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The purpose of the study is to investigate school counselors' support of youth experiencing homelessness going to college. Using survey methods, school counselors reported their knowledge, perceived competence, advocacy, and actions related to supporting students experiencing homelessness in their college preparation. The results suggested that training and the number of students experiencing homelessness on counselors' caseloads were significantly related to their knowledge and competence. Knowledge, competence, and advocacy all impacted the number of interventions utilized by participants. The implications of these results for school counselors and counselor educators are discussed.

The distinction between natural sign languages and sign-supported speech is a controversial topic and difficult to assess purely on structural terms because of language contact. Here, we consider British Sign Language (BSL) and Sign Supported English (SSE) with reference to Irvine and Gal's (2000. Language ideology and linguistic differentiation. In P. V. Kroskrity (ed.), "Regimes of language," 35-84. Oxford: Currey) framework on linguistic differentiation. Using interview data from 121 deaf BSL signers from the BSL Corpus, we show that this framework allows us to better understand how BSL and SSE are defined by BSL signers. We refer to the semiotic processes of this framework: iconisation, fractal recursivity, and erasure. BSL, including its varieties, is strongly associated with deaf communities in Britain. Specific grammatical forms in BSL that differ markedly from English constructions are presented as exemplars of sign language use (iconisation), oppositions between deafness and hearingness are repeatedly applied to different social groups (fractal recursivity and iconisation), and occurrences that may not align with this opposition are rarely acknowledged (erasure). We suggest that these semiotic processes are motivated by language maintenance and educational policies. We conclude with a discussion on how deaf signers distinguish between BSL and SSE, suggesting distinctions made are ideologically driven with political and historical roots and better understood from a translanguaging perspective.

Since its inception nearly a half century ago, CHARMM has been playing a central role in computational biochemistry and biophysics. Commensurate with the developments in experimental research and advances in computer hardware, the range of methods and applicability of CHARMM have also grown. This review summarizes major developments that occurred after 2009 when the last review of CHARMM was published. They include the following: new faster simulation engines, accessible user interfaces for convenient workflows, and a vast array of simulation and analysis methods that encompass quantum mechanical, atomistic, and coarse-grained levels, as well as extensive coverage of force fields. In addition to providing the current snapshot of the CHARMM development, this review may serve as a starting point for exploring relevant theories and computational methods for tackling contemporary and emerging problems in biomolecular systems. CHARMM is freely available for academic and nonprofit research at https://academiccharmm.org/program.

Resistance to the current Androgen Receptor Signaling Inhibitor (ARSI) therapies has led to higher incidences of therapy-induced neuroendocrine-like prostate cancer (t-NEPC). This highly aggressive subtype with predominant small-cell-like characteristics is resistant to taxane chemotherapies and has a dismal overall survival. t-NEPCs are mostly treated with platinum-based drugs with a combination of etoposide or taxane and have less selectivity and high systemic toxicity, which often limit their clinical potential. During t-NEPC transformation, adenocarcinomas lose their luminal features and adopt neuro-basal characteristics. Whether the adaptive neuronal characteristics of t-NEPC are responsible for such taxane resistance remains unknown. Pathway analysis from patient gene-expression databases indicates that t-NEPC upregulates various neuronal pathways associated with enhanced cellular networks. To identify transcription factor(s) (TF) that could be important for promoting the gene expression for neuronal characters in t-NEPC, we performed ATAC-Seq, acetylated-histone ChIP-seq, and RNA-seq in our NE-like cell line models and analyzed the promoters of transcriptionally active and significantly enriched neuroendocrine-like (NE-like) cancer-specific genes. Our results indicate that Pax5 could be an important transcription factor for neuronal gene expression and specific to t-NEPC. Pathway analysis revealed that Pax5 expression is involved in axonal guidance, neurotransmitter regulation, and neuronal adhesion, which are critical for strong cellular communications. Further results suggest that depletion of Pax5 disrupts neurite-mediated cellular communication in NE-like cells and reduces surface growth factor receptor activation, thereby, sensitizing them to docetaxel therapies. Moreover, t-NEPC-specific hydroxymethylation of Pax5 promoter CpG islands favors Pbx1 binding to induce Pax5 expression. Based on our study, we concluded that continuous exposure to ARSI therapies leads to epigenetic modifications and Pax5 activation in t-NEPC, which promotes the expression of genes necessary to adopt taxane-resistant NE-like cancer. Thus, targeting the Pax5 axis can be beneficial for reverting their taxane sensitivity.

Grasslands are one of the most common land-cover types, providing important ecosystem services globally, yet few studies have examined grassland critical-zone functioning throughout hillslopes. This study characterised a coastal grassland over a small hillslope at Point Reyes National Seashore, California, using multidisciplinary techniques, combining remotely-sensed, geophysical, plant, and soil measurements. Clustering techniques delineated the study area into four landscape zones, up-, mid-, and down-slope, and a bordering riparian ecotone, which had distinct environmental properties that varied spatially across the site, with depth, and time. Soil moisture increased with depth and down slope towards a bordering riparian zone, and co-varied with soil CO2 flux rates both spatially and temporally. This highlighted three distinct controls of soil moisture on soil respiration: CO2 fluxes were inhibited by high moisture content in the down-slope during the wet winter months, and converged across landscape positions in the dry summer months, while also displaying post-rain pulses. The normalised difference vegetation index (NDVI) ranged from 0.32 (September)–0.80 (April) and correlated positively with soil moisture and aboveground biomass, moving down slope. Yet, NDVI, aboveground biomass, and soil moisture were not correlated to soil organic carbon (SOC) content (0.4%–4.5%), which was highest in the mid-slope. The SOC content may instead be linked to shifts in dominant grassland species and their rhizosphere properties with landscape position. This multidisciplinary characterisation highlighted significant heterogeneity in grassland properties with landscape position, and demonstrated an approach that could be used to characterise other critical-zone environments on hillslopes.

Macrophages are innate immune cells that interact with complex extracellular matrix environments, which have varied stiffness, composition, and structure, and such interactions can lead to the modulation of cellular activity. Collagen is often used in the culture of immune cells, but the effects of substrate functionalization conditions are not typically considered. Here, we show that the solvent system used to attach collagen onto a hydrogel surface affects its surface distribution and organization, and this can modulate the responses of macrophages subsequently cultured on these surfaces in terms of their inflammatory activation and expression of adhesion and mechanosensitive molecules. Collagen was solubilized in either acetic acid (Col-AA) or N-(2-hydroxyethyl)piperazine-N'-ethanesulfonic acid (HEPES) (Col-HEP) solutions and conjugated onto soft and stiff polyacrylamide (PA) hydrogel surfaces. Bone marrow-derived macrophages cultured under standard conditions (pH 7.4) on the Col-HEP-derived surfaces exhibited stiffness-dependent inflammatory activation; in contrast, the macrophages cultured on Col-AA-derived surfaces expressed high levels of inflammatory cytokines and genes, irrespective of the hydrogel stiffness. Among the collagen receptors that were examined, leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) was the most highly expressed, and knockdown of the Lair-1 gene enhanced the secretion of inflammatory cytokines. We found that the collagen distribution was more homogeneous on Col-AA surfaces but formed aggregates on Col-HEP surfaces. The macrophages cultured on Col-AA PA hydrogels were more evenly spread, expressed higher levels of vinculin, and exerted higher traction forces compared to those of cells on Col-HEP. These macrophages on Col-AA also had higher nuclear-to-cytoplasmic ratios of yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), key molecules that control inflammation and sense substrate stiffness. Our results highlight that seemingly slight variations in substrate deposition for immunobiology studies can alter critical immune responses, and this is important to elucidate in the broader context of immunomodulatory biomaterial design.

Abstract The development of optical sensors for label-free quantification of cell parameters has numerous uses in the biomedical arena. However, using current optical probes requires the laborious collection of sufficiently large datasets that can be used to calibrate optical probe signals to true metabolite concentrations. Further, most practitioners find it difficult to confidently adapt black box chemometric models that are difficult to troubleshoot in high-stakes applications such as biopharmaceutical manufacturing. Replacing optical probes with contactless short-wave infrared (SWIR) hyperspectral cameras allows efficient collection of thousands of absorption signals in a handful of images. This high repetition allows for effective denoising of each spectrum, so interpretable linear models can quantify metabolites. To illustrate, an interpretable linear model called L-SLR is trained using small datasets obtained with a SWIR HSI camera to quantify fructose, viable cell density (VCD), glucose, and lactate. The performance of this model is also compared to other existing linear models, namely Partial Least Squares (PLS) and Non-negative Matrix Factorization (NMF). Using only 50% of the dataset for training, reasonable test performance of mean absolute error (MAE) and correlations (r2) are achieved for glucose (r2 = 0.88, MAE = 37 mg/dL), lactate (r2 = 0.93, MAE = 15.08 mg/dL), and VCD (r2 = 0.81, MAE = 8.6 × 105 cells/mL). Further, these models are also able to handle quantification of a metabolite like fructose in the presence of high background concentration of similar metabolite with almost identical chemical interactions in water like glucose. The model achieves reasonable quantification performance for large fructose level (100–1000 mg/dL) quantification (r2 = 0.92, MAE = 25.1 mg/dL) and small fructose level (

Abstract High-grade serous ovarian carcinoma (HGSOC) has a significant hereditary component, only half of which is explained. Previously, we performed germline exome sequencing on BRCA1 and BRCA2-negative HGSOC patients, revealing three proposed and 43 novel candidate genes enriched with rare loss-of-function variants. For validation, we undertook case-control analyses using genomic data from disease-free controls. This confirms enrichment for nearly all previously identified genes. Additionally, one-hundred-and-eleven HGSOC tumours from variant carriers were sequenced alongside other complementary studies, seeking evidence of biallelic inactivation as supportive evidence. PALB2 and ATM validate as HGSOC predisposition genes, with 6/8 germline carrier tumours exhibiting biallelic inactivation accompanied by characteristic mutational signatures. Among candidate genes, only LLGL2 consistently shows biallelic inactivation and protein expression loss, supporting it as a novel HGSOC susceptibility gene. The remaining candidate genes fail to validate. Integrating case-control analyses with tumour sequencing is thus crucial for accurate gene discovery in familial cancer studies.

Background: A multi-phase Canadian study was conducted as part of a large-scale community and academic research partnership focused on understanding and improving the employment experiences of people with intellectual disabilities. Method: This multi-method study utilized a sequential approach, using findings from qualitative interviews (n = 28) to inform an online survey (n = 149). Participants were invited to share their experiences with paid employment or with persons with intellectual disabilities. Results: Thematic analysis of data across interview and survey findings resulted in six themes: (1) assumptions and attitudes, (2) knowledge and awareness, (3) accessibility of processes, (4) use of accommodations, (5) workplace relationships, and (6) supports and resources. Conclusions: A holistic and systemic approach has the potential to improve inclusive employment experiences of people with intellectual disabilities. Action is needed mainly at the policy and employer level to reduce barriers and improve on facilitating measures reinforced by the themes shared in this study.

UNLABELLED: The period of the year from spring to fall, when clocks in most parts of the United States are set one hour ahead of standard time, is called daylight saving time, and its beginning and ending dates and times are set by federal law. The human biological clock is regulated by the timing of light and darkness, which then dictates sleep and wake rhythms. In daily life, the timing of exposure to light is generally linked to the social clock. When the solar clock is misaligned with the social clock, desynchronization occurs between the internal circadian rhythm and the social clock. The yearly change between standard time and daylight saving time introduces this misalignment, which has been associated with risks to physical and mental health and safety, as well as risks to public health. In 2020, the American Academy of Sleep Medicine (AASM) published a position statement advocating for the elimination of seasonal time changes, suggesting that evidence best supports the adoption of year-round standard time. This updated statement cites new evidence and support for permanent standard time. It is the position of the AASM that the United States should eliminate seasonal time changes in favor of permanent standard time, which aligns best with human circadian biology. Evidence supports the distinct benefits of standard time for health and safety, while also underscoring the potential harms that result from seasonal time changes to and from daylight saving time. CITATION: Rishi MA, Cheng JY, Strang AR, et al. Permanent standard time is the optimal choice for health and safety: an American Academy of Sleep Medicine position statement. J Clin Sleep Med. 2024;20(1):121-125.

This paper is a follow-up to determine the accuracy of the predictions stated in a previously published article titled "Higher Education in the Midst of a Pandemic: A Dean's Perspective" (Rowley, 2020). Those predictions were more like educated guesses since the paper was written in 2020, the year the pandemic was beginning to spread across the country. It was certain significant changes would occur, but the nature and scope of these changes were unknown at the time. As mentioned in the above referenced paper, the difficulty of predicting the future was the fact that there were no predetermined guidelines for how to offer academic programs to students in the midst of a serious, widespread health crisis. College administrators were called upon to flexibly respond to a changed environment they had not previously experienced. This paper will review the predictions made in the areas of college sustainability, financial viability, enrollment, program delivery, technology, library and student services, and the college experience.

The increasing popularity of outdoor learning (OL) amongst researchers and practitioners highlighted the need to further investigate primary teacher trainees (PTTs) perception towards it and how this may be related to their nature connection. Participants were PTTs who were considering attending Forest School (FS) Training Level 1 as part of their Initial Teacher Education (ITE) course. This mixed-methods research employed the Nature Relatedness (NR) scale to measure trainees' relationship with nature. Semi-structured interviews with those who chose to attend FS training were conducted to ascertain their perceptions and attitudes towards the training. Through Thematic Analysis of interviews five themes emerged, including favourable perceptions of FS Training and OL for their future teaching career and a positive nature connection. A significant difference in the mean NR scores was identified with higher NR scores for the group who chose to attend the FS training in comparison with those who did not.

This article reports on research investigating the aspirations of pupils in primary schools located in low-socioeconomic areas in one English county. The research adopted a qualitative approach to explore aspirations, self-efficacy, opinions regarding the merits of investment in education, and notions of perceived future selves. The research also considered the expectations of parents and teachers providing insight into how they support children's aspirations and expose them to opportunities and ideas. The study utilised various trigger activities as a precursor to focus groups. The findings show a distinct gap between pupils' conception of their current selves and their future selves whereby there is uncertainty and insecurity about the appropriate steps needed to make informed choices and realise aspirations. Parents and extended family are the predominant idea source for aspirations and their assistance is recognised, above all, as important by pupils. Aspirations are also fashioned by pupils' gender-specific ideas about certain jobs and cultural exposure to the media. Pupils discern the importance of working hard and performing well at school. Most parents just want their child to be happy in the future and, as such, would support their child's career choices believing these could be achieved although believing qualifications are important, and the job market restricted. Teachers want their pupils to have options but identify barriers to achieving aspirations as worklessness in families, the locality of the school, low self-efficacy and unrealistic aspirations.

The present study explored LGBTQ+ (lesbian, gay, bisexual, transgender, queer, and other non heterosexual/cisgender identities) engineering students' navigation of engineering educational contexts and reported the impacts of the engineering educational culture on LGBTQ+ students' well-being. Drawing from a sample of ten LGBTQ+ university students in the United States, we found that students described cultural norms sustained through minimal tolerance for and the avoidance of identity talk or expression. Systemic homogeneous cultural norms redefine safety expectations for LGBTQ+ engineering students while normalizing expectations that LGBTQ+ students be silent and tolerate mistreatment. Participants also described the consequences of invisibility and identity conflict that they face for being different within an inequitable field. These findings bring attention to a culture within engineering programs that silences LGBTQ+ expression and leaves students feeling isolated. Further research is needed to explore the effect of affirming communities on LGBTQ+ engineering students' well-being. We conclude with research and clinical implications for working with LGBTQ+ engineering students.

Technical standards are resources that are important for engineering and engineering technology students due to ABET accreditation requirements and future professional use of the documents. Previous studies have surveyed librarians at Association of Research Libraries (ARL) institutions with engineering programs and librarians at universities with top-ranked engineering programs about standards. This study fills a gap by focusing on librarians at institutions with engineering technology programs. We surveyed 34 academic librarians at institutions with four-year bachelor programs in the disciplines of mechanical engineering technology or electrical and electronics engineering technology to learn about standards access and challenges at their libraries, standards education for students, and librarians' standards-related professional development experiences and needs. Key findings include: standards access and standards education efforts are skewed towards larger institutions; librarians encounter significant cost challenges in providing standards access; few librarians receive education about standards until moving into their careers; and there is a need for self-paced librarian training materials focused on standards. Further education for librarians about standards and increased standards access has the potential to have a significant impact on many students, given the reach of librarians in their liaison roles.

Natural history museums are vital repositories of specimens, samples and data that inform about the natural world; this Formal Comment revisits a Perspective that advocated for the adoption of compassionate collection practices, querying whether it will ever be possible to completely do away with whole animal specimen collection.

BackgroundPatients undergoing mechanical ventilation often develop rapid diaphragmatic atrophy, respiratory muscle weakness, and dysfunction, which are associated with prolonged duration of ventilation. This study aimed to evaluate whether Inspiratory Muscle Training (IMT) facilitates weaning from mechanical ventilation and enhances muscle strength in critically ill, subacute adult patients, while examining the relationship between IMT and relevant clinical laboratory values.MethodsIn this randomized clinical trial, patients admitted to the intensive care unit requiring mechanical ventilation for more than 2 days, with stable hemodynamics and resolved acute conditions, were enrolled. Participants were randomly assigned to the IMT or no-IMT group. The IMT group received training twice daily, 5 days a week, for three consecutive weeks. The primary outcome was ventilator duration. The primary outcome measure was the number of days until liberation from mechanical ventilation. The secondary outcomes of interest were respiratory muscle strength and biomarker levels.ResultsThirty-three subjects (17 in the IMT group, 16 in the no-IMT group) were included in the final analysis. The IMT group had significantly shorter ventilator days (12.6 ± 5.2 vs. 18.1 ± 8.8, p = 0.04). IMT intervention significantly reduced rapid shallow breathing index and improved respiratory muscle strength, with greater maximum inspiratory pressure (p

BackgroundReal-world COVID-19 vaccine effectiveness (VE) studies are investigating exposures of increasing complexity accounting for time since vaccination. These studies require methods that adjust for the confounding that arises when morbidities and demographics are associated with vaccination and the risk of outcome events. Methods based on propensity scores (PS) are well-suited to this when the exposure is dichotomous, but present challenges when the exposure is multinomial. ObjectiveThis simulation study aimed to investigate alternative methods to adjust for confounding in VE studies that have a test-negative design. MethodsAdjustment for a disease risk score (DRS) is compared with multivariable logistic regression. Both stratification on the DRS and direct covariate adjustment of the DRS are examined. Multivariable logistic regression with all the covariates and with a limited subset of key covariates is considered. The performance of VE estimators is evaluated across a multinomial vaccination exposure in simulated datasets. ResultsBias in VE estimates from multivariable models ranged from –5.3% to 6.1% across 4 levels of vaccination. Standard errors of VE estimates were unbiased, and 95% coverage probabilities were attained in most scenarios. The lowest coverage in the multivariable scenarios was 93.7% (95% CI 92.2%-95.2%) and occurred in the multivariable model with key covariates, while the highest coverage in the multivariable scenarios was 95.3% (95% CI 94.0%-96.6%) and occurred in the multivariable model with all covariates. Bias in VE estimates from DRS-adjusted models was low, ranging from –2.2% to 4.2%. However, the DRS-adjusted models underestimated the standard errors of VE estimates, with coverage sometimes below the 95% level. The lowest coverage in the DRS scenarios was 87.8% (95% CI 85.8%-89.8%) and occurred in the direct adjustment for the DRS model. The highest coverage in the DRS scenarios was 94.8% (95% CI 93.4%-96.2%) and occurred in the model that stratified on DRS. Although variation in the performance of VE estimates occurred across modeling strategies, variation in performance was also present across exposure groups. ConclusionsOverall, models using a DRS to adjust for confounding performed adequately but not as well as the multivariable models that adjusted for covariates individually.

ABSTRACT Incidences of fluconazole (FLC) resistance among Candida glabrata clinical isolates are a growing issue in clinics. The pleiotropic drug response network in C. glabrata confers azole resistance and is defined primarily by the Zn2Cys6 zinc cluster-containing transcription factor Pdr1 and target genes such as CDR1, which encodes an ATP-binding cassette transporter protein thought to act as an FLC efflux pump. Mutations in the PDR1 gene that render the transcription factor hyperactive are the most common cause of fluconazole resistance among clinical isolates. The phenothiazine class drug fluphenazine and a molecular derivative, CWHM-974, which both exhibit antifungal properties, have been shown to induce the expression of Cdr1 in Candida spp. We have used a firefly luciferase reporter gene driven by the CDR1 promoter to demonstrate two distinct patterns of CDR1 promoter activation kinetics: gradual promoter activation kinetics that occur in response to ergosterol limitations imposed by exposure to azole and polyene class antifungals and a robust and rapid CDR1 induction occurring in response to the stress imposed by fluphenazines. We can attribute these different patterns of CDR1 induction as proceeding through the promoter region of this gene since this is the only segment of the gene included in the luciferase reporter construct. Genetic analysis indicates that the signaling pathways responsible for phenothiazine and azole induction of CDR1 overlap but are not identical. The short time course of phenothiazine induction suggests that these compounds may act more directly on the Pdr1 protein to stimulate its activity.IMPORTANCECandida glabrata has emerged as the second-leading cause of candidiasis due, in part, to its ability to acquire high-level resistance to azole drugs, a major class of antifungal that acts to block the biosynthesis of the fungal sterol ergosterol. The presence of azole drugs causes the induction of a variety of genes involved in controlling susceptibility to this drug class, including drug transporters and ergosterol biosynthetic genes such as ERG11. We found that the presence of azole drugs leads to an induction of genes encoding drug transporters and ERG11, while exposure of C. glabrata cells to antifungals of the phenothiazine class of drugs caused a much faster and larger induction of drug transporters but not ERG11. Coupled with further genetic analyses of the effects of azole and phenothiazine drugs, our data indicate that these compounds are sensed and responded to differentially in the yeast cell.

Organo-mineral and organo-metal associations play an important role in the retention and accumulation of soil organic carbon (SOC). Recent studies have demonstrated a positive correlation between calcium (Ca) and SOC content in a range of soil types. However, most of these studies have focused on soils that contain calcium carbonate (pH > 6). To assess the importance of Ca-SOC associations in lower pH soils, we investigated their physical and chemical interaction in the grassland soils of Point Reyes National Seashore (CA, USA) at a range of spatial scales. Multivariate analyses of our bulk soil characterisation dataset showed a strong correlation between exchangeable Ca (CaExch; 5-8.3 c.molc kg-1) and SOC (0.6-4%) content. Additionally, linear combination fitting (LCF) of bulk Ca K-edge X-ray absorption near-edge structure (XANES) spectra revealed that Ca was predominantly associated with organic carbon across all samples. Scanning transmission X-ray microscopy near-edge X-ray absorption fine structure spectroscopy (STXM C/Ca NEXAFS) showed that Ca had a strong spatial correlation with C at the microscale. The STXM C NEXAFS K-edge spectra indicated that SOC had a higher abundance of aromatic/olefinic and phenolic C functional groups when associated with Ca, relative to C associated with Fe. In regions of high Ca-C association, the STXM C NEXAFS spectra were similar to the spectrum from lignin, with moderate changes in peak intensities and positions that are consistent with oxidative C transformation. Through this association, Ca thus seems to be preferentially associated with plant-like organic matter that has undergone some oxidative transformation, at depth in acidic grassland soils of California. Our study highlights the importance of Ca-SOC complexation in acidic grassland soils and provides a conceptual model of its contribution to SOC preservation, a research area that has previously been unexplored.Supplementary informationThe online version contains supplementary material available at 10.1007/s10533-023-01059-2.