Search

Objective Materials and Methods Results Conclusion This retrospective study aimed to compare the outcomes of dinoprostone vaginal insert (PROPESS) and double balloon cook catheter (DBC) in term nulliparous pregnancies.A total of 1682 cases were enrolled, all of which were divided into two groups: PROPESS and DBC. The primary outcomes were rate of vaginal delivery (VD) and cesarean section (CS) and successful VD within 24 h and CS indications; the secondary outcomes were labor duration, oxytocin augmentation, complications during labor, maternal/neonatal outcomes, and predictors of successful VD within 24 h.There was no statistical difference in the rates of VD between the PROPESS group (73.74%) and the DBC group (77.73%) (p = 0.36). The VD rate within 24 h was significantly higher in PROPESS group than in the DBC group (55.45% vs. 38.43%, p < 0.001). The occurrence of nonreassuring fetal heart rate (NRFHR) patterns was higher in the CS indications of the PROPESS group than in the DBC group (56.86% vs. 37.81%, p < 0.001). The oxytocin augmentation was significantly lower in the PROPESS group than in the DBC group (52.79% vs. 94.9%, p < 0.001). The incidence of chorioamnionitis was significantly higher in the DBC group as compared with PROPESS group (4.36% vs. 1.34%, p < 0.001), while neonatal outcomes were comparable between the two groups. PROPESS (p < 0.001, odds ratio [OR] 2.478, 95% confidence interval [CI] 1.718–3.574), oxytocin augmentation (p < 0.001, OR 32.759, 95% CI 20.654–51.958), and amniotomy (p = 0.016, OR 1.897, 95% CI 1.331–2.704) were predictors of VD within 24 h.The effectiveness of delivery was comparable between the two groups. The PROPESS group resulted in a high successful VD rate within 24 h, although accompanied by NRFHR occurrence. Two cases with fetal presentation change (cephalic to breech) and four cases with umbilical cord prolapse were observed in the DBC group. PROPESS, oxytocin augmentation, and amniotomy were associated with VD interval within 24 h. [ABSTRACT FROM AUTHOR]

Background: Induction of labor (IOL) is common with one in four labors being induced in the United States (US). IOL has been associated with lower birth satisfaction. Video education can address gaps in education and promote anticipatory guidance. Prior studies in obstetrics have focused on randomized designs in English-speaking patients, leaving opportunities to explore how these tools perform in a pragmatic fashion with diverse patient populations. Our objective was to evaluate the effects of a video education tool on patient satisfaction and knowledge of IOL experience in English and Spanish-speaking patients scheduled for IOL at a tertiary care hospital. Methods: This was a single site pragmatic implementation of a quality improvement measure at an academic hospital. A bilingual survey was developed to evaluate the impact of an educational video on birth satisfaction and knowledge of IOL procedures. The video is freely available in English and Spanish. Baseline postpartum surveys were collected from June to July 2021. The video was subsequently recommended by providers when scheduling IOLs. Post-intervention surveys were collected from September to November 2021 after an implementation period. Groups were compared using t-tests for satisfaction scores and chi-square analyses for categorical variables. Results: Thirty-two participants completed the baseline survey and 72 completed the post-implementation survey with response rates of 88.9% and 91.1%, respectively. There were no statistically significant changes between mean total satisfaction scores (26.9 vs 28.0 out of 40.0, p = 0.290). 61 participants were English speaking (58%) and 43 Spanish (42%). Thirty (42%) patients reported watching the video. Correct identification of amniotomy use improved in the post-intervention group (p = 0.002). No changes were seen in anticipated duration of labor nor in whether patients would choose to be induced again. Conclusions: Recommendation of video education before scheduled IOL was associated with little improvement in knowledge about IOL, but no significant improvement in patient satisfaction. While video education has improved these measures in randomized trials, our study demonstrated that real-world implementation and patient uptake may be initially difficult. This study may help providers emphasize direct education and counseling and promote optimal implementation of innovative educational media. [ABSTRACT FROM AUTHOR]

Background: Induction therapy with basiliximab is recommended in kidney transplant (KT) recipients with a low immunological risk (LIR) profile. Whether basiliximab is associated with a decreased risk of acute rejection (AR) and graft loss is controversial. Methods: In our institution, LIR patients (absence of anti-HLA antibodies before KT) are inducted with basiliximab in case of living-donor KT, while deceased-donor KT recipients receive no induction. Maintenance immunosuppression is similar, including a combination of tacrolimus (Tac), mycophenolate (MPA) and steroids. In this single-center retrospective study, we included all adult LIR patients who underwent KT between 1 January 2015 and 31 December 2022. Results: Of the 471 patients included, 354 received no induction and 117 received basiliximab. The median (IQR) number of HLA A-B-DR mismatches was 3 (2–3) and 2 (2–4) in the no induction group and the basiliximab group, respectively. The cumulative incidences in the no induction group vs. the basiliximab group of acute rejection and graft loss over 5 years post-KT were similar at 8.9% vs. 7.8% (p = 0.8) and 8.5% vs. 4.2% (p = 0.063), respectively. In multivariable Cox regression analysis, delayed graft function emerged as an independent risk factor for acute rejection (hazard ratio [HR] 2.75, 95% confidence interval [CI] 1.23–6.13, p = 0.014) and graft loss (HR 9.32, CI 4.10–21.1, p < 0.001). Conclusions: Basiliximab did not provide any advantage in terms of rate of acute rejection and graft survival within 5 years post KT compared with a strategy without induction therapy in patients with a low immunological risk profile receiving triple maintenance immunosuppression Tac/MPA/steroids. [ABSTRACT FROM AUTHOR]

This article is a literature driven reflection about a radiologist's experience of using health libraries in England's National Health Service, as a consultant after returning from a Clinical Fellowship in New Zealand. It is a collaboration between a Consultant Interventional Radiologist and two Academic Librarians. It attempts to reflect on the lived experience of the radiologist and locate that experience within the wider Library and Information Science (LIS) context. Findings include new suggestions about how librarians can support staff in career transition and apply their experience of the COVID-19 pandemic to forge pragmatic relationships within the health care community. [ABSTRACT FROM AUTHOR]

The hot pressing process for 100% coriander-based fiberboards was optimized using an induction RocTool system, which offers rapid mold heating and cooling. The fiberboards were made using deoiled press cake as a protein binder and extrusion-refined straw as reinforcement. Doehlert's experimental design was used to evaluate the influence of pressure (10–50 MPa), molding time (60–300 s), and mold temperature (155–205 °C) on fiberboard properties, energy consumption, cost, and environmental impact. The results showed that the RocTool device allows for better temperature control during shaping throughout the mold, resulting in mechanical properties that are both more homogeneous across the entire surface of the panel and, more importantly, substantially improved. Using the isoresponse curves, the optimal hot pressing conditions were 35 MPa, 300 s, and 205 °C, corresponding to a 40.6 MPa flexural strength. However, it was observed that to achieve an MDF-like fiberboard with minimal production costs, much less restrictive molding conditions were sufficient, i.e., 32.5 MPa, 170 s, and 160 °C. The study revealed that maximum thermopressing conditions emitted 3.87 kg of CO2 eq., while conditions leading to the MDF-like board reduced emissions to 1.45 kg CO2 eq., resulting in a more environmentally friendly material. [ABSTRACT FROM AUTHOR]

More research related to effective ways to support and retain teachers in the teaching profession is necessary as the need for science and mathematics teachers continues to grow. Understanding how teachers perceive challenges and experience support early in their career can contribute to building environments which foster teacher retention. This mixed‐method study explored the influences on the self‐efficacy and career satisfaction of a group of 21 early‐career (2–6 years of classroom experience) secondary science and mathematics teachers who participated in a traditional university preparation program and scholarship program to prepare them for teaching in high‐need school districts. Using data from an efficacy survey and semistructured interviews, this study measured changes in teacher efficacy and described teacher leadership experiences, perceived teaching challenges, and valued supports. Results found no change in teachers' self‐efficacy scores although mean outcome expectancy scores decreased. Teachers' identification as a teacher leader was correlated with science or mathematics teaching self‐efficacy. Qualitative coding of the interviews revealed ways in which assessments, workload, school structures and polices, administration, students, and teacher community either contributed to teachers reported difficulties or supported them as early‐career teachers. The discussion offers suggestions for ways to increase secondary science and mathematics teachers' job satisfaction. [ABSTRACT FROM AUTHOR]

Background: Current models of loneliness emphasise the role of maladaptive cognitions in causing and/or maintaining loneliness. However, standardised paradigms to experimentally examine the role of maladaptive cognition in loneliness are lacking, making it difficult to establish causality. This paper tested a mock online chat paradigm designed to induce changes in negative affect (loneliness, depression, and anxiety), and strength of belief in lonely thoughts, by manipulating comparative and normative fit. Methods: Participants (N = 59) were randomised into either the loneliness arm (i.e., loneliness induction chat followed by a social connectedness induction chat), or the social connectedness arm (i.e., two separate social connectedness induction chats), and subsequently completed outcome measures. Results: The experimental paradigm significantly and specifically increased lonely affect; however, this was associated with non-significant changes in strength of belief in lonely thoughts. The social connectedness induction chat led to significant reductions in broad negative affect for both groups, with these effects accruing across chats for participants in the social connectedness arm. Conclusion: Experimentally manipulating comparative and normative fit to either emphasise differences or similarities between an individual and group members is an effective paradigm for increasing lonely affect or decreasing general negative affect, respectively. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to evaluate low‐dose oral misoprostol induction, and compare different methods used in second‐line induction in patients with a Bishop score less than 6. Methods: This retrospective study analyzed the medical history and courses of pregnancy of all patients induced with first‐line of low‐dose oral misoprostol (50 μg every 4 h with a total of 200 μg/24 h) from April 2021 to June 2022 in a university hospital center, and reported outcomes according to the second‐line method of induction. Results: Among 437 labor inductions with low‐dose oral misoprostol, 120 patients required a second‐line induction. Predictive factors of first‐line failure were higher body mass index (P = 0.011), absence of premature rupture of membranes (P = 0.021) and earlier term of pregnancy (P < 0.001). Regarding second methods of induction of labor, time from induction to delivery was shorter in the oxytocin group than the dinoprostone and misoprostol groups (24.0 vs. 41 and 51.0 h, respectively; P < 0.001), and was also significantly shorter in the dinoprostone than the misoprostol group (P = 0.048). Cesarean section rates did not differ between the three groups (P = 0.651). There were no clinically significant differences in adverse events between the groups. Conclusion: Normal body mass index, previous rupture of membranes and later term of induction of labor were the three favoring success factors during first‐line oral misoprostol. In cases of a Bishop score <6, oxytocin may be the best option to reduce duration to delivery, with the same maternal‐fetal outcomes, including a similar rate of vaginal delivery. Synopsis: If a Bishop score was <6 after 24 h oral misoprostol, oxytocin could be the best method to reduce duration to delivery. [ABSTRACT FROM AUTHOR]

Resurgence is defined as an increase in a previously extinguished target response (B1) resulting from the worsening of conditions for a more recently reinforced alternative response (B2). Worsening includes extinction or reductions in rate, amount, and immediacy of delivery of food or some other phylogenetically important event (PIE). In the first part of the article, we apply the laws of allocation, induction, and covariance to understand not only resurgence of operant activity previously covarying with the PIE (B1) but also a constellation of ontogenetic and phylogenetic activities both related to the PIE (B0) and unrelated to the PIE (BN). In the second part, we discuss how induction might be incorporated into and provide alternative processes within an existing matching‐based framework, resurgence as choice (RaC). We begin to identify how this range of activities could depend on changes in the relative competitive weight (V) of all available activities (B1, B2, B0, BN) in addition to only those receiving explicit training (B1, B2). Future empirical and theoretical research is needed within this framework to provide a more complete understanding of resurgence and behavior more generally. [ABSTRACT FROM AUTHOR]

In the developing mammalian kidney, nephron formation is initiated by a subset of nephron progenitor cells (NPCs). Wnt input activates a ß-catenin (Ctnnb1)-driven, transcriptional nephrogenic program and the mesenchymal to epithelial transition (MET) of NPCs. Using an in vitro mouse NPC culturemodel, we observed that activation of the Wnt pathway results in the aggregation of induced NPCs, which is an initiating step in the MET program. Genetic removal showed aggregation was dependent on ß-catenin. Modulating extracellular Ca2+ levels showed cell-cell contacts were Ca2+ dependent, suggesting a role for cadherin (Cdh)-directed cell adhesion. Molecular analysis identified Cdh2, Cdh4 and Cdh11 in NPCs, and the ß-catenin directed upregulation of Cdh3 and Cdh4 accompanying the MET of induced NPCs. Mutational analysis of ß-catenin supported a role for a Lef/Tcf-ß-cateninmediated transcriptional response in the cell aggregation process. Genetic removal of all four cadherins, and independent removal of a-catenin or of ß-catenin-a-catenin interactions, abolished aggregation, but not the inductive response to Wnt pathway activation. These findings, and data in an accompanying article highlight the role of ß-catenin in linking transcriptional programs to the morphogenesis of NPCs in mammalian nephrogenesis. [ABSTRACT FROM AUTHOR]

In vivo and in vitro studies argue that concentration-dependent Wnt signaling regulates mammalian nephron progenitor cell (NPC) programs. Canonical Wnt signaling is regulated through the stabilization of ß-catenin, a transcriptional co-activator when complexed with Lef/Tcf DNA-binding partners. Using the GSK3ß inhibitor CHIR99021 (CHIR) to block GSK3ß-dependent destruction of ß-catenin, we examined dose-dependent responses to ß-catenin in mouse NPCs, using mRNA transduction to modify gene expression. Low CHIR-dependent proliferation of NPCs was blocked on ß-catenin removal, with evidence of NPCs arresting at the G2-M transition. While NPC identity was maintained following ß-catenin removal, mRNA-seq identified low CHIR and ß-catenin dependent genes. High CHIR activated nephrogenesis. Nephrogenic programming was dependent on Lef/Tcf factors and ß-catenin transcriptional activity. Molecular and cellular features of early nephrogenesis were driven in the absence of CHIR by a mutated stabilized form of ß-catenin. Chromatin association studies indicate low and high CHIR response genes are likely direct targets of canonical Wnt transcriptional complexes. Together, these studies provide evidence for concentration-dependent Wnt signaling in the regulation of NPCs and provide new insight into Wnt targets initiating mammalian nephrogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: Real-world studies comparing TNT and CRT are vital for advancing the treatment of LARC. Our study provides valuable insights reflecting the diverse patient populations and varied clinical practices encountered and demonstrates the advantage of TNT, providing a superior alternative to standard CRT and potentially enhancing treatment outcomes and quality of life. Total neoadjuvant therapy (TNT) has emerged as a promising approach for managing locally advanced rectal cancer (LARC), aiming to enhance resectability, increase pathological complete response (pCR), improve treatment compliance, survival, and sphincter preservation. This study compares the clinical outcomes of TNT, with either induction or consolidation chemotherapy, to those of the standard chemoradiotherapy (CRT). In this retrospective multi-institutional study, patients with stage II-III LARC who underwent CRT or TNT from seven oncology centers between 2021 and 2024 were retrospectively analyzed. The TNT group was categorized into induction or consolidation groups based on the sequence of chemotherapy and radiotherapy. Clinical and pathological data and treatment outcomes, including pCR, event-free survival (EFS), and overall survival (OS), were analyzed. Among the 276 patients, 105 received CRT and 171 underwent TNT. The TNT group showed significantly higher pCR (21.8% vs. 2.9%, p < 0.001) and lower lymphatic (26.3% vs. 42.6%, p = 0.009), vascular (15.8% vs. 32.7%, p = 0.002), and perineural invasion rates (20.3% vs. 37.6%, p = 0.003). Furthermore, 16.9% of TNT patients opted for non-operative management (NOM), compared to 0.9% in the CRT group (p < 0.001). The median interval between the end of radiotherapy and surgery was longer in the TNT group (17.6 weeks vs. 8.8 weeks, p < 0.001). The 3-year EFS was 58.3% for CRT and 71.1% for TNT (p = 0.06). TNT is associated with higher pCR, lower lymphatic and vascular invasion rates, and higher rates of NOM compared to CRT. This supports the use of TNT as a viable treatment strategy for LARC, offering potential benefits in quality of life. [ABSTRACT FROM AUTHOR]

Background: Engineering bacteria with the purpose of optimizing the production of interesting molecules often leads to a decrease in growth due to metabolic burden or toxicity. By delaying the production in time, these negative effects on the growth can be avoided in a process called a two-stage fermentation. Main text: During this two-stage fermentation process, the production stage is only activated once sufficient cell mass is obtained. Besides the possibility of using external triggers, such as chemical molecules or changing fermentation parameters to induce the production stage, there is a renewed interest towards autoinducible systems. These systems, such as quorum sensing, do not require the extra interference with the fermentation broth to start the induction. In this review, we discuss the different possibilities of both external and autoinduction methods to obtain a two-stage fermentation. Additionally, an overview is given of the tuning methods that can be applied to optimize the induction process. Finally, future challenges and prospects of (auto)inducible expression systems are discussed. Conclusion: There are numerous methods to obtain a two-stage fermentation process each with their own advantages and disadvantages. Even though chemically inducible expression systems are well-established, an increasing interest is going towards autoinducible expression systems, such as quorum sensing. Although these newer techniques cannot rely on the decades of characterization and applications as is the case for chemically inducible promoters, their advantages might lead to a shift in future inducible expression systems. [ABSTRACT FROM AUTHOR]

Aficamten, a small molecule selective inhibitor of cardiac myosin, was characterised in preclinical in vitro and in vivo studies. Protein binding in human plasma was 10.4% unbound and ranged from 1.6% to 24.9% unbound across species. Blood-to-plasma ratios ranged from 0.69 to 1.14 across species. Aficamten hepatic clearance in human was predicted to be low from observed high metabolic stability in vitro in human liver microsomes. Aficamten demonstrated high permeability in Caco-2 cell monolayers. Aficamten in vivo clearance was low across species at 8.8, 2.1, 3.3, and 11 mL/min/kg in mouse, rat, dog, and monkey, respectively. The volume of distribution was low-to-high ranging from 0.53 in rat to 11 L/kg in dog. Oral bioavailability ranged from 41% in monkey to 98% in mouse. Aficamten was metabolised in vitro to eight metabolites with hydroxylated metabolites M1a and M1b predominating. CYP phenotyping indicated multiple CYPs (2C8, 2C9, 2D6, and 3A4) contributing to the metabolism of aficamten. Human clearance (1.1 mL/min/kg) and volume of distribution (6.5 L/kg) were predicted using 4-species allometry employing 'rule-of-exponents'. A predicted 69 hour half-life is consistent with observed half-life in human Phase-1. No CYP-based drug-drug interaction liability as a precipitant was predicted for aficamten. [ABSTRACT FROM AUTHOR]

In this paper, we analyse conceptions of induction and certainty in Wolff and Crusius, highlighting their competing conceptions of physics. We discuss (i) the perspective of Wolff, who assigned induction an important role in physics, but argued that physics should be an axiomatic science containing certain statements, and (ii) the perspective of Crusius, who adopted parts of the ideal of axiomatic physics but criticized the scope of Wolff's ideal of certain science. Against interpretations that take Wolff's proofs in physics to be based on empirical statements that are probable, we show how inductively established statements, coupled with assumptions concerning the uniformity of nature, can be certain according to Wolff. We examine Crusius' little known work on physics and show that he attacked Wolff, arguing that many statements of physics are probable. We provide a discussion of the reception of methodological rules similar to Newton's Regulae Philosophandi, discussing different interpretations of such rules. We conclude by briefly hinting at how the debate between Wolff and Crusius provides historical context for understanding Kant's philosophy of natural science. [ABSTRACT FROM AUTHOR]

Buprenorphine is a Food and Drug Administration-approved therapy for opioid use disorder, with proven efficacy in treatment retention and reduction in opioid use and mortality. Low-dose buprenorphine initiation or microinduction is a novel means of initiation that may allow for an easier transition in patients. Trauma patients have high rates of opioid use disorder and patient directed discharges (PDD). We hypothesized that patients initiated on a buprenorphine microinduction program would have increased protocol completion and fewer PDD compared with patients initiated historically on a traditional induction. Our retrospective cohort study compared buprenorphine microinduction and traditional induction in trauma patients at an urban level one trauma center between December 2020 and June 2022. Patients aged 18-89 y with traumatic injuries who received buprenorphine were included. Our primary outcome was in-hospital protocol completion, defined as reaching 16 mg of buprenorphine within 24 h or a documented stable dose. Statistical analysis was performed using chi-square for categorical variables and two sample t -tests for continuous variables. Ninety-eight patients were included, with 46 initiating with microinduction and 52 initiating with traditional induction. There was no difference in protocol completion, (P = 0.29) and 83% of subjects who started an induction protocol completed it. Those who completed a protocol were more likely to be discharged home (P = 0.0002), had less PDD (P = 0.001), and had an increased likelihood of attending outpatient addiction clinic follow-up (P = 0.038). Regardless of the protocol type, buprenorphine induction can be implemented in trauma patients with high protocol completion rates. In our population, those who complete a protocol had a higher likelihood of discharge home and postdischarge follow-up in addiction medicine clinic. [ABSTRACT FROM AUTHOR]

This paper uses insider research within a Cultural Historical Activity Theory (CHAT) framework to examine the lived induction-to-teaching experiences of twelve new academics at a case-study Northern UK university. A CHAT lens foregrounds contradictions as a source for change in the induction-to-teaching process. Data generated through semi-structured interviews with these academics were analysed and, informed by CHAT, allowed us to discern contradictions in sociocultural and structural aspects of the induction activity systems which significantly impact new academics' experiences. Examining these contradictions enabled us to identify interventions for enhancing academic induction policy and practice within the case-study University, but also more widely. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion This study aimed to assess whether a partial term prelabor rupture of membranes (partial TPROM) had an impact on the spontaneous onset of labor compared to complete TPROM.We performed a retrospective study in a French level III maternity hospital. We included all singleton cephalic pregnancies presenting with prelabor rupture of membranes ≥37 weeks gestational age. Patients with a partial TPROM (P group) were compared to patients with a complete TPROM (C group). Induction of labor was performed following expectative management of 24–48 h, and antibiotic prophylaxis was started 12 h after rupture. Our main outcome measure was the rate of patients who had spontaneous labor 24 h following prelabor rupture.Overall, 389 women were included in the study, 148 in the P group, 241 in the C group. The proportion of women who went into spontaneous labor in the 24 h following TPROM was significantly lower in the P group (45% vs 64%, P < 0.001). A partial TPROM was a predictive factor for absence of labor at 24 h following rupture (adjusted odds ratio: 0.44 [0.29–0.68]). There were more cases of induction of labor (50% vs 20%, P < 0.001) and antibiotic prophylaxis (91% vs 73%, P < 0.001) in the P group. However, obstetrical and neonatal outcomes were comparable between the two groups.Compared to complete TPROM, partial TPROM is associated with a lower probability of spontaneous labor in the 24 h following rupture. The persistence of a residual membrane has been identified as a risk factor for delaying labor beyond 24 h. [ABSTRACT FROM AUTHOR]

Construction of relay protections of electrical installations without the use of bulky metal- and insulation-intensive measuring current transformers (CTs) was repeatedly discussed at Conferences of the International Council on Large Electric Systems (CIGRE) as a challenge for the electric power industry. In the article, the authors present resource-saving reed switch current protection for 6–10-kV electrical installations connected to switchgear cells, which is an alternative to traditional protections. The scientific novelty of the work lies in (a) reed switch protection design on the basis of measuring the magnetic induction in different modes and at different points inside a cell, and we prove that inductance values are sufficient to detect phase short-circuits in electrical installations fed from this cell and derive the dependence of the induction on the position of an inductance coil inside the cell; (b) proven possibility of using the simplest formula of the Biot–Savart law for the calculations if the experimentally obtained coefficients are introduced into it; (c) development of a technique for calculating the parameters of the overcurrent protection based on reed switches. Experimental results are presented in graphical form and clearly show the points of EMS maxima and minima. Settings for resource-saving current protection are selected and a feasibility study of the effectiveness of resource-saving overcurrent protection is carried out. A technical and economical assessment of the efficiency of the suggested overcurrent protection is conducted. [ABSTRACT FROM AUTHOR]

Simple Summary: The current review summarizes the new potential treatment strategies for patients with early-stage non-small cell lung cancer with immunotherapy and targeted therapies and defines the current challenges for making treatment decisions with these approaches in daily practice. The recent advent of tyrosine kinase inhibitors (TKIs) and immune checkpoint blockers (ICBs) in early-stage non-small cell lung cancer (NSCLC) has dramatically modified treatment strategies by improving the prognosis in this setting. Osimertinib and alectinib, both TKIs, have shown significant improvements in outcomes for patients with resected EGFR- and ALK-positive NSCLC, respectively, changing the standard of care in these subgroups. More recently, the LAURA trial showed the efficacy of osimertinib after chemoradiotherapy in patients with unresectable stage III NSCLC harboring EGFR mutations. Numerous trials are still ongoing to investigate neoadjuvant/perioperative TKIs in several oncogene-driven NSCLC. In addition, several ICBs have been tested and approved as adjuvant (atezolizumab and pembrolizumab), neoadjuvant (nivolumab), and perioperative treatments (pembrolizumab) for patients with resectable early-stage NSCLC. Despite these advances, many challenges remain regarding the use of TKIs and ICBs in this setting, including the optimal duration of adjuvant TKI or induction ICB therapy, the role of minimal residual disease to identify patients at high-risk of disease relapse and to guide adjuvant treatment decisions, and the role of adjuvant chemotherapy in resected oncogene-driven NSCLC. Furthermore, potential predictive biomarkers for efficacy are needed to eventually intensify the entire perioperative strategies. This review aims to summarize and discuss the available evidence, the ongoing trials, and the challenges associated with TKI- and ICB-based approaches in early-stage NSCLC. [ABSTRACT FROM AUTHOR]

Background: The efficacy of highly restrictive dietary therapies such as exclusive enteral nutrition (EEN) in the induction of remission in Crohn's disease (CD) are well established, however, ongoing issues exist with its poor palatability, restrictions, and adherence. The primary aim of this review is to evaluate the current evidence for the efficacy of exclusively solid food diets on the induction and maintenance of clinical and biochemical remission in CD. Secondary aims include impact on endoscopic healing and quality of life. Methods: A systematic review of all randomised controlled trials (RCTs), open-label randomised trials and head-to-head clinical trials assessing solid food diet intervention in patients with active or inactive Crohn's disease was conducted. Studies included adult and paediatric patients with a verified disease activity index at baseline and follow up (Harvey Bradshaw Index, HBI; Crohn's disease activity index, CDAI and paediatric CDAI, PCDAI). Additional secondary endpoints varied between studies, including endoscopic and biochemical responses, as well as quality of life measures. Two authors independently performed critical appraisals of the studies, including study selection and risk of bias assessments. Results: 14 studies were included for review, with several studies suggesting clinically significant findings. Clinical remission was achieved in a paediatric population undertaking the Mediterranean diet (MD) (moderate risk of bias). In adults, the Crohn's disease exclusion diet (CDED) was comparable to the CDED with partial enteral nutrition (PEN) diet in induction of remission (moderate risk of bias). A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet was also shown to decrease symptoms in patients with quiescent or mildly active CD (high risk of bias), however, this was not corroborated by other low FODMAP diet studies. Conclusions: There are promising outcomes for the MD and CDED in inducing clinical remission in mild to moderate CD. The results need to be interpreted with caution due to design limitations, including issues with combining outcomes among CD and UC patients, and small sample size. The current evidence for solid food dietary therapy in CD is limited by the lack of high quality studies and moderate to high bias. Future well designed studies are needed to confirm their efficacy. [ABSTRACT FROM AUTHOR]

Background: The reason why some multiple sclerosis (MS) patients show disease activity after alemtuzumab (ALM) is still unclear, but ocrelizumab (OCR) could represent an interesting sequential therapeutic approach. Objectives: To investigate safety and efficacy of OCR in MS patients with disease activity after two ALM courses. Methods: Observational retrospective multi-centers Italian cohort study. Results: Seventy-two subjects were included. Mean follow-up (FU) was 2.4 (±1) years. Forty-five patients (62.5%) experienced at least one adverse event (AE), with infections accounting for 96.7% of cases. A reduction in total lymphocytes was observed between OCR start and 6 months FU, driven by BCD19+ lymphocytes depletion (p < 0.001). Immunoglobulin M (IgM) levels decreased between OCR start and 6 months FU (p < 0.001). At 2-year FU, relapse, magnetic resonance imaging (MRI) activity and disability worsening-free survival were 92.1%, 90.8%, and 89.2%. The evidence of inflammatory activity between the two ALM courses was associated with higher risk of relapse, MRI activity, and NEDA-3 status loss in relapsing-remitting multiple sclerosis (RRMS; p = 0.02, p = 0.05, p = 0.01, respectively). Conclusions: OCR after two ALM courses seemed to be safe and effective. Early IgM hypogammaglobulinemia occurred in a high proportion of patients. The evidence of inflammatory activity between ALM courses seemed to increase the risk of MS re-activation on OCR treatment. [ABSTRACT FROM AUTHOR]

Language teachers come from diverse and multilingual backgrounds. This also generally characterises preparation programmes that have been developed to prepare elementary and secondary school language teachers for increasingly globalised, pluralistic, interconnected classrooms. Despite variations, there is value in attempting to identify common denominators in research related to the preparation of such teachers. This paper surveys 20 years of research published in journals focusing on language learning and teaching. Content analysis and thematic analysis was performed to generate salient categories related to language teacher preparation, induction and retention. Five key themes emerged: reflective practice and its role in preparation programmes and induction; ongoing formal and informal support in the early years of teaching; teachers' beliefs and their identity; pedagogical and content knowledge; and the sociocultural context of teaching. Despite the focus on journals devoted to language learning and teaching, findings overwhelmingly related to teacher preparation in general. We discuss these findings and then offer suggestions specifically for school L2 language teacher preparation, induction and retention with an emphasis on early career teachers. Such recommendations can guide language teacher preparation programmes as well as the professional trajectory of teachers in the field, ultimately increasing the chances of retention in the long term. [ABSTRACT FROM AUTHOR]

Georg Henrik von Wright (1916–2003) started his studies in theoretical philosophy at the University of Helsinki in 1934. His teacher, Professor Eino Kaila (1890–1958), was an associate of the Vienna Circle who had changed the course of Finnish philosophy with his own version of logical empiricism. Under Kaila's supervision, von Wright wrote his early studies on probability and defended his doctoral thesis The Logical Problem of Induction in 1941. Von Wright met Ludwig Wittgenstein in Cambridge in 1939 and 1947 and eventually became his successor there in 1948–1951. Later, von Wright characterized these two philosophers as his "father figures": "Kaila had turned me into a logical positivist or empiricist. Wittgenstein, on the other hand, thoroughly eradicated this personality of mine." This article studies von Wright's changing relation to logical empiricism. The main sources include his correspondence with Kaila in 1937–1958 and his books Den logiska empirismen (in Swedish in 1943; in Finnish in 1945) and Logik, filosofi och språk (in Swedish in 1957, in Finnish in 1958). In his "Intellectual Autobiography" (1989), von Wright described the former book as "a farewell to the philosophy of my student years". Wittgenstein's influence can be seen in von Wright's denial of the unity of science and his cool cultural pessimism as expressed in his critical essays. But it is also evident that logic and exact thinking continued to be central tools and ingredients of his subsequent and highly appreciated work as an analytic philosopher. [ABSTRACT FROM AUTHOR]

I.J. Good's "On the Principle of Total Evidence" (1967) looms large in decision theory and Bayesian epistemology. Good proves that in Savage 's (1954) decision theory, a coherent agent always prefers to collect, rather than ignore, free evidence. It is now well known that Good's result was prefigured in an unpublished note by Frank Ramsey (Skyrms 2006). The present paper highlights another early forerunner to Good's argument, appearing in Janina Hosiasson's "Why do We Prefer Probabilities Relative to Many Data?" (1931), that has been neglected in the literature. Section 1 reviews Good's argument and the problem it was meant to resolve; call this the value of evidence problem. Section 2 offers a brief history of the value of evidence problem and provides biographical background to contextualize Hosiasson's contribution. Section 3 explicates the central argument of Hosiasson's paper and considers its relationship to Good's (1967). [ABSTRACT FROM AUTHOR]

Rifampicin is a strong inducer of cytochrome P450 (CYP3A4) and P-glycoprotein (P-gp/ABCB1), leading to profound drug–drug interactions. In contrast, the chemically related rifabutin does not show such pronounced induction properties in vivo. The aim of our study was to conduct a comprehensive analysis of the different induction potentials of rifampicin and rifabutin in primary human hepatocytes and to analyze the mechanism of potential differences. Therefore, we evaluated CYP3A4/ABCB1 mRNA expression (polymerase chain reaction), CYP3A4/P-gp protein expression (immunoaffinity–liquid chromatography–mass spectrometry, IA-LC-MS/MS), CYP3A4 activity (testosterone hydroxylation), and considered intracellular drug uptake after treatment with increasing rifamycin concentrations (0.01–10 µM). Furthermore, rifamycin effects on the protein levels of CYP2C8, CYP2C9, and CYP2C19 were analyzed (IA-LC-MS/MS). Mechanistic analysis included the evaluation of possible suicide CYP3A4 inhibition (IC50 shift assay) and drug impact on translational efficiency (cell-free luminescence assays). Rifabutin accumulated 6- to 15-fold higher in hepatocytes than rifampicin, but induced CYP3A4 mRNA comparably to rifampicin (e. g. rifampicin 61-fold vs. rifabutin 44-fold, 72 h). While rifampicin for example enhanced protein (10 µM: 21-fold) and activity levels considerably (53-fold), rifabutin only slightly increased CYP3A4 protein expression (10 µM: 3.3-fold) or activity (11-fold) compared to rifampicin after 72 h. Both rifamycins similarly influenced expression of other eliminating proteins. A potential CYP3A4 suicide inhibition by a specific rifabutin metabolite or disruption of ribosome function were excluded experimentally. In conclusion, the lack of protein enhancement, could explain rifabutin's weaker induction-related drug–drug interaction risk in vivo. [ABSTRACT FROM AUTHOR]

Measures aimed at newly qualified teachers (NQTs) in Norway are characterized by ambitious policy expectations, though with leeway for practitioners. This article investigates how NQTs perceive practices enacted to include them in the teaching profession while identifying the actors of such practices. We use practice architectures theory and the notion of ecology of educational practices to analyze conditions associated with mentoring and induction practice. Findings show that NQTs in Norway perceive mentoring and follow-up arrangements as limited and poorly adapted to their needs. We emphasize the need to take seriously tensions linked to mentoring practices, which become evident when NQTs problematize issues such as long-term temporary employment and school leaders as mentors. We argue for prioritizing mentoring practices and the closer follow-up of new teachers; the study illustrates how this may happen through better coupling between mentoring practices and other educational practices. [ABSTRACT FROM AUTHOR]

AbstractEnzyme-mediated pharmacokinetic drug-drug interactions can be caused by altered activity of drug metabolizing enzymes in the presence of a perpetrator drug, mostly via inhibition or induction. We identified a gap in the literature for a state-of-the art detailed overview assessing this type of DDI risk in the context of drug development. This manuscript discusses in vitro and in vivo methodologies employed during the drug discovery and development process to predict clinical enzyme-mediated DDIs, including the determination of clearance pathways, metabolic enzyme contribution, and the mechanisms and kinetics of enzyme inhibition and induction. We discuss regulatory guidance and highlight the utility of in silico physiologically-based pharmacokinetic modeling, an approach that continues to gain application and traction in support of regulatory filings. Looking to the future, we consider DDI risk assessment for targeted protein degraders, an emerging small molecule modality, which does not have recommended guidelines for DDI evaluation. Our goal in writing this report was to provide early-career researchers with a comprehensive view of the enzyme-mediated pharmacokinetic DDI landscape to aid their drug development efforts. [ABSTRACT FROM AUTHOR]

Accurate calculation of non-covalent interaction energies in nucleotides is crucial for understanding the driving forces governing nucleic acid structure and function, as well as developing advanced molecular mechanics forcefields or machine learning potentials tailored to nucleic acids. Here, we dissect the nucleotides' structure into three main constituents: nucleobases (A, G, C, T, and U), sugar moieties (ribose and deoxyribose), and phosphate group. The interactions among these fragments and between fragments and water were analyzed. Different quantum mechanical methods were compared for their accuracy in capturing the interaction energy. The non-covalent interaction energy was decomposed into electrostatics, exchange-repulsion, dispersion, and induction using two ab initio methods: Symmetry-Adapted Perturbation Theory (SAPT) and Absolutely Localized Molecular Orbitals (ALMO). These calculations provide a benchmark for different QM methods, in addition to providing a valuable understanding of the roles of various intermolecular forces in hydrogen bonding and aromatic stacking. With SAPT, a higher theory level and/or larger basis set did not necessarily give more accuracy. It is hard to know which combination would be best for a given system. In contrast, ALMO EDA2 did not show dependence on theory level or basis set; additionally, it is faster. [ABSTRACT FROM AUTHOR]

Background: Bone marrow mesenchymal stem cells (BMSCs) can differentiate into Schwann cells (SCs) during peripheral nerve injury; in our previous research, we showed that SC-derived exosomes (SC-exos) played a direct induction role while fibroblast-derived exosomes (Fb-exos) had no obvious induction role. The induction role of neural stem cell (NSC)-derived exosomes (NSC-exos) has also been widely confirmed. However, no studies have compared the induction effects of these three types of cells at the same time. Therefore, by investigating the effect of these three cell-derived exosomes upon the induction of BMSCs to differentiate into SCs, this study explored the role of different exosomes in promoting the differentiation of stem cells into SCs cells, and conducted a comparison between the two groups by RNA sequencing to further narrow the range of target genes and related gene pathways in order to study their related mechanisms. Materials and methods: We extracted exosomes from SCs, fibroblasts (Fb) and neural stem cells (NSC) and then investigated the ability of these exosomes to induce differentiation into BMSCs under different culture conditions. The expression levels of key proteins and gene markers were detected in induced cells by fluorescence immunoassays, western blotting and polymerase chain reaction (PCR); then, we statistically compared the relative induction effects under different conditions. Finally, we analyzed the three types of exosomes by RNA-seq to predict target genes and related gene pathways. Results: BMSCs were cultured by three media: conventional (no induction), pre-induction or pre-induction + original induction medium (ODM) with exosomes of the same cell origin under different culture conditions. When adding the three different types of exosomes separately, the overall induction of BMSCs to differentiate into SCs was significantly increased (P < 0.05). The induction ability was ranked as follows: pre-induction + ODM + exosome group > pre-induction + exosome group > non-induction + exosome group. Using exosomes from different cell sources under the same culture conditions, we observed the following trends under the three culture conditions: RSC96-exos group ≥ NSC-exos group > Fb-exos group. The overall ability to induce BMSCs into SCs was significantly greater in the RSC96-exos group and the NSC-exos group. Although there was no significant difference in induction efficiency when comparing these two groups, the overall induction ability of the RSC96-exos group was slightly higher than that of the NSC-exos group. By combining the differentiation induction results with the RNA-seq data, the three types of exosomes were divided into three comparative groups: RSC vs. NSC, RSC vs. Fb and NSC vs. Fb. We identified 203 differentially expressed mRNA target genes in these three groups. Two differentially expressed genes were upregulated simultaneously, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). We did not identify any co-upregulated target genes for the miRNAs, but did identify one target gene of the lncRNAs, namely ENSRNOG00000065005. Analysis identified 90 GO terms related to nerves and axons in the mRNAs; in addition, KEGG enrichment and GASA analysis identified 13 common differential expression pathways in the three groups. Conclusions: Our analysis found that pre-induction + ODM + RSC96/NSC-exos culture conditions were most conducive with regards to induction and differentiation. RSC96-exos and NSC-exos exhibited significantly greater differentiation efficiency of BMSCs into SCs. Although there was no statistical difference, the data indicated a trend for RSC96-exos to be advantageous We identified 203 differentially expressed mRNAs between the three groups and two differentially expressed target mRNAs were upregulated, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). 90 GO terms were related to nerves and axons. Finally, we identified 13 common differentially expressed pathways across our three types of exosomes. It is hoped that the efficiency of BMSCs induction differentiation into SCs can be improved, bringing hope to patients and more options for clinical treatment. [ABSTRACT FROM AUTHOR]

Transitioning to clean cooking fuels is not only part of achieving SDG7 but also makes a significant contribution to mitigating climate change by reducing carbon emissions. Research projects and pilots across a number of countries in Africa and South Asia have been exploring the suitability and energy performance of different cooking appliances and fuels. The paper presents the first statistical analysis across these multiple datasets to determine the range of energy required to cook dishes using different technologies and fuels. The paper draws out distinctions between African and Asian dishes, notably the impact of energy-intensive dishes prepared mostly in Africa. The paper demonstrates that the standard efficiency-based approaches to comparing the performance of stoves are not appropriate to modern electric cooking devices, so a novel alternative approach based on specific energy consumption and termed energy ratios is developed. Charcoal stoves are shown to use 15 times as much energy as electric pressure cookers (EPCs) to cook African dishes, and a detailed review of how the EPC works explains why this should be. Energy ratios provide a basis for estimating carbon emission reductions associated with transitioning to modern cooking fuels and also for estimating household cooking costs. Fuel and electricity prices from studies show that the cost of cooking with an EPC can be only 20% of the cost of cooking with charcoal, which highlights the potential for modern, energy-efficient electric cooking devices to defy the conventional wisdom of the energy ladder. [ABSTRACT FROM AUTHOR]

Purpose: The goal of the current paper is to explore how induction of STs in VET schools can be improved by embedding induction in the broader human resources management (HRM) system. To this end, we will present and discuss the theoretical underpinning and the quantitative and qualitative outcomes of an online reflection instrument "Startwijzer," developed in the Netherlands and which is based on literature on induction on one hand and on HRM literature on the other. In doing so the paper aims to contribute to induction theory and to formulate suggestions as to how provide STs with a smooth landing. Design/methodology/approach: In the period 2018–2023, the Startwijzer was filled out by starting teachers (STs), their coaches, HRM officers, team leaders and managers working in various VET schools. Descriptive analyses were done on respondents" (n = 629) scores on 13 indicators, with a three-point-Likert-scale (where 1 = "in order", 2 = "doubt" and 3 = "in order") in SPSS. Also differences among stakeholders were examined. Respondents' explanations of their scores were analyzed thematically, within and across indicators, to reach a deeper understanding of how STs can be provided a smooth landing. Findings: With AMO-theory of performance (Appelbaum et al., 2001) – stating that performance is a function of: abilities (A); motivation (M) and opportunities offered to exert expertise (O) – as conceptual model, 13 indicators relevant for effective induction were distinguished. (A): Timely Recruitment; Lesson Observations; Individual Coaching; Personal Development Plan; Reflection on Teaching Practice; Development of Professional Identity; (M): Exchange of Mutual Expectancies; Distinction among Performance Assessment and Guidance; Differentiation among STs; (O) Provision of Practical Information; Enculturation; Appointment of Coaches; Workload reduction. Respondents were generally very positive about the help and care provided informally by colleagues but less satisfied with the formal procedures. Originality/value: The paper bridges the literature on induction and that of human resources management (HRM). While the positive impact of HRM on employee outcomes such as performance, commitment and well-being has been attested by numerous studies (e.g. Combs et al., 2006), it is only recently that the potential benefits of HRM for teachers have been acknowledged (e.g. Runhaar, 2017). The theoretical elaboration as well as the empirical evidence discussed in the current paper suggest that unless induction activities are embedded in school HRM policy, STs already start their careers 1–0 down and it might be difficult for them to catch up. [ABSTRACT FROM AUTHOR]

Some scholars claim that epistemology of science and machine learning are actually overlapping disciplines studying induction, respectively affected by Hume's problem of induction and its formal machine‐learning counterpart, the "no‐free‐lunch" (NFL) theorems, to which even advanced AI systems such as LLMs are not immune. Extending Kevin Korb's view, this paper envisions a hierarchy of disciplines where the lowermost is a basic science, and, recursively, the metascience at each level inductively learns which methods work best at the immediately lower level. Due to Hume's dictum and NFL theorems, no exact metanorms for the good performance of each object science can be obtained after just a finite number of levels up the hierarchy, and the progressive abstractness of each metadiscipline and consequent ill‐definability of its methods and objects makes science—as defined by a minimal standard of scientificity—cease to exist above a certain metalevel, allowing for a still rational style of inquiry into science that can be called "philosophical." Philosophical levels, transitively reflecting on science, peculiarly manifest a non–empirically learned urge to self‐reflection constituting the properly normative aspect of philosophy of science. [ABSTRACT FROM AUTHOR]

In this paper Venn's account of probability inference and induction is examined, tracing their differences as well as how they ‘co-operate’ in inferences from particulars to particulars. We discuss the role of mathematical idealizations in making probability inferences, the celebrated rule of succession and we delve into the nature of the reference class problem arguing that for Venn it is a common problem for both induction and inference in probability. Our approach is both historical and philosophical attempting to sketch Venn's position both in the philosophy of probability and induction of his time and in relation to the twentieth-century frequentism. [ABSTRACT FROM AUTHOR]

Background: Bone marrow mesenchymal stem cells (BMSCs) can differentiate into Schwann cells (SCs) during peripheral nerve injury; in our previous research, we showed that SC-derived exosomes (SC-exos) played a direct induction role while fibroblast-derived exosomes (Fb-exos) had no obvious induction role. The induction role of neural stem cell (NSC)-derived exosomes (NSC-exos) has also been widely confirmed. However, no studies have compared the induction effects of these three types of cells at the same time. Therefore, by investigating the effect of these three cell-derived exosomes upon the induction of BMSCs to differentiate into SCs, this study explored the role of different exosomes in promoting the differentiation of stem cells into SCs cells, and conducted a comparison between the two groups by RNA sequencing to further narrow the range of target genes and related gene pathways in order to study their related mechanisms. Materials and methods: We extracted exosomes from SCs, fibroblasts (Fb) and neural stem cells (NSC) and then investigated the ability of these exosomes to induce differentiation into BMSCs under different culture conditions. The expression levels of key proteins and gene markers were detected in induced cells by fluorescence immunoassays, western blotting and polymerase chain reaction (PCR); then, we statistically compared the relative induction effects under different conditions. Finally, we analyzed the three types of exosomes by RNA-seq to predict target genes and related gene pathways. Results: BMSCs were cultured by three media: conventional (no induction), pre-induction or pre-induction + original induction medium (ODM) with exosomes of the same cell origin under different culture conditions. When adding the three different types of exosomes separately, the overall induction of BMSCs to differentiate into SCs was significantly increased (P < 0.05). The induction ability was ranked as follows: pre-induction + ODM + exosome group > pre-induction + exosome group > non-induction + exosome group. Using exosomes from different cell sources under the same culture conditions, we observed the following trends under the three culture conditions: RSC96-exos group ≥ NSC-exos group > Fb-exos group. The overall ability to induce BMSCs into SCs was significantly greater in the RSC96-exos group and the NSC-exos group. Although there was no significant difference in induction efficiency when comparing these two groups, the overall induction ability of the RSC96-exos group was slightly higher than that of the NSC-exos group. By combining the differentiation induction results with the RNA-seq data, the three types of exosomes were divided into three comparative groups: RSC vs. NSC, RSC vs. Fb and NSC vs. Fb. We identified 203 differentially expressed mRNA target genes in these three groups. Two differentially expressed genes were upregulated simultaneously, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). We did not identify any co-upregulated target genes for the miRNAs, but did identify one target gene of the lncRNAs, namely ENSRNOG00000065005. Analysis identified 90 GO terms related to nerves and axons in the mRNAs; in addition, KEGG enrichment and GASA analysis identified 13 common differential expression pathways in the three groups. Conclusions: Our analysis found that pre-induction + ODM + RSC96/NSC-exos culture conditions were most conducive with regards to induction and differentiation. RSC96-exos and NSC-exos exhibited significantly greater differentiation efficiency of BMSCs into SCs. Although there was no statistical difference, the data indicated a trend for RSC96-exos to be advantageous We identified 203 differentially expressed mRNAs between the three groups and two differentially expressed target mRNAs were upregulated, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). 90 GO terms were related to nerves and axons. Finally, we identified 13 common differentially expressed pathways across our three types of exosomes. It is hoped that the efficiency of BMSCs induction differentiation into SCs can be improved, bringing hope to patients and more options for clinical treatment. [ABSTRACT FROM AUTHOR]

Pharmaceutical incompatibility of clove oil due to its immiscibility in water may affect the safety, efficacy, appearance, and stability of the drug during immersion anesthesia. Though there are reports of using ethanol to enhance the anesthetic efficacy of clove oil, there are no reports of quantitative calculations of anesthetic efficacy and stages of anesthesia for this combination. To overcome this issue, a study was designed to enhance the miscibility of clove oil in water by incorporating ethanol as an interphase. Two trials were conducted using clove oil at concentrations of 50 and 100 mg/L, respectively, dissolved in ethanol at a 1:10 ratio. These trials were performed on tilapia fishes (Oreochromis mossambicus) to evaluate the time required for anesthesia induction, duration (maintenance time), and recovery from anesthesia. The results of the study showed an induction time of 1 min for the 100 mg/L concentration and 10 min for the 50 mg/L concentration. The duration of action was observed to be 12 min for the 100 mg/L concentration and 31 min for the 50 mg/L concentration, respectively. The recovery times were 10 min and 3 min for the 100 mg/L and 50 mg/L doses, respectively. Changes associated with various stages and planes for surgical anesthesia were also documented in this study. This study concludes that the mixture of clove oil and ethanol serves as a more effective general anesthetic for fish compared to conventional clove oil immersion anesthesia. [ABSTRACT FROM AUTHOR]

The role of a special educator is one of many different hats, including teacher, interventionist, comforter, parent, counselor, therapist, and administrator. These varying roles, particularly when working with students with emotional behavioral disorders, create one of the most emotionally taxing and challenging jobs in public education, which in turn leads to increased educator burnout and attrition. However, this does not need to be the fate of special educators. The purpose of this article is to (a) review one current support system widely implemented in the field for teachers of children with emotional behavioral disorders, (b) discuss the benefits of mentorship in the teaching workforce, (c) identify some of the barriers to mentorship, and (d) identify areas of reform for more effective mentorship practices. [ABSTRACT FROM AUTHOR]

The problem of getting rid of expensive and metal-intensive current transformers has been declared by CIGRE as strategically important for the electric power industry. However, almost all traditional current protections receive information from measuring current transformers. In this work, a resource-saving reed switch overcurrent protection without current transformers is suggested, which can be used as an alternative to traditional current protections for 6–10 kV electrical installations connected to a switchgear cell. The protection is designed following the novel method we have developed based on inductance coils. Inductance coils measure the electromotive force under different operation modes of an electrical installation and at different points inside the switchgear cell it is connected to; the EMF values are recalculated in the values of magnetic induction, and reed switches are mounted instead of inductance coils at the points where the magnetic induction is maximal. Moreover, these values are sufficient to detect phase-to-phase short circuits in the electrical installation. The dependence of the induction value on the position of an inductance coil inside the cell is derived with the use of the simplest formula of the Biot–Savart law. The results can be used at large and small industrial enterprises, electric power stations, and substations of plants; they can be interesting for the scientific community because they help to solve the topical problem of the electric power industry. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of transdermal glycerol trinitrate skin patches as an additive and effective agent for facilitating cervical ripening for labour induction. Methods: This was a double-blinded prospective randomised clinical trial carried out in a major obstetric unit in India. Women who planned for labour induction were randomly allocated for induction either by combined application of glycerol trinitrate skin patches [GTN patch] and intracervical dinoprostone gel or by the gel only. Sample randomisation was done using a stratified block randomisation technique with a sealed envelope. The numbers designating the group allocation sequence were concealed from doctors, research staff, and investigators. Six hourly improvements were assessed in the modified Bishop's score, induction-delivery time interval, the need for oxytocin, maternal side effects and foetal outcomes. Data were analysed using SPSS software. Results and discussion: Recruitment Bishop scores, parity and gestational age were matched in both cases and the control group. The modified Bishop's score was statistically improved in study groups, as evidenced compositely and irrespective of parity. The two groups appeared to have no significant differences regarding other outcomes. The additional application of the GTN patch seems helpful to accelerate the progress of labour but could not yield any favourable labour outcome. The GTN patch does not impose additional feto-maternal adverse effects apart from increased incidences of headaches. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cell (hPSC)-derived red blood cells (RBCs) possess great potential for compensating shortages in transfusion medicine. For better RBC generation from hPSCs, we compared the cell seeding density in the embryoid body formation-based hPSC induction protocol. In the selection of low- and high-density inoculation conditions, we found that low-density culture performed better in the final RBC product with more cell output and increased average cellular hemoglobin content. An elaborate study using flow cytometry demonstrated that low inoculation density promoted endothelial-to-hematopoietic transition, followed by improved hematopoietic progenitor formation and erythrocyte generation. The improved transformation from glycolysis to mitochondrial oxidation and reduced apoptosis might be responsible for this effect. Hints from RNA sequencing suggested that molecules involved in microenvironment interaction and metabolic regulation might respond for the different developmental potential. The possible mediators between outer message and intracellular response could be the nutrition sensors FOXO, PRKAA1 (AMPK), and MTOR genes. It is possible that low inoculation density triggered metabolic regulation signals, promoted mitochondrial oxidation, and resulted in enhanced cell amplification and hematopoietic differentiation. The low cell culture density will improve RBC generation from hPSCs. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing heart transplants are at risk of rejection which can have significant morbidity and mortality. Induction immunosuppression at the time of transplant reduces the early risk and has additional benefits. The induction agent of choice within our program was changed from rabbit antithymocyte‐globulin (rATG) to basiliximab, so it was necessary to evaluate whether this had any impact on patient outcomes. Objectives: Our primary objective was to describe rejection, infection, and other outcomes in adult heart transplant patients at the University of Alberta Hospital in Edmonton, Canada. Methods: This study was a nonrandomized, retrospective cohort study. Results: Sixty‐three patients were included with median ages 50 years versus 54 years. More female patients received rATG (20% vs. 42.4%). The most common indication for transplant in both cohorts was ICM (63.3% vs. 57.6%). Patients who received rATG had significantly higher PRA (0% vs. 43%, p <.001). Acute rejection episodes were similar between basiliximab and rATG at 3 months (16.7% vs. 15.1%; p = 1.0) and 6‐months (30.0% vs. 18.1%; p =.376). Infections were not statistically different with basiliximab compared to rATG at 3‐months, 43.3% vs. 63.6% and at 6‐months 60.0% vs. 66.7%). There were no fatalities in either group. Conclusions: Our study did not demonstrate differences in rejection with basiliximab compared to rATG. Mortality did not differ, but basiliximab‐treated patients had fewer infections and infection‐related hospitalizations than those treated with rATG. Larger studies with longer durations are needed to more completely describe the differences in rejection and infectious outcomes. [ABSTRACT FROM AUTHOR]

Carbamazepine (CBZ) is commonly prescribed for epilepsy and frequently used in polypharmacy. However, concerns arise regarding its ability to induce the metabolism of other drugs, including itself, potentially leading to the undertreatment of co-administered drugs. Additionally, CBZ exhibits nonlinear pharmacokinetics (PK), but the root causes have not been fully studied. This study aims to investigate the mechanisms behind CBZ's nonlinear PK and its induction potential on CYP3A4 and CYP2C9 enzymes. To achieve this, we developed and validated a physiologically based pharmacokinetic (PBPK) parent–metabolite model of CBZ and its active metabolite Carbamazepine-10,11-epoxide in GastroPlus®. The model was utilized for Drug–Drug Interaction (DDI) prediction with CYP3A4 and CYP2C9 victim drugs and to further explore the underlying mechanisms behind CBZ's nonlinear PK. The model accurately recapitulated CBZ plasma PK. Good DDI performance was demonstrated by the prediction of CBZ DDIs with quinidine, dolutegravir, phenytoin, and tolbutamide; however, with midazolam, the predicted/observed DDI AUClast ratio was 0.49 (slightly outside of the two-fold range). CBZ's nonlinear PK can be attributed to its nonlinear metabolism caused by autoinduction, as well as nonlinear absorption due to poor solubility. In further applications, the model can help understand DDI potential when CBZ serves as a CYP3A4 and CYP2C9 inducer. [ABSTRACT FROM AUTHOR]

This article examines how deduction preserves certainty and how much certainty it can preserve according to Descartes's Rules for the Direction of the Mind. I argue that the certainty of a deduction is a matter of four conditions for Descartes. First, certainty depends on whether the conjunction of simple propositions is composed with necessity or contingency. Second, a deduction approaches the certainty of an intuition depending on how many "acts of conceiving" it requires and—third—the complexity or difficulty of the acts of thinking, which is determined by the content of the thoughts and on external factors. Fourth, certainty depends on the intellectual aptitude of the person using the deduction. A deduction lacks certainty when it relies on memory such that it is not apprehended with immediacy. However, the mental capacity and speed of a mind can be increased by training the special mental faculties of perspicacity and discernment. Increasing one's intellectual aptitude allows for more steps of a deduction to be inferred in fewer acts of conceiving, thereby helping preserve the certainty of a deduction. [ABSTRACT FROM AUTHOR]

Background: We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long‐term outcomes compared to other induction agents. Methods: Using pediatric kidney transplant recipient data in the UNOS database between January 1, 2000, and June 30, 2022, multivariate logistic regression, multivariable Cox regression, and survival analyses were utilized to estimate the likelihoods of 1st‐year and all‐time hospitalizations, acute rejection, CMV infection, delayed graft function (DGF), graft loss, and patient mortality among recipients of three common induction regimens (ATG, alemtuzumab, and basiliximab). Results: There were no differences in acute rejection or graft failure among induction or maintenance regimens. Basiliximab was associated with lower odds of DGF in deceased donor recipients (OR 0.77 [0.60–0.99], p =.04). Mortality was increased in patients treated with steroid‐containing maintenance (HR 1.3 [1.005–1.7] p =.045). Alemtuzumab induction correlated with less risk of CMV infection than ATG (OR 0.76 [0.59–0.99], p =.039). Steroid‐containing maintenance conferred lower rate of PTLD compared to steroid‐free maintenance (HR 0.59 [0.4–0.8] p =.001). Alemtuzumab was associated with less risk of hospitalization within 1 year (OR 0.79 [0.67–0.95] p =.012) and 5 years (HR 0.54 [0.46–0.65] p <.001) of transplantation. Steroid maintenance also decreased 5 years hospitalization risk (HR 0.78 [0.69–0.89] p <.001). Conclusions: Pediatric KTRs may be safely treated with alemtuzumab induction without increased risk of acute rejection, DGF, graft loss, or patient mortality. The decreased risk of CMV infections and lower hospitalization rates compared to other agents make alemtuzumab an attractive choice for induction in pediatric KTRs, especially in those who cannot tolerate ATG. [ABSTRACT FROM AUTHOR]

A substantial number of social science studies have shown a lack of conceptual clarity, inadequate understanding of the nature of the empirical research approaches, and undue preference for deduction, which have caused much confusion, created paradigmatic incommensurability, and impeded scientific advancement. This study, through conceptual review and analysis of canonical discussions of concepts and the reasoning approaches of deduction and induction and their applications in social science theorization by philosophers and social scientists, is purported to unveil the logical nature of empirical research and examine the legitimacy of the preference of deduction among social scientists. The findings note that conceptual clarity as the foundation of social science research, exchange, and replication can be achieved through interdisciplinary stress of conceptual analyses to establish universal measurements and that the primacy of deduction in social sciences needs to concede to or be balanced with induction for new knowledge, more discoveries, and scientific advancement. The study recommends that institutions and researchers of social sciences invest more in conceptual analysis and inductive research through collaboration and separate efforts. [ABSTRACT FROM AUTHOR]

• MRI may reduce induction of labor rates for macrosomia in a hypothetical cohort. • Repeating Boulvain's trial using MRI would result in similar rates of shoulder dystocia. • There is possible clinical utility of MRI in the management of macrosomia. To simulate the outcomes of Boulvain's trial by using magnetic resonance imaging (MRI) for estimated fetal weight (EFW) as a second-line confirmatory imaging. Data derived from the Boulvain's trial and the study PREMACRO (PREdict MACROsomia) were used to simulate a 1000-patient trial. Boulvain's trial compared induction of labor (IOL) to expectant management in suspected macrosomia, whereas PREMACRO study compared the performance of ultrasound-EFW (US-EFW) and MRI-EFW in the prediction of birthweight. The primary outcome was the incidence of significant shoulder dystocia (SD). Cesarean delivery (CD), hyperbilirubinemia (HB), and IOL at < 39 weeks of gestation (WG) were selected as secondary outcomes. A subgroup analysis of the Boulvain's trial was performed to estimate the incidence of the primary and secondary outcomes in the true positive and false positive groups for the two study arms. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) for the prediction of macrosomia by MRI-EFW at 36 WG were calculated, and a decision tree was constructed for each outcome. The PPV of US-EFW for the prediction of macrosomia in the PREMACRO trial was 56.3 %. MRI-EFW was superior to US-EFW as a predictive tool resulting in lower rates of induction for false-positive cases. Repeating Boulvain's trial using MRI-EFW as a second-line test would result in similar rates of SD (relative risk [RR]:0.36), CD (RR:0.84), and neonatal HB (RR:2.6), as in the original trial. Increasing the sensitivity and specificity of MRI-EFW resulted in a similar relative risk for SD as in Boulvain's trial, but with reduced rates of IOL < 39 WG, and improved the RR of CD in favor of IOL. We found an inverse relationship between IOL rate and incidence of SD for both US-EFW and MRI-EFW, although overall rates of IOL, CD, and neonatal HB would be lower with MRI-derived estimates of fetal weight. The superior accuracy of MRI-EFW over US-EFW for the diagnosis of macrosomia could result in lower rates of IOL without compromising the relative advantages of the intervention but fails to demonstrate a significant benefit to justify a replication of the original trial using MRI-EFW as a second-line test. [ABSTRACT FROM AUTHOR]

Background Aims Materials and Methods Results Conclusion Excess intravenous fluid for women requiring an induction of labour may adversely affect the duration of labour and maternal/neonatal outcomes.This study aimed to determine the difference in duration of labour and outcomes with a low background infusion rate, compared to liberal background intravenous fluid management.A double blind randomised controlled pilot study was performed on 200 women who underwent induction of labour at a single institution. Women were randomised to an intravenous rate of 40 mL/h versus 250 mL/h of Hartmann's solution. Fluid boluses were strictly controlled to limit bias. This trial was registered with the Australian clinical trial registry: ACTRN12621001298808.Analysis of the total amount of fluid received showed good separation with Group 1 (40 mL/h) receiving 1,736 mL less than Group 2 (250 mL/h), median (interquartile range) 841 mL (458, 1691) versus 2,577 mL (1620, 4326) (P < 0.001). Median duration of labour was shorter in Group 1 by 24 min (P = ns). Subset analysis of nulliparous women showed that duration of labour was shorter in Group 1 by 83.5 min (P = ns).As this was a pilot study, a significant difference in duration of labour or secondary outcomes was not seen. Given the increasing numbers of nulliparous women having an induction of labour, potential for adverse maternal and neonatal outcomes and the associated higher rate of operative birth, this study guides power calculations and supports proof of concept for future research into optimum fluid management during induction of labour for these women. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic joint infection is a serious complication following joint replacement. The development of bacterial biofilms bestows antibiotic resistance and restricts treatment via implant retention surgery. Electromagnetic induction heating is a novel technique for antibacterial treatment of metallic surfaces that has demonstrated in-vitro efficacy. Previous studies have always employed stationary, non-portable devices. This study aims to assess the in-vitro efficacy of induction-heating disinfection of metallic surfaces using a new Portable Disinfection System based on Induction Heating. Methods: Mature biofilms of three bacterial species: S. epidermidis ATCC 35,984, S. aureus ATCC 25,923, E. coli ATCC 25,922, were grown on 18 × 2 mm cylindrical coupons of Titanium-Aluminium-Vanadium (Ti6Al4V) or Cobalt-chromium-molybdenum (CoCrMo) alloys. Study intervention was induction-heating of the coupon surface up to 70ºC for 210s, performed using the Portable Disinfection System (PDSIH). Temperature was monitored using thermographic imaging. For each bacterial strain and each metallic alloy, experiments and controls were conducted in triplicate. Bacterial load was quantified through scraping and drop plate techniques. Data were evaluated using non-parametric Mann-Whitney U test for 2 group comparison. Statistical significance was fixed at p ≤ 0.05. Results: All bacterial strains showed a statistically significant reduction of CFU per surface area in both materials. Bacterial load reduction amounted to 0.507 and 0.602 Log10 CFU/mL for S. aureus on Ti6Al4V and CoCrMo respectively, 5.937 and 3.500 Log10 CFU/mL for E. coli, and 1.222 and 0.372 Log10 CFU/mL for S. epidermidis. Conclusions: Electromagnetic induction heating using PDSIH is efficacious to reduce mature biofilms of S aureus, E coli and S epidermidis growing on metallic surfaces of Ti6Al4V and CoCrMo alloys. [ABSTRACT FROM AUTHOR]

Simple Summary: The Formosan serow is a wild goat found only in the mountains of Taiwan. In this cross-over study, two different drug combinations were used to anesthetize five adult Formosan serows in a zoo environment, namely dexmedetomidine–tiletamine–zolazepam and dexmedetomidine–ketamine. Each animal received each of the drug combinations for general anesthesia at least once, with an interval of at least 12 months between anesthesia administrations. While dexmedetomidine–tiletamine–zolazepam induced anesthesia faster than ketamine–dexmedetomidine, these animals experienced problems such as paddling, prolonged recovery, and ataxia. The animals in the dexmedetomidine–tiletamine–zolazepam group had lower breathing rates and body temperatures than those in the dexmedetomidine–ketamine group. In summary, the dexmedetomidine–tiletamine–zolazepam combination anesthetized the Formosan serows rapidly but recovery was more eventful. Formosan serows are endemic to the mountainous regions of Taiwan. This crossover study aimed to assess and compare the anesthetic induction and recovery using either dexmedetomidine–tiletamine–zolazepam (DZ) or dexmedetomidine–ketamine (DK) by intramuscular injection from a blow-dart in a zoo environment. Ten anesthetic procedures were performed with five adult Formosan serows. Each participant was anesthetized with both combinations at least once with a minimal 12-month washout. The average dosages were 22.6 ± 8.3 µg/kg and 35.8 ± 2.5 µg/kg for dexmedetomidine and 185.6 ± 123.6 and 357.8 ± 25.2 µg/kg for atipamezole for the DZ and DK groups, respectively. The doses of tiletamine–zolazepam and ketamine were 2.1 ± 0.25 mg/kg and 3.6 ± 0.3 mg/kg, respectively, in the DZ and DK groups. All participants were induced within 10 min (median: 8 min for both groups), except one serow in the DK group with an induction time of 22 min. Serows in the DZ group had a lower respiratory rate (p = 0.016) and lower rectal temperature (p = 0.008) than those in the DK group. The quality of recovery was poor for DZ because of paddling, prolonged recovery, and ataxia after antagonism of dexmedetomidine with atipamezole. The induction of anesthesia with dexmedetomidine–tiletamine–zolazepam was uneventful and rapid. However, recovery from this combination was not smooth. [ABSTRACT FROM AUTHOR]

Natural melanin is a sustainable and environmentally friendly pigment. The structural properties of melanin are of great significance for its functional applications. In this study, the preliminary composition and structure of melanin extracted from the induced cultures of Lasiodiplodia theobromae were qualitatively characterized by ultraviolet-visible (UV) spectrophotometer, elemental analysis (EA), Fourier transform infrared spectrometer (FTIR), nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The results showed that the secreted melanin contained many functional groups such as hydroxy groups, alkanes and aromatic rings, which belonged to benzoquinone structure and aliphatic structure. The melanin secreted by Lasiodiplodia theobromae can be identified as a type of allomelanin. This research work is expected to provide a reference for the application of melanin in various fields in the future. In this study, we have obtained different types of nano-melanins secreted by Lasiodiplodia theobromae through induction, and identified the structure of nano-melanins through various chemical qualitative testing methods (UV, EA, FTIR, NMR, EPR, UPLC-MS). It was found that the nano-melanins contain multiple functional groups such as hydroxyl, alkanes, aromatic rings, and belong to the benzoquinone and aliphatic structures. Thus, the melanin secreted by Lasiodiplodia theobromae can be identified as a type of heteromelanin. [ABSTRACT FROM AUTHOR]