Heterogeneity evidence and linkage studies on Charcot-Marie-Tooth disease

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder originally localized to chromosome 1 by linkage to the Duffy blood group. Studies have since shown that the disorder may be heterogeneous, as not all families show this linkage. We tested genetic heterogeneity by the HOMOG computer program in 15 CMT1 pedigrees informative for Duffy. We detected no evidence for heterogeneity in this sample, but when we combined results with previously published lod scores, heterogeneity was statistically significant. Twelve of the 15 families studied did not show linkage to Duffy. We found six of these families to be informative for a chromosome 19 marker, apolipoprotein CII(ApoC2). Despite a previous report showing probable linkage of a non-Duffy-linked CMT1 pedigree to two chromosome 19 markers, we did not detect significant linkage of ApoC2 to CMT1 in these families.

Familial typical migraine: Linkage to chromosome 19p13 and evidence for genetic heterogeneity

Migraine is a frequent familial disorder that, in common with most multifactorial disorders, has an unknown etiology. The authors identified several families with multiple individuals affected by typical migraine using a single set of diagnostic criteria and studied these families for cosegregation between the disorder and markers on chromosome 19, the location of a mutation that causes a rare form of familial hemiplegic migraine (FHM). One large tested family showed both cosegregation and significant allele sharing for markers situated within or adjacent to the FHM locus. Multipoint GENEHUNTER results indicated significant excess allele sharing across a 12.6- cM region containing the FHM Ca2+ channel gene, CACNL1A4 (maximum nonparametric linkage Z score = 6.64, p = 0.0026), with a maximum parametric lod score of 1.92 obtained for a (CAG)(n) triplet repeat polymorphism situated in exon 47 of this gene. The CAG expansion did not, however, appear to be the cause of migraine in this pedigree. Other tested families showed neither cosegregation nor excess allele sharing to chromosome 19 markers. HOMOG analysis indicated heterogeneity, generating a maximum HLOD score of 3.6. It was concluded that Chr19 mutations either in the CACNL1A4 gene or a closely linked gene are implicated in some pedigrees with familial typical migraine, and that the disorder is genetically heterogeneous.

Spatial and developmental heterogeneity of calcium signaling in olfactory ensheathing cells

Olfactory ensheathing cells (OECs) are specialized glial cells in the mammalian olfactory system supporting growth of axons from the olfactory epithelium into the olfactory bulb. OECs in the olfactory bulb can be subdivided into OECs of the outer nerve layer and the inner nerve layer according to the expression of marker proteins and their location in the nerve layer. In the present study, we have used confocal calcium imaging of OECs in acute mouse brain slices and olfactory bulbs in toto to investigate physiological differences between OEC subpopulations. OECs in the outer nerve layer, but not the inner nerve layer, responded to glutamate, ATP, serotonin, dopamine, carbachol, and phenylephrine with increases in the cytosolic calcium concentration. The calcium responses consisted of a transient and a tonic component, the latter being mediated by store-operated calcium entry. Calcium measurements in OECs during the first three postnatal weeks revealed a downregulation of mGluR(1) and P2Y(1) receptor-mediated calcium signaling within the first 2 weeks, suggesting that the expression of these receptors is developmentally controlled. In addition, electrical stimulation of sensory axons evoked calcium signaling via mGluR(1) and P2Y(1) only in outer nerve layer OECs. Downregulation of the receptor-mediated calcium responses in postnatal animals is reflected by a decrease in amplitude of stimulation-evoked calcium transients in OECs from postnatal days 3 to 21. In summary, the results presented reveal striking differences in receptor responses during development and in axon-OEC communication between the two subpopulations of OECs in the olfactory bulb.

University of Glasgow (qirdcsuog) at TREC Crowdsourcing 2011 : TurkRank-network-based worker ranking in crowdsourcing

For TREC Crowdsourcing 2011 (Stage 2) we propose a networkbased approach for assigning an indicative measure of worker trustworthiness in crowdsourced labelling tasks. Workers, the gold standard and worker/gold standard agreements are modelled as a network. For the purpose of worker trustworthiness assignment, a variant of the PageRank algorithm, named TurkRank, is used to adaptively combine evidence that suggests worker trustworthiness, i.e., agreement with other trustworthy co-workers and agreement with the gold standard. A single parameter controls the importance of co-worker agreement versus gold standard agreement. The TurkRank score calculated for each worker is incorporated with a worker-weighted mean label aggregation.

Heterogeneity of clinical and environmental isolates of Mycobacterium fortuitum using repetitive element sequence-based PCR: municipal water an unlikely source of community-acquired infections

M. fortuitum is a rapidly growing mycobacterium associated with community-acquired and nosocomial wound, soft tissue, and pulmonary infections. It has been postulated that water has been the source of infection especially in the hospital setting. The aim of this study was to determine if municipal water may be the source of community-acquired or nosocomial infections in the Brisbane area. Between 2007 and 2009, 20 strains of M. fortuitum were recovered from municipal water and 53 patients’ isolates were submitted to the reference laboratory. A wide variation in strain types was identified using repetitive element sequence-based PCR, with 13 clusters of ≥2 indistinguishable isolates, and 28 patterns consisting of individual isolates. The clusters could be grouped into seven similar groups (>95% similarity). Municipal water and clinical isolates collected during the same time period and from the same geographical area consisted of different strain types, making municipal water an unlikely source of sporadic human infection.

A model of workplace safety incorporating worker interactions and simple interventions

Although there was substantial research into the occupational health and safety sector over the past forty years, this generally focused on statistical analyses of data related to costs and/or fatalities and injuries. There is a lack of mathematical modelling of the interactions between workers and the resulting safety dynamics of the workplace. There is also little work investigating the potential impact of different safety intervention programs prior to their implementation. In this article, we present a fundamental, differential equation-based model of workplace safety that treats worker safety habits similarly to an infectious disease in an epidemic model. Analytical results for the model, derived via phase plane and stability analysis, are discussed. The model is coupled with a model of a generic safety strategy aimed at minimising unsafe work habits, to produce an optimal control problem. The optimal control model is solved using the forward-backward sweep numerical scheme implemented in Matlab.

Considering research enquiry into biophilic urbanism and office worker productivity

In cities, people spend a significant portion of their time indoors, much of which is in office buildings. The quality and nature of these spaces have the potential to be a strong determinant of people’s health and wellbeing. There is a body of evidence that suggests experiences of nature increase the rate of attention recovery, reduce stress, depression and anxiety, and increase cognitive abilities. Further, the presence of nature inside buildings (such as pot plants and internal green walls) can improve indoor air quality, potentially reducing illness and increasing cognitive function. Urban design that integrates nature into the built environment to provide these benefits, among others, is called ‘biophilic urbanism’ and is the subject of growing international interest and research. The potential for these benefits to increase worker productivity in office buildings is of particular interest, as this could significantly increase the financial performance of office building-based organisations. However, productivity is a complex concept that is difficult to define, and affected by a multitude of factors, which make it difficult to measure. This inability to quantify productivity increases from investments in nature- experiences in office buildings is currently a significant barrier to such investments. Within this context, this paper considers opportunities for research to explore the relationship between office-based nature experiences and productivity, by reviewing existing research in this field and reflecting on the authors’ own experiences. This review has a particular focus on the importance of quantifying this link in order to encourage private property owners to voluntarily integrate nature into buildings to provide city-wide ecosystem service benefits. The paper begins with a contextual overview of how biophilic urbanism can potentially increase worker productivity. Existing methods of measuring and evaluating the performance of biophilic urbanism within the context of office buildings are then explored, along with a discussion of issues with such methods that are currently limiting investment in biophilic urbanism to increase worker productivity and wellbeing. This includes a summary of a survey within a Perth office building to explore the impact of views of nature through a window. Drawing on these insights, the paper makes recommendations regarding opportunities for focusing future investigations to enhance understanding of how biophilic urbanism can contribute to increased wellbeing and productivity in office buildings. This paper builds on work conducted as part of the Sustainable Built Environment National Research Centre Project 1.5, Harnessing the Potential of Biophilic Urbanism in Australia, which considered the role of nature integrated into the built environment in responding to emerging challenges of climate change, resource shortages and population pressures, while providing a host of co- benefits to a range of stakeholders.

Considering research enquiry into biophilic urbanism and office worker productivity

In cities, people spend a significant portion of their time indoors, much of which is in office buildings. The quality and nature of these spaces have the potential to be a strong determinant of people’s health and wellbeing. There is a body of evidence that suggests experiences of nature increase the rate of attention recovery, reduce stress, depression and anxiety, and increase cognitive abilities. Further, the presence of nature inside buildings (such as pot plants and internal green walls) can improve indoor air quality, potentially reducing illness and increasing cognitive function. Urban design that integrates nature into the built environment to provide these benefits, among others, is called ‘biophilic urbanism’ and is the subject of growing international interest and research. The potential for these benefits to increase worker productivity in office buildings is of particular interest, as this could significantly increase the financial performance of office building-based organisations. However, productivity is a complex concept that is difficult to define, and affected by a multitude of factors, which make it difficult to measure. This inability to quantify productivity increases from investments in nature- experiences in office buildings is currently a significant barrier to such investments. Within this context, this paper considers opportunities for research to explore the relationship between office-based nature experiences and productivity, by reviewing existing research in this field and reflecting on the authors’ own experiences. This review has a particular focus on the importance of quantifying this link in order to encourage private property owners to voluntarily integrate nature into buildings to provide city-wide ecosystem service benefits. The paper begins with a contextual overview of how biophilic urbanism can potentially increase worker productivity. Existing methods of measuring and evaluating the performance of biophilic urbanism within the context of office buildings are then explored, along with a discussion of issues with such methods that are currently limiting investment in biophilic urbanism to increase worker productivity and wellbeing. This includes a summary of a survey within a Perth office building to explore the impact of views of nature through a window. Drawing on these insights, the paper makes recommendations regarding opportunities for focusing future investigations to enhance understanding of how biophilic urbanism can contribute to increased wellbeing and productivity in office buildings. This paper builds on work conducted as part of the Sustainable Built Environment National Research Centre Project 1.5, Harnessing the Potential of Biophilic Urbanism in Australia, which considered the role of nature integrated into the built environment in responding to emerging challenges of climate change, resource shortages and population pressures, while providing a host of co- benefits to a range of stakeholders.

Role of intratumoural heterogeneity in cancer drug resistance : molecular and clinical perspectives

Drug resistance continues to be a major barrier to the delivery of curative therapies in cancer. Historically, drug resistance has been associated with over-expression of drug transporters, changes in drug kinetics or amplification of drug targets. However, the emergence of resistance in patients treated with new-targeted therapies has provided new insight into the complexities underlying cancer drug resistance. Recent data now implicate intratumoural heterogeneity as a major driver of drug resistance. Single cell sequencing studies that identified multiple genetically distinct variants within human tumours clearly demonstrate the heterogeneous nature of human tumours. The major contributors to intratumoural heterogeneity are (i) genetic variation, (ii) stochastic processes, (iii) the microenvironment and (iv) cell and tissue plasticity. Each of these factors impacts on drug sensitivity. To deliver curative therapies to patients, modification of current therapeutic strategies to include methods that estimate intratumoural heterogeneity and plasticity will be essential.

Heterogeneity on the technical efficiency in Japanese airports

This paper evaluates the production activities of Japanese airports by using a finite mixture model that allows controlling for unobserved heterogeneity. In doing so, a stochastic frontier latent class model, which allows the existence of different technologies, is adopted to estimate production frontiers. This procedure not only enables the identification of different groups of Japanese airports but also permits the analysis of their production efficiency. The main result is that there are two groups of Japanese airports, both following completely different "technologies" to obtain passengers and cargo, suggesting that business strategies need to be adapted to the characteristics of the airports. Some managerial implications are developed.

Technical efficiency, regulation and heterogeneity in Japanese airports

In this paper, the random stochastic frontier model is used to estimate the technical efficiency of Japanese airports, with regulation and heterogeneity included in the variables. The airports are ranked according to their productivity for the period 1987-2005 and homogeneous and heterogeneous variables in the cost function are disentangled. Policy implications are derived.

Regulation, pollution and heterogeneity in Japanese steam power generation companies

In this paper, the random stochastic frontier model is used to estimate the technical efficiency of Japanese steam power generation companies taking into regulation and pollution. The companies are ranked according to their productivity for the period 1976-2003 and homogenous and heterogeneous variables in the cost function are disentangled. Policy implication is derived.

Migrant worker empowerment in online communities

Our literature review shows that several scholars have conceptualized empowerment in online communities according to context and setting. In general, empowerment by the Internet can be described as the capacity of the Internet to provide information, interactions and collaborations (Amichai-Hamburger, McKenna, & Tal, 2008). Interactions within a social networking site enable people to construct their online identity which potentially empowers them (Zhao, Grasmuck, & Martin, 2008). From a consumer orientation, consumers feel empowered through accessing information which potentially improves their understanding and knowledge in decision making processes (Tina, Kathryn, & Gary, 2006). In health contexts, participation in online communities is seen to empower individuals in coping with health issues (Høybye, Johansen, & Tjørnhøj-Thomsen, 2005; Pitts, 2004; Sharf, 1997; Cornelia F. van Uden-Kraan et al., 2008). In educational contexts, online collaboration processes can empower lecturers and students (Ravid, Kalman, & Rafaeli, 2008). The literature shows that studies of empowerment in online communities are an emerging concept