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We draw on cognitive and behavioural theories and on the artificial intelligence literature in order to propose a framework of future operator – workstation interaction in the 'Industry 4.0' era. We name the proposed framework 'Operator – Workstation Interaction 4.0'. The latter's capabilities permit an adaptive, ongoing interaction that aims to improve operator safety, performance, well-being, and satisfaction as well as the factory's production measures. The framework is composed of three subsystems: (1) the observation subsystem which observes the operator and the processes occurring in the workstation, (2) the analysis subsystem which generates understanding and implications of the observations output, (3) the reaction subsystem which determines if and how to respond. The paper describes these elements and illustrate them using an example of a fatigued worker. The contributions, implications, and limitations of the proposed framework are discussed, and future research directions are presented. [ABSTRACT FROM AUTHOR]

Disease-modifying therapies (DMTs) are widely used in neuroimmunological diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Although these treatments are known to predispose patients to infections and affect their responses to vaccination, little is known about the impact of DMTs on the myeloid cell compartment. In this study, we use mass cytometry to examine DMT-associated changes in the innate immune system in untreated and treated patients with MS (n = 39) or NMOSD (n = 23). We also investigated the association between changes in myeloid cell phenotypes and longitudinal responsiveness to homologous primary, secondary, and tertiary SARS-CoV-2 mRNA vaccinations. Multiple DMT-associated myeloid cell clusters, in particular CD64+HLADRlow granulocytes, showed significant correlations with B and T cell responses induced by vaccination. Our findings suggest the potential role of myeloid cells in cellular and humoral responses following vaccination in DMT-treated patients with neuroimmunological diseases. Patients with autoimmune diseases require immunosuppressive treatments that affect their responses to infection and vaccination. Here, using mass cytometry, the authors to identify a role for myeloid cells in cellular and humoral responses following vaccination against SARS-CoV-2 in patients with neuroimmunological diseases. [ABSTRACT FROM AUTHOR]

A left ventricular assist device (LVAD) is a mechanical device that treats advanced heart failure. Patients coping with an LVAD need extensive instrumental and medical support, which is usually provided by the spouse. Therefore, it seems that dyadic coping strategies play a crucial role as either mitigators or hinderers of couples' illness management in the context of LVADs. The aim of this research was to formulate a typology of dyadic coping strategies applied by these couples, as unfolded in their mutual and individual subjective experiences. The research was performed in collaboration with an LVAD implantation unit at a medium-sized hospital in Israel. Couples (N = 17) participated in an in-depth dyadic interview using a semi-structured interview guide, and the data collected were analyzed using content analysis. Our findings suggest that couples coping with an LVAD develop strategies for handling fear, processing and accepting their illness narratives, adjusting their level of independence and intimacy, and utilizing humor. Moreover, our analysis showed that each couple utilized a unique mix of dyadic coping strategies. To the best of our knowledge, the current study is the first to explore the dyadic coping strategies of couples coping with an LVAD. Our results may constitute a base for developing dyadic intervention programs and clinical recommendations to improve the quality of life and relationships of patients and their spouses while coping with LVAD implementation. [ABSTRACT FROM AUTHOR]

Patients with inflammatory bowel disease (IBD) treated with anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of the COVID-19 BNT162b2 vaccine compared to those not treated with anti-TNFα (non-anti-TNFα) or to healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients with IBD stratified by therapy compared to HCs. Subjects enrolled in a prospective, controlled, multi-center Israeli study received two BNT162b2 doses. Anti-S levels, functional activity, specific B cells, antigen cross-reactivity, anti-nucleocapsid levels, adverse events and IBD disease score were detected longitudinally. In total, 240 subjects, 151 with IBD (94 not treated with anti-TNFα and 57 treated with anti-TNFα) and 89 HCs participated. Six months after vaccination, patients with IBD treated with anti-TNFα had significantly impaired BNT162b2 responses, specifically, more seronegativity, decreased specific circulating B cells and cross-reactivity compared to patients untreated with anti-TNFα. Importantly, all seronegative subjects were patients with IBD; of those, >90% were treated with anti-TNFα. Finally, IBD activity was unaffected by BNT162b2. Altogether these data support the earlier booster dose administration in these patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Skin eruptions are prevalent among patients with inflammatory bowel diseases (IBD), often associated with therapies and frequently leading to dermatological consults and treatment interruptions. We aimed to assess the impact of joint shared decision-making in a multidisciplinary (MDT) IBD-DERMA clinic. Methods: This retrospective cohort study assessed a consecutive group of patients with IBD who were referred for consultation in an MDT clinic at a tertiary referral center in Israel. Results: Over 1 year, 118 patients were evaluated in the MDT-IBD-DERMA clinic: 68 (57.6%) males; age – 35.2 ± 13.5 years, disease duration – 7.1 (interquartile range: 3.7–13.9) years; Crohn's disease – 94/118 (79.6%). Skin eruption induced by an anti–tumor necrosis factor (TNF) were the most common diagnoses [46/118 (39%)], including psoriasiform dermatitis (PD) – 31/46 (67.4%) and inflammatory alopecia (IA) – 15/46 (32.6%). Of these, 18 patients (39.1%) continued the anti-TNF agent concomitantly with a topical or systemic anti-inflammatory agent to control the eruption. The remaining 28 patients (60.9%) discontinued the anti-TNF, of whom 16/28 (57.1%) switched to ustekinumab. These strategies effectively treated the majority [38/46 (82.6%)] of patients. Continuation of the anti-TNF was possible in a significantly higher proportion of patients with PD: 12/31 (38.7%) than only one in the IA group, p = 0.035. There was a higher switch to ustekinumab among the IA 7/15 (46.6%) compared with the PD 7/31 (22.6%) group, P =.09. Following IBD-DERMA advised intervention, IBD deteriorated in 9/4 6(19.5%) patients, 5/9 on ustekinumab (PD versus IA, P = NS). Conclusion: Shared decision-making in an integrated IBD-DERMA clinic allowed successful control of skin eruptions while preserving control of the underlying IBD in more than 80% of cases. Patients with IA profited from a switch to ustekinumab. [ABSTRACT FROM AUTHOR]

Oligodendrocyte precursor cells (OPCs) are present in demyelinated lesions of multiple sclerosis (MS) patients. However, their differentiation into functional oligodendrocytes is insufficient, and most lesions evolve into nonfunctional astroglial scars. Blockade of bone morphogenetic protein (BMP) signaling induces differentiation of OPCs into myelin-producing oligodendrocytes. We studied the effect of specific blockade of BMP-2/4 signaling, by intravenous (IV) treatment with anti-BMP-2/4 neutralizing mAb in both the inflammatory model of relapsing experimental autoimmune encephalomyelitis (R-EAE) and the cuprizone-toxic model of demyelination in mice. Administration of anti-BMP-2/4 to R-EAE-induced mice, on day 9 post-immunization (p.i.), ameliorated R-EAE signs, diminished the expression of phospho-SMAD1/5/8, primarily within the astrocytic lineage, increased the numbers of de novo immature and mature oligodendrocytes, and reduced the numbers of newly generated astrocytes within the spinal cord as early as day 18 p.i. This effect was accompanied with elevated remyelination, manifested by increased density of remyelinating axons (0.8 < g-ratios < 1), and reduced fully demyelinated and demyelinating axons, in the anti-BMP-2/4-treated R-EAE mice, studied by electron microscopy. No significant immunosuppressive effect was observed in the CNS and in the periphery, during the peak of the first attack, or at the end of the experiment. Moreover, IV treatment with anti-BMP-2/4 mAb in the cuprizone-challenged mice augmented the numbers of mature oligodendrocytes and remyelination in the corpus callosum during the recovery phase of the disease. Based on our findings, the specific blockade of BMP-2/4 has a therapeutic potential in demyelinating disorders such as MS, by inducing early oligodendrogenesis-mediated remyelination in the affected tissue. [ABSTRACT FROM AUTHOR]

This paper suggests a new technique to facilitate consistent transition between planning and production stages of small lots of complex products (in quantities that do not justify full automation). Despite the usage of modern approaches such as design for assembly and design for manufacturing the typical product planning ends up before production planning begins, instead of having a unified seamless planning process. This paper presents a new three stage technique to fill the gap between product planning and production. The paper shows how to generate a rigorous production plan by: (1) extending the Bill-of-Materials to include additional required information, (2) constructing an assembly ‘method prototype’ and (3) using the ‘method prototype’ to calculate time standards for executing the assembly. A case study illustrates the proposed technique. [ABSTRACT FROM PUBLISHER]

Background and Aims: Skin eruptions are prevalent among patients with inflammatory bowel diseases (IBD), often associated with therapies and frequently leading to dermatological consults and treatment interruptions. We aimed to assess the impact of joint shared decision-making in a multidisciplinary (MDT) IBD-DERMA clinic. Methods: This retrospective cohort study assessed a consecutive group of patients with IBD who were referred for consultation in an MDT clinic at a tertiary referral center in Israel. Results: Over 1 year, 118 patients were evaluated in the MDT-IBD-DERMA clinic: 68 (57.6%) males; age – 35.2 ± 13.5 years, disease duration – 7.1 (interquartile range: 3.7–13.9) years; Crohn's disease – 94/118 (79.6%). Skin eruption induced by an anti–tumor necrosis factor (TNF) were the most common diagnoses [46/118 (39%)], including psoriasiform dermatitis (PD) – 31/46 (67.4%) and inflammatory alopecia (IA) – 15/46 (32.6%). Of these, 18 patients (39.1%) continued the anti-TNF agent concomitantly with a topical or systemic anti-inflammatory agent to control the eruption. The remaining 28 patients (60.9%) discontinued the anti-TNF, of whom 16/28 (57.1%) switched to ustekinumab. These strategies effectively treated the majority [38/46 (82.6%)] of patients. Continuation of the anti-TNF was possible in a significantly higher proportion of patients with PD: 12/31 (38.7%) than only one in the IA group, p = 0.035. There was a higher switch to ustekinumab among the IA 7/15 (46.6%) compared with the PD 7/31 (22.6%) group, P =.09. Following IBD-DERMA advised intervention, IBD deteriorated in 9/4 6(19.5%) patients, 5/9 on ustekinumab (PD versus IA, P = NS). Conclusion: Shared decision-making in an integrated IBD-DERMA clinic allowed successful control of skin eruptions while preserving control of the underlying IBD in more than 80% of cases. Patients with IA profited from a switch to ustekinumab. [ABSTRACT FROM AUTHOR]

In this study, we suggest combining the monitoring of actual examination time used with grades in order to assess examination time extensions in terms of access provision and expected outcome. Using naturally-occurring data collected from a large sample (N = 2315) of undergraduate engineering students, we argue that extended examination time may be regarded as providing equal access when a disabled student actually utilizes more examination time than a normally achieving student, regardless of the grade obtained. We further argue that extended examination time may be regarded as resulting in the expected outcome when a disabled student either (a) utilizes less or equal examination time and achieve grades that are lower than a normally achieving student, or (b) utilizes more examination time and achieve grades that are equal to a normally achieving student. In our data, equal access was provided in all courses (i.e. disabled students utilized more time than normal achievers), but the expected outcome (i.e. equal grades) was not observed in software and English examinations. The results of this study emphasize the importance of monitoring actual time usage in addition to performance measures when assessing examination time extensions. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate how learning disabilities (LDs), in combination with accommodations, affect the performance of a decision-tree to predict the stability of academic behaviour of undergraduate engineering students. Additionally, this study presents several examples to illustrate how a college could use the resultant model to choose the appropriate accommodation to give a student with a learning disability, from among a set of possible accommodations. The findings show that: (1) The models yield superior performance in predicting the stability category for a given student when the LD and accommodation factors are included; (2) Different types of accommodation action have different effects on the stability of academic behaviour, depending on the student pattern. Such a model could be useful for engineering faculties, as it would allow them to predict the stability of academic behaviour and to provide early intervention for students who are likely to need additional support. [ABSTRACT FROM AUTHOR]

Security and intelligence agencies around the world invest considerable resources in preventing terrorist attacks, as these may cause strategic damage, national demoralization, infringement of sovereignty, and government instability. Recently, data-mining techniques have evolved to allow identification of patterns and associations in criminal data that were not apparent using traditional analysis. The aim of this paper is to illustrate how to use interpretable classification algorithms to identify subgroups ("patterns") of terrorist incidents that share common characteristics and that result in mass fatalities. This approach can produce insights far beyond those of conventional macro-level studies that use hypothesis-testing and regression models. In addition to this methodological contribution, from a practical perspective, exploring the characteristics identified in the "patterns" can lead to prevention strategies, such as alteration of the physical or systemic environment. This is in line with situational crime prevention (SCP) theory. We apply our methodology to the Global Terrorism Database (GTD). We present three examples in which terror attacks that are described by a particular pattern (set of characteristics) resulted in a high probability of mass casualties, while attacks that differ in just one of these characteristics (i.e., month of attack, geographical area targeted, or type of attack) resulted in far fewer casualties. We propose exploration of the differentiating characteristic as a means of reducing the probability of mass-fatality terrorist incidents. [ABSTRACT FROM AUTHOR]

Background: The pathophysiology of multiple sclerosis involves an autoimmune and a neurodegenerative mechanism. Central nervous system-infiltrating immune cells in multiple sclerosis also possess a neuroprotective activity through secretion of neurotrophins, such as brain-derived neurotrophic factor. Fingolimod was shown to slow the progression of disability and loss of brain volume.Objective: The objective of this study was to explore whether fingolimod induces secretion of neurotrophins by immune cells.Methods: Blood was drawn from 21 patients before the initiation of treatment with fingolimod and at 6 and 12 months of follow-up. The levels of the neurotrophic factors brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, β-nerve growth factor, neurotrophin-3, neurotrophin-4, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor were screened in the supernatants of separated T cells and monocyte cultures using a customized, multiplex enzyme-linked immunosorbent assay. Brain-derived neurotrophic factor levels were further validated by a specific enzyme-linked immunosorbent assay.Results: Treatment with fingolimod significantly increased brain-derived neurotrophic factor secretion from T cells. A specific enzyme-linked immunosorbent assay confirmed these results in the supernatant of T cells after 6 and 12 months of therapy.Conclusions: T cells that reach the bloodstream of fingolimod-treated patients with multiple sclerosis may contribute to the neuroprotective effect of this therapy by increased secretion of brain-derived neurotrophic factor. This mechanism of action of fingolimod in patients with multiple sclerosis has not been previously reported. [ABSTRACT FROM AUTHOR]

Background and Aims: Many inflammatory bowel disease (IBD) patients do not respond to medical therapy. Tofacitinib is a first-in-class, partially selective inhibitor of Janus kinase, recently approved for treating patients with ulcerative colitis (UC). We describe our experience with the use of tofacitinib for treatment of patients with moderate-to-severe IBD.Methods: This is a retrospective, observational study of the use of tofacitinib in IBD. Patients with medically resistant IBD were treated orally with 5 mg or 10 mg twice daily. Clinical response and adverse events were assessed at 8, 26, and 52 weeks. Objective response was assessed endoscopically, radiologically, and biochemically.Results: 58 patients (53 UC, 4 Crohn's, 1 pouchitis) completed at least 8 weeks of treatment with tofacitinib. 93% of the patients previously failed treatment with anti-TNF. At 8 weeks of treatment, 21 patients (36%) achieved a clinical response, and 19 (33%) achieved clinical remission. Steroid-free remission at 8 weeks was achieved in 15 patients (26%). Of the 48 patients followed for 26 weeks, 21% had clinical, steroid-free remission. Of the 26 patients followed for 12 months, 27% were in clinical, steroid-free remission. Twelve episodes of systemic infections were noted, mostly while on concomitant steroids. One episode of herpes zoster infection was noted during follow-up.Conclusions: In this cohort of patients with moderate-to-severe, anti-TNF resistant IBD, tofacitinib induced clinical response in 69% of the patients. 27% were in clinical, steroid-free remission by 1 year of treatment. Tofacitinib is an effective therapeutic option for this challenging patient population. [ABSTRACT FROM AUTHOR]

Using a grounded theory approach and real-time data capturing the expressions and behaviors of help givers and recipients in the course of their interactions at work, we generated a typology of interactive and episodic helping behaviors (both help giving and receiving) and applied it to explore if, when, and how the behavioral configurations of the two dyad partners changed from one exchange episode to the next. Our findings suggest that certain configurations of helping behavior often shifted in a rather predictable manner over the course of the helping exchange in response to the behavior of the dyad partner, whereas other configurations were "static," tending to be repeated by dyad partners once they first appeared. By examining help giving and receiving as a pattern in a stream of dynamic, dyadic, and cross-episodic behaviors, and more importantly, developing a typology allowing scholars to differentiate between different types of dyadic patterns, our study provides important insights into the varying nature of helping trajectories, as well as the way in which exchange dynamics may predict change or stability in specific helping exchanges. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is common in patients with inflammatory bowel diseases. The vitamin D receptor (VDR) is a nuclear hormone receptor mediating the activity of vitamin D hormone. Our previous studies showed that intestinal epithelial VDR signaling inhibits colitis by protecting the mucosal epithelial barrier, and this activity is independent of non-epithelial immune VDR actions. Interleukin (IL)-10-deficient mouse is a chronic colitis model that develops colitis due to aberrant immune responses. Here we used IL-10 null (IL-10KO) model to assess the anti-colitic activity of epithelial VDR in the setting of an aberrant immune system. Methods: We crossed IL-10KO mice with villin promoter-driven human (h) VDR transgenic (Tg) mice to generate IL-10KO mice that carry the hVDR transgene in intestinal epithelial cells (IL-10KO/Tg). IL-10KO and IL-10KO/Tg littermates were studied in parallel and followed for up to 25 weeks. Results: By 25 weeks of age, accumulatively 79 % IL-10KO mice developed prolapse, whereas only 40 % IL-10KO/Tg mice did so ( P < 0.001). Compared with IL-10KO mice, IL-10KO/Tg littermates showed markedly reduced mucosal inflammation in both small and large intestines, manifested by attenuation in immune cell infiltration and histological damage and a marked decrease in pro-inflammatory cytokine production. IL-10KO/Tg mice also showed reduced intestinal epithelial cell apoptosis as a result of diminished PUMA induction and caspase 3 activation. Conclusion: These observations demonstrate that targeting hVDR expression to intestinal epithelial cells is sufficient to attenuate spontaneous colitis caused by an ill-regulated immune system, confirming a critical role of the epithelial VDR signaling in blocking colitis development. [ABSTRACT FROM AUTHOR]

Member Assistance Programs (MAPs) are peer-based Employee Assistance Programs (EAPs) that originated in the United States and have been transferred to other countries. The current case study aims at exploring the cross-cultural transferability of MAPs by comparing the first MAP established in Israel with the prototypical American program. The observed differences are explained on the basis of cross-cultural organizational theory. In addition, empirically-testable hypotheses regarding the cross-cultural variations of MAPs are developed. The implications for EAP and MAP research and practice are discussed. [ABSTRACT FROM AUTHOR]

The effect of the inflammatory response on regenerative processes in the brain is complex. This complexity is even greater when the cause of the tissue damage is an autoimmune response. Multiple sclerosis (MS) is an immune-mediated disease in which demyelination foci are formed in the central nervous system. The degree of repair through oligodendrocyte regeneration and remyelination is insufficient. Ephrins are membrane-bound ligands activating tyrosine kinase signaling proteins that are known to have an inhibitory effect on oligodendrocyte regeneration. In this study, we examined the expression of ephrins on immune cells of 43 patients with relapsing-remitting (RR) MS compared to 27 matched healthy controls (HC). We found an increased expression of ephrin-A2, -A3 and -B3, especially on T cell subpopulations. We also showed overexpression of ephrins on immune cells of patients with RR-MS that increases the forward signaling pathway and that expression of ephrins on immune cells has an inhibitory effect on the differentiation of oligodendrocyte precursor cells (OPCs) in vitro. Our study findings support the concept that the immune activity of T cells in patients with RR-MS has an inhibitory effect on the differentiation capacity of OPCs through the expression and forward signaling of ephrins. [ABSTRACT FROM AUTHOR]

Forchlorfenuron (FCF) is a synthetic plant cytokinin that has been shown to alter yeast and mammalian septin organization. Septins are a highly conserved family of GTP-binding cytoskeletal proteins. Mammalian septins are involved in diverse cellular processes including tumorigenesis. We have been studying the interaction between septin 9 isoform 1 (SEPT9_i1) and hypoxia inducible factor-1α (HIF-1α), the oxygen regulated subunit of HIF-1. HIF-1 is a key transcription factor in the hypoxic responses pathway, and its activation has been observed in carcinogenesis and numerous cancers. SEPT9_i1/HIF-1α interaction plays an important role in upregulation of HIF-1 transcriptional activity by preventing HIF-1α’s ubiquitination and degradation leading to increased tumor growth and angiogenesis. We tested the hypothesis whether FCF affects SEPT9_i1 filamentous structures and consequently HIF-1 pathway in cancer cells. We showed that FCF suppresses tumorigenic properties, including proliferation, migration and transformation, in prostate cancer cells. FCF did not alter SEPT9_i1 steady state protein expression levels but it affected its filamentous structures and subcellular localization. FCF induced degradation of HIF-1α protein in a dose- and time-dependent manner. This inhibition was also shown in other common cancer types tested. Rapid degradation of HIF-1α protein levels was accompanied by respective inhibition in HIF-1α transcriptional activity. Moreover, HIF-1α protein half-life was markedly decreased in the presence of FCF compared with that in the absence of FCF. The FCF-induced degradation of HIF-1α was mediated in a significant part via the proteasome. To the best of our knowledge, this is the first demonstration of specific manipulation of septin filaments by pharmacological means having downstream inhibitory effects on the HIF-1 pathway. [ABSTRACT FROM AUTHOR]