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Rubric-based observations of pre- and inservice teachers are common practice in schools. Popular observation tools often result in minimal variation in ratings between teachers, require extensive training and time demands for raters, and provide minimal feedback for professional development. Alternatively, direct observation methods are evidenced to effectively measure instructional behaviors. Applying direct observation to audio recordings would produce quantitative scores and provide valuable feedback to teachers about their instruction. As such, the purpose of the present pilot study was to examine the reliability and efficiency of using audio recordings to measure practices related to explicit instruction. Fleiss's kappa was modeled to determine the reliability of multiple raters. Regression and correlation examined the strength and direction of the relationship between the full length of a teacher's lesson and the first 20 min of the lesson. Results indicate that using audio recordings is reliable with kappas ranging from 0.45 to 0.80. Based on regression analyses, the first 20 min of a teacher's lesson is predictive of the rates of behaviors observed in a full lesson. Correlations suggest large, positive relationships between rates of behaviors in the first 20 min and the full lesson. Recommendations for future studies of audio-recorded observations and progress monitoring teacher behavior are discussed.

Murat Adam is head of policy and curriculum for the European ministry of education. Political pressure is rising. Media channels across the European federation are labeling the continent as the most recent member of the education periphery. In Mr Adam's world, curricular authority transpires from the big 3, the North American Union (NAU), China, and Russia. Credibility and endorsement are educational currencies--institutional capital as Bourdieu once defined it, reigns. Mr Adam's battle is already lost, member states of the European federation have lost their educational means of production, but he cannot afford to admit that. European teachers' credentials increasingly force graduates into care taking jobs at digital day cares. These are a response to US teachers' and practitioners' revolts of the late 20s, linked to perceived multisensory impoverishment of digitally schooled children. Just like in South Asia, Africa, and South America, digital day cares merely provide the digital and social framework and setup K-12 students to listen to internationally accredited professionals teach from China, Russia, and the NAU. Day and night shifts are common. He knows that the European federation lost the contest, by the time it decided not to invest into its own internet infrastructure. The educational first world's curricular authority would not have been possible without the three nations' proprietary server architecture, which commodified bandwidth and connectivity. The internet of the past is nothing more than a front for the three de-facto mutually exclusive digital ecosystems, provided by China, the NAU, and Russia.

The Landesinitiative openaccess.nrw is a project of the Digitale Hochschule NRW (DH.NRW), which is a cooperative association of 42 universities in North Rhine-Westphalia, consisting of universities, universities of applied sciences, art and music colleges as well as private and church-run universities. It is funded by the NRW Ministry of Culture and Science. In a preliminary project, which included interviews with the university libraries and an online needs assessment, a large number of requirements for the state initiative were evaluated and the main project, which was launched in 2022, was aligned with the requirementrogram areas.

ABSTRACT Transmission of genetic material from one generation to the next is a fundamental feature of all living cells. In eukaryotes, a macromolecular complex called the kinetochore plays crucial roles during chromosome segregation by linking chromosomes to spindle microtubules. Little is known about this process in evolutionarily diverse protists. Within the supergroup Discoba, Euglenozoa forms a speciose group of unicellular flagellates—kinetoplastids, euglenids, and diplonemids. Kinetoplastids have an unconventional kinetochore system, while euglenids have subunits that are conserved among most eukaryotes. For diplonemids, a group of extremely diverse and abundant marine flagellates, it remains unclear what kind of kinetochores are present. Here, we employed deep homology detection protocols using profile-versus-profile Hidden Markov Model searches and AlphaFold-based structural comparisons to detect homologies that might have been previously missed. Interestingly, we still could not detect orthologs for most of the kinetoplastid or canonical kinetochore subunits with few exceptions including a putative centromere-specific histone H3 variant (cenH3/CENP-A), the spindle checkpoint protein Mad2, the chromosomal passenger complex members Aurora and INCENP, and broadly conserved proteins like CLK kinase and the meiotic synaptonemal complex proteins SYCP2/3 that also function at kinetoplastid kinetochores. We examined the localization of five candidate kinetochore-associated proteins in the model diplonemid, Paradiplonema papillatum. PpCENP-A shows discrete dots in the nucleus, implying that it is likely a kinetochore component. PpMad2, PpCLKKKT10/19, PpSYCP2L1KKT17/18, and PpINCENP reside in the nucleus, but no clear kinetochore localization was observed. Altogether, these results point to the possibility that diplonemids evolved a hitherto unknown type of kinetochore system.IMPORTANCEA macromolecular assembly called the kinetochore is essential for the segregation of genetic material during eukaryotic cell division. Therefore, characterization of kinetochores across species is essential for understanding the mechanisms involved in this key process across the eukaryotic tree of life. In particular, little is known about kinetochores in divergent protists such as Euglenozoa, a group of unicellular flagellates that includes kinetoplastids, euglenids, and diplonemids, the latter being a highly diverse and abundant component of marine plankton. While kinetoplastids have an unconventional kinetochore system and euglenids have a canonical one similar to traditional model eukaryotes, preliminary searches detected neither unconventional nor canonical kinetochore components in diplonemids. Here, we employed state-of-the-art deep homology detection protocols but still could not detect orthologs for the bulk of kinetoplastid-specific nor canonical kinetochore proteins in diplonemids except for a putative centromere-specific histone H3 variant. Our results suggest that diplonemids evolved kinetochores that do not resemble previously known ones.

Railway tracks, like all civil works, experience degradation after being put into service, thus losing their initial design conditions. This degradation manifests itself mainly through misalignment and specific deterioration mechanisms of each component, which reduces safety and comfort during the passage of trains. In order to maintain their operational capabilities or prolong their service life, continuous monitoring, diagnosis and maintenance processes are carried out. These actions aim to restore the physical, mechanical and geometrical properties necessary for track operation.In practice, rail managers often employ hegemonic techniques such as geometric measurements to detect defects and routine maintenance to realign, known as tamping. Although these practices have proven to be effective, in some cases they do not technically and economically competently solve the root problem. For this reason, diagnosis should be multidisciplinary and incorporate various disciplines associated with the track components.This paper aims to highlight the importance and impact of geotechnical diagnosis in the management of railway networks. To achieve this, the article has the following structure: (a) Railway track components: the main elements of the track are described and the role of geotechnical components in the stability of the infrastructure is highlighted, (b) Track degradation: The main deterioration of the track, such as loss of geometry, and its relation to the wear of the geotechnical elements are addressed, (c) Monitoring and monitoring: the most commonly used geotechnical inspection methods and their effectiveness in the analysis of granular material are presented, (d) Geotechnical diagnosis: Current maintenance management is analyzed and guidelines for a comprehensive diagnosis are suggested, highlighting cases where poor assessment has generated problems, (e) Maintenance techniques: Preservation methods are reviewed, stressing the importance of accurate diagnosis for their effectiveness, and (f) Future perspectives: Trends such as the use of artificial intelligence and advanced data management in the railway sector are explored.

A vast multitude of tasks in histopathology could potentially benefit from the support of artificial intelligence (AI). Many examples have been shown in the literature and first commercial products with FDA or CE-IVDR clearance are available. However, two key challenges remain: (1) a scarcity of thoroughly annotated images, respectively the laboriousness of this task, and (2) the creation of robust models that can cope with the data heterogeneity in the field (domain generalization). In this work, we investigate how the combination of prototypical few-shot classification models and data augmentation can address both of these challenges. Based on annotated data sets that include multiple centers, multiple scanners, and two tumor entities, we examine the robustness and the adaptability of few-shot classifiers in multiple scenarios. We demonstrate that data from one scanner and one site are sufficient to train robust few-shot classification models by applying domain-specific data augmentation. The models achieved classification performance of around 90% on a multiscanner and multicenter database, which is on par with the accuracy achieved on the primary single-center single-scanner data. Various convolutional neural network (CNN) architectures can be used for feature extraction in the few-shot model. A comparison of nine state-of-the-art architectures yielded that EfficientNet B0 provides the best trade-off between accuracy and inference time. The classification of prototypical few-shot models directly relies on class prototypes derived from example images of each class. Therefore, we investigated the influence of prototypes originating from images from different scanners and evaluated their performance also on the multiscanner database. Again, our few-shot model showed a stable performance with an average absolute deviation in accuracy compared to the primary prototypes of 1.8% points. Finally, we examined the adaptability to a new tumor entity: classification of tissue sections containing urothelial carcinoma into normal, tumor, and necrotic regions. Only three annotations per subclass (e.g., muscle and adipose tissue are subclasses of normal tissue) were provided to adapt the few-shot model, which obtained an overall accuracy of 93.6%. These results demonstrate that prototypical few-shot classification is an ideal technology for realizing an interactive AI authoring system as it only requires few annotations and can be adapted to new tasks without involving retraining of the underlying feature extraction CNN, which would in turn require a selection of hyper-parameters based on data science expert knowledge. Similarly, it can be regarded as a guided annotation system. To this end, we realized a workflow and user interface that targets non-technical users.

Sense of Okayness (SOK) is an emerging concept that describes a person’s ability to remain stable and unshaken in the face of life transitions and hardships. This quality enables effective stress regulation and heightened tolerance to uncertainty. To investigate the possible role of the parasympathetic nervous system (PNS) in mediating the relationship between SOK and stress regulation among older individuals, an analytical sample of N = 69 participants (74% women) with a mean age of 78.75 years (SD age = 6.78) was recruited for a standardized cognitive assessment and stress induction. Baseline heart rate variability (HRV), measured via electrocardiogram (ECG), and SOK assessments were conducted prior to stress induction, along with a baseline cognitive evaluation. Subsequently, participants were subjected to a psychosocial stress paradigm, followed by either a 30-minute SOK elevation intervention (n = 40) or a control condition with nature sounds (n = 29). A second cognitive assessment was administered post-intervention, with continuous HRV measurement through ECG. The results revealed significant HRV changes due to the experimental intervention, though no significant differences were observed between the SOK intervention and control groups. Interestingly, individuals with high trait SOK displayed more stable HRV trajectories, exhibiting a smaller decline during the stress intervention and a milder increase during both the stressor and SOK intervention phases. Overall, these findings do suggest a significant association between SOK, parasympathetic activity, and stress reactivity. These results prompt further investigation into whether personality patterns, such as a strong SOK, may be linked to reduced vagal reactivity and better coping in old age.

Transforming railway stations and their surroundings into multimodal transportation hubs (MMTHs) involves numerous actors at different scales and from different economic sectors and levels of government. Successful transformations offer a wide range of benefits to sustainable development, including increased public transportation use and mixed-use, high-density station districts. Intensive collaboration and, ideally, co-creation are critical to achieving these outcomes through MMTHs; however, orchestrating all involved actors is challenging and requires supporting methods, and the knowledge required to develop and refine methods is scarce and rarely subjected to systematic analysis. Based on 15 semistructured interviews and two design thinking workshops attended by 13 and 20 MMTH experts, our study shows that the challenges of co-creating MMTHs relate not only to professional matters but also to managing collaboration and implementation among a large number of actors with various roles and interests. In this paper, we develop design guidelines for reviewing and evaluating two current methods and a prototypical method (the functional model) with the goal of identifying potential improvements and supporting MMTH co-creation in Switzerland. These guidelines cover the broad spectrum of co-creation activities, from organization and design collaboration with relevant actors to the development of a shared vision to support financing and the planning process. The functional model encompasses many aspects of the design guidelines and closes gaps between actors across different scales, economic sectors, and governmental levels. Due to the relatively low effort involved, the method can be repeated as needed throughout MMTH development, which often takes several years. Our study demonstrates that existing MMTH co-creation methods require improvement, and the design guidelines developed here suit this purpose. Our work thus contributes to the further development of MMTH co-creation methods, ultimately supporting sustainable development such as CO2 emission reduction and responsible land use.

Somatostatin receptor type 2 (SSTR2) is one of the five subtypes of somatostatin receptors and is overexpressed on the surface of most gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs), pituitary tumors, paraganglioma, and meningioma, as well as hepatocellular carcinoma and breast cancer. Chimeric antigen receptor (CAR) T-cells are genetically engineered to express an artificial, T-cell activating binder, leading upon ligation to biocidal activity against target-antigen expressing cells. Adaptor-CAR T-cells recognize, via the CAR, a tag on an antigen-binding molecule, building an activating bridge between the CAR and the target cell. We hypothesized that a novel fluorescent-peptide antagonist of SSTR2, called Octo-Fluo, in combination with anti-FITC adaptor CAR (AdFITC(E2)-CAR) T-cells, may function as an on-off tunable activating bridge between the CAR and SSTR2 expressing target cells. In vitro studies confirmed the binding of Octo-Fluo to Bon1-SSTR2 mCherry-Luc cells without evidence of internalization. AdFITC(E2)-CAR T-cells were activated and efficiently induced Bon1-SSTR2 cell death in vitro, in an Octo-Fluo concentration-dependent manner. Similarly, AdFITC(E2)-CAR T-cells in combination with Octo-Fluo efficiently infiltrated the tumor and eliminated Bon1-SSTR2 tumors in immunodeficient mice in therapeutic settings. Both, AdFITC(E2)-CAR T-cell tumor infiltration and biocidal activity were Octo-Fluo concentration-dependent, with high doses of Octo-Fluo, saturating both the CAR and the SSTR2 antigen independently, leading to the loss of tumor infiltration and biocidal activity due to the loss of bridge formation. Our findings demonstrate the potential of using AdFITC(E2)-CAR T-cells with Octo-Fluo as a versatile, on-off tunable bispecific adaptor for targeted CAR T-cell immunotherapy against SSTR2-positive NETs.

Background: The standard of care for unresectable locally advanced NSCLC is concurrent chemotherapy and radiation (CRT) followed by adjuvant durvalumab, established by the PACIFIC trial, which revealed acceptable although higher rates of pneumonitis with durvaluamb than placebo. We retrospectively reviewed patients with locally advanced NSCLC from 2018 to 2022 treated with definitive CRT (≥60 Gy) followed by at least one dose of adjuvant durvalumab. Objective: To review the incidence of pneumonitis and contributing factors, and also to review grade 5 pneumonitis (G5) events. Methods: We identified 78 cases with a median age of 70.0 years and a median follow-up of 36 months. All patients received CRT of at least 60 Gy at 2 Gy per fraction. A total of 22 patients (28.2%) completed 12 months of durvalumab. The cumulative incidence of any-grade pneumonitis was 28.2%. Pneumonitis rate in grades 1, 2, 3, 4, and 5 was 1.3%, 10.3%, 7.7%, 0.0%, and 9.0%, respectively. Results: Multivariate analysis did not reveal significant factors associated with G5 pneumonitis. There were 8 patients who received radiation therapy doses above standard limits and, of these, only two developed G5 pneumonitis. All patients with G5 pneumonitis had multiple comorbidities or previous malignancy treated with systemic therapy. The median overall survival was 31.1 months and the median progression-free survival was 12.7 months. Conclusions: We report comparable overall rates of pneumonitis relative to published data with higher rates of G5 pneumonitis. Patients with high-dose radiation therapy (≥60 Gy) and Eastern Cooperative Oncology Group performance status greater than or equal to 2 may tolerate adjuvant durvalumab, though providers should exercise caution in patients with extensive comorbidities.

Cardiac amyloidosis is a disease characterised by the accumulation of amyloid protein in the heart tissue. There are several types of amyloidosis, but the most common types affecting the heart are ATTR amyloidosis (caused by transthyretin protein) and AL amyloidosis (caused by abnormal immunoglobulin light chains). Cardiac amyloidosis causes typical signs and symptoms of heart failure. Diagnosis involves a combination of imaging tests such as echocardiography and cardiac magnetic resonance imaging, as well as nuclear imaging scans and tissue biopsies to confirm the presence of amyloid deposits in the heart. Treatment of cardiac amyloidosis depends on the type and severity of the disease and includes medications to manage symptoms as well as treatments targeting the underlying cause of amyloidosis. Importantly, cardiac amyloidosis is a serious condition requiring specialised care from a multidisciplinary team including cardiologists and haematologists as well as other specialists familiar with the management of this rare disease. This is crucial, as early diagnosis and treatment are important for improving outcomes.

At the time of breast cancer diagnosis, most patients meet the diagnostic criteria to be classified as obese or overweight. This can significantly impact patient outcome: breast cancer patients with obesity (body mass index > 30) have a poorer prognosis compared to patients with a lean BMI. Obesity is associated with hyperleptinemia, and leptin is a well-established driver of metastasis in breast cancer. However, the effect of hyperleptinemia on angiogenesis in breast cancer is less well-known. Angiogenesis is an important process in breast cancer because it is essential for tumor growth beyond 1mm3 in size as well as cancer cell circulation and metastasis. This review investigates the role of leptin in regulating angiogenesis, specifically within the context of breast cancer and the associated tumor microenvironment in obese patients.

In Milchviehställen mit Laufhöfen bestehen aufgrund der größeren emittierenden Flächenanteile Zielkonflikte zwischen Tierwohl und Umweltschutz. Eine mögliche Lösung ist die Strukturierung der Laufhöfe mit nicht überdachten Hochboxen und überdachten Fressplätzen. Diese Gestaltung ermöglicht den Tieren ein vollständiges Spektrum an bedürfnis- und artgerechten Verhaltensweisen auf dem Laufhof und reduziert gleichzeitig die emissionsaktiven Flächen. In der vorliegenden Untersuchung wurden Wildtierkamerabilder ausgewertet, um den Anteil an Kühen zu ermitteln, die den Laufhof nutzen. Zusätzlich wurde auf vier Betrieben die Nutzung der verschiedenen Funktionsbereiche der strukturierten Laufhöfe ausgewertet. In drei Betrieben mit vergleichbarem Stall- und Laufhofdesign wurde speziell die Nutzung der Hochboxen durch die Kühe analysiert. Im Durchschnitt wurden 14 % der Tiere einer Herde im Beobachtungszeitraum tagsüber zwischen 8:00 und 14:00 Uhr auf den Laufhöfen gezählt. Auf den strukturierten Laufhofvarianten verteilten sich die Tiere relativ gleichmäßig auf die Funktionsbereiche, wobei die Hochboxen sowohl zum Liegen als auch zum Stehen genutzt wurden. Es wurden jedoch große Unterschiede zwischen den Betrieben festgestellt, selbst wenn die Laufhofstrukturen ähnlich waren. Diese Ergebnisse unterstreichen den Bedarf an weiterer Forschung zur optimalen Gestaltung von Laufhöfen, um die Balance zwischen Tierwohl und Umweltschutz effektiv zu verbessern.

Ein Liegeboxenlaufstall kann entweder in Längs- oder Queraufstallung (Kammstall) ausgeführt werden. Auf einem neu gebauten Milchviehbetrieb mit automatischem Melksystem (AMS) und Spaltenboden wurde die Kammstallgeometrie gewählt und dadurch für die Kühe über fünf Gänge Zugang zu einem angegliederten Laufhof ermöglicht. Ein Ortungssystem bot die Möglichkeit, die Aufenthaltsorte der Kühe zu analysieren. Es wurde insbesondere der Frage nachgegangen, ob es eine Bevorzugung bestimmter Gänge gab und wie der Laufhof frequentiert wurde. Dabei stellte sich heraus, dass der äußere Gang, obwohl hier im Gegensatz zu den anderen Gängen nur eine Liegeboxenreihe angrenzte und er am weitesten vom Melksystem entfernt war, länger genutzt wurde. Für die Verbesserung von Emissionsschutz und Tierwohl könnte es interessant sein, zu prüfen, ob eine Anpassung der Gangbreiten in Kammställen vorteilhaft wäre

In the published version of this paper, the list of members of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium and their affiliations contained minor errors in the affiliations. The original Article has been corrected to include the corrected list.

Fibroblast-activation protein (FAP) is a serine protease classified in the dipeptidyl peptidase 4 (DPP4) family. FAP is predominantly expressed in activated fibroblasts such as the cancer-associated fibroblasts (CAFs). FAP expression in CAFs is associated with tumor progression and poor prognosis in solid cancers. Recently, radiolabeled FAP inhibitors (FAPI) has been developed, which enables positron emission tomography (PET) imaging of FAP. FAPI PET/CT can provide a higher tumor-to-background ratio (TBR) than 18F-fludeoxyglucose PET/CT in various cancers, and thus has attracted substantial attention. As studies on FAPI PET grow in number and size, incidental findings related to non-oncologic conditions have been increasingly reported. FAPI PET uptake has been reported in various conditions such as benign tumors, fibrotic, granulomatosis, scarring/wound, degenerative diseases, and inflammatory diseases.The knowledge of physiological and non-oncologic causes of FAPI uptake is indispensable for accurate FAPI PET/CT interpretation and can help appropriate management of incidental findings on FAPI PET/CT in patients referred for cancer staging indications. In this review article, we describe for each organ system (Brain, Oral mucosa, Salivary Glands, Thyroid, Lung, Myocardium, Breast, Esophagus, Stomach, Intestine, Liver, Gallbladder, Pancreas, Spleen, Kidney, , Uterus, Bone marrow, Joints, Muscle, Vessels, Lymph nodes), the patterns of physiological FAPI uptake and the main causes of non-oncological uptake reported from the literature with FAPI-02, FAPI-04 and FAPI-46. We also illustrate some examples from our institutional database at UCLA.

El Gigante rockshelter in western Honduras provides a deeply stratified archaeological record of human-environment interaction spanning the entirety of the Holocene. Botanical materials are remarkably well preserved and include important tree (e.g., ciruela (Spondias), avocado (Persea americana)) and field (maize (Zea mays), beans (Phaseolus), and squash (Cucurbita)) crops. Here we provide a major update to the chronology of tree and field crop use evident in the sequence. We report 375 radiocarbon dates, a majority of which are for short-lived botanical macrofossils (e.g., maize cobs, avocado seeds, or rinds). Radiocarbon dates were used in combination with stratigraphic details to establish a Bayesian chronology for ~9,800 identified botanical samples spanning the last 11,000 years. We estimate that at least 16 discrete intervals of use occurred during this time, separated by gaps of ~100-2,000 years. The longest hiatus in rockshelter occupation was between ~6,400 and 4,400 years ago and the deposition of botanical remains peaked at ~2,000 calendar years before present (cal BP). Tree fruits and squash appeared early in the occupational sequence (~11,000 cal BP) with most other field crops appearing later in time (e.g., maize at ~4,400 cal BP; beans at ~2,200 cal BP). The early focus on tree fruits and squash is consistent with early coevolutionary partnering with humans as seed dispersers in the wake of megafaunal extinction in Mesoamerica. Tree crops predominated through much of the Holocene, and there was an overall shift to field crops after 4,000 cal BP that was largely driven by increased reliance on maize farming.

We investigate the interpretation of disjunction in child and adult Romanian via a replication of Tieu et al. (2017). Specifically, we target the simple disjunction 'sau' ‘or’ (with two intonation patterns: neutral and marked), and the complex disjunction markers 'sau…sau' and 'fie…fie' ‘either…or’. In a predictive Truth Value Judgment Task, participants evaluated a puppet’s disjunctive guesses ('The hen pushed the bus or the plane') after seeing the outcome. Adults assigned predominantly exclusive interpretations to both simple and complex disjunctions ('The hen pushed only one'). Children, however, generally interpreted 'sau' (with both intonational patterns) and 'sau…sau' inclusively (The hen pushed one and possibly both), while they interpreted 'fie…fie' conjunctively ('The hen pushed both'). It would appear that at an initial developmental stage, morphological/prosodic markedness does not affect children’s interpretation of disjunction. We discuss several possible accounts for the observed variation among complex disjunctions in child Romanian.

Some elementary students may exhibit challenging externalizing or internalizing behaviors in addition to difficulty with mathematics. In this study, we explored the behavioral patterns of 441 third-grade students with and without mathematics difficulty (MD). Compared with students without MD, students with MD demonstrated higher rates of externalizing and internalizing behaviors. We then randomly assigned 162 third-grade students with MD to receive a 10-week word-problem intervention or to be in a business-as-usual comparison group. Within the word-problem intervention, students with MD who exhibited higher occurrences of externalizing behaviors performed significantly lower on a word-problem measure than students without as many occurrences of externalizing behaviors. Response to the word-problem intervention did not differ based on internalizing behavior patterns.

Whilst the potential of fish effluents as nutrient sources for crop production has been demonstrated, their use in the European Union remains prohibited in organic farming. In this study, we investigate the efficacy in greenhouse basil cultivation of two types of fish effluents (filtered ‘fish water’ and unfiltered ‘fish sludge’) from an aquaponic system, and assess their role in maintaining and enhancing soil fertility as well as their potential to create a ’living soil’, which are two of the prerequisites for organic certification in the EU. To evaluate the contribution of fish effluents to plant growth in comparison with soil nutrients, basil plants were grown in pots containing two types of substrate: compost-free (without organic matter) and with compost (with organic matter). The results indicate that fish water and fish sludge demonstrate significant potential as fertilisers and outperform compost in certain parameters, such as plant biomass. The results also align with existing literature by demonstrating the positive impact of compost on soil microbial diversity, underscoring its role in fostering plant health. Although the treatments did not show differences in microbial composition at the genus level, the higher microbial diversity observed following fish effluent application highlights its potential for promoting ’living soil’. This research underscores the need for continued exploration of the implications of compost application in conjunction with fish effluent fertilisation on soil microbial communities and the production of specialty crops such as herbs.

Previous studies suggest that students who attend school consistently are more likely to perceive a connection to their school, teacher, and peers. This mixed-methods study was set in a public middle school in the Pacific Northwest. Extant attendance data and responses to a researcher-generated survey of students who met the state's definition for chronic absenteeism were analyzed to explore changes in students' self-reported feelings of being connected to school, teacher relationships, peer relationships, and school climate before the COVID-19 pandemic and during Comprehensive Distance Learning (CDL). Survey responses from 105 middle school students, all identified as chronically absent in the current school year based on attendance data, suggest a decrease in the way in which positive school relationships are formed, peer relationships are nurtured and maintained, and school climate is cultivated during CDL. These changes have had a significant impact on the degree to which students feel connected to school in a virtual environment. Implications for practice are discussed.

PURPOSE: To assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer. METHODS: Secondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed. Random assignment was stratified by lymph node status; lymph node-positive patients (n = 459) were allocated to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). Primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586) were conducted in 2020. The 70-gene signature identified genomic low-risk and high-risk patients. Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling assessed the long-term distant recurrence-free interval (DRFI). Swedish high-quality registries allowed a complete follow-up of 20 years. RESULTS: In estrogen receptor-positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio [HR], 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively). Significant goserelin-tamoxifen interaction was observed (P = .016). Genomic low-risk patients (n = 305) significantly benefitted from tamoxifen (HR, 0.24; 95% CI, 0.10 to 0.60), and genomic high-risk patients (n = 158) from goserelin (HR, 0.24; 95% CI, 0.10 to 0.54). Increased risk from the addition of tamoxifen to goserelin was seen in genomic high-risk patients (HR, 3.36; 95% CI, 1.39 to 8.07). Moreover, long-lasting 20-year tamoxifen benefit was seen in genomic low-risk patients, whereas genomic high-risk patients had early goserelin benefit. CONCLUSION: This study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor-positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics. Combined goserelin and tamoxifen therapy showed no benefit over single treatment. Long-term follow-up to assess treatment benefit is critical.

Exoplanet science is one of the most thriving fields of modern astrophysics. A major goal is the atmospheric characterization of dozens of small, terrestrial exoplanets in order to search for signatures in their atmospheres that indicate biological activity, assess their ability to provide conditions for life as we know it, and investigate their expected atmospheric diversity. None of the currently adopted projects or missions, from ground or in space, can address these goals. In this White Paper, submitted to ESA in response to the Voyage 2050 Call, we argue that a large space-based mission designed to detect and investigate thermal emission spectra of terrestrial exoplanets in the mid-infrared wavelength range provides unique scientific potential to address these goals and surpasses the capabilities of other approaches. While NASA might be focusing on large missions that aim to detect terrestrial planets in reflected light, ESA has the opportunity to take leadership and spearhead the development of a large mid-infrared exoplanet mission within the scope of the "Voyage 2050" long-term plan establishing Europe at the forefront of exoplanet science for decades to come. Given the ambitious science goals of such a mission, additional international partners might be interested in participating and contributing to a roadmap that, in the long run, leads to a successful implementation. A new, dedicated development program funded by ESA to help reduce development and implementation cost and further push some of the required key technologies would be a first important step in this direction. Ultimately, a large mid-infrared exoplanet imaging mission will be needed to help answer one of humankind's most fundamental questions: "How unique is our Earth?"

Our objective was to develop version 1.0 of a novel framework for response evaluation criteria in prostate-specific membrane antigen (PSMA) PET/CT (RECIP) and a composite response classification that combines responses by prostate-specific antigen (PSA) measurements and by RECIP 1.0 (PSA + RECIP). Methods: This was an international multicenter, retrospective study. One hundred twenty-four men with metastatic castration-specific prostate cancer (mCRPC) who underwent 177Lu-PSMA therapy and received PSMA PET/CT at baseline and at an interim time point of 12 wk were included. Pairs of baseline interim PET/CT scans were interpreted by consensus among 3 masked readers for appearance of new lesions. Tumor lesions were segmented, and total PSMA-positive tumor volume (PSMA-VOL) was obtained. Appearance of new lesions and changes in PSMA-VOL were combined to develop RECIP 1.0, which included classifications of complete response (RECIP-CR: absence of any PSMA-ligand uptake on interim PET/CT), partial response (RECIP-PR: decline ≥ 30% in PSMA-VOL and no appearance of new lesions), progressive disease (RECIP-PD: increase ≥ 20% in PSMA-VOL and appearance of new lesions), and stable disease (RECIP-SD: any condition but RECIP-PR or RECIP-PD). Changes in PSA levels at 12 wk by Prostate Cancer Working Group Criteria 3 were recorded. PSA + RECIP results were defined as response (PSA decline ≥ 50% or RECIP-PR/CR) or progression (PSA increase ≥ 25% or RECIP-PD). The study's primary outcome measure was the prognostic value of RECIP 1.0 for overall survival (OS). The secondary outcome measure was the prognostic accuracy (C-index) of PSA + RECIP versus PSA responses. Results: Patients with RECIP-PD (n = 39; 8.3 mo) had a shorter OS than patients with stable disease (RECIP-SD) (n = 47; 13.1 mo; P < 0.001) or RECIP-PR (n = 38; 21.7 mo; P < 0.001). In identifying responders and progressors, PSA + RECIP had C-indices superior to those of PSA only: 0.65 versus 0.62 (P = 0.028) and 0.66 versus 0.63 (P = 0.044), respectively. Conclusion: PSMA PET/CT by RECIP 1.0 is prognostic for OS and can be used as a response biomarker to monitor early efficacy of 177Lu-PSMA in men with mCRPC. PSA + RECIP may be used as a novel composite endpoint in mCRPC clinical trial design.