Search

Context. Thanks to recent progress in the field of optical interferometry, instrument sensitivities have now reached the level achieved in the domain of new space missions dedicated to exoplanet and stellar studies. Combining interferometry with other observational approaches enables the determination of stellar parameters and helps improve our understanding of stellar physics. Aims. In this paper, we aim to demonstrate a new way of using stellar atmosphere models for a joint interpretation of spectroscopic and interferometric observations. Methods. Starting from a discrete grid of one-dimensional (1D) stellar atmosphere models, we developed a training algorithm, based on an artificial neural network, capable of estimating the spectrum and intensity profile of a star over a range of wavelengths and viewing angles. A minimisation algorithm based on the trained function allowed for the simultaneous fitting of the observational spectrum and interferometric complex visibilities. As a result, coherent and precise stellar parameters can be extracted. Results. We show the ability of the trained function to match the modelled intensity profiles of stars in the effective temperature range of 4500–7000 K and surface gravity range of 3 to 5 dex, with a relative precision to the model that is better than 0.05%. Using simulated interferometric data and actual spectroscopic measurements, we demonstrated the performance of our algorithm on a sample of five benchmark stars. Using this method, we achieved an accuracy within 0.5% for the angular diameter, radius, and surface gravity, and within 20 K for the effective temperature. Conclusions. This paper demonstrates a new method of using interferometric data combined with spectroscopic observations. This approach offers an improved determination of the radius, effective temperature, and surface gravity of stars. [ABSTRACT FROM AUTHOR]

Group B Streptococcus (GBS) is a major cause of pneumonia, sepsis, and meningitis in infants younger than 3 months of age. Furthermore, GBS infection in pregnant women is associated with stillbirths and pre-term delivery. It also causes disease in immunocompromised adults and the elderly, but the highest incidence of the disease occurs in neonates and young infants. At this time, there are no licensed vaccines against GBS. Complete GBS genome sequencing has helped identify genetically conserved and immunogenic proteins, which could serve as vaccine immunogens. In this study, in silico reverse vaccinology method were used to evaluate the prevalence and conservation of GBS proteins in invasive and colonizing isolates from South African infants and women, respectively. Furthermore, this study aimed to predict potential GBS vaccine targets by evaluating metrics such as antigenicity, physico-chemical properties, subcellular localization, secondary and tertiary structures, and epitope prediction and conservation. A total of 648 invasive and 603 colonizing GBS isolate sequences were screened against a panel of 89 candidate GBS proteins. Ten of the 89 proteins were highly genetically conserved in invasive and colonizing GBS isolates, nine of which were computationally inferred proteins (gbs2106, SAN_1577, SAN_0356, SAN_1808, SAN_1685, SAN_0413, SAN_0990, SAN_1040, SAN_0226) and one was the surface Immunogenic Protein (SIP). Additionally, the nine proteins were predicted to be more antigenic than the SIP protein (antigenicity score of > 0.6498), highlighting their potential as GBS vaccine antigen targets. [ABSTRACT FROM AUTHOR]

Digital gaming has become a major global cultural industry, and many popular video games feature cityscapes. While scholars have critiqued the neoliberal and dystopian representations of urban environments, much less attention is given to how video games offer players a sense of belonging: an immersive city where they can feel at home. Game developers create affective urban worlds to attract and maintain a large player base for continuous revenue. We argue that high-budget and popular video games balance a chaotic urban gamescape with opportunities for privatized homemaking that keep players engaged. First, they use emergent gameplay to simulate the urban environment as sensational places where players must prepare for unpredictable, often dangerous, and violent encounters. Second, they provide players with homemaking opportunities and the means to own and curate private spaces. These opportunities, however, reflect and perpetuate a privatized purpose of homemaking that perpetuates gendered and capitalistic assumptions, socializing players into engaging with urban life in a very selective manner. While we analyze several video games, GTA V provides a specific example of how this homemaking is monetized. Our analysis combines scholarly debates on affective geographies and gamescapes. [ABSTRACT FROM AUTHOR]

Invasive species require adequate reliable detection methods to mitigate their further spread and impact. However, the reliability of molecular detection methods is often hampered by both false positives (Error type I) and false negatives (Error type II). At present, the reliability of the four published molecular detection methods for small hive beetles (SHB), Aethina tumida, has not been rigorously evaluated considering their extensive genetic diversity. Here, we performed intra- and interlaboratory comparisons of the four available methods using SHB samples representing 78 regions from 27 countries on five continents, beetles from the same genus (Aethina concolor, A. inconspicua, A. flavicollis and A. major), as well as western honey bees, Apis mellifera, and ectoparasitic mites Varroa destructor. The data show that the Idrissou et al. (2018) and Li et al. (2018) methods avoid both false positives and false negatives probably due to lower sensitivity to nucleotide mismatches on the primer and probe's target sequences. Further, the Li et al. (2018) method can be considered more sensitive because the fluorescent amplification curve crosses the threshold at lower Cq values compared to the Idrissou et al. (2018) one. In light of our data, the Li et al. (2018) method is the most reliable molecular diagnostic tool for SHB. We therefore recommend using this method as it will contribute to management efforts of this invasive species. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is a major public health issue, posing harmful consequences for individuals and society. Recent advances in addiction research have highlighted the therapeutic potential of ketamine-assisted therapy for AUD. However, the exact mechanisms underlying its effectiveness remain unknown. Aims: This double-blind, pilot study aimed to investigate esketamine combined with mindfulness-based intervention (MBI) to examine whether esketamine enhances engagement in MBI for individuals with alcohol misuse problems and whether enhanced engagement has any impact on alcohol-related outcomes. Methods: In all, 28 individuals with alcohol problems were randomly assigned to receive sublingual esketamine hydrochloride (AWKN002: 115.1 mg) or vitamin C (placebo) in an oral thin film and took part in 2 weeks of daily MBI. Participants were assessed on various self-report measures, including mindfulness, engagement in MBI (physical and psychological), alcohol cravings and consumption. Results: Esketamine enhanced psychological engagement with a daily MBI, compared to placebo, and led to transient decreases in alcohol cravings. Esketamine also resulted in significantly greater mystical experiences and dissociative states compared to placebo. Conclusions: The findings suggest that esketamine may improve treatment outcomes when combined with mindfulness-based therapies through its ability to increase engagement with meditative practice. [ABSTRACT FROM AUTHOR]

This study examines how the relationship between life course and mobility of owner-occupants is affected by periods of economic and housing market downturn and recovery. The impact of 'period effects' are largely unknown. Using Dutch register data, we compare the probabilities of moving in view of partnership, children and employment status for 2012–2014 and 2014–2016. We find that the downturn period is associated with lower mobility, yet the association is different for various household situations. Mobility to ownership in the crisis was particularly constrained for stable couples, employed owners and households with children. Moves to the rental sector were less period sensitive. Only owners who became unemployed were more likely to move into rental during crisis. 'Delayed mobility' has been found for moving in together, separation, households who had children, and job change. So, periods of crisis and recovery structure how home-owners adapt to life-course changes. Our findings imply that period effects should be accounted for in residential mobility studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hypofibrinogenemia has been shown to predict massive transfusion and is associated with higher mortality in severely injured patients. However, the role of empiric fibrinogen replacement in bleeding trauma patients remains controversial. We sought to determine the effect of empiric cryoprecipitate as an adjunct to a balanced transfusion strategy (1:1:1). STUDY DESIGN: This study is a subanalysis of patients treated at the single US trauma center in a multicenter randomized controlled trial. Trauma patients (more than 15 years) were eligible if they had evidence of active hemorrhage requiring emergent surgery or interventional radiology, massive transfusion protocol (MTP) activation, and received at least 1 unit of blood. Transfer patients, those with injuries incompatible with life, or those injured more than 3 hours earlier were excluded. Patients were randomized to standard MTP (STANDARD) or MTP plus 3 pools of cryoprecipitate (CRYO). Primary outcomes included all-cause mortality at 28 days. Secondary outcomes were transfusion requirements, intraoperative and postoperative coagulation laboratory values, and quality-of-life measures (Glasgow outcome score-extended). RESULTS: Forty-nine patients (23 in the CRYO group and 26 in the STANDARD group) were enrolled between May 2021 and October 2021. Time to randomization was similar between groups (14 vs 24 minutes, p = 0.676). Median time to cryoprecipitate was 41 minutes (interquartile range 37 to 48). There were no differences in demographics, arrival physiology, laboratory values, or injury severity. Intraoperative and ICU thrombelastography values, including functional fibrinogen, were similar between groups. There was no benefit to CRYO with respect to post-emergency department transfusions (intraoperative and ICU through 24 hours), complications, Glasgow outcome score, or mortality. CONCLUSIONS: In this study of severely injured, bleeding trauma patients, empiric cryoprecipitate did not improve survival or reduce transfusion requirements. Cryoprecipitate should continue as an "on-demand" addition to a balanced transfusion strategy, guided by laboratory values and should not be given empirically. [ABSTRACT FROM AUTHOR]

This article examines the case of Moms 4 Housing, a group of Black mothers who occupied a vacant house in Oakland, California as an attempt to advance a human right to housing. It argues that the U.S. penchant for rights discrimination, the idea that one must choose between whose and which rights matter, contributes to the need for a rhetorical strategy of rights-blurring. Building on previous scholarship that establishes a history of Black women connecting civil rights to human rights as a rhetorical strategy in the United States, this article explains how rights-blurring actually operates. It also demonstrates how this strategy functions in conversations about property rights in the United States and in the context of a twenty-first century direct-action protest. [ABSTRACT FROM AUTHOR]

BACKGROUND: Whole blood transfusion is associated with benefits including improved survival, coagulopathy, and decreased transfusion requirements. The majority of whole blood transfusion is in the form of low-titer O-positive whole blood (LTOWB). Practice at many trauma centers withholds the use of LTOWB in women of childbearing potential due to concerns of alloimmunization. The purpose of this article is to review the evidence for LTOWB transfusion in female trauma patients and generate guidelines for its application. STUDY DESIGN: Literature and evidence for LTOWB transfusion in hemorrhagic shock are reviewed. The rates of alloimmunization and subsequent obstetrical outcomes are compared to the reported outcomes of LTOWB vs other resuscitation media. Literature regarding patient experiences and preferences in regards to the risk of alloimmunization is compared to current trauma practices. RESULTS: LTOWB has shown improved outcomes in both military and civilian settings. The overall risk of alloimmunization for Rhesus factor (Rh)- female patients in hemorrhagic shock exposed to Rh+ blood is low (3% to 20%). Fetal outcomes in Rh-sensitized patients are excellent compared to historical standards, and treatment options continue to expand. The majority of female patients surveyed on the risk of alloimmunization favor receiving Rh+ blood products to improve trauma outcomes. Obstetrical transfusion practices have incorporated LTOWB with excellent results. CONCLUSIONS: The use of whole blood resuscitation in trauma is associated with benefits in the resuscitation of severely injured patients. The rate at which severely injured, Rh-negative patients develop anti-D antibodies is low. Treatments for alloimmunized pregnancies have advanced, with excellent results. Fears of alloimmunization in female patients are likely overstated and may not warrant the withholding of whole blood resuscitation. The benefits of whole blood resuscitation likely outweigh the risks of alloimmunization. [ABSTRACT FROM AUTHOR]

Magnetic fields are now widely recognized as critical at many scales to galactic dynamics and structure, including multiphase pressure balance, dust processing, and star formation. Using imposed magnetic fields cannot reliably model the interstellar medium's (ISM) dynamical structure nor phase interactions. Dynamos must be modeled. ISM models exist of turbulent magnetic fields using small-scale dynamo (SSD). Others model the large-scale dynamo (LSD) organizing magnetic fields at the scale of the disk or spiral arms. Separately, neither can fully describe the galactic magnetic field dynamics nor topology. We model the LSD and SSD together at a sufficient resolution to use the low explicit Lagrangian resistivity required. The galactic SSD saturates within 20 Myr. We show that the SSD is quite insensitive to the presence of an LSD and is even stronger in the presence of a large-scale shear flow. The LSD grows more slowly in the presence of SSD, saturating after 5 Gyr versus 1–2 Gyr in studies where the SSD is weak or absent. The LSD primarily grows in warm gas in the galactic midplane. Saturation of the LSD occurs due to α -quenching near the midplane as the growing mean-field produces a magnetic α that opposes the kinetic α. The magnetic energy in our models of the LSD shows a slightly sublinear response to increasing resolution, indicating that we are converging toward the physical solution at 1 pc resolution. Clustering supernovae in OB associations increases the growth rates for both the SSD and the LSD, compared to a horizontally uniform supernova distribution. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the influence of children's autism characteristics, sensory profiles and feeding difficulties on caregiver‐reported impact at mealtimes. Background: Caregivers of children (5–12 years) with a diagnosis of Autism Spectrum Disorder completed an online survey examining (a) demographic characteristics, (b) children's autism characteristics (Social Communication Questionnaire), (c) sensory profiles (Sensory Profile 2–short form), (d) feeding difficulties (Behavioural Paediatrics Feeding Assessment Scale, BPFAS) and (c) caregiver‐reported impact of feeding difficulties (Feeding‐Swallowing Impact Survey, FS‐IS). Results: Seventy‐eight caregivers completed surveys for 80 children. Children with clinically significant feeding difficulties on the BPFAS (n = 55, 68.8%) had higher levels of caregiver‐reported impact on daily activities, worry and feeding difficulties compared to children without clinically significant feeding difficulties (FS‐IS; U = 257.000, z = −4.471, p < 0.01). Spearman's rank correlation showed a statistically significant, moderate correlation between BPFAS total frequency score and FS‐IS Daily activities score, rs (98) = 0.56, p < 0.01, indicating that as the frequency of feeding difficulties increased, the impact of these feeding difficulties on caregivers also increased. Using multiple regression, a model comprising of the three factors was statistically significant (F[1, 78] = 87.75, p < 0.001, adj. R2 = 0.52), with children's frequency of feeding difficulties the strongest predictor of caregiver‐reported impact with a moderate effect size (r = 0.49). Conclusion: Autistic children's feeding difficulties had a greater impact on caregivers than autism or sensory profiles, with the frequency of feeding difficulties and the caregiver impact of these feeding difficulties positively correlated. The findings demonstrate that efforts to understand and address feeding difficulties in autistic children must extend beyond the children to include their families. [ABSTRACT FROM AUTHOR]

C11-oxy C19 and C11-oxy C21 steroids have been identified as novel steroids but their function remains unclear. This study aimed to investigate the pre-receptor regulation of C11-oxy steroids by 11β-hydroxysteroid dehydrogenase (11βHSD) interconversion and potential agonist and antagonist activity associated with the androgen (AR) and progesterone receptors (PRA and PRB). Steroid conversions were investigated in transiently transfected HEK293 cells expressing 11βHSD1 and 11βHSD2, while CV1 cells were utilised for agonist and antagonist assays. The conversion of C11-hydroxy steroids to C11-oxo steroids by 11βHSD2 occurred more readily than the reverse reaction catalysed by 11βHSD1, while the interconversion of C11-oxy C19 steroids was more efficient than C11-oxy C21 steroids. Furthermore, 11-ketodihydrotestosterone (11KDHT), 11-ketotestosterone (11KT) and 11β-hydroxydihydrotestosterone (11OHDHT) were AR agonists, while only progestogens, 11β-hydroxyprogesterone (11βOHP4), 11β-hydroxydihydroprogesterone (11βOHDHP4), 11α-hydroxyprogesterone (11αOHP4), 11α-hydroxydihydroprogesterone (11αOHDHP4), 11-ketoprogesterone (11KP4), 5α-pregnan-17α-diol-3,11,20-trione (11KPdione) and 21-deoxycortisone (21dE) exhibited antagonist activity. C11-hydroxy C21 steroids, 11βOHP4, 11βOHDHP4 and 11αOHP4 exhibited PRA and PRB agonistic activity, while only C11-oxo steroids, 11KP4 and 11-ketoandrostanediol (11K3αdiol) demonstrated PRB agonism. While no steroids antagonised the PRA, 11OHA4, 11β-hydroxytestosterone (11OHT), 11KT and 11KDHT exhibited PRB antagonism. The regulatory role of 11βHSD isozymes impacting receptor activation is clear—C11-oxo androgens exhibit AR agonist activity; only C11-hydroxy progestogens exhibit PRA and PRB agonist activity. Regulation by the downstream metabolites of active C11-oxy steroids at the receptor level is apparent—C11-hydroxy and C11-oxo metabolites antagonize the AR and PRB, progestogens the former, androgens the latter. The findings highlight the intricate interplay between receptors and active as well as "inactive" C11-oxy steroids, suggesting novel regulatory tiers. [ABSTRACT FROM AUTHOR]

This paper assesses the role of parental gifts in neighbourhood sorting among young adult homebuyers. We make use of high-quality individual-level registry data for two large urban metropolitan areas in the Netherlands. While previous studies have shown that young adults receiving gifts purchase more expensive housing, little is known about the role of gifts in where young adults buy. Our study finds that parental gifts flow into the housing market in a spatially-uneven way. Movers supported by substantial parental gifts are more likely to enter owner-occupied housing in high-status and gentrifying urban neighbourhoods compared to movers without gifts. This study shows that this can only partially be explained by household and parental characteristics and by the uneven distribution of housing values. The remaining effect suggests that parental gifts also play a role in trade-offs regarding spatial residential decision-making. The conclusion discusses the ramifications of our findings for debates on (re)production of class and intra-generational inequalities through housing, and provides avenues for further research. [ABSTRACT FROM AUTHOR]

The antimicrobial peptides SAAP-148 and Ab-Cath were encapsulated in oleyl-modified hyaluronic acid (OL-HA) nanogels to improve these peptides' selectivity index. The physicochemical properties, antimicrobial activity, and cytotoxicity of the AMP-loaded OL-HA nanogels were studied in vitro. Results showed good physicochemical properties of the nanogels; polydisperse nanogels (PDI=0.2) ranging in size from 181 to 206 nm, with high negative surface charge (−47 to −48 mV) and moderate encapsulation efficiency (EE=53–63%). Encapsulation of SAAP-148 or Ab-Cath in nanogels maintained antimicrobial activity against antimicrobial resistant Staphylococcus aureus and Acinetobacter baumannii , while reducing the peptides' hemolytic activity against human erythrocytes and cytotoxicity against human primary skin fibroblasts. Thus, encapsulation in OL-HA nanogels improved the overall selectivity index of SAAP-148 and Ab-Cath and their potential as therapeutics to combat AMR bacterial infections. [Display omitted] Antimicrobial peptides (AMPs) are promising alternatives to antibiotics for treatment of antimicrobial resistant (AMR) bacterial infections. However, their narrow therapeutic window due to in vivo toxicity and limited stability hampers their clinical use. Here, we evaluated encapsulation of two amphiphilic AMPs, SAAP-148 and snake cathelicidin Ab-Cath, into oleyl-modified hyaluronic acid (OL-HA) nanogels to improve their selectivity index. The AMP-loaded OL-HA nanogels ranged 181–206 nm in size with a PDI of 0.2, highly negative surface charge (−47 to −48 mV) and moderate encapsulation efficiency (53–63%). The AMP-loaded OL-HA nanogels displayed similar activity in vitro as AMP solutions against AMR Staphylococcus aureus and Acinetobacter baumannii , with a dose-dependent effect over time. Importantly, the AMP-loaded OL-HA nanogels showed decreased cytotoxicity towards human erythrocytes and primary skin fibroblast, thereby improving the selectivity index of SAAP-148 and Ab-Cath by 2- and 16.8-fold, respectively. Particularly, the selectivity of Ab-Cath-loaded OL-HA nanogels has great clinical potential, with an index that reached ≥ 300 for S. aureus and ≥ 3000 for A. baumannii. These findings indicate that OL-HA nanogels are a promising drug delivery system to reduce the cytotoxicity of AMPs without substantially affecting their antimicrobial activity, thereby increasing their selectivity index and potential as therapeutics to combat AMR bacterial infections. [ABSTRACT FROM AUTHOR]

The editorial in the "Proceedings of the Institution of Civil Engineers: Bridge Engineering" focuses on managing and preserving historic bridges and structures worldwide. It emphasizes the importance of sharing knowledge and experience to meet the demands of traffic while preserving culturally significant historical fabric. The issue includes papers on rehabilitation of historic bridges, bridge engineering challenges, and asset management strategies. The papers cover topics such as bridge scour, modular construction, fatigue of steel decks, and seismic performance of bridge piers, offering valuable insights for the conservation and service life extension of bridge assets. [Extracted from the article]

In this work we consider a generalization of graph flows. A graph flow is, in its simplest formulation, a labelling of the directed edges with real numbers subject to various constraints. A common constraint is conservation in a vertex, meaning that the sum of the labels on the incoming edges of this vertex equals the sum of those on the outgoing edges. One easy fact is that if a flow is conserving in all but one vertex, then it is also conserving in the remaining one. In our generalization we do not label the edges with real numbers, but with elements from an arbitrary group, where this fact becomes false in general. As we will show, graphs with the property that conservation of a flow in all but one vertex implies conservation in all vertices are precisely the planar graphs. [ABSTRACT FROM AUTHOR]

• eHMIs reduced response times compared to no eHMI. • The flash eHMI was effective in attracting and subsequently releasing attention. • Gaze-contingent window negatively affected response times and saccades. • Variations in light intensity confound pupil diameter as a measure of mental workload. • Study highlights the importance of considering peripheral vision in eHMI design. Automated vehicles need to prioritize pedestrian safety. One way to achieve this is through external human–machine interfaces (eHMIs) that send visual signals to pedestrians. eHMIs can be either text-based or light-based. However, there has been limited research on the effects of these types of eHMI on human information processing and attention allocation. This study aimed to fill this gap by using a gaze-contingent approach, which blurs the view outside a circular aperture, to test the hypothesis that text-based eHMIs, which require focused or foveal attention, result in longer response times compared to light-based eHMIs, which can be understood using peripheral vision. In this study, 23 participants watched animated video clips of traffic situations involving automated vehicles with either no eHMI, a flashing-light eHMI, or a text-based eHMI. Their eye movements were tracked, and they were asked to press the spacebar when they felt it was safe to cross the road. The results showed faster response times when an eHMI was present, with no significant difference between the two types of eHMIs. Further analysis suggested that the flashing-light eHMI captured attention briefly, while the text-based eHMI held attention for a longer period. When no eHMI was present, participants focused on the approaching vehicle for the longest time. The gaze-contingent window resulted in fewer eye movements and slower response times. In conclusion, the study showed that the gaze-contingent window negatively affected response times and eye movements, emphasizing the importance of considering peripheral vision when designing eHMIs for pedestrian safety. [ABSTRACT FROM AUTHOR]

To compare the effectiveness and safety of Dinoprostone Gel (DG), Misoprostol Vaginal Insert (MVI) and Dinoprostone Vaginal Insert (DVI) for induction of labour (IOL) in twin pregnancies. Retrospective cohort study of twin pregnancies > 34 + 0 weeks gestation that underwent induction of labour (IOL) with DG, MVI or DVI between December 2016 and November 2019 in a Tertiary NHS hospital, North West England, UK. Delivery characteristics, maternal complications and neonatal outcomes were compared between the three groups. A total of 87 twin pregnancies were included for analysis. 27 women received DG, 34 received MVI and 26 DVI. The MVI cohort had a higher proportion of nulliparous women (55.9%) compared to the DG and DVI cohorts, 29.6% and 38.5% respectively. No other differences amongst demographic characteristics were considered clinically significant. DG demonstrated a significantly quicker time to delivery (minutes) compared to DVI (1021 ± 556 versus 1649 ± 852; P = 0.0026). Significantly fewer women required terbutaline for hyperstimulation/tachysystole in the DG group compared to MVI (0% vs 32%; RR 0.05; 95% CI 0.003–0.88). Both DG and MVI groups required significantly less oxytocin following artificial rupture of membranes compared to DVI (33% vs 65%; RR 0.51; 95% CI 0.28–0.93) and (29% vs 65%; RR 0.45; 95% CI 0.25–0.81). There were no significant differences in mode of delivery, maternal complications and neonatal outcomes. Our data suggests that for women with a twin pregnancy considering a planned labour that induction with DG, MVI and DVI appear to be equally safe and effective IOL methods. These results should be interpreted with caution due to the study being underpowered to detect significant adverse outcomes. In order to determine the optimal method of IOL in twins, direct randomised comparison is needed. [ABSTRACT FROM AUTHOR]

Background: Trigeminal ganglia (TG) neurons are an important site of lifelong latent varicella-zoster virus (VZV) infection. Although VZV-specific T-cells are considered pivotal to control virus reactivation, their protective role at the site of latency remains uncharacterized. Methods: Paired blood and TG specimens were obtained from ten latent VZV-infected adults, of which nine were co-infected with herpes simplex virus type 1 (HSV-1). Short-term TG-derived T-cell lines (TG-TCL), generated by mitogenic stimulation of TG-derived T-cells, were probed for HSV-1- and VZV-specific T-cells using flow cytometry. We also performed VZV proteome-wide screening of TG-TCL to determine the fine antigenic specificity of VZV reactive T-cells. Finally, the relationship between T-cells and latent HSV-1 and VZV infections in TG was analyzed by reverse transcription quantitative PCR (RT-qPCR) and in situ analysis for T-cell proteins and latent viral transcripts. Results: VZV proteome-wide analysis of ten TG-TCL identified two VZV antigens recognized by CD8 T-cells in two separate subjects. The first was an HSV-1/VZV cross-reactive CD8 T-cell epitope, whereas the second TG harbored CD8 T-cells reactive with VZV specifically and not the homologous peptide in HSV-1. In silico analysis showed that HSV-1/VZV cross reactivity of TG-derived CD8 T-cells reactive with ten previously identified HSV-1 epitopes was unlikely, suggesting that HSV-1/VZV cross-reactive T-cells are not a common feature in dually infected TG. Finally, no association was detected between T-cell infiltration and VZV latency transcript abundance in TG by RT-qPCR or in situ analyses. Conclusions: The low presence of VZV- compared to HSV-1-specific CD8 T-cells in human TG suggests that VZV reactive CD8 T-cells play a limited role in maintaining VZV latency. [ABSTRACT FROM AUTHOR]

Background and Objectives: Blood group O contains lower levels of factor VIII and von Willebrand factor. Higher incidence of bleeding among group O is reported in multiple contexts. Results of studies vary regarding outcomes stratified by blood group in trauma. We systematically reviewed the literature for outcomes related to blood group in trauma patients. Meta‐analysis of studies evaluating mortality related to blood group was performed. Materials and Methods: The PubMed and Embase databases were searched for studies analysing relationships between blood group and outcomes in trauma patients. Preferred Reporting Items in Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed. We synthesized outcomes data related to blood group. Meta‐analysis compared mortality rates between group O and non‐O patients. Results: Inclusion criteria were met by 13 studies. Statistically significant differences by blood group were reported in 3 of 10 (30%) studies evaluating mortality, 2 of 3 (66.7%) evaluating mortality from haemorrhage and 2 of 9 (22.2%) evaluating transfusion requirement. Meta‐analysis was performed on seven studies evaluating mortality (total n = 11,835). There was significant heterogeneity among studies (I2 = 86%, p < 0.00001). No difference was found in mortality between group O and non‐O patients (relative risk = 1.21, 95% confidence interval = 0.89–1.64, p = 0.23). Conclusion: Existing literature does not consistently demonstrate a mortality difference between trauma patients with O and non‐O blood groups. High variability in the methods and results among studies limits this conclusion, and further research is needed to delineate under what circumstances blood group may influence outcomes. [ABSTRACT FROM AUTHOR]

Triple-crossover randomized controlled intervention trial to test whether reduced exposure to household NO2 or fine particles results in reduced symptoms among children with persistent asthma. Children (n = 126) aged 5–11 years with persistent asthma living in homes with gas stoves and levels of NO2 15 ppb or greater recruited in Connecticut and Massachusetts (2015–2019) participated in an intervention involving three air cleaners configured for: (1) NO2 reduction: sham particle filtration and real NO2 scrubbing; (2) particle filtration: HEPA filter and sham NO2 scrubbing; (3) control: sham particle filtration and sham NO2 scrubbing. Air cleaners were randomly assigned for 5-week treatment periods using a three-arm crossover design. Outcome was number of asthma symptom-days during final 14 days of treatment. Treatment effects were assessed using repeated measures, linear mixed models. Measured NO2 was lower (by 4 ppb, p <.0001) for NO2-reducing compared to control or particle-reducing treatments. NO2-reducing treatment did not reduce asthma morbidity compared to control. In analysis controlling for measured NO2, there were 1.8 (95% CI −0.3 to 3.9, p =.10) fewer symptom days out of 14 in the particle-reducing treatment compared to control. It remains unknown if using an air cleaner alone can achieve levels of NO2 reduction large enough to observe reductions in asthma symptoms. We observed that in small, urban homes with gas stoves, modest reductions in asthma symptoms occurred using air cleaners that remove fine particles. An intervention targeting exposures to both NO2 and fine particles is complicated and further research is warranted. NCT02258893. [ABSTRACT FROM AUTHOR]

BACKGROUND: The recent pandemic exposed a largely unrecognized threat to medical resources, including daily available blood products. Some of the most severely injured patients who arrive in extremis consume tremendous resources yet succumb shortly after arrival. We sought to identify cut points available early in the patient's resuscitation that predicted 100% mortality. STUDY DESIGN: Cut points were developed from a previously collected data set of all level 1 trauma patients admitted January 2010 to December 2016. Objective values available on or shortly after arrival were evaluated. Once generated, we then validated these variables against (1) a prospective data set November 2017 to October 2021 of severely injured patients and (2) a multicenter, randomized trial of hemorrhagic shock patients. Analyses were conducted using STATA 17.0 (College Station, TX), generating positive predictive value (PPV), negative predictive value, sensitivity, and specificity. RESULTS: The development data set consisted of 9,509 patients (17% mortality), with 2,137 (24%) and 680 (24%) in the two validation data sets. Several combinations of arrival vitals and labs had 100% PPV. Patients undergoing CPR in the field or on arrival (with subsequent return of spontaneous circulation) required lower fibrinolysis LY-30 (30%) than those with systolic blood pressures of ≤50 (30 to 50%), ≤70 (80 to 90%), and ≤90 mmHg (90%). Using a combination of these validated variables, the Suspension of Transfusions and Other Procedures (STOP) criteria were developed, with each element predicting 100% mortality, allowing physicians to cease further resuscitative efforts. CONCLUSIONS: The use of evidence-based STOP criteria provides cut points of futility to help guide early decisions for discontinuing aggressive treatment of severely injured patients arriving in extremis. [ABSTRACT FROM AUTHOR]

Chronic wound infections colonized by bacteria are becoming more difficult to treat with current antibiotics due to the development of antimicrobial resistance (AMR) as well as biofilm and persister cell formation. Synthetic antibacterial and antibiofilm peptide (SAAP)-148 is an excellent alternative for treatment of such infections but suffers from limitations related to its cationic peptidic nature and thus instability and possible cytotoxicity, resulting in a narrow therapeutic window. Here, we evaluated SAAP-148 encapsulation in nanogels composed of octenyl succinic anhydride (OSA)-modified hyaluronic acid (HA) to circumvent these limitations. SAAP-148 was efficiently (>98%) encapsulated with high drug loading (23%), resulting in monodispersed anionic OSA-HA nanogels with sizes ranging 204–253 nm. Nanogel lyophilization in presence of polyvinyl alcohol maintained their sizes and morphology. SAAP-148 was sustainedly released from lyophilized nanogels (37–41% in 72 h) upon reconstitution. Lyophilized SAAP-148-loaded nanogels showed similar antimicrobial activity as SAAP-148 against planktonic and biofilm-residing AMR Staphylococcus aureus and Acinetobacter baumannii. Importantly, formulated SAAP-148 showed reduced cytotoxicity against human erythrocytes, primary human skin fibroblasts and human keratinocytes. Additionally, lyophilized SAAP-148-loaded nanogels eradicated AMR S. aureus and A. baumannii colonizing a 3D human epidermal model, without inducing any cytotoxicity in contrast to SAAP-148. These findings indicate that OSA-HA nanogels increase SAAP-148′s therapeutic potential for treatment of skin wound infections. [ABSTRACT FROM AUTHOR]

Synthetic antimicrobial and antibiofilm peptide (SAAP-148) commits significant antimicrobial activities against antimicrobial resistant (AMR) planktonic bacteria and biofilms. However, SAAP-148 is limited by its low selectivity index, i.e., ratio between cytotoxicity and antimicrobial activity, as well as its bioavailability at infection sites. We hypothesized that formulation of SAAP-148 in PLGA nanoparticles (SAAP-148 NPs) improves the selectivity index due to the sustained local release of the peptide. The aim of this study was to investigate the physical and functional characteristics of SAAP-148 NPs and to compare the selectivity index of the formulated peptide with that of the peptide in solution. SAAP-148 NPs displayed favorable physiochemical properties [size = 94.1 ± 23 nm, polydispersity index (PDI) = 0.08 ± 0.1, surface charge = 1.65 ± 0.1 mV, and encapsulation efficiency (EE) = 86.7 ± 0.3%] and sustained release of peptide for up to 21 days in PBS at 37 °C. The antibacterial and cytotoxicity studies showed that the selectivity index for SAAP-148 NPs was drastically increased, by 10-fold, regarding AMR Staphylococcus aureus and 20-fold regarding AMR Acinetobacter baumannii after 4 h. Interestingly, the antibiofilm activity of SAAP-148 NPs against AMR S. aureus and A. baumannii gradually increased overtime, suggesting a dose–effect relationship based on the peptide's in vitro release profile. Using 3D human skin equivalents (HSEs), dual drug SAAP-148 NPs and the novel antibiotic halicin NPs provided a stronger antibacterial response against planktonic and cell-associated bacteria than SAAP-148 NPs but not halicin NPs after 24 h. Confocal laser scanning microscopy revealed the presence of SAAP-148 NPs on the top layers of the skin models in close proximity to AMR S. aureus at 24 h. Overall, SAAP-148 NPs present a promising yet challenging approach for further development as treatment against bacterial infections. [ABSTRACT FROM AUTHOR]

To better address twenty-first-century challenges, research institutions often develop and publish research impact strategies, but as a tool, impact strategies are poorly understood. This study provides the first formal analysis of impact strategies from the UK, Canada, Australia, Denmark, New Zealand and Hong Kong, China, and from independent research institutes. Two types of strategy emerged. First, ‘achieving impact’ strategies tended to be bottom-up and co-productive, with a strong emphasis on partnerships and engagement, but they were more likely to target specific beneficiaries with structured implementation plans, use boundary organisations to co-produce research and impact, and recognise impact with less reliance on extrinsic incentives. Second, ‘enabling impact’ strategies were more topdown and incentive-driven, developed to build impact capacity and culture across an institution, faculty or centre, with a strong focus on partnerships and engagement, and they invested in dedicated impact teams and academic impact roles, supported by extrinsic incentives including promotion criteria. This typology offers a new way to categorise, analyse and understand research impact strategies, alongside insights that may be used by practitioners to guide the design of future strategies, considering the limitations of top-down, incentive-driven approaches versus more bottom-up, co-productive approaches. [ABSTRACT FROM AUTHOR]

Objectives: Ovarian cancer has the worst overall survival rate of all gynecologic malignancies. For the majority of patients, the 5-year overall survival rate of less than 50% has hardly improved over the last decades. To improve the outcome of patients with all subtypes of ovarian cancer, large-scale fundamental and translational research is needed. To accommodate these types of ovarian cancer research, we have established a Dutch nationwide, interdisciplinary infrastructure and biobank: the Archipelago of Ovarian Cancer Research (AOCR). The AOCR will facilitate fundamental and translational ovarian cancer research and enhance interdisciplinary, national and international collaboration.Design: The AOCR biobank is a prospective ovarian cancer biobank in which biomaterials are collected, processed and stored in a uniform matter for future (genetic) scientific research. All 19 Dutch hospitals in which ovarian cancer surgery is performed participate and collaborate in the AOCR biobank.Participants/materials, Setting, Methods: Patients of 16 years and older with suspected or diagnosed ovarian, Fallopian tube or primary peritoneal cancer are recruited for participation. Patients who agree to participate give written informed consent for collection, storage and issue of their biomaterials for future studies. After inclusion, different blood samples are taken at various predefined time points both before and during treatment. In case of a diagnostic paracentesis or biopsy, the residual biomaterials of these procedures are stored in the biobank. During surgery, primary tumor tissue and, if applicable, tissue from metastatic sites are collected and stored. From each patient, a representative histological hematoxylin and eosin stained slide is digitalized for research purposes, including reassessment by a panel of gynecologic pathologists. Clinical and pathological data are obtained on a per-study basis from Dutch registries. Research proposals for the issue of biomaterials and data are evaluated by both the Archipelago Scientific Committee and the Steering Committee. Researchers using the biomaterials from the AOCR biobank are encouraged to enrich the biobank with data and materials resulting from their analyses and experiments.Limitations: The implementation and first four years of collection are financed by an infrastructural grant from the Dutch Cancer Society. Therefore, the main limitation is that the costs for sustaining the biobank after the funding period will have to be covered. This coverage will come from incorporation of budget for biobanking in future grant applications and from fees from external researchers and commercial parties using the biomaterials stored in the AOCR biobank. Moreover, we will apply for grants aimed at sustaining and improving research infrastructures and biobanks.Conclusions: With the establishment of the Dutch nationwide, interdisciplinary Archipelago of Ovarian Cancer Research infrastructure and biobank, fundamental and translational research on ovarian cancer can be greatly improved. The ultimate aim of this infrastructure is that it will lead to improved diagnostics, treatment and survival of patients with ovarian cancer. [ABSTRACT FROM AUTHOR]

In this article we rely on accent evaluation to test the 'intersectional invisibility hypothesis'1 that social cognition about men (but not women) is overrepresented in group-level beliefs.2 As a case in point, we investigate the evaluation of male and female Moroccan accents to gain insight into impression formation of Muslims in the Netherlands, and to find out whether stereotypical qualities associated with Moroccan-Dutch people, such as aggressive, macho, and criminal, are in fact associated with Moroccan-Dutch men. Two matched-guise experiments featuring regional and ethnic accents of Dutch (one with male speakers, one with female speakers) confirm the intersectional invisibility hypothesis, but the inclusion of traditional and modern prestige measures in accent evaluation research results in arguably richer stereotype and prejudice accounts, and in this sense, the present investigation adds nuance and shade to Gloria Wekker's (2016) pessimistic account of racism in Dutch society. Male Moroccan-Dutch speech is strongly deprecated and is always deemed inferior to indigenous speech; at the same time it is also found to be the most dynamically prestigious of all accents. Female Moroccan-Dutch speech does not engender extreme reactions, but it is not regarded as dynamic either and a long way from being accepted as indigenous speech. [ABSTRACT FROM AUTHOR]

Demethylation of transposons can activate the expression of nearby genes and cause imprinted gene expression in the endosperm; this demethylation is hypothesized to lead to expression of transposon small interfering RNAs (siRNAs) that reinforce silencing in the next generation through transfer either into egg or embryo. Here we describe maize (Zea mays) maternal derepression of r1 (mdr1), which encodes a DNA glycosylase with homology to Arabidopsis thaliana DEMETER and which is partially responsible for demethylation of thousands of regions in endosperm. Instead of promoting siRNA expression in endosperm, MDR1 activity inhibits it. Methylation of most repetitive DNA elements in endosperm is not significantly affected by MDR1, with an exception of Helitrons. While maternally-expressed imprinted genes preferentially overlap with MDR1 demethylated regions, the majority of genes that overlap demethylated regions are not imprinted. Double mutant megagametophytes lacking both MDR1 and its close homolog DNG102 result in early seed failure, and double mutant microgametophytes fail pre-fertilization. These data establish DNA demethylation by glycosylases as essential in maize endosperm and pollen and suggest that neither transposon repression nor genomic imprinting is its main function in endosperm. [ABSTRACT FROM AUTHOR]

Trabectedin is a chemotherapeutic used to treat advanced soft tissue sarcoma and relapsed platinum-sensitive ovarian cancer. Although it is associated with a low incidence of cardiotoxicity, when this occurs it can be fatal or significantly compromise the quality of life in patients with advanced cancer. Here, we present a series of 4 cases where trabectedin-treated sarcoma patients developed cardiovascular complications. Similar to previous literature describing this association, all patients had prior treatment with anthracyclines and presented at different time points following treatment initiation. Each patient presented with exertional breathlessness and was found to have severely impaired left ventricular systolic function (ejection fraction ≤35%), and 1 patient had concurrent atrial fibrillation with a fast ventricular rate. All of the patients were treated with neurohormonal blockade, and a multi-disciplinary decision was made to stop trabectedin in 3 patients and continue in 1 patient. Two of the 4 patients had an improvement in their left ventricular systolic function. It is unclear what effect preceeding anthracycline or tyrosine kinase inhibitor treatment has in priming patients to develop cardiotoxicity in this setting. Our case series adds to the evidence surrounding this association and highlights that trabectedin-associated cardiotoxicity can present in an insidious fashion. [ABSTRACT FROM AUTHOR]

Introduction: Ultrasound is the examination of choice for the diagnosis of hypertrophic pyloric stenosis (HPS). A correct diagnosis is dependent on the technique and measurement accuracy. However, in the world literature there is a wide range of values suggested for the diagnosis of this condition. The current minimum measurements used to diagnose HPS seem excessively large, and therefore, we set out to redefine these values. Methods: A retrospective study was performed on 607 patients (615 scans) being investigated for HPS. The length and transverse diameter of the pyloric canal, and thickness of the pyloric muscle were measured. All results were correlated with clinical and surgical findings. Results: In this study, the muscle thickness in the normal group was <2.0 mm than in HPS infants having a muscle thickness of 2.0–5.0 mm. All the pyloric canal lengths in the normal group were <5.0 mm than in those with HPS having a length of 10.0–24.0 mm. The transverse diameters ranged from 6.0 to 11.0 mm in the normal group compared with those with HPS having a diameter between 8.0 and 16.0 mm. Conclusions: The current criteria for sonographic diagnosis of HPS should be redefined. The canal length is the single most important discriminator, with a clear separation between normal and abnormal. The commonly used 16.0‐mm measurement is too long and should be reduced to 10.0 mm (without the risk of false positives). In many cases, the muscle thickness in those with HPS is as low as 2.0 mm, considerably less than the 3.0 mm that is currently used. The transverse diameter is not a useful discriminator for HPS. The use of current values will delay the diagnosis and timely treatment of this condition. [ABSTRACT FROM AUTHOR]

One-step RT-qPCR TaqMan assays have been developed for six plant viruses with considerable economic impact in the growing of tulip and lily bulbs: lily mottle virus, lily symptomless virus, lily virus X, Plantago asiatica mosaic virus, tulip breaking virus and tulip virus X. To enhance efficacy and cost-efficiency these assays were combined into multiplex panels. Four different multiplex panels were designed, each consisting of three virus assays and an adapted assay for the housekeeping gene nad5 of lilies and tulips, that acts as an internal amplification control. To eliminate false negative results due to variation in the viral genome sequences, for each target virus two assays were developed on distinct conserved genomic regions. Specificity, PCR efficiency and compatibility of primers and probes were tested using gBlock constructions. Diagnostic samples were used to evaluate the strategy. High Throughput Sequencing of a set of the diagnostic samples, further verified the presence or absence of the viruses in the RNA samples and sequence variations in the target genes. This interchangeable multiplex panel strategy may be a valuable tool for the detection of viruses in certification, surveys and virus diagnostics. [Display omitted] • Development of interchangeable multiplex panels for One-step RT-qPCR TaqMan assays. • Use of two target genes decreases false negative results for virus detection. • DNA gBlocks used for target quantification. • Plant host specific internal RNA amplification control. • HTS conformation clarify discord between different RT-qPCR assays for the same virus. [ABSTRACT FROM AUTHOR]

A male in his 40s presented to the trauma center via air ambulance after colliding with a cement wall at highway speeds. Cross-sectional imaging revealed a right ventricular pseudoaneurysm, confirmed by echocardiography. He was taken emergently to the operating room where he was found to have a pericardial laceration, hemopericardium and a right ventricular rupture, which was primarily repaired. Postoperatively, the patient was transferred to intensive care and after 34 days in the hospital was ultimately discharged home. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that the signaling activity of the cytosolic pathogen sensor retinoic acid-inducible gene-I (RIG-I) is modulated by a variety of posttranslational modifications (PTMs) to fine-tune the antiviral type I interferon (IFN) response. Whereas K63-linked ubiquitination of the RIG-I caspase activation and recruitment domains (CARDs) catalyzed by TRIM25 or other E3 ligases activates RIG-I, phosphorylation of RIG-I at S8 and T170 represses RIG-I signal transduction by preventing the TRIM25-RIG-I interaction and subsequent RIG-I ubiquitination. While strategies to suppress RIG-I signaling by interfering with its K63-polyubiquitin-dependent activation have been identified for several viruses, evasion mechanisms that directly promote RIG-I phosphorylation to escape antiviral immunity are unknown. Here, we show that the serine/threonine (Ser/Thr) kinase US3 of herpes simplex virus 1 (HSV-1) binds to RIG-I and phosphorylates RIG-I specifically at S8. US3-mediated phosphorylation suppressed TRIM25-mediated RIG-I ubiquitination, RIG-I-MAVS binding, and type I IFN induction. We constructed a mutant HSV-1 encoding a catalytically-inactive US3 protein (K220A) and found that, in contrast to the parental virus, the US3 mutant HSV-1 was unable to phosphorylate RIG-I at S8 and elicited higher levels of type I IFNs, IFN-stimulated genes (ISGs), and proinflammatory cytokines in a RIG-I-dependent manner. Finally, we show that this RIG-I evasion mechanism is conserved among the alphaherpesvirus US3 kinase family. Collectively, our study reveals a novel immune evasion mechanism of herpesviruses in which their US3 kinases phosphorylate the sensor RIG-I to keep it in the signaling-repressed state. IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes lifelong latency in the majority of the human population worldwide. HSV-1 occasionally reactivates to produce infectious virus and to facilitate dissemination. While often remaining subclinical, both primary infection and reactivation occasionally cause debilitating eye diseases, which can lead to blindness, as well as life-threatening encephalitis and newborn infections. To identify new therapeutic targets for HSV-1-induced diseases, it is important to understand the HSV-1-host interactions that may influence infection outcome and disease. Our work uncovered direct phosphorylation of the pathogen sensor RIG-I by alphaherpesvirus-encoded kinases as a novel viral immune escape strategy and also underscores the importance of RNA sensors in surveilling DNA virus infection. [ABSTRACT FROM AUTHOR]

Because many Americans' encounters with homelessness are limited to what they see in entertainment and news media, this study examines how those representations have changed over time through an analysis of 35 years of films about homelessness. Analyzing the ways that homelessness appears in film advances our understanding of the role of the public screen in contemporary political life. We argue here that rhetoricians would benefit from considering the public screen a contextual field and expanding what this field includes. Additionally, we identify two key dimensions of the likely contextual fields audiences may draw on in subsequent public deliberation about homelessness—visibility and agency—and offer an approach to the rhetorical analysis of film that can illuminate such fields for a wide array of social and political issues. [ABSTRACT FROM AUTHOR]

With more than 3000 species, the jewel beetle genus Agrilus is considered the largest genus of the animal kingdom. Some of the species have been recognized as harmful to plants, but the majority of the genus remains unassessed. With A. planipennis it was found that, when introduced to a new environment, even (formerly) rare species only known to buprestid specialists can become invasive and cause enormous economic and environmental losses. One of the lesser‐known species is Agrilus dureli, which has recently been found causing an outbreak on Salix species in China, leading to extensive dieback of the infested trees. In this article, the risk of A. dureli to European and Mediterranean plants is assessed. [ABSTRACT FROM AUTHOR]