Optogenetic modulation of hippocampal oscillations ameliorates spatial cognition and hippocampal dysrhythmia following early-life seizures.

There is increasing human and animal evidence that brain oscillations play a critical role in the development of spatial cognition. In rat pups, disruption of hippocampal rhythms via optogenetic stimulation during the critical period for memory development impairs spatial cognition. Early-life seizures are associated with long-term deficits in spatial cognition and aberrant hippocampal oscillatory activity. Here we asked whether modulation of hippocampal rhythms following early-life seizures can reverse or improve hippocampal connectivity and spatial cognition. We used optogenetic stimulation of the medial septum to induce physiological 7 Hz theta oscillations in the hippocampus during the critical period of spatial cognition following early-life seizures. Optogenetic stimulation of the medial septum in control and rats subjected to early-life seizures resulted in precisely regulated frequency-matched hippocampal oscillations. Rat pups receiving active blue light stimulation performed better than the rats receiving inert yellow light in a test of spatial cognition. The improvement in spatial cognition in these rats was associated with a faster theta frequency and higher theta power, coherence and phase locking value in the hippocampus than rats with early-life seizures receiving inert yellow light. These findings indicate that following early life seizures, modification of hippocampal rhythms may be a potential novel therapeutic modality.

Early-life seizures alter habit behavior formation and fronto-striatal circuit dynamics.

Obsessive compulsive disorder (OCD) can occur comorbidly with epilepsy; both are complex, disruptive disorders that lower quality of life. Both OCD and epilepsy are disorders of hyperexcitable circuits, but it is unclear whether common circuit pathology may underlie the co-occurrence of these two neuropsychiatric disorders. Here, we induced early-life seizures (ELS) in rats to examine habit formation as a model for compulsive behaviors. Compulsive, repetitive behaviors in OCD utilize the same circuitry as habit formation. We hypothesized that rats with ELS could be more susceptible to habit formation than littermate controls, and that altered behavior would correspond to altered signaling in fronto-striatal circuits that underlie decision-making and action initiation. Here, we show instead that rats with ELS were significantly less likely to form habit behaviors compared with control rats. This behavioral difference corresponded with significant alterations to temporal coordination within and between brain regions that underpin the action to habit transition: 1) phase coherence between the lateral orbitofrontal cortex and dorsomedial striatum (DMS) and 2) theta-gamma coupling within DMS. Finally, we used cortical electrical stimulation as a model of transcranial magnetic stimulation (TMS) to show that temporal coordination of fronto-striatal circuits in control and ELS rats are differentially susceptible to potentiating and suppressive stimulation, suggesting that altered underlying circuit physiology may lead to altered response to therapeutic interventions such as TMS.

Spatially structured relationships between white banana prawn (Penaeus merguiensis) catch and riverine flow in the Northern Prawn Fishery, Australia.

Water resource development can lead to the significant alteration of natural flow regimes, which can have impacts on the many aquatic species that rely on both freshwater and estuarine environments to successfully complete their lifecycles. In tropical northern Australia, annual catches of commercially harvested white banana prawns (WBP) are highly variable in response to environmental conditions, namely rainfall and subsequent riverine flow. However, little is known about the spatial extent to which flow from individual rivers influences offshore WBP catch. In this study, we quantify how the relationship between WBP catch in the Gulf of Carpentaria is influenced by flow from the Mitchell River, Queensland Australia. We used a Bayesian framework to model both prawn presence and catch per unit effort, and found evidence that multiple components of the flow regime contribute to fishery catch. We also found evidence to suggest that the relationships between prawn presence and flow were spatially structured across the fishing ground. Our results suggest that attributing fishery catch to a single river remains challenging, though highlights the importance of maintaining natural flow regimes to support a highly valuable commercial fishery species in the face of potential water resource development.

Differential impact of hormone receptor status on survival and recurrence for HER2 receptor-positive breast cancers treated with Trastuzumab.

INTRODUCTION: Hormone receptor status has major implications for treatment and survival of breast cancer. Yet the impact of hormone receptor status on outcome after Trastuzumab has received little attention. The objective here was to explore any differential effects of Trastuzumab treatment (Trast +ve) on Luminal B HER2 or HER2+(ER-) breast cancer subtypes. METHODS: A cohort of 469 HER2 receptor-positive breast cancers was categorised by molecular subtype and Trastuzumab treatment. Effects of Trastuzumab treatment on survival, locoregional recurrence and distant metastasis were investigated by subtype, using univariate and multivariate analysis. RESULTS: Trast +ve Luminal B HER2 patients had significant improvements in 5-year DFS (p < 0.001) and OS (p < 0.001), while Trast +ve HER2+(ER-) patients had significant improvements in 5-year DFS (p = 0.012) alone. Only Trast +ve Luminal B HER2 cancers displayed a significant reduction in LRR rates (p < 0.001). A significant reduction in distant metastasis rates was seen in Trast +ve Luminal B HER2 (p < 0.001) and HER2+(ER-) (p = 0.009) cancers. Interestingly, bone metastasis rates in Trast +ve Luminal B HER2 cancers demonstrated the greatest reduction (36.2-6.7%). Multivariate analysis of Trast +ve patients found no difference in distant metastasis rates (p = 0.96) between subtypes. Significantly, lower LRR rates were seen in Trast +ve Luminal B HER2 cancers, compared to Trast +ve HER2+(ER-) (p = 0.018). CONCLUSION: An enhanced response to Trastuzumab was seen in Luminal B HER2 cancers. We highlight how Trastuzumab treatment changed the natural history of the HER2 receptor-positive breast cancer, demonstrating improved efficacy in changing the outcome of hormone receptor-positive patients.

Elasticity in Amorphous Solids: Nonlinear or Piecewise Linear?

Quasistatic strain-controlled measurements of stress versus strain curves in macroscopic amorphous solids result in a nonlinear-looking curve that ends up either in mechanical collapse or in a steady state with fluctuations around a mean stress that remains constant with increasing strain. It is therefore very tempting to fit a nonlinear expansion of the stress in powers of the strain. We argue here that at low temperatures the meaning of such an expansion needs to be reconsidered. We point out the enormous difference between quenched and annealed averages of the stress versus strain curves and propose that a useful description of the mechanical response is given by a stress (or strain) -dependent shear modulus for which a theoretical evaluation exists. The elastic response is piecewise linear rather than nonlinear.

Advanced Practice Providers' Perceptions of Patient Workload: Results of a Multi-Institutional Survey.

OBJECTIVE: This study examines data collected from a survey of advanced practice providers' (APPs') perceptions of reasonable versus actual APP-to-patient ratios and other factors that affect workload burden in both inpatient and outpatient clinical settings. BACKGROUND: Advanced practice providers provide accessible, cost-effective, and quality care in a growing number of specialty practices across multiple patient care settings. They are caring for higher volumes of patients and assuming more responsibilities while continuing to navigate highly complex healthcare systems. Limited evidence or benchmark data exist that would assist in determining optimal workload and staffing models that include APPs. METHODS: A group of advanced practice leaders developed and distributed a 43-question survey of workload factors to a highly diverse APP workforce. RESULTS: There were 1466 APPs across 37 areas of practice who responded to the survey distributed in 14 separate organizations. The perceived reasonable workload was lower than the actual workload for 22 specialty practice areas. The analysis included years of experience as an APP, work hours, on-call commitment, nonclinical responsibilities, and time spent in documentation, direct patient care, and performing procedures. CONCLUSIONS: There is a consensus among APPs, within their practice area, about what constitutes a reasonable patient assignment, despite the variability in APP experience, organizational culture, processes, and patient acuity.

Assessing climate change impacts on wetlands in a flow regulated catchment: A case study in the Macquarie Marshes, Australia.

Globally wetlands are increasingly under threat due to changes in water regimes as a result of river regulation and climate change. We developed the Exploring CLimAte Impacts on Management (EXCLAIM) decision support system (DSS), which simulates flow-driven habitat condition for 16 vegetation species, 13 waterbird species and 4 fish groups in the Macquarie catchment, Australia. The EXCLAIM DSS estimates impacts to habitat condition, considering scenarios of climate change and water management. The model framework underlying the DSS is a probabilistic Bayesian network, and this approach was chosen to explicitly represent uncertainties in climate change scenarios and predicted ecological outcomes. The results suggest that the scenario with no climate change and no water resource development (i.e. flow condition without dams, weirs or water license entitlements, often regarded as a surrogate for 'natural' flow) consistently has the most beneficial outcomes for vegetation, waterbird and native fish. The 2030 dry climate change scenario delivers the poorest ecological outcomes overall, whereas the 2030 wet climate change scenario has beneficial outcomes for waterbird breeding, but delivers poor outcomes for river red gum and black box woodlands, and fish that prefer river channels as habitats. A formal evaluation of the waterbird breeding model showed that higher numbers of observed nest counts are typically associated with higher modelled average breeding habitat conditions. The EXCLAIM DSS provides a generic framework to link hydrology and ecological habitats for a large number of species, based on best available knowledge of their flood requirements. It is a starting point towards developing an integrated tool for assessing climate change impacts on wetland ecosystems.

Bayesian Networks as a screening tool for exposure assessment.

A tiered approach to contamination exposure assessment is currently adopted in many countries. Increasing the site-specific information in exposure assessments is generally recommended when guideline values for contaminants in soil are exceeded. This work details a Bayesian Network (BN) approach to developing a site-specific environmental exposure assessment that focuses on the simple mapping and assessment of assumptions and the effect of new data on assessment outcomes. The BN approach was applied to a floodplain system in New South Wales, Australia, where site-specific information about elevated antimony (Sb) concentrations and distribution in soils was available. Guidelines for exposure assessment in Australia are used as a template for this site, although the approach is generic. The BN-based assessment used an iterative approach starting with limited soil Sb data (41 samples ranging from 0 to 18 mg kg-(1) Sb) and extending the model with more detailed Sb data (145 samples ranging from 0 to 40 mg kg-(1) Sb). The analyses identified dominant exposure pathways and assessed the sensitivity of these pathways to changes in assumptions and the level of site-specific information available. In particular, there was a 10.8% probability of exceeding the tolerable daily intake of Sb in the case study when the limited soil Sb data was used, which increased to 26.2% with the more detailed sampling regime. There was also a 47% decrease in the probability of overexposure to Sb when the dermal bioavailability of arsenic (a similar metalloid) was used as a surrogate measure instead of a default bioavailability of 100%. We conclude that the BN approach to soil exposure assessment has merit both in the context of Australian and international soil exposure assessments.

Stimulus-locked auditory information facilitates real-time visuo-motor sequence learning.

Prior research investigating whether and how multisensory information facilitates skill learning is quite mixed; whereas some research points to congruent information improving learning, other work suggests that people become reliant on the redundant information, such that its removal ultimately detracts from the ability to perform a unisensory task. We examined this question using the Serial Interception Sequence Learning (SISL) task, a visuo-motor paradigm in which participants implicitly learn a sequence embedded in noise. We investigated whether adding auditory information in different ways would enhance real time sequence learning and whether any benefits of multisensory learning would persist with visual-only testing. Auditory information was used either as feedback on the visuo-motor task (Experiments 1 and 2) or was presented synchronously with visual information during learning (Experiment 3). Robust sequence-specific performance advantages occurred across conditions and experiments; however, auditory information enhanced real-time performance only when it was synchronized with visual information. Participants were significantly more accurate, faster, and more precise with stimulus-locked auditory information during training. Notably, these benefits did not generalize to the visual-only context, suggesting that the benefits of stimulus-locked auditory information are primarily useful only when the perceptual information is present.

The Psychological Science Accelerator's COVID-19 rapid-response dataset.

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data.

The 25(OH)D level needed to maintain a favorable bisphosphonate response is ≥33 ng/ml.

UNLABELLED: Why only some osteoporotic patients maintain response to prolonged bisphosphonate therapy is unknown. We examined bisphosphonate response and its association with serum 25 hydroxy vitamin D (25(OH)D) level in a "real world" setting. Serum 25(OH)D level was strongly associated with maintaining bisphosphonate response arguing that vitamin D may be involved in optimizing prolonged bisphosphonate therapy. INTRODUCTION: This study examined the maintenance of bisphosphonate response in the "real world" setting and the association between 25(OH)D and bisphosphonate response using an established composite definition of response. METHODS: Postmenopausal women with low bone mineral density (BMD) treated with bisphosphonates were identified from two New York City practices. Patients were excluded for a history of chronic steroid use, metabolic bone disease, or bisphosphonate non-adherence. Patients were categorized as bisphosphonate non-responders if they had a T-score < -3 that persisted between dual-energy X-ray absorptiometry (DEXA) scans, a >3% decrease in BMD, or an incident fracture on bisphosphonate therapy, criteria based on the EUROFORS trial. Demographic and clinical data including mean 25(OH)D levels between DEXA scans were obtained. Mean 25(OH)D levels were compared between responders and non-responders and multiple logistic regression analysis was performed to identify factors associated with non-response. RESULTS: A total of 210 patients were studied. A favorable response to bisphosphonate therapy was seen in 47% (N = 99/210). Patients with a mean 25(OH)D ≥33 ng/ml had a ~4.5-fold greater odds of a favorable response (P < 0.0001). 25(OH)D level was significantly associated with response - a 1 ng/ml decrease in 25(OH)D was associated with ~5% decrease in odds of responding (odds ratio = 0.95; 95% confidence interval, 0.92-0.98; P = 0.0006). CONCLUSIONS: Patients with a mean 25(OH)D ≥33 ng/ml had a substantially greater likelihood of maintaining bisphosphonate response. This threshold level of 25(OH)D is higher than that considered adequate by the Institute of Medicine, arguing that higher levels may be required for specific therapeutic outcomes.

Mask wearing affects emotion perception.

To reduce the spread of COVID-19, mask wearing has become ubiquitous in much of the world. We studied the extent to which masks impair emotion recognition and dampen the perceived intensity of facial expressions by naturalistically inducing positive, neutral, and negative emotions in individuals while they were masked and unmasked. Two groups of online participants rated the emotional intensity of each presented image. One group rated full faces (N=104); the other (N=102) rated cropped images where only the upper face was visible. We found that masks impaired the recognition of and rated intensity of positive emotions. This happened even when the faces were cropped and the lower part of the face was not visible. Masks may thus reduce positive emotion and/or expressivity of positive emotion. However, perception of negativity was unaffected by masking, perhaps because unlike positive emotions like happiness which are signaled more in the mouth, negative emotions like anger rely more on the upper face.

A multi-lab test of the facial feedback hypothesis by the Many Smiles Collaboration.

Following theories of emotional embodiment, the facial feedback hypothesis suggests that individuals' subjective experiences of emotion are influenced by their facial expressions. However, evidence for this hypothesis has been mixed. We thus formed a global adversarial collaboration and carried out a preregistered, multicentre study designed to specify and test the conditions that should most reliably produce facial feedback effects. Data from n = 3,878 participants spanning 19 countries indicated that a facial mimicry and voluntary facial action task could both amplify and initiate feelings of happiness. However, evidence of facial feedback effects was less conclusive when facial feedback was manipulated unobtrusively via a pen-in-mouth task.

Adhesive strips versus subcuticular suture for mediansternotomy wound closure.

BACKGROUND AND AIM: This prospective randomized study was undertaken to compare the use of the 3M™ Steri-Strip™ S Surgical Skin closure system with a running absorbable subcuticular suture technique for skin closure following a mediansternotomy for cardiac surgical procedures. METHODS: Thirty-six patients undergoing a mediansternotomy for a cardiac surgical procedure were prospectively randomized to either Steri-Strip S or subcuticular suture for wound closure. The wounds were evaluated on postoperative days 7 and 21 for erythema, edema, pain, cosmesis, and the time taken to close the incision. RESULTS: Skin closure with Steri-Strip S was faster (5.33 ± 1.32 minutes steri-strips vs. 6.07 ± 0.91 sutures; p = 0.06) and resulted in significantly less erythema and edema, but no difference in pain or cosmesis after seven days. Following 21 days, there was no difference in pain, edema, or cosmesis between the groups. However, patients receiving steri-strips continue to have less erythema. CONCLUSIONS: Both Steri-Strip S and absorbable sutures are effective techniques for skin closure following a mediansternotomy incision for cardiac surgical procedures. Steri-Strip S can decrease the amount of erythema, but results in no significant difference in pain, cosmesis, or edema compared to the traditional subcuticular wound closure technique.

Explaining Crossmodal Correspondences Between Colours and Tastes.

For centuries, if not millennia, people have associated the basic tastes (e.g., sweet, bitter, salty, and sour) with specific colours. While the range of tastes may have changed, and the reasons for wanting to connect the senses in this rather surprising way have undoubtedly differed, there would nevertheless appear to be a surprisingly high degree of consistency regarding this crossmodal mapping among non-synaesthetes that merits further consideration. Traditionally, colour-taste correspondences have often been considered together with odour-colour and flavour-colour correspondences. However, the explanation for these various correspondences with the chemical senses may turn out to be qualitatively different, given the presence of identifiable source objects in the case of food aromas/flavours, but not necessarily in the case of basic tastes. While the internalization of the crossmodal statistics of the environment provides one appealing account for the existence of colour-taste correspondences, emotional mediation may also be relevant. Ultimately, while explaining colour-taste correspondences is of both theoretical and historical interest, the growing awareness of the robustness of colour-taste correspondences would currently seem to be of particular relevance to those working in the fields of design and multisensory experiential marketing.

Delivering the Multisensory Experience of Dining-Out, for Those Dining-In, During the Covid Pandemic.

In many parts of the world, restaurants have been forced to close in unprecedented numbers during the various Covid-19 pandemic lockdowns that have paralyzed the hospitality industry globally. This highly-challenging operating environment has led to a rapid expansion in the number of high-end restaurants offering take-away food, or home-delivery meal kits, simply in order to survive. While the market for the home delivery of food was already expanding rapidly prior to the emergence of the Covid pandemic, the explosive recent growth seen in this sector has thrown up some intriguing issues and challenges. For instance, concerns have been raised over where many of the meals that are being delivered are being prepared, given the rise of so-called "dark kitchens." Furthermore, figuring out which elements of the high-end, fine-dining experience, and of the increasingly-popular multisensory experiential dining, can be captured by those diners who may be eating and drinking in the comfort of their own homes represents an intriguing challenge for the emerging field of gastrophysics research; one that the chefs, restaurateurs, restaurant groups, and even the food delivery companies concerned are only just beginning to get to grips with. By analyzing a number of the high-end fine-dining home food delivery options that have been offered (in the UK and in the US) in this narrative review, we highlight a number of promising directions for those wanting to optimize the at-home multisensory dining experience, wherever in the world they might be.

The effects of compassion-based feedback on wellbeing ratings during a professional assessment healthcare task.

BACKGROUND: There is a need for higher education policy to consider how student nurses might be supported to help them to develop the resilience and mental wellbeing needed to cope with stressful environments. Reviews and qualitative research in this area suggest that compassion can improve wellbeing, however, compassion-based feedback is yet to be explored as a pedagogical intervention using quantitative methods. PURPOSE: To explore the effect of different feedback types on subjective wellbeing. METHODS: In this experimental design, nursing students were presented with three feedback types, 'compassion-based feedback, simple descriptive feedback, and utilitarian feedback' and were asked to provide post-trial ratings of subjective wellbeing, in relation to each type, whilst undertaking a nursing-related task. Participants also rated the helpfulness of 'Type of Feedback'. RESULTS: We report a significant difference of 'Type of Feedback' with higher ratings of wellbeing when participants were presented with compassion-based feedback. CONCLUSION: Compassion-based feedback could lead to higher wellbeing in educational tasks related to nursing.

A preliminary study to identify and distinguish southern tropical populations of Ganoderma boninense from oil palm via mating assays, sequence data, and microsatellite markers.

Morphological studies suggest that the major pathogen causing basal stem rot of oil palm in Papua New Guinea and Solomon Islands is Ganoderma boninense. This study presents the first evidence for conspecificity of G. boninense from four countries where basal stem rot is prevalent. Seventy-three dikaryotic isolates of Ganoderma boninense from Indonesia, Malaysia, Papua New Guinea, and Solomon Islands were studied via mating tests, analyses of nuc internal transcribed spacer ITS1-5.8S-ITS2 sequences, and microsatellite genotyping. Sequence similarity in the ITS1-5.8S-ITS2 region was >99%, and all exotic isolates successfully mated with Papua New Guinea tester strains. Transfer of nuclei during mating was also confirmed via microsatellite markers for the first time in this species. Four microsatellite primers were used to generate evidence for 33 alleles in the four populations. All isolates studied had unique genetic fingerprints but alleles were also shared, suggesting gene flow. Heterozygosities were lower than expected in Indonesian and Papua New Guinea populations, consistent with the possibility of localized inbreeding.

Stepped Treatment for Attention-Deficit/Hyperactivity Disorder and Aggressive Behavior: A Randomized, Controlled Trial of Adjunctive Risperidone, Divalproex Sodium, or Placebo After Stimulant Medication Optimization.

OBJECTIVE: Stimulant medications are the most prevalent first-line pharmacotherapy for attention-deficit/hyperactivity disorder, but children with aggressive behavior often receive multiagent treatment. There is sparse evidence for the benefits of adjunctive medications when stimulant monotherapy provides inadequate benefit for aggressive behavior, yet the adverse effects of common adjuncts are well established. This study compared the efficacy in reducing aggressive behavior of risperidone (RISP), divalproex sodium (DVPX), and placebo (PBO) added to stimulant medication among childrenwhose symptoms persisted after individually optimized stimulant treatment. METHOD: This trial enrolled 6- to 12-year-old with attention-deficit/hyperactivity disorder, a disruptive disorder, significant aggressive behavior, and prior stimulant treatment. Open, systematically titrated stimulant treatment identified patients with inadequate reductions in aggressive behavior, who were then randomly assigned to receive adjunctive RISP, DVPX, or PBO under double-blinded conditions for 8 weeks. Family-based behavioral treatment was offered throughout the trial. The primary outcome was the parent-completed Retrospective Modified Overt Aggression Scale. RESULTS: Participants included 175 children (mean [SD] age 9.48 [2.04] years, 19% female). Of participants, 151 completed the stimulant optimization phase, with aggression remitting among 96 (63%), and 45 were randomly assigned to adjunctive treatment groups. The adjunctive RISP group showed greater reductions in aggression ratings than the PBO group (least squares means difference [ΔLSM], -2.33; 95% CI, -3.83 to -0.82; effect size [ES], -1.32), as did the DVPX group (ΔLSM, -1.60; 95% CI, -3.18 to -0.03; ES, -0.91). Mean standardized body mass index scores increased more among RISP-treated participants than participants receiving PBO (ΔLSM, 1.54; 95% CI, 0.68 to 2.40; ES, 0.58). CONCLUSION: High response rate during the trial's open stimulant optimization phase suggests that rigorous titration of stimulant medication and concurrent behavioral therapy may avert the need for additional medications. Among nonremitters, RISP and DVPX were efficacious adjunctive treatments, although RISP was associated with weight gain. CLINICAL TRIAL REGISTRATION INFORMATION: Effectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder (The SPICY Study); https://www.clinicaltrials.gov; NCT00794625.

Grape expectations: the role of cognitive influences in color-flavor interactions.

Color conveys critical information about the flavor of food and drink by providing clues as to edibility, flavor identity, and flavor intensity. Despite the fact that more than 100 published papers have investigated the influence of color on flavor perception in humans, surprisingly little research has considered how cognitive and contextual constraints may mediate color-flavor interactions. In this review, we argue that the discrepancies demonstrated in previously-published color-flavor studies may, at least in part, reflect differences in the sensory expectations that different people generate as a result of their prior associative experiences. We propose that color-flavor interactions in flavor perception cannot be understood solely in terms of the principles of multisensory integration (the currently dominant theoretical framework) but that the role of higher-level cognitive factors, such as expectations, must also be considered.