A model eye for fluorescent characterization of retinal cultures and tissues

Many human neural or neurodegenerative diseases strongly affect the ocular and retinal environment showing peculiar alterations which can be employed as specific disease biomarkers. The noninvasive optical accessibility of the retina makes the ocular investigation a potentially competitive strategy for screening, thus the development of retinal biomarkers is rapidly growing. Nevertheless, a tool to study and image biomarkers or biological samples in a human-like eye environment is still missing. Here we report on a modular and versatile eye model designed to host biological samples, such as retinal cultures differentiated from human induced pluripotent stem cells and ex-vivo retinal tissue, but also suited to host any kind of retinal biomarkers. We characterized the imaging performance of this eye model on standard biomarkers such as Alexa Fluor 532 and Alexa Fluor 594

Glucocorticoids rescue cell surface trafficking of R451C Neuroligin3 and enhance synapse formation

Neuroligins are synaptic cell adhesion proteins with a role in synaptic function, implicated in neurodevelopmental disorders. The autism spectrum disorder-associated substitution Arg451Cys (R451C) in NLGN3 promotes a partial misfolding of the extracellular domain of the protein leading to retention in the endoplasmic reticulum (ER) and the induction of the unfolded protein response (UPR). The reduced trafficking of R451C NLGN3 to the cell surface leads to altered synaptic function and social behavior. A screening in HEK-293 cells overexpressing NLGN3 of 2662 compounds (FDA-approved small molecule drug library), led to the identification of several glucocorticoids such as alclometasone dipropionate, desonide, prednisolone sodium phosphate, and dexamethasone (DEX), with the ability to favor the exit of full-length R451C NLGN3 from the ER. DEX improved the stability of R451C NLGN3 and trafficking to the cell surface, reduced the activation of the UPR, and increased the formation of artificial synapses between HEK-293 and hippocampal primary neurons. The effect of DEX was validated on a novel model system represented by neural stem progenitor cells and differentiated neurons derived from the R451C NLGN3 knock-in mouse, expressing the endogenous protein. This work shows a potential rescue strategy for an autism-linked mutation affecting cell surface trafficking of a synaptic protein

Recent Trends and Perspectives on Defect-Oriented Testing

Electronics employed in modern safety-critical systems require severe qualification during the manufacturing process and in the field, to prevent fault effects from manifesting themselves as critical failures during mission operations. Traditional fault models are not sufficient anymore to guarantee the required quality levels for chips utilized in mission-critical applications. The research community and industry have been investigating new test approaches such as device-aware test, cell-aware test, path-delay test, and even test methodologies based on the analysis of manufacturing data to move the scope from OPPM to OPPB. This special session presents four contributions, from academic researchers and industry professionals, to enable better chip quality. We present results on various activities towards this objective, including device-aware test, software-based self-test, and memory test

Implementing nudges for suicide prevention in real-world environments: project INSPIRE study protocol

Background: Suicide is a global health issue. There are a number of evidence-based practices for suicide screening, assessment, and intervention that are not routinely deployed in usual care settings. The goal of this study is to develop and test implementation strategies to facilitate evidence-based suicide screening, assessment, and intervention in two settings where individuals at risk for suicide are especially likely to present: primary care and specialty mental health care. We will leverage methods from behavioral economics, which involves understanding the many factors that influence human decision making, to inform strategy development. Methods: We will identify key mechanisms that limit implementation of evidence-based suicide screening, assessment, and intervention practices in primary care and specialty mental health through contextual inquiry involving behavioral health and primary care clinicians. Second, we will use contextual inquiry results to systematically design a menu of behavioral economics-informed implementation strategies that cut across settings, in collaboration with an advisory board composed of key stakeholders (i.e., behavioral economists, clinicians, implementation scientists, and suicide prevention experts). Finally, we will conduct rapid-cycle trials to test and refine the menu of implementation strategies. Primary outcomes include clinician-reported feasibility and acceptability of the implementation strategies. Discussion: Findings will elucidate ways to address common and unique barriers to evidence-based suicide screening, assessment, and intervention practices in primary care and specialty mental health care. Results will yield refined, pragmatically tested strategies that can inform larger confirmatory trials to combat the growing public health crisis of suicide

Towards a framework for attention cueing in instructional animations: Guidelines for research and design

This paper examines the transferability of successful cueing approaches from text and static visualization research to animations. Theories of visual attention and learning as well as empirical evidence for the instructional effectiveness of attention cueing are reviewed and, based on Mayer’s theory of multimedia learning, a framework was developed for classifying three functions for cueing: (1) selection—cues guide attention to specific locations, (2) organization—cues emphasize structure, and (3) integration—cues explicate relations between and within elements. The framework was used to structure the discussion of studies on cueing in animations. It is concluded that attentional cues may facilitate the selection of information in animations and sometimes improve learning, whereas organizational and relational cueing requires more consideration on how to enhance understanding. Consequently, it is suggested to develop cues that work in animations rather than borrowing effective cues from static representations. Guidelines for future research on attention cueing in animations are presented

Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey

<p>Abstract</p> <p>Background</p> <p>The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications.</p> <p>Methods</p> <p>A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period.</p> <p>Results</p> <p>Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay.</p> <p>Conclusion</p> <p>Results confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.</p

Main clinical features in patients at their first psychiatric admission to Italian acute hospital psychiatric wards. The PERSEO study

BACKGROUND: Few data are available on subjects presenting to acute wards for the first time with psychotic symptoms. The aims of this paper are (i) to describe the epidemiological and clinical characteristics of patients at their first psychiatric admission (FPA), including socio-demographic features, risk factors, life habits, modalities of onset, psychiatric diagnoses and treatments before admission; (ii) to assess the aggressive behavior and the clinical management of FPA patients in Italian acute hospital psychiatric wards, called SPDCs (Servizio Psichiatrico Diagnosi e Cura = psychiatric service for diagnosis and management). METHOD: Cross-sectional observational multi-center study involving 62 Italian SPDCs (PERSEO – Psychiatric EmeRgency Study and EpidemiOlogy). RESULTS: 253 FPA aged <= 40 were identified among 2521 patients admitted to Italian SPDCs over the 5-month study period. About half of FPA patients showed an aggressive behavior as defined by a Modified Overt Aggression Scale (MOAS) score greater than 0 Vs 46% of non-FPA patients (p = 0.3651). The most common was verbal aggression, while about 20% of FPA patients actually engaged in physical aggression against other people. 74% of FPA patients had no diagnosis at admission, while 40% had received a previous psychopharmacological treatment, mainly benzodiazepines and antidepressants. During SPDC stay, diagnosis was established in 96% of FPA patients and a pharmacological therapy was prescribed to 95% of them, mainly benzodiazepines, antipsychotics and mood stabilizers. CONCLUSION: Subjects presenting at their first psychiatric ward admission have often not undergone previous adequate psychiatric assessment and diagnostic procedures. The first hospital admission allows diagnosis and psychopharmacological treatment to be established. In our population, aggressive behaviors were rather frequent, although most commonly verbal. Psychiatric symptoms, as evaluated by psychiatrists and patients, improved significantly from admission to discharge both for FPA and non-FPA patients

Learning from multimedia and hypermedia

Computer-based multimedia and hypermedia resources (e.g., the world wide web) have become one of the primary sources of academic information for a majority of pupils and students. In line with this expansion in the field of education, the scientific study of learning from multimedia and hypermedia has become a very active field of research. In this chapter we provide a short overview with regard to research on learning with multimedia and hypermedia. In two review sections, we describe the educational benefits of multiple representations and of learner control, as these are the two defining characteristics of hypermedia. In a third review section we describe recent scientific trends in the field of multimedia/hypermedia learning. In all three review sections we will point to relevant European work on multimedia/hypermedia carried out within the last 5 years, and often carried out within the Kaleidoscope Network of Excellence. According to the interdisciplinary nature of the field this work might come not only from psychology, but also from technology or pedagogy. Comparing the different research activities on multimedia and hypermedia that have dominated the international scientific discourse in the last decade reveals some important differences. Most important, a gap seems to exist between researchers mainly interested in a “serious” educational use of multimedia/ hypermedia and researchers mainly interested in “serious” experimental research on learning with multimedia/hypermedia. Recent discussions about the pros and cons of “design-based research” or “use-inspired basic research” can be seen as a direct consequence of an increasing awareness of the tensions within these two different cultures of research on education

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p