A STUDY OF EFFECTIVE CHARACTERISTICS MOST VALUED IN SUPERINTENDENTS BY PRINCIPALS

The purpose of this study was to examine the effective characteristics of superintendents through the principal’s perception. The perceptions of principals were compared to those of superintendents. A one-way ANOVA was used to interpret and analyze the data for this study. All superintendents and principals in public schools in Indiana were invited to participate in this study. This study was conducted by administering a survey to public school district superintendents and principals in Indiana. The Effective Characteristics of Superintendents survey was developed by me to quantitatively measure the perceptions of superintendents and principals with research from the ISLLC standards, theorists, educational paradigms, and research of best practices. Superintendents’ and principals’ perceptions were measured on how likely they agreed with the practice. A total of 119 superintendents and 256 principals submitted complete responses to the Effective Characteristics survey. Other variables measured were demographic location and population size of the school district. Data were analyzed through one-way ANOVA testing and the null hypotheses were tested at the .05 probability level or better. As a result of the research and subsequent data analysis, the following conclusions are proposed. For the descriptive data both superintendents and principals rated the three most frequent responses for vision as trust, implementation and development, and setting high goals. The highest rated three responses for management placed higher value on making genuine decisions, analyzing data, and inspiring others to follow goals. Highest rated responses for collaboration were working with the principal, communicating with stakeholders, and creating a collaboration culture. The three highest ratings for instructional leadership skills were professional development, develop skills to be globally competitive, and challenge staff members as the highest rated characteristics for instructional leadership skills. Principals’ perceptions were different with the descriptive data in the area of vision. Principals perceived setting high goals and expectations as higher, whereas superintendents rated a safe learning environment. Both perceived implementation and development and trust as effective characteristics of superintendents. Significant differences existed in Research Question 2 and 11 for vision and instructional leadership skills with location. The examination of the results of the one-way ANOVA on the whole sample population determined that significant differences with the model existed with the location types. Rural locations scored the importance of vision and instructional leadership skills significantly lower than urban and suburban respondents. There were no differences in position type on principals and superintendent’s perceptions on the effective characteristics for vision, collaboration, and instructional leadership skills. No significant difference was found in the independent sample t test regarding effective characteristics for superintendents in these three areas based on position type. The examination of the results of the one-way ANOVA determined that no significant differences regarding effective characteristics for superintendents in the area of collaboration and management. These results suggest that principals did not perceive any differences from superintendents among these effective characteristics in the areas of vision, management, collaboration, and instructional leadership skills

Cell type-specific changes in Wnt signaling and neuronal differentiation in the developing mouse cortex after prenatal alcohol exposure during neurogenesis

Fetal Alcohol Spectrum Disorder (FASD) encompasses an array of effects of prenatal alcohol exposure (PAE), including physical abnormalities and cognitive and behavioral deficits. Disruptions of cortical development have been implicated in multiple PAE studies, with deficits including decreased progenitor proliferation, disrupted neuronal differentiation, aberrant radial migration of pyramidal neurons, and decreased cortical thickness. While several mechanisms of alcohol teratogenicity have been explored, how specific cell types in the brain at different developmental time points may be differentially affected by PAE is still poorly understood. In this study, we used single nucleus RNA sequencing (snRNAseq) to investigate whether moderate PAE from neurulation through peak cortical neurogenesis induces cell type-specific transcriptomic changes in the developing murine brain. Cluster analysis identified 25 neuronal cell types, including subtypes of radial glial cells (RGCs), intermediate progenitor cells (IPCs), projection neurons, and interneurons. Only Wnt-expressing cortical hem RGCs showed a significant decrease in the percentage of cells after PAE, with no cell types showing PAE-induced apoptosis as measured by caspase expression. Cell cycle analysis revealed only a subtype of RGCs expressing the downstream Wnt signaling transcription factor Tcf7l2 had a decreased percentage of cells in the G2/M phase of the cell cycle, suggesting decreased proliferation in this RGC subtype and further implicating disrupted Wnt signaling after PAE at this early developmental timepoint. An increased pseudotime score in IPC and projection neuron cell types indicated that PAE led to increased or premature differentiation of these cells. Biological processes affected by PAE included the upregulation of pathways related to synaptic activity and neuronal differentiation and downregulation of pathways related to chromosome structure and the cell cycle. Several cell types showed a decrease in Wnt signaling pathways, with several genes related to Wnt signaling altered by PAE in multiple cell types. As Wnt has been shown to promote proliferation and inhibit differentiation at earlier stages in development, the downregulation of Wnt signaling may have resulted in premature neuronal maturation of projection neurons and their intermediate progenitors. Overall, these findings provide further insight into the cell type-specific effects of PAE during early corticogenesis

Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough

Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth

Multilingual RECIST classification of radiology reports using supervised learning.

OBJECTIVES The objective of this study is the exploration of Artificial Intelligence and Natural Language Processing techniques to support the automatic assignment of the four Response Evaluation Criteria in Solid Tumors (RECIST) scales based on radiology reports. We also aim at evaluating how languages and institutional specificities of Swiss teaching hospitals are likely to affect the quality of the classification in French and German languages. METHODS In our approach, 7 machine learning methods were evaluated to establish a strong baseline. Then, robust models were built, fine-tuned according to the language (French and German), and compared with the expert annotation. RESULTS The best strategies yield average F1-scores of 90% and 86% respectively for the 2-classes (Progressive/Non-progressive) and the 4-classes (Progressive Disease, Stable Disease, Partial Response, Complete Response) RECIST classification tasks. CONCLUSIONS These results are competitive with the manual labeling as measured by Matthew's correlation coefficient and Cohen's Kappa (79% and 76%). On this basis, we confirm the capacity of specific models to generalize on new unseen data and we assess the impact of using Pre-trained Language Models (PLMs) on the accuracy of the classifiers

Thymus-specific serine protease contributes to the diversification of the functional endogenous CD4 T cell receptor repertoire

Thymus-specific serine protease expression in stromal as well as hematopoietic cells in the thymus is needed for diversification of the endogenous repertoire of TCRs specific for a particular protein antigen

PLoS Pathog

Cytomegalovirus (CMV) is a leading infectious cause of morbidity in immune-compromised patients. γδ T cells have been involved in the response to CMV but their role in protection has not been firmly established and their dependency on other lymphocytes has not been addressed. Using C57BL/6 αβ and/or γδ T cell-deficient mice, we here show that γδ T cells are as competent as αβ T cells to protect mice from CMV-induced death. γδ T cell-mediated protection involved control of viral load and prevented organ damage. γδ T cell recovery by bone marrow transplant or adoptive transfer experiments rescued CD3ε-/- mice from CMV-induced death confirming the protective antiviral role of γδ T cells. As observed in humans, different γδ T cell subsets were induced upon CMV challenge, which differentiated into effector memory cells. This response was observed in the liver and lungs and implicated both CD27+ and CD27- γδ T cells. NK cells were the largely preponderant producers of IFNγ and cytotoxic granules throughout the infection, suggesting that the protective role of γδ T cells did not principally rely on either of these two functions. Finally, γδ T cells were strikingly sufficient to fully protect Rag-/-γc-/- mice from death, demonstrating that they can act in the absence of B and NK cells. Altogether our results uncover an autonomous protective antiviral function of γδ T cells, and open new perspectives for the characterization of a non classical mode of action which should foster the design of new γδ T cell based therapies, especially useful in αβ T cell compromised patients

Il meticciato nell'Italia contemporanea. Storia, memorie e cultura di massa.

L'idea diffusa degli "italiani brava gente" e della diversit\ue0 della nostra storia rispetto alla storia USA, segnata da razzismo istituzionale, si fonda sul silenziamento del passato coloniale e razzista italiano. Il ripudio della categoria di razza da parte dell'Italia repubblicana e la smentita scientifica dell'esistenza biologica della categoria non hanno cancellato la presenza della razza, formazione storico-culturale che paradossalmente esiste e non esiste. Priva di referenti oggettivi nella realt\ue0, la razza produce in essa effetti significativi, opera sia come categoria sociale e strumento di esclusione, sia come costruzione simbolica e istanza identitaria. A fronte del silenziamento del meticciato storico nell'uso pubblico della storia e nella memoria nazionali del secondo dopoguerra, il saggio sottolinea la presenza diffusa del meticciato nei prodotti della cultura di massa italiani contemporanei e ne indaga i significati con gli strumenti degli studi critici sulla razza e in prospettiva comparata tra Italia e Stati Uniti

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Role of defective monocyte interleukin-10 release in tumor necrosis factor-alpha overproduction in alcoholics cirrhosis

Monocytes of patients with alcoholic cirrhosis produce higher amounts of tumor necrosis factor-alpha (TNF-alpha) after lipopolysaccharide (LPS) stimulation. The mechanisms of the overproduction remain undefined. IL-10 (IL-10) is an antiinflammatory cytokine known to downregulate TNF-alpha secretion by monocytes. The present study analyzes IL-10 production by monocytes and its control on TNF-alpha secretion in alcoholic cirrhosis. LPS-stimulated monocytes from alcoholic cirrhotics (n = 13) showed decreased IL-10 (median, 240 pg/mL [40 to 500] upsilon 513 pg/mL [152 to 1,335]; P = .01) compared with controls (n = 13). Cells from cirrhotic patients were normally responsive to recombinant IL-10, which induced a dose dependent decrease of TNF-alpha secretion. On the other hand, preincubation with anti-IL-10 monoclonal antibodies led to significant increase in TNF-alpha secretion in controls (median, 7,325 to 16,800 pg/mL; P = .002) but not in cells from cirrhotic patients (16,535 to 20,450 pg/mL; P = .14), abolishing the difference in TNF-alpha production between cirrhotic patients and controls. It is concluded that defective IL-10 secretion by monocytes from alcoholic cirrhotic patients could be involved in the characteristics TNF-alpha overproduction observed in this disease.Journal ArticleResearch Support, Non-U.S. Gov'tFLWINinfo:eu-repo/semantics/publishe

High-throughput generation of midbrain dopaminergic neuron organoids from reporter human pluripotent stem cells

Summary: Here, we describe a high-throughput 3D differentiation protocol for deriving midbrain dopaminergic neurons from human pluripotent stem cells. The use of organoids has become prevalent in disease modeling, but there is a high demand for more homogeneous cultures. Our approach is advantageous for large-scale production of uniform midbrain organoids that can be maintained in diverse formats, and our reporters allow for sorting of dopaminergic neurons. The maturing long-term organoid cultures can be used as a model for the entire midbrain.For complete details on the use and execution of this protocol, please refer to Ahfeldt et al. (2020)