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BackgroundResearch is needed to understand and address barriers to risk management for women at high (≥20% lifetime) risk for breast cancer, but recruiting this population for research studies is challenging. ObjectiveThis paper compares a variety of recruitment strategies used for a cross-sectional, observational study of high-risk women. MethodsEligible participants were assigned female at birth, aged 25-85 years, English-speaking, living in the United States, and at high risk for breast cancer as defined by the American College of Radiology. Individuals were excluded if they had a personal history of breast cancer, prior bilateral mastectomy, medical contraindications for magnetic resonance imaging, or were not up-to-date on screening mammography per American College of Radiology guidelines. Participants were recruited from August 2020 to January 2021 using the following mechanisms: targeted Facebook advertisements, Twitter posts, ResearchMatch (a web-based research recruitment database), community partner promotions, paper flyers, and community outreach events. Interested individuals were directed to a secure website with eligibility screening questions. Participants self-reported method of recruitment during the eligibility screening. For each recruitment strategy, we calculated the rate of eligible respondents and completed surveys, costs per eligible participant, and participant demographics. ResultsWe received 1566 unique responses to the eligibility screener. Participants most often reported recruitment via Facebook advertisements (724/1566, 46%) and ResearchMatch (646/1566, 41%). Community partner promotions resulted in the highest proportion of eligible respondents (24/46, 52%), while ResearchMatch had the lowest proportion of eligible respondents (73/646, 11%). Word of mouth was the most cost-effective recruitment strategy (US $4.66 per completed survey response) and paper flyers were the least cost-effective (US $1448.13 per completed survey response). The demographic characteristics of eligible respondents varied by recruitment strategy: Twitter posts and community outreach events resulted in the highest proportion of Hispanic or Latina women (1/4, 25% and 2/6, 33%, respectively), and community partner promotions resulted in the highest proportion of non-Hispanic Black women (4/24, 17%). ConclusionsAlthough recruitment strategies varied in their yield of study participants, results overall support the feasibility of identifying and recruiting women at high risk for breast cancer outside of clinical settings. Researchers must balance the associated costs and participant yield of various recruitment strategies in planning future studies focused on high-risk women.

IntroductionWomen are at a higher risk of developing Alzheimer’s disease (AD), and the decline in estrogens post-menopause is thought of as a factor increasing this risk. Estradiol (E2) is important in supporting cholinergic neuronal integrity, and cholinergic functioning may be negatively impacted following the loss of E2 post-menopause. The use of exogenous E2 has been observed to enhance cholinergically mediated cognitive performance in healthy post-menopausal women, which indicates a potentially protective mechanism. However, E2 is often co-administered with progestin or progesterone to prevent endometrial proliferation. Progesterone/progestins have previously been shown to have a detrimental effect on E2-mediated biological and cognitive effects mediated by cholinergic systems in preclinical models, therefore the present study aimed to assess whether progesterone would modify the effect of E2 to influence cognition during cholinergic blockade.MethodsTwenty participants completed 3-months of oral E2 treatment with micronized progesterone (mPRO) or with placebo (PLC) in a repeated-measures within-subjects crossover design, in which they also completed five anticholinergic challenge days per hormone treatment condition. During the challenge participants were administered low or high doses of the nicotinic cholinergic antagonist mecamylamine, the muscarinic cholinergic antagonist scopolamine, or placebo. Following drug administration participants performed cognitive tests sensitive to cholinergic tone, assessing attention, episodic memory, and working memory.ResultsSignificant decrements were found on some tasks when participants were taking E2+mPRO compared to E2 alone. Specifically, under more challenging task conditions and larger anticholinergic doses, participants showed poorer performance on the Critical Flicker Fusion task and the Stroop test and responded more conservatively on the N-back working memory task. Other tasks showed no differences between treatments under cholinergic blockade.DiscussionThe findings show that mPRO when taken in concert with E2, was detrimental to effortful cognitive performance, in the presence of cholinergic blockade. These results are important for assessing the impact of combined postmenopausal hormone treatment on cognitive performance that is dependent on cholinergic functioning after menopause.

Abstract Compared with non‐Hispanic White women, Latina women are less likely to receive genetic counseling (GC) and testing (GT) following BC diagnosis. This study used secondary data analysis to explore beliefs about GC among Latina BC survivors in and outside the US mainland. GC/GT‐naïve, high‐risk, Spanish‐preferring Latina BC survivors (n = 52) in FL and PR completed the Behavioral Beliefs about GC scale. Participants reported high positive beliefs about GC (M = 4.19, SD = 0.92); the majority agreed that GC was beneficial to understand cancer risk (90%) and promote discussion (87%) in their family. Participants reported low‐to‐moderate scores for barriers (Ms = 1.53–3.40; SDs = 0.59–0.90). The most frequently endorsed barriers were desire for additional GC information (M = 3.44; SD = 0.90), and GC logistic concerns (M = 2.71; SD = 0.80). No statistically significant differences for barriers and benefits scales were identified by place of residence (all ps ≥ 0.12). These findings highlight the importance of delivering culturally sensitive GC information to high‐risk Latina BC survivors.

Purpose Chemotherapy-related cognitive impairment (CRCI) is a distressing and increasingly recognized long-term sequela reported by breast cancer patients following cancer treatment. There is an urgent but unmet clinical need for treatments that improve CRCI. In this context, we proposed the use of a novel cognitive enhancement strategy called Neuroflex to target CRCI experienced by breast cancer survivors. Methods The primary aim of this pilot study was to evaluate the feasibility and acceptability of Neuroflex, a novel digital cognitive enhancement strategy, in breast and gynecologic cancer survivors with CRCI. Secondary analyses focused on whether improvements in performance on Neuroflex were associated with improvement in subjective cognitive complaints and objective cognitive performance measures. Results Participants ( N = 21) completed an average of 7.42 hours of Neuroflex training per week, an average of 44.5 (±1.01) hours total, and had a 100% completion rate. Participants exhibited significant improvement in self-reported cognitive function as well as significant improvement on tasks of verbal learning and memory and auditory working memory. Participants also exhibited improvement in mood, as well as improvement on a disability assessment. Conclusions Results demonstrate feasibility and that breast cancer survivors are capable of completing a lengthy and challenging cognitive training program. Secondly, Neuroflex may confer specific cognitive benefits to both self-reported and objective performance. Results strongly support further investigation of Neuroflex in a larger controlled trial to establish efficacy for CRCI symptoms. Further studies may also result in optimization of this digital intervention for women with CRCI.

Delays in healthcare, including breast cancer screening, were documented during the coronavirus disease 2019 (COVID-19) pandemic. However, no studies have examined the impact of COVID-19 on healthcare among women at high (≥20 % lifetime) risk for breast cancer. This study fills that gap. Between August 2020 and January 2021, high-risk women (N = 225) living in the United States (US) completed an online survey assessing COVID-related healthcare disruptions. Descriptive statistics characterized the frequency of breast cancer screening (mammogram and breast magnetic resonance imaging [MRI]) since the beginning of the COVID-19 pandemic. Multivariable linear regression analysis with backward selection examined demographic characteristics associated with COVID-related healthcare disruptions. Since March 2020, 40 % of participants had received a mammogram and 12 % had received a screening breast MRI. On average, participants reported low levels of COVID-related healthcare disruptions (M = 1.97 on a 0–4 scale, higher = more disruptions). Participants who were younger (β = -0.21, p = 0.002) and not working (β = 0.18, p = 0.009) reported more COVID-related healthcare disruptions. Compared to non-Hispanic White participants, those from any other racial or ethnic group reported fewer COVID-related healthcare disruptions (β = −0.15, p = 0.020). Although few high-risk women received breast cancer screening after the declaration of the COVID-19 pandemic, they reported overall low levels of COVID-related healthcare disruptions. Results identify subgroups of high-risk women whose healthcare may have been more affected by the pandemic. Efforts to encourage US women at high risk for breast cancer to return to routine preventive care (including breast cancer screening) may need to be targeted towards women who are younger, not working, and non-Hispanic White.

Abstract Consensus and evidence suggest that cascade testing is critical to achieve the promise of cancer genetic testing. However, barriers to cascade testing include effective family communication of genetic risk information and family members’ ability to cope with genetic risk. These barriers are further complicated by the developmental needs of unaffected family members during critical windows for family communication and adaptation. Peer support could address these barriers. We provide two illustrative examples of ongoing BRCA1/2-related clinical trials that apply a peer support model to improve family communication and functioning. Peer support can augment currently available genetic services to facilitate adjustment to and effective use of cancer genetic risk information. Importantly, this scalable approach can address the presence of cancer risk within families across multiple developmental stages. This applies a family-centered perspective that accommodates all potentially at-risk relatives. This peer support model can be further applied to emerging topics in clinical genetics to expand reach and impact.

OBJECTIVES/GOALS: To identify an electroencephalographic (EEG) signature of SOR in adults with TS METHODS/STUDY POPULATION: We will recruit 60 adults with CTD and 60 sex- and age-matched healthy controls to complete scales assessing severity of SOR (Sensory Gating Inventory, SGI), tics, and psychiatric symptoms. Subjects will then be monitored on dense-array scalp EEG during sequential auditory and tactile sensory gating paradigms, as such paradigms have been shown to correlate with self-report measures of SOR in other populations. Single-trial EEG data will be segmented into 100-ms epochs and spectrally deconvoluted into standard frequency bands (delta, theta, alpha, beta, gamma) for pre-defined regions of interest. We will conduct between-group contrasts (Wilcoxon rank-sum) of band-specific sensory gating indices and within-group correlations (Spearman rank correlations) between sensory gating indices and SGI scores. RESULTS/ANTICIPATED RESULTS: We hypothesize that, relative to controls, adults with CTD exhibit impaired sensory gating and that extent of impairment correlates with severity of SOR. 14 adults with CTD (9 men, 5 women) and 16 controls (10 men, 6 women) have completed the protocol to date. Within this sample, adults with CTD showed significantly reduced sensory gating compared to controls in frontal (CTD median 0.12 dB (interquartile range -0.15–0.70 dB); control -0.37 dB (-0.80–-0.13 dB); p = 0.01) and parietal (CTD 0.17 dB (-0.08–0.50 dB); control -0.20 dB (-0.43–0.10 dB); p = 0.01) gamma band during the 100-200 ms epoch in the tactile paradigm. No significant between-group differences were evident for the auditory paradigm. Among adults with CTD, multiple sensory gating indices significantly correlated with SGI scores. Enrollment continues. DISCUSSION/SIGNIFICANCE: Results aim to clarify the extent of sensory gating impairment in TS and identify a clinical correlate of neurophysiologic dysfunction in the disorder. Such knowledge has direct implications for identification of candidate neurophysiologic biomarkers, an express goal of the National Institutes of Health.

Measurement(s) surf zone waves • swash hydrodynamics • surf zone flow velocity • morphology • sediment Technology Type(s) Gauge or Meter Device • Lidar • velocimetry • mechanical profiler • optical backscatter sensor • Pressure transducers Factor Type(s) Wave height • Wave period • beach morphology Sample Characteristic - Environment beach • shingle beach Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13194872

Abstract Consideration of heart health for cancer survivors is increasingly important, as improved cancer survivorship has resulted in a growing number of survivors affected by cardiovascular disease. However, there is limited knowledge of cardio-oncology among both patients and a variety of health professionals. Thus, efforts are needed to increase awareness about cardio-oncology. Social media represents one potential opportunity to disseminate information about cardio-oncology to a large audience. We highlight one example of a social media educational/advocacy campaign conducted on Twitter (a “Twitter Chat”) that garnered nearly 1.2 million impressions (views by Twitter users) in just 24 h. We provide both quantitative and qualitative data to support the efficacy of using Twitter for such educational/advocacy campaigns, and describe key features that contributed to its success. Twitter Chats inexpensively utilize innovative technology to provide education and foster community. Long-term studies are needed to understand whether Twitter Chats can change knowledge and behavior related to cardio-oncology.

Background: Sensory over-responsivity (SOR) refers to excessively intense and/or prolonged behavioral responses to environmental stimuli typically perceived as non-aversive. SOR is prevalent in several neurodevelopmental disorders, including chronic tic disorders (CTDs) and obsessive-compulsive disorder (OCD). Few studies have examined the extent and clinical correlates of SOR across disorders, limiting insights into the phenomenon's transdiagnostic clinical and biological relevance. Such cross-disorder comparisons are of particular interest for CTDs and OCD given their frequent co-occurrence. Objective: We sought to compare the magnitude of SOR between adults with CTD and adults with OCD and to identify the clinical factors most strongly associated with SOR across these disorders. Methods: We enrolled 207 age- and sex-matched participants across four diagnostic categories: CTD without OCD (designated “CTD/OCD-”; n = 37), CTD with OCD (“CTD/OCD+”; n = 32), OCD without tic disorder (“OCD”; n = 69), and healthy controls (n = 69). Participants completed a self-report battery of rating scales assessing SOR (Sensory Gating Inventory, SGI), obsessive-compulsive symptoms (Dimensional Obsessive-Compulsive Scale, DOCS), inattention and hyperactivity (Adult ADHD Self-Report Screening Scale for DSM-5, ASRS-5), anxiety (Generalized Anxiety Disorder-7), and depression (Patient Health Questionnaire-9). CTD participants were also administered the Yale Global Tic Severity Scale (YGTSS). To examine between-group differences in SOR, we compared SGI score across all groups and between pairs of groups. To examine the relationship of SOR with other clinical factors, we performed multivariable linear regression. Results: CTD/OCD-, CTD/OCD+, and OCD participants were 86.7%, 87.6%, and 89.5%, respectively, more likely to have higher SGI total scores than healthy controls. SGI total score did not differ between CTD/OCD-, CTD/OCD+, and OCD groups. In the regression model of log-transformed SGI total score, OCD diagnosis, DOCS score, and ASRS-5 score each contributed significantly to model goodness-of-fit, whereas CTD diagnosis and YGTSS total tic score did not. Conclusion: SOR is prevalent in adults with CTD and in adults with OCD but does not significantly differ in magnitude between these disorders. Across CTD, OCD, and healthy control adult populations, SOR is independently associated with both obsessive-compulsive and ADHD symptoms, suggesting a transdiagnostic relationship between these sensory and psychiatric manifestations. Future cross-disorder, longitudinal, and translational research is needed to clarify the role and prognostic import of SOR in CTDs, OCD, and other neurodevelopmental disorders.

Late-life depression (LLD) is a debilitating condition that is associated with poor response to antidepressant medications and deficits in cognitive performance. Nicotinic cholinergic stimulation has emerged as a potentially effective candidate to improve cognitive performance in patients with cognitive impairment. Previous studies of nicotinic stimulation in animal models and human populations with cognitive impairment led to examining potential cognitive and mood effects of nicotinic stimulation in older adults with LLD. We report results from a pilot study of transdermal nicotine in LLD testing whether nicotine treatment would enhance cognitive performance and mood. The study used electroencephalography (EEG) recordings as a tool to test for potential mechanisms underlying the effect of nicotine. Eight non-smoking participants with LLD completed EEG recordings at baseline and after 12 weeks of transdermal nicotine treatment (NCT02816138). Nicotine augmentation treatment was associated with improved performance on an auditory oddball task. Analysis of event-related oscillations showed that nicotine treatment was associated with reduced beta desynchronization at week 12 for both standard and target trials. The change in beta power on standard trials was also correlated with improvement in mood symptoms. This pilot study provides preliminary evidence for the impact of nicotine in modulating cortical activity and improving mood in depressed older adults and shows the utility of using EEG as a marker of functional engagement in nicotinic interventions in clinical geriatric patients.

Aging is associated with an increased prevalence of vascular health conditions that are linked to a disruption in the cerebral vasculature and white matter microstructural organization. In people with cardiovascular risk factors, increased cerebral arterial pulsatility is associated with poorer white matter microstructural organization and cognitive functioning. This study examines the relationship among arterial pulsatility, white matter microstructural organization, and cognitive ability in a healthy adult lifespan sample. One hundred and eighty-nine adults were divided into a younger adult (50 years, n = 92). The latter were further subdivided into two subgroups with (CV+, n = 25) and without (CV−, n = 67) cardiovascular risk factors. Arterial pulsatility was measured using cardiac-gated phase-contrast flow quantification sequence and three indexes of whole-brain white matter microstructural organization [i.e., fractional anisotropy (FA), radial diffusivity (RaD), mean diffusivity (MD)] were derived from diffusion-weighted imaging (DWI). Cognitive ability was assessed using global cognitive functioning (MoCA) and a measure of working memory [sensitivity (d′) from a 2-back task]. Neither the whole group analysis nor the younger adult group showed an association between measures of arterial pulsatility, global white matter microstructural organization, and cognition. In older adults, higher MD and RaD were associated with increased arterial pulsatility and poorer working memory performance. The indirect pathway from arterial pulsatility to working memory performance via both MD and RaD measures was significant in this group. Interestingly, a comparison of CV+ and CV− subgroups showed that this mediating relationship was only evident in older adults with at least one CV risk factor. These findings are consistent with cardiovascular risk factors as underlying arterial, white matter, and cognitive decline in cognitively normal older adults.

An extensive record of current velocities at all levels in the water column is an indispensable requirement for a tidal resource assessment and is fully necessary for accurate determination of available energy throughout the water column as well as estimating likely energy capture for any particular device. Traditional tidal prediction using the least squares method requires a large number of harmonic parameters calculated from lengthy acoustic Doppler current profiler (ADCP) measurements, while long-term in situ ADCPs have the advantage of measuring the real current but are logistically expensive. This study aims to show how these issues can be overcome with the use of a neural network to predict current velocities throughout the water column, using surface currents measured by a high-frequency radar. Various structured neural networks were trained with the aim of finding the network which could best simulate unseen subsurface current velocities, compared to ADCP data. This study shows that a recurrent neural network, trained by the Bayesian regularisation algorithm, produces current velocities highly correlated with measured values: r2 (0.98), mean absolute error (0.05 ms−1), and the Nash–Sutcliffe efficiency (0.98). The method demonstrates its high prediction ability using only 2 weeks of training data to predict subsurface currents up to 6 months in the future, whilst a constant surface current input is available. The resulting current predictions can be used to calculate flow power, with only a 0.4% mean error. The method is shown to be as accurate as harmonic analysis whilst requiring comparatively few input data and outperforms harmonics by identifying non-celestial influences; however, the model remains site specific.

New antibiotics are needed against antibiotic-resistant gram-negative bacteria. The repurposed antifungal drug, ciclopirox, equally blocks antibiotic-susceptible or multidrug-resistant Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae clinical isolates, indicating that it is not affected by existing resistance mechanisms. Toward understanding how ciclopirox blocks growth, we screened E. coli mutant strains and found that disruption of genes encoding products involved in galactose salvage, enterobacterial common antigen synthesis, and transport of the iron binding siderophore, enterobactin, lowered the minimum inhibitory concentration of ciclopirox needed to block growth of the mutant compared to the isogenic parent strain. We found that ciclopirox induced enterobactin production and that this effect is strongly affected by the deletion of the galactose salvage genes encoding UDP-galactose 4-epimerase, galE, or galactose-1-phosphate uridylyltransferase, galT. As disruption of ECA synthesis activates the regulation of capsular synthesis (Rcs) phosphorelay, which inhibits bacterial swarming and promotes biofilm development, we test whether ciclopirox prevents activation of the Rcs pathway. Sub-inhibitory concentrations of ciclopirox increased swarming of the E. coli laboratory K12 strain BW25113 but had widely varying effects on swarming or surface motility of clinical isolate E. coli, A. baumannii, and K. pneumoniae. There was no effect of ciclopirox on biofilm production, suggesting it does not target Rcs. Altogether, our data suggest ciclopirox-mediated alteration of lipopolysaccharides stimulates enterobactin production and affects bacterial swarming.

A Correction to this paper has been published: https://doi.org/10.1038/s41597-021-00874-2.

Event-related potential (ERP) studies using the task-switching paradigm show that multiple ERP components are modulated by activation of proactive control processes involved in preparing to repeat or switch task and reactive control processes involved in implementation of the current or new task. Our understanding of the functional significance of these ERP components has been hampered by variability in their robustness, as well as their temporal and scalp distribution across studies. The aim of this study is to examine the effect of choice of reference electrode or spatial filter on the number, timing and scalp distribution of ERP elicited during task-switching. We compared four configurations, including the two most common (i.e., average mastoid reference and common average reference) and two novel ones that aim to reduce volume conduction (i.e., reference electrode standardization technique (REST) and surface Laplacian) on mixing cost and switch cost effects in cue-locked and target-locked ERP waveforms in 201 healthy participants. All four spatial filters showed the same well-characterized ERP components that are typically seen in task-switching paradigms: the cue-locked switch positivity and target-locked N2/P3 effect. However, both the number of ERP effects associated with mixing and switch cost, and their temporal and spatial resolution were greater with the surface Laplacian transformation which revealed rapid temporal adjustments that were not identifiable with other spatial filters. We conclude that the surface Laplacian transformation may be more suited to characterize EEG signatures of complex spatiotemporal networks involved in cognitive control.

The coastal zone hosts a great number of activities that require knowledge of the spatial characteristics of the wave field, which in coastal seas can be highly heterogeneous. Information of this type can be obtained from HF radars, which offer attractive performance characteristics in terms of temporal and spatial resolution. This paper presents the validation of radar-derived fields of directional wave spectra. These were retrieved from measurements collected with an HF radar system specifically deployed for wave measurement, using an established inversion algorithm. Overall, the algorithm reported accurate estimates of directional spectra, whose main distinctive characteristic was that the spectral energy was typically spread over a slightly broader range of frequencies and directions than in their in situ-measured counterparts. Two errors commonly reported in previous studies, namely the overestimation of wave heights and noise related to short measurement periods, were not observed in our results. The maximum wave height recorded by two in situ devices differed by 30 cm on average from the radar-measured values, and with the exception of the wave spreading, the standard deviations of the radar wave parameters were between 3% and 20% of those obtained with the in situ datasets, indicating the two were similarly grouped around their means. At present, the main drawback of the method is the high quality signal required to perform the inversion. This is in part responsible for a reduced data return, which did not exceed 55% at any grid cell over the eight-month period studied here.

Coastal evolution occurs on a wide range of time-scales, from storms, seasonal and inter-annual time-scales to longer-term adaptation to changing environmental conditions. Measuring campaigns typically either measure morphological evolution on a short-time scale (days) with high frequency (hourly) or long-time scales (years) but intermittently (monthly). This leaves an important observational gap that limits morphological variability assessments. Traditional echo sounding measurements on this long time-scale and high-frequency sampling require a significant financial injection. Shore-based video systems with high spatiotemporal resolution can bridge this gap. For the first time, hourly Kalman filtered video-derived bathymetries covering 1.5 years of morphological evolution with an hourly resolution obtained at Porhtowan, UK are presented. Here, the long-term hourly dataset is used and aims to show its added value for, and provide an in-depth, morphological analyses with unprecedented temporal resolution. The time-frame includes calm and extreme (storm) wave conditions in a macro-tidal environment. The video-derived bathymetries allow hourly beach state classification while before this was not possible due to the dependence on foam patterns of wave breaking (e.g., saturation during storms). The study period covers extreme storm erosion during the most energetic winter season in 60 years (2013–2014). Recovery of the beach takes place on several time-scales: (1) an immediate initial recovery after the storm season (first 2 months), (2) limited recovery during low energetic summer conditions and (3) accelerated recovery as the wave conditions picked up in the subsequent fall—under wave conditions that are typically erosive. The video-derived bathymetries are shown to be effective in determining bar-positions, outer-bar three-dimensionality and volume analyses with an unprecedented hourly temporal resolution.