bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis and Discussion of Atmospheric Precursor of European Heat Summers
Authors: Träger-Chatterjee Christine , Müller Richard W. , Bendix Jörg
Published: November 2014

The prediction of summers with notable droughts and heatwaves on the seasonal scale is challenging, especially in extratropical regions, since their development is not yet fully understood. Thus, monitoring and analysis of such summers are important tasks to close this knowledge gap. In a previous paper, the authors presented hints that extreme summers are connected with specific conditions during the winter-spring transition season. Here, these findings are further discussed and analysed in the context of the Earth’s circulation systems. No evidence for a connection between the North Atlantic Oscillation or the Arctic Oscillation during the winter-spring transition and extremely hot and dry summers is found. However, inspection of the geopotential at 850 hPa shows that a Greenland-North Sea-Dipole is connected with extreme summers in Central Europe. This motivated the introduction of the novel Greenland-North Sea-Dipole-Index, GNDI. However, using this index as predictor would lead to one false alarm and one missed event in the time series analysed (1958–2011). Hints are found that the disturbance of the “dipole-summer” connection is due to El Niño/Southern Oscillation (ENSO). To consider the ENSO effect, the novel Central European Drought Index (CEDI) has been developed, which is composed of the GNDI and the Bivariate ENSO Time Series Index. The CEDI enables a correct indication of all extremely hot and dry summers between 1958 and 2011 without any false alarm.
Synthesis and Characterization of Screen Printed Zn0.97Cu0.03O Thick Film for Semiconductor Device Applications
Authors: Zargar Rayees Ahmad , Khan Sharief Ud Din , Khan Mohd Shahid , Arora Manju , Hafiz Aurangzeb Khurram
Published: November 2014

The studies on doped ZnO thick films deposited over large surface area are still a very promising area of research and development. We report characteristic properties of thick film of Zn0.97Cu0.03O prepared by the economic screen printing technique. The film was characterized by XRD, SEM, diffused reflectance, FTIR, and dark resistivity measurement techniques. The XRD and SEM studies revealed polycrystalline, single phase, porous, and granular surface morphology of this Cu doped ZnO thick films. The direct band gap energy of this film determined by diffuse reflectance technique is 3.18 eV. IR transmission spectrum measured in 4000–600 cm−1 region at ambient temperature confirmed the incorporation of Cu2+ ions in ZnO lattice. The DC resistivity measurements reveal semiconducting nature of the sample with activation energy of 0.66 eV.
Environmental Sustainability Evaluation of Apparel Product: A Case Study on Knitted T-Shirt
Authors: Islam Md. Mazedul , Khan Md. Mashiur Rahman
Published: November 2014

The work reported in this paper presents the assessment of environmental performances of selected branded apparel T-Shirt products made by Bangladesh. The study is based on a standard evaluation tool named Higg Index which is basically used widely to measure the environmental sustainability of various apparel products. Higg Index is an internal self-assessment tool created by the outdoor apparel industry and Nike’s apparel environmental design tool which aims to aggregate information on the environmental performance of products. The Index considers performance across the full life-cycle of a product, including impacts from “input materials, manufacturing, packaging, transportation, use, and end-of-life.” Selected apparel branded T-Shirt products from S. Oliver, BUTex-Innovation, PUMA, Esprit, Aarong, and Yellow were taken into consideration. The results indicate that newly developed ecofriendly T-shirt and foreign branded products named S. Oliver, PUMA, and Esprit gained higher score but local branded product like Aarong and Yellow gained lower score in terms of environmental sustainability based on Higg Index assessment tool. Moreover, many weaknesses and opportunities for improvement of both local and foreign branded T-Shirt products have been identified and suggested which would eventually lead the fashion designer, apparel manufacturer, stakeholder, and consumer towards greener apparel products.
Kimura Disease Manifesting as Synchronous Bilateral Parotid Swelling in a Young Middle-Eastern Patient
Authors: Faras Fatemah , Abo-Alhassan Fawaz , Al-Sebeih Khalid , Bastaki Jassem
Published: November 2014

Kimura disease is a rare, benign, chronic inflammatory swelling of the subcutaneous tissue, lymph nodes, and glandular tissue. Characteristic features of the disease include, but not limited to, painless subcutaneous head and neck swelling, blood and tissue eosinophilia, and markedly elevated immunoglobulin E (IgE) levels. Herein, we report a rare case of Kimura disease manifesting as synchronous bilateral parotid swelling of 12 years duration in a 33-year-old Middle-Eastern man. To our knowledge only few cases have been reported in the literature involving bilateral parotid glands, and this is the first case to be reported in the Middle East.
IgG4-Related Disease: A Multispecialty Condition
Authors: Usêda Santana Iuri , da Fonseca Emanuela Pimenta , Santiago Mittermayer Barreto
Published: November 2014

IgG4-related disease (IgG4-RD) is a recently recognized group of conditions, characterized by tumor-like swelling of involved organs, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, variable degrees of fibrosis, and elevated serum IgG4 concentrations. Currently IgG4-RD is recognized as a systemic condition that can affect several organs and tissues. Herein we report the case of a 34-year-old male patient who was admitted to our hospital with diffuse abdominal pain, weight loss, and painful stiffness in his neck. He had a history of tumoral mass of the left maxillary region, right palpebral ptosis with protrusion of the eyeball, and chronic dry cough for about 6 years. Laboratory tests revealed polyclonal hypergammaglobulinemia and increased serum IgG4 levels. Immunohistochemical staining of the maxillary biopsy was compatible with IgG4-RD. He had an excellent response to corticosteroid therapy. This case highlights that IgG4-RD should be included in the differential diagnosis with multisystem diseases.
Residual Fistula of Fourth Branchial Arch Anomalies and Recurrent Left-Side Cervical Abscess: Clinical Case and Review of the Literature
Authors: Hallak Bassel , Bouayed Salim , Leishman Crispin , Sandu Kishore
Published: November 2014

Congenital fourth branchial arch anomalies are uncommon entities. Most of these anomalies are diagnosed in childhood. The majority of cases occur on the left side. The clinical presentation of these anomalies varies with age. A respiratory distress is the usual clinical presentation in neonates, cervical cutaneous fistulas in late childhood or acute suppurative thyroiditis. Multiples diagnostic options have been described with different modalities of treatment. The majority of cases of fourth branchial arch anomalies are described only in case reports. We report a clinical case of recurrent cervical abscess in a young woman due to a residual fistula of fourth branchial arch.
Prognostic Value of Plasma Pentraxin-3 Levels in Patients with Stable Coronary Artery Disease after Drug-Eluting Stent Implantation
Authors: Haibo Liu , Xiaofang Guo , Chunming Wang , Jie Yuan , Guozhong Chen , Limei Zhang , Yong Cao , Yu Fang , Yingchun Bao , Wangjun Yu , Junbo Ge
Published: November 2014

Pentraxin-3 (PTX3) is an inflammatory marker thought to be more specific to cardiovascular inflammation than C-reactive protein (CRP). Our aim was to assess the prognostic value of PTX3 in patients with stable coronary artery disease (CAD) after drug eluting stent (DES) implantation. Plasma PTX3 levels were measured before percutaneous coronary intervention (PCI) and at 24 h post-PCI in 596 consecutive patients with stable CAD. Patients were followed up for a median of 3 years (range 1–5) for major adverse cardiovascular events (MACEs). We found that the post-PCI plasma PTX3 levels were significantly higher at 24 h after PCI than pre-PCI, patients with MACEs had higher post-PCI PTX3 levels compared with MACEs-free patients, patients with higher post-PCI PTX3 levels (median > 4.384 ng/mL) had a higher risk for MACEs than those with PTX3 < 4.384 ng/mL, and post-PCI PTX3, cTnI, multiple stents, and age but not high-sensitivity CRP (hsCRP) were independently associated with the prevalence of MACEs after DES implantation. The present study shows that post-PCI PTX3 may be a more reliable inflammatory predictor of long-term MACEs in patients with stable CAD undergoing DES implantation than CRP. Measurement of post-PCI PTX3 levels could provide a rationale for risk stratification of patients with stable CAD after DES implantation.
Central Retinal Vein Occlusion in a Patient with Retinal Vasculitis and Crohn’s Disease
Authors: Figueiredo Lígia , Rothwell Renata , Brandão Arnaldo , Fonseca Sofia
Published: November 2014

The authors report a rare case of a 47-year-old woman with Crohn’s disease (CD) who presented with retinal vasculitis and central retinal vein occlusion (CRVO) during remission. The patient complained of sudden painless visual loss in her left eye (OS). Ophthalmologic evaluation revealed a best corrected visual acuity (BCVA) of 20/20 in the right eye and hand movements in OS. Ophthalmoscopy and fluorescein angiography of OS showed signs of nonischemic CRVO and extensive vasculitis. She was treated with oral prednisolone, mercaptopurine, and intravitreal bevacizumab in OS. After 1 month of treatment, VA of OS improved to 5/10 and after 1 year it was 10/10 with complete resolution of retinal vasculitis and nonischemic CRVO.
Concurrent Medullary, Papillary, and Follicular Thyroid Carcinomas and Simultaneous Cushing's Syndrome
Authors: Mazeh Haggi , Orlev Amir , Mizrahi Ido , Gross David J. , Freund Herbert R.
Published: November 2014

Background: Papillary thyroid carcinoma is the most common thyroid cancer (85%). Follicular thyroid carcinoma is the second most common type of thyroid cancer, accounting for up to 10% of all thyroid cancers. Medullary thyroid carcinoma accounts for only 5-8% of thyroid cancers. Concurrent medullary, follicular, and papillary carcinomas of the thyroid gland are extremely rare and reported scarcely. Case Report: A 72-year-old male presented with nonspecific neck pain. The workup revealed a nodular thyroid gland with a follicular lesion on fine-needle aspiration. Total thyroidectomy was performed and pathological examination identified a 25-mm follicular carcinoma, two papillary microcarcinomas, and two medullary microcarcinomas. The genetic workup was negative and no other family members were diagnosed with any endocrinopathy. Two months after surgery, the patient was diagnosed with Cushing's syndrome that was treated with laparoscopic left adrenalectomy. On 3-year follow-up, the patient is asymptomatic with no evidence of recurrent disease. Conclusion: We present a rare case of a patient with follicular, papillary, and medullary thyroid carcinoma, and Cushing's syndrome. To date, no known genetic mutation or syndrome can account for this combination of neoplastic thyroid and adrenal pathologies, although future research may prove differently.
The Role of Catholicism in the Development of Lithuanian National Identity
Authors: Zapor Cruz Miranda
Published: November 2014

Over the course of nine centuries in Lithuania, the Catholic Church transitioned from military threat, to foreign occupier, to key component of national identity. This article will take an historical look at the Catholic Church in Lithuania and the process by which Catholic faith became culturally and politically embedded in Lithuanian national identity. An examination of the interplay between the Catholic Church and the Lithuanian nation demonstrates that the Church was instrumental in the formation and growth of national identity, which reached its climax in the close identification of Catholicism with nationalism in the anti-Soviet dissent movements of the 1980s and 1990s.
Resisting the Rosicrucians
Authors: Smith Wm. Bradford
Published: November 2014

In The Rosicrucian Enlightenment Frances Yates theorized that the occult philosophy described in the Rosicrucian Manifestos of 1614 were attached to a political alliance uniting Protestant England with the Palatinate. Though modern scholars have largely rejected Yates’s argument, at least two writers in the early seventeenth century argued along similar lines, linking the Rosicrucians to the revolt that placed the Palatine Elector on the Bohemian throne, initiating the Thirty Years’ War. Friedrich Förner, Suffragan-Bishop of Bamberg, and Jean Boucher, a noted French controversialist, both saw the Rosicrucians as an occult conspiracy working to undermine Catholic states from within. The two author’s attack on the Rosicrucians contained a veiled critique of Renaissance monarchy. In the end both authors proposed a form of constitutional government intended to remedy the worst defects of Renaissance absolutism and ensure the survival of Catholicism in an age of religious war.
Oky ontatechiata
Authors: Labelle Kathryn Magee
Published: November 2014

This article focuses on the Wendat Panic of 1635–1645.While details of popular moral panics such as the Salem Trials of the 1690s are replete, historians continue to question not only the general characteristics of witchcraft in Native society (how it functioned on a day-to-day basis) but also more specific queries concerning the degree to which Native witchcraft was a colonial product and the influence of social structures such as gender and class on accusations. By applying an ethnohistorical approach to several seventeenth-century Wendat case studies, brief glimpses into the Wendat world are uncovered and serve to answer some of these questions. Taken as a whole, an investigation into the Wendat experience places unique Wendat notions of witchcraft within the more general human historical context of the early modern world.
A Genealogy of Muslims Dying in France
Authors: Ural Nur Yasemin
Published: November 2014

The question of the death of a Muslim in France engenders a discussion on the forms and limits of secularisation in the public sphere. Contrary to other public institutions like schools, hospitals and prisons, the particularity of mortuary spaces lies in their nearly uncontested religious character, also recognised by the French state. Despite the fact that repatriation remains to be the dominant practice among French Muslims, the descending generations, who overtly declare their identities as Muslim and European at the same time, seek to obtain their place within the European public sphere. Yet accommodating deceased bodies of Muslims within the so-called secular cemeteries represents a real challenge in terms of space, recognition of religious identities and application of Islamic funerary rites. The regulations imposed by the French authorities seem to pose serious problems to Muslims, who desire to be buried in accordance with the requirements of their religion. In this respect the cemetery becomes a realm of spatio-temporal struggle, where subjectivities are formed via negotiations between the subjects—dead or alive—and state apparatuses. This article aims to reflect on the power struggles in the development of the mortuary space from a historical perspective. It will then attempt to shed light on the legal possibility of the construction of the only French Muslim cemetery inaugurated in Strasbourg in 2012.
The deepwater demersal ichthyofauna of the western Coral Sea
Authors: LAST PETER R. , POGONOSKI JOHN J. , GLEDHILL DANIEL C. , WHITE WILLIAM T. , WALKER CHRIS J.
Published: November 2014

The highly diverse deepwater demersal ichthyofauna of the western Coral Sea was first systematically surveyed in two exploratory voyages in 1985 and 1986, and these fish assemblages have not been investigated at the same level since. Only recently have catch data and specimens, obtained from these first voyages almost 3 decades ago, been rigorously investigated and analysed. Some 393 species of fishes from 125 families were collected during the 1985 voyage which surveyed the northeastern Australian continental margin, and the Saumarez and Queensland Plateaus. A checklist of the species caught is provided. Levels of endemicity of deepwater fishes in the western Coral Sea are very high with about 50% of well-studied groups, such as sharks and rays, confined to this relatively small geographic region. A very high proportion of species caught during this voyage were either undescribed (78 species or 20%) or new Australian records (96 species or 24%) at the time of the survey. Another 68 species (17%) are the subject of further taxonomic investigation or are currently undergoing formal description. The fauna exhibits some intraregional differences in structure. Biogeographically informative fishes such as skates appear to be cryptically partitioned within the region, differing in composition to other Australian regions and those of French territories to the east. Strong depth-related partitioning of the fauna is also evident, and its structure follows zonation patterns observed across the wider Australian region. Given the high level of micro-endemicity and regional uniqueness of the fauna, there is a compelling argument for the existence of a faunal gyre in the Coral Sea.  New gap-filling surveys are needed to better define the structure of this fauna and determine its distribution.
Canines make the difference: a new species of Hypsugo (Chiroptera: Vespertilionidae) from Laos and Vietnam
Authors: GÖRFÖL TAMÁS , CSORBA GÁBOR , EGER JUDITH L. , SON NGUYEN TRUONG , FRANCIS CHARLES M.
Published: November 2014

Hypsugo was regarded as a subgenus of Pipistrellus by many authors, but its generic distinctiveness is now widely accepted. According to recent taxonomic arrangements, nine species are known to occur in Southeast Asia. During the investigation of material recently collected from Lao PDR and Vietnam we identified an additional species and hence describe it here as Hypsugo dolichodon n. sp. It resembles H. pulveratus, but is larger with conspicuously long canines and differs considerably in the DNA barcode gene sequence.
Statistical Postprocessing of High-Resolution Regional Climate Model Output
Authors: Mendoza Pablo A. , Rajagopalan Balaji , Clark Martyn P. , Ikeda Kyoko , Rasmussen Roy M.
Published: November 2014

Statistical postprocessing techniques have become essential tools for downscaling large-scale information to the point scale, and also for providing a better probabilistic characterization of hydrometeorological variables in simulation and forecasting applications at both short and long time scales. In this paper, the authors assess the utility of statistical postprocessing methods for generating probabilistic estimates of daily precipitation totals, using deterministic high-resolution outputs obtained with the Weather Research and Forecasting (WRF) Model. After a preliminary assessment of WRF simulations over a historical period, the performance of three postprocessing techniques is compared: multinomial logistic regression (MnLR), quantile regression (QR), and Bayesian model averaging (BMA)—all of which use WRF outputs as potential predictors. Results demonstrate that the WRF Model has skill in reproducing observed precipitation events, especially during fall/winter. Furthermore, it is shown that the spatial distribution of skill obtained from statistical postprocessing is closely linked with the quality of WRF precipitation outputs. A detailed comparison of statistical precipitation postprocessing approaches reveals that, although the poorest performance was obtained using MnLR, there is not an overall best technique. While QR should be preferred if skill (i.e., small probability forecast errors) and reliability (i.e., match between forecast probabilities and observed frequencies) are target properties, BMA is recommended in cases when discrimination (i.e., prediction of occurrence versus nonoccurrence) and statistical consistency (i.e., equiprobability of the observations within their ensemble distributions) are desired. Based on the results obtained here, the authors believe that future research should explore frameworks reconciling hierarchical Bayesian models with the use of the extreme value theory for high precipitation events.
Agricultural Advisors as Climate Information Intermediaries: Exploring Differences in Capacity to Communicate Climate
Authors: Haigh Tonya , Morton Lois Wright , Lemos Maria Carmen , Knutson Cody , Prokopy Linda Stalker , Lo Yun Jia , Angel Jim
Published: November 2014

Although agricultural production faces chronic stress associated with extreme precipitation events, high temperatures, drought, and shifts in climate conditions, adoption of climate information into agricultural decision making has been relatively limited. Agricultural advisors have been shown to play important roles as information intermediaries between scientists and farmers, brokering, translating, and adding value to agronomic and economic information of use in agricultural management decision making. Yet little is known about the readiness of different types of agricultural advisors to use weather and climate information to help their clients manage risk under increasing climate uncertainty. More than 1700 agricultural advisors in four midwestern states (Nebraska, Indiana, Iowa, and Michigan) completed a web-based survey during the spring of 2012 about their use of weather and climate information, public or private sector employment, and roles as information intermediaries in three advising specializations: agronomic, conservation, and financial. Key findings reveal that advisors who specialize in providing agronomic information are positively inclined toward acting as weather and climate information intermediaries, based on influence and willingness to use climate information in providing many types of operational and tactical advice. Advisors who provide conservation advice appear to be considering weather and climate information when providing tactical and strategic land-use advice, but advisors who provide financial advice seem less inclined to act as climate information intermediaries. These findings highlight opportunities to increase the capacity of different types of advisors to enable them to be effective weather and climate information intermediaries.
After the end of multiculturalism: Public service media and integrationist imaginaries for the governance of difference
Authors: Titley Gavan
Published: November 2014

This article assesses the public service media (PSM) ‘turn to diversity’ in several European contexts and examines the ways in which this emerges from a rejection of multiculturalism that is at once politically sustained and analytically inchoate. It approaches PSM as national institutions conditioned to mediate coherent images of society. In contemporary European societies, this positions PSM in a field in which integrationist imaginaries of the nation are insistent, but under conditions of social complexity, which render homogeneous visions of the nation difficult to mediate. In this context, diversity has developed as a framework for mediating, and being held to mediate, lived multiculture. However, recent research suggests that this shift to diversity both depoliticizes the ‘politics of difference’ and may also further the prevalent integration politics currently in the ascendant in Western Europe.
Treatment of relapsed classical Hodgkin lymphoma in the brentuximab vedotin era
Authors: Graf Solomon A. , Gopal Ajay K.
Published: November 2014

Classical Hodgkin lymphoma (HL) relapses after or is refractory to upfront multiagent chemotherapy in 20%–30% of patients. Effective salvage therapy for relapsed or refractory HL is limited, and advancements are needed. Brentuximab vedotin (BV), an anti-CD30 antibody–drug conjugate, has demonstrated significant activity and manageable toxicities in advanced HL. Currently approved as a monotherapy for patients with HL that is relapsed or refractory to multiple lines of chemotherapy or autologous stem cell transplantation, BV is now being evaluated earlier in the course of disease and in combination with other therapies. This review discusses the successful translation of BV from its conception to the clinical setting and highlights ongoing trials that may ultimately expand its role in relapsed or refractory HL and improve outcomes for patients.
Iron clad: iron homeostasis and the diagnosis of hereditary iron overload
Authors: Heeney Matthew M.
Published: November 2014

Iron is an ubiquitous metal of vital importance to the normal physiologic processes of many organisms. Over the last 2 decades, the discovery of mutations in genes leading to hereditary disorders of iron overload, iron deficiency, and iron maldistribution have accelerated our understanding of human iron homeostasis. This chapter provides an updated overview of the human iron cycle, regulation of iron homeostasis, and how perturbations in these homeostatic mechanisms lead to iron overload disease and provides strategies for the diagnosis of hereditary iron overload.
Early or delayed transplantation for multiple myeloma in the era of novel therapy: does one size fit all?
Authors: Richardson Paul G. , Laubach Jacob P. , Munshi Nikhil C. , Anderson Kenneth C.
Published: November 2014

For the last 20 years, high-dose therapy with autologous stem cell transplantation (ASCT) for multiple myeloma has been considered a standard frontline treatment for younger patients with adequate organ function. With the introduction of novel agents, specifically thalidomide, bortezomib, and lenalidomide, the role of ASCT has changed in several ways. First, novel agents have been incorporated successfully as induction regimens, increasing the response rate before ASCT, and are now being used as part of both consolidation and maintenance with the goal of extending progression-free and overall survival. These approaches have shown considerable promise with significant improvements in outcome. Furthermore, the efficacy of novel therapeutics has also led to the investigation of these agents upfront without the immediate application of ASCT, and compelling preliminary results have been reported. Next-generation novel agents and the use of monoclonal antibodies have raised the possibility of not only successful salvage strategies to facilitate delayed transplantation for younger patients, but also the prospect of an nontransplantation approach achieving the same outcome. Moreover, this could be achieved without incurring acute toxicity or long-term complications that are inherent to high-dose alkylation, and melphalan exposure in particular. At present, the role of ASCT has therefore become an area of debate: should it be used upfront in all eligible patients, or should it be used as a salvage treatment at the time of progression for patients achieving a high quality of response with initial therapy? There is a clear need to derive a consensus that is useful for clinicians considering both protocol-directed and non-protocol-directed options for their patients. Participation in ongoing prospective randomized trials is considered vital. While preliminary randomized data from studies in Europe favor early ASCT with novel agents, differences in both agents and the combinations used, as well as limited information on overall survival and benefit for specific patient subsets, suggest that one size does not fit all. Specifically, the optimal approach to treatment of younger patients eligible for ASCT remains a key area for further research. A rigid approach to its use outside of a clinical study is difficult to justify and participation in prospective studies should be a priority.
Prevention and treatment of venous thromboembolism in patients with cancer
Authors: Lee Agnes Y.Y.
Published: November 2014

Robust evidence remains scarce in guiding best practice in the prevention and treatment of venous thromboembolism in patients living with cancer. Recommendations from major consensus guidelines are largely based on extrapolated data from trials performed mostly in noncancer patients, observational studies and registries, studies using surrogate outcomes, and underpowered randomized controlled trials. Nonetheless, a personalized approach based on individual risk assessment is uniformly recommended for inpatient and outpatient thromboprophylaxis and there is consensus that anticoagulant prophylaxis is warranted in selected patients with a high risk of thrombosis. Prediction tools for estimating the risk of thrombosis in the hospital setting have not been validated, but the use of prophylaxis in the ambulatory setting in those with a high Khorana score is under active investigation. Symptomatic and incidental thrombosis should be treated with anticoagulant therapy, but little is known about the optimal duration. Pharmacologic options for prophylaxis and treatment are still restricted to unfractionated heparin, low molecular weight heparin, and vitamin K antagonists because there is currently insufficient evidence to support the use of target-specific, non-vitamin K-antagonist oral anticoagulants. Although these agents offer practical advantages over traditional anticoagulants, potential drug interaction with chemotherapeutic agents, gastrointestinal problems, hepatic and renal impairment, and the lack of rapid reversal agents are important limitations that may reduce the efficacy and safety of these drugs in patients with active cancer. Clinicians and patients are encouraged to participate in clinical trials to advance the care of patients with cancer-associated thrombosis.
Management of incidental splanchnic vein thrombosis in cancer patients
Authors: Kreuziger Lisa Baumann , Ageno Walter , Lee Agnes
Published: November 2014

A 75-year-old male with metastatic pancreatic cancer is undergoing chemotherapy with gemcitabine. A portal vein thrombosis was incidentally found on surveillance CT scan. He does not report any new abdominal pain or ascites. Should anticoagulation be used to treat asymptomatic portal vein thrombosis?
Intermediate-risk acute myeloid leukemia therapy: current and future
Authors: Döhner Konstanze , Paschka Peter
Published: November 2014

In recent years, research in molecular genetics has been instrumental in deciphering the molecular heterogeneity of acute myeloid leukemia (AML), in particular the subset of patients with “intermediate-risk” cytogenetics. However, at present, only the markers NPM1, CEBPA, and FLT3 have entered clinical practice. Treatment of intermediate-risk AML patients eligible for intensive therapy has not changed substantially. The “3 + 7” induction therapy still represents the standard of care. The addition of the immunoconjugate gemtuzumab ozogamicin to therapy has been shown to improve outcome; however, the drug is not approved for this use. A common standard for postremission therapy is the administration of repeated cycles of intermediate- to high-dose cytarabine. Allogeneic stem cell transplantation may offer a survival benefit for many patients with intermediate-risk AML. Patients are best selected based on the genetic profile of the leukemia cells and the risk associated with the transplantation itself. A myriad of novel agents targeting mutant leukemia drivers or deregulated pathways are in clinical development. In the past, many novel compounds have not met expectations; nonetheless, with the rapid developments in comprehensive molecular profiling and new drug design, there is the prospect of personalizing therapy and improving patient outcome.
RBCs as targets of infection
Authors: McCullough Jeffrey
Published: November 2014

RBCs can be targets of infection directly or indirectly. When the microorganism enters the RBC directly, RBC damage becomes a fundamental aspect of the disease process. Malaria is the best example of an organism that directly targets the RBC, but others are Babesia and Bartonella. RBCs can also be indirect targets of infectious agents. This can occur when molecules are bound to the surface of the RBC, leading to immunologic clearance; when microorganism-produced toxins damage the RBC membrane, leading to hemolysis; when previous crypt-antigens are exposed, leading to accelerated removal; when microorganism-produced toxins alter RBC antigens to a different phenotype, or when microorganism suppression of erythropoiesis occurs due to specific binding to RBC precursors.
Reproductive issues in sickle cell disease
Authors: Smith-Whitley Kim
Published: November 2014

As medical advances improve survival, reduce disease-related morbidity, and improve quality of life, reproductive issues will take higher priority in the sickle cell disease (SCD) community. A wide variety of topics are addressed in this chapter, including fertility, gonadal failure, erectile dysfunction, and menstrual issues in SCD. Etiologies of impaired male fertility are multifactorial and include hypogonadism, erectile dysfunction, sperm abnormalities, and complications of medical therapies. Much less is known about the prevalence and etiology of infertility in women with SCD. Other reproductive issues in women included in this review are pain and the menstrual cycle, contraception, and preconception counseling. Finally, long-term therapies for SCD and their impact on fertility are presented. Transfusional iron overload and gonadal failure are addressed, followed by options for fertility preservation after stem cell transplantation. Focus is placed on hydroxyurea therapy given its benefits and increasing use in SCD. The impact of this agent on spermatogenesis, azoospermia, and the developing fetus is discussed.
Does hydroxyurea prevent pulmonary complications of sickle cell disease?
Authors: Buckner Tyler W. , Ataga Kenneth I.
Published: November 2014

A 27-year-old man with sickle cell disease (HbSS) presents to the sickle cell clinic for follow-up after a screening echocardiogram revealed an increased tricuspid regurgitant velocity of 2.7 m/s. He has a history of 2 painful crises per year and has been hospitalized 3 times over the past 10 years for management of painful crises. He had one episode of acute chest syndrome at age 15 that was treated with an RBC exchange transfusion, supplemental oxygen, and intravenous antibiotics; he did not require mechanical ventilation. He has not had additional episodes of acute chest syndrome and does not have a history of stroke, retinopathy, or leg ulcers. The patient has never been treated with hydroxyurea. He wants to know whether hydroxyurea will prevent future pulmonary complications related to sickle cell disease.
Thrombotic microangiopathy and indications for therapeutic plasma exchange
Authors: Adamski Jill
Published: November 2014

Thrombotic microangiopathy (TMA) is a clinicopathological condition associated with a wide variety of medical conditions. TMA is classically characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombi that cause end-organ damage. The most prominent diagnoses associated with TMA are thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Although TTP and HUS can have similar clinical and laboratory features and are often lumped together as a combined entity referred to as “TTP/HUS,” the pathologic processes causing TMA and optimal therapies for these conditions are different. Empiric use of therapeutic plasma exchange (TPE) in the setting of TMA is common. The high risk of morbidity and mortality associated with some causes of TMA justify rapid institution of this relatively low-risk procedure. However, many causes of TMA do not respond to TPE and prolonged courses of exchange in the absence of an underlying diagnosis may cause a detrimental delay in appropriate medical therapy. The American Society of Apheresis has published guidelines for the use of TPE for several distinct conditions associated with TMA. This list is not comprehensive and the use of TPE for other causes of TMA may be considered if the mechanism of the underlying disease process provides a clear rationale for this intervention.
Smoothing the crescent curve: sickle cell disease
Authors: Talano Julie-An , Cairo Mitchell S.
Published: November 2014

Sickle cell disease (SCD) is an inherited disorder secondary to a point mutation at the sixth position of the beta chain of human hemoglobin that results in the replacement of valine for glutamic acid. This recessive genetic abnormality precipitates the polymerization of the deoxygenated form of hemoglobin S that induces a major distortion of red blood cells (sickle red blood cells), which decreases sickle red blood cell deformability, leading to chronic hemolysis and vasoocclusion. These processes can result in severe complications, including chronic pain, end organ dysfunction, stroke, and early mortality. The only proven curative therapy for patients with SCD is myeloablative conditioning and allogeneic stem cell transplantation from HLA-matched sibling donors. In this review, we discuss the most recent advances in allogeneic stem cell transplantation in SCD, including more novel approaches such as reduced toxicity conditioning and the use of alternative allogeneic donors (matched unrelated donors, umbilical cord blood transplantation, haploidentical donors) and autologous gene correction stem cell strategies. Prospects are bright for new stem cell approaches for patients with SCD that will enable curative stem and genetic correction therapies for a greater number of patients suffering from this chronic and debilitating condition.
Eliminating SCID row: new approaches to SCID
Authors: Kohn Donald B.
Published: November 2014

Treatments for patients with SCID by hematopoietic stem cell transplantation (HSCT) have changed this otherwise lethal primary immune deficiency disorder into one with an increasingly good prognosis. SCID has been the paradigm disorder supporting many key advances in the field of HSCT, with first-in-human successes with matched sibling, haploidentical, and matched unrelated donor allogeneic transplantations. Nevertheless, the optimal approaches for HSCT are still being defined, including determining the optimal stem cell sources, the use and types of pretransplantation conditioning, and applications for SCID subtypes associated with radiosensitivity, for patients with active viral infections and for neonates. Alternatively, autologous transplantation after ex vivo gene correction (gene therapy) has been applied successfully to the treatment of adenosine deaminase–deficient SCID and X-linked SCID by vector-mediated gene addition. Gene therapy holds the prospect of avoiding risks of GVHD and would allow each patient to be their own donor. New approaches to gene therapy by gene correction in autologous HSCs using site-specific endonuclease-mediated homology-driven gene repair are under development. With newborn screening becoming more widely adopted to detect SCID patients before they develop complications, the prognosis for SCID is expected to improve further. This chapter reviews recent advances and ongoing controversies in allogeneic and autologous HSCT for SCID.
Optimal disease surveillance strategies in non-Hodgkin lymphoma
Authors: Cohen Jonathon B. , Flowers Christopher R.
Published: November 2014

Given the paucity of randomized controlled trial data, defining the ideal strategy for surveillance imaging in patients with non-Hodgkin lymphoma (NHL) has become increasingly challenging. The routine use of frequent surveillance scans has been a common component of patient care. Emerging data from prospective and retrospective observational studies and modeling approaches have highlighted the performance characteristics of imaging modalities and the challenges with this form of secondary screening. The majority of patients with relapsed lymphoma have clinical signs or symptoms that prompt further evaluation, and only a small proportion of patients experience relapse detected on a routine scan while being otherwise asymptomatic. Surveillance imaging is costly, may expose patients to minimal risks of mortality due to radiation-related secondary malignancies, and can lead to false-positive findings, leading to unnecessary biopsies. In addition, no prospective study has demonstrated a significant improvement in overall survival for those patients whose disease is discovered on a routine scan versus those who present with clinical symptoms. In this chapter, we examine the baseline risks of relapse for various NHL subtypes that provide the context for surveillance, review the data on imaging modalities, and establish a framework for discussing optimal surveillance strategies with individual patients. Patients should be counseled on the risks and benefits of routine surveillance imaging and decisions regarding surveillance should be made on an individual basis using patient-specific risk factors, response to induction therapy, and patient preferences with a bias toward using surveillance imaging in the 2 years after treatment only in those NHL patients with the greatest likelihood of benefit.
What is the role of hemodialysis for dabigatran-associated major bleeding?
Authors: Kim Benjamin , Garcia David A.
Published: November 2014

A 70-year-old male with a history of atrial fibrillation who is being anticoagulated with dabigatran etexilate presents to the emergency room with melena. He reports taking his most recent dose of dabigatran more than 2 hours ago. On examination, he is hypotensive and tachycardic, and he continues to have melanotic stools. Laboratory testing reveals a calculated creatinine clearance of 15 mL/min, a prothrombin time of 16.5 seconds (reference range: 11.8-15.2 seconds), an international normalized ratio of 1.2 (reference range: 0.9-1.2), and an activated partial thromboplastin time of 50 seconds (reference range: 22.2-33.0 seconds). You are asked by the emergency medicine physician whether hemodialysis should be considered to decrease the patient's plasma dabigatran level.
Screening for and management of hepatitis B virus reactivation in patients treated with anti-B-cell therapy
Authors: Kusumoto Shigeru , Tobinai Kensei
Published: November 2014

Reactivation of hepatitis B virus (HBV) is a potentially fatal complication after anti-B-cell therapy. It can develop not only in patients seropositive for hepatitis B surface antigen (HBsAg), but also in those with resolved HBV infection who are seronegative for HBsAg but seropositive for antibodies against hepatitis B core antigen (anti-HBc) and/or antibodies against HBsAg (anti-HBs). The risk of HBV reactivation depends on the balance between replication of the virus and the immune response of the host. Anti-CD20 monoclonal antibody—rituximab in combination with steroid-containing chemotherapy (R-CHOP: rituximab + cyclophosphamide + hydroxydaunorubicin + vincristine + prednisone/prednisolone)—is an important risk factor for HBV reactivation in HBsAg-negative patients. More obviously, HBsAg-positive patients are considered to be at very high risk for HBV reactivation and, in the rituximab era, 59%–80% of these patients develop HBV reactivation after R-CHOP-like chemotherapy. Patients with resolved HBV infection should also be considered at high risk of HBV reactivation, the incidence of which is reported to be 9%–24% in such lymphoma patients. All patients should be screened to identify risk groups for HBV reactivation before initiating anti-B-cell therapy by measuring serum HBV markers including HBsAg, anti-HBc and anti-HBs. To prevent the development of hepatitis due to HBV reactivation after anti-B-cell therapy, antiviral prophylaxis is recommended for HBsAg-positive patients and/or patients in whom HBV DNA is detectable at baseline, whereas regular monitoring of HBV DNA-guided preemptive antiviral therapy is a reasonable and useful approach for patients with resolved HBV infection.
Biology of BM failure syndromes: role of microenvironment and niches
Authors: Balderman Sophia R. , Calvi Laura M.
Published: November 2014

The BM microenvironment and its components regulate hematopoietic stem and progenitor cell (HSC) fate. An abnormality in the BM microenvironment and specific dysfunction of the HSC niche could play a critical role in initiation, disease progression, and response to therapy of BM failure syndromes. Therefore, the identification of changes in the HSC niche in BM failure syndromes should lead to further knowledge of the signals that disrupt the normal microenvironment. In turn, niche disruption may contribute to disease morbidity, resulting in pancytopenia and clonal evolution, and its understanding could suggest new therapeutic targets for these conditions. In this chapter, we briefly review the evidence for the importance of the BM microenvironment as a regulator of normal hematopoiesis, summarize current knowledge regarding the role of dysfunctions in the BM microenvironment in BM failure syndromes, and propose a strategy through which niche stimulation can complement current treatment for myelodysplastic syndrome.
Geriatric perspective: how to assess fitness for chemotherapy in acute myeloid leukemia
Authors: Klepin Heidi D.
Published: November 2014

Characterizing “fitness” in the context of therapeutic decisions for older adults with acute myeloid leukemia (AML) is challenging. Available evidence is strongest in identifying those older adults who are frail at the time of diagnosis by characterizing performance status and comorbidity burden. However, many older adults with adequate performance status and absence of major comorbidity are “vulnerable” and may experience clinical and functional decline when stressed with intensive therapies. More refined assessments are needed to differentiate between fit and vulnerable older adults regardless of chronologic age. Geriatric assessment has been shown to add information to routine oncology assessment and improve risk stratification for older adults with AML. This review highlights available evidence for assessment of “fitness” among older adults diagnosed with AML and discusses future treatment and research implications.
The role of androgens in experimental rodent mammary carcinogenesis
Authors: Choi Jaesung , Psarommatis Basil , Gao Yan Ru , Zheng Yu , Handelsman David J , Simanainen Ulla
Published: November 2014

Breast cancer is currently the most frequent, fatal cancer of women in western countries. While estrogens have a widely understood involvement in breast cancer, a significant but not yet fully understood role for androgens has also been suggested. The principal androgen, testosterone, is the obligate steroidal precursor of estradiol, but can equally be metabolized into dihydrotestosterone, a more potent, pure androgen. Both androgens exert their distinctive biological effects via the androgen receptor, which is coexpressed with estrogen receptor alpha in 80 to 90% of breast cancers. The hormonal control of breast development and pathology has been examined experimentally through the use of animal models, notably mice and rats. This review summarizes the data from experimental rodent models on the effects of androgens in experimental breast cancer, aiming to address the importance of androgens and the androgen receptor in the origins and pathogenesis of breast cancers, as well as to discuss potential biomarker and therapeutic opportunities arising from novel insights based on the experimental research.