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Introduction: Blood-brain barrier (BBB) integrity is fundamental to brain homeostasis, enabling control of substance exchange and safeguarding neurons against harmful toxins, pathogens, and immune cells that lead to dysregulation and inflammation involved in ageing and neurodegenerative diseases (NDD). The cyclized peptide NX210c is a thrombospondin type 1 repeat analogue derived from subcommissural organ-spondin. It exerts beneficial effects in animal models of NDD owing to its effects on neurons and endothelial cells. NX210c demonstrated a good safety profile in a single ascending dose phase 1a clinical study. The present multiple ascending dose phase 1b study was performed to evaluate the tolerability and pharmacological effects of repeated doses of NX210c in healthy elderly (age: > 55 years) volunteers., Methods: This was a randomized, placebo-controlled, double-blind study (EudraCT No. 2022-002868-76), investigating safety/tolerability, pharmacokinetics, and pharmacodynamics (including blood and cerebrospinal fluid biomarkers). Participants received 5 or 10 mg/kg NX210c or placebo (10-min infusion) thrice weekly for 4 weeks in an ascending dose fashion. Follow-up was conducted 2 weeks after last dosing., Results: The investigation included 29 participants. No serious adverse events were recorded and all adverse events were mild. Dedicated central nervous system testing did not reveal neurotoxicity. Biomarker evaluation showed a statistically significant reduction in blood claudin-5 and a trend toward reduction of blood homocysteine. In silico data modelling revealed salient pharmacokinetic-pharmacodynamic relationships, including reduction of claudin-5, neurofilament light chain, and SPARC-like protein 1 release, and degradation of homocysteine., Conclusion: Multiple doses of NX210c exhibited a good safety profile, showed non-cumulative pharmacokinetics, and exerted pharmacodynamic effects on biomarkers linked to BBB integrity. The effects of NX210c on claudin-5 and biomarkers influencing BBB integrity-and the overarching brain protection it offers-provide a novel therapeutic strategy targeting an underlying driver of neurodegenerative conditions for which disease-modifying treatments are limited or not available., Competing Interests: Declarations. Conflict of Interest: Daniël Dumas and Philip Kremer are employed by CHDR. Juliette Le Douce, Sébastien Marie, Sighild Lemarchant, and Annette Janus are employed by Axoltis Pharma. Yann Godfrin is the CEO and a shareholder of Axoltis Pharma. Giuseppe Pasculli and Pauline Bambury are employed by InSilicoTrials. Ethical Approval: This clinical study was conducted in full compliance with the protocol, principles of the Declaration of Helsinki, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Good Clinical Practice guidelines, and the laws and regulations of France and the Netherlands., (© 2024. The Author(s).)

Little is known about the epidemiology of leptospirosis in the Dominican Republic, the second most populous country in the Caribbean. We report on findings from a multi-stage household survey across two regions in the country that reveals a previously under-estimated burden of human Leptospira infection. Our findings, based on the reference-standard microscopic agglutination test, indicate a complex picture of serogroup diversity, spatial heterogeneity in infection and risk, and a marked discrepancy between reported cases and serologically estimated infections. Given an overall seroprevalence of 11.3% (95% CI: 10.8-13.0%) and a lower estimated force of infection (0.30% per year [0.27%-0.35%]) the number of infections may exceed national reported case data by 145-fold or more. Icterohaemorrhagiae, associated with severe Weil's disease, was the most commonly identified serogroup with a serogroup-specific prevalence of 4.4%. Consistent with other settings, risk factors including age, male sex, and rat exposure were associated with higher seroprevalence. Our study highlights the need for targeted public health interventions informed by serogroup-specific dynamics, detailed spatial analyses, knowledge of local animal reservoirs, and strengthened laboratory surveillance to effectively control this pathogen., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: EJN is the PI on a US CDC funded U01 award that funded the study, and CLL, AK, DD, MdSA, ACR, HM, SG, MCE, WD, NI, GA, BH, KD, and MB have received salaries, consultancy fees, or travel paid through this award. EZG and BL are employees of the US CDC. BH, CT, LC, FP, and RSR are employees of the Ministry of Ministry of Health and Social Assistance, Dominican Republic, that was subcontracted with funds from the US CDC award. AK is supported by the Wellcome Trust, UK. CLL is supported by the Australian National Health and Medical Research Council. We declare no other competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Obstructive sleep apnea (OSA) is a frequent pathology with clinical implications. Its comorbidity with the complaint of insomnia is common, and has been increasingly studied in recent years, due to the multiple negative synergies highlighted by these two conditions, notably on all-cause excess mortality, cardiovascular risk, quality of life and sleep, as well as mental health. This comorbidity between insomnia and sleep apnea has recently been referred to as COMISA («co-morbid insomnia and sleep apnea»). In this article, we explore the relationship between OSA and insomnia, as well as its consequences and currently available treatments, through an analysis of the existing literature., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Individual immune responses to SARS-CoV-2 are well-studied, while the combined effect of these responses on population-level immune dynamics remains poorly understood. Given the key role of population immunity on pathogen transmission, delineation of the factors that drive population immune evolution has critical public health implications., Methods: We enrolled individuals 5 years and older selected using a multistage cluster survey approach in the Northwest and Southeast of the Dominican Republic. Paired blood samples were collected mid-pandemic (Aug 2021) and late pandemic (Nov 2022). We measured serum pan-immunoglobulin antibodies against the SARS-CoV-2 spike protein. Generalized Additive Models (GAMs) and random forest models were used to analyze the relationship between changes in antibody levels and various predictor variables. Principal component analysis and partial dependence plots further explored the relationships between predictors and antibody changes., Findings: We found a transformation in the distribution of antibody levels from an irregular to a normalized single peak Gaussian distribution that was driven by titre-dependent boosting. This led to the convergence of antibody levels around a common immune setpoint, irrespective of baseline titres and vaccination profile., Interpretation: Our results suggest that titre-dependent kinetics driven by widespread transmission direct the evolution of population immunity in a consistent manner. These findings have implications for targeted vaccination strategies and improved modeling of future transmission, providing a preliminary blueprint for understanding population immune dynamics that could guide public health and vaccine policy for SARS-CoV-2 and potentially other pathogens., Funding: The study was primarily funded by the Centers for Disease Control and Prevention grant U01GH002238 (EN). Salary support was provided by Wellcome Trust grant 206250/Z/17/Z (AK) and the Australian National Health and Medical Research Council Investigator grant APP1158469 (CLL)., Competing Interests: Declaration of interests EJN is the PI on a US Centers for Disease Control and Prevention (CDC) funded U01 award that funded the study. AK and CLL are co-investigators on the same award. DD, MdSA, SG, MCE, WD, GA, MB, and KWR have received salary support, consultancy fees, or travel paid through this award. BL is an employee of the US CDC. CTP, LC, IMS and RSR are employees of the Ministry of Ministry of Health and Social Assistance, Dominican Republic, that was subcontracted with funds from the US CDC award. AK is supported by the Wellcome Trust, UK. CLL is supported by the Australian National Health and Medical Research Council. CDC staff supported the design and manuscript editing. We declare no other competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Medulloblastoma (MB) is the most prevalent paediatric brain tumour. Despite improvements in patient survival with current treatment strategies, the quality of life of these patients remains poor owing to the sequelae and relapse risk. An alternative, or, in addition to the current standard treatment, could be considered immunotherapy, such as Natural Killer cells (NK). NK cells are cytotoxic innate lymphoid cells that play a major role in cancer immunosurveillance. To date, the mechanism of cytotoxicity of NK cells, especially regarding the steps of adhesion, conjugation, cytotoxic granule polarisation in the cell contact area, perforin and granzyme release in two and three dimensions, and therapeutic efficacy in vivo have not been precisely described., Materials and Methods: Each step of NK cytotoxicity against the three MB cell lines was explored using confocal microscopy for conjugation, Elispot for degranulation, flow cytometry, and luminescence assays for target cell necrosis and lysis and mediators released by cytokine array, and then confirmed in a 3D spheroid model. Medulloblastoma-xenografted mice were treated with NK cells. Their persistence was evaluated by flow cytometry, and their efficacy in tumour growth and survival was determined. In addition, their effects on the tumour transcriptome were evaluated., Results: NK cells showed variable affinities for conjugation with MB target cells depending on their subgroup and cytokine activation. Chemokines secreted during NK and MB cell co-culture are mainly associated with angiogenesis and immune cell recruitment. NK cell cytotoxicity induces MB cell death in both 2D and 3D co-culture models. NK cells initiated an inflammatory response in a human MB murine model by modulating the MB cell transcriptome., Conclusion: Our study confirmed that NK cells possess both in vitro and in vivo cytotoxic activity against MB cells and are of interest for the development of immunotherapy., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Gauthier et al.)

Objective: This study investigates the role of trust in shaping COVID-19 vaccine acceptance in the Dominican Republic (DR) during the COVID-19 pandemic., Design: Cross-sectional household survey., Setting: Randomly selected households across 134 clusters in the DR, from 30 June 2021 to 12 October 2021., Participants: 5999 participants ≥16 years of age were enrolled., Outcome Measures: COVID-19 vaccine hesitancy (CVH) data were collected from participants ≥16 years of age and analysed as both an ordinal and binary variable., Results: Overall, CVH was low (5.2% (95% CI 4.6% to 5.8%)), but more common among younger individuals, women and individuals of Mestizo ethnicity. Higher trust in local government, national government, scientists and local doctors (considered official sources) was associated with lower odds of CVH (OR 0.89 (95% CI 0.72 to 0.88), 0.89 (95% CI 0.81 to 0.98), 0.87 (95% CI 0.80 to 0.94) and 0.70 (95% CI 0.62 to 0.80), respectively). Higher trust in religious leaders, social media and traditional media (considered unofficial sources) was associated with higher odds of CVH, with respective ORs of 1.32 (95% CI 1.18 to 1.47), 1.30 (95% CI 1.19 to 1.41) and 1.08 (95% CI 0.97 to 1.22)., Conclusion: We report findings on CVH from a national household survey in the DR and identify overall low rates of CVH but marked heterogeneity by age, gender and ethnicity. Trust in unofficial versus official sources of information is associated with increased CVH. These findings highlight and quantify the importance of trust as a key parameter when considering public health communication strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Proper hand hygiene (HH), which includes sanitizing with alcohol-based hand rub (ABHR) (or handwashing with soap and water if ABHR is unavailable), is key for preventing healthcare-associated infections (HCAI), including COVID-19. Understanding drivers of HH is key to improving adherence., Aim: This study aims to explore drivers and barriers to HH practice at two hospitals in the Dominican Republic in the context of the COVID-19 pandemic to inform development of HH behaviour change interventions., Methods: We conducted in-depth interviews with 20 hospital staff during September 2021. We used the COM-B (capability, opportunity, motivation, behaviour) model to explore HH experiences and preferences. Interviews were recorded, transcribed, coded, and analysed using a thematic approach., Results: A total of 11 parent codes and 27 sub-codes were identified, and 1145 coded segments were analysed. Use of handwashing with soap and water and/or sanitizing with ABHR was reported by all participants; handwashing was generally preferred. Participants expressed knowledge of proper HH methods (capability), but inconsistent supplies and lack of time presented HH challenges (opportunity). Interviewees described practicing HH to protect themselves and their families from COVID-19 and other infections (reflective motivation) or out of habit (automatic motivation)., Discussion: By understanding and addressing underlying factors affecting HH, hospitals can decrease the risk of HCAIs. Our findings suggest that interventions implemented to improve HH in these hospitals should target motivation and opportunity. These findings informed a multimodal intervention to increase ABHR access and implement message-tested communications campaigns; end-point assessments will provide insights into the intervention's impact.

There is high-level interest in diversifying workforces, which has led organizations-including the U.S. Armed Forces-to reevaluate recruiting and selection practices. The U.S. Coast Guard (USCG) has encountered particular difficulties in diversifying its workforce, and it relies mainly on the Armed Services Vocational Aptitude Battery (ASVAB) for assigning active-duty recruits to one of 19 specialized training schools. When recruits' scores fall below ASVAB entrance standards, the USCG sometimes offers admission waivers. Alternatively, recruits can retest until their ASVAB scores meet the entrance standard. Retesting has shown mixed results in the personnel selection literature, so our main interest is to determine whether retesting or waivers best support USCG recruits' training school outcomes, especially for recruits identifying as an underrepresented minority (URM). We use data from 16,624 USCG recruits entering between 2013 and 2021 and fit augmented inverse propensity weighted models to assess differences in training outcomes by pathway to admission while accounting for self-selection into pathways. Our analyses found (a) no difference in training outcomes between recruits who qualified from their initial scores and recruits who retested, (b) recruits who received waivers were less likely to complete training school on time and spent more time in remedial training when they failed training school compared to those who retested, and (c) improvement in training outcomes for retesting over waivers was larger for recruits identifying as an URM. Results suggest that retesting may be an effective strategy for workforce diversification and for improving outcomes among recruits identifying as an URM. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Incidence of COVID-19 has been associated with sociodemographic factors. We investigated variations in SARS-CoV-2 seroprevalence at sub-national levels in the Dominican Republic and assessed potential factors influencing variation in regional-level seroprevalence. Data were collected in a three-stage cross-sectional national serosurvey from June to October 2021. Seroprevalence of antibodies against the SARS-CoV-2 spike protein (anti-S) was estimated and adjusted for selection probability, age, and sex. Multilevel logistic regression was used to estimate the effect of covariates on seropositivity for anti-S and correlates of 80% protection (PT 80 ) against symptomatic infection for the ancestral and Delta strains. A total of 6683 participants from 134 clusters in all 10 regions were enrolled. Anti-S, PT80 for the ancestral and Delta strains odds ratio varied across regions, Enriquillo presented significant higher odds for all outcomes compared with Yuma. Compared to being unvaccinated, receiving ≥2 doses of COVID-19 vaccine was associated with a significantly higher odds of anti-S positivity (OR 85.94, [10.95-674.33]) and PT 80 for the ancestral (OR 4.78, [2.15-10.62]) and Delta strains (OR 3.08, [1.57-9.65]) nationally and also for each region. Our results can help inform regional-level public health response, such as strategies to increase vaccination coverage in areas with low population immunity against currently circulating strains.

To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission.

Individual differences in the timing of developmental processes are often of interest in longitudinal studies, yet common statistical approaches to modeling change cannot directly estimate the timing of when change occurs. The time-to-criterion framework was recently developed to incorporate the timing of a prespecified criterion value; however, this framework has difficulty accommodating contexts where the criterion value differs across people or when the criterion value is not known a priori, such as when the interest is in individual differences in when change starts or stops. This article combines aspects of reparameterized quadratic models and multiphase models to provide information on the timing of change. We first consider the more common situation of modeling decelerating change to an offset point, defined as the point in time at which change ceases. For increasing trajectories, the offset occurs when the criterion attains its maximum ("inverted J-shaped" trajectories). For decreasing trajectories, offset instead occurs at the minimum. Our model allows for individual differences in both the timing of offset and ultimate level of the outcome. The same model, reparameterized slightly, captures accelerating change from a point of onset ("J-shaped" trajectories). We then extend the framework to accommodate "S-shaped" curves where both the onset and offset of change are within the observation window. We provide demonstrations that span neuroscience, educational psychology, developmental psychology, and cognitive science, illustrating the applicability of the modeling framework to a variety of research questions about individual differences in the timing of change. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

In creativity research, ideational flexibility, the ability to generate ideas by shifting between concepts, has long been the focus of investigation. However, psychometric work to develop measurement procedures for flexibility has generally lagged behind other creativity-relevant constructs such as fluency and originality. Here, we build from extant research to theoretically posit, and then empirically validate, a text-mining based method for measuring flexibility in verbal divergent thinking (DT) responses. The empirical validation of this method is accomplished in two studies. In the first study, we use the verbal form of the Torrance Test of Creative Thinking (TTCT) to demonstrate that our novel flexibility scoring method strongly and positively correlates with traditionally used TTCT flexibility scores. In the second study, we conduct a confirmatory factor analysis using the Alternate Uses Task to show reliability and construct validity of our text-mining based flexibility scoring. In addition, we also examine the relationship between personality facets and flexibility of ideas to provide criterion validity of our scoring methodology. Given the psychometric evidence presented here and the practicality of automated scores, we recommend adopting this new method which provides a less labor-intensive and less costly objective measurement of flexibility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Grajzel, Acar, Dumas, Organisciak and Berthiaume.)

Background: Population-level SARS-CoV-2 immunological protection is poorly understood but can guide vaccination and non-pharmaceutical intervention priorities. Our objective was to characterise cumulative infections and immunological protection in the Dominican Republic., Methods: Household members ≥5 years were enrolled in a three-stage national household cluster serosurvey in the Dominican Republic. We measured pan-immunoglobulin antibodies against the SARS-CoV-2 spike (anti-S) and nucleocapsid glycoproteins, and pseudovirus neutralising activity against the ancestral and B.1.617.2 (Delta) strains. Seroprevalence and cumulative prior infections were weighted and adjusted for assay performance and seroreversion. Binary classification machine learning methods and pseudovirus neutralising correlates of protection were used to estimate 50% and 80% protection against symptomatic infection., Findings: Between 30 Jun and 12 Oct 2021 we enrolled 6683 individuals from 3832 households. We estimate that 85.0% (CI 82.1-88.0) of the ≥5 years population had been immunologically exposed and 77.5% (CI 71.3-83) had been previously infected. Protective immunity sufficient to provide at least 50% protection against symptomatic SARS-CoV-2 infection was estimated in 78.1% (CI 74.3-82) and 66.3% (CI 62.8-70) of the population for the ancestral and Delta strains respectively. Younger (5-14 years, OR 0.47 [CI 0.36-0.61]) and older (≥75-years, 0.40 [CI 0.28-0.56]) age, working outdoors (0.53 [0.39-0.73]), smoking (0.66 [0.52-0.84]), urban setting (1.30 [1.14-1.49]), and three vs no vaccine doses (18.41 [10.69-35.04]) were associated with 50% protection against the ancestral strain., Interpretation: Cumulative infections substantially exceeded prior estimates and overall immunological exposure was high. After controlling for confounders, markedly lower immunological protection was observed to the ancestral and Delta strains across certain subgroups, findings that can guide public health interventions and may be generalisable to other settings and viral strains., Funding: This study was funded by the US CDC., Competing Interests: E.J.N. is the PI on a US CDC funded U01 award that funded the study, and C.L.L., A.K., D.D., M.d.S.A., A.C.R., H.M., S.G., M.C.E., W.D., N.I., G.A., B.H., K.D., M.B., E.F., and L.I. have received salaries, consultancy fees, or travel paid through this award. E.Z.G., B.L., and A.E.-B. are employees of the US CDC. B.H., C.T., L.C., F.P., and R.S.-R. are employees of the Ministry of Ministry of Health and Social Assistance, Dominican Republic, that was subcontracted with funds from the US CDC award. A.K. and E.F. are supported by the Welcome Trust, UK. D.B. had a patent for COVID-19 vaccine licensed to Janssen. We declare no other competing interests., (© 2022 The Author(s).)

The equal odds baseline model of creative scientific productivity proposes that the number of high-quality works depends linearly on the number of total works. In addition, the equal odds baseline implies that the percentage of high-quality works and total number of works are uncorrelated. The tilted funnel hypothesis proposes that the linear regression implied by the equal odds baseline is heteroscedastic with residual variance in the quality of work increasing as a function of quantity. The aim of the current research is to leverage Bayesian statistical modeling of the equal odds baseline. Previous work has examined the tilted funnel by means of frequentist quantile regression, but Bayesian quantile regression based on the asymmetric Laplace model allows for only one conditional quantile at a time. Hence, we propose additional Bayesian methods, including Poisson modeling to study conditional variance as a function of quantity. We use a classical small sample of eminent neurosurgeons, as well as the brms Bayesian R package, to accomplish this work. In addition, we provide open code and data to allow interested researchers to extend our work and utilize the proposed modeling alternatives.

Administration of plasma therapy may contribute to viral control and survival of COVID-19 patients receiving B-cell-depleting agents that impair humoral immunity. However, little is known on the impact of anti-CD20 pre-exposition on the kinetics of SARS-CoV-2-specific antibodies. Here, we evaluated the relationship between anti-spike immunoglobulin G (IgG) kinetics and the clinical status or intra-host viral evolution after plasma therapy in 36 eligible hospitalized COVID-19 patients, pre-exposed or not to B-cell-depleting treatments. The majority of anti-CD20 pre-exposed patients (14/17) showed progressive declines of anti-spike IgG titres following plasma therapy, contrasting with the 4/19 patients who had not received B-cell-depleting agents (p = 0.0006). Patients with antibody decay also depicted prolonged clinical symptoms according to the World Health Organization (WHO) severity classification (p = 0.0267) and SARS-CoV-2 viral loads (p = 0.0032) before complete virus clearance. Moreover, they had higher mutation rates than patients able to mount an endogenous humoral response (p = 0.015), including three patients with one to four spike mutations, potentially associated with immune escape. No relevant differences were observed between patients treated with plasma from convalescent and/or mRNA-vaccinated donors. Our study emphasizes the need for an individualized clinical care and follow-up in the management of COVID-19 patients with B-cell lymphopenia., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Continuity of key water, sanitation, and hygiene (WASH) infrastructure and WASH practices-for example, hand hygiene-are among several critical community preventive and mitigation measures to reduce transmission of infectious diseases, including COVID-19 and other respiratory diseases. WASH guidance for COVID-19 prevention may combine existing WASH standards and new COVID-19 guidance. Many existing WASH tools can also be modified for targeted WASH assessments during the COVID-19 pandemic. We partnered with local organizations to develop and deploy tools to assess WASH conditions and practices and subsequently implement, monitor, and evaluate WASH interventions to mitigate COVID-19 in low- and middle-income countries in Latin America and the Caribbean and Africa, focusing on healthcare, community institution, and household settings and hand hygiene specifically. Employing mixed-methods assessments, we observed gaps in access to hand hygiene materials specifically despite most of those settings having access to improved, often onsite, water supplies. Across countries, adherence to hand hygiene among healthcare providers was about twice as high after patient contact compared to before patient contact. Poor or non-existent management of handwashing stations and alcohol-based hand rub (ABHR) was common, especially in community institutions. Markets and points of entry (internal or external border crossings) represent congregation spaces, critical for COVID-19 mitigation, where globally-recognized WASH standards are needed. Development, evaluation, deployment, and refinement of new and existing standards can help ensure WASH aspects of community mitigation efforts that remain accessible and functional to enable inclusive preventive behaviors., Competing Interests: Competing Interests: The authors have declared that no competing interests exist.

The extracellular matrix (ECM) offers the opportunity to create a biomaterial consisting of a microenvironment with interesting biological and biophysical properties for improving and regulating cell functions. Animal-derived ECM are the most widely used as an alternative to human tissues that are of very limited availability. However, incomplete decellularization of these tissues presents a high risk of immune rejection and disease transmission. In this study, we present an innovative method to extract human ECM derived from the Wharton's jelly (WJ-ECMaa) of umbilical cords as a novel biomaterial to be used in tissue engineering. WJ-ECMaa was very efficiently decellularized, suggesting its possible use in allogeneic conditions. Characterization of its content allowed the identification of type I collagen as its main component. Various other matrix proteins, playing an important role in cell adhesion and proliferation, were also detected. WJ-ECMaa applied as a surface coating was analyzed by fluorescent labeling and atomic force microscopy. The results revealed a particular arrangement of collagen fibers not previously described in the literature. This biomaterial also presented better cytocompatibility compared to the conventional collagen coating. Moreover, it showed adequate hemocompatibility, allowing its use as a surface with direct contact with blood. Application of WJ-ECMaa as a coating of the luminal surface of umbilical arteries for a use in vascular tissue engineering, has improved significantly the cellularization of this surface by allowing a full and homogeneous cell coverage. Taking these results together, our novel extraction method of human ECM offers a very promising biomaterial with many potential applications in tissue engineering such as the one presented direct in vascular tissue engineering. Further characterization of the composition and functionality will help explore the ways it can be used in tissue engineering applications, especially as a scaffold or a surface coating., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fayon, Helle, Francius, Vincourt, Regnault, Dumas, Menu and El Omar.)

Background: When students generate ideas, important inter-individual variance exists both in the quantity and the quality of ideas they are able to produce (e.g., perfectionists who have few highly creative ideas or mass producers who produce a lot of uncreative ideas). In educational psychology research on creativity, the relation between the quantity and quality of ideas has not been well understood, limiting progress in this area., Aims: We conceptualized Ideational Fluency as a phenomenon that requires participants to 'survive' to produce more ideas, and where dropping out of the ideational process was analogous to 'dying'. Using this novel paradigm, we aimed to test the relations among Fluency (as a dependent variable); and creative Expertise, Originality and self-reported Personality attributes (as independent variables)., Sample and Method: Participants were drawn from three groups: those with demonstrated expertise in stage or screen acting (n = 104); undergraduates being trained in the same domain (n = 100), and adults with no acting training or experience (n = 92). Participants responded to the Alternate Uses Task; Non-parametric and semi-parametric survival models were fit to their Ideational Fluency; and average and maximum Originality scores, as well as self-reported Personality attributes, were used as covariates., Results: Across all participants, the Ideational Fluency survival function showed an S-shape, but the Expertise grouping interacted with that pattern. The survival rate of professional actors decreased more rapidly during the first few ideas, but after the 5th idea, professional actors displayed a clear advantage in survival rate. Participants who were less original on average but who showed a high maximum Originality, as well as those participants who reported more Assertiveness and less Industriousness, also survived further into the Ideational process., Conclusions: Contrary to our hypothesis, professional actors' advantage in Fluency did not manifest in the survival model until after the 5th idea generated. A quantity-quality trade-off was observed with average Originality being associated with shorter survival, but that trade-off was not observed with maximum Originality, which was associated with longer survival., (© 2021 The British Psychological Society.)

The year 2021 has seen many breakthroughs in general internal medicine, despite the ongoing COVID-19 pandemic, with multiple implications in our daily clinical practice. From shorter antibiotic treatment duration in community-acquired pneumonia, to new indications for colchicine treatment, without forgetting better targets of hemoglobin for transfusion, questioning of the interest of high dose vitamin D substitution when preventing falls in older patients and finally disappointing hopes for new indications of albumin substitution in cirrhosis, the literature is full of new evidence. Each year, the chief residents of the internal medicine ward in Lausanne university hospital (CHUV) in Switzerland meet up to share their readings: here is a selection of ten articles, chosen, summarized, and commented for you., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

The practice of routine outcome monitoring (ROM) has grown in popularity and become a fixture in feedback-supported clinical practice and research. However, if the interpretation of an ROM measure changes over time, treatment outcome scores may be inaccurate and produce erroneous or misguided interpretations of client progress and therapist efficacy. The current study examined whether factorial invariance held when using the Behavioral Health Measure (BHM-20) longitudinally in a clinical sample (n = 12,467). Using multidimensional item response theory-based models for the investigation of the BHM-20 factor structure, at a single time point and then longitudinally. Based on the original factor structure of the BHM-20 a unidimensional model, a three-factor orthogonal model, and a three-factor correlated model were fit to the data, indicating poor model fit with the proposed three-factor or unidimensional models. Next, using exploratory factor analysis and subsequent multidimensional item response theory procedures, a new 4-factor (General Distress, Life Functioning, Anxiety, and Alcohol/Drug Use) model was proposed with improved model-fit statistics. Finally, when testing the longitudinal invariance of the BHM-17 over 10 sessions of treatment, it was found to be fully consistent. The current study proposes the use of a 17-item, 4-factor model for a new understanding of the BHM-17. Implications for use in ROM and limitations are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Due to their very poor prognosis and a fatal outcome, secondary brain tumors are one of the biggest challenges in oncology today. From the point of view of the early diagnosis of these brain micro- and macro-tumors, the sensitivity and specificity of the diagnostic tools constitute an obstacle. Molecular imaging, such as Positron Emission Tomography (PET), is a promising technique but remains limited in the search for cerebral localizations, given the commercially available radiotracers. Indeed, the [ 18 F]FDG PET remains constrained by the physiological fixation of the cerebral cortex, which hinders the visualization of cerebral metastases. Tumor angiogenesis is recognized as a crucial phenomenon in the progression of malignant tumors and is correlated with overexpression of the neuropilin-1 (NRP-1) receptor. Here, we describe the synthesis and the photophysical properties of the new gallium-68 radiolabeled peptide to target NRP-1. The KDKPPR peptide was coupled with gallium-68 anchored into a bifunctional NODAGA chelating agent, as well as Cy5 for fluorescence detection. The Cy5 absorbance spectra did not change, whereas the molar extinction coefficient (ε) decreased drastically. An enhancement of the fluorescence quantum yield (φ F ) could be observed due to the better water solubility of Cy5. [ 68 Ga]Ga-NODAGA-K(Cy5)DKPPR was radiosynthesized efficiently, presented hydrophilic properties (log D = -1.86), and had high in vitro stability (>120 min). The molecular affinity and the cytotoxicity of this new chelated radiotracer were evaluated in vitro on endothelial cells (HUVEC) and MDA-MB-231 cancer cells (hormone-independent and triple-negative line) and in vivo on a brain model of metastasis in a nude rat using the MDA-MB-231 cell line. No in vitro toxicity has been observed. The in vivo preliminary experiments showed promising results, with a high contrast between the healthy brain and metastatic foci for [ 68 Ga]Ga-NODAGA-K(Cy5)DKPPR.

Albumin has multiple physiological functions such as maintenance of oncotic pressure, binding of plasmatic molecule, immunomodulation and endothelial stabilization. Considering potential negative effects of hypoalbuminemia, the question of albumin substitution arises. For cirrhotic patients, indications for substitution are well established with a scientific consensus for spontaneous bacterial peritonitis, paracentesis-induced circulatory dysfunction and hepatorenal syndrome. However, in the case of hepatic encephalopathy or of hypoalbuminemia in non-cirrhotic patients, the scientific consensus is absent, and the results of clinical studies differ. In this article, we present the different indications of albumin substitution by examining the most recent studies., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Lactic acid bacteria (LAB) have been studied for several decades to understand and determine their mechanism and interaction within the matrix into which they are introduced. This study aimed to determine the spatial distribution of Lacticaseibacillus rhamnosus GG (LGG) in a dairy matrix and to decipher its behaviour towards milk components, especially fat globules. Two strains of this widely studied bacterium with expected probiotic effects were used: LGG WT with pili on the cell surface and its pili-depleted mutant-LGG Δ spaCBA -in order to determine the involvement of these filamentous proteins. In this work, it was shown that LGG Δ spaCBA was able to limit creaming with a greater impact than the wild-type counterpart. Moreover, confocal imaging evidenced a preferential microbial distribution as aggregates for LGG WT, while the pili-depleted strain tended to be homogenously distributed and found as individual chains. The observed differences in creaming are attributed to the indirect implication of SpaCBA pili. Indeed, the bacteria-to-bacteria interaction surpassed the bacteria-to-matrix interaction, reducing the bacterial surface exposed to raw milk. Conversely, LGG Δ spaCBA may form a physical barrier responsible for preventing milk fat globules from rising to the surface.

In these times of COVID-19 pandemic, concern has been raised about the potential effects of SARS-CoV-2 infection on immunocompromised patients, particularly on those receiving B-cell depleting agents and having therefore a severely depressed humoral response. Convalescent plasma can be a therapeutic option for these patients. Understanding the underlying mechanisms of convalescent plasma is crucial to optimize such therapeutic approach. Here, we describe a COVID-19 patient who was deeply immunosuppressed following rituximab (anti-CD20 monoclonal antibody) and concomitant chemotherapy for chronic lymphoid leukemia. His long-term severe T and B cell lymphopenia allowed to evaluate the treatment effects of convalescent plasma. Therapeutic outcome was monitored at the clinical, biological and radiological level. Moreover, anti-SARS-CoV-2 antibody titers (IgM, IgG and IgA) and neutralizing activity were assessed over time before and after plasma transfusions, alongside to SARS-CoV-2 RNA quantification and virus isolation from the upper respiratory tract. Already after the first cycle of plasma transfusion, the patient experienced rapid improvement of pneumonia, inflammation and blood cell counts, which may be related to the immunomodulatory properties of plasma. Subsequently, the cumulative increase in anti-SARS-CoV-2 neutralizing antibodies due to the three additional plasma transfusions was associated with progressive and finally complete viral clearance, resulting in full clinical recovery. In this case-report, administration of convalescent plasma revealed a stepwise effect with an initial and rapid anti-inflammatory activity followed by the progressive SARS-CoV-2 clearance. These data have potential implications for a more extended use of convalescent plasma and future monoclonal antibodies in the treatment of immunosuppressed COVID-19 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zimmerli, Monti, Fenwick, Eckerle, Beigelman-Aubry, Pellaton, Jaton, Dumas, Stamm, Infanti, Andreu-Ullrich, Germann, Mean, Vollenweider, Stadelmann, Prella, Comte, Guery, Gachoud and Rufer.)

2020 has continued to bring important progress in all areas of internal medicine, impacting our daily practice. From a shift to oral stepdown antibiotics in infectious endocarditis, to new indications for apixaban, SLGT-2 inhibitors and macrolide antibiotics, passing by the catheter-based renal denervation in hypertension, early paracentesis in cirrhosis and new diagnostic criteria in pulmonary embolism, internal medicine journals are full of novelties. Every year, the chief residents of internal medicine at the Swiss University Hospital of Lausanne meet up to share their readings: here is their selection of eleven articles, summarized and commented for you., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Scedosporium species rank second among the filamentous fungi capable to colonize chronically the respiratory tract of patients with cystic fibrosis (CF). Nevertheless, there is little information on the mechanisms underpinning their virulence. Iron acquisition is critical for the growth and pathogenesis of many bacterial and fungal genera that chronically inhabit the CF lungs. In a previous study, we showed the presence in the genome of Scedosporium apiospermum of several genes relevant for iron uptake, notably SAPIO_CDS2806, an ortholog of sidD , which drives the synthesis of the extracellular hydroxamate-type siderophore fusarinine C (FsC) and its derivative triacetylfusarinine C (TAFC) in Aspergillus fumigatus . Here, we demonstrate that Scedosporium apiospermum sidD gene is required for production of an excreted siderophore, namely, N α -methylcoprogen B, which also belongs to the hydroxamate family. Blockage of the synthesis of N α -methylcoprogen B by disruption of the sidD gene resulted in the lack of fungal growth under iron limiting conditions. Still, growth of ΔsidD mutants could be restored by supplementation of the culture medium with a culture filtrate from the parent strain, but not from the mutants. Furthermore, the use of xenosiderophores as the sole source of iron revealed that S. apiospermum can acquire the iron using the hydroxamate siderophores ferrichrome or ferrioxamine, i.e., independently of N α -methylcoprogen B production. Conversely, N α -methylcoprogen B is mandatory for iron acquisition from pyoverdine, a mixed catecholate-hydroxamate siderophore. Finally, the deletion of sidD resulted in the loss of virulence in a murine model of scedosporiosis. Our findings demonstrate that S. apiospermum sidD gene drives the synthesis of a unique extracellular, hydroxamate-type iron chelator, which is essential for fungal growth and virulence. This compound scavenges iron from pyoverdine, which might explain why S. apiospermum and Pseudomonas aeruginosa are rarely found simultaneously in the CF lungs., (Copyright © 2020 Le Govic, Havlíček, Capilla, Luptáková, Dumas, Papon, Le Gal, Bouchara and Vandeputte.)

As a profession, acting is marked by a high-level of economic and social riskiness concomitantly with the possibility for artistic satisfaction and/or public admiration. Current understanding of the psychological attributes that distinguish professional actors is incomplete. Here, we compare samples of professional actors (n = 104), undergraduate student actors (n = 100), and non-acting adults (n = 92) on 26 psychological dimensions and use machine-learning methods to classify participants based on these attributes. Nearly all of the attributes measured here displayed significant univariate mean differences across the three groups, with the strongest effect sizes being on Creative Activities, Openness, and Extraversion. A cross-validated Least Absolute Shrinkage and Selection Operator (LASSO) classification model was capable of identifying actors (either professional or student) from non-actors with a 92% accuracy and was able to sort professional from student actors with a 96% accuracy when age was included in the model, and a 68% accuracy with only psychological attributes included. In these LASSO models, actors in general were distinguished by high levels of Openness, Assertiveness, and Elaboration, but professional actors were specifically marked by high levels of Originality, Volatility, and Literary Activities., Competing Interests: Michael Doherty’s affiliation with Actor’s Equity Association did not and does not alter our adherence to PLOS ONE policies on sharing data and material.

Background: The originality of divergent thinking (DT) production is one of the most critical indicators of creative potential. It is commonly scored using the statistical infrequency of responses relative to all responses provided in a given sample., Aims: Response frequency estimates vary in terms of measurement precision. This issue has been widely overlooked and is addressed in the current study., Sample and Method: Secondary data analysis of 202 participants was performed. A total of 900 uniquely identified responses were generated on three DT tasks and subjected to a 1-parameter logistic model with a response as the unit of measurement which allowed for the calculation of response-level conditional reliability (and marginal reliability as an overall summary of measurement precision)., Results: Marginal reliability of response propensity estimates ranged from .62 to .67 across the DT tasks. Unique responses in the sample (the basis for the classic uniqueness scoring) displayed the lowest conditional reliability (across tasks: ≈ .50). Reliability increased nonlinearly as a function of both the frequency of occurrence predicted by the model (conditional reliability) and sample size (conditional and marginal reliability)., Conclusions: This study indicates that the common practice of frequency-based originality scoring with typical sample sizes (e.g., N = 100 to N = 200) yields unacceptable levels of measurement precision (i.e., in particular for highly original responses). We further offer recommendations to mitigate the lack of measurement precision of frequency-based originality scores for DT research., (© 2019 The Authors. British Journal of Educational Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Background: A major review of Victoria's ambulance services identified the need to improve public awareness of the role of ambulances as an emergency service. A communications campaign was developed to address this challenge. This research paper expands on an initial evaluation of the campaign by focusing on the long-term behavioural outcomes., Methods: The behavioural evaluation involved two types of data collection - administrative data (routine collection from various health services) and survey data (cross-sectional community-wide surveys to measure behavioural intentions)., Results: Behavioural intentions for accessing two of the targeted non-emergency services increased after the second phase of the campaign commenced. There was also a significant change in the slope of call trends for emergency ambulances. This decrease is also likely attributed to the second phase of the campaign as significant level effects were identified 3 and 9 months after it commenced., Conclusions: A long-term campaign developed through evidence review, stakeholder consultation and behavioural theory was successful in reducing the number of daily calls requesting an emergency ambulance in Victoria and in increasing intentions to use alternative services. This research highlights the importance of collaborative intervention design along with the importance of implementing a robust monitoring and evaluation framework.

Dynamic measurement modeling (DMM) is a psychometric paradigm that uses longitudinal data to estimate individual students' growth in measured skills over the course of an educational program (i.e., growth scores). DMM represents a more formal way of assessing learning progress across the health professions education continuum. In this article, the authors provide justification for this approach in health professions education and demonstrate its proof-of-concept use with three time points of United States Medical Licensing Examination Step exams to generate growth scores for 454 current and recent medical learners. The authors demonstrate that learners vary substantially on their growth scores, and those growth scores exhibit psychometric reliability. In addition, growth scores significantly and positively correlated with indicators of medical learner readiness (e.g., undergraduate grade point average and Medical College Admission Test scores). These growth scores were also capable of significantly and positively correlating with future ratings of clinical competencies during internship as assessed through a survey sent to their program directors at the end of the first postgraduate year (e.g., patient care, interpersonal skills). These preliminary findings of reliability and validity for DMM growth scores provide initial evidence for further investigation into the suitability of a dynamic measurement paradigm in health professions education.

In the last decade, there has been an increasing interest in the potential health effects associated with the consumption of lactic acid bacteria (LAB) in foods. Some of these bacteria such as Lactobacillus rhamnosus GG (LGG) are known to adhere to milk components, which may impact their distribution and protection within dairy matrices and therefore is likely to modulate the efficiency of their delivery. However, the adhesive behavior of most LAB, as well as its effect on food structuration and on the final bacterial distribution within the food matrix remain very poorly studied. Using a recently developed high-throughput approach, we have screened a collection of 73 LAB strains for their adhesive behavior toward the major whey protein β-lactoglobulin. Adhesion was then studied by genomics in relation to common bacterial surface characteristics such as pili and adhesion-related domain containing proteins. Representative adhesive and non-adhesive strains have been studied in further depth through biophysical measurement using atomic force microscopy (AFM) and a relation with bacterial distribution in whey protein isolate (WPI) solution has been established. AFM measurements have revealed that bacterial adhesion to β-lactoglobulin is highly specific and cannot be predicted accurately using only genomic information. Non-adhesive strains were found to remain homogeneously distributed in solution whereas adhesive strains gathered in flocs. These findings show that several LAB strains are able to adhere to β-lactoglobulin, whereas this had only been previously observed on LGG. We also show that these adhesive interactions present similar characteristics and are likely to impact bacterial location and distribution in dairy matrices containing β-lactoglobulin. This may help with designing more efficient dairy food matrices for optimized LAB delivery.

Annulus fibrosus (AF) impairment is associated with reherniation, discogenic pain, and disc degeneration after surgical partial discectomy. Due to a limited intrinsic healing capacity, defects in the AF persist over time and it is hence necessary to adopt an appropriate strategy to close and repair the damaged AF. In this study, a cell-free biodegradable scaffold made of polycaprolactone (PCL), electrospun, aligned microfibers exhibited high levels of cell colonization, alignment, and AF-like extracellular matrix deposition when evaluated in an explant culture model. The biomimetic multilayer fibrous scaffold was then assessed in an ovine model of AF impairment. After 4 weeks, no dislocation of the implants was detected, and only one sample out of six showed a partial delamination. Histological and immunohistochemical analyses revealed integration of the implant with the surrounding tissue as well as homogeneously aligned collagen fiber organization within each lamella compared to the disorganized and scarcer fibrous tissue in a randomly organized control fibrous scaffold. In conclusion, this biomimetic electrospun implant exhibited promising properties in terms of AF defect closure, with AF-like neotissue formation that fully integrated with the surrounding ovine tissue., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: In Victoria, Australia, emergency calls requesting an ambulance have been increasing at a rate higher than population growth. While most of these calls are for genuine emergencies, many do not require an immediate ambulance response. A collaborative research approach was undertaken to address this issue. The aim of this paper was to evaluate the effectiveness of applying a behaviour change approach to this challenge by first addressing antecedents of behaviour (attitudes, awareness and knowledge)., Methods: The project included a formative research phase to inform the design of a mass media campaign and subsequent evaluation of the campaign., Results: Results indicated that the campaign was successful in increasing community attitudes towards ambulances as being for emergencies only, particularly among those familiar with the campaign material and with other health service options (such as telephone advice lines)., Conclusions: These findings provide support for adopting the Forum approach to increase the chances that a mass media campaign will achieve its stated objectives. Recommendations for future campaign activities are discussed.

Clinical reasoning-the steps up to and including establishing a diagnosis and/or therapy-is a fundamentally important mental process for physicians. Unfortunately, mounting evidence suggests that errors in clinical reasoning lead to substantial problems for medical professionals and patients alike, including suboptimal care, malpractice claims, and rising health care costs. For this reason, cognitive strategies by which clinical reasoning may be improved-and that many expert clinicians are already using-are highly relevant for all medical professionals, educators, and learners.In this Perspective, the authors introduce one group of cognitive strategies-termed relational reasoning strategies-that have been empirically shown, through limited educational and psychological research, to improve the accuracy of learners' reasoning both within and outside of the medical disciplines. The authors contend that relational reasoning strategies may help clinicians to be metacognitive about their own clinical reasoning; such strategies may also be particularly well suited for explicitly organizing clinical reasoning instruction for learners. Because the particular curricular efforts that may improve the relational reasoning of medical students are not known at this point, the authors describe the nature of previous research on relational reasoning strategies to encourage the future design, implementation, and evaluation of instructional interventions for relational reasoning within the medical education literature. The authors also call for continued research on using relational reasoning strategies and their role in clinical practice and medical education, with the long-term goal of improving diagnostic accuracy.

In tissue engineering approaches, the quality of substitutes is a key element to determine its ability to treat cartilage defects. However, in clinical practice, the evaluation of tissue-engineered cartilage substitute quality is not possible due to the invasiveness of the standard procedure, which is to date histology. The aim of this work was to validate a new innovative system performed from two-photon excitation laser adapted to an optical macroscope to evaluate at macroscopic scale the collagen network in cartilage tissue-engineered substitutes in confrontation with gold standard histologic techniques or immunohistochemistry to visualize type II collagen. This system permitted to differentiate the quality of collagen network between ITS and TGF-β1 treatments. Multiscale large field imaging combined to multimodality approaches (SHG-TCSPC) at macroscopical scale represent an innovative and non-invasive technique to monitor the quality of collagen network in cartilage tissue-engineered substitutes before in vivo implantation.

Recent methodological work has highlighted the promise of nonlinear growth models for addressing substantive questions in the behavioral sciences. In this article, we outline a second-order nonlinear growth model in order to measure a critical notion in development and education: potential. Here, potential is conceptualized as having three components-ability, capacity, and availability-where ability is the amount of skill a student is estimated to have at a given timepoint, capacity is the maximum amount of ability a student is predicted to be able to develop asymptotically, and availability is the difference between capacity and ability at any particular timepoint. We argue that single timepoint measures are typically insufficient for discerning information about potential, and we therefore describe a general framework that incorporates a growth model into the measurement model to capture these three components. Then, we provide an illustrative example using the public-use Early Childhood Longitudinal Study-Kindergarten data set using a Michaelis-Menten growth function (reparameterized from its common application in biochemistry) to demonstrate our proposed model as applied to measuring potential within an educational context. The advantage of this approach compared to currently utilized methods is discussed as are future directions and limitations.

Relational reasoning, or the ability to discern meaningful patterns within a stream of information, is a critical cognitive ability associated with academic and professional success. Importantly, relational reasoning has been described as taking multiple forms, depending on the type of higher order relations being drawn between and among concepts. However, the reliable and valid measurement of such a multidimensional construct of relational reasoning has been elusive. The Test of Relational Reasoning (TORR) was designed to tap 4 forms of relational reasoning (i.e., analogy, anomaly, antinomy, and antithesis). In this investigation, the TORR was calibrated and scored using multidimensional item response theory in a large, representative undergraduate sample. The bifactor model was identified as the best-fitting model, and used to estimate item parameters and construct reliability. To improve the usefulness of the TORR to educators, scaled scores were also calculated and presented. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Because of its fundamental relevance to scientific innovation, artistic expression, and human ingenuity, creativity has long been the subject of systematic psychological investigation. Concomitantly, the far-reaching effects of stereotypes on various cognitive and social processes have been widely researched. Bridging these two literatures, we show in a series of two studies that stereotypes related to creativity can both enhance and diminish individuals' performance on a divergent thinking task. Specifically, Study 1 demonstrated that participants asked to take on a stereotypically uninhibited perspective performed significantly better on a divergent thinking task than those participants who took on a stereotypically inhibited perspective, and a control group. Relatedly, Study 2 showed that the same effect is found within-subjects, with divergent thinking significantly improving when participants invoke an uninhibited stereotype. Moreover, we demonstrate the efficacy of Latent Semantic Analysis as an objective measure of the originality of ideas, and discuss implications of our findings for the nature of creativity. Namely, that creativity may not be best described as a stable individual trait, but as a malleable product of context and perspective.

There is currently great interest in the development of efficient and specific carrier delivery platforms for systemic photodynamic therapy. Therefore, we aimed to develop covalent conjugates between the photosensitizer chlorin e6 (Ce6) and PAMAM G4.5 dendrimers. Singlet oxygen generation (SOG) efficiency and fluorescence emission were moderately affected by the covalent binding of the Ce6 to the dendrimer. Compared to free Ce6, PAMAM anchored Ce6 displays a much higher photodynamic effect, which is ascribable to better internalization in a tumor cell model. Intracellular fate and internalization pathway of our different compounds were investigated using specific inhibition conditions and confocal fluorescence microscopy. Free Ce6 was shown to enter the cells by a simple diffusion mechanism, while G4.5-Ce6-PEG internalization was dependent on the caveolae pathway, whereas G4.5-Ce6 was subjected to the clathrin-mediated endocytosis pathway. Subcellular localization of PAMAM anchored Ce6, PEGylated or not, was very similar suggesting that the nanoparticles behave similarly in the cells. As a conclusion, we have demonstrated that PEGylated G4.5 PAMAM-Ce6 dendrimers may offer effective biocompatible nanoparticles for improved photodynamic treatment in a preclinical tumor model.