bluuebunny/crossref_metadata_2025 huggingface dataset:
The complexity of computing a Nash equilibrium
Authors: Daskalakis Constantinos , Goldberg Paul W. , Papadimitriou Christos H.
Published: January 2009

How long does it take until economic agents converge to an equilibrium? By studying the complexity of the problem of computing a mixed Nash equilibrium in a game, we provide evidence that there are games in which convergence to such an equilibrium takes prohibitively long. Traditionally, computational problems fall into two classes: those that have a polynomial-time algorithm and those that are NP-hard. However, the concept of NP-hardness cannot be applied to the rare problems where "every instance has a solution"---for example, in the case of games Nash's theorem asserts that every game has a mixed equilibrium (now known as the Nash equilibrium, in honor of that result). We show that finding a Nash equilibrium is complete for a class of problems called PPAD, containing several other known hard problems; all problems in PPAD share the same style of proof that every instance has a solution.
The national tech agenda 2009
Authors: Weiss Aaron
Published: January 2009

In the U.S. the new year also ushers in a new and much-anticipated government, the administration of President-elect Barack Obama. Considering that Obama's most popular campaign theme was "hope," it is not surprising that he will find himself in the position of a figurative Santa Claus---deluged by the wish lists of thousands of competing interests. There is hardly a field---from the environment to education to scientific research to public transportation---where advocates haven't pinned big hopes on the Obama administration to advance their agendas.
Methods for extracting place semantics from Flickr tags
Authors: Rattenbury Tye , Naaman Mor
Published: January 2009

We describe an approach for extracting semantics for tags, unstructured text-labels assigned to resources on the Web, based on each tag's usage patterns. In particular, we focus on the problem of extracting place semantics for tags that are assigned to photos on Flickr, a popular-photo sharing Web site that supports location (latitude/longitude) metadata for photos. We propose the adaptation of two baseline methods, inspired by well-known burst-analysis techniques, for the task; we also describe two novel methods, TagMaps and scale-structure identification. We evaluate the methods on a subset of Flickr data. We show that our scale-structure identification method outperforms existing techniques and that a hybrid approach generates further improvements (achieving 85% precision at 81% recall). The approach and methods described in this work can be used in other domains such as geo-annotated Web pages, where text terms can be extracted and associated with usage patterns.
Conference announcement
Authors: Das Sanmay , Ostrovsky Michael
Published: January 2009

We announce a new conference series, the Conferences on Auctions, Market Mechanisms, and Their Applications (AMMA), and the first edition of this conference, to be held in Boston in May 2009.
Diversification in the internet economy
Authors: Singh Sudhir Kumar , Roychowdhury Vwani , Gunadhi Himawan , Rezaei Behnam
Published: January 2009

We investigate market forces that would lead to the emergence of new classes of players in the sponsored search advertising market. We report a multi-fold diversification triggered by an inherent feature of the sponsored search market, namely, capacity constraints, arising from the fact that there is a limit on the number of available advertisement slots, especially for the popular keywords. As a result, a significant pool of interested advertisers are left out. We present a comparative study of two scenarios motivated by capacity constraints - one where the additional capacity is provided by for-profit agents (or, mediators), who compete for slots in the original auction, draw traffic, and run their own sub-auctions, and the other, where the additional capacity is provided by the auctioneer herself, by essentially acting as a mediator and running a single combined auction. The quality of the additional capacity is measured by its fitness factor. We observe that the single combined-auction model seems inferior to the mediator-based model and market becomes more capacity efficient in the latter. For instance, the revenue of the auctioneer always increases when mediators are involved, unlike the auctioneer based scenario where often there is a tradeoff between the revenue and the capacity. Further, the social value (i.e. efficiency) always increases when mediators are involved. Thus, our analysis indicates that there are significant opportunities for diversification in the internet economy and we should expect it to continue to develop richer structure, with room for different types of market entities and mechanisms to coexist.
Solution to exchanges 7.2 puzzle
Authors: Søensen Troels Bjerre
Published: January 2009

This is a solution to the editors puzzle from Issue 7.2 of SIGecom Exchanges. The puzzle is about predicting what products one can expect to see in a market with given positive and negative synergies between products. The full puzzle can be found online at the SIGecom website [Conitzer 2008].
Issues with network address translation for SCTP
Authors: Hayes David A. , But Jason , Armitage Grenville
Published: January 2009

A Stream Control Transmission Protocol (SCTP) capable Network Address Translation (NAT) device is necessary to support the wider deployment of the SCTP protocol. The key issues for an SCTP NAT are SCTP's control chunk multiplexing and multi-homing features. Control chunk multiplexing can expose an SCTP NAT to possible Denial of Service attacks. These can be mitigated through the use of chunk and parameter processing limits.

Multiple and changing IP addresses during an SCTP association, mean that SCTP NATs cannot operate in the way conventional UDP/TCP NATs operate. Tracking these multiple global IP addresses can help in avoiding lookup table conflicts, however, it can also result in circumstances that can lead to NAT state inconsistencies. Our analysis shows that tracking global IP addresses is not necessary in most expected practical installations.

We use our FreeBSD SCTP NAT implementation, alias_sctp to examine the performance implications of tracking global IP addresses. We find that typical memory usage doubles and that the processing requirements are significant for installations that experience high association arrival rates.

In conclusion we provide practical recommendations for a secure stable SCTP NAT installation.
60GHz
Authors: Yang L. Lily
Published: January 2009

60 GHz is considered the most promising technology to deliver gigabit wireless for indoor communications. We propose to integrate 60 GHz radio with the existing Wi-Fi radio in 2.4/5 GHz band to take advantage of the complementary nature of these different bands. This integration presents an opportunity to provide a unified technology for both gigabit Wireless Personal Area Networks (WPAN) and Wireless Local Area Networks (WLAN), thus further reinforcing the technology convergence that is already underway with the widespread adoption of Wi-Fi technology. Many open research questions remain to make this unified solution work seamlessly for WPAN and WLAN.
You must be joking...
Authors: Faloutsos Michalis
Published: January 2009

It is clearly a time of change. Naturally, I am talking about the change of person in the top post: "Le Boss Grand" Christophe Diot is replaced by "Canadian Chief, Eh?" Srinivasan Keshav. Coincidence? No, my friends. This change of the guards in the most powerful position in CCR, and, by some stretch of the imagination, in SIGCOMM, and, by arbitrary extension, in the scientific world at large, is just the start of a period of change that will be later known as the Great Changes. Taking the cue from that, I say, let's change.
Calibrated Pulse-Thermography Procedure for Inspecting HDPE
Authors: Omar Mohammed A. , Zhou Yi , Parvataneni Rohit , Planting Eric
Published: January 2009

This manuscript discusses the application of a pulse-thermography modality to evaluate the integrity of a high-density polyethylene HDPE joint for delamination, in nonintrusive manner. The inspected HDPE structure is a twin-cup shape, molded through extrusion, and the inspection system comprises a high-intensity, short-duration radiation pulse to excite thermal emission; the text calibrates the experiment settings (pulse duration, and detector sampling rate) to accommodate HDPE bulks thermal response. The acquired thermal scans are processed through new contrast computation named “self-referencing”, to investigate the joint tensile strength and further map its adhesion interface in real-time. The proposed system (hardware, software combination) performance is assessed through an ultrasound C-scan validation and further benchmarked using a standard pulse phase thermography (PPT) routine.
Discrimination between Ictal and Seizure‐Free EEG Signals Using Empirical Mode Decomposition
Authors: Pachori Ram Bilas
Published: January 2009

A new method for analysis of electroencephalogram (EEG) signals using empirical mode decomposition (EMD) and Fourier‐Bessel (FB) expansion has been presented in this paper. The EMD decomposes an EEG signal into a finite set of band‐limited signals termed intrinsic mode functions (IMFs). The mean frequency (MF) for each IMF has been computed using FB expansion. The MF measure of the IMFs has been used as a feature in order to identify the difference between ictal and seizure‐free intracranial EEG signals. It has been shown that the MF feature of the IMFs has provided statistically significant difference between ictal and seizure‐free EEG signals. Simulation results are included to illustrate the effectiveness of the proposed method.
Islet Specific Wnt Activation in Human Type II Diabetes
Authors: Lee Seung-Hee , Demeterco Carla , Geron Ifat , Abrahamsson Annelie , Levine Fred , Itkin-Ansari Pamela
Published: January 2009

The Wnt pathway effector gene TCF7L2 has been linked to type II diabetes, making it important to study the role of Wnt signaling in diabetes pathogenesis. We examined the expression of multiple Wnt pathway components in pancreases from normal individuals and type II diabetic individuals. Multiple members of the Wnt signaling pathway, including TCF7L2, Wnt2b, β‐catenin, pGSK3β, TCF3, cyclinD1, and c‐myc, were undetectable or expressed at low levels in islets from nondiabetic individuals, but were also upregulated specifically in islets of type II diabetic patients. Culture of pancreatic tissue and islet isolation led to Wnt activation that was reversed by the Wnt antagonist sFRP, demonstrating that Wnt activation in that setting was due to soluble Wnt factors. These data support a model in which the Wnt pathway plays a dynamic role in the pathogenesis of type II diabetes and suggest manipulation of Wnt signaling as a new approach to β‐cell‐directed diabetes therapy.
MCA Model for Simulating the Failure of Microinhomogeneous Materials
Authors: Tan Yunliang , Teng Guirong , Li Haitao
Published: January 2009

A special cellular automaton (CA) model called mechanical cellular automaton (MCA) is built, in which inhomogeneity of material cell can be evaluated by Weibull′s distribution function. In MCA, such material physical parameters as energy or strength and anisotropy defined by the different transferring energies along different directions are adopted. To simulate a crack or a weak zone, a cluster of weak energy cells are disposed. By the MCA, examples of failure evolving process of material containing one crack, two parallel cracks, and two cracks by bridge conjunction are simulated. The results show for inhomogeneous materials that their failure behaviors are much different from homogeneous ones, self‐organization must be considered, and traditional homogeneous mechanics cannot be applied by copying word to word.
Proposal of a New Hypothesis on the Development of Colorectal Epithelial Neoplasia: Nonspecific Inflammation – Colorectal Paneth Cell Metaplasia – Colorectal Epithelial Neoplasia
Authors: Wada Ryo
Published: January 2009

Colorectal epithelial neoplasia (CR-EN), both adenoma and adenocarcinoma, may develop from the essential tubules of the colorectum. In order to conclude the carcinogenesis of the colorectal cancer more clearly, the biological features including the genetic abnormality of the nonneoplastic mucosal epithelium of colon and rectum, which coexist in connection with CR-EN, should be investigated. In this review, the importance of Paneth cell metaplasia of colorectum as one of the original mucosal regions of the development of CR-EN, and the new hypothesis on the development of CR-EN (nonspecific inflammation – colorectal Paneth cell metaplasia – colorectal epithelial neoplasia) are examined.
Pathological Diagnosis of Early Colorectal Carcinoma and Its Clinical Implications
Authors: Fujimori Takahiro , Fujii Shigehiko , Saito Natsuko , Sugihara Kenichi
Published: January 2009

This review consists of 6 sections: (1) pathological diversity of cancer and the correlation between ‘zokushutsu’ (budding/sprouting) and lymph node metastasis; (2) genetic analysis and metastasis in the gastrointestinal tract; (3) conditions requiring resection after endoscopic treatment; (4) improvement of methods used to measure depth of submucosal invasion in the Ip type; (5) Japanese morphological classification of colorectal neoplastic lesions in terms of the clinical pathology and genetics of laterally spreading tumors; (6) villous tumors.
Primary Aldosteronism
Authors: Carey Robert M.
Published: January 2009

Background: Hypertension is one of the world’s leading risk factors for morbidity and mortality. Most affected individuals have primary hypertension, while the most common cause of secondary hypertension is primary aldosteronism (6–10%). Primary Aldosteronism: Clinical manifestations include hypertension, hypokalemic alkalosis, renal dysfunction, nephrogenic diabetes insipidus, muscle weakness, paresthesias, tetany and, in severe cases, paralysis. The cardiovascular risks for patients with primary aldosteronism are greater than those for patients with primary hypertension. Compared with normotensive subjects, patients with primary aldosteronism have a 4.2-fold greater risk of stroke, a 6.5-fold greater risk of myocardial infarction and a 12.1-fold greater risk of atrial fibrillation. Diagnosis: Patients with hypertension are screened for primary aldosteronism based on the plasma aldosterone to plasma renin activity ratio. A value >30 constitutes a positive result. The diagnosis must be confirmed using one of four available aldosterone suppression tests. Lateralization of aldosterone hypersecretion is documented by adrenal venous sampling. Management: The foundation of primary aldosteronism management is normalization of circulating aldosterone and/or mineralocorticoid blockade. Optimal treatment of unilateral disease is adrenalectomy; spironolactone is the treatment of choice for bilateral disease.
Is Epigenetics an Important Link between Early Life Events and Adult Disease?
Authors: Waterland Robert A.
Published: January 2009

Background: Epigenetic mechanisms provide one potential explanation for how environmental influences in early life cause long-term changes in chronic disease susceptibility. Whereas epigenetic dysregulation is increasingly implicated in various rare developmental syndromes and cancer, the role of epigenetics in complex chronic diseases, such as cardiovascular disease, type 2 diabetes and obesity, remains largely uncharacterized. Extensive work in animal models is required to develop specific hypotheses that can be practicably tested in humans. Animal Models: We have developed a mouse model showing that methyl donor supplementation prevents transgenerational amplification of obesity, suggesting a role for DNA methylation in the developmental establishment of body weight regulation. Conclusions: Coupling such models with recently developed epigenomic technologies should ultimately enable us to determine if epigenetics is an important link between early life events and adult disease.
Recent Progress in the Genetics of Diabetes
Authors: Rich Stephen S. , Onengut-Gumuscu Suna , Concannon Patrick
Published: January 2009

Background: Nearly 21 million people in the United States, or 7% of the population, are estimated to have diabetes. The incidence and prevalence of diabetes differ by ethnicity; however, both type 1 diabetes (T1D) and type 2 diabetes (T2D) occur in all groups. The etiology of diabetes is multifactorial, involving both genetic and environmental factors. Advances in technology, leading to the identification of over a dozen candidate genes, have accelerated the search for genetic factors contributing to the risk of diabetes. To date, surprisingly little data exist to suggest there are common genetic pathways leading to development of T1D and T2D. These common forms of diabetes have complex genetic (and environmental) risk factors, making prediction and prevention difficult. Nonetheless, detection of diabetes susceptibility genes may facilitate identification of novel pathways that can serve as therapeutic targets and lead to disease prevention.
Pitfalls of Insulin-Like Growth Factor I Assays
Authors: Bidlingmaier Martin
Published: January 2009

Background: Immunoassays that measure circulating concentrations of insulin-like growth factor I (IGF-I) are increasingly used to diagnose and monitor growth hormone (GH)-related diseases. Specifically, IGF-I measured by immunoassay is used to diagnose GH deficiency and acromegaly, and to monitor treatment efficacy in patients with acromegaly, particularly those treated with the GH receptor antagonist pegvisomant, as measurement of circulating GH is no longer suitable for monitoring disease activity. While techniques for measuring IGF-I have evolved over the decades, immunoassays are still the primary tool used in routine laboratories. Immunoassays depend on the interaction between antibodies and the analyte, and all factors that modify the accessibility of the epitopes recognized by the antibodies can influence results. With IGF-I assays, interference from binding proteins is an important variable affecting assay results. Conclusions: It is generally accepted that assay- and age-specific reference ranges are mandatory for meaningful interpretation of IGF-I concentrations. High-quality, method-specific reference ranges and a high degree of methodological consistency in the assay are essential for reliable comparison of results across studies and for long-term monitoring of individual patients.
Use of Recombinant Human Growth Hormone in Children with Thalassemia
Authors: Geffner Mitchell E. , Karlsson Hanna
Published: January 2009

Background: Growth failure occurs in children with chronic anemias and, in particular, in approximately 30% of those with thalassemia. Methods: We assessed recombinant human growth hormone (rhGH) use in a large cohort of children with thalassemia enrolled in the Pfizer International Growth Study Database (KIGS). Results: We identified 147 short children with thalassemia who were treated with rhGH in KIGS. Of these, approximately 40% had a primary diagnosis of GH deficiency (GHD). They had low birth weight, short parents, reduced genetic height potential, low insulin-like growth factor I levels and delayed bone age. Treatment with rhGH for 1 year resulted in a significantly increased growth rate regardless of underlying GH or pubertal status. Although the resultant growth rates for thalassemic children were significantly higher than at baseline, they were less than those seen in similarly treated short children with or without GHD. Conclusions: GH testing should be performed in short thalassemic children, and those with GHD should be treated with rhGH. The value of rhGH therapy in short thalassemic children without GHD is less clear-cut and requires further study regarding final height outcome.
Update on the Role of Aromatase Inhibitors in Growth Disorders
Authors: Dunkel Leo
Published: January 2009

Background: Without oestrogen action, the fusion of the growth plates is postponed and longitudinal growth continues for an exceptionally long period of time. Aromatase inhibitors that block oestrogen biosynthesis have therefore emerged as a new potential treatment option for children with short stature. Results from three prospective randomised controlled trials using potent third-generation aromatase inhibitors have recently been published. These studies all show that treatment with the aromatase inhibitors letrozole and anastrozole effectively delays bone maturation and increases predicted adult height in boys with constitutional delay of growth and puberty (CDGP), idiopathic short stature and growth hormone deficiency. Long-term follow-up data from the study in which boys with CDGP were treated with letrozole for 1 year during adolescence suggest that the achieved gain in predicted adult height also results in taller final adult height. Conclusions: Until the safety profile of aromatase inhibitors, particularly their qualitative effects on bone development, is established, use of these agents must be considered experimental in treating short stature.
Management of Idiopathic Short Stature: Psychological Endpoints, Assessment Strategies and Cognitive-Behavioral Intervention
Authors: Noeker Meinolf
Published: January 2009

Background: In 2007, a Conference on Idiopathic Short Stature (ISS) endorsed the definition of ISS as a statistical (auxologic) rather than a medical (pathologic) deviation from the norm. Consequently, the ultimate criteria for evaluation of treatment in ISS shift from medical to psychological endpoints. Objective: This review synthesizes empirical evidence of psychological outcomes in treated and untreated subjects with ISS, recommendations from the recent ISS Consensus Conference, theoretical concepts from pediatric psychology and rationales used for various intervention strategies to better evaluate and manage psychological endpoints in ISS in accordance with the Consensus Conference definition. Methods: Different measures of psychological outcome in ISS are reviewed to explain apparent heterogeneity among empirical study findings. Key issues include: (1) adaptation to major stressors associated with short stature (e.g., bullying, peer relations) and the correlation of adaptation failure with low socioeconomic status and impaired quality of life in adulthood; (2) development of valid and sensitive assessment tools; (3) clinical decision-making based on psychological assessment, ethical principles concerning informed consent and expectation of benefit from psychological treatment and (4) intervention approaches including counselling, cognitive-behavioral therapy, assertiveness training and growth hormone therapy. Conclusions: There are different but complementary strategies for medical and psychological enhancement of psychosocial outcome in subjects with ISS.
Two Puzzling Cases of Thyroid Dysgenesis
Authors: Kuehnen P. , Grueters A. , Krude H.
Published: January 2009

Background: In the last couple of years, different genes that play major roles in embryonic thyroid development have been identified. Several mutations, e.g., NKX2.1, FOXE1 and PAX8, were identified in patients with congenital hypothyroidism due to thyroid dysgenesis. However, the pathophysiology of most cases of thyroid dysgenesis remains unknown. Due to the sporadic occurrence and discordance observed in monozygotic twins, a classic genetic hypothesis for thyroid dysgenesis is improbable. Case Report: We present two pairs of monozygotic twins discordant for thyroid dysgenesis that exemplify these conceptual difficulties. Conclusions: Identification of the epigenetic differences observed in monozygotic twins discordant for thyroid dysgenesis may be crucial in discovering the pathogenesis of thyroid dysgenesis.
Treatment of Growth Hormone Deficiency in Adults
Authors: Johannsson Gudmundur
Published: January 2009

Background: The Growth Hormone Research Society held a Consensus Workshop in Sydney, Australia, in March 2007 to review advances in the management of growth hormone (GH) deficiency in adults and to update consensus recommendations. Objective: This short review summarizes key background information presented at the workshop and the consensus recommendations that followed. Conclusions: The benefits of GH replacement in GH-deficient adults are evident throughout life. Clinical response to treatment should be assessed by monitoring biochemistry values, body composition and quality of life. There is no evidence that GH replacement increases the risk of tumour recurrence or de novo malignancy.
Cushing’s Disease in Dogs and Humans
Authors: de Bruin C. , Meij B.P. , Kooistra H.S. , Hanson J.M. , Lamberts S.W.J. , Hofland L.J.
Published: January 2009

Background: Cushing’s disease (CD) is a common endocrinological disorder in dogs with an estimated incidence of 1 to 2 cases/1,000 dogs/year. This is in contrast to humans in whom CD is rare. The clinical presentation of CD, however, is highly similar between dogs and humans, with characteristic signs, such as abdominal obesity, weight gain, fatigue, muscle atrophy and skin changes. Canine CD may therefore serve as an animal model for human CD, especially since therapeutic canine hypophysectomy can generate substantial amounts of primary corticotroph adenoma tissue for in vitro research purposes. In a recent study, we found that dopamine (DA) D2 and somatostatin (SS) receptor subtypes are well expressed in canine corticotroph adenomas, but there are some distinct differences compared with the expression profile observed in human CD. These differences need to be considered when using canine CD as a model to evaluate the efficacy of novel DA/SS compounds for potential use in human CD. Case Report: This case involves an 8-year-old female dog that developed signs of exercise intolerance, muscle weakness and polyuria/polydipsia due to an adrenocorticotropic hormone-secreting pituitary adenoma. The dog underwent curative transsphenoidal hypophysectomy and has remained in complete remission in the 3.5 years since surgery.
Endocrine Diseases in Animals
Authors: Kooistra H.S. , Galac S. , Buijtels J.J.C.W.M. , Meij B.P.
Published: January 2009

Background: Several endocrine disorders that affect humans also occur as endocrinopathies in companion animals. Spontaneous endocrine disorders in animals may provide valuable information for their counterparts in human endocrinology. For example, the discovery of progesterone-induced growth hormone production in the mammary gland of dogs may have important consequences for understanding the pathogenesis of breast cancer in women. In addition, the majority of diabetic cats have a type of diabetes mellitus that closely resembles type 2 diabetes mellitus in humans and therefore may serve as an animal model for this disease in humans. This review describes several endocrine diseases in companion animals that are quite similar to those in humans and emphasizes their usefulness as spontaneous animal models for human endocrine disorders.
Cardiopulmonary Exercise Testing in the Functional and Prognostic Evaluation of Patients with Pulmonary Diseases
Authors: Ferrazza A.M. , Martolini D. , Valli G. , Palange P.
Published: January 2009

Exercise testing is increasingly utilized to evaluate the level of exercise intolerance in patients with lung and heart diseases. Cardiopulmonary exercise testing (CPET) is considered the gold standard to study a patient’s level of exercise limitation and its causes. The 2 CPET protocols most frequently used in the clinical setting are the maximal incremental and the constant work rate tests. The aim of this review is to focus on the main respiratory diseases for which exercise tolerance is indicated; for example, chronic obstructive pulmonary disease, interstitial lung disease, primary pulmonary hypertension and cystic fibrosis. This review also focuses on the variables/indices that are utilized in the functional and prognostic evaluation. The recognition of abnormal response patterns of ventilatory, cardiac and metabolic limitation to exercise may help in the diagnostic evaluation. In addition, CPET indexes can provide important functional and prognostic information regarding patients with pulmonary disease. Exercise indices, such as peak oxygen uptake (V’O2 peak), ventilatory equivalents for carbon dioxide production (V’E-/V’CO2) and arterial oxygen saturation (SpO2), have in fact proven to be better predictors of prognosis than lung function measurements obtained at rest. Moreover, useful information on the effects of therapeutic interventions may be obtained by CPET by studying the changes in endurance capacity during high-intensity constant work rate protocols.
Complications of Suppurative Otitis Media: Still a Problem in the 21st Century
Authors: Mostafa Badr Eldin , El Fiky Lobna M. , El Sharnouby Mohammed M.
Published: January 2009

The purpose of this study was to review the incidence of complicated suppurative otitis media in 10 years at a tertiary referral university hospital. During this period, 3,364 patients with suppurative otitis media (acute and chronic) were admitted to the department. The number of patients presenting with complications was 422 (12.54%). The ratio of extracranial to intracranial complications was nearly 1:1. The most frequent extracranial complication was mastoiditis while the most frequent intracranial one was lateral sinus thrombophlebitis. Multiple complications may present in the same patient. The onset of complications was insidious and 96% of the patients were already aware of their disease. There were 6 mortalities (1.42%), and additional morbidity was recorded in 16 patients (3.79%). Changes in the clinical picture should always alert the physician to the onset of a complication. Complications tended to occur in young patients from a lower socioeconomic class and without sex preponderance. Physicians should be aware of the continuing incidence of complications and the subtleness of their onset and investigate patients for the presence of more than one complication.
Corneal Penetration into Rabbit Aqueous Humor Is Comparable between Preserved and Preservative-Free Tafluprost
Authors: Pellinen Pertti , Lokkila Jukka
Published: January 2009

Background: Some studies have shown that benzalkonium chloride (BAK), a preservative used in antiglaucoma medications, can increase corneal permeability by acting as a penetration enhancer. Tafluprost is a new prostaglandin F2α analog in clinical use for the treatment of ocular hypertension and glaucoma. Methods: This study evaluated the corneal penetration of preservative-free tafluprost 0.0015% eye drops and tafluprost 0.0015% eye drops preserved with 0.01% BAK into the aqueous humor of rabbits. Results: After the administration of a single topical dose (30 μl), the maximum concentrations at 45 min of tafluprost acid in aqueous humor were 4.50 ng/ml for preservative-free tafluprost and 3.99 ng/ml for preserved tafluprost. The area under the concentration-time curves from 45 min to 3 h was 5.14 ng h/ml for the preservative-free formulation and 4.54 ng h/ml for the preserved formulation. Conclusions: These data indicate that BAK does not affect the corneal penetration of tafluprost into the rabbit aqueous humor.
Lower Prevalence of Depression in Hemodialysis Patients Who Use Polysulfone Dialyzers
Authors: Hsu Heng Jung , Chen Chih-Ken , Wu Mai-Szu
Published: January 2009

Background: Depression is common in dialysis patients and is also associated with the presence of chronic inflammation. Dialysis patients who use polysulfone dialyzers are less likely to have inflammation. It is unknown whether the use of polysulfone dialyzers is associated with lower prevalence of depression. Method: The aim of this cross-sectional study is to examine the association between the use of polysulfone dialyzers and depression in dialysis patients. This association was examined by use of univariate and multivariate analysis. Results: Depression affected 35% of our hemodialysis patients. Compared with nondepressed patients, depressed patients were more likely to be male, thinner (lower body mass index), and have more comorbidities. Depression was also associated with the use of cellulose derivative dialyzers (p = 0.008). In multivariate analysis with stepwise regression, gender, albumin, number of comorbidities, and BMI lost their significance. However, the use of polysulfone dialyzers remained correlated with a lower prevalence of depression (odds ratio 0.063, 95% confidence interval 0.01–0.43; p = 0.005). This indicates that the type of dialyzer is independently associated with depression in these hemodialysis patients. Conclusion: The prevalence of depression was lower in patients using polysulfone dialyzers than cellulose derivative dialyzers. Using more biocompatible dialyzers appears to be associated with better mental health in hemodialysis patients.
Aggressive Natural Killer Cell Leukemia: Is Epstein-Barr Virus Negativity an Indicator of a Favorable Prognosis?
Authors: Ko Young Hyeh , Park Sanghui , Kim Kihyun , Kim Seok Jin , Kim Won Seog
Published: January 2009

Aggressive natural killer (NK) cell leukemia (ANKL) is a prototype of an Epstein-Barr virus (EBV)-associated lymphoid malignancy, which is characterized by a fulminant clinical course and a median survival interval <2 months. EBV negativity in ANKL is uncommon, and the characteristics of EBV-negative ANKL are not well defined. We compared the clinicopathological characteristics of EBV-negative ANKL patients (group 1, n = 2) with those of EBV-positive ANKL patients (group 2, n = 14) and reviewed the literature for reports on EBV-negative ANKL cases. EBV-negative and EBV-positive ANKL patients had similar clinical and pathological characteristics, but EBV-negative patients had a longer survival than EBV-positive patients (11.5 vs. 1.5 months, respectively). EBV-negative patients achieved complete remission, but tumors often relapsed after a short interval. In conclusion, EBV-negative ANKL is an uncommon malignancy that pursues a less aggressive clinical course than EBV-positive ANKL.
Spontaneous Resolution of Cystic Hygroma and Hydrops in a Fetus with Noonan’s Syndrome
Authors: Kiyota Asuka , Tsukimori Kiyomi , Yumoto Yasuo , Hojo Satoshi , Morokuma Seiichi , Fukushima Kotaro , Takahata Yasushi , Nakayama Hideki , Wake Norio
Published: January 2009

Many studies have shown that the prognosis of cystic hygroma associated with hydrops fetalis is poor. We report a rare case of fetal cystic hygroma and hydrops fetalis that spontaneously resolved with subsequent delivery at 37 weeks of a living female infant with Noonan’s syndrome. The prognostic significance of prenatal resolution of cystic hygroma and hydrops is uncertain. Serial evaluation of affected fetuses with ultrasound imaging may help clarify pathogenesis of cystic hygroma with associated hydrops, as well as mechanisms underlying spontaneous resolution.
Partial Inhibition of the Proteasome Enhances the Activity of the Myelin Basic Protein Promoter
Authors: Calatayud C.A. , García C.I. , Paez P.M. , Pasquini J.M. , Soto E.F. , Pasquini L.A.
Published: January 2009

We have previously shown that low concentrations of a specific proteasome inhibitor accelerate exit from the cell cycle and enhance oligodendroglial cell (OLGc) differentiation. To elucidate the mechanisms involved in this process, OLGcs of the N20.1 cell line, transfected with a reporter gene driven by the MBP promoter, were treated with proteasome inhibitors and/or inhibitors of different signaling pathways. Partial proteasome inhibition resulted in enhanced activation of the MBP promoter which involved the tyrosine kinase, PI3-Akt and PKC pathways, accompanied by an increase in the levels of p21Cip1, p27Kip1 and Sp1 and by a decrease in Nkx2.2. Binding of Sp1 to DNA was also increased. These results were not observed when the Sp1 binding site was mutated. We conclude that the enhanced activation of the MBP promoter induced by partial inhibition of the proteasome could be due, at least in part, to the stabilization of p27Kip1 and Sp1.
Pitfalls in the Diagnosis and Therapy of Infections in Elderly Patients – A Mini-Review
Authors: Bellmann-Weiler Rosa , Weiss Günter
Published: January 2009

Extended life expectancy is paralleled by an increasing number of patients older than 65 years suffering from severe infections. Infections in this group of patients are generally more severe and associated with an increased risk of death. This is related to several factors which are discussed in this review. Specifically, immunosenescence and an atypical presentation of infection-associated symptoms with a subsequent delay of diagnosis and initiation of antimicrobial treatment are cornerstones in this dilemma. In addition, comorbidities and comedications, a changing spectrum of pathogens with a higher percentage of multiresistant pathogens, and more importantly, an altered pharmacokinetics of antimicrobial drugs are further contributing factors to the adverse outcome of infections in elderly subjects. Infections in the elderly demand special attention in terms of diagnosis and treatment. As the mortality rates are high, special emphasis must be put on preventive measures including effective vaccination strategies and establishment of hygiene standards to prevent transmission of multiresistant pathogens among elderly patients, both in health care centers and nursing homes.
Codon and Aminoacid Usage Patterns in Mycobacteria
Authors: Scapoli C. , Bartolomei E. , De Lorenzi S. , Carrieri A. , Salvatorelli G. , Rodriguez-Larralde A. , Barrai I.
Published: January 2009

The large number of organisms and of genes sequenced at the present time permits now to study molecular evolution in such lower clades as genera, species, and subspecies. Here, we focus our attention on the genus Mycobacterium, in which we examined codon and aminoacid usage in 13 species, and in 12 subspecies for a total of 8,836,513 codons from 26,755 sequences. Within the genus Mycobacterium, frequencies of codon and aminoacid usage correlate between species and between subspecies. In the groups studied, aminoacid molecular weight and codon degeneracy influence correlations between frequencies, while GC content is the main factor influencing the effective number of codons. The coding GC, which is highly correlated with total genomic GC content, seems to be the main factor influencing present synonymous codon usage in the genus. In particular, the GC content at the 3rd base position seems to shape heavily the effective number of codons, giving indication that here mutational bias dominates over translational selection. Evolutionary trees based on codon and aminoacid usage are consistent with traditional phylogenies of species within the genus.
Rapid Initial Reduction of Hyperenhanced Myocardium After Reperfused First Myocardial Infarction Suggests Recovery of the Peri-Infarction Zone
Authors: Engblom Henrik , Hedström Erik , Heiberg Einar , Wagner Galen S. , Pahlm Olle , Arheden Håkan
Published: January 2009

Background—

The time course and magnitude of infarct involution, functional recovery, and normalization of infarct-related electrocardiographic (ECG) changes after acute myocardial infarction (MI) are not completely known in humans. We sought to explore these processes early after MI and during infarct-healing using cardiac MRI.

Methods and Results—

Twenty-two patients with reperfused first-time MI were examined by MRI and ECG at 1, 7, 42, 182, and 365 days after infarction. Global left ventricular function and regional wall thickening were assessed by cine MRI, and injured myocardium was depicted by delayed contrast-enhanced MRI. Infarct size by ECG was estimated by QRS scoring. The reduction of hyperenhanced myocardium occurred predominantly during the first week after infarction (64% of the 1-year reduction). Furthermore, during the first week the amount of nonhyperenhanced myocardium increased significantly (
P
<0.001), although the left ventricular mass remained unchanged. Left ventricular ejection fraction increased gradually, whereas the greater the regional transmural extent of hyperenhancement at day 1, the later the recovery of regional wall thickening. Regional wall thickening decreased progressively with increasing initial transmural extent of hyperenhancement (
P
trend
<0.0001). The time course and magnitude of decrease in QRS score corresponded with the reduction of hyperenhanced myocardium.

Conclusions—

The early reduction of hyperenhanced myocardium may reflect recovery of hyperenhanced, reversibly injured myocardium, which must be considered when predicting functional recovery from delayed contrast-enhanced MRI findings early after infarction. Also, the time course and magnitude for reduction of hyperenhanced myocardium were associated with normalization of infarct-related ECG changes.
Declining Severity of Myocardial Infarction From 1987 to 2002
Authors: Myerson Merle , Coady Sean , Taylor Herman , Rosamond Wayne D. , Goff David C.
Published: January 2009

Background—

Death rates for coronary heart disease have been declining in the United States, but the reasons for this decline are not clear. One factor that could contribute to this decline is a reduction in the severity of acute myocardial infarction (MI). We hypothesized that for those patients hospitalized in the Atherosclerosis Risk in Communities (ARIC) Study with acute incident MI, there was a decline in MI severity from 1987 to 2002.

Methods and Results—

The community surveillance component of the ARIC Study consisted of tracking residents 35 to 74 years of age with hospitalized MI or fatal coronary heart disease in 4 diverse communities. For incident, hospitalized MI, a probability sample of hospital discharges was validated and an MI classification was assigned according to an algorithm consisting of chest pain, ECG evidence, and cardiac biomarkers. Severity indicators were chosen from abstracted hospital charts validated as a definite or probable MI. With few exceptions, the MI severity indicators suggested a significant decline in the severity of MI during the period of 1987 to 2002. The percent of MI cases with major ECG abnormalities decreased as evidenced by a 1.9%/y (
P
=0.002) decline in the proportion of those with initial ST-segment elevation, a 3.9%/y (
P
<0.001) decline in those with subsequent Q-waves, and a 4.5%/y (
P
<0.001) decline in those with any major Q wave. Maximum creatine kinase and creatine kinase-MB values declined (5.2% and 7.6%;
P
<0.001,
P
<0.001 per year, respectively), although in the later years, maximum troponin I values remained stable (1.1%/y decline;
P
=0.66). The percent with shock declined (5.7%/y;
P
<0.001), although those with congestive heart failure remained stable. A combined severity score, the Predicting Risk of Death in Cardiac Disease Tool (PREDICT) score, also declined (0.2%/y;
P
<0.001). Results for blacks paralleled those of the entire group, as did results for women.

Conclusions—

Evidence from ARIC community surveillance suggests that the severity of acute MI has declined among community residents hospitalized for incident MI. This reduction in severity may have contributed, along with other factors, to the decline in death rates for coronary heart disease.
Endothelial Progenitor Cells Restore Renal Function in Chronic Experimental Renovascular Disease
Authors: Chade Alejandro R. , Zhu Xiangyang , Lavi Ronit , Krier James D. , Pislaru Sorin , Simari Robert D. , Napoli Claudio , Lerman Amir , Lerman Lilach O.
Published: January 2009

Background—

Endothelial progenitor cells (EPCs) promote neovascularization and endothelial repair. Renal artery stenosis (RAS) may impair renal function by inducing intrarenal microvascular injury and remodeling. We investigated whether replenishment with EPCs would protect the renal microcirculation in chronic experimental renovascular disease.

Methods and Results—

Single-kidney hemodynamics and function were assessed with the use of multidetector computed tomography in vivo in pigs with RAS, pigs with RAS 4 weeks after intrarenal infusion of autologous EPCs, and controls. Renal microvascular remodeling and angiogenic pathways were investigated ex vivo with the use of micro–computed tomography, histology, and Western blotting. EPCs increased renal expression of angiogenic factors, stimulated proliferation and maturation of new vessels, and attenuated renal microvascular remodeling and fibrosis in RAS. Furthermore, EPCs normalized the blunted renal microvascular and filtration function.

Conclusions—

The present study shows that a single intrarenal infusion of autologous EPCs preserved microvascular architecture and function and decreased microvascular remodeling in experimental chronic RAS. It is likely that restoration of the angiogenic cascade by autologous EPCs involved not only generation of new vessels but also acceleration of their maturation and stabilization. This contributed to preserving the blood supply, hemodynamics, and function of the RAS kidney, supporting EPCs as a promising therapeutic intervention for preserving the kidney in renovascular disease.
Ambient Air Pollution Exaggerates Adipose Inflammation and Insulin Resistance in a Mouse Model of Diet-Induced Obesity
Authors: Sun Qinghua , Yue Peibin , Deiuliis Jeffrey A. , Lumeng Carey N. , Kampfrath Thomas , Mikolaj Michael B. , Cai Ying , Ostrowski Michael C. , Lu Bo , Parthasarathy Sampath , Brook Robert D. , Moffatt-Bruce Susan D. , Chen Lung Chi , Rajagopalan Sanjay
Published: January 2009

Background—

There is a strong link between urbanization and type 2 diabetes mellitus. Although a multitude of mechanisms have been proposed, there are no studies evaluating the impact of ambient air pollutants and the propensity to develop type 2 diabetes mellitus. We hypothesized that exposure to ambient fine particulate matter (<2.5 μm; PM
2.5
) exaggerates diet-induced insulin resistance, adipose inflammation, and visceral adiposity.

Methods and Results—

Male C57BL/6 mice were fed high-fat chow for 10 weeks and randomly assigned to concentrated ambient PM
2.5
or filtered air (n=14 per group) for 24 weeks. PM
2.5
-exposed C57BL/6 mice exhibited marked whole-body insulin resistance, systemic inflammation, and an increase in visceral adiposity. PM
2.5
exposure induced signaling abnormalities characteristic of insulin resistance, including decreased Akt and endothelial nitric oxide synthase phosphorylation in the endothelium and increased protein kinase C expression. These abnormalilties were associated with abnormalities in vascular relaxation to insulin and acetylcholine. PM
2.5
increased adipose tissue macrophages (F4/80
+
cells) in visceral fat expressing higher levels of tumor necrosis factor-α/interleukin-6 and lower interleukin-10/
N
-acetyl-galactosamine specific lectin 1. To test the impact of PM
2.5
in eliciting direct monocyte infiltration into fat, we rendered FVBN mice expressing yellow fluorescent protein (YFP) under control of a monocyte-specific promoter (c-
fms
, c-
fms
YFP
) diabetic over 10 weeks and then exposed these mice to PM
2.5
or saline intratracheally. PM
2.5
induced YFP cell accumulation in visceral fat and potentiated YFP cell adhesion in the microcirculation.

Conclusion—

PM
2.5
exposure exaggerates insulin resistance and visceral inflammation/adiposity. These findings provide a new link between air pollution and type 2 diabetes mellitus.