Quality of life in women with early-stage and metastatic hormone receptor-positive, HER2-negative breast cancer receiving endocrine therapy.

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.

Defining disease severity in atopic dermatitis and psoriasis for the application to biomarker research: an interdisciplinary perspective.

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.

Atopic dermatitis (AD), and psoriasis are long-term skin conditions that can significantly affect people's lives, especially when symptoms are severe. Approximately 10% of adults and 20% of children are affected by AD, while psoriasis affects around 5% of people in the UK. Both conditions are associated with debilitating physical symptoms (such as itch) and have been linked to depression and anxiety. Biomarkers are naturally occurring chemicals in the human body and have potential to enhance the longer-term management of AD and psoriasis. Currently, there are no routinely used biomarkers that can identify people who experience or will go on to develop severe AD and psoriasis. For this reason, research is under way to understand which biomarkers are linked to severity. In this study, a multidisciplinary team of skin researchers from across Europe, along with patient groups, discussed the complexities of studying severity-related biomarkers. We identified a number of severity measurement approaches and there were recommendations for future biomarker research, including (i) considering multiple measures as no single measure can encompass all aspects of severity, (ii) exploring severity measures recorded by both healthcare professionals and patients, as each may capture different aspects, and (iii) accounting for influencing factors, such as different treatment approaches, that may impact AD and psoriasis severity, which make it challenging to compare findings across studies. Overall, we anticipate that the insights gained from these discussions will increase the likelihood of biomarkers being effectively applied in real-world settings, to ultimately improve outcomes for people with AD and psoriasis.

Functional materials discovery using energy-structure-function maps.

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 metal-organic 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 energy-structure-function 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, energy-structure-function 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.

Laser to laser power conversion with remote signaling.

We demonstrate laser power conversion using an edge-coupled waveguide configuration. A laser with an emission energy of 0.87 eV (1427 nm) optically pumps a second with an emission energy of 0.80 eV (1540 nm), achieving the maximum possible open circuit voltage of 0.83 V due to optically pumped lasing. A fiber to device power conversion efficiency of 33% is achieved with internal power conversion efficiency ranging from 57% to 51%. The voltage at maximum power is 0.6 V, which is a record for the wavelength range. The same optically pumped device is used for effectively power-free 500 Mbps upstream data transmission, enabling compact powering and signaling for emerging applications in minimally invasive medical interventions and remote photonics.

Computational modelling of solvent effects in a prolific solvatomorphic porous organic cage.

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.

A Novel Combination Therapy for Patients With Dry Eye Disease: A Pilot Study.

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.

Face-selective neurons maintain consistent visual responses across months.

Face perception in both humans and monkeys is thought to depend on neurons clustered in discrete, specialized brain regions. Because primates are frequently called upon to recognize and remember new individuals, the neuronal representation of faces in the brain might be expected to change over time. The functional properties of neurons in behaving animals are typically assessed over time periods ranging from minutes to hours, which amounts to a snapshot compared to a lifespan of a neuron. It therefore remains unclear how neuronal properties observed on a given day predict that same neuron's activity months or years later. Here we show that the macaque inferotemporal cortex contains face-selective cells that show virtually no change in their patterns of visual responses over time periods as long as one year. Using chronically implanted microwire electrodes guided by functional MRI targeting, we obtained distinct profiles of selectivity for face and nonface stimuli that served as fingerprints for individual neurons in the anterior fundus (AF) face patch within the superior temporal sulcus. Longitudinal tracking over a series of daily recording sessions revealed that face-selective neurons maintain consistent visual response profiles across months-long time spans despite the influence of ongoing daily experience. We propose that neurons in the AF face patch are specialized for aspects of face perception that demand stability as opposed to plasticity.

Single-unit activity during natural vision: diversity, consistency, and spatial sensitivity among AF face patch neurons.

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.

One month in the life of a neuron: longitudinal single-unit electrophysiology in the monkey visual system.

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.

Electronic and optical properties at organic/organic interfaces in organic solar cells.

In organic photovoltaic (OPV) devices the formation of free charges from a singlet excited state is the key step in converting light to electrical energy. However, questions still remain as to why the process is so fast and efficient in some OPV devices while not in others. Currently, it is not understood how the binding energy of the charge transfer state formed at an organic/organic interface, ~40 kT, is overcome in order to create free charge carriers. Given the difficulty of experimentally probing the electronic processes occurring at the organic/organic interface, it falls to theoretical and computational studies to provide essential insights into the processes occurring on the microscopic level. In this review we will cover the contributions made by theoretical studies to improve our understanding of the organic/organic interface. We will address the advantages and disadvantages of different theoretical approaches to studying the numerous interesting effects observed, such as shifts in the HOMO and LUMO levels due to the electrostatic environment, increased localization due to disorder, and the general impact of molecular orientation on different molecular properties. Further, we will discuss the currently proposed mechanisms of charge separation at the organic/organic interface and the implications that these mechanisms have on the choice of materials for use in OPV devices.

A novel, multi-ingredient supplement to manage elevated blood lipids in patients with no evidence of cardiovascular disease: a pilot study.

CONTEXT: Recent changes in usage guidelines have created the potential for millions more Americans to be prescribed statin medications. Caution should be advised because the risk of adverse effects of statins may outweigh their benefits and preclude their preventive use for patients without confirmed cardiovascular disease (CVD) who present with elevated blood lipids. However, statins have shown some benefit in primary CVD prevention. Red yeast rice (RYR) is a dietary supplement that has been demonstrated to reduce low-density lipoprotein (LDL) cholesterol levels in blood and omega-3 polyunsaturated fatty acids have been shown to reduce blood levels of triglycerides (TGs). Although effective, quality control issues aggravate risk of adverse effects for both of these supplements. Furthermore, low dosages per capsule, which require patients to manage and consume many capsules per day, also may reduce patient compliance to supplementation regimens. OBJECTIVES: The authors' objective was to determine the effects of a multi-ingredient supplement (MIS) featuring RYR for primary support of cardiovascular (CV) health in patients who present no CVD history or symptoms other than elevated blood lipids. The MIS was formulated intentionally with a lower dosage of RYR than that used in prior studies in order to reduce the occurrence of adverse effects. Secondary to the objective of managing blood lipids, the authors were interested in determining the effects of the MIS in combination with a high-potency omega-3 polyunsaturated fatty acid supplement and its effect on TG levels and observing whether adverse effects would inhibit patient compliance. DESIGN: The research team designed an open-label pilot study following a pre-post pragmatic design. Setting • The study took place at 2 primary care settings. PARTICIPANTS: Nineteen patients with hypercholesterolemia were participants in the study. All participants were required to confirm that they had not taken any other pharmaceutical or supplement therapy to treat cholesterol for at least 30 d prior to baseline, establishing a washout period. At completion of the intervention, 3 participants were excluded for noncompliance with the protocol, although they had taken the supplements as directed. INTERVENTION(S): The recommended serving of the MIS supplement consisted of 1 softgel that contained 9 ingredients: a proprietary blend of RYR, bioflavonoids, polycosanol, 525 mg omega-3 fatty acids in the natural TG form (294 mg eicosapentaenoic acid [EPA], 147 mg docosahexaenoic acid [DHA]) as well as other supporting ingredients, resveratrol, coenzyme Q10 (CoQ10), folic acid vitamin B3 (niacin), B6, B12, and black pepper. Each serving of the omega-3 supplement contained 834 mg of omega-3 polyunsaturated fatty acids in the natural TG form (484 mg EPA, 234 mg DHA) and 33 IU vitamin E, (D-α-tocopherol). The studys participants were assigned to a group based on their initial TG levels. Participants with TG levels <140 mg/dL took the MIS only, and participants whose initial TG levels exceeded 140 mg/dL were assigned to take both the MIS and the omega-3 supplement, receiving 1384 mg of omega-3 daily (778 mg EPA, 381 mg DHA). All participants confirmed by poststudy survey that they took the recommended serving of 1 softgel/d of the assigned supplement(s) for a minimum of 30 d. OUTCOME MEASURE(S): At baseline and follow-up, standard venous blood labs were drawn and processed at nationally accredited labs. Although not standardized, all reports contained: total cholesterol, high-density lipoprotein (HDL), LDL, and TG levels. The research team acknowledges that this lack of standardization and additional lipid data, such as very low-density lipoprotein, is a limitation of the study. RESULTS: Total cholesterol and LDL decreased significantly, by 12.0% (P = .0004) and 17.3% (P = .0001), respectively, for the 16 participants taking the MIS supplement. Participants with an LDL at baseline greater than 145 mg/dL (n = 7) benefited even more, with total cholesterol and LDL decreasing significantly by 17.1% (P = .01) and 24.5% (P = .0014), respectively. Although the results were not significant, adding the omega-3 supplement to the protocol resulted in a decrease in the TGs of the subgroup taking both supplements (n = 8), with that measure decreasing by 13.1% (P = .27) from baseline compared with a decrease of 2% (P = .95) for all participants. The subgroup taking both the MIS and omega-3 supplements experienced similar decreases in total cholesterol and LDL as participants taking only the MIS. No side effects were reported by participants, and all participants completed the assigned protocol. CONCLUSIONS: The MIS supplement decreased total cholesterol and LDL significantly and offers a promising therapy for the management of cholesterol that may enable better patient compliance. The addition of an omega-3 supplement also decreased TGs in the subgroup that received both therapies, although this decrease was not significant, potentially because of the underpowered size of the subgroup. The research team plans future studies with more robust lipid testing and larger numbers of participants to support the findings of the current study.

The Acceptability of post-stroke cognitive testing through the lens of the theory of acceptability, a qualitative study.

Background: Cognitive impairment is common after stroke and screening is recommended. However, there is a lack of evidence on the best way to assess cognition after stroke and a tendency to focus on the clinician rather than stroke survivor. The Theoretical Framework of Acceptability (TFA) was developed to better understand the factors that contribute to the acceptability of healthcare interventions from the patient perspective. We aimed to explore the acceptability of post-stroke cognitive assessment from the stroke survivor perspective, using the TFA as a lens. Methods: We analysed interviews conducted with people admitted to hospital after stroke. Inclusion criteria: ≥18 years, able to provide informed consent. Semi-structured interviews were conducted 1-3 weeks after discharge from hospital in the participant's home to explore the experience of cognitive assessment in hospital. Interviews were audio recorded and transcribed verbatim. Data were analysed using framework analysis, with a framework underpinned by the TFA. Results: Of the 13 participants interviewed, 8 were male, 6 lived in the most deprived SIMD quintile. Ages were 62-84 years. Five themes were identified that describe the factors that influence acceptability of cognitive screening from the patient perspective: (1) participation motives; (2) trust in health professionals; (3) perceived risks of harm; (4) information provision; (5) burden of testing. Conclusion: Clinical teams should be confident that stroke survivors expect cognitive testing and understand its rational. However, the provision of information and results of cognitive testing should be person-centred.

Is Immunotherapy Beneficial in Patients with Oncogene-Addicted Non-Small Cell Lung Cancers? A Narrative Review.

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.

Genomic Landscape of NSCLC in the Republic of Ireland.

Introduction: The identification of genomic "targets" through next-generation sequencing (NGS) of patient's NSCLC tumors has resulted in a rapid expansion of targeted treatment options for selected patients. This retrospective study aims to identify the proportion of patients with advanced NSCLC in the Republic of Ireland whose tumors harbor actionable genomic alterations through broad NGS panel testing. Methods: Institutional review board approval was obtained before study initiation. Patients with NSCLC whose tumors underwent genomic testing through the largest available NGS panel at a nationally funded Cancer Molecular Diagnostics laboratory (St. James's Hospital) between June 2017 and June 2022 were identified. Patient demographics and tumor-related data were collected by retrospective review from all cancer centers in Ireland, referring to the Cancer Molecular Diagnostics laboratory. A total of 203 (9%) tumor samples were excluded due to insufficient neoplastic cell content. Genomic data were collected through retrospective search of Ion Reporter software. The spectrum and proportion of patients with oncogenic driver mutations were evaluated using descriptive statistics (SPSS version 29.0). Results: In total, 2052 patients were identified. Patients were referred from 23 different hospital sites and all four geographic regions (Leinster = 1091, 53%; Munster = 763, 37.2%; Connacht = 191, 9.3%; Ulster = 7, 0.3%). Median age was 69 (range: 26-94) years; 53% were male. The most common tumor histologic subtype was adenocarcinoma (77%, n = 1577). An actionable genomic alteration was identified in 1099 cases (53%), the most common of which was KRAS (n = 657, 32%). Less frequently, NSCLC tumors harbored the following: MET exon 14 skipping (n = 53, 2.6%), MET amplification (n = 26, 1.3%), EGFR (n = 181, 8.8%), HER2 (n = 35, 1.7%), and BRAF (n = 72, 3.5%) mutations. Fusions were detected in 76 patients (3.7%) including ALK (n = 44, 58%), RET (n = 11, 14.5%), ROS1 (n = 16, 21%), and FGFR3 (n = 5, 6.6%), whereas no NTRK fusion was identified. Co-alterations were detected in 114 patients (5.6%), the most common of which was KRAS/PIK3CA (n = 19, 17%), EGFR/PIK3CA (n = 10, 8.5%), and KRAS/IDH1 (n = 9, 8%). Other co-alterations of interest identified included KRAS G12A/ROS1 fusion (n = 1) and KRAS G12C/BRAF G469A (n = 2). Conclusions: This is the first retrospective study to comprehensively characterize the genomic landscape of NSCLC in Ireland, using the broadest available NGS panel. Actionable alterations were identified in 53.4% of the patients, and KRAS was the most common oncogenic driver alteration. Our study revealed a lower prevalence of patients whose tumor harbors ALK, ROS1, and RET fusions, compared with similar data sets.

Review of clinical practice guidelines relating to cognitive assessment in stroke.

PURPOSE: To assess the content, quality, and supporting evidence base of clinical practice guidelines (CPGs) with reference to cognitive assessment in stroke. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.Implications for rehabilitationCognitive 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.

Parallel functional subnetworks embedded in the macaque face patch system.

During normal vision, our eyes provide the brain with a continuous stream of useful information about the world. How visually specialized areas of the cortex, such as face-selective patches, operate under natural modes of behavior is poorly understood. Here we report that, during the free viewing of movies, cohorts of face-selective neurons in the macaque cortex fractionate into distributed and parallel subnetworks that carry distinct information. We classified neurons into functional groups on the basis of their movie-driven coupling with functional magnetic resonance imaging time courses across the brain. Neurons from each group were distributed across multiple face patches but intermixed locally with other groups at each recording site. These findings challenge prevailing views about functional segregation in the cortex and underscore the importance of naturalistic paradigms for cognitive neuroscience.

Research protocol - Assessing Post-Stroke Psychology Longitudinal Evaluation (APPLE) study: A prospective cohort study in stroke.

Background: Cognitive and mood problems have been highlighted as priorities in stroke research and guidelines recommend early screening. However, there is limited detail on the preferred approach.We aimed to (1) determine the optimal methods for evaluating psychological problems that pre-date stroke; (2) assess the test accuracy, feasibility and acceptability of brief cognitive and mood tests used at various time-points following stroke; (3) describe temporal changes in cognition and mood following stroke and explore predictors of change. Methods: We established a multi-centre, prospective, observational cohort with acute stroke as the inception point - Assessing Post-stroke Psychology Longitudinal Evaluation (APPLE). We approached patients admitted with stroke or transient ischaemic attack (TIA) from 11 different hospital sites across the United Kingdom. Baseline demographics, clinical, functional, cognitive, and mood data were collected. Consenting stroke survivors were followed up with more extensive evaluations of cognition and mood at 1, 6, 12 and 18 months. Results: Continuous recruitment was from February 2017 to February 2019. With 357 consented to full follow-up. Eighteen-month assessments were completed in September 2020 with permissions in-place for longer term in-person or electronic follow-up. A qualitative study has been completed, and a participant sample biobank and individual participant database are both available. Discussion: The APPLE study will provide guidance on optimal tool selection for cognitive and mood assessment both before and after stroke, as well as information on prognosis and natural history of neuropsychological problems in stroke. The study data, neuroimaging and tissue biobank are all available as a resource for future research.

Persistence time of charge carriers in defect states of molecular semiconductors.

Charge carriers in organic crystals are often trapped in point defects. The persistence time of the charge in these defect states is evaluated by computing the escape rate from this state using non-adiabatic rate theory. Two cases are considered (i) the hopping between separate identical defect states and (ii) the hopping between a defect state and the bulk (delocalized) states. We show that only the second process is likely to happen with realistic defect concentrations and highlight that the inclusion of an effective quantum mode of vibration is essential for accurate computation of the rate. The computed persistence time as a function of the trap energy indicates that trap states shallower than ∼0.3 eV cannot be effectively investigated with some slow spectroscopic techniques such as THz spectroscopy or EPR commonly used to study the nature of excess charge in semiconductors.

Acupuncture, Shingles, and Allergen Immunotherapy.

Background: The Varicella-zoster virus (VZV) remains dormant in the dorsal root ganglia and can become reactive later in a person's life. Factors such as stress, trauma, chronic disease, systemic illness, immune disorders, and age-related decline in host immunologic responses can potentially incite reactivation. Activation of VZV resulting in shingles following acupuncture has been reported in the literature previously, and some mechanisms have been proposed for this observation. Case: A patient with a history of total thyroidectomy for thyroid cancer presented with chronic neck pain. She was clinically and biochemically in a euthyroid state and on thyroid replacement therapy. She had a history of chickenpox, at age 13, and seasonal allergies. After her first acupuncture session, she received an allergy shot for her seasonal allergies. A day after the procedure, she developed a vesicular rash and was subsequently diagnosed with acute Herpes zoster. Subsequent acupuncture was withheld following this event. She received acyclovir and applied topical Aloe vera to the cutaneous lesions, and developed mild scarring, but did not experience postherpetic neuralgia. Conclusions: Acupuncture is a minor trauma that can predispose a patient to reactivation of VZV and shingles in the setting of immune activation with allergen immunotherapy.

Dynamic Suppression of Average Facial Structure Shapes Neural Tuning in Three Macaque Face Patches.

The visual perception of identity in humans and other primates is thought to draw upon cortical areas specialized for the analysis of facial structure. A prominent theory of face recognition holds that the brain computes and stores average facial structure, which it then uses to efficiently determine individual identity, though the neural mechanisms underlying this process are controversial. Here, we demonstrate that the dynamic suppression of average facial structure plays a prominent role in the responses of neurons in three fMRI-defined face patches of the macaque. Using photorealistic face stimuli that systematically varied in identity level according to a psychophysically based face space, we found that single units in the AF, AM, and ML face patches exhibited robust tuning around average facial structure. This tuning emerged after the initial excitatory response to the face and was expressed as the selective suppression of sustained responses to low-identity faces. The coincidence of this suppression with increased spike timing synchrony across the population suggests a mechanism of active inhibition underlying this effect. Control experiments confirmed that the diminished responses to low-identity faces were not due to short-term adaptation processes. We propose that the brain's neural suppression of average facial structure facilitates recognition by promoting the extraction of distinctive facial characteristics and suppressing redundant or irrelevant responses across the population.