bluuebunny/crossref_metadata_2025 huggingface dataset:
Heparin-Induced Thrombocytopenia Screening and Management in Pediatric Patients
Authors: Takemoto Clifford M. , Streiff Michael B.
Published: December 2011

The diagnosis and management of heparin-induced thrombocytopenia (HIT) in pediatric patients poses significant challenges. The cardinal findings in HIT, thrombocytopenia and thrombosis with heparin exposure, are seen commonly in critically ill children, but are most often secondary to etiologies other than HIT. However, without prompt diagnosis, discontinuation of heparin, and treatment with an alternative anticoagulant such as a direct thrombin inhibitor (DTI), HIT can result in life- and limb-threatening thrombotic complications. Conversely, DTIs are associated with higher bleeding risks than heparin in adults and their anticoagulant effects are not rapidly reversible; furthermore, the experience with their use in pediatrics is limited. Whereas immunoassays are widely available to aid in diagnosis, they carry a significant false positive rate. Age-dependent differences in the coagulation and immune system may potentially affect manifestations of HIT in children, but have not been extensively examined. In this chapter, diagnostic approaches and management strategies based on a synthesis of the available pediatric studies and adult literature on HIT are discussed.
Bleeding and Clotting Disorders in Pediatric Liver Disease
Authors: Wicklund Brian M.
Published: December 2011

The coagulopathy of liver disease in pediatric patients presents an unusual set of challenges. Little pediatric data have been published, so this review is based largely on adult studies. There is a precarious balance between deficiencies of clotting factors and anticoagulation factors in liver disease that result in abnormal prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests that would suggest a bleeding tendency, yet the patients can form a clot and are at risk of thromboembolic disease. Attention has centered on thromboelastography and thrombin-generation assays to clarify the patient's ability to control bleeding, but these tests are not routinely available to many treating physicians.
Stem Cell Transplantation for Multiple Myeloma: Current and Future Status
Authors: Giralt Sergio
Published: December 2011

High-dose melphalan with autologous stem cell support has been an integral part of myeloma therapy for more than 25 years, either as salvage therapy or as consolidation of an initial remission. Although multiple phase 3 trials have demonstrated that this therapy results in higher response rates and longer remission times than conventional chemotherapy, the use of thalidomide, lenalidomide, and bortezomib as induction therapy has limited the clinical relevance of these trials. Moreover, ongoing trials have shown that initial induction therapy may affect transplantation outcome, and that long-term disease control can be achieved in a substantial number of patients with a variety of posttransplantation maintenance therapies. This article summarizes the results of ongoing and recently published clinical trials and describes how they have affected current transplantation recommendations.
Current Treatment of Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia
Authors: Fielding Adele K.
Published: December 2011

The author discusses both the standards of care and more controversial areas in the treatment of Philadelphia chromosome–positive acute lymphoblastic leukemia.
Myelodysplastic/Myeloproliferative Neoplasms
Authors: Cazzola Mario , Malcovati Luca , Invernizzi Rosangela
Published: December 2011

According to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues, myelodysplastic/myeloproliferative neoplasms are clonal myeloid neoplasms that have some clinical, laboratory, or morphologic findings that support a diagnosis of myelodysplastic syndrome, and other findings that are more consistent with myeloproliferative neoplasms. These disorders include chronic myelomonocytic leukemia, atypical chronic myeloid leukemia (BCR-ABL1 negative), juvenile myelomonocytic leukemia, and myelodysplastic/myeloproliferative neoplasms, unclassifiable. The best characterized of these latter unclassifiable conditions is the provisional entity defined as refractory anemia with ring sideroblasts associated with marked thrombocytosis. This article focuses on myelodysplastic/myeloproliferative neoplasms of adulthood, with particular emphasis on chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts associated with marked thrombocytosis. Recent studies have partly clarified the molecular basis of these disorders, laying the groundwork for the development of molecular diagnostic and prognostic tools. It is hoped that these advances will soon translate into improved therapeutic approaches.
Posttransplantation Vaccination: Concepts Today and on the Horizon
Authors: Rezvani Katayoun
Published: December 2011

Allogeneic hematopoietic stem cell transplantation (allogeneic HSCT) remains a curative treatment for hematological malignancies resistant to other treatment approaches through the unique GVL effect. However, relapse remains a major cause of treatment failure after allogeneic HSCT for patients with high-risk hematological malignancies. Further improvements in exploiting the GVL effect to prevent relapse in high-risk leukemias while minimizing toxicity have focused on the use of targeted antileukemic immunotherapy. These strategies include methods to boost the GVL effect with leukemia vaccines or the adoptive transfer of leukemia-specific lymphocytes. Vaccines can be classified as those against defined antigens such as minor histocompatibility antigens (mHags) or leukemia-associated antigens (PR1, WT1, and BCR-ABL) and those that have broad “antileukemic” activity such as engineered irradiated leukemia cells or leukemia-derived dendritic cells (DCs). The unique posttransplantation milieu, which is characterized by lymphopenia, regulatory T-cell depletion, and the release of growth factors, provides a unique opportunity for effective antitumor immunotherapy and augmenting specific GVL responses. This review focuses on approaches to enhancimg the GVL response by combining allogeneic HSCT with vaccination.
Tyrosine Kinase Inhibitor Use in Pediatric Philadelphia Chromosome–Positive Acute Lymphoblastic Anemia
Authors: Hunger Stephen P.
Published: December 2011

Until recently, pediatric Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) was associated with an extremely poor outcome when treated with chemotherapy alone, and only modest survival benefits were obtained with the widespread use of hematopoietic stem cell transplantation (HSCT). The development of first-generation (imatinib) and second-generation (dasatinib and nilotinib) tyrosine kinase inhibitors (TKIs) that target the BCR-ABL1 fusion protein produced by the Ph chromosome revolutionized the treatment of chronic myelogenous leukemia (CML). The Children's Oncology Group (COG) AALL0031 trial showed that the addition of imatinib to intensive chemotherapy did not cause increased toxicity and resulted in 3-year event-free survival rates that were more than double those of historical control data from the pre-imatinib era. These findings create a new paradigm for integrating molecularly targeted agents with conventional chemotherapy and call for a reassessment of the routine use of HSCT for children and adolescents with Ph+ ALL. Second-generation TKIs have theoretical advantages over imatinib, and are now being tested in Ph+ ALL. The focus of contemporary trials is to define the optimal use of chemotherapy, HSCT, and TKI in Ph+ ALL. In the coming years, it is anticipated that additional agents will become available to potentiate TKI therapy and/or circumvent TKI resistance in Ph+ ALL. Recent genomic studies have identified a subtype of high-risk pediatric B-cell-precursor ALL with a gene-expression profile similar to that of Ph+ ALL, suggestive of active kinase signaling. Many of these Ph-like ALL cases harbor chromosome rearrangements and mutations that dysregulate cytokine receptor and kinase signaling, and these leukemias may also be candidates for TKI therapy.
Pulmonary Hypertension, Tricuspid Regurgitant Velocity Screening, and the Nitric Oxide Pathway
Authors: Hassell Kathryn L.
Published: December 2011

Chronic pulmonary complications, including pulmonary hypertension (PH), are common in sickle cell disease (SCD), especially in adults with sickle cell anemia (SCA). The underlying pathophysiology is complex and variable, involving multiple biological systems. Recent emphasis has been placed on the pleotropic biological factor nitric oxide (NO). An elevated tricuspid regurgitant velocity (TRV) appears to have limitations in specificity in SCA, but may indicate the presence of PH, a diagnosis confirmed by right heart catheterization. TRV has been used in recent clinical trials to identify or define subjects with PH for enrollment into PH-specific interventions; these include sildenafil, which enhances NO-induced vasorelaxation. Results from a controlled trial show no benefit and an unexpected increase in adverse events, emphasizing the biological complexities of SCA. Management remains principally supportive, includes recognition and treatment of comorbidities, and may incorporate individualized PH-specific strategies (despite recent trials) based on appropriate diagnostic testing. Ultimately, therapy is likely to be multimodal and tailored to the processes identified to be the most contributory in a given individual. Based on the relative prevalence of the conditions, routine screening for asthma in children with SCD and by Doppler echocardiography to measure TRV as an initial screen for PH in adults with SCA may be warranted. Data are limited regarding the clinical utility of screening in other forms of SCD and the pediatric population. This article offers an individual perspective on practical and challenging clinical considerations.
Novel Approaches to the Treatment of Acute Myeloid Leukemia
Authors: Roboz Gail J.
Published: December 2011

Approximately 12 000 adults are diagnosed with acute myeloid leukemia (AML) in the United States annually, the majority of whom die from their disease. The mainstay of initial treatment, cytosine arabinoside (ara-C) combined with an anthracycline, was developed nearly 40 years ago and remains the worldwide standard of care. Advances in genomics technologies have identified AML as a genetically heterogeneous disease, and many patients can now be categorized into clinicopathologic subgroups on the basis of their underlying molecular genetic defects. It is hoped that enhanced specificity of diagnostic classification will result in more effective application of targeted agents and the ability to create individualized treatment strategies. This review describes the current treatment standards for induction, consolidation, and stem cell transplantation; special considerations in the management of older AML patients; novel agents; emerging data on the detection and management of minimal residual disease (MRD); and strategies to improve the design and implementation of AML clinical trials.
Primary Prophylaxis in Sickle Cell Disease: Is It Feasible? Is It Effective?
Authors: Thompson Alexis A.
Published: December 2011

Consideration of primary prophylaxis to prevent complications of sickle cell disease (SCD) requires a clear understanding of the earliest manifestations of SCD-related organ injury, a reliable clinical or laboratory tool to detect organ dysfunction, and evidence that an intervention instituted in the presymptomatic state can mitigate disease progression. This review examines the pathophysiology of SCD in organs that may be potential targets for intervention, our current capacity to evaluate early SCD manifestations, results of clinical trials, and opportunities for future interventions.
Vascular Effects of the Red Blood Cell Storage Lesion
Authors: Roback John D.
Published: December 2011

Transfusion of RBCs is often clinically necessary—and life-saving—for anemic patients. RBCs can be stored for up to 42 days between the time of donation and the time of transfusion. For many years, investigators have studied the biochemical changes that occur in RBCs stored before transfusion (the RBC “storage lesion”). More recently, clinical studies have suggested that RBC units stored for long periods (often described as > 14-21 days) may mediate adverse effects in the recipient, leading to morbidity and mortality. Unfortunately, these effects are difficult to identify and study because there are no agreed-upon mechanisms for these adverse events and few good assays to study them in individual transfusion recipients. We have proposed the hypothesis of insufficient NO bioavailability (INOBA) to explain the adverse events associated with transfusion of older RBC units. INOBA postulates that the combination of impaired NO production and increased NO scavenging by stored RBCs, together with reduced NO synthesis by dysfunctional endothelial cells, collectively reduce NO levels below a critical threshold in vascular beds. In this situation, inappropriate vasoconstriction occurs, leading to reduced blood flow and insufficient O2 delivery to end organs. If confirmed, the INOBA hypothesis may lead to improved methods for blood storage and collection, as well as new screening and matching tools for blood donors and transfusion recipients.
Dyskeratosis Congenita
Authors: Dokal Inderjeet
Published: December 2011

Dyskeratosis congenita (DC) is a multisystem inherited syndrome exhibiting marked clinical and genetic heterogeneity. In its classic form, it is characterized by mucocutaneous abnormalities, BM failure, and a predisposition to cancer. BM failure is the principal cause of premature mortality. Studies over the last 15 years have led to significant advances, with 8 DC genes (DKC1, TERC, TERT, NOP10, NHP2, TIN2, C16orf57, and TCAB1) having been characterized. Seven of these are important in telomere maintenance either because they encode components of the telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the shelterin complex (TINF2). DC is therefore principally a disease of defective telomere maintenance and patients usually have very short telomeres. The genetic advances have led to the unification of DC with several other disorders, including the severe multisystem disorders Hoyeraal-Hreidarsson and Revesz syndromes, as well as a subset of patients with aplastic anemia, myelodysplasia, leukemia, and idiopathic pulmonary fibrosis. This wide spectrum of diseases ranging from classic DC to aplastic anemia can be regarded as disorders of defective telomere maintenance—“the telomereopathies.” These advances have increased our understanding of normal hematopoiesis and highlighted the important role of telomerase and telomeres in human biology. They are also facilitating the diagnosis (especially when presentation is atypical) and management of DC.
Congenital Sideroblastic Anemias: Iron and Heme Lost in Mitochondrial Translation
Authors: Fleming Mark D.
Published: December 2011

The congenital sideroblastic anemias (CSAs) are an uncommon, diverse class of inherited hematopoietic disorders characterized by pathological deposition of iron in the mitochondria of erythroid precursors. In recent years, the genetic causes of several clinically distinctive forms of CSA have been elucidated, which has revealed common themes in their pathogenesis. In particular, most, if not all, can be attributed to disordered mitochondrial heme synthesis, iron-sulfur cluster biogenesis, or pathways related to mitochondrial protein synthesis. This review summarizes the clinical features, molecular genetics, and pathophysiology of each of the CSAs in the context of these pathways.
Immunomodulating Drugs in Myelodysplastic Syndromes
Authors: Adès Lionel , Fenaux Pierre
Published: December 2011

Based on immune mechanisms that appear to play an important role in the pathophysiology of at least part of the lower-risk myelodysplastic syndrome (MDS), the immunomodulating drug (IMID) thalidomide and its derivative lenalidomide (LEN) have been used in MDS, principally in lower-risk MDS. LEN has become the first-line US Food and Drug Administration (FDA)–approved treatment for lower-risk MDS with 5q deletion (del5q), in which its main mechanism of action is probably a direct cytotoxic activity on the del5q clone. This possibly specific effect is currently being investigated in higher-risk MDS—and even acute myeloid leukemia (AML)—with del5q, but LEN has also demonstrated some efficacy in MDS and AML without del5q. Thalidomide also has some activity in lower-risk MDS without del5q, but its side effects limit its practical use in these patients.
Diagnosis and Management of Aplastic Anemia
Authors: Guinan Eva C.
Published: December 2011

Aplastic anemia remains a diagnosis of exclusion. Our ability to reliably diagnose, and therefore exclude, a variety of inherited or acquired diseases with similar phenotypes has improved markedly. An efficient diagnostic plan is important because time from diagnosis to treatment is related to outcome regardless of the therapeutic option chosen. HSCT remains the mainstay of therapy for those with matched sibling donors, and results have improved even further in recent years. For those without a sibling donor, the high response and overall survival rates of combined immunosuppressive therapy (IST) have proven robust. Nonetheless, incomplete response, relapse, and progression to myelodysplasia/leukemia have more clearly emerged as significant long-term issues. Improvements in outcome of alternative donor transplantation and the use of established and novel immunosuppressive agents provide multiple alternatives for treating refractory or relapsed patients. Best practices in this regard are not yet clearly established and may vary by a variety of demographic and treatment-specific factors. Regardless of the type of therapeutic approach, patients require ongoing monitoring for occurrence of disease and/or therapy-related side effects.
Therapy for Aplastic Anemia
Authors: DeZern Amy E. , Guinan Eva C.
Published: December 2011

A 24-year-old man from Ecuador presents to your clinic with dyspnea on exertion, bruising, and petechiae. He is noted to be pancytopenic with ANC 430, hemoglobin 7.4 g/dL (reticulocyte count 0.9%), and platelets 18 000. His BM biopsy is hypocellular for age. Ultimately, he is diagnosed with severe aplastic anemia. He is the only child of 2 South American parents without any matches in the unrelated donor registry, including cord blood. He is red cell– and platelet transfusion–dependent. He has been recommended therapy with antithymocyte globulin and cyclosporine but declined it. He seeks recommendations about new alternatives to this regimen to improve his chance of response.
Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study
Authors: Gris Jean-Christophe , Bouvier Sylvie , Molinari Nicolas , Galanaud Jean-Philippe , Cochery-Nouvellon Éva , Mercier Érik , Fabbro-Peray Pascale , Balducchi Jean-Pierre , Marès Pierre , Quéré Isabelle , Dauzat Michel
Published: December 2011

The incidence of thrombosis in the purely obstetric form of antiphospholipid syndrome is uncertain. We performed a 10-year observational study of 1592 nonthrombotic women who had experienced 3 consecutive spontaneous abortions before the 10th week of gestation or 1 fetal death at or beyond the 10th week of gestation. We compared the frequencies of thrombotic events among women positive for antiphospholipid Abs (n = 517), women carrying the F5 6025 or F2 rs1799963 polymorphism (n = 279), and women with negative thrombophilia screening results (n = 796). The annual rates of deep vein thrombosis (1.46%; range, 1.15%-1.82%), pulmonary embolism (0.43%; range, 0.26%-0.66%), superficial vein thrombosis (0.44%; range, 0.28%-0.68%), and cerebrovascular events (0.32%; range, 0.18%-0.53%) were significantly higher in aPLAbs women than in the other groups despite low-dose aspirin primary prophylaxis. Women carrying 1 of the 2 polymorphisms did not experience more thrombotic events than women who screened negative for thrombophilia. Lupus anticoagulant was a risk factor for unprovoked proximal and distal deep and superficial vein thrombosis and women in the upper quartile of lupus anticoagulant activity had the highest risk. Despite data suggesting that aPLAbs may induce pregnancy loss through nonthrombotic mechanisms, women with purely obstetric antiphospholipid syndrome are at risk for thrombotic complications.
Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes
Authors: Li Hailan , Lee Jong-Hyuk , Kim Su Yeon , Yun Hye-Young , Baek Kwang Jin , Kwon Nyoun Soo , Yoon Yoosik , Jeong Ji Hoon , Kim Dong-Seok
Published: December 2011

Background

Phosphatidylcholine (PPC) formulation is used for lipolytic injection, even though its mechanism of action is not well understood.

Methods

The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD), and a PPC formulation. Western blot analysis was performed to examine PPC-induced signaling pathways.

Results

PPC, SD, and PPC formulation significantly decreased 3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not cytotoxic to CCD-25Sk human fibroblasts at concentrations <1 mg/ml, whereas SD and PPC formulation were cytotoxic. Western blot analysis demonstrated that PPC alone led to the phosphorylation of the stress signaling proteins, such as p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and activated caspase-9, -8, -3 as well as cleavage of poly(ADP-ribose) polymerase. However, SD did not activate the apoptotic pathways. Instead, SD and PPC formulation induced cell membrane lysis, which may lead to necrosis of cells.

Conclusions

PPC results in apoptosis of 3T3-L1 cells.
SERPINE2 haplotype as a risk factor for panlobular type of emphysema
Authors: Kukkonen Mari K , Tiili Emmi , Hämäläinen Satu , Vehmas Tapio , Oksa Panu , Piirilä Päivi , Hirvonen Ari
Published: December 2011

Background

SERPINE2 (serpin peptidase inhibitor, clade E, member 2) has previously been identified as a positional candidate gene for chronic obstructive pulmonary disease (COPD) and has subsequently been associated to COPD and emphysema in several populations. We aimed to further examine the role of SERPINE2 polymorphisms in the development of pulmonary emphysema and different emphysema subtypes.

Methods

Four single nucleotide polymorphisms (SNPs) in SERPINE2 were analyzed from 951 clinically and radiologically examined Finnish construction workers. The genotype and haplotype data was compared to different emphysematous signs confirmed with high-resolution computed tomography (HRCT), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), diffusing capacity (DLCO), and specific diffusing capacity (DLCO/VA).

Results

Three of the studied SERPINE2 SNPs (rs729631, rs975278, and rs6748795) were found to be in tight linkage disequilibrium. Therefore, only one of these SNPs (rs729631) was included in the subsequent analyses, in addition to the rs840088 SNP which was in moderate linkage with the other three studied SNPs. The rs729631 SNP showed a significant association with panlobular emphysema (p = 0.003). In further analysis, the variant allele of the rs729631 SNP was found to pose over two-fold risk (OR 2.22, 95% CI 1.05-4.72) for overall panlobular changes and over four-fold risk (OR 4.37, 95% CI 1.61-11.86) for pathological panlobular changes. A haplotype consisting of variant alleles of both rs729631 and rs840088 SNPs was found to pose an almost four-fold risk for overall panlobular (OR 3.72, 95% CI 1.56-8.90) and subnormal (OR 3.98, 95% CI 1.55-10.20) emphysema.

Conclusions

Our results support the previously found association between SERPINE2 polymorphisms and pulmonary emphysema. As a novel finding, our study suggests that the SERPINE2 gene may in particular be involved in the development of panlobular changes, i.e., the same type of changes that are involved in alpha-1-antitrypsin (AAT) -deficiency.
The so-called "Spanish model" - Tobacco industry strategies and its impact in Europe and Latin America
Authors: Schneider Nick K , Sebrié Ernesto M , Fernández Esteve
Published: December 2011

Background

To demonstrate the tobacco industry rationale behind the "Spanish model" on non-smokers' protection in hospitality venues and the impact it had on some European and Latin American countries between 2006 and 2011.

Methods

Tobacco industry documents research triangulated against news and media reports.

Results

As an alternative to the successful implementation of 100% smoke-free policies, several European and Latin American countries introduced partial smoking bans based on the so-called "Spanish model", a legal framework widely advocated by parts of the hospitality industry with striking similarities to "accommodation programmes" promoted by the tobacco industry in the late 1990s. These developments started with the implementation of the Spanish tobacco control law (Ley 28/2005) in 2006 and have increased since then.

Conclusion

The Spanish experience demonstrates that partial smoking bans often resemble tobacco industry strategies and are used to spread a failed approach on international level. Researchers, advocates and policy makers should be aware of this ineffective policy.
Partial nephrectomy using porcine small intestinal submucosa
Authors: Schnoeller Thomas J , de Petriconi Robert , Hefty Robert , Jentzmik Florian , Waalkes Sandra , Zengerling Friedemann , Schrader Mark , Schrader Andres J
Published: December 2011

Background

Whenever technically feasible and oncologically justified, nephron-sparing surgery is the current standard of care for localized renal cell carcinomas (RCC). The main complications of partial nephrectomy, especially for large and centrally located tumors, are urinary leakage and parenchymal bleeding. We prospectively evaluated the pros and cons of using porcine small intestinal submucosa (SIS, Surgisis®) to close the renal defect after nephron-sparing surgery.

Methods

We used Surgisis® (Cook medical, Bloomington, IN, USA) to secure and compress the capsular defect after tumor resection in 123 patients submitted to 129 partial nephrectomies between August 2003 and February 2011.

Results

The median tumor size was 3.7 cm (range 1.1-13.0 cm). Procedures were performed with cold ischemia in 24 cases (18.2%), with warm ischemia in 46 (35.6%), and without ischemia in 59 cases (44.8%). In the total group of patients, 4 (3.1%) developed urinary fistula, and only 2 (1.6%) required postoperative transfusions due to hemorrhage after the application of the small intestinal submucosa membrane.

Conclusion

Small intestinal submucosa is an easy-to-use biomaterial for preventing complications such as postoperative bleeding and urinary fistula in nephron-sparing surgery, especially in cases where tumor excision causes significant renal capsular and/or renal pelvic defects.
Fano-Rashba effect in thermoelectricity of a double quantum dot molecular junction
Authors: Liu YS , Hong XK , Feng JF , Yang XF
Published: December 2011

We examine the relation between the phase-coherent processes and spin-dependent thermoelectric effects in an Aharonov-Bohm (AB) interferometer with a Rashba quantum dot (QD) in each of its arm by using the Green's function formalism and equation of motion (EOM) technique. Due to the interplay between quantum destructive interference and Rashba spin-orbit interaction (RSOI) in each QD, an asymmetrical transmission node splits into two spin-dependent asymmetrical transmission nodes in the transmission spectrum and, as a consequence, results in the enhancement of the spin-dependent thermoelectric effects near the spin-dependent asymmetrical transmission nodes. We also examine the evolution of spin-dependent thermoelectric effects from a symmetrical parallel geometry to a configuration in series. It is found that the spin-dependent thermoelectric effects can be enhanced by controlling the dot-electrode coupling strength. The simple analytical expressions are also derived to support our numerical results.

PACS numbers: 73.63.Kv; 71.70.Ej; 72.20.Pa
Real-time stereo vision system using adaptive weight cost aggregation approach
Authors: Ding Jingting , Liu Jilin , Zhou Wenhui , Yu Haibin , Wang Yanchang , Gong Xiaojin
Published: December 2011

Many vision applications require high-accuracy dense disparity maps in real time. Due to the complexity of the matching process, most real-time stereo applications rely on local algorithms in the disparity computation. These local algorithms generally suffer from matching ambiguities as it is difficult to find appropriate support for each pixel. Recent research shows that algorithms using adaptive cost aggregation approach greatly improve the quality of disparity map. Unfortunately, although these improvements are excellent, they are obtained at the expense of high computational. This article presents a hardware implementation for speeding up these methods. With hardware friendly approximation, we demonstrate the feasibility of implementing this expensive computational task on hardware to achieve real-time performance. The entire stereo vision system, includes rectification, stereo matching, and disparity refinement, is realized using a single field programmable gate array. The highly parallelized pipeline structure makes system be capable to achieve 51 frames per second for 640 × 480 stereo images. Finally, the success of accuracy improvement is demonstrated on the Middlebury dataset, as well as tests on real scene.
Automated target tracking and recognition using coupled view and identity manifolds for shape representation
Authors: Venkataraman Vijay , Fan Guoliang , Yu Liangjiang , Zhang Xin , Liu Weiguang , Havlicek Joseph P
Published: December 2011

We propose a new couplet of identity and view manifolds for multi-view shape modeling that is applied to automated target tracking and recognition (ATR). The identity manifold captures both inter-class and intra-class variability of target shapes, while a hemispherical view manifold is involved to account for the variability of viewpoints. Combining these two manifolds via a non-linear tensor decomposition gives rise to a new target generative model that can be learned from a small training set. Not only can this model deal with arbitrary view/pose variations by traveling along the view manifold, it can also interpolate the shape of an unknown target along the identity manifold. The proposed model is tested against the recently released SENSIAC ATR database and the experimental results validate its efficacy both qualitatively and quantitatively.
Objective assessment of motor fatigue in multiple sclerosis using kinematic gait analysis: a pilot study
Authors: Sehle Aida , Mündermann Annegret , Starrost Klaus , Sailer Simon , Becher Inna , Dettmers Christian , Vieten Manfred
Published: December 2011

Background

Fatigue is a frequent and serious symptom in patients with Multiple Sclerosis (MS). However, to date there are only few methods for the objective assessment of fatigue. The aim of this study was to develop a method for the objective assessment of motor fatigue using kinematic gait analysis based on treadmill walking and an infrared-guided system.

Patients and methods

Fourteen patients with clinically definite MS participated in this study. Fatigue was defined according to the Fatigue Scale for Motor and Cognition (FSMC). Patients underwent a physical exertion test involving walking at their pre-determined patient-specific preferred walking speed until they reached complete exhaustion. Gait was recorded using a video camera, a three line-scanning camera system with 11 infrared sensors. Step length, width and height, maximum circumduction with the right and left leg, maximum knee flexion angle of the right and left leg, and trunk sway were measured and compared using paired t-tests (α = 0.005). In addition, variability in these parameters during one-minute intervals was examined. The fatigue index was defined as the number of significant mean and SD changes from the beginning to the end of the exertion test relative to the total number of gait kinematic parameters.

Results

Clearly, for some patients the mean gait parameters were more affected than the variability of their movements while other patients had smaller differences in mean gait parameters with greater increases in variability. Finally, for other patients gait changes with physical exertion manifested both in changes in mean gait parameters and in altered variability. The variability and fatigue indices correlated significantly with the motoric but not with the cognitive dimension of the FSMC score (R = -0.602 and R = -0.592, respectively; P < 0.026).

Conclusions

Changes in gait patterns following a physical exertion test in patients with MS suffering from motor fatigue can be measured objectively. These changes in gait patterns can be described using the motor fatigue index and represent an objective measure to assess motor fatigue in MS patients. The results of this study have important implications for the assessments and treatment evaluations of fatigue in MS.
Significance of genomic instability in breast cancer in atomic bomb survivors: analysis of microarray-comparative genomic hybridization
Authors: Oikawa Masahiro , Yoshiura Koh-ichiro , Kondo Hisayoshi , Miura Shiro , Nagayasu Takeshi , Nakashima Masahiro
Published: December 2011

Background

It has been postulated that ionizing radiation induces breast cancers among atomic bomb (A-bomb) survivors. We have reported a higher incidence ofHER2andC-MYConcogene amplification in breast cancers from A-bomb survivors. The purpose of this study was to clarify the effect of A-bomb radiation exposure on genomic instability (GIN), which is an important hallmark of carcinogenesis, in archival formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer by using microarray-comparative genomic hybridization (aCGH).

Methods

Tumor DNA was extracted from FFPE tissues of invasive ductal cancers from 15 survivors who were exposed at 1.5 km or less from the hypocenter and 13 calendar year-matched non-exposed patients followed by aCGH analysis using a high-density oligonucleotide microarray. The total length of copy number aberrations (CNA) was used as an indicator of GIN, and correlation with clinicopathological factors were statistically tested.

Results

The mean of the derivative log ratio spread (DLRSpread), which estimates the noise by calculating the spread of log ratio differences between consecutive probes for all chromosomes, was 0.54 (range, 0.26 to 1.05). The concordance of results between aCGH and fluorescence in situ hybridization (FISH) forHER2gene amplification was 88%. The incidence ofHER2amplification and histological grade was significantly higher in the A-bomb survivors than control group (P = 0.04, respectively). The total length of CNA tended to be larger in the A-bomb survivors (P = 0.15). Correlation analysis of CNA and clinicopathological factors revealed that DLRSpread was negatively correlated with that significantly (P = 0.034, r = -0.40). Multivariate analysis with covariance revealed that the exposure to A-bomb was a significant (P = 0.005) independent factor which was associated with larger total length of CNA of breast cancers.

Conclusions

Thus, archival FFPE tissues from A-bomb survivors are useful for genome-wide aCGH analysis. Our results suggested that A-bomb radiation may affect the increased amount of CNA as a hallmark of GIN and, subsequently, be associated with a higher histologic grade in breast cancer found in A-bomb survivors.
A case-cohort study of human herpesvirus 8 seropositivity and incident prostate cancer in Tobago
Authors: McDonald Alicia C , Jenkins Frank J , Bunker Clareann H , Wilson John W , Patrick Alan L , Weissfeld Joel L
Published: December 2011

Background

We previously reported a cross-sectional association between the presence of human herpesvirus 8 (HHV-8) serum antibodies and screen-detected prostate cancer in men living in Tobago. In the same study population, we examined the association between HHV-8 seropositivity and incident prostate cancer discovered at later screenings.

Methods

In 40-81 year-old men without prostate cancer discovered at initial digital rectal examination (DRE) and prostate-specific antigen (PSA) screening, a case-cohort design measured the association between baseline HHV-8 seropositivity (modified immunofluorescence assay for antibodies against HHV-8 lytic antigens) and incident prostate cancer detected at DRE and PSA screenings three or five years later.

Results

Analyses included 486 unique individuals, 96 incident prostate cancer cases, and 415 randomly selected subjects representing an at-risk cohort. By design, the random sub-cohort contained 25 incident prostate cancer cases. In the sub-cohort, the frequency of HHV-8 seropositivity increased across age groupings (40-49 years: 3.5%, 50-59 years: 13.6%, and ≥ 60 years: 22.9%). HHV-8 seropositivity was higher in men with elevated (≥ 4.0 ng/mL) than men with non-elevated PSA at initial screening (30.4% vs. 9.9% seropositive; crude odds ratio (OR) 3.96, 95% confidence interval (CI) 1.53-10.2; age-adjusted OR 2.42, 95% CI 0.91-6.47). HHV-8 seropositivity did not increase incident prostate cancer risk (age-adjusted hazard ratio (HR) 0.88, 95% CI 0.46-1.69).

Conclusions

Case-cohort analysis did not identify association between HHV-8 seropositivity and incident prostate cancer. However, analyses uncovered possible association between HHV-8 and PSA (a marker of prostate inflammation). Co-occurrence of HHV-8 seropositivity and PSA elevation may explain cross-sectional association between HHV-8 and PSA screen-detected prostate cancer.
Dendritic cell-associated lectin 2 (DCAL2) defines a distinct CD8α− dendritic cell subset
Authors: Kasahara Shinji , Clark Edward A
Published: December 2011

CLRs on DCs play important roles in immunity and are expressed selectively on certain DC subsets. Murine DCAL2 (myeloid inhibitory C-type lectin/Clec12a) is a type-II CLR with an ITIM. Using a mouse DCAL2-specific mAb, we found that DCAL2 is expressed at relatively high levels on APCs and that DCAL2 expression can be used to divide CD8α– DCs into DCAL2+DCIR2– and DCAL2–DCIR2+ subpopulations. CD8α–DCAL2+ DC, CD8α–DCIR2+ DC, and CD8α+DCAL2+ DC subsets each express different levels of TLRs and respond to unique classes of TLR ligands by producing distinct sets of cytokines. Whereas CD8α–DCAL2+ DCs robustly produce cytokines, including IL-12, in response to CpG, CD8α–DCIR2+ DCs produce only TNF-α and IL-10 in modest amounts when stimulated with zymosan. However, CD8α–DCIR2+ DCs, unlike the other DC subsets, strongly up-regulate OX40L when stimulated with bacterial flagellin. As predicted from their cytokine expression, CD8α–DCAL2+ DCs efficiently induced Th1 responses in the presence of CpG in vitro and in vivo, whereas CD8α–DCIR2+ DCs induced Th2 cells in response to flagellin. Thus, CD8α–DCAL2+ DCs comprise a distinct CD8α– DC subset capable of supporting Th1 responses. DCAL2 is a useful marker to identify a Th1-inducing CD8α– DC population.
Exposure to Di(2-ethyl-hexyl) phthalate (DEHP) in Utero and during Lactation Causes Long-Term Pituitary-Gonadal Axis Disruption in Male and Female Mouse Offspring
Authors: Pocar Paola , Fiandanese Nadia , Secchi Camillo , Berrini Anna , Fischer Bernd , Schmidt Juliane S. , Schaedlich Kristina , Borromeo Vitaliano
Published: December 2011

The present study examined the effects in mice of exposure to di(2-ethyl-hexyl) phthalate (DEHP) throughout pregnancy and lactation on the development and function of the pituitary-gonadal axis in male and female offspring once they have attained adulthood. Groups of two to three dams were exposed with the diet from gestational d 0.5 until the end of lactation, at 0, 0.05, 5, and 500 mg DEHP/kg · d. The experiment was repeated three times (total: seven to 10 dams per treatment). The 500-mg dose caused complete pregnancy failure, whereas exposure to doses of 0.05 and 5 mg did not affect pregnancy and litter size. In total, about 30 male and 30 female offspring per group were analyzed. Offspring of the DEHP-treated groups, compared with controls, at sexual maturity showed: 1) lower body weight (decrease 20–25%, P < 0.001); 2) altered gonad weight (testes were ∼13% lighter and ovaries ∼40% heavier; P < 0.001); 3) poor germ cell quality (semen was ∼50% less concentrated and 20% less viable, and ∼10% fewer oocytes reached MII stage, P < 0.001); 4) significant lower expression of steroidogenesis and gonadotropin-receptor genes in the gonads; and 5) up-regulated gonadotropin subunit gene expression in the pituitary. In conclusion, our findings suggest that, in maternally exposed male and female mice, DEHP acts on multiple pathways involved in maintaining steroid homeostasis. Specifically, in utero and lactational DEHP exposure may alter estrogen synthesis in both sexes. This, in turn, induces dysregulation of pituitary-gonadal feedback and alters the reproductive performance of exposed animals.
The Leap of Faith from Disease Treatment to Lifestyle Prevention: The Genealogy of a Policy Idea
Authors: Larsen Lars Thorup
Published: December 2011

Since the 1970s public health policy has attempted to counter the rise of chronic diseases by getting individuals to make healthy choices about smoking, alcohol, diet, and physical exercise. Inspired by the so-called new perspective of the 1974 Lalonde report, this shift from disease treatment to prevention has been a key focus of public health policy to this day. Every generation of public health reports presents prevention as the answer to past failures, but the continuous experience of failure is strangely coexistent with a fundamental belief in the ability of lifestyle prevention to produce large health improvements. The article tracks the genealogy of lifestyle prevention as policy idea across three generations of U.S. and Danish public health reports and finds a systematic interpretation of lifestyle prevention as being more successful and promising than acute medical treatment.
Ants might use different view-matching strategies on and off the route
Authors: Wystrach Antoine , Beugnon Guy , Cheng Ken
Published: December 2011

Individual foraging ants are known to rely on views of their surroundings for route learning and for pinpointing goals. Different strategies have been proposed to explain how ants might process visual information for navigation, but little is known about the actual development and nature of the view-based strategies used by ants in complex natural environments. Here, we constrained the knowledge of Melophorus bagoti ants to either the nest vicinity or a curved route (length 10 m) and analysed their initial direction when released at both novel and familiar locations. In parallel, we used 360 deg pictures of the scene as a basis for modelling different navigational strategies. We propose here a new hypothesis based on skyline height comparison to explain how ants home from novel locations. Interestingly, this strategy succeeded well at novel locations but failed on familiar terrain. By contrast, the use of a visual compass strategy failed at novel locations but could explain the results on familiar routes. We suggest that ants might switch between skyline height comparison and a visual compass strategy, depending on whether they are on familiar terrain or not. How ants could switch between strategies and how their memories develop are discussed in turn.
Hypoxia tolerance in elasmobranchs. I. Critical oxygen tension as a measure of blood oxygen transport during hypoxia exposure
Authors: Speers-Roesch Ben , Richards Jeffrey G. , Brauner Colin J. , Farrell Anthony P. , Hickey Anthony J. R. , Wang Yuxiang S. , Renshaw Gillian M. C.
Published: December 2011

The critical O2 tension of whole-animal O2 consumption rate (), or Pcrit, is the water PO2 (PwO2) at which an animal transitions from an oxyregulator to an oxyconformer. Although Pcrit is a popular measure of hypoxia tolerance in fishes because it reflects the capacity for O2 uptake from the environment at low PwO2, little is known about the interrelationships between Pcrit and blood O2 transport characteristics and increased use of anaerobic metabolism during hypoxia exposure in fishes, especially elasmobranchs. We addressed this knowledge gap using progressive hypoxia exposures of two elasmobranch species with differing hypoxia tolerance. The Pcrit of the hypoxia-tolerant epaulette shark (Hemiscyllium ocellatum, 5.10±0.37 kPa) was significantly lower than that of the comparatively hypoxia-sensitive shovelnose ray (Aptychotrema rostrata, 7.23±0.40 kPa). Plasma [lactate] was elevated above normoxic values at around Pcrit in epaulette sharks, but increased relative to normoxic values at PwO2 below Pcrit in shovelnose rays, providing equivocal support for the hypothesis that Pcrit is associated with increased anaerobic metabolism. The , arterial PO2 and arterial blood O2 content (CaO2) were similar between the two species under normoxia and decreased in both species with progressive hypoxia, but as PwO2 declined, epaulette sharks had a consistently higher and CaO2 than shovelnose rays, probably due to their significantly greater in vivo haemoglobin (Hb)–O2 binding affinity (in vivo Hb–O2P50=4.27±0.57 kPa for epaulette sharks vs 6.35±0.34 kPa for shovelnose rays). However, at PwO2 values representing the same percentage of each species' Pcrit (up to ∼175% of Pcrit), Hb–O2 saturation and CaO2 were similar between species. These data support the hypothesis that Hb–O2P50 is an important determinant of Pcrit and suggest that Pcrit can predict Hb–O2 saturation and CaO2 during hypoxia exposure, with a lower Pcrit being associated with greater O2 supply at a given PwO2 and consequently better hypoxia tolerance. Thus, Pcrit is a valuable predictor of environmental hypoxia tolerance and hypoxia exposures standardized at a given percentage of Pcrit will yield comparable levels of arterial hypoxaemia, facilitating cross-species comparisons of responses to hypoxia.