Search

In the environment of Alpine glacier forefields, bacteria represent the functional link between initial soil development and secondary colonization. An important question is whether soil bacteria are adapted to the poor nutrient availability in this environment and whether selection processes significantly limit their local expansion along the gradients of chemical and biological factors. To address these questions, we used a two-dimensional sampling strategy at our study site, the Damma glacier forefield, Switzerland, to characterize the soil environment by selected biogeochemical parameters. Our results revealed two contrasting sites that differed in time since deglaciation (‘young’ and ‘old’ soil, ≤ 13 years and > 53 years of ice-free conditions) and vegetation cover (threefold increase), but also showed significant differences in soil properties thought to be relevant for the successional development of glacier forefield soils, such as pH (0.5-fold decrease), ammonium (0.5-fold decrease) concentration, and the content of total organic carbon (10-fold increase). Isolated strains, affiliated to the genus Pseudomonas, according to their 16S rDNA profile, were tested experimentally for local adaptation by a reciprocal transfer experiment. The bacteria from both young and old soils showed a significant interaction with their local environment; the direction of the interaction, however, did not follow the expected pattern of local adaptation. The significant genoype-with-environment interaction indicates a limited local expansion of soil bacteria in the Damma glacier forefield over the range of only 110 m. The lack of local adaptation could be explained by environmental constraints such as exclusion of competition, different migration behaviour of bacteria from young and old soil, or the ability of early colonizing bacteria to survive under the glacier ice. [ABSTRACT FROM AUTHOR]

Background: To reduce their decisional uncertainty, health policy decision-makers rely more often on experts or their intuition than on evidence-based knowledge, especially in times of urgency. However, this practice is unacceptable from an evidence-based medicine (EbM) perspective. Therefore, in fast-changing and complex situations, we need an approach that delivers recommendations that serve decision-makers' needs for urgent, sound and uncertainty-reducing decisions based on the principles of EbM., Aims: The aim of this paper is to propose an approach that serves this need by enriching EbM with theory., Materials and Methods: We call this the EbM+theory approach, which integrates empirical and theoretical evidence in a context-sensitive way to reduce intervention and implementation uncertainty., Results: Within this framework, we propose two distinct roadmaps to decrease intervention and implementation uncertainty: one for simple and the other for complex interventions. As part of the roadmap, we present a three-step approach: applying theory (step 1), conducting mechanistic studies (EbM+; step 2) and conducting experiments (EbM; step 3)., Discussion: This paper is a plea for integrating empirical and theoretical knowledge by combining EbM, EbM+ and theoretical knowledge in a common procedural framework that allows flexibility even in dynamic times. A further aim is to stimulate a discussion on using theories in health sciences, health policy, and implementation., Conclusion: The main implications are that scientists and health politicians - the two main target groups of this paper-should receive more training in theoretical thinking; moreover, regulatory agencies like NICE may think about the usefulness of integrating elements of the EbM+theory approach into their considerations., (© 2023 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Immature spinal cord, unlike adult, has an ability to repair itself following injury. Evidence for regeneration, structural repair and development of substantially normal locomotor behaviour comes from studies of marsupials due to their immaturity at birth. We have compared morphological, cellular and molecular changes in spinal cords transected at postnatal day (P)7 or P14, from 3 h to 2 weeks post-injury, in South American opossums ( Monodelphis domestica). A bridge between severed ends of cords was apparent 5 days post-injury in P7 cords, compared to 2 weeks in P14. The volume of neurofilament (axonal) material in the bridge 2 weeks after injury was 30% of control in P7- but < 10% in P14-injured cords. Granulocytes accumulated at the site of injury earlier (3 h) in P7 than in P14 (24 h)-injured animals. Monocytes accumulated 24 h post-injury and accumulation was greater in P14 cords. Accumulation of GFAP-positive astrocytes at the lesion occurred earlier in P14-injured cords. Neurites and growth cones were identified ultrastructurally in contact with astrocytes forming the bridge. Results using mouse inflammatory gene arrays showed differences in levels of expression of many TGF, TNF, cytokine, chemokine and interleukin gene families. Most of the genes identified were up-regulated to a greater extent following injury at P7. Some changes were validated and quantified by RT-PCR. Overall, the results suggest that at least some of the greater ability to recover from spinal cord transection at P7 compared to P14 in opossums is due to differences in inflammatory cellular and molecular responses. [ABSTRACT FROM AUTHOR]

Abstract Clinically, high-dose treatment with the glucocorticosteroid, methylprednisolone (MP), within 8 h after spinal cord injury, has been shown to improve neurological recovery. The current standard of care is to administer MP as a bolus of 30 mg/kg followed by a 23-h infusion of 5.4 mg/kg/h to spinal cord injured patients. To better understand the role of MP in neuroprotection, we have studied how MP administration affects macrophage accumulation, tissue loss, and axonal dieback at 1, 2, 4 and 8 weeks after a complete transection of the eighth thoracic spinal cord in the adult rat. A 30 mg/kg dose of MP was administered intravenously at 5 min, and 2 and 4 h after injury. The number of ED1 (antibody against microglia/macrophages) -positive cells was quantified in a 500-μm-wide strip of tissue directly adjacent and parallel to the transection. At all time points, MP treatment led to a significant decrease in the number of ED1-positive cells in both rostral and caudal stumps. Over the 2-month post-transection period, the average MP-induced reduction in the number of ED1-positive cells was 82% in the rostral cord stump and 66% in the caudal stump. Using a computerized image analysis system, it was observed that MP treatment resulted in a significant reduction in tissue loss in both cord stumps at 2, 4 and 8 week post-injury. Over the 2-month post-lesion period, the average MP-induced reduction in tissue loss in the caudal cord stump was higher than that in the rostral stump; 48 versus 37%, respectively. Immunostaining for neurofilaments and growth-associated protein-43 (GAP-43) revealed the presence of numerous axons near and in the lesion site. Anterograde neuronal tracing with biotinylated dextran amine showed that, in MP-treated animals, dieback of vestibulospinal fibres, but not of corticospinal fibres, was significantly diminished at all time points studied. In addition, with MP administration, 1 and 2 weeks after injury, an increase in the number of vestibulospinal fibres was found at 1 and 2 mm from the transection, suggesting transient regenerative sprouting of these fibres. The results demonstrate that treatment with MP shortly after spinal cord transection in the adult rat led to a long-term reduction of ED1-positive cells and spinal tissue loss, reduced dieback of vestibulospinal fibres, and a transient sprouting of vestibulospinal fibres near the lesion at 1 and 2 weeks post-lesion. The possible relationships between the inflammatory changes, spinal tissue sparing, and axonal survival and sprouting are complex and need to be further explored. [ABSTRACT FROM AUTHOR]

Frequent utilization of wild Cicer species in chickpea (Cicer arietinum L.) improvement programs, as well as the regeneration of these wild species for efficient conservation in genebanks, is hindered due to photoperiod and/or temperature sensitivity (vernalization). In this study, the response to four extended photoperiod treatments (15, 18, 21, and 24 h) was compared with a control (12 h) for phenology and growth in terms of reduction in number of days to first flowering, as well as for yield‐related traits in cultivated chickpea and seven annual wild Cicer species. The study revealed that wild Cicer species required long photoperiods (varying from 15 to 18 h) for transition from the vegetative to reproductive phase. Optimum photoperiods also improved agronomic traits such as pod number and seed yield per plant. Of the photoperiods studied, 18 h was the most appropriate photoperiod treatment for both reducing the vegetative phase and for efficient regeneration in C. reticulatum Ladiz. Fifteen hours was the most appropriate photoperiod in C. judaicum Boiss. and C. yamashitae Kitamura. Both 15 and 18 h were the most appropriate photoperiods in C. bijugum K.H. Rech. and C. pinnatifidum Jaub. & Sp., depending on the objective (15 h for regeneration and 18 h for reducing vegetative phase). Cicer chorassanicum (Bunge) M. Pop. and C. cuneatum Hochst. ex A. Rich. showed a weak response to all the extended photoperiod treatments. These results contribute to enhanced utilization of wild Cicer species for chickpea improvement through synchronization of flowering facilitating hybridization and for efficient regeneration by using species‐specific extended photoperiod treatments. [ABSTRACT FROM AUTHOR]

Poor survival of cells transplanted into the CNS is a widespread problem and limits their therapeutic potential. Whereas substantial loss of transplanted cells has been described, the extent of acute cell loss has not been quantified previously. To assess the extent and temporal profile of transplanted cell death, and the contributions of necrosis and apoptosis to this cell death following spinal cord injury, different concentrations of Schwann cells (SCs), lentivirally transduced to express green fluorescent protein (GFP), were transplanted into a 1-week-old moderate contusion of the adult rat thoracic spinal cord. In all cases, transplanted cells were present from 10 min to 28 days. There was a 78% reduction in SC number within the first week, with no significant decrease thereafter. Real-time polymerase chain reaction showed a similar 80% reduction in GFP-DNA within the first week, confirming that the decrease in SC number was due to death rather than decreased GFP transgene expression. Cells undergoing necrosis and apoptosis were identified using antibodies against the calpain-mediated fodrin breakdown product and activated caspase 3, respectively, as well as ultrastructurally. Six times more SCs died during the first week after transplantation by necrosis than apoptosis, with the majority of cell death occurring within the first 24 h. The early death of transplanted SCs indicates that factors present, even 1 week after a moderate contusion, are capable of inducing substantial transplanted cell death. Intervention by strategies that limit necrosis and/or apoptosis should be considered for enhancing acute survival of transplanted cells.

Meckel syndrome (MKS) is a rare lethal autosomal recessive disorder characterized by the presence of occipital encephalocele, cystic kidneys, fibrotic changes of the liver and polydactyly. Joubert syndrome (JS)-related disorders (JSRDs) or cerebello-oculo-renal syndromes (CORS) are a group of recessively inherited conditions characterized by a molar tooth sign (MTS) on cranial MRI, a set of core clinical features (developmental delay/mental retardation, hypotonia, ataxia, episodic breathing abnormalities, abnormal eye movements) and variable involvement of other systems including renal, ocular, central nervous system, craniofacial, hepatic, and skeletal. A significant clinical overlap between MKS and JSRD/CORS has been recognized in the literature. We describe a group of 10 Hutterite patients, of which 7 had been previously diagnosed with MKS, with a JSRD. Clinical features include variable early mortality, cognitive handicap, a characteristic dysmorphic facial appearance, hypotonia, ataxia, abnormal breathing pattern, nystagmus, and MTS on MRI. Additional features include occipital encephalocele, posterior fossa fluid collections resembling Dandy-Walker malformation, hydrocephalus, coloboma, and renal disease. This JSRD is a recognizable dysmorphic syndrome characterized by hypertelorism, deep-set eyes, down-slanting palpebral fissures, ptosis, arched eyebrows with medial sparseness, square nasal tip, short philtrum with tented upper lip, open mouth with down-turned corners, and posteriorly rotated low-set ears. Renal disease is present in 70% of patients and is characterized by cystic kidneys, abnormalities in renal function and hypertension. Homozygous deletions of NPHP1 and the known loci for JS/JSRD and MKS were excluded by identity-by-descent mapping studies suggesting that this condition in the Hutterites represents yet another locus for a JSRD., ((c) 2007 Wiley-Liss, Inc.)

Rationale, Aims, and Objectives: The disciplinary profile and the quality of production of knowledge on Corona pandemic is studied. This scientific field is called 'Medical Corona Science'., Methods: Criteria of analytical philosophy of science and science studies are systematically applied., Results: It is shown that mainly auxiliary medical disciplines such as virology and epidemiology but not clinical disciplines provide Corona knowledge. We see a laboratory-centered, technology- and data-driven science, largely ignoring clinical issues. Therefore we call these approaches "Medical Corona Science" (MCS). We see the need to adapt to features of a 'post-normal science', a 'mode 2 science' and of 'Integration and Implementation Science', especially as clinical knowledge must be integrated. There is also a severe lack of theoretical considerations that could help to frame the pandemic as a complex dynamic system., Conclusions: We suggest a deeper meta-scientific discussion of the epistemic value of MCS and propose the application of tools from systems science., (© 2022 John Wiley & Sons Ltd.)

We introduce a construction for discrete gradient operators that can be directly applied to arbitrary polygonal surface as well as polyhedral volume meshes. The main idea is to associate the gradient of functions defined at vertices of the mesh with diamonds: the region spanned by a dual edge together with its corresponding primal element — an edge for surface meshes and a face for volumetric meshes. We call the operator resulting from taking the divergence of the gradient Diamond Laplacian. Additional vertices used for the construction are represented as affine combinations of the original vertices, so that the Laplacian operator maps from values at vertices to values at vertices, as is common in geometry processing applications. The construction is local, exactly the same for all types of meshes, and results in a symmetric negative definite operator with linear precision. We show that the accuracy of the Diamond Laplacian is similar or better compared to other discretizations. The greater versatility and generally good behavior come at the expense of an increase in the number of non‐zero coefficients that depends on the degree of the mesh elements. [ABSTRACT FROM AUTHOR]

In humans and other adult mammals, axon regeneration is difficult in axotomized neurons. Therefore, spinal cord injury (SCI) is a devastating event that can lead to permanent loss of locomotor and sensory functions. Moreover, the molecular mechanisms of axon regeneration in vertebrates are not very well understood, and currently, no effective treatment is available for SCI. In striking contrast to adult mammals, many nonmammalian vertebrates such as reptiles, amphibians, bony fishes and lampreys can spontaneously resume locomotion even after complete SCI. In recent years, rapid progress in the development of next-generation sequencing technologies has offered valuable information on SCI. In this review, we aimed to provide a comparison of axon regeneration process across classical model organisms, focusing on crucial genes and signalling pathways that play significant roles in the regeneration of individually identifiable descending neurons after SCI. Considering the special evolutionary location and powerful regenerative ability of lamprey and zebrafish, they will be the key model organisms for ongoing studies on spinal cord regeneration. Detailed study of SCI in these model organisms will help in the elucidation of molecular mechanisms of neuron regeneration across species., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Spinal cord injury (SCI) is a devastating traumatic injury often causing permanent loss of function. The challenge of treating SCI stems from the development of a complex pathophysiology at the site of injury, involving multiple biochemical cascades, widespread inflammation, blood supply interruption, inhibitory scar formation, and poor regrowth of injured axons. Clinical options are limited to surgical stabilization and attempt to ameliorate secondary damage following injury. Gene therapy has significant potential to tackle multiple aspects of SCI and improve functional outcomes. The emergence of a diverse array of biomaterial‐based nonviral nanoparticle vectors capable of delivering gene‐modifying nucleic acids offers the potential to improve the efficiency and specificity of genetic cargos for spinal cord regeneration. In this review, the progress that has been made in the field of SCI repair and the different types of nanoparticles and nucleic acid cargoes that have been used are outlined, placing a particular focus on the different cell types and pathways targeted. While many challenges remain, a perspective on the future of the field of nanoparticle‐mediated gene delivery for SCI is provided, including using biomaterial scaffolds engineered specifically for SCI to deliver gene therapeutics and the exciting opportunities that exist in the post‐COVID landscape. [ABSTRACT FROM AUTHOR]

Nursing scholars continuously refine nursing knowledge and the philosophical foundations of nursing practice. They advance nursing knowledge by creating new knowledge and weighing the relevance of developments in cognate sciences. Nurse philosophers go further by providing epistemological and ontological arguments for explanations of nursing phenomena. In this article, I engage with Bender's arguments about why mechanisms should have more primacy as carriers of nursing knowledge. Despite the careful scholarship involved, Bender's arguments need to be more convincing. Accordingly, this article encourages debate about Bender's arguments for reorientating nursing science to mechanisms. I begin by suggesting that the claim that the theory‐practice divide can be overcome by reorientating to mechanisms is acceptable only if we accept Bender's depiction of the challenge. Then I question the ontology Bender relies on to justify reorientating nursing science. After that, I argue that mechanisms in models that parallel analytical sociology undermine the kind of nursing science Bender advocates. I illustrate my arguments with a social mechanism thought experiment. Then I explain why Bender's arguments cannot escape the received view of science or inform emancipatory nursing action without theory. Finally, I mention some caveats and implications for nursing science. [ABSTRACT FROM AUTHOR]

Policy PointsMore rigorous methodologies and systematic approaches should be encouraged in the science of scaling. This will help researchers better determine the effectiveness of scaling, guide stakeholders in the scaling process, and ultimately increase the impacts of health innovations.The practice and the science of scaling need to expand worldwide to address complex health conditions such as noncommunicable and chronic diseases.Although most of the scaling experiences described in the literature are occurring in the Global South, most of the authors publishing on it are based in the Global North. As the science of scaling spreads across the world with the aim of reducing health inequities, it is also essential to address the power imbalance in how we do scaling research globally. Context: Scaling of effective innovations in health and social care is essential to increase their impact. We aimed to synthesize the evidence base on scaling and identify current knowledge gaps. Methods: We conducted an umbrella review according to the Joanna Briggs Institute Reviewers' Manual. We included any type of review that 1) focused on scaling, 2) covered health or social care, and 3) presented a methods section. We searched MEDLINE (Ovid), Embase, PsycINFO (Ovid), CINAHL (EBSCO), Web of Science, The Cochrane Library, Sociological Abstracts (ProQuest), Academic Search Premier (EBSCO), and ProQuest Dissertations & Theses Global from their inception to August 6, 2020. We searched the gray literature using, e.g., Google and WHO‐ExpandNet. We assessed methodological quality with AMSTAR2. Paired reviewers independently selected and extracted eligible reviews and assessed study quality. A narrative synthesis was performed. Findings: Of 24,269 records, 137 unique reviews were included. The quality of the 58 systematic reviews was critically low (n = 42). The most frequent review type was systematic review (n = 58). Most reported on scaling in low‐ and middle‐income countries (n = 59), whereas most first authors were from high‐income countries (n = 114). Most reviews concerned infectious diseases (n = 36) or maternal–child health (n = 28). They mainly focused on interventions (n = 37), barriers and facilitators (n = 29), frameworks (n = 24), scalability (n = 24), and costs (n = 14). The WHO/ExpandNet scaling definition was the definition most frequently used (n = 26). Domains most reported as influencing scaling success were building scaling infrastructure (e.g., creating new service sites) and human resources (e.g., training community health care providers). Conclusions: The evidence base on scaling is evolving rapidly as reflected by publication trends, the range of focus areas, and diversity of scaling definitions. Our study highlights knowledge gaps around methodology and research infrastructures to facilitate equitable North–South research relationships. Common efforts are needed to ensure scaling expands the impacts of health and social innovations to broader populations. [ABSTRACT FROM AUTHOR]

Aerogel‐based biomaterials are increasingly being considered for biomedical applications due to their unique properties such as high porosity, hierarchical porous network, and large specific pore surface area. Depending on the pore size of the aerogel, biological effects such as cell adhesion, fluid absorption, oxygen permeability, and metabolite exchange can be altered. Based on the diverse potential of aerogels in biomedical applications, this paper provides a comprehensive review of fabrication processes including sol‐gel, aging, drying, and self‐assembly along with the materials that can be used to form aerogels. In addition to the technology utilizing aerogel itself, it also provides insight into the applicability of aerogel based on additive manufacturing technology. To this end, how microfluidic‐based technologies and 3D printing can be combined with aerogel‐based materials for biomedical applications is discussed. Furthermore, previously reported examples of aerogels for regenerative medicine and biomedical applications are thoroughly reviewed. A wide range of applications with aerogels including wound healing, drug delivery, tissue engineering, and diagnostics are demonstrated. Finally, the prospects for aerogel‐based biomedical applications are presented. The understanding of the fabrication, modification, and applicability of aerogels through this study is expected to shed light on the biomedical utilization of aerogels. [ABSTRACT FROM AUTHOR]

Schwann cells are functional cells in nerve regeneration and are commonly used as seed cells in tissue engineering. Enhanced Schwann cell migration capacity improves recovery effects, and thus, the identification of Schwann cells with greater migration ability is of great importance. In the present study, we examined the biological activities of Schwann cells collected from rat sciatic nerves (SN) and dorsal root ganglia (DRG). Observations from transwell migration assay and wound healing assay demonstrate that DRG Schwann cells migrate at a faster speed as compared with SN Schwann cells. Sequencing and bioinformatics suggest that differentially expressed genes between SN and DRG Schwann cells are associated with cell motility and migration. miR‐140 and miR‐200, two microRNAs (miRNAs) that are highly expressed in SN Schwann cells negatively influence Schwann cell migration and thus may be key regulators of Schwann cell phenotype. Igsf10, Plxna2, and Lcp1 are screened as candidate downstream targets of miR‐140 and miR‐200 based on bioinformatic analysis and their expression correlation with miRNAs. Our comparative analysis displays the unique characteristics of Schwann cells in different anatomical localizations and demonstrates that DRG Schwann cells are suitable seed cells for tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR]

This paper presents a comprehensive study of biogenic dimethylated sulfur compounds and methane (CH4) from 27 March to 16 April 2018 (spring) and from 24 July to 10 August 2018 (summer) in the Yellow Sea and Bohai Sea. The overall distributions of dimethylsulfide (DMS), dimethylsulfoniopropionate (DMSP, precursor of DMS), dimethylsulfoxide (DMSO, oxidation product of DMS) and CH4 in surface waters were characterized by elevated concentrations in summer and in coastal waters, coupled to phytoplankton biomass and terrestrially sourced inputs. Surface waters were oversaturated with CH4. The flux distributions of DMS and CH4 were generally consistent with their concentration distributions. In situ incubation experiments revealed that microbial consumption was the main removal mechanism for DMS, which could remove up to 72.1% of the total DMS compared to sea‐to‐air exchange in the surface layer. High DMS release and enhanced DMS yields (34%–62%) suggested more obvious influence from high DMSP concentrations (1 or 5 μm L−1) on DMS production in oligotrophic waters with lower bacterial sulfur demand in contrast to near‐shore waters. Positive correlations were found between CH4 and DMSP (dissolved) in summer and DMSO (particulate and dissolved) in spring. A DMSP addition experiment suggested that DMSP could act as a precursor for aerobic methanogenesis, and CH4 preferentially occurs under nitrogen‐stressed conditions in the surface layers of the Yellow Sea and Bohai Sea. Plain Language Summary: Dimethylated sulfur (DMS) is considered to be a cooling‐effect biogenic gas derived from the decomposition of dimethylsulfoniopropionate (DMSP). DMSP is associated with the aerobic production of methane (CH4), a powerful greenhouse gas with global warming potential. Oceanic emission remains a highly uncertain term in the budgets of atmospheric CH4 and DMS because of sparse sampling and the variable marine environment. In order to clarify their key biogeochemical processes and provide more field data for quantifying global and regional budgets, distributions and emission fluxes of DMS and CH4, and possible CH4 production from DMSP in upper waters, were investigated in the Yellow Sea and Bohai Sea. Biogenic dimethylated sulfur compounds including DMS, DMSP, dimethylsulfoxide (the oxidation product of DMS), and CH4 exhibited high concentrations in summer and in coastal waters mainly due to the influence of phytoplankton biomass and terrestrial sources. Surface waters were oversaturated with CH4, and the flux distributions of DMS and CH4 generally followed their concentration distributions. High levels of DMSP had a more obvious influence on DMS emission in offshore waters because of various microbial demands. CH4 was found to be produced from DMSP in oxic waters, especially in offshore waters with nitrate limitation. Key Points: Dimethylsulfoniopropionate (DMSP)‐dependent methane production preferentially occurs under nitrate limitation in the offshore waters of the Yellow Sea and Bohai SeaThe distributions of the sea‐to‐air flux of dimethylsulfide (DMS) and CH4 are consistent with their concentrations in surface watersHigh levels of DMSP have a more obvious influence on DMS release in offshore waters with lower sulfur demand compared to near‐shore waters [ABSTRACT FROM AUTHOR]

Quantum Mechanics (QM) stands alone as a (very) successful physical theory, but the meaning of its variables and the status of many quantities in the mathematical formalism is obscure. This unique situation prompted the need for attribution of a physical meaning to the latter, a procedure known as interpretation. On the other hand, the study of QM is usually presented, even to future scientists, within the only framework developed by Bohr and the Copenhagen researchers, known as the Copenhagen interpretation. As a contribution to the understanding and teaching of Quantum Mechanics, aimed to a broader and deeper appreciation of its fundamentals, including contemplating alternatives and updated interpretations for physicists and philosophers interested in the study of exact sciences (through Ontology, Epistemology, Logic or the Theory of Knowledge), we present a set of Conceptual Diagrams elaborated and designed to expose and facilitate the visualization of elements intervening in any interpretation of Quantum Mechanics and apply them to several well‐developed cases of the latter. [ABSTRACT FROM AUTHOR]

Social entrepreneurship has emerged as an important means of addressing grand challenges. Although research on the topic has accelerated, scholars have yet to articulate an overarching framework that links the different pathways taken by social entrepreneurs with the positive effects of these efforts. To address this shortcoming, we conducted a systematic literature review which enabled us to conceptually differentiate between social value and social change as distinct outcomes of social entrepreneurship and identify seven pathways for achieving these outcomes. Building on our analysis, we outline a research agenda for questions pertaining to: the dynamics between social value and social change; how contextual factors and social entrepreneurs influence various pathways; design principles of business models and innovations that facilitate social value and social change; and defining, measuring, and ensuring accountability for social value and social change. [ABSTRACT FROM AUTHOR]

Systems engineering activities in the concept and development phases have evolved continuously for decades. The deployment of digital thread, digital engineering, MBSE approaches, and modeling and simulation techniques have driven part of this evolution. Despite this trend, requirements are still largely textual and expressed in natural language, and requirements engineering activities are still often document‐based. However, model‐based requirements‐engineering approaches have emerged in recent years and have demonstrated significant benefits, including improved requirements quality, less ambiguity, and early and efficient verification and validation. The goal of this paper is to present the current outcomes and perspectives of setting up an Integrated Digital Requirements Engineering approach as developed within our company. This approach seeks to optimize usability and maximize benefits to support end‐to‐end V&V activities while fully integrating into MBSE workflows. [ABSTRACT FROM AUTHOR]

Aim: People living with ulcerative colitis (UC) have two broad treatment avenues, namely medical or surgical therapy. The choice between these can depend on patient preference as well as the receipt of relevant information. The aim of this study was to define the informational needs of patients with UC. Method: A postal survey was designed to capture respondent demographics, treatment experienced within the previous 12 months and informational preferences by rating a long list of items. It was delivered through two hospitals that provide tertiary inflammatory bowel disease services. Descriptive analyses were performed to describe demographics and experiences. Principal component analysis was carried out using a varimax rotation to investigate informational needs. Results: A total of 101 responses were returned (20.1% response rate). The median age of respondents was 45 years and the median time since diagnosis was 10 years. Control preferences skewed towards shared (42.6%) or patient‐led but clinician‐informed (35.6%). Decision regret was low for the population (median 12.5/100, range 0–100). Key informational needs related to medical therapy were benefits and risks of long‐term therapy, burden of hospital attendance, reproductive health, need for steroid treatment and impact on personal life. For surgery, these were stoma information, effect on daily life, effect on sexual and reproductive health, risks and benefits and disruption of life due to surgery. Conclusion: This study has identified key areas for discussion when counselling patients about treatment decisions around medical therapy and surgery for UC. [ABSTRACT FROM AUTHOR]

This article strengthens the relationship between childhood studies and biblical studies by introducing the field of childist biblical criticism to other child‐focused disciplines. A brief overview explains why studying children in the Bible is critical for understanding this ancient text and its world. Most of the article focuses on the tools used for gathering evidence and the methodologies used in childist scholarship. Discussion of the terms 'childist' and 'childism' then urges adoption of both terms as conveying positive meaning. Throughout the discussion and explicitly in the conclusion, this article shows what childist biblical studies contribute to the wider movement of childism and securing children's rights. [ABSTRACT FROM AUTHOR]

Biomolecular communication demands that interactions between parts of a molecular system act as scaffolds for message transmission. It also requires an organized system of signs—a communicative agency—for creating and transmitting meaning. The emergence of agency, the capacity to act in a given context and generate end‐directed behaviors, has baffled evolutionary biologists for centuries. Here, I explore its emergence with knowledge grounded in over two decades of evolutionary genomic and bioinformatic exploration. Biphasic processes of growth and diversification exist that generate hierarchy and modularity in biological systems at widely ranging time scales. Similarly, a biphasic process exists in communication that constructs a message before it can be transmitted for interpretation. Transmission dissipates matter‐energy and information and involves computation. Agency emerges when molecular machinery generates hierarchical layers of vocabularies in an entangled communication network clustered around the universal Turing machine of the ribosome. Computations canalize biological systems to perform biological functions in a dissipative quest to structure long‐lived occurrents. This occurs within the confines of a "triangle of persistence" that maximizes invariance with trade‐offs between economy, flexibility, and robustness. Thus, learning from previous historical and circumstantial experiences unifies modules in a hierarchy that expands the agency of systems. [ABSTRACT FROM AUTHOR]

Third, researchers may try to link a supply chain related predictor at the firm level to an outcome that is highly distal from that predictor. For example, given the central role that firm size plays in shaping firms' actions and outcomes, a study that examines how firms' R&D investment affects firm-level innovation (measured using patent counts) without controlling for firm size would diminish statistical identification. Keywords: archival data; logistics; mechanisms; supply chain; theory EN archival data logistics mechanisms supply chain theory 292 299 8 07/21/23 20230701 NES 230701 INTRODUCTION A welcomed addition to the logistics and supply chain management (L&SCM) research landscape has been growth in the use of archival data, defined as data collected by an entity outside the research team (Miller et al., [19]). An example here is the numerous factors that affect company-level return on assets (ROA) relative to a variable like inventories, so isolating a theorized mechanism tends to be much harder if the former measure is the dependent variable, a concern also noted by Richey et al. ([30]). [Extracted from the article]

Aquatic ecosystems play an important role in global methane cycling and many field studies have reported methane supersaturation in the oxic surface mixed layer (SML) of the ocean and in the epilimnion of lakes. The origin of methane formed under oxic condition is hotly debated and several pathways have recently been offered to explain the "methane paradox." In this context, stable isotope measurements have been applied to constrain methane sources in supersaturated oxygenated waters. Here we present stable carbon isotope signatures for six widespread marine phytoplankton species, three haptophyte algae and three cyanobacteria, incubated under laboratory conditions. The observed isotopic patterns implicate that methane formed by phytoplankton might be clearly distinguished from methane produced by methanogenic archaea. Comparing results from phytoplankton experiments with isotopic data from field measurements, suggests that algal and cyanobacterial populations may contribute substantially to methane formation observed in the SML of oceans and lakes. Plain Language Summary: Methane plays an important role in atmospheric chemistry and physics as it contributes to global warming and to the destruction of ozone in the stratosphere. Knowing the sources and sinks of methane in the environment is a prerequisite for understanding the global atmospheric methane cycle but also to better predict future climate change. Measurements of the stable carbon isotope composition of carbon—the ratio between the heavy and light stable isotope of carbon—help to identify methane sources in the environment and to distinguish them from other formation processes. We identified the carbon isotope fingerprint of methane released from phytoplankton including algal and cyanobacterial species. The observed isotope signature improves our understanding of methane cycling in the surface layers of aquatic environments helping us to better estimate methane emissions to the atmosphere. Key Points: Stable carbon isotope values of methane emitted from six phytoplankton cultures incubated in the laboratoryIsotope fractionation between methane source signature and biomass of widespread algal and cyanobacterial speciesIsotopic patterns of methane released by phytoplankton may be clearly distinguished from methane formed by methanogenic archaea [ABSTRACT FROM AUTHOR]

White matter deficits are a common neuropathologic finding in neurologic disorders, including HIV‐associated neurocognitive disorders (HAND). In HAND, the persistence of white matter alterations despite suppressive antiretroviral (ARV) therapy suggests that ARVs may be directly contributing to these impairments. Here, we report that a frontline ARV, bictegravir (BIC), significantly attenuates remyelination following cuprizone‐mediated demyelination, a model that recapitulates acute demyelination, but has no impact on already formed mature myelin. Mechanistic studies utilizing primary rat oligodendrocyte precursor cells (OPCs) revealed that treatment with BIC leads to significant decrease in mature oligodendrocytes accompanied by lysosomal deacidification and impairment of lysosomal degradative capacity with no alterations in lysosomal membrane permeability or total lysosome number. Activation of the endolysosomal cation channel TRPML1 prevents both lysosomal deacidification and impairment of oligodendrocyte differentiation by BIC. Lastly, we show that deacidification of lysosomes by compounds that raise lysosomal pH is sufficient to prevent maturation of oligodendrocytes. Overall, this study has uncovered a critical role for lysosomal acidification in modulating oligodendrocyte function and has implications for neurologic diseases characterized by lysosomal dysfunction and white matter abnormalities. [ABSTRACT FROM AUTHOR]

In the field of phylogenetic systematics, the terms homology and homologue and their relationship to cladistic terms such as character, character state, synapomorphy and symplesiomorphy, as well as their relationships to each other, have been and are still discussed frequently. A recent re‐emergence of concepts of homology/homologue free of any reference to explanatory hypotheses prompted us to explore these concepts and their relationships to each other as well as to the concept of morpheme, as introduced recently. All concepts are examined with regard to their ontological status and their bearing in the epistemological process in morphology and phylogenetic systematics. To us, morphemes, homologues and in partem character states refer to things (concrete objects in the ontological sense). However, although morphemes are exclusively descriptive, the latter two represent objects of causal explanations. Homologue always refers to the things themselves, yet a character state also can be a property or the absence of a thing. In this context, a character as a transformation series of character states does not represent a thing but a natural kind. Character states of one character are connected by homology relationships, i.e. common descent. Synapomorphy and symplesiomorphy represent different states of a single transformation series. A nonexplanatory, purely descriptive, concept of homologues is contradictory to its original as well as the post‐Darwinian, evolutionary, concept which refers to causal relationships between parts of organisms and their correspondences in the archetype or ancestor, respectively. Character states, homologues and synapomorphies/symplesiomorphies can only be approximated in the form of hypotheses. We argue that the high value of the concept of homology and its related concepts for evolutionary biology should be maintained by acknowledging their explanatory nature and that dilution with nonexplanatory (even idealistic) definitions should be avoided. [ABSTRACT FROM AUTHOR]

In this paper, we attempt to rehabilitate the notion of role by linking sociological role theory to recent work on motivational, affective, and cognitive neuroscience specifying the internal mechanisms behind motivated action. We argue that there is nothing inherently problematic or retrogressive in the idea of "role," once its link to a purely normative account of motivated action is severed. Instead, by conceptualizing roles as emerging and persisting around structured reward systems, we are able to incorporate contemporary motivational science such that rewards become the proximate causal mechanisms currently missing in role theory. Consequently, a key implication of our argument is that the best way to link role, action, and structures is by reviving the idea of institutions as literal reward systems, which allows us to envision roles as the mechanisms via which the pursuit and delivery of rewards and goal‐objects are routinized. Implications for a motivational theory of roles, rewards, and institutions is discussed. [ABSTRACT FROM AUTHOR]

This study offers fresh ontological insights by examining generative causality through the Qualitative Comparative Analysis (QCA) counterfactual lens, in conjunction with Critical Realism and the practice of retroduction. Specifically, it claims that Information Systems (IS) researchers could retroduce generative mechanisms by leveraging the QCA counterfactual approach to causation because retroduction is about conjecturing hypothetical mechanisms that would generate the outcome of interest in a counterfactual fashion. Drawing on an example of typological theorising, this study calls for a renewed effort in the use of retroduction in the study of IS phenomena. In addition, this study sheds new light on the overarching approach for conducting Critical Realist (case study) research. A number of theoretical, methodological, and practical implications are discussed. [ABSTRACT FROM AUTHOR]

During development, dramatic changes in myelination, growth of neural networks and changes in grey‐to‐white matter ratio build up the astonishingly plastic brain of a child. The progressive increase in myelination insulates the nervous system, which, in turn, modifies the mechanical microenvironment of the brain spatiotemporally. A growing body of evidence demonstrates the role of mechanical forces in growth, differentiation, maturation and electrical properties of neurons. However, due to limitations in imaging resolution, the exact relationship between myelination, axonal organization and the mechanical properties of nerves at the cellular level is still unknown. Here, we propose a novel approach to study the direct relationship between axonal viscoelasticity with changing fibre anisotropy and myelination during development. With the use of atomic force microscopy (AFM) with in situ fluorescent imaging of the primary neuron‐oligodendrocyte co‐cultures, we found that as axons are progressively myelinated in vitro, their stiffness increases. Direct quantification of myelin along axons using immunofluorescence also demonstrated a positive correlation between increased myelination over time and increased axonal stiffness (p =.001). Notably, AFM measurements along a single axon showed that the Young's modulus measured across myelinated regions were significantly higher than those of adjacent unmyelinated segments at all time points (p <.0001). Force‐relaxation analysis also demonstrated that myelin sheath dominates the regulation of viscoelasticity of axons temporally. Collectively, our findings indicate a direct link between myelination, axonal orientation and viscoelasticity, providing important insights about the mechanical environment in the paediatric brain, with direct implications for our understanding of developmental brain disorders and paediatric brain injury. [ABSTRACT FROM AUTHOR]

A 7‐year‐old, neutered golden retriever was evaluated for acute episodes of weakness, ataxia and disorientation, low blood glucose and inappropriately high insulin levels. Results of computed tomography revealed irregular enlargement of the distal tip of the right pancreas associated with thrombosis of the pancreaticoduodenal and first jejunal vein. A partial pancreatectomy with en bloc excision of the thrombosed vessels was performed. The distal duodenum and proximal jejunum maintained normal peristalsis and remained viable, obviating the need for concurrent intestinal resection and anastomosis. Histopathology confirmed a completely excised insulinoma with an associated tumour thrombus (vascular invasion of tumour). The dog remains alive with no evidence of recurrence 18 months after surgery. [ABSTRACT FROM AUTHOR]

Background/Hypothesis: Risk factor control of diabetes mellitus (DM) and especially dyslipidemia remains unsatisfactory in patients with atherosclerotic cardiovascular disease (ASCVD). We aimed to analyze the knowledge of low‐density lipoprotein cholesterol (LDL‐C) and glycated hemoglobin (HbA1c) treatment goals, subjective level of information, and information needs in very high‐risk patients with ASCVD. Methods: ASCVD patients (n = 210; 75 ± 9 years; 71.4% male; 89.5% coronary disease) with DM (96.7% type 2) completed a questionnaire assessing knowledge of HbA1c and LDL‐C treatment goals and subjective level of information and information needs on disease‐related topics of DM and ASCVD. Serum LDL‐C and HbA1c were measured. Results: HbA1c goal (<7.0% in 60.6%) was attained more frequently than LDL‐C goal (<70 mg/dl in 39.9%; p <.01). Significantly more participants named the correct goal for HbA1c compared to LDL‐C (52.9% vs. 2.4%; p <.01). Subjective levels of information were higher and information needs were lower for DM than for ASCVD (p <.01 for all topics). No associations of knowledge of treatment goals and level of information with the attainment of treatment goals for HbA1c and LDL‐C were found. However, in multivariate regression, higher levels of education were associated with knowledge of treatment goals (HbA1c: odds ratio [OR] 1.32, 95% confidence interval [CI] 1.01–1.72, p =.04; LDL‐C: OR 2.32, 95% CI 1.07–5.03; p =.03). Conclusion: In very high‐risk patients with ASCVD, a deficit of knowledge of treatment goals to control dyslipidemia exists when compared to DM, patients felt significantly better informed for topics of DM than for ASCVD and display higher information needs for topics of ASCVD. [ABSTRACT FROM AUTHOR]

The phenotypic instability of adult tissue-derived Schwann cell-like cells (SCLCs) as revealed upon withdrawal of glia-inducing culture supplements limits their clinical utility for cell therapy and disease modelling. We previously overcame this limitation by co-culturing bone marrow-derived SCLCs with neurons purified from developing rat and subsequently human sensory neurons such that direct contact between cell types accomplished the cell-intrinsic switch to the Schwann cell fate. Here, our search for juxtacrine instructive signals found both Notch ligands and neuregulin-1 type III localized on the surface of DRG neurons via live cell immunocytochemistry. Bypassing ligand-induced release of the Notch intracellular domain (NICD) by transient transfection of SCLCs with the pAdlox/V5-His-NICD construct was shown to upregulate ErbB2/3. Interaction of ErbB2/3 with neuregulin-1 type III (NRG1 type III) as presented on neurons then mediated the switch to the Schwann cell fate as demonstrated by expression of S100β/p75/ Sox10/Krox20. In contrast, treatment of cocultures with γ-secretase inhibitor perturbed Notch signalling in SCLCs and consequently deterred both upregulation of ErbB2/3 and the transition to the Schwann cell fate. Taken together, juxtacrine signalling via Notch is key to the upregulation of ErbB receptors for neuregulin-driven commitment of SCLCs to the Schwann cell fate., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Early environments can have significant and lasting effects on brain, body, and behavior across the lifecourse. Here, we address current research efforts to understand how experiences impact neurodevelopment with a new perspective integrating two well-known conceptual frameworks - the Developmental Origins of Health and Disease (DOHaD) and sensitive/critical period frameworks. Specifically, we consider how prenatal experiences characterized in the DOHaD model impact two key neurobiological mechanisms of sensitive/critical periods for adapting to and learning from the postnatal environment. We draw from both animal and human research to summarize the current state of knowledge on how particular prenatal substance exposures (psychoactive substances and heavy metals) and nutritional profiles (protein-energy malnutrition and iron deficiency) each differentially impact brain circuits' excitation/GABAergic inhibition balance and myelination. Finally, we highlight new research directions that emerge from this integrated framework, including testing how prenatal environments alter sensitive/critical period timing and learning and identifying potential promotional/buffering prenatal exposures to impact postnatal sensitive/critical periods. We hope this integrative framework considering prenatal influences on postnatal neuroplasticity will stimulate new research to understand how early environments have lasting consequences on our brains, behavior, and health., (© 2024 The Authors. Infancy published by Wiley Periodicals LLC on behalf of International Congress of Infant Studies.)

We discuss in this work, the contradictory position in modern Physics between the existence of a microphysical quantum reality and macrophysical classical one. After discussing some basic concepts in Philosophy, we revisit the situation of Quantum Mechanics results, particularly after the confirmation of violations of Bell's theorem, and its significance to create a tension between the micro and the macro world, which is very fundamental and unsolved. [ABSTRACT FROM AUTHOR]