Innovation and productivity among heterogeneous firms

This paper examines the links between firm innovation and productivity using the largest cross-country panel dataset assembled for this purpose to date. We use harmonized and comparable data on a total of 40,577 small, medium and large firms surveyed in the World Bank Enterprise Surveys (WBES) and provide some support for the reported patterns previously found in the innovation literature. Our results indicate that estimates from studies using cross-section data may be upward biased but nevertheless, innovative firms are significantly and economically more productive in both the manufacturing and services sectors

Can analyses of electronic patient records be independently and externally validated? The effect of statins on the mortality of patients with ischaemic heart disease: a cohort study with nested case-control analysis

Objective To conduct a fully independent and external validation of a research study based on one electronic health record database, using a different electronic database sampling the same population. Design Using the Clinical Practice Research Datalink (CPRD), we replicated a published investigation into the effects of statins in patients with ischaemic heart disease (IHD) by a different research team using QResearch. We replicated the original methods and analysed all-cause mortality using: (1) a cohort analysis and (2) a case-control analysis nested within the full cohort. Setting Electronic health record databases containing longitudinal patient consultation data from large numbers of general practices distributed throughout the UK. Participants CPRD data for 34 925 patients with IHD from 224 general practices, compared to previously published results from QResearch for 13 029 patients from 89 general practices. The study period was from January 1996 to December 2003. Results We successfully replicated the methods of the original study very closely. In a cohort analysis, risk of death was lower by 55% for patients on statins, compared with 53% for QResearch (adjusted HR 0.45, 95% CI 0.40 to 0.50; vs 0.47, 95% CI 0.41 to 0.53). In case-control analyses, patients on statins had a 31% lower odds of death, compared with 39% for QResearch (adjusted OR 0.69, 95% CI 0.63 to 0.75; vs OR 0.61, 95% CI 0.52 to 0.72). Results were also close for individual statins. Conclusions Database differences in population characteristics and in data definitions, recording, quality and completeness had a minimal impact on key statistical outputs. The results uphold the validity of research using CPRD and QResearch by providing independent evidence that both datasets produce very similar estimates of treatment effect, leading to the same clinical and policy decisions. Together with other non-independent replication studies, there is a nascent body of evidence for wider validity

Haplotype analysis of the PPARgamma Pro12Ala and C1431T variants reveals opposing associations with body weight.

BACKGROUND: Variation at the PPARG locus may influence susceptibility to type 2 diabetes and related traits. The Pro12Ala polymorphism may modulate receptor activity and is associated with protection from type 2 diabetes. However, there have been inconsistent reports of its association with obesity. The silent C1431T polymorphism has not been as extensively studied, but the rare T allele has also been inconsistently linked to increases in weight. Both rare alleles are in linkage disequilibrium and the independent associations of these two polymorphisms have not been addressed. RESULTS: We have genotyped a large population with type 2 diabetes (n = 1107), two populations of non-diabetics from Glasgow (n = 186) and Dundee (n = 254) and also a healthy group undergoing physical training (n = 148) and investigated the association of genotype with body mass index. This analysis has demonstrated that the Ala12 and T1431 alleles are present together in approximately 70% of the carriers. By considering the other 30% of individuals with haplotypes that only carry one of these polymorphisms, we have demonstrated that the Ala12 allele is consistently associated with a lower BMI, whilst the T1431 allele is consistently associated with higher BMI. CONCLUSION: This study has therefore revealed an opposing interaction of these polymorphisms, which may help to explain previous inconsistencies in the association of PPARG polymorphisms and body weight

Activity clamp provides insights into paradoxical effects of the anti-seizure drug carbamazepine

A major challenge in experimental epilepsy research is to reconcile the effects of anti-epileptic drugs (AEDs) on individual neurons with their network-level actions. Highlighting this difficulty, it is unclear why carbamazepine (CBZ), a front-line AED with a known molecular mechanism, has been reported to increase epileptiform activity in several clinical and experimental studies. We confirmed in an in vitro mouse model (both sexes) that the frequency of interictal bursts increased following CBZ perfusion. To address the underlying mechanisms we developed a method, activity clamp, to distinguish the response of individual neurons from network-level actions of CBZ. We first recorded barrages of synaptic conductances from neurons during epileptiform activity, and then replayed them in pharmacologically isolated neurons under control conditions and in the presence of CBZ. CBZ consistently decreased the reliability of the second action potential in each burst of activity. Conventional current clamp recordings using excitatory ramp or square step current injections failed to reveal this effect. Network modelling showed that a CBZ-induced decrease of neuron recruitment during epileptic bursts can lead to an increase in burst frequency at the network level, by reducing the refractoriness of excitatory transmission. By combining activity clamp with computer simulations, the present study provides a potential explanation for the paradoxical effects of CBZ on epileptiform activity.SIGNIFICANCE STATEMENTThe effects of anti-epileptic drugs on individual neurons are difficult to separate from their network-level actions. Although carbamazepine has a known anti-epileptic mechanism, it has also been reported to paradoxically increase epileptiform activity in clinical and experimental studies. To investigate this paradox during realistic neuronal epileptiform activity we developed a method, activity clamp, to distinguish effects of carbamazepine on individual neurons from network-level actions. We demonstrate that carbamazepine consistently decreases the reliability of the second action potential in each burst of epileptiform activity. Network modelling shows that this effect on individual neuronal responses could explain the paradoxical effect of carbamazepine at the network level

Statins are underused in recent-onset Parkinson's disease with increased vascular risk : findings from the UK Tracking Parkinson's and Oxford Parkinson's Disease Centre (OPDC) discovery cohorts

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.Peer reviewedPublisher PD

Risk, precaution and science: towards a more constructive policy debate. Talking point on the precautionary principle

Few issues in contemporary risk policy are as momentous or contentious as the precautionary principle. Since it first emerged in German environmental policy, it has been championed by environmentalists and consumer protection groups, and resisted by the industries they oppose (Raffensperger & Tickner, 1999). Various versions of the principle now proliferate across different national and international jurisdictions and policy areas (Fisher, 2002). From a guiding theme in European Commission (EC) environmental policy, it has become a general principle of EC law (CEC, 2000; Vos & Wendler, 2006). Its influence has extended from the regulation of environmental, technological and health risks to the wider governance of science, innovation and trade (O'Riordan & Cameron, 1994)

Decision Making for Inconsistent Expert Judgments Using Negative Probabilities

In this paper we provide a simple random-variable example of inconsistent information, and analyze it using three different approaches: Bayesian, quantum-like, and negative probabilities. We then show that, at least for this particular example, both the Bayesian and the quantum-like approaches have less normative power than the negative probabilities one.Comment: 14 pages, revised version to appear in the Proceedings of the QI2013 (Quantum Interactions) conferenc

Zebrafish as a model for cardiac disease; Cryo-EM structure of native cardiac thin filaments from Danio Rerio.

Actin, tropomyosin and troponin, the proteins that comprise the contractile apparatus of the cardiac thin filament, are highly conserved across species. We have used cryo-EM to study the three-dimensional structure of the zebrafish cardiac thin and actin filaments. With 70% of human genes having an obvious zebrafish orthologue, and conservation of 85% of disease-causing genes, zebrafish are a good animal model for the study of human disease. Our structure of the zebrafish thin filament reveals the molecular interactions between the constituent proteins, showing that the fundamental organisation of the complex is the same as that reported in the human reconstituted thin filament. A reconstruction of zebrafish cardiac F-actin demonstrates no deviations from human cardiac actin over an extended length of 14 actin subunits. Modelling zebrafish homology models into our maps enabled us to compare, in detail, the similarity with human models. The structural similarities of troponin-T in particular, a region known to contain a hypertrophic cardiomyopathy 'hotspot', confirm the suitability of zebrafish to study these disease-causing mutations

Misinterpreting carbon accumulation rates in records from near-surface peat

Peatlands are globally important stores of carbon (C) that contain a record of how their rates of C accumulation have changed over time. Recently, near-surface peat has been used to assess the effect of current land use practices on C accumulation rates in peatlands. However, the notion that accumulation rates in recently formed peat can be compared to those from older, deeper, peat is mistaken – continued decomposition means that the majority of newly added material will not become part of the long-term C store. Palaeoecologists have known for some time that high apparent C accumulation rates in recently formed peat are an artefact and take steps to account for it. Here we show, using a model, how the artefact arises. We also demonstrate that increased C accumulation rates in near-surface peat cannot be used to infer that a peatland as a whole is accumulating more C – in fact the reverse can be true because deep peat can be modified by events hundreds of years after it was formed. Our findings highlight that care is needed when evaluating recent C addition to peatlands especially because these interpretations could be wrongly used to inform land use policy and decisions

Airports at Risk: The Impact of Information Sources on Security Decisions

Security decisions in high risk organizations such as airports involve obtaining ongoing and frequent information about potential threats. Utilizing questionnaire survey data from a sample of airport employees in European Airports across the continent, we analyzed how both formal and informal sources of security information affect employee's decisions to comply with the security rules and directives. This led us to trace information network flows to assess its impact on the degree employees making security decisions comply or deviate with the prescribed security rules. The results of the multivariate analysis showed that security information obtained through formal and informal networks differentially determine if employee will comply or not with the rules. Information sources emanating from the informal network tends to encourage employees to be more flexible in their security decisions while formal sources lead to be more rigid with complying with rules and protocols. These results suggest that alongside the formal administrative structure of airports, there exists a diverse and pervasiveness set of informal communications networks that are a potent factor in determining airport security levels