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Introduction: To evaluate use and utility of the Fetal Alcohol Spectrum Disorder (FASD) Hub Australia website. Methods: Online REDCap user survey incorporating the Website Evaluation Questionnaire, open ended questions, Google metrics data and an accessibility audit. Results: Seventy‐six participants: researchers (32%), health professionals (29%) and policymakers/advocates (16%) completed the survey. Most were from Australia (95%) and were likely or very likely to recommend the FASD Hub to colleagues (92%), friends (74%) and patients (72%). The mean Website Evaluation Questionnaire score was at least 3.45/5 for all dimensions (ease of use, hyperlinks, structure, relevance, comprehension, completeness, layout, search option); range 3.45 (search option) to 4.04 (relevance). Participants found the content trustworthy (92%) but wanted more information for, and to support, Aboriginal and Torres Strait Islander peoples, and improved search capacity. Google metrics identified 25,534 unique users over 6 months (82% new users); 83% aged 18–44 years, 72% female and 35% international. Conclusions: Users found the FASD Hub accessible, authoritative and useful and suggested improvements. [ABSTRACT FROM AUTHOR]

Objective: In 2020, one study by Strait and colleagues raised awareness that the clinical images in rheumatology educational materials underrepresent people with skin of color (P‐SOC). Since then, publishers of rheumatology educational materials have focused on addressing this shortcoming. This study investigates the change in representation of P‐SOC following the review of Strait et al. Methods: We used the methods of the aforementioned study to collect images from commonly referenced rheumatology educational materials and categorized the skin tones within them as "light" or "dark." We calculated the proportional change in images depicting dark skin tones between 2020 and 2022 from the American College of Rheumatology (ACR) Image Library, the 10th edition of Kelley's Textbook of Rheumatology, and New England Journal of Medicine (NEJM) as well as between 2020 and 2024 from rheumatology articles within UpToDate. We compared results using one‐sided Z‐tests. Results: Overall, the proportion of images depicting dark skin tones increased 40.6% (P < 0.0001). The 10th edition of Kelley's Textbook of Rheumatology most significantly increased inclusion of P‐SOC (90.1%; P = 0.0039), with ACR Image Library, UpToDate, and NEJM also enhancing representation (41.9%, P < 0.0001; 31.0%, P = 0.0083; 28.2%, P = 0.3046, respectively). Conclusion: This study assesses the progress of rheumatology educational materials toward equitable representation of P‐SOC. It demonstrates that awareness coupled with focused efforts from educational publishers can enhance the proportion of images depicting dark skin tones, thereby enriching the quality of foundational knowledge relayed to rheumatology providers with the goal of improving health experiences and outcomes for P‐SOC with rheumatic diseases. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to compare early outcomes of de novo LCPT (once‐daily extended‐release tacrolimus) to IR TAC (twice‐daily immediate‐release tacrolimus) in a predominantly African American (AA) adult kidney transplant population. Methods: This is a single center, retrospective cohort study. Patients were divided into two cohorts: IR TAC (administered between January 1, 2017, and January 31, 2019) and LCPT (administered between February 1, 2019, and May 31, 2020). Primary endpoints were changes in tacrolimus trough levels (ng/mL) and estimated glomerular filtration rate up to 12 months post‐transplantation. Clinical endpoints included graft survival, delayed graft function, biopsy‐proven rejection, CMV viremia, and BK. A propensity score weighted generalized linear mixed effects model was used for analysis. Results: The rate of change in tacrolimus levels was significantly higher in the LCPT cohort compared to the IR TAC cohort at 14 days post‐discharge (.2455 ng/mL per day vs..1073 ng/mL, respectively; p <.001). Subsequently, the LCPT cohort had a slightly higher rate of decline (–.015 ng/mL per day vs. –.010 ng/mL with IR TAC; p =.0894) up to 12 months post‐discharge. Although eGFR was similar between the two cohorts at 12 months post‐transplant, the rate of increase was slower in the LCPT cohort (.1371 mL/min per day vs..1852 mL/min per day, p =.0314). No significant differences were found in graft survival, DGF, BPAR, CMV, or BK infection. Conclusion: This study demonstrates that despite higher early trough levels with immediate post‐transplant LCPT use, clinical outcomes are comparable to IR TAC at one‐year post‐transplant. Notably, LCPT use does not increase the incidence of DGF and that this formulation of CNI can be used as first line therapy post‐transplant. [ABSTRACT FROM AUTHOR]

Summary: An 18‐year‐old multiparous Thoroughbred mare with a 2‐month‐old foal at foot presented for investigation of colic. A right dorsal displacement of the large colon with a retroflexion of the pelvic flexure was corrected under general anaesthesia and interventional recovery using head and tail ropes was performed. The mare made multiple attempts to stand, using the ropes for support before achieving and maintaining a standing position. The following day, marked swelling around the perineal and vulval region was noted, combined with reduced tail tone. Urination, but not defaecation, had been observed following surgery. Transrectal ultrasonography indicated formation of a haematoma adjacent and ventral to the caudal sacral and first coccygeal vertebrae. Initial radiographic evaluation was suggestive of an oblique fracture of the caudal endplate of the first coccygeal vertebra, which was confirmed on repeat radiography 7 days later. Treatment included cold compresses to reduce swelling, multimodal analgesia, dietary modification to soften faecal consistency and regular manual evacuation of the rectum to avoid impaction. The mare was discharged after 19 days hospitalisation, gradually recovered the ability to defaecate and produced a viable foal the following year without assistance. [ABSTRACT FROM AUTHOR]

As healthcare delivery continues to evolve and expand, nurse educators must prepare advanced practice registered nursing (APRN) students to use telehealth technology safely, effectively, and confidently. The aims of this study were to describe APRN students' beliefs and confidence regarding the delivery of care via telehealth in their future practice. To evaluate these aims, a single group comparison study was conducted. APRN students received an intervention comprised of multimodal telehealth instruction, which involved the simulated application of telehealth with standardized patients. Students' beliefs regarding telehealth did not significantly change between the pre‐ and post‐intervention, in which all areas were rated high pre‐intervention. Students reported an increase in their perception and confidence post‐intervention. Integration of telehealth into the APRN curriculum is essential to instil knowledge and confidence as healthcare technology advances. [ABSTRACT FROM AUTHOR]

A 5‐year 7‐month‐old, entire, male Chow Chow presented with paraparesis and ataxia due to a previously diagnosed T11–T12 spinal diverticulum. Due to the progression of clinical signs, magnetic resonance imaging was indicated to reassess the lesion. Preoperative rectal temperature was unable to be assessed due to temperament; however, it was likely the patient would be hyperthermic as it had been hyperthermic (40.6°C) under general anaesthesia 4 months earlier. Consequently, measures were taken to attempt to reduce body temperature before general anaesthesia. While under general anaesthesia for imaging, the patient was confirmed to be markedly hyperthermic. This report details the management of a patient with hyperthermia under general anaesthesia. The patient was gradually cooled before recovery from anaesthesia. Once recovered from anaesthesia and normothermic, the patient was discharged home the same day. Follow‐up confirmed no adverse effects. [ABSTRACT FROM AUTHOR]

Nearly half a century ago, two papers postulated the likelihood of lunar lava tube caves using mathematical models. Today, armed with an array of orbiting and fly‐by satellites and survey instrumentation, we have now acquired cave data across our solar system—including the identification of potential cave entrances on the Moon, Mars, and at least nine other planetary bodies. These discoveries gave rise to the study of planetary caves. To help advance this field, we leveraged the expertise of an interdisciplinary group to identify a strategy to explore caves beyond Earth. Focusing primarily on astrobiology, the cave environment, geology, robotics, instrumentation, and human exploration, our goal was to produce a framework to guide this subdiscipline through at least the next decade. To do this, we first assembled a list of 198 science and engineering questions. Then, through a series of social surveys, 114 scientists and engineers winnowed down the list to the top 53 highest priority questions. This exercise resulted in identifying emerging and crucial research areas that require robust development to ultimately support a robotic mission to a planetary cave—principally the Moon and/or Mars. With the necessary financial investment and institutional support, the research and technological development required to achieve these necessary advancements over the next decade are attainable. Subsequently, we will be positioned to robotically examine lunar caves and search for evidence of life within Martian caves; in turn, this will set the stage for human exploration and potential habitation of both the lunar and Martian subsurface. Plain Language Summary: We have now acquired cave data across our solar system—including the identification of potential cave entrances on the Moon, Mars, and at least nine other planetary bodies. These discoveries gave rise to the study of planetary caves. To help advance this field, we conducted an expert‐opinion based social survey to identify a strategy to explore caves beyond Earth. We focused primarily on astrobiology, the cave environment, geology, robotics, instrumentation, and human exploration. First, we assembled a list of 198 science and engineering questions. Then, through a series of social surveys, 114 scientists and engineers winnowed down the list to the top 53 highest priority questions. This exercise resulted in identifying emerging and crucial research areas that require robust development to ultimately support a robotic mission to a planetary cave—principally the Moon and/or Mars. With the necessary financial investment and institutional support, the research and technological development required to achieve these necessary advancements over the next decade are attainable. Subsequently, we will be positioned to robotically examine lunar caves and search for evidence of life within Martian caves; in turn, this will set the stage for human exploration and potential habitation of both the lunar and Martian subsurface. Key Points: Robotics and instrument advancements identified as linchpin focal areas for in situ study of planetary cavesResearch and technological development required for lunar and/or Martian cave exploration is achievable in next decade with proper investmentFirst application of systematic and statistically rigorous social survey to identify science and engineering requirements in planetary science [ABSTRACT FROM AUTHOR]

Objective: Lupus presents earlier and more severely among patients with skin of color (SOC), and this population experiences worse outcomes. Providers rely on medical education materials when developing skills to care for patients, yet these resources historically underrepresent patients with SOC and marginalize vulnerable populations. In this study, we investigated if this publication bias extends to images depicting patients with lupus. Methods: We reviewed published images of patients with lupus from rheumatology, dermatology, and internal medicine textbooks and medical journals, SOC atlases, online image libraries, UpToDate, and Google Images. We selected materials published from 2014 to 2019 that were available through our university's online medical library. We used the search terms "lupus" and "lupus rash" to identify images. We rated the skin color in each image using the New Immigrant Survey Skin Color Scale and categorized them as light, medium, or dark. We compared the frequencies of published skin tones with chi‐square and odds ratio analyses. Results: We assessed the skin tone of 1,417 images. The significant majority (56.4%) of the images represented light skin (χ2 = 490.14, P < 0.001). After SOC atlases, journals were the most inclusive of images depicting dark skin tones. The specialty of dermatology was most inclusive of medium and darker skin tones. Conclusion: Published images of lupus underrepresent patients with SOC, which may limit providers' ability to deliver care to the patients who are at greatest risk for complications. [ABSTRACT FROM AUTHOR]

This study evaluates a simple clinical audit tool for assessing quality of care and blood pressure control among persons with hypertension in primary care clinics. A systematic random sampling of persons with diabetes mellitus (DM) and hypertension (HTN) attending five health centers in Kingston, Jamaica, was conducted. A modified Ministry of Health paper-based audit tool captured quality of care and outcome indicators (blood pressure and glycemic control). Additional chart audits were conducted by a physician and nurse to assess reliability. One hundred and forty-nine charts were audited between January and September 2017. One hundred and thirty-eight persons (92.6%) had hypertension (27 men and 111 women); 77 persons (51.7%) had DM (14 men and 63 women). The median age was 64 years old. Approximately two-thirds of persons with HTN and DM had electrolytes, lipid profile, and ECG done within the last year. One-fifth of persons with hypertension (18.5% men and 19.8% women, P = 1.000) had adequate blood pressure control with greater control among persons with HTN only compared to persons with both DM and HTN. Poor glycemic control was recorded for 69% of persons with DM (57% men and 71% women, P = .297). Moderate to substantial inter-rater agreement was observed for quality of care indicators. Our findings confirmed that hypertension and glycemic control are inadequate among persons attending primary care clinics in Jamaica's capital city. Simplified clinical audits can provide important quality of care and outcome indicators without losing the meaningfulness of the data collected. [ABSTRACT FROM AUTHOR]

The Chicxulub impact caused a crash in productivity in the world's oceans which contributed to the extinction of ∼75% of marine species. In the immediate aftermath of the extinction, export productivity was locally highly variable, with some sites, including the Chicxulub crater, recording elevated export production. The long‐term transition back to more stable export productivity regimes has been poorly documented. Here, we present elemental abundances, foraminifer and calcareous nannoplankton assemblage counts, total organic carbon, and bulk carbonate carbon isotope data from the Chicxulub crater to reconstruct changes in export productivity during the first 3 Myr of the Paleocene. We show that export production was elevated for the first 320 kyr of the Paleocene, declined from 320 kyr to 1.2 Myr, and then remained low thereafter. A key interval in this long decline occurred 900 kyr to 1.2 Myr post impact, as calcareous nannoplankton assemblages began to diversify. This interval is associated with fluctuations in water column stratification and terrigenous flux, but these variables are uncorrelated to export productivity. Instead, we postulate that the turnover in the phytoplankton community from a post‐extinction assemblage dominated by picoplankton (which promoted nutrient recycling in the euphotic zone) to a Paleocene pelagic community dominated by relatively larger primary producers like calcareous nannoplankton (which more efficiently removed nutrients from surface waters, leading to oligotrophy) is responsible for the decline in export production in the southern Gulf of Mexico. Plain Language Summary: The end Cretaceous mass extinction was caused by the impact of an asteroid in what is now the Yucatán Peninsula, México. The impact ejected aerosols and dust into the air that reduced sunlight transmission, causing a severe decline in photosynthesis and the collapse of marine food webs. However, the change in the amount of organic matter created by photosynthesizing plankton that was delivered to the seafloor (export productivity) was variable across the oceans. At some places, including the Chicxulub crater, export productivity was actually high immediately after the impact. We produced a ∼3‐million ‐year record of export productivity in the crater to determine how long it remained elevated and why it eventually declined. Export production was very high for the first 320,000 years after the impact, declined from 320,000 to 1,200,000 years after the impact, and then remained low. We found that this production was not related to the input of nutrients nor the degree of stratification of the ocean, but instead was probably driven by the increase in the cell size of phytoplankton. Larger phytoplankton removed nutrients from the surface waters as they sank, prompting an increase in species which are better adapted to low‐nutrient waters. Key Points: Export productivity at Chicxulub was elevated for 1.2 Myr post K‐Pg; it was very high for the first 0.32 Myr and declined from 0.32–1.2 MyrThe final decline in export productivity ∼0.9–1.2 Myr is associated with the termination of calcareous nannoplankton disaster assemblagesExport productivity change is not correlated with stratification or terrigenous input and was likely driven by changes in the phytoplankton [ABSTRACT FROM AUTHOR]

Within the literature, there is overlap in the histopathological features described in eosinophilic folliculitis associated with chronic lymphocytic leukemia (CLL), eosinophilic dermatosis of hematologic malignancy, and acneiform follicular mucinosis. These disorders are described with varying degrees of superficial and deep lymphocytic and eosinophilic inflammation demonstrating perivascular, perifollicular, and folliculocentric involvement with or without follicular mucin deposition. Given significant histopathological overlap, these diagnoses may represent a continuum on a spectrum of dermatoses. Here, we present two cases with histopathological elements that reflect components of this clinicopathological spectrum and compare our findings with previously reported cases to compare and contrast reported features. Our first case is a 71‐year‐old African American man with long‐standing CLL who developed a pruritic erythematous papular eruption on the face and chest with biopsy revealing a dense folliculotropic lymphocytic infiltrate with conspicuous eosinophils and follicular mucinosis. Our second case is a 70‐year‐old Caucasian man recently diagnosed with CLL/small lymphocytic lymphoma who developed an erythematous papular rash on the neck and face with biopsy revealing superficial and deep perivascular and periadnexal lymphocytic inflammation with scattered eosinophils. Characterization of our two cases and comparison with available literature suggest that these disorders may represent a continuum of dermatoses. [ABSTRACT FROM AUTHOR]

Although primary pancreatic lymphoma is a rare cause of pancreatic mass, this diagnosis should be considered during work‐up. Furthermore, when adequate diagnostic material is available from biopsy, complete workup of the lymphoma, including not only type but also subtype when applicable, should be performed. [ABSTRACT FROM AUTHOR]

Objective: This article positions the special issue on telepsychology amidst the COVID‐19 pandemic, which has dramatically accelerated the adoption and dissemination of telepsychology. Method: The article makes general observations about the themes emerging in the special issue with considerations for application, training, theory‐driven research, and policy. It then presents as a case example the rapid deployment during the pandemic of telepsychology doctoral training and services at the Virginia Commonwealth University (VCU) Primary Care Psychology Collaborative. Results: Facilitators to VCU telepsychology deployment included trainee and supervisor resources, strong telepsychology training, and prior experience. Barriers to overcome included limited clinic capacity, scheduling, technology, and accessibility and diversity issues. Lessons learned involved presenting clinical issues, supervision, and working with children and adolescents. Conclusions: Telepsychology is crucial for psychological service provision, during the COVID‐19 pandemic more than ever, and that is unlikely to change as psychologists and patients increasingly continue to appreciate its value. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To date, most investigations of mental health in pregnant women have focused on depression or substance use. This study aimed to (a) delineate the relationships between symptoms of attention‐deficit/hyperactivity disorder (ADHD) and prenatal health behaviors and (b) explore whether the symptom clusters of ADHD differentially predict prenatal health behaviors (e.g., physical strain, healthy eating, prenatal vitamin use). Method: A total of 198 pregnant women (mean age = 27.94 years) completed measures of ADHD symptoms, prenatal health behaviors, and depression. Results: Inattention, hyperactivity, and impulsivity/emotional lability all evidenced significant relationships with the prenatal health behaviors, each differentially predicting different prenatal health behaviors. Conclusion: As decreased engagement in adequate prenatal health behaviors puts both the mother and fetus at risk for negative birth outcomes, future research should work to develop a brief ADHD screen to be used in obstetric clinics and should investigate these relationships within a sample of women with a diagnosis of ADHD. [ABSTRACT FROM AUTHOR]

Abstract: A randomized, parallel‐dose study assessed the pharmacokinetics (PK) and pharmacodynamics (PD) of etanercept in 61 patients with rheumatoid arthritis (RA) who received doses from 10 mg once‐weekly to 50 mg twice‐weekly for 4 weeks. Empiric application of a maximal‐effect (Emax) model to pooled steady‐state concentrations (Css) and PD markers provided half‐maximal‐effect concentration estimates of 567, 573, 465, 87, and 159 ng/mL for change from baseline in number of swollen joints, number of painful joints, erythrocyte sedimentation rate, interleukin‐6, and matrix metalloproteinase‐3, respectively. Css >∼2,000 ng/mL did not appear to offer additional benefit. It was concluded that the middle doses, 10 mg twice‐weekly, 50 mg every 2 weeks, and 50 mg once‐weekly, would provide Css in the target range of 500–2,000 ng/mL. The revised US Food and Drug Administration guideline for development of medicines for treatment of RA encourages a study design incorporating PK/PD assessment to inform later studies. [ABSTRACT FROM AUTHOR]

Background and Purpose: Extracerebral venous congestion can precipitate intracranial hypertension due to obstruction of cerebral blood outflow. Conditions that increase right atrial pressure, such as hypervolemia, are thought to increase resistance to jugular venous outflow and contribute to cerebro-venous congestion. Cerebral pulsatility index (CPI) is considered a surrogate marker of distal cerebrovascular resistance and is elevated with intracranial hypertension. Thus, we sought to test the hypothesis that elevated right atrial pressure is associated with increased CPI compared to normal right atrial pressure.Methods: We retrospectively reviewed 61 consecutive patients with subarachnoid hemorrhage. We calculated CPI from transcranial Doppler studies and correlated these with echocardiographic measures of right atrial pressure. CPIs were compared from patients with elevated and normal right atrial pressure.Results: There was a significant difference between CPI obtained from all patients with elevated right atrial pressure compared to those with normal right atrial pressure (P < .0001). This finding was consistent in sensitivity analysis that compared right and left hemispheric CPI from patients with both elevated and normal right atrial pressure.Conclusion: Patients with elevated right atrial pressure had significantly higher CPI compared to patients with normal right atrial pressure. These findings suggest that cerebro-venous congestion due to impaired jugular venous outflow may increase distal cerebrovascular resistance as measured by CPI. Since elevated CPI is associated with poor outcome in numerous neurological conditions, future studies are needed to elucidate the significance of these results in other populations. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the long-term clinical and imaging efficacy of etanercept in patients with early, active nonradiographic axial spondyloarthritis (SpA).Methods: Adult patients who satisfied the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA (but not the modified New York radiographic criteria), with symptom duration >3 months to <5 years, and who were unresponsive to ≥2 nonsteroidal antirheumatic drugs (NSAIDs) received double-blind etanercept 50 mg/week or placebo for 12 weeks, followed by open-label etanercept 50 mg/week to week 104. Clinical, magnetic resonance imaging (MRI; Spondyloarthritis Research Consortium of Canada [SPARCC] scores), and safety outcomes at 104 weeks were analyzed.Results: Of 215 randomized patients (etanercept: n = 106; placebo: n = 109), 205 entered the study (etanercept/etanercept: n = 100; placebo/etanercept: n = 105) and 169 completed the open-label period (etanercept/etanercept: n = 83; placebo/etanercept: n = 86). At week 104, 61 of 81 (75%), 49 of 81 (61%), 48 of 80 (60%), and 57 of 81 (70%) patients who received etanercept throughout the trial achieved ASAS20, ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease, and Bath Ankylosing Spondylitis Disease Activity Index criteria for 50% improvement (BASDAI 50) scores, respectively (observed). From baseline to week 104, continued improvements in clinical outcomes (ASDAS-C-reactive protein: -1.5 and -1.7; BASDAI: -3.3 and -3.8 [last observation carried forward]), and SPARCC MRI scores (sacroiliac joint: -6.0 and -3.4; spinal: -2.1 and -0.8 [observed]) were seen in patients receiving etanercept/etanercept and placebo/etanercept. During the study, 8% in the etanercept/etanercept group and 7% in the placebo/etanercept group had serious adverse events; no new safety signals were seen.Conclusion: Patients with early, active nonradiographic axial SpA and an inadequate response to at least 2 NSAIDs demonstrated improvement in clinical and imaging outcomes that were sustained through 104 weeks of etanercept treatment. [ABSTRACT FROM AUTHOR]

Purpose: In vivo imaging of the pulmonary vasculature in small animals is difficult yet highly desirable in order to allow study of the effects of a host of dynamic biological processes such as hypoxic pulmonary vasoconstriction. Here the authors present an approach for the quantification of changes in the vasculature. Methods: A contrast free angiography technique is validated in silico through the use of computergenerated images and in vivo through microcomputed tomography (µCT) of live mice conducted using a laboratory-based x-ray source. Subsequent image processing on µCT data allowed for the quantification of the caliber of pulmonary vasculature without the need for external contrast agents. These measures were validated by comparing with quantitative contrast microangiography in the same mice. Results: Quantification of arterial diameters from the method proposed in this study is validated against laboratory-based x-ray contrast microangiography. The authors find that there is a high degree of correlation (R = 0.91) between measures from microangiography and their contrast free method. Conclusions: A technique for quantification of murine pulmonary vasculature without the need for contrast is presented. As such, this technique could be applied for longitudinal studies of animals to study changes to vasculature without the risk of premature death in sensitive mouse models of disease. This approach may also be of value in the clinical setting. [ABSTRACT FROM AUTHOR]

ABSTRACT The Trans-Mexican Volcanic Belt (TMVB) provides an excellent setting for reconstruction of late Quaternary climate from different natural archives. Moreover, human impact on the landscape since the mid-Holocene provides a good opportunity to investigate the complex interplay of natural and anthropogenic forcing of landscape change. However, despite the wealth of records, understanding of the environmental history of the region and its wider significance for climate change across the northern neotropics remains incomplete. We present a radiocarbon-dated, multiple-proxy (sedimentology, sedimentary geochemistry, ostracods, diatoms, stable isotopes) record of climatic and environmental change based on the lacustrine sediments from La Piscina de Yuriria, a hydrologically closed volcanic crater in the northern TMVB. Much of the last glacial interval was characterized by low effective moisture associated with a weakened North American Monsoon (NAM) although the interval from 30 000 to 27 500 a BP experienced abrupt changes in rainfall. The period corresponding to the Lateglacial stadial was also dry and the lake may have dried out at this time. There was a change to wetter but variable conditions during the early Holocene as the NAM strengthened. Progressive drying during the later Holocene was accompanied by phases of catchment disturbance, which were partly the result of human impact. [ABSTRACT FROM AUTHOR]

Gram-negative pathogens often use conserved type three secretion systems (T3SS) for virulence. The Shigella type three secretion apparatus (T3SA) penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. The protein Spa47 localizes to the base of the apparatus and is speculated to be an ATPase that provides the energy for T3SA formation and secretion. Here, we developed an expression and purification protocol, producing active Spa47 and providing the first direct evidence that Spa47 is a bona fide ATPase. Additionally, size exclusion chromatography and analytical ultracentrifugation identified multiple oligomeric species of Spa47 with the largest greater than 8 fold more active for ATP hydrolysis than the monomer. An ATPase inactive Spa47 point mutant was then engineered by targeting a conserved Lysine within the predicted Walker A motif of Spa47. Interestingly, the mutant maintained a similar oligomerization pattern as active Spa47, but was unable to restore invasion phenotype when used to complement a spa47 null S. flexneri strain. Together, these results identify Spa47 as a Shigella T3SS ATPase and suggest that its activity is linked to oligomerization, perhaps as a regulatory mechanism as seen in some related pathogens. Additionally, Spa47 catalyzed ATP hydrolysis appears to be essential for host cell invasion, providing a strong platform for additional studies dissecting its role in virulence and providing an attractive target for anti-infective agents. [ABSTRACT FROM AUTHOR]

As Ireland prepares to mark the centenary of the 1916 Easter Rising, Heather Jones traces how this failed military insurrection against British rule - mounted by a small, unrepresentative minority of Irish republicans - has evolved as a source of pride, division and controversy across the island over the course of a tumultuous century. [ABSTRACT FROM AUTHOR]

To meet product quality and cost parameters for therapeutic monoclonal antibody (mAb) production, cell lines are required to have excellent growth, stability, and productivity characteristics. In particular, cell line generation stability is critical to the success of a program, especially where high cell line generation numbers are required for large in-market supply. However, a typical process for developing such cell lines is laborious, lengthy, and costly. In this study, we applied a FLP/FRT recombinase-mediated cassette exchange (RMCE) system to build a site-specific integration (SSI) system for mAb expression in the commercially relevant CHOK1SV cell line. Using a vector with a FRT-flanked mAb expression cassette, we generated a clonal cell line with good productivity, long-term production stability, and low mAb gene-copy number indicating the vector was located in a 'hot-spot.' A SSI host cell line was made by removing the mAb genes from the 'hot-spot' by RMCE, creating a 'landing pad' containing two recombination cassettes that allow targeting of one or two copies of recombinant genes. Cell lines made from this host exhibited excellent growth and productivity profiles, and stability for at least 100 generations in the absence of selection agents. Importantly, while clones containing two copies had higher productivity than single copy clones, both were stable over many generations. Taken together, this study suggests the use of FLP-based RMCE to develop SSI host cells for mAb production in CHOK1SV offers significant savings in both resources and overall cell line development time, leading to a shortened 'time-to-clinic' for therapeutic mAbs. [ABSTRACT FROM AUTHOR]

Noninvasive imaging of the murine pulmonary vasculature is challenging due to the small size of the animal, limits of resolution of the imaging technology, terminal nature of the procedure, or the need for intravenous contrast. We report the application of laboratory‐based high‐speed, high‐resolution x‐ray imaging, and image analysis to detect quantitative changes in the pulmonary vascular tree over time in the same animal without the need for intravenous contrast. Using this approach, we detected an increased number of vessels in the pulmonary vascular tree of animals after 30 min of recovery from a brief exposure to inspired gas with 10% oxygen plus 5% carbon dioxide (mean ± standard deviation: 2193 ± 382 at baseline vs. 6177 ± 1171 at 30 min of recovery; P < 0.0001). In a separate set of animals, we showed that the total pulmonary blood volume increased (P = 0.0412) while median vascular diameter decreased from 0.20 mm (IQR: 0.15‐0.28 mm) to 0.18 mm (IQR: 0.14‐0.26 mm; P = 0.0436) over the respiratory cycle from end‐expiration to end‐inspiration. These findings suggest that the noninvasive, nonintravenous contrast imaging approach reported here can detect dynamic responses of the murine pulmonary vasculature and may be a useful tool in studying these responses in models of disease. We used laboratory‐based high‐speed, high‐resolution x‐ray imaging previously available only in a synchrotron setting to image the lungs of healthy mice under conditions of normal mechanical ventilation and in a separate experiment, ventilation with hypoxic/hypercarbic gas. We then applied postprocessing image analysis to segment the vasculature from our noncontrast imaging to generate three‐dimensional pulmonary vascular trees for quantitative analysis, and detected quantitative changes in vessels over time in the same animal. Our findings suggest that the noninvasive, noncontrast, in vivo imaging approach reported here can detect dynamic responses of the murine pulmonary vasculature and may be a useful tool in studying these responses in models of disease. [ABSTRACT FROM AUTHOR]