Mutations in neuroligin-3 in male mice impact behavioral flexibility but not relational memory in a touchscreen test of visual transitive inference

Cognitive dysfunction including disrupted behavioral flexibility is central to neurodevelopmental disorders such as Autism Spectrum Disorder (ASD). A cognitive measure that assesses relational memory, and the ability to flexibly assimilate and transfer learned information is transitive inference. Transitive inference is highly conserved across vertebrates and disrupted in cognitive disorders. Here, we examined how mutations in the synaptic cell-adhesion molecule neuroligin-3 (Nlgn3) that have been documented in ASD impact relational memory and behavioral flexibility. We first refined a rodent touchscreen assay to measure visual transitive inference, then assessed two mouse models of Nlgn3 dysfunction (Nlgn3−/y and Nlgn3R451C). Deep analysis of touchscreen behavioral data at a trial level established we could measure trajectories in flexible responding and changes in processing speed as cognitive load increased. We show that gene mutations in Nlgn3 do not disrupt relational memory, but significantly impact flexible responding. Our study presents the first analysis of reaction times in a rodent transitive inference test, highlighting response latencies from the touchscreen system are useful indicators of processing demands or decision-making processes. These findings expand our understanding of how dysfunction of key components of synaptic signaling complexes impact distinct cognitive processes disrupted in neurodevelopmental disorders, and advance our approaches for dissecting rodent behavioral assays to provide greater insights into clinically relevant cognitive symptoms

Open process innovation: A multi-method study on the involvement of customers and consultants in public sector BPM

Following calls to enhance risk-sensitivity of second generation Operational Risk-Aware Information Systems (ORISs), this paper aims to address the lack of ontological/epistemological grounding for the concept of Operational Risk (OR). Herein, OR is regarded both as a property of a real system and as a representational phenomenon forming part of the core of ORIS in line with Weber’s (2003) view of the core of IS. The paper explores how the ontological/epistemological position of the Critical Realist philosophy of science assists in the Requirements Definition of ORISs by providing an ontology-driven representation of the heterogeneous nature of OR. The retroductive mode of logical inference enabled by Critical Realism supports the discovery of OR causal mechanisms when the historical data about operational loss events is limited. The ontological/epistemological position suggested in the paper contributes to better understanding and representation of OR, informs OR assessment in conditions of a constantly changing socio-economical environment, and so assists in the Requirements Definition of ORISs

Selection for inpatient rehabilitation after severe stroke: What factors influence rehabilitation assessor decision making?

Objectives: This study aimed to identify factors that assessors considered important in decision-making regarding suitability for inpatient rehabilitation after acute severe stroke.Design: Multi-site prospective observational cohort study. Subjects: Consecutive acute, severe stroke patients and their assessors for inpatient rehabilitation. Methods: Rehabilitation assessors completed a questionnaire, rating the importance (10 point visual analogue scale) and direction (positive, negative or neutral) of 15 patient related and 2 organisational items potentially affecting their decision regarding patients’ acceptance to rehabilitation. Results: Of the 75 patients referred to rehabilitation and included in this study 61 (81.3%) were accepted for inpatient rehabilitation. The items considered to be most important in the decision to accept the patient for rehabilitation were pre-morbid cognition, pre-morbid mobility and pre-morbid communication. For those not accepted the most important items were current mobility, social support and current cognition. Factor analysis revealed 3 underlying factors, interpreted as post-stroke status, pre-morbid status, and social attributes, accounting for 61.8% of the total variance. All were independently associated with acceptance for rehabilitation (p < 0.05). Conclusions: This study highlights the importance of pre-morbid function and social factors in addition to post-stroke function in the decision making process for acceptance to rehabilitation following severe stroke. Future models for selection for rehabilitation should consider inclusion of these factors

An Early Mobilization Protocol Successfully Delivers More and Earlier Therapy to Acute Stroke Patients: Further Results From Phase II of AVERT.

Background: The optimal physical therapy dose in acute stroke care is unknown. The authors hypothesized that physical therapy would be significantly different between treatment arms in a trial of very early and frequent mobilization (VEM) and that immobility-related adverse events would be associated with therapy dose. Methods: This study was a single-blind, multicenter, randomized control trial. Patients admitted to a stroke unit <24 hours of stroke randomized to standard care (SC) or intervention, SC plus additional early out-of-bed therapy (VEM). Timing, amount, and type of therapy recorded throughout the trial. Adverse events were recorded to 3 months. Results: A total of 71 patients (SC n = 33, VEM n = 38) received 788 therapy sessions in the first 2 weeks of stroke. Schedule (hours to first mobilization, dose per day, frequency and session duration) and nature (percentage out-of-bed activity) of therapy differed significantly between groups (P ≤ .001 for all components). Mobilization was earlier, happened on average 3 times per day in those receiving VEM, with the proportion of out-of-bed activity double in VEM session (median SC 42.5%, VEM 85.5%). SC consisted of 17 minutes of occupational and physiotherapy per day and was the same between groups. Number of immobility-related adverse events 3 months poststroke was not associated with therapy dose or frequency. Conclusions: The authors detailed usual care and intervention therapy provided to patients from admission to 14 days after stroke. The therapy schedule was markedly different in the intervention arm, but whether this schedule reduces complications or improves outcome is unknown

Performance of AAOmega: the AAT multi-purpose fibre-fed spectrograph

AAOmega is the new spectrograph for the 2dF fibre-positioning system on the Anglo-Australian Telescope. It is a bench-mounted, double-beamed design, using volume phase holographic (VPH) gratings and articulating cameras. It is fed by 392 fibres from either of the two 2dF field plates, or by the 512 fibre SPIRAL integral field unit (IFU) at Cassegrain focus. Wavelength coverage is 370 to 950nm and spectral resolution 1,000-8,000 in multi-Object mode, or 1,500-10,000 in IFU mode. Multi-object mode was commissioned in January 2006 and the IFU system will be commissioned in June 2006. The spectrograph is located off the telescope in a thermally isolated room and the 2dF fibres have been replaced by new 38m broadband fibres. Despite the increased fibre length, we have achieved a large increase in throughput by use of VPH gratings, more efficient coatings and new detectors - amounting to a factor of at least 2 in the red. The number of spectral resolution elements and the maximum resolution are both more than doubled, and the stability is an order of magnitude better. The spectrograph comprises: an f/3.15 Schmidt collimator, incorporating a dichroic beam-splitter; interchangeable VPH gratings; and articulating red and blue f/1.3 Schmidt cameras. Pupil size is 190mm, determined by the competing demands of cost, obstruction losses, and maximum resolution. A full suite of VPH gratings has been provided to cover resolutions 1,000 to 7,500, and up to 10,000 at particular wavelengths.Comment: 13 pages, 4 figures; presented at SPIE, Astronomical Telescopes and Instrumentation, 24 - 31 May 2006, Orlando, Florida US

Theory of terahertz electric oscillations by supercooled superconductors

We predict that below T_c a regime of negative differential conductivity (NDC) can be reached. The superconductor should be supercooled to T<T_c in the normal phase under DC voltage. In such a nonequilibrium situation the NDC of the superconductor is created by the excess conductivity of the fluctuation Cooper pairs. We propose NDC of supercooled superconductors to be used as an active medium for generation of electric oscillations. Such generators can be used in the superconducting electronics as a new type THz source of radiation. Oscillations can be modulated by the change of the bias voltage, electrostatic doping by a gate electrode when the superconductor is the channel of a field effect transistor, or by light. When small amplitude oscillations are stabilized near the critical temperature T_c the generator can be used as a bolometer. The essential for the applications NDC is predicted by the solution of the Boltzmann kinetic equation for the metastable in the normal phase Cooper pairs. Boltzmann equation for fluctuation Cooper pairs is a result of state-of-the-art application of the microscopic theory of superconductivity. Our theoretical conclusions are based on some approximations like time dependent Ginzburg-Landau theory, but nevertheless can reliably predict appearance of NDC. The maximal frequency at which superconductors can operate as generators is determined by the critical temperature \hbar omega_max ~ k_B T_c. For high-T_c superconductors this maximal frequency falls well inside the terahertz range. Technical conditions to avoid nucleation of the superconducting phase are briefly discussed. We suggest that nanostructured high-T_c superconductors patterned in a single chip can give the best technical performance of the proposed oscillator.Comment: 7 page

Hashimotos’ thyroiditis: Epidemiology, pathogenesis, clinic and therapy

Hashimoto's thyroiditis (HT), the most frequent autoimmune thyroid disorders (AITDs), is the leading cause of hypothyroidism in the iodine-sufficient areas of the world. About 20-30% of patients suffers from HT, whose cause is thought to be a combination of genetic susceptibility and environmental factors that causes the loss of immunological tolerance, with a consequent autoimmune attack to the thyroid tissue and appearance of the disease. The pathologic features of lymphocytic infiltration, especially of T cells, and follicular destruction are the histological hallmark of autoimmune thyroiditis (AIT), that lead to gradual atrophy and fibrosis. An important role in the immune-pathogenesis of AITDs is due to chemokines and cytokines. In about 20% of patients, AITDs are associated with other organ specific/systemic autoimmune disorders. Many studies have demonstrated the relationship between papillary thyroid cancer and AITD. The treatment of hypothyroidism, as result of AIT, consists in daily assumption of synthetic levothyroxine

Timing and Dose of Upper Limb Motor Intervention After Stroke: A Systematic Review

This systematic review aimed to investigate timing, dose, and efficacy of upper limb intervention during the first 6 months poststroke. Three online databases were searched up to July 2020. Titles/abstracts/full-text were reviewed independently by 2 authors. Randomized and nonrandomized studies that enrolled people within the first 6 months poststroke, aimed to improve upper limb recovery, and completed preintervention and postintervention assessments were included. Risk of bias was assessed using Cochrane reporting tools. Studies were examined by timing (recovery epoch), dose, and intervention type. Two hundred and sixty-one studies were included, representing 228 (n=9704 participants) unique data sets. The number of studies completed increased from one (n=37 participants) between 1980 and 1984 to 91 (n=4417 participants) between 2015 and 2019. Timing of intervention start has not changed (median 38 days, interquartile range [IQR], 22–66) and study sample size remains small (median n=30, IQR 20–48). Most studies were rated high risk of bias (62%). Study participants were enrolled at different recovery epochs: 1 hyperacute (<24 hours), 13 acute (1–7 days), 176 early subacute (8–90 days), 34 late subacute (91–180 days), and 4 were unable to be classified to an epoch. For both the intervention and control groups, the median dose was 45 (IQR, 600–1430) min/session, 1 (IQR, 1–1) session/d, 5 (IQR, 5–5) d/wk for 4 (IQR, 3–5) weeks. The most common interventions tested were electromechanical (n=55 studies), electrical stimulation (n=38 studies), and constraint-induced movement (n=28 studies) therapies. Despite a large and growing body of research, intervention dose and sample size of included studies were often too small to detect clinically important effects. Furthermore, interventions remain focused on subacute stroke recovery with little change in recent decades. A united research agenda that establishes a clear biological understanding of timing, dose, and intervention type is needed to progress stroke recovery research. Prospective Register of Systematic Reviews ID: CRD42018019367/CRD42018111629

SYNOPSIS AND PROSPECTS OF AUTOIMMUNOLOGY DEVELOPMENT WORLDWIDE (AFTER THE MATERIALS OF THE 11th INTERNATIONAL CONGRESS IN LISBON, MAY 16-20, 2018). PROCEEDING I: FIRST ACADEMY OF AUTOIMMUNITY

A review article is an aftermath of the 11th International Congress on Autoimmunity and First Academy of Autoimmunity, happened 14th to 20th May, 2018 in Lisbon. The first part of paper discusses the formation, main problems and prospects for the development of Autoimmunology as a new integral branch of fundamental and clinical Medicine engaged in the research, diagnosis, treatment and prevention of autoimmune diseases of various organs and systems, totally circa 90 of them. A summary of all lectures conducted during the Academy of Autoimmunity is given, including a discussion of the newest and controversial aspects of the development of the modern concepts of the immune system, autoimmunity and autoimmune pathology. Article reviews data on the current problems of Immunology associated with the use of large databases of clinical and laboratory findings and extrapolation of animal experimentation data to humans. The newest ideas about congenital immunity, including the populations of innate lymphoid cells, on the role of various groups of receptors of the innate immunity system, on the participation of the mechanisms of innate immunity in pathogenesis of autoimmune disorders are highlighted. Modern concepts of antigen presentation are offered, including classification of dendritic cells, alternative pathways of macrophage activation, as well as on costimulatory and inhibitory interactions of ligands and receptors of lymphocytes and antigen-presenting cells. The latest data about the subpopulations of T lymphocytes and their role, including the functions of Tfh cells and the relationships of these subpopulations with various immune responses are highlighted. Influence of microbiota on T cell subpopulations is discussed. The main regularities of the phenomenon of immunological memory are formulated. The questions of antibody production and B lymphocyte functions are considered taking into account recently discovered mechanisms of intracellular penetration of immunoglobulins and details of affinity maturation of lymphoid clones. The new therapeutic approaches in the treatment of autoimmune diseases associated with influences on B and T lymphocytes are described. Mechanisms of central and peripheral autotolerance have been highlighted, taking into account data on the function of the AIRE gene and T regulators. The role of T regulators in placentation is considered. The role of interleukin-2 and its recombinant analogues in immune interactions is interpreted in a new way, taking into account not only their immunostimulating, but, under certain conditions, immunosuppressive potential also. Considerable attention has been paid to the inhibitory receptors of T lymphocytes and to immuno-biotherapeutic effects on them. The history and current status of Oncoimmunology and the use of blockers of inhibitory T lymphocyte receptors in Oncology, including the side effects of treatment with check-point inhibitors, are briefly discussed. Information was given on the held on 21-23 September 2018 2nd Academy of Autoimmunity in St. Petersburg