Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u

Clostridium difficile Infections amongst Patients with Haematological Malignancies: A Data Linkage Study

OBJECTIVES: Identify risk factors for Clostridium difficile infection (CDI) and assess CDI outcomes among Australian patients with a haematological malignancy. METHODS: A retrospective cohort study involving all patients admitted to hospitals in Western Australia with a haematological malignancy from July 2011 to June 2012. Hospital admission data were linked with all hospital investigated CDI case data. Potential risk factors were assessed by logistic regression. The risk of death within 60 and 90 days of CDI was assessed by Cox Proportional Hazards regression. RESULTS: There were 2085 patients of whom 65 had at least one CDI. Twenty percent of CDI cases were either community-acquired, indeterminate source or had only single-day admissions in the 28 days prior to CDI. Using logistic regression, having acute lymphocytic leukaemia, neutropenia and having had bacterial pneumonia or another bacterial infection were associated with CDI. CDI was associated with an increased risk of death within 60 and 90 days post CDI, but only two deaths had CDI recorded as an antecedent factor. Ribotyping information was available for 33 of the 65 CDIs. There were 19 different ribotypes identified. CONCLUSIONS: Neutropenia was strongly associated with CDI. While having CDI is a risk factor for death, in many cases it may not be a direct contributor to death but may reflect patients having higher morbidity. A wide variety of C. difficile ribotypes were found and community-acquired infection may be under-estimated in these patients

Cardiovascular MR evaluation of symptomatic severe aortic stenosis: association of circumferential myocardial strain and mortality

Background It is unknown whether circumferential strain is associated with prognosis after treatment of aortic stenosis (AS). We aimed to characterise strain in severe AS, using myocardial tagging cardiovascular magnetic resonance (CMR), prior to and following Transcatheter Aortic Valve Implantation (TAVI) and Surgical Aortic Valve Replacement (SAVR), and determine whether abnormalities in strain were associated with outcome. Methods CMR was performed pre- and 6 m post-intervention in 98 patients (52 TAVI, 46 SAVR; 77 ± 8 years) with severe AS. TAVI patients were older (80.9 ± 6.4 vs. 73.0 ± 7.0 years, p  −18.7% was associated with significantly reduced survival. Conclusion TAVI and SAVR procedures are associated with comparable declines in rotational LV mechanics at 6 m, with largely unchanged strain and strain rates. Pre-operative peak mid LV circumferential strain is associated with post-operative mortality

HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder

The mortality from transitional cell carcinoma (TCC) of the urinary bladder increases significantly with the progression of superficial or locally invasive disease (pTa/pT1) to detrusor muscle-invasive disease (pT2+). The most common prognostic markers in clinical use are tumour stage and grade, which are subject to considerable intra- and interobserver variation. Polysomy 17 and HER2/neu gene amplification and protein overexpression have been associated with more advanced disease. Standardised techniques of fluorescence in situ hybridisation and immunohistochemistry, which are currently applied to other cancers with a view to offering anti-HER2/neu therapies, were applied to tumour pairs comprising pre- and postinvasive disease from 25 patients undergoing treatment for bladder cancer. In the preinvasive tumours, increased HER2/neu copy number was observed in 76% of cases and increased chromosome 17 copy number in 88% of cases, and in the postinvasive group these values were 92 and 96%, respectively (not significantly different P=0.09 and 0.07, respectively). HER2 gene amplification rates were 8% in both groups. Protein overexpression rates were 76 and 52%, respectively, in the pre- and postinvasive groups (P=0.06). These results suggest that HER2/neu abnormalities occur prior to and persist with the onset of muscle-invasive disease. Gene amplification is uncommon and other molecular mechanisms must account for the high rates of protein overexpression. Anti-HER2/neu therapy might be of use in the treatment of TCC

Assessment of explanatory models of mental illness: effects of patient and interviewer characteristics

Background: Explanatory models (EMs) refer to patients’ causal attributions of illness and have been shown to affect treatment preference and outcome. Reliable and valid assessment of EMs may be hindered by interviewer and respondent disparities on certain demographic characteristics, such as ethnicity. The present study examined (a) whether ethnic minority patients reported different EMs to ethnically similar interviewers in comparison with those with a different ethnicity, and (b) whether this effect was related to respondents’ social desirability, the perceived rapport with the interviewer and level of uncertainty toward their EMs. Methods: A total of 55 patients of Turkish and Moroccan origins with mood and anxiety disorders were randomly assigned to ethnically similar or dissimilar interviewers. EMs were assessed, using a semi-structured interview, across 11 different categories of causes. Results: Participants who were interviewed by an ethnically similar interviewer perceived interpersonal, victimization and religious/mystical causes as more important, whereas interviews by ethnically dissimilar interviewers generated higher scores on medical causes. These effects were not mediated by the perceived rapport with the interviewer, and social desirability had a modest impact on the results. Higher uncertainty among participants toward medical and religious/mystical causes seemed to be associated with greater adjustment in the report of these EMs. Conclusion: The findings have significant implications for interviewer selection in epidemiological research and clinical practice

University–industry linkages and academic engagements: individual behaviours and firms’ barriers. Introduction to the special section

The article introduces the special section on “University–industry linkages and academic engagements: Individual behaviours and firms’ barriers”. We first revisit the latest developments of the literature and policy interest on university–industry research. We then build upon the extant literature and unpack the concept of academic engagement by further exploring the heterogeneity of UI linkages along a set of dimensions and actors involved. These are: (1) Incentives and behaviours of individual academic entrepreneurs; (2) Firms’ barriers to cooperation with public research institutions; (3) Individual behaviours, incentives and organizational bottlenecks in late developing countries. We summarize the individual contributions along these dimensions. There are overlooked individual characteristics that affect the degree of engagement of academics and scholars in cooperating with other organizations, of which gender and the non-academic background of individuals are most crucial. The notion of academic engagement should be enlarged to aspects that go beyond the commercialization or patenting of innovation, but embrace social and economic impact more at large. From the perspective of the firm, barriers to innovation might exert an effect on the likelihood to cooperate with universities and public research institutes, most especially to cope with lack of finance or access to frontier knowledge. We finally propose a research agenda that addresses the challenges ahead

Compliance assessment of ambulatory Alzheimer patients to aid therapeutic decisions by healthcare professionals

<p>Abstract</p> <p>Background</p> <p>Compliance represents a major determinant for the effectiveness of pharmacotherapy. Compliance reports summarising electronically compiled compliance data qualify healthcare needs and can be utilised as part of a compliance enhancing intervention. Nevertheless, evidence-based information on a sufficient level of compliance is scarce complicating the interpretation of compliance reports. The purpose of our pilot study was to determine the compliance of ambulatory Alzheimer patients to antidementia drugs under routine therapeutic use using electronic monitoring. In addition, the forgiveness of donepezil (i.e. its ability to sustain adequate pharmacological response despite suboptimal compliance) was characterised and evidence-based guidance for the interpretation of compliance reports was intended to be developed.</p> <p>Methods</p> <p>We determined the compliance of four different antidementia drugs by electronic monitoring in 31 patients over six months. All patients were recruited from the gerontopsychiatric clinic of a university hospital as part of a pilot study. The so called medication event monitoring system (MEMS) was employed, consisting of a vial with a microprocessor in the lid which records the time (date, hour, minute) of every opening. Daily compliance served as primary outcome measure, defined as percentage of days with correctly administered doses of medication. In addition, pharmacokinetics and pharmacodynamics of donepezil were simulated to systematically assess therapeutic undersupply also incorporating study compliance patterns. Statistical analyses were performed with SPSS and Microsoft Excel.</p> <p>Results</p> <p>Median daily compliance was 94% (range 48%-99%). Ten patients (32%) were non-compliant at least for one month. One-sixth of patients taking donepezil displayed periods of therapeutic undersupply. For 10 mg and 5 mg donepezil once-daily dosing, the estimated forgiveness of donepezil was 80% and 90% daily compliance or two and one dosage omissions at steady state, respectively. Based on the simulation findings we developed rules for the evidence-based interpretation of donepezil compliance reports.</p> <p>Conclusions</p> <p>Compliance in ambulatory Alzheimer patients was for the first time assessed under routine conditions using electronic monitoring: On average compliance was relatively high but variable between patients. The approach of pharmacokinetic/pharmacodynamic <it>in silico </it>simulations was suitable to characterise the forgiveness of donepezil suggesting evidence-based recommendations for the interpretation of compliance reports.</p

Acromioclavicular joint reconstruction with coracoacromial ligament transfer using the docking technique

<p>Abstract</p> <p>Background</p> <p>Symptomatic Acromioclavicular (AC) dislocations have historically been surgically treated with Coracoclavicular (CC) ligament reconstruction with transfer of the Coracoacromial (CA) ligament. Tensioning the CA ligament is the key to success.</p> <p>Methods</p> <p>Seventeen patients with chronic, symptomatic Type III AC joint or acute Type IV and V injuries were treated surgically. The distal clavicle was resected and stabilized with CC ligament reconstruction using the CA ligament. The CA ligament was passed into the medullary canal and tensioned, using a modified 'docking' technique. Average follow-up was 29 months (range 12–57).</p> <p>Results</p> <p>Postoperative ASES and pain significantly improved in all patients (p = 0.001). Radiographically, 16 (94%) maintained reduction, and only 1 (6%) had a recurrent dislocation when he returned to karate 3 months postoperatively. His ultimate clinical outcome was excellent.</p> <p>Conclusion</p> <p>The docking procedure allows for tensioning of the transferred CA ligament and healing of the ligament in an intramedullary bone tunnel. Excellent clinical results were achieved, decreasing the risk of recurrent distal clavicle instability.</p

Happy Aged People Are All Alike, While Every Unhappy Aged Person Is Unhappy in Its Own Way

Aging of the world's population represents one of the most remarkable success stories of medicine and of humankind, but it is also a source of various challenges. The aim of the collaborative cross-cultural European study of adult well being (ESAW) is to frame the concept of aging successfully within a causal model that embraces physical health and functional status, cognitive efficacy, material security, social support resources, and life activity. Within the framework of this project, we show here that the degree of heterogeneity among people who view aging in a positive light is significantly lower than the degree of heterogeneity of those who hold a negative perception of aging. We base this conclusion on our analysis of a survey involving 12,478 people aged 50 to 90 from six West European countries. We treat the survey database as a bipartite network in which individual respondents are linked to the actual answers they provide. Taking this perspective allows us to construct a projected network of respondents in which each link indicates a statistically validated similarity of answers profile between the connected respondents, and to identify clusters of individuals independently of demographics. We show that mental and physical well-being are key factors determining a positive perception of aging. We further observe that psychological aspects, like self-esteem and resilience, and the nationality of respondents are relevant aspects to discriminate among participants who indicate positive perception of aging

Protein Expression in the Nucleus Accumbens of Rats Exposed to Developmental Vitamin D Deficiency

Introduction: Developmental vitamin D (DVD) deficiency is a candidate risk factor for schizophrenia. Animal models have confirmed that DVD deficiency is associated with a range of altered genomic, proteomic, structural and behavioural outcomes in the rat. Because the nucleus accumbens has been implicated in neuropsychiatric disorders, in the current study we examined protein expression in this region in adult rats exposed to DVD deficienc