bluuebunny/crossref_metadata_2025_split huggingface dataset:
When Black Swans Aren't: On Better Recognition, Assessment, and Forecasting of Large Scale, Large Impact, and Rare Event Change
Authors: Werther Guntram Fritz Albin 
Published: March 2013

AbstractThe article discusses professional best practice implications stemming from differing varieties of thinking about black swans. The possibilities of rare event recognition in general, and the conforming limits on the forecasting art that arise from different views of possibilities is addressed. In particular, assessing how different philosophical groundings partner with methodological and practice implications to shape and limit practice possibilities is highlighted. Opportunities for securing comparative advantages—individual, organizational, and societal—are revealed by introducing holistic methods for better recognizing, assessing, and managing emerging large scale, large impact, rare events thought by most people to be unpredictable black swans. To achieve this, the article uses mainstream model and analyst failure dynamics to develop a way to better recognize and time large scale, large impact rare event emergence.As part of this discussion, the article assesses the philosophical and factual bases of Nassim Taleb's famous book, The Black Swan: The Impact of the Highly Improbable, and argues that strong‐version black swan perspectives (views that meaningful forecasting is not possible in an essentially chaotic world where rare black swans shape reality) are significantly responsible for placing unreal limits on the very possibilities of improving professional best practices, they being grounded in philosophical traditions that needlessly constrain better training, and competent risk assessment and futures forecasting.
Recent Research Developments Affecting Nonlife Insurance—The CAS Risk Premium Project 2011 Update
Authors: Eling Martin 
Published: March 2013

AbstractThis article summarizes the results of the 2011 Risk Premium Project (RPP) continual update. The aim of RPP is to review the actuarial and finance literature on the theory and empirics of risk assessment for property–casualty insurance. We find that behavioral insurance and new instruments of alternative risk transfer are popular fields of research in nonlife insurance. Capital allocation and enterprise risk management, too, are currently very important research topics. Moreover, the financial crisis has stimulated new work on corporate governance and insurance.
Open‐Market Stock Repurchases by Insurance Companies and Signaling
Authors: Huang Gow‐Cheng , Liano Kartono , Manakyan Herman , Pan Ming‐Shiun 
Published: March 2013

AbstractThe signaling hypothesis of share repurchases implies that management uses repurchases to signal either that their firm's future operating performance will improve or that shares of their stock are simply underpriced by the market. This study examines which of the two interpretations can better explain open‐market share repurchase programs announced by insurance companies. We find no evidence that future‐operating performance of insurers improves following the repurchase announcement. In addition, changes in future operating performance cannot explain the announcement‐period abnormal return. Instead, the stock undervaluation prior to the repurchase announcement can significantly explain the announcement‐period abnormal return, particularly for life insurers. Overall, our results suggest that the positive market reaction to insurers’ open‐market share repurchase announcements is due to the stock undervaluation by the market, but not due to positive information content about future operating performance conveyed in the repurchase announcement.
Personal Lines Risk Management and Insurance Simulation Game
Authors: Kerr Dana A. , Avila Stephen M. 
Published: March 2013

AbstractThis article examines the use of a Personal Lines Risk Management and Insurance Simulation Game in an introductory risk management and insurance (RMI) course. Business simulations and other case study teaching methods are a way to increase student engagement in the classroom, which can translate into a greater likelihood of higher learning outcomes. Because no one knows for sure what will happen in the future, there is a fundamental trade‐off that influences all RMI decisions: incur a known cost today in order to reduce risk in the future even though a loss may never materialize or refuse the immediate cost that would have reduced risk even though a future loss event might still occur. It is difficult to convince students of the consequences of such decisions because most realize that the individual likelihood of suffering an insurable loss is quite small. Students also fail to understand the complexity of making these trade‐off decisions multiple times in a given period for each different loss exposure they face. A description of the purpose of the game, innovative features, Smith Family Case Study, game specifics, and objectives and grading for the game have been provided. This article can be used as a step‐by‐step guide to implement this simulation in RMI courses at other universities to increase student engagement and enhance student learning.
Sequence‐based typing identified a new HLA‐B*40 allele, HLA‐B*40:124:02
Authors: Li D.‐M. , Shan X.‐Y. , Ni L. , Wang L. , Zhang Z.‐X. 
Published: March 2013

The sequence of a novel allele, HLA‐B*40:124:02, differs from HLA‐B*40:42 by three‐nucleotide exchanges in exon 3.
Bacillus thuringiensis israelensis (Bti) for the control of dengue vectors: systematic literature review
Authors: Boyce R. , Lenhart A. , Kroeger A. , Velayudhan R. , Roberts B. , Horstick O. 
Published: March 2013

AbstractObjectiveTo systematically review the literature on the effectiveness of Bacillus thuringiensis israelensis (Bti), when used as a single agent in the field, for the control of dengue vectors.MethodSystematic literature search of the published and grey literature was carried out using the following databases: MEDLINE, EMBASE, Global Health, Web of Science, the Cochrane Library, WHOLIS, ELDIS, the New York Academy of Medicine Gray Literature Report, Africa‐Wide and Google. All results were screened for duplicates and assessed for eligibility. Relevant data were extracted, and a quality assessment was conducted using the CONSORT 2010 checklist.ResultsFourteen studies satisfied the eligibility criteria, incorporating a wide range of interventions and outcome measures. Six studies were classified as effectiveness studies, and the remaining eight examined the efficacy of Bti in more controlled settings. Twelve (all eight efficacy studies and 4 of 6 effectiveness studies) reported reductions in entomological indices with an average duration of control of 2–4 weeks. The two effectiveness studies that did not report significant entomological reductions were both cluster‐randomised study designs that utilised basic interventions such as environmental management or general education on environment control practices in their respective control groups. Only one study described a reduction in entomological indices together with epidemiological data, reporting one dengue case in the treated area compared to 15 dengue cases in the untreated area during the observed study period.ConclusionWhile Bti can be effective in reducing the number of immature Aedes in treated containers in the short term, there is very limited evidence that dengue morbidity can be reduced through the use of Bti alone. There is currently insufficient evidence to recommend the use of Bti as a single agent for the long‐term control of dengue vectors and prevention of dengue fever. Further studies examining the role of Bti in combination with other strategies to control dengue vectors are warranted.
Spaces of rational curves on complete intersections
Authors: Beheshti Roya , Kumar N. Mohan 
Published: March 2013

AbstractWe prove that the space of smooth rational curves of degree $e$ on a general complete intersection of multidegree $(d_1, \ldots , d_m)$ in $\mathbb {P}^n$ is irreducible of the expected dimension if $\sum _{i=1}^m d_i \lt (2n+m+1)/3$ and $n$ is sufficiently large. This generalizes a result of Harris, Roth and Starr [Rational curves on hypersurfaces of low degree, J. Reine Angew. Math. 571 (2004), 73–106], and is achieved by proving that the space of conics passing through any point of a general complete intersection has constant dimension if $\sum _{i=1}^m d_i$ is small compared to $n$.
Families of canonically polarized manifolds over log Fano varieties
Authors: Lohmann Daniel 
Published: March 2013

AbstractLet $(X,D)$ be a dlt pair, where $X$ is a normal projective variety. We show that any smooth family of canonically polarized varieties over $X\setminus \,{\rm Supp}\lfloor D \rfloor $ is isotrivial if the divisor $-(K_X+D)$ is ample. This result extends results of Viehweg–Zuo and Kebekus–Kovács. To prove this result we show that any extremal ray of the moving cone is generated by a family of curves, and these curves are contracted after a certain run of the minimal model program. In the log Fano case, this generalizes a theorem by Araujo from the klt to the dlt case. In order to run the minimal model program, we have to switch to a $\mathbb Q$-factorialization of $X$. As $\mathbb Q$-factorializations are generally not unique, we use flops to pass from one $\mathbb Q$-factorialization to another, proving the existence of a $\mathbb Q$-factorialization suitable for our purposes.
MR safety assessment of potential RF heating from cranial fixation plates at 7 T
Authors: Kraff Oliver , Wrede Karsten H. , Schoemberg Tobias , Dammann Philipp , Noureddine Yacine , Orzada Stephan , Ladd Mark E. , Bitz Andreas K. 
Published: March 2013

Purpose:The increasing number of clinically oriented MRI studies at 7 T motivates the safety assessment of implants, since many 7 T research sites conservatively exclude all subjects with metallic implants, regardless of type or location. The purpose of this study was to investigate potential RF‐induced heating during a 7 T MRI scan using a self‐built transmit/receive RF coil in patients with implants used for refixation of the bone flap after craniotomy. Going beyond standard ASTM safety tests, a comprehensive test procedure for safety assessments at 7 T is presented which takes into account the more complex coupling of the electromagnetic field with the human body and the implant as well as polarization effects.Methods:The safety assessment consisted of three main investigations using (1) numerical simulations in simplified models, (2) electric and magnetic field measurements and validation procedures in homogeneous phantoms, and (3) analysis of exposure scenarios in a heterogeneous human body model including thermal simulations. Finally, 7 Tin vivo images show the degree of image artifact around the implants.Results:The simulations showed that the field distortions remain localized within the direct vicinity of the implants. A parallel E‐field polarization was found to be the most relevant component in creating local SAR deviations, resulting in a 10% increase in 10‐g‐averaged SAR and 53% in 1‐g‐averaged SAR. Using a heterogeneous human head model, the implants caused field distortions and SAR elevations in the numerical simulations which were distinctly lower than the maximum local SAR value caused by the RF coil alone. Also, the position of the maximum 10‐g‐averaged SAR remained unchanged by the presence of the implants. Similarly, the maximum absolute local temperature remained below 39 °C in the thermal simulations. Only minor artifacts from the implants were observed in thein vivo images that would not likely affect the diagnostic image quality in patients.Conclusions:The findings suggested no evidence for noteworthy RF‐related heating in humans after craniotomy using the described implants and for the particular RF coil that was used in this study. Here, identical transmit power restrictions apply with or without the implants. For other RF coils, the maximum permissible input power should be reduced by 10% until further simulations may indicate otherwise.
Pharmacokinetic Evaluation of the Interaction between Hepatitis C Virus Protease Inhibitor Boceprevir and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Atorvastatin and Pravastatin
Authors: Hulskotte E. G. J. , Feng H.-P. , Xuan F. , Gupta S. , van Zutven M. G. J. A. , O'Mara E. , Wagner J. A. , Butterton J. R. 
Published: March 2013

ABSTRACT

Boceprevir is a potent orally administered inhibitor of hepatitis C virus and a strong, reversible inhibitor of CYP3A4, the primary metabolic pathway for many 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Thus, the aim of the present study was to investigate drug-drug interactions between atorvastatin or pravastatin and boceprevir. We conducted a single-center, open-label, fixed-sequence, one-way-crossover study with 20 healthy adult volunteers. Subjects received single-dose atorvastatin (40 mg) or pravastatin (40 mg) on day 1, followed by boceprevir (800 mg three times daily) for 7 to 10 days. Repeat single doses of atorvastatin or pravastatin were administered in the presence of steady-state boceprevir. Atorvastatin exposure increased in the presence of boceprevir, with atorvastatin area under the concentration-time curve from time zero to infinity after single dosing (AUC
inf
) increasing 2.3-fold (90% confidence interval [CI], 1.85, 2.90) and maximum observed concentration in plasma (
C
max
) 2.7-fold (90% CI, 1.81, 3.90). Pravastatin exposure was slightly increased in the presence of boceprevir, with pravastatin AUC
inf
increasing 1.63-fold (90% CI, 1.03, 2.58) and
C
max
1.49-fold (90% CI, 1.03, 2.14). Boceprevir exposure was generally unchanged when the drug was coadministered with atorvastatin or pravastatin. All adverse events were mild and consistent with the known safety profile of boceprevir. The observed 130% increase in AUC of atorvastatin supports the use of the lowest possible effective dose of atorvastatin when coadministered with boceprevir, without exceeding a maximum daily dose of 40 mg. The observed 60% increase in pravastatin AUC with boceprevir coadministration supports the initiation of pravastatin treatment at the recommended dose when coadministered with boceprevir, with close clinical monitoring.
The Animal Food Supplement Sepiolite Promotes a Direct Horizontal Transfer of Antibiotic Resistance Plasmids between Bacterial Species
Authors: Rodríguez-Beltrán Jerónimo , Rodríguez-Rojas Alexandro , Yubero Elva , Blázquez Jesús 
Published: March 2013

ABSTRACT
Animal fodder is routinely complemented with antibiotics together with other food supplements to improve growth. For instance, sepiolite is currently used as a dietary coadjuvant in animal feed, as it increases animal growth parameters and improves meat and derived final product quality. This type of food additive has so far been considered innocuous for the development and spread of antibiotic resistance. In this study, we demonstrate that sepiolite promotes the direct horizontal transfer of antibiotic resistance plasmids between bacterial species. The conditions needed for plasmid transfer (sepiolite and friction forces) occur in the digestive tracts of farm animals, which routinely receive sepiolite as a food additive. Furthermore, this effect may be aggravated by the use of antibiotics supplied as growth promoters.
Multifaceted Mechanisms of HIV Inhibition and Resistance to CCR5 Inhibitors PSC-RANTES and Maraviroc
Authors: Lobritz Michael A. , Ratcliff Annette N. , Marozsan Andre J. , Dudley Dawn M. , Tilton John C. , Arts Eric J. 
Published: March 2013

ABSTRACT
Small-molecule CCR5 antagonists, such as maraviroc (MVC), likely block HIV-1 through an allosteric, noncompetitive inhibition mechanism, whereas inhibition by agonists such as PSC-RANTES is less defined and may involve receptor removal by cell surface downregulation, competitive inhibition by occluding the HIV-1 envelope binding, and/or allosteric effects by altering CCR5 conformation. We explored the inhibitory mechanisms of maraviroc and PSC-RANTES by employing pairs of virus clones with differential sensitivities to these inhibitors. Intrinsic PSC-RANTES-resistant virus (YA versus RT) or those selected in PSC-RANTES treated macaques (M584 versus P3-4) only displayed resistance in multiple-cycle assays or with a CCR5 mutant that cannot be downregulated. In single-cycle assays, these HIV-1 clones displayed equal sensitivity to PSC-RANTES inhibition, suggesting effective receptor downregulation. Prolonged PSC-RANTES exposure resulted in desensitization of the receptor to internalization such that increasing virus concentration (substrate) could saturate the receptors and overcome PSC-RANTES inhibition. In contrast, resistance to MVC was observed with the MVC-resistant HIV-1 (R3 versus S2) in both multiple- and single-cycle assays and with altered virus concentrations, which is indicative of allosteric inhibition. MVC could also mediate inhibition and possibly resistance through competitive mechanisms.
Differing Effects of Interleukin-10 on Cutaneous and Pulmonary Francisella tularensis Live Vaccine Strain Infection
Authors: Metzger Dennis W. , Salmon Sharon L. , Kirimanjeswara Girish 
Published: March 2013

ABSTRACTWe investigated the role of interleukin-10 (IL-10) in cutaneous and pulmonary infection withFrancisella tularensis. We found that after intradermal challenge of mice with the live vaccine strain (LVS) ofF. tularensis, splenic IL-10 levels increased rapidly and reached a peak 5 days after infection. However, IL-10 expression after infection was detrimental, since IL-10−/−mice showed increased bacterial clearance and were resistant to an infectious dose (>106CFU/mouse) that was uniformly lethal for IL-10+/+mice. Furthermore, IL-10+/+mice treated with neutralizing anti-IL-10R monoclonal antibody were able to survive lethal cutaneous LVS challenge. The presence of IL-10 appeared to restrain the expression of IL-17, since high levels of splenic IL-17 were observed after intradermal LVS infection only in IL-10−/−mice. Furthermore, treatment with neutralizing anti-IL-17R antibody ablated the enhanced survival observed in IL-10−/−mice. However, neutralization of IL-10 activity in IL-17R−/−mice failed to provide protection. Thus, IL-10 suppresses a protective IL-17 response that is necessary for resistance to cutaneous LVS infection. Surprisingly, however, IL-10−/−mice were significantly more susceptible to pulmonary infection with LVS. Finally, although IL-10 is a critical and novel regulator of immunity toF. tularensisLVS infection, its effects were masked during infection with the highly virulent SchuS4 strain. Taken together, these findings suggest that differentially regulating expression of the IL-10 pathway in various tissues could ultimately have prophylactic and therapeutic benefits for protection against tularemia.
Clearance of Staphylococcus aureus Nasal Carriage Is T Cell Dependent and Mediated through Interleukin-17A Expression and Neutrophil Influx
Authors: Archer Nathan K. , Harro Janette M. , Shirtliff Mark E. 
Published: March 2013

ABSTRACT

The anterior nares of humans are the major reservoir for
Staphylococcus aureus
colonization. Approximately 20% of the healthy human population is persistently and 80% is intermittently colonized with
S. aureus
in the nasal cavity. Previous studies have shown a strong causal connection between
S. aureus
nasal carriage and increased risk of nosocomial infection, as well as increased carriage due to immune dysfunction. However, the immune responses that permit persistence or mediate clearance of
S. aureus
on the nasal mucosa are fundamentally undefined. In this study, we developed a carriage model in C57BL/6J mice and showed that clearance begins 14 days postinoculation. In contrast, SCID mice that have a deficient adaptive immune response are unable to eliminate
S. aureus
even after 28 days postinoculation. Furthermore, decolonization was found to be T cell mediated but B cell independent by evaluating carriage clearance in T-cell receptor β/δ (TCR-β/δ) knockout (KO) and IgH-μ KO mice, respectively. Upregulation of the cytokines interleukin 1β (IL-1β), KC (also termed CXC ligand 1 [CXCL1]), and IL-17A occurred following inoculation with intranasal
S. aureus
. IL-17A production was crucial for clearance, since IL-17A-deficient mice were unable to effectively eliminate
S. aureus
carriage. Subsequently, cell differential counts were evaluated from nasal lavage fluid obtained from wild-type and IL-17A-deficient colonized mice. These counts displayed IL-17A-dependent neutrophil migration. Antibody-mediated depletion of neutrophils in colonized mice caused reduced clearance compared to that in isotype-treated controls. Our data suggest that the Th17-associated immune response is required for nasal decolonization. This response is T cell dependent and mediated via IL-17A production and neutrophil influx. Th17-associated immune responses may be targeted for strategies to mitigate distal infections originating from persistent
S. aureus
carriage in humans.
Infection with Francisella tularensis LVSclpBLeads to an Altered yet Protective Immune Response
Authors: Barrigan Lydia M. , Tuladhar Shraddha , Brunton Jason C. , Woolard Matthew D. , Chen Ching-ju , Saini Divey , Frothingham Richard , Sempowski Gregory D. , Kawula Thomas H. , Frelinger Jeffrey A. 
Published: March 2013

ABSTRACTBacterial attenuation is typically thought of as reduced bacterial growth in the presence of constant immune pressure. Infection withFrancisella tularensiselicits innate and adaptive immune responses. Severalin vivoscreens have identifiedF. tularensisgenes necessary for virulence. Many of these mutations renderF. tularensisdefective for intracellular growth. However, some mutations have no impact on intracellular growth, leading us to hypothesize that theseF. tularensismutants are attenuated because they induce an altered host immune response. We were particularly interested in theF. tularensisLVS (live vaccine strain)clpB(FTL_0094) mutant because this strain was attenuated in pneumonic tularemia yet induced a protective immune response. The attenuation of LVSclpBwas not due to an intracellular growth defect, as LVSclpBgrew similarly to LVS in primary bone marrow-derived macrophages and a variety of cell lines. We therefore determined whether LVSclpBinduced an altered immune response compared to that induced by LVSin vivo. We found that LVSclpBinduced proinflammatory cytokine production in the lung early after infection, a process not observed during LVS infection. LVSclpBprovoked a robust adaptive immune response similar in magnitude to that provoked by LVS but with increased gamma interferon (IFN-γ) and interleukin-17A (IL-17A) production, as measured by mean fluorescence intensity. Altogether, our results indicate that LVSclpBis attenuated due to altered host immunity and not an intrinsic growth defect. These results also indicate that disruption of a nonessential gene(s) that is involved in bacterial immune evasion, likeF. tularensisclpB, can serve as a model for the rational design of attenuated vaccines.