In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin’s lymphoma (NHL)

Background The analysis of cellular networks and pathways involved in oncogenesis has increased our knowledge about the pathogenic mechanisms that underlie tumour biology and has unmasked new molecular targets that may lead to the design of better anti-cancer therapies. Recently, using a high resolution loss of heterozygosity (LOH) analysis, we identified a number of potential tumour suppressor genes (TSGs) within common LOH regions across cases suffering from two of the most common forms of Non-Hodgkin’s lymphoma (NHL), Follicular Lymphoma (FL) and Diffuse Large B-cell Lymphoma (DLBCL). From these studies LOH of the protein tyrosine phosphatase receptor type J (PTPRJ) gene was identified as a common event in the lymphomagenesis of these B-cell lymphomas. The present study aimed to determine the cellular pathways affected by the inactivation of these TSGs including PTPRJ in FL and DLBCL tumourigenesis. Results Pathway analytical approaches identified that candidate TSGs located within common LOH regions participate within cellular pathways, which may play a crucial role in FL and DLBCL lymphomagenesis (i.e., metabolic pathways). These analyses also identified genes within the interactome of PTPRJ (i.e. PTPN11 and B2M) that when inactivated in NHL may play an important role in tumourigenesis. We also detected genes that are differentially expressed in cases with and without LOH of PTPRJ, such as NFATC3 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3). Moreover, upregulation of the VEGF, MAPK and ERBB signalling pathways was also observed in NHL cases with LOH of PTPRJ, indicating that LOH-driving events causing inactivation of PTPRJ, apart from possibly inducing a constitutive activation of these pathways by reduction or abrogation of its dephosphorylation activity, may also induce upregulation of these pathways when inactivated. This finding implicates these pathways in the lymphomagenesis and progression of FL and DLBCL. Conclusions The evidence obtained in this research supports findings suggesting that FL and DLBCL share common pathogenic mechanisms. Also, it indicates that PTPRJ can play a crucial role in the pathogenesis of these B-cell tumours and suggests that activation of PTPRJ might be an interesting novel chemotherapeutic target for the treatment of these B-cell tumours.

A non-fullerene electron acceptor based on fluorene and diketopyrrolopyrrole building blocks for solution-processable organic solar cells with an impressive open-circuit voltage

A novel solution-processable non-fullerene electron acceptor 6,6′-(5,5′-(9,9-dioctyl-9H-fluorene-2,7-diyl)bis(thiophene-5,2-diyl))bis(2,5-bis(2-ethylhexyl)-3-(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione) (DPP1) based on fluorene and diketopyrrolopyrrole conjugated moieties was designed, synthesized and fully characterized. DPP1 exhibited excellent solubility and high thermal stability which are essential for easy processing. Upon using DPP1 as an acceptor with the classical electron donor poly(3-hexylthiophene), solution processable bulk-heterojunction solar cells afforded a power conversion efficiency of 1.2% with a high open-circuit voltage (1.1 V). As per our knowledge, this value of open circuit voltage is one of the highest values reported so far for a bulk-heterojunction device using DPP1 as a non-fullerene acceptor.

Sustainability Non-Price Incentives and Rewards: A Collaborative Procurement Perspective

Construction scholars suggest that procurement processes can be used as mechanisms to change construction industry practices. This paper discusses industry changes as a response to the calls for integration of sustainability ideals into construction practices. Because major infrastructure construction has been identified as a key producer of greenhouse gas emissions (GHGE), this study explores collaborative procurement models that have been used to facilitate mitigation of GHGE. The study focuses on the application of non-price incentives and rewards that work together as a binary mechanism. Data were collected using mixed-methods: government document content analysis was complemented with data collected through focus groups and individual interviews with both clients and contractors. This report includes examples of greening procurement agendas for three Australian road authorities relating to collaborative procurement project delivery models. Three collaborative procurement models, Alliance Consortium, Early Contractor Involvement and Public Private Partnerships provide evidence of construction projects that were completed early. It can also be argued that both clients and contractors are rewarded through collaborative project delivery. The incentive of early completion is rewarded with reduction of GHGE. This positive environmental outcome, based on a dual benefit and non-price sustainability criteria, suggests a step towards changed industry practices though the use of green procurement models.

Corporate governance quality, audit fees and non-audit services fees

This paper extends prior research on the relationship between governance quality and auditor remuneration.We examine the influence of audit committee effectiveness (ACE), a proxy for governance quality, on audit fees (AF) and non-audit services fees (NASF) using a new composite measure comprising audit committee independence, expertise, diligence and size. We find that after controlling for board of director characteristics, there is a significant positive association between ACE and AF only for larger clients. Our results indicate that effective audit committees undertake more monitoring which results in wider audit scope and higher audit fees. Contrary to our expectations, we find the association between ACE and NASF to be positive and significant, especially for larger clients. This suggests that larger clients are more likely to purchase non-audit services (NAS) even in the presence of effective audit committees probably due to the complexity of their activities. Overall, our findings support regulatory initiatives aimed at improving corporate governance quality.

Ross River virus disease activity associated with naturally occurring non-tidal flood events in Australia : A systematic review

Ross River virus (RRV) disease is the most common and widespread mosquito-borne disease in Australia, resulting in considerable health and economic cost to communities. While naturally occurring non-tidal flood events may enhance mosquito abundance, little is known about the impact of such events on RRV transmission. This paper critically reviews the existing evidence for an association between naturally occurring non-tidal flood events and RRV transmission. A systematic literature search was conducted on RRV transmission related to flooding and inundation from rain and riverine overflow. Overall, the evidence to support a positive association between flooding and RRV outbreaks is largely circumstantial, with the literature mostly reporting only coincidental occurrence between the two. However, for the Murray River, river flow and height (surrogates of flooding) were positively and significantly associated with RRV transmission. The association between non-tidal flooding and RRV transmission has not been studied comprehensively. More frequent flood events arising from climate change may result in increased outbreaks of RRV disease. Understanding the link between flood events and RRV transmission is necessary if resources for mosquito spraying and public health warnings are to be utilized more effectively and efficiently.

Systematic review of pharmacologic and non-pharmacologic interventions to manage cognitive alterations after chemotherapy for breast cancer

Purpose Cognitive alterations are reported in breast cancer patients receiving chemotherapy. This has adverse effects on patients’ quality of life and function. This systematic review investigates the effectiveness of pharmacologic and non-pharmacologic interventions to manage cognitive alterations associated with breast cancer treatment. Methods Medline via EBSCOhost, CINAHL and Cochrane CENTRAL were searched for the period January 1999 to May 2014 for prospective randomized controlled trials related to the management of chemotherapy-associated cognitive alterations. Included studies investigated the management of chemotherapy-associated cognitive alterations and used subjective or objective measures in patients with breast cancer during or after chemotherapy. Two authors independently extracted data and assessed the risk of bias. Results Thirteen studies involving 1138 participants were included. Overall, the risk of bias for the 13 studies were either high (n=11) or unclear (n=2). Pharmacologic interventions included psychostimulants (n=4), epoetin alfa (n=1), and Ginkgo biloba (n=1). Non-pharmacologic interventions were cognitive training (n=5) and physical activity (n=2). Pharmacologic agents were ineffective except for self-reported cognitive function in an epoetin alfa study. Cognitive training interventions demonstrated benefits in self-reported cognitive function, memory, verbal function and language and orientation/attention. Physical activity interventions were effective in improving executive function and self-reported concentration. Conclusion Current evidence does not favor the pharmacologic management of cognitive alterations associated with breast cancer treatment. Cognitive training and physical activity interventions appear promising, but additional studies are required to establish their efficacy. Further research is needed to overcome methodological shortfalls such as heterogeneity in participant characteristics and non-standardized neuropsychological outcome measures.

Multilingual lexical resources to detect cognates in non-aligned texts

The identification of cognates between two distinct languages has recently start- ed to attract the attention of NLP re- search, but there has been little research into using semantic evidence to detect cognates. The approach presented in this paper aims to detect English-French cog- nates within monolingual texts (texts that are not accompanied by aligned translat- ed equivalents), by integrating word shape similarity approaches with word sense disambiguation techniques in order to account for context. Our implementa- tion is based on BabelNet, a semantic network that incorporates a multilingual encyclopedic dictionary. Our approach is evaluated on two manually annotated da- tasets. The first one shows that across different types of natural text, our method can identify the cognates with an overall accuracy of 80%. The second one, con- sisting of control sentences with semi- cognates acting as either true cognates or false friends, shows that our method can identify 80% of semi-cognates acting as cognates but also identifies 75% of the semi-cognates acting as false friends.

Non-monetised multi-objective decision making system for road management

This paper presents a performance-based optimisation approach for conducting trade-off analysis between safety (roads) and condition (bridges and roads). Safety was based on potential for improvement (PFI). Road condition was based on surface distresses and bridge condition was based on apparent age per subcomponent. The analysis uses a non-monetised optimisation that expanded upon classical Pareto optimality by observing performance across time. It was found that achievement of good results was conditioned by the availability of early age treatments and impacted by a frontier effect preventing the optimisation algorithm from realising of the long-term benefits of deploying actions when approaching the end of the analysis period. A disaggregated bridge condition index proved capable of improving levels of service in bridge subcomponents.

Analyzing busway station potential capacity under mixed stopping and non-stopping operation

Busway stations are the interface between passengers and services. The station is crucial to line operation as it is typically the only location where buses can pass each other. Congestion may occur here when buses manoeuvring into and out of the platform lane interfere with bus flow, or when a queue of buses forms upstream of the platform lane blocking the passing lane. Further, some systems include operation where express buses do not observe the station, resulting in a proportion of non-stopping buses. It is important to understand the operation of the station under this type of operation and its effect on busway capacity. This study uses microscopic simulation to treat the busway station operation and to analyse the relationship between station potential capacity where all buses stop, and Mixed Potential Capacity where there is a mixture of stopping and non-stopping buses. First, the micro simulation technique is used to analyze the All Stopping Buses (ASB) scenario and then statistical model is tuned and calibrated for a specified range of controlled scenarios of dwell time characteristics Subsequently, a mathematical model is developed for Mixed Stopping Buses (MSB) Potential Capacity by introducing different proportions of express (or non-stopping) buses. The proposed models for a busway station bus capacity provide a better understanding of operation and are useful to transit agencies in busway planning, design and operation.

Analysing busway station capacity under mixed stopping and non-stopping operation

Busway stations are the interface between passengers and services. The station is crucial to line operation as it is typically the only location where buses can pass each other. Congestion may occur here when buses manoeuvring into and out of the platform lane interfere with bus flow, or when a queue of buses forms upstream of the platform lane blocking the passing lane. Further, some systems include operation where express buses do not observe the station, resulting in a proportion of non-stopping buses. It is important to understand the operation of the station under this type of operation and its effect on busway capacity. This study uses microscopic simulation to treat the busway station operation and to analyse the relationship between station potential capacity where all buses stop, and Mixed Potential Capacity where there is a mixture of stopping and non-stopping buses. First, the micro simulation technique is used to analyze the All Stopping Buses (ASB) scenario and then statistical model is tuned and calibrated for a specified range of controlled scenarios of dwell time characteristics Subsequently, a mathematical model is developed for Mixed Stopping Buses (MSB) Potential Capacity by introducing different proportions of express (or non-stopping) buses. The proposed models for a busway station bus capacity provide a better understanding of operation and are useful to transit agencies in busway planning, design and operation.

Poverty and non-communicable diseases in South Africa

Background: High levels of wealth inequality with improved health statistics in South Africa (SA) provide an important opportunity to investigate non-communicable diseases (NCDs) among the poor. Aims: This paper uses two distinct national data sets to contrast patterns of mortality in rich and poor areas and explore the associations between poverty, risk factors, health care and selected NCDs diseases in South African adults. Methods: Causes of premature mortality in 1996 experienced in the poorest magisterial districts are compared with those in the richest, using average household wealth to classify districts. Logistic and multinomial regression are used to investigate the association of a household asset index and selected chronic conditions, related risk factors and healthcare indicators using data from the 1998 South African Demographic and Health Survey. Results: NCDs accounted for 39% and 33% of premature mortality in rich and poor districts respectively. The household survey data showed that the risk factors hypertension and obesity increased with increasing wealth, while most of the lifestyle factors, such as light smoking, domestic exposure to ``smoky'' fuels and alcohol dependence were associated with poverty. Treatment status for hypertension and asthma was worse for poor people than for rich people. Conclusions: The study suggests that NCDs and lifestyle-related risk factors are prevalent among the poor in SA and treatment for chronic diseases is lacking for poor people. The observed increase in hypertension and obesity with wealth suggests that unless comprehensive health promotion strategies are implemented, there will be an unmanageable chronic disease epidemic with future socioeconomic development in SA.

Demographics and discharge outcomes of dysvascular and non-vascular lower limb amputees at a subacute rehabilitation unit: A 7-year series

Objective To examine personal and social demographics, and rehabilitation discharge outcomes of dysvascular and non-vascular lower limb amputees. Methods In total, 425 lower limb amputation inpatient rehabilitation admissions (335 individuals) from 2005 to 2011 were examined. Admission and discharge descriptive statistics (frequency, percentages) were calculated and compared by aetiology. Results Participants were male (74%), aged 65 years (s.d. 14), born in Australia (72%), had predominantly dysvascular aetiology (80%) and a median length of stay 48 days (interquartile range (IQR): 25–76). Following amputation, 56% received prostheses for mobility, 21% (n = 89) changed residence and 28% (n = 116) required community services. Dysvascular amputees were older (mean 67 years, s.d. 12 vs 54 years, s.d. 16; P < 0.001) and recorded lower functional independence measure – motor scores at admission (z = 3.61, P < 0.001) and discharge (z = 4.52, P < 0.001). More nonvascular amputees worked before amputation (43% vs 11%; P < 0.001), were prescribed a prosthesis by discharge (73% vs 52%; P < 0.001) and had a shorter length of stay (7 days, 95% confidence interval: –3 to 17), although this was not statistically significant. Conclusions Differences exist in social and demographic outcomes between dysvascular and non-vascular lower limb amputees.