bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunity to infection in IL‐17‐deficient mice and humans
Authors: Cypowyj Sophie , Picard Capucine , Maródi László , Casanova Jean‐Laurent , Puel Anne
Published: September 2012

Mice with defective IL‐17 immunity display a broad vulnerability to various infectious agents at diverse mucocutaneous surfaces. In humans, the study of patients with various primary immunodeficiencies, including autosomal dominant hyper‐IgE syndrome caused by dominant‐negative STAT3 mutations and autosomal recessive autoimmune polyendocrinopathy syndrome type 1 caused by null mutations in AIRE, has suggested that IL‐17A, IL‐17F and/or IL‐22 are essential for mucocutaneous immunity to Candida albicans. This hypothesis was confirmed by the identification of rare patients with chronic mucocutaneous candidiasis (CMC) due to autosomal recessive IL‐17RA deficiency and autosomal dominant IL‐17F deficiency. Heterozygosity for gain‐of‐function mutations in STAT1 in additional patients with CMC was recently shown to inhibit the development of IL‐17 T cells. Although the infectious phenotype of patients with CMC and inborn errors of IL‐17 immunity remains to be finely delineated, it appears that human IL‐17A and IL‐17F display redundancy for protective immunity in natural conditions that is not seen in their mouse orthologs in experimental conditions.
Malaria infection alters the expression of B‐cell activating factor resulting in diminished memory antibody responses and survival
Authors: Liu Xue Q. , Stacey Katryn J. , Horne‐Debets Joshua M. , Cridland Jasmyn A. , Fischer Katja , Narum David , Mackay Fabienne , Pierce Susan K. , Wykes Michelle N.
Published: August 2012

Malaria is a major cause of morbidity worldwide with reports of over 200–500 million infected individuals and nearly 1 million deaths each year. Antibodies have been shown to play a critical role in controlling the blood stage of this disease; however, in malaria‐endemic areas antibody immunity is slow to develop despite years of exposure to Plasmodium spp. the causative parasite. Using rodent Plasmodium yoelii YM, we provide evidence that malarial infections result in a decrease in the proportion of DCs that express the B‐cell survival factor, BAFF, resulting in a decreased ability of these DCs to support memory B‐cell differentiation into antibody secreting cells (ASCs) and/or the survival of ASCs. Further, compared with infected WT mice, ASC numbers were significantly increased in malaria‐infected transgenic mice that either overexpressed BAFF or mice with BAFF‐independent B‐cell survival (B‐cell‐restricted TRAF3 deletion). Remarkably, BAFF‐overexpressing mice were protected from lethal malaria infections, indicating the significance of the role BAFF plays in determining the outcome of malaria infections. These findings describe a previously unappreciated mechanism by which Plasmodium spp. can depress the generation of protective antibody responses.
Competing Electronic and Size Effects When Substituting 3d Elements for Nb in Nb3Ru5B2 En Route to the Quaternary Phases (Nb2–xScx)4gNb2aRu5B2 (1 ≤ x < 2), Nb3–xMxRu5B2 (M = Ti, V; x ≈ 1), and Nb2+xM1–xRu5B2 (M = Cr, Mn, Fe, Co, Ni; 0 < x ≤ 0.5)
Authors: Hermus Martin , Fokwa Boniface P. T.
Published: August 2012

Single crystals and polycrystalline samples of (Nb2–xScx)4gNb2aRu5B2 (1 ≤ x < 2), Nb3–xMxRu5B2 (M = Ti, V; x ≈ 1), and Nb2+xM1–xRu5B2 (M = Cr, Mn, Fe, Co, Ni; 0 < x ≤ 0.5) were synthesized from the elements and characterized by single‐crystal and powder X‐ray diffraction as well as energy‐dispersive X‐ray analysis. These phases are substitutional variants of the recently reported Nb3Ru5B2 phase and crystallize in the Ti3Co5B2‐type structure (tetragonal, space group P4/mbm, no. 127). The structure consists of layers of ruthenium atoms that build trigonal, tetragonal, and pentagonal prisms, in which the other atoms are incorporated. The larger 3d metals, Sc, Ti, and V are found on the larger pentagonal prisms, together with niobium, and also (except for Sc) on the tetragonal prisms. The smaller 3d metals, Cr–Ni, are only found on the tetragonal prisms, but also mix with niobium. DFT calculations on the ternary phase Nb3Ru5B2 suggested that the reason for this site mixing can be found in its electronic structure and the application of the rigid band model proposed a valence electron (VE) range between ca. 58 and 64 for the derived stable phases. All synthesized quaternary phases fit very well within this VE range.
Enantioselective Friedel–Crafts Alkylation of N‐Methylindoles with Nitroalkenes Catalyzed by Chiral Bifunctional Abietic‐Acid‐Derived Thiourea‐ZnII Complexes
Authors: Huang Wei‐gen , Wang Heng‐shan , Huang Guo‐bao , Wu Yong‐ming , Pan Ying‐ming
Published: August 2012

The catalytic asymmetric Friedel–Crafts alkylation of N‐methylindoles with nitroalkenes catalyzed by bifunctional abietic‐acid‐derived thiourea‐ZnII complexes was investigated. Various types of the nitroalkylated indoles were synthesized under mild conditions and obtained with excellent yields (up to 99 %) and good enantioselectivities (up to 86 % ee). These chiral thiourea catalysts are easily available from the commercial abietic acid.
Synthesis of Spinosyn Analogues for Modern Crop Protection
Authors: Tietze Lutz F. , Schützenmeister Nina , Grube Alexander , Scheffer Timo , Baag Mohammad Merajuddin , Granitzka Markus , Stalke Dietmar
Published: September 2012

New spinosyn analogues 3 with an arene group as ring A and containing a L‐rhamnose moiety have been prepared. The key step in the synthesis of 3 is a Pd‐catalyzed twofold Heck reaction of glycosylated bromoarene 4, containing an iodovinyl side chain and a tri‐O‐methyl‐L‐rhamnose moiety with the cyclopentene‐annulated macrolactone 5. Compounds 3 may be of interest as new insecticides.
Probabilistic performance assessment of low‐ductility reinforced concrete frames retrofitted with dissipative braces
Authors: Freddi F. , Tubaldi E. , Ragni L. , Dall'Asta A.
Published: August 2012

The paper illustrates a probabilistic methodology for assessing the vulnerability of existing reinforced concrete (RC) buildings with limited ductility capacity retrofitted by means of dissipative braces. The aim is to highlight the most important parameters controlling the capacity of these coupled systems and specific aspects concerning the response uncertainties. The proposed methodology is based on the use of local engineering demand parameters for monitoring the seismic response and on the development of component and system fragility curves before and after the retrofit. In the first part of the paper, the methodology is illustrated by highlighting its advantages with respect to the existing approaches. Then, its capability and effectiveness are tested by considering a benchmark two‐dimensional RC frame designed for gravity‐loads only. The frame is retrofitted by introducing elasto‐plastic dissipative braces designed for different levels of base shear capacity. The obtained results show the effectiveness of the methodology in describing the changes in the response and in the failure modalities before and after the retrofit, for different retrofit levels. Moreover, the retrofit effectiveness is evaluated by introducing proper synthetic parameters describing the fragility curves and by stressing the importance of employing local engineering demand parameters (EDPs) rather than global EDPs in the seismic risk evaluation of coupled systems consisting in low‐ductility RC frames and dissipative braces. Copyright © 2012 John Wiley & Sons, Ltd.
An Examination of Adults on Antipsychotic Medication at Risk for Metabolic Syndrome: A Comparison with Obese and Eating Disorder Populations
Authors: Stiles‐Shields Colleen , Bogue Cynthia , Grange Daniel Le , Yohanna Daniel
Published: August 2012

Little research has explored how eating disorders (ED) may be involved in the increased risk for metabolic syndrome in adults on antipsychotic medication. This pilot study compared participants on antipsychotic medication with obese and ED samples with respect to demographic and psychosocial factors. Participants (antipsychotic medication n = 12; obese n = 12; ED n = 12), were adults presenting to an outpatient psychiatry department (83.3% women; M age = 45.75 ± 11.5). Analysis of variance, analysis of covariance and chi‐square tests were used to compare the samples. Participants on antipsychotic medications had a significantly lower mean body mass index than the obese (p < .001) and ED (p < .05) samples, as well as significantly lower Restraint Total scores (p < .05) and subjective binge episode frequency (p < .05) than the ED sample. The lack of significant differences that occurred between the antipsychotic medication sample and two eating disorder samples significantly different from one another indicates that this population may have unique symptomology and treatment needs. Copyright © 2012 John Wiley & Sons, Ltd and Eating Disorders Association.
Sensing with boots and trousers — qualitative field observations of shallow soil moisture patterns
Authors: Rinderer Michael , Kollegger Andrea , Fischer Benjamin M. C. , Stähli Manfred , Seibert Jan
Published: September 2012

While soil moisture patterns can be interesting traits to investigate spatio‐temporal heterogeneity of catchments relevant for various physical processes of soil–atmosphere interaction and soil water redistribution, many of the existing methods to capture spatial patterns are time consuming, expensive or need site‐specific calibration. In this study we present a quick and inexpensive supplementary field method for classifying soil wetness in wet environments. The seven wetness classes are based on qualitative indicators, which one can touch, hear or see on the soil surface. To counter critics that such qualitative methods are considerably affected by subjectivity, we performed systematic testing of the method by taking qualitative measurements in the field with 20 non‐expert raters. We then analyzed these in terms of degree of agreement and assessed the results against gravimetric sampling and time domain reflectometry measurements. In 70% of all classifications raters agreed on the wetness class assigned to the marked sampling locations and in 95% they were not off by more than one wetness class. The seven quantitative wetness classes agreed with gravimetric and time domain reflectometry measurements, although intermediate to wet classes showed an overlap of their range whereas the driest classes showed considerable spread. Despite some potential to optimize the method, it has been shown to be a reliable supplement to existing quantitative techniques for assessing soil moisture patterns in wet environments. Copyright © 2012 John Wiley & Sons, Ltd.
Targeting the hedgehog signal transduction pathway at the level of GLI inhibits neuroblastoma cell growth in vitro and in vivo
Authors: Wickström Malin , Dyberg Cecilia , Shimokawa Takashi , Milosevic Jelena , Baryawno Ninib , Fuskevåg Ole M. , Larsson Rolf , Kogner Per , Zaphiropoulos Peter G. , Johnsen John I.
Published: September 2012

Hedgehog (HH) signaling is an important regulator of embryogenesis that has been associated with the development of several types of cancer. HH signaling is characterized by Smoothened (SMO)‐dependent activation of the GLI transcription factors, which regulate the expression of critical developmental genes. Neuroblastoma, an embryonal tumor of the sympathetic nervous system, was recently shown to express high levels of key molecules in this signaling cascade. Using compounds blocking SMO (cyclopamine and SANT1) or GLI1/GLI2 (GANT61) activity revealed that inhibition of HH signaling at the level of GLI was most effective in reducing neuroblastoma growth. GANT61 sensitivity positively correlated to GLI1 and negatively to MYCN expression in the neuroblastoma cell lines tested. GANT61 downregulated GLI1, c‐MYC, MYCN and Cyclin D1 expression and induced apoptosis of neuroblastoma cells. The effects produced by GANT61 were mimicked by GLI knockdown but not by SMO knockdown. Furthermore, GANT61 enhanced the effects of chemotherapeutic drugs used in the treatment of neuroblastoma in an additive or synergistic manner and reduced the growth of established neuroblastoma xenografts in nude mice. Taken together this study suggests that inhibition of HH signaling is a highly relevant therapeutic target for high‐risk neuroblastoma lacking MYCN amplification and should be considered for clinical testing.
Enhanced antitumoral activity of oncolytic herpes simplex virus with gemcitabine using colorectal tumor models
Authors: Esaki Shinichi , Goshima Fumi , Kimura Hiroshi , Murakami Shingo , Nishiyama Yukihiro
Published: September 2012

To enhance the oncolytic activity of herpes simplex viruses (HSVs) control of immune‐suppression and immune‐resistance by cancer cells is important. Myeloid‐derived suppressor cells (MDSCs), which interfere with tumor‐suppressive environments, are inhibited by gemcitabine (GEM) treatment. We investigated the oncolytic activity and systemic antitumor immunity induced by oncolytic HSVs in combination with GEM treatment. A mouse model with subcutaneous tumors on both sides of the lateral flanks was used. A highly attenuated HSV type 1, strain HF10, was inoculated into one side of each tumor three times following intraperitoneal injection of GEM. Histopathological changes and IFN‐γ secretion of the tumor and leukocytes in the spleen were analyzed. These treatments were repeated to enhance oncolytic activity. HF10 inoculation reduced tumor growth only on the HF10‐treated side. HF10 inoculation following GEM treatment resulted in greater reduction of tumor growth on the HF10‐treated tumor; furthermore, reduction of tumors on the contralateral untreated side was also observed. Necrosis of the tumor was observed in areas where HSV‐infected cells were detected. F4/80+ macrophages around the tumor were eliminated, and CD4+ T and CD8+ T cells increased in the spleen. A single injection of GEM decreased CD11b+/Gr‐1+ MDSCs while retaining CD4+ T cells and CD8+ T cells. Repetition of this treatment regimen resulted in even greater reduction of tumor growth on both sides and complete rejection in some of the mice. Intratumoral injection of oncolytic HSVs following GEM injection reduced MDSCs. Repeated treatment with oncolytic HSVs following GEM resulted in enhanced oncolytic activity.
Drug Testing in the Workplace
Authors: Phan Hieu M. , Yoshizuka Keith , Murry Daryl J. , Perry Paul J.
Published: September 2012

Congress passed the Drug‐Free Workplace Act in April 1988, which resulted in the Mandatory Guidelines for Federal Workplace Drug Testing Programs. The intent was to establish a substance‐free work environment for all federal workers by requiring that all federal employees pass a urine drug test before employment. These guidelines specifically, and exclusively, focus on testing urine specimens for metabolites of marijuana, cocaine, phencyclidine, opiates (focusing on heroin metabolites), and amphetamines (including Ecstasy). Since then, there have been many scientific, technical, and legal challenges to the validity of urine drug testing. In response, the Substance Abuse and Mental Health Services Administration, a division operating under the executive branch of the United States Department of Health and Human Services, put forth, through many revisions, strict procedural guidelines and specimen validity‐testing criteria to manage suspicious or adulterated samples during and after urine collection. This review focuses on the legal ramifications, the procedural process, and the sensitivity and specificity of the two urine drug tests used for workplace drug testing: immunoassay and gas chromatography–mass spectrometry. Moreover, we dissect the problematic issue of cross‐sensitivity between illicit and prescription drugs, and how this affects the validity of future urine drug testing.
Emerging Antiplatelet Therapy for Coronary Artery Disease and Acute Coronary Syndrome
Authors: Packard Kathleen A. , Campbell Jennifer A. , Knezevich Jon T. , Davis Estella M.
Published: September 2012

Antiplatelet therapy is used widely with proven benefit for the prevention of further ischemic cardiac complications in patients with known coronary artery disease (CAD) and a history of acute coronary syndrome (ACS). The limitations of conventional antiplatelet therapy with aspirin, clopidogrel, or prasugrel, as well as the fact that rates of recurrent ischemic events still remain high with use of these agents, underscore the need to investigate alternate agents that may further reduce event rates while limiting bleeding risk. The selection of antiplatelet therapy is further influenced by the following: ticagrelor was approved in July 2011 by the United States Food and Drug Administration (FDA),and clopidogrel is slated to become available as a generic productin 2012. We provide an overview of emerging agents for the treatment of CAD and ACS, including the reversible P2Y12 antagonists ticagrelor, cangrelor, and elinogrel, and a new class of oral protease‐activated receptor‐1 (PAR‐1) inhibitors, vorapaxar and atopaxar.The recentlyapproved P2Y12 antagonists prasugrel and ticagrelor demonstrate enhanced ability to prevent adverse cardiac outcomes. However, this comes at a cost of a potential increased risk of bleeding. New adverse effects have also emerged, including dyspnea for all of the reversible P2Y12 antagonists (ticagrelor, cangrelor, and elinogrel) and ventricular pauses for ticagrelor. In addition, the newer P2Y12 antagonists have a faster onset and offset. Two of these agents, cangrelor and elinogrel, are available as intravenous formulations, which may provide additional benefits in patients whoundergo coronary artery bypass graft (CABG) surgery. Trials with the PAR‐1 inhibitors have also shown trends toward reductions in cardiac events, but not without the possibility of increased bleeding. More than ever, as the arsenal of antiplatelet therapy expands, health care providers need to understand the pharmacologic and pharmacodynamic differences between conventional and emerging antiplatelet therapies forpatients with ACS and CAD. Health care providers must also carefully assess patient‐specific factors such as risk of thrombosis, concomitant disease states, age, drug adherence, and aspirin dose, and plan for those patients who will be undergoing CABG when selecting antiplatelet therapy in order to optimally balance bleeding and thrombosis risk.
A Systematic Review of the Evidence for Pharmacist Care of Patients With Dyslipidemia
Authors: Charrois Theresa L. , Zolezzi Monica , Koshman Sheri L. , Pearson Glen , Makowsky Mark , Durec Tamara , Tsuyuki Ross T.
Published: September 2012

Study Objective

To evaluate the effect of pharmacist care on patients with dyslipidemia.

Design

Systematic review of 21 randomized controlled trials.

Patients

A total of 5416 patients who received enhanced pharmacist care or standard care as part of a research study.

Measurements and Main Results

Nineteen databases and four trial registries were systematically searched from inception through February 21, 2010, with an update in September 2011. In addition, Web sites of relevant professional associations, scientific meetings, and research groups were reviewed, and manual searches of select journals were performed. A total of 8771 articles were identified, and 21 studies included. Data from the studies were analyzed using a random‐effects model. The primary outcome measure assessed was the difference between the groups (pharmacist intervention vs standard care) in low‐density lipoprotein cholesterol (LDL) level at the end of follow‐up. Secondary outcome measures included the difference between the groups at the end of follow‐up in total cholesterol, high‐density lipoprotein cholesterol, and triglyceride levels; and the proportion of patients who achieved target lipid parameters, underwent lipid panel measurements, adhered to therapy, and/or were instructed to change their lipid‐lowering therapy. At the end of follow‐up, the mean LDL level was 10.7 mg/dl lower in the enhanced pharmacy care groups compared with the standard care groups (95% confidence interval [CI] –16.9 to –4.6 mg/dl), with moderate heterogeneity. The mean total cholesterol level was significantly lower in the enhanced pharmacy care groups compared with the standard care groups; however, these results were highly heterogeneous. Patients who received enhanced pharmacist care were also more likely than those receiving standard care to achieve target lipid parameters (odds ratio [OR] 2.46, 95% CI 1.43–4.25) and to have a lipid panel ordered or recommended by a pharmacist during the study (OR 2.05, 95% CI 1.30–3.24). Patients in the pharmacist intervention groups were almost twice as likely as patients in the standard care groups to have a change in lipid‐lowering therapy (OR 1.82, 95% CI 1.09–3.06). Adherence data could not be analyzed.

Conclusion

This systematic review showed that enhanced pharmacist care improves lipid parameters, notably LDL levels, in patients with dyslipidemia. These results point to the benefit that pharmacist care can provide across the spectrum of dyslipidemia management, from screening patients to treating them to assisting them in the attainment of clinical targets.
Advantages and Disadvantages of Etomidate Use for Intubation of Patients with Sepsis
Authors: J. Cherfan Antoine , Arabi Yaseen M. , Al‐Dorzi Hasan M. , Kenny Lisa P.
Published: September 2012

Etomidate is a potent imidazole hypnotic used widely in single doses in the rapid sequence intubation of critically ill patients with sepsis due to its presumed hemodynamic safety, fast onset, and short duration of action. However, the literature is conflicting regarding the hemodynamic advantages of etomidate over other induction agents, and its safety in this population is a matter of strong debate in the critical care community as the drug is associated with suppression of adrenal steroidogenesis, which can last up to 72 hours after a single dose, primarily through potent inhibition of the 11β‐hydroxylase enzyme. However, the clinical impact of this adrenal suppressive effect is not certain. The use of continuous‐infusion etomidate in critically ill patients was abandoned more than 20 years ago due to reports of increased mortality. Nevertheless, mortality data of single‐dose etomidate are still controversial, with no strong evidence of benefit over other agents and a tendency toward harm (keeping in mind the limitations of the available literature). Proponents of single‐dose etomidate use in patients with sepsis suggest that the increased mortality associated with etomidate is merely a reflection of the patients' severity of illness and not related to the drug itself, whereas others believe that the drug causes true harm and increases mortality in this population. In view of the lack of a clear clinical advantage of etomidate over other agents used in rapid sequence intubation, it would be prudent to favor other agents until further conclusive evidence of etomidate safety is available in critically ill patients with sepsis.
Everolimus: Targeted Therapy on the Horizon for the Treatment of Breast Cancer
Authors: Barnett Chad M.
Published: September 2012

The mammalian target of rapamycin (mTOR) is a signaling kinase of the phosphatidylinositol 3‐kinase/protein kinase B (also known as Akt) signaling pathway that mediates cell growth and metabolism. Dysregulation of the mTOR pathway creates a favorable environment for the development and progression of many cancers, including breast cancer, and is associated with the development of resistance to endocrine therapy and to the anti–human epidermal growth factor receptor‐2 (HER2) monoclonal antibody trastuzumab. Therefore, the addition of mTOR inhibitors to conventional breast cancer therapy has the potential to enhance therapeutic efficacy and/or overcome innate or acquired resistance. Everolimus, an mTOR inhibitor with demonstrated preclinical activity against breast cancer cell lines, has been shown to reverse Akt‐induced resistance to hormonal therapy and trastuzumab. Phase I–II clinical trials have demonstrated that everolimus has promising clinical activity in women with HER2‐positive, HER2‐negative, and estrogen receptor–positive breast cancer when combined with HER2‐targeted therapy, cytotoxic chemotherapy, and hormonal therapy, respectively. Everolimus is generally well tolerated; hematologic abnormalities and stomatitis are most common adverse events when this drug is combined with cytotoxic chemotherapy. Based on these promising results, everolimus is currently under evaluation in a series of phase III Breast Cancer Trials of Oral Everolimus (BOLERO) trials of women with HER2‐positive and estrogen receptor–positive breast cancer. Results of these trials will help to establish the role of everolimus in the treatment of clinically important breast cancer subtypes.
Importance of Direct Patient Care in Advanced Pharmacy Practice Experiences
Authors: Rathbun R. Chris , Hester E. Kelly , Arnold Lindsay M. , Chung Allison M. , Dunn Steven P. , Harinstein Lisa M. , Leber Molly , Murphy Julie A. , Schonder Kristine S. , Wilhelm Sheila M. , Smilie Kristine B.
Published: September 2012

The Accreditation Council for Pharmacy Education issued revised standards (Standards 2007) for professional programs leading to the Doctor of Pharmacy degree in July 2007. The new standards require colleges and schools of pharmacy to provide pharmacy practice experiences that include direct interaction with diverse patient populations. These experiences are to take place in multiple practice environments (e.g., community, ambulatory care, acute care medicine, specialized practice areas) and must include face‐to‐face interactions between students and patients, and students and health care providers. In 2009, the American College of Clinical Pharmacy (ACCP) identified concerns among their members that training for some students during the fourth year of pharmacy curriculums are essentially observational experiences rather than encounters where students actively participate in direct patient care activities. These ACCP members also stated that there is a need to identify effective mechanisms for preceptors to balance patient care responsibilities with students’ educational needs in order to fully prepare graduates for contemporary, patient‐centered practice. The 2010 ACCP Educational Affairs Committee was charged to provide recommendations to more effectively foster the integration of pharmacy students into direct patient care activities during advanced pharmacy practice experiences (APPEs). In this commentary, the benefits to key stakeholders (pharmacy students, APPE preceptors, clerkship sites, health care institutions, academic pharmacy programs) of this approach are reviewed. Recommendations for implementation of direct patient care experiences are also provided, together with discussion of the practical issues associated with delivery of effective APPE. Examples of ambulatory care and acute care APPE models that successfully integrate pharmacy students into the delivery of direct patient care are described. Enabling students to engage in high‐quality patient care experiences and to assume responsibility for drug therapy outcomes is achievable in a variety of practice settings. In our opinion, such an approach is mandatory if contemporary pharmacy education is to be successful in producing a skilled workforce capable of affecting drug therapy outcomes.
Antimicrobial Stewardship in Patients with Cancer
Authors: Tverdek Frank P. , Rolston Kenneth V. , Chemaly Roy F.
Published: September 2012

Consensus guidelines recommend antimicrobial stewardship in all hospitals with the following goals in mind: appropriate and judicious use of antimicrobial agents leading to increased drug safety, reduced antimicrobial utilization, reduction in the development and selection of resistant organisms, cost containment, and improved patient outcomes. Patients with cancer, especially those with hematologic malignancies and neutropenia, develop serious infections often and receive antimicrobial therapy frequently. Consequently, there is considerable opportunity to practice antimicrobial stewardship in this population. Several antimicrobial stewardship strategies such as antimicrobial restriction, cycling, prospective audit and feedback, and de‐escalation have been evaluated in patients with cancer. The primary focus has been on the prevention and treatment of bacterial infections in febrile neutropenic patients. These efforts should be expanded to include fungal, viral, and other infections.
ESTIMATION OF TIME‐VARYING ADJUSTED PROBABILITY OF INFORMED TRADING AND PROBABILITY OF SYMMETRIC ORDER‐FLOW SHOCK
Authors: Preve Daniel , Tse Yiu‐Kuen
Published: August 2012

Recently, Duarte and Young (2009) studied the probability of informed trading (PIN) proposed by Easley et al. (2002) and decomposed it into two parts: the adjusted PIN (APIN) as a measure of asymmetric information and the probability of symmetric order‐flow shock (PSOS) as a measure of illiquidity. They provide some cross‐section estimates of these measures using daily data over annual periods. In this paper we propose a method to estimate daily APIN and PSOS by extending the method in Tay et al. (2009) using high‐frequency transaction data. Our empirical results show that while PIN is positively contemporaneously correlated with variance, APIN is not. On the other hand, PSOS is positively correlated with daily average effective spread and variance, which is consistent with the interpretation of PSOS as a measure of illiquidity. Compared to APIN, PSOS exhibits clustering and sporadic bursts over time. Copyright © 2012 John Wiley & Sons, Ltd.
Steroid Concentrations and Immunoexpression of Steroidogenic Enzymes in Ovaries of Aged Bank Voles: Effect of Photoperiod
Authors: Galas Jerzy , Starowicz Agnieszka , Knapczyk‐Stwora Katarzyna , Tabarowski Zbigniew , Szołtys Maria
Published: September 2012

The main objective of the present study was to establish morphological and steroidogenic changes occurring in the ovaries of senescent bank voles, with respect to the photoperiod of rearing. Obtained results revealed less pronounced changes in the ovaries of females reared in a long photoperiod (LD). Their gonads still possessed some healthy follicles and old corpora lutea (CLs). Senescence‐related changes encompassed the presence of abnormal follicles, large regions containing extra‐follicular luteinized granulosa cells and numerous clusters of hypertrophied theca/interstitial cells, exhibiting strong expression of 3β‐hydroxysteroid dehydrogenase (3β‐HSD) and much weaker that of cytochrome P450c17. More pronounced changes were observed in animals reared in short day (SD) conditions and included the presence of only few, usually abnormal follicles and/or remnants of CLs in the surface region, and the isle‐like clusters of cells in the ovarian medulla. The clusters were composed of cells generally featuring strong 3β‐HSD and/or P450c17 immunoreaction. Steroid content analysis revealed that progesterone dominated in the ovaries of LD bank voles and androgens in SD animals, while estradiol content was very low in both investigated groups. These studies showed for the first time morphological and steroidogenic changes found in the ovaries of senescent bank voles and indicated an important role of length light conditions in the process of reproductive aging. J. Exp. Zool. 317A:622–629, 2012. © 2012 Wiley Periodicals, Inc.
Sedimentology of a debris‐rich, perhumid valley glacier margin in the Rakaia Valley, South Island, New Zealand
Authors: Hyatt Olivia M. , Shulmeister James , Evans David J. A. , Thackray Glenn D. , Rieser Uwe
Published: August 2012

The sedimentology and stratigraphy of a multi‐phase glaciation sequence dating to Marine Isotope Stage 6 in the Rakaia Valley, South Island, New Zealand, is presented. This outcrop presents an example of the depositional signature of an end member of temperate valley glaciation, where voluminous sediment supply in a tectonically active setting combines with high annual temperatures and low seasonality to generate significant year‐round glacifluvial activity. Such glacial systems produce geological–climatic units that are dominated by thick sequences of aggradational gravels and proglacial lake sediments trapped behind outwash heads during deglaciation. At Bayfields Cliff, outwash sequences record an oscillating glacier margin marked by a sequence of glacier‐fed, Gilbert‐type deltas. The deltas are cut by numerous small‐scale, syndepositional, normal faults indicating both loss of glacier support and melt‐out of buried ice. A larger‐scale thrust fault system reflects late‐stage ice overrun. Braid plain gravels and chaotic disturbed glacial lake sediments are also recorded. A notable feature of these systems is the virtual absence of till in an environment with much other evidence for proximal ice. Cumulatively we regard these sediment–landform associations as diagnostic of debris‐laden, perhumid, temperate valley glacier systems. Copyright © 2012 John Wiley & Sons, Ltd.
Coarse clast ridge sequences as suitable archives for past storm events? Case study on the Houtman Abrolhos, Western Australia
Authors: Scheffers Anja M. , Scheffers Sander R. , Kelletat Dieter H. , Squire Peter , Collins Lindsay , Feng Yuexing , Zhao Jian‐Xin , Joannes‐Boyau Renaud , May Simon Matthias , Schellmann Gerhard , Freeman Heather
Published: August 2012

Prehistoric storm records are relatively scarce in most parts of the world. This article presents storm records derived from coral rubble‐based geological archives of the Houtman Abrolhos Archipelago located off the west coast of Australia, where the southernmost coral reefs of the Indian Ocean are found. Winter storm swell from the circum‐Antarctic ‘Brave Westerlies’, as well as tropical cyclone waves, have left numerous ridge systems on dozens of islands of the archipelago, all composed of coral rubble from adjacent reefs. At three islands, seven ridge systems were dated by three different methods: U‐series (68 dates), radiocarbon (64 dates), electron spin resonance (7 dates); 139 radiometric dates span the last 5500 years of the Holocene. In contrast to the geomorphological interpretation, the age sequences show ‘inversions’, hiatuses and different ages for the same ridge, all pointing to complicated ridge formation processes. Time gaps, some exceeding 1000 years, are interpreted as phases of erosion and not as phases without storm activity. Copyright © 2012 John Wiley & Sons, Ltd.
Calibration of the in situ cosmogenic 14C production rate in New Zealand's Southern Alps
Authors: Schimmelpfennig Irene , Schaefer Joerg M. , Goehring Brent M. , Lifton Nathaniel , Putnam Aaron E. , Barrell David J. A.
Published: August 2012

In situ cosmogenic 14C (in situ 14C) analysis from quartz‐bearing rocks is a novel isotopic tool useful for quantifying recent surface exposure histories (up to ∼25 ka). It is particularly powerful when combined with longer‐lived cosmogenic isotopes such as 10Be. Recent advances in the extraction of in situ 14C from quartz now permit the routine application of this method. However, only a few experiments to calibrate the production rate of in situ 14C in quartz have been published to date. Here, we present a new in situ 14C production rate estimate derived from a well‐dated debris flow deposit in the Southern Alps, New Zealand, previously used to calibrate 10Be production rates. For example, based on a geomagnetic implementation of the Lal/Stone scaling scheme we derive a spallogenic production rate of 11.4 ± 0.9 atoms 14C (g quartz)−1 a−1 and a 14C/10Be spallogenic production rate ratio of 3.0 ± 0.2. The results are comparable with production rates from previous calibrations in the northern hemisphere. Copyright © 2012 John Wiley & Sons, Ltd.
Cochlear implant programs: Balancing clinical and financial sustainability
Authors: McKinnon Brian J.
Published: September 2012

Objectives/Hypothesis:

In 2006, a tertiary academic medical center's adult and pediatric cochlear implant program was closed due to financial losses. Using business practices known as supply chain and revenue management, the objective was to establish a new cochlear implant program that was financially viable.

Study Design:

Retrospective cohort study using a nonequivalent historical comparison group design.

Methods:

Using available financial data from the period of 1999 to 2006, cost and revenue figures were estimated, and a business plan developed using supply chain and revenue management principles to re‐establish the cochlear implant program in 2007. Actual cost and revenue data from 2007 to 2011, the current program, were assessed for current financial performance and compared to the historical data.

Results:

In comparing the period of 1999 to 2006 to the period of 2007 to 2011, the net loss per implanted patient went from $22,365 to $976. Profitable gross and net margins were achieved for all payers except Medicaid, for which the loss per case remained unchanged. This per case loss may change with receipt of pending Medicaid Upper Payment Limit supplemental payments.

Conclusions:

Use of supply chain and revenue management principles markedly improved the financial performance of the re‐established cochlear implant program. With improved cost and revenue outcomes, the overall negative net margin was reduced. Physicians who learn and use supply chain and revenue management methods can work to ensure that their patients will have continued access to cochlear implant surgery, and are applicable to any clinical services or procedures that must meet the challenge of achieving financial sustainability. Laryngoscope, 2013
Follicular carcinoma of the thyroid with massive invasion into the cervical and mediastinum great veins: Our own experience and literature review
Authors: Nakashima Torahiko , Nakashima Atsuhiro , Murakami Daisuke , Toh Satoshi , Shiratsuchi Hideki , Yasumatsu Ryuji , Tominaga Ryuji , Komune Shizuo
Published: September 2012

Thyroid carcinomas with massive intralumen invasion of the great veins are extremely rare and reported to have poor prognosis. We report a case of a poorly differentiated follicular carcinoma of the thyroid with extensive invasion into the bilateral internal jugular veins, brachiocephalic vein, and superior vena cava. All of the seven major drainage veins from the thyroid were involved by tumor thrombus. The patient was successfully treated by surgical resection including removal of the tumor thrombus and repair of the great veins. The importance of preoperative radiological findings, treatment, and outcome are discussed along with a literature review.
Crystal Polymorphism and Spherulites in Poly(butylene adipate) Diluted with Strongly Versus Weakly Interacting Amorphous Polymers
Authors: Lugito Graecia , Woo Eamor M.
Published: August 2012

Polymorphism and ring‐banded spherulites in poly(butylene adipate) (PBA) diluted with poly(vinyl acetate) (PVAc) or poly(hydroxyether of bisphenol A) (phenoxy) were studied. For neat PBA, polymorphism and ring‐banded spherulites occur at overlapped Tc = 28–31 °C (4 °C range). By comparison, ring bands of crystallized PBA/PVAc blend remain similar to neat PBA; while for PBA/phenoxy blend, ring bands are completely disrupted (revealed by surface AFM phase images), owing to strong interchain interactions between PBA and phenoxy. The results summarily demonstrate that the Tc range for polymorphism becomes much wider (Tc = 19–32 °C) with the addition of the amorphous polymers and reveals the phenomenon of ring bands in PBA is not correlated or attributed to its α+β polymorphism.
Post‐Modification of Organoiron Poly(alkynyl methacrylate)s with Dicobalt Hexacarbonyl
Authors: Abd‐El‐Aziz Alaa S. , Winram Diana J. , Shipman Patrick O. , Rock Christopher L. , Vandel Mason S. , Patrick Brian O.
Published: August 2012

Radical polymerization of organoiron (alkynyl methacrylate)s afforded a series of organoiron poly(alkynyl methacrylate)s with the ability to coordinate dicobalt hexacarbonyl. The polymers were post‐modified with dicobalt hexacarbonyl moieties through reaction with dicobaltoctacarbonyl. Gel permeation chromatography indicated that the polymers possessed weight average molecular weights between 17 800 Da and 33 900 Da with PDIs between 1.3 and 1.6. Thermal analysis revealed that the polymers possess glass transition temperatures between 78 and 138 °C.
Hypercyclic composition operators on Hv0‐spaces
Authors: Miralles Alejandro , Wolf Elke
Published: August 2012

We consider analytic self‐maps φ on \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathbf {D}$\end{document} and prove that the composition operator Cφ acting on \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$H_{v}^0$\end{document} is hypercyclic if φ is an automorphism or a hyperbolic non‐automorphic symbol with no fixed point. We give examples of weights v and parabolic non‐automorphisms φ on \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\mathbf {D}$\end{document} which yield non‐hypercyclic composition operators Cφ on \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$H_{v}^0$\end{document}.
17O NMR studies of ortho‐substituent effects in substituted phenyl tosylates
Authors: Nummert Vilve , Mäemets Vahur , Piirsalu Mare , Koppel Ilmar A.
Published: August 2012

17O NMR spectra for 35 ortho‐, para‐, and meta‐substituted phenyl tosylates (phenyl 4‐methylbenzenesulfonates), 4‐CH3‐C6H4SO2OC6H4‐X, at natural abundance in acetonitrile at 50 °C were recorded. The 17O NMR chemical shifts, δ(17O), of the sulfonyl (SO2) and the single‐bonded phenoxy (OPh) oxygens for para and meta derivatives correlated well with dual substituent parameter treatment using the Taft inductive, σI, and resonance, σºR, constants. The influence of ortho substituents on the sulfonyl oxygen and the single‐bonded phenoxy oxygen chemical shifts, δ(17O), was found to be nicely described by the Charton equation: δ(17O)ortho = δ(17O)H + ρIσI + ρRσ°R + δEsB when the data treatment was performed separately for electron‐donating +R substituents and electron‐attracting −R substituents. Electron‐attracting meta and para substituents in the phenyl moiety caused deshielding while the electron‐donating meta, para and ortho +R substituents produce shielding effects on the sulfonyl (SO2) and single‐bonded phenoxy (OPh) oxygens. The influence of ortho inductive and resonance effects in the case of +R substituents was found to be approximately twice higher than the corresponding influence from the para position. Due to the steric effect of ortho substituents a decrease in shielding of the oxygens at the sulfonyl group (δEsB > 0, EsB < 0) was detected. Copyright © 2012 John Wiley & Sons, Ltd.
Baustelle Chemie
Authors: Rupp Severine
Published: September 2012

Viele Chemiegebäude an Universitäten haben ihre besten Tage hinter sich: Der Beton bröckelt, Risse sind notdürftig geflickt und Abzüge drohen auszufallen. Marburg baut neu, Göttingen dagegen saniert bei laufendem Betrieb.
Aufschluss nach Kjeldahl: Infrarot oder konventionelle Erhitzung
Authors: Hilz Hauke , Eilers Annika , Märkle Gunda , Beninga Claus , Rieger Eva‐Maria
Published: September 2012

Bei der Stickstoffbestimmung nach Kjeldahl erhitzt in konventionellen Geräten ein Heizblock die Proben. Inzwischen gibt es Geräte, die dazu Infrarotstrahler verwenden. Wie sich beide Heizmethoden auf Aufschlusszeit, Analysenergebnis und Handhabbarkeit auswirken, zeigt ein Vergleich am Beispiel Haferflocken.
Wasseranalytik mit einem Fluoreszenzspektrometer
Authors: Nehm Rainer , Birke Frank
Published: September 2012

Um bei organischen Spurenstoffen im Wasser nicht nur Summenparameter, sondern auch die Einzelsubstanzen zu bestimmen, eignet sich ein Fluoreszenzspektrometer, das Emission und Absorption parallel misst.
A real time procedure for affinely dependent parametric model order reduction using interpolation on Grassmann manifolds
Authors: Son Nguyen Thanh
Published: September 2012

Model order reduction helps to reduce the computational time in dealing with large dynamical systems, for example, during simulation, control, optimization. In many cases, the considered model depends on parameters; Model order reduction techniques are, therefore, preferred to symbolically preserve this dependence or to be adaptive to the change of the model caused by the variation in the values of the parameters. In this paper, we first present the application of the interpolation technique on Grassmann manifolds to this problem. We then improve the method for the models whose system matrices depend affinely on parameters by considerably reducing the computational complexity on the basis of analyzing the structure of sums of singular value decompositions and decomposing the whole procedure into offline and online stages. A numerical example is shown to illustrate the method as well as to prove its effectiveness. Copyright © 2012 John Wiley & Sons, Ltd.
Influence of processing parameters on the structure of melt blended polyethylene/organoclay nanocomposites produced by a masterbatch route
Authors: Besco Stefano , Modesti Michele , Lorenzetti Alessandra
Published: August 2012

Melt compounding is one of the most used methods to produce thermoplastic‐based nanocomposites. The aim of this study is the assessment of the effects of processing set‐up and conditions on the structure and properties of low‐density polyethylene/organically modifies layered silicate (OMLS) nanocomposites obtained by a two‐step process by concentrate masterbatch route. Concentrate masterbatch formulation and dilution have been investigated to correlate processing parameters with final nanocomposites structure by means of morphological and physical characterization. Even if a good dispersion/intercalation occurred regarding concentrate masterbatch, the probability of a further OMLS dispersion during the masterbatch dilution process depends remarkably on the extruder mixing capacity, with important consequences for the industrial application of masterbatch technology in net shape forming processes. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers
A Real‐World Evaluation of Oral Vancomycin for Severe Clostridium difficile Infection: Implications for Antibiotic Stewardship Programs
Authors: Le Frank , Arora Vaneet , Shah Dhara N. , Salazar Miguel , Palmer Hannah R. , Garey Kevin W.
Published: September 2012

Study Objective

To assess antibiotic treatment patterns and clinical outcomes of patients with Clostridium difficile infection (CDI) based on underlying severity of CDI disease.

Design

Retrospective analysis of data from a prospective cohort study.

Setting

Large tertiary care university hospital.

Patients

One hundred forty‐four patients (mean ± SD age 63 ± 17 yrs) with CDI who received metronidazole (intravenous or oral) or oral vancomycin as their initial therapy option between 2006 and 2008.

Measurements and Main Results

Patients were stratified by severity of illness and treatment, and outcomes assessed were clinical response, relapse of disease, all‐cause inpatient mortality, and length of hospital stay. Mild‐moderate CDI disease was present in 85 patients (59%) and severe disease in 59 patients (41%). Overall, oral vancomycin was given to 16 patients (11%); use of this drug did not differ according to severity of infection. Among patients with severe disease, clinical success occurred in 32 (63%) of 51 patients given metronidazole and in all 8 patients (100%) given vancomycin (p=0.04). Inpatient mortality and hospital length of stay were lower in patients with severe CDI who were given oral vancomycin, although these results were not statistically significant.

Conclusion

Oral vancomycin was not commonly used for severe CDI. An improved clinical response rate was observed in patients with severe CDI given oral vancomycin; this outcome supported results from clinical trials. Antibiotic stewardship teams could play a major role in providing guidance on CDI treatment based on severity.