618 research outputs found
Sustainable product development strategies: Business planning and performance implications
Copyright © 2012 by Institution of Mechanical Engineers. This is the author's accepted manuscript. The final published article is available from the link below.Manufacturing firms are under many financial and competitive pressures which focus attention on the performance of their manufacturing processes. In this paper the opportunities for improving the environmental impact of products within the constraints of existing manufacturing infrastructure are examined. Approaches which support sustainability in two aspects are proposed, firstly, the provision of products to the users in ways which extend the product life and secondly, manufacturing approaches which reduce resource usage. This paper outlines three different sustainable development strategies for different product types and describes the cost implications for manufacturers across the life-cycle. The performance measures affected by these strategies are examined drawing on product development case studies from a number of high technology sectors to highlight the different approaches taken. The results are intended to aid manufacturers during the earliest stages of business planning to consider alternative product development approaches which are more sustainable
The Relationship Between Diabetes-Related Attitudes and Patients' Self- Reported Adherence
This study involved 1202 patients who were placed into low adherence or high adherence groups based on their answers to questionnaires. The attitudes of each group were compared for a variety of adherence behaviors. Patients who reported high levels of adherence tended to have attitudes more in accord with diabetes experts. Members of the high adherence group strongly supported the need for special training for health care professionals who treat diabetes, favored team care, accepted the importance of patient compliance, acknowledged the seriousness of non-insulin-dependent diabetes mellitus (NIDDM), and recognized the relationship between glucose control and complications. Differences in attitudes between high- and low adherence groups were more prevalent for difficult adherence areas, eg, diet and exercise, than for easy adherence areas, eg, carrying sweets or diabetic identification. An understanding of patients' attitudes can help diabetes educators and patients develop realistic and relevant self-care plans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68603/2/10.1177_014572179301900407.pd
Associations between health-related quality of life, physical function and fear of falling in older fallers receiving home care
Falls and injuries in older adults have significant consequences and costs, both personal and to society. Although having a high incidence of falls, high prevalence of fear of falling and a lower quality of life, older adults receiving home care are underrepresented in research on older fallers. The objective of this study is to determine the associations between health-related quality of life (HRQOL), fear of falling and physical function in older fallers receiving home care
Evolutionary relationships between Rhynchosporium lolii sp. nov. and other Rhynchosporium species on grass.
Copyright: 2013 King et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe fungal genus Rhynchosporium (causative agent of leaf blotch) contains several host-specialised species, including R. commune (colonising barley and brome-grass), R. agropyri (couch-grass), R. secalis (rye and triticale) and the more distantly related R. orthosporum (cocksfoot). This study used molecular fingerprinting, multilocus DNA sequence data, conidial morphology, host range tests and scanning electron microscopy to investigate the relationship between Rhynchosporium species on ryegrasses, both economically important forage grasses and common wild grasses in many cereal growing areas, and other plant species. Two different types of Rhynchosporium were found on ryegrasses in the UK. Firstly, there were isolates of R. commune that were pathogenic to both barley and Italian ryegrass. Secondly, there were isolates of a new species, here named R. lolii, that were pathogenic only to ryegrass species. R. lolii was most closely related to R. orthosporum, but exhibited clear molecular, morphological and host range differences. The species was estimated to have diverged from R. orthosporum ca. 5735 years before the present. The colonisation strategy of all of the different Rhynchosporium species involved extensive hyphal growth in the sub-cuticular regions of the leaves. Finally, new species-specific PCR diagnostic tests were developed that could distinguish between these five closely related Rhynchosporium species.Peer reviewedFinal Published versio
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Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora
Background
The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years.
Results
Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology.
Conclusions
Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record
Neutrino masses from new generations
We reconsider the possibility that Majorana masses for the three known
neutrinos are generated radiatively by the presence of a fourth generation and
one right-handed neutrino with Yukawa couplings and a Majorana mass term. We
find that the observed light neutrino mass hierarchy is not compatible with low
energy universality bounds in this minimal scenario, but all present data can
be accommodated with five generations and two right-handed neutrinos. Within
this framework, we explore the parameter space regions which are currently
allowed and could lead to observable effects in neutrinoless double beta decay,
conversion in nuclei and experiments. We
also discuss the detection prospects at LHC.Comment: 28 pages, 4 figures. Version to be published. Some typos corrected.
Improved figures 3 and
Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience
Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue
E-readers and the death of the book: or, new media and the myth of the disappearing medium
The recent emergence of e-readers and e-books has b
rought the death of the book to the centre of
current debates on new media. In this article, we a
nalyse alternative narratives that surround the
possibility of the disappearance of print books, do
minated by fetishism, fears about the end of
humanism, and ideas of techno-fundamentalist progre
ss. We argue that, in order to comprehend
such narratives, we need to inscribe them in the br
oader history of media. The emergence of new
media, in fact, has often been accompanied by narra
tives about the possible disappearance of
older media: the introduction of television, for in
stance, inspired claims about the forthcoming
death of film and radio. As a recurrent narrative s
haping the reception of media innovation, the
myth of the disappearing medium helps us to make se
nse of the transformations that media
change provokes in our everyday life
Major reduction of malaria morbidity with combined vitamin A and zinc supplementation in young children in Burkina Faso: a randomized double blind trial
BACKGROUND: Vitamin A and zinc are crucial for normal immune function, and may play a synergistic role for reducing the risk of infection including malaria caused by Plasmodium falciparum. METHODS: A randomized, double-blind, placebo-controlled trial of a single dose of 200 000 IU of vitamin A with daily zinc supplementation was done in children of Sourkoudougou village, Burkina Faso. Children aged from 6 to 72 months were randomized to receive a single dose of 200 000 IU of vitamin A plus 10 mg elemental zinc, six days a week (n = 74) or placebo (n = 74) for a period of six months. Cross-sectional surveys were conducted at the beginning and the end of the study, and children were evaluated daily for fever. Microscopic examination of blood smear was done in the case of fever (temperature > or =37.5 degrees C) for malaria parasite detection. RESULTS: At the end of the study we observed a significant decrease in the prevalence malaria in the supplemented group (34%) compared to the placebo group (3.5%) (p < 0.001). Malaria episodes were lower in the supplemented group (p = 0.029), with a 30.2% reduction of malaria cases (p = 0.025). Time to first malaria episode was longer in the supplemented group (p = 0.015). The supplemented group also had 22% fewer fever episodes than the placebo group (p = 0.030). CONCLUSION: These results suggest that combined vitamin A plus zinc supplementation reduces the risk of fever and clinical malaria episodes among children, and thus may play a key role in malaria control strategies for children in Africa
Active Site Conformational Dynamics in Human Uridine Phosphorylase 1
Uridine phosphorylase (UPP) is a central enzyme in the pyrimidine salvage pathway, catalyzing the reversible phosphorolysis of uridine to uracil and ribose-1-phosphate. Human UPP activity has been a focus of cancer research due to its role in activating fluoropyrimidine nucleoside chemotherapeutic agents such as 5-fluorouracil (5-FU) and capecitabine. Additionally, specific molecular inhibitors of this enzyme have been found to raise endogenous uridine concentrations, which can produce a cytoprotective effect on normal tissues exposed to these drugs. Here we report the structure of hUPP1 bound to 5-FU at 2.3 Å resolution. Analysis of this structure reveals new insights as to the conformational motions the enzyme undergoes in the course of substrate binding and catalysis. The dimeric enzyme is capable of a large hinge motion between its two domains, facilitating ligand exchange and explaining observed cooperativity between the two active sites in binding phosphate-bearing substrates. Further, a loop toward the back end of the uracil binding pocket is shown to flexibly adjust to the varying chemistry of different compounds through an “induced-fit” association mechanism that was not observed in earlier hUPP1 structures. The details surrounding these dynamic aspects of hUPP1 structure and function provide unexplored avenues to develop novel inhibitors of this protein with improved specificity and increased affinity. Given the recent emergence of new roles for uridine as a neuron protective compound in ischemia and degenerative diseases, such as Alzheimer's and Parkinson's, inhibitors of hUPP1 with greater efficacy, which are able to boost cellular uridine levels without adverse side-effects, may have a wide range of therapeutic applications
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