bluuebunny/crossref_metadata_2025_split huggingface dataset:
Results of a Randomized Trial of Chlorambucil Versus Fludarabine for Patients With Untreated Waldenström Macroglobulinemia, Marginal Zone Lymphoma, or Lymphoplasmacytic Lymphoma
Authors: Leblond Véronique , Johnson Steve , Chevret Sylvie , Copplestone Adrian , Rule Simon , Tournilhac Olivier , Seymour John Francis , Patmore Russell D. , Wright David , Morel Pierre , Dilhuydy Marie-Sarah , Willoughby Sara , Dartigeas Caroline , Malphettes Marion , Royer Bruno , Ewings Maeve , Pratt Guy , Lejeune Julie , Nguyen-Khac Florence , Choquet Sylvain , Owen Roger G. 
Published: December 2012

PurposeTreatment options for patients with Waldenström macroglobulinemia (WM) and closely related disorders include alkylating agents, purine analogs, and monoclonal antibodies. No large randomized studies have yet been reported comparing any of these approaches.Patients and MethodsThe randomized WM1 study (Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia) was undertaken in 101 centers in five countries enrolling 414 eligible patients (339 with WM, 37 with non–mucosa-associated lymphoid tissue marginal zone lymphoma, and 38 with lymphoplasmacytic lymphoma) who were randomly assigned to receive chlorambucil or fludarabine. The primary end point was the overall response rate (ORR).ResultsOn the basis of intent-to-treat analysis, the ORR was 47.8% (95% CI, 40.9% to 54.8%) in the fludarabine arm versus 38.6% (95% CI, 32.0% to 45.7%) in the chlorambucil arm (P = .07). With a median follow-up of 36 months (interquartile range, 18 to 58 months), median progression-free survival (PFS), and duration of response (DR) were significantly improved in the fludarabine arm compared with the chlorambucil arm: PFS, 36.3 versus 27.1 months (P = .012) and DR, 38.3 versus 19.9 months (P < .001). In patients with WM, median overall survival (OS) was not reached in the fludarabine arm versus 69.8 months in the chlorambucil arm (95% CI, 61.6 to 79.8 months; P = .014). Grade 3 to 4 neutropenia was significantly higher among patients treated with fludarabine (36%) compared with patients treated with chlorambucil (17.8%; P < .001). Second malignancies were significantly more frequent in the chlorambucil arm with 6-year cumulative incidence rate of 20.6% versus 3.7% in the fludarabine arm (P = .001).ConclusionIn the complete intent-to-treat study population, fludarabine significantly improved PFS compared with chlorambucil, and in patients with WM, it improved OS.
Impact of Medication Reconciliation on Medication Error Rates in Community Hospital Cardiac Care Units
Authors: Benson John M. , Snow Greg 
Published: December 2012

Background/Objective Medication reconciliation has become a practice standard across the country. We conducted a prospective study to measure the impact of medication reconciliation on the rates of medication error in cardiac care units. Methods We used 2 cardiac care units of similar size and case mix index (a measure of patient acuity) at separate hospitals to measure the difference in changes in medication error rates when medication reconciliation was implemented in the study unit, but not the control unit. A total of 457 patients were enrolled. Medication histories were recorded and compared with medication orders at admission to the units and upon transfer or discharge from the units. Errors were categorized as omission, incorrect drug order details, therapeutic duplication, missing information, medication allergy, drug interaction, incorrect therapeutic substitution, or contraindication. Adjudication of errors was done by a 3-pharmacist panel that was blinded to study group. A Poisson regression model was used to determine the significance of the difference in error rate changes between the study and control units. Results Errors were found in 325 of 7,203 orders reviewed (4.5%). Medication error rates decreased from 7.2% to 3.4% in the study group (3.8% absolute error reduction) and from 4.3% to 3.3% in the control group (1% absolute error reduction). The difference in changes in error rates between groups was statistically significant ( P < .0001). Conclusion Medication reconciliation has been one of the most costly and difficult health care quality improvement initiatives in recent history. Based on our findings, it appears that significant reductions in medication errors, the primary purpose for its implementation, can be achieved.
Azithromycin-Induced Hepatotoxicity
Authors: Kim Mina , Hynicka Lauren M. 
Published: December 2012

Objective To report a case of hepatotoxicity in a patient receiving azithromycin. Case Summary A 38-year-old female was admitted for an acute exacerbation of her liver disease. The patient received a course of azithromycin 2 weeks prior to admission for a respiratory tract infection. On admission, the patient had elevated liver function tests (LFTs), ascites, jaundice with sclera icterus, and abdominal pain. Etiologies such as infection and worsening liver disease were ruled out, and the patient's symptoms and transaminitis were attributed to azithromycin-induced hepatotoxicity. The patient was medically managed with diuretics and discharged after the symptoms stabilized and LFTs were trending down. Discussion There are 6 previous case reports of patients experiencing azithromycin-induced hepatotoxicity. The patient's presentation and onset of symptoms after azithromycin initiation were similar to other patients. Although this patient had a history of steatohepatitis, progression of liver disease was ruled out and other etiologies were considered unlikely. The patient's laboratory values supported cholestatic liver injury, and the most likely cause of the transaminitis and symptoms was attributed to azithromycin. Although azithromycin is usually well-tolerated and liver injury is a rare adverse effect, there is increasing literature surrounding azithromycin-induced hepatotoxicity. The Naranjo adverse drug reaction probability scale revealed a possible interaction between azithromycin and the hepatotoxic adverse event. Conclusions We report a possible case of azithromycin-induced hepatotoxicity. Even though hepatotoxicity is an uncommon side effect of azithromycin, prescribers should be cognizant of this potential adverse effect in order to discontinue therapy as necessary and prevent re-exposure to the medication.
Low 25-Hydroxyvitamin D and Risk of Type 2 Diabetes: A Prospective Cohort Study and Metaanalysis
Authors: Afzal Shoaib , Bojesen Stig E , Nordestgaard Børge G 
Published: December 2012

BACKGROUNDVitamin D deficiency has been implicated in decreased insulin secretion and increased insulin resistance, hallmarks of type 2 diabetes mellitus. We tested the hypothesis that low plasma 25-hydroxyvitamin D [25(OH)D] is associated with increased risk of type 2 diabetes in the general population.METHODSWe measured 25(OH)D in 9841 participants from the general population, of whom 810 developed type 2 diabetes during 29 years of follow-up. Analyses were adjusted for sex, age, smoking status, body mass index, income, physical activity, HDL cholesterol, and calendar month of blood draw.RESULTSLower 25(OH)D concentrations, by clinical categories or seasonally adjusted quartiles, were associated with higher cumulative incidence of type 2 diabetes (trend, P = 2×10−7 and P = 4×10−10). Multivariable adjusted hazard ratios of type 2 diabetes were 1.22 (95% CI 0.85–1.74) for 25(OH)D &lt;5 vs ≥20 μg/L and 1.35 (1.09–1.66) for lowest vs highest quartile. Also, the multivariable adjusted hazard ratio of type 2 diabetes for a 50% lower concentration of 25(OH)D was 1.12 (1.03–1.21); the corresponding hazard ratio for those ≤58 years old was 1.26 (1.15–1.41). Finally, in a metaanalysis of 16 studies, the odds ratio for type 2 diabetes was 1.50 (1.33–1.70) for the bottom vs top quartile of 25(OH)D.CONCLUSIONSWe observed an association of low plasma 25(OH)D with increased risk of type 2 diabetes. This finding was substantiated in a metaanalysis.
Diurnal Rhythm rather than Dietary Iron Mediates Daily Hepcidin Variations
Authors: Schaap Charlotte CM , Hendriks Jan CM , Kortman Guus AM , Klaver Siem M , Kroot Joyce JC , Laarakkers Coby MM , Wiegerinck Erwin T , Tjalsma Harold , Janssen Mirian CH , Swinkels Dorine W 
Published: December 2012

BACKGROUND
The iron-regulating hormone hepcidin is a promising biomarker in the diagnosis of iron disorders. Concentrations of hepcidin have been shown to increase during the day in individuals who are following a regular diet. It is currently unknown whether these increases are determined by an innate rhythm or by other factors. We aimed to assess the effect of dietary iron on hepcidin concentrations during the day.

METHODS
Within a 7-day interval, 32 volunteers received an iron-deficient diet on 1 day and the same diet supplemented with 65 mg ferrous fumarate at 0815 and 1145 on another day. Blood was drawn to assess ferritin, hepcidin-25, and transferrin saturation (TS) throughout both days at 4 time points between 0800 (fasted) and 1600. A linear mixed model for repeated data was used to analyze the effect of iron intake on TS and hepcidin concentrations.

RESULTS
Baseline values of hepcidin at 0800 correlated significantly with ferritin (r = 0.61). During the day of an iron-deficient diet the mean TS was similar both in men and in women, whereas hepcidin increased. During the day with iron supplementation the mean TS was significantly higher both in men and in women, and the mean hepcidin was moderately but significantly higher in women (1.0 nmol/L, 95% CI, 0.2–1.8) but not in men (0.0 nmol/L, 95% CI, −0.8 to 0.8).

CONCLUSIONS
Our data demonstrate that ferritin sets the basal hepcidin concentrations and suggest that innate diurnal rhythm rather than dietary iron mediates the daily hepcidin variations. These findings will be useful for optimizing sampling protocols and will facilitate the interpretation of hepcidin as an iron biomarker.
Moderne Unternehmen in der vorindustriellen Zeit: Das Beispiel der Porzellanmanufaktur Meißen
Authors: Monti Alessandro 
Published: December 2012

Abstract
Analysis covering the early development of modern companies and the rise of strategies like marketing, pricing and product management has traditionally dated the beginning of modern business activity to the industrial revolution and the second half of the 19th century. Although this research on modern business history has recently received increasing attention, it remains rather unclear what makes a company truly “modern” and what the defining characteristics of such companies are. In addition, there is limited insight into whether the rise of modern companies might have started before the prevailing historical period of the 19th century. The following work tries to close this gap by providing a framework for identifying modern business operations and presenting a set of key elements that can be used as criteria for modern companies. It will be shown that modern companies can be traced back to as early as the beginning of the 18th century. This is achieved by presenting the case of the Meissen porcelain factory, which has been manufacturing porcelain since 1710, adopting a unique blend of modern market strategies.
Handlung, Firma, Unternehmen. Zur Institutionalisierung der modernen Unternehmung im 19. Jahrhundert
Authors: Banken Ralf 
Published: December 2012

Abstract
The article focusses on the development of companies’ legal forms and the institutionalisation of modern enterprises in the early 19th century German economic system. It demonstrates that the development of multiple modern enterprises in Germany after 1800 preceded the evolvement of statutory company legal forms, as modern company law was not introduced until the Allgemeines Deutsches Handelsgesetzbuch of 1861. By this time, the economic systems surrounding modern enterprises were already widespread and had become generally accepted institutions in economic life. The article concludes by analysing the institutionalisation of a company as a case in hand. The case study demonstrates – by taking Werner Sombart’s consideration of businesses “gaining independence” from their owners into account – that even the institutionalisation of one of the early large-scale enterprises –the Gutehoffnungshütte concern – involved a lengthy process, and was not achieved by the enterprises’ foundation or its choice of company legal form alone.
Experientia lucrativa? Erfahrungswissen und Wissenserfahrung im europäischen Mittelalter
Authors: Kintzinger Martin 
Published: December 2012

Abstract
In this essay Martin Kintzinger takes as his starting point observations on the current debate regarding knowledge and asserts a lack of reflection on the status of knowledge in pre-modern societies. In Sebastian Brant’s work ‘Narrenschiff’ and other contemporary critical writings, Kintzinger finds evidence that the medieval critique of experts was not by necessity a critique of expertise per se. Rather, it often was a critique of an expertise based on purely theoretical book learning, deemed unpractical and inapplicable. Significantly, there existed a counter-conception of an expert who possessed both theoretical knowledge and practical experience and who was deemed practically able to cure disease, or give valuable legal advice etc. Of course, the term experientia was first used in this context only around 1600. But Kintzinger argues that experience-based knowledge, which is associated with inductive inference and the modern natural sciences, was not a product of the early modern period. Rather, the notion of experience as a warrant of true knowledge was heavily rooted in medieval thought. This essay subsequently traces the emergence of the notion of experience to Scholasticism, to the thought of Thomas Aquinas and Albert the Great and to the medieval debate on the dualism between the arts and science, and between empiricus and theoricus respectively.
Surface Modified Boehmite Aluminas: A Versatile Approach to Nano-scale Particle Dispersion and Nanocomposites
Authors: Baxter Steven L. 
Published: December 2012

AbstractCertain forms of monohydrate aluminum oxide, commonly known as boehmite or pseudoboehmite alumina, are known to disperse in water at low pH to nano-scale dimensions. The upsurge of interest in nano-scale structures has prompted our study of the surface modification of nano-scale boehmite aluminas with organic acids in order to achieve dispersion of these materials in non-aqueous systems and alkaline aqueous systems.This paper discusses the variety of modifiers used to achieve compatibilization and dispersion of nano-sized particles of these boehmite aluminas in aqueous and organic matrices. Organic modification of a variety of crystallite sizes (5-60 nm) and shapes (plates, needles, blocks) has been achieved, including materials of high aspect ratio. We describe the properties of these dispersions, including primary particle size, dispersed particle size, and surface charge. Finally, we present physical property data of polymer nanocomposites prepared from these materials. These materials are based on a commercial process which has been in operation for over 40 years and which has global production capacities of 70,000 tons per annum.
Antiviral Agents Derived from Novel 1-adamantyl Singlet Nitrenes
Authors: Kesel Andreas J , Weiss Hans-Christoph , Schönleber Andreas , Day Craig W , Barnard Dale L , Detorio Mervi A , Schinazi Raymond F 
Published: December 2012

Background: Amantadine constitutes an interesting, diamond crystal lattice-shaped, antivirally active amine with an inhibitory effect on influenza A viruses causing common ‘flu’ in humans. Unfortunately, amantadine forfeited most of its therapeutic potential because of resistance development in recent influenza A virus isolates. The antiviral efficacy of amantadine congeners can be chemically modified, resulting in re-constitution, improvement and/or extension of antiviral activities mediated by amino-adamantyls. Methods: Newly synthesized compounds were evaluated towards HIV type-1 (HIV-1) replication in primary human lymphocytes. One N-phenacyl amantadine derivative was investigated for inhibiting the in vitro replication of respiratory viruses (influenza A viruses, influenza B virus, human parainfluenza virus type 3 and severe acute respiratory syndrome coronavirus). Results: Two ketone-stabilized 1-adamantyl singlet nitrenes were discovered serendipitously. To our best knowledge these are the first persistently stable nitrenes to be reported. Their structure was proved by determining the X-ray single crystal structure of one hydrolytic elaboration product. This salt adduct revealed an incommensurately modulated crystal structure, which was solved by extensive computational refinement. We could show that ketone-stabilized 1-adamantyl singlet nitrenes are versatile synthons for the synthesis of antiviral drug candidates. An amantadine–folate conjugate was inhibitory on HIV-1 replication in primary human lymphocytes, and one N-phenacyl amantadine derivative was inhibitory towards low pathogenic avian influenza A virus (H5N1) replication in vitro. Conclusions: These results indicate that the aromatic-aliphatic ketone-stabilized 1-adamantyl singlet nitrenes, beyond being of fundamental interest in organic chemistry, represent versatile synthons for the synthesis of new amantadine-related potentially antiviral drugs.
Topical SMIP-7.7, a Toll–Like Receptor 7 Agonist, Protects against Genital Herpes Simplex Virus Type-2 Disease in the Guinea Pig Model of Genital Herpes
Authors: Bernstein David I , Cardin Rhonda D , Bravo Fernando J , Earwood Julie , Clark Jennifer R , Li Yongkai , Mishra Pranab , Li Chun , Nayak Bishnu P , Miller Andrew T , Wu Tom Y-H , Cooke Michael P , Valiante Nicholas M 
Published: December 2012

Background: Development of more effective therapies for genital herpes simplex virus type-2 (HSV-2) infections remains a priority. The toll-like receptors (TLR) are attractive targets for the immunomodulation of primary and recurrent genital herpes infection. The guinea pig model of genital HSV-2 disease was therefore used to evaluate the efficacy of a new TLR-7 agonist, SMIP-7.7. Methods: The effects of SMIP-7.7 at concentrations between 0.90% and 0.09% were compared to the vehicle control or Aldara® (3M Health Care Limited, Northridge, CA, USA) as treatment for genital HSV-2 infections. Following intravaginal inoculation of Hartley guinea pigs with 106 pfu HSV-2 (MS strain), animals were treated intravaginally beginning at 36 h post-infection. Animals were evaluated for acute disease, acute virus replication, recurrent disease and shedding, as well as infection of the dorsal root ganglia. Results: Treatment with SMIP-7.7 significantly decreased mean total lesion scores during primary infection (all doses, P<0.01 compared with vehicle control, and similar to Aldara®). Vaginal virus titres were reduced in treated animals compared with vehicle control ( P<0.001 for each treatment versus vehicle control on day 4). Treatment with SMIP-7.7 also significantly decreased the number of recurrent lesion days, the number of days with recurrent virus shedding and the infection of the dorsal root ganglia compared to the vehicle control, and was similar to Aldara®. As opposed to Aldara®, SMIP-7.7 did not induce fever or weight loss during treatment. Conclusions: SMIP-7.7 improves the outcome of primary and recurrent HSV-2 disease comparable to Aldara® but without some of the side effects associated with Aldara®.
Classification of the First Mechanical Azimuth Thruster According to New PC Class Rules
Authors: Rauti Timo 
Published: December 2012

Abstract
The number of azimuth thrusters configured for ice conditions is constantlyincreasing. This is due to the common tendency of widening the range ofoperation of a particular ship in terms of weather conditions, operating modesand geographical areas to achieve more business opportunities throughout theoperating life of the ship. The other major factor is the large potential foroil and gas in the arctic waters. It is also estimated that the number oficebreakers using azimuth propulsion will increase in the near future as theexisting fleet will be modernized and new vessels are built.
The new PC rules have recently been introduced and that has changed theclassification process significantly. Although being clearly more accurate, thenew rules require much more calculation work and have several parametersrelated to the thruster itself.
A first Azimuth thruster has now been classified according to the new PCrules. The thruster, type UUC 505, was originally classified according to DetNorske Veritas Ice-10 ice class which represents an ice class (at the lighterend) for arctic conditions. The thruster was then subsequently classifiedaccording to Det Norske Veritas PC4 ice rules.
The purpose of this presentation is to highlight the practical issues andthe increased workload that the new PC rules have brought on to theclassification process. Also it will highlight some points in the rules whereclarification is needed.
Pipeline Mechanical Damage Assessment Using Finite Element Methods
Authors: Hanif W. , Kenny S. 
Published: December 2012

Abstract
Onshore and offshore pipelines may be subjected to mechanical damage duringinstallation and operation due to environmental loads, external forces andthird parties. The type and severity of pipe damage may influence operational, repair and intervention strategies. For conventional pipelines, the assessmentof mechanical damage plays a role in the development of integrity managementprograms that can be of greater significance for pipeline systems located inremote, harsh environments. The current study highlights the effect of plaindents and interaction of plain dents with girth weld on pipe mechanicalresponse using continuum finite element methods. The modelling procedures arecalibrated with available physical datasets and also demonstrate excellentcorrelation with third party simulations. Confidence in the numericalsimulation tool provides a basis to evaluate the effects of mechanical damagethrough a broader parameter study and assess effects on fatigue lifeperformance.