Measuring and improving adaptive capacity in resilient systems by means of an integrated DEA-Machine learning approach.

Resilient systems strive to enhance the safety of complex systems through building and developing adaptive technological and organizational capacities. This study aims at analyzing and improving the level of adaptive capacity in a petrochemical plant by means of an integrated quantitative approach. The data were gathered by a questionnaire whose reliability is examined by statistical methods. To compute and analyze the influence of resilience engineering (RE) indicators, teamwork, and redundancy on adaptive capacity, data envelopment analysis (DEA) method was used. The results indicate that teamwork and redundancy have a positive effect on enhancing the level of adaptive capacity. Multilayer perceptron (MLP), a machine learning approach, was used to estimate the level of adaptive capacity on the basis of a dataset. The results of DEA and MLP approaches are confirmed by statistical methods. To the best of our knowledge, this is the first study that measures quantitatively and improves adaptive capacity by an integrated DEA-MLP approach based on the stress-strain model. The outcomes of this study could assist managers and other decision-makers of complex systems to compute and improve the level of adaptive capacity for coping with upcoming events in abnormal conditions.

Perceptions of physiotherapists towards research: a mixed methods study.

OBJECTIVES: To explore the perceptions of physiotherapists towards the use of and participation in research. DESIGN: Concurrent mixed methods research, combining in-depth interviews with three questionnaires (demographics, Edmonton Research Orientation Survey, visual analogue scales for confidence and motivation to participate in research). SETTING: One physiotherapy department in a rehabilitation hospital, consisting of seven specialised areas. PARTICIPANTS: Twenty-five subjects {four men and 21 women, mean age 38 [standard deviation (SD) 11] years} who had been registered as a physiotherapist for a mean period of 15 (SD 10) years participated in this study. They were registered with the New Zealand Board of Physiotherapy, held a current practising certificate, and were working as a physiotherapist or physiotherapy/allied health manager at the hospital. MAIN OUTCOME MEASURE: The primary outcome measure was in-depth interviews and the secondary outcome measures were the three questionnaires. RESULTS: Physiotherapists were generally positive towards research, but struggled with the concept of research, the available literature and the time to commit to research. Individual confidence and orientation towards research seemed to influence how these barriers were perceived. CONCLUSION: This study showed that physiotherapists struggle to implement research in their daily practice and become involved in research. Changing physiotherapists' conceptions of research, making it more accessible and providing dedicated research time could facilitate increased involvement in the physiotherapy profession.

Responsibility for controlled drugs in operating departments.

The difficulties experienced with the recruitment and retention of registered nurses has made it necessary for NHS trusts to review the traditional role of nurses and to transfer some of their duties to other groups of staff in order to maintain services. For example, in the operating department, operating department assistants and operating department practitioners (ODAs/ODPs) are undertaking some of the duties that were previously the responsibility of nurses. This article presents the findings of a survey to determine the extent to which ODAs/ODPs have access to controlled drugs in operating theatres. The survey was initially undertaken by the author in Welsh hospitals during 1998. The mixed responses generated discussion in the Duthie Review Committee (Committee Chairman, personal communication, Royal Pharmaceutical Society of Great Britain (RPSGB), 1999) and led to a collaborative exercise based on a random selection of NHS trust hospitals in England, Scotland and Northern Ireland to obtain a broader data across the UK. Despite a clear legal position concerning possession, the survey showed that practice varied widely and that some trusts may be contravening the Misuse of Drugs Regulations 1985 in order to keep the service running when registered nurses are not available.

Relationships between prescription and non-prescription drug use in an elderly population.

This paper explores, at an epidemiological level, the relationship between categories of over-the-counter (OTC) and prescribed (Rx) drugs in a community-resident elderly population. A total of 2818, randomly selected, older adults were interviewed at home about their use of prescribed and non-prescribed medication and other health-related factors. For comparative purposes OTC drugs were classified into 16 therapeutic groups-identical to those used by other researchers; prescribed drugs were classified into 45 British National Formulary (BNF) therapeutic sub-categories. Analyses revealed significant association between certain BNF categories and OTC categories, which may have a clinical explanation. These include a 3-fold increase (P<0.01) of OTC laxative use by those prescribed an antidepressant, and a 4-fold increase (P<0.001) in OTC antacid use among those prescribed oral corticosteroids. Our findings may indicate an attempt by older people to control side effects of prescription medicines with OTC preparations. This study, in part, supports the call by the Royal College of Physicians for further research to determine the effect of interactions (be they pharmacological, behavioural or otherwise) between OTC and prescribed medicines.

Hepatic portal infiltrates in mice immunized with syngeneic lymphoid cells: connotations for models of autoimmune liver disease.

The aim of this study was to investigate liver histology in mice after immunization with the conserved self molecule dihydrolipoamide dehydrogenase, E3, a subunit of the mitochondrial 2-OADC enzyme family identified as the M2 autoantigen in the liver disease, primary biliary cirrhosis. Mice were immunized by a novel procedure. The autoantigen E3 was introduced by pinocytosis into hypertonically treated syngeneic lymphoid cells to facilitate intracellular antigen processing and presentation and the generation of a cytolytic T cell response. Liver sections were examined and scored for evidence of an inflammatory response by two independent procedures: standard microscopy with visual scoring, and automated scanning with computerized scoring. There was a close correlation between read-outs of liver histology by standard microscopy and automated scanning, using the index of mononuclear cellular infiltrations in hepatic portal tracts. Such infiltrates were prominent in the immunized mice, but, unexpectedly, the degree of infiltration was similar in mice injected with autoantigen (E3)-loaded syngeneic cells, or syngeneic cells treated only with hypertonic medium. The equivalent changes in the liver with the experimental and control protocol is indicative of the reactivity of the liver to any provocative immune stimulus, and is cautionary for protocols designed for the induction of autoimmune liver disease in experimental animals.

Is the number of surgical day cases a good indicator of rising drug costs?

There have been various attempts to reduce the expenditure on drugs-limited lists, drug formularies, prescribing policies, etc. The number of occupied beds in hospitals has fallen, and other indicators of hospital work have altered little. In spite of this, the expenditure on drugs by the hospitals in Wales has continued to rise. Taking two groups (antibiotics and anaesthetic agents) as examples of the high-cost drugs, the expenditure has been related to a number of indicators of the workload of a hospital. No clear relationship between any one indicator has been demonstrated although the number of surgical day cases is an important factor.

Polymorphonuclear neutrophils release 35S-labelled proteoglycans into cartilage during frustrated phagocytosis.

Rabbit peritoneal polymorphonuclear neutrophils (PMN), incubated in medium containing [35S]sulphate, incorporated 35S into proteoglycan and protein fractions. Approximately 46% of the 35S-labelled macromolecules associated with the PMN cells after 1 h of incubation were recovered in a cytoplasmic granule extract, the majority being present in azurophil granules. Analysis of the azurophil granule fraction showed that approximately 90% of the 35S-labelled macromolecules were proteoglycans. When challenged with heat-aggregated rabbit gamma-globulin in the presence of cytochalasin B and cGMP, PMN were induced to release granular enzymes but did not release 35S-labelled proteoglycans into the incubation medium. When incubated with articular cartilage slices, PMN released their granule 35S-labelled proteoglycan into the medium and into the cartilage matrix. Granule enzymes and 35S-labelled granule proteoglycan were extracted from the cartilage tissue after incubation and 35S-labelled macromolecules were detected in the cartilage tissue by autoradiography.

Characterization of the specificity of a naturally-occurring monoclonal anti-thymocyte autoantibody derived from an unimmunized, neonatal Balb/c mouse.

The immune repertoire of healthy unimmunized Balb/c mice contains a significant proportion of B lymphocytes which produce natural autoantibodies. The majority of these predominantly CD5+ B lymphocytes, secrete autoantibodies which react with conserved intracellular autoantigens such as actin, myosin and DNA. Significantly fewer autoreactive B lymphocytes produce natural autoantibodies reactive with cell surface autoantigens. In the present study, the specificity of monoclonal IgM kappa anti-thymocyte autoantibodies from hybridoma NMT-1 (NMT-1 maAbs), derived from the spleen of an unimmunized 8-day-old inbred Balb/c mouse has been examined. Anti-thymocyte NMT-1 maAbs reacted with cell surface molecules on 86-87% thymocytes from mice 1-28 days of age. Thymus-restricted expression of the identified autoantigen was demonstrated by the lack of detectable reactivity of NMT-1 maAbs to cell surface molecules of Balb/c mouse splenocytes, PBLs, lymph node, peritoneal and bone marrow cells and tissues including brain, liver and kidney. Furthermore, multiparameter flow cytometry demonstrated an association between the expression of the cell surface autoantigen identified by NMT-1 maAbs and thymocyte maturation as 94-97% of the CD4+ CD8+ thymocytes expressed the identified autoantigen which was largely absent from CD3+ thymocytes and not expressed in the peripheral immune system. Tissue distribution, flow cytometry and competition analysis indicated differences between identified T lymphocyte markers, including Thy-1, and the autoantigen identified by NMT-1 maAbs in this study. Immunoprecipitation analysis, however, revealed that NMT-1 maAbs reacted with 14.5 and 18.3 kDa Thy-1-related autoantigens within Balb/c mouse thymocyte membrane extracts, possibly unique glycosylated forms of the Thy-1 molecule.

Rapid isolation of rat brain nuclei on percoll gradients.

A rapid isotonic method for fractionation of nuclei from rat brain is described. This procedure is based on the use of discontinuous colloidal silica gel (Percoll) gradients. We start from a 63,000-g purified nuclear pellet (fraction P3) isolated from gray matter and white matter separately. This is followed by fractionation of fraction P3 in an initial differential centrifugation step on five-step Percoll gradients producing six nuclear fractions designated 1, 2, 3 (gray matter) and 4, 5, 6 (white matter). Fractions 2, 4, and 5 obtained from this centrifugation are heterogeneous. These fractions are subfractionated further under isopycnic conditions using five-step Percoll gradients to yield subfractions 2b, 4b, and 5c. Three methods were used to characterize the nuclear types. First, light and electron microscopic examination was used to identify the nuclei in each preparation and to assess the purity of each preparation. Second, the activities of RNA polymerase I and II were monitored. Third, the protein/DNA ratios of the nuclear fractions were determined. Fraction 1 was enriched in neuronal nuclei; fractions 2b and 4b in astrocytic nuclei; and fractions 3, 5c, and 6 in nuclei of oligodendrocytes. RNA polymerase I and II activity was highest in fraction 1, which also displayed the highest protein/DNA ratio. Electron microscopy showed that the various classes of nuclei are congruent to 90% pure. Therefore, the procedure described here is suitable for obtaining highly purified neuronal and three types of glial nuclei from rat brain.

Pharmacokinetics, tissue distribution, and cell localization of [35S]methionine-labeled recombinant human and murine alpha interferons in mice.

The pharmacokinetics, tissue distribution, cell localization, and penetration into tumor xenografts of recombinant [35S]methionine-labeled human alpha interferon (HuIFN-alpha) and murine alpha interferon (MuIFN-alpha) were examined in mice. Both interferons (IFNs) were removed from the blood in a rapid biphasic manner; HuIFN-alpha was cleared faster than MuIFN-alpha. Tissues were analyzed for radioactivity and over 90% of the IFNs was accounted for. The IFNs were detected predominantly in liver, kidney, gastrointestinal tract, pancreas, spleen, and lung. The levels of MuIFN-alpha compared with HuIFN-alpha were greater in the liver, spleen, and lung and less in the kidney, pancreas, and gastrointestinal tract. Heart, brain, testes, thymus, lymph nodes, fat, skin, and skeletal muscle contained much lower but measurable levels of both IFNs. There was penetration of HuIFN-alpha into tumor xenografts. The pharmacokinetics of IFN-alpha were independent of the strain of mouse, BALB/c or CBA, immune deprivation, or the presence of a tumor xenograft. Autoradiography of tissue sections from mice given injections of HuIFN-alpha or MuIFN-alpha indicated focal radioactivity in proximal convoluted tubules in the kidney and diffuse radioactivity in the liver, gastrointestinal tract, and pancrease. MuIFN-alpha, but not HuIFN-alpha, showed intense localization in cells in hepatic sinusoids, marginal zones in the spleen, and pulmonary alveolar walls, suggesting uptake by cells of the monocyte/macrophage lineage in these sites. The study shows the utility of biosynthetic labeling for pharmacokinetic studies of cytokines, clear differences in tissue distribution of IFN-alpha according to its species of origin, and targeting of homologous IFN-alpha to cells of the monocytic lineage.