In vitro activity of gepotidacin and comparator antimicrobials against isolates of nontuberculous mycobacteria (NTM).

Novel antimicrobials are needed to treat rising nontuberculous mycobacteria (NTM) infections. Using standard broth microdilution methods, 68 NTM isolates were tested against gepotidacin, a new, first-in-class, oral triazaacenaphthylene bacterial topoisomerase inhibitor. MICs varied (0.25 to >64 µg/mL) with the lowest being M. fortuitum complex (0.25-8 µg/mL), M. mucogenicum complex (1-2 µg/mL), M. kansasii (0.25-8 µg/mL), and M. marinum (4-16 µg/mL). Testing greater numbers of some species is suggested to better understand gepotidacin activity against NTM.

A magnetoencephalography study of first-time mothers listening to infant cries.

Studies using magnetoencephalography (MEG) have identified the orbitofrontal cortex (OFC) to be an important early hub for a "parental instinct" in the brain. This complements the finding from functional magnetic resonance imaging studies linking reward, emotion regulation, empathy, and mentalization networks to the "parental brain." Here, we used MEG in 43 first-time mothers listening to infant and adult cry vocalizations to investigate the link with mother-infant postpartum bonding scores and their level of sleep deprivation (assessed using both actigraphy and sleep logs). When comparing brain responses to infant versus adult cry vocalizations, we found significant differences at around 800-1,000 ms after stimuli onset in the primary auditory cortex, superior temporal gyrus, hippocampal areas, insula, precuneus supramarginal gyrus, postcentral gyrus, and posterior cingulate gyrus. Importantly, mothers with weaker bonding scores showed decreased brain responses to infant cries in the auditory cortex, middle and superior temporal gyrus, OFC, hippocampal areas, supramarginal gyrus, and inferior frontal gyrus at around 100-300 ms after the stimulus onset. In contrast, we did not find correlations with sleep deprivation scores. The significant decreases in brain processing of an infant's distress signals could potentially be a novel signature of weaker infant bonding in new mothers and should be investigated in vulnerable populations.

Listening to School Nurses' Voices: A Mixed Methods Study on the Continued Impact of COVID-19 on School Nursing Practice.

School closures in March 2020 due to the COVID-19 pandemic precipitated losses of critical student resources as physical, mental, emotional, and social needs escalated. Identifying the challenges, strategies, and changes in school nurse (SN) practice in Massachusetts during this pandemic is fundamental to understanding how to manage future anticipated pandemics while protecting children, communities, and SNs. The purpose of this mixed-methods descriptive study in the second year of the global pandemic was to (a) listen to SN voices through a novel online survey including the prompts of challenges, strategies, and practice changes and (b) describe the SN experience of COVID-19 response in Massachusetts schools, including identification of intent to leave school nursing. Responses were analyzed using descriptive qualitative analysis (n = 73). The prompts each elicited subthemes that coalesced to a cohesive theme: Finding one's way required the support of others to pave untraversed roads.

Emergence of Inducible Macrolide Resistance in Mycobacterium chelonae Due to Broad-Host-Range Plasmid and Chromosomal Variants of the Novel 23S rRNA Methylase Gene, erm(55).

Macrolides are a mainstay of therapy for infections due to nontuberculous mycobacteria (NTM). Among rapidly growing mycobacteria (RGM), inducible macrolide resistance is associated with four chromosomal 23S rRNA methylase (erm) genes. Beginning in 2018, we detected high-level inducible clarithromycin resistance (MICs of ≥16µg/mL) in clinical isolates of Mycobacterium chelonae, an RGM species not previously known to contain erm genes. Using whole-genome sequencing, we identified a novel plasmid-mediated erm gene. This gene, designated erm(55)P, exhibits <65% amino acid identity to previously described RGM erm genes. Two additional chromosomal erm(55) alleles, with sequence identities of 81% to 86% to erm(55)P, were also identified and designated erm(55)C and erm(55)T. The erm(55)T is part of a transposon. The erm(55)P allele variant is located on a putative 137-kb conjugative plasmid, pMchErm55. Evaluation of 133 consecutive isolates from 2020 to 2022 revealed 5 (3.8%) with erm(55). The erm(55)P gene was also identified in public data sets of two emerging pathogenic pigmented RGM species: Mycobacterium iranicum and Mycobacterium obuense, dating back to 2008. In both species, the gene appeared to be present on plasmids homologous to pMchErm55. Plasmid-mediated macrolide resistance, not described previously for any NTM species, appears to have spread to multiple RGM species. This has important implications for antimicrobial susceptibility guidelines and treatment of RGM infections. Further spread could present serious consequences for treatment of other macrolide-susceptible RGM. Additional studies are needed to determine the transmissibility of pMchErm55 and the distribution of erm(55) among other RGM species.

First Probe of Sub-GeV Dark Matter beyond the Cosmological Expectation with the COHERENT CsI Detector at the SNS.

The COHERENT Collaboration searched for scalar dark matter particles produced at the Spallation Neutron Source with masses between 1 and 220 MeV/c^{2} using a CsI[Na] scintillation detector sensitive to nuclear recoils above 9 keV_{nr}. No evidence for dark matter is found and we thus place limits on allowed parameter space. With this low-threshold detector, we are sensitive to coherent elastic scattering between dark matter and nuclei. The cross section for this process is orders of magnitude higher than for other processes historically used for accelerator-based direct-detection searches so that our small, 14.6 kg detector significantly improves on past constraints. At peak sensitivity, we reject the flux consistent with the cosmologically observed dark-matter concentration for all coupling constants α_{D}<0.64, assuming a scalar dark-matter particle. We also calculate the sensitivity of future COHERENT detectors to dark-matter signals which will ambitiously test multiple dark-matter spin scenarios.

Measurement of Electron-Neutrino Charged-Current Cross Sections on

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50 MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.2_{-1.8}^{+2.1}×10^{-40} cm^{2}. This corresponds to a value that is ∼41% lower than predicted using the MARLEY event generator with a measured Gamow-Teller strength distribution. In addition, the observed visible spectrum from charged-current scattering on ^{127}I has been measured between 10 and 55 MeV, and the exclusive zero-neutron and one-or-more-neutron emission cross sections are measured to be 5.2_{-3.1}^{+3.4}×10^{-40} and 2.2_{-0.5}^{+0.4}×10^{-40} cm^{2}, respectively.

Performance metrics for models designed to predict treatment effect.

BACKGROUND: Measuring the performance of models that predict individualized treatment effect is challenging because the outcomes of two alternative treatments are inherently unobservable in one patient. The C-for-benefit was proposed to measure discriminative ability. However, measures of calibration and overall performance are still lacking. We aimed to propose metrics of calibration and overall performance for models predicting treatment effect in randomized clinical trials (RCTs). METHODS: Similar to the previously proposed C-for-benefit, we defined observed pairwise treatment effect as the difference between outcomes in pairs of matched patients with different treatment assignment. We match each untreated patient with the nearest treated patient based on the Mahalanobis distance between patient characteristics. Then, we define the Eavg-for-benefit, E50-for-benefit, and E90-for-benefit as the average, median, and 90th quantile of the absolute distance between the predicted pairwise treatment effects and local-regression-smoothed observed pairwise treatment effects. Furthermore, we define the cross-entropy-for-benefit and Brier-for-benefit as the logarithmic and average squared distance between predicted and observed pairwise treatment effects. In a simulation study, the metric values of deliberately "perturbed models" were compared to those of the data-generating model, i.e., "optimal model". To illustrate these performance metrics, different modeling approaches for predicting treatment effect are applied to the data of the Diabetes Prevention Program: 1) a risk modelling approach with restricted cubic splines; 2) an effect modelling approach including penalized treatment interactions; and 3) the causal forest. RESULTS: As desired, performance metric values of "perturbed models" were consistently worse than those of the "optimal model" (Eavg-for-benefit ≥ 0.043 versus 0.002, E50-for-benefit ≥ 0.032 versus 0.001, E90-for-benefit ≥ 0.084 versus 0.004, cross-entropy-for-benefit ≥ 0.765 versus 0.750, Brier-for-benefit ≥ 0.220 versus 0.218). Calibration, discriminative ability, and overall performance of three different models were similar in the case study. The proposed metrics were implemented in a publicly available R-package "HTEPredictionMetrics". CONCLUSION: The proposed metrics are useful to assess the calibration and overall performance of models predicting treatment effect in RCTs.

The effectiveness of community-based palliative care programme components: a systematic review.

BACKGROUND: There is evidence that community-based palliative care programmes can improve patient outcomes and caregiver experiences cost-effectively. However, little is known about which specific components within these programmes contribute to improving the outcomes. AIM: To systematically review research that evaluates the effectiveness of community-based palliative care components. DESIGN: A systematic mixed studies review synthesising quantitative, qualitative and mixed-methods study findings using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PROSPERO: ID # CRD42022302305. DATA SOURCES: Four databases were searched in August 2021 (CINAHL, Web of Science, ProQuest Federated and PubMed including MEDLINE) and a close review of included article references. Inclusion criteria required articles to evaluate a single, specific component of a community-based palliative care programme either within an individual programme or across several programmes. RESULTS: Overall, a total of 1,674 articles were identified, with 57 meeting the inclusion criteria. Of the included studies, 21 were qualitative, 25 were quantitative and 11 had mixed methods. Outcome measures consistently examined included patient/caregiver satisfaction, hospital utilisation and home deaths. The components of standardised sessions (interdisciplinary meetings about patients), volunteer engagement and early intervention contributed to the success of community-based palliative care programmes. CONCLUSIONS: Certain components of community-based palliative care programmes are effective. Such components should be implemented and tested more in low- and middle-income countries and key and vulnerable populations such as lower-income and marginalised racial or ethnic groups. In addition, more research is needed on the cost-effectiveness of individual programme components.

Dynamic Patterns and Modeling of Early COVID-19 Transmission by Dynamic Mode Decomposition.

INTRODUCTION: Understanding the transmission patterns and dynamics of COVID-19 is critical to effective monitoring, intervention, and control for future pandemics. The aim of this study was to investigate the spatial and temporal characteristics of COVID-19 transmission during the early stage of the outbreak in the US, with the goal of informing future responses to similar outbreaks. METHODS: We used dynamic mode decomposition (DMD) and national data on COVID-19 cases (April 6, 2020-October 9, 2020) to model the spread of COVID-19 in the US as a dynamic system. DMD can decompose the complex evolution of disease cases into linear combinations of simple spatial patterns or structures (modes) with time-dependent mode amplitudes (coefficients). The modes reveal the hidden dynamic behaviors of the data. We identified geographic patterns of COVID-19 spread and quantified time-dependent changes in COVID-19 cases during the study period. RESULTS: The magnitude analysis from the dominant mode in DMD showed that California, Louisiana, Kansas, Georgia, and Texas had higher numbers of COVID-19 cases than other areas during the study period. States such as Arizona, Florida, Georgia, Massachusetts, New York, and Texas showed simultaneous increases in the number of COVID-19 cases, consistent with data from the Centers for Disease Control and Prevention. CONCLUSION: Results from DMD analysis indicate that certain areas in the US shared similar trends and similar spatiotemporal transmission patterns of COVID-19. These results provide valuable insights into the spread of COVID-19 and can inform policy makers and public health authorities in designing and implementing mitigation interventions.

Hearing Aid Loan Program for Hearing Loss at the End of Life.

This article describes a hearing aid loan program to provide free amplification devices for patients at the end of life to help them communicate more effectively at this critical time. It includes steps for establishing such a program, addressing challenges, and the role of the informal caregiver throughout the intervention. Healthcare professionals and social workers are encouraged to develop similar programs and use the information here as helpful suggestions to consider for their programs.

Parenting style in childhood and attitudes toward caregiving in adulthood: a qualitative study.

This study aims to explore how relationships with parents during childhood can influence an individual's attitude toward caregiving later in life. The qualitative data came from 47 respondents who care for adult loved ones, with a caregiver mean age of 46.7. The respondents reflected on their recent experience of providing care for their loved ones and how experiences with their caregivers growing up may have influenced their caregiving attitudes. Using a codebook thematic analysis, themes were generated linking childhood experiences to current attitudes toward caregiving. Themes included reciprocating good care, performing obligatory care, and stopping the generational transference of negative care. For most participants, providing quality care for adult loved ones happened regardless of whether the one's childhood experiences with caregivers were positive or negative. Knowledge about the impact of childhood experiences can help health professionals develop interventions to support family caregivers that consider childhood experiences with parents.

Effectiveness of Skill-Building Interventions for Informal Caregivers of Adults with Cancer: a Systematic Review.

Over 19 million people worldwide were diagnosed with cancer in 2020. Informal caregivers of adults with cancer play an important role in helping their loved ones with cancer yet often receive little support in developing the necessary skills for caregiving. A systematic review of skill-building interventions for informal caregivers of adults with cancer was conducted across three electronic databases for academic articles published through February 2022. PRISMA reporting guidelines were followed throughout this review, the Mixed Methods Appraisal Tool was used to assess study quality, and results were summarized in a narrative synthesis. The main components of skill-building interventions examined include caregiving preparedness, communication, and self-care. Nine of the 11 included articles showed that interventions effectively built skills for informal caregivers. The articles reviewed had a wide variety of intervention strategies, outcome measures, and study designs. Two of the 11 articles mentioned vulnerable and key groups, and no studies were performed in low- and middle-income countries. Findings generally support implementing skill-building interventions for informal caregivers of adults with cancer; however, further research is necessary to determine the most effective approaches for improving caregiver skills and reaching vulnerable and key populations.

The Perspective of Administrators of Intellectual Disability Organizations on the COVID-19 Pandemic.

OBJECTIVE: To learn about the challenges, policies, and needed resources to serve people with intellectual disability and protect staff during the COVID-19 pandemic. From the perspective of intellectual disability service providers. METHODS: We conducted in-depth qualitative interviews with 16 intellectual disability organization administrators throughout Illinois, USA from November 2020 through February 2021. We coded and analyzed the data using thematic analysis. RESULTS: Three major themes emerged: (1) COVID-19 caused considerable challenges to people with intellectual disability and staff and service providers, (2) intellectual disability organizations reinvented service provisions in response to COVID-19 challenges, and (3) the interrelatedness of intellectual disability organizations, public policies, and community entities became evident. CONCLUSIONS: Exhibiting responsiveness to needs and developing innovative solutions were strategies championed by intellectual disability organizations during the pandemic. Fostering collaboration with community entities may assist these organizations in navigating pandemic challenges and developing resilient infrastructure for future environmental threats.

Measurement of the Coherent Elastic Neutrino-Nucleus Scattering Cross Section on CsI by COHERENT.

We measured the cross section of coherent elastic neutrino-nucleus scattering (CEvNS) using a CsI[Na] scintillating crystal in a high flux of neutrinos produced at the Spallation Neutron Source at Oak Ridge National Laboratory. New data collected before detector decommissioning have more than doubled the dataset since the first observation of CEvNS, achieved with this detector. Systematic uncertainties have also been reduced with an updated quenching model, allowing for improved precision. With these analysis improvements, the COHERENT Collaboration determined the cross section to be (165_{-25}^{+30})×10^{-40} cm^{2}, consistent with the standard model, giving the most precise measurement of CEvNS yet. The timing structure of the neutrino beam has been exploited to compare the CEvNS cross section from scattering of different neutrino flavors. This result places leading constraints on neutrino nonstandard interactions while testing lepton flavor universality and measures the weak mixing angle as sin^{2}θ_{W}=0.220_{-0.026}^{+0.028} at Q^{2}≈(50 MeV)^{2}.

Construction and case study of a novel lung cancer risk index.

PURPOSE: This study constructs a lung cancer risk index (LCRI) that incorporates many modifiable risk factors using an easily reproducible and adaptable method that relies on publicly available data. METHODS: We used meta-analysis followed by Analytic Hierarchy Process (AHP) to generate a lung cancer risk index (LCRI) that incorporates seven modifiable risk factors (active smoking, indoor air pollution, occupational exposure, alcohol consumption, secondhand smoke exposure, outdoor air pollution, and radon exposure) for lung cancer. Using county-level population data, we then performed a case study in which we tailored the LCRI for use in the state of Illinois (LCRIIL). RESULTS: For both the LCRI and the LCRIIL, active smoking had the highest weights (46.1% and 70%, respectively), whereas radon had the lowest weights (3.0% and 5.7%, respectively). The weights for alcohol consumption were 7.8% and 14.7% for the LCRI and the LCRIIL, respectively, and were 3.8% and 0.95% for outdoor air pollution. Three variables were only included in the LCRI: indoor air pollution (18.5%), occupational exposure (13.2%), and secondhand smoke exposure (7.6%). The Consistency Ratio (CR) was well below the 0.1 cut point. The LCRIIL was moderate though significantly correlated with age-adjusted lung cancer incidence (r = 0.449, P < 0.05) and mortality rates (r = 0.495, P < 0.05). CONCLUSION: This study presents an index that incorporates multiple modifiable risk factors for lung cancer into one composite score. Since the LCRI allows data comprising the composite score to vary based on the location of interest, this measurement tool can be used for any geographic location where population-based data for individual risk factors exist. Researchers, policymakers, and public health professionals may utilize this framework to determine areas that are most in need of lung cancer-related interventions and resources.

Diet quality is associated with primary melanoma thickness.

BACKGROUND: Patients' diets can influence the outcome of several common cancers, but the effect on melanoma prognosis is unknown. OBJECTIVE: To assess the association between quality of melanoma patients' prediagnosis diets and primary tumour thickness, the main prognostic indicator for melanoma. METHODS: We used baseline data from patients newly diagnosed with tumour stage Ib to IV cutaneous melanoma, with completed questionnaires about food intake in the past year and other factors. Diet quality was measured by the Healthy Eating Index (HEI) and melanoma thickness was extracted from histopathology reports. We estimated prevalence ratios (PRadj ) and 95% confidence intervals (CIs) adjusted for confounding factors using Poisson regression models to assess associations between HEI scores and melanoma thickness. RESULTS: Of 634 study patients, 238 (38%) had melanomas >2 mm thick at diagnosis. Patients with the highest HEI scores were significantly less likely to be diagnosed with thick melanoma than patients with lowest HEI scores (PRadj 0.93, 95% CI 0.86-0.99) (Ptrend = 0.03). There was no evidence of effect modification by age, sex, previous melanoma or comorbidities. CONCLUSIONS: Melanoma thickness at diagnosis is significantly associated with quality of patients' diets before diagnosis.

Polygenic risk score as a determinant of risk of keratinocyte cancer in an Australian population-based cohort.

BACKGROUND: Keratinocyte cancer (KC) risk is determined by genetic and environmental factors. Genetic risk can be quantified by polygenic risk scores (PRS), which sum the combined effects of single nucleotide polymorphisms (SNPs). OBJECTIVES: Our objective here was to evaluate the contribution of the summed genetic score to predict the KC risk in the phenotypically well-characterized Nambour population. METHODS: We used PLINK v1.90 to calculate PRS for 432 cases, 566 controls, using 78 genome-wide independent SNPs that are associated with KC risk. We assessed the association between PRS and KC using logistic regression, stratifying the cohort into three risk groups (high 20%, intermediate 60%, low 20%). RESULTS: The fully adjusted model including traditional risk factors (phenotypic and sun exposure-related), showed a significant 50% increase in odds of KC per standard deviation of PRS (odds ratio (OR) = 1.51; 95% confidence interval (CI) = 1.30-1.76, P = 5.75 × 10-8 ). Those in the top 20% PRS had over three times the risk of KC of those in the lowest 20% (OR = 3.45; 95% CI = 2.18-5.50, P = 1.5 × 10-7 ) and higher absolute risk of KC per 100 person-years of 2.96 compared with 1.34. Area under the ROC curve increased from 0.72 to 0.74 on adding PRS to the fully adjusted model. CONCLUSIONS: These results show that PRS can enhance the prediction of KC above traditional risk factors.

Creation and Evaluation of the Illinois Cancer Risk Index as a Predictor of Four Common Cancers.

INTRODUCTION: Nearly half of all cancer deaths in the US are attributed to 4 common cancers: lung, colorectal, breast, and prostate. Illinois residents experience higher rates of cancer death from all 4 cancers compared with the US overall. We developed the Illinois Cancer Risk Index (ICRI), which incorporates many predictors of these cancers into a single summary measure, to identify Illinois counties that would benefit most from public health intervention. METHODS: We identified 90 county-level predictors of 4 common cancers, used multicollinearity testing to reduce this number to 61, and applied factor analysis to extract and analyze 4 factors representing 25 variables. Next, we created the ICRI by regressing the 4 factors on our outcome of interest - an age-adjusted common cancers mortality rate (CCMR), incorporating the direction of the ß-coefficients from regression models to sum factor scores. Finally, we mapped and assessed the geographic distributions of both ICRI and CCMR by county across the state. RESULTS: The ICRI was positively associated with the CCMR (r = 0.59, P < .001) and explained 32.2% of the variance in the CCMR across Illinois. The ICRI showed distinct geospatial patterns across the state, with the highest risk counties located in the east-central, far northern, and southern regions. The CCMR showed similar geospatial patterns. CONCLUSION: Our study identifies counties in Illinois that may benefit most from interventions that target multiple cancer risk factors simultaneously. The ICRI may be adapted for use in other geographic locations where data are available.

Developing a Needs Assessment Process to Address Gaps in a Local System of Care.

Early diagnosis and access to behavioral health services can improve the health outcomes for young children suffering from mental illness. Often, children and their families' behavioral health needs are not met due to a broken local system of care. Developing a deep understanding of the situation by exploring all stakeholders' needs across a community in conjunction with a comprehensive review of the existing scientific literature prepared one rural midwestern county to build a better local system of care. This study's unique aspects include visual mapping using art in focus groups and close collaboration between a public mental health board, academic faculty, student researchers, local behavioral health organizations, and schools. Major themes found about the existing barriers were dysfunctional patterns in families, lack of resources, reliance on the school system, and lack of access to healthcare professionals. Other communities can use this approach as a model for a local needs assessment.

First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon.

We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39} cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.