Implementing Longitudinal Wellbeing Interventions and Evaluation Among Midwestern Healthcare Workers During COVID-19.

BACKGROUND: The impact of the COVID-19 pandemic on the mental health of healthcare workers throughout the world has been reported, but most studies have been cross-sectional and excluded the Midwestern U.S. healthcare workforce. OBJECTIVE: This study aimed to longitudinally assess the psychological wellbeing and wellness strategies used by a Midwestern academic health system's workforce at multiple points throughout waves of the COVID-19 pandemic to inform ongoing implementation of appropriate wellness activities. METHODS: An anonymous REDCap survey linked within our team-developed wellness education was posted in the employee online newsletter in April (T1), July (T2), October 2020 (T3), and May 2021 (T4). Surveys were open to all employees (approx. 9000) for approximately 12 days at each time point. Anxiety, depressive symptoms, stress, self-efficacy, and self-care activities were assessed. Following each data collection, team members discussed findings and planned wellness education implementation. RESULTS: Response ranged from n = 731 (T1) to n = 172 (T4). Moderate to severe stress was reported by 29.5% (n = 203) of respondents at T1 and 34.0% (n = 108) at T2. At T3, all psychological symptoms significantly increased (p < .001) as COVID-19 surged, with 48.5% (n = 141) of respondents reporting moderate to severe stress. At T4, stress significantly declined (p < .001). Exercise was the most frequently reported coping strategy. CONCLUSIONS: Mental health symptoms reported by a Midwestern healthcare workforce increased during surges of COVID-19 hospitalizations. Individuals in non-patient contact roles experienced symptom levels similar to and at times with greater severity than healthcare personnel with patient contact roles.

Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype.

Breast cancer leptomeningeal metastasis (BCLM), where tumour cells grow along the lining of the brain and spinal cord, is a devastating development for patients. Investigating this metastatic site is hampered by difficulty in accessing tumour material. Here, we utilise cerebrospinal fluid (CSF) cell-free DNA (cfDNA) and CSF disseminated tumour cells (DTCs) to explore the clonal evolution of BCLM and heterogeneity between leptomeningeal and extracranial metastatic sites. Somatic alterations with potential therapeutic actionability were detected in 81% (17/21) of BCLM cases, with 19% detectable in CSF cfDNA only. BCLM was enriched in genomic aberrations in adherens junction and cytoskeletal genes, revealing a lobular-like breast cancer phenotype. CSF DTCs were cultured in 3D to establish BCLM patient-derived organoids, and used for the successful generation of BCLM in vivo models. These data reveal that BCLM possess a unique genomic aberration profile and highlight potential cellular dependencies in this hard-to-treat form of metastatic disease.

Microwave-Frequency Scanning Gate Microscopy of a Si/SiGe Double Quantum Dot.

Conventional transport methods provide quantitative information on spin, orbital, and valley states in quantum dots but lack spatial resolution. Scanning tunneling microscopy, on the other hand, provides exquisite spatial resolution at the expense of speed. Working to combine the spatial resolution and energy sensitivity of scanning probe microscopy with the speed of microwave measurements, we couple a metallic tip to a Si/SiGe double quantum dot (DQD) that is integrated with a charge detector. We first demonstrate that the dc-biased tip can be used to change the occupancy of the DQD. We then apply microwaves through the tip to drive photon-assisted tunneling (PAT). We infer the DQD level diagram from the frequency and detuning dependence of the tunneling resonances. These measurements allow the resolution of ∼65 µeV excited states, an energy consistent with valley splittings in Si/SiGe. This work demonstrates the feasibility of scanning gate experiments with Si/SiGe devices.

Cancer-Associated Fibroblasts Suppress CD8+ T-cell Infiltration and Confer Resistance to Immune-Checkpoint Blockade.

Immune-checkpoint blockade (ICB) promotes antitumor immune responses and can result in durable patient benefit. However, response rates in breast cancer patients remain modest, stimulating efforts to discover novel treatment options. Cancer-associated fibroblasts (CAF) represent a major component of the breast tumor microenvironment and have known immunosuppressive functions in addition to their well-established roles in directly promoting tumor growth and metastasis. Here we utilized paired syngeneic mouse mammary carcinoma models to show that CAF abundance is associated with insensitivity to combination αCTLA4 and αPD-L1 ICB. CAF-rich tumors exhibited an immunologically cold tumor microenvironment, with transcriptomic, flow cytometric, and quantitative histopathologic analyses demonstrating a relationship between CAF density and a CD8+ T-cell-excluded tumor phenotype. The CAF receptor Endo180 (Mrc2) is predominantly expressed on myofibroblastic CAFs, and its genetic deletion depleted a subset of αSMA-expressing CAFs and impaired tumor progression in vivo. The addition of wild-type, but not Endo180-deficient, CAFs in coimplantation studies restricted CD8+ T-cell intratumoral infiltration, and tumors in Endo180 knockout mice exhibited increased CD8+ T-cell infiltration and enhanced sensitivity to ICB compared with tumors in wild-type mice. Clinically, in a trial of melanoma patients, high MRC2 mRNA levels in tumors were associated with a poor response to αPD-1 therapy, highlighting the potential benefits of therapeutically targeting a specific CAF subpopulation in breast and other CAF-rich cancers to improve clinical responses to immunotherapy. SIGNIFICANCE: Paired syngeneic models help unravel the interplay between CAF and tumor immune evasion, highlighting the benefits of targeting fibroblast subpopulations to improve clinical responses to immunotherapy.

Two-qubit silicon quantum processor with operation fidelity exceeding 99.

Silicon spin qubits satisfy the necessary criteria for quantum information processing. However, a demonstration of high-fidelity state preparation and readout combined with high-fidelity single- and two-qubit gates, all of which must be present for quantum error correction, has been lacking. We use a two-qubit Si/SiGe quantum processor to demonstrate state preparation and readout with fidelity greater than 97%, combined with both single- and two-qubit control fidelities exceeding 99%. The operation of the quantum processor is quantitatively characterized using gate set tomography and randomized benchmarking. Our results highlight the potential of silicon spin qubits to become a dominant technology in the development of intermediate-scale quantum processors.

Contained: why it's better to display some products without a package.

Across varying marketplace contexts (e.g., grocery stores, restaurants, e-commerce) managers display products with and without packaging, seemingly arbitrarily. Does displaying a product packaged as opposed to unpackaged influence consumers' product responses? Six controlled experiments and an Instagram study address this question. We focus primarily on food products but show our results extend to non-food products that are natural (i.e., originate from plants, animals, or humans). We propose that, in addition to its physical function, packaging acts as a symbolic barrier that separates the product from nature, decreasing perceived product naturalness and leading to less favorable product responses. Consistent with our theorizing, the negative effects of packaging attenuate when product information or retail signage highlights the product's connection to nature and are contingent on the importance of product naturalness. Our findings have implications for strategic use of packaging in physical and digital merchandising and sustainability initiatives aimed at reducing packaging. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11747-021-00800-3.

Assessing CSF ctDNA to Improve Diagnostic Accuracy and Therapeutic Monitoring in Breast Cancer Leptomeningeal Metastasis.

PURPOSE: Cerebrospinal fluid (CSF) cytology is the gold standard diagnostic test for breast cancer leptomeningeal metastasis (BCLM), but has impaired sensitivity, often necessitating repeated lumbar puncture to confirm or refute diagnosis. Further, there is no quantitative response tool to assess response or progression during BCLM treatment. EXPERIMENTAL DESIGN: Facing the challenge of working with small-volume samples and the lack of common recurrent mutations in breast cancers, cell-free DNA was extracted from the CSF and plasma of patients undergoing investigation for BCLM (n = 30). ctDNA fraction was assessed by ultra-low-pass whole genome sequencing (ulpWGS), which does not require prior tumor sequencing. RESULTS: In this proof-of-concept study, ctDNA was detected (fraction ≥0.10) in the CSF of all 24 patients with BCLM+ (median ctDNA fraction, 0.57), regardless of negative cytology or borderline MRI imaging, whereas CSF ctDNA was not detected in the six patients with BCLM- (median ctDNA fraction 0.03, P < 0.0001). Plasma ctDNA was only detected in patients with extracranial disease progression or who had previously received whole brain radiotherapy. ctDNA fraction was highly concordant with mutant allele fraction measured by tumor mutation-specific ddPCR assays (r = 0.852; P < 0.0001). During intrathecal treatment, serial monitoring (n = 12 patients) showed that suppression of CSF ctDNA fraction was associated with longer BCLM survival (P = 0.034), and rising ctDNA fraction was detectable up to 12 weeks before clinical progression. CONCLUSIONS: Measuring ctDNA fraction by ulpWGS is a quantitative marker demonstrating potential for timely and accurate BCLM diagnosis and therapy response monitoring, with the ultimate aim to improve management of this poor-prognosis patient group.

CaringGuidance™ after breast cancer diagnosis eHealth psychoeducational intervention to reduce early post-diagnosis distress.

PURPOSE: Significant cancer-related distress affects 30-60% of women diagnosed with breast cancer. Fewer than 30% of distressed patients receive psychosocial care. Unaddressed distress is associated with poor treatment adherence, reduced quality of life, and increased healthcare costs. This study aimed to evaluate the preliminary efficacy of a new web-based, psychoeducational distress self-management program, CaringGuidance™ After Breast Cancer Diagnosis, on newly diagnosed women's reported distress. METHODS: One-hundred women, in five states, diagnosed with breast cancer within the prior 3 months, were randomized to 12 weeks of independent use of CaringGuidance™ plus usual care or usual care alone. The primary multidimensional outcome, distress, was measured with the Distress Thermometer (DT), the Center for Epidemiologic Studies Depression Scale (CES-D), and the Impact of Events Scale (IES) at baseline and months 1, 2, and 3. Intervention usage was continually monitored by the data analytic system imbedded within CaringGuidance™. RESULTS: Although multilevel models showed no significant overall effects, post hoc analysis showed significant group differences in slopes occurring between study months 2 and 3 on distress (F(1,70) = 4.91, p = .03, η2 = .065) measured by the DT, and depressive symptoms (F(1, 76) = 4.25, p = .043, η2 = .053) favoring the intervention. CONCLUSIONS: Results provide preliminary support for the potential efficacy of CaringGuidance™ plus usual care over usual care alone on distress in women newly diagnosed with breast cancer. This analysis supports and informs future study of this self-management program aimed at filling gaps in clinical distress management.

Effects of social constraints and web-based psychoeducation on cancer-related psychological adjustment early-after breast cancer diagnosis.

Purpose: Social constraints are interactions between individuals that result in preventing one's disclosure of thoughts and emotions needed to facilitate cognitive processing of a traumatic event such as a breast cancer diagnosis. This study explored women's perceived social constraints from spouse/partners (S/P) and family/friends (F/F) in the first months after diagnosis while engaged in a study of CaringGuidance™ After Breast Cancer Diagnosis, a web-based, psychoeducational, self-management intervention aimed at women's psychological adjustment. Design: Randomized, controlled, pilot study. Sample: 100 women within 0-3 months of first, stage 0-II breast cancer diagnosis. Methods: Subjects were randomized to self-guided use of CaringGuidance™ for three months plus usual care or usual care alone. Social constraints (S/P) and (F/F), distress, depressive-symptoms, intrusive/avoidant thoughts, and coping were measured at baseline, 1, 2, and 3 months. Findings: The CaringGuidance™ group experienced a significantly greater decrease in perceived social constraints from S/P and F/F over three months than the usual care group. Change in social constraints from F/F significantly moderated change in depressive-symptoms and intrusive/avoidant thoughts, but the same was not true for change in S/P constraints. Conclusions: CaringGuidance™ holds promise as an intervention for newly diagnosed women to self-manage perceptions of social constraints. Implications for Psychosocial Providers: Providers should assess newly diagnosed women's perceptions of social constraining behavior from F/F, recognizing the potential significant impact of these interactions on psychological adjustment.

Examination of evaluative threat in worry: Insights from the Error-Related Negativity (ERN).

Recent research suggests atypical error-monitoring is important to understanding pathological anxiety. Because uncertainty is a transdiagnostic factor associated with anxiety and related disorders, recent research has begun to examine the influence of uncertainty in error-monitoring. Moreover, task irrelevant threat has been shown to influence cognitive performance in individuals with maladaptive anxiety. The current study aims to merge these literatures by examining the influence of task-irrelevant uncertain evaluative threat on error-monitoring using an event-related brain potential, the error-related negativity (ERN). Considering extensive literature indicating a relationship between worry and the ERN, worry was included as a continuous predictor in the analyses. Participants were randomly assigned to either a condition of negative or uncertain evaluative threat to determine their influence on error-monitoring in a Flankers task. Results for the ERN suggest that the ERN was significantly reduced only for the uncertain evaluative threat condition. The current study suggests that uncertain evaluative threat distractors result in a subsequent reduction in error-monitoring. This is consistent with literature suggesting that anxiety impairs inhibition of attentional processing of task irrelevant threatening information. This study adds to the burgeoning literature on the malleability of the ERN. Future research is needed to determine the mechanisms underlying this effect.

Preparation and Characterization of C60/Graphene Hybrid Nanostructures.

Physical thermal deposition in a high vacuum environment is a clean and controllable method for fabricating novel molecular nanostructures on graphene. We present methods for depositing and passively manipulating C60 molecules on rippled graphene that advance the pursuit of realizing applications involving 1D C60/graphene hybrid structures. The techniques applied in this exposition are geared towards high vacuum systems with preparation areas capable of supporting molecular deposition as well as thermal annealing of the samples. We focus on C60 deposition at low pressure using a homemade Knudsen cell connected to a scanning tunneling microscopy (STM) system. The number of molecules deposited is regulated by controlling the temperature of the Knudsen cell and the deposition time. One-dimensional (1D) C60 chain structures with widths of two to three molecules can be prepared via tuning of the experimental conditions. The surface mobility of the C60 molecules increases with annealing temperature allowing them to move within the periodic potential of the rippled graphene. Using this mechanism, it is possible to control the transition of 1D C60 chain structures to a hexagonal close packed quasi-1D stripe structure.

Integrated Treatment of PTSD and Substance Use Disorders: Examination of Imaginal Exposure Length.

Efforts to improve the efficiency of prolonged exposure (PE) therapy for posttraumatic stress disorder (PTSD) have demonstrated that reducing the length of imaginal exposures does not negatively affect treatment outcome. A recent adaptation of PE, called Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure [COPE], integrates substance use disorder treatment with PE in the same timeframe (twelve 90-minute sessions, 8 of which include imaginal exposure). The current study, which represents a subanalysis of a larger randomized controlled trial, examined how the length of imaginal exposures (nonrandomized and measured continually) related to PTSD, substance use, and depression in a sample of military veterans (N = 31) who completed the COPE treatment. Participants completed an average of 11.5 of the 12 therapy sessions and 7.2 of the 8 imaginal exposures during treatment. Results of 3 linear mixed models indicate that PTSD, substance use, and depressive symptoms all improved over the course of treatment (ps < .001; η2 ranged between .17 and .40), and that the length of imaginal exposures did not significantly interact with any outcome. Although preliminary, the findings suggest that it may be feasible to shorten imaginal exposures without mitigating treatment gains. Implications for treatment are discussed.

Concreteness of idiographic worry and anticipatory processing.

BACKGROUND AND OBJECTIVES: Worry and anticipatory processing are forms of repetitive negative thinking (RNT) that are associated with maladaptive characteristics and negative consequences. One key maladaptive characteristic of worry is its abstract nature (Goldwin & Behar, 2012; Stöber & Borkovec, 2002). Several investigations have relied on inductions of worry that are social-evaluative in nature, which precludes distinctions between worry and RNT about social-evaluative situations. The present study examined similarities and distinctions between worry and anticipatory processing on potentially important maladaptive characteristics. METHODS: Participants (N = 279) engaged in idiographic periods of uninstructed mentation, worry, and anticipatory processing and provided thought samples during each minute of each induction. Thought samples were assessed for concreteness, degree of verbal-linguistic activity, and degree of imagery-based activity. RESULTS: Both worry and anticipatory processing were characterized by reduced concreteness, increased abstraction of thought over time, and a predominance of verbal-linguistic activity. However, worry was more abstract, more verbal-linguistic, and less imagery-based relative to anticipatory processing. Finally, worry demonstrated reductions in verbal-linguistic activity over time, whereas anticipatory processing demonstrated reductions in imagery-based activity over time. LIMITATIONS: Worry was limited to non-social topics to distinguish worry from anticipatory processing, and may not represent worry that is social in nature. Generalizability may also be limited by use of an undergraduate sample. CONCLUSIONS: Results from the present study provide support for Stöber's theory regarding the reduced concreteness of worry, and suggest that although worry and anticipatory processing share some features, they also contain characteristics unique to each process.

Relations among social support, PTSD symptoms, and substance use in veterans.

Social support plays a significant role in the development, maintenance, and treatment of posttraumatic stress disorder (PTSD). However, there has been little investigation of social support with PTSD and its frequent comorbid conditions and related symptoms. Substance use disorders (SUDs) are 1 set of conditions that have yet to be investigated in combination with PTSD and social support. As compared with civilians, veterans are at increased risk for developing both PTSD and SUD. In this study, veterans (N = 171) with symptoms of PTSD (76% met diagnostic criteria) and SUD (83% met diagnostic criteria for any dependence) were recruited and completed clinician-rated and self-report measures of PTSD, SUD, and social support. Overall, low social support was reported in the sample. When controlled for the other disorder's symptoms, PTSD symptoms demonstrated a significant negative relation and SUD symptoms demonstrated a significant positive relation to social support. The PTSD findings are consistent with previous studies on PTSD and social support without SUD comorbidity. However, the SUD findings are inconsistent with previous studies, which focused primarily on older veterans. Together, these findings highlight the significance of social support in individuals with PTSD and SUD and promote future research within comorbid presentations. (PsycINFO Database Record

Trait attentional control influences the relationship between repetitive negative thinking and psychopathology symptoms.

Repetitive negative thinking (RNT) has been implicated in several disorders (e.g., Clark (2005)). However, little research has examined how RNT influences other risk factors of psychopathology, such as attentional control. This study used prospective methodology to determine if relationships among various RNT styles and symptoms of psychological disorders are indirectly influenced by facets of attentional control. The sample included 376 participants who completed measures of RNT (worry, rumination, anticipatory processing, obsessions, intrusive thoughts and panic cognitions), psychopathology (generalized anxiety disorder, depression, social anxiety, obsessive-compulsive disorder, posttraumatic stress disorder, and panic disorder), and attentional control at two time points. Several relationships between RNT forms and symptom levels were indirectly predicted by the focusing subscale of attentional control; however, the patterns of these relationships differed based on the disorder. The shifting subscale did not indirectly predict any relationship. Therefore, it appears that low focusing may be a particular risk factor for the development of later RNT and/or psychopathology symptoms.

Electrocortical Evidence of Enhanced Performance Monitoring in Social Anxiety.

Self-focused attention is thought to be a key feature of social anxiety disorder. Yet few studies have used event-related potentials (ERPs) to examine whether socially anxious individuals display greater monitoring of their performance and attention to their errors. Similarly, only a few studies have used ERPs to examine how social anxiety is related to processing of performance feedback. Individuals with high (n=26) and low (n=28) levels of social anxiety completed a trial-and-error learning task. Self-focus was manipulated using false heart-rate feedback during a random subset of trials. Performance feedback was given using emotional and neutral faces in a positive context (correct=happy face; incorrect=neutral face) and negative context (correct=neutral face; incorrect=disgust face) in order to investigate biased interpretation and attention to feedback. Socially anxious subjects displayed enhanced amplitude of the ERN and CRN, suggesting greater response monitoring, and enhanced Pe amplitude, suggesting greater processing of errors relative to the low social anxiety group. No group differences were observed with respect to feedback processing. Before learning stimulus-response mappings in the negative context, the FRN was larger for self-focus compared to standard trials and marginally larger for socially anxious subjects compared to controls. These findings support cognitive models and suggest avenues for future research.

Worry and Discrimination of Threat and Safety Cues: An Event-Related Potential Investigation.

Overgeneralization of fear to safety cues is increasingly being studied in order to further our understanding of the maintenance of anxiety disorders. The current study used event-related potentials (ERPs) to evaluate whether worry affects anticipation and processing of threat and neutral pictures during a conditioning task. Fifty-two high (n=24) and low (n=28) worriers completed a paradigm in which a neutral stimulus indicated the valence of a second stimulus, either a threat or neutral picture. Results found that worriers displayed reduced anticipatory responses to both stimulus types as indexed by the stimulus preceding negativity, although they displayed an increased stimulus preceding negativity to threatening images during the second half of the task. In addition, high and low worriers differed in processing of threat and neutral images as indexed by the late positive potential. These findings support the overgeneralization of fear literature, suggesting that worriers display difficulty discriminating safety cues from threat cues, and this affects the attentional resources devoted to subsequent stimuli. Implications of these results are discussed.

Temperature Evolution of Quasi-one-dimensional C60 Nanostructures on Rippled Graphene.

We report the preparation of novel quasi-one-dimensional (quasi-1D) C60 nanostructures on rippled graphene. Through careful control of the subtle balance between the linear periodic potential of rippled graphene and the C60 surface mobility, we demonstrate that C60 molecules can be arranged into a quasi-1D C60 chain structure with widths of two to three molecules. At a higher annealing temperature, the quasi-1D chain structure transitions to a more compact hexagonal close packed quasi-1D stripe structure. This first experimental realization of quasi-1D C60 structures on graphene may pave a way for fabricating new C60/graphene hybrid structures for future applications in electronics, spintronics and quantum information.

The comparative efficacy of first- versus second-generation electronic cigarettes in reducing symptoms of nicotine withdrawal.

BACKGROUND AND AIMS: Currently, electronic cigarettes (e-cigarettes) are studied as though they are a homogeneous category. However, there are several noteworthy differences in the products that fall under this name, including potential differences in the efficacy of these products as smoking cessation aids. The current study examined the comparative efficacy of first- and second-generation e-cigarettes in reducing nicotine withdrawal symptoms in a sample of current smokers with little or no experience of using e-cigarettes. DESIGN: Twenty-two mildly to moderately nicotine-dependent individuals were randomized to a cross-over design in which they used first- and second-generation e-cigarettes on separate days with assessment of withdrawal symptoms directly prior to and after product use. SETTING AND PARTICIPANTS: A community-based sample recruited in the Midwest region of the United States reported a mean age of 28.6 [standard deviation (SD) = 12.9]. The majority were male (56.5%), Caucasian (91.3%), reported smoking an average of 15.2 (SD = 9.6) tobacco cigarettes per day, and a mean baseline carbon monoxide (CO) level of 18.7 parts per million (p.p.m.). MEASUREMENTS: Symptoms of withdrawal from nicotine were measured via the Mood and Physical Symptoms Scale. FINDINGS: Analysis of changes in withdrawal symptoms revealed a significant time × product interaction F(1, 21) = 5.057, P = 0.036, n(2) P = 0.202. Participants experienced a larger reduction in symptoms of nicotine withdrawal after using second-generation compared with first-generation e-cigarettes. CONCLUSIONS: Second-generation e-cigarettes seem to be more effective in reducing symptoms of nicotine withdrawal than do first-generation e-cigarettes.

The influence of stress on the affective modulation of the startle response to nicotine cues.

Recent research suggesting that nicotine cues are appetitive in nature promotes the affective modulation of the startle reflex (AMSR) paradigm as a potentially valuable psychophysiological tool for elucidating mechanisms involved in nicotine addiction. Despite numerous studies indicating stress as a key factor in nicotine dependence, specific behavioral mechanisms linking stress and smoking have yet to be explicated. The current study aimed to determine the effects of stress, a negative affective state intimately linked with nicotine use, on the psychophysiological responding of nicotine dependent individuals during smoking cues. Twenty-nine nicotine dependent individuals were randomly assigned to the trier social stress test or control condition directly prior to administration of the AMSR paradigm, which examined their physiological responses to appetitive, neutral, aversive, and nicotine cue images. Both groups evinced significantly decreased startle magnitudes in response to nicotine cues as compared to aversive images. However, exposure to stress did not significantly modulate the startle reflex while viewing nicotine cues. Stress induction does not appear to modulate the AMSR paradigm when evaluating responses to nicotine images. These findings suggest that AMSR is robust to effects of acute stress induction in nicotine dependent individuals which may increase its viability as a clinical tool for assessing success in smoking cessation interventions.