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Review of Eric Patterson and J. Daryl Charles, eds., _Just War and Christian Traditions_

This study reports a dense, late summer phytoplankton bloom in the Southern Ocean that accumulated unusually high levels of organic matter and supported feeding hot spots for birds and whales. The authors show that this recurring open ocean bloom is driven by anomalies in easterly winds that push sea ice southwards and favour the upwelling of deep waters enriched in hydrothermal iron.

A review of Kate Jackson-Meyer, _Tragic Dilemmas in Christian Ethics

Stem cells often possess immature mitochondria with few inner membrane invaginations, which increase as stem cells differentiate. Despite this being a conserved feature across many stem cell types in numerous organisms, how and why mitochondria undergo such remodelling during stem cell differentiation has remained unclear. Here, using Drosophila germline stem cells (GSCs), we show that Complex V drives mitochondrial remodelling during the early stages of GSC differentiation, prior to terminal differentiation. This endows germline mitochondria with the capacity to generate large amounts of ATP required for later egg growth and development. Interestingly, impairing mitochondrial remodelling prior to terminal differentiation results in endoplasmic reticulum (ER) lipid bilayer stress, Protein kinase R-like ER kinase (PERK)-mediated activation of the Integrated Stress Response (ISR) and germ cell death. Taken together, our data suggest that mitochondrial remodelling is an essential and tightly integrated aspect of stem cell differentiation. This work sheds light on the potential impact of mitochondrial dysfunction on stem and germ cell function, highlighting ER lipid bilayer stress as a potential major driver of phenotypes caused by mitochondrial dysfunction.

Abstract Precopulatory courtship plays an essential role in the insemination process and influences postcopulatory behavior between males and females. Male precopulatory oral stimulation of female genitals is rare for invertebrates. Here, we describe an intriguing oral sexual courtship in a cryptic desert beetle Platyope mongolica Faldermann. The males repeatedly contact the female's genitals using their mouths to gain consent to mate. Furthermore, the rate at which males contact the female's genitals relates to the copulation success in a series of observations. However, interference in oral sexual contacts decreased the proportion of successful copulation. Further no‐choice tests found homosexual behavior between males with antenna removed. We report the precopulatory oral sexual behavior and its important role for copulation success in P. mongolica for the first time. These findings highlight the significance of oral sexual courtship in sexual selection.

Previous research has assessed the affects release from football academies has on psychological distress and athletic identity of players. However, there has been no qualitative research exploring players' experiences of the release process. This study retrospectively explored players' lived experiences of being released from a professional football academy, having completed a scholarship (from ages 16–18). Four male football players (age 21.6 ± 1.5 years) who had experienced release from professional academies participated in in-depth semi-structured interviews. Data were analyzed using Interpretative Phenomenological Analysis. Four super-ordinate themes were interpreted from the data: Foreshadowing release—“left out in the cold”, The process of release, Support during the process of release and New beginnings—“there's a bigger world than just playing football every day”. Players reported that their contract meeting was a traumatic experience, and they experienced psychological difficulties in the longer-term following release. Factors that compounded the players' release were: a lack of aftercare being provided by the players' professional clubs for their wellbeing, and a disuse of social support, which hindered their transition out of full-time football. Context relevant recommendations are made to help improve the release process for elite youth football players.

Introduction: Approximately two million people present to the emergency department (ED) with eye-related complaints each year in the United States. Differentiating pathologies that need urgent consultation from those that do not is imperative. For some physicians, ocular ultrasound has eclipsed the dilated fundoscopic exam as the standard posterior segment evaluation in the ED. Case report: A 60-year-old female presented with sudden onset visual disturbance in her right eye. Point-of-care ultrasound showed a hyperechoic band in the posterior segment concerning for a retinal detachment. Ophthalmology was consulted and diagnosed the patient with a condition known as Valsalva retinopathy. The patient was discharged from the ED with expectant management. Conclusion: This case highlights an important differential diagnosis that should be considered when ocular ultrasound demonstrates a hyperechoic band in the posterior segment. While previous literature has demonstrated that emergency physicians are able to accurately identify posterior segment pathology using ultrasound, there is limited information regarding their ability to differentiate between pathologies, some of which may not require urgent consultation. We highlight the important differentials that should be considered when identifying posterior segment pathology on point-of-care ultrasound and their appropriate dispositions.

Knowing the magnitude and timing of pelagic primary production is important for ecosystem and carbon sequestration studies, in addition to providing basic understanding of phytoplankton functioning. In this study we use data from an ecosystem cruise to Kong Håkon VII Hav, in the Atlantic sector of the Southern Ocean, in March 2019 and more than two decades of satellite-derived ocean color to study phytoplankton bloom phenology. During the cruise we observed phytoplankton blooms in different bloom phases. By correlating bloom phenology indices (i.e., bloom initiation and end) based on satellite remote sensing to the timing of changes in environmental conditions (i.e., sea ice, light, and mixed layer depth) we studied the environmental factors that seemingly drive phytoplankton blooms in the area. Our results show that blooms mainly take place in January and February, consistent with previous studies that include the area. Sea ice retreat controls the bloom initiation in particular along the coast and the western part of the study area, whereas bloom end is not primarily connected to sea ice advance. Light availability in general is not appearing to control the bloom termination, neither is nutrient availability based on the autumn cruise where we observed non-depleted macronutrient reservoirs in the surface. Instead, we surmise that zooplankton grazing plays a potentially large role to end the bloom, and thus controls its duration. The spatial correlation of the highest bloom magnitude with marked topographic features indicate that the interaction of ocean currents with sea floor topography enhances primary productivity in this area, probably by natural fertilization. Based on the bloom timing and magnitude patterns, we identified five different bloom regimes in the area. A more detailed understanding of the region will help to highlight areas with the highest relevance for the carbon cycle, the marine ecosystem and spatial management. With this gained understanding of bloom phenology, it will also be possible to study potential shifts in bloom timing and associated trophic mismatch caused by environmental changes.

OBJECTIVE:The role of Th1 and Th17 lymphocyte responses in human infection and sepsis of elderly patients has yet to be clarified. DESIGN:A prospective observational study of patients with sepsis, infection only and healthy controls. SETTING:The acute medical wards and intensive care units in a 1000 bed university hospital. PATIENTS:32 patients with sepsis, 20 patients with infection, and 20 healthy controls. Patients and controls were older than 65 years of age. Patients with recognised underlying immune compromise were excluded. METHODS:Phenotype, differentiation status and cytokine production by T lymphocytes were determined by flow cytometry. MEASUREMENTS:The differentiation states of circulating CD3+, CD4+, and CD8+ T cells were characterised as naive (CD45RA+, CD197+), central memory (CD45RA-, CD197+), effector memory (CD45RA-, CD197-), or terminally differentated (CD45RA+, CD197-). Expression of IL-12 and IL-23 receptors, and the transcription factors T-bet and RORγt, was analysed in circulating T lymphocytes. Expression of interferon- γ and IL-17A were analysed following stimulation in vitro. RESULTS:CD4+ T cells from patients with infection predominantly expressed effector-memory or terminally differentiated phenotypes but CD4+ T cells from patients with severe sepsis predominantly expressed naive phenotypes (p

While scientific vocabulary is important, it can often become problematic for students. Sometimes, those words can become a barrier to participation or act as a gatekeeper to success in the science classroom. Under the Next Generation Science Standards, middle school students are expected to model Earth-Moon-Sun motions to explain Moon phases, eclipses, and seasons (NGSS Lead States, 2013). Using a phenomenography lens, we investigated the ways in which students seeing the Moon in nature and related classroom experiences translate into a mental model of lunar phases and how vocabulary is used to communicate these models. Eighth-grade students from three urban middle school classrooms were assessed for spatial ability and understanding of lunar phases. Girls and boys of both high and low spatial ability were interviewed to explore their Moon phase understanding and causal thinking before and after an astronomy unit. One school employed the school district's astronomy curriculum while the other used the REAL Curriculum. Students engaged in babbling (i.e., inarticulate but somewhat correct descriptions) and gargling (i.e., using many technical terms without evidence of understanding) with much greater frequency in pre-interviews. Students who developed correct vocabulary and used it comfortably in interviews were more likely to also display correct Moon phase conceptions. REAL Curriculum's project-based approach to teaching astronomy and related vocabulary through hands-on, contextualized projects and activities (e.g., Moon observation journals) produced greater vocabulary gains.

Background: the role of innate immunity in human sepsis must be fully clarified to identify potential avenues for novel immune adjuvant sepsis therapies. Methods: A prospective observational study was performed including patients with sepsis (septic group), infection without sepsis (infection group), and healthy controls (control group) in the setting of acute medical wards and intensive care units in a 1000-bed university hospital. A total of 42 patients with sepsis, 30 patients with infection, and 30 healthy controls were studied. The differentiation states of circulating mucosal associated invariant T (MAIT) cells and Natural Killer T (NKT) cells were characterised as naive (CD45RA+, CD197+), central memory (CD45RA−, CD197+), effector memory (CD45RA−, CD197−), or terminally differentiated (CD45RA+, CD197−). The differentiation states of circulating gamma-delta T lymphocytes were characterised as naive (CD45RA+, CD27+), central memory (CD45RA−, CD27+), effector memory (CD45RA−, CD27−), or terminally differentiated (CD45RA+, CD27−). The expression of IL-12 and IL-23 receptors, the transcription factors T-Bet and RORγt, and interferon-γ and IL-17a were analysed. Results: MAIT cell counts were lower in the septic group (p = 0.002) and the infection group (p < 0.001) than in the control group. The MAIT cell T-Bet expression in the infection group was greater than in the septic group (p = 0.012). The MAIT RORγt expression in the septic group was lower than in the control group (p = 0.003). The NK cell counts differed in the three groups (p < 0.001), with lower Natural Killer (NK) cell counts in the septic group (p < 0.001) and in the infection group (p = 0.001) than in the control group. The NK cell counts increased in the septic group in the 3 weeks following the onset of sepsis (p = 0.028). In lymphocyte stimulation experiments, fewer NK cells expressed T-Bet in the septic group than in the infection group (p = 0.002), and fewer NK cells expressed IFN-γ in the septic group than in the control group (p = 0.002). The NKT cell counts were lower in the septic group than both the control group (p = 0.05) and the infection group (p = 0.04). Fewer NKT cells expressed T-Bet in the septic group than in the infection group (p = 0.004). Fewer NKT cells expressed RORγt in the septic group than in the control group (p = 0.003). Fewer NKT cells expressed IFN-γ in the septic group than in both the control group (p = 0.002) and the infection group (p = 0.036). Conclusion: The clinical presentation of infection and or sepsis in patients is linked with a mosaic of changes in the innate lymphocyte Th1 and Th17 phenotypes. The manipulation of the innate lymphocyte phenotype offers a potential avenue for immune modulation in patients with sepsis.

BACKGROUND: For children aged 6-11 years with uncontrolled severe atopic dermatitis (AD), 16 weeks of treatment with dupilumab resulted in substantial clinical benefit compared with placebo with an acceptable safety profile. However, longer-term safety and efficacy data are important to inform longitudinal AD management. OBJECTIVES: This analysis of data from an open-label extension study (LIBERTY AD PED-OLE, NCT02612454) reports the long-term safety, efficacy, and pharmacokinetics of dupilumab in children with severe AD who had participated in the pivotal dupilumab LIBERTY AD PEDS study (NCT03345914). METHODS: Enrolled patients initially received subcutaneous dupilumab 300 mg every 4 weeks (q4w). The q4w regimen could be uptitrated to dupilumab dose regimens of 200 or 300 mg every 2 weeks (q2w; for body weight

[This corrects the article DOI: 10.1371/journal.pgen.1005625.].

Abstract The heterotrimeric G‐protein complex is minimally composed of Gα, Gβ, and Gγ subunits. In the classic scenario, the G‐protein complex is the nexus in signaling from the plasma membrane, where the heterotrimeric G‐protein associates with heptahelical G‐protein‐coupled receptors (GPCRs), to cytoplasmic target proteins called effectors. Although a number of effectors are known in metazoans and fungi, none of these are predicted to exist in their canonical forms in plants. To identify ab initio plant G‐protein effectors and scaffold proteins, we screened a set of proteins from the G‐protein complex using two‐hybrid complementation in yeast. After deep and exhaustive interrogation, we detected 544 interactions between 434 proteins, of which 68 highly interconnected proteins form the core G‐protein interactome. Within this core, over half of the interactions comprising two‐thirds of the nodes were retested and validated as genuine in planta. Co‐expression analysis in combination with phenotyping of loss‐of‐function mutations in a set of core interactome genes revealed a novel role for G‐proteins in regulating cell wall modification.

BackgroundAdults aged ≥ 60 years are often underrepresented in atopic dermatitis (AD) clinical trials; age-related comorbidities may impact treatment efficacy and safety.ObjectiveThe aim was to report dupilumab efficacy and safety in patients aged ≥ 60 years with moderate-to-severe AD.MethodsData were pooled from four randomized, placebo-controlled dupilumab trials of patients with moderate-to-severe AD (LIBERTY AD SOLO 1 and 2, LIBERTY AD CAFÉ, and LIBERTY AD CHRONOS) and stratified by age (

Curly, described almost a century ago, is one of the most frequently used markers in Drosophila genetics. Despite this the molecular identity of Curly has remained obscure. Here we show that Curly mutations arise in the gene dual oxidase (duox), which encodes a reactive oxygen species (ROS) generating NADPH oxidase. Using Curly mutations and RNA interference (RNAi), we demonstrate that Duox autonomously stabilizes the wing on the last day of pupal development. Through genetic suppression studies, we identify a novel heme peroxidase, Curly Su (Cysu) that acts with Duox to form the wing. Ultrastructural analysis suggests that Duox and Cysu are required in the wing to bond and adhere the dorsal and ventral cuticle surfaces during its maturation. In Drosophila, Duox is best known for its role in the killing of pathogens by generating bactericidal ROS. Our work adds to a growing number of studies suggesting that Duox's primary function is more structural, helping to form extracellular and cuticle structures in conjunction with peroxidases.

Introduction. Severe sepsis in humans may be related to an underlying profound immune suppressive state. We investigated the link between gene expression of immune regulatory cytokines and the range of illness severity in patients with infection and severe sepsis. Methods. A prospective observational study included 54 ICU patients with severe sepsis, 53 patients with infection without organ failure, and 20 healthy controls. Gene expression in peripheral blood mononuclear cells (PBMC) was measured using real-time polymerase chain reaction. Results. Infection differed from health by decreased expression of the IL2, and IL23 and greater expression of IL10 and IL27. Severe sepsis differed from infection by having decreased IL7, IL23, IFNγ, and TNFα gene expression. An algorithm utilising mRNA copy number for TNFα, IFNγ, IL7, IL10, and IL23 accurately distinguished sepsis from severe sepsis with a receiver operator characteristic value of 0.88. Gene expression was similar with gram-positive and gram-negative infection and was similar following medical and surgical severe sepsis. Severity of organ failure was associated with serum IL6 protein levels but not with any index of cytokine gene expression in PBMCs. Conclusions. Immune regulatory cytokine gene expression in PBMC provides a robust method of modelling patients’ response to infection.

A growing body of psychology-based scholarship identifies emerging adulthood as a distinct, transitional stage of life and work characterized by several features, wherein relatively little is known regarding moral development. This study is part of a 3-year, longitudinal project involving recent graduates across six U.S. universities who studied journalism and media-related fields. Guided by emerging adulthood, moral psychology, and media exemplar research, this study analyzes results for 110 graduates who completed an online survey regarding their personality traits, virtuous character, moral reasoning, and ethical ideology. It constitutes the first detailed portrait of moral identity of emerging adults in media-related fields.

This paper presents machine learning classification on simulated data of permeable conducting spheres in air and seawater irradiated by low frequency electromagnetic pulses. Classification accuracy greater than 90% was achieved. The simulated data were generated using an analytical model of a magnetic dipole in air and seawater placed 1.5–3.5 m above the center of the sphere in 50 cm increments. The spheres had radii of 40 cm and 50 cm and were of permeable materials, such as steel, and non-permeable materials, such as aluminum. A series RL circuit was analytically modeled as the transmitter coil, and an RLC circuit as the receiver coil. Additive white Gaussian noise was added to the simulated data to test the robustness of the machine learning algorithms to noise. Multiple machine learning algorithms were used for classification including a perceptron and multiclass logistic regression, which are linear models, and a neural network, 1D convolutional neural network (CNN), and 2D CNN, which are nonlinear models. Feature maps are plotted for the CNNs and provide explainability of the salient parts of the time signature and spectrogram data used for classification. The pulses investigated, which expand the literature, include a two-sided decaying exponential, Heaviside step-off, triangular, Gaussian, rectangular, modulated Gaussian, raised cosine, and rectangular down-chirp. Propagation effects, including dispersion and frequency dependent attenuation, are encapsulated by the analytical model, which was verified using finite element modeling. The results in this paper show that machine learning methods are a viable alternative to inversion of electromagnetic induction (EMI) data for metallic sphere classification, with the advantage of real-time classification without the use of a physics-based model. The nonlinear machine learning algorithms used in this work were able to accurately classify metallic spheres in seawater even with significant pulse distortion caused by dispersion and frequency dependent attenuation. This paper presents the first effort towards the use of machine learning to classify metallic objects in seawater based on EMI sensing. [ABSTRACT FROM AUTHOR]

Background: Prurigo nodularis (PN) is an intensely pruritic disease characterized by itchy nodules on the trunk/extremities; it is often accompanied by skin pain and sleep disruption with negative impacts on the quality of life (QoL). The patient‐reported outcome (PRO) instruments, Worst Itch‐Numeric Rating Scale (WI‐NRS), Skin Pain‐NRS, Sleep‐NRS and Dermatology Life Quality Index (DLQI) have been psychometrically validated and the clinically meaningful within‐patient improvement thresholds (responder definition) have been established through data pooled from the two Phase‐3 trials (PRIME, NCT04183335 and PRIME2, NCT04202679) of dupilumab in adults with PN uncontrolled on topical therapies. Objectives: To estimate the proportion of dupilumab‐treated patients (vs. placebo) achieving clinically meaningful improvement in itch, skin pain, sleep and QoL, either alone or in combination, from the data pooled from PRIME and PRIME2 trials. Methods: The patient‐level data pooled from the two Phase‐3 trials (N = 311) were used for this post hoc analysis. Thresholds of clinically meaningful within‐patient improvement in PRO instrument scores from baseline at Week 24 used for defining responders were 4 (WI‐NRS and Skin Pain‐NRS), 2 (Sleep‐NRS) and 9 points (DLQI). The proportion of dupilumab‐treated patients, versus placebo, achieving the thresholds, and the time taken to achieve the thresholds were evaluated for the individual and combination of PROs. Results: Responder rates were significantly higher with dupilumab, versus placebo at Week 24 for WI‐NRS (58.8% vs. 19.0%, p < 0.0001), Skin Pain‐NRS (49.7% vs. 20.9%, p < 0.0001), Sleep‐NRS (42.5% vs. 23.4%, p < 0.0001) and DLQI (64.7% vs. 22.8%, p < 0.0001). Proportion of patients achieving simultaneous improvement in symptoms and QoL (24.8% vs. 6.3%, p < 0.0001) were significantly higher in dupilumab‐treated patients versus placebo. The time needed for achieving clinically meaningful improvement in symptoms were significantly lower in dupilumab‐treated patients, versus placebo. Conclusions: Significantly greater proportion of dupilumab‐treated patients with PN, versus placebo, demonstrated clinically meaningful improvements in PRO measures of symptoms and QoL. [ABSTRACT FROM AUTHOR]

Background: Prurigo nodularis (PN) also known as chronic prurigo, is a chronic inflammatory skin disease characterized by intensely itchy nodules/lesions which occur due to intensive scratching. PN management is, in part, based on clinician evaluations of PN lesions, which can be supported by clinician‐reported outcomes (ClinRO) such as the Prurigo Activity and Severity (PAS) instrument. A 5‐item version of PAS was included in recent phase‐3 dupilumab PN trials (PRIME [NCT04183335]/PRIME2 [NCT04202679]). The PAS score was derived using the unweighted sum of 3‐items of the 5‐item PAS (range, 0–11; higher score indicates worse activity and severity): Item 2 (number of lesions), Item 5a (percentage of lesions with excoriations/crusts) and Item 5b (percentage of healed lesions) for use in clinical practice and for communication of treatment benefit to physicians. Objectives: To evaluate the measurement properties of PAS score and derive within‐patient (responder definition) and between‐group improvement thresholds for interpreting changes in PAS score in patients with PN. Methods: The data source was the pooled treatment group, intention‐to‐treat (ITT) data from the phase‐3 PRIME (NCT04183335) and PRIME2 (NCT04202679) studies evaluating the efficacy of dupilumab in adult patients with PN with ≥20 nodules and severe itch uncontrolled with topical therapies. PAS score reliability, validity and sensitivity to change were evaluated, and anchor‐ and distribution‐based methods were applied to derive meaningful change thresholds. Results: The pooled ITT population included 311 patients (mean age 49.5 years, 65.3% female). Adequate to good psychometric properties were demonstrated for PAS score. The within‐patient meaningful improvement threshold was estimated as 3.0 points (absolute change) and 37% (per cent change). A 1.7‐point (absolute change) and 20% (per cent change) improvement were estimated to reflect a between‐group meaningful change in PAS score. Conclusions: PAS score is a simple, clinically relevant indicator of PN lesion activity and severity supported by suitable psychometric performance. [ABSTRACT FROM AUTHOR]