bluuebunny/crossref_metadata_2025 huggingface dataset:
Pandemic H1N1 influenza-associated myocarditis in a patient with Castleman’s disease
Authors: Roca B , Penades M , Resino E
Published: April 2013

We report on a patient with longstanding multicentric Castleman’s disease, hyaline-vascular type, who presented with nearly-fatal myocarditis associated with a 2009 pandemic H1N1 influenza virus infection. This is the first case of such an association described in the literature.
A case of valproate-induced hyperammonaemic encephalopathy
Authors: Lucie O , Nazir F , Spilg E
Published: April 2013

We report the case of a 65-year-old woman with hyperammonaemic encephalopathy induced by sodium valproate. This is a rare complication of treatment with sodium valproate. The encephalopathy can be reversible on withdrawal of treatment and does carry a risk of morbidity and mortality. This case demonstrates the importance of recognising this potential complication of a drug in common use.
Input processing of Chinese by ab initio learners
Authors: Han ZhaoHong , Liu Zehua
Published: April 2013

We report on a study of first-exposure learners with different first languages (L1s: English, Japanese) to examine their ability to process input for form and meaning. We used a rich set of tasks to tap respectively into processing, comprehension, imitation, and working memory. We show that there are advantages to having a first language (L1) that brings familiarity with the target language. We also show that when presented with natural auditory input, learners are able to process form only minimally. These findings are inconsistent with other studies that suggest that segmentation is easy and rapid. Additionally, we show that such learners comprehend meaning by relying on ‘top-down’ strategies. These findings challenge some of the claims on Input Processing theory.
Pseudoprogression in patients with glioblastoma: added value of arterial spin labeling to dynamic susceptibility contrast perfusion MR imaging
Authors: Choi Young Jun , Kim Ho Sung , Jahng Geon-Ho , Kim Sang Joon , Suh Dae Chul
Published: April 2013

Background

Pseudoprogression is a treatment-related reaction with an increase in contrast-enhancing lesion size, followed by subsequent improvement. Differentiating tumor recurrence from pseudoprogression remains a problem in neuro-oncology.

Purpose

To validate the added value of arterial spin labeling (ASL), compared with dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI) alone, in distinguishing early tumor progression from pseudoprogression in patients with newly diagnosed glioblastoma multiforme (GBM).

Material and Methods

We retrospectively evaluated 117 consecutive patients with newly diagnosed GBM who underwent surgical resection and concurrent chemoradiotherapy (CCRT) as standard treatment modality. Sixty-two patients who developed contrast-enhancing lesions were assessed by both ASL and DSC perfusion MRI and classified into groups of early tumor recurrence ( n = 34) or pseudoprogression ( n = 28) based on pathologic analysis or clinical–radiologic follow-up. We used a qualitative analysis and semi-quantitative grade system on the basis of the tumor perfusion signal intensity into those equal to white matter (grade I), gray matter (grade II), and blood vessels (grade III) on ASL imaging. ASL grade was correlated with histogram parameters derived from DSC perfusion MRI.

Results

Pseudoprogression was observed in 15 (53.6%) patients with ASL grade I, 13 (46.4%) with grade II, and 0 (0%) with grade III, with early tumor progression observed in seven (20.6%) patients with ASL grade I, 11 (32.3%) with grade II, and 16 (47.1%) with grade III ( P = 0.0022). DSC perfusion histogram parameters differed significantly among ASL grades. ASL grade was an independent predictor differentiating pseudoprogression from early tumor progression (odds ratio, 4.73; P = 0.0017). On qualitative review, adjunctive ASL produced eight (12.9%) more accurate results than DSC perfusion MRI alone.

Conclusion

ASL improves the diagnostic accuracy of DSC perfusion MRI in differentiating pseudoprogression from early tumor progression.
Managing a sustainable, low carbon supply chain in the English National Health Service: The views of senior managers
Authors: Grose Jane , Richardson Janet
Published: April 2013

Objectives:

In an effort to reduce costs and respond to climate change, health care providers (Trusts) in England have started to change how they purchase goods and services. Many factors, both internal and external, affect the supply chain. Our aim was to identify those factors, so as to maintain future supply and business continuity in health and social care.

Methods:

Qualitative interviews with 20 senior managers from private and public sector health service providers and social care providers in south west England. Interviews were recorded, transcribed and thematically analysed.

Results:

There were four areas of concern: contradictions with government legislation which caused confusion about how best to deliver sustainable solutions; procurement was unclear and created multiple approaches to purchasing bulk items at low cost; internal organizational systems needed to be reconsidered to embed sustainability; and embedding sustainability requires a review of organizational systems. There are examples of sustainability solutions throughout the National Health Service (NHS) but the response continues to be patchy. More research is needed into why some Trusts and some staff do not recognize the benefits of a core approach or find the systems unable to respond.

Conclusions:

The NHS is one of the major purchasers of goods and services in England and is therefore in an excellent position to encourage sustainable resource management, manufacturing, use and disposal.
Improving the assessment of prescribing: use of a ‘substitution index’
Authors: Kunisawa Susumu , Otsubo Tetsuya , Lee Jason , Imanaka Yuichi
Published: April 2013

Objectives

To analyse the current and potential utilization of generic drugs in Japan, to examine the maximum possible cost savings from generic drug use and to develop a fairer measure to assess the level of generic drug substitution.

Methods

We conducted a cross-sectional retrospective analysis of nine million dispensing records during January to March 2010 in Kyoto Prefecture. Maximum potential quantity-based shares were defined as the quantity of generic drugs used plus the quantity of branded drugs that could have been replaced by generic drugs divided by the quantity of all drugs dispensed. We developed a ‘substitution index’, defined as the proportion of generic drugs out of the total drugs substitutable with generic drugs (based on quantity rather than cost).

Results

Generic drugs had a quantity-based share of 17.9%, a cost-based share of 8.9% and a maximum potential quantity-based share of 50.1%, which is lower than the actual generic drug shares of some other countries. The maximum possible cost savings as a result of generic drug substitution was 16.5%. We also observed wide variations in maximum potential quantity-based shares between health care sectors and health care institutions.

Conclusions

Simple comparisons based on quantity-based shares may misrepresent the actual generic drug use. A substitution index that takes into account the maximum potential quantity-based share of generic drugs as a fairer measure may promote more realistic goals and encourage generic drug usage.
Europe's ‘Horizon 2020’ science funding programme: how is it shaping up?
Authors: Galsworthy Michael , McKee Martin
Published: April 2013

Over the past 15 years, the European Union (EU) has spent around €80 billion on science research via Framework Programmes (FP5, FP6 and FP7). In 2014, a new programme, Horizon 2020, will likely invest another €70 billion over 6 years. Health research has been a major part: between 12% and 17% was spent on official FP5 and FP6 health research lines, although our work categorizing all EU science projects puts the health-related investment proportion nearer to 20%. Here, we compare our analyses and experiences with the European Commission's own impact assessments and plans that inform the Horizon 2020 programme. Much is moving in the right direction but some key gaps are overlooked. We discuss four areas: red tape, what to fund, harnessing informatics and neglect of Eastern Europe.
Plasma pentraxin 3 may be a better marker of peripheral artery disease in hemodialysis patients than C-reactive protein
Authors: Zhou Yijun , Ni Zhaohui , Zhang Jiwei , Zhang Weiming , Wu Qingwei , Shen Guijuan , Wang Yongmei , Qian Jiaqi
Published: April 2013

Pentraxin 3 (PTX3) is a novel inflammatory cytokine produced in atherosclerotic plaque. We hypothesized that this marker may be a better predictor of peripheral artery disease (PAD) than C-reactive protein (CRP) in hemodialysis (HD) patients. The ankle–brachial index (ABI) was measured in HD patients. PTX3 levels in 116 HD patients and 30 healthy blood donors were measured by ELISA. A total of 116 HD patients (age: 56.44 ± 14.08 years) were enrolled; 21 (18%) patients had PAD. PTX3 was significantly higher in PAD versus non-PAD patients (5.55 ± 2.63 vs 2.32 ± 1.29 ng/mL; p < 0.001). In a univariate analysis, ABI correlated significantly with age, blood glucose and triglycerides, and plasma PTX3 ( r = -0.548, p < 0.001) and high-sensitivity (hs)CRP ( r = -0.495, p < 0.001). Using ROC curve analysis for PAD, PTX3 (cut-off value 4.06 ng/mL, AUC 0.901, p < 0.0001) showed a significantly better positive predictive value than hsCRP (cut-off value 3.33 mg/L, AUC 0.640, p < 0.05). Logistic regression analysis further confirmed that PTX3 (OR = 9.755, p = 0.001) was an independent predictor of PAD. In conclusion, we demonstrated that PTX3 may be a better marker of PAD than hsCRP, and independently correlated with PAD in HD patients.
Brain and induced pluripotent stem cell-derived neural stem cells as an in vitro model of neurodegeneration in ataxia-telangiectasia
Authors: Carlessi Luigi , Poli Elena Fusar , Delia Domenico
Published: April 2013

The ataxia telangiectasia mutated (ATM) kinase is a key transducer of the cellular response to DNA double strand breaks and its deficiency causes ataxia-telangiectasia (A-T), a pleiotropic genetic disorder primarily characterized by cerebellar neuropathy, immunodeficiency and cancer predisposition. While enormous progress has been achieved in elucidating the biochemical and functional regulation of ATM in DNA damage response, and more recently in redox signalling and antioxidant defence, the factors that make neurons in A-T extremely vulnerable remain unclear. Given also that ATM knockout mice do not recapitulate the central nervous system phenotype, a number of human neural stem cell (hNSC) model systems have been developed to provide insights into the mechanisms of neurodegeneration associated with ATM dysfunction. Here we review the hNSC systems developed by us an others to model A-T.
CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches
Authors: Williams Karin , Motiani Karan , Giridhar Premkumar Vummidi , Kasper Susan
Published: April 2013

The stem cell niche provides a regulatory microenvironment for cells as diverse as totipotent embryonic stem cells to cancer stem cells (CSCs) which exhibit stem cell-like characteristics and have the capability of regenerating the bulk of tumor cells while maintaining self-renewal potential. The transmembrane glycoprotein CD44 is a common component of the stem cell niche and exists as a standard isoform (CD44s) and a range of variant isoforms (CD44v) generated though alternative splicing. CD44 modulates signal transduction through post-translational modifications as well as interactions with hyaluronan, extracellular matrix molecules and growth factors and their cognate receptor tyrosine kinases. While the function of CD44 in hematopoietic stem cells has been studied in considerable detail, our knowledge of CD44 function in tissue-derived stem cell niches remains limited. Here we review CD44s and CD44v in both hematopoietic and tissue-derived stem cell niches, focusing on their roles in regulating stem cell behavior including self-renewal and differentiation in addition to cell-matrix interactions and signal transduction during cell migration and tumor progression. Determining the role of CD44 and CD44v in normal stem cell, CSC and (pre)metastatic niches and elucidating their unique functions could provide tools and therapeutic strategies for treating diseases as diverse as fibrosis during injury repair to cancer progression.
Endovascular repair of a pseudoaneurysm of the popliteal artery following arthroscopic knee surgery: case report and review of literature
Authors: Aburahma Zachary , Hass Stephen M
Published: April 2013

We report a case of a pseudoaneurysm of the popliteal artery following arthroscopic knee surgery. Endovascular repair was successfully used as the treatment for this patient and studies have shown this to be a safe alternative to surgery.
Repetitive bypass and revisions with extensions for limb salvage after multiple previous failures
Authors: Lipsitz Evan C , Veith Frank J , Cayne Neal S , Harvey John , Rhee Soo J
Published: April 2013

The optimal treatment of patients facing imminent amputation after multiple (≥2) failed prior ipsilateral bypasses is unclear. We analyzed a group of patients undergoing multiple lower extremity bypasses for limb salvage to assess the utility of attempting multiple revascularizations. From 1990 to 2005, 105 revascularization procedures were performed in 55 limbs of 54 patients with imminent limb-threatening lower extremity ischemia after failure of ≥2 prior infrainguinal bypasses in the same leg. Fifty-five operations were the third procedure (Group A) and 50 operations were the fourth or more (Group B). We compared primary/secondary patency and limb salvage rates by Society for Vascular Surgery criteria. Limb salvage rates did not differ between patients undergoing a third bypass and those undergoing four or more bypasses at one year (62 versus 65%, NS) or at three years (58 versus 61%, NS). Secondary patency was not different between groups (76 versus 76%, P = NS) at one and three years (71 versus 70%, NS). Primary patency also did not differ between the two groups, at one year (24 versus 35%, NS), or at three years (11 versus 15%, NS). No differences were observed in morbidity and mortality rates between the groups. In conclusion, the likelihood of success of repetitive limb revascularization was unrelated to the number of previous failures. The expected incremental failure rate with each successive bypass was not found. These results, coupled with the three-year limb salvage rate of over 50% in patients who otherwise would have required amputation, lend support to aggressive use of limb revascularization in selected patients even after two or more failed bypasses.
Anomalous splenic artery aneurysm
Authors: Wong Sydney S N , Lindsay T F , Roche-Nagle G
Published: April 2013

Aneurysms of the splenic artery are the most common visceral aneurysm. A splenomesenteric trunk, which involves the splenic artery arising from the superior mesenteric artery (SMA), is rare and occurs in less than 1% of patients. Thus splenic artery aneurysms (SAAs) with an anomalous origin from the SMA are quite rare. We report our experience with the surgical management of a 2.6-cm aneurysm involving a splenic artery arising from the SMA in a 40-year-old woman. This was treated with surgical resection with preservation of the spleen. A discussion about SAAs and the management of aneurysms arising from a splenomesenteric trunk follows.
The deep femoral artery, a readily available inflow vessel for lower limb revascularization: a single-center experience
Authors: Silverberg Daniel , Sheick-Yousif Basheer , Yakubovitch Dmitry , Halak Moshe , Schneiderman Jacob
Published: April 2013

The deep femoral artery (DFA) offers several advantages as an inflow vessel in lower-extremity bypasses. We report a single-center experience using the DFA as an inflow artery for lower-extremity revascularization. We reviewed all patients who underwent a lower-extremity bypass utilizing the DFA as the inflow vessel. Demographics, indications for surgery, indication for use of the DFA, type of conduits and target vessels were recorded. Follow-up data included resolution of symptoms, bypass graft patency, major amputations and survival. Over 2.5 years, 23 patients were treated with a DFA-inflow bypass. Eighteen (78%) suffered from wounds and five (22%) from rest pain. The proximal, middle and distal DFA was used in 8, 14 and 1 patients, respectively. Indications for using the DFA were limited vein conduit (16) and a hostile groin (5). All patients experienced initial resolution of their ischemic symptoms. The primary patency at two years was 93%. The survival rate was 83%. In conclusion, the DFA is an excellent and underutilized alternative inflow artery in patients requiring lower limb revascularization. It offers excellent patency rates and should be considered in patients with hostile groins or insufficient lengths of a vein conduit.
Plugging and sealing technique by Onyx to prevent type II endoleak in ruptured abdominal aortic aneurysm
Authors: Larzon Thomas , Hörer Tal
Published: April 2013

Control of back bleeding from the hypogastric artery into the aneurysm after endovascular aneurysm repair (EVAR) of a ruptured aortoiliac aneurysm may be necessary in order to avoid a type II endoleak. It is an emergency situation and selective catheterization and embolization of the hypogastric artery may be time-consuming and more importantly, it has to be performed before complete exclusion of the aneurysm has been established. We describe a plugging and sealing technique that embolizes the hypogastric artery after the exclusion of a ruptured aortoiliac aneurysm using the embolizing agent Onyx. The mortality rate of the 16 patients treated in our institute with this technique was 25% (4/16) at 30-day and 31% (5/16) at 90-day follow up. One patient had a type II endoleak at one-year follow-up. The EVAR procedure can focus completely on controlling the acute life-threatening situation, with the embolization performed at the end of the procedure.
Endotension-related aortic sac rupture treated by endograft relining
Authors: Filippi F , Tirotti C , Stella N , Rizzo L , Taurino M
Published: April 2013

Endovascular aortic aneurysm repair is an effective alternative to open surgical repair in high risk patient. Endotension is an unpredictable late and rare complication of EVAR. Clinical significance and choice of technique for treatment are controversial. At present, there are no cases of endotension-related aneurysmal sac rupture reported in literature, altough it is frequently associated with late surgical conversion. In this case report is described a case of a patient treated with a first generation Gore Excluder™ endograft for abdominal aortic aneurysm, with late aneurysmal sac enlargement without evidence of endoleak and subsequent contained rupture without anemia and shock. We have successfully treated the patient by endovascular procedure, through bilateral percutaneous femoral approach, with relining technique. Three years CT scan follow-up showed the endograft patency and size sac reduction.
Regionalization of services improves access to emergency vascular surgical care
Authors: Roche-Nagle G , Bachynski K , Nathens A B , Angoulvant D , Rubin B B
Published: April 2013

Management of vascular surgical emergencies requires rapid access to a vascular surgeon and hospital with the infrastructure necessary to manage vascular emergencies. The purpose of this study was to assess the impact of regionalization of vascular surgery services in Toronto to University Health Network (UHN) and St Michael's Hospital (SMH) on the ability of CritiCall Ontario to transfer patients with life- and limb-threatening vascular emergencies for definitive care. A retrospective review of the CritiCall Ontario database was used to assess the outcome of all calls to CritiCall regarding patients with vascular disease from April 2003 to March 2010. The number of patients with vascular emergencies referred via CritiCall and accepted in transfer by the vascular centers at UHN or SMH increased 500% between 1 April 2003-31 December 2005 and 1 January 2006-31 March 2010. Together, the vascular centers at UHN and SMH accepted 94.8% of the 1002 vascular surgery patients referred via CritiCall from other hospitals between 1 January 2006 and 31 March 2010, and 72% of these patients originated in hospitals outside of the Toronto Central Local Health Integration Network. Across Ontario, the number of physicians contacted before a patient was accepted in transfer fell from 2.9 ± 0.4 before to 1.7 ± 0.3 after the vascular centers opened. In conclusion, the vascular surgery centers at UHN and SMH have become provincial resources that enable the efficient transfer of patients with vascular surgical emergencies from across Ontario. Regionalization of services is a viable model to increase access to emergent care.
Approach to the vascular complications of lumbar disc surgery
Authors: Bozok Sahin , Ilhan Gokhan , Destan Bugra , Gokalp Orhan , Gunes Tevfik
Published: April 2013

The objective of this study was to demonstrate the role of major surgery on patients presenting with vascular complications after lumbar disc surgery. A retrospective analysis of seven cases treated surgically in two tertiary care centers between August 2001 and June 2010 was carried out. The average age of patients (three women and four men) was 35.8 ± 7.2. The most common vessel injured was the left common iliac artery occurring in five patients (71.4%), followed by the left common iliac vein injury detected in two patients (28.5%). Transperitoneal approach was preferred in all cases and primary suturing, graft interposition and end-to-end anastomoses were the surgical methods used for the repair of vascular injury. No mortality was seen in our series during the follow-up period of two years; however, the most noteworthy complication was paraplegia occurring in one patient. Vascular injury occurring at lumbar discus surgery has a considerable potential for morbidity and mortality. A high index of suspicion is necessary for early diagnosis. In hemodynamically instable patients, the transperitoneal approach provides better exposure and more effective control of hemorrhage, while minimal angiography and endovascular intervention should be preserved for hemodynamically stable cases.
Student and infection prevention and control nurses’ hand hygiene decision making in simulated clinical scenarios: a qualitative research study of hand washing, gel and glove use choices
Authors: Lee Karen
Published: April 2013

Final year nursing students and infection prevention and control nurses were recorded verbalising their hand hygiene decision-making while working through clinical scenarios on a computer, to understand what factors they were taking into account in choosing a decontamination method (hand washing or alcohol based hand rub/gel) or to wear gloves. Results demonstrated an overuse of gloves, and underuse of gel. Three main themes emerged: ‘Experience or expectation’; this was what they had seen on placement, or it was what ‘we’ do. ‘Just in case,’ was characterised by an awareness that what they would do wasn’t actually necessary but they tended to do it anyway. Thirdly, ‘gel doesn’t feel clean,’ was characterised by a feeling that using gel didn’t make the nurses feel clean after ‘dirty’ tasks, even though gel is actually more effective. There was little evidence that participants were making risk assessments based on the individual patient characteristics given, or the tasks, as they had been taught to do. Choice of hand decontamination agent and whether to use gloves appeared to be based on an habitual characterisation of whether the task was ‘clean’ or ‘dirty,’ with a very low threshold for ‘dirty’ based on an excessive perception of risk to the student.
The importance of local criteria in the diagnosis of metabolic syndrome in Saudi Arabia
Authors: Bahijri Suhad M. , Al Raddadi Rajaa M.
Published: April 2013

The clustering of risk factors predisposing an individual to cardiovascular morbidity and mortality are usually referred to as the ‘metabolic syndrome’ (MS). Several definitions exist, causing confusion to practicing clinicians. A consensus definition was reached by several major organizations stating that the presence of any three of five risk factors (abdominal obesity, elevated triglyceride, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose) constitutes a diagnosis. Cutoff points for each of the risk factors were defined, taking into account ethnicity in case of abdominal obesity. The prevalence of MS has been reported to be on the rise globally, and was mainly attributed to changes in diet and lifestyle, in addition to genetic factors and metabolic susceptibility. The risk of cardiovascular disease (CVD) has almost doubled and the risk of developing type 2 diabetes mellitus (T2DM) has increased fivefold in individuals diagnosed with MS. The prevalence T2DM in Saudi Arabia is increasing, making it an epidemic health hazard. Intervention programs to decrease the risk of progression from MS to full T2DM, and later CVD have been successful in many countries. Therefore, diagnosing MS is important to address risk factors and to prevent progression to the more serious chronic conditions.

The prevalence of MS in Saudi adults varies from 16% to 40% depending on the definition used and the study location. Use of the consensus definition might decrease the number of missed cases. However, in the absence of local cutoff points for various risk factors for MS, the use of ratios such as waist/hip ratio and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, and family history of diabetes and CVD might aid diagnosis. Priority should be given to establishing national normal ranges, screening programs for hyperglycemia and hypertension, and community-directed programs to combat obesity and inactivity.
What Makes the Names of Middle-earth So Fitting? Elements of Style in the Namecraft of J. R. R. Tolkien
Authors: Robinson Christopher L
Published: April 2013

AbstractWhat makes a name ‘fitting’? Or, in closely related formulations, what makes a name ‘sound right’ or ‘ring true’? From the Cratylus to present-day studies in literary onomastics, the usual answer is that a name is fitting, right, or true for the person, place, or thing that bears it. The names in J. R. R. Tolkien’s fiction are fitting in this sense, reflecting by way of their source words, sound symbolism, or etymology some characteristic of their designees. At the same time, however, Tolkien insists that a name fit not only its designee, but also the phonological and morphological style of the nomenclature to which it belongs, as well as the linguistic scheme of his invented world. These elements of style are determined at the level of the nomenclature as a whole, independently from concerns with the motivation of individual names. The personal and place names of Middle-earth are thus fitting in more than the usual sense.
Dickensian Eponyms
Authors: Abel Ernest L
Published: April 2013

AbstractCharles Dickens created almost a thousand fictional characters, many of whom have become synonyms for distinctive types of people or their pecu- liar traits. This article surveys seventeen Dickensian eponyms, cites their first appearance as such, and provides examples of their usage in magazines, books, and the Internet.
Study on mechanical and magnetic properties of Cu/Ni multilayer composite fabricated by accumulative roll bonding process
Authors: Eslami A H , Zebarjad S Mojtaba , Moshksar M M
Published: April 2013

Accumulative roll bonding (ARB) has been used as a severe plastic deformation process for the production of high strength materials. In the current research, multilayered copper/nickel composites were produced by the ARB process using nickel and copper strips. Tensile and magnetic behaviours of produced composites were investigated by universal tensile machine and magnetic device detector (vibrating sample magnetometers) respectively. It was observed that as passes of ARB proceeded, nickel layers were necked and fractured gradually. After five roll bonding passes, a multilayer copper/nickel composite including homogeneously distributed fragmented nickel layers in the copper matrix was achieved. Magnetic and mechanical properties of these composites were studied within different stages of the ARB process. With increasing strain during ARB passes, strength, microhardness and elongation of these composites increased. Enhancement of the strength is higher than the tensile strength of copper/copper multilayered strips produced by the ARB process. In addition, it has been found that the magnetic properties, e.g. retentivity, coercivity and magnetic saturation of the multilayer composite, were significantly influenced by the changes in microstructural and grain size.
Convergence analysis of an iterative algorithm for monotone operators
Authors: Cho Sun Young , Li Wenling , Kang Shin Min
Published: April 2013

In this paper, an iterative algorithm is proposed to study some nonlinear operators which are inverse-strongly monotone, maximal monotone, and strictly pseudocontractive. Strong convergence of the proposed iterative algorithm is obtained in the framework of Hilbert spaces.

MSC:47H05, 47H09.
A subgraph isomorphism algorithm and its application to biochemical data
Authors: Bonnici Vincenzo , Giugno Rosalba , Pulvirenti Alfredo , Shasha Dennis , Ferro Alfredo
Published: April 2013

Background

Graphs can represent biological networks at the molecular, protein, or species level. An important query is to find all matches of a pattern graph to a target graph. Accomplishing this is inherently difficult (NP-complete) and the efficiency of heuristic algorithms for the problem may depend upon the input graphs. The common aim of existing algorithms is to eliminate unsuccessful mappings as early as and as inexpensively as possible.

Results

We propose a new subgraph isomorphism algorithm which applies a search strategy to significantly reduce the search space without using any complex pruning rules or domain reduction procedures. We compare our method with the most recent and efficient subgraph isomorphism algorithms (VFlib, LAD, and our C++ implementation of FocusSearch which was originally distributed in Modula2) on synthetic, molecules, and interaction networks data. We show a significant reduction in the running time of our approach compared with these other excellent methods and show that our algorithm scales well as memory demands increase.

Conclusions

Subgraph isomorphism algorithms are intensively used by biochemical tools. Our analysis gives a comprehensive comparison of different software approaches to subgraph isomorphism highlighting their weaknesses and strengths. This will help researchers make a rational choice among methods depending on their application. We also distribute an open-source package including our system and our own C++ implementation of FocusSearch together with all the used datasets (http://ferrolab.dmi.unict.it/ri.html). In future work, our findings may be extended to approximate subgraph isomorphism algorithms.
Constant or fluctuating hyperglycemias increases cytomembrane stiffness of human umbilical vein endothelial cells in culture: roles of cytoskeletal rearrangement and nitric oxide synthesis
Authors: Chen Xianxian , Feng Lie , Jin Hua
Published: April 2013

Background

Previous studies have implicated continuous or intermittent hyperglycemia in altered endothelium-derived nitric oxide (NO) synthesis. NO can regulate both the F-actin cytoskeleton and endothelial cell membrane stiffness. Atomic force microscopy (AFM) is a powerful tool that can be used to study plasma membrane deformability at the single cell level. As membrane stiffness is partially dependent on filamentous F-actin, the interdependence of these parameters can be studied through the combined approaches of AFM and laser scanning confocal microscopy (LSCM). In the present study, we evaluated the effects of constant or fluctuating hyperglycemia on endothelial-derived NO synthesis, the cytoskeletal contribution and endothelial cell membrane stiffness.

Results

Compared to control cells cultured in low glucose (5 mM), constant (25 mM) or fluctuating (25/5 mM) high glucose significantly decreased NO release along with stiffening of endothelial cell membranes and F-actin rearrangement. The non-selective nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) exerted similar effects on endothelial cells. Increasing concentrations of L-NAME (from 0.1 to 1 mM) exacerbated these effects in a concentration-dependent manner.

Conclusions

Result from the present study suggest that stiffening endothelial cell membranes are associated with decreased NO synthesis, which was established through the F-actin cytoskeletal redistribution. The precise mechanisms of hyperglycemia-induced endothelial dysfunction require further investigation.
Fast immunosensing technique to detect Legionella pneumophila in different natural and anthropogenic environments: comparative and collaborative trials
Authors: Bedrina Begoña , Macián Sonia , Solís Inmaculada , Fernández-Lafuente Roberto , Baldrich Eva , Rodríguez Guillermo
Published: April 2013

Background

Legionellosis is an uncommon form of pneumonia. After a clinical encounter, the necessary antibiotic treatment is available if the diagnosis is made early in the illness. Before the clinical encounter, early detection of the main pathogen involved,Legionella pneumophila, in hazardous environments is important in preventing infectious levels of this bacterium. In this study a qualitative test based on combined magnetic immunocapture and enzyme-immunoassay for the fast detection ofLegionella pneumophilain water samples was compared with the standard method, in both comparative and collaborative trials. The test was based on the use of anti-Legionella pneumophilaantibodies immobilized on magnetic microspheres. The final protocol included concentration by filtration, resuspension and immunomagnetic capture. The whole assay took less than 1 hour to complete.

Results

A comparative trial was performed against the standard culture method (ISO 11731) on both artificially and naturally contaminated water samples, for two matrices: chlorinated tap water and cooling tower water. Performance characteristics of the test used as screening with culture confirmation resulted in sensitivity, specificity, false positive, false negative, and efficiency of 96.6%, 100%, 0%, 3.4%, and 97.8%, respectively. The detection limit at the level under which the false negative rate increases to 50% (LOD50) was 93 colony forming units (CFU) in the volume examined for both tested matrices. The collaborative trial included twelve laboratories. Water samples spiked with certified reference materials were tested. In this study the coincidence level between the two methods was 95.8%.

Conclusion

Results demonstrate the applicability of this immunosensing technique to the rapid, simple, and efficient detection ofLegionella pneumophilain water samples. This test is not based on microbial growth, so it could be used as a rapid screening technique for the detection ofL. pneumophilain waters, maintaining the performance of conventional culture for isolation of the pathogen and related studies.
Increased risk of deep neck infection among HIV-infected patients in the era of highly active antiretroviral therapy—a population-based follow-up study
Authors: Liu Ching-Feng , Weng Shih-Feng , Lin Yung-Song , Lin Chih-Sheng , Lien Ching-Feng , Wang Jhi-Joung
Published: April 2013

Background

Deep neck infections (DNIs) in HIV-infected patients often produce severe complications, even death. Data on the incidence rates and risks of DNI among HIV-infected patients are scarce, particularly with the widespread use of highly active antiretroviral therapy (HAART). We evaluated the incidence rates and risks for DNI among HIV-infected patients and observed the long-term trends.

Methods

A total of 9888 new HIV-infected patients diagnosed in 2001–2007 were included and matched with 49440 randomly selected subjects. The HIV-infected subjects were offered free access to HAART. All subjects were traced until December 2009. A Kaplan-Meier analysis generated the cumulative DNI incidence rate. The adjusted hazard ratio was computed using Cox proportional hazard regressions.

Results

From the HIV-infected and comparison cohorts, 222 individuals (57.01 cases per 10000 person-years) and 735 individuals (35.54 cases per 10000 person-years) developed DNI, respectively. The log rank test indicated that patients with HIV had a significantly higher 8-year incidence rate of DNI than the control group (P < 0.0001). The adjusted hazard ratio for developing DNI after an HIV attack during the mean 3.94 years follow-up period was 1.59. The incidence rate and relative risk of DNI were 74.58 (per 10000 person-years) and 2.05 (P < 0.0001). Both figures were highest in the first follow-up year and decreased year-by-year thereafter.

Conclusion

The risk of developing DNI is significantly elevated among HIV-infected patients, even with free access to HAART. Additional research is needed to examine the role of HAART in reducing the risk.
In vitro and in vivo effects of geranylgeranyltransferase I inhibitor P61A6 on non-small cell lung cancer cells
Authors: Zimonjic Drazen B , Chan Lai N , Tripathi Veenu , Lu Jie , Kwon Ohyun , Popescu Nicholas C , Lowy Douglas R , Tamanoi Fuyuhiko
Published: April 2013

Background

Lung cancer is the leading cause of cancer-related mortality. Therapies against non-small cell lung cancer (NSCLC) are particularly needed, as this type of cancer is relatively insensitive to chemotherapy and radiation therapy. We recently identified GGTI compounds that are designed to block geranylgeranylation and membrane association of signaling proteins including the Rho family G-proteins. One of the GGTIs is P61A6 which inhibits proliferation of human cancer cells, causes cell cycle effects with G1 accumulation and exhibits tumor-suppressing effects with human pancreatic cancer xenografts. In this paper, we investigated effects of P61A6 on non-small cell lung cancer (NSCLC) cells in vitro and in vivo.

Methods

Three non-small cell lung cancer cell lines were used to test the ability of P61A6 to inhibit cell proliferation. Further characterization involved analyses of geranylgeranylation, membrane association and activation of RhoA, and anchorage-dependent and –independent growth, as well as cell cycle effects and examination of cell cycle regulators. We also generated stable cells expressing RhoA-F, which bypasses the geranylgeranylation requirement of wild type RhoA, and examined whether the proliferation inhibition by P61A6 is suppressed in these cells. Tumor xenografts of NSCLC cells growing in nude mice were also used to test P61A6’s tumor-suppressing ability.

Results

P61A6 was shown to inhibit proliferation of NSCLC lines H358, H23 and H1507. Detailed analysis of P61A6 effects on H358 cells showed that P61A6 inhibited geranylgeranylation, membrane association of RhoA and caused G1 accumulation associated with decreased cyclin D1/2. The effects of P61A6 to inhibit proliferation could mainly be ascribed to RhoA, as expression of the RhoA-F geranylgeranylation bypass mutant rendered the cells resistant to inhibition by P61A6. We also found that P61A6 treatment of H358 tumor xenografts growing in nude mice reduced their growth as well as the membrane association of RhoA in the tumors.

Conclusion

Thus, P61A6 inhibits proliferation of NSCLC cells and causes G1 accumulation associated with decreased cyclin D1/2. The result with the RhoA-F mutant suggests that the effect of P61A6 to inhibit proliferation is mainly through the inhibition of RhoA. P61A6 also shows efficacy to inhibit growth of xenograft tumor.
Sexually transmitted infections among HIV-infected women in Thailand
Authors: Asavapiriyanont Suvanna , Lolekha Rangsima , Roongpisuthipong Anuvat , Wiratchai Amornpan , Kaoiean Surasak , Suksripanich Orapin , Chalermchockcharoenkit Amphan , Ausavapipit Jaruensook , Srifeungfung Somporn , Pattanasin Sarika , Katz Kenneth A
Published: April 2013

Background

Data on sexually transmitted infections (STI) prevalence among HIV-infected women in Thailand are limited. We studied, among HIV-infected women, prevalence of STI symptoms and signs; prevalence and correlates of having any STI; prevalence and correlates ofChlamydia trachomatis(CT) orNeisseria gonorrhoeae(GC) among women without CT and/or GC symptoms or signs; and number of women without CT and/or GC symptoms or signs needed to screen (NNS) to detect one woman with CT and/or GC overall, among pregnant women, and among women ≤25 years.

Methods

During October 2004–September 2006, HIV-infected women at 3 obstetrics and gynecology clinics were asked about sexual behaviors and STI symptoms, physically examined, and screened for chlamydia, gonorrhea, trichomoniasis, and syphilis. Multivariate logistic regression was used to identify correlates of infections. NNS was calculated using standard methods.

Results

Among 1,124 women, 526 (47.0%) had STI symptoms or signs, 469 (41.7%) had CT and/or GC symptoms or signs, and 133 (11.8%) had an STI. Correlates of having an STI included pregnancy and having STI signs. Among 469 women and 655 women with vs. without CT and/or GC symptoms or signs, respectively, 43 (9.2%) vs. 31 (4.7%), 2 (0.4%) vs. 9 (1.4%), and 45 (9.6%) vs. 38 (5.8%) had CT, GC, or “CT or GC”, respectively; correlates included receiving care at university hospitals and having sex with a casual partner within 3 months. NNS for women overall and women ≤25 years old were 18 (95% CI, 13-25) and 11 (95% CI, 6-23), respectively; and for pregnant and non-pregnant women, 8 (95% CI, 4-24) and 19 (95% CI, 14-27), respectively.

Conclusions

STI prevalence among HIV-infected women, including CT and GC among those without symptoms or signs, was substantial. Screening for CT and GC, particularly for pregnant women, should be considered.
Artemisinin-based combination therapy availability and use in the private sector of five AMFm phase 1 countries
Authors: Davis Ben , Ladner Joel , Sams Kelley , Tekinturhan Ebru , de Korte Donald , Saba Joseph
Published: April 2013

Background

In 2009, the Global Fund to Fight AIDS, Tuberculosis and Malaria established the Affordable Medicines Facility-malaria (AMFm) in order to increase access to quality-assured artemisinin combination therapy (QAACT). AMFm Phase 1, which includes nine pilot programmes in eight countries, was launched in 2009. The objective of this study was to assess anti-malarial stock and purchase patterns at private outlets in five AMFm Phase 1 countries in regard to three of the core AMFm goals: increase the affordability of QAACT, increase the availability of QAACT, and crowd out artemisinin monotherapies and other substandard therapies.

Methods

The study was conducted between April and May 2012 and included interviews with personnel in 598 private pharmaceutical outlets in Ghana, Kenya, Nigeria, Tanzania, and Uganda. Questionnaires were administered at private retail outlets and the data were analyzed to assess within- and between-country differences in QAACT price, availability, and popularity.

Results

AMFm medications were less expensive than their non-AMFm counterparts, yet prices for both types were above country-specific suggested retail prices. Market penetration of AMFm QAACT in both urban and rural areas was high, although stock-outs of both AMFm and non-AMFm products were more common in rural compared with urban outlets in Ghana and Kenya (p = 0.0013). Government recommendation was the most significant factor influencing anti-malarial stock choices in urban (41.5%) and rural (31.9%) outlets. The three top-selling anti-malarials reported for both urban and rural areas in each country were, with the exception of rural Uganda and urban Nigeria, combination therapies.

Conclusions

Results from this study indicate that the AMFm has not fully achieved its affordability and crowd-out objectives. Still, the final purchase price of AMFm QAACT was substantially lower than non-AMFm equivalents. Moreover, for both urban and rural areas, AMFm QAACT availability was found to be high, and the various forms of QAACT were the best-selling products among all anti-malarials. These findings suggest a continued need for initiatives like the AMFm that improve the affordability and accessibility of QAACT. Similar programmes may be especially effective if employed in combination with rapid diagnostic testing to ensure the appropriate use of these products.
Clinicopathologic characteristics at diagnosis and the survival of patients with medullary breast carcinoma in China: a comparison with infiltrating ductal carcinoma-not otherwise specified
Authors: Cao A-Yong , He Min , Huang Liang , Shao Zhi-Ming , Di Gen-Hong
Published: April 2013

Background

Few studies have addressed the biological features of medullary breast carcinoma (MBC) in the context of clinical outcomes. We sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between MBC and infiltrating ductal carcinoma-not otherwise specified (IDC-NOS) using a large database.

Methods

A total of 2,202 cases with pure IDC-NOS and 188 cases with typical MBC meeting the inclusion criteria were identified. The clinical and biological features, the overall survival (OS) and recurrence/metastasis-free survival (RFS) were compared for both groups.

Results

There were a higher proportion of patients diagnosed prior to 40 years of age in the MBC group compared to the IDC-NOS group. MBC cases demonstrated less aggressive tumor features such as lower tumor stage, smaller tumor size and a lower proportion of nodal involvement than IDC-NOS; however, immunohistochemical staining revealed that MBC displayed the triple-negative phenotype more often than IDC-NOS cases (40.4% versus 26.2%; P <0.001). Although the clinical behavior of MBC was not commensurate with its pathologic features, women diagnosed with MBC had a lower frequency of recurrence/metastasis (P = 0.032) and death (P = 0.042) than those with IDC-NOS, and the 10-year OS and RFS were significantly higher for MBC (91% and 74%) compared to IDC-NOS (81% and 64%). Moreover, multivariate analysis revealed that TNM stage was a statistically significant factor for survival.

Conclusions

MBC in Chinese women demonstrated less aggressive behavior and better prognosis than IDC-NOS. This favorable outcome was maintained after 10 years.