bluuebunny/crossref_metadata_2025 huggingface dataset:
Protective Effect of Solanum nigrum Leaves Extract on Immobilization Stress Induced Changes in Rat’s Brain
Authors: Zaidi Syed Kashif , Hoda Md. Nasrul , Tabrez Shams , Ansari Shakeel Ahmed , Jafri Mohammad Alam , Shahnawaz Khan Mohd , Hasan Shirin , Alqahtani Mohammed H. , Mohammed Abuzenadah Adel , Banu Naheed
Published: February 2014

The prophylactic or curative antioxidant efficacy of crude extract and the active constituent of S. nigrum leaves were evaluated in modulating inherent antioxidant system altered due to immobilization stress in rat brain tissues, in terms of measurement of glutathione (GSH), lipid peroxidation (thiobarbituric acid reactive substances, TBARS), and free radical scavenging enzymes activities. Rats were treated with single dose of crude extract of S. nigrum prior to and after 6 h of immobilization stress exposure. Exposure to immobilization stress resulted in a decrease in the brain levels of glutathione, SOD, GST, and catalase, with an increase in thiobarbituric acid reactive substances (TBARS) levels. Treatment of S. nigrum extract and its active constituents to both pre‐ and poststressed rats resulted in significant modulation in the above mentioned parameters towards their control values with a relative dominance by the latter. Brain is vulnerable to stress induced prooxidant insult due to high levels of fat content. Thus, as a safe herbal medication the S. nigrum leaves extract or its isolated constituents can be used as nutritional supplement for scavenging free radicals generated in the brain due to physical or psychological stress or any neuronal diseases per se.
Genetic Characterization of Infectious Bursal Disease Viruses Associated with Gumboro Outbreaks in Commercial Broilers from Asyut Province, Egypt
Authors: Mohamed Moemen A. , Elzanaty Kamal E. S. , Bakhit Bakhit M. , Safwat Marwa M.
Published: February 2014

Ten infectious bursal disease virus (IBDV) field strains were isolated from 15 broiler flocks located in various parts of Asyut, Egypt. Seven strains were subjected to comparative sequencing and phylogenetic analyses to help provide optimal control program for protection against IBDV infection. Sequence analysis of a 530 bp hypervariable region in the VP2 gene revealed that the rate of identity and homology was around 95.6~99.1%. Sequence characterization revealed the 7 strains identified as vvIBDV with the four amino acids residues typical of vvIBDV (242I, 256I, 294I, 299S). The BURSA-VAC vaccine was the nearest vaccine in sequence similarity to the local examined IBDV strains followed by CEVACIBDL then Bursine plus and Nobilis Gumboro indicating its probable success in the face of incoming outbreaks when using these vaccines. Phylogenetic analysis revealed that the presence of three clusters for the examined strains and are grouped with reference very virulent IBDVs of European and Asian origin (Japanese and Hong Kong) strains suggesting the different ancestors of our isolates. The antigenic index showed a number of changes on the major and minor hydrophilic antigenic peaks of the virus surface structures indicating a new genetic evolution of the surface structure epitopes that may lead to vaccination failure and reemergence of the disease.
Prolonged Survival of a Refractory Acute Myeloid Leukemia Patient after a Third Hematopoietic Stem Cell Transplantation with Umbilical Cord Blood following a Second Relapse
Authors: Lee Suk-young , Kurita Naoki , Maie Koichiro , Seki Masanori , Yokoyama Yasuhisa , Suzukawa Kazumi , Hasegawa Yuichi , Chiba Shigeru
Published: February 2014

Although hematopoietic stem cell transplantation (HSCT) has been considered to be the only way for potential cure of relapsed acute myeloid leukemia (AML), there has been no report on a third HSCT in patients with multiple relapsed AML. Here, we report a case of 53-year-old female who received a successful third allogeneic HSCT after relapse of AML following a second allogeneic HSCT. She was treated with a toxicity reduced conditioning regimen and received direct intrabone cord blood transplantation (CBT) using a single unit of 5/6 HLA-matched cord blood as a graft source. Graft-versus-host disease prophylaxis was performed with a single agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission for 8 months since the direct intrabone CBT. This report highlights not only the importance of individually adjusted approach but also the need for further investigation on the role of HSCT as a treatment modality in patients with refractory or multiple relapsed AML.
Neonatal Meningitis by Multidrug ResistantElizabethkingia meningosepticumIdentified by 16S Ribosomal RNA Gene Sequencing
Authors: Shailaja V. V. , Reddy Ashok Kumar , Alimelu M. , Sadanand L. N. R.
Published: February 2014

Clinical and microbiological profile of 9 neonates with meningitis byElizabethkingia meningosepticumidentified by 16S ribosomal gene sequencing was studied. All the clinical isolates were resistant to cephalosporins, aminoglycosides, trimethoprim-sulfamethoxazole,β-lactam combinations, carbapenems and only one isolate was susceptible to ciprofloxacin. All the isolates were susceptible to vancomycin. Six of nine neonates died even after using vancomycin, based on susceptibility results.E. meningosepticummeningitis in neonates results in high mortality rate. Though the organism is susceptible to vancomycin in vitro, its efficacy in vivo is questionable and it is difficult to determine the most appropriate antibiotic for treatingE. meningosepticummeningitis in neonates.
Generalized Predator-Prey Model with Nonlinear Impulsive Control Strategy
Authors: Qin Wenjie , Tang Guangyao , Tang Sanyi
Published: February 2014

A generalized predator-prey model concerning integrated pest management and nonlinear impulsive control measures is proposed and analyzed. The main purpose is to understand how resource limitation affects the successful pest control and pest outbreaks. The threshold conditions for the stability of the pest-free periodic solution are given firstly. Once the threshold value exceeds a critical level, both pest and its natural enemy populations can oscillate periodically. Secondly, in order to address how the limited resources affect the pest control, as an example the Holling II functional response function is chosen. The numerical results show that predator-prey model with limited resource has complex dynamical behavior. In addition, it is confirmed that the model has the coexistence of pests and natural enemies for a wide range of parameters.
The Severity of Ischemia Varies in Sprague-Dawley Rats from Different Vendors
Authors: Nikolova Simona , Lee Ting-Yim , Bartha Robert
Published: February 2014

The purpose of this study was to compare acute cerebral perfusion measured by computed tomography, stroke lesion volume measured by magnetic resonance imaging, and motor function in Sprague-Dawley rats supplied by Charles River (Charles River, Quebec, Canada) and Harlan (Harlan, Michigan, USA). During the acute stages of ischemia (<3 hours), Sprague-Dawley rats supplied by Harlan had a greater reduction in blood flow (67%) than rats supplied by Charles River (37%). MRI at days 1 and 6 after ischemia showed larger lesions in the Charles River animals compared to Harlan animals (P<0.05) at both time points. Lesion volume decreased in both Charles River and Harlan rats at day 6 compared to day 1 (P<0.05) and corresponded to lesion size on histology. The Harlan animals had significant functional deficits (P<0.05) one day after surgery in postural hang reflex, forelimb placement, and tactile fraction first tests, whereas rats supplied by Charles River had no significant functional impairment as a result of surgery. The current study provides evidence that differences in response to ischemia between rats of the same strain supplied by different vendors should be an important consideration when animals are selected for the study of cerebral ischemia.
Germinoma with Involvement of Midline and Off-Midline Intracranial Structures
Authors: Loto Monica Graciela , Danilowicz Karina , González Abbati Santiago , Torino Rafael , Misiunas Alejandro
Published: February 2014

Germinomas are malignant intracranial germ tumors, usually found in suprasellar regions. Less than 10% are localized in off-middle structures, and synchronous involvement of both structures has only exceptionally been published. A case of an 18-year-old male patient with progressive right-sided hemiparesis and panhypopituitarism was reviewed. Brain MRI showed a solid mass involving pituitary and hypothalamus with thickening of pituitary stalk, high intensity lesions on T2-weighted imaging in left internal capsule, caudate nucleus, globus pallidus, and mild atrophy of the left internal capsule and cerebral peduncle. Nonadenomatous lesions were considered in the differential diagnosis. Alfa-fetoprotein (AFP) levels were negative in both serum and cerebrospinal fluid (CSF), whileβ-human chorionic gonadotrophin (β-HCG) levels were slightly increased in CSF. A transsphenoidal biopsy identified a germinoma. Four cycles of chemotherapy with bleomicine, etoposide, and cysplatin were given, followed by radiotherapy, but patients died due to a recidiva.Conclusion. Germinoma must be considered in patients with insipidus diabetes with a sellar mass with thickening of pituitary stalk; and ectopic germinoma must be suspected in patients with slowly progressive hemiparesis with cerebral hemiatrophy. Even with a rare condition, colocalization of midline and off-midline germinoma must be suspected in the presence of these typical signs of both localizations.
An Asian Patient with Myoclonus-Dystonia (DYT11) Responsive to Deep Brain Stimulation of the Globus Pallidus Internus
Authors: Uruha Akinori , Kimura Katsuo , Okiyama Ryoichi
Published: February 2014

We describe the case of a 42-year-old Japanese woman with childhood-onset myoclonus, dystonia, and psychiatric symptoms, including anxiety, phobia, and exaggerated startle response. The diagnosis was confirmed as myoclonus-dystonia (DYT11) by identifying a mutation in the gene encodingε-sarcoglycan. Interestingly, while motor-related symptoms in DYT11 generally improve with alcohol ingestion, the patient’s symptoms were exacerbated by alcohol intake. Her severe and medically intractable symptoms were alleviated by bilateral deep brain stimulation of the globus pallidus internus, with myoclonus and dystonia scores showing 70% improvement after the surgery compared to presurgical scores. This is the first report of a genetically confirmed case of DYT11 in Japan. This paper together with other recent reports collectively demonstrates that DYT11 patients are distributed worldwide, including Asia. Thus, a diagnosis of DYT11 should be considered when clinicians encounter a patient with childhood-onset myoclonus and/or dystonia with psychiatric symptoms, regardless of ethnic background.
Pancreatic Resections in Renal Failure Patients: Is It Worth the Risk?
Authors: Norman K. S. , Domingo S. R. , Wong L. L.
Published: February 2014

Background. Chronic kidney disease affects 20 million US patients, with nearly 600,000 on dialysis. Long-term survival is limited and the risk of complex pancreatic surgery in this group is questionable. Previous studies are limited to case reports and small case series and a large database may help determine the true risk of pancreatic surgery in this population. Methods. The American College of Surgeons National Surgical Quality Improvement Program database was queried (2005–2011) for patients who underwent pancreatic resection. Renal failure was defined as the clinical condition associated with rapid, steadily increasing azotemia (rise in BUN) and increasing creatinine above 3 mg/dL. Operative trends and short-term outcomes were reviewed for those with and without renal failure (RF). Results. In 18,533 patients, 28 had RF. There was no difference in wound infections, neurologic or cardiovascular complications. Compared to non-RF patients, those with RF had more unplanned intubation (OR 4.89, 95% CI 1.85–12.89), bleeding requiring transfusion (OR 3.12, 95% CI 1.37–14.21), septic shock (OR 8.86, 95% CI 3.75–20.91), higher 30-day mortality (21.4% versus 2.3%, P<0.001) and longer hospital stay (23 versus 12 days, P<0.001). Conclusions. RF patients have much higher morbidity and mortality after pancreatic resections and surgeons should consider this before proceeding.
Pulse Waveform Classification Using Support Vector Machine with Gaussian Time Warp Edit Distance Kernel
Authors: Jia Danbing , Zhang Dongyu , Li Naimin
Published: February 2014

Advances in signal processing techniques have provided effective tools for quantitative research in traditional Chinese pulse diagnosis. However, because of the inevitable intraclass variations of pulse patterns, the automatic classification of pulse waveforms has remained a difficult problem. Utilizing the new elastic metric, that is, time wrap edit distance (TWED), this paper proposes to address the problem under the support vector machines (SVM) framework by using the Gaussian TWED kernel function. The proposed method, SVM with GTWED kernel (GTWED-SVM), is evaluated on a dataset including 2470 pulse waveforms of five distinct patterns. The experimental results show that the proposed method achieves a lower average error rate than current pulse waveform classification methods.
Effects of Paliperidone Palmitate on Coagulation: An Experimental Study
Authors: Yılmaz Enver Demirel , Motor Sedat , Sefil Fatih , Pınar Neslihan , Kokacya Hanifi , Kisa Mustafa , Oktar Suleyman
Published: February 2014

Objective. The aim of the present study was to examine the effects of a new antipsychotic drug paliperidone palmitate on hemogram and coagulation parameters in rats.Materials and Methods. Experiments were performed on 22 female albino Wistar rats (8–12 weeks old). Control group was given drinking water as vehicle (0.3 mL). PAL-1 rats were given 1 mg/kg paliperidone palmitate (in 0.3 mL drinking water) by oral gavage once a day for ten days and PAL-3 rats received 3 mg/kg paliperidone palmitate (in 0.3 mL drinking water) by oral gavage for ten days. Blood samples were drawn from the heart 24 hours after the last drug dose, and hemogram and coagulation parameters were measured with automated analyzers.Results. Hemogram did not change in the paliperidone treated groups compared to the controls. Factor VIII levels decreased in the PAL-1 and PAL-3 groups; and this decrease was significantly greater in the PAL-3. Factor IX levels decreased in PAL-3 rats, but its levels also increased in PAL-1 rats compared to the control.Discussion. Paliperidone has led to changes in the serum levels of coagulation factors VIII and IX in rats. As a result, paliperidone may be causing thromboembolism or bleeding in a dose-independent manner.
A New Approach for Clustered MCs Classification with Sparse Features Learning and TWSVM
Authors: Zhang Xin-Sheng
Published: February 2014

In digital mammograms, an early sign of breast cancer is the existence of microcalcification clusters (MCs), which is very important to the early breast cancer detection. In this paper, a new approach is proposed to classify and detect MCs. We formulate this classification problem as sparse feature learning based classification on behalf of the test samples with a set of training samples, which are also known as a “vocabulary” of visual parts. A visual information-rich vocabulary of training samples is manually built up from a set of samples, which include MCs parts and no-MCs parts. With the prior ground truth of MCs in mammograms, the sparse feature learning is acquired by thelP-regularized least square approach with the interior-point method. Then we designed the sparse feature learning based MCs classification algorithm using twin support vector machines (TWSVMs). To investigate its performance, the proposed method is applied to DDSM datasets and compared with support vector machines (SVMs) with the same dataset. Experiments have shown that performance of the proposed method is more efficient or better than the state-of-art methods.
CuO‐In2O3Core‐Shell Nanowire Based Chemical Gas Sensors
Authors: Li Xiaoxin , Li Xiaogan , Chen Ning , Li Xinye , Zhang Jianwei , Yu Jun , Wang Jing , Tang Zhenan
Published: February 2014

The CuO‐In2O3 core‐shell nanowire was fabricated by a two‐step method. The CuO nanowire core (NWs) was firstly grown by the conventional thermal oxidation of Cu meshes at 500°C for 5 hours. Then, the CuO nanowires were immersed into the suspension of amorphous indium hydroxide deposited from the In(AC)3 solution by ammonia. The CuO nanowires coated with In(OH)3 were subsequently heated at 600°C to form the crystalline CuO‐In2O3 core‐shell structure, with In2O3 nanocrystals uniformly anchored on the CuO nanowires. The gas sensing properties of the formed CuO‐In2O3 core‐shell nanowires were investigated by various reducing gases such as hydrogen, carbon monoxide, and propane at elevated temperature. The sensors using the CuO‐In2O3 nanowires show improved sensing performance to hydrogen and propane but a suppressed response to carbon monoxide, which could be attributed to the enhanced catalytic properties of CuO with the coated porous In2O3 shell and the p‐n junction formed at the core‐shell interface.
Asymptotic Analysis of SPTA-Based Algorithms for No-Wait Flow Shop Scheduling Problem with Release Dates
Authors: Ren Tao , Zhang Chuan , Lin Lin , Guo Meiting , Xie Xionghang
Published: February 2014

We address the scheduling problem for a no-wait flow shop to optimize total completion time with release dates. With the tool of asymptotic analysis, we prove that the objective values of two SPTA-based algorithms converge to the optimal value for sufficiently large-sized problems. To further enhance the performance of the SPTA-based algorithms, an improvement scheme based on local search is provided for moderate scale problems. New lower bound is presented for evaluating the asymptotic optimality of the algorithms. Numerical simulations demonstrate the effectiveness of the proposed algorithms.
Diffusion-Weighted Magnetic Resonance Imaging Findings of Kidneys with Obstructive Uropathy: Differentiation between Benign and Malignant Etiology
Authors: Kalayci Tugce Ozlem , Apaydin Melda , Sönmezgöz Fitnet , Çalık Sinan , Bedel Koruyucu Melike
Published: February 2014

Purpose. In this study, we aimed to evaluate the capability of diffusion-weighted magnetic resonance imaging (DWI) in differentiation between benign and malignant etiology of obstructive uropathy.Materials and Methods. DWI was performed in 41 patients with hydronephrotic kidneys and 26 healthy volunteers. MR imaging was performed using a 1.5 T whole-body superconducting MR scanner. The signal intensities of the renal parenchyma on DWI and apparent diffusion coefficient (ADC) maps were noted. DWI was performed with the following diffusion gradientbvalues: 100, 600, and 1000 s/mm2. A large circular region of interest was placed in the corticomedullary junction of the kidneys. For statistical analysis, the independent-samplesttest was used.Results. The mean renal ADC values forb100,b600, andb1000 in hydronephrosis patients with benign and malignant etiology and the healthy volunteers of the control group were analysed. ADC measurements of renal parenchyma in all hydronephrotic kidneys with benign and malignant etiology were found to be statistically low compared to those of normal kidneysP<0.05.Conclusions. There were significant differences in the ADC values of obstructed kidneys compared to those of normal kidneys. Obstructed kidneys with malignant etiology had lower ADC values forb1000 compared to obstructed kidneys with benign etiology, but these alterations were statistically insignificant.
Finite-Time Boundedness Analysis for a Class of Switched Linear Systems with Time-Varying Delay
Authors: Zhong Yanke , Chen Tefang
Published: February 2014

The problem of finite-time boundedness for a class of switched linear systems with time-varying delay and external disturbance is investigated. First of all, the multiply Lyapunov function of the system is constructed. Then, based on the Jensen inequality approach and the average dwell time method, the sufficient conditions which guarantee the system is finite-time bounded are given. Finally, an example is employed to verify the validity of the proposed method.
Hemozoin Inhibition and Control of Clinical Malaria
Authors: Ihekwereme Chibueze Peter , Esimone Charles Okechukwu , Nwanegbo Edward Chieke
Published: February 2014

Malaria has a negative impact on health and social and economic life of residents of endemic countries. The ultimate goals of designing new treatment for malaria are to prevent clinical infection, reduce morbidity, and decrease mortality. There are great advances in the understanding of the parasite-host interaction through studies by various scientists. In some of these studies, attempts were made to evaluate the roles of malaria pigment or toxins in the pathogenesis of malaria. Hemozoin is a key metabolite associated with severe malaria anemia (SMA), immunosuppression, and cytokine dysfunction. Targeting of this pigment may be necessary in the design of new therapeutic products against malaria. In this review, the roles of hemozoin in the morbidity and mortality of malaria are highlighted as an essential target in the quest for effective control of clinical malaria.
Periventricular Lesions Help Differentiate Neuromyelitis Optica Spectrum Disorders from Multiple Sclerosis
Authors: Raz Eytan , Loh John P. , Saba Luca , Omari Mirza , Herbert Joseph , Lui Yvonne , Kister Ilya
Published: February 2014

Objective.To compare periventricular lesions in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOsd).Materials and Methods.Sagittal and axial fluid attenuated inversion recovery (FLAIR) sequences of 20 NMOsd and 40 group frequency-matched MS patients were evaluated by two neuroradiologists. On axial FLAIR, periventricular area was characterized as free of lesions/smooth-bordered (“type A”) or jagged-bordered (“type B”) pattern. On sagittal FLAIR, the images were evaluated for presence of “Dawson’s fingers.”Results.Type A pattern was observed in 80% of NMOsd patients by Reader 1 and 85% by Reader 2 but only in 5% MS patients by either Reader. Type B was seen in 15% NMOsd patients by Reader 1 and 20% by Reader 2 and in 95% MS patients by either Reader. Dawson’s fingers were observed in no NMOsd patients by Reader 1 and 5% by Reader 2. In MS, Dawson’s fingers were seen in 92.5% patients by Reader 1 and 77.5% by Reader 2. The differences in periventricular patterns and Dawson’s finger detection between NMOsd and MS were highly significant (P<0.001).Conclusions. Dawson’s fingers and “jagged-bordered” periventricular hyperintensities are typical of MS and almost never seen in NMOsd, which suggests a practical method for differentiating the two diseases.
Vemurafenib Cooperates with HPV to Promote Initiation of Cutaneous Tumors
Authors: Holderfield Matthew , Lorenzana Edward , Weisburd Ben , Lomovasky Lisa , Boussemart Lise , Lacroix Ludovic , Tomasic Gorana , Favre Michel , Vagner Stephan , Robert Caroline , Ghoddusi Majid , Daniel Dylan , Pryer Nancy , McCormick Frank , Stuart Darrin
Published: February 2014

Treatment with RAF inhibitors such as vemurafenib causes the development of cutaneous squamous cell carcinomas (cSCC) or keratoacanthomas as a side effect in 18% to 30% of patients. It is known that RAF inhibitors activate the mitogen—activated protein kinase (MAPK) pathway and stimulate growth of RAS-mutated cells, possibly accounting for up to 60% of cSCC or keratoacanthoma lesions with RAS mutations, but other contributing events are obscure. To identify such events, we evaluated tumors from patients treated with vemurafenib for the presence of human papilloma virus (HPV) DNA and identified 13% to be positive. Using a transgenic murine model of HPV-driven cSCC (K14-HPV16 mice), we conducted a functional test to determine whether administration of RAF inhibitors could promote cSCC in HPV-infected tissues. Vemurafenib treatment elevated MAPK markers and increased cSCC incidence from 22% to 70% in this model. Furthermore, 55% of the cSCCs arising in vemurafenib-treated mice exhibited a wild-type Ras genotype, consistent with the frequency observed in human patients. Our results argue that HPV cooperates with vemurafenib to promote tumorigenesis, in either the presence or absence of RAS mutations. Cancer Res; 74(8); 2238–45. ©2014 AACR.
Intrinsic Subtypes from PAM50 Gene Expression Assay in a Population-Based Breast Cancer Cohort: Differences by Age, Race, and Tumor Characteristics
Authors: Sweeney Carol , Bernard Philip S. , Factor Rachel E. , Kwan Marilyn L. , Habel Laurel A. , Quesenberry Charles P. , Shakespear Kaylynn , Weltzien Erin K. , Stijleman Inge J. , Davis Carole A. , Ebbert Mark T.W. , Castillo Adrienne , Kushi Lawrence H. , Caan Bette J.
Published: February 2014

Background: Data are lacking to describe gene expression–based breast cancer intrinsic subtype patterns for population-based patient groups.

Methods: We studied a diverse cohort of women with breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1 mm punches from fixed tumor tissue. Quantitative reverse-transcriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier.

Results: In a subcohort of 1,319 women, the overall subtype distribution based on PAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrine-positive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores from PAM50 were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, PTrend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3–8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR = 0.5 (95% CI, 0.3–0.9).

Conclusions: Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression–based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes.

Impact: Subtyping in a population-based cohort revealed distinct profiles by age and race. Cancer Epidemiol Biomarkers Prev; 23(5); 714–24. ©2014 AACR.
Turning the Tide Against Cancer Through Sustained Medical Innovation: The Pathway to Progress
Authors: Abernethy Amy , Abrahams Edward , Barker Anna , Buetow Ken , Burkholder Randy , Dalton William S. , Foti Margaret , Frueh Felix , Gaynor Richard B. , Kean Marcia , Khan Zeba , Lessor Tracy , Lichtenfeld J. Leonard , Mendelsohn John , van't Veer Laura
Published: February 2014

An ever-expanding understanding of the molecular basis of the more than 200 unique diseases collectively called cancer, combined with efforts to apply these insights to clinical care, is forming the foundation of an era of personalized medicine that promises to improve cancer treatment. At the same time, these extraordinary opportunities are occurring in an environment of intense pressure to contain rising healthcare costs. This environment presents a challenge to oncology research and clinical care, because both are becoming progressively more complex and expensive, and because the current tools to measure the cost and value of advances in care (e.g., comparative effectiveness research, cost-effectiveness analysis, and health technology assessments) are not optimized for an ecosystem moving toward personalized, patient-centered care. Reconciling this tension will be essential to maintaining progress in a cost-constrained environment, especially because emerging innovations in science (e.g., increasing identification of molecular biomarkers) and in clinical process (implementation of a learning healthcare system) hold potential to dramatically improve patient care, and may ultimately help address the burden of rising costs. For example, the rapid pace of innovation taking place within oncology calls for increased capability to integrate clinical research and care to enable continuous learning, so that lessons learned from each patient treated can inform clinical decision making for the next patient. Recognizing the need to define the policies required for sustained innovation in cancer research and care in an era of cost containment, the stakeholder community must engage in an ongoing dialogue and identify areas for collaboration. This article reflects and seeks to amplify the ongoing robust discussion and diverse perspectives brought to this issue by multiple stakeholders within the cancer community, and to consider how to frame the research and regulatory policies necessary to sustain progress against cancer in an environment of constrained resources. Clin Cancer Res; 20(5); 1081–6. ©2014 AACR.
Upregulation of Store Operated Ca2+ Channel Orai1, Stimulation of Ca2+ Entry and Triggering of Cell Membrane Scrambling in Platelets by Mineralocorticoid DOCA
Authors: Liu Guoxing , Liu Guilai , Alzoubi Kousi , Umbach Anja T. , Pelzl Lisann , Borst Oliver , Gawaz Meinrad , Lang Florian
Published: February 2014

Background/Aims: Mineralocorticoid excess leads to vascular injury, which is partially due to hypertension but in addition involves increased concentration of cytosolic Ca2+ concentration in platelets, key players in the pathophysiology of occlusive vascular disease. Mineralocorticoids are in part effective by rapid nongenomic mechanisms including phosphatidylinositide-3-kinase (PI3K) signaling, which involves activation of the serum & glucocorticoid inducible kinase (SGK) isoforms. SGK1 has in turn been shown to participate in the regulation of the pore forming Ca2+ channel protein Orai1 in platelets. Orai1 accomplishes entry of Ca2+, which is in turn known to trigger cell membrane scrambling. Platelets lack nuclei but are able to express protein by translation, which is stimulated by PI3K signaling. The present study explored whether the mineralocorticoid desoxycorticosterone acetate (DOCA) influences platelet Orai1 protein abundance, cytosolic Ca2+-activity ([Ca2+]i), phosphatidylserine abundance at the cell surface and/or cell volume. Methods: Orai1 protein abundance was estimated utilizing CF™488A conjugated antibodies, [Ca2+]i utilizing Fluo3-fluorescence, phosphatidylserine abundance utilizing FITC-labelled annexin V, and cell volume utilizing forward scatter in flow cytometry. Results: DOCA (10 µg/ml) treatment of murine platelets was followed by a significant increase of Orai1 protein abundance, [Ca2+]i, percentage of phosphatidylserine exposing platelets and platelet swelling. The effect on [Ca2+]i, phosphatidylserine abundance and cell volume were completely abrogated by addition of the specific SGK inhibitor EMD638683 (50 µM) Conclusions: The mineralocorticoid DOCA upregulates Orai1 protein abundance in the cell membrane, thus increasing [Ca2+]i and triggering phosphatidylserine abundance, effects paralleled by platelet swelling.
Fine-Needle Aspiration Cytology of Thyroid Nodules with Hürthle Cells: Cytomorphologic Predictors for Neoplasms, Improving Diagnostic Accuracy and Overcoming Pitfalls
Authors: Kasper K.A. , Stewart III J. , Das K.
Published: February 2014

Objectives: Hürthle cells (HCs) are follicular-derived oncocytic cells seen in a variety of neoplastic and nonneoplastic pathologic entities of the thyroid gland. This study was to report our experience of the surgical outcome on the finding of HCs on fine-needle aspiration biopsies (FNABs) of thyroid nodules, to identify cytologic predictors of HC neoplasms and an attempt to overcome diagnostic pitfalls. Study Design: This was a retrospective study of all FNAB of thyroid nodules with findings of HCs with subsequent surgical resection. The FNAB slides of 70 thyroid nodules were blindly reviewed for specific cytomorphologic characteristics. The cytologic findings were correlated with the corresponding final surgical pathology diagnosis. Results: The patients ranged in age from 25 to 78 years with a male:female ratio of 1:2. There were 19 false-negative and 4 false-positive cases. Overall high cellularity, scant colloid and >90% HCs on FNAB are consistently seen in a neoplastic HC process. All cases of Hashimoto's thyroiditis were associated with prominent nucleoli and 92% of cases demonstrating transgressing vessels were neoplastic. Conclusion: Diagnostic accuracy can be improved by following the current Bethesda classification system. A constellation of cytomorphologic features in conjunction with clinical findings can be considered a strong predictor of a neoplastic process.
Stroke Outcomes Measures Must Be Appropriately Risk Adjusted to Ensure Quality Care of Patients
Authors: Fonarow Gregg C. , Alberts Mark J. , Broderick Joseph P. , Jauch Edward C. , Kleindorfer Dawn O. , Saver Jeffrey L. , Solis Penelope , Suter Robert , Schwamm Lee H.
Published: February 2014

Abstract—

Because stroke is among the leading causes of death, disability, hospitalizations, and healthcare expenditures in the United States, there is interest in reporting outcomes for patients hospitalized with acute ischemic stroke. The American Heart Association/American Stroke Association, as part of its commitment to promote high-quality, evidence-based care for cardiovascular and stroke patients, fully supports the development of properly risk-adjusted outcome measures for stroke. To accurately assess and report hospital-level outcomes, adequate risk adjustment for case mix is essential. During the development of the Centers for Medicare & Medicaid Services 30-day stroke mortality and 30-day stroke readmission measures, concerns were expressed that these measures were not adequately designed because they do not include a valid initial stroke severity measure, such as the National Institutes of Health Stroke Scale. These outcome measures, as currently constructed, may be prone to mischaracterizing the quality of stroke care being delivered by hospitals and may ultimately harm acute ischemic stroke patients. This article details (1) why the Centers for Medicare & Medicaid Services acute ischemic stroke outcome measures in their present form may not provide adequate risk adjustment, (2) why the measures as currently designed may lead to inaccurate representation of hospital performance and have the potential for serious unintended consequences, (3) what activities the American Heart Association/American Stroke Association has engaged in to highlight these concerns to the Centers for Medicare & Medicaid Services and other interested parties, and (4) alternative approaches and opportunities that should be considered for more accurately risk-adjusting 30-day outcomes measures in patients with ischemic stroke.
Leukoaraiosis Predicts Cortical Infarct Volume After Distal Middle Cerebral Artery Occlusion
Authors: Henninger Nils , Khan Muhib A. , Zhang Jiaying , Moonis Majaz , Goddeau Richard P.
Published: February 2014

Background and Purpose—

Leukoaraiosis (LA) predominantly affects the subcortical white matter, but mounting evidence suggests an association with cortical microvascular dysfunction and potentially decreased cortical ischemic tolerance. Thus, we sought to assess whether preexisting LA is predictive of the cortical infarct volume after middle cerebral artery branch occlusion and whether it relates to a worse outcome.

Methods—

We analyzed data from 117 consecutive patients with middle cerebral artery branch occlusion as documented by admission computed tomography angiography. Baseline clinical, laboratory, and outcome data, as well as final cortical infarct volumes, were retrospectively analyzed from a prospectively collected database. LA severity was assessed on admission computed tomography using the van Swieten scale grading the supratentorial white matter hypoattenuation. Infarct volume predicting a favorable 90-day outcome (modified Rankin Scale score ≤2) was determined by receiver operating characteristic curves. Multivariable linear and logistic regression analyses were used to identify independent predictors of the final infarct volume and outcome.

Results—

Receiver operating characteristic curve analyses indicated that a final infarct volume of ≤27 mL best predicted a favorable 90-day outcome. Severe LA (odds ratio, 11.231; 95% confidence interval, 2.526–49.926;
P
=0.001) was independently associated with infarct volume >27 mL. Severe LA (odds ratio, 3.074; 95% confidence interval, 1.055–8.961;
P
=0.040) and infarct volume >27 mL (odds ratio, 9.156; 95% confidence interval, 3.191–26.270;
P
<0.001) were independent predictors of a poor 90-day outcome (modified Rankin Scale, 3–6).

Conclusions—

The presence of severe, subcortical LA contributes to larger cortical infarct volumes and worse functional outcomes adding to the notion that the brain is negatively affected beyond LA’s macroscopic boundaries.
Frampton’s Demon: A Mathematical Interpretation of Hollis Frampton’s Zorns Lemma
Authors: Enns Clint
Published: February 2014

Hollis Frampton’s much-discussed film Zorns Lemma is a complex and fascinating film that has a labyrinthine structure, alluding to a mathematical reading of the film as a visual metaphor for Max Zorn’s famous axiom Zorn’s Lemma. In the extensive literature about Zorns Lemma, there have been many different interpretations offered; however, none of these readings has provided a satisfactory mathematical interpretation of the film. After first providing an overview of Zermelo’s Axiom of Choice and some of its equivalent statements, this article provides a mathematical interpretation of Zorns Lemma that shows the film as a cinematic/poetic demonstration of the Axiom of Choice, a statement that is mathematically equivalent to Zorn’s Lemma. In addition, this paper explores some of the consequences of such an interpretation, including one that connects the film to the ideas Frampton was exploring in Magellan.
wUbi-Pen: Sensory Feedback Stylus Interacting with Graphical User Interface
Authors: Kyung Ki-Uk , Lee Jun-Young , Park Junseok , Srinivasan Mandayam A.
Published: February 2014

In this work, we designed an interactive stylus interface for touch-screen devices, the wUbi-Pen haptic stylus. The stylus has functions of providing both vibration and impact with a single actuator, and it is a stand-alone system including its own battery and communication module. We present a new interaction scheme on the graphical user interface (GUI) based on sensory feedback events for clicking, drag-and-drop, moving, sliding, highlighting, and drawing. Experiments evaluating stylus performance indicated that the haptic cues improved precise control of GUI elements. A simple interactive digital sketchbook was also implemented, which provided a variety of haptic feedback while drawing and touching objects.
Stereoscopic Viewing Enhances Visually Induced Motion Sickness but Sound Does Not
Authors: Keshavarz Behrang , Hecht Heiko
Published: February 2014

Optic flow in visual displays or virtual environments often induces motion sickness (MS). We conducted two studies to analyze the effects of stereopsis, background sound, and realism (video vs. simulation) on the severity of MS and related feelings of immersion and vection. In Experiment 1, 79 participants watched either a 15-min-long video clip taken during a real roller coaster ride, or a precise simulation of the same ride. Additionally, half of the participants watched the movie in 2D, and the other half in 3D. MS was measured using the Simulator Sickness Questionnaire (SSQ) and the Fast Motion Sickness Scale (FMS). Results showed a significant interaction for both variables, indicating highest sickness scores for the real roller coaster video presented in 3D, while all other videos provoked less MS and did not differ among one another. In Experiment 2, 69 subjects were exposed to a video captured during a bicycle ride. Viewing mode (3D vs. 2D) and sound (on vs. off) were varied between subjects. Response measures were the same as in Experiment 1. Results showed a significant effect of stereopsis; MS was more severe for 3D presentation. Sound did not have a significant effect. Taken together, stereoscopic viewing played a crucial role in MS in both experiments. Our findings imply that stereoscopic videos can amplify visual discomfort and should be handled with care.
Satisfaction of Spiritual Needs and Self-Rated Health among Churchgoers
Authors: Krause Neal , Hayward R. David , Brucec Deborah , Wooleverc Cynthia
Published: February 2014

Research indicates that greater involvement in religion may be associated with better physical health. The purpose of this study is to see if the satisfaction of spiritual needs is associated with health. This model that contains the following core hypotheses: (1) Individuals who attend church more often are more likely to receive spiritual support from fellow church members than people who attend worship services less frequently (spiritual support is informal encouragement from fellow church members to adopt and implement religious issues in daily life); (2) receiving more spiritual support is associated with stronger feelings of belonging in a congregation; (3) individuals who feel they belong in their congregations are more likely to feel their spiritual needs have been met; and (4) people who feel their spiritual needs have been met are more likely to rate their health in a favorable manner. The data provide support for each of these relationships.
Taxonomic reassessment of Calamagrostis garhwalensis (Poaceae: Agrostidinae)
Authors: PASZKO BEATA
Published: February 2014

Calamagrostis garhwalensis (Poaceae: Agrostidinae) described from northwestern India has been taxonomically controversial. The distinctiveness of this enigmatic and uncommon species is assessed and its taxonomic status partly clarified. Putative relationships among C. garhwalensis and its close relatives from northwestern India, such as C. emodensis, C. gamblei, C. stolizkai and the C. pseudophragmites complex are characterized with a morphometric analysis. The presence of rachilla extensions has been overstated as a diagnostic characteristic for C. garhwalensis. Specimens other than the type previously designated as C. garhwalensis belong in other species. New records of C. garhwalensis are reported from northwestern India and southwestern China.
The Varied Impacts of El Niño–Southern Oscillation on Pacific Island Climates
Authors: Murphy Bradley F. , Power Scott B. , McGree Simon
Published: February 2014

El Niño–Southern Oscillation (ENSO) drives interannual climate variability in many tropical Pacific island countries, but different El Niño events might be expected to produce varying rainfall impacts. To investigate these possible variations, El Niño events were divided into three categories based on where the largest September–February sea surface temperature (SST) anomalies occur: warm pool El Niño (WPE), cold tongue El Niño (CTE), and mixed El Niño (ME), between the other two.

Large-scale SST and wind patterns for each type of El Niño show distinct and significant differences, as well as shifts in rainfall patterns in the main convergence zones. As a result, November to April rainfall in many Pacific island countries is significantly different among the El Niño types. In western equatorial Pacific islands, CTE events are associated with drier than normal conditions whereas ME and WPE events are associated with significantly wetter than normal conditions. This is due to the South Pacific convergence zone and intertropical convergence zone moving equatorward and merging in CTE events. Rainfall in the convergence zones is enhanced during ME and WPE and the displacement is smaller. La Niña events also show robust impacts that most closely mirror those of ME events.

In the northwest and southwest Pacific strong CTE events have much larger impacts on rainfall than ME and WPE, as SST anomalies and correspondingly large-scale surface wind and rainfall changes are largest in CTE. While variations in rainfall exist between different types of El Niño and the significant impacts on Pacific countries of each event are different, the two extreme CTE events have produced the most atypical impacts.
Future Change of Northern Hemisphere Summer Tropical–Extratropical Teleconnection in CMIP5 Models*
Authors: Lee June-Yi , Wang Bin , Seo Kyong-Hwan , Kug Jong-Seong , Choi Yong-Sang , Kosaka Yu , Ha Kyung-Ja
Published: February 2014

Two dominant global-scale teleconnections in the Northern Hemisphere (NH) extratropics during boreal summer season (June–August) have been identified: the western North Pacific–North America (WPNA) and circumglobal teleconnection (CGT) patterns. These teleconnection patterns are of critical importance for the NH summer seasonal climate prediction. Here, how these teleconnections will change under anthropogenic global warming is investigated using representative concentration pathway 4.5 (RCP4.5) experiments by 20 coupled models that participated in phase 5 of the Coupled Model Intercomparison Project (CMIP5). The six best models are selected based on their performance in simulation of the two teleconnection patterns and climatological means and variances of atmospheric circulation, precipitation, and sea surface temperature. The selected models capture the CGT and its relationship with the Indian summer monsoon (ISM) reasonably well. The models can also capture the WPNA circulation pattern but with striking deficiencies in reproducing its associated rainfall anomalies due to poor simulation of the western North Pacific summer monsoon rainfall. The following changes are anticipated in the latter half of twenty-first century under the RCP4.5 scenario: 1) significant weakening of year-to-year variability of the upper-level circulation due to increased atmospheric stability, although the moderate increase in convective heating over the tropics may act to strengthen the variability; 2) intensification of the WPNA pattern and major spectral peaks, particularly over the eastern Pacific–North America and North Atlantic–Europe sectors, which is attributed to the strengthening of its relationship with the preceding mature phase of El Niño–Southern Oscillation (ENSO); and 3) weakening of the CGT due to atmospheric stabilization and decreasing relationship with ISM as well as weakening of the ISM–ENSO relationship.