A Real-time Calculus Approach for Integrating Sporadic Events in Time-triggered Systems

In time-triggered systems, where the schedule table is predefined and statically configured at design time, sporadic event-triggered (ET) tasks can only be handled within specially dedicated slots or when time-triggered (TT) tasks finish their execution early. We introduce a new paradigm for synthesizing TT schedules that guarantee the correct temporal behavior of TT tasks and the schedulability of sporadic ET tasks with arbitrary deadlines. The approach first expresses a constraint for the TT task schedule in the form of a maximal affine envelope that guarantees that as long as the schedule generation respects this envelope, all sporadic ET tasks meet their deadline. The second step consists of modeling this envelope as a burst limiting constraint and building the TT schedule via simulating a modified Least-Laxity-First (LLF) scheduler. Using this novel technique, we show that we achieve equal or better schedulability and a faster schedule generation for most use-cases compared to other approaches inspired by, e.g., hierarchical scheduling. Moreover, we present an extension to our method that finds the most favourable schedule for TT tasks with respect to ET schedulability, thus increasing the probability of the computed TT schedule remaining feasible when ET tasks are later added or changed

L’intégration d’un traitement psychologique en réadaptation cardiaque à l’Hôpital Montfort : une diminution des risques associés aux maladies cardiaques

Les buts de cette étude étaient l’intégration et la mise à l’épreuve d’un traitement psychologique au sein du Service de réadaptation cardiaque à l’Hôpital Montfort. Des patients (hommes et femmes), âgés entre 35 et 85 ans, avec une maladie cardiaque et qui se plaignaient de symptômes d’anxiété et de dépression ont participé à cette étude. Les résultats suggèrent que la thérapie cognitivo-comportementale (TCC) peut réduire de façon significative les symptômes de dépression et d’anxiété chez les patients cardiaques. Dans notre échantillon (N = 11), les patients ayant suivi au moins dix séances de traitement ont présenté une diminution importante de leurs symptômes, et personne ne répondait aux critères d’un diagnostic de dépression ou d’anxiété après l’intervention.The goals of the study were to introduce and test a psychological treatment at the Montfort Hospital’s Cardiac Rehabilitation Service. The participants were male and female patients between the ages of 35 and 85 with heart disease who reported symptoms of anxiety and depression. The results suggest that cognitive-behavioural therapy (CBT) may significantly reduce symptoms of depression and anxiety in cardiac patients. In our sample (N = 11), patients completing at least 10 treatment sessions showed a significant decrease in their symptoms, and none met the criteria for a diagnosis of depression or anxiety after the treatment

Transcript abundance of photorhabdus insect-related (Pir) toxin in Manduca sexta and Galleria mellonella infections

In this study, we assessed pirAB toxin transcription in Photorhabdus luminescens laumondii (strain TT01) (Enterobacteriaceae) by comparing mRNA abundance under in vivo and in vitro conditions. In vivo assays considered both natural and forced infections with two lepidopteran hosts: Galleria mellonella and Manduca sexta. Three portals of entry were utilized for the forced infection assays: (a) integument; (b) the digestive route (via mouth and anus); and (c) the tracheal route (via spiracles). We also assessed plu4093-2 transcription during the course of a natural infection; this is when the bacteria are delivered by Heterorhabditis bacteriophora nematodes. Transcript abundance in G. mellonella was higher than in M. sexta at two of the observed time points: 15 and 18 h. Expression of pirAB plu4093-2 reached above endogenous control levels at 22 h in G. mellonella but not in M. sexta. Overall, pirAB plu4093-2 transcripts were not as highly expressed in M. sexta as in G. mellonella, from 15 to 22 h. This is the first study to directly compare pirAB plu4093-2 toxin transcript production considering different portals of entry

Exploring tandem ruthenium-catalyzed hydrogen transfer and SNAr chemistry

A hydrogen-transfer strategy for the catalytic functionalization of benzylic alcohols via electronic arene activation, accessing a diverse range of bespoke diaryl ethers and aryl amines in excellent isolated yields (38 examples, 70% average yield), is reported. Taking advantage of the hydrogen-transfer approach, the oxidation level of the functionalized products can be selected by judicious choice of simple and inexpensive additives

Mental health stigma at primary health care centres in Lebanon: qualitative study

Background: Mental health-related stigma is a global public health concern and a major barrier to seeking care. In this study, we explored the role of stigma as a barrier to scaling up mental health services in primary health care (PHC) centres in Lebanon. We focused on the experiences of Healthcare Providers (HCPs) providing services to patients with mental health conditions (MHCs), the views of policy makers, and the perceptions of stigma or discrimination among individuals with MHCs. This study was conducted as part of INDIGO-PRIMARY, a larger multinational stigma reduction programme. Methods: Semi-structured qualitative interviews (n = 45) were carried out with policy makers (n = 3), PHC management (n = 4), PHC staff (n = 24), and service users (SUs) (n = 14) between August 2018 and September 2019. These interviews explored mental health knowledge, attitudes and behaviour of staff, challenges of providing treatment, and patient outcomes. All interviews were coded using NVivo and a thematic coding framework. Results: The results of this study are presented under three themes: (1) stigma at PHC level, (2) stigma outside PHC centres, and (3) structural stigma. SUs did not testify to discrimination from HCPs but did describe stigmatising behaviour from their families. Interestingly, at the PHC level, stigma reporting differed among staff according to a power gradient. Nurses and social workers did not explicitly report incidents of stigma but described patients with MHCs as uncooperative, underscoring their internalized negative views on mental health. General practitioners and directors were more outspoken than nurses regarding the challenges faced with mental health patients. Mental health professionals revealed that HCPs still hold implicitly negative views towards patients with MHCs however their attitude has improved recently. Our analysis highlights five layers of stigma affecting SUs. Conclusion: This qualitative study reveals that stigma was still a key concern that affects patients with MHC. SUs reported experiencing overt stigmatising behaviour in the community but less explicit discrimination in a PHC setting. Our findings emphasise the importance of (1) combatting structural stigma through legal reform, (2) addressing interpersonal stigma, (3) committing PHC management to deliver high quality mental health integrated services, and (4) reducing intrapersonal stigma by building public empathy. Keywords: Mental health Stigma; Primary health care (PHC); Qualitative researc

Reading faces: differential lateral gaze bias in processing canine and human facial expressions in dogs and 4-year-old children

Sensitivity to the emotions of others provides clear biological advantages. However, in the case of heterospecific relationships, such as that existing between dogs and humans, there are additional challenges since some elements of the expression of emotions are species-specific. Given that faces provide important visual cues for communicating emotional state in both humans and dogs, and that processing of emotions is subject to brain lateralisation, we investigated lateral gaze bias in adult dogs when presented with pictures of expressive human and dog faces. Our analysis revealed clear differences in laterality of eye movements in dogs towards conspecific faces according to the emotional valence of the expressions. Differences were also found towards human faces, but to a lesser extent. For comparative purpose, a similar experiment was also run with 4-year-old children and it was observed that they showed differential processing of facial expressions compared to dogs, suggesting a species-dependent engagement of the right or left hemisphere in processing emotions

Sex-Specific Associations Between Trauma Exposure, Pubertal Timing, and Anxiety in Black Children

Recent research has linked early life stress (ELS), such as trauma exposure, with early puberty. Early puberty has also been identified as a risk factor for poor mental health outcomes. However, these two paths have primarily been examined independently. In addition, more studies have examined these associations in girls than boys, and findings for boys remain mixed. We hypothesized that early puberty (relative to peers) would be positively associated with both prior trauma exposure and concurrent anxiety symptoms. We anticipated that these associations might differ by sex. We tested these hypotheses within a cross-sectional sample of 133 8- to 13-year-old Black girls and boys with trauma exposure. The association between trauma and accelerated pubertal timing was sex-specific: it was positive for girls and negative for boys. We stratified subsequent analyses by sex. Regression analyses indicated that early puberty relative to peers predicted more anxiety symptoms for girls but not boys, after accounting for trauma exposure. A statistical mediation analysis indicated that, for girls, the positive association between trauma exposure and anxiety was partially mediated by pubertal timing. These results indicate that trauma exposure may have sex-specific effects on pubertal timing and anxiety risk in Black children. We also found that, for girls, trauma may increase risk for adverse outcomes by prompting earlier puberty, which is linked to higher anxiety. These findings are consistent with cascading effects of trauma across development, and highlight the need for further study of sex-specific mechanisms

Cancer cell CCR2 orchestrates suppression of the adaptive immune response.

C-C chemokine receptor type 2 (CCR2) is expressed on monocytes and facilitates their recruitment to tumors. Though breast cancer cells also express CCR2, its functions in these cells are unclear. We found that Ccr2 deletion in cancer cells led to reduced tumor growth and approximately twofold longer survival in an orthotopic, isograft breast cancer mouse model. Deletion of Ccr2 in cancer cells resulted in multiple alterations associated with better immune control: increased infiltration and activation of cytotoxic T lymphocytes (CTLs) and CD103+ cross-presenting dendritic cells (DCs), as well as up-regulation of MHC class I and down-regulation of checkpoint regulator PD-L1 on the cancer cells. Pharmacological or genetic targeting of CCR2 increased cancer cell sensitivity to CTLs and enabled the cancer cells to induce DC maturation toward the CD103+ subtype. Consistently, Ccr2-/- cancer cells did not induce immune suppression in Batf3-/- mice lacking CD103+ DCs. Our results establish that CCR2 signaling in cancer cells can orchestrate suppression of the immune response

New Insights Into the Clinical and Molecular Spectrum of the Novel CYFIP2-Related Neurodevelopmental Disorder and Impairment of the WRC-Mediated Actin Dynamics

Purpose: A few de novo missense variants in the cytoplasmic FMRP-interacting protein 2 (CYFIP2) gene have recently been described as a novel cause of severe intellectual disability, seizures, and hypotonia in 18 individuals, with p.Arg87 substitutions in the majority. Methods: We assembled data from 19 newly identified and all 18 previously published individuals with CYFIP2 variants. By structural modeling and investigation of WAVE-regulatory complex (WRC)-mediated actin polymerization in six patient fibroblast lines we assessed the impact of CYFIP2 variants on the WRC. Results: Sixteen of 19 individuals harbor two previously described and 11 novel (likely) disease-associated missense variants. We report p.Asp724 as second mutational hotspot (4/19 cases). Genotype–phenotype correlation confirms a consistently severe phenotype in p.Arg87 patients but a more variable phenotype in p.Asp724 and other substitutions. Three individuals with milder phenotypes carry putative loss-of-function variants, which remain of unclear pathogenicity. Structural modeling predicted missense variants to disturb interactions within the WRC or impair CYFIP2 stability. Consistent with its role in WRC-mediated actin polymerization we substantiate aberrant regulation of the actin cytoskeleton in patient fibroblasts. Conclusion: Our study expands the clinical and molecular spectrum of CYFIP2-related neurodevelopmental disorder and provides evidence for aberrant WRC-mediated actin dynamics as contributing cellular pathomechanism