Assessing willingness to pay for children's COVID-19 vaccination among healthcare providers and users using a theory-based discrete choice experiment.

Improving vaccine coverage among children is crucial to prevent the long-term consequences of COVID-19 infections and the emergence of resistant COVID-19 variants, especially in resource-scarce settings. This study determined factors influencing the willingness to take and pay for COVID-19 vaccine for children among Vietnamese healthcare professionals and the public. A Theory-Based discrete-choice experiment was focused on a different topic related to vaccines, including the COVID-19 vaccine for children, Monkeypox, the adult COVID-19 booster, the HIV vaccine, and a potential future pandemic. The recruitment period was from April to August 2022, and a total of 5700 Vietnamese individuals aged 16 and above from various regions of the country participated in the study. The data for the sub-study on the COVID-19 vaccination for children was completed by 891 of these participants. Most participants agreed on vaccination for all children. Among healthcare professionals it was 76.2% and 69.3% for the general population. Healthcare professionals were the main source of vaccine information (70.7%). Payment options of 50%, 100%, and full subsidy were the most popular. Concerns about vaccine characteristics were associated with lower acceptance among healthcare professionals and the general public. The burden of historical medical expenses negatively correlated with willingness to pay for vaccination, while service satisfaction positively correlated with willingness to pay. To develop an effective vaccination program among children in Vietnam, providing accurate information and satisfying vaccine services, primarily through knowledgeable and professional healthcare providers, can improve the willingness to vaccinate and pay for the COVID-19 vaccine.

Structural determination of oleanane-28,13ß-olide and taraxerane-28,14ß-olide fluoro-lactonization products from the reaction of oleanolic acid with SelectfluorTM.

The X-ray crystal structure data of 12-α-fluoro-3ß-hy-droxy-olean-28,13ß-olide methanol hemisolvate, 2C30H47FO3·CH3OH, (1), and 12-α-fluoro-3ß-hy-droxy-taraxer-28,14ß-olide methanol hemisolvate, 2C30H47FO3·CH3OH, (2), are described. The fluoro-lactonization of oleanolic acid using SelectfluorTM yielded a mixture of the six-membered δ-lactone (1) and the unusual seven-membered γ-lactone (2) following a 1,2-shift of methyl C-27 from C-14 to C-13.

Prevalence of depressive symptoms among urban school adolescents in Vietnam: The role of youth, family, and school relationships.

BACKGROUND: Adolescents frequently encounter a spectrum of psychiatric conditions, predominantly depressive and anxiety disorders, along with various behavioral disturbances. OBJECTIVE: This investigation aims to delineate the prevalence of depressive disorders among adolescents in urban Vietnam and to elucidate the interrelationships between familial and school-related dynamics and adolescent depression. MATERIALS AND METHODS: A cross-sectional survey was conducted in 2022, involving 507 students aged 15 to 17 from high schools in Hanoi, Vietnam. Reynolds Adolescent Depression Scale - Second Edition (RADS-2) was used to assess the presence of depressive symptoms. Social-demographic characteristics, adolescent-family and adolescent-school relationships, and academic environment characteristics of high school students were interviewed. Multivariate Tobit regression models were employed to discern contributory factors across four domains of RADS-2. RESULTS: Among the 507 adolescents, the mean scores on the RADS scale were 15.1 ± 4.2 for the dysphoric mood domain, 16.4 ± 4.0 for the anhedonia-negative domain, 13.1 ± 4.4 for the negative self-evaluation domain, and 12.4 ± 3.7 for the somatic complaints domain. The analysis indicated that adolescents with suboptimal parental relationships, absence of confidants, frequent parental conflicts, exposure to parental arguments, substantial exam-related stress, or overwhelming academic demands were more likely to exhibit elevated depressive symptoms. Conversely, adolescents who were satisfied with their friendships at school and received care, support from teachers or friends, and involved in school's extracurricular activities lower exhibited levels of depression. CONCLUSIONS: Findings reveal the significant impact of family and peer relationships, as well as academic stress, on the development of depressive symptoms. These significant results inform the design and development of future interventions aimed at mitigating depression risks among high school students, emphasizing the crucial roles of both educational institutions and family dynamics.

Clock-Line-Mediated Sisyphus Cooling.

We demonstrate subrecoil Sisyphus cooling using the long-lived ^{3}P_{0} clock state in alkaline-earth-like ytterbium. A 1388-nm optical standing wave nearly resonant with the ^{3}P_{0}→^{3}D_{1} transition creates a spatially periodic light shift of the ^{3}P_{0} clock state. Following excitation on the ultranarrow clock transition, we observe Sisyphus cooling in this potential, as the light shift is correlated with excitation to ^{3}D_{1} and subsequent spontaneous decay to the ^{1}S_{0} ground state. We observe that cooling enhances the loading efficiency of atoms into a 759-nm magic-wavelength one-dimensional (1D) optical lattice, as compared to standard Doppler cooling on the ^{1}S_{0}→^{3}P_{1} transition. Sisyphus cooling yields temperatures below 200 nK in the weakly confined, transverse dimensions of the 1D optical lattice. These lower temperatures improve optical lattice clocks by facilitating the use of shallow lattices with reduced light shifts while retaining large atom numbers to reduce the quantum projection noise. This Sisyphus cooling can be pulsed or continuous and is applicable to a range of quantum metrology applications.

Arrhythmias During Pregnancy: Ventricular Tachycardia in the Setting of Maternal Beta Thalassemia Minor.

Non-sustained ventricular tachycardia (NSVT) poses significant risks during pregnancy, particularly in patients with underlying conditions such as ß-thalassemia. We present a case of a 29-year-old pregnant woman with a history of ß-thalassemia minor who experienced NSVT at 27 weeks gestation. Despite initial concerns for structural heart disease, the workup was unrevealing. Challenges in medication selection and risk assessment were addressed in the context of maternal and fetal well-being. This case underscores the importance of a multidisciplinary approach involving cardiology, obstetrics, and hematology in managing NSVT during pregnancy, emphasizing risk stratification, collaborative decision-making, and long-term follow-up to ensure optimal outcomes for both mother and fetus.

CH-π Interactions Are Required for Human Galectin-3 Function.

Glycan-binding proteins, or lectins, recognize distinct structural elements of polysaccharides, to mediate myriad biological functions. Targeting glycan-binding proteins involved in human disease has been challenging due to an incomplete understanding of the molecular mechanisms that govern protein-glycan interactions. Bioinformatics and structural studies of glycan-binding proteins indicate that aromatic residues with the potential for CH-π interactions are prevalent in glycan-binding sites. However, the contributions of these CH-π interactions to glycan binding and their relevance in downstream function remain unclear. An emblematic lectin, human galectin-3, recognizes lactose and N-acetyllactosamine-containing glycans by positioning the electropositive face of a galactose residue over the tryptophan 181 (W181) indole forming a CH-π interaction. We generated a suite of galectin-3 W181 variants to assess the importance of these CH-π interactions to glycan binding and function. As determined experimentally and further validated with computational modeling, variants with smaller or less electron-rich aromatic side chains (W181Y, W181F, W181H) or sterically similar but nonaromatic residues (W181M, W181R) showed poor or undetectable binding to lactose and attenuated ability to bind mucins or agglutinate red blood cells. The latter functions depend on multivalent binding, highlighting that weakened CH-π interactions cannot be overcome by avidity. Two galectin-3 variants with disrupted hydrogen bonding interactions (H158A and E184A) showed similarly impaired lactose binding. Molecular simulations demonstrate that all variants have decreased binding orientation stability relative to native galectin-3. Thus, W181 collaborates with the endogenous hydrogen bonding network to enhance binding affinity for lactose, and abrogation of these CH-π interactions is as deleterious as eliminating key hydrogen bonding interactions. These findings underscore the critical roles of CH-π interactions in carbohydrate binding and lectin function and will aid the development of novel lectin inhibitors.

Genomic Epidemiology of Mycobacterium abscessus on the Island of Montréal Not Suggestive of Healthcare-associated Person-to-Person Transmission.

BACKGROUND: Mycobacterium abscessus complex (MABC), an opportunistic nontuberculous mycobacteria (NTM), can lead to poor clinical outcomes in pulmonary infections. Conflicting data exist on person-to-person transmission of MABC within and across healthcare facilities. To investigate further, a comprehensive retrospective study across five healthcare institutions on the Island of Montréal was undertaken. METHODS: We analyzed the genomes of 221 MABC isolates obtained from 115 individuals (2010-2018) to identify possible links. Genetic similarity, defined as ≤25 single-nucleotide polymorphisms (SNPs), was investigated through a blinded epidemiological inquiry. RESULTS: Bioinformatics analyses identified 28 sequence types (STs), including globally observed dominant circulating clones (DCCs). Further analysis revealed 210 isolate pairs within the SNP threshold. Among these pairs, there was one possible lab contamination where isolates from different patients processed in the same lab differed by only 2 SNPs. There were 37 isolate pairs from patients who had provided specimens from the same hospital; however, epidemiological analysis found no evidence of healthcare-associated person-to-person transmission between these patients. Additionally, pan-genome analysis showed higher discriminatory power than core genome analysis for examining genomic similarity. CONCLUSIONS: Genomics alone is insufficient to establish MABC transmission, particularly considering the genetic similarity and wide distribution of DCCs, although pan-genome analysis has the potential to add further insight. Our findings indicate that MABC infections in Montréal are unlikely attributable to healthcare-associated person-to-person transmission.

Work-Related Musculoskeletal Problems: A Look at How Employers View Causes.

Causation concepts for work-related musculoskeletal disorders vary among authors and academic disciplines. The major causation concepts are single-event and repetitive motion. The aim of this short communication is to share findings from a recent survey of United States employers conducted by the U.S. Bureau of Labor Statistics about work-related musculoskeletal cases, and, more specifically, about whether the employers regard the causes of their employees' musculoskeletal problems as being from a single exposure or from multiple exposures. Recommendations are offered for using terminology consistent with employer understandings.

Evolution and host-specific adaptation of Pseudomonas aeruginosa.

The major human bacterial pathogen Pseudomonas aeruginosa causes multidrug-resistant infections in people with underlying immunodeficiencies or structural lung diseases such as cystic fibrosis (CF). We show that a few environmental isolates, driven by horizontal gene acquisition, have become dominant epidemic clones that have sequentially emerged and spread through global transmission networks over the past 200 years. These clones demonstrate varying intrinsic propensities for infecting CF or non-CF individuals (linked to specific transcriptional changes enabling survival within macrophages); have undergone multiple rounds of convergent, host-specific adaptation; and have eventually lost their ability to transmit between different patient groups. Our findings thus explain the pathogenic evolution of P. aeruginosa and highlight the importance of global surveillance and cross-infection prevention in averting the emergence of future epidemic clones.

Multidisciplinary Velopharyngeal Dysfunction Evaluation Helps Detect Non-classic Cases of 22q11.2 Deletion.

OBJECTIVE: To explore the role of multidisciplinary velopharyngeal dysfunction (VPD) assessment in diagnosing 22q11.2 deletion syndrome (22q) in children. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary VPD clinic at a tertiary pediatric hospital. PATIENTS, PARTICIPANTS: Seventy-five children with genetically confirmed 22q evaluated at the VPD clinic between February 2007 and February 2023, including both previously diagnosed patients and those newly diagnosed as a result of VPD evaluation. INTERVENTIONS: Comprehensive review of medical records, utilizing ICD-10 codes and an institutional tool for keyword searches, to identify patients and collect data on clinical variables and outcomes. MAIN OUTCOME MEASURES: Characteristics of children with 22q, pathways to diagnosis, and clinical presentations that led to genetic testing for 22q. RESULTS: Of the 75 children, 9 were newly diagnosed with 22q following VPD evaluation. Non-cleft VPI was a significant indicator for 22q in children not previously diagnosed, occurring in 100% of newly diagnosed cases compared to 52% of cases with existing 22q diagnosis (P = .008). Additional clinical findings leading to diagnosis included congenital heart disease, craniofacial abnormalities, and developmental delays. CONCLUSIONS: VPD evaluations, particularly the presence of non-cleft VPI, play a crucial role in identifying undiagnosed cases of 22q. This underscores the need for clinicians, including plastic surgeons, otolaryngologists, and speech-language pathologists, to maintain a high degree of suspicion for 22q in children presenting with VPI without a clear etiology. Multidisciplinary approaches are essential for early diagnosis and management of this complex condition.

Investigating the stability of aromatic carboxylic acids in hydrated magnesium sulfate under UV irradiation to assist detection of organics on Mars.

The Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) instrument onboard the Mars 2020 Perseverance rover detected so far some of the most intense fluorescence signals in association with sulfates analyzing abraded patches of rocks at Jezero crater, Mars. To assess the plausibility of an organic origin of these signals, it is key to understand if organics can survive exposure to ambient Martian UV after exposure by the Perseverance abrasion tool and prior to analysis by SHERLOC. In this work, we investigated the stability of organo-sulfate assemblages under Martian-like UV irradiation and we observed that the spectroscopic features of phthalic and mellitic acid embedded into hydrated magnesium sulfate do not change for UV exposures corresponding to at least 48 Martian sols and, thus, should still be detectable in fluorescence when the SHERLOC analysis takes place, thanks to the photoprotective properties of magnesium sulfate. In addition, different photoproduct bands diagnostic of the parent carboxylic acid molecules could be observed. The photoprotective behavior of hydrated magnesium sulfate corroborates the hypothesis that sulfates might have played a key role in the preservation of organics on Mars, and that the fluorescence signals detected by SHERLOC in association with sulfates could potentially arise from organic compounds.

Physical reserve and its underpinning functional neural networks moderate the relationship between white matter hyperintensity and postural balance in older adults with subcortical ischemic vascular cognitive impairment.

White matter hyperintensities (WMH) are markers of subcortical ischemic vascular cognitive impairment (SIVCI) associated with impaired postural balance. Physical reserve (PR) is a recently established construct that reflects one's capacity to maintain physical function despite brain pathology. This cross-sectional study aims to map functional networks associated with PR, and examining the relationship between PR, WMH, and postural balance. PR was defined in 22 community-dwelling older adults with SIVCI. Functional networks of PR were computed using general linear model. Subsequent analyses examined whether PR and relevant networks moderated the relationship between WMH and postural balance under two conditions-eyes open while standing on foam (EOF) or on floor (EONF). We found that PR and the relevant networks-frontoparietal network (FPN) and default mode network (DMN)-significantly moderated the association between WMH and postural balance. For individuals with high PR, postural balance remained stable regardless of the extent of WMH load; whereas for those with low PR, postural balance worsened as WMH load increased. These results suggest the attenuated effects of WMH on postural stability due to PR may be underpinned by functional neural network reorganization in the FPN and DMN as a part of compensatory processes.

Why does one trust? A 360-degree perspective on the role of position power in weighting trustworthiness factors.

The purpose of the current paper is to explore the influence of the perceived trustworthiness factors of ability, benevolence and integrity on general and specific trust across supervisors, subordinates and peers with the same focal referent. This study used a 360-degree approach to examine how positional power asymmetries influence the relationship between trustworthiness and trust for a general and situation-specific referent. Data were obtained from military supervisors (N = 200), peers (N = 123), and subordinates (N = 85). Measures of trustworthiness and trust of a common military officer were obtained. Supervisors and subordinates differed in their relative weighting of trustworthiness factors (i.e. ability, benevolence, and integrity) when evaluating general and specific trust. Peers evidenced no difference in the relative weighting of trustworthiness factors. The relationship between benevolence and specific trust was stronger for subordinates than for supervisors. One implication of our findings is that trust can develop differently in bottom-up versus top-down organizational relationships. This study provides evidence that supervisors and subordinates emphasize different aspects of trustworthiness when evaluating their trust of a focal officer, and this process was different for general versus specific trust referents. The study also extends previous research by replicating previous findings across raters.

Comparing suicide completion rates in bipolar I versus bipolar II disorder: A systematic review and meta-analysis.

BACKGROUND: Bipolar disorder (BD) has a high disease burden and the highest mortality risk in BD comes from suicide. Bipolar disorder type II (BD-II) has been described as a milder form of bipolar disorder; however, extant literature is inconsistent with this description and instead describe illness burden and notably suicidality comparable to persons with bipolar I disorder (BD-I). Towards quantifying the hazard of BD-II, herein we aim via systematic review and meta-analysis to evaluate the rates of completed suicide in BD-I and BD-II. METHOD: We conducted a literature search on PubMed, OVID (Embase, Medline) and PsychINFO databases from inception to June 30th, 2023, according to PRISMA guidelines. Articles were selected based on the predetermined eligibility criteria. A meta-analysis was performed, comparing the risk of completed suicide between individuals diagnosed with BD-I to BD-II. RESULTS: Four out of eight studies reported higher suicide completion rates in persons living with BD-II when compared to persons living with BD-I; however, two of the studies reported non-significance. Two studies reported significantly higher suicide completion rates for BD-I than BD-II. The pooled odds ratio of BD-II suicide rates to BD-I was 1.00 [95 % CI = 0.75, 1.34]. LIMITATIONS: The overarching limitation is the small number of studies and heterogeneity of studies that report on suicide completion in BD-I and BD-II. CONCLUSION: Our study underscores the severity of BD-II, with a risk for suicide not dissimilar from BD-I. The greater propensity to depression, comorbidity and rapid-cycling course reported in BD-II are contributing factors to the significant mortality hazard in BD-II.

Altered functional connectivity subserving expressed emotion environments in schizophrenia: An fNIRS study.

Living in high-expressed emotion (EE) environments, characterized by critical, hostile, or over-involved family attitudes, has been linked to increased relapse rates among individuals with schizophrenia (SZ). In our previous work (Wang et al., 2023), we conducted the first feasibility study of using functional near-infrared spectroscopy (fNIRS) with our developed EE stimuli to examine cortical hemodynamics in SZ. To better understand the neural mechanisms underlying EE environmental factors in SZ, we extended our investigation by employing functional connectivity (FC) analysis with a graph theory approach to fNIRS signals. Relative to healthy controls (N=40), individuals with SZ (N=37) exhibited altered connectivity across the medial prefrontal cortex (mPFC), left ventrolateral prefrontal cortex (vlPFC), and left superior temporal gyrus (STG) while exposed to EE environments. Notably, while individuals with SZ were exposed to high-EE environments, (i) reduced connectivity was observed in these brain regions and (ii) the left vlPFC-STG coupling was found to be associated with the negative symptom severity. Taken together, our FC findings suggest individuals with SZ experience a more extensive disruption in neural functioning and coordination, particularly indicating an increased susceptibility to high-EE environments. This further supports the potential utility of integrating fNIRS with the created EE stimuli for assessing EE environmental influences, paving the way for more targeted therapeutic interventions.

Risk of VMAT2 inhibitors on suicidality and parkinsonism: report utilizing the United States Food and Drug Administration adverse event reporting system.

Prescription of vesicular monoamine transporter 2 (VMAT2) inhibitors, valbenazine, deutetrabenazine, and tetrabenazine, is becoming increasingly common in persons treated with antipsychotics. Reported suicidality and parkinsonism are safety concerns with VMAT2 inhibitors. Herein, we aim to evaluate the aforementioned safety outcomes using the FDA Adverse Event Reporting System. Reporting odds ratios (RORs) and lower limits of 95% confidence intervals of information components (IC025) were calculated to quantify VMAT2 inhibitor-associated adverse events. Acetaminophen was the reference agent. Suicidal ideation was significantly associated with VMAT2 inhibitors, with RORs ranging from 2.38 to 10.67 and IC025 ranging from 0.73 to 2.39. Increased odds of suicidal behavior was observed with tetrabenazine (ROR 3.011, IC025 0.0087), but not deutetrabenazine or valbenazine. Decreased odds of suicide attempts and completed suicide were observed with VMAT2 inhibitors, with RORs ranging from 0.011 to 0.10 (all IC025 < 0). Increased odds of parkinsonism were reported for all VMAT2 inhibitors, with RORs and IC025 ranging from 19.49 to 25.37 and 1.66 to 2.93, respectively. The mixed results with VMAT2 inhibitor-associated suicidality and parkinsonism do not establish causal relationships. The parameters of suicidality may be explained by underlying psychiatric disorders.

The central executive network moderates the relationship between posttraumatic stress symptom severity and gastrointestinal related issues.

Although most adults experience at least one traumatic event in their lifetime, a smaller proportion will go on to be clinically diagnosed with post-traumatic stress disorder (PTSD). Persons diagnosed with PTSD have a greater likelihood of developing gastrointestinal (GI) disorders. However, the extent to which subclinical levels of post-traumatic stress (PTS) correspond with the incidence of GI issues in a normative sample is unclear. Resting state fMRI, medical history, psychological survey, and anthropometric data were acquired from the Enhanced Nathan Kline Institute-Rockland Sample (n = 378; age range 18-85.6 years). The primary aim of this study was to test the main effect of subclinical PTS symptom severity on the number of endorsed GI issues. The secondary aim was to test the moderating effect of high versus low resting state functional connectivity (rsFC) of the central executive network (CEN) on the relationship between PTS symptom severity and GI issues. Trauma Symptom Checklist-40 (TSC-40) scores were positively associated with the number of endorsed GI issues (b = -0.038, SE = .009, p < .001). The interaction between TSC-40 scores and rsFC within the CEN was significant on GI issues after controlling for sociodemographic and cardiometabolic variables (b = -0.031, SE = .016, p < .05), such that above average rsFC within the CEN buffered the effect of TSC-40 scores on GI issues. Our findings of higher rsFC within the CEN moderating the magnitude of coincidence in PTS and GI symptom severity may reflect the mitigating role of executive control processes in the putative stress signaling mechanisms that contribute to gut dysbiosis.

Malaria prevalence and use of control measures in an area with persistent transmission in Senegal.

INTRODUCTION: In Senegal, the widespread use of vector control measures has resulted in a significant reduction in the malaria burden and led the country to consider the possibility of elimination. Given this shift and changing context, it is important to characterize the malaria burden across all age groups to guide decision-making on programmatic interventions to interrupt transmission and ultimately eradicate the disease. In Senegal, there is a lack of information on malaria prevalence among certain populations, particularly among adolescents and adults. This study sought to assess the magnitude of malaria infections in all age groups, as well as malaria associated factors in an area of persistent transmission in Senegal. METHODS: A cross-sectional household survey was conducted in four health posts (Khossanto, Mamakhona, Diakhaling and Sambrambougou), of the health district of Saraya, in November 2021, among individuals over 6 months of age. Households were selected using multistage sampling. Consented participants were screened for malaria parasites by microscopic examination of blood smears, and hemoglobin levels were measured using the Hemocue HB 301TM analyzer. Socio-demographic information of the participants, household heads, household assets, and information on ownership and use of preventive measures were collected using a structured questionnaire. Weighted generalized mixed effects logistic regression model was used to identify factors associated with microscopically confirmed malaria infection. RESULTS: A total of 1759 participants were enrolled in the study. Overall, about 21% of participants were classified as having Plasmodium infection; children aged 5-10 years old (26.6%), adolescents aged 10-19 years old (24.7%), and children under five years of age (20.5%) had higher rates of infection compared to adults (13.5%). Plasmodium falciparum accounted for 99.2% of the malaria infections, and most infections (69%) were asymptomatic. Around one-third of study participants had anemia (hemoglobin level <11.0 g/dl), with under five children bearing the highest burden (67.3%). Multivariate analysis showed that the odds of having a malaria infection were around 2 times higher among participants in Khossanto compared to Diakhaling (aOR = 1.84, 95% CI:1.06-3.20). Participants aged 5-9 years were more likely to have malaria infection compared to under five children (aOR = 1.40, 95% CI:1.02-1.91). Factors associated with anemia were P. falciparum infection (aOR = 1.36, p = 0.027), females (aOR = 2.16, p = 0.000), under-five age group (aOR = 13.01, p = 0.000). CONCLUSION: Malaria burden was considerable among adolescents and under ten children living in an area of persistent transmission, with adolescents more commonly presenting as asymptomatic. Interventions tailored to this specific group of the population are needed to better control the disease and reduce its burden.

Genetics of flight in spongy moths (Lymantria dispar ssp.): functionally integrated profiling of a complex invasive trait.

BACKGROUND: Flight can drastically enhance dispersal capacity and is a key trait defining the potential of exotic insect species to spread and invade new habitats. The phytophagous European spongy moths (ESM, Lymantria dispar dispar) and Asian spongy moths (ASM; a multi-species group represented here by L. d. asiatica and L. d. japonica), are globally invasive species that vary in adult female flight capability-female ASM are typically flight capable, whereas female ESM are typically flightless. Genetic markers of flight capability would supply a powerful tool for flight profiling of these species at any intercepted life stage. To assess the functional complexity of spongy moth flight and to identify potential markers of flight capability, we used multiple genetic approaches aimed at capturing complementary signals of putative flight-relevant genetic divergence between ESM and ASM: reduced representation genome-wide association studies, whole genome sequence comparisons, and developmental transcriptomics. We then judged the candidacy of flight-associated genes through functional analyses aimed at addressing the proximate demands of flight and salient features of the ecological context of spongy moth flight evolution. RESULTS: Candidate gene sets were typically non-overlapping across different genetic approaches, with only nine gene annotations shared between any pair of approaches. We detected an array of flight-relevant functional themes across gene sets that collectively suggest divergence in flight capability between European and Asian spongy moth lineages has coincided with evolutionary differentiation in multiple aspects of flight development, execution, and surrounding life history. Overall, our results indicate that spongy moth flight evolution has shaped or been influenced by a large and functionally broad network of traits. CONCLUSIONS: Our study identified a suite of flight-associated genes in spongy moths suited to exploration of the genetic architecture and evolution of flight, or validation for flight profiling purposes. This work illustrates how complementary genetic approaches combined with phenotypically targeted functional analyses can help to characterize genetically complex traits.

Determinants of beta-lactam PK/PD target attainment in critically ill patients: A single center retrospective study.

PURPOSE: We aimed to identify factors associated with achieving target BL plasma concentrations and describe real world data for therapeutic drug monitoring (TDM). METHODS: A retrospective single center study was conducted. We collected data from patients admitted to ICU with at least one BL TDM. We assessed the proportion of patients attaining the recommended plasma concentrations (i.e 100%fT > 4 to 8 MIC). Univariate and multivariate analyses was performed to identify the determinants of BL target attainment. RESULTS: 156 patients were included. At the first dosing, 34% achieved target BL plasma concentrations, 50% were overdosed, and 16% were underdosed. Median time for 1st TDM were 4 (SD = 2.9) days. Multivariate analysis revealed that CKD-EPI estimated glomerular filtration rate (OR = 1.02; CI [1.01; 1.03]; p < 0.0001) and total body weight (OR = 1.03; CI [1.01; 1.04]; p = 0.0048) were the main determinant of BL target attainment. Conversely, Continuous Renal Replacement Therapy (OR = 0.28; CI [0.09; 0.89]; p = 0.0318) and meropenem use (OR = 0.31; CI [0.14; 0.69]; p = 0.0041) were identified as risk factors for overdosing. No factor was associated with underdosing. CONCLUSION: Achieving target BL plasma concentrations remains challenging in ICUs. Identifying predictive factors of BL target attainment would favor implementing rapid dosing optimization strategies in both under and overdosing high risk patients.