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Abstract Background Many common diseases exhibit uncontrolled mTOR signaling, prompting considerable interest in the therapeutic potential of mTOR inhibitors, such as rapamycin, to treat a range of conditions, including cancer, aging-related pathologies, and neurological disorders. Despite encouraging preclinical results, the success of mTOR interventions in the clinic has been limited by off-target side effects and dose-limiting toxicities. Improving clinical efficacy and mitigating side effects require a better understanding of the influence of key clinical factors, such as sex, tissue, and genomic background, on the outcomes of mTOR-targeting therapies. Results We assayed gene expression with and without rapamycin exposure across three distinct body parts (head, thorax, abdomen) of D. melanogaster flies, bearing either their native melanogaster mitochondrial genome or the mitochondrial genome from a related species, D. simulans. The fully factorial RNA-seq study design revealed a large number of genes that responded to the rapamycin treatment in a sex-dependent and tissue-dependent manner, and relatively few genes with the transcriptional response to rapamycin affected by the mitochondrial background. Reanalysis of an earlier study confirmed that mitochondria can have a temporal influence on rapamycin response. Conclusions We found significant and wide-ranging effects of sex and body part, alongside a subtle, potentially time-dependent, influence of mitochondria on the transcriptional response to rapamycin. Our findings suggest a number of pathways that could be crucial for predicting potential side effects of mTOR inhibition in a particular sex or tissue. Further studies of the temporal response to rapamycin are necessary to elucidate the effects of the mitochondrial background on mTOR and its inhibition.

IntroductionThis study investigates the confounding effects of reverse-coded items on the measurement of confidence in mathematics using data from the 2019 Trends in International Mathematics and Science Study (TIMSS).MethodsThe sample came from the Saudi Arabian cohort of 8th graders in 2019 involving 4,515 students. Through mixture modeling, two subgroups responding in similar ways to reverse-coded items were identified representing approximately 9% of the sample.ResultsTheir response to positively valenced and negatively valenced items showed inconsistency and the observed unexpected response patterns were further verified using Lz*, U3, and the number of Guttman errors person fit indicators. Psychometric analyses on the full sample and the truncated sample after deleting the aberrant responders indicated significant improvements in both internal consistency reliability and factorial validity.DiscussionIt was concluded that reverse-coded items contribute to systematic measurement error that is associated with distorted item level parameters that compromised the scale’s reliability and validity. The study underscores the need for reconsideration of reverse-coded items in survey design, particularly in contexts involving younger populations and low-achieving students.

Background Abdominal aortic aneurysm (AAA) screening/surveillance is implemented widely. Those in AAA-surveillance are at high-risk of cardiovascular-events. We developed an intervention, called CRISP, using intervention-mapping, to reduce cardiovascular-risk in AAA-surveillance. This study tested the CRISP intervention in routine clinical-care. Methods The CRISP intervention, consisting of a nurse-led cardiovascular risk assessment and subsequent lifestyle change support using a self-care workbook and low-intensity nurse input was delivered in two screening/surveillance programmes. Those consenting to take part were followed-up with cardiovascular-assessments. Fidelity of intervention-delivery was assessed quantitatively/qualitatively. Results 40 men (mean age 75 ± 7 years) took part over four months and followed-up for a minimum six months. A sub-group of 25 patients and nine Health Care Professionals (HCPs) were interviewed. The median number of risk-factors that patients chose to focus on was two (range 0 to 4), with physical activity (n=17) being the most popular. Participants who had a ‘red light’ risk factor for stress, low mood, smoking or alcohol intake were offered a referral to appropriate services. Two were offered referral to mental-health services and took it up, three declined referrals to smoking or alcohol support services. The fidelity of intervention-delivery (a score intervention components delivered to each patient based on a score from 0 to 5, with 5 being highest delivery fidelity) was generally low. The highest mean score (on a 0-5 scale) for the nurse assessment was 1.5 for engaging the participant, lowest 0.5 for exploring the importance for selected lifestyle behaviours. In qualitative interviews, the intervention was liked by patients/HCPs. Based on qualitative interviews and observations, the low fidelity of intervention-delivery was due to intervention-training not being detailed. Conclusions CRISP can be delivered in AAA-surveillance, but fidelity of delivery is low. The intervention and its training need to be refined/tested before wider implementation. Registration ISRCTN9399399518/11/20).

Abstract Background For students to feel happy and supported in school, it is important that their views are taken seriously and integrated into school policies. However, limited information is available how the voices of immigrant students are considered in European school contexts. This study generated evidence from written documents to ascertain how student voice practices are described at school websites. Methods Between 2 March and 8 April 2021, we reviewed the policy documents publicly available on school websites. The schools located in areas of high immigration in six European countries: Austria, England, Finland, Germany, Romania, and Switzerland. The READ approach was used to guide the steps in the document analysis in the context of policy studies (1) ready the materials, 2) data extraction, 3) data analysis, 4) distil the findings). A combination of qualitative and quantitative approaches with descriptive statistics (n, %, Mean, SD, range) was used for analysis. Results A total of 412 documents (305 schools) were extracted. Based on reviewing school websites, reviewers’strongly agreed’ in seven documents (2%) that information related to seeking student voices could be easily found. On the contrary, in 247 documents (60%), reviewers strongly indicated that information related to seeking student voices was missing. No clear characteristics could be specified to identify those schools were hearing students’ voices is well documented. The most common documents including statements related to student voice were anti-bullying or violence prevention strategies (75/412) and mission statements (72/412). Conclusions Our document analysis based on publicly accessible school websites suggest that student voices are less frequently described in school written policy documents. Our findings provide a baseline to further monitor activities, not only at school level but also to any governmental and local authorities whose intention is to serve the public and openly share their values and practices with community members. A deeper understanding is further needed about how listening to student voices is realized in daily school practices.

Kate E Lee,1 Violet Y Tu,1 Adam S Faye2 1Department of Medicine, Duke University School of Medicine, Durham, NC, USA; 2Department of Gastroenterology, New York University School of Medicine, New York, NY, USACorrespondence: Adam S Faye, Medicine & Population Health, NYU Langone Division of Gastroenterology, New York University, 303 East 33rd Street, New York, NY, 10016, USA, Tel +1 (855) 698-4232, Fax +1 212-263-3096, Email adam.faye@nyulangone.orgAbstract: Refractory Crohn’s disease, defined as ongoing inflammation despite the trial of multiple advanced therapies, impacts a number of individuals with Crohn’s disease, and leads to significant burden in quality of life and cost. Interventions such as early implementation of advanced therapies, optimization of current therapies prior to switching to an alternative, as well as understanding the overlapping pathophysiology between immune-mediated disorders, however, can help shift the current landscape and reduce the number of patients with refractory disease. As such, in this review we summarize the key takeaways of the latest research in the management of moderate-to-severe Crohn’s disease, focusing on maximization of our currently available medications, while also exploring topics such as combination advanced therapies. We also describe evidence for emerging and alternative therapeutic modalities, including fecal microbiota transplant, exclusive enteral feeding, hyperbaric oxygen, stem cell therapy, bone marrow transplant, and posaconazole, with a focus on both the potential impact and specific indications for each.Keywords: Crohn’s disease, surgery, advanced therapies, biologics

Ilhame Anwar,1 Aissatou Faye,1 Jessica Pereira Gonçalves,1 Laélia Briand Madrid,1 Gwenaëlle Maradan,2 Laurence Lalanne,3,4,* Marie Jauffret-Roustide,5– 7,* Marc Auriacombe,8– 10,* Perrine Roux1 1Aix Marseille Univ, Inserm, IRD, SESSTIM, Sciences Economiques & Sociales de la Santé & Traitement de l’Information Médicale, ISSPAM, Marseille, France; 2ORS PACA, Observatoire régional de la santé Provence-Alpes-Côte d’Azur, Marseille, France; 3INSERM 1114, Department of Psychiatry and Addictology, University Hospital of Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France; 4Department of Psychiatry and Addictology, University Hospital of Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, 67000, France; 5CERMES3 (Inserm U988/UMR CNRS 8211/EHESS/Paris Descartes University), Paris, France; 6British Columbia Center on Substance Use, Vancouver, Canada; 7Baldy Center on Law and Social Policy, Buffalo University, New York, NY, USA; 8Univ. Bordeaux, Bordeaux, France; 9Addiction Team (Laboratoire de psychiatrie)/SANPSY, CNRS USR 3413, Bordeaux, France; 10Pôle Addictologie, CH Charles Perrens and CHU de Bordeaux, Bordeaux, France*These authors contributed equally to this workCorrespondence: Ilhame Anwar, Sciences Economiques et Sociales de la Santé et Traitement de l’Information Médicale (SESSTIM), Faculté des sciences médicales et paramédicales, 27 Bd Jean Moulin 13385 Marseille Cedex 5, Marseille, France, Email ilhame.anwar@inserm.frPurpose: Injection drug use is strongly associated with stigmatization by loved ones, healthcare providers, and society in general. This stigmatization can have negative consequences on the health of people who inject drugs (PWID) and limit their access to care. Women who inject drugs face greater stigma than men because of gendered social norms and the intersectional effect between gender and drug use identities. For this analysis, we aimed to study discrimination - which is closely linked to stigmatization - experienced by PWID, considering the intersectionality between drug use discrimination and gender discrimination in the French context.Methods: We used data from the COSINUS cohort study, conducted between June 2016 and May 2019 in four French cities. We selected 427 of the 665 PWID who regularly injected drugs enrolled in COSINUS, at three months of follow-up, and performed multivariable logistic regression to identify factors associated with self-reported drug use discrimination.Results: Women comprised 20.6% of the study sample. Sixty-nine percent of the participants declared drug use discrimination and 15% gender discrimination. In the multivariable regression analysis, PWID who had hurried injection out of fear of being seen were almost twice as likely to have experienced drug use discrimination (OR [95% CI]: 1.77 [1.15, 2.74], p = 0.010). Likewise, women experiencing gender discrimination were almost three times as likely to have experienced drug use discrimination (OR [95% CI]: 2.84 [1.07,7.56], p=0.037).Conclusion: Women who inject drugs experienced gender and drug use intersectional discrimination. This could be a reason for the low attendance rates of women in healthcare settings. In addition, discrimination negatively impacted injection drug use practices (eg, hurried injection), particularly for people with unstable housing who injected in public spaces. We recommend introducing adapted services in healthcare facilities for women who inject drugs, and creating a favorable social and physical environment for all PWID in order to improve their health and access to care.Keywords: gender, injection drug use, intersectionality, discrimination

IntroductionMobilizing existing creative, cultural and community assets is seen as a crucial pathway to improving public health. Schools have been identified as key institutional community assets and arts-in-nature practice has been shown to promote children’s mental health. The ‘Branching Out’ research investigated how an established arts-in-nature practice called ‘Artscaping’ could be scaled up through the mobilization of community assets including school staff and local volunteers to reach more children in primary schools.MethodsThe Branching Out model was piloted in six primary schools across Cambridgeshire with ‘Community Artscapers’ delivering 1.5-h Artscaping sessions with children outdoors for 8 weeks. Interviews were conducted with 11 Community Artscapers (six school staff and five volunteers) and four school leaders reflecting on their experiences of the Branching Out model and the data was subject to a reflexive thematic analysis.ResultsThe findings presented here discuss themes relating to mobilizing community assets, including framing the opportunity, recruiting and sustaining volunteers, training and supporting Community Artscapers, and tensions in roles and responsibilities. They also cover impacts for the children, including mental health provision, freedom in creativity and being outside, personal development, emotional impacts, and social connection, as well as impacts for the Community Artscapers, including making a difference, emotional wellbeing, personal and professional development, and connection and community.DiscussionThese findings are considered in terms of their alignment with public health policy drivers and the potential for the Branching Out model to become replicable and self-sustaining across schools to promote children’s mental health as a public health intervention.

The purpose of the present study was to understand students’ school readiness as a function of student and teacher behaviors but also school size and class size using both linear and non-linear analytical approaches. Data came from 21,903 schools distributed across 80 countries as per the 2018 cohort of the PISA database. Results pointed to a preference for the Cusp model in that the relationship between school and class sizes with achievement proved to be best described by the non-linearity of the Cusp catastrophe model. The critical benchmarks were a school size of 801 students and a class size of 27 students for which increases beyond those thresholds were linked to nonlinearity and unpredictability in school readiness. For this reason, we suggest using the cusp catastrophe model from Nonlinear Dynamical Systems Theory (NDST) to understand more fully such complex phenomena.

The purpose of the present study was to test the efficacy and appropriateness of the 4-point response option of the Principal’s Goals Scale of the SASS (1999–2000) survey. Competing dichotomous models with various conceptualizations were constructed and tested against the original polytomous conceptualization. Participants were 8,524 principals from whom 64% were males and 36% females. Principals’ goals were assessed using a 6-item scale anchored across points reflecting proximity to achieving a goal. The original polytomous conceptualization was contrasted to a dichotomous two-pole conceptualization using a model with freely estimated discriminations (two-parameter logistic model, 2PL) as well as the Rasch model assuming equal discrimination parameters. Results indicated that the 2PL dichotomous model provided the most optimal model fit. Furthermore, item-related, and person-related estimates pointed to enhanced accuracy and validity for the dichotomous model conceptualization compared to the polytomous model. It is suggested that a dichotomous scaling system is considered in subsequent measurements of the scale as a means of enhancing the accuracy and validity of the measured trait.

Frailty is a hot topic in the field of multiple myeloma (MM). Clinicians have realised that frail myeloma patients can struggle with treatment, resulting in dose reductions and treatment discontinuation, which risk shorter progression-free and overall survival. Efforts have focused on the validity of existing frailty scores and on the development of new indices to identify frail patients more accurately. This review article explores the challenges of the existing frailty scores, including the International Myeloma Working Group (IMWG) frailty score, the revised Myeloma Co-morbidity Index (R-MCI), and the Myeloma Risk Profile (MRP). We conclude that the missing link is for frailty scoring to translate into a tool useful in real-world clinical practice. The future of frailty scores lies in their ability to be woven into clinical trials, to create a robust clinical evidence base for treatment selection and dose modification, and also to identify a cohort of patients who merit additional support from the wider MM multidisciplinary team.

Η σχολική ετοιμότητα των παιδιών προσχολικής ηλικίας έχει αναγνωριστεί ως ένας σημαντικός προβλεπτικός παράγοντας για τη μετέπειτα σχολική τους προσαρμογή στο δημοτικό σχολείο. Παρόλο που η βιβλιογραφία έχει υπογραμμίσει τη σημασία της σχολικής ετοιμότητας, υπάρχουν ελάχιστα εργαλεία για την αξιολόγησή της στην Ελλάδα. Σκοπός αυτής της μελέτης ήταν ο σχεδιασμός και ο έλεγχος των ψυχομετρικών χαρακτηριστικών μιας νέας Κλίμακας Αξιολόγησης Σχολικής Ετοιμότητας για Παιδιά Προσχολικής Ηλικίας (Κ.Α.Σ.Ε.Π.Π.Η.). Η κατασκευή της Κλίμακας βασίστηκε στη σχετική βιβλιογραφία, στο ελληνικό Αναλυτικό Πρόγραμμα (Α.Π.) Σπουδών και στις αντιλήψεις των εκπαιδευτικών (νηπιαγωγών και δασκάλων της Α΄ Δημοτικού). Πραγματοποιήθηκε μια πρώτη μελέτη, στην οποία συμμετείχαν 24 νηπιαγωγοί που συμπλήρωσαν την Κλίμακα για 102 παιδιά 5-6 ετών, για να διερευνηθεί η δομή και αξιοπιστία της. Στη συνέχεια, σε δεύτερη μελέτη, 80 νηπιαγωγοί (40 Γενικής Αγωγής και 40 Ειδικής Αγωγής) συμπλήρωσαν την Κλίμακα για 280 παιδιά 5-6 ετών (200 τυπικής ανάπτυξης και 80 παιδιά με Ειδικές Εκπαιδευτικές Ανάγκες), για να επιβεβαιωθεί η δομή της Κλίμακας και να διερευνηθεί η συγχρονική εγκυρότητά της. Την επόμενη χρονιά, 280 παιδιά επαναξιολογήθηκαν ως προς τις αντίστοιχες δεξιότητες στην Α΄ Δημοτικού για να διερευνηθεί η προβλεπτική εγκυρότητα της Κλίμακας. Από τις αναλύσεις προέκυψαν δύο βασικοί παράγοντες (μαθησιακές και κοινωνικο-συναισθηματικές δεξιότητες) με έξι επιμέρους παράγοντες (προφορικός λόγος, δεξιότητες γραμματισμού, μαθηματικές δεξιότητες, κινητικές δεξιότητες, δεξιότητες αυτορρύθμισης και αυτονομίας & κοινωνικής αλληλεπίδρασης). Επίσης, αναδείχθηκε ότι η Κλίμακα χαρακτηρίζεται από υψηλά επίπεδα αξιοπιστίας καθώς και συγχρονικής και προβλεπτικής εγκυρότητας. Τα αποτελέσματα συζητούνται ως προς την αξιοποίηση της Κ.Α.Σ.Ε.Π.Π.Η. από τις/τους νηπιαγωγούς και άλλους ειδικούς για την αξιολόγηση της σχολικής ετοιμότητας των παιδιών στο νηπιαγωγείο.

Background: In 2017, WHO recognized scabies as a neglected tropical disease. The optimal treatment is not well defined in some communities. Objective: This study aimed to compare ivermectin and benzyl benzoate in the treatment of scabies in Koranic schools (or "daara") in Dakar (region). Methods: This was a prospective randomized trial conducted from January to October 2018 in Senegal. Any resident living in the selected "daara" and diagnosed with scabies was included. The administered treatments were benzyl benzoate (BB) or ivermectin. At the outset, if one case of scabies was diagnosed, all residents received treatment. Ivermectin was given at the dose of 200 mg/kg. The same treatment was repeated on day 7 for each group, the endpoint was at D14, and the data were analyzed with STATA 14. Results: Fifteen "daara" were included. Of the 959 residents, 70 were diagnosed with scabies: prevalence of 7.29%. All patients except one were male; the mean age was 9.98 years (4-17). At D14, in the BB arm, cure rate was 42.85% (n = 15) while in the ivermectin arm, this rate was 5.71% (n = 2) with a significant difference (p = 0.01). On D28, the cure rate was still higher in the BB group 57.14 (n=20) versus ivermectin 21.42 (n = 6) with a significant difference (p = 0.004). On D42, all patients except eight were cured. At D14, we found a link between the cure rate, the number of people in the room (p = 0.01), and the number of showers per week (p = 0.01) but no link with the number of people per "daara" (p = 0.163). At D28, we found a link between the cure rate, the number of people sleeping in the room (p = 0.03), and the number of showers per week (p = 0.01) but not with the number of people per "daara" (p = 0.07). Conclusion: In Koranic schools, the cure rate is higher with benzyl benzoate compared to ivermectin.

Abstract Background The present study aimed to evaluate the self-regulatory properties of anger on the performance of individuals under various motivational dispositions using an experimental design. Methods The participants were 99 university students who participated in response to extra credit. The performance of the participants was evaluated using the Tower of Hanoi task. Their anger was measured using a facial expression recognition system and arousal was assessed using a heart-rate monitoring device. Two motivational dispositions were assessed: performance goals with normative evaluative standards and performance goals with a focus on outcomes. Results The results indicated that a nonlinear function explained the relationship between anger, arousal, and achievement under different goal conditions. Specifically, the Cusp Catastrophe Model showed that anger levels beyond a critical point were associated with the unpredictability of performance during the normative goal condition, suggesting that anger disturbed the relationship between arousal and achievement. Interestingly, a linear model was relevant for explaining the same relationships during the outcome goal condition. Conclusion Thus, this study concluded that anger plays a more salient role when coupled with the pressures arising from employing interpersonal evaluative standards.

In the UK, approximately 5820 new cases of multiple myeloma (MM) are diagnosed each year. This number has increased by a third since the early 1990s. Considerable progress has been achieved in our ability to treat MM as a result of the development of new chemotherapeutic agents. MM is a disease more commonly seen in elderly individuals who frequently have pre-existing co-morbidities and are subject to social pressures that impact adversely on their quality of life (QOL). As their lives are extended by more effective treatment of MM, there is a greater need to address such issues. This review will focus on the holistic needs of a patient with MM, and how all members of the multidisciplinary team have a role. The aim is to advocate for centres to support MM patients to live well with their condition.

Abstract The climate science and applications communities need a broad and demand‐driven concept to assess physical climate conditions that are relevant for impacts on human and natural systems. Here, we augment the description of the “climatic impact‐driver” (CID) approach adopted in the Working Group I (WGI) contribution to the Intergovernmental Panel on Climate Change (IPCC) Sixth Assessment Report. CIDs are broadly defined as “physical climate system conditions (e.g., means, events, and extremes) that affect an element of society or ecosystems. Depending on system tolerance, CIDs and their changes can be detrimental, beneficial, neutral, or a mixture of each across interacting system elements and regions.” We give background information on the IPCC Report process that led to the development of the 7 CID types (heat and cold, wet and dry, wind, snow and ice, coastal, open ocean, and other) and 33 distinct CID categories, each of which may be evaluated using a variety of CID indices. This inventory of CIDs was co‐developed with WGII to provide a useful collaboration point between physical climate scientists and impacts/risk experts to assess the specific climatic phenomena driving sectoral responses and identify relevant CID indices within each sector. The CID Framework ensures that a comprehensive set of climatic conditions informs adaptation planning and risk management and may also help prioritize improvements in modeling sectoral dynamics that depend on climatic conditions. CIDs contribute to climate services by increasing coherence and neutrality when identifying and communicating relevant findings from physical climate research to risk assessment and planning activities.

The purpose of the present study was to test the measurement invariance of the baby pediatric symptom checklist (BPSC) across gender and age as a means to provide for valid comparisons in point estimates across groups. A secondary goal involved confirming the earlier identified factor structure and re-examining the presence of differentially item functioning in the BPSC across grouping variables. Participants were 601 children (322 boys and 279 girls) aged below 1 year (n = 294) and 1 year to 12 months (n = 307). Data were collected as part of the National Health Interview Survey in 2020. Results related to gender indicated satisfying all five levels of measurement and structural invariance. When testing measurement invariance across age groups, a few modifications were necessary. Specifically, partial metric invariance was satisfied after freeing slope estimates of items 1 and 2, partial scalar after freeing intercept terms of items 6 and 10, and partial residual invariance through freeing error terms of items 2 and 12. These non-invariant estimates, however, provide support for partial invariance and do not invalidate the comparison of latent means. The BPSC can be used for the valid assessment of social–emotional skills in infants up to the age of 18 months.

Context: Patients with advanced cancer from Saudi Arabia are often not well informed about diagnoses, prognoses, and treatment options. Poor communication can lead to health-care decisions that insufficiently meet patients’ preferences, concerns, and needs and that subsequently affect patients’ quality of life. Objectives: The purpose of this study is to examine the relationship between provider communication behaviors and the quality of life of patients with advanced cancer. Method: A cross-sectional, correlation design was used in the present study, in which 159 patients with confirmed diagnoses of stage III or IV solid cancer were surveyed. Results: The mean summary score of the patients’ quality of life was 57.31. We found a significant relationship between provider communication behaviors and patient quality of life (β = 0.18, b = 0.35, SE = 0.15, p = 0.021). In addition, R2 shows that only 3.4% of variance in patient quality of life is predicated on provider communication behaviors. Conclusions: The relationship between provider communication behaviors and patient quality of life was low (r = 0.18). A possible reason for this is that provider communication behaviors are not the only factor that affects patient quality of life; other variables, such as the patient’s age, cancer type, and level of awareness, can also have an effect. Another possible explanation is that communication behaviors between patients and providers may vary depending on the level of cultural contact.

The purpose of this study was to analyze the effectiveness of scripted biology curriculum as a means of providing students with the information required to increase content knowledge, while comparing curriculum developed by the teacher that utilizesthe Understanding by Design (UbD) framework (Wiggins & McTighe, 2005). The study used a mixed method, concurrent triangulation design which revealed that there was a significant difference between student growth from the pretest to the posttest. The teacher reflection logs and student focus groups identified two themes regarding science content knowledge: instructional/learning style and using discussion within the instructional cycle for both curricula. It was evident that the increase in content knowledge was associated with the utilization of discussion during the learning cycle. The teacher reflection logs and student focus groups also identified two themes when looking at the perception of the learning environment: the effect of teacher relationship on instruction and the effect of time on the learning environment. According to the instrument used, both groups of students showed growth, however, there was a larger gain among the students receiving the Understanding by Design curriculum. A major contributing factor for the growth among all students was the relationship the teacher had with them to meet their individual academic needs.

In educational and clinical settings, few norm-referenced tests have been utilized until now usually focusing on a single or a few language subcomponents, along with very few language rating scales for parents and educators. The need for a comprehensive language assessment tool for preschool and early school years children which could form the basis for valid and reliable screening and diagnostic decisions, led to the development of a new norm-referenced digital tool called Logometro®. The aim of the present study is to describe Logometro® as well as its psychometric characteristics. Logometro® evaluates an array of oral language skills across the different language domains such as phonological awareness, listening comprehension, vocabulary knowledge (receptive and expressive), narrative speech, morphological awareness, pragmatics, as well emergent literacy skills (letter sound knowledge and invented writing) in Greek-speaking 4–7 years old children. More specifically, Logometro® has been designed in order to: (a) map individual language development paths as well as difficulties, (b) provide a descriptive profile of children’s oral language and emergent literacy skills, and (c) assist in the identification of children who are at risk for Developmental Language Disorder (DLD) or Specific Learning Disabilities (SLD). The sample consisted of 926 children aged from 4 to 7 years, which were recruited from diverse geographical provinces and represented a variety of socioeconomic backgrounds in Greece. Eight hundred participants were typically developing children (Nboys = 384 and Ngirls = 416), 126 children (NSLI = 44 and NSLD = 82) represented children with Special Educational Needs, and 126 children were typically developing peers matched for gender and age with the clinical groups. The administration lasted 90 min, depending on the participant’s age and competence. Validity (construct, criterion, convergent, discriminant, and predictive) as well as internal consistency and test–retest reliability were assessed. Results indicated that Logometro® is characterized by good psychometric properties and can constitute a norm-referenced battery of oral language and emergent literacy skills. It could be used to inform the professionals as well as the researchers about a child’s language strengths and weaknesses and form the basis on which they can design an appropriate individualized intervention if needed.

Science scores among US fourth-grade students have declined compared to their international counterparts in recent years. Recent results show that teachers are the most impactful influence on student success and accountability. Teacher preparedness and professional development are two key areas that serve as indicators of providing relevant and essential information for students' success. A correlational quantitative study was conducted to assess the relationship between teacher preparedness and professional development on fourth-grade students' science achievement. The TIMSS 2019 data were secured from the Boston College, TIMSS, and PIRLS International websites. The data was evaluated using the SPSS 27 Hierarchical Linear Regression. The study's population included 70 teachers and 1208 students representing schools located in the United States. Results indicated that teachers who graduate with science majors have the greatest impact on students' science outcomes. Specific professional development topics that teachers studied also served as key indicators of student science success. Topics that specify the objectives found in the "Next Generation Science" curriculum had the greatest impact. The topics included future science pedagogy, critical thinking, and past and future student needs. Thus, recruitment of teachers with science majors should be the focus of human resources recruitment officers, and quality, well-developed professional development must focus on the "Next Generation Science Curriculum."

Abstract Background In addition to their well characterized role in cellular energy production, new evidence has revealed the involvement of mitochondria in diverse signaling pathways that regulate a broad array of cellular functions. The mitochondrial genome (mtDNA) encodes essential components of the oxidative phosphorylation (OXPHOS) pathway whose expression must be coordinated with the components transcribed from the nuclear genome. Mitochondrial dysfunction is associated with disorders including cancer and neurodegenerative diseases, yet the role of the complex interactions between the mitochondrial and nuclear genomes are poorly understood. Results Using a Drosophila model in which alternative mtDNAs are present on a common nuclear background, we studied the effects of this altered mitonuclear communication on the transcriptomic response to altered nutrient status. Adult flies with the ‘native’ and ‘disrupted’ genotypes were re-fed following brief starvation, with or without exposure to rapamycin, the cognate inhibitor of the nutrient-sensing target of rapamycin (TOR). RNAseq showed that alternative mtDNA genotypes affect the temporal transcriptional response to nutrients in a rapamycin-dependent manner. Pathways most greatly affected were OXPHOS, protein metabolism and fatty acid metabolism. A distinct set of testis-specific genes was also differentially regulated in the experiment. Conclusions Many of the differentially expressed genes between alternative mitonuclear genotypes have no direct interaction with mtDNA gene products, suggesting that the mtDNA genotype contributes to retrograde signaling from mitochondria to the nucleus. The interaction of mitochondrial genotype (mtDNA) with rapamycin treatment identifies new links between mitochondria and the nutrient-sensing mTORC1 (mechanistic target of rapamycin complex 1) signaling pathway.

The purpose of the present study was to test the hypothesis that goal orientation is associated with divergent forms of emotional reactivity under frustration. Goal orientations were assessed using bifurcations of performance goals described earlier. Physiological stress levels were measured via a blood volume pulse analysis after individuals were subjected to a computerized Stroop task using a malfunctioning mouse to induce enhanced frustration. The results indicated that performance-avoidance goals were associated with the highest levels of emotional reactivity, with normative outcome goals being significantly more detrimental than ability goals. We concluded that the motivation to avoid failure or to outperform others is the most detrimental determinant of stress and needs to be avoided by all means. Instead, it is suggested that educators emphasize performance using personal best outcomes or by valuing engagement, deep processing and task completion.

BackgroundNeutrophil activation drives lung complications after cardiopulmonary bypass (CPB). Evidence suggests the healthy, ventilated lung may beneficially re-condition pro-inflammatory neutrophils. However, evidence in humans is lacking, due to a paucity of good models. CPB with simultaneous central venous and bilateral pulmonary vein sampling provides an opportunity to model effects of one-lung ventilation. The study's primary objectives were to establish a model of intra-operative, bilateral pulmonary vein sampling and to determine whether neutrophil function differed after passing through inflated or deflated lungs.MethodsSeventeen patients having "on pump" coronary artery bypass grafting (CABG) with one-lung ventilation (in two cohorts with tidal volume 2ml kg-1 and FiO2 0.21, or tidal volume 4 ml kg-1 and FiO2 0.5 respectively) were recruited. Cohort 1 consisted of 9 patients (7 male, median age 62.0 years) and Cohort 2 consisted of 8 male patients (median age 65.5 years). Recruitment was via prospective screening of scheduled elective and non-elective CABG procedures with cardiopulmonary bypass. Each patient had five blood samples taken-central venous blood pre-operatively; central venous blood pre-CPB; central venous blood post-CPB; pulmonary venous blood draining the ventilated lung post-CPB; and pulmonary venous blood draining the deflated lung post-CPB. Neutrophil phagocytosis and priming status were quantified. Plasma cytokines were measured.ResultsPhagocytosis and priming were not significantly different in neutrophils returning from the ventilated lung as compared to the non-ventilated lung. Plasma IL-6, IL-8 and IL-10 were significantly elevated by CPB.ConclusionsThe intra-operative, bilateral pulmonary vein sampling model provides unique opportunities to assess biological effects of interventions to one lung, with the other lung acting as an internal control. Single-lung ventilation during CPB had no significant effects on neutrophil function.

During the COVID-19 pandemic, virtual observations were utilised in teacher education programmes internationally (Murtagh, 2022; Mynott et al., 2022; Ó Grádaigh et al., 2021). In Scotland, virtual observations have been continued as part of teacher education programmes and this article explores student perspectives on their continued use. A situative analysis (Clarke et al., 2018) was used to explore questionnaire and interview data from student teachers. The analytical process examined the data and utilised memoing to consider emergent themes against the situation of virtual observations in teacher education. There is a duality to the findings. On the one hand, students express preference for in-person observation when they consider the process to be assessment-focused. Conversely, when not considering virtual observations as assessment, the ability to reflect more deeply on their practice, increase their control and agency over the observation and reduce the stress surrounding observations are all themes that emerged from the data. Therefore, the data suggests that further innovation moving from summative to formative observations might increase the benefits of virtual observations. Limited research exists on virtual observations. The literature that is available often focuses on university staff. This article considers virtual observations from the student perspective and provides clear feedback on how a pandemic response has been developed for post-pandemic purposes. The findings of this article can be further explored and built upon, and this will enhance the use of virtual observations within teacher education.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Simultaneous inhibition of soluble epoxide hydrolase (sEH) and fatty acid amide hydrolase (FAAH) with a single small molecule represents a novel therapeutic approach in treating inflammatory pain, since both targets are involved in pain and inflammation processes. In this study using multi-target directed ligands methodology we designed and synthesized 7 quinolinyl-based dual sEH/FAAH inhibitors, using an optimized microwave-assisted Suzuki-Miyaura coupling reaction and tested their potency in human FAAH and human, rat, and mouse sEH inhibition assays. The structure-activity relationship study showed that quinolinyl moiety is well tolerated in the active sites of both enzymes, yielding several very potent dual sEH/FAAH inhibitors with the IC50 values in the low nanomolar range. The most potent dual inhibitor 4d was further evaluated in stability assay in human and rat plasma where it performed better than the standard Warfarin while in vivo study revealed that 1 mg/kg 4d can inhibit acute inflammatory pain in male rats to a similar degree as the traditional nonsteroidal anti-inflammatory drug ketoprofen (30 mg/kg) after intraperitoneal injection. ADMET prediction studies for this dual inhibitor show favorable pharmacokinetic properties which will guide the future in vivo evaluations.