Knowledge and development : a cross-section approach

This paper assesses the effects of knowledge on economic growth. By using an array of indicators, each of which represents an aspect of knowledge, as independent variables in cross-section regressions that span 92 countries for the period 1960 to 2000, they show that knowledge is a significant determinant of long-term economic growth. In particular, the authors find that the stock of human capital, the level of domestic innovation and technological adaptation, and the level of information and communications technologies (ICT) infrastructure all exert statistically significant positive effects on long-term economic growth. More specifically with regard to the growth effects of the human capital stock, they find that an increase of 20 percent in the average years of schooling of a population tends to increase the average annual economic growth by 0.15 percentage point. In terms of innovation, the authors find that a 20 percent increase in the annual number of USPTO patents granted is associated with an increase of 3.8 percentage points in annual economic growth. Lastly, when the ICT infrastructure, measured by the number of telephones per 1,000 persons, is increased by 20 percent, they find that annual economic growth tends to increase by 0.11 percentage point.Environmental Economics&Policies,Labor Policies,Public Health Promotion,Economic Theory&Research,Health Monitoring&Evaluation,Environmental Economics&Policies,Economic Growth,Health Monitoring&Evaluation,Achieving Shared Growth,Economic Theory&Research

Eye Tracking during High Speed Navigation at Sea

Purpose: Professional high speed sea navigational procedures are based on turn points, courses, dangers and steering cues in the environment. Since navigational aids have become less expensive and due to the fact that electronic sea charts can be integrated with both radar and transponder information, it may be assumed that traditional navigation by using paper based charts and radar will play a less significant role in the future, especially among less experienced navigators. Possible navigational differences between experienced and non-experienced boat drivers is thus of interest with regards to their use of navigational aids. It may be assumed that less experienced navigators rely too much on the information given by the electronic sea chart, despite the fact that it is based on GPS information that can be questioned, especially in littoral waters close to land.Method: This eye tracking study investigates gaze behaviour from 16 experienced and novice boat drivers during high speed navigation at sea.Results: The results show that the novice drivers look at objects that are close to themselves, like instrumentation, while the experienced look more at objects far away from the boat. This is in accordance with previous research on car drivers. Further, novice boat drivers used the electronic navigational aids to a larger extent than the experienced, especially during high speed conditions. The experienced drivers focused much of their attention on objects outside the boat.Conclusions: The findings verify that novice boat drivers tend to rely on electronic navigational aids. Experienced drivers presumably use the navigational aids to verify what they have observed in the surrounding environment and further use the paper based sea chart to a larger extent than the novice drivers

The opportunity prior: a proof-based prior for criminal cases

One of the greatest challenges to the use of probabilistic reasoning in the assessment of criminal evidence is the ‘problem of the prior’, i.e. the difficulty in establishing an acceptable prior probability of guilt. Even strong supporters of a Bayesian approach have often preferred to ignore priors and focus on the likelihood ratio (LR) of the evidence. But to calculate if the probability of guilt, given the evidence reaches the probability required for conviction (the standard of proof), the LR has to be combined with a prior. In this article, we propose a solution to the ‘problem of the prior’: the defendant shall be treated as a member of the set of ‘possible perpetrators’ defined as the people who had the same or better opportunity as the defendant to commit the crime. For this purpose, we introduce the concept of an ‘extended crime scene’. The number of people who had the same or better opportunity as the defendant is the number of people who were just as close or closer to the crime scene, in time and space. We demonstrate how the opportunity prior is incorporated into a generic Bayesian network model that allows us to integrate other evidence about the case

The Opportunity Prior: A Simple and Practical Solution to the Prior Probability Problem for Legal Cases

One of the greatest impediments to the use of probabilistic reasoning in legal arguments is the difficulty in agreeing on an appropriate prior probability for the ultimate hypothesis, (in criminal cases this is normally “Defendant is guilty of the crime for which he/she is accused”). Even strong supporters of a Bayesian approach prefer to ignore priors and focus instead on considering only the likelihood ratio (LR) of the evidence. But the LR still requires the decision maker (be it a judge or juror during trial, or anybody helping to determine beforehand whether a case should proceed to trial) to consider their own prior; without it the LR has limited value. We show that, in a large class of cases, it is possible to arrive at a realistic prior that is also as consistent as possible with the legal notion of ‘innocent until proven guilty’. The approach can be considered as a formalisation of the ‘island problem’ whereby if it is known the crime took place on an island when n people were present, then each of the people on the island has an equal prior probability 1/n of having carried out the crime. Our prior is based on simple location and time parameters that determine both a) the crime scene/time (within which it is certain the crime took place) and b) the extended crime scene/time which is the ‘smallest’ within which it is certain the suspect was known to have been ‘closest’ in location/time to the crime scene. The method applies to cases where we assume a crime has taken place and that it was committed by one person against one other person (e.g. murder, assault, robbery). The paper considers both the practical and legal implications of the approach. We demonstrate how the opportunity prior probability is naturally incorporated into a generic Bayesian network model that allows us to integrate other evidence about the case

IKK/NF-κB regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis

Nuclear factor κB (NF-κB) is involved in multiple skeletal muscle disorders, but how it functions in differentiation remains elusive given that both anti- and promyogenic activities have been described. In this study, we resolve this by showing that myogenesis is controlled by opposing NF-κB signaling pathways. We find that myogenesis is enhanced in MyoD-expressing fibroblasts deficient in classical pathway components RelA/p65, inhibitor of κB kinase β (IKKβ), or IKKγ. Similar increases occur in myoblasts lacking RelA/p65 or IKKβ, and muscles from RelA/p65 or IKKβ mutant mice also contain higher fiber numbers. Moreover, we show that during differentiation, classical NF-κB signaling decreases, whereas the induction of alternative members IKKα, RelB, and p52 occurs late in myogenesis. Myotube formation does not require alternative signaling, but it is important for myotube maintenance in response to metabolic stress. Furthermore, overexpression or knockdown of IKKα regulates mitochondrial content and function, suggesting that alternative signaling stimulates mitochondrial biogenesis. Together, these data reveal a unique IKK/NF-κB signaling switch that functions to both inhibit differentiation and promote myotube homeostasis

FAS and NF-κB signalling modulate dependence of lung cancers on mutant EGFR

Human lung adenocarcinomas with activating mutations in EGFR (epidermal growth factor receptor) often respond to treatment with EGFR tyrosine kinase inhibitors (TKIs), but the magnitude of tumour regression is variable and transient. This heterogeneity in treatment response could result from genetic modifiers that regulate the degree to which tumour cells are dependent on mutant EGFR. Through a pooled RNA interference screen, we show that knockdown of FAS and several components of the NF-κB pathway specifically enhanced cell death induced by the EGFR TKI erlotinib in EGFR-mutant lung cancer cells. Activation of NF-κB through overexpression of c-FLIP or IKK (also known as CFLAR and IKBKB, respectively), or silencing of IκB (also known as NFKBIA), rescued EGFR-mutant lung cancer cells from EGFR TKI treatment. Genetic or pharmacologic inhibition of NF-κB enhanced erlotinib-induced apoptosis in erlotinib-sensitive and erlotinib-resistant EGFR-mutant lung cancer models. Increased expression of the NF-κB inhibitor IκB predicted for improved response and survival in EGFR-mutant lung cancer patients treated with EGFR TKI. These data identify NF-κB as a potential companion drug target, together with EGFR, in EGFR-mutant lung cancers and provide insight into the mechanisms by which tumour cells escape from oncogene dependence

Adipose tissue pathways involved in weight loss of cancer cachexia

White adipose tissue (WAT) constitutes our most expandable tissue and largest endocrine organ secreting hundreds of polypeptides collectively termed adipokines. Changes in WAT mass induce alterations in adipocyte secretion and function, which are linked to disturbed whole-body metabolism. Although the mechanisms controlling this are not clear they are dependent on changes in gene expression, a complex process which is regulated at several levels. Results in recent years have highlighted the role of small non-coding RNA molecules termed microRNAs (miRNAs), which regulate gene expression via post-transcriptional mechanisms. The aim of this thesis was to characterize global gene expression levels and describe novel miRNAs and adipokines controlling the function of human WAT in conditions with pathological increases or decreases in WAT mass. Obesity and cancer cachexia were selected as two models since they are both clinically relevant and characterized by involuntary changes in WAT mass. In Study I, expressional analyses were performed in subcutaneous WAT from cancer patients with or without cachexia and obese versus non-obese subjects. In total, 425 transcripts were found to be regulated in cancer cachexia. Pathway analyses based on this set of genes revealed that processes involving extracellular matrix, actin cytoskeleton and focal adhesion were significantly downregulated, whereas fatty acid metabolism was upregulated comparing cachectic with weight-stable cancer subjects. Furthermore, by overlapping these results with microarray data from an obesity study, many transcripts were found to be reciprocally regulated comparing the two conditions. This suggests that WAT gene expression in cancer cachexia and obesity are regulated by similar, albeit opposing, mechanisms. In Study II, the focus was on the family of fibroblast growth factors (FGFs), members of which have recently been implicated in the development of obesity and insulin resistance. A retrospective analysis of global gene expression data identified several FGFs (FGF1/2/7/9/13/18) to be expressed in WAT. However, only one, FGF1, was actively secreted from WAT and predominantly so from the adipocyte fraction. Moreover, FGF1 release was increased in obese compared to non-obese subjects, but was not normalized by weight loss. Although the clinical significance of these findings is not yet clear, it can be hypothesized that FGF1 may play a role in WAT growth, possibly by promoting fat cell proliferation and/or differentiation. In Study III, we identified adipose miRNAs regulated in obesity. Out of eleven miRNAs regulated by changes in body fat mass, ten controlled the production of the pro-inflammatory chemoattractant chemokine (C-C motif) ligand 2 (CCL2) when overexpressed in fat cells and for two, miR-126 and -193b, signaling circuits were defined. In Study IV, a novel adipokine, semaphorin 3C (SEMA3C), was identified by combining transcriptome and secretome data. Detailed studies focusing on SEMA3C revealed that this factor was secreted from adipocytes and induced the expression of extracellular matrix and matricellular genes in preadipocytes. Furthermore, SEMA3C mRNA levels correlated with interstitial fibrosis and insulin resistance in WAT derived from subjects with a wide range in BMI. In summary, the results presented in this thesis have delineated transcriptional alterations in WAT in two clinically relevant conditions, obesity and cancer cachexia. This has allowed the identification of novel adipokines and microRNAs with potential pathophysiological importance. These findings form the basis for further studies aiming at understanding the central role of WAT in disorders associated with metabolic complications