Adaptation strategies for self-organising electronic institutions

For large-scale systems and networks embedded in highly dynamic, volatile, and unpredictable environments, self-adaptive and self-organising (SASO) algorithms have been proposed as solutions to the problems introduced by this dynamism, volatility, and unpredictability. In open systems it cannot be guaranteed that an adaptive mechanism that works well in isolation will work well — or at all — in combination with others. In complexity science the emergence of systemic, or macro-level, properties from individual, or micro-level, interactions is addressed through mathematical modelling and simulation. Intermediate meso-level structuration has been proposed as a method for controlling the macro-level system outcomes, through the study of how the application of certain policies, or norms, can affect adaptation and organisation at various levels of the system. In this context, this thesis describes the specification and implementation of an adaptive affective anticipatory agent model for the individual micro level, and a self-organising distributed institutional consensus algorithm for the group meso level. Situated in an intelligent transportation system, the agent model represents an adaptive decision-making system for safe driving, and the consensus algorithm allows the vehicles to self-organise agreement on values necessary for the maintenance of “platoons” of vehicles travelling down a motorway. Experiments were performed using each mechanism in isolation to demonstrate its effectiveness. A computational testbed has been built on a multi-agent simulator to examine the interaction between the two given adaptation mechanisms. Experiments involving various differing combinations of the mechanisms are performed, and the effect of these combinations on the macro-level system properties is measured. Both beneficial and pernicious interactions are observed; the experimental results are analysed in an attempt to understand these interactions. The analysis is performed through a formalism which enables the causes for the various interactions to be understood. The formalism takes into account the methods by which the SASO mechanisms are composed, at what level of the system they operate, on which parts of the system they operate, and how they interact with the population of the system. It is suggested that this formalism could serve as the starting point for an analytic method and experimental tools for a future systems theory of adaptation.Open Acces

Conservation and restoration of a keystone species : understanding the settlement preferences of the European oyster (Ostrea edulis)

The project was funded by the Nesbit Cleland Trust (St Abbs Marine Station), Royal Haskoning DHV and Scottish Natural Heritage with additional support from the Dornoch Environmental Enhancement Project (DEEP: a partnership between Heriot-Watt University, the Marine Conservation Society and the Glenmorangie Whisky Company: A15R10520) and the MASTS pooling initiative (the Marine Alliance for Science and Technology for Scotland) funded by the Scottish Funding Council, United Kingdom (grant reference HR09011). Additional funding was provided by a MASTS PECRE grant. The authors wish to thank the staff of the Danish Shellfish Centre for their kind support.The European oyster Ostrea edulis is a keystone species that is internationally recognised as ‘threatened and declining’ in the NE Atlantic by OSPAR and several nations have consequently adopted strategies for its conservation and restoration. Understanding the settlement behaviour of O. edulis larvae is crucial to inform these strategies. We compared the efficiency of several treatments in triggering settlement. The most effective settlement occurred with the presence of conspecifics: 100% settled in <23 h. Marine stones with habitat-associated biofilms induced 81% settlement that started after a 45 h delay. Sterile shells and terrestrial stones did not induce more settlement than control treatments. These results indicate that O. edulis larvae are gregarious and finely-tuned to settle in response to cues which are indicative of their adult habitat requirements. The role of chemical cues in mediating settlement, and the importance of this to restoration, are discussed.Publisher PDFPeer reviewe

NORA moving forward: Developing an oyster restoration network in Europe to support the Berlin Oyster Recommendation

1. The Native Oyster Restoration Alliance (NORA) supports the protection and ecological restoration of the native European oyster, Ostrea edulis, and its habitat across its current and historical biogeographical range. NORA works to overcome barriers to the conservation, restoration, and recovery of the European oyster by providing a platform for the NORA community to collaborate and participate in knowledge exchange. NORA seeks to support responsible restoration practice, in compliance with biosecurity and sustainability. 2. Against this background, the NORA community formulated a series of specific recommendations, the Berlin Oyster Recommendation, to support native oyster restoration by developing and applying best practice with the aim to recover healthy and resilient marine ecosystems. In combination with the Standards for Ecological Restoration (SER) and the Restoration Guidelines for Shellfish Reefs, the Berlin Oyster Recommendation is a relevant tool for successful and sustainable oyster restoration in Europe. 3. The establishment of NORA working groups will support the implementation and further development of the six corresponding recommendations. Current NORA working groups cover site selection, biosecurity, production, and monitoring. The site selection working group will address the identification of suitable sites for oyster restoration to support policy relevant decision making and the conservation, reinforcement, or reintroduction of native oysters. The biosecurity working group will develop biosecurity guidelines for native oyster restoration in Europe. The production working group will assess the potential of standards for seed oyster production and supply in order to enhance production appropriate for restoration purposes. In close collaboration with the Native Oyster Network – UK & Ireland (NON), the monitoring working group will produce a monitoring guidelines handbook to provide metrics and methods that will be suitable across the range of O. edulis projects in Europe for the documentation of restoration success and ecosystem recovery. 4. The Berlin Oyster Recommendation was examined and interpreted by NORA experts in the context of the further development of joint guidelines for the practice of successful and sustainable native oyster restoration

Human marginal zone B cell development from early T2 progenitors.

B cells emerge from the bone marrow as transitional (TS) B cells that differentiate through T1, T2, and T3 stages to become naive B cells. We have identified a bifurcation of human B cell maturation from the T1 stage forming IgMhi and IgMlo developmental trajectories. IgMhi T2 cells have higher expression of α4β7 integrin and lower expression of IL-4 receptor (IL4R) compared with the IgMlo branch and are selectively recruited into gut-associated lymphoid tissue. IgMhi T2 cells also share transcriptomic features with marginal zone B cells (MZBs). Lineage progression from T1 cells to MZBs via an IgMhi trajectory is identified by pseudotime analysis of scRNA-sequencing data. Reduced frequency of IgMhi gut-homing T2 cells is observed in severe SLE and is associated with reduction of MZBs and their putative IgMhi precursors. The collapse of the gut-associated MZB maturational axis in severe SLE affirms its existence in health

Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma

The impact of bridging therapy (BT) on CD19-directed chimeric antigen receptor T-cell (CD19CAR-T) outcomes in large B-cell lymphoma (LBCL) is poorly characterised. Current practice is guided by physician preference rather than established evidence. Identification of effective BT modalities and factors predictive of response could improve CAR-T intention to treat and clinical outcomes. We assessed BT modality and response in 375 adult LBCL patients in relation to outcomes following axicabtagene ciloleucel (Axi-cel) or tisagenlecleucel (Tisa-cel). The majority of patients received BT with chemotherapy (57%) or radiotherapy (17%). We observed that BT was safe for patients, with minimal morbidity/mortality. We showed that complete or partial response to BT conferred a 42% reduction in disease progression and death following CD19CAR-T therapy. Multivariate analysis identified several factors associated with likelihood of response to BT, including response to last line therapy, the absence of bulky disease, and the use of Polatuzumab-containing chemotherapy regimens. Our data suggested that complete/partial response to BT may be more important for Tisa-cel than Axi-cel, as all Tisa-cel patients with less than partial response to BT experienced frank relapse within 12 months of CD19CAR-T infusion. In summary, BT in LBCL should be carefully planned towards optimal response and disease debulking, to improve CD19CAR-T patient outcomes. Polatuzumab-containing regimens should be strongly considered for all suitable patients, and failure to achieve complete/partial response to BT pre-Tisa-cel may prompt consideration of further lines of BT where possible

Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10−12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10−10). At 13q34, the signal is located 5’ of the gene IRS2 and 3’ of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk