Trivalent and quadrivalent seasonal influenza vaccine in adults aged 60 and older: a systematic review and network meta-analysis.

OBJECTIVES: To compare the efficacy of influenza vaccines of any valency for adults 60 years and older. DESIGN AND SETTING: Systematic review with network meta-analysis (NMA) of randomised controlled trials (RCTs). MEDLINE, EMBASE, JBI Evidence-Based Practice (EBP) Database, PsycINFO, and Cochrane Evidence -Based Medicine database were searched from inception to 20 June 20, 2022. Two reviewers screened, abstracted, and appraised articles (Cochrane Risk of Bias (ROB) 2.0 tool) independently. We assessed certainty of findings using Confidence in Network Meta-Analysis and Grading of Recommendations, Assessment, Development and Evaluations approaches. We performed random-effects meta-analysis and network meta-analysis (NMA), and estimated odds ratios (ORs) for dichotomous outcomes and incidence rate ratios (IRRs) for count outcomes along with their corresponding 95% confidence intervals (CIs) and prediction intervals. PARTICIPANTS: Older adults (≥60 years old) receiving an influenza vaccine licensed in Canada or the USA (vs placebo, no vaccine, or any other licensed vaccine), at any dose. MAIN OUTCOME MEASURES: Laboratory-confirmed influenza (LCI) and influenza-like illness (ILI). Secondary outcomes were the number of vascular adverse events, hospitalisation for acute respiratory infection (ARI) and ILI, inpatient hospitalisation, emergency room (ER) visit for ILI, outpatient visit, and mortality, among others. RESULTS: We included 41 RCTs and 15 companion reports comprising 8 vaccine types and 206 032 participants. Vaccines may prevent LCI compared with placebo, with high-dose trivalent inactivated influenza vaccine (IIV3-HD) (NMA: 9 RCTs, 52 202 participants, OR 0.23, 95% confidence interval (CI) (0.11 to 0.51), low certainty of evidence) and recombinant influenza vaccine (RIV) (OR 0.25, 95%CI (0.08 to 0.73), low certainty of evidence) among the most efficacious vaccines. Standard dose trivalent IIV3 (IIV3-SD) may prevent ILI compared with placebo, but the result was imprecise (meta-analysis: 2 RCTs, 854 participants, OR 0.39, 95%CI (0.15 to 1.02), low certainty of evidence). Any HD was associated with prevention of ILI compared with placebo (NMA: 9 RCTs, 65 658 participants, OR 0.38, 95%CI (0.15 to 0.93)). Adjuvanted quadrivalent IIV (IIV4-Adj) may be associated with the least vascular adverse events, but the results were very uncertain (NMA: eight 8 RCTs, 57 677 participants, IRR 0.18, 95%CI (0.07 to 0.43), very low certainty of evidence). RIV on all-cause mortality may be comparable to placebo (NMA: 20 RCTs, 140 577 participants, OR 1.01, 95%CI (0.23 to 4.49), low certainty of evidence). CONCLUSIONS: This systematic review demonstrated efficacy associated with IIV3-HD and RIV vaccines in protecting older persons against LCI. RIV vaccine may reduce all-cause mortality when compared with other vaccines, but the evidence is uncertain. Differences in efficacy between influenza vaccines remain uncertain with very low to moderate certainty of evidence. PROSPERO REGISTRATION NUMBER: CRD42020177357.

Interventions on gender equity in the workplace: a scoping review.

BACKGROUND: Various studies have demonstrated gender disparities in workplace settings and the need for further intervention. This study identifies and examines evidence from randomized controlled trials (RCTs) on interventions examining gender equity in workplace or volunteer settings. An additional aim was to determine whether interventions considered intersection of gender and other variables, including PROGRESS-Plus equity variables (e.g., race/ethnicity). METHODS: Scoping review conducted using the JBI guide. Literature was searched in MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, ERIC, Index to Legal Periodicals and Books, PAIS Index, Policy Index File, and the Canadian Business & Current Affairs Database from inception to May 9, 2022, with an updated search on October 17, 2022. Results were reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension to scoping reviews (PRISMA-ScR), Sex and Gender Equity in Research (SAGER) guidance, Strengthening the Integration of Intersectionality Theory in Health Inequality Analysis (SIITHIA) checklist, and Guidance for Reporting Involvement of Patients and the Public (GRIPP) version 2 checklist. All employment or volunteer sectors settings were included. Included interventions were designed to promote workplace gender equity that targeted: (a) individuals, (b) organizations, or (c) systems. Any comparator was eligible. Outcomes measures included any gender equity related outcome, whether it was measuring intervention effectiveness (as defined by included studies) or implementation. Data analyses were descriptive in nature. As recommended in the JBI guide to scoping reviews, only high-level content analysis was conducted to categorize the interventions, which were reported using a previously published framework. RESULTS: We screened 8855 citations, 803 grey literature sources, and 663 full-text articles, resulting in 24 unique RCTs and one companion report that met inclusion criteria. Most studies (91.7%) failed to report how they established sex or gender. Twenty-three of 24 (95.8%) studies reported at least one PROGRESS-Plus variable: typically sex or gender or occupation. Two RCTs (8.3%) identified a non-binary gender identity. None of the RCTs reported on relationships between gender and other characteristics (e.g., disability, age, etc.). We identified 24 gender equity promoting interventions in the workplace that were evaluated and categorized into one or more of the following themes: (i) quantifying gender impacts; (ii) behavioural or systemic changes; (iii) career flexibility; (iv) increased visibility, recognition, and representation; (v) creating opportunities for development, mentorship, and sponsorship; and (vi) financial support. Of these interventions, 20/24 (83.3%) had positive conclusion statements for their primary outcomes (e.g., improved academic productivity, increased self-esteem) across heterogeneous outcomes. CONCLUSIONS: There is a paucity of literature on interventions to promote workplace gender equity. While some interventions elicited positive conclusions across a variety of outcomes, standardized outcome measures considering specific contexts and cultures are required. Few PROGRESS-Plus items were reported. Non-binary gender identities and issues related to intersectionality were not adequately considered. Future research should provide consistent and contemporary definitions of gender and sex. TRIAL REGISTRATION: Open Science Framework https://osf.io/x8yae .

Controlled-release hydromorphone and risk of infection in adults: a systematic review.

BACKGROUND: Preliminary evidence suggests that people who inject drugs (PWID) may be at an increased risk of developing infective endocarditis (IE), hepatitis C virus (HCV) infection, and/or human immunodeficiency virus (HIV) infection from hydromorphone controlled-release formulation. The hypothesized mechanism is related to insolubility of the drug, which promotes reuse, leading to contamination of injecting equipment. However, this relationship has not been confirmed. We aimed to conduct a systematic review including adult PWID exposed to controlled-release hydromorphone and the risk of acquiring IE, HCV, and HIV. METHODS: We searched MEDLINE, EMBASE, and Evidence Based Medicine reviews from inception until September 2021. Following pilot testing, two reviewers conducted all screening of citations and full-text articles, as well as abstracted data, and appraised risk of bias using the Newcastle-Ottawa scale and Effective Practice and Organization of Care tool. Equity issues were examined using the PROGRESS-PLUS framework. Discrepancies were resolved consistently by a third reviewer. Meta-analysis was not feasible due to heterogeneity across the studies. RESULTS: After screening 3,231 citations from electronic databases, 722 citations from unpublished sources/reference scanning, and 626 full-text articles, five studies were included. Five were cohort studies, and one was a case-control study. The risk of bias varied across the studies. Two studies reported on gender, as well as other PROGRESS-PLUS criteria (race, housing, and employment). Three studies focused specifically on the controlled-release formulation of hydromorphone, whereas two studies focused on all formulations of hydromorphone. One retrospective cohort study found an association between controlled-release hydromorphone and IE, whereas a case-control study found no evidence of an association. One retrospective cohort study found an association between the number of hydromorphone controlled-release prescriptions and prevalence of HCV. None of the studies specifically reported on associations with HIV. DISCUSSION: Very few studies have examined the risk of IE, HCV, and HIV infection after exposure to controlled-release hydromorphone. Very low-quality and scant evidence suggests uncertainty around the risks of blood-borne infections, such as HCV and IE to PWID using this medication.

Use of Berlin EXCOR cannulas in both venovenous and venoarterial central extracorporeal membrane oxygenation configurations overcomes the problem of cannula instability while bridging infants and young children to lung transplant.

Objectives: Infants and young children awaiting lung transplantation present challenges that often preclude successful extracorporeal membrane oxygenation support as a bridge to transplantation. Instability of neck cannulas often results in the need for intubation, mechanical ventilation, and muscle relaxation creating a worse transplant candidate. With the use of Berlin Heart EXCOR cannulas (Berlin Heart, Inc) in both venoarterial and venovenous central cannulation configurations, 5 pediatric patients were successfully bridged to lung transplant. Methods: We performed a single-center retrospective case review of central extracorporeal membrane oxygenation cannulation used as a bridge to lung transplantation cases performed at Texas Children's Hospital between 2019 and 2021. Results: Six patients, 2 with pulmonary veno-occlusive disease (15-month-old male and 8-month-old male), 1 with ABCA3 mutation (2-month-old female), 1 with surfactant protein B deficiency (2-month-old female), 1 with pulmonary arterial hypertension in the setting of D-transposition of the great arteries after repair as a neonate (13-year-old male), and 1 with cystic fibrosis and end-stage lung disease, were supported for a median of 56.3 days on extracorporeal membrane oxygenation while awaiting transplantation. All patients were extubated after initiation of extracorporeal membrane oxygenation, participating in rehabilitation until transplant. No complications due to central cannulation and use of the Berlin Heart EXCOR cannulas were observed. One patient with cystic fibrosis developed fungal mediastinitis and osteomyelitis resulting in discontinuation of mechanical support and death. Conclusions: Novel use of Berlin Heart EXCOR cannulas for central cannulation eliminates the problem of cannula instability allowing extubation, rehabilitation, and bridge to lung transplant for infants and young children.

Implemented machine learning tools to inform decision-making for patient care in hospital settings: a scoping review.

OBJECTIVES: To identify ML tools in hospital settings and how they were implemented to inform decision-making for patient care through a scoping review. We investigated the following research questions: What ML interventions have been used to inform decision-making for patient care in hospital settings? What strategies have been used to implement these ML interventions? DESIGN: A scoping review was undertaken. MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) were searched from 2009 until June 2021. Two reviewers screened titles and abstracts, full-text articles, and charted data independently. Conflicts were resolved by another reviewer. Data were summarised descriptively using simple content analysis. SETTING: Hospital setting. PARTICIPANT: Any type of clinician caring for any type of patient. INTERVENTION: Machine learning tools used by clinicians to inform decision-making for patient care, such as AI-based computerised decision support systems or "'model-based'" decision support systems. PRIMARY AND SECONDARY OUTCOME MEASURES: Patient and study characteristics, as well as intervention characteristics including the type of machine learning tool, implementation strategies, target population. Equity issues were examined with PROGRESS-PLUS criteria. RESULTS: After screening 17 386 citations and 3474 full-text articles, 20 unique studies and 1 companion report were included. The included articles totalled 82 656 patients and 915 clinicians. Seven studies reported gender and four studies reported PROGRESS-PLUS criteria (race, health insurance, rural/urban). Common implementation strategies for the tools were clinician reminders that integrated ML predictions (44.4%), facilitated relay of clinical information (17.8%) and staff education (15.6%). Common barriers to successful implementation of ML tools were time (11.1%) and reliability (11.1%), and common facilitators were time/efficiency (13.6%) and perceived usefulness (13.6%). CONCLUSIONS: We found limited evidence related to the implementation of ML tools to assist clinicians with patient healthcare decisions in hospital settings. Future research should examine other approaches to integrating ML into hospital clinician decisions related to patient care, and report on PROGRESS-PLUS items. FUNDING: Canadian Institutes of Health Research (CIHR) Foundation grant awarded to SES and the CIHR Strategy for Patient Oriented-Research Initiative (GSR-154442). SCOPING REVIEW REGISTRATION: https://osf.io/e2mna.

Injustice, quality of life, and psychiatric symptoms in people with migraine.

OBJECTIVE: To describe and examine the relationships between perceived injustice, quality of life (QoL), and psychiatric symptoms through a mixed-methods, cross-sectional observational study design in people with migraine. METHOD: Participants completed a series of online quantitative questionnaires, including the Injustice Experience Questionnaire (IEQ). Then, 10 participants took part in qualitative phenomenological interviews. RESULTS: One hundred twenty-seven participants were included in the sample. Correlations revealed higher IEQ scores were strongly associated with lower QoL (r = -.676, p < .001). Higher scores on the IEQ were related to higher migraine attack frequency (r = .403, p < .001), migraine pain intensity (r = .352, p < .001), no association with reports of nausea/vomiting (r = .110, p = .220), and higher report of allodynia symptoms (r = .281, p < .001). Participants who reported a migraine with aura in the past year reported higher IEQ scores than people with no aura in the past year (t[125] = -2.34, p = .02). Higher IEQ scores were associated with higher anxiety (r = .447, p < .001) and depression symptom scores (r = .495, p < .001). The phenomenological interviews revealed 4 core themes describing perceived injustice and QoL with migraine: coping, loss, illness burden, and misunderstanding. CONCLUSION: Higher levels of perceived injustice showed lower levels of QoL, was associated with higher headache frequency attack severity, and rates of depressive and anxiety symptoms. Participants described their QoL similarly, regardless of reported high or low levels of perceived injustice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Rigidity transitions in zero-temperature polygons.

We study geometrical clues of a rigidity transition due to the emergence of a system-spanning state of self-stress in underconstrained systems of individual polygons and spring networks constructed from such polygons. When a polygon with harmonic bond edges and an area spring constraint is subject to an expansive strain, we observe that convexity of the polygon is a necessary condition for such a self-stress. We prove that the cyclic configuration of the polygon is a sufficient condition for the self-stress. This correspondence of geometry and rigidity is akin to the straightening of a one dimensional chain of springs to rigidify it. We predict the onset of the rigidity transition and estimate the transition strain using purely geometrical methods. These findings help determine the rigidity of an area-preserving polygon just by knowing its geometry. Since two-dimensional spring networks can be considered as a network of polygons, we look for similar geometric features in underconstrained spring networks under isotropic expansive strain. We observe that all polygons attain convexity at the rigidity transition such that the fraction of convex, but not cyclic, polygons predicts the onset of the rigidity transition. Acyclic polygons in the network correlate with larger tensions, forming effective force chains.

The unique role of stigma in migraine-related disability and quality of life.

BACKGROUND: Stigma is increasingly recognized as an important social feature of living with migraine. METHODS: Adults with migraine recruited from neurology offices completed the validated Stigma Scale for Chronic Illnesses 8-item version (SSCI-8); two outcome measures (the Migraine Disability Assessment [MIDAS] and the Migraine-Specific Quality of Life Questionnaire v 2.1 [MSQ]); and measures of allodynia (Allodynia Symptom Checklist [ASC-12]), pain cognition (Pain Catastrophizing Scale [PCS]), and psychiatric symptoms (Patient Reported Measurement Information System Anxiety [PROMIS-A] and Depression [PROMIS-D]). Pearson and Spearman correlations evaluated bivariate relationships, and linear (MSQ) and logistic (MIDAS Severe Disability, scores ≥21) regressions evaluated the unique variance associated with SSCI-8 beyond other study variables. Conditional process analysis evaluated mediation hypotheses between study variables. RESULTS: Participants (n = 121) reported levels of stigma on par with other chronic illnesses (SSCI-8 M = 53.0, standard deviation [SD] = 7.8), with 25/127 (19.6%) reporting clinically significant levels of stigma (SSCI-8 T-score ≥ 60). Higher SSCI-8 scores were associated with higher monthly headache day frequency (r = 0.35), MIDAS (ρ = 0.41), ASC-12 (r = 0.24, p < 0.01), PCS (r = 0.46), both PROMIS-A (r = 0.43) and D (r = 0.42), and lower MSQ subscale scores (Role Restriction r = -0.50; Role Prevention r = -0.48; Emotion Function r = -0.50), all ps <0.001 unless otherwise noted. The SSCI-8 contributed significantly beyond migraine symptoms and other psychological factors for MSQ Emotion Function (5% unique variance) and MIDAS Severe Disability (6% of unique variance). The SSCI-8 mediated relationships between headache frequency and the MSQ subscales and MIDAS Severe Disability. The PCS mediated relationships between the SSCI-8 and MSQ subscales. The PROMIS-D mediated relationships between the SSCI-8 and MSQ Role Restriction and MSQ Role Prevention. CONCLUSIONS: Migraine stigma has medium to large associations with migraine outcomes and psychiatric symptoms and is independently associated with migraine disability and emotion-related quality of life. Migraine stigma is an important contributor to the relationship between headache frequency and migraine outcomes.

Global evidence on falls and subsequent social isolation in older adults: a scoping review.

BACKGROUND: Falls are a leading cause of injury-related hospitalizations among adults aged 65 years and older and may result in social isolation. OBJECTIVE: To summarise evidence on falls and subsequent social isolation and/or loneliness in older adults through a scoping review. ELIGIBILITY CRITERIA: Studies were eligible for inclusion if the population had a mean age of 60 years or older, they examined falls and subsequent social isolation, loneliness, fear of falling or risk factors and were primary studies (eg, experimental, quasi-experimental, observational and qualitative). SOURCES OF EVIDENCE: MEDLINE, CINAHL, Embase, Ageline and grey literature from inception until 11 January 2021. CHARTING METHODS: A screening and charting form was developed and pilot-tested. Subsequently, two reviewers screened citations and full-text articles, and charted the evidence. RESULTS: After screening 4993 citations and 304 full-text articles, 39 studies were included in this review. Participants had a history of falling (range: 11% to 100%). Most studies were conducted in Europe (44%) and North America (33%) and were of the cross-sectional study design (66.7%), in the community (79%). Studies utilised 15 different scales. Six studies examined risk factors for social isolation and activity restriction associated with fear of falling. Six studies reported mental health outcomes related to falls and subsequent social isolation. CONCLUSIONS: Consistency in outcome measurement is recommended, as multiple outcomes were used across the included studies. Further research is warranted in this area, given the ageing population and the importance of falls and social isolation to the health of older adults. SCOPING REVIEW REGISTRATION NUMBER: 10.17605/OSF.IO/2R8HM.

Sleep duration and eating behaviours among adolescents: a scoping review. / Durée du sommeil et comportements alimentaires chez les adolescents : un examen de la portée.

INTRODUCTION: In the past decade, investigations of the relationship between sleep duration and eating behaviours have been emerging; however, a formal synthesis of the literature focussed on adolescent populations has not yet been conducted. We conducted a scoping review of the literature examining the relationship between sleep duration and eating behaviours in adolescents. Gaps in the research and directions for future research were identified based on the findings. METHODS: A systematic search was employed on four research databases: PubMed, PsycInfo, CINAHL and Scopus; relevant grey literature was also reviewed. Studies that reported on the relationship between sleep duration and eating behaviours among high school-aged adolescents were included in the review. Data were extracted, charted and synthesized into a narrative. Consistent with the purpose of a scoping review, the methodological quality of the studies was not appraised. Stakeholders were consulted to validate the findings and provide insight into the interpretation and identification of pressing gaps in the research that remain to be addressed. RESULTS: In total, 61 studies published between 2006 and 2021 met the criteria for review. Existing research focussed heavily on examining sleep duration in relation to intake of food from certain food groups, beverages and processed foods, and relied on a population study design, cross-sectional analyses and self-report measures. CONCLUSION: Future research is needed to understand the link between sleep duration and eating-related cognition, eating contexts and disordered eating behaviours in order to better understand how ensuring sufficient sleep among adolescents can be leveraged to support healthier eating practices and reduce diet-related risks.

Barriers and Motivators to Opioid Treatment Among Suburban Women Who Are Pregnant and Mothers in Caregiver Roles.

Women of childbearing age who misuse opioids are a particularly vulnerable population, and their barriers to treatment are unique because of their caregiver roles. Research on treatment for opioid use generally draws from urban and rural areas. This study fills a gap in research that focuses on barriers and motivators to opioid treatment in suburban areas. The aim of this study was to give voice to suburban pregnant women and mothers caring for children while using opioids. Ethnographic methods were used for recruitment, and 58 in-depth interviews were analyzed using a modified grounded theory approach. Barriers to medication-assisted treatment (MAT) included stigma, staff attitudes, and perceptions the women had about MAT treatment. Barriers associated with all types of treatment included structural factors and access difficulties. Relationships with partners, friends, family, and providers could be barriers as well as motivators, depending on the social context of the women's situation. Our findings suggest increasing treatment-seeking motivators for mothers and pregnant women by identifying lack of resources, more empathetic consideration of social environments, and implementing structural changes to overcome barriers. Findings provide a contemporary understanding of how suburban landscapes affect mothers' treatment-seeking for opioid dependence and suggest the need for more focus on emotional and structural resources rather than strict surveillance of women with opioid dependence who are pregnant or caring for children.

Investigating the mental health implications of urban environments with neuroscientific methods and mobile technologies: A systematic literature review.

Urbanization is an ongoing global process that is influencing and shaping individual mental health and well-being. This paper aims to provide an overview of the current literature containing state-of-the-art neuroscientific and mobile technologies that have been used to investigate the mental health implications of urban environments. Searches for peer-reviewed primary research articles were conducted in PubMed and SCOPUS, returning 33,443 papers; 90 empirical articles published from 1981 to 2021 were included in the final synthesis. Central findings suggest virtual reality and mobile electroencephalography to be the most commonly used methods, and demanding mood, affect, and health phenomena or states to be the most common concepts of study in both physical built settings and natural urban spaces. Recommendations for both future practice and study noting particular opportunities for future methodological contributions are discussed.

Unsupervised structure classes vs. supervised property classes of silicon quantum dots using neural networks.

Machine learning classification is a useful technique to predict structure/property relationships in samples of nanomaterials where distributions of sizes and mixtures of shapes are persistent. The separation of classes, however, can either be supervised based on domain knowledge (human intelligence), or based entirely on unsupervised machine learning (artificial intelligence). This raises the questions as to which approach is more reliable, and how they compare? In this study we combine an ensemble data set of electronic structure simulations of the size, shape and peak wavelength for the optical emission of hydrogen passivated silicon quantum dots with artificial neural networks to explore the utility of different types of classes. By comparing the domain-driven and data-driven approaches we find there is a disconnect between what we see (optical emission) and assume (that a particular color band represents a special class), and what the data supports. Contrary to expectation, controlling a limited set of structural characteristics is not specific enough to classify a quantum dot based on color, even though it is experimentally intuitive.

The pure and representative types of disordered platinum nanoparticles from machine learning.

The development of interpretable structure/property relationships is a cornerstone of nanoscience, but can be challenging when the structural diversity and complexity exceeds our ability to characterise it. This is often the case for imperfect, disordered and amorphous nanoparticles, where even the nomenclature can be unspecific. Disordered platinum nanoparticles have exhibited superior performance for some reactions, which makes a systematic way of describing them highly desirable. In this study we have used a diverse set of disorder platinum nanoparticles and machine learning to identify the pure and representative structures based on their similarity in 121 dimensions. We identify two prototypes that are representative of separable classes, and seven archetypes that are the pure structures on the convex hull with which all other possibilities can be described. Together these nine nanoparticles can explain all of the variance in the set, and can be described as either single crystal, twinned, spherical or branched; with or without roughened surfaces. This forms a robust sub-set of platinum nanoparticle upon which to base further work, and provides a theoretical basis for discussing structure/property relationships of platinum nanoparticles that are not geometrically ideal.

Machine learning reveals multiple classes of diamond nanoparticles.

Generating samples of nanoparticles with specific properties that allow for structural diversity, rather than requiring structural precision, is a more sustainable prospect for industry, where samples need to be both targeted to specific applications and cost effective. This can be better enabled by defining classes of nanoparticles and characterising the properties of the class as a whole. In this study, we use machine learning to predict the different classes of diamond nanoparticles based entirely on the structural features and explore the populations of these classes in terms of the size, shape, speciation and charge transfer properties. We identify 9 different types of diamond nanoparticles based on their similarity in 17 dimensions and, contrary to conventional wisdom, find that the fraction of sp2 or sp3 hybridized atoms are not strong determinants, and that the classes are only weakly related to size. Each class has been describe in such way as to enable rapid assignment using microanalysis techniques.

Relationship Between Anxiety and Cognition in Multiple Sclerosis: Implications for Treatment.

BACKGROUND: Anxiety, which is very prevalent in multiple sclerosis (MS) but understudied, has been shown to negatively affect cognition in many different populations. Slowed information processing speed underlies most cognitive impairments in MS, including verbal learning. The aim of this study was to look at how anxiety influences cognition-specifically processing speed and verbal learning-in MS. METHODS: Eligibility criteria were adults (≥18 years) who had a diagnosis of clinically definite MS and had participated in neuropsychological research projects. A retrospective medical record review was conducted on the neuropsychological testing data. Two hierarchical multiple regressions were conducted to determine the unique contributions of processing speed and anxiety on verbal learning in MS, after adjusting for demographic and disability variables. Two separate mediation analyses were conducted to determine the relationship between processing speed, verbal learning, and anxiety. RESULTS: Participants (N = 141) ranged in age from 18-91 years. Based on the multiple regression analyses, processing speed (ß = 0.55, ΔR 2 = 0.27, P < .001) and anxiety (ß = -0.34, ΔR 2 = 0.11, P < .001) were uniquely significant predictors of verbal learning. Based on the mediation analyses, there was a significant indirect effect of anxiety on verbal learning through processing speed (ab = -0.31, 95% CI = -0.60 to -0.09). There was also a significant indirect effect of processing speed on verbal learning through anxiety (ab = -0.05, 95% CI = 0.01 to 0.12). CONCLUSIONS: Results suggest a bidirectional relationship of anxiety and processing speed on verbal learning in MS. Anxiety has a significant effect on cognition and should not be overlooked. Interventions targeting anxiety may improve cognition in MS.

High Tensile Strength of Engineered ß-Solenoid Fibrils via Sonication and Pulling.

We present estimates of ultimate tensile strength (UTS) for two engineered ß-solenoid protein mutant fibril structures (spruce budworm and Rhagium inquisitor antifreeze proteins) derived from sonication-based measurements and from force pulling molecular dynamics simulations, both in water. Sonication experiments generate limiting scissioned fibrils with a well-defined length-to-width correlation for the mutant spruce budworm protein and the resultant UTS estimate is 0.66 ± 0.08 GPa. For fibrils formed from engineered R. inquisitor antifreeze protein, depending upon geometry, we estimate UTSs of 3.5 ± 3.2-5.5 ± 5.1 GPa for proteins with interfacial disulfide bonds, and 1.6 ± 1.5-2.5 ± 2.3 GPa for the reduced form. The large error bars for the R. inquisitor structures are intrinsic to the broad distribution of limiting scission lengths. Simulations provide pulling velocity-dependent UTSs increasing from 0.2 to 1 GPa in the available speed range, and 1.5 GPa extrapolated to the speeds expected in the sonication experiments. Simulations yield low-velocity values for the Young's modulus of 6.0 GPa. Without protein optimization, these mechanical parameters are similar to those of spider silk and Kevlar, but in contrast to spider silk, these proteins have a precisely known sequence-structure relationship.

Molecular dynamics-based strength estimates of beta solenoid proteins.

The use of beta solenoid proteins as functionalizable, nanoscale, self-assembling molecular building blocks may have many applications, including templating the growth of wires or higher-dimensional structures. By understanding their mechanical strengths, we can efficiently design the proteins for specific functions. We present a study of the mechanical properties of seven beta solenoid proteins using GROMACS molecular dynamics software to produce force/torque-displacement data, implement umbrella sampling of bending/twisting trajectories, produce Potentials of Mean Force (PMFs), extract effective spring constants, and calculate rigidities for two bending and two twisting directions for each protein. We examine the differences between computing the strength values from force/torque-displacement data alone and PMF data, and show how higher precision estimates can be obtained from the former. In addition to the analysis of the methods, we report estimates for the bend/twist persistence lengths for each protein, which range from 0.5-3.4 µm. We note that beta solenoid proteins with internal disulfide bridges do not enjoy enhanced bending or twisting strength, and that the strongest correlate with bend/twist rigidity is the number of hydrogen bonds per turn. In addition, we compute estimates of the Young's modulus (Y) for each protein, which range from Y = 3.5 to 7.2 GPa.