bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustainability of improvements in access to outpatient specialist care in the Netherlands
Authors: van der Voort Marc R , van Wijngaarden Jeroen , Janssen Stan , Berden Bart , van Merode Frits 
Published: October 2013

Objectives To improve access to specialist outpatient clinics without adding capacity, Dutch hospitals applied the concept of ‘Advanced Access’. Our aim was to determine whether initial improvements are sustained for three years and to identify the factors that influence sustainability. Methods Qualitative case studies in 14 outpatient specialist clinics. Access measurements at the start, finish and three years after the project were compared. Analysis of sustained and new interventions. Interviews with 52 practitioners, analysed with the constant comparative method to identify general factors that influence sustainability. Results Eleven out of 14 clinics were able to sustain or improve their reduced delays; two did not and for one it is uncertain. The clinics maintained the majority of the interventions and all introduced new interventions. Three generic factors emerged that influenced their ability to sustain the results: increased responsiveness to better match supply and demand; clinical leadership and incentives; and a shared belief that they can and should control access together. Conclusions Reduction of delays in access can be sustained if the way of thinking and the planning system becomes demand driven and flexible and if care providers experience benefits. Unlike previous studies, senior management support and formal training was not relevant though clinical leadership and informal socialization was. Making multidisciplinary teams responsible for improvement appears to be vital.
A community pain service solution-focused pain management programme: delivery and preliminary outcome data
Authors: Simm Rebecca , Iddon Joanne , Barker Chris 
Published: October 2013

Summary points 1. This article introduces a rationale for a solution-focused approach to a community-based pain management programme (PMP), describing delivery and preliminary outcome data. 2. It suggests PMPs can be feasibly run in the community without necessity for hospital care setting. 3. A community setting is also advantageous in that it allows maintenance of social networks and close third-sector links to support long-term, sustained mental well-being. 4. Solution-focused psychological approaches help the clinician tap into patient expertise and develop rich descriptions of the patient’s preferred future, enhancing self-efficacy and empowerment. 5. Evaluation found significant statistical and clinical improvements in pre–post pain self-efficacy, mental well-being and function (but findings were limited by internal and external validity and no significant effect was found on pain levels). 6. Statistically significant change was maintained at 10 weeks for self-efficacy and function (and for the latter, clinically significant change was also maintained); improvements in mental well-being showed maintenance at all measured time points (up to 12 months) in terms of both statistical and clinical significant changes.
Primary care practitioner and patient understanding of the concepts of multimorbidity and self-management: A qualitative study
Authors: Kenning Cassandra , Fisher Louise , Bee Penny , Bower Peter , Coventry Peter 
Published: October 2013

Objectives: The aim of this article is to offer insight into how professionals and patients understand and experience multimorbidity and how these accounts differ, and how they affect attitudes and engagement with self-management. Methods: Semi-structured interviews with 20 primary healthcare practitioners and 20 patients with at least 2 long-term conditions (including coronary heart disease, diabetes, osteoarthritis, chronic obstructive pulmonary disease and depression). Thematic analysis was used, and themes were identified using an open-coding method. Results: Practitioners associated multimorbidity with complexity and uncertainty in the clinic, leading to emotional strain and ‘heart sink’. Patient accounts differed. Some described multimorbidity as problematic when it exacerbated their symptoms and caused emotional and psychological strain. Others did not perceive multimorbidity as problematic. Self-management was seen by practitioners and patients to be a key element of managing multiple conditions, but drivers for prompting and engaging in self-management differed between patients and practitioners. Conclusion: This study suggests that recommendations for clinical practice for multimorbid patients should take into account the gap in perceptions between practitioner and patients about experiences of multimorbidity. Not least, practice would need to reflect the tension between practitioners’ and patients’ accounts about the role and benefits of self-management in the presence of multimorbidity.
Functional and differential proteomic analyses to identify platelet derived factors affecting ex vivo expansion of mesenchymal stromal cells
Authors: Kinzebach Sven , Dietz Lisa , Klüter Harald , Thierse Hermann-Josef , Bieback Karen 
Published: October 2013

Abstract

Background
Multilineage differentiation, immunomodulation and secretion of trophic factors render mesenchymal stromal cells (MSC) highly attractive for clinical application. Human platelet derivatives such as pooled human platelet lysate (pHPL) and thrombin-activated platelet releasate in plasma (tPRP) have been introduced as alternatives to fetal bovine serum (FBS) to achieve GMP-compliance. However, whereas both pHPL and tPRP support similar proliferation kinetics of lipoaspirate-derived MSC (LA-MSC), only pHPL significantly accelerates bone marrow-derived MSC (BM-MSC) expansion. To identify functionally bioactive factors affecting ex vivo MSC expansion, a differential proteomic approach was performed and identified candidate proteins were evaluated within a bioassay.

Results
Two dimensional difference gel electrophoresis (2D-DIGE), MALDI-TOF analyses and complementary Western blotting revealed 20 differential protein species. 14 candidate proteins occured at higher concentrations in pHPL compared to tPRP and 6 at higher concentrations in tPRP. The candidate proteins fibrinogen and apolipoprotein A1 differentially affected LA- and BM-MSC proliferation.
In a second set of experiments, reference cytokines known to foster proliferation in FBS were tested for their effects in the human supplements. Interestingly although these cytokines promoted proliferation in FBS, they failed to do so when added to the humanized system.

Conclusions
The differential proteomic approach identified novel platelet derived factors differentially acting on human MSC proliferation. Complementary testing of reference cytokines revealed a lack of stimulation in the human supplements compared to FBS. The data describe a new coherent approach to combine proteomic technologies with functional testing to develop novel, humanized, GMP-compliant conditions for MSC expansion.
Performance of a HRP-2/pLDH based rapid diagnostic test at the Bangladesh-India-Myanmar border areas for diagnosis of clinical malaria
Authors: Elahi Rubayet , Mohon Abu Naser , Khan Wasif A , Haque Rashidul , Alam Mohammad Shafiul 
Published: October 2013

AbstractBackgroundThe rapid diagnostic test (RDT) has been adopted in contemporary malaria control and management programmes around the world as it represents a fast and apt alternative for malaria diagnosis in a resource-limited setting. This study assessed the performance of a HRP-2/pLDH based RDT (Parascreen® Pan/Pf) in a laboratory setting utilizing clinical samples obtained from the field.MethodsWhole blood samples were obtained from febrile patients referred for malaria diagnosis by clinicians from two different Upazila Health Complexes (UHCs) located near the Bangladesh-India and Bangladesh-Myanmar border where malaria is endemic. RDT was performed on archived samples and sensitivity and specificity evaluated with expert microscopy (EM) and quantitative PCR (qPCR).ResultsA total of 327 clinical samples were made available for the study, of which 153 werePlasmodium falciparum-positive and 54 werePlasmodium vivax-positive. In comparison with EM, forP. falciparummalaria, the RDT had sensitivity: 96.0% (95% CI, 91.2-98.3) and specificity: 98.2% (95% CI, 94.6-99.5) and forP. vivax, sensitivity: 90.7% (95% CI, 78.9-96.5) and specificity: 98.9% (95% CI, 96.5-99.7). Comparison with qPCR showed, forP. falciparummalaria, sensitivity: 95.4% (95% CI, 90.5-98.0) and specificity: 98.8% (95% CI, 95.4-99.7) and forP. vivaxmalaria, sensitivity: 89.0% (95% CI,77.0-95.4) and specificity: 98.8% (95% CI, 96.5-99.7). Sensitivity varied according to different parasitaemia for falciparum and vivax malaria diagnosis.ConclusionParascreen® Pan/Pf Rapid test for malariashowed acceptable sensitivity and specificity in border belt endemic areas of Bangladesh when compared with EM and qPCR.
Molecular characterization and impacts of a strain of Grapevine leafroll-associated virus 2 causing asymptomatic infection in a wine grape cultivar
Authors: Poojari Sudarsana , Alabi Olufemi J , Naidu Rayapati A 
Published: October 2013

AbstractBackgroundGrapevine leafroll (GLD) is considered as the most economically important virus disease affecting wine grapes (Vitis viniferaL.) in many grapevine-growing regions. GLD produces distinct symptoms in red- and white-berried cultivars. In this study, we determined the complete genome sequence of an asymptomatic strain ofGrapevine leafroll-associated virus 2(GLRaV-2) and studied its impacts on fruit yield and berry quality attributes in an own-rooted, red-berried wine grape cultivar.FindingsThe complete genome of GLRaV-2 obtained from a red-berried wine grape cultivar Sangiovese, designated as GLRaV-2-SG, was determined to be 16,474 nucleotides in length. In pairwise comparisons, using complete genome sequences of GLRaV-2 strains available in GenBank, GLRaV-2-SG was more closely related to GLRaV-2-OR1 from Oregon, USA, and GLRaV-2-93/955 from South Africa, and distantly related to GLRaV-2-BD from Italy and GLRaV-2-RG from USA. Fruit yield estimates and berry quality analysis at the time of commercial harvest indicated that GLRaV-2-SG had little impact on fruit yield and total soluble solids, juice pH and total anthocyanins of berry skin.ConclusionsBecause so little is known about the effects of asymptomatic virus infections in wine grapes, this study expanded our knowledge of the occurrence and impacts of GLRaV-2 causing asymptomatic infections. Our results indicated that an asymptomatic strain of GLRaV-2 may not cause significant effects to overall fruit yield and berry quality in own-rooted vines, but can affect its host in more subtle ways. Since disease symptoms are not apparent, relying on visual symptoms during disease surveys may result in the escape of asymptomatic strains of GLRaV-2. Thus, it is necessary to use appropriate diagnostic assays for reliable detection of viruses causing asymptomatic infections.
Tricuspid valve obstruction and right heart failure due to a giant right atrial myxoma arising from the superior vena cava
Authors: Xiao Zheng-hua , Hu Jia , Zhu Da , Shi Ying-kang , Zhang Er-yong 
Published: October 2013

Abstract
Myxomas are the most common primary cardiac tumors. The cardiac myxomas are mostly diagnosed within the atria, and only a few such tumors are reported to have arisen from atrioventricular valves or pulmonary vessels. The authors here present a case of 59-year-old Chinese woman who was hospitalized for exacerbating symptoms of tricuspid stenosis and right heart failure. Echocardiography revealed a giant right atrial myxoma arising from an extremely rare site, the anterior wall of the superior vena cava. With the aid of transesophageal echocardiography, the surgical resection was performed successfully with the patient achieving complete recovery.
The neurology of rhizomelic chondrodysplasia punctata
Authors: Bams-Mengerink Annemieke M , Koelman Johannes HTM , Waterham Hans , Barth Peter G , Poll-The Bwee Tien 
Published: October 2013

Abstract

Background
To describe the neurologic profiles of Rhizomelic chondrodysplasia punctata (RCDP); a peroxisomal disorder clinically characterized by skeletal abnormalities, congenital cataracts, severe growth and developmental impairments and immobility of joints. Defective plasmalogen biosynthesis is the main biochemical feature.

Methods
Observational study including review of clinical and biochemical abnormalities, genotype, presence of seizures and neurophysiological studies of a cohort of 16 patients with RCDP.

Results
Patients with the severe phenotype nearly failed to achieve any motor or cognitive skills, whereas patients with the milder phenotype had profound intellectual disability but were able to walk and had verbal communication skills. Eighty-eight percent of patients developed epileptic seizures. The age of onset paralleled the severity of the clinical and biochemical phenotype. Myoclonic jerks, followed by atypical absences were most frequently observed. All patients with clinical seizures had interictal encephalographic evidence of epilepsy. Visual evoked (VEP) and brain auditory potential (BAEP) studies showed initial normal latency times in 93% of patients. Deterioration of VEP occurred in a minority in both the severe and the milder phenotype. BAEP and somatosensory evoked potentials (SSEP) were more likely to become abnormal in the severe phenotype. Plasmalogens were deficient in all patients. In the milder phenotype levels of plasmalogens were significantly higher in erythrocytes than in the severe phenotype. Phytanic acid levels ranged from normal to severely increased, but had no relation with the neurological phenotype.

Conclusion
Neurodevelopmental deficits and age-related occurrence of seizures are characteristic of RCDP and are related to the rest-activity in plasmalogen biosynthesis. Evoked potential studies are more likely to become abnormal in the severe phenotype, but are of no predictive value in single cases of RCDP.
Rituximab and abatacept but not tocilizumab impair antibody response to pneumococcal conjugate vaccine in patients with rheumatoid arthritis
Authors: Crnkic Kapetanovic Meliha , Saxne Tore , Jönsson Göran , Truedsson Lennart , Geborek Pierre 
Published: October 2013

Abstract
Introduction
The objective of the study was to investigate the impact of newer biologic treatments including rituximab, abatacept and tocilizumab on antibody response following pneumococcal vaccination using a 7-valent conjugate vaccine in patients with established rheumatoid arthritis (RA).

Methods
Patients with RA receiving rituximab, abatacept or tocilizumab as monotherapy or combined with methotrexate (MTX) participated in the study. Specific IgG antibodies against 23F and 6B serotypes were measured at vaccination and 4 to 6 weeks after vaccination using standardised ELISA. Geometric mean antibody levels (GML) were calculated. Antibody response (AR) was defined as the ratio between post- and pre-vaccination antibody levels and a positive antibody response (posAR) was AR ≥2.

Results
In total, 88 patients were enrolled in the study. Of 55 patients treated with rituximab, 26 (46%) were on concomitant MTX. Of patients receiving abatacept (n = 17) and tocilizumab (n = 16) biologic treatment was given in combination with MTX in 13 (76%) and 9 (56%) patients, respectively. Patients treated with rituximab had significantly lower AR compared to those on tocilizumab, as well as compared to previously reported RA patients on MTX and controls (spondylarthropathy patients treated with NSAIDs and/or analgesics). In total, 10.3% of patients on rituximab monotherapy and no patient on rituximab + MTX had posAR for both serotypes. For abatacept and tocilizumab the corresponding figures were 17.6% and 50%.

Conclusion
In this cohort of patients with established RA, treatment with rituximab and abatacept was associated with diminished antibody response but this was most pronounced for rituximab. Pneumococcal conjugate vaccine administrated during ongoing tocilizumab treatment seems to be associated with sufficient antibody response. Pneumococcal vaccination should preferably be encouraged before initiation of rituximab or abatacept treatment.

Trial registration
NCT00828997 and EudraCT EU2007-006539-29.
Top Notch cancer stem cells by paracrine NF-κB signaling in breast cancer
Authors: Zhang Weizhou , Grivennikov Sergei I 
Published: October 2013

AbstractCancer stem cells are likely to play critical roles in metastasis, therapy resistance, and recurrence of hematological and solid malignancies. It is well known that the stem cell niche plays a key role for asymmetric division and homeostasis of normal stem cells, whereas cancer stem cells seem to use these niches. Among many pathways involved in self-renewal of cancer stem cells, nuclear factor-kappa B (NF-κB) signaling has been documented to promote their expansion in a cell-autonomous fashion. A recent study, however, suggests that paracrine NF-κB activation promotes the expansion of cancer stem cells through the activation of Notch in basal-type breast cancer cells.
Microdomains in the membrane landscape shape antigen-presenting cell function
Authors: Zuidscherwoude Malou , de Winde Charlotte M , Cambi Alessandra , van Spriel Annemiek B 
Published: October 2013

ABSTRACTThe plasma membrane of immune cells is a highly organized cell structure that is key to the initiation and regulation of innate and adaptive immune responses. It is well-established that immunoreceptors embedded in the plasma membrane have a nonrandom spatial distribution that is important for coupling to components of intracellular signaling cascades. In the last two decades, specialized membrane microdomains, including lipid rafts and TEMs, have been identified. These domains are preformed structures (“physical entities”) that compartmentalize proteins, lipids, and signaling molecules into multimolecular assemblies. In APCs, different microdomains containing immunoreceptors (MHC proteins, PRRs, integrins, among others) have been reported that are imperative for efficient pathogen recognition, the formation of the immunological synapse, and subsequent T cell activation. In addition, recent work has demonstrated that tetraspanin microdomains and lipid rafts are involved in BCR signaling and B cell activation. Research into the molecular mechanisms underlying membrane domain formation is fundamental to a comprehensive understanding of membrane-proximal signaling and APC function. This review will also discuss the advances in the microscopy field for the visualization of the plasma membrane, as well as the recent progress in targeting microdomains as novel, therapeutic approach for infectious and malignant diseases.
Effects of Neurokinin B Administration on Reproductive Hormone Secretion in Healthy Men and Women
Authors: Jayasena Channa N. , Comninos Alexander N. , De Silva Akila , Abbara Ali , Veldhuis Johannes D. , Nijher Gurjinder M. K. , Ganiyu-Dada Zainab , Vaal Meriel , Stamp Gordon , Ghatei Mohammad A. , Bloom Stephen R. , Dhillo Waljit S. 
Published: October 2013

Background:Neurokinin B (NKB) is a member of the tachykinin family of peptides. Inactivating mutations in the tachykinin 3 or tachykinin 3 receptor gene are associated with pubertal failure and congenital hypogonadotrophic hypogonadism in humans. This suggests that NKB may have a critical role in human reproduction. The effects of NKB administration have not been investigated previously in humans.Aim:The aim of this study was to determine the effects of iv administration of NKB on gonadotrophin secretion in healthy male and female volunteers.Methods:A total of 23 healthy men and 11 healthy women participated in the study. After an initial dose-finding study (study 1), men received a 4-hour infusion of vehicle (gelofusin) followed by a 4-hour infusion of NKB (2.56 or 5.12 nmol/kg/h) (study 2), and an 8-hour infusion of vehicle or NKB during different visits (study 3). Healthy women underwent a dose-finding study consisting of a 3-hour NKB administration during the follicular phase of the menstrual cycle, and the maximum dose of NKB was also tested during the preovulatory and midluteal phases of menstrual cycle (study 4).Results:Mean LH, FSH, and T secretion were not significantly altered during a 90-minute infusion of NKB (0.4–5.12 nmol/kg/h), or a 4-hour infusion of NKB (5.12 nmol/kg/h). No alterations in gonadotrophin secretion or LH pulsatility were observed during an 8-hour infusion of NKB when compared with vehicle. Doses of 0.64–5.12 nmol/kg/h NKB did not significantly alter LH, FSH, or estradiol secretion in healthy women during the follicular phase of the menstrual cycle. Finally, 5.12 nmol/kg/h did not significantly alter reproductive hormone secretion during the preovulatory or midluteal phases of the menstrual cycle.Conclusions:This is the first clinical study of NKB administration. None of the doses of NKB tested were associated with significant alterations in reproductive hormone secretion in healthy male or female volunteers. These novel data add to our understanding of the physiological actions of NKB in human reproduction.
Stabilization and Modification of Gold Nanocube Surfaces with Layered Silicate
Authors: Eguchi Miharu , Ito Masae , Ishibashi Taka-aki 
Published: October 2013

Abstract
The surface stability of metal nanoparticles was enhanced by adsorption of layered silicate (so-called “clay”) on metal nanocubes whose surface was protected by a surfactant. The strong adsorption of the layered silicate to the metal nanocubes via the surfactant eliminated the need for using excess surfactant for metal nanoparticle dispersion. Furthermore, the surface of the negatively charged hybrids was demonstrated to be modifiable with cationic molecules.
Pricing and Revenue Management: The Value of Coordination
Authors: Kocabıyıkoğlu Ayşe , Popescu Ioana , Stefanescu Catalina 
Published: October 2013

The integration of systems for pricing and revenue management must trade off potential revenue gains against significant practical and technical challenges. This dilemma motivates us to investigate the value of coordinating decisions on prices and capacity allocation in a stylized setting. We propose two pairs of sequential policies for making static decisions—on pricing and revenue management—that differ in their degree of integration (hierarchical versus coordinated) and their pricing inputs (deterministic versus stochastic). For a large class of stochastic, price-dependent demand models, we prove that these four heuristics admit tractable solutions satisfying intuitive sensitivity properties. We further evaluate numerically the performance of these policies relative to a fully coordinated model, which is generally intractable. We find it interesting that near-optimal performance is usually achieved by a simple hierarchical policy that sets prices first, based on a nonnested stochastic model, and then uses these prices to optimize nested capacity allocation. This tractable policy largely outperforms its counterpart based on a deterministic pricing model. Jointly optimizing price and allocation decisions for the high-end segment improves performance, but the largest revenue benefits stem from adjusting prices to account for demand risk. This paper was accepted by Yossi Aviv, operations management.