bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal safety considerations for implantable micro-coil design
Authors: Whalen Andrew J , Fried Shelley I
Published: July 2023

Micro magnetic stimulation of the brain via implantable micro-coils is a promising novel technology for neuromodulation. Careful consideration of the thermodynamic profile of such devices is necessary for effective and safe designs. Objective. We seek to quantify the thermal profile of bent wire micro-coils in order to understand and mitigate thermal impacts of micro-coil stimulation. Approach. In this study, we use fine wire thermocouples and COMSOL finite element modeling to examine the profile of the thermal gradients generated near bent wire micro-coils submerged in a water bath during stimulation. We tested a range of stimulation parameters previously reported in the literature such as voltage amplitude, stimulus frequency, stimulus repetition rate and coil wire materials. Main results. We found temperature increases ranging from <1 °C to 8.4 °C depending upon the stimulation parameters tested and coil wire materials used. Numerical modeling of the thermodynamics identified hot spots of the highest temperatures along the micro-coil contributing to the thermal gradients and demonstrated that these thermal gradients can be mitigated by the choice of wire conductor material and construction geometry. Significance. ISO standard 14708-1 designates a thermal safety limit of 2 °C temperature increase for active implantable medical devices. By switching the coil wire material from platinum/iridium to gold, our study achieved a 5–6-fold decrease in the thermal impact of coil stimulation. The thermal gradients generated from the gold wire coil were measured below the 2 °C safety limit for all stimulation parameters tested.
Suitable Cutoff Value of Aldosterone to Renin Concentration Ratio Measured by Chemiluminescence for Screening Primary Aldosteronism Among Hypertensive Population in Sichuan
Authors: Tang Jia , Chen Tao , Tan Lu , Xu Jing , Xu Chen-xiao , Huang Lu , Tian Hao-ming , Ren Yan
Published: July 2023

Background

To explore the suitable cutoff value of aldosterone to renin concentration ratio (ARR) detected by chemiluminescence immunoassay for primary aldosteronism (PA) screening among hypertensive population in Sichuan, China.

Methods

423 hypertensive patients screened for PA in Department of Endocrinology and Metabolism of West China Hospital of Sichuan University from October 2020 to May 2022 were included in this study. Blood samples were collected 2 hours after the patients were in an upright position. Chemiluminescence was used to measure the concentrations of aldosterone and renin. Receiver operating characteristic curve was used to determine the optimal cutoff value of ARR.

Results

The 423 patients with hypertension included 199 PA and 224 essential hypertension. Youden index was the highest when the upright ARR was 2.4 (ng/dl)/(mU/l), and the sensitivity and specificity for PA were 95.5% and 94.2%, respectively. The most suitable upright ARR cutoff values for male and female were 2.0 and 2.4 (ng/dl)/(mU/l), and the sensitivity were 96.5%, 95.6%, the specificity was 95.3%, 91.5%, respectively. The most suitable cutoff values of upright ARR in the ≤40, >40 to <60, and ≥60-year-old patients with hypertension were 1.4, 2.3, and 2.7 (ng/dl)/(mU/l), respectively.

Conclusions

The suitable upright ARR cutoff value may be 2.4 (ng/dl)/(mU/l) for PA among hypertensive population in Sichuan. In male, the suitable cutoff value of ARR is lower than female. The cutoff value of ARR is increased with age.
The Importance of the Morel Emotional Numbing Test Instructions: A Diagnosis Threat Induction Study
Authors: Williamson Emily S , Arentsen Timothy J , Roper Brad L , Pedersen Heather A , Shultz Laura A , Crouse Ellen M
Published: July 2023

Objective

Marketed as a validity test that detects feigning of posttraumatic stress disorder (PTSD), the Morel Emotional Numbing Test for PTSD (MENT) instructs examinees that PTSD may negatively affect performance on the measure. This study explored the potential that MENT performance depends on inclusion of “PTSD” in its instructions and the nature of the MENT as a performance validity versus a symptom validity test (PVT/SVT).

Method

358 participants completed the MENT as a part of a clinical neuropsychological evaluation. Participants were either administered the MENT with the standard instructions (SIs) that referenced “PTSD” or revised instructions (RIs) that did not. Others were administered instructions that referenced “ADHD” rather than PTSD (AI). Comparisons were conducted on those who presented with concerns for potential traumatic-stress related symptoms (SI vs. RI-1) or attention deficit (AI vs. RI-2).

Results

Participants in either the SI or AI condition produced more MENT errors than those in their respective RI conditions. The relationship between MENT errors and other S/PVTs was significantly stronger in the SI: RI-1 comparison, such that errors correlated with self-reported trauma-related symptoms in the SI but not RI-1 condition. MENT failure also predicted PVT failure at nearly four times the rate of SVT failure.

Conclusions

Findings suggest that the MENT relies on overt reference to PTSD in its instructions, which is linked to the growing body of literature on “diagnosis threat” effects. The MENT may be considered a measure of suggestibility. Ethical considerations are discussed, as are the construct(s) measured by PVTs versus SVTs.
Travelling in style to AGU
Authors: Patterson Cameron
Published: July 2023

Cameron Patterson expands on the latest plans for his upcoming train odyssey to AGU
Egg mimicry, not the sight of a common cuckoo, is the cue for parasitic egg rejection
Authors: Štětková Gabriela , Šulc Michal , Jelínek Václav , Hughes Anna , Honza Marcel
Published: July 2023

Many studies have found that if hosts observe a brood parasite at their nest, they use it as a cue to reject parasitic eggs. However, most previous work has simulated brood parasitic events by exposing a stuffed parasite near a host’s nest. Responses to the presence of a real parasite have not yet been adequately studied under natural conditions. We therefore investigated whether great reed warblers (Acrocephalus arundinaceus) are more likely to reject a parasitic egg if they see a parasitizing common cuckoo (Cuculus canorus) at their nest than if the parasite approaches the host nest unnoticed. Using video recordings of 70 nests, we showed that spotting a cuckoo at the nest did not increase the rejection rate of parasitic eggs, even if hosts saw the cuckoo repeatedly. Hosts instead used the level of mimicry in the background color for cuckoo egg rejection. Since not every visit by the cuckoo leads to parasitism, seeing the brood parasite may not be a reliable enough cue for the host. Therefore, our results suggest that the sight of a cuckoo at the nest may not have as severe consequences for it as previously thought.
Intracellular gene transfer and codon usage of cytoplasmic genomes in green plants
Authors: Zhang Ting-Ting , Zhang Yang-Yan , Wang Xiao-Ling , Zhang Chen-Qi , Shi Wen-Hua , Fu Ai-Gen , Fang Min-Feng , Zhang Xiao , Li Zhong-Hu
Published: July 2023

Intracellular gene transfer is widely recognized as one of the most important driving forces for species evolution. Here we investigated transferred cytoplasmic motifs in green plants including spore-bearing plants and seed-bearing plants (hereafter termed spore plants and seed plants) . Our analyses revealed that gene transfer in spore plants was characterized by shorter motifs than that of seed plants. Several spore species did not exhibit intracellular gene transfer. Meanwhile, high frequency transferred tRNA genes were identified with average values of minimum free energy at moderate level. From the chloroplast to the mitochondrial genome, trnP was found to have transferred with high frequency in green plants. In gene transfer from the mitochondrial to the chloroplast genome, trnN was found to be a highly transferred gene. We observed that several tRNA genes including trnF, trnW, and trnN were involved in bidirectional transfer, which may be related to application strategy of functional protein-coding genes in a plant’s adaptive evolution. Codon Adaptation Index (CAI) analysis showed that codon usage was unbalanced in spore and seed plants. CAI values for seed plants were higher than those for spore plants in general, which may reveal rapid divergence adaptability of codon usage in the former. These results provide novel insights into gene transfer and codon usage within cytoplasmic genomes.
Same, same … but different!
Authors: Lewis Simon J G
Published: July 2023

This scientific commentary refers to ‘Severe cholinergic terminal loss in newly diagnosed dementia with Lewy bodies’ by Okkels et al. (https://doi.org/10.1093/brain/awad192).
Distinct neuroinflammatory signatures exist across genetic and sporadic amyotrophic lateral sclerosis cohorts
Authors: Rifai Olivia M , O’Shaughnessy Judi , Dando Owen R , Munro Alison F , Sewell Michael D E , Abrahams Sharon , Waldron Fergal M , Sibley Christopher R , Gregory Jenna M
Published: July 2023

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of upper and lower motor neurons. ALS is on a pathogenetic disease spectrum with frontotemporal dementia, referred to as ALS-frontotemporal spectrum disorder (ALS-FTSD). For mutations associated with ALS-FTSD, such as the C9orf72 hexanucleotide repeat expansion, the molecular factors associated with heterogeneity along this spectrum require further characterization.

Here, using a targeted NanoString molecular barcoding approach, we interrogate neuroinflammatory dysregulation and heterogeneity at the level of gene expression in post-mortem motor cortex tissue from a cohort of clinically heterogeneous C9-ALS-FTSD cases.

We identified 20 dysregulated genes in C9-ALS-FTSD, with enrichment of microglial and inflammatory response gene sets. Two genes with significant correlations to available clinical metrics were selected for validation: FKBP5, a correlate of cognitive function, and brain-derived neurotrophic factor (BDNF), a correlate of disease duration. FKBP5 and its signalling partner, NF-κB, appeared to have a cell type-specific staining distribution, with activated (i.e. nuclear) NF-κB immunoreactivity in C9-ALS-FTSD. Expression of BDNF, a correlate of disease duration, was confirmed to be higher in individuals with long compared to short disease duration using BaseScope™ in situ hybridization. Our analyses also revealed two distinct neuroinflammatory panel signatures (NPS), NPS1 and NPS2, delineated by the direction of expression of proinflammatory, axonal transport and synaptic signalling pathways. We compared NPS between C9-ALS-FTSD cases and those from sporadic ALS and SOD1-ALS cohorts and identified NPS1 and NPS2 across all cohorts. Moreover, a subset of NPS was also able to separate publicly available RNA sequencing data from independent C9-ALS and sporadic ALS cohorts into two inflammatory subgroups.

Importantly, NPS subgroups did not clearly segregate with available demographic, genetic, clinical or pathological features, highlighting the value of molecular stratification in clinical trials for inflammatory subgroup identification. Our findings thus underscore the importance of tailoring therapeutic approaches based on distinct molecular signatures that exist between and within ALS-FTSD cohorts.
Superior Accuracy of Aspergillus Plasma Cell-Free DNA Polymerase Chain Reaction Over Serum Galactomannan for the Diagnosis of Invasive Aspergillosis
Authors: Mah Jordan , Nicholas Veronica , Tayyar Ralph , Moreno Angel , Murugesan Kanagavel , Budvytiene Indre , Banaei Niaz
Published: July 2023

Background

Invasive aspergillosis (IA) in immunocompromised hosts carries high morbidity and mortality. Diagnosis is often delayed because definitive diagnosis requires invasive specimen collection, while noninvasive testing with galactomannan is moderately accurate. Plasma cell-free DNA polymerase chain reaction (cfDNA PCR) represents a novel testing modality for the noninvasive diagnosis of invasive fungal disease (IFD). We directly compared the performance of Aspergillus plasma cfDNA PCR with serum galactomannan for the diagnosis of IA during routine clinical practice.

Methods

We conducted a retrospective study of all patients with suspected IFD who had Aspergillus plasma cfDNA PCR testing at Stanford Health Care from 1 September 2020 to 30 October 2022. Patients were categorized into proven, probable, possible, and no IA based on the EORTC/MSG definitions. Primary outcomes included the clinical sensitivity and specificity for Aspergillus plasma cfDNA PCR and galactomannan.

Results

Overall, 238 unique patients with Aspergillus plasma cfDNA PCR test results, including 63 positives and 175 nonconsecutive negatives, were included in this study. The majority were immunosuppressed (89.9%) with 22.3% 30-day all-cause mortality. The overall sensitivity and specificity of Aspergillus plasma cfDNA PCR were 86.0% (37 of 43; 95% confidence interval [CI], 72.7–95.7) and 93.1% (121 of 130; 95% CI, 87.4–96.3), respectively. The sensitivity and specificity of serum galactomannan in hematologic malignancies/stem cell transplants were 67.9% (19 of 28; 95% CI, 49.3–82.1) and 89.8% (53 of 59; 95% CI, 79.5–95.3), respectively. The sensitivity of cfDNA PCR was 93.0% (40 of 43; 95% CI, 80.9–98.5) in patients with a new diagnosis of IA.

Conclusions

Aspergillus plasma cfDNA PCR represents a more sensitive alternative to serum galactomannan for noninvasive diagnosis of IA.
Extracting IP parameters of rock samples using machine learning
Authors: He Ziang , Cai Hongzhu , Li Shuai , Xian Jinchi , Hu Xiangyun
Published: July 2023

The induced polarization (IP) phenomenon describes the variation of resistivity with frequency and this geophysical method has been widely used to classify rock properties. Various experimental models have been developed to describe the mechanism of IP effect. The model based on the generalized effective-medium theory of induced polarization (GEMTIP) is an extension of the classic Cole–Cole model by considering electromagnetic inductions. Compared to the Cole–Cole model, the GEMTIP model can effectively incorporate rock composition and morphology to provide a more precise complex resistivity response. However, adding one more grain type to the GEMTIP model will result in adding three more parameters to the inversion process. Even for the GEMTIP model with only three-phase spherical grains, seven parameters need to be inverted. In general, the inversion of GEMTIP model with more than three phases is characterized by high uncertainty. Traditional geophysical inversion methods such as global optimization and least-squares optimization have certain limitations in inverting IP parameters. The effectiveness of least-squares optimization algorithm depends on the setting of initial inversion parameters. Efficiently processing massive amounts of data is challenging for both least-squares optimization and global optimization algorithms. Considering the powerful search and generalization capabilities of neural network (NN), we develop a machine learning (ML) approach for efficient inversion of IP parameters based on long short-term memory (LSTM) networks with physical constraints. Compared with traditional methods, ML method can significantly reduce the computational cost and produce reliable inversion results. To validate the effectiveness of ML approach, we first conduct multiple synthetic model studies based on the Cole–Cole and the GEMTIP models, respectively. We then further demonstrate the effectiveness of NNs in recovering IP parameters from rock samples using measured data from man-made and field rock samples. The results show that the developed method can effectively obtain accurate inversion results based on Cole–Cole and GEMTIP models.
Context matters—the phased development of an adaptable food literacy intervention: Up for Cooking
Authors: Harms Lisa S E , van Assema Patricia , Gubbels Jessica S , Gerards Sanne M P L , Linssen Evelyne , Vonken Lieve , Bessems Kathelijne M H H
Published: July 2023

Adapting interventions to the context increases the impact and sustainability of interventions. Literature acknowledges the need to adapt existing interventions and that these adaptations should be clearly reported. However, little is known about how to incorporate adaptation from the beginning. This paper argues that interventions should be developed and adaptations should be made using an ongoing non-linear approach. An action-oriented research approach with feedback loops is proposed. We illustrate this with the development of a food literacy intervention ‘Up for Cooking’ (Dutch: Zin in Koken) and present lessons learned in developing, implementing and studying such adaptable interventions. Interventions should clearly define and differentiate the intervention function and form. Implementers, in turn, should be encouraged to tailor interventions within a form that fits with a specific context. Sufficient time, continuous adaptation based on co-creation, feedback loops and interdisciplinary collaboration are important prerequisites for the development of adaptable interventions.
A mixed-method study of perceptions of cigarette pack inserts among adult smokers from New York and South Carolina exposed as part of a randomized controlled trial
Authors: Hackworth Emily E , Budiongan Julia R , Lambert Victoria C , Kim Minji , Ferguson Stuart G , Niederdeppe Jeff , Hardin James , Thrasher James F
Published: July 2023

While many countries require prominent pictorial health warning labels (PHWLs) on the outside of cigarette packs to communicate the harms of smoking, there is evidence that cigarette pack inserts that contain efficacy messages may enhance the effectiveness of PHWLs. The US Food and Drug Administration (FDA) has regulatory authority to communicate with smokers through inserts. While current labeling regulations do not require inclusion of inserts, the FDA could implement them in the future. This study assesses US smokers’ perceptions of cigarette package inserts at the conclusion of a two-week randomized trial on cigarette labeling where half of participants were exposed to insert messages (two response-efficacy messages and two self-efficacy messages) in their packs. Participants (n = 359) completed a 30- to 60-min interview with both quantitative and qualitative assessments, including measures of recall and perceived message effectiveness (PME) for specific inserts. Correlates of recall and PME were estimated using mixed-effects regression models. Qualitative responses to PME items were analyzed using thematic analysis. Response-efficacy messages had higher PME and recall than self-efficacy messages. People had diverse responses to the inserts, including that they were positive, thought-provoking, and helpful. Reactions to and perceptions of the inserts indicate potential benefits of integrating efficacy messages into labeling policies.
Identifiability of causal effects in test-negative design studies
Authors: Shrier Ian , Stovitz Steven D , Textor Johannes
Published: July 2023

Causal directed acyclic graphs (DAGs) are often used to select variables in a regression model to identify causal effects. Outcome-based sampling studies, such as the ‘test-negative design’ used to assess vaccine effectiveness, present unique challenges that are not addressed by the common back-door criterion. Here we discuss intuitive, graphical approaches to explain why the common back-door criterion cannot be used for identification of population average causal effects with outcome-based sampling studies. We also describe graphical rules that can be used instead in outcome-based sampling studies when the objective is limited to determining if the causal odds ratio is identifiable, and illustrate recent changes to the free online software Dagitty which incorporate these principles.
L
2 norm error estimates of BDF methods up to fifth-order for the phase field crystal model
Authors: Liao Hong-lin , Kang Yuanyuan
Published: July 2023

The well-known backward difference formula (BDF) of the third, the fourth and the fifth orders are investigated for time integration of the phase field crystal model. By building up novel discrete gradient structures of the BDF-$\textrm{k}$ ($\textrm{k}=3,4,5$) formulas, we establish energy dissipation laws at the discrete levels and then obtain a priori solution estimates for the associated numerical schemes; however, we can not build any discrete energy dissipation law for the corresponding BDF-6 scheme because the BDF-6 formula itself does not have any discrete gradient structures. With the help of the discrete orthogonal convolution kernels and Young-type convolution inequalities, some concise $L^{2}$ norm error estimates (with respect to the starting data in the $L^{2}$ norm) are established via the discrete energy technique. To the best of our knowledge, this is the first time such type $L^{2}$ norm error estimates of non-A-stable BDF schemes are obtained for nonlinear parabolic equations. Numerical examples are presented to verify and support the theoretical analysis.
Integral Points on Varieties With Infinite Étale Fundamental Group
Authors: Achenjang Niven T , Morrow Jackson S
Published: July 2023

We study integral points on varieties with infinite étale fundamental groups. More precisely, for a number field $F$ and $X/F$ a smooth projective variety, we prove that for any geometrically Galois cover $\varphi \colon Y \to X$ of degree at least $2\dim (X)^{2}$, there exists an ample line bundle $\mathscr{L}$ on $Y$ such that for a general member $D$ of the complete linear system $|\mathscr{L}|$, $D$ is geometrically irreducible and any set of $\varphi (D)$-integral points on $X$ is finite. We apply this result to varieties with infinite étale fundamental group to give new examples of irreducible, ample divisors on varieties for which finiteness of integral points is provable.
Dynamic modelling predicts lactate and IL-1β as interventional targets in metabolic-inflammation-clock regulatory loop in glioma
Authors: Sharma Shalini , Gowda Pruthvi , Lathoria Kirti , Mitra Mithun K , Sen Ellora
Published: July 2023

In an attempt to understand the role of dysregulated circadian rhythm in glioma, our recent findings highlighted the existence of a feed-forward loop between tumour metabolite lactate, pro-inflammatory cytokine IL-1β and circadian CLOCK. To further elucidate the implication of this complex interplay, we developed a mathematical model that quantitatively describes this lactate dehydrogenase A (LDHA)-IL-1β-CLOCK/BMAL1 circuit and predicts potential therapeutic targets. The model was calibrated on quantitative western blotting data in two glioma cell lines in response to either lactate inhibition or IL-1β stimulation. The calibrated model described the experimental data well and most of the parameters were identifiable, thus the model was predictive. Sensitivity analysis identified IL-1β and LDHA as potential intervention points. Mathematical models described here can be useful to understand the complex interrelationship between metabolism, inflammation and circadian rhythm, and in designing effective therapeutic strategies. Our findings underscore the importance of including the circadian clock when developing pharmacological approaches that target aberrant tumour metabolism and inflammation.

Insight box  The complex interplay of metabolism-inflammation-circadian rhythm in tumours is not well understood. Our recent findings provided evidence of a feed-forward loop between tumour metabolite lactate, pro-inflammatory cytokine IL-1β and circadian CLOCK/BMAL1 in glioma. To elucidate the implication of this complex interplay, we developed a mathematical model that quantitatively describes this LDHA-IL-1β-CLOCK/BMAL1 circuit and integrates experimental data to predict potential therapeutic targets. The study employed a multi-start optimization strategy and profile likelihood estimations for parameter estimation and assessing identifiability. The simulations are in reasonable agreement with the experimental data. Sensitivity analysis found LDHA and IL-1β as potential therapeutic points. Mathematical models described here can provide insights to understand the complex interrelationship between metabolism, inflammation and circadian rhythm, and in identifying effective therapeutic targets.
Trend, prevalence and predictors of successful vaginal birth after caesarean section in Ethiopia: a systematic review and meta-analysis
Authors: Balis Bikila , Bekele Habtamu , Hunde Aboma Diriba , Abdisa Lemesa , Lami Magarsa
Published: July 2023

Background

Vaginal birth after caesarean section (VBAC) is an alternative to a caesarean section (CS) in the absence of repeat or new indications for primary CS. There is a knowledge gap regarding the trend and successful VBAC in Ethiopia. Therefore this systematic review and meta-analysis aimed to assess the trend, pooled prevalence of successful VBAC and its predictors in Ethiopia.

Methods

Electronic databases (SCOPUS, CINAHL, Embase, PubMed and Web of Science), Google Scholar and lists of references were used to search works of literature in Ethiopia. Stata version 14 was used for analysis and the odds ratios of the outcome variable were determined using the random effects model. Heterogeneity among the studies was assessed by computing values for I2 and p-values. Also, sensitivity analyses and funnel plots were done to assess the stability of pooled values to outliers and publication bias, respectively.

Results

A total of 12 studies with a sample size of 2080 were included in this study. The overall success rate of VBAC was 52% (95% confidence interval 42 to 65). Cervical dilatation ≥4 cm at admission, having a prior successful vaginal delivery and VBAC were the predictors of successful VBAC.

Conclusions

Meta-analyses and sensitivity analyses showed the stability of the pooled odds ratios and the funnel plots did not show publication bias. The pooled prevalence of successful VBAC was relatively low compared with existing evidence. However, the rate was increasing over the last 3 decades, which implies it needs more strengthening and focus to decrease maternal morbidity and mortality by CS complications. Promoting VBAC by emphasizing factors favourable for its success during counselling mothers who previously delivered by CS to enhance the prevalence of VBAC.
Buttons, Devices, and Adults: How Preschool Children Designed an IoT Programming Tool
Authors: Silva Neto Benedito , Rodriguez Carla , Neris Vania
Published: July 2023

Preschool children may interact with the Internet of Things (IoT) devices and program the behavior of these products. However, not much is known about the children’s ideas for a software programming tool. This research aimed at investigating how children aged from 4 to 6 years perceive the programming of IoT devices and, from practice with them, build a prototype of a programming environment for them. To this end, three Participatory Design techniques were adapted and applied to (and with) 30 children. A final prototype was built and its usability was assessed with the participation of six children. Photos and videos collected during the empirical assessment were later analysed using the Content Analysis Method. During the design, children relied on buttons and explicitly represented the IoT devices and adults in the user interfaces. They also adopted a top-down approach to programming IoT devices. Lessons learned for the design of these solutions are discussed.
Making the case for precision dosing: visualizing the variability of cefepime exposures in critically ill adults
Authors: Chang Jack , Liu Jiajun , Alshaer Mohammad H , Venugopalan Veena , Maranchick Nicole , Peloquin Charles A , Rhodes Nathaniel J , Scheetz Marc H
Published: July 2023

Objective

To investigate and describe the variability in cefepime exposures among ‘real-world’, critically ill patients by using population pharmacokinetic modelling and simulations, and with translation of these findings to visualizations.

Methods

A cohort of adult medical ICU patients who received cefepime with therapeutic drug monitoring was studied. Two compartment models were developed to estimate cefepime clearance (Model 1) and simulate cefepime exposures among 1000 patients, each with identical creatinine clearance of 60 mL/min and receiving a regimen of cefepime 1 gram IV over 30 minutes, every 8 hours (Model 2). Variability in the relationship between cefepime clearance and creatinine clearance (CrCL) was visualized, and a random, representative sample of 10 simulated patients was utilized to illustrate variability in cefepime exposures.

Results

A total of 75 adult medical ICU patients (52% female) and 98 serum cefepime samples were included in the study. Population parameter estimates for cefepime displayed a wide range of variation in Model 1 (CV: 45% to 95%), with low bias at the individual level at 0.226 mg/L but high bias in the population model 10.6 mg/L. Model 2 displayed similar fits, demonstrating that correcting for individual patient creatinine clearance slightly improves the bias of the population model (bias = 4.31 mg/L). Among 10 simulated patients that a clinician would deem similar from a dosing perspective (i.e. equivalent creatinine clearance), maximum concentrations after three simulated doses varied more than 8-fold from 41.2 to 339 mg/L at the 5th and 95th percentiles, and clearance profiles were highly different.

Conclusion

Creatinine clearance estimates alone are inadequate for predicting cefepime exposures. Wide variations in cefepime exposure exist among ICU patients, even for those with similar kidney function estimates. Current population adjustment schemes based solely on creatinine clearance will result in unintended high and low exposures leading to safety and efficacy concerns, respectively.
Augmented Renal Function in Burn Patients: Occurrence and Discordance With Commonly Used Methods to Assess Renal Function
Authors: Mueller Scott W , Blass Brittany , Molina Kyle C , Gibson Cameron , Krsak Martin , Kohler Amber D , Deeter Lyndsay , Stalilonis Jennifer , Wiktor Arek J
Published: July 2023

Augmented renal clearance (ARC) is defined by supraphysiologic renal function and is associated with drug failure due to subtherapeutic drug exposure. Burn patients are cited as being at high risk for ARC, yet rates of ARC have not been well described. This retrospective study described the prevalence and incidence of ARC, and compared 12-hour urine collection values (CrCl-12) vs. common estimates of renal function in assessed patients at an American Burn Association-verified burn center. All thermally injured burn patients with a CrCl-12 result were included. ARC was defined as a CrCl-12 >130 ml/min. Cockcroft-Gault, modification of diet in renal disease (MDRD), and CKD-EPI-2021 estimates were calculated. Over 13 months, 163 CrCl-12 results were collected in 68 patients at a median of 9 days from admission with an average value of 160 ml/min. The median total body surface area (total body surface area [TBSA]%) was 17.25%. ARC prevalence was 70.6% with an incidence of 66.3% in all CrCl-12 assessments. Those with ARC were less likely to have heart failure, P = .007. Age, TBSA%, and trauma were not different between those with or without ARC. ARC incidences in those with TBSAs of ≥20%, <20%, or <10%, were 70.5%, 58.6%, and 76.7%, respectively. Agreement of Cockcroft-Gault, MDRD, and CKD-EPI-2021 to CrCl-12 was moderate to weak and frequently failed to identify ARC. ARC is common in burn patients, regardless of TBSA%. Widely accepted estimations of renal function may be incorrect resulting in under-dosing of medications. Additional research is required to identify burn patients at greatest risk for ARC and subsequent dosing strategies to maintain pharmacologic efficacy without unduetoxicity.
On the gamma-ray emission from the core of the Sagittarius dwarf galaxy
Authors: Evans Addy J , Strigari Louis E , Svenborn Oskar , Albert Andrea , Harding J Patrick , Hooper Dan , Linden Tim , Pace Andrew B
Published: July 2023

We use Fermi-LAT data to analyse the faint gamma-ray source located at the centre of the Sagittarius (Sgr) dwarf spheroidal galaxy. In the 4FGL-DR3 catalogue, this source is associated with the globular cluster, M54. We investigate the spectral energy distribution and spatial extension of this source, with the goal of testing two hypotheses: (1) the emission is due to millisecond pulsars within M54, or (2) the emission is due to annihilating dark matter from the Sgr halo. For the pulsar interpretation, we consider a two-component model which describes both the lower-energy magnetospheric emission and possible high-energy emission arising from inverse Compton scattering. We find that this source has a point-like morphology at low energies, consistent with magnetospheric emission, and find no evidence for a higher-energy component. For the dark matter interpretation, we find the signal favours a dark matter mass of mχ = 29.6 ± 5.8 GeV and an annihilation cross section of $\sigma v = (2.1 \pm 0.59) \times 10^{-26} \, \text{cm}^3$ s−1 for the $b \bar{b}$ channel (or mχ = 8.3 ± 3.8 GeV and $\sigma v = (0.90 \pm 0.25) \times 10^{-26} \, \text{cm}^3$ s−1 for the τ+τ− channel), when adopting a J-factor of $J=10^{19.6} \, \text{GeV}^2 \, \text{cm}^{-5}$. This parameter space is consistent with gamma-ray constraints from other dwarf galaxies and with dark matter interpretations of the Galactic Centre Gamma-Ray Excess.
The effect of tidal forces on the Jeans instability criterion in star-forming regions
Authors: Zavala-Molina Rafael , Ballesteros-Paredes Javier , Gazol Adriana , Palau Aina
Published: July 2023

Recent works have proposed the idea of a tidal screening scenario, in which gravitationally unstable fragments in the vicinity of a protostar will compete for the gas reservoir in a star-forming clump. In this contribution, we propose to properly include the action of an external gravitational potential in the Jeans linear instability analysis as proposed by Jog. We found that an external gravitational potential can reduce the critical mass required for the perturbation to collapse if the tidal forces are compressive or increase it if the tidal forces are disruptive. Our treatment provides (a) new mass and length collapse conditions; (b) a simple equation for observers to check whether their observed fragments can collapse; and (c) a simple equation to compute whether collapse-induced turbulence can produce the levels of observed fragmentation. Our results suggest that, given envelopes with similar mass and density, the flatter ones should produce more stars than the steeper ones. If the density profile is a power law, the corresponding power-law index separating these two regimes should be about 1.5. We finally applied our formalism to 160 fragments identified within 18 massive star-forming cores of previous works. We found that considering tides, 49 per cent of the sample may be gravitationally unstable and that it is unlikely that turbulence acting at the moment of collapse has produced the fragmentation of these cores. Instead, these fragments should have formed earlier when the parent core was substantially flatter.
Accreting black holes skewing and bending the optical emission from massive Wolf–Rayet companions – a case study of IC10 X-1
Authors: Bhattacharya Sayantan , Christodoulou Dimitris M , Chene André-Nicolas , Laycock Silas G T , Binder Breanna A , Kazanas Demosthenes
Published: July 2023

We present a statistical analysis of the He ii 4686 emission line in the spectra of the black hole and Wolf–Rayet (WR) star of the high-mass X-ray binary IC10 X-1. This line is visibly skewed, and the third moment (skewness) varies with the binary’s orbital phase. We describe a new method of extracting such weak/faint features lying barely above a noisy continuum. Using the moments of these features, we have been able to decompose these skewed lines into two symmetric Gaussian profiles as a function of the orbital phase. The astrophysical implications of this decomposition are significant due to the complex nature of wind–accretion stream interactions in such binary systems. Previous studies have already shown a 0.25 phase lag in the radial velocity curve of the star and the X-ray eclipse, which indicates that the He ii emitters might be in the stellar wind, hence not tracing the star’s orbital motion. Results from this work further suggest the existence of two separate emitting regions, one in the stellar wind in the shadow of the WR star and another in the accretion stream that impacts the black hole’s outer accretion disc; and the observed skewed He ii lines can be reproduced by superposition of the two corresponding time-dependent Gaussian emission profiles.
Hydrogen addition reactions of a three-membered ring in the solid state: c-C3H2O
Authors: Ibrahim Mohamad , Guillemin Jean-Claude , Krim Lahouari
Published: July 2023

Due to the relatively high abundance of hydrogen radicals in the interstellar medium, the H-addition reaction of unsaturated organic molecules in the solid phase and at very low temperatures is considered to play an important role in the chemical complexity of organic substances in the Universe. However, when interacting with hydrogen atoms, all unsaturated functional groups that may be present in several organic species exhibit different behaviours that can significantly alter the reaction pathways from one species to another. By coupling FTIR spectroscopy and temperature programmed desorption mass spectrometry, we have investigated the H + c-C3H2O (cyclopropenone) solid-state reaction using two different experimental methods. We show that cyclopropenone reacts with hydrogen atoms under interstellar medium conditions, leading to propynal (HCCCHO), propadienone (CH2CCO), and two thermodynamically most stable isomers of c-C3H2O. In excess of H atoms, the hydrogenation of cyclopropenone also leads to propenal (CH2CHCHO), propanal (CH3CH2CHO), c-C3H4O (cyclopropanone), in addition to two alcohols, namely cyclopropanol (c-C3H6O) and propanol (CH3CH2CH2OH).
Formation of H2 on polycyclic aromatic hydrocarbons under conditions of the ISM: an ab initio molecular dynamics study
Authors: Barrera Nicolás F , Fuentealba Patricio , Muñoz Francisco , Gómez Tatiana , Cárdenas Carlos
Published: July 2023

Understanding how the H2 molecule is formed under the chemical conditions of the interstellar medium (ISM) is critical to the whole chemistry of it. Formation of H2 in the ISM requires a third body acting as a reservoir of energy. Polycyclic aromatic hydrocarbons (PAHs) are excellent candidates to play that role. In this work, we simulated the collisions of hydrogen atoms with coronene to form H2 via the Eley–Rideal mechanism. To do so, we used Born–Oppenheimer (ab initio) molecular dynamics simulations. Our results show that adsorption of H atoms and subsequent release of H2 readily happen on coronene for H atoms with kinetic energy as large as 1 eV. Special attention is paid to dissipation and partition of the energy released in the reactions. The capacity of coronene to dissipate collision and reaction energies varies with the reaction site. Inner sites dissipate energy easier and faster than edge sites, thus evidencing an interplay between the potential energy surface around the reaction centre and its ability to cool the projectile. As for the recombination of H atoms and the subsequent formation of H2, it is observed that $\sim 15~{{\ \rm per\ cent}}$ of the energy is dissipated by the coronene molecule as vibrational energy and the remaining energy is carried by H2. The H2 molecules desorb from coronene with an excited vibrational state (υ ≥ 3), a large amount of translational kinetic energy (≥0.4 eV), and with a small activation of the rotational degree of freedom.
Paralogous translation factors target distinct mRNAs to differentially regulate tolerance to oxidative stress in yeast
Authors: Cunningham Joanne , Sfakianos Aristeidis P , Kritsiligkou Paraskevi , Kershaw Christopher J , Whitmarsh Alan J , Hubbard Simon J , Ashe Mark P , Grant Chris M
Published: July 2023

Translation initiation factor 4G (eIF4G) is an integral component of the eIF4F complex which is key to translation initiation for most eukaryotic mRNAs. Many eIF4G isoforms have been described in diverse eukaryotic organisms but we currently have a poor understanding of their functional roles and whether they regulate translation in an mRNA specific manner. The yeast Saccharomyces cerevisiae expresses two eIF4G isoforms, eIF4G1 and eIF4G2, that have previously been considered as functionally redundant with any phenotypic differences arising due to alteration in eIF4G expression levels. Using homogenic strains that express eIF4G1 or eIF4G2 as the sole eIF4G isoforms at comparable expression levels to total eIF4G, we show that eIF4G1 is specifically required to mediate the translational response to oxidative stress. eIF4G1 binds the mRNA cap and remains associated with actively translating ribosomes during oxidative stress conditions and we use quantitative proteomics to show that eIF4G1 promotes oxidative stress-specific proteome changes. eIF4G1, but not eIF4G2, binds the Slf1 LARP protein which appears to mediate the eIF4G1-dependent translational response to oxidative stress. We show similar isoform specific roles for eIF4G in human cells suggesting convergent evolution of multiple eIF4G isoforms offers significant advantages especially where translation must continue under stress conditions.
Role of DNA–DNA sliding friction and nonequilibrium dynamics in viral genome ejection and packaging
Authors: Fizari Mounir , Keller Nicholas , Jardine Paul J , Smith Douglas E
Published: July 2023

Many viruses eject their DNA via a nanochannel in the viral shell, driven by internal forces arising from the high-density genome packing. The speed of DNA exit is controlled by friction forces that limit the molecular mobility, but the nature of this friction is unknown. We introduce a method to probe the mobility of the tightly confined DNA by measuring DNA exit from phage phi29 capsids with optical tweezers. We measure extremely low initial exit velocity, a regime of exponentially increasing velocity, stochastic pausing that dominates the kinetics and large dynamic heterogeneity. Measurements with variable applied force provide evidence that the initial velocity is controlled by DNA–DNA sliding friction, consistent with a Frenkel–Kontorova model for nanoscale friction. We confirm several aspects of the ejection dynamics predicted by theoretical models. Features of the pausing suggest that it is connected to the phenomenon of ‘clogging’ in soft matter systems. Our results provide evidence that DNA–DNA friction and clogging control the DNA exit dynamics, but that this friction does not significantly affect DNA packaging.
Dynamic structure of T4 gene 32 protein filaments facilitates rapid noncooperative protein dissociation
Authors: Cashen Ben A , Morse Michael , Rouzina Ioulia , Karpel Richard L , Williams Mark C
Published: July 2023

Bacteriophage T4 gene 32 protein (gp32) is a model single-stranded DNA (ssDNA) binding protein, essential for DNA replication. gp32 forms cooperative filaments on ssDNA through interprotein interactions between its core and N-terminus. However, detailed understanding of gp32 filament structure and organization remains incomplete, particularly for longer, biologically-relevant DNA lengths. Moreover, it is unclear how these tightly-bound filaments dissociate from ssDNA during complementary strand synthesis. We use optical tweezers and atomic force microscopy to probe the structure and binding dynamics of gp32 on long (∼8 knt) ssDNA substrates. We find that cooperative binding of gp32 rigidifies ssDNA while also reducing its contour length, consistent with the ssDNA helically winding around the gp32 filament. While measured rates of gp32 binding and dissociation indicate nM binding affinity, at ∼1000-fold higher protein concentrations gp32 continues to bind into and restructure the gp32–ssDNA filament, leading to an increase in its helical pitch and elongation of the substrate. Furthermore, the oversaturated gp32–ssDNA filament becomes progressively unwound and unstable as observed by the appearance of a rapid, noncooperative protein dissociation phase not seen at lower complex saturation, suggesting a possible mechanism for prompt removal of gp32 from the overcrowded ssDNA in front of the polymerase during replication.
Synthetic Cooling Agents in Australian-Marketed E-cigarette Refill Liquids and Disposable E-cigarettes: Trends Follow the U.S. Market
Authors: Jenkins Caitlin , Morgan Jody , Kelso Celine
Published: July 2023

Introduction

E-cigarettes are becoming increasingly popular in Australia, especially amongst the younger population. The synthetic cooling molecules WS-3 and WS-23 have been identified in e-cigarette products from the United States and Europe. The extent of inclusion of these synthetic coolants in Australian e-liquids is unknown, particularly in newer disposable e-cigarettes.

Aims and Methods

E-cigarettes and e-liquids were purchased within Australia and anonymously donated by Australian users. Nicotine, WS-3, WS-23, and menthol were quantified in the e-liquids using gas chromatography-mass spectrometry (GC-MS).

Results

WS-23 and nicotine were detected in all of the disposable e-cigarettes with WS-23 often present in high concentrations. There was no correlation between cooling terms in the flavor name and the inclusion of cooling agents. Only three bottled e-liquids were found to contain WS-23 while none contained WS-3 above the limit of detection.

Conclusions

Synthetic coolants were a common addition in disposable e-cigarettes while rarely added to e-liquid bottle refills. Their inclusion in these products is reflective of trends observed in United States and European e-cigarette products.

Implications

The increase in synthetic cooling agents as components of e-liquids, particularly disposable e-cigarette devices, has been observed within Australian samples across a range of brands and flavors. WS-23 was present in every disposable e-cigarette analyzed in this study, often in relatively high concentrations. Its inhalational toxicology should be considered when evaluating the safety of these products.
Accountability enablers? The role of transnational activism in the use of the multilateral development bank grievance mechanisms
Authors: Gunaydin Eda , Park Susan
Published: July 2023

The proliferation of concerns over the transparency, accountability, and democracy of international organizations has contributed to an increase in accountability mechanisms to hold global governors to account, by both state and non-state actors. Much of the scholarly focus on this subject has been on how levers of accountability can improve global governance for Member States and actors seeking to improve decision-making, and thus outputs. This article instead examines how individuals and communities, or neglected publics, are using accountability mechanisms designed to provide them with recourse for environmental and social harm. It probes the use of the grievance mechanisms for the multilateral development banks to examine what kinds of actors use them (e.g., international nongovernmental organizations, nongovernmental organizations, or project-affected people [PAP]) and to what effect. To explore these questions, we analyze 500 complaints submitted to the grievance mechanisms of the World Bank Group; the Asian, African, and Inter-American Development Banks; and the European Bank for Reconstruction and Development. The results demonstrate that claims for recourse come from a range of primarily local actors, but that PAP in developing countries will more often achieve positive outcomes from the grievance mechanism process if they receive assistance from international and national nongovernmental organizations. These findings therefore demonstrate that transnational activists can fulfill a facilitating role as “accountability enablers” and that domestic representatives are especially effective in problem-solving processes, while international representatives are especially effective in compliance processes.