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The early stages of mussel farming are often inefficient with a large proportion of seed (spat) typically lost early in the production cycle. An effective approach for decreasing such losses is to grow spat to larger sizes in nursery systems prior to seeding. However, for such an approach to be commercially viable, spat must first be separated from their settlement substrates into a single seed format, that is, singulated. This study investigated the efficacy of three commercial protease enzymes (Enzidase PAP, PXT and BAP) and chlorine (NaOCl) in singulating Greenshell mussel (Perna canaliculus) spat from spat‐collector ropes. Two distinct experiments involved immersing segments of spat collector rope in seawater solutions with varying concentrations (2.5% or 5%) of each enzyme or chlorine (NaOCl) for different exposure times (10, 30 and 60 min for enzymes; 2 and 5 min for chlorine). After the singulation experiments, all spat were recovered with sieves and reintroduced into the tanks with renewed seawater. After 24 h of rearing, the recovery of alive spat was measured. Results indicate that in Experiment 1, involving spat ∼5 mm in size, the singulation rate was up to 65% for protease enzymes (i.e., in the case of 5% PAP at 30 min) and 61% for chlorine (i.e., at 5% for 2 min). In Experiment 2, involving spat ∼1.5 mm in size, the singulation rate was up to 85% for protease enzymes (i.e., in the case of 5% PXT for 60 min) and 78% for chlorine (i.e., of 2.5% for 5 min). However, these treatments generally resulted in elevated spat mortality, which was exacerbated by increasing concentrations and exposure times, resulting in recovery rates of up to 35% (i.e., for 2.5% PAP for 30 min) in Experiment 1 and 26.0% (i.e., for 5% chlorine for 2 min) in Experiment 2. These findings emphasise the necessity for consideration of chemical concentrations and exposure times to optimise the singulation process while highlighting challenges in achieving high post‐singulation survival rates. These insights contribute to ongoing efforts aimed at improving the efficiency and sustainability of mussel farming practices, demonstrating the potential utility of protease enzymes and chlorination in singulating spat from settlement substrate prior to their transfer to nursery systems for further ongrowing. For mussel spat to be grown in nursery culture systems they must first be separated from their associated settlement substrate (i.e., singualted). This work demonstrated that protease enzymes and chlorination is an effective approach for separating Greenshell mussel spat from spat‐catching ropes. [ABSTRACT FROM AUTHOR]

In April 2023, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in partnership with the National Institute of Child Health and Human Development, the National Institute on Aging, and the Office of Behavioral and Social Sciences Research, hosted a 2‐day online workshop to discuss neural plasticity in energy homeostasis and obesity. The goal was to provide a broad view of current knowledge while identifying research questions and challenges regarding neural systems that control food intake and energy balance. This review includes highlights from the meeting and is intended both to introduce unfamiliar audiences with concepts central to energy homeostasis, feeding, and obesity and to highlight up‐and‐coming research in these areas that may be of special interest to those with a background in these fields. The overarching theme of this review addresses plasticity within the central and peripheral nervous systems that regulates and influences eating, emphasizing distinctions between healthy and disease states. This is by no means a comprehensive review because this is a broad and rapidly developing area. However, we have pointed out relevant reviews and primary articles throughout, as well as gaps in current understanding and opportunities for developments in the field. [ABSTRACT FROM AUTHOR]

SUMMARY: Transcriptome‐wide association studies (TWAS) can provide single gene resolution for candidate genes in plants, complementing genome‐wide association studies (GWAS) but efforts in plants have been met with, at best, mixed success. We generated expression data from 693 maize genotypes, measured in a common field experiment, sampled over a 2‐h period to minimize diurnal and environmental effects, using full‐length RNA‐seq to maximize the accurate estimation of transcript abundance. TWAS could identify roughly 10 times as many genes likely to play a role in flowering time regulation as GWAS conducted data from the same experiment. TWAS using mature leaf tissue identified known true‐positive flowering time genes known to act in the shoot apical meristem, and trait data from a new environment enabled the identification of additional flowering time genes without the need for new expression data. eQTL analysis of TWAS‐tagged genes identified at least one additional known maize flowering time gene through trans‐eQTL interactions. Collectively these results suggest the gene expression resource described here can link genes to functions across different plant phenotypes expressed in a range of tissues and scored in different experiments. Significance Statement: Large, deep and rapidly sampled RNA‐seq data produce great TWAS results, and discovering genes known to act in other tissues and using data from other experiments suggests these data can be reused to study other traits. [ABSTRACT FROM AUTHOR]

Background Purpose Materials and Methods Results Conclusions MR‐integrated proton therapy is under development. It consists of the unique challenge of integrating a proton pencil beam scanning (PBS) beam line nozzle with an magnetic resonance imaging (MRI) scanner. The magnetic interaction between these two components is deemed high risk as the MR images can be degraded if there is cross‐talk during beam delivery and image acquisition.To create and benchmark a self‐consistent proton PBS nozzle model for empowering the next stages of MR‐integrated proton therapy development, namely exploring and de‐risking complete integrated prototype system designs including magnetic shielding of the PBS nozzle.Magnetic field (COMSOL Multiphysics${\text{Multiphysics}}$) and radiation transport (Geant4) models of a proton PBS nozzle located at OncoRay (Dresden, Germany) were developed according to the manufacturers specifications. Geant4 simulations of the PBS process were performed by using magnetic field data generated by the COMSOL Multiphysics${\text{Multiphysics}}$ simulations. In total 315 spots were simulated which consisted of a 40×30cm2$40\times 30\,{\text{cm}}^{2}$ scan pattern with 5 cm spot spacings and for proton energies of 70, 100, 150, 200, and 220 MeV. Analysis of the simulated deflection at the beam isocenter plane was performed to determine the self‐consistency of the model. The magnetic fringe field from a sub selection of 24 of the 315 spot simulations were directly compared with high precision magnetometer measurements. These focused on the maximum scanning setting of ±$\pm$ 20 cm beam deflection as generated from the second scanning magnet in the PBS for a proton beam energy of 220 MeV. Locations along the beam line central axis (CAX) were measured at beam isocenter and downstream of 22, 47, 72, 97, and 122 cm. Horizontal off‐axis positions were measured at 22 cm downstream of isocenter (±$\pm$ 50, ±$\pm$ 100, and ±$\pm$ 150 cm from CAX).The proton PBS simulations had good spatial agreement to the theoretical values in all 315 spots examined at the beam line isocenter plane (0–2.9 mm differences or within 1.5 % of the local spot deflection amount). Careful analysis of the experimental measurements were able to isolate the changes in magnetic fields due solely to the scanning magnet contribution, and showed 1.9 ±$\pm$ 1.2 μT$\bf{\mu} {\text{T}}$–9.4 ±$\pm$ 1.2 μT$\bf{\mu} {\text{T}}$ changes over the range of measurement locations. Direct comparison with the equivalent simulations matched within the measurement apparatus and setup uncertainty in all but one measurement point.For the first time a robust, accurate and self‐consistent model of a proton PBS nozzle assembly has been created and successfully benchmarked for the purposes of advancing MR‐integrated proton therapy research. The model will enable confidence in further simulation based work on fully integrated designs including MRI scanners and PBS nozzle magnetic shielding in order to de‐risk and realize the full potential of MR‐integrated proton therapy. [ABSTRACT FROM AUTHOR]

The significant clinical benefits of human epidermal growth factor receptor 2 (HER2)‐targeted therapeutic agents have revolutionized the clinical treatment landscape in a variety of human solid tumours. Accordingly, accurate evaluation of HER2 status in these different tumour types is critical for clinical decision making to select appropriate patients who may benefit from life‐saving HER2‐targeted therapies. HER2 biomarker scoring criteria is different in different organ systems, and close adherence to the corresponding HER2 biomarker testing guidelines and their updates, if available, is essential for accurate evaluation. In addition, knowing the unusual patterns of HER2 expression is also important to avoid inaccurate evaluation. In this review, we discuss the key considerations when evaluating HER2 status in solid tumours for clinical decision making, including tissue handling and preparation for HER2 biomarker testing, as well as pathologist's readout of HER2 testing results in breast carcinomas, gastroesophageal adenocarcinomas, colorectal adenocarcinomas, gynaecologic carcinomas, and non‐small cell lung carcinomas. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the accuracy of different dosimeters and the treatment planning system (TPS) for assessing the skin dose due to the electron streaming effect (ESE) on a 1.5 T magnetic resonance (MR)‐linac. Method: Skin dose due to the ESE on an MR‐linac (Unity, Elekta) was investigated using a solid water phantom rotated 45° in the x‐y plane (IEC61217) and centered at the isocenter. The phantom was irradiated with 1 × 1, 3 × 3, 5 × 5, 10 × 10, and 22 × 22 cm2 fields, gantry at 90°. Out‐of‐field doses (OFDs) deposited by electron streams generated at the entry and exit surface of the angled phantom were measured on the surface of solid water slabs placed ±20.0 cm from the isocenter along the x‐direction. A high‐resolution MOSkin™ detector served as a benchmark due to its shallower depth of measurement that matches the International Commission on Radiological Protection (ICRP) recommended depth for skin dose assessment (0.07 mm). MOSkin™ doses were compared to EBT3 film, OSLDs, a diamond detector, and the TPS where the experimental setup was modeled using two separate calculation parameters settings: a 0.1 cm dose grid with 0.2% statistical uncertainty (0.1 cm, 0.2%) and a 0.2 cm dose grid with 3.0% statistical uncertainty (0.2 cm, 3.0%). Results: OSLD, film, the 0.1 cm, 0.2%, and 0.2 cm, 3.0% TPS ESE doses, underestimated skin doses measured by the MOSkin™ by as much as –75.3%, –7.0%, –24.7%, and –41.9%, respectively. Film results were most similar to MOSkin™ skin dose measurements. Conclusions: These results show that electron streams can deposit significant doses outside the primary field and that dosimeter choice and TPS calculation settings greatly influence the reported readings. Due to the steep dose gradient of the ESE, EBT3 film remains the choice for accurate skin dose assessment in this challenging environment. [ABSTRACT FROM AUTHOR]

In this study, single nucleotide polymorphisms were used to investigate kinship and philopatry for the Critically Endangered green sawfish, Pristis zijsron, in Western Australia.Sampling was conducted in an important nursery area: the Ashburton River estuary and adjacent tidal creeks. Kinship was inferred from the genotypes of 104 sawfish sampled between 2011 and 2014 (n = 31), and 2020 and 2022 (n = 73).The total number of dams contributing across all sites and time periods was estimated to be between 50 and 56.Fifty‐two full sibling dyads, 90 half sibling dyads and 72 third‐degree dyads were detected, involving 58, 67, and 46 P. zijsron, respectively. Of these, 34 half sibling dyads were related maternally and 56 related paternally, including multiple maternal and paternal half siblings pupped in different years, suggesting both female and male philopatry. Catch data indicated that two groups of maternal half siblings were littermates, demonstrating multiple paternity. A high degree of relatedness was found across the study area, with 88% of P. zijsron related to at least one other individual up to the third‐degree.Evidence for female philopatry in P. zijsron highlights the importance of protecting nursery areas for this species. The occurrence of philopatric behaviour in male and female P. zijsron suggests that dispersal might be limited in both sexes of this species, highlighting the need to investigate the amount of genetic diversity and incidence of inbreeding within remaining populations. [ABSTRACT FROM AUTHOR]

Enteric septicemia of catfish (ESC), caused by the gram‐negative enteric bacteria Edwardsiella ictaluri, is a significant threat to catfish aquaculture in the southeastern United States. Antibiotic intervention can reduce mortality; however, antibiotic use results in an imbalance, or dysbiosis, of the gut microbiota, which may increase susceptibility of otherwise healthy fish to enteric infections. Herein, recovery of the intestinal microbiota and survivability of channel catfish in response to ESC challenge was evaluated following a 10‐day course of florfenicol and subsequent probiotic or prebiotic supplementation. Following completion of florfenicol therapy, fish were transitioned to a basal diet or diets supplemented with a probiotic or prebiotic for the remainder of the study. Digesta was collected on Days 0, 4, 8 and 12, beginning on the first day after cessation of antibiotic treatment, and gut microbiota was characterized by Illumina sequencing of the 16S rRNA gene (V4 region). Remaining fish were challenged with E. ictaluri and monitored for 32 days post‐challenge. Florfenicol administration resulted in dysbiosis characterized by inflated microbial diversity, which began to recover in terms of diversity and composition 4 days after cessation of florfenicol administration. Fish fed the probiotic diet had higher survival in response to ESC challenge than the prebiotic (p =.019) and negative control (p =.029) groups. [ABSTRACT FROM AUTHOR]

Ca2+ entry into nigrostriatal dopamine (DA) neurons and axons via L‐type voltage‐gated Ca2+ channels (LTCCs) contributes, respectively, to pacemaker activity and DA release and has long been thought to contribute to vulnerability to degeneration in Parkinson's disease. LTCC function is greater in DA axons and neurons from substantia nigra pars compacta than from ventral tegmental area, but this is not explained by channel expression level. We tested the hypothesis that LTCC control of DA release is governed rather by local mechanisms, focussing on candidate biological factors known to operate differently between types of DA neurons and/or be associated with their differing vulnerability to parkinsonism, including biological sex, α‐synuclein, DA transporters (DATs) and calbindin‐D28k (Calb1). We detected evoked DA release ex vivo in mouse striatal slices using fast‐scan cyclic voltammetry and assessed LTCC support of DA release by detecting the inhibition of DA release by the LTCC inhibitors isradipine or CP8. Using genetic knockouts or pharmacological manipulations, we identified that striatal LTCC support of DA release depended on multiple intersecting factors, in a regionally and sexually divergent manner. LTCC function was promoted by factors associated with Parkinsonian risk, including male sex, α‐synuclein, DAT and a dorsolateral co‐ordinate, but limited by factors associated with protection, that is, female sex, glucocerebrosidase activity, Calb1 and ventromedial co‐ordinate. Together, these data show that LTCC function in DA axons and isradipine effect are locally governed and suggest they vary in a manner that in turn might impact on, or reflect, the cellular stress that leads to parkinsonian degeneration. [ABSTRACT FROM AUTHOR]

To prevent catfish idiopathic anaemia, diets fortified with iron have been adopted as a regular practice on commercial catfish farms to promote erythropoiesis. However, the effects of prolonged exposure of excess dietary iron on production performance and disease resistance for hybrid catfish (Ictalurus punctatus × I. furcatus) remains unknown. Four experimental diets were supplemented with ferrous monosulphate to provide 0, 500, 1000, and 1500 mg of iron per kg of diet. Groups of 16 hybrid catfish juveniles (~22.4 g) were stocked in each of 20, 110‐L aquaria (n = 5), and experimental diets were offered to the fish to apparent satiation for 12 weeks. At the end of the study, production performance, survival, condition indices, as well as protein and iron retention were unaffected by the dietary treatments. Blood haematocrit and the iron concentration in the whole‐body presented a linear increase with the increasing the dietary iron. The remaining fish from the feeding trial was challenged with Edwardsiella ictaluri. Mortality was mainly observed for the dietary groups treated with iron supplemented diets. The results for this study suggest that iron supplementation beyond the required levels does affect the blood production, and it may increase their susceptibility to E. ictaluri infection. [ABSTRACT FROM AUTHOR]

The nutritional condition of seed mussels (spat) at the time of seeding is thought to play a major role in influencing spat losses on mussel farms, with nutritionally compromised spat thought to be more likely to be lost from aquaculture substrata than those in good condition. New Zealand's Greenshell™ mussel (Perna canaliculus) aquaculture industry relies almost exclusively (∼85%) on wild caught spat, with the vast majority, typically > 90%, lost shortly after being seeded onto coastal mussel farms. This study sought to quantify the extent of the variability in the nutritional condition (i.e., calorific, protein, lipid and carbohydrate content) of samples of spat used by the Greenshell™ industry between 2014 and 2021 (i.e., wild caught and hatchery produced) as a first step towards determining whether variability in nutritional condition may be a significant contributor to the marked variation observed in spat performance after it is seeded onto coastal farms. All parameters measured were highly variable among wild spat samples, with all but lipid content varying, including for samples of wild spat harvested at different times within the same month. Furthermore, there were no clear patterns in the nutritional condition of spat across months or years, suggesting environmental factors that limit feeding during the harvest and transport of spat may be contributing to marked differences in the quality of spat being used by the industry to seed farms. These results provide a baseline for assessing the nutritional condition of Greenshell™ spat and point towards a need to develop interventions to improve the quality of wild spat supply for this industry to help and prevent the ongoing massive losses of spat from farms. These measures could include, testing nutritional condition of spat at harvest or prior to seeding, development of nursery culture methods and development of artificial spat feeds that have the potential to replace live phytoplankton during nursery culture. [ABSTRACT FROM AUTHOR]

In the United States, catfish are primarily farmed in earthen ponds, resulting in an aquatic environment influenced both by management practices and natural ecological processes. Profiling pond water microbiota can be useful for understanding what conditions may lead to microbial communities associated with production issues and could inform management practices. The aim of this study was to identify appropriate methods for bacterial community profiling of catfish pond water with nanopore sequencing of the 16S rRNA gene. To this end, two forward primers, two reverse primers, and three different polymerase chain reaction (PCR) cycle numbers were tested on a mock community consisting of aquaculture‐relevant bacteria. The optimized protocol was applied to water samples obtained from three experimental catfish ponds sampled in May, June, August, and September 2020. Applying these methods to pond samples allowed for the identification of 1488 genera, primarily within four dominating phyla: Actinobacteriota, Bacteroidota, Cyanobacteria, and Firmicutes. High variation was observed between individual ponds and sampling timepoints; only 18 of the 1488 genera were found in relative abundances ≥1% in all ponds from at least one sampling point. Despite this variation, consistent results could be observed. Samples obtained from the month of September had the highest number of observed genera, and samples from June had the lowest. Overall, these data demonstrated individual ponds represent distinct microcosms composed of unique bacterial communities, although this pond effect was secondary to the influence of sampling month on pond community composition. [ABSTRACT FROM AUTHOR]

In the article "Postmortem Opportunity: A Biblical and Theological Assessment of Salvation After Death," theologian James Beilby explores the question of the destiny of those who never heard the gospel of Christ or heard a distorted version of it. Beilby argues for his own version of a postmortem opportunity theory, in which individuals who never heard the gospel or heard a distorted version of it will be given a chance to repent and believe in Christ after death. He supports his arguments with interdisciplinary research, including philosophy, biblical studies, and church history. While Beilby's work is thought-provoking and challenges long-held beliefs, it is important to note that he argues from within the Arminian tradition and does not thoroughly address how his theory could fit within other theological traditions. [Extracted from the article]

Background: Older adults are often prescribed medications that are potentially dangerous and geriatricians have specialized training in treating polypharmacy that may benefit these patients. To examine this, we compared potentially inappropriate medication (PIM) prescribing rates between geriatricians and similar general internists in the United States. Methods: Using national cross‐sectional data from 2013 to 2019, we compared annual PIM prescribing rates between 2815 outpatient geriatricians certified by the American Board of Internal Medicine in 1994–2018 and general internists matched 1:1 on IM certification exam score and year, residency exam pass rate, gender, and US birth and/or US medical school. PIM prescribing was based on the Healthcare Effectiveness Data and Information Set (HEDIS) PIM physician annual prescribing measures which consider medications flagged as potentially inappropriate in the American Geriatric Society Beers Criteria® guideline. We also examined prescribing of appropriate alternative medications. Prescribing rates were calculated as the percentage a physician's patients with Medicare fee‐for‐service part D enrollment seen in the outpatient setting in a given year (mean: 150 patients per physician) with a PIM prescription they prescribed. Results: Across 30,677 physician‐year observations, geriatricians were 16.7% less likely (95% confidence interval (CI): −19.8 to −13.7, p < 0.001) to prescribe a PIM (7.2% versus 8.7% of patients respectively) and 2.7% more likely (95% CI: 0.8 to 4.5, p = 0.004) to prescribe an appropriate alternative medication (52.0% versus 50.7% of patients respectively). Lower PIM prescribing was observed for most medication sub‐types including central nervous system, anticholinergic, pain, and endocrine medications. In sensitivity analyses, differences in prescribing were similar when comparing recently trained physicians with more experienced physicians. Conclusion: Findings suggest geriatricians in the United States prescribe PIMs at lower rates than general internists. This highlights the value geriatricians provide as well as opportunities to embed key principles of geriatric care into internal medicine training and health care delivery systems. See related editorial by David B. Reuben in this issue. [ABSTRACT FROM AUTHOR]

Treating atopic dermatitis (AD) in pregnant or breastfeeding women, and in women and men with AD aspiring to be parents is difficult and characterized by uncertainty, as evidence to inform decision‐making on systemic anti‐inflammatory treatment is limited. This project mapped consensus across dermatologists, obstetricians and patients in Northwestern Europe to build practical advice for managing AD with systemic anti‐inflammatory treatment in men and women of reproductive age. Twenty‐one individuals (sixteen dermatologists, two obstetricians and three patients) participated in a two‐round Delphi process. Full consensus was reached on 32 statements, partial consensus on four statements and no consensus on four statements. Cyclosporine A was the first‐choice long‐term systemic AD treatment for women preconception, during pregnancy and when breastfeeding, with short‐course prednisolone for flare management. No consensus was reached on second‐choice systemics preconception or during pregnancy, although during breastfeeding dupilumab and azathioprine were deemed suitable. It may be appropriate to discuss continuing an existing systemic AD medication with a woman if it provides good disease control and its benefits in pregnancy outweigh its risks. Janus kinase (JAK) inhibitors, methotrexate and mycophenolate mofetil should be avoided by women during preconception, pregnancy and breastfeeding, with medication‐specific washout periods advised. For men preconception: cyclosporine A, azathioprine, dupilumab and corticosteroids are appropriate; a 3‐month washout prior to conception is desirable for methotrexate and mycophenolate mofetil; there was no consensus on JAK inhibitors. Patient and clinician education on appropriate (and inappropriate) AD treatments for use in pregnancy is vital. A shared‐care framework for interdisciplinary management of AD patients is advocated and outlined. This consensus provides interdisciplinary clinical guidance to clinicians who care for patients with AD before, during and after pregnancy. While systemic AD medications are used uncommonly in this patient group, considerations in this article may help patients with severe refractory AD. [ABSTRACT FROM AUTHOR]

Growing seed mussels (spat) to larger sizes in single‐seed nursery culture systems prior to seeding onto coastal mussel farms is an effective approach for greatly reducing costly spat losses during this stage of mussel aquaculture. However, the production of single‐seed mussel spat in nursery culture systems relies on first separating spat from the settlement substrata to which they are attached, whether spat are settled in a hatchery or gathered from the wild. This study sought to determine whether chlorination could be an effective approach for separating wild Greenshell mussel (Perna canaliculus) spat from beachcast macroalgal material (Kaitaia spat material) harvested from a beach in northern New Zealand. The results demonstrate that chlorination (i.e. in solutions of up to 0.625% sodium hypochlorite) is a highly effective approach for separating spat, resulting in the detachment of up to 94.6% in one treatment without increasing mortality relative to controls. The effectiveness of chlorination was modulated by spat density, with increasing spat densities, lowering rates of detachment. While chlorination is effective at separating small spat (i.e. successfully separating 72.4% of spat <750 μm in shell length) overall spat densities, further investigation is required to determine how to effectively separate larger spat (i.e. with chlorination only successfully separating 21.5% of spat >750 μm). The high survival (relative to the control treatments) also suggests that chlorine concentrations and exposure durations could be increased from those used in this study. These results demonstrate that chlorination can be used to separate spat from substrate prior to their transfer to nursery systems for ongrowing, paving the way for such approaches for reducing spat losses to be integrated into the aquaculture production cycle. [ABSTRACT FROM AUTHOR]

Liver macrophages are critical components of systemic immune system defense mechanisms. F4/80high Kupffer cells (KCs) are the predominant liver‐resident macrophages and the first immune cells to contact pathogens entering the liver. F4/80low monocyte‐derived macrophages (MoMφs) are essential macrophages that modulate liver immune functions. Here we report a novel method of identifying subpopulations of these two populations using traditional flow cytometry and examine each subpopulation for its putative roles in the pathogenesis of an experimental non‐alcoholic steatohepatitis model. Using male C57BL/6 mice, we isolated and analyzed liver non‐parenchymal cells by flow cytometry. We identified F4/80high and F4/80low macrophage populations and characterized subpopulations using uniform manifold approximation and projection. We identified three subpopulations in F4/80high macrophages: CD163(+) KCs, CD163(−) KCs, and liver capsular macrophages. CD163(+) KCs had higher phagocytic and bactericidal activities and more complex cellular structures than CD163(−) KCs. We also identified four subpopulations of F4/80low MoMφs based on Ly6C and MHC class II expression: infiltrating monocytes, pro‐inflammatory MoMφs, Ly6C(−) monocytes, and conventional dendritic cells. CCR2 knock‐out mice expressed lower levels of these monocyte‐derived cells, and the count varied by subpopulation. In high‐fat‐ and cholesterol‐diet‐fed mice, only one subpopulation, pro‐inflammatory MoMφs, significantly increased in count. This indicates that changes to this subpopulation is the first step in the progression to non‐alcoholic steatohepatitis. The community can use our novel subpopulation and gating strategy to better understand complex immunological mechanisms in various liver disorders through detailed analysis of these subpopulations. [ABSTRACT FROM AUTHOR]

Bolbophorus damnificus is a digenetic trematode causing significant economic losses within the United States commercial catfish industry. The indirect life cycle is complex, requiring piscivorous birds, aquatic snails, and fish to complete. With federal protections on many piscivorous birds and no FDA‐approved therapeutic treatment for trematode infections in fish, management within the catfish industry is primarily limited to controlling the snail host. Planorbella trivolvis and Biomphalaria havanensis are snails commonly found in commercial catfish ponds and known to transmit B. damnificus. This study evaluated a low‐cost snail trap prototype for monitoring populations of these snails in efforts to better inform treatment regimes. Snail traps were deployed into ponds on a commercial catfish farm and checked weekly throughout the production season. All snails were identified and counted to evaluate trap efficacy. Traps captured significantly more snails in foodfish ponds than in fingerling ponds; however, this trend was not present in monthly box samples. B. havanensis was rarely collected and was only found consistently within one pond, while P. trivolvis was routinely collected from all ponds, although abundance varied widely among ponds. Snail traps could be a useful, low‐cost method to monitor snail populations within ponds and better inform control treatments. [ABSTRACT FROM AUTHOR]

Pelagic predators must contend with low prey densities that are irregularly distributed and dynamic in space and time. Based on satellite imagery and telemetry data, many pelagic predators will concentrate horizontal movements on ephemeral surface fronts—gradients between water masses—because of enhanced local productivity and increased forage fish densities.Vertical fronts (e.g. thermoclines, oxyclines) can be spatially and temporally persistent, and aggregate lower trophic level and diel vertically migrating organisms due to sharp changes in temperature, water density or available oxygen. Thus, vertical fronts represent a stable and potentially energy rich habitat feature for diving pelagic predators but remain little explored in their capacity to enhance foraging opportunities.Here, we use a novel suite of high‐resolution biologging data, including in situ derived oxygen saturation and video, to document how two top predators in the pelagic ecosystem exploit the vertical fronts created by the oxygen minimum zone of the eastern tropical Pacific.Prey search behaviour was dependent on dive shape, and significantly increased near the thermocline and hypoxic boundary for blue marlin Makaira nigricans and sailfish Istiophorus platypterus, respectively. Further, we identify a behaviour not yet reported for pelagic predators, whereby the predator repeatedly dives below the thermocline and hypoxic boundary (and by extension, below the prey). We hypothesize this behaviour is used to ambush prey concentrated at the boundaries from below.We describe how habitat fronts created by low oxygen environments can influence pelagic ecosystems, which will become increasingly important to understand in the context of global change and expanding oxygen minimum zones. We anticipate that our findings are shared among many pelagic predators where strong vertical fronts occur, and additional high‐resolution tagging is warranted to confirm this. [ABSTRACT FROM AUTHOR]

Cutaneous T‐cell lymphoma (CTCL) encompasses two main subtypes: mycosis fungoides and Sezary syndrome. Global response rates for the systemic treatment of mycosis fungoides and Sezary syndrome are approximately 30%, and none of these treatments are thought to be curative. C–C chemokine receptor type 4 (CCR4) and CD25 are encouraging targets for the treatment of CTCL and are individually targeted by mogamulizumab and denileukin diftitox, respectively. We developed a novel CCR4‐IL2 bispecific immunotoxin (CCR4‐IL2 IT) targeting both CCR4 and CD25. CCR4‐IL2 IT demonstrated superior efficacy against CCR4+CD25+CD30+ CTCL in an immunodeficient NSG mouse tumor model. Investigative New Drug‐enabling studies of CCR4–IL2 IT are ongoing, including Good Manufacturing Practice production and toxicology studies. In this study, we compared the in vivo efficacy of CCR4‐IL2 IT versus the US Food and Drug Administration–approved drug, brentuximab, using an immunodeficient mouse CTCL model. We demonstrated that CCR4–IL2 IT was significantly more effective in prolonging survival than brentuximab, and combination treatment of CCR4–IL2 IT and brentuximab was more effective than brentuximab or CCR4–IL2 IT alone in an immunodeficient NSG mouse CTCL model. Thus, CCR4–IL2 IT is a promising novel therapeutic drug candidate for CTCL treatment. [ABSTRACT FROM AUTHOR]

Objective: Men who work in skilled and unskilled trades and labor occupations (i.e., blue‐collar occupations), have high rates of obesity and associated comorbidities but are underrepresented in weight loss programs. A first step in engaging this group is to better understand their preferences for weight loss programs. Methods: Respondents were men working in trade and labor occupations, with overweight/obesity, and an interest in losing weight. A discrete choice experiment was developed, and the data were analyzed using mixed logit model. Respondent characteristics were tested as effect modifiers. Results: Respondents (N = 221, age (M ± SD) 45.0 ± 12.6, BMI 33.3 ± 6.3, 77% non‐Hispanic white) working in a variety of occupations (construction 31%, manufacturing 30%, transportation 25%, maintenance/repair 14%) participated in this study. Results indicate preferences for programs that encourage making smaller dietary changes, are delivered online, and do not incorporate competition. Results were consistent across sensitivity analyses and most respondent groups. Conclusions: The results suggest specific ways to make weight loss programs more appealing to men in trade and labor occupations. Using experimental methods to quantify preferences using larger, more representative samples would further assist in tailoring behavioral weight loss programs for under‐reached populations. [ABSTRACT FROM AUTHOR]

This case report describes a practical method for resolving a hard to localize abscess in a horse resulting from a traumatic injury near the stifle joint. When the horse presented for a chronic draining tract, a foreign body was suspected, with no external indication of location. Although ultrasonography was attempted to localize the abscess, the practitioner could not confidently identify the source of the draining tract. Radiography revealed a gas‐filled cavity approximately 28 cm proximal to the tract opening. In order to establish continuity between the tract opening and the presumed suppurative cavity, the practitioner developed a malleable radiopaque probe from readily available materials. Ultrasonography combined with the radiopaque probe allowed for confident localization and formulation of a surgical plan. The use of inexpensive available materials minimized cost and avoided delays in diagnosis and treatment. This improvised fistulographic method is suitable for practitioners at any skill level or practice setting. [ABSTRACT FROM AUTHOR]

Zoo‐based (ex situ) conservation breeding programs provide invaluable opportunities to uncover enigmatic behaviors and traits of focal species under managed care, which can support research and conservation management efforts. A suite of factors and a limited range have yielded population declines in the threatened narrow‐headed gartersnake (Thamnophis rufipunctatus). Better understanding its cryptic ecology and life history (e.g., reproductive ecology) offers conservation benefits. We analyzed data on courtship behavior, parity and litter size, offspring size, and neonatal growth from an ex situ T. rufipunctatus population at the Phoenix Zoo from 2009 to 2018. Courtship behavior and parturition phenology are likely linked with the North American monsoon season, yet the courtship window may be wider than realized. We document the first instances of interannual iteroparity and multigenerational rearing of successful breeders at the ex situ level. Litter sizes varied but were relative to maternal body mass, suggesting that fecundity may be driven by intrinsic condition (e.g., age and size) of breeding females. Mean offspring body masses were equivalent between sexes, and neonate growth trends were quadratic during their first 9 months. Sexual dimorphism became apparent around 4–5 months age. Much of these data are novel for T. rufipunctatus and provide insight into their reproductive ecology. Phenology of reproductive ecology and body size metrics can guide field surveillance, age estimations, and population ecology monitoring, as well as inform ex situ adaptive management practices. Strategies spanning the ex situ‐in situ spectrum are applicable to other imperiled taxa to better inform conservation management decisions. Research highlights: We report the first records of iteroparity and entirely ex situ reproductive generations for threatened narrow‐headed gartersnakes.Intrinsic body condition exhibits plasticity but may drive fecundity; sexual dimorphism develops around 4–5 months age.Reproductive phenology and age‐size data can aid in situ monitoring and conservation management. [ABSTRACT FROM AUTHOR]

Waldenström macroglobulinaemia (WM) is an indolent B‐cell malignancy characterised by the presence of IgM paraprotein, bone marrow infiltration by clonal small B lymphocytes with plasmacytic differentiation and the MYD88 L265P mutation in >90% of cases. Traditionally, WM has been treated with chemoimmunotherapy. Recent trials have demonstrated the efficacy and safety of Bruton tyrosine kinase inhibitors in WM, both as monotherapy and in combination with other drugs. There is emerging evidence on the use of other agents including B‐cell lymphoma 2 inhibitors and on the treatment of rare presentations of WM. In this update, the Medical and Scientific Advisory Group of Myeloma Australia reviews the available evidence on the treatment of WM since the last publication in 2017 and provides specific recommendations to assist Australian clinicians in the management of this disease. [ABSTRACT FROM AUTHOR]

Loss of quadriceps strength after total knee arthroplasty (TKA) is most pronounced acutely but persists long‐term, negatively impacting physical function in daily activities. Neuromuscular electrical stimulation (NMES) early after surgery is an effective adjuvant to standard of care rehabilitation (SOC) for attenuating strength loss following TKA, but the mechanisms whereby NMES maintains strength are unclear. This work aimed to determine the effects of early NMES on quadriceps strength and skeletal muscle fiber size 2 weeks after TKA compared to SOC. Patients scheduled for primary, unilateral TKA were enrolled and randomized into SOC (n = 9) or NMES plus SOC (n = 10) groups. NMES was started within 48 h of TKA, with 45‐min sessions twice a day for 2 weeks. Isometric quadriceps strength was assessed preoperatively and 2 weeks following TKA. Vastus lateralis muscle biopsies of the involved leg were performed at the same time points and immunohistochemistry conducted to assess muscle fiber cross‐sectional area and distinguish fiber types. Groups did not differ in age, body mass index, sex distribution, or preoperative strength. Both groups got weaker postoperatively, but the NMES group had higher normalized strength. After 2 weeks, the group receiving NMES and SOC had significantly greater MHC IIA and MHC IIA/IIX fiber size compared to SOC alone, with no group differences in MHC I fiber size. These results suggest that NMES mitigates early muscle weakness following TKA, in part, via effects on fast‐twitch, type II muscle fiber size. This investigation advances our understanding of how adjuvant, early postoperative NMES aids muscle strength recovery. [ABSTRACT FROM AUTHOR]

Avian piscivores cause direct economic losses to the aquaculture industry through predation, as well as indirect losses through transmission of digenetic trematodes. Bolbophorus damnificus is a trematode parasite associated with significant losses in catfish aquaculture. The complex life cycle involves the American white pelican Pelecanus erythrorhynchos, planorbid snails, and ictalurid catfish. With no approved therapeutics for B. damnificus in catfish Ictalurus spp. and federal protections on American white pelican, management is restricted to controlling snail hosts. Two snail species, marsh rams‐horn snail Planorbella trivolvis and ghost rams‐horn snail Biomphalaria havanensis, are common inhabitants of commercial catfish ponds and known to transmit B. damnificus. Previous work evaluated copper sulfate toxicity on marsh rams‐horn snails; however, data are lacking for ghost rams‐horn snails. Herein, laboratory‐reared adults of ghost rams‐horn snails and marsh rams‐horn snails were exposed to copper concentrations ranging from 0.16 to 3.38 mg/L Cu to evaluate 24‐, 48‐, and 72‐h acute toxicity. Additionally, sequential low‐dose treatments ranging from 0.1 to 0.8 mg/L Cu were evaluated on eggs, juveniles, and adults of ghost rams‐horn snails as a potentially safer treatment regime for ponds. Acute toxicity was similar between snail species for all exposure times. A 72‐h exposure produced an LC50 of 0.10 and 0.37 mg/L Cu for ghost rams‐horn snails and marsh rams‐horn snails, respectively. The LC50 values increased to 1.1 mg/L Cu for both species with 48‐h exposure. However, in the multiple low‐dose study, a single dose of 0.4 or 0.8 mg/L Cu was lethal to all adult snails after 1 week, as was 0.2 mg/L Cu after two doses. Four doses of 0.1 mg/L Cu or greater killed all ghost rams‐horn snail juveniles. Results indicate that marsh rams‐horn snails and ghost rams‐horn snails have similar sensitivity to copper, and multiple low‐dose treatments were effective against all life stages of ghost rams‐horn snails. These data indicate that copper can be an effective treatment for snail control in commercial catfish ponds. [ABSTRACT FROM AUTHOR]

Background and Purpose: The purpose was to explore the effects of transcutaneous trigeminal nerve stimulation (TNS) on neurochemical concentrations (brainstem, anterior cingulate cortex [ACC], dorsolateral prefrontal cortex [DLPFC], ventromedial prefrontal cortex [VMPFC], and the posterior cingulate cortex [PCC]) using ultrahigh‐field magnetic resonance spectroscopy. Methods: This double‐blinded study tested 32 healthy males (age: 25.4 ± 7.3 years) on two separate occasions where participants received either a 20‐minute TNS or sham session. Participants were scanned at baseline and twice post‐TNS/sham administration. Results: There were no group differences in concentration changes of glutamate, gamma‐aminobutyric acid, glutamine, myoinositol (mI), total N‐acetylaspartate, total creatine (tCr), and total choline between the baseline scan and the first post‐TNS/sham scan and between the first and second post‐TNS/sham scan in the brainstem, ACC, DLPFC, VMPFC, and PCC. Between the baseline scan and the second post‐TNS/sham scan, changes in tCr (mean difference = 0.280 mM [0.075 to 0.485], p =.026) and mI (mean difference = 0.662 mM [0.203 to 1.122], p =.026) in the DLPFC differed between groups. Post hoc analyses indicated that there was a decrease in tCr (mean change = –0.201 mM [–0.335 to –0.067], p =.003) and no change in mI (mean change = –0.327 mM [–0.737 to 0.083], p =.118) in the TNS group; conversely, there was no change in tCr (mean change = –0.100 mM [–0.074 to 0.274], p =.259) and an increase in mI (mean change = 0.347 mM [0.106 to 0.588], p =.005) in the sham group. Conclusion: These data demonstrate that a single session of unilateral TNS slightly decreased tCr concentrations in the DLPFC region. [ABSTRACT FROM AUTHOR]

Kissing bugs (Hempitera: Reduviidae) are obligately and exclusively blood feeding insects. Vertebrate blood is thought to provide insufficient B vitamins to insects, which rely on symbiotic relationships with bacteria that provision these nutrients. Kissing bugs harbour environmentally acquired bacteria in their gut lumen, without which they are unable to develop to adulthood. Rhodococcus rhodnii was initially identified as the sole symbiont of Rhodnius prolixus, but modern studies of the kissing bug microbiome suggest that R. rhodnii is not always present or abundant in wild‐caught individuals. We asked whether R. rhodnii or other bacteria alone could function as symbionts of R. prolixus. We produced insects with no bacteria (axenic) or with known microbiomes (gnotobiotic). Gnotobiotic insects harbouring R. rhodnii alone developed faster, had higher survival, and laid more eggs than those harbouring other bacterial monocultures, including other described symbionts of kissing bugs. R. rhodnii grew to high titre in the guts of R. prolixus while other tested species were found at much lower abundance. Rhodococcus species tested had nearly identical B vitamin biosynthesis genes, and dietary supplementation of B vitamins had a relatively minor effect on development and survival of gnotobiotic R. prolixus. Our results indicate that R. prolixus have a higher fitness when harbouring R. rhodnii than other bacteria tested, that this may be due to R. rhodnii existing at higher titres and providing more B vitamins to the host, and that symbiont B vitamin synthesis is probably a necessary but not sufficient function of gut bacteria in kissing bugs. [ABSTRACT FROM AUTHOR]

We measured the speciation of dissolved Mn from the surface to just above the hydrothermal vents at 9°50′N East Pacific Rise in the open ocean of the Pacific over a 3‐week period. Total dissolved Mn concentrations ranged from 2.2 to 135 nmol L−1 with a significant contribution of dissolved Mn(III) bound to humic acid in one third of our samples representing up to 64% of the total dissolved Mn. These humic complexes were mostly detected in the hydrothermal vent plume and at the redox boundaries of the oxygen minimum zone in the water column. In the hydrothermal plume, the Mn(III)‐humic acid stabilized the manganese in solution up to a ~ 10,000‐fold dilution of the venting water. In the upper water column, Mn(III)‐humic acid was only detected after a squall and rain event, which indicates that it is a transient species, persistent over days to weeks. This temporal variability highlights the importance of non‐steady‐state processes in the open ocean, which may help to explain previous observations of a dissolved Mn maximum within oceanic oxygen minimum zones. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy is continuously moving towards more precise dose delivery. The combination of online MR imaging and particle therapy, for example, radiation therapy using protons or carbon ions, could enable the next level of precision in radiotherapy. In particle therapy, research towards a combination of MR and particle therapy is well underway, but still far from clinical systems. The combination of high magnetic fields with particle therapy delivery poses several challenges for treatment planning, treatment workflow, dose delivery, and dosimetry. Purpose: To present a workflow for commissioning of a light ion beam line with an integrated dipole magnet to perform MR-guided particle therapy (MRgPT) research, producing not only basic beam data but also magnetic field maps for accurate dose calculation. Accurate dose calculation in magnetic field environments requires high-quality magnetic field maps to compensate for magnetic-field-dependent trajectory changes and dose perturbations. Methods: The research beam line at MedAustron was coupled with a resistive dipole magnet positioned at the isocenter. Beam data were measured for proton and carbon ions with and without an applied magnetic field of 1 T. Laterally integrated depth-dose curves (IDC) as well as beam profiles were measured in water while beam trajectories were measured in air. Based on manufacturer data, an in silico model of the magnet was created, allowing to extract highquality 3D magnetic field data. An existing GATE/Geant4 Monte Carlo (MC) model of the beam line was extended with the generated magnetic field data and benchmarked against experimental data. Results: A 3D magnetic field volume covering fringe fields until 50 mT was found to be sufficient for an accurate beam trajectory modeling. The effect on particle range retraction was found to be 2.3 and 0.3 mm for protons and carbon ions, respectively. Measured lateral beam offsets in water agreed within 0.4 and -0.5 mm with MC simulations for protons and carbon ions, respectively. Experimentally determined in-air beam trajectories agreed within 0.4 mm in the homogeneous magnetic field area. Conclusion: The presented approach based on in silico modeling and measurements allows to commission a beam line for MRgPT while providing benchmarking data for the magnetic field modeling, required for state-of -the art dose calculation methods. [ABSTRACT FROM AUTHOR]

This article discusses the book "Believing in Baptism: Understanding and Living God's Covenant Sign," which explores the meaning, significance, and practice of baptism in the Christian faith. The book includes two chapters on the biblical theology of the covenant, written by N. T. Wright, and emphasizes the role of sacraments as integral events. It also addresses practical implications of a covenantal theology of baptism, such as ministerial equality for all parishioners. The book is commended for its irenic tone and the inclusion of a fictional meeting of ministers with different baptismal beliefs. However, it may be challenging for readers unfamiliar with the Church of England or the Baptist tradition. Overall, it is considered an important resource for churches of all baptismal traditions and is recommended for ministers and theology courses on sacraments and ecclesiology. [Extracted from the article]

(C, D) Patient OS and PFS according to the R2ISS scoring in the R-ISS II cohort only. Keywords: cancer cytogenetics; myeloma; prognostic factors EN cancer cytogenetics myeloma prognostic factors e17 e21 5 01/16/23 20230115 NES 230115 To evaluate the performance of the second revision of the International Staging System 2 (R2ISS)[1] in a real-world cohort, we applied the scoring system to patients with newly-diagnosed multiple myeloma (NDMM) in the Myeloma and Related Diseases Registry (MRDR). The second revision of the International Staging System (R2-ISS) stratifies progression-free and overall survival in multiple myeloma: Real world data results in an Australian and New Zealand Population. [Extracted from the article]

Rotenone application has been reported to cause significant declines in zooplankton populations, with cladocerans and copepods being the most susceptible and possibly taking months to recover. Because copepods and cladocerans are preferred by fry of catfish Ictalurus spp., rotenone application could have significant effects on nursery pond production. Effects of rotenone on zooplankton and time required for recovery has not been studied in eutrophic aquaculture ponds typically drained and refilled yearly. We quantified rotenone application effects to either mostly drained ponds or full ponds (0.04 ha) in northwestern Mississippi on water quality, phytoplankton, zooplankton, and aquatic macroinvertebrates during May (23°C) and June (30°C) when most catfish fry ponds are stocked. For study 1, nine ponds were drained to about 15 cm of water. Six ponds were treated with 4 μL/L rotenone; three treated ponds were then treated with 4 mg/L potassium permanganate (KMnO4). The three additional ponds were drained but untreated. All ponds were then filled and fertilized with urea. In study 2, six full ponds were treated with 4 μL/L rotenone. Three of those ponds were then treated the next day with 4 mg/L KMnO4. An additional three ponds were left as untreated controls. Applying rotenone to the experimental ponds with 15 cm or less of water (study 1) had no effect on water quality, phytoplankton, or zooplankton. Neutralization with KMnO4 did not affect any measured variables. Desirable zooplankton numbers for catfish culture reached 100 organisms/L 11–14 d after treatment. In study 2, when a whole pond was treated with rotenone, desirable zooplankton numbers reached 100 organisms/L 7 d after treatment if neutralized with KMnO4 and about 11 d after treatment without neutralization. Rotenone treatment did not reduce predatory macroinvertebrate risk, and this should be addressed using additional management strategies. [ABSTRACT FROM AUTHOR]

Previous research suggests that predation by piscivorous colonial waterbirds may negatively influence the survival of Lost River Suckers (LRS) Deltistes luxatus and Shortnose Suckers (SNS) Chasmistes brevirostris in the Upper Klamath Basin (UKB), USA. However, estimates of predation from past studies, which were based on suckers with PIT tags, represent minimum estimates of sucker mortality because analyses did not account for the proportion of tags that were consumed by birds and deposited beyond their breeding colony. To address this uncertainty, we fed PIT‐tagged suckers to American white pelicans Pelecanus erythrorhynchos to estimate deposition probabilities. A hierarchical Bayesian model was then used to estimate predation rates (percentage of available tagged fish that were consumed) on juvenile suckers that were released as part of the Sucker Assisted Rearing Program (SARP) and on wild juvenile and adult LRS and SNS during 2009–2020. Pelican deposition probabilities were estimated to be 0.47 (95% credible interval = 0.36–0.60), indicating that for every 100 tags consumed, 47 tags on average were deposited on breeding colonies by birds. Deposition‐corrected estimates of predation rates were approximately two times greater than those previously reported and ranged annually from 4.3% (95% credible interval = 2.9–6.7%) to 8.5% (6.3–12.7%) on SARP juvenile suckers, from 4.3% (0.9–13.2%) to 10.5% (3.8–24.5%) on wild juvenile suckers, and from 0.1% (<0.1–0.3%) to 7.2% (2.8–16.4%) on adult suckers, depending on species and location. Results suggest that predation by colonial waterbirds, although not the original cause of sucker declines, was a substantial source of sucker mortality in some years. Future studies should consider models that jointly estimate both predation and survival and models that include environmental factors that potentially influence sucker susceptibility to avian predators in the UKB. [ABSTRACT FROM AUTHOR]

In the mid‐2010s, Edwardsiella tarda was reaffiliated into three discrete taxa (E. anguillarum, E. piscicida, and E. tarda), obscuring previous descriptions of E. tarda‐induced pathology in fish. To clarify ambiguity regarding the pathology of E. tarda, E. piscicida, and E. anguillarum infections in US farm‐raised catfish, channel catfish (Ictalurus punctatus), blue catfish (I. furcatus), and channel × blue catfish hybrids were challenged with comparable doses of each bacterium. The most severe pathology and mortality occurred in fish challenged with E. piscicida, supporting previous reports of increased pathogenicity in commercially important ictalurids, while E. anguillarum and E. tarda warrant only minimal concern. Acute pathologic lesions among bacterial species were predominantly necrotizing and characteristic of gram‐negative sepsis but became progressively granulomatous over time. After 100 days, survivors were exposed to the approximate median lethal doses of E. piscicida and E. ictaluri, revealing some cross‐protective effects among E. piscicida, E. anguillarum, and E. ictaluri. In contrast, no fish that survived E. tarda challenge demonstrated any protection against E. piscicida or E. ictaluri. This work supports reports of increased susceptibility of channel, blue, and hybrid catfish to E. piscicida, while highlighting potential cross‐protective affects among fish associated Edwardsiella spp. [ABSTRACT FROM AUTHOR]

Historic studies with sodium ion (Na+) micropipettes and first‐generation fluorescent probes suggested that an increase in heart rate results in higher intracellular Na+‐levels. Using a dual fluorescence indicator approach, we simultaneously assessed the dynamic changes in intracellular Na+ and calcium (Ca2+) with measures of force development in isolated excitable myocardial strip preparations from rat and human left ventricular myocardium at different stimulation rates and modeled the Na+‐effects on the sodium‐calcium exchanger (NCX). To gain further insight into the effects of heart rate on intracellular Na+‐regulation and sodium/potassium ATPase (NKA) function, Na+, and potassium ion (K+) levels were assessed in the coronary effluent (CE) of paced human subjects. Increasing the stimulation rate from 60/min to 180/min led to a transient Na+‐peak followed by a lower Na+‐level, whereas the return to 60/min had the opposite effect leading to a transient Na+‐trough followed by a higher Na+‐level. The presence of the Na+‐peak and trough suggests a delayed regulation of NKA activity in response to changes in heart rate. This was clinically confirmed in the pacing study where CE‐K+ levels were raised above steady‐state levels with rapid pacing and reduced after pacing cessation. Despite an initial Na+ peak that is due to a delayed increase in NKA activity, an increase in heart rate was associated with lower, and not higher, Na+‐levels in the myocardium. The dynamic changes in Na+ unveil the adaptive role of NKA to maintain Na+ and K+‐gradients that preserve membrane potential and cellular Ca2+‐hemostasis. [ABSTRACT FROM AUTHOR]

Objective: This study examined predictors of physical performance, a key aspect of quality of life, in children with excess weight. Methods: Participants were 269 children aged 6–12 years with a body mass index above the 85th percentile. Children completed a standardized physical performance task capturing lower extremity strength, balance, and gait speed. Height, weight, and waist circumference were objectively measured, and daily moderate‐vigorous physical activity (min/day) and sedentary time (% of day) were assessed with a 7‐day accelerometer protocol. Results: Physical performance task completion averaged 15.0 (SD = 2.5) seconds. Children with higher body mass index z‐scores and waist circumferences had significantly longer task completion times. The task took 1.8 additional seconds per 1.0 body mass index z‐score (p <.001), and 1.2 additional seconds for every 20 cm higher waist circumference (p <.001). Daily moderate‐vigorous physical activity and sedentary time were unrelated to physical performance, and did not moderate its associations with the adiposity measures. Conclusion: Among children with excess weight, physical performance declines with increasing levels of total and central adiposity. Daily activity levels do not moderate this association. Interventions that directly target weight reduction would likely yield the greatest improvement in physical performance in children with overweight or obesity. [ABSTRACT FROM AUTHOR]

Proliferative gill disease (PGD), caused by the myxozoan Henneguya ictaluri, is an important parasitic disease in U.S. catfish aquaculture. Continuous exposure of Channel Catfish Ictalurus punctatus to the actinospore stage of H. ictaluri results in a severe inflammatory response at the gills, leading to morbidity and death. Previous work indicates that the chemical cues in fish mucus that are recognized by myxozoan actinospores are not host specific. Building on these findings, the potential decoy effects of nonictalurid fish to actinospores of H. ictaluri were evaluated. Exposure of actinospores to gill mucus from multiple nonictalurid fishes resulted in actinospore activation for all fish species tested. Based on these findings, experimental transmission trials with potential interceptor fish were conducted. Individual Channel Catfish were co‐stocked with Western Mosquitofish Gambusia affinis at 0, 10, 25, or 50% of mean Channel Catfish biomass and exposed to 3,000 actinospores of H. ictaluri. Gill tissues were sampled at 24 h postchallenge, and parasite burden was estimated by H. ictaluri‐specific quantitative PCR. Results revealed that Western Mosquitofish stocked at 25% and 50% of catfish biomass reduced H. ictaluri DNA in Channel Catfish gills more than threefold. In a second study, catfish were exposed to pond water collected from an active PGD outbreak in the presence of Western Mosquitofish stocked at 25% of catfish biomass. Channel Catfish were sampled at 24 h and at 7 d after the last pond water exposure. At 24 h postexposure, catfish that were co‐stocked with Western Mosquitofish showed significantly lower H. ictaluri DNA than catfish stocked alone. This treatment effect was absent at 7 d postexposure, as parasite quantities within tissues had increased over 1,000×, with marked variability. Still, results indicate that the chemical cues that activate H. ictaluri actinospores are not specific to Channel Catfish. This work evinces a potential benefit of nonictalurid fish in combating H. ictaluri, suggesting that the presence of nonictalurid interceptor fish in catfish ponds may minimize PGD severity. [ABSTRACT FROM AUTHOR]

Edwardsiella piscicida is a growing problem for catfish aquaculture in the southeastern United States, particularly in channel (Ictalurus punctatus) x blue (I. furcatus) catfish hybrids. Research has shown E. piscicida isolates recovered from farmed catfish in Mississippi form at least five discrete phyletic groups, with no apparent differences in virulence in channel and hybrid catfish. Laboratory trials have shown a live‐attenuated E. ictaluri vaccine (340X2) cross‐protects against at least one E. piscicida isolate (S11–285) in channel and hybrid catfish, although it is unknown if this protection exists for other E. piscicida variants. To this end, channel and hybrid catfish were immunized by immersion with E. ictaluri 340X2. Thirty days later, fish were challenged by intracoelomic injection with representative E. piscicida variants from each phyletic group. Relative percent survival (RPS) for hybrids ranged from 54.7% to 77.8%, while RPS in channels ranged from 80.5% to 100%. A second study investigated whether channel and hybrid catfish exposed to heterologous E. piscicida isolates were similarly protected against wild‐type E. ictaluri. Fish were exposed by bath immersion to representative E. piscicida isolates from each phyletic group. Thirty days post‐immunization, fish were challenged by immersion with wild‐type E. ictaluri isolate S97–773. Regardless of variant, previous exposure to heterologous E. piscicida isolates significantly improved survival following E. ictaluri challenge. These findings suggest the presence of shared and conserved antigens among E. piscicida and E. ictaluri that could be exploited by application of polyvalent or cross‐protective vaccines. [ABSTRACT FROM AUTHOR]

Mimicking natural parameters and complexities in zoo conservation breeding programs can facilitate natural physiological and behavioral traits, which in turn can inform more effective species reintroduction efforts. To curtail population declines of threatened narrow‐headed gartersnakes (Thamnophis rufipunctatus), the Arizona Center for Nature Conservation/Phoenix Zoo partnered with a multiagency conservation working group to develop an ex situ propagation‐for‐release program. Initially, Zoo staff followed common snake husbandry protocols of manually inducing brumation (i.e., winter dormancy). Copulation was observed during the first few years, but no births resulted. Also, some older individuals developed post‐brumation health abnormalities, prompting a strategic reassessment. To facilitate propagation and improve health, Zoo staff applied ecological knowledge of T. rufipunctatus and an adaptive management strategy to implement key parameters for success: sociality, refugia, breeding and foraging behaviors, and natural brumation. Zoo staff developed a large multisnake enclosure that mimicked natural ecological and habitat complexities including a hibernaculum to stimulate natural brumation. Gartersnakes were left mostly unimpeded to conduct natural behaviors across seasons in the enriched environment. We referenced change in body mass after ten brumation periods as a proxy for health. Under natural brumation, gartersnakes did not lose body mass, and this shift resulted in fully ex situ parturition events—the first for this imperiled species. We highlight the efficacy of adaptive management and incorporation of natural parameters and environmental complexities into conservation breeding programs. These actions can improve the health and success of animals under managed care—processes applicable to a range of taxa targeted for conservation translocations. Research Highlights: •Adaptive management fostered improved husbandry of threatened narrow‐headed gartersnakes.•An enriched, habitat‐mimicked enclosure stimulated natural behaviors.•Allowing natural winter dormancy led to reproduction, a key goal for reintroduction. [ABSTRACT FROM AUTHOR]

This special issue presents a collection of ethnographic and archaeological articles that consider how humans inscribe landscapes with diverse forms of value. From natural resources to real estate markets, from cherished homelands to foreign speculative investment, the way we approach landscapes offers insights into value systems as they map onto and emerge from biophysical terrains. We argue that the "landscapes of value" analytic foregrounds such materiality to embed cyclical value making within particular places and times. We introduce this special issue by discussing the articles' contributions along four overlapping processes of landscape valuation: commodification, exclusion, speculation, and simplification. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to investigate off‐axis irradiation on the Australian MRI‐Linac using experiments and Monte Carlo simulations. Simulations are used to verify experimental measurements and to determine the minimum offset distance required to separate electron contamination from the photon field. Methods: Dosimetric measurements were performed using a microDiamond detector, Gafchromic® EBT3 film, and MOSkinTM. Three field sizes were investigated including 1.9 × 1.9, 5.8 × 5.8, and 9.7 × 9.6 cm2. Each field was offset a maximum distance, approximately 10 cm, from the central magnetic axis (isocenter). Percentage depth doses (PDDs) were collected at a source‐to‐surface distance (SSD) of 1.8 m for fields collimated centrally and off‐axis. PDD measurements were also acquired at isocenter for each off‐axis field to measure electron contamination. Monte Carlo simulations were used to verify experimental measurements, determine the minimum field offset distance, and demonstrate the use of a spoiler to absorb electron contamination. Results: Off‐axis irradiation separates the majority of electron contamination from an x‐ray beam and was found to significantly reduce in‐field surface dose. For the 1.9 × 1.9, 5.8 × 5.8, and 9.7 × 9.6 cm2 field, surface dose was reduced from 120.9% to 24.9%, 229.7% to 39.2%, and 355.3% to 47.3%, respectively. Monte Carlo simulations generally were within experimental error to MOSkinTM and microDiamond, and used to determine the minimum offset distance, 2.1 cm, from the field edge to isocenter. A water spoiler 2 cm thick was shown to reduce electron contamination dose to near zero. Conclusions: Experimental and simulation data were acquired for a range of field sizes to investigate off‐axis irradiation on an inline MRI‐Linac. The skin sparing effect was observed with off‐axis irradiation, a feature that cannot be achieved to the same extent with other methods, such as bolusing, for beams at isocenter. [ABSTRACT FROM AUTHOR]

The pathobiology of in situ pulmonary thrombosis in acute respiratory distress syndrome (ARDS) due to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection is incompletely characterized. In human pulmonary artery endothelial cells (HPAECs), hypoxia increases neural precursor cell expressed, developmentally downregulated 9 (NEDD9) and induces expression of a prothrombotic NEDD9 peptide (N9P) on the extracellular plasma membrane surface. We hypothesized that the SARS‐CoV‐2–ARDS pathophenotype involves increased pulmonary endothelial N9P. Paraffin‐embedded autopsy lung specimens were acquired from patients with SARS‐CoV‐2–ARDS (n = 13), ARDS from other causes (n = 10), and organ donor controls (n = 5). Immunofluorescence characterized the expression of N9P, fibrin, and transcription factor 12 (TCF12), a putative binding target of SARS‐CoV‐2 and known transcriptional regulator of NEDD9. We performed RNAsequencing on normal HPAECs treated with normoxia or hypoxia (0.2% O2) for 24 h. Immunoprecipitation‐liquid chromatography‐mass spectrometry (IPLC‐ MS) profiled protein–protein interactions involving N9P relevant to thrombus stabilization. Hypoxia increased TCF12 messenger RNA significantly compared to normoxia in HPAECs in vitro (+1.19‐fold, p = 0.001; false discovery rate = 0.005), and pulmonary endothelial TCF12 expression was increased threefold in SARS‐CoV‐2–ARDS versus donor control lungs (p < 0.001). Compared to donor controls, pulmonary endothelial N9P‐fibrin colocalization was increased in situ in non‐SARS‐CoV‐2–ARDS and SARSCoV‐ 2–ARDS decedents (3.7 ± 1.2 vs. 10.3 ± 3.2 and 21.8 ± 4.0 arb. units, p < 0.001). However, total pulmonary endothelial N9P was increased significantly only in SARS‐CoV‐2–ARDS versus donor controls (15 ± 4.2 vs. 6.3 ± 0.9 arb. units, p < 0.001). In HPAEC plasma membrane isolates, IP‐LCMS identified a novel protein–protein interaction between NEDD9 and the β3‐ subunit of the αvβ3‐integrin, which regulates fibrin anchoring to endothelial cells. In conclusion, lethal SARS‐CoV‐2–ARDS is associated with increased pulmonary endothelial N9P expression and N9P‐fibrin colocalization in situ. Further investigation is needed to determine the pathogenetic and potential therapeutic relevance of N9P to the thrombotic pathophenotype of SARS‐CoV‐ 2–ARDS. [ABSTRACT FROM AUTHOR]

Purpose: To present a first study on the treatment planning feasibility in perpendicular field MRI‐integrated proton therapy that considers the full transport of protons from the pencil beam scanning (PBS) assembly to the patient inside the MRI scanner. Methods: A generic proton PBS gantry was modeled as being integrated with a realistic split‐bore MRI system in the perpendicular orientation. MRI field strengths were modeled as 0.5, 1, and 1.5 T. The PBS beam delivery and dose calculation was modeled using the TOPAS Monte Carlo toolkit coupled with matRad as the optimizer engine. A water phantom, liver, and prostate plans were evaluated and optimized in the presence of the full MRI field distribution. A simple combination of gantry angle offset and small PBS nozzle skew was used to direct the proton beams along a path that closely follows the reference planning scenario, that is, without magnetic field. Results: All planning metrics could be successfully achieved with the inclusion of gantry angle offsets in the range of 8∘$^{\circ }$–29∘$^{\circ }$ when coupled with a PBS nozzle skew of 1.6∘$^{\circ }$–4.4∘$^{\circ }$. These two hardware‐based corrections were selected to minimize the average Euclidean distance (AED) in the beam path enabling the proton beams to travel inside the patient in a path that is close to the original path (AED smaller than 3 mm at 1.5 T). Final dose optimization, performed through further changes in the PBS delivery, was then shown to be feasible for our selection of plans studied yielding comparable plan quality metrics to reference conditions. Conclusions: For the first time, we have shown a robust method to account for the full proton beam deflection in a perpendicular orientation MRI‐integrated proton therapy. These results support the ongoing development of the current prototype systems. [ABSTRACT FROM AUTHOR]

Background and Purpose: In the current and rapidly evolving era of real‐time MRI‐guided radiotherapy, our radiation biology and dosimetry knowledge is being tested in a novel way. This paper presents the successful design and implementation of a portable device used to generate strong localized magnetic fields. These are ideally suited for small‐scale experiments that mimic the magnetic field environment inside an MRI‐linac system, or more broadly MRI‐guided particle therapy as well. Materials and Methods: A portable permanent magnet‐based device employing an adjustable steel yoke and magnetic field focusing cones has been designed, constructed, and tested. The apparatus utilizes two banks of Nd2$_{2}$Fe14$_{14}$B permanent magnets totaling around 50 kg in mass to generate a strong magnetic field throughout a small volume between two pole tips. The yoke design allows adjustment of the pole tip gap and exchanging of the focusing cones. Further to this, beam portal holes are present in the yoke and focusing cones, allowing for radiation beams of up to 5 ×$\times$ 5 cm2$^{2}$ to pass through the region of high magnetic field between the focusing cone tips. Finite element magnetic modeling was performed to design and characterize the performance of the device. Automated physical measurements of the magnetic field components at various locations were measured to confirm the performance. The adjustable pole gap and interchangeable cones allows rapid changing of the experimental set‐up to allow different styles of measurements to be performed. Results: A mostly uniform magnetic field of 1.2 T can be achieved over a volume of at least 3 ×$\times$ 3 ×$\times$ 3 cm3$^{3}$. This can be reduced in strength to 0.3 T but increased in volume to 10 ×$\times$ 10 ×$\times$ 10 cm3$^{3}$ via removal of the cone tips and/or adjustment of the steel yoke. Although small, these volumes are sufficient to house radiation detectors, cell culture dishes, and various phantom arrangements targeted at examining small radiation field dosimetry inside magnetic field strengths that can be changed with ease. Most important is the ability to align the magnetic field both perpendicular to, or inline with, the radiation beam. To date, the system has been successfully used to conduct published research in the areas of radiation detector performance, lung phantom dosimetry, and how small clinical electron beams behave in these strong magnetic fields. Conclusions: A portable, relatively inexpensive, and simple to operate device has successfully been constructed and used for performing radiation oncology studies around the theme of MRI‐guided radiotherapy. This can be in either inline and perpendicular magnetic fields of up to 1.2 T with x‐ray and particle beams. [ABSTRACT FROM AUTHOR]

Aims: Management of anal dysplasia relies upon the accurate diagnosis of anal biopsy specimens. As institutions move towards subspecialty signout (SSSO), decisions must be made regarding whether to assign anal biopsies to the gastrointestinal (GI) or gynaecological (GYN) pathology service. Materials and results: We identified 200 archival tissue biopsies of anal mucosa and circulated them among three GI pathologists and three GYN pathologists. Each pathologist separately scored each biopsy as normal, atypical, low‐grade squamous intra‐epithelial lesion (LSIL) or high‐grade squamous intra‐epithelial lesion (HSIL). Every case that was called HSIL by at least one pathologist was stained with p16 immunostain and a 'gold standard' interpretation of whether or not a case represented HSIL was made. The GI pathologists agreed on 97 (49%) cases prior to consensus; the GYN pathologists agreed on 33 (17%). The sensitivities of the three GI pathologists in detecting HSIL against the 'gold standard' were 47, 100 and 21% and for the GYN pathologists the sensitivities were 74, 89 and 84%; the sensitivities of the GI and GYN consensus diagnoses were 74% each. The specificities of the three GI pathologists in detecting HSIL were 99, 90 and 100% and for the GYN pathologists the specificities were 99, 92 and 91%; the specificities of both the GI and GYN consensus diagnoses were 100%. Conclusions: A mild to moderate degree of interobserver variability exists in the diagnosis of anal dysplasia among pathologists. Our study indicates the utility of some form of consensus conference, as overall agreement among GI pathologists and among GYN pathologists improved following in‐person consensus. [ABSTRACT FROM AUTHOR]