Search

Simulations of lattice gauge theories on noisy quantum hardware inherently suffer from violations of the gauge symmetry due to coherent and incoherent errors of the underlying physical system that implements the simulation. These gauge violations cause the simulations to become unphysical requiring the result of the simulation to be discarded. We investigate an active correction scheme that relies on detecting gauge violations locally and subsequently correcting them by dissipatively driving the system back into the physical gauge sector. We show that the correction scheme not only ensures the protection of the gauge symmetry, but it also leads to a longer validity of the simulation results even within the gauge-invariant sector. Finally, we discuss further applications of the scheme such as preparation of the many-body ground state of the simulated system.

BackgroundTransgender and gender-diverse individuals are particularly vulnerable to healthcare discrimination and related health sequelae.ObjectiveTo demonstrate diversity in demographics and explore variance in needs at the time of intake among patients seeking care at a large, urban gender health program.DesignWe present summary statistics of patient demographics, medical histories, and gender-affirming care needs stratified by gender identity and sexual orientation.ParticipantsWe reviewed all intake interviews with individuals seeking care in our gender health program from 2017 to 2020.Main measuresClients reported all the types of care in which they were interested at the time of intake as their "reason for call" (i.e., establish primary care, hormone management, surgical services, fertility services, behavioral health, or other health concerns).Key resultsOf 836 patients analyzed, 350 identified as trans women, 263 as trans men, and 223 as non-binary. The most prevalent sexual identity was straight among trans women (34%) and trans men (38%), whereas most (69%) non-binary individuals identified as pansexual or queer; only 3% of non-binary individuals identified as straight. Over half of patients reported primary care, hormone management, or surgical services as the primary reason for contacting our program. Straight, transgender women were more likely to report surgical services as their primary reason for contacting our program, whereas gay transgender men were more likely to report primary care as their reason.ConclusionsIndividuals contacting our gender health program to establish care were diverse in sexual orientation and gender-affirming care needs. Care needs varied with both gender identity and sexual orientation, but primary care, hormone management, and surgical services were high priorities across groups. Providers of gender-affirming care should inquire about sexual orientation and detailed treatment priorities, as trans and gender-diverse populations are not uniform in their treatment needs or goals.

Salmonella Typhimurium is associated with foodborne diseases worldwide, including in Peru, and its emerging antibiotic resistance (AMR) is now a global public health problem. Therefore, country-specific monitoring of the AMR emergence is vital to control this pathogen, and in these aspects, whole genome sequence (WGS)—based approaches are better than gene-based analyses. Here, we performed the antimicrobial susceptibility test for ten widely used antibiotics and WGS-based various analyses of 90 S. Typhimurium isolates (human, animal, and environment) from 14 cities of Peru isolated from 2000 to 2017 to understand the lineage and antimicrobial resistance pattern of this pathogen in Peru. Our results suggest that the Peruvian isolates are of Typhimurium serovar and predominantly belong to sequence type ST19. Genomic diversity analyses indicate an open pan-genome, and at least ten lineages are circulating in Peru. A total of 48.8% and 31.0% of isolates are phenotypically and genotypically resistant to at least one antibiotic, while 12.0% are multi-drug resistant (MDR). Genotype−phenotype correlations for ten tested drugs show >80% accuracy, and >90% specificity. Sensitivity above 90% was only achieved for ciprofloxacin and ceftazidime. Two lineages exhibit the majority of the MDR isolates. A total of 63 different AMR genes are detected, of which 30 are found in 17 different plasmids. Transmissible plasmids such as lncI-gamma/k, IncI1-I(Alpha), Col(pHAD28), IncFIB, IncHI2, and lncI2 that carry AMR genes associated with third-generation antibiotics are also identified. Finally, three new non-synonymous single nucleotide variations (SNVs) for nalidixic acid and eight new SNVs for nitrofurantoin resistance are predicted using genome-wide association studies, comparative genomics, and functional annotation. Our analysis provides for the first time the WGS-based details of the circulating S. Typhimurium lineages and their antimicrobial resistance pattern in Peru.

Malnourishment is a risk factor for childhood mortality, jeopardizing the health of children by aggravating pneumonia/acute respiratory infections and diarrheal diseases. Malnourishment causes morphophysiological changes resulting in stunting and wasting that have long-lasting consequences such as cognitive deficit and metabolic dysfunction. Using a pig model of malnutrition, the interplay between the phenotypic data displayed by the malnourished animals, the gene expression pattern along the intestinal tract, microbiota composition of the intestinal contents, and hepatic metabolite concentrations from the same animals were correlated using a multi-omics approach. Samples from the duodenum, jejunum, and ileum of malnourished (protein and calorie-restricted diet) and full-fed (no dietary restrictions) piglets were subjected to RNA-seq. Gene co-expression analysis and phenotypic correlations were made with WGCNA, while the integration of transcriptome with microbiota composition and the hepatic metabolite profile was done using mixOmics. Malnourishment caused changes in tissue gene expression that influenced energetic balance, cell proliferation, nutrient absorption, and response to stress. Repression of antioxidant genes, including glutathione peroxidase, in coordination with induction of metal ion transporters corresponded to the hepatic metabolite changes. These data indicate oxidative stress in the intestine of malnourished animals. Furthermore, several of the phenotypes displayed by these animals could be explained by changes in gene expression.

Hungatella hathewayi has been observed to be a member of the gut microbiome. Unfortunately, little is known about this organism in spite of being associated with human fatalities; it is important to understand virulence mechanisms and epidemiological prospective to cause disease. In this study, a patient with chronic neurologic symptoms presented to the clinic with subsequent isolation of a strain with phenotypic characteristics suggestive of Clostridium difficile. However, whole-genome sequence found the organism to be H. hathewayi. Analysis including publicly available Hungatella genomes found substantial genomic differences as compared to the type strain, indicating this isolate was not C. difficile. We examined the whole-genome of Hungatella species and related genera, using comparative genomics to fully examine species identification and toxin production. Orthogonal phylogenetic using the 16S rRNA gene and entire genome analyses that included genome distance analyses using Genome-to-Genome Distance (GGDC), Average Nucleotide Identity (ANI), and a pan-genome analysis with inclusion of available public genomes determined the speciation to be Hungatella. Two clearly differentiated groups were identified, one including a reference H. hathewayi genome (strain DSM-13,479) and a second group that was determined to be H. effluvii, which included our clinical isolate. Also, some genomes reported as H. hathewayi were found to belong to other genera, including Clostridium and Faecalicatena. We show that the Hungatella species have an open pan-genome reflecting high genomic diversity. This study highlights the importance of correctly assigning taxonomic identification, particularly in disease-associated strains, to better understand virulence and therapeutic options.

BackgroundThe role and implementation of tau PET imaging for predicting subsequent cognitive decline in Alzheimer's disease (AD) remains uncertain. This study was designed to evaluate the relationship between baseline [18F]GTP1 tau PET and subsequent longitudinal change across multiple cognitive measures over 18 months.MethodsOur analyses incorporated data from 67 participants, including cognitively normal controls (n = 10) and β-amyloid (Aβ)-positive individuals ([18F] florbetapir Aβ PET) with prodromal (n = 26), mild (n = 16), or moderate (n = 15) AD. Baseline measurements included cortical volume (MRI), tau burden ([18F]GTP1 tau PET), and cognitive assessments [Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), 13-item version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)]. Cognitive assessments were repeated at 6-month intervals over an 18-month period. Associations between baseline [18F]GTP1 tau PET indices and longitudinal cognitive performance were assessed via univariate (Spearman correlations) and multivariate (linear mixed effects models) approaches. The utility of potential prognostic tau PET cut points was assessed with ROC curves.ResultsUnivariate analyses indicated that greater baseline [18F]GTP1 tau PET signal was associated with faster rates of subsequent decline on the MMSE, CDR, and ADAS-Cog13 across regions of interest (ROIs). In multivariate analyses adjusted for baseline age, cognitive performance, cortical volume, and Aβ PET SUVR, the prognostic performance of [18F]GTP1 SUVR was most robust in the whole cortical gray ROI. When AD participants were dichotomized into low versus high tau subgroups based on baseline [18F]GTP1 PET standardized uptake value ratios (SUVR) in the temporal (cutoff = 1.325) or whole cortical gray (cutoff = 1.245) ROIs, high tau subgroups demonstrated significantly more decline on the MMSE, CDR, and ADAS-Cog13.ConclusionsOur results suggest that [18F]GTP1 tau PET represents a prognostic biomarker in AD and are consistent with data from other tau PET tracers. Tau PET imaging may have utility for identifying AD patients at risk for more rapid cognitive decline and for stratification and/or enrichment of participant selection in AD clinical trials. Trial registration ClinicalTrials.gov NCT02640092 . Registered on December 28, 2015.

Purpose Arthroscopy is one of the most common interventions in orthopedics. Hence it is important to train users early in order to ensure the safest possible identification of access portals (AP). This prospective study aimed to compare a palpatory (PalpMethod) with a sonographic (SonoMethod) method for AP location in the shoulder and knee joints.

Purpose Sonography training has become an important part of university medicine courses. This study explores the impact of digital and analog teaching resources on learning outcomes, knowledge retention, and student preferences and motivation in a flipped classroom setting.

IntroductionThe best way to impart knowledge to medical students is still unclear. Therefore, we designed a blended learning course in thoracic radiology including both “traditional” in-class time as well as online learning modules. The aims were (1) to investigate students’ attitudes toward this blended learning approach; and (2) to test whether it improved their knowledge about thoracic radiology.MethodsA prospective study was conducted at the local medical center; 156 fourth-year medical students completed this study. Before and after the course, students had to complete (1) questionnaires to investigate their attitudes (7-point Likert scale); and (2) an objective test to assess their knowledge (multiple-choice/free text questions; results as % of correct answers).ResultsRegarding (1), the course led to an improvement in all items compared to baseline, exemplary: interest in thoracic radiology (precourse 4.2 vs. 5.4 postcourse) and the fulfillment of students’ expressed requirements regarding the teaching content (4.5 precourse vs. 6.2 postcourse). Furthermore, the great majority (88%) of our participants wished for more online learning offerings in the future. Regarding (2), the course led to improved knowledge on the objective test (precourse: 40% vs. postcourse: 63% correct answers).ConclusionThis feasibility study showed the successful design and implementation of a blended learning approach in thoracic radiology. Furthermore, it revealed medical students’ positive attitudes toward this approach and showed an increased knowledge in thoracic radiology. Thus, such approaches might be used to enrich the teaching armamentarium in medical education and to further enhance interest and knowledge in thoracic diseases among medical students.

Abstract Background Alcohol use disorder (AUD) commonly causes hospitalization, particularly for individuals disproportionately impacted by structural racism and other forms of marginalization. The optimal approach for engaging hospitalized patients with AUD in treatment post-hospital discharge is unknown. We describe the rationale, aims, and protocol for Project ENHANCE (ENhancing Hospital-initiated Alcohol TreatmeNt to InCrease Engagement), a clinical trial testing increasingly intensive approaches using a hybrid type 1 effectiveness-implementation approach. Methods We are randomizing English and/or Spanish-speaking individuals with untreated AUD (n = 450) from a large, urban, academic hospital in New Haven, CT to: (1) Brief Negotiation Interview (with referral and telephone booster) alone (BNI), (2) BNI plus facilitated initiation of medications for alcohol use disorder (BNI + MAUD), or (3) BNI + MAUD + initiation of computer-based training for cognitive behavioral therapy (CBT4CBT, BNI + MAUD + CBT4CBT). Interventions are delivered by Health Promotion Advocates. The primary outcome is AUD treatment engagement 34 days post-hospital discharge. Secondary outcomes include AUD treatment engagement 90 days post-discharge and changes in self-reported alcohol use and phosphatidylethanol. Exploratory outcomes include health care utilization. We will explore whether the effectiveness of the interventions on AUD treatment engagement and alcohol use outcomes differ across and within racialized and ethnic groups, consistent with disproportionate impacts of AUD. Lastly, we will conduct an implementation-focused process evaluation, including individual-level collection and statistical comparisons between the three conditions of costs to providers and to patients, cost-effectiveness indices (effectiveness/cost ratios), and cost–benefit indices (benefit/cost ratios, net benefit [benefits minus costs). Graphs of individual- and group-level effectiveness x cost, and benefits x costs, will portray relationships between costs and effectiveness and between costs and benefits for the three conditions, in a manner that community representatives also should be able to understand and use. Conclusions Project ENHANCE is expected to generate novel findings to inform future hospital-based efforts to promote AUD treatment engagement among diverse patient populations, including those most impacted by AUD. Clinical Trial Registration: Clinicaltrials.gov identifier: NCT05338151.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by leukocytosis and left shift. The primary molecular alteration is the BCR::ABL1, chimeric oncoprotein with tyrosine kinase activity, responsible for the initial oncogenesis of the disease. Therapy of CML was revolutionized with the advent of tyrosine kinase inhibitors, but it is still not considered curative and may present resistance and serious adverse effects. Discoveries in CML inaugurated a new era in cancer treatment and despite all the advances, a new biomarker is needed to detect resistance and adverse effects. Circular RNAs (circRNAs) are a special type of non-coding RNA formed through a process called backsplicing. The majority of circRNAs are derived from protein-coding genes. CircHIPK3 is formed from the second exon of the HIPK3 gene and has been found in various pathologies, including different types of cancer. New approaches have demonstrated the potential of circular RNAs in cancer research, and circHIPK3 has shown promising results. It is often associated with cellular regulatory pathways, suggesting an important role in the molecular dynamics of tumors. The identification of biomarkers is an important tool for therapeutic improvement; thus we review the role of circHIPK3 and its potential as a biomarker in CML.

The use of telehealth, specifically virtual visits, has increased and adoption continues. Providers need effective training for how to communicate with patients to develop a connection during virtual visits. This article describes the implementation and evaluation of a course called Mastering Presence in Virtual Visits . Results show that although providers perceive lack of time, technology issues, and lacking experiential knowledge as barriers to enacting course behaviors, the course was feasible and acceptable. Following the course, providers rated key course behaviors as helpful for practice, and 80.7% of providers were likely to recommend the course to a colleague. The course shifted provider perceptions of the purpose, patient experience, and procedures in virtual visits. Prior to the course, providers perceived virtual visits as fundamentally different than in-person visits. However, after the course, they recognized the importance of connection in virtual visits and how to foster that connection. Providers continue to require support in conducting high-quality virtual visits. Online, asynchronous courses, developed in partnership with providers, are feasible and effective for encouraging behavior change. Key findings: When asked on a needs assessment in 2020, communication strategies to connect with patients in virtual visits were a top provider need. Partnering with providers to create online, communication training content is effective for increasing the acceptability of courses about virtual visits. Asynchronous, online courses can meet provider needs for communication strategies to connect with patients in virtual visits.

PurposeWe evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [18F]GTP1 tau positron-emission tomography (PET) in Alzheimer's disease and the suitability of describing the tau pathology burden temporal trajectories using linear mixed-effects models (LMEM).MethodsWe applied van Cittert iterative deconvolution (VC), 2-compartment, and 3-compartment, and the geometric transfer matrix plus region-based voxelwise methods to data acquired in an Alzheimer's disease natural history study over 18 months at a single imaging site. We determined the optimal PVC method by comparing the standardized uptake value ratio change (%ΔSUVR) between diagnostic and tau burden–level groups and the longitudinal repeatability derived from the LMEM. The performance of LMEM analysis for calculating %ΔSUVR was evaluated in a natural history study and in a multisite clinical trial of semorinemab in prodromal to mild Alzheimer's disease by comparing results to traditional per-visit estimates.ResultsThe VC, 2-compartment, and 3-compartment PVC methods had similar performance, whereas region-based voxelwise overcorrected regions with a higher tau burden. The lowest within-subject variability and acceptable group separation scores were observed without PVC. The LMEM-derived %ΔSUVR values were similar to the per-visit estimates with lower variability.ConclusionThe results indicate that the tested PVC methods do not offer a clear advantage or improvement over non-PVC images for the quantification of longitudinal [18F]GTP1 PET data. LMEM offers a robust framework for the longitudinal tau PET quantification with low longitudinal test–retest variability.Clinical trial registrationNCT02640092 and NCT03289143.

Introduction Pelvic floor disorders (PFDs) pose substantial physical and psychological burdens for a growing number of women. Given the ubiquity of these conditions and known patient reluctance to seek care, primary care providers (PCPs) have a unique opportunity to increase treatment and provide appropriate referrals for these patients.Methods An online survey was administered to PCPs to assess provider practices, knowledge, comfort managing and ease of referral for PFDs. Logistic regression was used to assess the association between demographic/practice characteristics of PCPs and two primary outcomes of interest: discomfort with management and difficulty with referral of PFDs.Results Of the 153 respondents to the survey, more felt comfortable managing stress urinary incontinence (SUI) and overactive bladder (OAB), compared with pelvic organ prolapse (POP) and faecal incontinence (FI) and were less likely to refer patients with urinary symptoms. Few providers elicited symptoms for POP and FI as compared with SUI and OAB. Provider variables that were significantly associated with discomfort with management varied by PFD, but tended to correlate with less exposure to PFDs (eg, those with fewer years of practice, and internal medicine and family physicians as compared with geriatricians); whereas the factors that were significantly associated with difficulty in referral, again varied by PFD, but were related to practice characteristics (eg, specialist network, type of practice, practice setting and quantity of patients).Conclusion These findings highlight the need to increase PCPs awareness of PFDs and develop effective standardised screening protocols, as well as collaboration with pelvic floor specialists to improve screening, treatment and referral for patients with PFDs.

This Note seeks to provoke a conversation about the rise in power of federal prosecutors at the expense of district court judges, focusing on the controlled-substances context. While referencing Robert Cover’s portrayal of the justice system as a “pyramid of violence,” this Note shows how the federal mandatory-minimum sentencing laws and the U.S. Sentencing Commission’s Sentencing Guidelines brought about this change. These sentencing schemes have anchored what prosecutors and judges deem an appropriate sentence. Prosecutors are thinking about sentences while deciding what charges to bring. After a discussion about sentencing legislation and current sentencing procedures, this Note identifies a need for reform in the federal criminal justice system. The elimination of mandatory sentencing laws, the normalization of departure from the Guidelines, and the creation of the executive prosecutor role are reforms identified in this Note.

ObjectivesTo assess (1) the relationship of consumers' assessment of overall nursing home quality to their assessment of specific dimensions of quality; and (2) the implications of this relationship for composite quality measures in Nursing Home Compare.DesignA survey conducted in 2017 elicited respondents' assessments of the quality of overall care and 13 specific dimensions of care.Settings and participantsThe sample consisted of 4449 respondents who either resided in a nursing home or had a family member who resided in a nursing home during the 6 months before the survey.MethodsWe estimated regression models to infer the relationship between consumers' assessments of overall quality and 13 specific dimensions of quality. The regression coefficients, indicating the implicit importance/weight assigned by respondents to each dimension as a component of the consumers' assessment of overall quality, were used to create a prototype composite quality measure.ResultsFor long-stay residents, 8 of the 13 quality dimensions were significantly associated with their overall ratings of quality. Five dimensions achieved significance for short-stay residents. The magnitude of importance weights varied substantially across dimensions of care.Conclusions and implicationsOur findings suggest that Nursing Home Compare could be improved by augmenting the technical information in the 5-Star composite measure with consumers' assessments of the additional, nontechnical dimensions of quality.