Randomness impacts the building of specific priors, visual exploration, and perception in object recognition.

Recognising objects is a vital skill on which humans heavily rely to respond quickly and adaptively to their environment. Yet, we lack a full understanding of the role visual information sampling plays in this process, and its relation to the individual's priors. To bridge this gap, the eye-movements of 18 adult participants were recorded during a free-viewing object-recognition task using Dots stimuli1. Participants viewed the stimuli in one of three orders: from most visible to least (Descending), least visible to most (Ascending), or in a randomised order (Random). This dictated the strength of their priors along the experiment. Visibility order influenced the participants' recognition performance and visual exploration. In addition, we found that while orders allowing for stronger priors generally led participants to visually sample more informative locations, this was not the case of Random participants. Indeed, they appeared to behave naïvely, and their use of specific object-related priors was fully impaired, while they maintained the ability to use general, task-related priors to guide their exploration. These findings have important implications for our understanding of perception, which appears to be influenced by complex cognitive processes, even at the basic level of visual sampling during object recognition.

A tale of two tumors: differential, but detrimental, effects of glioblastoma extracellular vesicles (EVs) on normal human brain cells.

Glioblastomas (GBMs) are dreadful brain tumors with abysmal survival outcomes. GBM EVs dramatically affect normal brain cells (largely astrocytes) constituting the tumor microenvironment (TME). EVs from different patient-derived GBM spheroids induced differential transcriptomic, secretomic, and proteomic effects on cultured astrocytes/brain tissue slices as GBM EV recipients. The net outcome of brain cell differential changes nonetheless converges on increased tumorigenicity. GBM spheroids and brain slices were derived from neurosurgical patient tissues following informed consent. Astrocytes were commercially obtained. EVs were isolated from conditioned culture media by ultrafiltration, ultraconcentration, and ultracentrifugation. EVs were characterized by nanoparticle tracking analysis, electron microscopy, biochemical markers, and proteomics. Astrocytes/brain tissues were treated with GBM EVs before downstream analyses. EVs from different GBMs induced brain cells to alter secretomes with pro-inflammatory or TME-modifying (proteolytic) effects. Astrocyte responses ranged from anti-viral gene/protein expression and cytokine release to altered extracellular signal-regulated protein kinase (ERK1/2) signaling pathways, and conditioned media from EV-treated cells increased GBM cell proliferation. Thus, astrocytes/brain slices treated with different GBM EVs underwent non-identical changes in various 'omics readouts and other assays, indicating "personalized" tumor-specific GBM EV effects on the TME. This raises concern regarding reliance on "model" systems as a sole basis for translational direction. Nonetheless, net downstream impacts from differential cellular and TME effects still led to increased tumorigenic capacities for the different GBMs.

Effects of expectation on face perception and its association with expertise.

Perceptual decisions are derived from the combination of priors and sensorial input. While priors are broadly understood to reflect experience/expertise developed over one's lifetime, the role of perceptual expertise at the individual level has seldom been directly explored. Here, we manipulate probabilistic information associated with a high and low expertise category (faces and cars respectively), while assessing individual level of expertise with each category. 67 participants learned the probabilistic association between a color cue and each target category (face/car) in a behavioural categorization task. Neural activity (EEG) was then recorded in a similar paradigm in the same participants featuring the previously learned contingencies without the explicit task. Behaviourally, perception of the higher expertise category (faces) was modulated by expectation. Specifically, we observed facilitatory and interference effects when targets were correctly or incorrectly expected, which were also associated with independently measured individual levels of face expertise. Multivariate pattern analysis of the EEG signal revealed clear effects of expectation from 100 ms post stimulus, with significant decoding of the neural response to expected vs. not stimuli, when viewing identical images. Latency of peak decoding when participants saw faces was directly associated with individual level facilitation effects in the behavioural task. The current results not only provide time sensitive evidence of expectation effects on early perception but highlight the role of higher-level expertise on forming priors.

Biomarkers of Motor Outcomes After Stroke.

Predicting motor outcomes after stroke based on clinical judgment alone is often inaccurate and can lead to inefficient and inequitable allocation of rehabilitation resources. Prediction tools are being developed so that clinicians can make evidence-based, accurate, and reproducible prognoses for individual patients. Biomarkers of corticospinal tract structure and function can improve prediction tool performance, particularly for patients with initially moderate to severe motor impairment. Being able to make accurate predictions for individual patients supports rehabilitation planning and communication with patients and families.

Behavioral and Neural Correlates of Visual Working Memory Reveal Metacognitive Aspects of Mental Imagery.

Mental imagery (MI) is the ability to generate visual phenomena in the absence of sensory input. MI is often likened to visual working memory (VWM): the ability to maintain and manipulate visual representations. How MI is recruited during VWM is yet to be established. In a modified orientation change-discrimination task, we examined how behavioral (proportion correct) and neural (contralateral delay activity [CDA]) correlates of precision and capacity map onto subjective ratings of vividness and number of items in MI within a VWM task. During the maintenance period, 17 participants estimated the vividness of their MI or the number of items held in MI while they were instructed to focus on either precision or capacity of their representation and to retain stimuli at varying set sizes (1, 2, and 4). Vividness and number ratings varied over set sizes; however, subjective ratings and behavioral performance correlated only for vividness rating at set size 1. Although CDA responded to set size as was expected, CDA did not reflect subjective reports on high and low vividness and on nondivergent (reported the probed number of items in mind) or divergent (reported number of items diverged from probed) rating trials. Participants were more accurate in low set sizes compared with higher set sizes and in coarse (45°) orientation changes compared with fine (15°) orientation changes. We failed to find evidence for a relationship between the subjective sensory experience of precision and capacity of MI and the precision and capacity of VWM.

Do lower limb motor-evoked potentials predict walking outcomes post-stroke?

BACKGROUND: This observational study examined whether lower limb (LL) motor-evoked potentials (MEPs) 1 week post-stroke predict recovery of independent walking, use of ankle-foot orthosis (AFO) or walking aid, at 3 and 6 months post-stroke. METHODS: Non-ambulatory participants were recruited 5 days post-stroke. Transcranial magnetic stimulation was used to determine tibialis anterior MEP status and clinical assessments (age, National Institutes of Health Stroke Scale (NIHSS), ankle dorsiflexion strength, LL motricity index, Berg Balance Test) were completed 1 week post-stroke. Functional Ambulation Category (FAC), use of AFO and walking aid were assessed 3 months and 6 months post-stroke. MEP status, alone and combined with clinical measures, and walking outcomes at 3 and 6 months were analysed with Pearson χ2 and multivariate binary logistic regression. RESULTS: Ninety participants were included (median age 72 years (38-97 years)). Most participants (81%) walked independently (FAC ≥ 4), 17% used an AFO, and 49% used a walking aid 3 months post-stroke with similar findings at 6 months. Independent walking was better predicted by age, LL strength and Berg Balance Test (accuracy 92%, 95% CI 85% to 97%) than MEP status (accuracy 73%, 95% CI 63% to 83%). AFO use was better predicted by NIHSS and MEP status (accuracy 88%, 95% CI 79% to 94%) than MEP status alone (accuracy 76%, 95% CI 65% to 84%). No variables predicted use of walking aids. CONCLUSIONS: The presence of LL MEPs 1-week post-stroke predicts independent walking at 3 and 6 months post-stroke. However, the absence of MEPs does not preclude independent walking. Clinical factors, particularly age, balance and stroke severity, more strongly predict independent walking than MEP status. LL MEP status adds little value as a biomarker for walking outcomes.

Applications of Repetitive Transcranial Magnetic Stimulation to Improve Upper Limb Motor Performance After Stroke: A Systematic Review.

BACKGROUND: Noninvasive brain stimulation (NIBS) is a promising technique for improving upper limb motor performance post-stroke. Its application has been guided by the interhemispheric competition model and typically involves suppression of contralesional motor cortex. However, the bimodal balance recovery model prompts a more tailored application of NIBS based on ipsilesional corticomotor function. OBJECTIVE: To review and assess the application of repetitive transcranial magnetic stimulation (rTMS) protocols that aimed to improve upper limb motor performance after stroke. METHODS: A PubMed search was conducted for studies published between 1st January 2005 and 1st November 2022 using rTMS to improve upper limb motor performance of human adults after stroke. Studies were grouped according to whether facilitatory or suppressive rTMS was applied to the contralesional hemisphere. RESULTS: Of the 492 studies identified, 70 were included in this review. Only 2 studies did not conform to the interhemispheric competition model, and facilitated the contralesional hemisphere. Only 21 out of 70 (30%) studies reported motor evoked potential (MEP) status as a biomarker of ipsilesional corticomotor function. Around half of the studies (37/70, 53%) checked whether rTMS had the expected effect by measuring corticomotor excitability (CME) after application. CONCLUSION: The interhemispheric competition model dominates the application of rTMS post-stroke. The majority of recent and current studies do not consider bimodal balance recovery model for the application of rTMS. Evaluating CME after the application rTMS could confirm that the intervention had the intended neurophysiological effect. Future studies could select patients and apply rTMS protocols based on ipsilesional MEP status.

Robust tobacco smoking self-report in two cohorts: pregnant women or men and women living with or without HIV.

Understanding the true burden of tobacco smoking on adverse pregnancy outcomes is critical in generating appropriate interventions to improve outcomes. Self-reporting of human behaviour that is associated with stigma is associated with underreporting in general and may bias the impact of smoking in studies; however, self-reporting is frequently the most practical method of gleaning this information. The objective of this study was to evaluate concordance between self-reported smoking and concentrations of plasma cotinine, a biomarker of smoking, among participants enrolled in two related HIV cohorts. A total of 100 pregnant women (76 living with HIV [LWH] and 24 negative controls) in their third trimester, and 100 men and non-pregnant women (43 LWH and 57 negative controls) were included. Among all participants, 43 pregnant women (49% LWH and 25% negative controls) and 50 men and non-pregnant women (58% LWH and 44% negative controls) were self-reported smokers. The odds of discordance between self-reported smoking and cotinine levels were not significantly different between self-reported smokers and non-smokers, nor between pregnant women and others, but were significantly increased, regardless of self-reported status, among people LWH compared to negative controls. The overall concordance between plasma cotinine and self-reported data among all participants was 94% with a sensitivity and specificity of 90% and 96%, respectively. Taken together, these data demonstrate that participant surveying in a non-judgemental context can lead to accurate and robust self-report smoking data among both persons LWH and not, including in the context of pregnancy.

Lymphedema is associated with CELSR1 in Phelan-McDermid syndrome.

Lymphedema is a troubling condition present in many disorders including the rare genetic disorder known as Phelan-McDermid syndrome (PMS). The neurobehavioral features of PMS, also known as 22q13.3 deletion syndrome, have been investigated, but little research exists on lymphedema in PMS. In this investigation, clinical and genetic data from 404 people with PMS were reviewed from the PMS-International Registry revealing a prevalence of 5% with lymphedema. Lymphedema was reported in 1 out of 47 people (2.1%) with PMS due to a SHANK3 variant and 19 out of 357 people (5.3%) with PMS due to 22q13.3 deletions. Lymphedema was more common among those in their teens or adulthood (p = 0.0011) and those with deletions >4 Mb. People with lymphedema had significantly larger deletions (mean 5.375 Mb) than those without lymphedema (mean 3.464 Mb, p = 0.00496). Association analysis identified a deletion of the CELSR1 gene to be the biggest risk factor (OR = 12.9 95% CI [2.9-56.2]). Detailed assessment of 5 subjects identified all had deletions of CELSR1, developed symptoms of lymphedema starting at age 8 or older, and typically responded well to standard therapy. In conclusion, this is the largest assessment of lymphedema in PMS to date and our results suggest that individuals with deletions >4 Mb or those with CELSR1 deletions should be assessed for lymphedema.

Age, gender, and setting's effect on community pharmacists' stress and confidence in the COVID-19 pandemic.

Background: Reports of increased stress among healthcare workers were commonplace during the early days of the COVID-19 pandemic, but little is known about community pharmacists' experiences. Objective: To characterize community pharmacists' stress and confidence during the early COVID-19 pandemic and identify associated factors. Methods: Pharmacists who worked in a brick-and-mortar community pharmacy (e.g., big-box, chain, independent, or grocery pharmacies) located in Connecticut and had regular face-to-face interaction with the public were surveyed. Survey items were selected from the Perceived Stress Scale-10 (PSS-10) and adapted from the Emergency Risk-Communication (ERC) framework. Data were analyzed using chi-square and ANOVA. Results: Survey results suggested pharmacists experienced moderate levels of stress, as negative responses to PSS-10 items ranged between 6.4% to 43.3%, respectively. Overall, pharmacists had high rates of confidence in their ability to manage the pandemic, agreeing or strongly agreeing that they could manage their own mental health (73.1%), and communicate the risks of the pandemic (72.0%). However, 28.0% reported that they had avoided talking about the pandemic because it made them feel "stressed, or nervous." Women and those working in chain community pharmacies tended to report significantly higher rates of stress to several items in the PSS-10 compared to men and pharmacists working in non-chain settings. Women and chain community pharmacists were also significantly more likely to report overall that they had avoided talking about public health risks because it made them feel anxious, stressed, or depressed (29.4% men vs. 34.5% women χ2 (4) > 22.6, p < 0.01). However, confidence to communicate critical risk messages neither differed between men and women (77.6% men vs. 68.8% women χ2 (4) > 8.3, p = 0.08), nor between chain and non-chain community pharmacists (71.0% chain vs. 73.7% non-chain χ2 (4) > 8.9, p = 0.32). Conclusion: Being female, younger age, and employed at a chain pharmacy were associated with higher rates of stress and lower self-confidence among community pharmacists during the COVID-19 pandemic.

Applying Design-Thinking Principles to Practice-Based Pharmacy Research.

Design thinking is an approach to problem solving that focuses on a solution to a problem. This systematic approach can be applied to practice-based research or implementation projects in your practice setting. It may be useful for starting new projects as well as revisiting past projects that may not have yielded meaningful results. The design-thinking process begins with identifying a problem or knowledge gap and then the steps include: (1) understanding the problem, (2) observing the problem, (3) defining the problem, (4) brainstorming possible solutions, (5) prototyping the best solution, and (6) testing the solution.

Face recognition ability is manifest in early dynamic decoding of face-orientation selectivity-Evidence from multi-variate pattern analysis of the neural response.

Although humans are considered to be face experts, there is a well-established reliable variation in the degree to which neurotypical individuals are able to learn and recognise faces. While many behavioural studies have characterised these differences, studies that seek to relate the neuronal response to standardised behavioural measures of ability remain relatively scarce, particularly so for the time-resolved approaches and the early response to face stimuli. In the present study we make use of a relatively recent methodological advance, multi-variate pattern analysis (MVPA), to decode the time course of the neural response to faces compared to other object categories (inverted faces, objects). Importantly, for the first time, we directly relate metrics of this decoding assessed at the individual level to gold-standard measures of behavioural face processing ability assessed in an independent task. Thirty-nine participants completed the behavioural Cambridge Face Memory Test (CFMT), then viewed images of faces and houses (presented upright and inverted) while their neural activity was measured via electroencephalography. Significant decoding of both face orientation and face category were observed in all individual participants. Decoding of face orientation, a marker of more advanced face processing, was earlier and stronger in participants with higher levels of face expertise, while decoding of face category information was earlier but not stronger for individuals with greater face expertise. Taken together these results provide a marker of significant differences in the early neuronal response to faces from around 100 ms post stimulus as a function of behavioural expertise with faces.

A technical assistance program approach for pharmacist clinical services integration in primary care organizations.

BACKGROUND: Little is known about the use of technical assistance (TA) programs to facilitate the integration of pharmacist clinical services in primary care settings. OBJECTIVE: Design, implement, and evaluate a TA program to advance pharmacist integration and clinical services in primary care. PRACTICE DESCRIPTION: Structured TA program for developing new or enhancing current integrated pharmacist services was utilized in 4 primary care organizations (i.e., federally qualified health center, accountable care organization, and an academic and regional health system). PRACTICE INNOVATION: Holistic TA program with a logic model, organizational stages of pharmacist integration, project prioritization, and implementation plans. EVALUATION METHODS: A mixed-methods contextual inquiry approach for integration of pharmacist clinical services. Quantitative analysis was used for TA program activities, time spent, pilot project data, and a web-based survey for post-TA program assessment. Coincidence analysis was used to assess organizational commitment to TA services. Qualitative analysis was used for data collected through semi-structured key informant interviews and team meeting activity reports. RESULTS: TA program team spent 1872 hours over 11 months on program development, logistics, implementation, and project oversight. TA services included 88 onsite and virtual meetings, 11 onsite pharmacist coaching sessions, 6 workflow mapping sessions, and updating online learning resources. Primary care organizations that had already hired a pharmacist were more likely to uptake TA services. Most useful TA methods were webinar meetings (89%) and on-site pharmacist coaching (88%). TA project results were used for strategic planning (73%), pharmacist value/impact assessment (72%), pharmacist capacity modeling (68%), and workflow design (65%). A key learning from the TA program was the importance of a qualified pharmacist with clinical service experience in primary care settings and population health teams. CONCLUSION: TA program for the pharmacist clinical service integration has broad application to primary care organizations with diverse organizational structures, payer mixes, and practice settings.

Dolutegravir-containing HIV therapy reversibly alters mitochondrial health and morphology in cultured human fibroblasts and peripheral blood mononuclear cells.

OBJECTIVES: Given the success of combination antiretroviral therapy (cART) in treating HIV viremia, drug toxicity remains an area of interest in HIV research. Despite newer integrase strand transfer inhibitors (InSTIs), such as dolutegravir (DTG) and raltegravir (RAL), having excellent clinical tolerance, there is emerging evidence of off-target effects and toxicities. Although limited in number, recent reports have highlighted the vulnerability of mitochondria to these toxicities. The aim of the present study is to quantify changes in cellular and mitochondrial health following exposure to current cART regimens at pharmacological concentrations. A secondary objective is to determine whether any cART-associated toxicities would be modulated by human telomerase reverse transcriptase (hTERT). METHODS: We longitudinally evaluated markers of cellular (cell count, apoptosis), and mitochondrial health [mitochondrial reactive oxygen species (mtROS), membrane potential (MMP) and mass (mtMass)] by flow cytometry in WI-38 human fibroblast with differing hTERT expression/localization and peripheral blood mononuclear cells. This was done after 9 days of exposure to, and 6 days following the removal of, seven current cART regimens, including three that contained DTG. Mitochondrial morphology was assessed by florescence microscopy and quantified using a recently developed deep learning-based pipeline. RESULTS: Exposure to DTG-containing regimens increased apoptosis, mtROS, mtMass, induced fragmented mitochondrial networks compared with non-DTG-containing regimens, including a RAL-based combination. These effects were unmodulated by telomerase expression. All effects were fully reversible following removal of drug pressure. CONCLUSION: Taken together, our observations indicate that DTG-containing regimens negatively impact cellular and mitochondrial health and may be more toxic to mitochondria, even among the generally well tolerated InSTI-based cART.

Orientation effects support specialist processing of upright unfamiliar faces in children and adults.

It is considerably harder to generalize identity across different pictures of unfamiliar faces, compared with familiar faces. This finding hints strongly at qualitatively distinct processing of unfamiliar face stimuli-for which we have less expertise. Yet, the extent to which face selective versus generic visual processes drive outcomes during this task has yet to be determined. To explore the relative contributions of each, we contrasted performance on a version of the popular Telling Faces Together unfamiliar face matching task, implemented in both upright and inverted orientations. Furthermore, we included different age groups (132 British children ages 6 to 11 years [69.7% White], plus 37 British White adults) to investigate how participants' experience with faces as a category influences their selective utilization of specialized processes for unfamiliar faces. Results revealed that unfamiliar face matching is highly orientation-selective. Accuracy was higher for upright compared with inverted faces from 6 years of age, which is consistent with selective utilization of specialized processes for upright versus inverted unfamiliar faces during this task. The effect of stimulus orientation did not interact significantly with age, and there was no graded increase in the magnitude of inversion effects observed across childhood. Still, a numerically larger inversion effect in adults compared to children provides a degree of support for developmental changes in these specialized face abilities with increasing age/experience. Differences in the pattern of errors across age groups are also consistent with a qualitative shift in unfamiliar face processing that occurs some time after 11 years of age. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Reliability of the evidence to guide decision-making in foot ulcer prevention in diabetes: an overview of systematic reviews.

BACKGROUND: Reliable evidence on the effectiveness of interventions to prevent diabetes-related foot ulceration is essential to inform clinical practice. Well-conducted systematic reviews that synthesise evidence from all relevant trials offer the most robust evidence for decision-making. We conducted an overview to assess the comprehensiveness and utility of the available secondary evidence as a reliable source of robust estimates of effect with the aim of informing a cost-effective care pathway using an economic model. Here we report the details of the overview. [PROSPERO Database (CRD42016052324)]. METHODS: Medline (Ovid), Embase (Ovid), Epistomonikos, Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effectiveness (DARE), and the Health Technology Assessment Journals Library were searched to 17th May 2021, without restrictions, for systematic reviews of randomised controlled trials (RCTs) of preventive interventions in people with diabetes. The primary outcomes of interest were new primary or recurrent foot ulcers. Two reviewers independently extracted data and assessed the risk of bias in the included reviews. FINDINGS: The overview identified 30 systematic reviews of patient education, footwear and off-loading, complex and other interventions. Many are poorly reported and have fundamental methodological shortcomings associated with increased risk of bias. Most concerns relate to vague inclusion criteria (60%), weak search or selection strategies (70%) and quality appraisal methods (53%) and inexpert conduct and interpretation of quantitative and narrative evidence syntheses (57%). The 30 reviews have collectively assessed 26 largely poor-quality RCTs with substantial overlap. INTERPRETATION: The majority of these systematic reviews of the effectiveness of interventions to prevent diabetic foot ulceration are at high risk of bias and fail to provide reliable evidence for decision-making. Adherence to the core principles of conducting and reporting systematic reviews is needed to improve the reliability of the evidence generated to inform clinical practice.

Second-Generation Human Immunodeficiency Virus Integrase Inhibitors Induce Differentiation Dysregulation and Exert Toxic Effects in Human Embryonic Stem Cell and Mouse Models.

BACKGROUND: Each year, approximately 1.1 million children are exposed in utero to human immunodeficiency virus antiretrovirals, yet their safety is often not well characterized during pregnancy. The Tsepamo study reported a neural tube defect signal in infants exposed to the integrase strand transfer inhibitor (InSTI) dolutegravir from conception, suggesting that exposure during early fetal development may be detrimental. METHODS: The effects of InSTIs on 2 human embryonic stem cell (hESC) lines were characterized with respect to markers of pluripotency, early differentiation, and cellular health. In addition, fetal resorptions after exposure to InSTIs from conception were analyzed in pregnant mice. RESULTS: At subtherapeutic concentrations, second-generation InSTIs bictegravir, cabotegravir, and dolutegravir decreased hESC counts and pluripotency and induced dysregulation of genes involved in early differentiation. At therapeutic concentrations, bictegravir induced substantial hESC death and fetal resorptions. It is notable that first-generation InSTI raltegravir did not induce any hESC toxicity or differentiation, at any concentration tested. CONCLUSIONS: Exposure to some InSTIs, even at subtherapeutic concentrations, can induce adverse effects in hESCs and pregnant mice. Given the increasingly prevalent use of second-generation InSTIs, including in women of reproductive age, it is imperative to further elucidate the effect of InSTIs on embryonic development, as well as their long-term safety after in utero exposure.

Glioblastoma Extracellular Vesicle-Specific Peptides Inhibit EV-Induced Neuronal Cytotoxicity.

WHO Grade 4 IDH-wild type astrocytoma (GBM) is the deadliest brain tumor with a poor prognosis. Meningioma (MMA) is a more common "benign" central nervous system tumor but with significant recurrence rates. There is an urgent need for brain tumor biomarkers for early diagnosis and effective treatment options. Extracellular vesicles (EVs) are tiny membrane-enclosed vesicles that play essential functions in cell-to-cell communications among tumor cells. We aimed to identify epitopes of brain tumor EVs by phage peptide libraries. EVs from GBM plasma, MMA plasma, or brain tumor cell lines were used to screen phage-displayed random peptide libraries to identify high-affinity peptides. We purified EVs from three GBM plasma pools (23 patients), one MMA pool (10 patients), and four brain tumor cell lines. We identified a total of 21 high-affinity phage peptides (12 unique) specific to brain tumor EVs. The peptides shared high sequence homologies among those selected by the same EVs. Dose-response ELISA demonstrated that phage peptides were specific to brain tumor EVs compared to controls. Peptide affinity purification identified unique brain tumor EV subpopulations. Significantly, GBM EV peptides inhibit brain tumor EV-induced complement-dependent cytotoxicity (necrosis) in neurons. We conclude that phage display technology could identify specific peptides to isolate and characterize tumor EVs.

Factors influencing primary care organization commitment to technical assistance for pharmacist clinical services integration.

BACKGROUND: While technical assistance (TA) has been utilized by primary care organizations (PCOs) for electronic health record installation and medical home recognition, little is known about PCOs' use of TA to optimize pharmacist clinical services and integration in team-based care or population health programs. In 2019, the Connecticut Office of Health Strategy's State Innovation Model Program funded a no-cost TA initiative for 9 PCOs to initiate and/or advance pharmacist clinical services. OBJECTIVE: To assess organizational, operational, and pharmacist factors that influenced PCO commitment to the TA program. METHODS: During the TA program, data were collected from multiple sources including PCO demographic data; discussions and meetings with PCO medical, pharmacy, and administrative leaders; on-site workflow observations; and pharmacist coaching sessions. Configurational comparative methods were applied using the data collected during the TA program. Candidate factors were identified and calibrated on the basis of the researchers' knowledge of the TA program, organizational readiness for change models, implementation science frameworks, and published literature. Each candidate factor was iteratively assessed until 13 factors were selected and calibrated by independently assigning each factor a dichotomous value across PCOs. Calibration differences between the researchers were discussed until consensus was reached. Solutions were modeled using the Coincidence Analysis (cna) package in R and RStudio (RStudio, PBC). RESULTS: Of the 9 PCOs, 4 committed to participating in the TA program. Only 1 factor, the presence of a hired pharmacist, consistently distinguished PCOs that committed from those that did not, with 100% coverage and 80% consistency. CONCLUSION: PCO commitment to participate in the TA program was best explained by the factor of already having hired a pharmacist. These results can inform future efforts to engage PCOs in TA, primary care policy initiatives, and future research to understand factors influencing PCO success with pharmacist clinical services integration.

The TWIST Tool Predicts When Patients Will Recover Independent Walking After Stroke: An Observational Study.

BACKGROUND: The likelihood of regaining independent walking after stroke influences rehabilitation and hospital discharge planning. OBJECTIVE: This study aimed to develop and internally validate a tool to predict whether and when a patient will walk independently in the first 6 months post-stroke. METHODS: Adults with stroke were recruited if they had new lower limb weakness and were unable to walk independently. Clinical assessments were completed one week post-stroke. The primary outcome was time post-stroke by which independent walking (Functional Ambulation Category score ≥ 4) was achieved. Cox hazard regression identified predictors for achieving independent walking by 4, 6, 9, 16, or 26 weeks post-stroke. The cut-off and weighting for each predictor was determined using ß-coefficients. Predictors were assigned a score and summed for a final TWIST score. The probability of achieving independent walking at each time point for each TWIST score was calculated. RESULTS: We included 93 participants (36 women, median age 71 years). Age < 80 years, knee extension strength Medical Research Council grade ≥ 3/5, and Berg Balance Test < 6, 6 to 15, or ≥ 16/56, predicted independent walking and were combined to form the TWIST prediction tool. The TWIST prediction tool was at least 83% accurate for all time points. CONCLUSIONS: The TWIST tool combines routine bedside tests at one week post-stroke to accurately predict the probability of an individual patient achieving independent walking by 4, 6, 9, 16, or 26 weeks post-stroke. If externally validated, the TWIST prediction tool may benefit patients and clinicians by informing rehabilitation decisions and discharge planning.