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Introduction Early discontinuation of endocrine therapy (ET) is higher among patients with early breast cancer (EBC) compared to patients with metastatic hormone receptor-positive (HR+) breast cancer (MBC). In our clinical experience the reasons for this may include a significant burden of ET side effects impacting quality of life (QOL) in patients with EBC. We hypothesized that QOL is lower in patients with HR + EBC compared to patients with HR + MBC on ET. Methods We conducted a cross-sectional observational study to assess QOL utilizing FACT-ES & EORTC QLQ C30 tools among patients with EBC and MBC receiving ET across 5 Irish hospitals. Results A total of 417 patients were enrolled—EBC (79% n  = 331) and MBC 21% (n  = 86). Using the FACT-ES, we found no difference in overall QOL by stage (139.2 vs 141, P  = .33). Patients with HR + MBC had a lower symptom burden from ET compared to HR + EBC (61.4 vs 54, P  < .01). In adjusted multivariate linear regression models, there was no difference in QOL for patients with EBC and MBC receiving ET. Conclusions There was no significant difference in overall QOL for patients with EBC and MBC. However, patients with EBC experienced more endocrine symptoms. In adjusted multivariate linear regression models, the stage did not predict QOL. Our results suggest that endocrine symptoms are significant contributors to impaired QOL for patients with EBC but the role of other determinants of QOL (eg, stage) is less clear. Future work could include the development of stage-specific QOL tools and utilization of electronic patient-reported outcomes (ePROs) to identify and manage emergent toxicities. [ABSTRACT FROM AUTHOR]

More severe atopic dermatitis and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) consortium (a large-scale European, interdisciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small-scale studies through to large multicentre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important codependencies and relationships across variables and domains. We prioritize definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a particular point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses, and validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalizable to current and future research efforts. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with non-small cell lung cancer (NSCLC) have a number of possible systemic treatment options, including targeted therapy, chemotherapy, immunotherapy, or antibody–drug conjugates. Approximately two thirds of lung adenocarcinomas have changes in single genes ('oncogenes' or oncogenic driver alterations), which drive the growth of these cancers. The role of immunotherapy in these cancers is debated, and may be different depending on the mutation present. In this review, we summarize current evidence regarding the use of immunotherapy in specific genomically driven subsets of lung adenocarcinoma. We analyze this in terms of specific mutations, focusing on both efficacy and toxicity, and potential future directions. Over the past 20 years, there has been a paradigm shift in the care of patients with non-small cell lung cancer (NSCLC), who now have a range of systemic treatment options including targeted therapy, chemotherapy, immunotherapy (ICI), and antibody–drug conjugates (ADCs). A proportion of these cancers have single identifiable alterations in oncogenes that drive their proliferation and cancer progression, known as "oncogene-addiction". These "driver alterations" are identified in approximately two thirds of patients with lung adenocarcinomas, via next generation sequencing or other orthogonal tests. It was noted in the early clinical development of ICIs that patients with oncogene-addicted NSCLC may have differential responses to ICI. The toxicity signal for patients with oncogene-addicted NSCLC when treated with ICIs also seemed to differ depending on the alteration present and the specific targeted agent used. Developing a greater understanding of the underlying reasons for these clinical observations has become an important area of research in NSCLC. In this review, we analyze the efficacy and safety of ICI according to specific mutations, and consider possible future directions to mitigate safety concerns and improve the outcomes for patients with oncogene-addicted NSCLC. [ABSTRACT FROM AUTHOR]

To assess the content, quality, and supporting evidence base of clinical practice guidelines (CPGs) with reference to cognitive assessment in stroke. We performed a systematic review to identify eligible CPGs pertaining to cognitive assessment in adult stroke survivors. We compared content and strength of recommendations. We used the AGREE-II (appraisal of guidelines for research and evaluation) tool to appraise the quality of the guideline. Eight eligible guidelines were identified and seven were rated as high quality (i.e., appropriately addressing at least four domains of the AGREE-II tool including "rigor of development"). There was heterogeneity in the recommendations offered and limited guidance on fundamental topics such as which cognitive test to use or when to perform testing. Generally, the lowest quality of evidence (expert opinion) was used to inform these recommendations. Although assessment of cognition is a key aspect of stroke care, there is a lack of guidance for clinicians. The limited evidence base, in part, reflects the limited research in the area. A prescriptive approach to cognitive assessment may not be suitable, but more primary research may help inform practice. Cognitive assessment in stroke exhibits substantial variation in practice, clinical practice guidelines rarely give prescriptive recommendations on which approach to take. Where guideline recommendations on cognitive assessment in stroke were made these were based on expert opinion. Our summary of the guideline content found certain areas of consensus, for example, routine assessment using validated tools. [ABSTRACT FROM AUTHOR]

Molecular crystals cannot be designed in the same manner as macroscopic objects, because they do not assemble according to simple, intuitive rules. Their structures result from the balance of many weak interactions, rather than from the strong and predictable bonding patterns found in metalorganic frameworks and covalent organic frameworks. Hence, design strategies that assume a topology or other structural blueprint will often fail. Here we combine computational crystal structure prediction and property prediction to build energystructurefunction maps that describe the possible structures and properties that are available to a candidate molecule. Using these maps, we identify a highly porous solid, which has the lowest density reported for a molecular crystal so far. Both the structure of the crystal and its physical properties, such as methane storage capacity and guest-molecule selectivity, are predicted using the molecular structure as the only input. More generally, energystructurefunction maps could be used to guide the experimental discovery of materials with any target function that can be calculated from predicted crystal structures, such as electronic structure or mechanical properties., Author(s): Angeles Pulido [1]; Linjiang Chen [2]; Tomasz Kaczorowski [2]; Daniel Holden [2]; Marc A. Little [2]; Samantha Y. Chong [2]; Benjamin J. Slater [2]; David P. McMahon [1]; Baltasar [...]

Background: The COVID-19 pandemic has resulted in radical changes in the delivery of healthcare worldwide. Our oncology service (at an Irish national cancer centre) rapidly transitioned to the use of telemedicine or virtual clinics (VC) to minimise potential risk of exposure to COVID-19 amongst an immunosuppressed, high-risk population. Our study aimed to evaluate the use of VC in this setting. Methods: An 18-point questionnaire was designed to investigate the patient experience of VC during the COVID-19 pandemic in Ireland and compliance with guidelines developed in Ireland to conduct VC and the role of VC in the future. Questionnaires were distributed following the receipt of verbal consent from patients during the VC. Descriptive statistics were utilised for data analysis using SPSS®. Results: One hundred and four patients returned completed surveys (n = 104/164, 63% response rate). Overall satisfaction levels were high with most patients (n = 58/100, 58%; no answer provided (NAP), n = 4) equally satisfied or nearly equally satisfied with VC in comparison to a usual clinic encounter. The majority of patients felt that there should be a role for VC in the future (n = 84/102, 82%; NAP, n = 2). The majority of patients (n = 61/99, 61%; NAP, n = 5) were very relieved to avoid a hospital visit due to perceived risk of potential exposure to COVID-19. Conclusion: The majority of oncology patients were satisfied with a VC encounter. VC may have a role in the future of medical care in Ireland post the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

We show that a hydrogen-bonded framework, TBAP-α, with extended π-stacked pyrene columns has a sacrificial photocatalytic hydrogen production rate of up to 3108 μmol g−1 h−1. This is the highest activity reported for a molecular organic crystal. By comparison, a chemically-identical but amorphous sample of TBAP was 20–200 times less active, depending on the reaction conditions, showing unambiguously that crystal packing in molecular crystals can dictate photocatalytic activity. Crystal structure prediction (CSP) was used to predict the solid-state structure of TBAP and other functionalised, conformationally-flexible pyrene derivatives. Specifically, we show that energy–structure–function (ESF) maps can be used to identify molecules such as TBAP that are likely to form extended π-stacked columns in the solid state. This opens up a methodology for the a priori computational design of molecular organic photocatalysts and other energy-relevant materials, such as organic electronics. [ABSTRACT FROM AUTHOR]

Crystal structure prediction methods can enable the in silico design of functional molecular crystals, but solvent effects can have a major influence on relative lattice energies, sometimes thwarting predictions. This is particularly true for porous solids, where solvent included in the pores can have an important energetic contribution. We present a Monte Carlo solvent insertion procedure for predicting the solvent filling of porous structures from crystal structure prediction landscapes, tested using a highly solvatomorphic porous organic cage molecule, CC1. Using this method, we can understand why the predicted global energy minimum structure for CC1 is never observed from solvent crystallisation. We also explain the formation of three different solvatomorphs of CC1 from three structurally-similar chlorinated solvents. Calculated solvent stabilisation energies are found to correlate with experimental results from thermogravimetric analysis, suggesting a future computational framework for a priori materials design that factors in solvation effects. [ABSTRACT FROM AUTHOR]

Context • Approximately 25% of the US population suffers from dry eyes or some abnormality of the exposed ocular surface. Investigation of effective modalities for their management is needed. Objective • The study intended to examine the efficacy of a proprietary, daily, Dry Eye Protocol consisting of daily use of a moist, heated, ocular compress and intake of an omega-3 dietary supplement in treatment of ocular surface disease. Design • The research team designed a 4-wk, clinically based, open-label, multicenter cohort study. Setting • The study took place at 6 private eye care practices throughout the United States: Beverly Hills, CA, USA; San Diego, CA, USA; Sunnyvale, CA, USA; Park City, UT, USA; Tarpon Spring, FL, USA; and Kennewick, WA, USA. Participants • Participants were adults between 18 and 75 y of age who had established ocular surface disease based on clinical findings and the results of testing using the ocular surface disease index (OSDI). Intervention • For period of 30 d, participants used a combined daily protocol that included (1) application of a moist, heated, eye compress and (2) a nutritional therapy via an omega-3 supplement in an oral triglyceride form. Outcome Measures • Measures included the OSDI and a test of tear break-up time (TBUT). Results • Of the original 35 participants, 33 completed the 4-wk protocol. The participants using the proprietary Dry Eye Protocol showed significant improvements from baseline, demonstrated by a 49% decrease in OSDI scores (P = .0015); and 46% of participants reported becoming asymptomatic of dry eye symptoms. A significant improvement was also observed in TBUT, increasing from 3.0 to 5.4 s. Conclusions • Daily use of the proprietary Dry Eye Protocol that included a high dosage of triglyceride omega-3 and use of a moist, heated, compress daily showed significant improvement for participants in OSDI and TBUT and should be considered to be a first-line therapy for patients with dry eye disease. [ABSTRACT FROM AUTHOR]

Several visual areas within the STS of the macaque brain respond strongly to faces and other biological stimuli. Determining the principles that govern neural responses in this region has proven challenging, due in part to the inherently complex stimulus domain of dynamic biological stimuli that are not captured by an easily parameterized stimulus set. Here we investigated neural responses in one fMRI-defined face patch in the anterior fundus (AF) of the STS while macaques freely view complex videos rich with natural social content. Longitudinal single-unit recordings allowed for the accumulation of each neuron's responses to repeated video presentations across sessions. We found that individual neurons, while diverse in their response patterns, were consistently and deterministically driven by the video content. We used principal component analysis to compute a family of eigenneurons, which summarized 24% of the shared population activity in the first two components. We found that the most prominent component of AF activity reflected an interaction between visible body region and scene layout. Close-up shots of faces elicited the strongest neural responses, whereas far away shots of faces or close-up shots of hindquarters elicited weak or inhibitory responses. Sensitivity to the apparent proximity of faces was also observed in gamma band local field potential. This category-selective sensitivity to spatial scale, together with the known exchange of anatomical projections of this area with regions involved in visuospatial analysis, suggests that the AF face patch may be specialized in aspects of face perception that pertain to the layout of a social scene. [ABSTRACT FROM AUTHOR]

Permanent ground deformations in unsaturated, compacted hillside fills under seismic loading conditions are discussed, with emphasis given to fill performance during the 1994 Northridge earthquake. These movements represent a significant yet often unrecognized hazard to developed hillside areas, as relatively modest deformations induced widespread damage totaling hundreds of millions of dollars during the Northridge event. The development of grading standards in the Los Angeles area is reviewed to place the seismic fill deformation problem in context with other issues that have shaped design and construction practices for hillside fills. Field observational data on fill performance during the Northridge earthquake is presented, and typical ground distress patterns are found to include cracking near cut/fill contacts, lateral extension and settlement of fill pads, and bulging of fill slope faces. For most sites, the prevalent mechanism of permanent ground deformation responsible for the fill movements is contractive volumetric strain accumulation within the unsaturated fill soils during strong earthquake shaking (that is, seismic compression).

Conventional recording methods generally preclude following the activity of the same neurons in awake animals across days. This limits our ability to systematically investigate the principles of neuronal specialization, or to study phenomena that evolve over multiple days such as experience- dependent plasticity. To redress this shortcoming, we developed a drivable, chronically implanted microwire recording preparation that allowed us to follow visual responses in inferotemporal (IT) cortex in awake behaving monkeys across multiple days, and in many cases across months. The microwire bundle and other implanted components were MRI compatible and thus permitted in the same animals both functional imaging and long-term recording from multiple neurons in deep structures within a region the approximate size of one voxel (<1 mm). The distinct patterns of stimulus selectivity observed in IT neurons, together with stable features in spike waveforms and interspike interval distributions, allowed us to track individual neurons across weeks and sometimes months. The long-term consistency of visual responses shown here permits large-scale mappings of neuronal properties using massive image libraries presented over the course of days. We demonstrate this possibility by screening the visual responses of single neurons to a set of 10,000 stimuli. [ABSTRACT FROM AUTHOR]

Exciton fission is a process that occurs in certain organic materials whereby one singlet exciton splits into two independent triplets. In photovoltaic devices these two triplet excitons can each generate an electron, producing quantum yields per photon of >100% and potentially enabling single-junction power efficiencies above 40%. Here, we measure fission dynamics using ultrafast photoinduced absorption and present a first-principles expression that successfully reproduces the fission rate in materials with vastly different structures. Fission is non-adiabatic and Marcus-like in weakly interacting systems, becoming adiabatic and coupling-independent at larger interaction strengths. In neat films, we demonstrate fission yields near unity even when monomers are separated by >5 Å. For efficient solar cells, however, we show that fission must outcompete charge generation from the singlet exciton. This work lays the foundation for tailoring molecular properties like solubility and energy level alignment while maintaining the high fission yield required for photovoltaic applications. [ABSTRACT FROM AUTHOR]

Summary: Humans are able to efficiently learn and remember complex visual patterns after only a few seconds of exposure []. At a cellular level, such learning is thought to involve changes in synaptic efficacy, which have been linked to the precise timing of action potentials relative to synaptic inputs []. Previous experiments have tapped into the timing of neural spiking events by using repeated asynchronous presentation of visual stimuli to induce changes in both the tuning properties of visual neurons and the perception of simple stimulus attributes []. Here we used a similar approach to investigate potential mechanisms underlying the perceptual learning of face identity, a high-level stimulus property based on the spatial configuration of local features. Periods of stimulus pairing induced a systematic bias in face-identity perception in a manner consistent with the predictions of spike timing-dependent plasticity. The perceptual shifts induced for face identity were tolerant to a 2-fold change in stimulus size, suggesting that they reflected neuronal changes in nonretinotopic areas, and were more than twice as strong as the perceptual shifts induced for low-level visual features. These results support the idea that spike timing-dependent plasticity can rapidly adjust the neural encoding of high-level stimulus attributes []. [Copyright &y& Elsevier]

Examines the social condition of Afro-Americans in the sport history at the University of Iowa in Iowa City, Iowa and by extension in U.S. higher education. Opportunities for social and cultural interaction for Black athletes in Iowa; Information on the book 'A Gallery of Iowa Sports Heroes: Five Decades of Cartoons,' by Jack Bender.

Auto TeleCare provided an automatic daily telephone service for people living alone. The business used an interactive voice response (IVR) system to call clients at a set time each day. The clients were required to press a button on their telephone to listen to a message (e.g. joke of the day), thereby indicating that they were alright. If the client did not respond, staff would call the given list of contacts to check on the client's welfare. The service was first offered in December 2003 and there was a lot of interest from clients and health-care groups. Although the technology was sophisticated, it was very simple for the clients to use. However, it was the marketing and advertising costs of the business that in the end proved to be too costly. The number of clients required for commercial viability was calculated to be 3000, and after nearly 15 months of business it was decided to close the business. [ABSTRACT FROM AUTHOR]

Focuses on questions raised by the discussion of seismic performance of hillside fills. Actual reasons behind the formation of ground and foundation deformations documented in the paper; Correctness of the use of settlement analysis procedure by Tokimatsu and Seed for fill soils.