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AbstractDespite the elevated importance of Data Science in Statistics, there exists limited research investigating how students learn the computing concepts and skills necessary for carrying out data science tasks. Computer Science educators have investigated how students debug their own code and how students reason through foreign code. While these studies illuminate different aspects of students’ programming behavior or conceptual understanding, a method has yet to be employed that can shed light on students’ learning processes. This type of inquiry necessitates qualitative methods, which allow for a holistic description of the skills a student uses throughout the computing code they produce, the organization of these descriptions into themes, and a comparison of the emergent themes across students or across time. In this article we share how to conceptualize and carry out the qualitative coding process with students’ computing code. Drawing on the Block Model to frame our analysis, we explore two types of research questions which could be posed about students’ learning. Supplementary materials for this article are available online.

Abstract Background Research and policy often focus on reducing attrition from educational trajectories leading to careers in science, technology, engineering, and mathematics (STEM), but many students change career plans within STEM. This study examined how changing career plans within STEM fields was associated with psychological indicators of career readiness. We conducted a large online survey of undergraduate students (N = 1,727) across 42 courses covering every major STEM discipline at a large U.S. research-intensive public university. Students reported about their career plans, whether plans had changed, motivation for those career plans, and satisfaction with and certainty of persisting with those plans. A trained team of coders classified whether students reported having STEM career plans at the time of the survey and at the beginning of college. Results Students who said they had changed career plans within STEM fields during college also reported lower motivation for their new career plans, satisfaction with those plans, and certainty of persisting in them, compared to students who retained consistent STEM career plans. With few exceptions, these associations held across students’ gender, race, year in school, and STEM field of study. Within-STEM career plan changes were very common, reported by 55% of fourth-year STEM students. Women reported changing career plans within STEM fields more often than men. Implications Results suggest that changing career plans within STEM is an important phenomenon to consider in preparing a qualified and diverse STEM workforce. Students who change career plans within STEM fields may need additional supports for their career motivation and satisfaction compared to students who do not change plans.

Abstract Background More than 50% of dogs with protein‐losing enteropathy (PLE) fail to respond to standard therapies. Octreotide, a somatostatin analogue, is used in cases of intestinal lymphangiectasia (IL) in humans with some success. Objectives Describe the use of octreotide in dogs with PLE including reason for and details of prescription, adverse effects, and apparent response. Animals Eighteen dogs with PLE, 13 with histopathology available. Ninety‐two percent (12/13) had IL diagnosed on biopsy. All 13 dogs had intestinal inflammatory infiltrates noted. Methods Multicenter, retrospective, descriptive study. Cases were volunteered for inclusion by individual attending veterinarians who reported the use of octreotide in cases of PLE. Results In 16/18 (89%) cases octreotide was prescribed to PLE dogs with a clinical suspicion or confirmed diagnosis of IL that were refractory to standard therapies. Median serum albumin at the time of octreotide prescription was 1.7 g/dL (range, 1.0‐3.1 g/dL). The median dose of octreotide prescribed was 20 μg/kg, SQ, daily with a range of 4‐39 μg/kg, SQ, daily. Adverse effects were noted in 3/18 (17%, 95% CI [4%, 41%]) of dogs; discontinuation of the drug was necessary in 1 dog. Improvement in clinical signs was noted in 6/12 (50%, 95% CI [21%, 79%]). Conclusions and Clinical Importance Octreotide was most commonly prescribed to dogs with PLE and suspected or confirmed IL that had failed to respond to standard therapies. Though a benefit to PLE dogs cannot be confirmed, octreotide was well tolerated by the majority of dogs at the doses prescribed in this study.

The United States’ National Science Foundation (NSF) ADVANCE program awards funding to universities to improve gender equality in the faculty ranks in Science, Technology, Engineering, and Mathematics (STEM). Our team at East Carolina University is using our award to educate men in the university about implicit and explicit gender bias and how they can and should use their power to help disrupt these systems. The program, adapted from other universities with past NSF ADVANCE funding, is in its infancy at our university, but there are initial signs of progress. This essay analyzes early data, grounded in sociological theories of gender so as to understand and make progress on structural change in our academic institution. The timeline for action and initial outcomes, including three specific scenarios, are presented. A discussion regarding the impact of the program and how it can be expanded and strengthened is also presented. We reflect on gendered tensions, and explore the limitations of “bringing men in” to correct structural power imbalances that have disproportionately benefitted them.

BackgroundRates of melanoma have increased dramatically in the United States over the past 25 years, and it has become among the most prevalent cancers for young adult women. Intentional skin tanning leads to a pattern of intense and intermittent UV radiation exposure that is associated with increased risk of melanoma. Frequent tanning is most common among young women and is linked to a variety of sociocultural pressures that negatively impact body image and drive appearance control behaviors. Unfortunately, there are no established interventions designed for frequent tanners. This intervention addresses this gap with unique content informed by body image and acceptance-based interventions. The intervention is delivered using Facebook secret groups, an approach designed to support behavior change and ensure scalability. ObjectiveThis study aims to describe the rationale and methodology of a randomized controlled trial of a melanoma prevention program targeting young women engaged in frequent indoor or outdoor UV tanning. MethodsParticipants are women aged 18-25 years who report high-risk tanning (ie, at least 10 indoor tanning sessions in the past 12 months or 10 outdoor sessions in the previous summer). After recruitment and screening, participants completed a baseline survey and were randomly assigned to receive the intervention or an attention-matched control condition. Both conditions were 8-week-long Facebook groups (approximately 25 members each) with daily posting of content. Follow-up surveys are administered at 3, 8, and 18 months after baseline. The primary trial outcome is the combined number of indoor and outdoor tanning sessions reported at the 8-month follow-up. Hypothesized intervention mediators are assessed at the 3-month follow-up. ResultsThis project was funded by a National Cancer Institute award (R01 CA218068), and the trial procedures were approved by the University of Kentucky Institutional Review Board in February 2020. Trial recruitment and enrollment occurred in 6 waves of data collection, which started in February 2022 and closed in May 2023. The study is closed to enrollment but remains open for follow-ups, and this protocol report was prepared before data analyses. As of February 2024, all participants have completed the 8-month follow-up assessment, and data collection is scheduled to close by the end of 2024 after the collection of the 18-month follow-up. ConclusionsThis trial will contribute unique knowledge to the field of skin cancer prevention, as no fully powered trials have examined the efficacy of an intervention designed for frequent indoor or outdoor tanning. The trial may also contribute evidence of the value in translating principles of body image and acceptance-based interventions into the field of skin cancer prevention and beyond. If successful, the use of the Facebook platform is intended to aid in dissemination as it provides a way to embed the intervention into individuals’ everyday routines. Trial RegistrationClinicalTrials.gov NCT03441321; https://clinicaltrials.gov/study/NCT03441321 International Registered Report Identifier (IRRID)DERR1-10.2196/56562

Abstract Inhibition of Janus kinase (JAK) family enzymes is a popular strategy for treating inflammatory and autoimmune skin diseases. In the clinic, small molecule JAK inhibitors show distinct efficacy and safety profiles, likely reflecting variable selectivity for JAK subtypes. Absolute JAK subtype selectivity has not yet been achieved. Here, we rationally design small interfering RNAs (siRNAs) that offer sequence-specific gene silencing of JAK1, narrowing the spectrum of action on JAK-dependent cytokine signaling to maintain efficacy and improve safety. Our fully chemically modified siRNA supports efficient silencing of JAK1 expression in human skin explant and modulation of JAK1-dependent inflammatory signaling. A single injection into mouse skin enables five weeks of duration of effect. In a mouse model of vitiligo, local administration of the JAK1 siRNA significantly reduces skin infiltration of autoreactive CD8+ T cells and prevents epidermal depigmentation. This work establishes a path toward siRNA treatments as a new class of therapeutic modality for inflammatory and autoimmune skin diseases.

Abstract The risk of severe adverse events related to thiopurine therapy can be reduced by personalizing dosing based on TPMT and NUDT15 genetic polymorphisms. However, the optimal genetic testing platform has not yet been established. In this study, we report on the TPMT and NUDT15 genotypes and phenotypes generated from 320 patients from a multicenter pediatric healthcare system using both Sanger sequencing and polymerase chain reaction genotyping (hereafter: genotyping) methods to determine the appropriateness of genotyping in our patient population. Sanger sequencing identified variant TPMT alleles including *3A (8, 3.2% of alleles), *3C (4, 1.6%), and *2 (1, 0.4%), and NUDT15 alleles including *2 (5, 3.6%) and *3 (1, 0.7%). For genotyped patients, variants identified in TPMT included *3A (12, 3.1%), *3C (4, 1%), *2 (2, 0.5%), and *8 (1, 0.25%), whereas NUDT15 included *4 (2, 1.9%) and *2 or *3 (1, 1%). Between Sanger sequencing and genotyping, no significant difference in allele, genotype, or phenotype frequency was identified for either TPMT or NUDT15. All patients who were tested using Sanger sequencing would have been accurately phenotyped for either TPMT (124/124), NUDT15 (69/69), or both genes (68/68) if they were assayed using the genotyping method. Considering 193 total TPMT and NUDT15 Sanger Sequencing tests reviewed, all tests would have resulted in an appropriate clinical recommendation if the test had instead been conducted using the comparison genotyping platforms. These results suggest that, in this study population, genotyping would be sufficient to provide accurate phenotype calls and clinical recommendations.

ABSTRACTFungal secondary metabolites (SMs) contribute to the diversity of fungal ecological communities, niches, and lifestyles. Many fungal SMs have one or more medically and industrially important activities (e.g., antifungal, antibacterial, and antitumor). The genes necessary for fungal SM biosynthesis are typically located right next to each other in the genome and are known as biosynthetic gene clusters (BGCs). However, whether fungal SM bioactivity can be predicted from specific attributes of genes in BGCs remains an open question. We adapted machine learning models that predicted SM bioactivity from bacterial BGC data with accuracies as high as 80% to fungal BGC data. We trained our models to predict the antibacterial, antifungal, and cytotoxic/antitumor bioactivity of fungal SMs on two data sets: (i) fungal BGCs (data set comprised of 314 BGCs) and (ii) fungal (314 BGCs) and bacterial BGCs (1,003 BGCs). We found that models trained on fungal BGCs had balanced accuracies between 51% and 68%, whereas training on bacterial and fungal BGCs had balanced accuracies between 56% and 68%. The low prediction accuracy of fungal SM bioactivities likely stems from the small size of the data set; this lack of data, coupled with our finding that including bacterial BGC data in the training data did not substantially change accuracies currently limits the application of machine learning approaches to fungal SM studies. With >15,000 characterized fungal SMs, millions of putative BGCs in fungal genomes, and increased demand for novel drugs, efforts that systematically link fungal SM bioactivity to BGCs are urgently needed.IMPORTANCEFungi are key sources of natural products and iconic drugs, including penicillin and statins. DNA sequencing has revealed that there are likely millions of biosynthetic pathways in fungal genomes, but the chemical structures and bioactivities of >99% of natural products produced by these pathways remain unknown. We used artificial intelligence to predict the bioactivities of diverse fungal biosynthetic pathways. We found that the accuracies of our predictions were generally low, between 51% and 68%, likely because the natural products and bioactivities of only very few fungal pathways are known. With >15,000 characterized fungal natural products, millions of putative biosynthetic pathways present in fungal genomes, and increased demand for novel drugs, our study suggests that there is an urgent need for efforts that systematically identify fungal biosynthetic pathways, their natural products, and their bioactivities.

Providing method descriptions that are more detailed than currently available in typical peer reviewed journals has been identified as an actionable area for improvement. In the biochemical and cell biology space, this need has been met through the creation of new journals focused on detailed protocols and materials sourcing. However, this format is not well suited for capturing instrument validation, detailed imaging protocols, and extensive statistical analysis. Furthermore, the need for additional information must be counterbalanced by the additional time burden placed upon researchers who may be already overtasked. To address these competing issues, this white paper describes protocol templates for positron emission tomography (PET), X-ray computed tomography (CT), and magnetic resonance imaging (MRI) that can be leveraged by the broad community of quantitative imaging experts to write and self-publish protocols in protocols.io. Similar to the Structured Transparent Accessible Reproducible (STAR) or Journal of Visualized Experiments (JoVE) articles, authors are encouraged to publish peer reviewed papers and then to submit more detailed experimental protocols using this template to the online resource. Such protocols should be easy to use, readily accessible, readily searchable, considered open access, enable community feedback, editable, and citable by the author.

Early response assessment is critical for personalizing cancer therapy. Emerging therapeutic regimens with encouraging results in the wild-type (WT) KRAS colorectal cancer (CRC) setting include inhibitors of epidermal growth factor receptor (EGFR) and glutaminolysis. Towards predicting clinical outcome, this preclinical study evaluated non-invasive positron emission tomography (PET) with (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) in treatment-sensitive and treatment-resistant WT KRAS CRC patient-derived xenografts (PDXs). Tumor-bearing mice were imaged with [18F]FSPG PET before and one week following the initiation of treatment with either EGFR-targeted monoclonal antibody (mAb) therapy, glutaminase inhibitor therapy, or the combination. Imaging was correlated with tumor volume and histology. In PDX that responded to therapy, [18F]FSPG PET was significantly decreased from baseline at 1-week post-therapy, prior to changes in tumor volume. In contrast, [18F]FSPG PET was not decreased in non-responding PDX. These data suggest that [18F]FSPG PET may serve as an early metric of response to EGFR and glutaminase inhibition in the WT KRAS CRC setting.

Abstract A growing number of studies have shown a connection between rhythmic processing and language skill. It has been proposed that domain-general rhythm abilities might help children to tap into the rhythm of speech (prosody), cueing them to prosodic markers of grammatical (syntactic) information during language acquisition, thus underlying the observed correlations between rhythm and language. Working memory processes common to task demands for musical rhythm discrimination and spoken language paradigms are another possible source of individual variance observed in musical rhythm and language abilities. To investigate the nature of the relationship between musical rhythm and expressive grammar skills, we adopted an individual differences approach in N = 132 elementary school-aged children ages 5–7, with typical language development, and investigated prosodic perception and working memory skills as possible mediators. Aligning with the literature, musical rhythm was correlated with expressive grammar performance (r = 0.41, p

Background: Stress responses are believed to involve corticotropin releasing factor (CRF), its two cognate receptors (CRF1 and CRF2), and the CRF-binding protein (CRFBP). Whereas decades of research has focused on CRF1, the role of CRF2 in the central nervous system (CNS) has not been thoroughly investigated. We have previously reported that CRF2, interacting with a C terminal fragment of CRFBP, CRFBP(10kD), may have a role in the modulation of neuronal activity. However, the mechanism by which CRF interacts with CRFBP(10kD) and CRF2 has not been fully elucidated due to the lack of useful chemical tools to probe CRFBP. Methods: We miniaturized a cell-based assay, where CRFBP(10kD) is fused as a chimera with CRF2, and performed a high-throughput screen (HTS) of 350,000 small molecules to find negative allosteric modulators (NAMs) of the CRFBP(10kD)-CRF2 complex. Hits were confirmed by evaluating activity toward parental HEK293 cells, toward CRF2 in the absence of CRFBP(10kD), and toward CRF1 in vitro. Hits were further characterized in ex vivo electrophysiology assays that target: 1) the CRF1+ neurons in the central nucleus of the amygdala (CeA) of CRF1:GFP mice that express GFP under the CRF1 promoter, and 2) the CRF-induced potentiation of N-methyl-D-aspartic acid receptor (NMDAR)-mediated synaptic transmission in dopamine neurons in the ventral tegmental area (VTA). Results: We found that CRFBP(10kD) potentiates CRF-intracellular Ca2+ release specifically via CRF2, indicating that CRFBP may possess excitatory roles in addition to the inhibitory role established by the N-terminal fragment of CRFBP, CRFBP(27kD). We identified novel small molecule CRFBP-CRF2 NAMs that do not alter the CRF1-mediated effects of exogenous CRF but blunt CRF-induced potentiation of NMDAR-mediated synaptic transmission in dopamine neurons in the VTA, an effect mediated by CRF2 and CRFBP. Conclusion: These results provide the first evidence of specific roles for CRF2 and CRFBP(10kD) in the modulation of neuronal activity and suggest that CRFBP(10kD)-CRF2 NAMs can be further developed for the treatment of stress-related disorders including alcohol and substance use disorders.

Abstract Metastatic dissemination in breast cancer is regulated by specialized intravasation sites called “tumor microenvironment of metastasis” (TMEM) doorways, composed of a tumor cell expressing the actin-regulatory protein Mena, a perivascular macrophage, and an endothelial cell, all in stable physical contact. High TMEM doorway number is associated with an increased risk of distant metastasis in human breast cancer and mouse models of breast carcinoma. Here, we developed a novel magnetic resonance imaging (MRI) methodology, called TMEM Activity-MRI, to detect TMEM-associated vascular openings that serve as the portal of entry for cancer cell intravasation and metastatic dissemination. We demonstrate that TMEM Activity-MRI correlates with primary tumor TMEM doorway counts in both breast cancer patients and mouse models, including MMTV-PyMT and patient-derived xenograft models. In addition, TMEM Activity-MRI is reduced in mouse models upon treatment with rebastinib, a specific and potent TMEM doorway inhibitor. TMEM Activity-MRI is an assay that specifically measures TMEM-associated vascular opening (TAVO) events in the tumor microenvironment, and as such, can be utilized in mechanistic studies investigating molecular pathways of cancer cell dissemination and metastasis. Finally, we demonstrate that TMEM Activity-MRI increases upon treatment with paclitaxel in mouse models, consistent with prior observations that chemotherapy enhances TMEM doorway assembly and activity in human breast cancer. Our findings suggest that TMEM Activity-MRI is a promising precision medicine tool for localized breast cancer that could be used as a non-invasive test to determine metastatic risk and serve as an intermediate pharmacodynamic biomarker to monitor therapeutic response to agents that block TMEM doorway-mediated dissemination.

Electronic cigarette use has dramatically increased over the last decade. With this recent technological development and wide range of constituents in various products, putative adverse effects on the brain and body have been largely unexplored. Here, we review current evidence linking electronic nicotine cigarette use with potential health consequences and provide evidence supporting an association between drug use and depression in humans. We also examine the biological effects of individual constituents in electronic cigarette aerosols, which include labeled ingredients, such as propylene glycol, vegetable glycerin, nicotine, and flavorants, as well as unlabeled ingredients found in the aerosols, such as carbonyls and heavy metals. Lastly, we examine the effects of electronic cigarette use on endogenous metabolism via changes in cytochrome P450 enzymes, which can thereby impact therapeutic outcomes. While the current evidence offers insight into the potential effects of electronic cigarette use on biological processes, further studies are necessary to determine the long-term clinical relevance of aerosol inhalation.

Abstract Background Insomnia is common in breast cancer survivors (BCS), affecting an estimated 30–50% of the 3.8 million BCS in the US. Insomnia is associated with health consequences for cardiometabolic and immune systems, neurobehavioral function, depression, fatigue, and quality of life and may put BCS at particular risk. While pharmacotherapy for insomnia may address symptoms in the short-term, cognitive behavioral therapy for insomnia (CBT-I) is considered the gold standard insomnia treatment. We describe our protocol to determine the efficacy of voice-activated delivery of CBT-I components on insomnia symptoms compared to a sleep education control among BCS. Methods We will conduct a 6-week, randomized controlled trial with two arms. Intervention arm participants will receive a smart speaker device and will be asked to engage with the program daily, using a voice-activated speaker with an accompanying smart-phone app. Control participants will have access to a website with basic information about CBT-I, sleep, and breast cancer survivorship and will be asked to engage with the website as desired. Discussion Our primary outcome is the Insomnia Severity Index total score. Secondary outcomes include sleep diary outcomes (sleep efficiency, wake after sleep onset, sleep onset latency, total sleep time, and sleep quality). This study will provide evidence on a promising modality to deliver elements of CBT-I for BCS experiencing insomnia. Trial Registration ClinicalTrials.gov NCT05233800 Released 3/25/2022.

Aim: Immune checkpoint inhibitor (ICI) efficacy is undefined for melanoma brain metastases (MBM) with concurrent corticosteroid exposure. Materials & methods: We retrospectively evaluated patients with untreated MBM who received corticosteroids (≥1.5 mg dexamethasone equivalent) within 30 days of ICI. mRECIST criteria and Kaplan–Meier methods defined intracranial progression-free survival (iPFS). The lesion size-response association was evaluated with repeated measures modeling. Results: A total of 109 MBM were evaluated. The patient level intracranial response rate was 41%. Median iPFS was 2.3 months and overall survival was 13.4 months. Larger lesions were more likely to progress, with diameter >2.05 cm most predictive of progression (OR: 18.9; 95% CI: 2.6–139.5; p = 0.004). There was no difference in iPFS with steroid exposure pre- versus post-ICI initiation. Conclusion: In the largest reported ICI+corticosteroid cohort, we identify size dependent MBM response.

Abstract Hispanic women have lower rates of use of infertility services than non-Hispanic White women. There are many barriers that impede access to infertility care including economic, geographic, cultural, and societal factors and there are disparities in treatment outcomes. Hispanic women are less likely to seek infertility care than non-Hispanic White women and even after infertility evaluation, Hispanic women are less likely to receive treatment for their infertility. Lower use of infertility treatments among Hispanic women is unlikely to be driven solely by economic factors. There is disappointingly little data on in-vitro fertilization treatment outcomes including the population of Hispanic women, and existing data has yielded conflicting results. Incomplete and variable reporting of race data across clinics raises the potential for misclassification bias and invalid study conclusions. Addressing disparities in access to reproductive medicine in the Hispanic population will required a multifaceted approach including expanded insurance coverage, improved education for both patients and providers, and additional research on barriers to care.

Abstract Introduction Children with developmental language disorder (DLD) exhibit cognitive deficits that interfere with their ability to learn language. Little is known about the functional neuroanatomical differences between children developing typically (TD) and children with DLD. Methods Using functional near‐infrared spectroscopy, we recorded oxygenated hemoglobin (O2hb) concentration values associated with neural activity in children with and without DLD during an auditory N‐back task that included 0‐back, 1‐back, and 2‐back conditions. Analyses focused on the left dorsolateral prefrontal cortex (DLPFC) and left inferior parietal lobule (IPL). Multilevel models were constructed with accuracy, response time, and O2hb as outcome measures, with 0‐back outcomes as fixed effects to control for sustained attention. Results Children with DLD were significantly less accurate than their TD peers at both the 1‐back and 2‐back tasks, and they demonstrated slower response times during 2‐back. In addition, children in the TD group demonstrated significantly greater sensitivity to increased task difficulty, showing increased O2hb to the IPL during 1‐back and to the DLPFC during the 2‐back, whereas the DLD group did not. A secondary analysis revealed that higher O2hb in the DLPFC predicted better task accuracy across groups. Conclusion When task difficulty increased, children with DLD failed to recruit the DLPFC for monitoring information and the IPL for processing information. Reduced memory capacity and reduced engagement likely contribute to the language learning difficulties of children with DLD.

Given the urgency of the COVID-19 pandemic, telehealth was swiftly implemented in the United States and shifted from an optional to an essential modality of care. This was important in both maintaining continuity of care, especially for those with chronic illnesses, and in evaluating individuals presenting with illness or acute needs. One of the primary benefits of telemedicine is convenience; however, this is juxtaposed with the various downsides that result from a lack of physical appointments and accessible technology. Notably, there are large barriers to achieving equity for certain communities, of which the most apparent is the “digital divide” that results from a lack of adequate broadband infrastructure and lower technology literacy among members of certain communities and those in rural areas. Without attention to factors that can improve availability, uptake, and experience, disparities will increase with telemedicine. As this technology becomes common practice, it will be important to provide equal reimbursement for in-person and telehealth visits, center patient design and cultural competency in telemedicine programs, and improve broadband and technology access, ensuring that the highest-quality care is delivered to all patients.

Despite recent advances in treatment and surveillance, metastatic melanoma still carries a poor prognosis. Large/giant congenital melanocytic nevi (CMNs) constitute a known risk factor for the condition, with the greatest risk for malignant transformation thought to be during childhood (median age at diagnosis of 3 years in a previous cohort). Herein, we present the case of a 30-year-old male who, after undergoing multiple excision/grafting procedures for a giant CMN as a child, was diagnosed with an NRAS-mutant, MDM2-amplified metastatic melanoma more than 20 years later. Response to ipilimumab/nivolumab immunotherapy, cisplatin/vinblastine/temozolomide chemotherapy, and nivolumab/relatlimab immunotherapy was poor. This case highlights the importance of lifetime monitoring with once-yearly dermatological examination (including lymph node palpation) in large/giant CMN patients, as well as the need for further clinical trials evaluating novel therapies for NRAS-mutant melanoma.

Summary: Background: The importance of deriving benefit and meaning has been identified among cancer caregivers, but this has yet to be examined in the context of rare cancers. We sought to characterize unmet needs and experiences of caregivers of patients with Erdheim-Chester disease (ECD) and other histiocytic neoplasms (HN) and to identify factors associated with finding benefit and meaning-making in providing care for patients with rare cancers. Methods: Caregivers of patients with ECD and other HN completed quantitative surveys. Linear univariable regression modeling examined associations between unmet needs, social and family support, and intolerance of uncertainty with benefit finding and meaning-making. A subset participated in qualitative interviews assessing experiences of rare cancer caregiving that were analyzed with applied thematic analysis (NCT039900428). Findings: Of caregivers (N = 92, M = 54 years old, 68% female) of patients with ECD (75%) and other HN (25%), 78% reported moderately or severely unmet support needs, most frequently informational (58%) and psychological/emotional (66%) needs. Caregivers with unmet informational, psychological/emotional, and social support needs, difficulty tolerating uncertainty, a longer duration of the patient's illness, lower social support, more family conflict, and higher anxiety and depression symptoms demonstrated less benefit finding and meaning-making (ps

The Matching Familiar Figures Test (MFFT) is a well-known and extensively used behavioral measure of reflection-impulsivity. However, the instrument has several deficiencies, including images designed for school-age children in the United States during the 1960s. Most importantly, an adult version of the instrument is currently unavailable and the lack of a single repository for the images raises questions regarding the MFFT’s validity and reliability. We developed a 21st century version of the MFFT using images that are familiar to adults and reside in a freely accessible repository. We conducted two studies examining validity and reliability issues. In Study 1, participants interacting with the MFFT-2021, versus those interacting with the original MFFT20, spent more time on the task, took more time in making their first response, and were more likely to complete the task without errors, even though the average number of errors was higher than the comparison group. The coherence of these results is evidence of convergent validity. Regarding predictive validity, the MFFT-2021 remained a reliable predictor of rational thinking, such that participants who demonstrated more reflection (less impulsivity) tended to avoid rational thinking errors. Also, performance on the MFFT-2021 predicted higher quality judgments in processing job characteristic cues with embedded interactions, a form of configural information processing. We also found evidence of concurrent validity: performance on the MFFT-2021 differed in a predictable manner for participants grouped by their performance on the Cognitive Reflection Test. In Study 2, we tested discriminant validity by comparing participant performance on the MFFT-2021 to their performance on the Information Sampling Task (IST), another behavioral measure of reflection-impulsivity used in studies of psychopharmacological and addiction behaviors. For our participants (undergraduate business students), we found that the MFFT was a stronger predictor of performance on rational thinking tasks, and, contrary to prior studies, our exploratory factor analysis identified separate factors for the MFFT-2021 and the IST, supporting discriminant validity, indicating that these two instruments measure different subtypes of reflection-impulsivity.

Compared to their written counterpart, oral assessments provide a wealth of information about student understanding. Instead of deciphering a static response, oral assessments provide instructors the opportunity to probe student explanations, obtaining a more complete picture of their understanding. Moreover, students explaining their conceptual reasoning is advocated in the 2016 GAISE guidelines. Additionally, oral exams allow for flexibility in how students can explain their thinking, potentially helping build students’ identities as statistical thinkers and speakers. Despite the facilities these assessments provide, oral assessments are rarely used in the statistics classroom. In this article I describe the important considerations to be attended to when implementing oral exams in the classroom, my experiences facilitating oral exams in my statistics courses, and some lessons I learned along the way. Supplementary materials for this article are available online.

Epidermal necrolysis, the unifying term for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), is a severe cutaneous drug reaction associated with high morbidity and mortality. Given the rarity of this disease, large-scale prospective research studies are limited. Significant institutional and geographical variations in treatment practices highlight the need for standardization of clinical assessment scores and prioritization of research outcome measures in epidermal necrolysis. At the present, clinical assessment is typically simplified to total body surface area (BSA) involvement, with little focus on morphology. Validated clinical scoring systems are used as mortality prognostication tools, with SCORTEN being the best-validated tool thus far, although the ABCD-10 has also been recently introduced. These tools are imperfect in that they tend to either overestimate or underestimate mortality in certain populations and are not designed to monitor disease progression. Although mortality is often used as a primary endpoint for epidermal necrolysis studies, this outcome fails to capture more nuanced changes in skin disease such as arrest of disease progression while also lacking a validated skin-directed inclusion criterion to stratify patients based on the severity of skin disease at study entry. In addition to mortality, many studies also use BSA stabilization or time to re-epithelialization as endpoints, although these are not clearly defined morphologically, and inter- and intra-rater reliability are unclear. More specific, validated cutaneous assessment scores are necessary in order advance therapeutic options for epidermal necrolysis. In this review, we summarize the strengths and weaknesses of current clinical assessment practices in epidermal necrolysis and highlight the need for standardized research tools to monitor cutaneous involvement throughout the hospitalization.

Predatory outer membrane vesicles (OMVs) secreted by myxobacteria fuse readily with the outer membranes of Gram-negative bacteria, introducing toxic cargo into their prey. Here we used a strain of the myxobacterium Myxococcus xanthus that produces fluorescent OMVs to assay the uptake of OMVs by a panel of Gram-negative bacteria. M. xanthus strains took up significantly less OMV material than the tested prey strains, suggesting that re-fusion of OMVs with producing organisms is somehow inhibited. The OMV killing activity against different prey correlated strongly with the predatory activity of myxobacterial cells, however, there was no correlation between OMV killing activity and their propensity to fuse with different prey. It has previously been proposed that M. xanthus GAPDH stimulates the predatory activity of OMVs by enhancing OMV fusion with prey cells. Therefore, we expressed and purified active fusion proteins of M. xanthus glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase (GAPDH and PGK; moonlighting enzymes with additional activities beyond their roles in glycolysis/gluconeogenesis) to investigate any involvement in OMV-mediated predation. Neither GAPDH nor PGK caused lysis of prey cells or enhanced OMV-mediated lysis of prey cells. However, both enzymes were found to inhibit the growth of Escherichia coli, even in the absence of OMVs. Our results suggest that fusion efficiency is not a determinant of prey killing, but instead resistance to the cargo of OMVs and co-secreted enzymes dictates whether organisms can be preyed upon by myxobacteria.

We describe a pre-clinical spinal cord motor neuron injury model that is minimal invasive, reproducible, focal and easily applied to small rodents. Retrograde axonal transport of a pro-apoptotic phosphatidylinosotol 3’-kinase inhibitor, wortmannin, via the sciatic nerve results in loss of ipsilateral lumbar motor neurons proportional to the level of drug administered. Motor neuron loss was detected by choline acetyltransferase (ChAT) immunostaining and with a transgenic thy1-eGFP marker. The short half-life of wortmannin generates minimal wound spread, and wortmannin does not affect axon transport, as determined by co-injection of a pseudorabies virus tracer. Using quantitative transcript analysis, we found that ChAT transcripts significantly decreased at 14 days post-delivery of 1 μg wortmannin, relative to sham controls, and remained low after 90 days. Smaller effects were observed with 200 ng and 100 ng wortmannin. Wortmannin also generated a transient and significant increase in astrocyte Gfap transcripts after 14 days with a return to control levels at 90 days. Treated mice had hind limb spasticity and a forced motor function defect that was quantified using a water exit test. Controls rapidly exit a shallow water tray, and wortmannin treated animals were up to 12-fold slower, a phenotype that persisted for at least 3 months. Thus the focal delivery of wortmannin to motor neurons generates a reproducible and scalable injury that can facilitate quantitative studies on neural regeneration and repair. The efficacy of sciatic nerve suicide transport can also explain neurotoxin-mediated selective loss of motor neurons in diseases such as amyotrophic lateral sclerosis. All procedures were performed at Rutgers under established Institutional Animal Care and Use protocols (eIACUC_TR201800022, approved on March 20, 2018).

Abstract Airports can affect birds by hindering acoustic communication. Here, we investigated the impacts of aircraft events on vocal behavior in wood thrush (Hylocichla mustelina) breeding one mile from an airport in Ithaca, NY, USA. We identified the number of wood thrush songs between 0500 and 0800 h at various distances from the airport and on days with various morning flight schedules. We also analyzed the number of sites from which birds sang during the peak of aircraft events (proxy of number of wood thrush). We found that birds sang more from 0600 to 0640 h when there were aircraft events during this period. This increased vocal behavior is likely explained by increased song output per individual wood thrush, rather than more wood thrush vocalizing. Increased song rate may negatively affect wood thrush fitness through increased energetic demands and/or time tradeoffs with other important behaviors, such as foraging. Identifying the noise thresholds associated with fitness costs (if any) and how different behavioral strategies (i.e. changing the pattern of vocalizations) may allow individuals to evade these costs would be useful for establishing conservation policy in breeding habitats used by passerines, such as the wood thrush.

HIV-1 vaccine efforts are primarily directed toward eliciting neutralizing antibodies (nAbs). However, vaccine trials and mother-to-child natural history cohort investigations indicate that antibody-dependent cellular cytotoxicity (ADCC), not nAbs, correlate with prevention. The ADCC characteristics associated with lack of HIV-1 acquisition remain unclear. Here, we examine ADCC and nAb properties in pretransmission plasma from HIV-1–exposed infants and from the corresponding transmitting and nontransmitting mothers’ breast milk and plasma. Breadth and potency (BP) were assessed against a panel of heterologous, nonmaternal variants. ADCC and neutralization sensitivity were estimated for the strains in the infected mothers. Infants who eventually acquired HIV-1 and those who remained uninfected had similar pretransmission ADCCBP. Viruses circulating in the transmitting and nontransmitting mothers had similar ADCC susceptibility. Infants with higher pretransmission ADCCBP and exposure to more ADCC-susceptible strains were less likely to acquire HIV-1. In contrast, higher preexisting infant neutralization BP and greater maternal virus neutralization sensitivity did not associate with transmission. Infants had higher ADCCBP closer to birth and in the presence of high plasma IgG relative to IgA levels. Mothers with potent humoral responses against their autologous viruses harbored more ADCC-sensitive strains. ADCC sensitivity of the exposure variants and preexisting ADCCBP influenced mother-to-child HIV-1 transmission during breastfeeding. Vaccination strategies that enhance ADCC are likely insufficient to prevent HIV-1 transmission because some strains may have low ADCC susceptibility.

Clinical trials are essential to modern medicine, but several barriers, including poor communication, hamper their successful completion. We examined the prevalence and correlates of invitation to participate in clinical trials among a nationally-representative sample of US adults using survey responses from the 2020 HINTS (Cycle 5). Analyses were conducted in 2021.Overall, 9% of respondents reported being invited to a clinical trial, a prevalence that is nearly half of previously reported rates in convenience samples recruited from health care settings. Compared to non-Hispanic Whites, Black respondents reported the higher prevalence of invitation (16.0%) whereas Asian respondents reported the lowest (2%). Prevalence of clinical trial invitation was significantly higher for the 65–74 age and the 75 + age groups. Prevalence of invitation was significantly higher among college graduates (12.0%) and lower for those residing in rural areas/small towns compared to metropolitan areas. Invitation was significantly higher among cancer patients/survivors (16.0%), patients with diabetes (11.7%) and with chronic lung disease (16.7%). Provider and patient factors there were associated with higher invitation rates included using web devices to communicate with providers or to aid health-related discussions, having a specific medical provider, and looking for health information online.This study establishes a population-based prevalence of clinical trial communication that can be monitored as health care providers/organizations increase their focus on enrollment activities. Targeted interventions to improve communication about clinical trials are needed to address socio-demographic disparities and are particularly important for Asian patients, patients with lower income, and those living in rural areas.

Abstract Background Large achievement and motivation gaps exist in science between students from higher and lower socioeconomic status (SES) backgrounds. Middle and high school are an important time to address these disparities, as science motivation typically declines for all students at this time, leading to particularly low science interest and achievement for lower SES students on average when the gaps are left unaddressed. Students’ control over their free time also increases at this time, providing opportunities for optional science experiences that may improve science attitudes and skills to combat these achievement and motivation gaps. Using a longitudinal dataset of 2252 middle and high school students from two regions in the USA, we investigate (1) disparities between higher and lower SES students in participation in optional summer science experiences and post-summer science attitudes and skills; (2) whether the child and family characteristics that predict participation in home-related, nature-related, and STEM camp experiences in the summer differ for higher and lower SES students; and (3) how participation in these types of optional summer science experiences contribute to post-summer science attitudes and skills when controlling for self-selection biases. Results Higher SES students reported greater participation in optional summer science experiences and higher post-summer science attitudes and sensemaking skills. Fascination for science was more important for participation in home-related and nature-related experiences for higher SES participants, whereas science competency beliefs were more important for lower SES participants. For STEM camp experiences, higher SES participants with higher competency beliefs and lower SES participants with lower scientific sensemaking skills were more likely to participate. After controlling for self-selection biases that may influence participation in these experiences, we found that home-related and nature-related experiences had a positive impact on students’ attitudes toward science. Conclusions Our findings suggest two pathways for increasing participation in optional summer science experiences for higher SES and lower SES students. Specifically, it may be helpful to support interest in science for higher SES students and competency beliefs for lower SES students. Greater participation in home-related and nature-related summer science experiences can also increase science attitudes during middle and high school.

This is a case report of a woman in her sixth decade of life diagnosed with primary angiosarcoma of the breast using mammography and ultrasound, confirmed with imaging-guided biopsy, and finally treated with surgery and radiation. Imaging studies obtained and discussed include mammography, ultrasonography, and MRI. Further discussion on the presenting symptoms, useful imaging modalities, and treatment options takes place. It is important to consider primary angiosarcoma of the breast, though rare, in any woman presenting with a palpable breast mass and, if feasible, an MRI will be most helpful in the diagnosis of this rare tumor. Keywords: Angiosarcoma, Primary angiosarcoma, Breast, Breast imaging

A 15-month old male presented with several months of abdominal distension. After undergoing thorough workup, he was found to have an intraabdominal mass on imaging. He underwent exploratory laparotomy and resection of a mesenteric mass along with a loop of associated small bowel. On pathology, the mass was consistent with a hibernoma. In retrospect, the mass may have been present on prenatal ultrasound.Hibernomas are rare, adipocytic tumors of brown fat origin. There have been less than 20 cases of pediatric hibernomas reported in the English literature. Moreover, there have been no previous reports of mesenteric hibernomas in children or those recognized on prenatal imaging. While lipomatous abdominal tumors are exceedingly rare in the neonatal population, this case report highlights that unusual volume of intra-abdominal fat seen on prenatal ultrasound may warrant repeat evaluation in the perinatal period.

Myxobacteria prey upon a broad range of microorganisms. Lawn assays are commonly used to quantify myxobacterial predation—myxobacterial suspensions are spotted onto prey lawns, and monitored via spot expansion. The diversity in motility behaviours of myxobacterial strains and differing assay protocols in myxobacteriology laboratories led us to develop a highly-specified assay, which was applied to 28 myxobacterial strains preying on seven phytopathogenic prey species. Generally, prey organisms showed no qualitative differences in their susceptibility/resistance to myxobacterial predation. For most myxobacteria, prey did not stimulate, and in ~50% of cases actively hindered colony expansion. Only ~25% of predator/prey strain combinations exhibited greater colony expansion than in the absence of nutrients. The activity of predatory strains against different prey correlated, implying effective predators may have relatively non-specific predation mechanisms (e.g., broad specificity proteases/lipases), but no correlation was observed between predatory activity and phylogeny. Predation on dead (but intact) or lysed prey cells gave greater colony expansion than on live prey. Occasional strains grew substantially faster on dead compared to lysed cells, or vice-versa. Such differences in accessing nutrients from live, dead and lysed cells indicates there are strain-specific differences in the efficiencies/machineries of prey killing and nutrient acquisition, which has important implications for the ecology of myxobacterial predators and their prey.

Background: Botulinum NeuroToxin-A (BoNT-A) relieves muscle spasticity and increases range of motion necessary for stroke rehabilitation. Determining the effects of BoNT-A therapy on brain neuroplasticity could help physicians customize its use and predict its outcome.Objective: The purpose of this study was to investigate the effects of Botulinum Toxin-A therapy for treatment of focal spasticity on brain activation and functional connectivity.Design: We used functional Magnetic Resonance Imaging (fMRI) to track changes in blood oxygen-level dependent (BOLD) activation and functional connectivity associated with BoNT-A therapy in nine chronic stroke participants, and eight age-matched controls. Scans were acquired before BoNT-A injections (W0) and 6 weeks after the injections (W6). The task fMRI scan consisted of a block design of alternating mass finger flexion and extension. The voxel-level changes in BOLD activation, and pairwise changes in functional connectivity were analyzed for BoNT-A treatment (stroke W0 vs. W6).Results: BoNT-A injection therapy resulted in significant increases in brain activation in the contralesional premotor cortex, cingulate gyrus, thalamus, superior cerebellum, and in the ipsilesional sensory integration area. Lastly, cerebellar connectivity correlated with the Fugl-Meyer assessment of motor impairment before injection, while premotor connectivity correlated with the Fugl-Meyer score after injection.Conclusion: BoNT-A therapy for treatment of focal spasticity resulted in increased brain activation in areas associated with motor control, and cerebellar connectivity correlated with motor impairment before injection. These results suggest that neuroplastic effects might take place in response to improvements in focal spasticity.

Introduction: When the metacarpal bones sustain severe osseous injury requiring reconstruction, functional recovery relies on the precise distribution of tension throughout full range of motion. While the small scale of hand structures compounds the effects of altering normal anatomy, literature lacks consensus recommendations for the acceptable degree of length alteration and/or appropriate methods of length estimation in reconstructive procedures. Length asymmetry has been reported in human metacarpal bones; however, studies assessing this phenomenon in living subjects with attention to functional implications or length prediction are lacking. Methods: Hand X-rays were obtained for 34 patients aged 25–80 without history of metacarpal trauma, joint degeneration, or pathologic bone metabolism. A scaled bivariate model predicted metacarpal length using an ipsilateral paired metacarpal and matching contralateral ratio: Estimate_Dx_R = Median_Dy_R * (Median_Dx_L/Median_Dy_L). A second set of predictions used the contralateral metacarpal as a control. Pearson correlation coefficients, paired t -tests, and chi-square tests evaluated the symmetry between bilateral metacarpal lengths and paired metacarpal ratios as well as the accuracy of each predictive method. Results: The contralateral control and target metacarpal differed significantly in digits 1, 2, 3, and 5. No significant difference in matched metacarpal ratios of the right and left hands was found. For all digits except 5D, bivariate model predictions generated were more strongly correlated with actual target length. Chi-square tests did not detect a significant difference in predictive value of the two models. Conclusion: The scaled bivariate model we describe may be useful and economic in generating accurate length estimates of metacarpals for reconstructive procedures.

Summary: In humans, pre-existing anti-HIV-1 neutralizing antibodies (nAbs) have not been associated with decreased HIV-1 acquisition. Here, we evaluate antibody-dependent cellular cytotoxicity (ADCC) present in pre-transmission infant and maternal plasma and breast milk (BM) against the contemporaneous maternal HIV-1 variants. HIV-1-exposed uninfected compared with HIV-1-exposed infected infants have higher ADCC and a combination of ADCC and nAb responses against their corresponding mother’s strains. ADCC does not correlate with nAbs, suggesting they are independent activities. The infected infants with high ADCC compared with low ADCC, but not those with higher ADCC plus nAbs, have lower morbidity up to 1 year after birth. A higher IgA to IgG ratio, observed in BM supernatants and in a higher proportion of the infected compared with the uninfected infants, associates with lower ADCC. Against the exposure strains, ADCC, more than nAbs, associates with both lower mother-to-child transmission and decreased post-infection infant morbidity.

Objective The goal of this study was to explore which enhanced recovery after surgery (ERAS) bundle items were most associated with decreased length of stay after surgery, most likely associated with decreased length of stay after surgery.Design A cohort study.Setting Large tertiary academic medical centre.Participants The study included 1318 women undergoing hysterectomy as part of our ERAS pathway between 1 February 2018 and 30 January 2020 and a matched historical cohort of all hysterectomies performed at our institution between 3 October 2016 and 30 January 2018 (n=1063).Intervention The addition of ERAS to perioperative care.This is a cohort study of all patients undergoing hysterectomy at an academic medical centre after ERAS implementation on 1 February 2018. Compliance and outcomes after ERAS roll out were monitored and managed by a centralised team. Descriptive statistics, multivariate regression, interrupted time series analysis were used as indicated.Main outcome measures Impact of ERAS process measure adherence on length of stay.Results After initiation of ERAS pathway, 1318 women underwent hysterectomy. There were more open surgeries after ERAS implementation, but cohorts were otherwise balanced. The impact of process measure adherence on length of stay varied based on surgical approach (minimally invasive vs open). For open surgery, compliance with intraoperative antiemetics (−30%, 95% CI −18% to 40%) and decreased postoperative fluid administration (−12%, 95% CI −1% to 21%) were significantly associated with reduced length of stay. For minimally invasive surgery, ambulation within 8 hours of surgery was associated with reduced length of stay (−53%, 95% CI −55% to 52%).Conclusions While adherence to overall ERAS protocols decreases length of stay, the specific components of the bundle most significantly impacting this outcome remain elusive. Our data identify early ambulation, use of antiemetics and decreasing postoperative fluid administration to be associated with decreased length of stay.

Cellulitis is frequently misdiagnosed owing to its clinical mimickers, collectively known as pseudocellulitis. This study investigated diffuse reflectance spectroscopy (DRS) alone and in combination with infrared thermography (IRT) for the differentiation of cellulitis from pseudocellulitis. A prospective cohort study at an urban academic hospital was conducted from March 2017 to March 2018. Patients presenting to the emergency department with presumed cellulitis were screened for eligibility, and 30 adult patients were enrolled. Dermatology consultation conferred a final diagnosis of cellulitis or pseudocellulitis. DRS measurements yielded a spectral ratio between 556 nm (deoxyhemoglobin peak) and 542 nm (oxyhemoglobin peak), and IRT measurements yielded temperature differentials between the affected and unaffected skin. Of the 30 enrolled patients, 30% were diagnosed with pseudocellulitis. DRS revealed higher spectral ratios in patients with cellulitis (P = 0.005). A single parameter model using logistic regression on DRS measurements alone demonstrated a classification accuracy of 77.0%. A dual parameter model using linear discriminant analysis on DRS and IRT measurements combined demonstrated a 95.2% sensitivity, 77.8% specificity, and 90.0% accuracy for cellulitis prediction. DRS and IRT combined diagnoses cellulitis with an accuracy of 90%. DRS and IRT are inexpensive and noninvasive, and their use may reduce cellulitis misdiagnosis.

Molecular imaging is the visual representation of biological processes that take place at the cellular or molecular level in living organisms. To date, molecular imaging plays an important role in the transition from conventional medical practice to precision medicine. Among all imaging modalities, positron emission tomography (PET) has great advantages in sensitivity and the ability to obtain absolute imaging quantification after corrections for photon attenuation and scattering. Due to the ability to label a host of unique molecules of biological interest, including endogenous, naturally occurring substrates and drug-like compounds, the role of PET has been well established in the field of molecular imaging. In this article, we provide an overview of the recent advances in the development of PET radiopharmaceuticals and their clinical applications in oncology.

OBJECTIVES:. To evaluate the link between early acute respiratory failure and functional morbidity in survivors using the plasma biomarkers interleukin-8, interleukin-1 receptor antagonist, thrombomodulin, and plasminogen activator inhibitor-1. We hypothesized that children with acute respiratory failure with higher levels of inflammation would have worse functional outcomes at discharge, as measured by Pediatric Overall Performance Category. DESIGN:. Secondary analysis of the Genetic Variation and Biomarkers in Children with Acute Lung Injury (R01HL095410) study. SETTING:. Twenty-two PICUs participating in the multisite clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (U01 HL086622) and the ancillary study (Biomarkers in Children with Acute Lung Injury). SUBJECTS:. Children 2 weeks to 17 years requiring invasive mechanical ventilation for acute airways and/or parenchymal lung disease. Patients with an admission Pediatric Overall Performance Category greater than 3 (severe disability, coma, or brain death) were excluded. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Among survivors, 387 patients had no worsening of Pediatric Overall Performance Category at discharge while 40 had worsening functional status, defined as any increase in Pediatric Overall Performance Category from baseline. There was no significant relationship between worsening of Pediatric Overall Performance Category and interleukin-8 or plasminogen activator inhibitor-1 on any day. There was no significant relationship between interleukin-1 receptor antagonist, or thrombomodulin, and worsening Pediatric Overall Performance Category on day 1. Plasma interleukin-1 receptor antagonist and thrombomodulin were significantly elevated on days 2 and 3 in those with worse functional status at discharge compared with those without. In multivariable analysis, interleukin-1 receptor antagonist and thrombomodulin were associated with a decline in functional status on days 2 and 3 after adjustment for age and highest oxygenation index. However, after adjusting for age and cardiovascular failure, only day 2 thrombomodulin levels were associated with a worsening in Pediatric Overall Performance Category. CONCLUSIONS:. Higher levels of interleukin-1 receptor antagonist or thrombomodulin following intubation were associated with worse Pediatric Overall Performance Category scores at hospital discharge in children who survive acute respiratory failure. These data suggest that persistent inflammation may be related to functional decline.

Perceptual learning theory suggests that perceptual grouping in mathematical expressions can direct students' attention toward specific parts of problems, thus impacting their mathematical reasoning. Using in-lab eye tracking and a sample of 85 undergraduates from a STEM-focused university, we investigated how higher-order operator position (HOO; i.e., multiplication/division operators and the presence of superfluous brackets impacted students' time to first fixation to the HOO, response time, and percent of correct responses). Students solved order-of-operations problems presented in six ways (3 HOO positions × presence of brackets). We found that HOO position and presence of superfluous brackets had separate and combined impacts on calculating arithmetic expressions. Superfluous brackets most influenced undergraduates' performance when higher-order operators were located in the center of mathematical expressions. Implications for learning and future directions are discussed about observing eye movements and gaining insights into students' processes when solving arithmetic expressions.

Vestibular evoked myogenic potentials (VEMPs) are a useful and increasingly popular component of the neuro-otology test battery. These otolith-dependent reflexes are produced by stimulating the ears with air-conducted sound or skull vibration and recorded from surface electrodes placed over the neck (cervical VEMPs) and eye muscles (ocular VEMPs). VEMP abnormalities have been reported in various diseases of the ear and vestibular system, and VEMPs have a clear role in the diagnosis of superior semicircular canal dehiscence. However there is significant variability in the methods used to stimulate the otoliths and record the reflexes. This review discusses VEMP methodology and provides a detailed theoretical background for the techniques that are typically used. The review also outlines the common pitfalls in VEMP recording and the clinical applications of VEMPs. Keywords: Otolith, Sound, Vibration, Vestibular, VEMP, Method

Abstract Introduction The purpose of this study was to characterize resting‐state cortical networks in chronic stroke survivors using electroencephalography (EEG). Methods Electroencephalography data were collected from 14 chronic stroke and 11 neurologically intact participants while they were in a relaxed, resting state. EEG power was normalized to reduce bias and used as an indicator of network activity. Correlations of orthogonalized EEG activity were used as a measure of functional connectivity between cortical regions. Results We found reduced cortical activity and connectivity in the alpha (p

Background: While vancomycin loading doses may facilitate earlier pharmacokinetic–pharmacodynamic target attainment, the impact of loading doses on clinical outcomes remains understudied. Critically ill patients are at highest risk of morbidity and mortality from methicillin resistant Staphylococcus aureus (MRSA) infection and hypothesized to most likely benefit from a loading dose. We sought to determine the association between receipt of a vancomycin loading dose and clinical outcomes in a cohort of critically ill adults. Methods: Four hundred and forty-nine critically ill patients with MRSA cultures isolated from blood or respiratory specimens were eligible for the study. Cohorts were established by receipt of a loading dose (⩾20 mg/kg actual body weight) or not. The primary outcome was clinical failure, a composite outcome of death within 30 days of first MRSA culture, blood cultures positive ⩾7 days, white blood cell count up to 5 days from vancomycin initiation, temperature up to 5 days from vancomycin initiation, or substitution (or addition) of another MRSA agent. Results: There was no difference in the percentage of patients experiencing clinical failure between the loading dose and no loading dose groups (74.8% versus 72.8%; p = 0.698). Secondary outcomes were also similar between groups, including mortality and acute kidney injury, as was subgroup analysis based on site of infection. Exploratory analyses, including assessment of loading dose based on quartiles and a multivariable logistic regression model showed no differences. Conclusion: Use of vancomycin loading doses was not associated with improved clinical outcomes in critically ill patients with MRSA infection.

This exploratory study assessed the use of functional Near Infrared Spectroscopy (fNIRS) to examine hemodynamic response patterns during sentence processing. Four groups of participants: monolingual English children, bilingual Chinese-English children, bilingual Chinese-English adults and monolingual English adults were given an agent selection syntactic processing task. Bilingual child participants were classified as simultaneous or sequential bilinguals to examine the impact of first language, age of second-language acquisition (AoL2A), and the length of second language experience on behavioral performance and cortical activation. Participants were asked to select the agent of four types of sentences: subject-verb-object (SVO), passive (PAS), subject-extracted relative clause (SR), and object-extracted relative clause (OR) adopted from the “Whatdunit” task by Montgomery et al. (2016). Semantic cues were removed by using inanimate nouns for agents and patients, which constrained participants to make decisions based on syntactic knowledge. Behavioral results showed greater accuracy for canonical SVO and SR sentence types than for noncanonical OR and PAS sentence types, which aligns with prior studies. Neuroimaging results revealed greater hemodynamic responses to relative clauses (i.e., SR and OR sentences) than to simple sentences (SVO and PAS), especially for Chinese-English bilinguals suggesting first-language transfer influencing sentence processing in English. The effects AoL2A and the length of second language experience showed no significant differences between simultaneous and sequential bilinguals or between bilingual adults and children for identifying the correct agent in each sentence. However, neuroimaging results demonstrated greater hemodynamic responses in right dorsolateral prefrontal cortex (DLPFC) and left inferior parietal lobule (IPL) in simultaneous bilinguals compared to sequential bilinguals and greater hemodynamic responses in left and right DLPFC and left IPL among bilingual adults. Different behavioral and neural hemodynamic response patterns afford new insights into the effects of syntactic knowledge on sentence processing.