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Summary The vast amount of publicly available genomic data requires analysis and visualization tools. Here, we present figeno, an application for generating publication-quality FIgures for GENOmics. Figeno particularly focuses on multi-region views across genomic breakpoints and on long reads with base modifications. In addition, we support epigenomic data including ATAC-seq, ChIP-seq or HiC, as well as whole genome sequencing data with copy numbers and structural variants. Availability and implementation Figeno is available as a python package with both a command line and graphical user interface. It can be installed via PyPI and the source code is available at https://github.com/CompEpigen/figeno. [ABSTRACT FROM AUTHOR]

Fatty liver disease or the accumulation of fat in the liver, has been reported to affect the global population. This comes with an increased risk for the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Yet, little is known about the effects of a diet containing high fat and alcohol towards epigenetic aging, with respect to changes in transcriptional and epigenomic profiles. In this study, we took up a multi-omics approach and integrated gene expression, methylation signals, and chromatin signals to study the epigenomic effects of a high-fat and alcohol-containing diet on mouse hepatocytes. We identified four relevant gene network clusters that were associated with relevant pathways that promote steatosis. Using a machine learning approach, we predict specific transcription factors that might be responsible to modulate the functionally relevant clusters. Finally, we discover four additional CpG loci and validate aging-related differential CpG methylation. Differential CpG methylation linked to aging showed minimal overlap with altered methylation in steatosis. [ABSTRACT FROM AUTHOR]

Aim: Osteoporotic thoracolumbar fractures are of increasing importance. To identify the optimal treatment strategy this multicentre prospective cohort study was performed. Purpose: Patients suffering from osteoporotic thoracolumbar fractures were included. Excluded were tumour diseases, infections and limb fractures. Age, sex, trauma mechanism, OF classification, OF-score, treatment strategy, pain condition and mobilization were analysed. Methods: A total of 518 patients' aged 75 ± 10 (41–97) years were included in 17 centre. A total of 174 patients were treated conservatively, and 344 were treated surgically, of whom 310 (90%) received minimally invasive treatment. An increase in the OF classification was associated with an increase in both the likelihood of surgery and the surgical invasiveness. Results: Five (3%) complications occurred during conservative treatment, and 46 (13%) occurred in the surgically treated patients. 4 surgical site infections and 2 mechanical failures requested revision surgery. At discharge pain improved significantly from a visual analogue scale score of 7.7 (surgical) and 6.0 (conservative) to a score of 4 in both groups (p < 0.001). Over the course of treatment, mobility improved significantly (p = 0.001), with a significantly stronger (p = 0.007) improvement in the surgically treated patients. Conclusion: Fracture severity according to the OF classification is significantly correlated with higher surgery rates and higher invasiveness of surgery. The most commonly used surgical strategy was minimally invasive short-segmental hybrid stabilization followed by kyphoplasty/vertebroplasty. Despite the worse clinical conditions of the surgically treated patients both conservative and surgical treatment led to an improved pain situation and mobility during the inpatient stay to nearly the same level for both treatments. [ABSTRACT FROM AUTHOR]

Purpose: To measure the flexural strength and Weibull characteristics of aged and nonaged printed interim dental material fabricated with different layer thickness. Material and methods: Bars (25×2×2 mm) were additively fabricated by using a polymer printer (Asiga Max) and an interim resin (Nexdent C&B MFH). Specimens were fabricated with the same printing parameters and postprocessing procedures, but with 7 different layer thickness: 50 (control or 50‐G group), 10 (10‐G group), 25 (25‐G group), 75 (75‐G group), 100 (100‐G group), 125 (125‐G group), and 150 μm (150‐G group). Two subgroups were created: nonaged and aged subgroups (n = 10). A universal testing machine was selected to measure flexural strength. Two‐parameter Weibull distribution values were computed. Two‐way ANOVA and Tukey tests were selected for statistical evaluation of the data (α = 0.05). Results: Artificial aging methods (p < 0.001) were a significant predictor of the flexural strength computed. Aged specimens acquired less flexural strength than nonaged specimens. The Weibull distribution obtained the highest shape for nonaged 50‐G and 75‐G group specimens compared with those of other nonaged groups, while the Weibull distribution showed the highest shape for aged 125‐G specimens. Conclusions: The flexural strength of the additively fabricated interim material examined was not influenced by the layer thickness at which the specimens were fabricated; however, artificial aging techniques reduced its flexural strength. Aged specimens presented lower Weibull distribution values compared with nonaged specimens, except for the 125‐G specimens. [ABSTRACT FROM AUTHOR]

Dislocation networks have been demonstrated to substantially enhance functional properties. As-sintered samples are virtually devoid of dislocations, new innovative techniques for introducing sufficiently high dislocation densities into polycrystalline ceramics are needed. While dislocation-based plasticity at high temperatures has been demonstrated for a large range of ceramic single crystals, plasticity in polycrystals is much less understood. Here, we demonstrate plastic strains in excess of several % based on dislocation motion in polycrystalline SrTiO3 at ≈ 1100 °C with 3.9 µm grain size. Ultra-high voltage electron microscopy reveals an associated increase in dislocation density by three orders of magnitude. Achievable strain rates are comparable to creep-based mechanisms and much less sensitive to applied stress than observed for metals. A specialized testing protocol allows quantification of the deformability via stress exponent, activation volume and activation enthalpy giving additional quantification. In conjunction with TEM images, the mechanical data gives insight into the underlying mechanisms. [ABSTRACT FROM AUTHOR]

A perfluorocarbon (PFC) investigated for treatment of traumatic brain injury (TBI) delivers oxygen to support brain function, but causes transient thrombocytopenia. TBI can cause acute inflammation with resulting thrombocytopenia; an interaction between the PFC effects and TBI inflammation might exacerbate thrombocytopenia. Therefore, PFC effects on platelet (PLT) function and hemostasis in a lipopolysaccharide (LPS) model of inflammation in the baboon were studied. Animals were randomized to receive saline ±LPS, and ± one of two doses of PFC. PLT count, transmission electron microscopy, and microparticle populations were quantified at baseline (BL) and at 2, 24, 48, 72, and 96 hours; hemostatic parameters for aggregometry and for blood clotting were measured at baseline (BL) and days 3 and 4. Injection of vehicle and LPS caused thrombocytopenia within hours; PFCs caused delayed thrombocytopenia beginning 48 hours post-infusion. LPS+PFC produced a more prolonged PLT decline and decreased clot strength. LPS+PFC increased ADP-stimulated aggregation, but PFC alone did not. Microparticle abundance was greatest in the LPS+PFC groups. LPS+PFC caused diffuse microvascular hemorrhage and death in 2 of 5 baboons in the low dose LPS-PFC group and 2 of 2 in the high dose LPS-PFC group. Necropsy and histology suggested death was caused by shock associated with hemorrhage in multiple organs. Abnormal morphology of platelets and red blood cells were notable for PFC inclusions. In summary, PFC infusion caused clinically significant thrombocytopenia and exacerbated LPS-induced platelet activation. The interaction between these effects resulted in decreased hemostatic capacity, diffuse bleeding, shock and death. [ABSTRACT FROM AUTHOR]

Rapid densification of ceramics has been realized and its merits were demonstrated through multiple approaches out of which UHS and flash sintering attract recent attention. So far, however, scalability remains difficult. A rise in throughput and scalability is enabled by the introduction of blacklight sintering powered by novel light source technology. Intense illumination with photon energy above the bandgap (blacklight) allows high absorption efficiency and, hence, very rapid, contactless heating for all ceramics. While heating the ceramic directly with light without any furnace promises scalability, it simultaneously offers highly accurate process control. For the technology transfer to industry, attainable material quality needs to be assured. Here, we demonstrate the excellent microstructure quality of blacklight‐sintered ceramics observed with ultrahigh voltage electron microscopy revealing an option to tune nanoporosity. Moreover, we confirm that electronic, electron, oxygen, and lithium‐ion conductivities are equal to conventionally sintered ceramics. This gives the prospect of transmitting the merits of rapid densification to the scale of industrial kilns. [ABSTRACT FROM AUTHOR]

Experimental demonstrations of tunable correlation effects in magic-angle twisted bilayer graphene have put two-dimensional moiré quantum materials at the forefront of condensed-matter research. Other twisted few-layer graphitic structures, boron-nitride, and homo- or hetero-stacks of transition metal dichalcogenides (TMDs) have further enriched the opportunities for analysis and utilization of correlations in these systems. Recent experiments within the latter material class confirmed the relevance of many-body interactions and demonstrated the importance of their extended range. Since the interaction, its range, and the filling can be tuned experimentally by twist angle, substrate engineering and gating, we here explore Fermi surface instabilities and resulting phases of matter of hetero-bilayer TMDs. Using an unbiased renormalization group approach, we establish in particular that hetero-bilayer TMDs are platforms to realize topological superconductivity with winding number ∣ N ∣ = 4 . We show that this state reflects in pronounced experimental signatures, such as distinct quantum Hall features. [ABSTRACT FROM AUTHOR]

Background and aims: Treatment with tumor necrosis factor α (TNFα) antagonists in IBD patients suffers from primary non-response rates of up to 40%. Biomarkers for early prediction of therapy success are missing. We investigated the dynamics of gene expression and DNA methylation in blood samples of IBD patients treated with the TNF antagonist infliximab and analyzed the predictive potential regarding therapy outcome. Methods: We performed a longitudinal, blood-based multi-omics study in two prospective IBD patient cohorts receiving first-time infliximab therapy (discovery: 14 patients, replication: 23 patients). Samples were collected at up to 7 time points (from baseline to 14 weeks after therapy induction). RNA-sequencing and genome-wide DNA methylation data were analyzed and correlated with clinical remission at week 14 as a primary endpoint. Results: We found no consistent ex ante predictive signature across the two cohorts. Longitudinally upregulated transcripts in the non-remitter group comprised TH2- and eosinophil-related genes including ALOX15, FCER1A, and OLIG2. Network construction identified transcript modules that were coherently expressed at baseline and in non-remitting patients but were disrupted at early time points in remitting patients. These modules reflected processes such as interferon signaling, erythropoiesis, and platelet aggregation. DNA methylation analysis identified remission-specific temporal changes, which partially overlapped with transcriptomic signals. Machine learning approaches identified features from differentially expressed genes cis-linked to DNA methylation changes at week 2 as a robust predictor of therapy outcome at week 14, which was validated in a publicly available dataset of 20 infliximab-treated CD patients. Conclusions: Integrative multi-omics analysis reveals early shifts of gene expression and DNA methylation as predictors for efficient response to anti-TNF treatment. Lack of such signatures might be used to identify patients with IBD unlikely to benefit from TNF antagonists at an early time point. [ABSTRACT FROM AUTHOR]

Prenatal exposure to endocrine disrupting chemicals can interfere with development, and has been associated with social-cognitive functioning and adverse health outcomes later in life. Exposure-associated changes of DNA methylation (DNAm) patterns have been suggested as a possible mediator of this relationship. This study investigated whether prenatal low-dose exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) is associated with altered DNAm patterns across the genome in a Western urban-industrial population. In 142 mother-infant pairs from the Duisburg Birth Cohort Study, PCBs and PCDD/Fs levels were quantified from maternal blood during late pregnancy and associated with DNAm levels in cord blood using the Illumina EPIC beadchip. The epigenome-wide association studies (EWAS) identified 32 significantly differentially methylated positions (DMPs) and eight differentially methylated regions (DMRs) associated with six congeners of PCB and PCDD in females or males (FDRs < 0.05). DMPs and DMRs mapped to genes involved in neurodevelopment, gene regulation, and immune functioning. Weighted gene correlation network analysis (WGCNA) showed 31 co-methylated modules (FDRs < 0.05) associated with one congener of PCDF levels in females. Results of both analytical strategies indicate that prenatal exposure to PCBs and PCDD/Fs is associated with altered DNAm of genes involved in neurodevelopment, gene expression and immune functioning. DNAm and gene expression levels of several of these genes were previously associated with EDC exposure in rodent models. Follow-up studies will clarify whether these epigenetic changes might contribute to the origin for adverse mental and health outcomes. [ABSTRACT FROM AUTHOR]

We study competing orders of spinless fermions in the triangular-lattice Hubbard model with nearest-neighbor interaction. We calculate the effective, momentum-resolved two-particle vertex in an unbiased way in terms of the functional renormalization group method and compare two different schemes for the momentum discretization, one based on dividing the Fermi surface into patches and one based on a channel decomposition. We study attractive and repulsive nearest-neighbor interaction and find a competition of pairing and charge instabilities. In the attractive case, a Pomeranchuk instability occurs at Van Hove filling and f-wave and p-wave pairing emerge when the filling is reduced. In the repulsive case, we obtain a charge density wave at Van Hove filling and extended p-wave pairing with reduced filling. The p-wave pairing solution is doubly degenerate and can realize chiral p + i p superconductivity with different Chern numbers in the ground state. We discuss implications for strongly correlated spin-orbit coupled hexagonal electron systems such as moiré heterostructures. [ABSTRACT FROM AUTHOR]

Self-medication using alcohol is a common coping response among individuals dealing with trauma as is driving under the influence of alcohol (DUI). A common intervention for drivers convicted of DUI, is an alcohol ignition interlock device (IID)—which requires breath samples before starting the car. If the sample is above a predetermined limit (.025), the car will not start, thus preventing impaired driving. IIDs are an effective intervention to reduce rates of drinking and driving among high risk populations; however, limited research has examined how traumatic experiences may impact performance on IIDs. This study is an archival analysis of the Managing Heavy Drinking (MHD) study of drivers in New York state. The MHD is a comprehensive study of drivers convicted of a DUI from 2015–2020. Participants (N = 121) completed questionnaires and provided consent to retrieve information from interlock providers. Outcome variable included high BAC lockout ratios (number of high BAC lockouts [BAC>.08]/number of clean blows [BAC ≤.025]). Other variables included demographic variables, alcohol treatment history, trauma experiences, and prior DUI history. Variables were entered into a structural equation model. In the final structural model, pathways that demonstrated a p-value of greater than.10 were dropped from the model. This produced acceptable overall model fit statistics (χ2 = 27.059(10), p=.003; CFI =.900; NFI =.898; RMSEA =.063). A significant pathway was found from the trauma measure to alcohol use (β =.132), and from alcohol use to interlock performance (β =.636). However, no significant relationship was found between trauma and interlock performance other than through alcohol use. The current study provides a useful framework upon which to understand the role traumatic experiences have on alcohol IID performance. Traumatic experiences are in of themselves insufficient to impact IID performance directly, but it may indirectly impact IID performance through increasing alcohol use. [ABSTRACT FROM AUTHOR]

This study examined co-occurring psychosocial problems among 120 women living with HIV (WLWH) in Washington, DC, USA. Participants completed a demographic survey, PHQ-9 (depressive symptoms), the Life Stressor Checklist (stressful events) and the PCL-C (PTSD symptoms in civilian populations). We calculated descriptive statistics and chi-square solutions for participant demographics. Classes of trauma history were established using latent class analysis (LCA). Latent indicators were extracted from participant self-reported traumatic histories on the LSC-R. Traumatic events have been found to be predictive of both depression. Latent class solution selection was guided by utility in evaluating and discriminating between classes as predictors of scales measuring depression or trauma exposure. Three distinct classes of trauma histories were identified: a high trauma (HT) class, an abuse/neglect (AN) class and a childhood trauma (CT) class. Binary logistic regression analyses determined whether trauma profiles predicted depression or PTSD after controlling for age, marital status, race and education. Participants in both the AN and CT class were over five times more likely than those in the HT class to endorse depressive symptoms. Classes differed significantly on whether they endorse depressive symptoms (p =.008) and marital status (p =.009), while PTSD appeared to trend toward significance (p =.085). [ABSTRACT FROM AUTHOR]

Background: Promoter methylation of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) is an acknowledged predictive epigenetic marker in glioblastoma multiforme and anaplastic astrocytoma. Patients with methylated CpGs in the MGMT promoter benefit from treatment with alkylating agents, such as temozolomide, and show an improved overall survival and progression-free interval. A precise determination of MGMT promoter methylation is of importance for diagnostic decisions. We experienced that different methods show partially divergent results in a daily routine. For an integrated neuropathological diagnosis of malignant gliomas, we therefore currently apply a combination of methylation-specific PCR assays and pyrosequencing. Results: To better rationalize the variation across assays, we compared these standard techniques and assays to deep bisulfite sequencing results in a cohort of 80 malignant astrocytomas. Our deep analysis covers 49 CpG sites of the expanded MGMT promoter, including exon 1, parts of intron 1 and a region upstream of the transcription start site (TSS). We observed that deep sequencing data are in general in agreement with CpG-specific pyrosequencing, while the most widely used MSP assays published by Esteller et al. (N Engl J Med 343(19):1350–1354, 2000. https://doi.org/10.1056/NEJM200011093431901) and Felsberg et al. (Clin Cancer Res 15(21):6683–6693, 2009. https://doi.org/10.1158/1078-0432.CCR-08-2801) resulted in partially discordant results in 22 tumors (27.5%). Local deep bisulfite sequencing (LDBS) revealed that CpGs located in exon 1 are suited best to discriminate methylated from unmethylated samples. Based on LDBS data, we propose an optimized MSP primer pair with 83% and 85% concordance to pyrosequencing and LDBS data. A hitherto neglected region upstream of the TSS, with an overall higher methylation compared to exon 1 and intron 1 of MGMT, is also able to discriminate the methylation status. Conclusion: Our integrated analysis allows to evaluate and redefine co-methylation domains within the MGMT promoter and to rationalize the practical impact on assays used in daily routine diagnostics. [ABSTRACT FROM AUTHOR]

This topical issue compiles a series of articles on recent developments in the functional renormalization group approach to correlated electron systems. In our Editorial, we provide some background on the motivation for the special issue and briefly introduce the topics covered in it. [ABSTRACT FROM AUTHOR]

Alcohol-impaired driving results in thousands of deaths annually. Alcohol ignition interlocks require a negative breath test to start a vehicle's engine, and 44 states have mandated some form of interlock law for drivers convicted of driving while intoxicated (DWI). The objective of this study was to estimate the association between interlock laws and fatal impaired-driving crashes. Differences in three interlock laws were evaluated by comparing alcohol-impaired passenger vehicle drivers involved in fatal crashes between 2001 and 2019 in the United States across state and time. State/time differences unrelated to interlock laws were controlled for by fitting a Poisson model. The exposure measure was the number of passenger vehicle drivers in fatal crashes that did not involve impaired drivers. Laws requiring interlocks for drivers convicted of DWI covered: repeat offenders, repeat offenders and high-BAC offenders, all offenders, or none. The number of states with all-offender interlock laws during the study period went from three in 2001 to 29 in 2019, and the number of states with any of the three laws increased from 16 to 44. All-offender laws were associated with 26% fewer drivers with 0.08+ BAC involved in fatal crashes, compared with no law. Repeat-offender laws were associated with a 9% reduction in impaired drivers, compared with no law. Repeat and high-BAC laws were associated with a 20% reduction in impaired drivers in fatal crashes, compared with no law. Laws mandating alcohol ignition interlocks, especially those covering all offenders, are an effective impaired-driving countermeasure that reduces the number of impaired drivers in fatal crashes. [ABSTRACT FROM AUTHOR]

Suppression of vitrinite reflectance is a well-known phenomenon and, if not recognised and corrected for, could potentially have a big impact on the results of thermal history and basin modelling, and seriously affect exploration decisions. The Malay Basin is known to have shown evidence of vitrinite reflectance (Ro) suppression in a selection of wells that were also analysed using the FAMM (Fluorescence Alteration of Multiple Macerals) technique. Analysis of available data suggests that potential vitrinite reflectance suppression may be identified using an empirical regression line which separates "suppressed" from "normal" Ro values based on the FAMM data. The "FAMM minimum regression line" was used to screen through Ro data from 142 wells (drilled between 1969 and 2005) in the Malay Basin and it is estimated that a quarter of those wells might be affected by suppression. Possible suppression was also noted in the Penyu Basin, where bottom-hole temperatures in some wells are consistently higher than Ro-derived temperatures. The regression line could be used as a tool for quick screening of legacy Ro data for potential suppression of vitrinite reflectance. At the very least, it could raise suspicion about the quality of the Ro data and trigger further investigation as to whether the suppression is "real", and help justify additional or specialised laboratory analyses such as FAMM and VIRF (Vitrinite-Inertinite Reflectance and Fluorescence) to correct for suppression. [ABSTRACT FROM AUTHOR]

Recently, the twist angle between adjacent sheets of stacked van der Waals materials emerged as a new knob to engineer correlated states of matter in two-dimensional heterostructures in a controlled manner, giving rise to emergent phenomena such as superconductivity or correlated insulating states. Here, we use an ab initio based approach to characterize the electronic properties of twisted bilayer MoS2. We report that, in marked contrast to twisted bilayer graphene, slightly hole-doped MoS2 realizes a strongly asymmetric px-py Hubbard model on the honeycomb lattice, with two almost entirely dispersionless bands emerging due to destructive interference. The origin of these dispersionless bands, is similar to that of the flat bands in the prototypical Lieb or Kagome lattices and co-exists with the general band flattening at small twist angle due to the moiré interference. We study the collective behavior of twisted bilayer MoS2 in the presence of interactions, and characterize an array of different magnetic and orbitally-ordered correlated phases, which may be susceptible to quantum fluctuations giving rise to exotic, purely quantum, states of matter. Twisted van der Waals systems are known to host flat electronic bands, originating from moire potential. Here, the authors predict from purely geometric considerations a new type of nearly dispersionless bands in twisted bilayer MoS2, resulting from destructive interference between effective lattice hopping matrix elements. [ABSTRACT FROM AUTHOR]

Background: Understanding the influence of genetic variants on DNA methylation is fundamental for the interpretation of epigenomic data in the context of disease. There is a need for systematic approaches not only for determining methylation quantitative trait loci (methQTL), but also for discriminating general from cell type-specific effects. Results: Here, we present a two-step computational framework MAGAR (https://bioconductor.org/packages/MAGAR), which fully supports the identification of methQTLs from matched genotyping and DNA methylation data, and additionally allows for illuminating cell type-specific methQTL effects. In a pilot analysis, we apply MAGAR on data in four tissues (ileum, rectum, T cells, B cells) from healthy individuals and demonstrate the discrimination of common from cell type-specific methQTLs. We experimentally validate both types of methQTLs in an independent data set comprising additional cell types and tissues. Finally, we validate selected methQTLs located in the PON1, ZNF155, and NRG2 genes by ultra-deep local sequencing. In line with previous reports, we find cell type-specific methQTLs to be preferentially located in enhancer elements. Conclusions: Our analysis demonstrates that a systematic analysis of methQTLs provides important new insights on the influences of genetic variants to cell type-specific epigenomic variation. [ABSTRACT FROM AUTHOR]

Introduction: Literature notes the efficacious use of alcohol ignition interlock devices (IID) in reducing rates of drinking and driving while installed on the vehicle. Some drivers who are convicted of driving while intoxicated (DWI) elect to have their license suspended/revoked instead of installing the device. These individuals represent a high‐risk subsample of drivers, yet limited literature has addressed this concern. The current study seeks to fill this gap using qualitative interviews addressing: (i) why do non‐installers make the choice to not install a mandated IID; and (ii) how are non‐installers managing without the IID? Methods: The study utilises the Managing Heavy Drinkers study of drivers in Erie County, New York, USA. Participants were purposively sampled from a group of non‐installers (n = 6; four females, two males) who completed semi‐structured interviews. Constructed grounded theory was used to develop a theoretical understanding of participant's experiences. Results: To understand why participants elect not to install the IID, thematic analysis revealed: alleviating constraints, predominantly the financial burdens associated with an IID, and institutional mistrust. Additionally, data revealed that participants are managing without the IID by mitigating apprehension. This included driving cautiously to avoid detection and utilising alternative transportation. Discussion and Conclusions: This study furthers understanding of why drivers convicted of a DWI elect not to install an IID. Future research should seek to identify barriers to IID installation. This work provides evidence for establishing institutional protocols that ensure drivers convicted of a DWI receive consistent and correct information about the IID process. [ABSTRACT FROM AUTHOR]

Background: Before the COVID‐19 pandemic, very little was known about the impact of social isolation on individuals' alcohol use and misuse. This study examines how socially isolated individuals with a history of heavy drinking used alcohol during the pandemic. Methods: Data for this study came from an add‐on to the Managing Heavy Drinking (MHD) longitudinal study of drivers convicted of DWI that was conducted in Erie County, New York. Pre‐COVID information (October 2019–March 2020) was augmented with a COVID‐19 questionnaire collected between July and August 2020. A total of 92 participants completed the COVID‐19 survey. Results: The sample of problem drinkers showed a significant increase after the pandemic outbreak in the average number of drinking days from 1.99 to 2.49 per week (p = 0.047), but a significant decrease in the average number of drinks per drinking day, from 3.74 to 2.74 (p = 0.003). The proportion of individuals who drank more frequently was greater among those who, before the outbreak had an Alcohol Use Disorders Identification Test (AUDIT) score <8 (26% increase) compared with those with an AUDIT score of >8 (13%). Alcohol treatment was also associated with the frequency of drinking, with individuals who were not in alcohol treatment showing a 16% increase in frequency compared with a 10% increase among those in treatment. Further, individuals who, after the outbreak worried about their health (30%) or finances (37%) reported greater increases in the frequency of drinking than those who did not worry about their health (17%) or finances (10%). Conclusions: Overall, the individuals in our sample showed small changes in the frequency andheaviness of drinking after the outbreak of COVID‐19, effects that opposite in direction from one another and thus resulted in no overall change in drinks consumed. Nonetheless, we identified factors that influenced the effects of the pandemic on drinking behavior among individuals convicted of DWI, which emphasizes the need to individualize these individuals' treatment, particularly in the context of dramatic environmental change. [ABSTRACT FROM AUTHOR]

. Alcohol ignition interlock devices (IID) reduce rates of drinking and driving. The interlock offers an opportune time for tailoring targeted interventions to develop habits to separate drinking from driving among this high-risk population. This study identified different types of IID users upon whom targeted interventions could be developed. Participants (N = 114) were assessed at IID installation and again six months later. Latent class analysis (LCA) was conducted using drinking environment, drinking motivation, social support, drug use, and problem drinking behaviors as indicators. Multivariate regression analyses were conducted comparing latent class assignment with impaired driving attempts. LCA supported a 4-class model where 14.8% of participants fell into the low use/high awareness class; 30.6% fell into the heavy use/high awareness class; 30.6% fell into the mixed use/high awareness class; and 24.0% fell into the moderate use/low awareness class. Drivers in the moderate use/low awareness condition had increased early morning BAC lockouts. These typologies demonstrate important differences within high risk drivers. Indeed, drivers who fell into the moderate use/low awareness class may not have considered their alcohol-related behaviors problematic. This information could lend itself to the development of targeted interventions to address subgroups of drinking drivers. [ABSTRACT FROM AUTHOR]

The question whether global symmetries can be realized in quantum-gravity-matter-systems has far-reaching phenomenological consequences. Here, we collect evidence that within an asymptotically safe context, discrete global symmetries of the form ℤn, n > 4, cannot be realized in a near-perturbative regime. In contrast, an effective-field-theory approach to quantum gravity might feature such symmetries, providing a mechanism to generate mass hierarchies in the infrared without the need for additional fine-tuning. [ABSTRACT FROM AUTHOR]

Background: Half of the offenders convicted of impaired driving in the United States are sentenced to install alcohol ignition interlock devices (IIDs), which prevent them from starting their vehicles if they have been drinking. No research has yet explored offenders' patterns of alcohol consumption and driving under the influence of alcohol (DUI) from the time before the arrest to the time period after the IID is installed. This study aims to fill that gap in knowledge. Methods: Using the Timeline Follow‐back interview procedure, we assessed the daily drinking of 153 convicted DUI offenders' self‐reported total alcohol consumption and rates of self‐reported driving after drinking over 4 phases: before DUI arrest, between arrest and IID installation, during the phase on the interlock, and after the interlock is removed. Because information about behaviors in each period was not available for every participant, comparisons were made using paired‐sample contrasts. Results: Compared with before the arrest, total alcohol use decreased by 50% in the 4‐month phase following arrest and before IID installation, though it did not change much afterward. The frequency of drinking and driving decreased sharply after the arrest (−82%), with further decrease upon installation of the interlock (−58%, p = 0.05). The frequency of drinking and driving after the IID was removed returned to preinstallation drinking and driving status (+58%, p = 0.01). Conclusions: Participants made significant adjustments to their drinking behavior by adhering to the traditional DUI driving restrictions in the postarrest phase. Although installation of an IID was not associated with a significant change in drinking, it further reduced the frequency of drinking and driving. Evaluations of the IID experience should take into account information on an individual's drinking and DUI behaviors not only before the IID was installed, but before the individual was arrested. [ABSTRACT FROM AUTHOR]

Wound healing is a complex process, and disturbance of even a single mechanism can result in chronic ulcers developing after exposure to the alkylating agent sulfur mustard (SM). A possible contributor may be SM-induced chronic senescent mesenchymal stem cells (MSCs), unable to fulfil their regenerative role, by persisting over long time periods and creating a proinflammatory microenvironment. Here we show that senescence induction in human bone marrow derived MSCs was time- and concentration-dependent, and chronic senescence could be verified 3 weeks after exposure to between 10 and 40 µM SM. Morphological changes, reduced clonogenic and migration potential, longer scratch closure times, differences in senescence, motility and DNA damage response associated genes as well as increased levels of proinflammatory cytokines were revealed. Selective removal of these cells by senolytic drugs, in which ABT-263 showed initial potential in vitro, opens the possibility for an innovative treatment strategy for chronic wounds, but also tumors and age-related diseases. [ABSTRACT FROM AUTHOR]

Narrow-diameter implants for overdenture applications have gained in popularity due to their ability to be placed with simplified and less traumatic surgical protocols in limited-width alveolar ridges. The decision of whether to use a flapped or flapless procedure must be guided by a thorough evaluation and evidence-based diagnosis. This article reviews current principles relating to the use of narrow-diameter implants, along with the advantages and disadvantages of current surgical protocols. The indications for the use of each surgical procedure are demonstrated by case reports that highlight diagnosis, surgical planning, and final treatment outcomes. [ABSTRACT FROM AUTHOR]

This article presents a study on the effect of implant distribution and number on the retention and stability of a simulated prosthesis. It examines differences between different attachment systems, the materials and methods used in the study and the decrease in resistance to posterior dislodging forces.