bluuebunny/crossref_metadata_2025_split huggingface dataset:
The first echinocandin: caspofungin
Authors: Cornely O.A. , Schmitz Karina , Aisenbrey Sabine 
Published: April 2011

Summary. The antifungal agent caspofungin is the first echinocandin that has been approved in the US and in Europe for treatment of invasive aspergillosis in adult patients who are refractory to or intolerant of conventional amphotericin B, its lipid‐based formulations, and/or itraconazole. It is given as a 70 mg loading dose and a 50 mg daily maintainance dose as a one hour infusion. Due to low intestinal absorption an oral formulation has not been developed. Caspofungin is active against Candida spp. and Aspergillus spp. by inhibition the synthesis of β‐(1,3)‐D‐glucan, a cell wall component. The drug is inactive against Cryptococcus spp., Fusarium spp., Trichosporon spp., Rhizopus spp., and Pseudoallescheria spp. In invasive aspergillosis caspofungin resulted in higher response rates compared to a historic control under standard therapy. Efficacy data on persistently febrile neutropenic patients are pending. In several multicenter randomised double blind trials on candida infections caspofungin proved to be at least non‐inferior to standard therapies. Reports of combination therapy or highly effective antifungal treatment (HEAT) in limited patient numbers are promising. New trials of combination therapy are warranted.Zusammenfassung. Caspofungin ist das erste Antimykotikum aus der Klasse der Echinocandine. Es ist in den USA und in Europa zugelassen zur Therapie invasiver Aspergillosen erwachsener Patienten, die auf eine Standardtherapie nicht ansprechen oder diese nicht vertragen. Caspofungin wird am ersten Tag mit 70 mg dosiert und danach mit einer Erhaltungsdosis von 50 mg als einstündige Infusion verabreicht. Wegen seiner geringen enteralen Resorption ist eine orale Formulierung nicht entwickelt worden. Caspofungin ist wirksam gegen Candida spp. und Aspergillus spp. durch die Inhibition der Synthese des β‐(1,3)‐D‐Glucans, das ein Bestandteil der Zellwand ist. Die Substanz ist unwirksam gegenüber Cryptococcus spp., Fusarium spp., Trichosporon spp., Rhizopus spp., und Pseudoallescheria spp. In der Therapie der invasiven Aspergillose war Caspofungin effektiver als Standardtherapien in einem historischen Vergleichskollektiv. Daten zur Effektivität persistierend febriler neutropenischer Patienten werden erwartet. In einigen randomisierten multizentrischen doppel‐blinden Studien zu Candida‐Infektionen zeigte sich Caspofungin zumindest als nicht‐unterlegen im Vergleich zu Standardtherapien. Berichte über Kombinationstherapien, die sog. hocheffektive antimykotische Therapie (HEAT) begrenzter Patientenzahlen sind vielversprechend. Weiter führende Kombinationsstudien sind erforderlich.
Understanding the pathological features of focality, grade and tumour volume of early‐stage prostate cancer as a foundation for parenchyma‐sparing prostate cancer therapies: active surveillance and focal targeted therapy
Authors: Mouraviev Vladimir , Villers Arnauld , Bostwick David G. , Wheeler Thomas M. , Montironi Rodolfo , Polascik Thomas J. 
Published: April 2011

What's known on the subject? and What does the study add?The recent shift of pathological stage migration towards earlier forms suggested great potential for the introduction of focal therapy into urological practice. A body of the literature showed increasing frequency of unilateral and unifocal lesions that can be efficiently treated with tumour ablative techniques.The internal panel of experts has done a comprehensive review of the largest mostly single institution studies and their own trials with the aim of evaluating a value of main pathological features of early stage prostate cancer as a background to developing a concept of focal therapy. Analysis data including latest developments will help to better understand the purpose, meaning and patient selection of different kinds of focal targeted ablation of prostate cancer.OBJECTIVE• To better understand the biology and incidence of the cancer foci within the prostate through a comprehensive literature review and a review of our own data, to establish the current level of knowledge regarding the pathological foundation for active surveillance (AS) or focal therapy (FT).PATIENTS AND METHODS• A systematic review of the literature was performed, searching PubMed® from January 1994 to July 2009.• Electronic searches were limited to the English language using the keywords ‘prostate cancer’, ‘histopathology’, ‘radical prostatectomy’, ‘pathological stage’ and ‘focal therapy’.• The authors’ own data were also analysed and are presented.RESULTS• Recent data have shown a significant pathological stage migration towards earlier disease comprising unilateral pT2a/b prostate cancer (PCa).• The cancer volume of the clinically significant tumour (index lesion) has been proposed as a driving force of PCa progression and therefore should be identified and treated at an early stage.• In general, most satellite lesions do not appear to be life‐threatening.• Other pathological features, such as Gleason score, extraprostatic extension and the spatial distribution of PCa within the prostate, remain important selective criteria for AS or FT.CONCLUSION• The present study reviews the current knowledge of cancer focality, aggression and tumour volume. Further research is needed to better understand the biologic behaviour of each of the tumour foci within a cancerous prostate, and to employ this information to selected patients for no therapy (AS), parenchyma‐preserving approaches (FT) or whole gland radical therapy.
THE DYNAMIC INTERACTION BETWEEN CORPORATE AND REGIONAL CULTURES: THE CASE OF SOUTHEAST NETHERLANDS
Authors: VAN REINE PETER PRUD'HOMME , DANKBAAR BEN 
Published: April 2011

ABSTRACTCulture is widely recognised as an important factor explaining innovative performance both at the level of individual organisations and at the level of regions. Such explanations run the danger of ending up with a rather static definition of culture. This paper presents a dilemma approach of innovation culture that acknowledges the complexity, dynamics and tensions between contradictory elements of culture. Six dilemmas of innovation culture are distinguished. Interaction between the ways in which regions and companies deal with these dilemmas will influence innovative performance at both levels. The approach is applied in an analysis of the region Southeast Netherlands. The findings emphasise the need to establish a dynamic balance in the different dilemmas of culture. Intermediary organisations can play an important role in bringing companies and regions together in this balancing act. Openness to outside influences (disturbing whatever balance has been reached), appears crucial to maintain innovative performance over time.
LOCAL ECONOMIC STRUCTURE AND SECTORAL EMPLOYMENT GROWTH IN GERMAN CITIES
Authors: ILLY ANNETTE , SCHWARTZ MICHAEL , HORNYCH CHRISTOPH , ROSENFELD MARTIN T.W. 
Published: April 2011

ABSTRACTThis study systematically examines the impact of fundamental elements of urban economic structure on sectoral employment growth in German cities (“urban growth”). We test four elements simultaneously – sectoral specialisation, diversification of economic activities, urban size and the impact of local competition. To account for the effect of varying spatial delimitations in the analysis of urban growth, we further differentiate between cities and planning regions as geographical units. Our regression results show a U‐shaped relationship between localisation economies and urban growth and positive effects of local competition on urban growth. With respect to diversification, we find positive effects on urban growth on the city level, but insignificant results on the level of the planning regions. The impact of urban size also differs between free cities and planning regions; in the former, a U‐shaped relationship is found, whereas the effect is inversely U‐shaped for the latter.
MORE THAN MEETS THE EYE: NEW RECORDINGS OF MEGALITHIC ART IN NORTH‐WEST IRELAND
Authors: HENSEY ROBERT , ROBIN GUILLAUME 
Published: April 2011

SummaryIn this paper new and previously known passage tomb art in north‐west Ireland is recorded using an innovative recording technique. The use of this method, which involves vector drawing from digital photographs taken with oblique lighting (VeDPOL), has clarified and increased the instances of megalithic carving in the north‐west of Ireland. At two monuments – Listoghil and Heapstown Cairn – the new recordings have allowed us to contextualize the art within the broader corpus of passage tomb motifs. Additionally, it is proposed that one of the carvings from Listoghil is of later prehistoric origin and not Neolithic as previously believed. Finally, and most importantly, this paper highlights a group of motifs recently found at Cairn B in the Carrowkeel‐Keashcorran complex. This discovery demonstrates for the first time that megalithic art was a feature of all four major passage tomb complexes in Ireland.
MORE EARLY HELLADIC SEALINGS FROM GERAKI IN LACONIA, GREECE
Authors: WEINGARTEN J. , MACVEAGH THORNE S. , PRENT M. , CROUWEL J.H. 
Published: April 2011

SummaryIn 2002, excavations conducted by the University of Amsterdam at the acropolis site of Geraki (Laconia) revealed a storage room attached to the EH II defensive wall, apparently a casemate built into that wall. Along with pottery and abundant destruction debris were many fragments of clay sealings, some stamped with seal impressions. Sealings had already been discovered at Geraki in 1997 (OJA 18.4, 1999 = Geraki I). Together with the new sealings, Geraki becomes second only to Lerna in terms of the quantity of published sphragistic material from the EH II Aegean. This report considers their significance in terms both of recent finds in the Aegean islands and western Anatolia and their implications for exchange relations across the Aegean. Two appendices describe the formation of the contexts of the new sealings, and a further 12 sealings found elsewhere on the site, suggesting still other areas with sealing activity on the acropolis.
Neuroplastin‐65 and a mimetic peptide derived from its homophilic binding site modulate neuritogenesis and neuronal plasticity
Authors: Owczarek Sylwia , Soroka Vladislav , Kiryushko Darya , Larsen Marianne Hald , Yuan Qionglan , Sandi Carmen , Berezin Vladimir , Bock Elisabeth 
Published: April 2011

J. Neurochem. (2011) 117, 984–994.AbstractNeuroplastin‐65 (Np65) is a brain‐specific cell adhesion molecule belonging to the immunoglobulin superfamily. Homophilic trans‐interaction of Np65 mediates adhesion between cells and modulates synaptic plasticity. This interaction solely occurs through the first immunoglobulin (Ig) module of Np65, but the exact binding mechanism has not yet been elucidated. In this study, we identify the homophilic binding motif of Np65 and show that a synthetic peptide modeled after this motif, termed enplastin, binds to Np65. We demonstrate that both Np65‐ and enplastin‐induced intracellular signaling depends on fibroblast growth factor receptor, p38 mitogen‐activated protein kinase, Ca2+/calmodulin‐dependent protein kinase, and cytoplasmic Ca2+ concentration. In addition, we show that interference with Np65 homophilic binding by enplastin has an inhibitory effect on Np65‐mediated neurite outgrowth in vitro and on the initial phase of spatial learning in rats.
Multiple inhibitory actions of lidocaine on Torpedo nicotinic acetylcholine receptors transplanted to Xenopus oocytes
Authors: Alberola‐Die Armando , Martinez‐Pinna Juan , González‐Ros José Manuel , Ivorra Isabel , Morales Andrés 
Published: April 2011

J. Neurochem. (2011) 117, 1009–1019.AbstractLidocaine is a local anaesthetic that blocks sodium channels, but also inhibits several ligand‐gated ion‐channels. The aim of this work was to unravel the mechanisms by which lidocaine blocks Torpedo nicotinic receptors transplanted to Xenopus oocytes. Acetylcholine‐elicited currents were reversibly blocked by lidocaine, in a concentration dependent manner. At doses lower than the IC50, lidocaine blocked nicotinic receptors only at negative potentials, indicating an open‐channel blockade; the binding site within the channel was at about 30% of the way through the electrical field across the membrane. In the presence of higher lidocaine doses, nicotinic receptors were blocked both at positive and negative potentials, acetylcholine dose–response curve shifted to the right and lidocaine pre‐application, before its co‐application with acetylcholine, enhanced the current inhibition, indicating all together that lidocaine also blocked resting receptors; besides, it increased the current decay rate. When lidocaine, at low doses, was co‐applied with 2‐(triethylammonio)‐N‐(2,6‐dimethylphenyl) acetamide bromide, edrophonium or 1,5‐bis(4‐allyldimethylammoniumphenyl)pentan‐3‐one dibromide, which are quaternary‐ammonium molecules that also blocked nicotinic receptors, there was an additive inhibitory effect, indicating that these molecules bound to different sites within the channel pore. These results prove that lidocaine blocks nicotinic receptors by several independent mechanisms and evidence the diverse and complex modulation of this receptor by structurally related molecules.
Effect of vitamin D3 supplementation on the pharmacokinetics of digoxin – a pilot study
Authors: Kota Bhavani P. , Abdul Mohi I. M. , Allen John D. , Kalagara Madan , Roufogalis Basil D. 
Published: April 2011

AbstractEmerging evidence from preclinical, clinical and epidemiological studies suggests that vitamin D3 plays vital roles in several diseases in addition to bone disorders. According to new medical evidence, it is being recommended that vitamin D3 intake to be increased for maximal benefits in human health. However, it is necessary to consider potential side effects of increased intake of vitamin D3. Vitamin D3 exerts its actions through the vitamin D receptor, which is known to be an important regulator of P‐glycoprotein (P‐gp). As P‐gp plays a significant role in limiting drug bioavailability, we undertook a study to compare single‐dose digoxin (a P‐gp substrate) pharmacokinetics in eight healthy male subjects before and after vitamin D3 supplementation (1000 IU per day). The geometric mean ratios for AUC0–3h, AUC0–48h and Cmax were 1.06 (90% CI 0.92, 1.21) and 1.02 (90% CI 0.97, 1.08) and 1.03 (95% CI 0.86, 1.24), respectively. The median for digoxin Tmax was 0.75 h before and after vitamin D3 ingestion. The mean plasma 25‐hydroxyvitamin D3 (25(OH)D3) levels remained constant after the intake of vitamin D3 (15.4 ± 3.7 and 14.4 ± 3.6 ng/mL, respectively), while there was a modest but statistically significant increase in plasma calcium levels, from 9.32–9.68 mg/dL (P = 0.0277). These results suggest that vitamin D3 supplementation (1000 IU per day) in human volunteers does not produce a P‐gp‐mediated drug interaction with orally administered digoxin.
Volumetric Misfit in CAD/CAM and Cast Implant Frameworks: A University Laboratory Study
Authors: Almasri Riad , Drago Carl J. , Siegel Sharon Crane , Hardigan Patrick C. 
Published: April 2011

Abstract Purpose: To compare the volumetric misfit between implant restorative platforms of implants and implant frameworks manufactured with two different technologies. One set of implant frameworks was made with a CAD/CAM protocol and a tactile probe; the second protocol consisted of frameworks made with the lost‐wax technique and conventional casting technology. Materials and Methods: In this laboratory study, an acrylic resin model with five “inter‐foraminal” implants was used as the “patient” model. Implant level impressions were made, and 10 definitive master casts were fabricated. The casts were verified using an index made on the patient model. Five cast high palladium noble alloy and five CAD/CAM titanium alloy frameworks were fabricated. The patient's implants and the frameworks’ implant restorative platforms were scanned with a tactile probe, and the data were digitized. The digitized implant restorative platforms of the frameworks were fit onto the patient's digitized implants via a software program, in a process called “lofting.” This computerized procedure simulated a 1‐screw test; the process was performed on both sides. The volumetric misfit between the implant restorative platforms of the frameworks and the patient's implants were measured. A Welch's t‐test was used to determine significant differences (p < 0.05) between the misfit of the two technologies. Wilcoxon Signed‐Rank tests were used to evaluate differences between the right and left sides. Results: On average, the volumetric misfit of the CAD/CAM frameworks was 1.8 mm3 less than the volumetric misfit of the cast alloy frameworks (p < 0.05). The Wilcoxon Signed‐Rank tests showed no significant differences between the right and left sides within both systems (p > 0.05). Conclusions: The scanning technology and computer software program used in this study demonstrated that the CAD/CAM implant frameworks had statistically significantly less volumetric misfit when compared with the cast implant frameworks. There were no significant differences between the right and left 1‐screw tests within the same type of frameworks.
Human Capital: Theoretical and Empirical Insights
Authors: BOTTONE GERMANA , SENA VANIA 
Published: April 2011

There is nothing more difficult to plan, more Doubtful of success, nor more dangerous to manage Than the creation of a new system. For the initiator has the enmity of all who would Profit by the preservation of the old system, and Merely lukewarm defenders in those who should gain By the new one. N. Machiavelli (1513)
AbstractThe purpose of this paper is twofold. First, we want to challenge the notion of “human capital” as “education, training and work experience” and suggest that it is the “quality of the workforce” that matters, here defined as the set of characteristics that allow workers to function in a specific institutional and historical context. Our main conclusion is that the quality of the workforce is affected by the institutional environment where the workers live and that therefore it can vary across countries and institutional contexts. Second, we want to show the empirical relevance of this last point by testing the extent to which the quality of institutions (here proxied by the governance indicators of Kaufmann et al. (2007)) can affect the quality of the workforce (proxied by the percentage of the working age population registered in a lifelong learning program). Our empirical analysis is conducted on a data‐set of 11 European countries observed over the period 1996–2006. The results indicate that countries with better governance indicators are also endowed with a more qualified workforce.
Characterization of blood components separated from donated whole blood after an overnight holding at room temperature with the buffy coat method
Authors: Lu Fa Qiang , Kang Wei , Peng Yu , Wang Wei Ming 
Published: April 2011

BACKGROUND: With buffy coat (BC) processing of whole blood (WB) donations, increase in WB storage time to facilitate overnight holding before the separation of blood components would be a logistically attractive development. This study undertakes a comparative in vitro characterization of blood components prepared from WB samples that were either processed within 8 hours or stored overnight at room temperature before processing by the BC method.STUDY DESIGN AND METHODS: The WB units (400 mL) collected were either processed within 8 hours (fresh blood) or stored overnight (overnight blood) at room temperature. WB units were separated into individual‐component red blood cells (RBCs), BC, and plasma. The in vitro quality of these blood components (RBCs, pooled platelet concentrates [PCs], and plasma) was analyzed during storage.RESULTS: Levels of 2,3‐diphosphoglycerate (2,3‐DPG) were found to be significantly lower immediately after processing, compared with the fresh WB samples, in RBCs that had been separated from an overnight‐hold sample. However, this difference was not apparent after 14 days of storage. In pooled PCs, measurements for glucose, lactate, PO2, PCO2, extent of shape change, and hypotonic shock response were similar. The platelet yield in PCs prepared from an overnight‐hold WB sample was significantly higher, while CD62P expression and annexin V binding were lower (p < 0.05). For frozen plasma (FP), no significant differences were observed for the coagulation factors (F)II, FVII, FV, F IX, FX, and FXI; fibrinogen; and von Willebrand factor content between the 8‐ and 24‐hour FP. The FVIII was the component that was most sensitive to the prolongation of production time and it only had 80% of the activity of the 8‐hour FP.CONCLUSION: These data suggest that blood components (RBCs, pooled PCs, and FP) separated from WB that has been stored overnight at room temperature by the BC method are of acceptable quality.
Bipolar disorder and adiposity: a study using whole body dual energy X-ray absorptiometry scans
Authors: Williams Lana J. , Pasco Julie A. , Jacka Felice N. , Henry Margaret J. , Dodd Seetal , Nicholson Geoffrey C. , Kotowicz Mark A. , Berk Michael 
Published: April 2011

Williams LJ, Pasco JA, Jacka FN, Henry MJ, Dodd S, Nicholson GC, Kotowicz MA, Berk M. Bipolar disorder and adiposity: a study using whole body dual energy X-ray absorptiometry scans.Objective:Previous research has demonstrated a relationship between adiposity and bipolar disorder, although data are derived predominantly from patient samples and use indirect methods of assessing adiposity. This study investigated the association between bipolar disorder and several indices of adiposity, including body fat mass as measured by dual energy X-ray absorptiometry (DXA), in a community-based sample.Methods:In this study, 21 women with bipolar disorder and 523 healthy controls were drawn from an age-stratified, random, community-based sample of women (20–93 years) participating in the Geelong Osteoporosis Study. Bipolar disorder was diagnosed utilising a semi-structured clinical interview. Anthropometric measurements (weight, height, waist and hip circumference) were taken and fat mass was determined from whole body DXA scans (Lunar DPX-L).ResultsThose with bipolar disorder tended to have greater adiposity. Age-adjusted mean (95% CI) values for bipolar versus controls according to adiposity indices were weight 75.6 (68.9–82.3) versus 72.6 (71.3–74.0) kg, waist circumference 89.8 (84.1–95.6) versus 87.3 (86.1–88.5) cm, waist:hip ratio 0.85 (0.82–0.87) versus 0.84 (0.83–0.84), body mass index 27.6 (25.1–30.1) versus 27.5 (27.0–28.0) kg/m2, fat mass 31.4 (26.5–36.3) versus 28.6 (27.5–29.5) kg and %body fat 40.4 (36.9–43.9) versus 38.0 (37.3–38.7)%; allp> 0.05. Further adjustment for height, smoking, alcohol, psychotropic medication, energy intake or physical activity did not influence these patterns.ConclusionAlthough a pattern suggestive of greater adiposity among those with bipolar disorder was observed, no significant differences were detected. We cannot exclude the possibility of a type II error. Further research with a larger sample may produce more conclusive results.