI at time of P2Y12inh initiation, with highest incidence in the clopidogrel group (n=84, 71%), followed by ticagrelor (n=9, 39%) and none with prasugrel. Within 1 year, MACE occurred in 12 PLWH, with DDI present at the time of 4 events. There were 29 bleeding events occurring within 1 year, including 17 events with DDI at time of event. However, 88% of DDI in patients with bleeding events were expected to decrease the efficacy of P2Y12inh. Though we observed high incidence of DDI between P2Y12inh and ART in PLWH, MACE and bleeding events at 1 year did not correlate with DDI. It remains unknown if DDI presence at P2Y12inh initiation with ART causes clinical outcomes of concern, or if underlying platelet reactivity in PLWH is associated with these events.

Dry spells trigger durian flowering in aseasonal tropics.

The flowering period of durian is influenced by weather conditions such as prolonged drought and low temperatures. However, the specific criteria and durations of these conditions remain unclear. This study aimed to identify weather conditions that trigger durian flowering by monitoring its phenology and analyzing the relationship between minimum temperature and rainfall using two types of durian- grafting type and seed-grown type. Three flowering events were observed in 2022 and two in 2023. Considering there were no differences in the number or timing of flowering events among the two types, it suggests that genetic background differences do not influence flowering phenology. All flowering events were best explained using the 15-day moving average of rainfall, with the peak of the first flowering occurring approximately 50 days after the 15-day moving average of rainfall fell below 1mm. These results suggest that drought accumulation over approximately 15 days may trigger the induction of durian flower buds. However, no correlation was determined between the minimum temperature and the first flowering date. These findings indicate that durian flowering is induced by milder drought conditions than those previously proposed. Differences in variety and climate may have led to results different from those reported in earlier studies. Long-term monitoring across multiple sites and varieties is required to discuss these differences further.

Abstract 4143227: Incidence of Hemorrhagic Stroke in Hypertrophic Cardiomyopathy

Background: Individuals with hypertrophic cardiomyopathy (HCM) have an elevated risk of ischemic stroke, primarily driven by the increased risk of atrial fibrillation (AF) development in this patient population. This risk remains elevated regardless of CHADS2VASC score; thus, anticoagulation is recommended for all HCM patients with AF. Given the known association between anticoagulant medications and hemorrhagic events, there is likely an assumed risk of hemorrhagic stroke in these individuals. Currently, the incidence of hemorrhagic stroke in HCM and its relationship to AF and anticoagulation has not been well-established in the literature. The goal of this study was to establish the presence of and risk factors for hemorrhagic stroke in individuals with HCM. Methods: A retrospective review of all HCM patients ages 18 and older in our institution’s health system was performed from 2019-2023. ICD 10 codes were used to identify individuals with hemorrhagic stroke. Patient charts were reviewed for additional data including demographics, comorbid conditions, anticoagulant prescription, and other inciting factors prior to the hemorrhagic event. Results: The study cohort comprised 343 HCM patients, of which 47.1% were female and 72.7% were Caucasian. Concurrently, 30% (n=103) had a diagnosis of AF. The overall incidence of hemorrhagic stroke was 2.9% (5.8%, n=6 in those with AF vs 1.7%, n=4 in those without AF); furthermore, AF was associated with a non-statistically significant increased risk of hemorrhagic stroke (RR = 3.36, 95% CI 0.97-11.7). Anticoagulant use at the time of hemorrhagic event was observed in 4 individuals (67%) with AF and 1 individual (25%) without AF. Head trauma and falls were frequently observed as precipitating events prior to hospital admission for hemorrhagic stroke, occurring in 83% (n = 5) of patients with AF and 50% (n = 2) of those without AF. Conclusions: While ischemic stroke and anticoagulant use are commonly studied in those with HCM, the incidence of hemorrhagic stroke in this population is not negligible. Risk of hemorrhagic events in HCM appears largely influenced by anticoagulant use, particularly in those with concurrent AF, and by head trauma. Given the known benefits of anticoagulation on ischemic stroke risk in the HCM population, appropriate counseling and careful attention to individual patient factors may be warranted in the administration of anticoagulants.

Abstract 4143219: Pressure-Volume Analysis by Three-Dimensional Echocardiography: A Novel Method to Estimate Left Ventricular Efficiency

Background: Left ventricular (LV) efficiency is a key pathophysiological marker in heart failure (HF). LV pressure curve estimation and three-dimensional (3D) volumes via echocardiography allows for non-invasive pressure-volume (PV) analysis and calculation of an index of efficiency (Figure 1). Aim: Validate efficiency index by 3D echocardiography by comparing it to invasive measurements and efficiency derived from Positron Emission Tomography (PET) metabolism. Methods: Two experimental models were utilized - one with canines (n=21) and another with sheep (n=12). In canines, echocardiography provided 3D LV volumes and valve event timings. The pressure curve was estimated by adjusting the time axis of a reference pressure curve to the valve events and its amplitude to measured peak LV pressure, which in clinical practice would be approximated as systolic brachial cuff pressure. Invasive pressure was measured by micromanometer and volume by subendocardial piezoelectric crystals. Non-invasive and invasive efficiency indices, calculated as the ratio of stroke work to total mechanical energy (Figure 1), were compared during baseline, right ventricular pacing, aortic constriction and dobutamine infusion. Twelve sheep implanted with a pacemaker underwent 8 weeks of rapid dyssynchronous DDD pacing to induce dilated HF. LV efficiency index was calculated as in Figure 1, using measurements from a PV-catheter calibrated to end-diastolic volume by cardiac MRI, and compared to efficiency calculated as stroke work divided by total LV glucose metabolism via PET/CT. Recordings were performed during AAI and DDD pacing, at baseline (n=3) and following 8 weeks pacing-induced HF (n=12). Results: In canines, non-invasive and invasive efficiency indices showed excellent agreement (r=0.95, p<0.0001; mean difference 0.4%, SD 3.4%) (Figure 2). In sheep, the efficiency index showed similar decline compared to efficiency by PET/CT after induction of HF and after switching from AAI to DDD pacing (p<0.05 for all interventions). Overall correlation between the methods was moderate (r=0.67, p=0.0001) but excellent in animals with longitudinal data (r=0.89, p=0.0001) (Figure 3). Conclusions: Efficiency index by 3D echocardiography is accurate and reflects changes in efficiency measured by PET/CT. It may thus be of interest for clinical use.

Sequestration of gene products by decoys enhances precision in the timing of intracellular events

Expressed gene products often interact ubiquitously with binding sites at nucleic acids and macromolecular complexes, known as decoys. The binding of transcription factors (TFs) to decoys can be crucial in controlling the stochastic dynamics of gene expression. Here, we explore the impact of decoys on the timing of intracellular events, as captured by the time taken for the levels of a given TF to reach a critical threshold level, known as the first passage time (FPT). Although nonlinearity introduced by binding makes exact mathematical analysis challenging, employing suitable approximations and reformulating FPT in terms of an alternative variable, we analytically assess the impact of decoys. The stability of the decoy-bound TFs against degradation impacts FPT statistics crucially. Decoys reduce noise in FPT, and stable decoy-bound TFs offer greater timing precision with less expression cost than their unstable counterparts. Interestingly, when both bound and free TFs decay at the same rate, decoy binding does not directly alter FPT noise. We verify these results by performing exact stochastic simulations. These results have important implications for the precise temporal scheduling of events involved in the functioning of biomolecular clocks, development processes, cell-cycle control, and cell-size homeostasis.

Comprehensive phylogenomic analysis of Zika virus: Insights into its origin, past evolutionary dynamics, and global spread

BackgroundZika virus (ZIKV), a Flaviviridae family member, has been linked to severe neurological disorders. Despite detailed studies on recent outbreaks, the early evolutionary history of ZIKV remains partially unclear. This study elucidates ZIKV origin and evolutionary dynamics, focusing on recombination events, early lineage diversification, and virus spread across continents. MethodsWe assessed recombination using multiple methods. We conducted Bayesian phylogenetic analyses to understand the evolutionary relationships and timing of key diversification events. Model selection was carried out to determine the most appropriate evolutionary model for our dataset. ResultsOur phylogenies revealed recent recombination between Singaporean and African lineages, indicating the co-circulation of diverse lineages during outbreaks. Thailand was identified as a crucial hub in the spread across Asia. The phylogenetic analysis suggests that the ZIKV lineage dates back to the eleventh century, with the first significant diversification occurring in the nineteenth century. The timing of the re-introduction of the Asian lineage into Africa and the delay between probable introduction and outbreak onset were also determined. ConclusionsThis study provides novel insights into ZIKV's origin and early evolutionary dynamics, highlighting Thailand's role in the spread of the virus in Asia and recent recombination events between distant lineages. These findings emphasize the need for continuous surveillance and a better understanding of ZIKV biology to forecast and mitigate future outbreaks.

Prospective stability of memory for peritraumatic dissociation and anxiety: Replication and extension examining PTSD treatment modality and response.

Retrospective memory for peritraumatic reactions occurring during or immediately after trauma exposure may decrease in intensity for some over treatment. This may be due to psychotherapy-specific memory processes, such as repeated accessing of the trauma memory. Additionally, it may be that recovery drives changes in memory for these experiences. Critical to examining these hypotheses is an effective control treatment that reduces symptoms but does not directly involve repeated retrieval of the trauma memory, such as pharmacotherapy. In a sample of 200 individuals with posttraumatic stress disorder, retrospective memory for dissociation and anxiety occurring around the index traumatic event (Peritraumatic Dissociative Experiences Questionnaire, Marmar et al., 1997; Stanford Acute Stress Reaction Questionnaire, Cardeña et al., 2000) was assessed before and after treatment in a randomized clinical trial (NCT00127673) comparing prolonged exposure and sertraline. Participants reported that their memory for dissociation and anxiety at the time of the trauma was less intense at posttreatment (d = 0.26-0.64). There was no difference between prolonged exposure and sertraline on these memory indices. However, treatment responders, using a clinically meaningful change cutoff score, remembered their reactions at the time of the trauma as less dissociative (d = 0.66) and less anxious (d = 1.19) at posttreatment than nonresponders. Retrospective memory for the intensity of reactions experienced at the time of the traumatic event decreased from pre- to posttreatment, with effects most pronounced for those who made clinically meaningful gains in treatment. Inclusion of a nonpsychotherapy intervention control argues that recovery processes may explain these shifts and point to potential mood-dependent memory effects. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

ИЗМЕНЕНИЯ ПРОДОЛЖИТЕЛЬНОСТИ БЕЗЛЕДНОГО ПЕРИОДА ПО ДАННЫМ БЕРЕГОВЫХ НАБЛЮДЕНИЙ В КАРСКОМ МОРЕ

Based on observations for the timing of ice events at 12 coastal stations in the Kara Sea, the longterm means and trends are calculated for start dates, end dates and duration of ice-free period (IFP) for 1979–2020. The obtained results were compared with the calculations for the same IFP parameters based on passive microwave remote sensing data. An increase in the duration of the ice-free period is observed at 9 of the 12 stations considered. This happens both due to the shift of the start dates of the IFP (observed at 8 out of 12 stations) to earlier dates, and due to the shift of the end dates of the IFP to later dates (noted at 11 out of 12 stations). A comparison of long-term means and trends of the start, end dates and duration of the IFP between satellite data and coastal observations confirms that remotes sensing microwave data (sea ice concentration) can be used to analyze the interannual variability of IFP characteristics in the coastal zone of the Kara Sea. It is shown, that the results obtained using the proposed modified threshold method (MPM) are in a better agreement with the coastal observation data than the widely used threshold 15 % method.

Expected First Occurrence Time of Uncertain Future Events in One-Dimensional Linear Systems

The rapid advancement of machine learning algorithms has significantly enhanced tools for monitoring system health, making data-driven approaches predominant in Prognostics and Health Management (PHM). In contrast, model-based approaches have seen modest progress, as they are often constrained by the need for prior knowledge of specific governing equations, limiting their applicability to a wide range of problems. Recently, rigorous theoretical foundations have been established to extend dynamical systems theory by incorporating prognosis of uncertain events. This article leverages this formal framework to introduce and demonstrate a fundamental mathematical result for one-dimensional linear dynamical systems. The presented theorem offers an exact expression for calculating the expected time at which an event will first occur in the future. Unlike typical thresholds, this event is triggered by a hazard zone, defined as an uncertain event likelihood function over the system's state space. Applications of this theorem can be found in implementing real-time prognostic frameworks, where it is crucial to quickly estimate the magnitude of impending failures. Emphasis is placed on minimizing computational burden to facilitate prognostic decision-making.

Center of mass kinematic reconstruction during steady-state walking using optimized template models.

Template models, such as the Bipedal Spring-Loaded Inverted Pendulum and the Virtual Pivot Point, have been widely used as low-dimensional representations of the complex dynamics in legged locomotion. Despite their ability to qualitatively match human walking characteristics like M-shaped ground reaction force (GRF) profiles, they often exhibit discrepancies when compared to experimental data, notably in overestimating vertical center of mass (CoM) displacement and underestimating gait event timings (touchdown/ liftoff). This paper hypothesizes that the constant leg stiffness of these models explains the majority of these discrepancies. The study systematically investigates the impact of stiffness variations on the fidelity of model fittings to human data, where an optimization framework is employed to identify optimal leg stiffness trajectories. The study also quantifies the effects of stiffness variations on salient characteristics of human walking (GRF profiles and gait event timing). The optimization framework was applied to 24 subjects walking at 40% to 145% preferred walking speed (PWS). The findings reveal that despite only modifying ground forces in one direction, variable leg stiffness models exhibited a >80% reduction in CoM error across both the B-SLIP and VPP models, while also improving prediction of human GRF profiles. However, the accuracy of gait event timing did not consistently show improvement across all conditions. The resulting stiffness profiles mimic walking characteristics of ankle push-off during double support and reduced CoM vaulting during single support.

Species Diversity, Host Association, and Evolutionary History of Cronartium: An Important Global Fungal Pathogen to Trees.

Pine stem rust, the most damaging and widespread forest disease occurring in pine trees in the Northern Hemisphere, is primarily caused by Cronartium species (Pucciniales, Melampsorineae). While the phylogenetic relationships of major Cronartium species have been largely elucidated, there is limited understanding of their species diversity and the evolutionary processes shaping their distribution patterns. In this work, we performed broad sampling and sequencing of Cronartium taxa in China together with additional sequence data and other accessions in NCBI to investigate the diversification and to estimate the divergence time of major evolutionary events in this genus. Molecular dating analysis suggested that the divergence of the genus Cronartium probably was around 91.78 Ma during the Upper Cretaceous. It is believed that Cronartium species may have originated in Asia and North America, with intercontinental dispersals occurring primarily during the Middle Eocene, Middle Miocene, and Pliocene. These dispersal events likely took place through the North Atlantic Land Bridge, the De Geer Route, and the Bering Land Bridge, and subsequently diverged through sporadic dispersal and vicariance events. Furthermore, our analysis of host associations revealed that the diversification of Cronartium species was correlated with their telial-hosts, and some species may have experienced host jump events, indicating a complex interplay between host specificity and pathogen-host interaction during Cronartium evolution.

Greening‐Induced Biophysical Impacts Lead to Earlier Spring and Autumn Phenology in Temperate and Boreal Forests

AbstractTree phenology, the timing of periodic biological events in trees, is highly sensitive to climate change. Previous studies have indicated that forest greening can impact the local climate by modifying the seasonal surface energy budget. However, the understanding of tree phenological responses to forest greening at large spatial scales remains limited. Utilizing satellite‐derived phenological and leaf area index data spanning from 2001 to 2021, herein we show that forest greening led to earlier spring and autumn phenology in both temperate and boreal forests. Our findings demonstrated that forest greening during winter and spring contributed to a reduction in surface albedo, resulting in biophysical warming and consequently advancing spring leaf phenology. Conversely, forest greening in summer and autumn induced biophysical cooling through increased evapotranspiration, leading to an earlier onset of autumn leaf phenology. Our findings highlight the significant impact of forest greening‐induced local seasonal climate changes on shaping tree phenology in temperate and boreal forests. It is crucial to consider these greening‐induced alterations in microclimate conditions when modeling changes in tree phenology under future climate warming scenarios.

Asymptotic normality of a relative error functional regression estimator under left truncation and right censoring

. In this article, we introduce a non parametric regression estimator based on a relative error criterion, for left truncated and right censored data with functional predictors. Left truncation and right censoring are common forms of incomplete data in survival analysis, where the event time of interest is only observed within a certain interval which adds some challenges to the regression task. We establish the asymptotic normality of our estimator and develop a procedure for constructing confidence intervals for the predicted responses. The theoretical results obtained are supported using simulation studies and a real data example from the energy field.

Characterization, outcomes and time to event predictors of urinary tract infections acquired during post-acute stroke inpatient rehabilitation: A comprehensive cohort study

ObjectivesTo i) compare baseline clinical and demographic characteristics of post-acute stroke inpatients who were diagnosed with first-time urinary tract infection (UTI) vs inpatients who were not ii) compare rehabilitation outcomes between both groups and iii) examine associations between time to UTI event and risk factors. DesignRetrospective observational cohort study SettingInstitution for inpatient neurological rehabilitation. ParticipantsInpatients (n=1683) admitted within 3 months post-stroke to a rehabilitation facility between 2005 and 2023. InterventionsNot applicable. Main Outcome MeasuresFunctional Independence Measure (FIM), Functional Ambulation Categories (FAC) at admission. Cox proportional hazards models analyzed the association between UTI event timing and risk factors. ResultsOf the (n=1683) included patients, 196 (11.6%) experienced a UTI. In 32.1% of cases, the UTI occurred during the first week after admission to rehabilitation and 47.9% of UTIs occurred during the first two weeks. Median (IQR) time to UTI was 16 (5-37) days since admission. Most common germs were Escherichia coli (40.5%), Klebsiella pneumoniae (23.7%) and Pseudomonas aeruginosa (6.4%). Patients who acquired a UTI had older age, higher stroke severity, higher proportion of dysphagia, hypertension, neglect, bilateral affectation, atrial fibrillation, hemiplegia, lower levels of functional independence and lower FAC. We identified no differences in sex, type of stroke (ischemic or hemorrhagic), time to admission, aphasia, diabetes, dyslipidemia, chronic obstructive pulmonary disease, dominant side affected and educational level between both groups. Patients with UTI presented significantly poorer rehabilitation outcomes including lower discharge FIM and FAC, larger LOS, lower FIM efficiency and decreased FIM effectiveness.Multivariable Cox proportional hazards identified hypertension HR=1.60(1.13-2.27), admission FIM HR=0.98(0.97-0.99), admission BMI HR=0.96(0.93-0.99) and admitted with catheter HR= 1.80(1.22-2.64) as significant predictors of time to first UTI event (Concordance-index = 0.754). ConclusionsUTIs identification, characterization, and predictive factors can support post-acute stroke mitigation strategies to minimize UTI-related complications and optimize rehabilitation outcomes.

Carotid plaque thickness predicts cardiovascular events and death in patients with chronic kidney disease

BackgroundClassical risk scoring systems underestimate the risk of cardiovascular disease in chronic kidney disease (CKD). Coronary artery calcium score (CACS) has improved prediction of cardiovascular events in patients with CKD. The maximal carotid plaque thickness (cPTmax) measured in ultrasound scans of the carotid arteries has demonstrated similar predictive value as CACS in the general population. This is the first study to investigate whether cPTmax can predict cardiovascular events in CKD and to compare the predictive value of cPTmax and CACS in CKD.MethodTwo hundred patients with CKD stage 3 from the Copenhagen CKD Cohort underwent ultrasound scanning of the carotid arteries. The assessment consisted of locating plaque and measuring the thickest part of the plaque, cPTmax. Based on the distribution of cPTmax, the participants were divided into 3 groups: No plaques, cPTmax 1.0–1.9 mm and cPTmax > 1.9 mm (median cPTmax = 1.9 mm among patients with plaques). To measure CACS, 175 of the patients underwent a non-contrast CT scan of the coronary arteries. The follow-up time spanned between the ultrasound scan and a predefined end-date or the time of first event, defined as a composite of major cardiovascular events or death of any cause (MACE).ResultsThe median follow-up time was 5.4 years during which 45 patients (22.5%) developed MACE. In a Cox-regression adjusted for classical cardiovascular risk factors, patients with cPTmax > 1.9 mm had a significantly increased hazard ratio of MACE (HR 3.2, CI: 1.1–9.3), p = 0.031) compared to patients without plaques. C-statistics was used to evaluate models for predicting MACE. The improvement in C-statistics was similar for the two models including classical cardiovascular risk factors plus cPTmax (0.247, CI: 0.181–0.312) and CACS (0.243, CI: 0.172–0.315), respectively, when compared to a model only controlled for time since baseline (a Cox model with no covariates).ConclusionOur results indicate that cPTmax may be useful for predicting MACE in CKD. cPTmax and CACS showed similar ability to predict MACE.

Modeling the Bioenergetics and Life History Traits of Chironomus riparius–Consequences of Food Limitation

Chironomids have a number of characteristics that make them a useful group for investigating the impact of environmental and chemical stressors on their life cycle stages. It is crucial to first understand sensitivities to environmental factors and provide a basis for interpreting the results of toxicity tests. We focused on Chironomus riparius–one of the most studied species in aquatic toxicity tests—to understand the changes during the larval stage under conditions of food abundance and limitation. We developed a model based on Dynamic Energy Budget (DEB) theory, a framework to capture the entire life cycle of an individual under varying food and temperature conditions. Available information from this study and the literature pointed out that the first three larval instars are immature and the fourth larval instar is mature, during which the organism saves, in two phases, energy for essential processes occurring during the subsequent non-feeding stages. The model can successfully predict the observed prolonged fourth instar duration under food limitation, the times of life history events (e.g., pupation and emergence), and egg production. This model has the potential to be integrated with toxicokinetic–toxicodynamic models to study the effects of toxicants on a variety of biological traits.