bluuebunny/crossref_metadata_2025 huggingface dataset:
Double-hit lymphomas: current paradigms and novel treatment approaches
Authors: Dunleavy Kieron
Published: November 2014

Double-hit lymphomas (DHLs) are a heterogeneous group of mature B-cell lymphomas that harbor concurrent rearrangements of MYC and BCL2 or, occasionally, BCL6. Several studies have now shown that they are associated with a very aggressive clinical course and poor outcome after standard R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy, with few patients surviving beyond 2 years. Due to their rarity, there is a paucity of data evaluating patient outcomes with alternative strategies to R-CHOP and no consensus on how they should be optimally managed. Recent studies have demonstrated that a significant proportion of diffuse large B-cell lymphoma (DLBCL) cases have high protein expression of MYC and BCL2 as detected by IHC. These so-called “double-expressor” DLBCLs are also associated with a poor outcome after R-CHOP, even when MYC and BCL2 rearrangements are absent. There is much interest in developing new strategies for DHL and better characterizing the underlying biology that drives their poor prognosis. Alternative chemotherapy platforms to R-CHOP, such as DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab), are under investigation for MYC-rearranged DLBCL, including DHL, and several novel small-molecule inhibitors of MYC and BCL2 are in development.
Balancing cure and long-term risks in acute lymphoblastic leukemia
Authors: Silverman Lewis B.
Published: November 2014

Cure rates for children and adolescents with acute lymphoblastic leukemia (ALL) have improved dramatically over the last few decades. With this success has come increasing recognition of the adverse late effects of treatment. The significant long-term sequelae in the earliest cohort of long-term survivors treated in the 1970s and 1980s are well documented. To reduce the incidence of these late effects, the majority of pediatric patients treated on more contemporary regimens receive less intensive treatment than did those treated 30-40 years ago. However, current therapies are not risk free; children treated with contemporary regimens remain at risk for developing long-term toxicities, including cardiac dysfunction, osteonecrosis, neurocognitive impairment, and second malignant neoplasms. One of the great challenges facing clinical investigators today is to identify interventions that will reduce the frequency and severity of long-term toxicities without adversely affecting cure rates. The use of dexrazoxane as a cardioprotectant (to prevent anthracycline-associated cardiotoxicity) and alternate-week dosing of dexamethasone (to reduce the risk of osteonecrosis) are examples of 2 such successful strategies. This article provides an overview of the long-term toxicities associated with current therapies and reviews results of clinical trials designed to minimize the burden of cure in long-term survivors.
Goals for chronic myeloid leukemia TK inhibitor treatment: how little disease is too much?
Authors: Mauro Michael J.
Published: November 2014

Tyrosine kinase inhibitors, now numbering 5 for the treatment of Philadelphia chromosome–positive leukemia, have proven ability to reduce clonal disease burden rapidly, dramatically, and durably, especially in chronic myeloid leukemia in the chronic phase. Deep molecular remissions are likely in most chronic phase patients and expectations on timing of response have been developed, validated as best as possible, and evolved over time. Increasing attention has been given to the initial decline of Bcr-Abl1 transcripts and the ultimate depth of molecular remission, overshadowing but not displacing the traditional role of cytogenetic response. This chapter reviews the evolution of response milestones for chronic phase chronic myeloid leukemia and tries to answer the question of how little disease is too much.
All transplantation-eligible patients with myeloma should receive ASCT in first response
Authors: Moreau Philippe , Attal Michel
Published: November 2014

In this last decade, one of the major advances in the management of multiple myeloma has been the introduction of the novel agents thalidomide, bortezomib, and lenalidomide as part of frontline treatment in young patients eligible for high-dose therapy (HDT) and autologous stem cell transplantation (ASCT). These drugs have markedly improved the rate of complete remission both before and after ASCT without substantially increasing toxicity. The implementation of an “optimal strategy” consisting of novel-agent-based induction, HDT, and the use of novel agents in consolidation and maintenance may result in a 5-year survival rate of 80% and cure might be considered in a subset of patients who present with good prognostic features at the time of diagnosis. Nevertheless, the high efficacy of the novel agents has led some groups to test these agents upfront without ASCT. At the end of 2014, preliminary randomized data favor early ASCT plus novel agents over novel agents alone. Therefore, the optimal approach to the treatment of multiple myeloma is still to propose the most effective treatment that should involve the use of frontline ASCT in young patients eligible for HDT.
New insights into treatment of venous thromboembolism
Authors: Moll Stephan
Published: November 2014

Several advances have occurred over the last 2 years in the clinical management of venous thromboembolism (VTE), as evidenced by several high-profile publications in top-tier medical journals. The translation of the knowledge gained into routine clinical practice is an important challenge so that VTE is managed optimally and established and new anticoagulants are used effectively and safely. This chapter reviews issues of VTE treatment from acute management to treatment of long-term complications, addressing new data gained in the last 2 years and putting them into a clinical context, with the goal of improved everyday VTE management.
Monitoring target-specific oral anticoagulants
Authors: Konkle Barbara A.
Published: November 2014

Target-specific oral anticoagulants are approved for use for the prevention of stroke in atrial fibrillation and for the prevention and treatment of venous thrombosis without the need for laboratory monitoring. However, there are clinical settings in which laboratory measurement of anticoagulant effect is needed. These may include patients with life-threatening bleeding or those requiring emergency surgery, in the setting of renal or hepatic failure, or patients with thrombosis on therapy. This chapter reviews the use of laboratory testing to assess the anticoagulant effect of these drugs. In addition, because these drugs can interfere with other laboratory testing, available data on these interactions are presented.
What is the effect of rivaroxaban on routine coagulation tests?
Authors: Siegal Deborah M. , Konkle Barbara A.
Published: November 2014

A 78-year-old female presents to the emergency department with a traumatic hip fracture. Her past medical history is significant for atrial fibrillation for which she receives rivaroxaban 20 mg daily. Her dose was last taken 12 hours ago. Routine bloodwork conducted in the emergency department shows prothrombin time, international normalized ratio, and activated partial thromboplastin time within the normal range, and estimated glomerular filtration rate of 50 mL/min/1.73 m2 (normal is >90 mL/min/1.73 m2) You are asked by the surgical team to confirm that it is safe to proceed with surgery at this time using neuraxial anesthesia.
Pharmacogenomics of antiplatelet drugs
Authors: Sabatine Marc S. , Mega Jessica L.
Published: November 2014

Clopidogrel, a platelet P2Y12 inhibitor, is one of the most widely prescribed drugs in cardiovascular medicine because it reduces ischemic and thrombotic complications. It is a prodrug requiring biotransformation into the active metabolite by the hepatic cytochrome 450 system, especially the CYP2C19 enzyme. Candidate gene studies and genome-wide association studies have identified loss-of-function CYP2C19 variants to be associated with a diminished pharmacologic response. Specifically, compared with noncarriers, carriers of at least one copy of a loss-of-function CYP2C19 allele have ∼30% lower levels of active clopidogrel metabolite and ∼25% relatively less platelet inhibition with clopidogrel. Moreover, in patients treated with clopidogrel predominantly for percutaneous coronary intervention, carriers of 1 or 2 CYP2C19 loss-of-function alleles are at increased risk for major adverse cardiovascular outcomes, with an ∼1.5-fold increase in the risk of cardiovascular death, myocardial infarction, or stroke as well as an ∼3-fold increase in risk for stent thrombosis. Tripling the dose of clopidogrel in carriers of a CYP2C19 loss-of-function allele can achieve on-treatment platelet reactivity comparable to that seen with the standard 75 mg dose in wild-type individuals, but the impact on clinical outcomes remains unknown. Alternatively, 2 third-generation P2Y12 inhibitors are available: prasugrel and ticagrelor. These drugs are superior to clopidogrel in reducing ischemic outcomes and are unaffected by CYP2C19 loss-of-function alleles.
Management of MPN beyond JAK2
Authors: Harrison Claire N. , Garcia Natalia Curto
Published: November 2014

Thrombocytosis has a large number of potential underlying causes, but the dominant group of hematological conditions for consideration in this setting are the myeloproliferative neoplasms (MPNs). In this chapter, we consider several key linked questions relating to the management of thrombocytosis in MPNs and discuss several issues. First, we discuss the differential diagnosis of thrombocytosis, which myeloid disorders to consider, and practical approaches to the discrimination of each individual MPN from other causes. Second, there have been several major advances in our understanding of the molecular biology of these conditions and we discuss how these findings are likely to be practically applied in the future. Third, we consider whether there is evidence that thrombocytosis contributes to the complications known to be associated with MPN: thrombosis, hemorrhage and transformation to leukemia and myelofibrosis. Last, we review current ideas for risk stratification and management of essential thrombocythemia and polycythemia vera as the 2 entities within the MPN family that are most frequently associated with thrombocytosis.
Risky business of inhibitors: HLA haplotypes, gene polymorphisms, and immune responses
Authors: Reipert Birgit M.
Published: November 2014

The development of neutralizing antibodies against factor VIII (FVIII inhibitors) and factor IX (FIX inhibitors) is the major complication in hemophilia care today. The antibodies neutralize the biological activity of FVIII and FIX and render replacement therapies ineffective. Antibodies are generated as a result of a cascade of tightly regulated interactions between different cells of the innate and the adaptive immune system located in distinct compartments. Any event that modulates the repertoire of specific B or T cells, the activation state of the innate and adaptive immune system, or the migration pattern of immune cells will therefore potentially influence the risk for patients to develop inhibitors. This chapter reviews our current understanding of different pathways of antibody development that result in different qualities of antibodies. Potential differences in differentiation pathways leading to high-affinity neutralizing or low-affinity non-neutralizing antibodies and the potential influence of gene polymorphisms such as HLA haplotype, FVIII haplotype, and polymorphisms of immunoregulatory genes are discussed.
Anticoagulation and in vitro fertilization and ovarian stimulation
Authors: Bates Shannon M.
Published: November 2014

Assisted reproductive technology is widely used to treat couples affected by infertility. Complications associated with assisted reproduction include venous thromboembolism, ovarian hyperstimulation syndrome, and recurrent implantation failure. It has also been proposed that thrombophilia may be associated with an increased likelihood of these events. Although data are limited, antithrombotic therapy is frequently used to enhance the likelihood of successful assisted reproduction. This chapter reviews the risks of venous and arterial thromboembolism associated with assisted reproduction, as well as available data regarding the impact of thrombophilia on the risks of thromboembolism and failure of implantation. The role of antithrombotic therapy in reducing the likelihood of these events, along with recommendations from various guidelines, are also discussed.
Replacing bad (F)actors: hemophilia
Authors: Doering Christopher B. , Spencer H. Trent
Published: November 2014

Hemophilia A and B are bleeding disorders that result from functional deficiencies in specific circulating blood clotting factors termed factor VIII (FVIII) and factor IX (FIX), respectively, and collectively display an incidence of 1 in 4000 male births. Stem cell transplantation therapies hold the promise of providing a cure for hemophilia, but currently available transplantable stem cell products do not confer endogenous FIX or FVIII biosynthesis. For this reason, stem cell–based approaches for hemophilia have focused primarily on genetic engineering of pluripotent or multipotent stem cells. While pluripotent stem cells have been branded with high expectation and promise, they remain poorly characterized in terms of clinical utility and safety. In contrast, adult-lineage-restricted stem cells are established agents in the clinical armamentarium. Of the clinically established stem cell types, hematopoietic stem cells (HSCs) are the most utilized and represent the standard of care for several genetic and acquired diseases. Furthermore, HSCs are ideal cellular vehicles for gene therapy applications because they self-renew, repopulate the entire blood lineage while concurrently amplifying the transgene copy number >106 fold, and also have direct access to the bloodstream. Current research on HSC transplantation gene therapy approaches for hemophilia A and B is focused on the following: (1) identification of safe and efficient methods of nucleic acid transfer, (2) optimization of transgene product expression, (3) minimization of conditioning-regimen-related toxicity while maintaining HSC engraftment, and (4) overcoming preexisting immunity. Based on the existing data and current rate of progress, clinical trials of HSC transplantation gene therapy for hemophilia are predicted to begin in the coming years.
Caring for the long-term survivor after allogeneic stem cell transplantation
Authors: Bhatia Smita
Published: November 2014

Survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk of developing long-term complications such as subsequent malignancies and cardiopulmonary compromise. The prevalence of chronic health conditions approaches 75% among allogeneic HCT survivors and that for severe or life-threatening conditions exceeds 20%. This chapter describes the burden of morbidity carried by HCT survivors to help healthcare providers and policy makers understand the scope of the problem and the need for life-long follow-up and proactive care for this vulnerable population.
The target-specific oral anticoagulants: practical considerations
Authors: Garcia David A.
Published: November 2014

More than 4 years have passed since the first approval of a target-specific oral anticoagulant (TSOAC) in the United States, and the number of clinicians who have prescribed (or considered prescribing) one or more of these medications is increasing. Although these agents may, in properly selected patients, offer advantages over more traditional therapies, their lack of familiarity can be intimidating. Clinicians who are prescribing the TSOACs face a number of management questions not definitively answered by the registration trials. This chapter reviews some of these situations, including updated information on the periprocedural management of TSOACs and the latest evidence about how to best measure TSOAC effect. The lack of an antidote and other considerations that may be relevant when deciding between newer and more traditional anticoagulant medications are also discussed.
Reversing targeted oral anticoagulants
Authors: Hoffman Maureane , Monroe Dougald M.
Published: November 2014

Dabigatran, rivaroxaban, and apixaban are orally active anticoagulants that are approved in many countries. Dabigatran inhibits thrombin, whereas rivaroxaban and apixaban are factor Xa inhibitors. In clinical trials, these novel oral anticoagulants were at least as effective as warfarin for preventing stroke in patients with atrial fibrillation, but with a lower rate of serious bleeding. However, the lack of true antidotes for these agents has caused concern when patients suffer life-threatening bleeding or trauma or require emergent invasive procedures. True antidotes are under development for all of these agents. In the meantime, activated and nonactivated prothrombin complex concentrates have been used as reversal agents. Factor VIIa may also be effective for reversal of the factor Xa inhibitors. Reversal of novel oral anticoagulants by these hemostatic agents has not been studied in bleeding human patients, so their true efficacy and appropriate dosing are not known.
New insights into genotype and phenotype of VWD
Authors: Flood Veronica H.
Published: November 2014

Recent advances in VWD research have improved our understanding of the genotype and phenotype of VWD. The VWF gene is highly polymorphic, with a large number of sequence variations reported in healthy individuals. This can lead to some difficulty when attempting to discern genotype–phenotype correlations because sequence variations may not represent disease. In type 1 VWD, mutations can be found throughout the VWF gene, but likely pathogenic sequence variations are found in only ∼2/3 of type 1 VWD patients. Sequence variations in type 2 VWD are located in the region corresponding to the defect in the VWF protein found in each type 2 variant. In type 3 VWD, sequence variations are not confined to a specific region of the VWF gene and also include large deletions that may not be picked up using conventional sequencing techniques. Use of genetic testing may be most helpful in diagnosis of type 2 VWD, in which a larger number of known, well characterized mutations are present and demonstration of one of these may help to confirm the diagnosis. Bleeding symptoms in general are more severe with decreasing VWF levels and more severe in type 2 and type 3 VWD compared with type 1 VWD. Prediction of phenotype for an individual patient, however, is still difficult, and the addition of genetic data will be most helpful in ascertaining the correct diagnosis for VWD patients.
Bloodless medicine: what to do when you can't transfuse
Authors: Resar Linda M.S. , Frank Steven M.
Published: November 2014

A better understanding of risks associated with allogeneic blood transfusions (ABTs), along with a growing population of patients who do not accept transfusions, have led to the emergence of new treatment paradigms with “bloodless medicine.” In this chapter, we review prior studies describing management and outcomes in patients who refuse transfusion (referred to as “bloodless patients” herein) and summarize the approaches used at our institution. Bloodless management for surgical patients includes treatment of preoperative anemia, use of autologous blood salvage, and minimizing blood loss with procedures. Other adjuncts for both medical and surgical patients include minimizing blood loss from laboratory testing using pediatric phlebotomy tubes and conservative testing. Anemia can be treated with erythropoiesis-stimulating agents, as well as iron, folate, and B12 when indicated. Although there are limited retrospective studies and no prospective studies to guide management, prior reports suggest that outcomes for surgical patients managed without ABTs are comparable to historic controls. A recent risk-adjusted, propensity-matched, case-control study of outcomes of all hospitalized patients who refused ABT at a large academic health center showed that bloodless management was not an independent predictor of adverse outcomes. Surprisingly, there was a lower overall mortality in the bloodless group and discharge hemoglobin levels were similar for both bloodless and control groups. Further research is now needed to optimize therapy and identify novel interventions to manage bloodless patients. Lessons learned from bloodless patients are likely to benefit all patients given recent evidence suggesting that patients who avoid ABTs do as well, if not better, than those who accept transfusions.
Five hematologic tests and treatments to question
Authors: Hicks Lisa K. , Bering Harriet , Carson Kenneth R. , Haynes Adam E. , Kleinerman Judith , Kukreti Vishal , Ma Alice , Mueller Brigitta U. , O'Brien Sarah H. , Panepinto Julie A. , Pasquini Marcelo C. , Rajasekhar Anita , Sarode Ravi , Wood William A.
Published: November 2014

Choosing Wisely® is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. The American Society of Hematology (ASH) released its first Choosing Wisely® list in 2013. Using the same evidence-based methodology as in 2013, ASH has identified 5 additional tests and treatments that should be questioned by clinicians and patients under specific, indicated circumstances. The ASH 2014 Choosing Wisely® recommendations include: (1) do not anticoagulate for more than 3 months in patients experiencing a first venous thromboembolic event in the setting of major, transient risk factors for venous thromboembolism; (2) do not routinely transfuse for chronic anemia or uncomplicated pain crises in patients with sickle cell disease; (3) do not perform baseline or surveillance computed tomography scans in patients with asymptomatic, early-stage chronic lymphocytic leukemia; (4) do not test or treat for heparin-induced thrombocytopenia if the clinical pretest probability of heparin-induced thrombocytopenia is low; and (5) do not treat patients with immune thrombocytopenia unless they are bleeding or have very low platelet counts.
Timing of allogeneic stem cell transplantation for myelodysplastic syndromes and aplastic anemia
Authors: Cutler Corey
Published: November 2014

Allogeneic hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) is a potentially curative procedure, but is associated with a significant risk of morbidity and mortality. With the recent approval of disease-modifying agents, the appropriate timing of allogeneic HSCT needs to be addressed. Similarly, the optimal use of these disease-modifying agents before HSCT needs to be determined. In severe aplastic anemia, HSCT is a proven cure, but HLA-matched sibling donors are found in fewer than 25% of newly diagnosed patients. The use of early unrelated donor HSCT is an evolving concept that will become more accepted as improvements in HSCT outcomes continue.
Closure of small and medium size umbilical hernias with the Proceed Ventral Patch in obese patients: a single center experience
Authors: Wassenberg Dirk , Zarmpis Nikolaos , Seip Nora , Ambe Peter C
Published: November 2014

Obesity is a risk factor for the development of umbilical hernia. Open hernia closure could be challenging in obese patients leading to high rates of recurrence. The aim of this study was to investigate the effectiveness and safety of hernia patches in the management of obese patients with umbilical hernias. All the patients included in this study were managed in the department of surgery of a primary care hospital in Germany. The data of patients undergoing umbilical hernia repair within a two-year period was retrospectively reviewed. Patients managed with the PVP were included for analysis. 24 obese patients were analyzed. Small and medium size patches were used in 15 and 9 patients respectively. The median duration of surgery was 40 min and the median length of hospital stay was 4d. The mean length of follow-up was 12 ± 9 months (range: 6–30 months). The rate of recurrence was 4.1% and the rate of complication was 8.3%. Obese patients presenting with small and medium size umbilical hernias could be safely and effectively managed with prosthetic patches like the Proceed Ventral Patch. However, the limited overlap zone following hernia closure with such a patch can be an issue.
Transcriptional fingerprints of antigen-presenting cell subsets in the human vaginal mucosa and skin reflect tissue-specific immune microenvironments
Authors: Duluc Dorothée , Banchereau Romain , Gannevat Julien , Thompson-Snipes Luann , Blanck Jean-Philippe , Zurawski Sandra , Zurawski Gerard , Hong Seunghee , Rossello-Urgell Jose , Pascual Virginia , Baldwin Nicole , Stecher Jack , Carley Michael , Boreham Muriel , Oh SangKon
Published: November 2014

Background

Dendritic cells localize throughout the body, where they can sense and capture invading pathogens to induce protective immunity. Hence, harnessing the biology of tissue-resident dendritic cells is fundamental for the rational design of vaccines against pathogens.

Methods

Herein, we characterized the transcriptomes of four antigen-presenting cell subsets from the human vagina (Langerhans cells, CD14- and CD14+ dendritic cells, macrophages) by microarray, at both the transcript and network level, and compared them to those of three skin dendritic cell subsets and blood myeloid dendritic cells.

Results

We found that genomic fingerprints of antigen-presenting cells are significantly influenced by the tissue of origin as well as by individual subsets. Nonetheless, CD14+ populations from both vagina and skin are geared towards innate immunity and pro-inflammatory responses, whereas CD14- populations, particularly skin and vaginal Langerhans cells, and vaginal CD14- dendritic cells, display both Th2-inducing and regulatory phenotypes. We also identified new phenotypic and functional biomarkers of vaginal antigen-presenting cell subsets.

Conclusions

We provide a transcriptional database of 87 microarray samples spanning eight antigen-presenting cell populations in the human vagina, skin and blood. Altogether, these data provide molecular information that will further help characterize human tissue antigen-presenting cell lineages and their functions. Data from this study can guide the design of mucosal vaccines against sexually transmitted pathogens.
Prediction of microstructure evolution during multi-stand shape rolling of nickel-base superalloys
Authors: Subramanian Kannan , Cherukuri Harish P
Published: November 2014

In this paper, a comprehensive numerical approach to predict the microstructure of nickel-base superalloys during multi-stand shape rolling is presented. This approach takes into account the severe deformation that occurs during each pass and also the possible reheating between passes. In predicting the grain size at the end of the rolling process, microstructural events such as dynamic recrystallization (DRX), metadynamic recrystallization (MDRX), and static grain growth are captured at every deformation step for superalloys. Empirical relationships between the average grain size from various microstructural processes and the macroscopic variables such as temperature (T) and effective strain (

ε

̄

) and strain rate (

ε

̄

̇

) form the basis for the current work. These empirical relationships are based on Avrami equations. The macroscopic variables are calculated using a finite element analysis package wherein the material being rolled is modeled as a non-Newtonian fluid with viscosity that depends on the effective strain rate, strain, and temperature. A two-dimensional transient thermal analysis is carried out between passes that can capture the MDRX and/or static grain growth during the microstructural evolution. The presented microstructure prediction algorithm continuously updates two families of grains, namely, the recrystallized family and strained family at the start of deformation in any given pass. In addition, the algorithm calculates various subgroups within these two families at every deformation step within a pass. As the material undergoes deformation between the rolls, recrystallization equations are invoked depending on critical strain and strain rate conditions that are characteristics of superalloys. This approach predicts the microstructural evolution based on recrystallization kinetics and static grain growth only. The methodology was successfully applied to predict the microstructure evolution during the multi-pass rolling of nickel-base superalloys. The predicted results for Alloy 718 for a 4-stand rolling followed by air cooling and for a 16-stand rolling followed by a combination of air and water cooling are also compared with experimental observations.
A Logarithmic Safety Staffing Rule for Contact Centers with Call Blending
Authors: Pang Guodong , Perry Ohad
Published: November 2014

We consider large contact centers that handle two types of jobs—inbound and outbound—simultaneously, a process commonly referred to as call blending. Inbound work arrives to the system according to an exogenous arrival process, whereas outbound work is generated by the contact center. We assume that there is an infinite supply of outbound work to process, and that inbound calls are prioritized over the outbound calls. We propose a logarithmic safety staffing rule, combined with a threshold control policy, ensuring that agents' utilization is very close to one at all times, but that there are practically always idle agents present. Specifically, we prove that it is possible to have almost all inbound calls answered immediately upon their arrival, in addition to satisfying a target long-run throughput rate of outbound calls, with at most a negligible proportion of those calls dropped. Simulation experiments demonstrate the effectiveness and accuracy of our analysis.

This paper was accepted by Assaf Zeevi, stochastic models and simulation.
COPE: towards a comprehensive assessment of caregiver need
Authors: Nolan Mike , Philp Ian
Published: November 2014

Supporting family carers is a common policy objective across Europe. However, if appropriate help is to be provided there is a need for a sensitive assessment process. This article describes the COPE project, the purpose of which is to develop a first-stage assesment tool that can be used to identify carers requiring a further in-depth consideration of their support needs.
Nurse who undertook a procedure outside her competence
Authors: Castledine George
Published: November 2014

Mrs MacLean was employed as a bank nurse by a large city NHS trust. She often used to work on the accident and emergency (A&E) unit, where the incident described here occurred.
Determining the Processed Cut Stock Recovery Rate from Standing Dead Beetle-Killed Lodgepole Pine Timber
Authors: Mackes Kurt , Eckhoff Mike
Published: November 2014

Colorado's forests have been decimated by a mountain pine beetle outbreak. The mountain pine beetle introduces a blue-stain fungus into the trees, lowering the economic value of the wood. As a result, forest product manufacturing opportunities using beetle-killed trees are limited. One possibility is to use beetle-killed trees to make cut stock, which is lumber that has been cut into specified length, width, and thickness requirements from a cant, lumber, or glued-up panels. The White River Conservation District commissioned this study to determine if a relationship existed between the amount of time beetle-killed trees remain standing dead and the recovery rate for cut stock material from those trees. Conducted in north-central Colorado and south-central Wyoming, this study found that enough material does exist in beetle-killed lodgepole pine trees to produce cut stock but that a tree's diameter at breast height is a better predictor for the cut stock recovery rate from the logs rather than the time spent standing dead on the stump. Given the increasing likelihood that beetle-killed trees will blow down as time passes, incentives for increased beetle-killed wood utilization should be developed quickly.
La Corte Suprema del Ecuador en el período democrático (1979-2013): entre la inestabilidad institucional y la influencia partidista
Authors: Basabe-Serrano Santiago , Llanos Escobar Santiago
Published: November 2014

Este artículo analiza la influencia partidista sobre la designación de jueces supremos en democracias con bajos niveles de institucionalización. A diferencia del enfoque clásico en el que se asume que cuando los presidentes son políticamente débiles el efecto consiguiente es la selección de jueces más independientes de los intereses partidistas, lo que aquí se propone es que frente a Ejecutivos sin recursos políticos suficientes es la legislatura la que asume el control de las cortes de justicia. En términos analíticos, mientras en el primer caso se trata de un juego principal-agente con un solo actor provisto de recursos dirimentes (presidente), en el segundo caso el juego tiene lugar con varios principales (partidos en legislatura). A través de datos inéditos sobre la Corte Suprema del Ecuador en funciones durante el período 1979-2013 y recurriendo a narrativas históricas se constata que los cambios en las mayorías legislativas suelen ser el antecedente de cambios en la conformación de dicho tribunal. Solamente en casos de presidentes fuertes, como Rafael Correa, el Poder Ejecutivo ha sido un actor determinante para controlar políticamente a los jueces supremos.
La geografía de las campañas presidenciales en México en 2012
Authors: Palma Esperanza , Morales Gilberto
Published: November 2014

La pregunta central de este artículo es ¿cómo se distribuyeron las visitas de los/as candidatos/as a la presidencia en 2012 en los municipios de México? Se muestran los resultados de una investigación acerca de los municipios, visitados por los/as candidatos/as a la presidencia en México durante la campaña de 2012, visitas que se pueden entender como parte de una estrategia terrestre. Se construyó una base de datos en la cual se registraron las visitas de cada candidato a los municipios, los cuales fueron clasificados de acuerdo a la posición electoral de cada partido. En la base de datos se registró el tema abordado en cada una de las visitas, con el fin de establecer una primera relación, a modo de hipótesis, entre el pronunciamiento de la candidata y los candidatos, y los lugares que visitaron en campaña. De tal manera, esta investigación aporta la información acerca de la relación entre las estrategias de los/as candidatos/as y la situación geográfica-territorial de sus partidos.
Reduction of Turbidity of Beet Sugar Solutions by Mechanical and Chemical Treatment
Authors: Abdel-Rahman El-Sayed Ali , Floeter Eckhard
Published: November 2014

The presence of practically non-dissolvable small particles in sugar solutions can cause haze during application and has to be minimal. Intermediate storage of thick sugar juice becomes increasingly common practice. In particular juices treated with anti-scale agents appear to be prone to turbidity development. This work on turbidity mitigation reports results on both laboratory and industrial level experiments. Different filter aids were tested and led to reduced turbidity levels. At industrial and lab scale reductions in the order of 30–54% and 50–70% were achieved respectively, which however remains insufficient to resolve the problem. The chemical mitigation by reduction of the hardness of the juice either by sodium carbonate or by ion exchanger treatment was investigated. While the reduction of the calcium concentration by dosing of sodium carbonate turned out to be basically possible, this remains less practical than the utilization of cation exchangers. Furthermore, it was found that application of anti-scale agents causes a reduction on the particle sizes that are found in thick juice samples after 2 months storage. Turbidity values of these samples were, independent of dosage and type of anti-scale agent, twice as high as in reference samples.
Improved area-based deformation analysis of a radio telescope’s main reflector based on terrestrial laser scanning
Authors: Holst Christoph , Nothnagel Axel , Blome Martin , Becker Philip , Eichborn Malwin , Kuhlmann Heiner
Published: November 2014

The main reflectors of radio telescopes deform due to gravitation when changing their elevation angle. This can be analyzed by scanning the paraboloid surface with a terrestrial laser scanner and by determining focal length variations and local deformations from best-fit approximations.

For the Effelsberg radio telescope, both groups of deformations are estimated from seven points clouds measured at different elevation angles of the telescope: the focal length decreases by 22.7 mm when tilting the telescope from 90 deg to 7.5 deg elevation angle. Variable deformations of ± 2 mm are detected as well at certain areas. Furthermore, a few surface panels seem to be misaligned.

Apart from these results, the present study highlights the need for an appropriate measurement concept and for preprocessing stepswhen using laser scanners for area-based deformation analyses. Especially, data reduction, object segmentation and laser scanner calibration are discussed in more detail. An omission of these steps would significantly degrade the deformation analysis and the significance of its results. This holds for all sorts of laser scanner based analyses.
Comparative effects of Orchis anatolica vs. the red Korean Panax ginseng treatments on testicular structure and function of adult male mice
Authors: Khouri Nabil A. , Daradka Haytham M. , Allouh Mohammed Z. , Alkofahi Ahmad S.
Published: November 2014

Background: The effects of Orchis anatolica plant roots on adult male mice testicular structure and function were explored and compared with those of the red Korean Panax ginseng.

Methods: Both plants were administered orally to two separate mice groups at a dose of 800 mg/kg/day for 35 days and compared with control group. After treatment, 5 mice of each group were sacrificed and total mice weights, reproductive organs’ weights, spermatogenesis, and androgenic serum markers were investigated. The remaining mice from all groups were allowed to mate with virgin female mice to explore male fertility potential.

Results: Results indicated that body and organs’ weights were increased significantly in mice treated with Orchis anatolica where only slight changes were observed in red Korean Panax ginseng treated and control mice. Intestinal testicular Leydig cells and germinal cells counts were elevated significantly in mice treated with Orchis anatolica plant when compared with the other two groups. Testicular dynamics parameters recorded in both testes and caudae epididymides were found to be increased only in Orchis anatolica treated mice. Although testosterone serum titer was observed to be elevated in both treated mice groups a marked elevation was observed only in Orchis anatolica treated mice. Follicular stimulating hormone blood serum titer was also elevated obtained in Orchis anatolica treated mice when compared with the other two groups. The fertility index of male mice treated with Orchis anatolica plant was enhanced to a greater value when allowed mating with virgin female mice if compared with male mice fertility index recorded in the other two groups.

Conclusions: We can conclude that Orchis anatolica plant could be more useful to improve testicular functions and structural parameters in mice when compared with red Korean Panax ginseng.
Tetrahydrobiopterin deficiency among Serbian patients presenting with hyperphenylalaninemia
Authors: Stojiljkovic Maja , Klaassen Kristel , Djordjevic Maja , Sarajlija Adrijan , Kecman Bozica , Ugrin Milena , Zukic Branka , Desviat Lourdes R. , Pavlovic Sonja , Perez Belen
Published: November 2014

Hyperphenylalaninemia (HPA) [phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiencies] is rare inborn metabolic disease characterized by elevated phenylalanine level in body fluids. In Serbia, 62 HPA patients have been identified through newborn screening since 1983. However, pterin pattern analysis is not performed. We present a patient initially diagnosed and treated as classical PKU. At 3 years of age, during infection with H1N1 influenza A virus, the patient first developed a neurologic crisis with encephalopathy and dystonic movements. We suspected that the patient is the first case of BH4 deficiency identified in Serbia. Genetic analyses showed that the patient does not have disease-causing variants of the
The Existence and Reality of Negative Facts
Authors: Kühl Carl Erik
Published: November 2014

The problem of the existence of negative facts as truthmakers for negative propositions was introduced by Bertrand Russell in 1918. In the debate since then, most writers have tended to reject their existence, Russell himself being the most conspicuous exception. Two other strategies have been offered. The first, usually called incompatibilism, actually goes back to Plato, whereas the second, the totality fact theory, was introduced by D. M. Armstrong in 1997. The aim of this paper is to show the problematic character of some of the presuppositions shared by all three of the strategies mentioned above – presuppositions that figure in most of the current discourse on the subject. First, the concept of a negative proposition is not clear: one needs to make a distinction between grammatically negative propositions and “ontologically” negative ones. Second, it turns out that propositions may be ontologically negative in many ways, each of which may call for a different specific analysis with respect to the question of the existence of what would be the corresponding negative facts. Third, at the bottomline, it is shown that we need a concept of the existence or
The Meaning of “Meaning” from a Hermeneutic Point of View
Authors: Hedberg Petra
Published: November 2014

What is the meaning of “meaning”, hermeneutically seen? How does the philosophical hermeneutics of Hans-Georg Gadamer relate to the different types of meaning that are at hand in other branches of philosophy, such as sentence meaning within analytic philosophy, uttered meaning within speech acts theory and the communicative/dialogical meaning of formal/transcendental pragmatics? The comprehensive framework of Gadamer’s hermeneutics forms the horizon of understanding of this paper, and of specific interest is how these different types of meaning relate to the hermeneutic framework. Can a hermeneutical sense of meaning be elaborated in contrast to these different senses of meaning? Or, can these different types of meaning, in a certain sense, also be seen as compatible with the wider hermeneutical framework of meaning?
(Im)politesse et gestion des faces dans deux types de situations communicatives: petits commerces et débats électoraux
Authors: Kerbrat-Orecchioni Catherine
Published: November 2014

L’objectif de cet article est à la fois théorique et descriptif: il s’agit de mettre à l’épreuve le modèle de la politesse comme face work élaboré par Brown et Levinson (1978, 1987) en le confrontant à deux types bien différents d’interactions authentiques se déroulant en France, les échanges commerciaux d’une part (plus précisément, ceux qui se déroulent dans les “petits commerces”) et les débats politico-médiatiques de l’autre (plus précisément, les débats de l’entre-deux-tours des élections présidentielles). Après avoir proposé un certain nombre d’aménagements au modèle “standard” (introduction de la notion de Face Flattering Act venant compléter celle de Face Threatening Act, et des catégories de “non-politesse” et de “polirudesse” venant compléter celles de “politesse” et d’“impolitesse”), on appliquera ces notions et catégories au double corpus d’analyse. La confrontation montre à la fois que celles-ci sont en gros opératoires, mais que leur application ne peut se faire sans la prise en compte des normes en vigueur dans les différents genres discursifs observés, normes qui déterminent de façon décisive la façon dont les locuteurs utilisent et interprètent les ressources que la langue met à leur disposition, en particulier en matière de politesse.
How dopamine shapes representations in auditory cortex
Authors: Puschmann Sebastian , Weis Tina , Thiel Christiane M.
Published: November 2014

The neural representation of sound in the auditory cortex is not invariably predetermined by its  acoustical properties, but it is constantly reshaped while the listener acquires new experiences. Such plastic changes are a prerequisite for lifelong learning and allow some degree of rehabilitation after brain injuries. Several neurotransmitter systems modulate these plastic changes. In this paper, we focus on how the neurotransmitter dopamine modulates learning-related plasticity in auditory cortex, and how animal and human research can complement each other in providing an experimental approach that has relevance for studying mechanisms of recovery of function
Prognose oraler (gingivaler) Plattenepithelkarzinome beim Hund nach chirurgischer Therapie
Authors: Kessler M. , Kühnel S.
Published: November 2014

Gegenstand und Ziel: Retrospektive Untersuchung von Hunden mit gingivalen Plattenepithelkarzinomen (PEK), bei denen therapeutisch eine Kieferresektion erfolgte.

Material und Methoden: Die Auswertung erstreckte sich auf 40 Hunde. Patienten, bei denen keine Komplettresektion des Tumors erfolgte oder die Metastasen aufwiesen, erhielten eine adjuvante Chemotherapie mit Carboplatin. Ermittelt wurden Rasse und Alter der Hunde, Tumorlokalisation, Komplikationen und Überlebenszeit sowie prognostische Faktoren.

Ergebnisse: Eine Rasseprädisposition konnte nicht festgestellt werden. Das mediane Alter betrug 9,5 Jahre (durchschnittlich 8,6 Jahre, Bereich 0,5–15,5 Jahre). Bei zwei Hunden (5%) bestand zum Zeitpunkt der Vorstellung eine Lymphknotenmetastasierung (N1). Die mediane Überlebenszeit (ÜZ) aller Patienten lag bei 44,8 Monaten. Bei 15 Tieren war der Tumor im Oberkiefer lokalisiert, bei 25 im Unterkiefer. Die mediane ÜZ der Hunde mit Unterkiefertumoren betrug 43 Monate (95%-Konfidenzintervall [95%-KI] 33–70), die der Tiere mit Tumoren im Oberkiefer 39 Monate (95%-KI 24). Ein signifikanter Unterschied in den Überlebenszeiten von Patienten mit Oberbzw. Unterkiefertumoren war nicht nachweisbar (p = 0,985). In der Multivarianzanalyse zeigte nur das Tumorstadium prognostische Bedeutung (p = 0,0047). Patienten mit Stadium N0 lebten median 44 Monate (95%-KI 36–80), die beiden Hunde mit Lymphknotenmetastasen (N1) überlebten 18 bzw. 70 Monate nach Kieferresektion und Chemotherapie. Bei fünf Tieren zeigte sich histologisch nur eine inkomplette Resektion. Die ÜZ dieser Patienten nach Kieferresektion und Chemotherapie lag zwischen 6 und 146 Monaten (median 24 Monate).

Schlussfolgerung und klinische Relevanz: Die Prognose von gingivalen PEK ist abhängig vom Tumorstadium. Bei Komplettresektion weisen sie eine günstige Prognose auf, die Mehrheit der Patienten kann als geheilt betrachtet werden. Das angeblich malignere Verhalten kaudal im Kiefer gelegener PEKs ließ sich in dieser Studie nicht nachvollziehen. Auch Patienten mit lokalen Lymphknotenmetastasen können befriedigende Überlebenszeiten erreichen. Kieferresektionen haben eine niedrige Komplikationsrate und gehen mit gutem funktionellem Ergebnis einher.