Myeloproliferative neoplasm patient symptom burden and quality of life: evidence of significant impairment compared to controls

The myeloproliferative neoplasms (MPN) including polycythaemia vera (PV), essential thrombocythaemia and primary myelofibrosis (PMF) are rare diseases contributing to significant morbidity. Symptom management is a prime treatment objective but current symptom assessment tools have not been validated compared to the general population. The MPN-symptom assessment form (MPN-SAF), a reliable and validated clinical tool to assess MPN symptom burden, was administered to MPN patients (n���=���106) and, for the first time, population controls (n���=���124) as part of a UK case���control study. Mean symptom scores were compared between patients and controls adjusting for potential confounders. Mean patient scores were compared to data collected by the Mayo Clinic, USA on 1,446 international MPN patients to determine patient group representativeness. MPN patients had significantly higher mean scores than controls for 25 of the 26 symptoms measured (P���<���0.05); fatigue was the most common symptom (92.4% and 78.1%, respectively). Female MPN patients suffered worse symptom burden than male patients (P���<���0.001) and substantially worse burden than female controls (P���<���0.001). Compared to the Mayo clinic patients, MPN-UK patients reported similar symptom burden but lower satiety (P���=���0.046). Patients with PMF reported the worst symptom burden (88.3%); significantly higher than PV patients (P���<���0.001). For the first time we report quality of life was worse in MPN-UK patients compared with controls (P���<���0.001).

Convergent genetic and expression data implicate immunity in Alzheimer's disease

<p>Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis.</p><p>Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain.</p><p>Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05).</p><p>Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics. (C) 2015 Published by Elsevier Inc. on behalf of The Alzheimer's Association.</p>

Risk in Private Finance Initiative Projects::A Public Sector Perspective

The management of public sector risk is increasingly seen as a priority area of UK government policy. This has been highlighted recently by the Prime Minister Gordon Brown who stated that ���the issue of public risk is one of the most challenging areas of policy-making for any government��� (Strategic Risk, 2008). In response to these challenges, the UK Prime Minister has appointed a new body - the Risk and Regulation Advisory Council (RRAC) which is tasked with improving the way risk to the public is understood and managed. One area of particular concern with regard to the governance of public sector risks involves projects procured via the Private Finance Initiative (PFI). These projects involve long-term contracts, complex multi-party interactions and thus create various risks to public sector clients. Today, most PFI actors acknowledge the potentially adverse effects of these risks and make an effort to prevent or mitigate undesirable results. As a consequence, issues of risk allocation, risk transfer and risk management have become central to the PFI procurement process. This paper provides an overview of the risk categories and risk types which are relevant to the public sector in PFI projects. It analyses risk as a feature of uncertain future project-related events and examines potential pitfalls which can be associated with PFI risk management on the basis of a case study of a high-profile PFI hospital in Scotland. The paper concludes that, despite the trend towards diminished risk profiles during the operational phase, the public sector continues to be exposed to significant risks when engaging in PFI-based procurement.

A Parametric Study Of A Turbogenerator On A Diesel-Electric Hybrid Bus

The fuel consumption of automotive vehicles has become a prime consideration to manufacturers and operators as fuel prices continue to rise steadily, and legislation governing toxic emissions becomes ever more strict. This is particularly true for bus operators as government fuel subsidies are cut or removed.<br/><br/>In an effort to reduce the fuel consumption of a diesel-electric hybrid bus, an exhaust recovery turbogenerator has been selected from a wide ranging literature review as the most appropriate method of recovering some of the wasted heat in the exhaust line. This paper examines the effect on fuel consumption of a turbogenerator applied to a 2.4-litre diesel engine.<br/><br/>A validated one-dimensional engine model created using Ricardo WAVE was used as a baseline, and was modified in subsequent models to include a turbogenerator downstream, and in series with, the turbocharger turbine. A fuel consumption map of the modified engine was produced, and an in-house simulation tool was then used to examine the fuel economy benefit delivered by the turbogenerator on a bus operating on various drive-cycles.<br/><br/>A parametric study is presented which examined the performance of turbogenerators of various size and power output. The operating strategy of the turbogenerator was also discussed with a view to maximising turbine efficiency at each operating point.<br/><br/>The performance of the existing turbocharger on the hybrid bus was also investigated; both the compressor and turbine were optimised and the subsequent benefits to the fuel consumption of the vehicle were shown.<br/><br/>The final configuration is then presented and the overall improvement in fuel economy of the hybrid bus was determined over various drive-cycles.<br/>

Address inaccuracy in health registration data: determinants and impacts

Access to demographic data that are complete, accurate and up-to-date is fundamental to many aspects of public health, government and academic work and for accurate interpretation of other databases. Health registration data are the prime source of demographic information for health and social care systems; for example, as an indicator of need, as a source of denominators to convert number of events into rates, or in the case of the residential address information as the basis for generating the call-recall invitation letters that are used for most screening programs (e.g. breast, colo-rectal and AAA screening). However, list inflation (ghosts, duplicates or emigrants) and a degree of address inaccuracy are recognised caveats with the health registration data and a recent NILS-related study on breast screening suggests that improved address accuracy might be a fast and efficient means of increasing screening uptake rates in cities and amongst deprived populations. In NI these data are collated by the BSO who uniquely in the UK also have access to data relating to prescribing, dental registrations and use of A&amp;E services. These can be used to supplement the standard demographic and address information by (i) indicating patients who are alive and resident in NI and (ii) providing an independent source of probably improved address information. This study will use the NI Unique Property Reference Number (UPRN), rather than the addresses per se which are difficult to work with, to compare the addresses registered in the BSO with those addresses in the enumerated 2011 census. Assuming that the census is a more accurate source of address information for individuals, a comparison of the health registration addresses with those recorded at the census, the aim of the proposed study will be to (i) characterise the amount and distributions of these differences, (ii) to see what proportion of those who do not attend for screening did not actually receive an invitation letter because the addresses were incorrect, (iii) to determine how much of the social gradient (and urban/rural differences) in screening uptake are due to address inaccuracies, (iv) a comparison of timing of address changes at the BSO will provide information on the delays in updating of addresses.

Collective synchrony increases prosociality towards non-performers and out-group members

Previous research has found that behavioural synchrony between people leads to greater prosocial tendencies towards co-performers. In this study we investigated the scope of this prosocial effect: does it extend beyond the performance group to an extended in-group (extended parochial prosociality) or even to other people in general (generalized prosociality)? Participants performed a simple rhythmic movement either in time (synchrony condition) or out of time (asynchrony condition) with each other. Before and during the rhythmic movement, participants were exposed to a prime that made salient an extended in-group identity. After the task, half the participants had the opportunity to help an extended in-group member; the other half had the opportunity to help an out-group member. We found a main effect of our synchrony manipulation across both help targets suggesting that the prosocial effects of synchrony extend to non-performers. Furthermore, there was a significantly higher proportion of participants willing to help an out-group member after moving collectively in synchrony. This study shows that under certain intergroup contexts synchrony can lead to generalized prosociality with performers displaying greater prosociality even towards out-group members.

Identity of a Tilapia Pheromone Released by Dominant Males that Primes Females for Reproduction

Knowledge of the chemical identity and role of urinary pheromones in fish is scarce, yet it is necessary in order to understand the integration of multiple senses in adaptive responses and the evolution of chemical communication [1]. In nature, Mozambique tilapia (Oreochromis mossambicus) males form hierarchies, and females mate preferentially with dominant territorial males, which they visit in aggregations or leks [2]. Dominant males have thicker urinary bladder muscular walls than subordinates or females and store large volumes of urine, which they release at increased frequency in the presence of subordinate males or preovulatory, but not postspawned, females [3���5]. Females exposed to dominant-male urine augment their release of the oocyte maturation-inducing steroid 17��,20��-dihydroxypregn-4-en-3-one (17,20��-P) [6]. Here we isolate and identify a male Mozambique tilapia urinary sex pheromone as two epimeric (20��- and 20��-) pregnanetriol 3-glucuronates. We show that both males and females have high olfactory sensitivity to the two steroids, which cross-adapt upon stimulation. Females exposed to both steroids show a rapid, 10-fold increase in production of 17,20��-P. Thus, the identified urinary steroids prime the female endocrine system to accelerate oocyte maturation and possibly promote spawning synchrony. Tilapia are globally important as a food source but are also invasive species, with devastating impact on local freshwater ecosystems [7, 8]. Identifying the chemical cues that mediate reproduction may lead to the development of tools for population control [9���11].

Injection moulding process optimization for microstructured parts production

Ao longo das ��ltimas d��cadas, a micromolda����o (u-molda����o) por inje����o de termopl��sticos ganhou um lugar de destaque no mercado de equipamentos eletr��nicos e de uma ampla gama de componentes mec��nicos. No entanto, quando o tamanho do componente diminui, os pressupostos geralmente aceites na molda����o por inje����o convencional deixam de ser v��lidos para descrever o comportamento reol��gico e termomec��nico do pol��mero na microimpress��o. Por isso, a compreens��o do comportamento din��mico do pol��mero �� escala micro bem como da sua carateriza����o, an��lise e previs��o das propriedades mec��nicas exige uma investiga����o mais alargada. O objetivo principal deste programa doutoral passa por uma melhor compreens��o do fen��meno f��sico intr��nseco ao processo da ��-molda����o por inje����o. Para cumprir com o objetivo estabelecido, foi efetuado um estudo param��trico do processo de ��-molda����o por inje����o, cujos resultados foram comparados com os resultados obtidos por simula����o num��rica. A caracteriza����o din��mica mec��nica das ��-pe��as foi efetuada com o objetivo de recolher os dados necess��rios para a previs��o do desempenho mec��nico das mesmas, a longo prazo. Finalmente, depois da calibra����o do modelo matem��tico do pol��mero, foram realizadas an��lises estruturais com o intuito de prever o desempenho mec��nico das ��-pe��as no longo prazo. Verificou-se que o desempenho mec��nico das ��-pe��as pode ser significativamente afetado pelas tens��es residuais de origem mec��nica e t��rmica. Estas ��ltimas, resultantes do processo de fabrico e das condi����es de processamento, por isso, devem ser consideradas na previs��o do desempenho mec��nico e do tempo de servi��o das u-molda����es.

Cooperative positioning for heterogeneous wireless systems

Future emerging market trends head towards positioning based services placing a new perspective on the way we obtain and exploit positioning information. On one hand, innovations in information technology and wireless communication systems enabled the development of numerous location based applications such as vehicle navigation and tracking, sensor networks applications, home automation, asset management, security and context aware location services. On the other hand, wireless networks themselves may bene t from localization information to improve the performances of di erent network layers. Location based routing, synchronization, interference cancellation are prime examples of applications where location information can be useful. Typical positioning solutions rely on measurements and exploitation of distance dependent signal metrics, such as the received signal strength, time of arrival or angle of arrival. They are cheaper and easier to implement than the dedicated positioning systems based on ngerprinting, but at the cost of accuracy. Therefore intelligent localization algorithms and signal processing techniques have to be applied to mitigate the lack of accuracy in distance estimates. Cooperation between nodes is used in cases where conventional positioning techniques do not perform well due to lack of existing infrastructure, or obstructed indoor environment. The objective is to concentrate on hybrid architecture where some nodes have points of attachment to an infrastructure, and simultaneously are interconnected via short-range ad hoc links. The availability of more capable handsets enables more innovative scenarios that take advantage of multiple radio access networks as well as peer-to-peer links for positioning. Link selection is used to optimize the tradeo between the power consumption of participating nodes and the quality of target localization. The Geometric Dilution of Precision and the Cramer-Rao Lower Bound can be used as criteria for choosing the appropriate set of anchor nodes and corresponding measurements before attempting location estimation itself. This work analyzes the existing solutions for node selection in order to improve localization performance, and proposes a novel method based on utility functions. The proposed method is then extended to mobile and heterogeneous environments. Simulations have been carried out, as well as evaluation with real measurement data. In addition, some speci c cases have been considered, such as localization in ill-conditioned scenarios and the use of negative information. The proposed approaches have shown to enhance estimation accuracy, whilst signi cantly reducing complexity, power consumption and signalling overhead.

An overview of chemosynthetic symbioses in bivalves from the North Atlantic and Mediterranean Sea

Deep-sea bivalves found at hydrothermal vents, cold seeps and organic falls are sustained by chemosynthetic bacteria that ensure part or all of their carbon nutrition. These symbioses are of prime importance for the functioning of the ecosystems. Similar symbioses occur in other bivalve species living in shallow and coastal reduced habitats worldwide. In recent years, several deep-sea species have been investigated from continental margins around Europe, West Africa, eastern Americas, the Gulf of Mexico, and from hydrothermal vents on the Mid-Atlantic Ridge. In parallel, numerous, more easily accessible shallow marine species have been studied. Herein we provide a summary of the current knowledge available on chemosymbiotic bivalves in the area ranging west-to-east from the Gulf of Mexico to the Sea of Marmara, and north-to-south from the Arctic to the Gulf of Guinea. Characteristics of symbioses in 53 species from the area are summarized for each of the five bivalve families documented to harbor chemosynthetic symbionts (Mytilidae, Vesicomyidae, Solemyidae, Thyasiridae and Lucinidae). Comparisons are made between the families, with special emphasis on ecology, life cycle, and connectivity. Chemosynthetic symbioses are a major adaptation to ecosystems and habitats exposed to reducing conditions. However, relatively little is known regarding their diversity and functioning, apart from a few ���model species��� on which effort has focused over the last 30 yr. In the context of increasing concern about biodiversity and ecosystems, and increasing anthropogenic pressure on oceans, we advocate a better assessment of the diversity of bivalve symbioses in order to evaluate the capacities of these remarkable ecological and evolutionary units to withstand environmental change.

Initial insights on the biodiversity potential of biosolar roofs: A London Olympic Park green roof case study

Cities dominated by impervious artificial surfaces can experience myriad negative environmental impacts. Restoration of green infrastructure has been identified as a mechanism for increasing urban resilience, enabling cities to transition towards sustainable futures in the face of climate-driven change. Building rooftops represent a viable space for integrating new green infrastructure into high density urban areas. Urban rooftops also provide prime locations for photovoltaic (PV) systems. There is increasing recognition that these two technologies can be combined to deliver reciprocal benefits in terms of energy efficiency and biodiversity targets. Scarcity of scientific evaluation of the interaction between PVs and green roofs means that the potential benefits are currently poorly understood. This study documents evidence from a biodiversity monitoring study of a substantial biosolar roof installed in the Queen Elizabeth Olympic Park. Vegetation and invertebrate communities were sampled and habitat structure measured in relation to habitat niches on the roof, including PV panels. Ninety-two plant species were recorded on the roof and variation in vegetation structure associated with proximity to PV panels was identified. Almost 50% of target invertebrate species collected were designated of conservation importance. Arthropod distribution varied in relation to habitat niches on the roof. The overall aim of the MPC green roof design was to create a mosaic of habitats to enhance biodiversity, and the results of the study suggest that PV panels can contribute to niche diversity on a green roof. Further detailed study is required to fully characterise the effects of PV panel density on biodiversity.

Difficulties generating self-compassion: An interpretative phenomenological analysis

The aim of the present study was to make an idiographic investigation about the difficulties that are encountered by people who self-identify as having difficulties with self-compassion. Although a growing number of studies have been carried out concerning the concept of self-compassion, most research designs were quantitative. Based on this gap, the current study expanded the scope to include a qualitative dimension of the recent literature on self-compassion and Interpretative Phenomenological Analysis (IPA) was adopted as methodological preference, which particularly monitors the lived experience of participants. In consequence of four in-depth semi-structured interviews, four super-ordinate themes emerged; the double-edged-sword: perfectionism, the flaws of compassion, the effects of a third person, and the advantages of self-criticism. In line with pre-existing research, these findings explored the reasons behind self-undermining behaviours and misconstructions about self-compassion, which are a barrier to gentle self-talk. Furthermore, unfavourable effects of the social environment prime participants to maladaptive perfectionism and excessive self-criticism, which are considered a success formula by the participants. This study's purpose is to present a detailed roadmap about the self-destructive journey of the people with low self-compassion. It will help researchers and clinicians to develop future interventions in order to cultivate kind and encouraging attitudes in self-critical people.

Seasonal variations in gross biochemical composition, percent edibility, and condition index of the clam Ruditapes Decussatus cultivated in the Ria Formosa (South Portugal)

The grooved carpet shell clam, Ruditapes decussatus (L. 1758), is one of the most popular and profitable molluscs exploited in rearing plots in the Mediterranean. However, annual catch has been declining steadily since the early nineties. In order to understand the seasonality of its nutritional value, thus providing an improved basis for economical valuation of the resource, gross biochemical composition, percentage edibility and condition index were investigated during a year with monthly periodicity in a commercially exploited population of the clam Ruditapes decussatus in the Ria Formosa, a temperate mesotidal coastal lagoon located in the south of Portugal. Our results show that total and non-protein nitrogen co-varied during the year, resulting in a protein content that peaked in the warmest months. Although complementary in summer, carbohydrate and lipid contents showed irregular annual trends. The observed seasonality was comparable to that shown by studies elsewhere at similar latitudes, and are underpinned by the reproductive cycle of the species. Our results show the clams to be at their prime nutritional value at the beginning of summer, when protein content peaks.