Prepared for a Symposium on Country Development at the European Meeting on Cybernetics and Systems Research, Vienna, Austria, April 2012 (Untitled). ACES Working Papers, April 2012

In Kazakhstan doctoral students are not expected to make a contribution to knowledge, as is required at Western universities. Rather, their task is to become familiar with what is known and then make policy recommendations for Kazakhstan. For example, how can the human capital in Kazakhstan be improved? This is a very broad subject for a PhD dissertation. However, it does require a holistic perspective, and such dissertation topics may create an opportunity for systems scientists. When Russell Ackoff created the Social Systems Sciences PhD program at the Wharton School of the University of Pennsylvania, he had his students solve practical problems for business or government managers. That program graduated a large number of people who became consultants. A few became academics in several countries. The program created a philosophy and methods for holistic management. Large issues in developing countries may be a source of clients for systems scientists who want to further develop philosophy, theories and methods by working with large social systems

A Short History of Cybernetics in the United States: The Origin of Cybernetics

Key events in the history of cybernetics and the American Society for Cybernetics are discussed, among them the origin of cybernetics in the Macy Foundation conferences in the late 1940s and early 1950s; different interpretations of cybernetics by several professional societies; reasons why the U.S. government did or did not support cybernetics in the 1950s, 1960s, and 1970s; early experiments in cyberspace in the 1970s; conversations with Soviet scientists in the 1980s; the development of „second order“ cybernetics; and increased interest in cybernetics in Europe and the United States in the 2000s, due at least in part to improved understanding of the assumptions underlying the cybernetics movement. The history of cybernetics in the United States is viewed from the perspective of the American Society for Cybernetics (ASC) and several questions are addressed as to its future.Key events in the history of cybernetics and the American Society for Cybernetics are discussed, among them the origin of cybernetics in the Macy Foundation conferences in the late 1940s and early 1950s; different interpretations of cybernetics by several professional societies; reasons why the U.S. government did or did not support cybernetics in the 1950s, 1960s, and 1970s; early experiments in cyberspace in the 1970s; conversations with Soviet scientists in the 1980s; the development of „second order“ cybernetics; and increased interest in cybernetics in Europe and the United States in the 2000s, due at least in part to improved understanding of the assumptions underlying the cybernetics movement. The history of cybernetics in the United States is viewed from the perspective of the American Society for Cybernetics (ASC) and several questions are addressed as to its future

Should knowledge of management be organized as theories or as methods?

The philosophy of science has traditionally assumed that knowledge should be organized in the form of theories. From theories propositions can be deduced that can be tested in experiments. Most propositions deduced from theories take the form of if-then statements. For example, if variable A increases, what happens to variable B, assuming that all other variables are held constant? However, an alternative way of organizing knowledge, in the form of producer-product relationships, was proposed by the philosopher E.A. Singer, Jr. and advocated by two of his students, C. West Churchman and Russell L. Ackoff. Whether to structure knowledge in the form of theories or methods is related to the question of whether there is a fundamental difference between the natural and the social sciences. As opposed to Karl Popper’s doctrine of the unity of method, this paper argues that structuring knowledge in the form of methods is appropriate in applied fields, particularly in management where a large part of the task is to achieve agreement among a group of knowing subjects on an appropriate set of actions

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant