bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shaping national mental health policy
Authors: Whiteford Harvey 
Published: April 2012

Abstract
From the perspective of those at the service delivery coalface, national mental health policy often seems a remote activity unrelated to their daily responsibilities. The concept of national policy can be vague and how it is formed opaque. The time taken from the beginnings of policy formulation to adoption and implementation can seem extraordinarily long. When national policy does become relevant it is often because it is driving change that the clinician or service manager finds confronting and difficult. It is therefore easy to be cynical about government policy, but most of us still want and expect explicit national mental health policy, the implementation of which drives improved services for people with mental illness and their families. For the creation of good policy, those working outside of government bureaucracies need to better understand, and be able to exert influence on, the policy-making process.
The aim of this chapter is to describe the policy development cycle and the factors that shape national mental health policy. A good understanding of these should enhance the capacity of service providers and others to influence the content and effectiveness of mental health policy. At the outset it is important to provide a caveat. This chapter is most relevant to countries that operate a democratic system of government. While many of the concepts discussed in the chapter will apply to policy development in any country with an organized system of government, the assumptions that underpin the policy cycle described in the chapter are most applicable in a democratically governed society.
Producing guidelines, protocols, and toolkits
Authors: Moore Troy A. , Miller Alexander L. , Kuipers Elizabeth 
Published: April 2012

Abstract
Over the past several decades, multiple factors have resulted in the development of guidelines, treatment protocols, and implementation toolkits in all branches of medicine, including psychiatry.
First, a number of studies showed that some accepted practices could not be shown to be effective when tested in randomized controlled trials (RCTs: Coffman et al., 1987; Gaebel, 1995; Gaebel et al., 2002; Kinon et al., 1998). The lack of practice effectiveness in randomized studies is often attributed to the interventions not being well defined (Michie et al., 2009).
Second, community surveys showed that many evidence-based practices were either not used, or not used properly (i.e. not used with fidelity to the key details of implementation of the practice) (Buchanan et al., 2002; Cradock et al., 2001; Howard et al., 2009; Young et al., 1998). Fidelity refers to the degree to which a particular programme follows a programme model, which is a well-defined set of interventions and procedures that helps individuals achieve some desired goal (Bond et al., 2000).
Third, studies of incorporation of evidence-based practices into everyday practice showed long delays (Codyre et al., 2008; Rosen et al., 2007; Ruggeri et al., 2008). Meanwhile, evaluation of the impact of continuing medical education programmes demonstrated their ineffectiveness in changing physician practices (Davis et al., 1995). Thus, it became clear that to affect actual medical practices, it would be necessary to put together detailed sets of recommendations, and the means to operationalize them.
Plasma Membrane Calcium ATPases Are Important Components of Receptor-Mediated Signaling in Plant Immune Responses and Development
Authors: Frei dit Frey Nicolas , Mbengue Malick , Kwaaitaal Mark , Nitsch Lisette , Altenbach Denise , Häweker Heidrun , Lozano-Duran Rosa , Njo Maria Fransiska , Beeckman Tom , Huettel Bruno , Borst Jan Willem , Panstruga Ralph , Robatzek Silke 
Published: April 2012

Abstract
Plasma membrane-resident receptor kinases (RKs) initiate signaling pathways important for plant immunity and development. In Arabidopsis (Arabidopsis thaliana), the receptor for the elicitor-active peptide epitope of bacterial flagellin, flg22, is encoded by FLAGELLIN SENSING2 (FLS2), which promotes plant immunity. Despite its relevance, the molecular components regulating FLS2-mediated signaling remain largely unknown. We show that plasma membrane ARABIDOPSIS-AUTOINHIBITED Ca2+-ATPase (ACA8) forms a complex with FLS2 in planta. ACA8 and its closest homolog ACA10 are required for limiting the growth of virulent bacteria. One of the earliest flg22 responses is the transient increase of cytosolic Ca2+ ions, which is crucial for many of the well-described downstream responses (e.g. generation of reactive oxygen species and the transcriptional activation of defense-associated genes). Mutant aca8 aca10 plants show decreased flg22-induced Ca2+ and reactive oxygen species bursts and exhibit altered transcriptional reprogramming. In particular, mitogen-activated protein kinase-dependent flg22-induced gene expression is elevated, whereas calcium-dependent protein kinase-dependent flg22-induced gene expression is reduced. These results demonstrate that the fine regulation of Ca2+ fluxes across the plasma membrane is critical for the coordination of the downstream microbe-associated molecular pattern responses and suggest a mechanistic link between the FLS2 receptor complex and signaling kinases via the secondary messenger Ca2+. ACA8 also interacts with other RKs such as BRI1 and CLV1 known to regulate plant development, and both aca8 and aca10 mutants show morphological phenotypes, suggesting additional roles for ACA8 and ACA10 in developmental processes. Thus, Ca2+ ATPases appear to represent general regulatory components of RK-mediated signaling pathways.
DELLA Signaling Mediates Stress-Induced Cell Differentiation in Arabidopsis Leaves through Modulation of Anaphase-Promoting Complex/Cyclosome Activity
Authors: Claeys Hannes , Skirycz Aleksandra , Maleux Katrien , Inzé Dirk 
Published: April 2012

Abstract
Drought is responsible for considerable yield losses in agriculture due to its detrimental effects on growth. Drought responses have been extensively studied, but mostly on the level of complete plants or mature tissues. However, stress responses were shown to be highly tissue and developmental stage specific, and dividing tissues have developed unique mechanisms to respond to stress. Previously, we studied the effects of osmotic stress on dividing leaf cells in Arabidopsis (Arabidopsis thaliana) and found that stress causes early mitotic exit, in which cells end their mitotic division and start endoreduplication earlier. In this study, we analyzed this phenomenon in more detail. Osmotic stress induces changes in gibberellin metabolism, resulting in the stabilization of DELLAs, which are responsible for mitotic exit and earlier onset of endoreduplication. Consequently, this response is absent in mutants with altered gibberellin levels or DELLA activity. Mitotic exit and onset of endoreduplication do not correlate with an up-regulation of known cell cycle inhibitors but are the result of reduced levels of DP-E2F-LIKE1/E2Fe and UV-B-INSENSITIVE4, both inhibitors of the developmental transition from mitosis to endoreduplication by modulating anaphase-promoting complex/cyclosome activity, which are down-regulated rapidly after DELLA stabilization. This work fits into an emerging view of DELLAs as regulators of cell division by regulating the transition to endoreduplication and differentiation.
Molecular phylogeny of the New World Dipsadidae (Serpentes: Colubroidea): a reappraisal
Authors: Grazziotin Felipe G. , Zaher Hussam , Murphy Robert W. , Scrocchi Gustavo , Benavides Marco A. , Zhang Ya‐Ping , Bonatto Sandro L. 
Published: April 2012

AbstractWe present a phylogenetic analysis of the New World dipsadids based on an expanded data matrix that includes 246 terminal taxa including 196 dipsadids. The species are sampled for eight genes (12S, 16S, cytb, nd2, nd4, bdnf, c‐mos, rag2). The data are explored using two distinct optimality procedures—maximum parsimony and maximum likelihood—and two alignment strategies—dynamic homology and static homology. Two previously unsampled dipsadid genera, Sordellina and Rhachidelus, are now included in the analysis. The definitions of the genera, Erythrolamprus, Clelia, Hypsirhynchus, Philodryas and Phimophis, and the tribes Alsophiini, Echinantherini and Conophiini, are revised. In order to maintain monophyly, the genus Umbrivaga is synonymized with Erythrolamprus, and two new genera are erected to accommodate Phimophis iglesiasi and Clelia rustica, as well as their closely related species. The West Indian genera Schwartzophis, Darlingtonia, Antillophis and Ocyophis are resurrected.© The Willi Hennig Society 2012.
Magnetic resonance tumor targeting imaging using gadolinium labeled human telomerase reverse transcriptase antisense probes
Authors: Ren Bing Xiu , Yang Fan , Zhu Gao Hong , Huang Zi Xing , Ai Hua , Xia Rui , Liu Xi Jiao , Lu Man , Song Bin 
Published: April 2012

To develop a molecular probe for MRI detection of human tumor telomerase reverse transcriptase (hTERT) mRNA expression. Uniformly phosphorothioate‐modified hTERT antisense oligonucleotide (ASON) homing hTERT mRNA was labeled with gadolinium (Gd) through the bifunctional chelator 1,4,7, 10‐tetraazacyclododecane‐N, N', N'', N'''‐tetraacetic acid (DOTA) stirred within 45 minutes at 60°C. The Gd labeled probes were characterized in vitro. The cellular uptake rate and biodistribution of 99mTc‐DOTA‐ASON was measured instead of that of Gd‐DOTA‐ASON. A549 lung adenocarcinoma model was established in BALB/c nude mice and Gd‐DOTA‐ASON was injected intraperitoneally and MR images were acquired using 7.0T Micro‐MRI (Bruker Biospec, Ettlingen, Germany) at different time points. Immunohistochemical analysis of telomerase activity of each xenograft was operated two days after in vivo imaging. The binding efficiency of Gd‐DOTA‐ASON reached as high as 71.7 ± 4.5% (n = 6). Gd‐DOTA‐ASON displayed perfect stability in fresh human serum at 37°C for 24 h. Compared with normal lung cells, A549 cells showed an obviously higher uptake of 99mTc‐DOTA‐ASON than that of lung cells (10.5 ± 2.7% vs. 4.8 ± 2.6%, P < 0.05). The signal intensity of A549 xenografts can be enhanced by Gd‐DOTA‐ASON and the signal to noise ratio (SNR) of tumor to muscle reached 2.37 and maintained a relatively high level within 6 h after injection. The activity of hTERT in A549 tumors can be suppressed by Gd‐DOTA‐ASON in pathological slices. The results of this study show that Gd‐DOTA‐ASON can be a promising intracellular MR contrast probe for targeting telomerase‐positive carcinomas. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02316.x, 2012)
Disease progression model in subjects with mild cognitive impairment from the Alzheimer's disease neuroimaging initiative: CSF biomarkers predict population subtypes
Authors: Samtani Mahesh N. , Raghavan Nandini , Shi Yingqi , Novak Gerald , Farnum Michael , Lobanov Victor , Schultz Tim , Yang Eric , DiBernardo Allitia , Narayan Vaibhav A. ,   the Alzheimer' s Disease Neuroimaging Initiative
Published: April 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Amnestic mild cognitive impairment MCI) represents the prodromal stage of Alzheimer's dementia and this disease progresses in a non‐linear fashion.• Disease progression depends on a variety of demographic, biochemical, genetic and cognitive factors.WHAT THIS STUDY ADDS• Baseline CSF biomarkers carry information about disease pathology and critical thresholds for these markers (Aβ and p‐tau181P) have been identified that allow segregation of the population into MCI progressers and non‐progressers.AIM The objective is to develop a semi‐mechanistic disease progression model for mild cognitive impairment (MCI) subjects. The model aims to describe the longitudinal progression of ADAS‐cog scores from the Alzheimer's disease neuroimaging initiative trial that had data from 198 MCI subjects with cerebrospinal fluid (CSF) information who were followed for 3 years.METHOD Various covariates were tested on disease progression parameters and these variables fell into six categories: imaging volumetrics, biochemical, genetic, demographic, cognitive tests and CSF biomarkers.RESULTS CSF biomarkers were associated with both baseline disease score and disease progression rate in subjects with MCI. Baseline disease score was also correlated with atrophy measured using hippocampal volume. Progression rate was also predicted by executive functioning as measured by the Trail B‐test.CONCLUSION CSF biomarkers have the ability to discriminate MCI subjects into sub‐populations that exhibit markedly different rates of disease progression on the ADAS‐cog scale. These biomarkers can therefore be utilized for designing clinical trials enriched with subjects that carry the underlying disease pathology.
Sex differences in cardiovascular drug‐induced adverse reactions causing hospital admissions
Authors: Rodenburg Eline M. , Stricker Bruno H. , Visser Loes E. 
Published: April 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Cardiovascular disease, disease outcome, drug treatment and drug response differ between men and women.WHAT THIS STUDY ADDS• Adverse drug reactions attributed to cardiovascular drugs that require hospital admission show differences between men and women, even after taking into account age and the total number of drug prescriptions.AIMS Cardiovascular disease in women is often underestimated. The effects of cardiovascular drugs differ between the sexes because of pharmacokinetic and pharmacodynamic differences. Adverse drug reactions (ADRs) within these drug classes may have serious consequences, leading to hospital admission. We aimed to study differences between men and women in hospital admissions for ADRs due to cardiovascular drugs.METHODS We conducted a nationwide study of all hospital admissions between 2000 and 2005 with data from the Dutch National Medical Register. Relative risks were calculated of hospital admissions due to ADRs to the different cardiovascular drug groups for women compared with men. By an ecological design, risks were adjusted for the total number of Dutch inhabitants and the total number of prescriptions.RESULTS In total, 14 207 of the hospital admissions (34% of all ADR‐related admissions) were attributed to cardiovascular drugs [7690 in women (54%; 95% confidence interval 53–55%)]. ‘Anticoagulants and salicylates’ (n= 8988), ‘high‐ and low‐ceiling diuretics’ (n= 2242) and ‘cardiotonic glycosides’ (n= 932) were responsible for the majority of the ADR‐related hospital admissions. The most pronounced sex differences were seen in users of low‐ceiling diuretics (relative risk 4.02; 95% confidence interval 3.12–5.19), cardiotonic glycosides (relative risk 2.38; 95% confidence interval 2.06–2.74), high‐ceiling diuretics (relative risk 2.10; 95% confidence interval 1.91–2.32) and coronary vasodilators (relative risk 0.77; 95% confidence interval 0.65–0.91).CONCLUSIONS Clear sex differences exist in ADRs requiring hospital admission for different cardiovascular drug groups. Sex differences should be taken into account in the prescription and evaluation of drugs.
Regional differences in symptomatic fever management among paediatricians in Switzerland: the results of a cross‐sectional Web‐based survey
Authors: Lava Sebastiano A. G. , Simonetti Giacomo D. , Ferrarini Alessandra , Ramelli Gian Paolo , Bianchetti Mario G. 
Published: April 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• In children antipyretic drugs should be prescribed to treat the general discomfort that accompanies fever. Nonetheless, a gap often exists between available evidence and clinical practice.• Fever is often a cause of fear among both parents and health care providers.• Prescription patterns of several drugs are modulated by socio‐cultural factors.WHAT THIS STUDY ADDS• Among the main regions of Switzerland there are significant regional differences in symptomatic fever management as well as in the perceived frequency of fear of fever.• Paediatricians active in the German speaking region less frequently differ from available recommendations than their colleagues active in the French and Italian speaking regions.AIMS In symptomatic fever management, there is often a gap between everyday clinical practice and current evidence. We were interested to see whether the three linguistic regions of Switzerland differ in the management of fever.METHODS A close‐ended questionnaire, sent to 900 Swiss paediatricians, was answered by 322 paediatricians. Two hundred and fourteen respondents were active in the German speaking, 78 in the French speaking and 30 in the Italian speaking region.RESULTS Paediatricians from the French and Italian speaking regions identify a lower temperature threshold for initiating a treatment and more frequently reduce it for children with a history of febrile seizures. A reduced general appearance leads more frequently to a lower threshold for treatment in the German speaking than in the French and Italian speaking areas. Among 1.5 and 5‐year‐old children the preference for the rectal route is more pronounced in the German than in the French speaking region. French speaking respondents more frequently prescribe ibuprofen and an alternating regimen with two drugs than German speaking respondents. Finally, the stated occurrence of exaggerated fear of fever was higher in the German and Italian speaking regions.CONCLUSIONS Switzerland offers the opportunity to compare three different regions with respect to management of febrile children. This inquiry shows regional differences in symptomatic fever management and in the perceived frequency of exaggerated fear of fever. The gap between available evidence and clinical practice is more pronounced in the French and in the Italian speaking regions than in the German speaking region.
A novel immunogenic CS1‐specific peptide inducing antigen‐specific cytotoxic T lymphocytes targeting multiple myeloma
Authors: Bae Jooeun , Song Weihua , Smith Robert , Daley John , Tai Yu‐Tzu , Anderson Kenneth C. , Munshi Nikhil C. 
Published: April 2012

SummaryThe CS1 antigen provides a unique target for the development of an immunotherapeutic strategy to treat patients with multiple myeloma (MM). This study aimed to identify HLA‐A2+ immunogenic peptides from the CS1 antigen, which induce peptide‐specific cytotoxic T lymphocytes (CTL) against HLA‐A2+ MM cells. We identified a novel immunogenic HLA‐A2‐specific CS1239‐247 (SLFVLGLFL) peptide, which induced CS1‐specific CTL (CS1‐CTL) to MM cells. The CS1‐CTL showed a distinct phenotype, with an increased percentage of effector memory and activated CTL and a decreased percentage of naïve CTL. CS1239‐247 peptide‐specific CD8+ T cells were detected by DimerX analyses and demonstrated functional activities specific to the peptide. The CTL displayed HLA‐A2‐restricted and antigen‐specific cytotoxicity, proliferation, degranulation and γ‐interferon (IFN‐γ) production against both primary MM cells and MM cell lines. In addition, the effector memory cells subset (CD45RO+CCR7−/CD3+CD8+) within CS1‐CTL showed a higher level of CD107a degranulation and IFN‐γ production as compared to effector cells (CD45RO−CCR7−/CD3+CD8+) against HLA‐A2+ primary MM cells or MM cell lines. In conclusion, this study introduced a novel immunogenic HLA‐A2‐specific CS1239‐247 peptide capable of inducing antigen‐specific CTL against MM cells that will provide a framework for its application as a novel MM immunotherapy.
Inhibitor incidence after intensive FVIII replacement for surgery in mild and moderate haemophilia A: a prospective national study in the Netherlands
Authors: Eckhardt Corien L. , Mauser‐Bunschoten Evelien P. , Peters Marjolein , Leebeek Frank W. G. , van der Meer Felix J. M. , Fijnvandraat Karin 
Published: April 2012

SummaryInhibitor development is currently the most severe complication in mild/moderate haemophilia A patients, causing increased bleeding tendency, hospitalization and mortality. It has been suggested that receiving high doses of factor VIII (FVIII) concentrates for surgical procedures is an important risk factor for inhibitor development in these patients. The current multicentre study aimed to determine prospectively the incidence of inhibitor development after intensive FVIII replacement therapy for surgical procedures in patients with mild/moderate haemophilia A. All consecutive patients with mild/moderate haemophilia A were included when they required at least 10 000 iu of FVIII concentrates (or 250 iu/kg) for 5 or more days for a surgical procedure. Potential clinical risk factors for inhibitor development and results of inhibitor tests were collected. Forty‐six patients with a median age of 54 years (interquartile range, 40–59 years) were included in the study. F8 genotyping revealed 20 different missense mutations. Patients received either recombinant (65%) or plasma‐derived FVIII concentrates (35%) by intermittent bolus injections (41%) or continuous infusion (57%). Two patients developed a low titre inhibitor post‐operatively. The incidence of inhibitor development following intensive treatment for surgery in this unselected prospective cohort of mild/moderate haemophilia A patients was 4% (95% confidence interval, 0·5–14·8).
Candidate gene polymorphisms and the risk for pregnancy‐related venous thrombosis
Authors: Dahm Anders E. A. , Bezemer Irene D. , Bergrem Astrid , Jacobsen Anne F. , Jacobsen Eva M. , Skretting Grethe , Rosendaal Frits R. , Sandset Per Morten 
Published: April 2012

SummaryVenous thrombosis (VT) is one of the leading causes of maternal death in the western world, but the genetic causes of pregnancy‐relatedVTare insufficiently understood. The aim of this study was to investigate the association between common genetic variations in candidate genes and pregnancy‐relatedVT. We undertook a hospital based case–control study of women withVTduring pregnancy or puerperium; controls were women giving birth without havingVT. Single nucleotide polymorphisms (SNPs) were selected in 49 pre‐specified candidate genes involved in coagulation, inflammation, and hormonal metabolism in 313 cases and 353 controls. We found new associations betweenSNPs and total pregnancy‐relatedVTin the genes encoding coagulation factorsVandVIII, and p‐selectin. Additional new associations betweenSNPs and antenatalVTwere found in the genes encoding the epidermal growth factor receptor, the pregnaneXreceptor, and proteinS. Of 21SNPs previously associated with thrombotic disease, rs2289252 inF11and rs3917643 inF3were associated with pregnancy‐relatedVT, while rs4524 inF5was associated with antenatalVT.