Functional and Psychiatric Correlates of Comorbid Post-Traumatic Stress Disorder and Alcohol Use Disorder.

Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are common comorbid conditions that affect large segments of the population. Individuals with comorbid PTSD/AUD face greater clinical and functional stressors than those with diagnoses of either PTSD or AUD alone. The purpose of this article is to review the phenomenology and functional associations of PTSD/AUD and address the common social, occupational, and psychological concerns associated with both disorders. Given the increased problems associated with comorbid PTSD/AUD, clinical and research efforts should focus on targeting functional and psychosocial problems in conjunction with psychiatric symptoms

Teachers’ Perceptions of the Implementation of the Literacy Common Core State Standards for English Language Learners and Students with Disabilities

This qualitative study explored the experiences of U.S. teachers of English language learners (ELLs) and students with disabilities (SWDs) as they sought to align the new Common Core State Standards (CCSS) with previously used standards and instructional approaches during the first year of CCSS implementation. Open-ended interviews were conducted with 20 ELL and SWD literacy teachers to investigate (1) the teachers’ experiences as they began the alignment of their curriculum and teaching methods with the CCSS, (2) the teachers’ perceptions of the support that they received and that they still require, and (3) the teachers’ perceptions of the challenges to and potential for implementation. Four themes emerged from analysis of the interview data: alignment to the CCSS, teacher comfort level, best teaching practices, and challenges of teaching literacy. The authors conclude that broad-based alliances across schools, districts, and communities are needed to support professional development that responds authentically to the challenges revealed, as well as understanding at all levels that time and support are critical for teachers of special needs students

Rapidly evolving protointrons in Saccharomyces genomes revealed by a hungry spliceosome.

Introns are a prevalent feature of eukaryotic genomes, yet their origins and contributions to genome function and evolution remain mysterious. In budding yeast, repression of the highly transcribed intron-containing ribosomal protein genes (RPGs) globally increases splicing of non-RPG transcripts through reduced competition for the spliceosome. We show that under these "hungry spliceosome" conditions, splicing occurs at more than 150 previously unannotated locations we call protointrons that do not overlap known introns. Protointrons use a less constrained set of splice sites and branchpoints than standard introns, including in one case AT-AC in place of GT-AG. Protointrons are not conserved in all closely related species, suggesting that most are not under positive selection and are fated to disappear. Some are found in non-coding RNAs (e. g. CUTs and SUTs), where they may contribute to the creation of new genes. Others are found across boundaries between noncoding and coding sequences, or within coding sequences, where they offer pathways to the creation of new protein variants, or new regulatory controls for existing genes. We define protointrons as (1) nonconserved intron-like sequences that are (2) infrequently spliced, and importantly (3) are not currently understood to contribute to gene expression or regulation in the way that standard introns function. A very few protointrons in S. cerevisiae challenge this classification by their increased splicing frequency and potential function, consistent with the proposed evolutionary process of "intronization", whereby new standard introns are created. This snapshot of intron evolution highlights the important role of the spliceosome in the expansion of transcribed genomic sequence space, providing a pathway for the rare events that may lead to the birth of new eukaryotic genes and the refinement of existing gene function

Impact and Experiences Relative to Critical Incidents and Critical Incident Stress Management

Purpose: Typically, athletic trainers (ATs) have relied on external support networks to debrief after a critical incident (CI). ATs report focusing on improving work-related processes after a CI rather than their emotional response to the CI. The purpose of this study was to identify both the short-term emotional impacts of CIs and what coping strategies ATs use to address their emotional response to CIs. Methods: We used a cross-sectional, web-based survey, distributed to a random sample of NATA members to explore the perceived effects of CIs on ATs. Participants (n=73, 36±11y) were primarily women (n=53, 72.6%), working in the college/university practice setting (n = 40, 54.8%), with 7±3y of experience. All participants experienced a CI within the previous 12 months. The data were analyzed using descriptive statistics for demographic variables and multi-analyst inductive coding for the open-ended items amongst a 4-person team. We used a modified consensual qualitative research (CQR) process to review and analyze the open-ended questions and identify domains and core ideas. Trustworthiness was established with multi-analyst triangulation and auditing. Results: Participants most commonly reported feelings of thinking too much (71%, n=52), anxiety (63%, n=46), sadness (60%, n=44), fatigue (53%, n=39), and sleep disturbance (49%, n=36) resulting from CIs. Common coping strategies used were exercise (63%, n=46), humor (44%, n=32), interacting with pets (41%, n=30), expressing oneself through crying (40%, n=29), and peer support (34%, n=25). Sixty-two participants (86%) responded to open-ended questions related to the outcomes of CIs. Four domains were identified from the open-ended responses. Those domains included 1) dissociation, 2) deteriorated emotional state, 3) disruption of daily activities, and 4) improved event or post-event processes. Conclusion: Various strategies are used by ATs to cope with CIs; however, the only ways in which ATs expressed that coping helped was with care delivery, not the emotional impact of the CI. The lack of responses relative to coping strategies that improve quality of life is potentially alarming. To build resilience and persistence, organizations should consider requiring support beyond process improvement that addresses the emotional impact of CIs

“I looked it up in DeepL” : machine translation and digital tools in the language classroom

This article looks at a widespread yet erroneous use of machine translation (MT): looking up single words, thus treating MT systems as online bilingual dictionaries (ODs). After a literature review of this trend in research about MT, we consider data from a large survey that we carried out in 2021 at all Swiss universities on MT use and users’ attitudes. When analysing users’ metalinguistic awareness, we discovered that non-translators perceive the text to translate, mostly at word level, leading to the misuse of MT systems as ODs. Moreover, the survey results revealed confusion between the different digital tools for language learning, namely MT, online parallel corpora like Linguee and ODs. We therefore suggest broadening the scope of MT literacy to include training learners in general digital literacy to enable them to use such tools appropriately

Resection Status, Age and Nodal Involvement Determine Survival among Patients Receiving Adjuvant Chemoradiotherapy in Pancreatic Adenocarcinoma

Context Pancreas cancer can potentially be cured by resection, but the role of adjuvant chemotherapy and/or chemoradiation has been controversial. Objectives To better define clinicopathological factors that may serve as predictive and/or prognostic variables. Patients Between 1984 and 2006, we retrospectively analyzed 91 patients with pancreas cancer treated with pancreaticoduodenectomy or total pancreatectomy followed by adjuvant 5-fluorouracil-based chemoradiation at the University of Pennsylvania. Final pathological coding including margin status was confirmed by a pathologist. Interventions Patients were treated with 48.6 to 63.0 Gy, and 96.7% completed their prescribed radiation dose. Main outcome measures The prognostic significance of demographic factors, stage, year of surgery, tumor location, grade, resection status, and number of positive lymph nodes on overall survival were examined. Results With a median follow-up of 6.5 years, the overall median survival was 2.3 years (95% CI 1.5-3.2 years), and the 5-year overall survival was 28.9%. In multivariate analysis, completeness of resection (P<0.001), fewer number of positive lymph nodes (0 vs. 1-2 vs. 3 or more) (P=0.004), and age less than, or equal to, 60 years (P=0.006) were all independently associated with improved overall survival. The overall survival reported in this study compares favorably with the results of other single-institution studies and with the RTOG 97-04 trial. Conclusions Adjuvant 5-FU-based chemoradiation following radical pancreatectomy can be delivered safely and results in comparatively good overall survival. The results of this analysis underscore the importance of resection status, number of involved lymph nodes and patient age as prognostic characteristics. These factors may be considered stratification variables for future post-pancreatectomy adjuvant therapy trials

TGF-b2 induction regulates invasiveness of theileria-transformed leukocytes and disease susceptibility

Theileria parasites invade and transform bovine leukocytes causing either East Coast fever (T. parva), or tropical theileriosis (T. annulata). Susceptible animals usually die within weeks of infection, but indigenous infected cattle show markedly reduced pathology, suggesting that host genetic factors may cause disease susceptibility. Attenuated live vaccines are widely used to control tropical theileriosis and attenuation is associated with reduced invasiveness of infected macrophages in vitro. Disease pathogenesis is therefore linked to aggressive invasiveness, rather than uncontrolled proliferation of Theileria-infected leukocytes. We show that the invasive potential of Theileria-transformed leukocytes involves TGF-b signalling. Attenuated live vaccine lines express reduced TGF-b2 and their invasiveness can be rescued with exogenous TGF-b. Importantly, infected macrophages from disease susceptible Holstein-Friesian (HF) cows express more TGF-b2 and traverse Matrigel with great efficiency compared to those from disease-resistant Sahiwal cattle. Thus, TGF-b2 levels correlate with disease susceptibility. Using fluorescence and time-lapse video microscopy we show that Theileria-infected, disease-susceptible HF macrophages exhibit increased actin dynamics in their lamellipodia and podosomal adhesion structures and develop more membrane blebs. TGF-b2-associated invasiveness in HF macrophages has a transcription-independent element that relies on cytoskeleton remodelling via activation of Rho kinase (ROCK). We propose that a TGF-b autocrine loop confers an amoeboid-like motility on Theileria-infected leukocytes, which combines with MMP-dependent motility to drive invasiveness and virulence

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

La Montología Global 4D: Hacia las Ciencias Convergentes y Transdisciplinarias de Montaña a través del Tiempo y el Espacio

With mountain studies we use integrative approaches for geoliteracy about productive socioecological landscapes, and motivate further transdisciplinary research in montology. We conceived this white paper as a confluence of individual expertise and collective reasoning towards forming synergistic research clusters dealing with convergent mountain science, to advance montology to a new level, whereby innovative thinking about sustainability science and regenerative development incorporates alternative propositions for maintenance, improvement, or regeneration of living conditions of mountainscapes. We seek to use this contemporary framing of sustainability and ecological restoration as the impetus to better understand nature-culture relations, framed on lived-in mountains that operate in four dimensions (length, width, depth, and time) oriented at maximizing the cross-cutting of themes around mountains as productive socioecological systems, in a new academic institutionalized convergent unit. We conclude with a call for consilient, sustainable, regenerative development in the world’s mountains.La utilización de los estudios de montaña requiere de narrativas integradoras para la geoalfabetización sobre paisajes socioecológicos productivos y motiva más investigaciones transdisciplinares en el campo de la montología. Concebimos este artículo como la confluencia de la experiencia individual y el razonamiento colectivo hacia la formación de grupos de investigación sinérgicos que se ocupan de la ciencia de montaña convergente, para hacer avanzar la montología a un nuevo nivel, mediante el cual el pensamiento innovador sobre la ciencia de la sustentabilidad y el desarrollo regenerativo incorpora propuestas alternativas para el mantenimiento, la mejora, o regeneración de las condiciones de vida de los paisajes de montaña. Buscamos utilizar este marco contemporáneo de sustentabilidad y restauración ecológica como el ímpetu para comprender mejor las relaciones de la naturaleza y la cultura, desde una perspectiva transdisciplinar, en montañas habitadas que operan en cuatro dimensiones (largo, ancho, alto y tiempo). El artículo está orientado a potenciar la transversalidad de temáticas en torno a las montañas como sistemas socioecológicos productivos, en una nueva disciplina académica institucionalizada y convergente. Concluimos con un llamado a un desarrollo regenerativo, sustentable y consiliente en las montañas del mundo

The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics

Background: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD; NCT03036150) trial was designed to assess the effect of the sodium–glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin on kidney and cardiovascular events in participants with CKD with and without type 2 diabetes (T2D). This analysis reports the baseline characteristics of those recruited, comparing them with those enrolled in other trials. Methods: In DAPA-CKD, 4304 participants with a urinary albumin:creatinine ratio (UACR) ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 were randomized to dapagliflozin 10 mg once daily or placebo. Mean eGFR was 43.1 mL/min/1.73 m2 and median UACR was 949 mg/g (108 mg/mmol). Results: Overall, 2906 participants (68%) had a diagnosis of T2D and of these, 396 had CKD ascribed to a cause other than diabetes. The most common causes of CKD after diabetes (n = 2510) were ischaemic/hypertensive nephropathy (n = 687) and chronic glomerulonephritis (n = 695), of which immunoglobulin A nephropathy (n = 270) was the most common. A total of 4174 participants (97%) were receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 1882 (43.7%) diuretics, 229 (5.3%) mineralocorticoid receptor antagonists and 122 (2.8%) glucagon-like peptide 1 receptor agonists. In contrast to the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), the DAPA-CKD trial enrolled participants with CKD due to diabetes and to causes other than diabetes. The mean eGFR of participants in the DAPA-CKD trial was 13.1 mL/min/1.73 m2 lower than in CREDENCE, similar to that in the Finerenone in Reducing Kidney Failure and Disease Progression in DKD (FIDELIO-DKD) trial and the Study Of diabetic Nephropathy with AtRasentan (SONAR). Conclusions: Participants with a wide range of underlying kidney diseases receiving renin–angiotensin system blocking therapy have been enrolled in the DAPA-CKD trial. The trial will examine the efficacy and safety of dapagliflozin in participants with CKD Stages 2–4 and increased albuminuria, with and without T2D