Limitations on flexible allocation of visual short-term memory resources with multiple levels of goal-directed attentional prioritization.

Studies suggest that visual short-term memory (VSTM) is a continuous resource that can be flexibly allocated using probabilistic cues that indicate test likelihood (i.e., goal-directed attentional priority to those items). Previous studies using simultaneous cues have not examined this flexible allocation beyond two distinct levels of priority. Moreover, previous studies have not examined whether there are individual differences in the ability to flexibly allocate VSTM resources, as well as whether this ability benefits from practice. The current study used a continuous report procedure to examine whether participants can use up to three levels of attentional priority to allocate VSTM resources via simultaneous probabilistic spatial cues. Three experiments were performed with differing priority levels, cues, and cue presentation times. Group level analysis demonstrated flexible allocation of VSTM resources; however, there was limited evidence that participants could use three goal-directed priority levels. A temporal analysis suggested that task fatigue, rather than practice effects, may interact with item priority. A Bayesian individual-differences analysis revealed that a minority of participants were using three levels of attentional priority, demonstrating that, while possible, it is not the predominant pattern of behaviour. Thus, we provided evidence that flexible allocation to three attention levels is possible under simultaneous cuing conditions for a minority of participants. Flexible allocation to three categories may be interpreted as a skill of high-performing participants akin to high memory capacity.

Picophotonic localization metrology beyond thermal fluctuations.

Despite recent tremendous progress in optical imaging and metrology1-6, there remains a substantial resolution gap between atomic-scale transmission electron microscopy and optical techniques. Is optical imaging and metrology of nanostructures exhibiting Brownian motion possible with such resolution, beyond thermal fluctuations? Here we report on an experiment in which the average position of a nanowire with a thermal oscillation amplitude of ∼150 pm is resolved in single-shot measurements with subatomic precision of 92 pm, using light at a wavelength of λ = 488 nm, providing an example of such sub-Brownian metrology with ∼λ/5,300 precision. To localize the nanowire, we employ a deep-learning analysis of the scattering of topologically structured light, which is highly sensitive to the nanowire's position. This non-invasive metrology with absolute errors down to a fraction of the typical size of an atom, opens a range of opportunities to study picometre-scale phenomena with light.

A Scoping Review of Measures Used in Early Intervention Services for Psychosis.

OBJECTIVE: The early intervention service (EIS) model for psychosis has been implemented with increasing frequency; yet, improving outcomes across domains for all patients remains challenging. Measurement-based care can strengthen outcomes by optimizing interventions and promoting alignment with standards, but it is still not widely deployed in EIS. The authors conducted a scoping review by systematically identifying and synthesizing measures used in EIS related to purpose (i.e., to assess patients, families, and programs), domains (e.g., symptoms, quality of life), and reporting perspectives (of patients, families, and clinicians). METHODS: EMBASE, MEDLINE, PsycINFO, CINAHL, and Cochrane Library databases were searched for pertinent literature published between 2000 and 2020. Two reviewers independently screened titles, abstracts, and full texts and extracted data. Measures were classified as clinician-reported outcome measures (CROMs), patient-reported outcome or experience measures (PROMs/PREMs), or family-reported outcome or experience measures (FROMs/FREMs). RESULTS: In total, 172 measures of 27 domains were identified from 115 articles. Nineteen measures had been used to assess programs on fidelity, service engagement, and satisfaction; 136 to assess patients on duration of untreated psychosis, symptoms, functioning, quality of life, and others; and 17 to assess families on coping and burden, background, and others. Sixty percent were CROMs, 30% were PROMs/PREMs, and 10% were FROMs/FREMs. CONCLUSIONS: Greater inclusion of PROMs and FROMs is needed because they align with the EIS philosophy of patient and family engagement and may improve shared decision making and outcomes. A comprehensive, meaningfully synthesized archive of measures can advance measurement-based care, services research, and data harmonization in early psychosis.

Coherently switching the focusing characteristics of all-dielectric metalenses.

Flat, gradient index, metasurface optics - in particular all-dielectric metalenses - have emerged and evolved over recent years as compact, lightweight alternative to their conventional bulk glass/crystal counterparts. Here we show that the focal properties of all-dielectric metalenses can be switched via coherent control, which is to say by changing the local electromagnetic field in the metalens plane rather than any physical or geometric property of the nanostructure or surrounding medium. The selective excitation of predominantly electric or magnetic resonant modes in the constituent cells of the metalens provides for switching, by design, of its phase profile enabling binary switching of focal length for a given lens type and, uniquely, switching between different (spherical and axicon) lens types.

Ballistic dynamics of flexural thermal movements in a nanomembrane revealed with subatomic resolution.

Flexural oscillations of freestanding films, nanomembranes, and nanowires are attracting growing attention for their importance to the fundamental physical and optical properties and device applications of two-dimensional and nanostructured (meta)materials. Here, we report on the observation of short-time scale ballistic motion in the flexural mode of a nanomembrane cantilever, driven by thermal fluctuation of flexural phonons, including measurements of ballistic velocities and displacements performed with subatomic resolution, using a free electron edge-scattering technique. Within intervals <10 µs, the membrane moves ballistically at a constant velocity, typically ~300 µm/s, while Brownian-like dynamics emerge for longer observation periods. Access to the ballistic regime provides verification of the equipartition theorem and Maxwell-Boltzmann statistics for flexural modes and can be used in fast thermometry and mass sensing during atomic absorption/desorption processes on the membrane.

Optical Control of Nanomechanical Brownian Motion Eigenfrequencies in Metamaterials.

Nanomechanical photonic metamaterials provide a wealth of active switching, nonlinear, and enhanced light-matter interaction functionalities by coupling optically and mechanically resonant subsystems. Thermal (Brownian) motion of the nanostructural components of such metamaterials leads to fluctuations in optical properties, which may manifest as noise, but which also present opportunity to characterize performance and thereby optimize design at the level of individual nanomechanical elements. We show that nanomechanical motion in an all-dielectric metamaterial ensemble of silicon-on-silicon-nitride nanowires can be controlled by light at sub-µW/µm2 intensities. Induced changes in nanowire temperature of just a few Kelvin and nonthermal optical forces generated within the structure change the few-MHz Eigenfrequencies and/or picometric displacement amplitudes of motion, and thereby metamaterial transmission. The tuning mechanism can provide active control of frequency response in photonic metadevices and may serve as a basis for bolometric, mass, and micro/nanostructural stress sensing.

Crosstalk between CD4 T cells and synovial fibroblasts from human arthritic joints promotes hyaluronan-dependent leukocyte adhesion and inflammatory cytokine expression in vitro.

The content and organization of hyaluronan (HA) in the extracellular matrix (ECM) have been identified as strong indicators of inflammation in joint disease, although the source and role of HA as an effector of inflammation is not clear. In this study, we established co-cultures of activated human CD4 T cells with fibroblast-like synoviocytes (FLS) from osteoarthritis (OA) and rheumatoid arthritis (RA) subjects and examined the role of HA in promoting inflammatory events. Co-cultures of RA FLS with activated CD4 T cells generated an HA-enriched ECM that promoted enhanced monocyte adhesion compared to co-cultures of OA FLS with activated CD4 T cells. In addition, both OA FLS and RA FLS co-cultures with activated CD4 T cells elicited significant increases in the expression of IL1ß, TNF, and IL6, with the increase in IL6 expression most prominent in RA co-cultures. Blocking HA synthesis and accumulation with 4-methylumbelliferone reduced expression of IL6, IL1ß, and TNF in both OA FLS and RA FLS co-cultures. The increase in HA synthesis in the co-cultures was mimicked by IL6 trans-signaling of FLS in the absence of CD4 T cells. Inhibition of HA synthesis blocked the increase in IL6 by RA FLS mediated by IL6 trans-signaling, suggesting that the HA synthetic pathway may be a key mediator in IL6 expression by FLS. Overall, our study indicates that HA-enriched ECM generated by co-cultures of activated CD4 T cells with FLS from human joints creates a pathogenic microenvironment by promoting adhesion of leukocytes and expression of inflammatory cytokines including IL6.

Deep-Learning-Assisted Focused Ion Beam Nanofabrication.

Focused ion beam (FIB) milling is an important rapid prototyping tool for micro- and nanofabrication and device and materials characterization. It allows for the manufacturing of arbitrary structures in a wide variety of materials, but establishing the process parameters for a given task is a multidimensional optimization challenge, usually addressed through time-consuming, iterative trial-and-error. Here, we show that deep learning from prior experience of manufacturing can predict the postfabrication appearance of structures manufactured by focused ion beam (FIB) milling with >96% accuracy over a range of ion beam parameters, taking account of instrument- and target-specific artifacts. With predictions taking only a few milliseconds, the methodology may be deployed in near real time to expedite optimization and improve reproducibility in FIB processing.

Visualization of Subatomic Movements in Nanostructures.

Electron microscopy, scanning probe, and optical super-resolution imaging techniques with nanometric resolution are now routinely available but cannot capture the characteristically fast (MHz-GHz frequency) movements of micro-/nano-objects. Meanwhile, optical interferometric techniques can detect high-frequency picometric displacements but only with diffraction-limited lateral resolution. Here, we introduce a motion visualization technique, based on the spectrally resolved detection of secondary electron emission from moving objects, that combines picometric displacement sensitivity with the nanometric spatial (positional/imaging) resolution of electron microscopy. The sensitivity of the technique is quantitatively validated against the thermodynamically defined amplitude of a nanocantilever's Brownian motion. It is further demonstrated in visualizing externally driven modes of cantilever, nanomechanical photonic metamaterial, and MEMS device structures. With a noise floor reaching ∼1 pm/Hz1/2, it can provide for the study of oscillatory movements with subatomic amplitudes, presenting new opportunities for the interrogation of motion in functional structures across the materials, bio- and nanosciences.

MRI and muscle enzymes do not support the diagnosis of local anesthetic myotoxicity: a descriptive case series.

BACKGROUND: The presence of thigh muscle edema as characterized by increased signal intensity on MRI has been used to support the diagnosis of presumed local anesthetic-induced myotoxicity reported after total knee arthroplasty (TKA) with continuous adductor canal block (CACB). However, neither postoperative baseline imaging appearance nor muscle enzyme values have been described in conjunction with this clinical scenario. Thus, the usefulness of MRI or enzymatic biomarkers of muscle injury for supporting the diagnosis of local anesthetic myotoxicity is unknown. METHODS: This descriptive case series documents postoperative MRI appearance of the ipsilateral upper leg, plus preoperative and postoperative creatine phosphokinase and aldolase values in volunteer patients who underwent uncomplicated TKA with CACB. RESULTS: In 27 volunteer patients with no postsurgical evidence of clinically relevant myotoxicity, anterior thigh muscle edema was universally evident on imaging (n=12) and muscle enzyme values (n=19) were normal or only slightly elevated. CONCLUSIONS: The non-specificity of these findings suggests that MRI and near normal muscle enzyme levels are of limited diagnostic value when there is clinical suspicion of local anesthetic myotoxicity in the setting of TKA with CACB. TRIAL REGISTRATION NUMBER: NCT04821245.

Dataset of the first report of pharmacogenomics profiling in an outpatient spine setting.

Here we describe the dataset of the first report of pharmacogenomics profiling in an outpatient spine setting with the primary aims to catalog: 1) the genes, alleles, and associated rs Numbers (accession numbers for specific single-nucleotide polymorphisms) analysed and 2) the genotypes and corresponding phenotypes of the genes involved in metabolizing 37 commonly used analgesic medications. The present description applies to analgesic medication-metabolizing enzymes and may be especially valuable to investigators who are exploring strategies to optimize pharmacologic pain management (e.g., by tailoring analgesic regimens to the genetically identified sensitivities of the patient). Buccal swabs were used to acquire tissue samples of 30 adult patients who presented to an outpatient spine clinic with the chief concern of axial neck and/or back pain. Array-based assays were then used to detect the alleles of genes involved in the metabolism of pain medications, including all common (wild type) and most rare variant alleles with known clinical significance. Both CYP450 isozymes - including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 - and the phase II enzyme UDP-glucuronosyltransferase-2B7 (UGT2B7) were examined. Genotypes/phenotypes were then used to evaluate each patient's relative ability to metabolize 37 commonly used analgesic medications. These medications included both non-opioid analgesics (i.e., aspirin, diclofenac, nabumetone, indomethacin, meloxicam, piroxicam, tenoxicam, lornoxicam, celecoxib, ibuprofen, flurbiprofen, ketoprofen, fenoprofen, naproxen, and mefenamic acid) and opioid analgesics (i.e., morphine, codeine, dihydrocodeine, ethylmorphine, hydrocodone, hydromorphone, oxycodone, oxymorphone, alfentanil, fentanyl, sufentanil, meperidine, ketobemidone, dextropropoxyphene, levacetylmethadol, loperamide, methadone, buprenorphine, dextromethorphan, tramadol, tapentadol, and tilidine). The genes, alleles, and associated rs Numbers that were analysed are provided. Also provided are: 1) the genotypes and corresponding phenotypes of the genes involved in metabolizing 37 commonly used analgesic medications and 2) the mechanisms of metabolism of the analgesic medications by primary and ancillary pathways. In supplemental spreadsheets, the raw and analysed pharmacogenomics data for all 30 patients evaluated in the primary research article are additionally provided. Collectively, the presented data offer significant reuse potential in future investigations of pharmacogenomics for pain management.

Contributions of post-learning REM and NREM sleep to memory retrieval.

It has become clear that sleep after learning has beneficial effects on the later retrieval of newly acquired memories. The neural mechanisms underlying these effects are becoming increasingly clear as well, particularly those of non-REM sleep. However, much is still unknown about the sleep and memory relationship: the sleep state or features of sleep physiology that associate with memory performance often vary by task or experimental design, and the nature of this variability is not entirely clear. This paper describes pertinent features of sleep physiology and provides a detailed review of the scientific literature indicating beneficial effects of post-learning sleep on memory retrieval. This paper additionally introduces a hypothesis which attributes these beneficial effects of post-learning sleep to separable processes of memory reinforcement and memory refinement whereby reinforcement supports one's ability to retrieve a given memory and refinement supports the precision of that memory retrieval in the context of competitive alternatives. It is observed that features of non-REM sleep are involved in a post-learning substantiation of memory representations that benefit memory performance; thus, memory reinforcement is primarily attributed to non-REM sleep. Memory refinement is primarily attributed to REM sleep given evidence of bidirectional synaptic plasticity in REM sleep and findings from studies of selective REM sleep deprivation.

Detection of sub-atomic movement in nanostructures.

Nanoscale objects move fast and oscillate billions of times per second. Such movements occur naturally in the form of thermal (Brownian) motion while stimulated movements underpin the functionality of nano-mechanical sensors and active nano-(electro/opto) mechanical devices. Here we introduce a methodology for detecting such movements, based on the spectral analysis of secondary electron emission from moving nanostructures, that is sensitive to displacements of sub-atomic amplitude. We demonstrate the detection of nanowire Brownian oscillations of ∼10 pm amplitude and hyperspectral mapping of stimulated oscillations of setae on the body of a common flea. The technique opens a range of opportunities for the study of dynamic processes in materials science, nanotechnology and biology.

Artificial intelligence for photonics and photonic materials.

Artificial intelligence (AI) is the most important new methodology in scientific research since the adoption of quantum mechanics and it is providing exciting results in numerous fields of science and technology. In this review we summarize research and discuss future opportunities for AI in the domains of photonics, nanophotonics, plasmonics and photonic materials discovery, including metamaterials.

First Report of Pharmacogenomic Profiling in an Outpatient Spine Setting: Preliminary Results from a Pilot Study.

OBJECTIVE: Pharmacogenomics may help personalize medicine and improve therapeutic selection. This is the first study investigating how pharmacogenomic testing may inform analgesic selection in patients with spine disease. We profile pharmacogenetic differences in pain medication-metabolizing enzymes across patients presenting at an outpatient spine clinic and provide preliminary evidence that genetic polymorphisms may help explain interpatient differences in preoperative pain refractory to conservative management. METHODS: Adults presenting to our outpatient spine clinic with chief symptoms of neck and/or back pain were prospectively enrolled over 9 months. Patients completed the Wong-Baker FACES and numeric pain rating scales for their chief pain symptom and provided detailed medication histories and cheek swab samples for genomic analysis. RESULTS: Thirty adults were included (mean age, 60.6 ± 15.3 years). The chief concern was neck pain in 23%, back pain in 67%, and combined neck/back pain in 10%. At enrollment, patient analgesic regimens comprised 3 ± 1 unique medications, including 1 ± 1 opioids. After genomic analysis, 14/30 patients (47%) were identified as suboptimal metabolizers of ≥1 medications in their analgesic regimen. Of these patients, 93% were suboptimal metabolizers of their prescribed opioid analgesic. Nonetheless, pain scores were similar between optimal and suboptimal metabolizer groups. CONCLUSIONS: This pilot study shows that a large proportion of the spine outpatient population may use pain medications for which they are suboptimal metabolizers. Further studies should assess whether these pharmacogenomic differences indicate differences in odds of receiving therapeutic benefit from surgery or if they can be used to generate more effective postoperative analgesic regimens.

Continuous beam steering by coherent light-by-light control of dielectric metasurface phase gradient.

Continuous and reversible tuning of the properties of optical metasurfaces, as a functionality that would enable a range of device applications, has been a focus of the metasurface research field in recent years. Tuning mechanisms proposed and demonstrated so far have generally relied upon changing the morphology of a metasurface or the intrinsic properties of its constituent materials. Here we introduce, via numerical simulation, an alternative approach to achieve continuous tuning of gradient metasurface response, and illustrate its potential application to the challenge of continuous beam steering, as required for example in LIDAR and machine vision systems. It is based upon the coherent illumination of a silicon nano-pillar metasurface with two counter-propagating beams. Control of the input beams' relative phase and intensity enables tuning of the individual nano-pillars' electromagnetic response and thereby the phase gradient of the array, which in turn steers the direction of the output beam continuously over an angular range of approximately 9 degrees.

Engagement in specialized early intervention services for psychosis as an interplay between personal agency and critical structures: A qualitative study.

BACKGROUND: Specialized early intervention programs for individuals experiencing a first episode of psychosis prioritize service engagement, generally operationalized as attendance, treatment completion, therapeutic alliance, and treatment adherence. However, there are critical theoretical and methodological gaps in understanding how service users experience and define their engagement with the service. OBJECTIVES: This study aimed to explore how current and former service users define their engagement with a specialized early intervention program. DESIGN: A qualitative descriptive approach was used to explore service users' decisions to use, remain involved with, and/or leave early intervention services. SETTING: This study took place in an early intervention service for psychosis in Montreal, Canada. PARTICIPANTS: Twenty-four participants who had experienced a first episode of psychosis and had been engaged in the service to varying degrees (fully engaged, partially engaged, disengaged) took part in in-depth interviews. METHODS: In-depth interviews were employed to collect rich insights into participants' experiences and perceptions. The interviews were transcribed and analysed using thematic analysis, beginning with an inductive approach and completing the analysis using a theoretical approach. During the analysis, our original notions of engagement and disengagement were challenged by theorizing engagement in terms of agency and structure. Researchers engaged in reflexive practices to maintain and promote research rigor and trustworthiness. RESULTS: Participants' narratives were thematically analyzed and organized into three themes: fluidity and temporality of engagement and disengagement; engagement as an ongoing negotiation; and critical structures and agency. Participants described engagement in a variety of ways, some of which were broader than service use and focused on self-care and commitment to recovery. These conceptions were subject to change as the individuals' perceptions of their needs changed. As needs changed, individuals also negotiated and renegotiated their care needs with themselves and with their treatment team. These exercises of agency were constrained by key structures: the treatment team, family and friends, and societal conceptions of mental health. CONCLUSIONS: Our study findings argue for an expanded definition of engagement which prioritizes individuals' experience and acknowledges the steps towards recovery that they may make outside of the purview of the service. It also underlines the importance of a treatment structure which aligns with individuals' needs for both support and autonomy.

Hyperarousal Is Associated with Socioemotional Processing in Individuals with Insomnia Symptoms and Good Sleepers.

Despite complaints of difficulties in waking socioemotional functioning by individuals with insomnia, only a few studies have investigated emotion processing performance in this group. Additionally, the role of sleep in socioemotional processing has not been investigated extensively nor using quantitative measures of sleep. Individuals with insomnia symptoms (n = 14) and healthy good sleepers (n = 15) completed two nights of at-home polysomnography, followed by an afternoon of in-lab performance testing on tasks measuring the processing of emotional facial expressions. The insomnia group self-reported less total sleep time, but no other group differences in sleep or task performance were observed. Greater beta EEG power throughout the night was associated with higher intensity ratings of happy, fearful and sad faces for individuals with insomnia, yet blunted sensitivity and lower accuracy for good sleepers. Thus, the presence of hyperarousal differentially impacted socioemotional processing of faces in individuals with insomnia symptoms and good sleepers.

Multiparameter Analysis Identifies Heterogeneity in Knee Osteoarthritis Synovial Responses.

OBJECTIVE: Synovial membrane inflammation is common in osteoarthritis (OA) and increases cartilage injury. However, synovial fluid and histology studies suggest that OA inflammatory responses are not homogeneous. Greater understanding of these responses may provide new insights into OA disease mechanisms. We undertook this study to develop a novel multiparameter approach to phenotype synovial responses in knee OA. METHODS: Cell composition and soluble protein production were measured by flow cytometry and multiplex enzyme-linked immunosorbent assay in synovium collected from OA patients undergoing knee replacement surgery (n = 35). RESULTS: Testing disaggregation conditions showed that aggressive digestion improved synovial cell yield and mesenchymal staining by flow cytometry, but it negatively impacted CD4+ T cell and CD56+ natural killer cell staining. Less aggressive digestion preserved these markers and showed highly variable T cell infiltration (range 0-43%; n = 32). Correlation analysis identified mesenchymal subpopulations associated with different nonmesenchymal populations, including macrophages and T cells (CD45+CD11b+HLA-DR+ myeloid cells with PDPN+CD73+CD90-CD34- mesenchymal cells [r = 0.65, P < 0.0001]; and CD45+CD3+ T cells with PDPN+CD73+CD90+CD34+ mesenchymal cells [r = 0.50, P = 0.003]). Interleukin-6 (IL-6) measured by flow cytometry strongly correlated with IL-6 released by ex vivo culture of synovial tissue (r = 0.59, P = 0.0012) and was highest in mesenchymal cells coexpressing CD90 and CD34. IL-6, IL-8, complement factor D, and IL-10 release correlated positively with tissue cellularity (P = 0.0042, P = 0.018, P = 0.0012, and P = 0.038, respectively). Additionally, increased CD8+ T cell numbers correlated with retinol binding protein 4 (P = 0.033). Finally, combining flow cytometry and multiplex data identified patient clusters with different types of inflammatory responses. CONCLUSION: We used a novel approach to analyze OA synovium, identifying patient-specific inflammatory clusters. Our findings indicate that phenotyping synovial inflammation may provide new insights into OA patient heterogeneity and biomarker development.

New findings on the significance of Jebel Moya in the eastern Sahel.

This paper presents new excavation data and new radiometric dates for Jebel Moya, south-central Sudan. These data suggest revisions to previous chronological understandings of the site. New excavations, initiated in 2017, show a longer, more continuous occupation of the site than has been previously recognised. Archaeozoological and archaeobotanical analyses provide evidence for domesticated taxa. Archaeobotanical evidence is dominated by domesticated sorghum (Sorghum bicolor), radiocarbon dated to c. 2550-2210 BC. Faunal remains include cattle and goat/sheep. A late third-millennium BC date on the human skeleton excavated in the 2017 season also shows that mortuary activity began early in the site's history, contemporary with domesticated faunal and botanical remains. These initial results indicate the long-term association of the site with pastoralism and agriculture and with environmental change. Jebel Moya's continued potential to serve as a chronological and cultural reference point for future studies in south-central Sudan and the eastern Sahel is reinforced.