Perinatal Gene Transfer to the Liver

The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases can be managed using conventional medicines whereas others are, as yet, untreatable. In this review we consider the application of early intervention gene therapy in neonatal and fetal preclinical studies. We appraise the tools of this technology, including lentivirus, adenovirus and adeno-associated virus (AAV)-based vectors. We highlight the application of these for a range of diseases including hemophilia, urea cycle disorders such as ornithine transcarbamylase deficiency, organic acidemias, lysosomal storage diseases including mucopolysaccharidoses, glycogen storage diseases and bile metabolism. We conclude by assessing the advantages and disadvantages associated with fetal and neonatal liver gene transfer

Two Types of K⁺ Channel Subunit, Erg1 and KCNQ2/3, Contribute to the M-Like Current in a Mammalian Neuronal Cell

The potassium M current was originally identified in sympathetic ganglion cells, and analogous currents have been reported in some central neurons and also in some neural cell lines. It has recently been suggested that the M channel in sympathetic neurons comprises a heteromultimer of KCNQ2 and KCNQ3 (Wang et al., 1998) but it is unclear whether all other M-like currents are generated by these channels. Here we report that the M-like current previously described in NG108–15 mouse neuroblastoma x rat glioma cells has two components, “fast” and “slow”, that may be differentiated kinetically and pharmacologically. We provide evidence from PCR analysis and expression studies to indicate that these two components are mediated by two distinct molecular species of K+ channel: the fast component resembles that in sympathetic ganglia and is probably carried byKCNQ2/3 channels, whereas the slow component appears to be carried by merg1a channels. Thus, the channels generating M-like currents in different cells may be heterogeneous in molecular composition

The Effects of Communication on the Partnership Solution to the Commons

© 2017, Springer Science+Business Media Dordrecht. Organizing individual appropriators into output sharing groups has been found to effectively solve the tragedy of the commons problem. We experimentally investigate the robustness of this solution by introducing different channels of communication that naturally arise from group competitions. In the absence of communication, we confirm that output sharing can introduce sufficient free riding to offset over-harvesting and results in full efficiency. Allowing local communication within output-sharing groups substantially decreases this efficiency enhancement because it reduces free riding and boosts between-group competition. Yet the efficiency level is still significantly higher than that achieved when global communication is allowed among all appropriators in a conventional common pool resource without output sharing. The efficiency-reducing effect of local communication is mitigated when random partners instead of fixed partners are sharing output over time, and is nearly eliminated when random partners are formed with users who belong to different communication groups

Appropriation from a common pool resource: effects of the characteristics of the common pool resource, the appropriators and the existence of communication

© 2017 by World Scientific Publishing Co. Pte. Ltd. All rights reserved. There is a growing literature that studies the management of Common Pool Resources (CPRs) within the context of controlled laboratory experiments. A major thesis of this work is that non-binding communication (cheap talk) among appropriators of the commons may be sufficient to permit them to manage the commons efficiently without requiring an outside regulator. In this chapter we compare three CPR environments in controlled laboratory sessions with and without non-binding communication. We identify the nature of the differences across the environments and propose several new environments that may support a conjecture that cognitive differences induced by the framing of the sessions leads to the differences we find. Our results suggest that the success of nonbinding communication in reducing over-appropriation from a CPR may be dependent upon the characteristics of the CPR's yield function, the nature of the communication and the number of appropriators

A scoping review of registered nurses' delegating care and support to unlicenced care and support workers

Aim: To scope the international literature about registered nurses delegated models of care to unlicenced workers, identify gaps and reflect upon how the evidence relates to nursing in multiple contexts. Design: Scoping review of the peer reviewed literature from the year 2000 onwards, using the PRISMA-ScR checklist. Methods: The study searched the following databases in February 2022: CINAHL, Medline, ProQuest, and SCOPUS, and included keywords, Boolean operators and subject headings relevant to registered nurses delegating the provision of care to unlicenced workers. Results: A total of 49 articles met the eligibility criteria for this study, and relevant data were extractedThree models of delegation were highlighted within the literature: direct, indirect and a mixture of both. The data highlighted that direct delegation mainly occurred in acute contexts, with delegation decreasing with increasing patient acuity and/or complexity but the threshold of when this would occur was not clear. There was one intervention study that measured patient outcomes which could aid in the determination of what is effective delegation. For studies that did report on it (n = 6), there were few examples of better patient outcomes in cases where care was delegated from registered nurses to unlicenced workers. Conclusions: The scoping review highlighted heterogeneity in practice areas and methods of delegation practice. A key gap in literature is the absence of studies focusing on patient outcomes, with a clear baseline to measure and identify effective delegation practices. Additionally, the legal and logistical implications presented in both direct and indirect delegation practices is not evident in the literature. Implications for the Profession: Decisions related to delegation are often made at the service level and prescribed to those who work within the service, suggesting that models of indirect delegation are in fact not delegation at all, rather a re-distribution of nurses' work. Relevance to clinical practice: Delegation is a vital component of the scope of practice of registered nurses. This review has highlighted unique differences in delegation by practice context, where the proliferation of unlicensed workers in certain contexts places a vastly different professional and legal burden on the registered nurse

A scoping review to inform an auditing framework evaluating healthcare environments for inclusion of people with intellectual disability and/or autism

People with intellectual disability and/or autism are likely to be in hospital more often, for longer, and have poorer health outcomes. Few audit tools exist to identify their barriers in mainstream healthcare environments. This study aimed to identify evidence of audit characteristics of healthcare contexts specifically for people with intellectual disability and/or autism, for conceptual development of an auditing framework. A scoping review of evaluations of healthcare environments was completed in January 2023. Findings were presented using the PAGER framework. Of the sixteen studies identified, most originated in the UK, nine focused on intellectual disability, four on autism, and three were concerned with mixed diagnosis. Six domains for auditing healthcare environments were identified: care imperatives, communication to individuals, understanding communication from individuals, providing supportive environments of care, supporting positive behaviour, and actions to make things go well. Further research is recommended to refine an audit framework

The Evolutionary Pathway to Obligate Scavenging in Gyps Vultures

The evolutionary pathway to obligate scavenging in Gyps vultures remains unclear. We propose that communal roosting plays a central role in setting up the information transfer network critical for obligate scavengers in ephemeral environments and that the formation of a flotilla-like foraging group is a likely strategy for foraging Gyps vultures. Using a spatial, individual-based, optimisation model we find that the communal roost is critical for establishing the information network that enables information transfer owing to the spatial-concentration of foragers close to the roost. There is also strong selection pressure for grouping behaviour owing to the importance of maintaining network integrity and hence information transfer during foraging. We present a simple mechanism for grouping, common in many animal species, which has the added implication that it negates the requirement for roost-centric information transfer. The formation of a flotilla-like foraging group also improves foraging efficiency through the reduction of overlapping search paths. Finally, we highlight the importance of consideration of information transfer mechanisms in order to maximise the success of vulture reintroduction programmes

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

Decision-making in international business

This paper distinguishes three domains of international business theory: the boundaries of the multinational enterprise, the external environment of the enterprise and its internal structure. The central concern of internalisation theory is the boundaries of the firm. Any general theory of international business must analyse the external environment and internal structure as well. Competition dominates the external environment whilst co-operation dominates internal structure. Different models of decision-making are required for each. Different theories of decision-making must therefore be integrated in order to transform internalisation theory into a general theory of international business. This paper examines how this can be done

Competition-based model of pheromone component ratio detection in the moth

For some moth species, especially those closely interrelated and sympatric, recognizing a specific pheromone component concentration ratio is essential for males to successfully locate conspecific females. We propose and determine the properties of a minimalist competition-based feed-forward neuronal model capable of detecting a certain ratio of pheromone components independently of overall concentration. This model represents an elementary recognition unit for the ratio of binary mixtures which we propose is entirely contained in the macroglomerular complex (MGC) of the male moth. A set of such units, along with projection neurons (PNs), can provide the input to higher brain centres. We found that (1) accuracy is mainly achieved by maintaining a certain ratio of connection strengths between olfactory receptor neurons (ORN) and local neurons (LN), much less by properties of the interconnections between the competing LNs proper. An exception to this rule is that it is beneficial if connections between generalist LNs (i.e. excited by either pheromone component) and specialist LNs (i.e. excited by one component only) have the same strength as the reciprocal specialist to generalist connections. (2) successful ratio recognition is achieved using latency-to-first-spike in the LN populations which, in contrast to expectations with a population rate code, leads to a broadening of responses for higher overall concentrations consistent with experimental observations. (3) when longer durations of the competition between LNs were observed it did not lead to higher recognition accuracy