bluuebunny/crossref_metadata_2025_split huggingface dataset:
The personalization of care services and the early impact on staff activity patterns
Authors: Jacobs Sally , Abell Jessica , Stevens Martin , Wilberforce Mark , Challis David , Manthorpe Jill , Fernandez Jose-Luis , Glendinning Caroline , Jones Karen , Knapp Martin , Moran Nicola , Netten Ann 
Published: July 2011

• Summary: This study examines the early impact on care coordinators’ (care managers’) work activity patterns of implementing the current personalization agenda within English local authorities. The Individual Budget (IB) pilots operated between 2005 and 2007 and provided a basis for personalization that, ultimately, sought to give personal care budgets to every eligible service user in England. Of particular interest was how the pilots impacted upon the roles, responsibilities and activity of care coordinators, who are expected to play a key role in this transformation of social care. A self-administered diary schedule was completed by 249 care coordinators, including teams directly involved in delivering IBs and a comparative sample of teams not involved in the pilots. These data were supplemented by semi-structured interviews with 48 care coordinators and 43 team managers. • Findings: The study found that on most measures there were no differences in working patterns between care managers with and without IB holders on their caseload. However, the results do show that – contrary to expectations – more time was spent assessing needs, and that more time generally was required to conduct support planning activities. • Application: The findings are necessarily dependent upon the early experiences of the pilot phase of IBs. As personal budgets are rolled out across all eligible service users, it will be interesting to examine whether the time-use of frontline staff, and indeed the wider organization, structure and function of local authority frontline teams, changes further.
7/7 and connective memory: Interactional trajectories of remembering in post-scarcity culture
Authors: Hoskins Andrew 
Published: July 2011

The 2005 London bombings is both marked by and is a marker of a post-scarcity memorial-media boom. There is a new contagion of the past driven by a memorial culture unstoppably equipped with the availability, portability and pervasiveness of digital devices, enabling the instant aggregation and archiving of everything. The ‘digital’, it can be said, insinuates itself in the past. In such circumstances, what are the prospects for the development and maintenance of individual memories? And, how can we consider such questions beyond the traditional dichotomous models of memory that assume memory as an orientation to something once complete and residual, and thus always already partial and in decline? This article employs a concept of ‘connective memory’ as a sensitizing tool to highlight the moment of connection as the moment of memory. Through examining the archival (institutional) and individual remembrances of the London bombings, I treat ‘memory’ as a trajectory of connections that contribute to but also collide with the emergent post-scarcity memorial-media boom.
The histone methyltransferase inhibitor, DZNep, up-regulates TXNIP, increases ROS production, and targets leukemia cells in AML
Authors: Zhou Jianbiao , Bi Chonglei , Cheong Lip-Lee , Mahara Sylvia , Liu Shaw-Cheng , Tay Kian-Ghee , Koh Tze-Loong , Yu Qiang , Chng Wee-Joo 
Published: July 2011

Abstract
Recent studies have shown that 3-Deazaneplanocin A (DZNep), a histone methyltransferase inhibitor, disrupts polycomb-repressive complex 2 (PRC2), and preferentially induces apoptosis in cancer cells, including acute myeloid leukemia (AML). However, the underlying molecular mechanisms are not well understood. The present study demonstrates that DZNep induces robust apoptosis in AML cell lines, primary cells, and targets CD34+CD38− leukemia stem cell (LSC)–enriched subpopulations. Using RNA interference (RNAi), gene expression profiling, and ChIP, we identified that TXNIP, a major redox control molecule, plays a crucial role in DZNep-induced apoptosis. We show that disruption of PRC2, either by DZNep treatment or EZH2 knockdown, reactivates TXNIP, inhibits thioredoxin activity, and increases reactive oxygen species (ROS), leading to apoptosis. Furthermore, we show that TXNIP is down-regulated in AML and is a direct target of PRC2-mediated gene silencing. Consistent with the ROS accumulation on DZNep treatment, we also see a signature of endoplasmic reticulum (ER) stress-regulated genes, commonly associated with cell survival, down-regulated by DZNep. Taken together, we uncover a novel molecular mechanism of DZNep-mediated apoptosis and propose that EZH2 may be a potential new target for epigenetic treatment in AML.
Rapamycin and IL-2 reduce lethal acute graft-versus-host disease associated with increased expansion of donor type CD4+CD25+Foxp3+ regulatory T cells
Authors: Shin Ho-Jin , Baker Jeanette , Leveson-Gower Dennis B. , Smith Aaron T. , Sega Emanuela I. , Negrin Robert S. 
Published: July 2011

Abstract
Previous work has demonstrated that both rapamycin (RAPA) and IL-2 enhance CD4+CD25+Foxp3+ regulatory T-cell (Treg) proliferation and function in vitro. We investigated whether the combination of RAPA plus IL-2 could impact acute GVHD induction after bone marrow transplantation (BMT). RAPA plus IL-2 resulted in improved survival and a reduction in acute GVHD lethality associated with an increased expansion of donor type CD4+Foxp3+ Tregs and reduced CD4+CD25− conventional T cells (Tcons). RAPA plus IL-2, but not either drug alone, increased both expansion of donor natural Tregs and conversion of induced Tregs from donor CD25− Tcons while IL-2 alone increased conversion of Tregs from CD25− Tcon. RAPA plus IL-2 treatment resulted in less production of IFN-γ and TNF, cytokines known to be important in the initiation of acute GVHD. These studies indicate that the pharmacologic stimulation of T cells with IL-2 and the suppression of Tcon proliferation with RAPA result in a selective expansion of functional Tregs and suppression of acute GVHD.
The vitronectin-binding function of PAI-1 exacerbates lung fibrosis in mice
Authors: Courey Anthony J. , Horowitz Jeffrey C. , Kim Kevin K. , Koh Timothy J. , Novak Margaret L. , Subbotina Natalya , Warnock Mark , Xue Bing , Cunningham Andrew K. , Lin Yujing , Goldklang Monica P. , Simon Richard H. , Lawrence Daniel A. , Sisson Thomas H. 
Published: July 2011

AbstractPlasminogen activator inhibitor-1 (PAI-1) is increased in the lungs of patients with pulmonary fibrosis, and animal studies have shown that experimental manipulations of PAI-1 levels directly influence the extent of scarring that follows lung injury. PAI-1 has 2 known properties that could potentiate fibrosis, namely an antiprotease activity that inhibits the generation of plasmin, and a vitronectin-binding function that interferes with cell adhesion to this extracellular matrix protein. To determine the relative importance of each PAI-1 function in lung fibrogenesis, we administered mutant PAI-1 proteins that possessed either intact antiprotease or vitronectin-binding activity to bleomycin-injured mice genetically deficient in PAI-1. We found that the vitronectin-binding capacity of PAI-1 was the primary determinant required for its ability to exacerbate lung scarring induced by intratracheal bleomycin administration. The critical role of the vitronectin-binding function of PAI-1 in fibrosis was confirmed in the bleomycin model using mice genetically modified to express the mutant PAI-1 proteins. We conclude that the vitronectin-binding function of PAI-1 is necessary and sufficient in its ability to exacerbate fibrotic processes in the lung.
Accumulation of oxidative DNA damage restricts the self-renewal capacity of human hematopoietic stem cells
Authors: Yahata Takashi , Takanashi Tomomi , Muguruma Yukari , Ibrahim Abd Aziz , Matsuzawa Hideyuki , Uno Tomoko , Sheng Yin , Onizuka Makoto , Ito Mamoru , Kato Shunichi , Ando Kiyoshi 
Published: July 2011

Abstract
Stem cells of highly regenerative organs including blood are susceptible to endogenous DNA damage caused by both intrinsic and extrinsic stress. Response mechanisms to such stress equipped in hematopoietic stem cells (HSCs) are crucial in sustaining hematopoietic homeostasis but remain largely unknown. In this study, we demonstrate that serial transplantation of human HSCs into immunodeficient mice triggers replication stress that induces incremental elevation of intracellular reactive oxygen species (ROS) levels and the accumulation of persistent DNA damage within the human HSCs. This accumulation of DNA damage is also detected in HSCs of clinical HSC transplant patients and elderly individuals. A forced increase of intracellular levels of ROS by treatment with a glutathione synthetase inhibitor aggravates the extent of DNA damage, resulting in the functional impairment of HSCs in vivo. The oxidative DNA damage activates the expression of cell-cycle inhibitors in a HSC specific manner, leading to the premature senescence among HSCs, and ultimately to the loss of stem cell function. Importantly, treatment with an antioxidant can antagonize the oxidative DNA damage and eventual HSC dysfunction. The study reveals that ROS play a causative role for DNA damage and the regulation of ROS have a major influence on human HSC aging.
Applicability of a “Pick a Winner” trial design to acute myeloid leukemia
Authors: Hills Robert K. , Burnett Alan K. 
Published: July 2011

AbstractRandomized clinical trials remain the gold standard to establish efficacy and safety of new treatments. In acute myeloid leukemia, large trials have been associated with gradual improvement in outcome over 2 decades in younger patients without major differences emerging between treatments. By contrast, in older patients, improvement has been minimal, which justifies a new approach to identifying effective treatments. Given the urgent unmet need, and with the emergence of several novel agents or combinations that are likely to be expensive, large benefits are probably required to change clinical practice. To address this issue, we have evolved a “Pick a Winner” randomized progressive design with a rolling incorporation of novel treatments (drug X), which has been tested in older patients with acute myeloid leukemia. The rationale, operational characteristics, and initial experience of such an approach in the context of the United Kingdom National Cancer Research Institute AML16 trial are presented.
Bone morphogenetic protein-2 functions as a negative regulator in the differentiation of myoblasts, but not as an inducer for the formations of cartilage and bone in mouse embryonic tongue
Authors: Aoyama Kayoko , Yamane Akira , Suga Takeo , Suzuki Erika , Fukui Tadayoshi , Nakamura Yoshiki 
Published: July 2011

Abstract

Background
In vitro studies using the myogenic cell line C2C12 demonstrate that bone morphogenetic protein-2 (BMP-2) converts the developmental pathway of C2C12 from a myogenic cell lineage to an osteoblastic cell lineage. Further, in vivo studies using null mutation mice demonstrate that BMPs inhibit the specification of the developmental fate of myogenic progenitor cells. However, the roles of BMPs in the phases of differentiation and maturation in skeletal muscles have yet to be determined. The present study attempts to define the function of BMP-2 in the final stage of differentiation of mouse tongue myoblast.

Results
Recombinant BMP-2 inhibited the expressions of markers for the differentiation of skeletal muscle cells, such as myogenin, muscle creatine kinase (MCK), and fast myosin heavy chain (fMyHC), whereas BMP-2 siRNA stimulated such markers. Neither the recombinant BMP-2 nor BMP-2 siRNA altered the expressions of markers for the formation of cartilage and bone, such as osteocalcin, alkaline phosphatase (ALP), collagen II, and collagen X. Further, no formation of cartilage and bone was observed in the recombinant BMP-2-treated tongues based on Alizarin red and Alcian blue stainings. Neither recombinant BMP-2 nor BMP-2 siRNA affected the expression of inhibitor of DNA binding/differentiation 1 (Id1). The ratios of chondrogenic and osteogenic markers relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH, a house keeping gene) were approximately 1000-fold lower than those of myogenic markers in the cultured tongue.

Conclusions
BMP-2 functions as a negative regulator for the final differentiation of tongue myoblasts, but not as an inducer for the formation of cartilage and bone in cultured tongue, probably because the genes related to myogenesis are in an activation mode, while the genes related to chondrogenesis and osteogenesis are in a silencing mode.
SR-A ligand and M-CSF dynamically regulate SR-A expression and function in primary macrophages via p38 MAPK activation
Authors: Nikolic Dejan , Calderon Lindsay , Du Liqin , Post Steven R 
Published: July 2011

AbstractBackgroundInflammation is characterized by dynamic changes in the expression of cytokines, such as M-CSF, and modifications of lipids and proteins that result in the formation of ligands for Class A Scavenger Receptors (SR-A). These changes are associated with altered SR-A expression in macrophages; however, the intracellular signal pathways involved and the extent to which SR-A ligands regulate SR-A expression are not well defined. To address these questions, SR-A expression and function were examined in resident mouse peritoneal macrophages incubated with M-CSF or the selective SR-A ligand acetylated-LDL (AcLDL).ResultsM-CSF increased SR-A expression and function, and required the specific activation of p38 MAPK, but not ERK1/2 or JNK. Increased SR-A expression and function returned to basal levels 72 hours after removing M-CSF. We next determined whether prolonged incubation of macrophages with SR-A ligand alters SR-A expression. In contrast to most receptors, which are down-regulated by chronic exposure to ligand, SR-A expression was reversibly increased by incubating macrophages with AcLDL. AcLDL activated p38 in wild-type macrophages but not in SR-A-/- macrophages, and p38 activation was specifically required for AcLDL-induced SR-A expression.ConclusionsThese results demonstrate that in resident macrophages SR-A expression and function can be dynamically regulated by changes in the macrophage microenvironment that are typical of inflammatory processes. In particular, our results indicate a previously unrecognized role for ligand binding to SR-A in up-regulating SR-A expression and activating p38 MAPK. In this way, SR-A may modulate inflammatory responses by enhancing macrophage uptake of modified protein/lipid, bacteria, and cell debris; and by regulating the production of inflammatory cytokines, growth factors, and proteolytic enzymes.
European priorities for research on health care organizations and service delivery
Authors: Hansen Johan , Schäfer Willemijn , Black Nick , Groenewegen Peter 
Published: July 2011

Objectives: To provide an overview of the principal areas of research on health care organization and service delivery and to identify priority areas from a European comparative perspective. Given the large quantity of articles produced on health care organizations, we focus on primary care and hospital care. Method: A combination of methods was used for describing past and current research: (i) bibliometric analyses of published research in Pubmed and Embase 2000-09; (ii) a further classification of research based on a sample of 1,010 articles; and (iii) an identification of relevant EU-funded projects over the period 2000-10. An online survey of experts was carried out to identify priorities. The results were refined through conference discussions. Results: Research into health care organizations varies considerably across Europe. This is only partly associated with differences in countries’ gross domestic product or population. Studies were categorized into four main domains: intra-organizational control; inter-organizational relations; patient relations; and governance and accountability. Past and current research may not reflect future priorities as the domain of ‘inter-organizational relations’ is regarded by most experts as the top priority for the future, while the smallest share in the sample of published research and EU-funded projects fell into that category. Expert views show considerable homogeneity, regardless of their role in the health care system or their country. Specific future priorities include the integration of care across organizational boundaries (including the relationship between primary and secondary care), patient involvement and participation and workforce skill-mix. Conclusions: The research priorities identified in this study relate to important shared challenges in Europe's health care systems. This makes cross-border learning important, especially given the clear geographical variation in health services research (HSR) funding and capacity in Europe.
Health technology assessment: Research trends and future priorities in Europe
Authors: Nielsen Camilla PalmhøJ , Funch Tina Maria , Kristensen Finn Børlum 
Published: July 2011

Objective: To provide an overview of health services research related to health technology assessment (HTA) and to identify research priorities from a European perspective. Methods: Several methods were used: systematic review of articles indexed with the MeSH term ‘technology assessment’ in PubMed from February 1999-2009; online survey among experts; and conference workshop discussions. Results: Research activity in HTA varies considerably across Europe. The research was categorised into six areas: (1) the breadth of analysis in HTA (such as economic, organizational and social aspects); (2) HTA products developed to meet the needs of policy-makers (such as horizon scanning, mini-HTA, and core HTA); (3) handling life-cycle perspectives in relation to technologies; (4) topics that challenge existing methods and for which HTA should be developed to address the themes more comprehensively (such as public health interventions and organizational interventions); (5) development of HTA capacity and programmes; and (6) links between policy and HTA. An online survey showed that the three areas that were given priority were the relationship between HTA and policy-making (71%), the impact of HTA (62%) and incorporating patient aspects in HTA (50%). Policy-makers highlighted HTA and innovation processes as their main research priority (42%). Areas that the systematic review identified as future priorities include issues within the six existing research areas such as disinvestment, developing evidence for new technologies, assessing the wider effects of technology use, and determining how HTA affects decision-making. In addition, relative effectiveness and individualized treatments are areas of growing interest. Conclusions: The research priorities identified are important for obtaining high quality and cost-effective health care in Europe. Managing the introduction, use and phasing out of technologies challenges health services throughout Europe, and these processes need to be improved to successfully manage future more general challenges. An ageing population and a diminishing workforce both require strong efforts to ensure effective and well-organized use of human resources and technologies. Furthermore, Europe needs to focus on innovation. This is closely linked to use of technologies and calls for future research.
New Brontotheriidae (Mammalia, Perissodactyla) from the early and middle Eocene of Pakistan with implications for mammalian paleobiogeography
Authors: Missiaen Pieter , Gunnell Gregg F. , Gingerich Philip D. 
Published: July 2011

Brontotheriids are common in Eocene faunas of North America and Asia but are poorly known from the Indian subcontinent. Here we describe three new late early Eocene brontotheriids from Pakistan, found in the upper part of the upper Ghazij Formation and representing the oldest Asian brontotheres. Eotitanops pakistanensis n. sp. is a small, primitive species, Balochititanops haqi n. gen. n. sp. is slightly larger and more derived, and fragmentary specimens identified as cf. Balochititanops sp. appear to represent a third, larger taxon.Improved knowledge of early brontotheres from North America permits better taxonomic resolution of some middle Eocene brontothere remains from Pakistan. ‘Eotitanops’ dayi from the Kuldana Formation is shown to be closer to Palaeosyops and is renamed Palaeosyops dayi n. comb. A new astragalus from the Baska Formation probably represents Pakotitanops latidentatus. A previously described humerus and a new calcaneum, both from the Subathu Formation, are tentatively referred to Mulkrajanops moghliensis.Phylogenetic interpretation suggests that Eotitanops pakistanensis is as primitive as the North American species of this basal brontothere genus, and also, within the limits of stratigraphic resolution, Eotitanops appeared on both continents at the same time. The origin of brontotheres is therefore equally likely to have been in Asia or in North America. The presence of the primitive brontotheres Eotitanops and Palaeosyops in Indo-Pakistan and North America indicates faunal exchange, almost certainly through Asia, although the direction of dispersal cannot be determined. The postulated high-latitude exchange coincides with a warm interval known as the Early Eocene Climatic Optimum.
Lessons on Corporate “Sustainability” Disclosure from Deepwater Horizon
Authors: Lewis Sanford 
Published: July 2011

The BP oil spill highlighted shortcomings of current financial and sustainability reporting standards and practice. “Integrated reporting” aims to combine financial and social/environmental information into a single annual corporate report. But without more stringent standards, integrated reports would neglect substantial risks and, as BP's sustainability reports demonstrate, create false impressions of good practice. To be of value, integration must: Require timely disclosure of enforcement notices, orders and allegations issued by regulators. Require disclosure of credible scientific reports and concerns indicative of potentially catastrophic risks of a company's products and activities, regardless of scientific uncertainty. Require review and disclosures of a firm's safety culture. Require disclosure of any facts or circumstances needed to ensure that the management's self-portrait of its sustainability strategies, goals and progress is not materially misleading. In conducting its misleading reporting, BP largely followed Global Reporting Initiative (GRI) guidelines. GRI is soliciting input, beginning in summer 2011, on how to revise those guidelines. Since GRI may prove a leading source for sustainability disclosure rules in integrating reporting, lessons learned from the BP experience must be applied to the next GRI revisions.