bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of therapeutic hypothermia in unconscious patients after near-hanging
Authors: Lee Byung Kook , Jeung Kyung Woon , Lee Hyoung Youn , Lim Jae Hoon
Published: September 2011

Background

Hanging has been increasingly used to commit suicide. There is no specific treatment besides general intensive care after near-hanging. Therapeutic hypothermia (TH) has been used in unconscious patients after near-hanging.

Objective

To describe the outcomes in unconscious patients after near-hanging in order to determine whether TH improves the outcome of near-hanging injury.

Methods

Medical charts were reviewed of unconscious patients after near-hanging who presented to Chonnam National University Hospital between January 2006 and December 2010 and who were considered to be eligible for TH. According to local policy, unconscious survivors after near-hanging, whether or not they experienced cardiac arrest at the scene, were treated with TH if this was agreed by next-of-kin.

Results

There were 16 survivors of asphyxial cardiac arrest after near-hanging, of whom 13 received TH. Among them, only one (7.7%, 95% CI 1.4% to 33.3%) attained Cerebral Performance Category (CPC) 1; the other 15 patients had poor neurological outcomes (CPC 5 in seven patients and CPC 4 in eight patients). Nine of the patients did not experience cardiac arrest at the scene and of these, four received TH and five received normothermic treatment. All patients who did not have cardiac arrest recovered and were discharged with CPC 1.

Conclusion

In this study, outcomes in unconscious near-hanging patients with cardiac arrest were poor despite treatment with TH. Before recommending TH in near-hanging patients, a prospective, randomised controlled study is required.
Kai
Authors: Grudin Jonathan
Published: September 2011

Timelines provides perspectives on HCI history, glancing back at a road that sometimes took unexpected branches and turns. History is not a dry list of events; it is about points of view and differing interpretations.

Jonathan Grudin, Editor
Introducing your new chair
Authors: Harper Simon
Published: September 2011

Welcome to the Autumn Issue of the SIGWEB Newsletter, as your new Chair I'd like to extend my thanks to everyone who voted for me and supported my application and assure all members of the special interest group that I will be doing my very best for our community over my two-year term. I'd also like to thank our outgoing Chair, Ethan Munson, for doing such an excellent job over the past five years, and leaving to me a healthy and expanding community. In this article I'd like to expand more on my election pledges including ideas how these pages can be accomplished, give a brief summary of the health of our SIG, to discuss the state of our major conferences, and finally to make you aware of my academic background within the Web and Hypertext community.
Towards a comprehensive theory of monadic effects
Authors: Filinski Andrzej
Published: September 2011

It has been more than 20 years since monads were proposed as a unifying concept for computational effects, in both formal semantics and functional programs. Over that period, there has been substantial incremental progress on several fronts within the ensuing research area, including denotational, operational, and axiomatic characterizations of effects; principles and frameworks for combining effects; prescriptive vs. descriptive effect-type systems; specification vs. implementation of effects; and realizations of effect-related theoretical constructions in practical functional languages, both eager and lazy. Yet few would confidently claim that programs with computational effects are by now as well understood, and as thoroughly supported by formal reasoning techniques, as types and terms in purely functional settings.

This talk outlines (one view of) the landscape of effectful functional programming, and attempts to assess our collective progress towards the goal of a broad yet coherent theory of monadic effects. We are not quite there yet, but intriguingly, many potential ingredients of such a theory have been repeatedly discovered and developed, with only minor variations, in seemingly unrelated contexts. Some stronger-than-expected ties between the research topics mentioned above also instill hope that there is indeed a natural, comprehensive theory of monadic effects, waiting to be fully explicated.
Balanced trees inhabiting functional parallel programming
Authors: Morihata Akimasa , Matsuzaki Kiminori
Published: September 2011

Divide-and-conquer is an important technique in parallel programming. However, algebraic data structures do not fit divide-and-conquer parallelism. For example, the usual pointer-based implementation of lists cannot efficiently be divided at their middle, which prevents us from developing list-iterating divide-and-conquer parallel programs. Tree-iterating programs possibly face a similar problem, because trees might be ill-balanced and list-like shapes. This paper examines parallel programming based on balanced trees: we consider balanced-tree structures and develop recursive functions on them. By virtue of their balancing nature, either bottom-up or top-down recursive functions exploit divide-and-conquer parallelism. Our main contribution is to demonstrate the promise of this approach. We propose a way of systematically developing balanced trees from parallel algorithms, and then, we show that efficient parallel programs on them can be developed by equational reasoning powered by Reynolds' relational parametricity. We consider functions that operate either lists or binary trees, and show that our methods can uniformly deal with both cases. The developed parallel programs are purely functional, correct by construction, and sometimes even simpler than known algorithms.
Implicit self-adjusting computation for purely functional programs
Authors: Chen Yan , Dunfield Jana , Hammer Matthew A. , Acar Umut A.
Published: September 2011

Computational problems that involve dynamic data, such as physics simulations and program development environments, have been an important subject of study in programming languages. Building on this work, recent advances in self-adjusting computation have developed techniques that enable programs to respond automatically and efficiently to dynamic changes in their inputs. Self-adjusting programs have been shown to be efficient for a reasonably broad range of problems but the approach still requires an explicit programming style, where the programmer must use specific monadic types and primitives to identify, create and operate on data that can change over time.

We describe techniques for automatically translating purely functional programs into self-adjusting programs. In this implicit approach, the programmer need only annotate the (top-level) input types of the programs to be translated. Type inference finds all other types, and a type-directed translation rewrites the source program into an explicitly self-adjusting target program. The type system is related to information-flow type systems and enjoys decidable type inference via constraint solving. We prove that the translation outputs well-typed self-adjusting programs and preserves the source program's input-output behavior, guaranteeing that translated programs respond correctly to all changes to their data. Using a cost semantics, we also prove that the translation preserves the asymptotic complexity of the source program.
Programming assurance cases in Agda
Authors: Takeyama Makoto
Published: September 2011

Agda is a modern functional programming language equipped with an interactive proof assistant as its developing environment. Its features include dependent types, type universe, inductive and coinductive families of types, pattern matching, records, and nested parameterized modules. Based on the "propositions as types, proofs as programs" correspondence in Martin-Löf's Type Theory, Agda lets users to construct, verify, and execute a smooth mixture of programs and proofs.

Using Agda is similar to using an editor in a modern IDE. Users have more direct control over how programs / proofs are written than in automation-oriented systems using command-scripts for proof construction. Agda thus encourages users to express their ideas with more sophisticated dependently typed programming and less logical proofs. Programming techniques for readability and maintainability now translate to techniques for writing verified documents for human communication.

Agda has been developed at Chalmers University of Technology by Ulf Norell and others. A growing international community of developers and users applies it in research, education, and industry. At AIST in Japan, we aim to introduce its merits to construction, verification, maintenance, and run-time evaluation of "assurance cases", which are documented bodies of systems assurance arguments used as the hub for assurance- and risk-communication among stakeholders.

The talk gives an overview of Agda and presents our current effort on programming assurance cases in Agda.
On the bright side of type classes
Authors: Devriese Dominique , Piessens Frank
Published: September 2011

We present instance arguments: an alternative to type classes and related features in the dependently typed, purely functional programming language/proof assistant Agda. They are a new, general type of function arguments, resolved from call-site scope in a type-directed way. The mechanism is inspired by both Scala's implicits and Agda's existing implicit arguments, but differs from both in important ways. Our mechanism is designed and implemented for Agda, but our design choices can be applied to other programming languages as well.

Like Scala's implicits, we do not provide a separate structure for type classes and their instances, but instead rely on Agda's standard dependently typed records, so that standard language mechanisms provide features that are missing or expensive in other proposals. Like Scala, we support the equivalent of local instances. Unlike Scala, functions taking our new arguments are first-class citizens and can be abstracted over and manipulated in standard ways. Compared to other proposals, we avoid the pitfall of introducing a separate type-level computational model through the instance search mechanism. All values in scope are automatically candidates for instance resolution. A final novelty of our approach is that existing Agda libraries using records gain the benefits of type classes without any modification.

We discuss our implementation in Agda (to be part of Agda 2.2.12) and we use monads as an example to show how it allows existing concepts in the Agda standard library to be used in a similar way as corresponding Haskell code using type classes. We also demonstrate and discuss equivalents and alternatives to some advanced type class-related patterns from the literature and some new patterns specific to our system.
An efficient non-moving garbage collector for functional languages
Authors: Ueno Katsuhiro , Ohori Atsushi , Otomo Toshiaki
Published: September 2011

Motivated by developing a memory management system that allows functional languages to seamlessly inter-operate with C, we propose an efficient non-moving garbage collection algorithm based on bitmap marking and report its implementation and performance evaluation.

In our method, the heap consists of sub-heaps

H
i

|
c
≤
i
≤
B
of exponentially increasing allocation sizes (

H
i

for 2

i

bytes) and a special sub-heap for exceptionally large objects. Actual space for each sub-heap is dynamically allocated and reclaimed from a pool of fixed size allocation segments. In each allocation segment, the algorithm maintains a bitmap representing the set of live objects. Allocation is done by searching for the next free bit in the bitmap. By adding meta-level bitmaps that summarize the contents of bitmaps hierarchically and maintaining the current bit position in the bitmap hierarchy, the next free bit can be found in a small constant time for most cases, and in log
32
(
segmentSize
) time in the worst case on a 32-bit architecture. The collection is done by clearing the bitmaps and tracing live objects. The algorithm can be extended to generational GC by maintaining multiple bitmaps for the same heap space. The proposed method does not require compaction and objects are not moved at all. This property is significant for a functional language to inter-operate with C, and it should also be beneficial in supporting multiple native threads.

The proposed method has been implemented in a full-scale Standard ML compiler. Our benchmark tests show that our non-moving collector performs as efficiently as a generational copying collector designed for functional languages.
Secure distributed programming with value-dependent types
Authors: Swamy Nikhil , Chen Juan , Fournet Cédric , Strub Pierre-Yves , Bhargavan Karthikeyan , Yang Jean
Published: September 2011

Distributed applications are difficult to program reliably and securely. Dependently typed functional languages promise to prevent broad classes of errors and vulnerabilities, and to enable program verification to proceed side-by-side with development. However, as recursion, effects, and rich libraries are added, using types to reason about programs, specifications, and proofs becomes challenging.

We present F*, a full-fledged design and implementation of a new dependently typed language for secure distributed programming. Unlike prior languages, F* provides arbitrary recursion while maintaining a logically consistent core; it enables modular reasoning about state and other effects using affine types; and it supports proofs of refinement properties using a mixture of cryptographic evidence and logical proof terms. The key mechanism is a new kind system that tracks several sub-languages within F* and controls their interaction. F* subsumes two previous languages, F7 and Fine. We prove type soundness (with proofs mechanized in Coq) and logical consistency for F*.

We have implemented a compiler that translates F* to .NET bytecode, based on a prototype for Fine. F* provides access to libraries for concurrency, networking, cryptography, and interoperability with C#, F#, and the other .NET languages. The compiler produces verifiable binaries with 60% code size overhead for proofs and types, as much as a 45x improvement over the Fine compiler, while still enabling efficient bytecode verification.

To date, we have programmed and verified more than 20,000 lines of F* including (1) new schemes for multi-party sessions; (2) a zero-knowledge privacy-preserving payment protocol; (3) a provenance-aware curated database; (4) a suite of 17 web-browser extensions verified for authorization properties; and (5) a cloud-hosted multi-tier web application with a verified reference monitor.
Sybil defenses via social networks
Authors: Yu Haifeng
Published: September 2011

The sybil attack in distributed systems refers to individual malicious users joining the system multiple times under multiple fake identities. Sybil attacks can easily invalidate the overarching prerequisite of many fault-tolerant designs which assume that the fraction of malicious nodes is not too large. This article presents a tutorial and survey on effective sybil defenses leveraging social networks. Since this approach of sybil defenses via social networks was introduced 5 years ago, it has attracted much more attention from the research community than many other alternatives. We will first explain the intuitions and insights behind this approach, and then survey a number of specific sybil defense mechanisms based on this approach, including SybilGuard, SybilLimit, SybilInfer, Gatekeeper, SumUp, Whanau, and Ostra. We will also discuss some practical implications and deployment considerations of this approach.
In the network
Authors: Varis Nuutti , Manner Jukka
Published: September 2011

The increasing performance of commodity computer hardware has spawned new use cases for the personal computer. Specialized, cost effective network devices, such as firewalls and intrusion detection systems can be implemented with off the shelf components. At the heart of the performance increase is the computer microarchitecture, comprised of the CPU, peripheral buses and the memory interface. Intel has recently unveiled their next generation core microarchitecture called "Sandy Bridge". In this paper, we present some initial network I/O performance results of the Sandy Bridge microarchitecture platform. The results are compared to the previous Intel microarchitecture, "Nehalem".
On the efficiency of perfect simulation in monotone queueing networks
Authors: Anselmi Jonatha Anselmi , Gaujal Bruno
Published: September 2011

We consider Jackson queueing networks (JQN) with finite capacity constraints and analyze the temporal computational complexity of sampling from their stationary distribution. In the context of perfect sampling, the monotonicity of JQNs ensures that it is the coupling time of extremal sample-paths. In the context of approximate sampling, it is given by the mixing time. We give a sufficient condition to prove that the coupling time of JQNs with M queues is
O
(
M
∑
M
i=1
C
i
), where C
i
denotes the capacity (buffer size) of queue
i
. This condition lets us deal with networks having arbitrary topology, for which the best bound known is exponential in the C
i
's or in
M
. Then, we use this result to show that the mixing time of JQNs is log
2
1/∈
O
(
M
∑
M
i=1
C
i
), where ∈ is a precision threshold. The main idea of our proof relies on a recursive formula on the coupling times of special sample-paths and provides a methodology for analyzing the coupling and mixing times of several monotone Markovian networks.
The Anatomy of Teleneurosurgery in China
Authors: Gao Xiaohong
Published: September 2011

With its huge population and vast territory, China faces a great challenge in providing modern advanced health care services to all parts of the country. The advances of information communication technologies (ICTs) and the advent of internet have revolutionised the means in the delivery of healthcare via telemedicine to remote and underserved populations, which to a certain extent has been very well exploited in China, especially where 70% peasants residing in the rural areas. This paper reviews the latest development in telemedicine infrastructure in China with the focus on the development of teleneurosurgery, drawing from the results gained from a 3-year networking project between Europe and China on telemedicine (TIME, 2005–2007) funded by European Commission under Asia ICT programme, with an aim to shape up envisages of future medical care in China. Comparison with its counterparts in Europe is also addressed.
Breast-Volume Displacement Using an Extended Glandular Flap for Small Dense Breasts
Authors: Ogawa Tomoko , Hanamura Noriko , Yamashita Masako , Kimura Hiroko , Kashikura Yumi
Published: September 2011

We defined the glandular flap including fat in the subclavicular area as an extended glandular flap, which has been used for breast-conserving reconstruction in the upper portion of the breast. Indication. The excision volume was 20% to 40% of the breast volume, and the breast density was dense. Surgical Technique. The upper edge of the breast at the subclavicular area was drawn in the standing position before surgery. After partial mastectomy, an extended glandular flap was made by freeing the breast from both the skin and the pectoralis fascia up to the preoperative marking in the subclavicular area. It is important to keep the perforators of the internal mammary artery and/or the branches of the lateral thoracic artery intact while making the flap. Results. Seventeen patients underwent remodeling using an extended glandular flap. The cosmetic results at 1 year after the operation: excellent in 11, good in 1, fair in 3, and poor in 2. All cases of unacceptable outcome except one were cases with complications, and more than 30% resection of moderate or large size breasts did not obtain an excellent result for long-term followup. Conclusion. This technique is useful for performing the breast-conserving reconstruction of small dense breasts.
Development of Adaptive Acoustic Impedance Control Technologies of Acoustic Duct Liner
Authors: Kobayashi Hiroshi , Ozaki Schunichi , Yokochi Makoto
Published: September 2011

This paper describes the development of adaptive acoustic impedance control (AAC) technologies to achieve a larger fan noise reduction, by adaptively adjusting reactance and resistance of the acoustic liner impedance. For the actual proof of the AAC technology III performance, the advanced fan noise absorption control duct liner II was made on trial basis, with the simple control system and the plain device. And, then, the duct liner II was examined for the AAC technology I, II, and III models, using the high speed fan test facility. The test results made clear that the duct liner II of the AAC technology III model could achieve the fan noise reduction higher than O.A. SPL 10 dB (A) at the maximum fan speed 6000 rpm, containing the reduction of fundamental BPF tone of 18 dB and 2nd BPF tone of 10 dB in response to the fan peed change from 3000 to 6000 rpm.
Echocardiographic Assessment of Preload Responsiveness in Critically Ill Patients
Authors: Levitov Alexander , Marik Paul E.
Published: September 2011

Fluid challenges are considered the cornerstone of resuscitation in critically ill patients. However, clinical studies have demonstrated that only about 50% of hemodynamically unstable patients are volume responsive. Furthermore, increasing evidence suggests that excess fluid resuscitation is associated with increased mortality. It therefore becomes vital to assess a patient's fluid responsiveness prior to embarking on fluid loading. Static pressure (CVP, PAOP) and echocardiographic (IVC diameter, LVEDA) parameters fails to predict volume responsiveness. However, a number of dynamic echocardiographic parameters which are based on changes in vena-caval dimensions or cardiac function induce by positive pressure ventilation or passive leg raising appear to be highly predictive of volume responsiveness.
Dispersal Evolution in Neoplasms: The Role of Disregulated Metabolism in the Evolution of Cell Motility
Authors: Aktipis C. Athena , Maley Carlo C. , Pepper John W.
Published: September 2011

Here, we apply the theoretical framework of dispersal evolution to understand the emergence of invasive and metastatic cells. We investigate whether the dysregulated metabolism characteristic of cancer cells may play a causal role in selection for cell motility, and thus to the tissue invasion and metastasis that define cancer. With an agent-based computational model, we show that cells with higher metabolism evolve to have higher rates of movement and that “neoplastic” cells with higher metabolism rates are able to persist in a population of “normal” cells with low metabolic rates, but only if increased metabolism is accompanied by increased motility. This is true even when the cost of motility is high. These findings suggest that higher rates of cell metabolism lead to selection for motile cells in premalignant neoplasms, which may preadapt cells for subsequent invasion and metastasis. This has important implications for understanding the progression of cancer from less invasive to more invasive cell types. Cancer Prev Res; 5(2); 266–75. ©2011 AACR.
Causes of Delay and Associated Mortality in Patients Transferred With ST-Segment–Elevation Myocardial Infarction
Authors: Miedema Michael D. , Newell Marc C. , Duval Sue , Garberich Ross F. , Handran Chauncy B. , Larson David M. , Mulder Steven , Wang Yale L. , Lips Daniel L. , Henry Timothy D.
Published: September 2011

Background—

Regional ST-segment–elevation myocardial infarction systems are being developed to improve timely access to primary percutaneous coronary intervention (PCI). System delays may diminish the mortality benefit achieved with primary PCI in ST-segment–elevation myocardial infarction patients, but the specific reasons for and clinical impact of delays in patients transferred for PCI are unknown.

Methods and Results—

This was a prospective, observational study of 2034 patients transferred for primary PCI at a single center as part of a regional ST-segment–elevation myocardial infarction system from March 2003 to December 2009. Despite long-distance transfers, 30.4% of patients (n=613) were treated in ≤90 minutes and 65.7% (n=1324) were treated in ≤120 minutes. Delays occurred most frequently at the referral hospital (64.0%, n=1298), followed by the PCI center (15.7%, n=317) and transport (12.6%, n=255). For the referral hospital, the most common reasons for delay were awaiting transport (26.4%, n=535) and emergency department delays (14.3%, n=289). Diagnostic dilemmas (median, 95.5 minutes; 25th and 75th percentiles, 72–127 minutes) and nondiagnostic initial ECGs (81 minutes; 64–110.5 minutes) led to delays of the greatest magnitude. Delays caused by cardiac arrest and/or cardiogenic shock had the highest in-hospital mortality (30.6%), in contrast with nondiagnostic initial ECGs, which, despite long treatment delays, did not affect mortality (0%). Significant variation in both the magnitude and clinical impact of delays also occurred during the transport and PCI center segments.

Conclusions—

Treatment delays occur even in efficient systems for ST-segment–elevation myocardial infarction care. The clinical impact of specific delays in interhospital transfer for PCI varies according to the cause of the delay.
Renminbi Internationalization: Prospects and Implications for Economic Integration in East Asia
Authors: Park Yung Chul , Song Chi-Young
Published: September 2011

This paper argues that renminbi (RMB) internationalization and China's strategic interests in ASEAN will combine to deepen economic integration and pave the way for creating a de facto RMB bloc consisting of the 10 ASEAN countries, China, Hong Kong, and Taiwan—a grouping we call ASEAN+New3. Such a currency bloc is likely to weaken the initiatives of the existing ASEAN+3 (China, Japan, and Korea) for regional monetary-financial cooperation because neither Japan nor can Korea join the new currency bloc for economic and political reasons. This paper also argues that RMB internationalization would delay the resolution of the trade imbalance between East Asia and the United States because China would be pressured by the other members of ASEAN+New3 to maintain stability of the RMB vis-à-vis the U.S. dollar.
Relationship of Lower-Troposphere Cloud Cover and Cosmic Rays: An Updated Perspective
Authors: Agee Ernest M. , Kiefer Kandace , Cornett Emily
Published: September 2011

An updated assessment has been made of the proposed hypothesis that galactic cosmic rays (GCRs) are positively correlated with lower-troposphere global cloudiness. A brief review of the many conflicting studies that attempt to prove or disprove this hypothesis is also presented. It has been determined in this assessment that the recent extended quiet period between solar cycles 23 and 24 has led to a record-high level of GCRs, which in turn has been accompanied by a record-low level of lower-troposphere global cloudiness. This represents a possible observational disconnect, and the update presented here continues to support the need for further research on the GCR–cloud hypothesis and its possible role in the science of climate change.
Perfusion safety: new initiatives and enduring principles
Authors: Kurusz M
Published: September 2011

Perfusion safety has been studied and discussed extensively for decades. Many initiatives occurred through efforts of professional organizations to achieve recognition, establish accreditation and certification, promote consensus practice guidelines, and develop peer-reviewed journals as sources for dissemination of clinical information. Newer initiatives have their basis in other disciplines and include systems approach, Quality Assurance/Quality Improvement processes, error recognition, evidence-based methodologies, registries, equipment automation, simulation, and the Internet. Use of previously established resources such as written protocols, checklists, safety devices, and enhanced communication skills has persisted to the present in promoting perfusion safety and has reduced current complication rates to negligible levels.
Histological and global gene expression analysis of the 'lactating' pigeon crop
Authors: Gillespie Meagan J , Haring Volker R , McColl Kenneth A , Monaghan Paul , Donald John A , Nicholas Kevin R , Moore Robert J , Crowley Tamsyn M
Published: September 2011

Background

Both male and female pigeons have the ability to produce a nutrient solution in their crop for the nourishment of their young. The production of the nutrient solution has been likened to lactation in mammals, and hence the product has been called pigeon 'milk'. It has been shown that pigeon 'milk' is essential for growth and development of the pigeon squab, and without it they fail to thrive. Studies have investigated the nutritional value of pigeon 'milk' but very little else is known about what it is or how it is produced. This study aimed to gain insight into the process by studying gene expression in the 'lactating' crop.

Results

Macroscopic comparison of 'lactating' and non-'lactating' crop reveals that the 'lactating' crop is enlarged and thickened with two very obvious lateral lobes that contain discrete rice-shaped pellets of pigeon 'milk'. This was characterised histologically by an increase in the number and depth of rete pegs extending from the basal layer of the epithelium to the lamina propria, and extensive proliferation and folding of the germinal layer into the superficial epithelium. A global gene expression profile comparison between 'lactating' crop and non-'lactating' crop showed that 542 genes are up-regulated in the 'lactating' crop, and 639 genes are down-regulated. Pathway analysis revealed that genes up-regulated in 'lactating' crop were involved in the proliferation of melanocytes, extracellular matrix-receptor interaction, the adherens junction and the wingless (wnt) signalling pathway. Gene ontology analysis showed that antioxidant response and microtubule transport were enriched in 'lactating' crop.

Conclusions

There is a hyperplastic response in the pigeon crop epithelium during 'lactation' that leads to localised cellular stress and expression of antioxidant protein-encoding genes. The differentiated, cornified cells that form the pigeon 'milk' are of keratinocyte lineage and contain triglycerides that are likely endocytosed as very low density lipoprotein (VLDL) and repackaged as triglyceride in vesicles that are transported intracellularly by microtubules. This mechanism is an interesting example of the evolution of a system with analogies to mammalian lactation, as pigeon 'milk' fulfils a similar function to mammalian milk, but is produced by a different mechanism.
Clonal diversity of the glutamate dehydrogenase gene in Giardia duodenalisfrom Thai Isolates: evidence of genetic exchange or Mixed Infections?
Authors: Siripattanapipong Suradej , Leelayoova Saovanee , Mungthin Mathirut , Thompson RC Andrew , Boontanom Parima , Saksirisampant Wilai , Tan-ariya Peerapan
Published: September 2011

Background

The glutamate dehydrogenase gene (gdh) is one of the most popular and useful genetic markers for the genotypic analysis of Giardia duodenalis (syn. G. lamblia, G. intestinalis), the protozoan that widely causes enteric disease in humans. To determine the distribution of genotypes of G. duodenalis in Thai populations and to investigate the extent of sequence variation at this locus, 42 fecal samples were collected from 3 regions of Thailand i.e., Central, Northern, and Eastern regions. All specimens were analyzed using PCR-based genotyping and recombinant subcloning methods.

Results

The results showed that the prevalence of assemblages A and B among these populations was approximately equal, 20 (47.6%) and 22 (52.4%), respectively. Sequence analysis revealed that the nucleotide diversity of assemblage B was significantly greater than that in assemblage A. Among all assemblage B positive specimens, the allelic sequence divergence within isolates was detected. Nine isolates showed mixed alleles, ranged from three to nine distinct alleles per isolate. Statistical analysis demonstrated the occurrence of genetic recombination within subassemblages BIII and BIV was likely.

Conclusion

This study supports increasing evidence that G. duodenalis has the potential for genetic exchange.
Aberrant upregulation of 14-3-3ơ expression serves as an inferior prognostic biomarker for gastric cancer
Authors: Zhou Wei-hua , Tang Fang , Xu Jie , Wu Xing , Feng Zhi-ying , Li Hai-gang , Lin Dong-jun , Shao Chun-kui , Liu Quentin
Published: September 2011

Background

14-3-3ơ is an intracellular, phosphoserine binding protein and proposed to be involved in tumorigenesis. However, the expression dynamics of 14-3-3ơ and its clinicopathological/prognostic significance in human tumors are still controversial.

Methods

The method of immunohistochemistry (IHC) and Western blot were utilized to examine the protein expression of 14-3-3ơ in gastric cancer and paired normal adjacent gastric mucosal tissues. Receive operating characteristic (ROC) curve analysis was employed to determine a cutoff score for 14-3-3ơ expression in a training set (n = 66). For validation, the ROC-derived cutoff score was subjected to analysis of the association of 14-3-3ơ expression with patient outcome and clinical characteristics in a testing set (n = 86) and overall patients (n = 152).

Results

The expression frequency and expression levels of 14-3-3ơ were significantly higher in gastric cancer than in normal gastric mucosal tissues. Correlation analysis demonstrated that high expression of 14-3-3ơ in gastric cancer was significantly correlated with clinical stage and tumor invasion. Furthermore, in the testing set and overall patients, Kaplan-Meier analysis showed that elevated 14-3-3ơ expression predicted poorer overall survival (OS) and progression-free survival (PFS). Importantly, high 14-3-3ơ expression was also associated with shortened survival time in stage III and stage IV gastric cancer patients. Multivariate analyses revealed that 14-3-3ơ expression was an independent prognostic parameter in gastric cancer.

Conclusions

These findings provide evidence that high expression of 14-3-3ơ may be important in the tumor progression and servers as an independent molecular marker for poor prognosis of gastric cancer. Thus, overexpression of 14-3-3ơ identifies patients at high risk and is a novel therapeutic molecular target for this tumor.
Human pericardium graft in the management of bleb's complication performed in childhood: a case report
Authors: Papaconstantinou Dimitris , Georgalas Ilias , Taliantzis Sergios , Koutsandrea Chrysanthi , Ladas Ioannis , Georgopoulos Gerassimos
Published: September 2011

Background

To report a case with hypotony due to late leakage of the filtering bleb performed during childhood and treated surgically using human pericardium graft.

Case Presentation

A man with hypotony related to bleb's leakage in his right eye was presented. During his childhood trabeculectomy was performed to manage ocular hypertension due to pediatric glaucoma. Biomicroscopy revealed choroidal tissue incarcerated in the sclerectomy under the conjunctiva. Bleb revision was performed. Human pericardium graft was used to cover the sclerectomy and a new bleb with controlled outflow was created. The intraocular pressure (IOP) and Seidel test represent the main outcomes. Intraoperative and postoperative complications were recorded. Fifteen days postoperatively the IOP was of 7 mmHg and the bleb seemed to filter properly. Five months later the IOP was 9 mmHg and no complications were noticed. During the follow up time, the Seidel test was negative.

Conclusion

We used human pericardium graft with no complications in a case of bleb leakage performed for pediatric glaucoma.
The "Alzheimer's disease signature": potential perspectives for novel biomarkers
Authors: Davinelli Sergio , Intrieri Mariano , Russo Claudio , Di Costanzo Alfonso , Zella Davide , Bosco Paolo , Scapagnini Giovanni
Published: September 2011

Alzheimer's disease is a progressive and neurodegenerative disorder which involves multiple molecular mechanisms. Intense research during the last years has accumulated a large body of data and the search for sensitive and specific biomarkers has undergone a rapid evolution. However, the diagnosis remains problematic and the current tests do not accurately detect the process leading to neurodegeneration. Biomarkers discovery and validation are considered the key aspects to support clinical diagnosis and provide discriminatory power between different stages of the disorder. A considerable challenge is to integrate different types of data from new potent approach to reach a common interpretation and replicate the findings across studies and populations. Furthermore, long-term clinical follow-up and combined analysis of several biomarkers are among the most promising perspectives to diagnose and manage the disease. The present review will focus on the recent published data providing an updated overview of the main achievements in the genetic and biochemical research of the Alzheimer's disease. We also discuss the latest and most significant results that will help to define a specific disease signature whose validity might be clinically relevant for future AD diagnosis.
Polyclonal antibody cocktails generated using DNA vaccine technology protect in murine models of orthopoxvirus disease
Authors: Golden Joseph W , Zaitseva Marina , Kapnick Senta , Fisher Robert W , Mikolajczyk Malgorzata G , Ballantyne John , Golding Hana , Hooper Jay W
Published: September 2011

Background

Previously we demonstrated that DNA vaccination of nonhuman primates (NHP) with a small subset of vaccinia virus (VACV) immunogens (L1, A27, A33, B5) protects against lethal monkeypox virus challenge. The L1 and A27 components of this vaccine target the mature virion (MV) whereas A33 and B5 target the enveloped virion (EV).

Results

Here, we demonstrated that the antibodies produced in vaccinated NHPs were sufficient to confer protection in a murine model of lethalOrthopoxvirusinfection. We further explored the concept of using DNA vaccine technology to produce immunogen-specific polyclonal antibodies that could then be combined into cocktails as potential immunoprophylactic/therapeutics. Specifically, we used DNA vaccines delivered by muscle electroporation to produce polyclonal antibodies against the L1, A27, A33, and B5 in New Zealand white rabbits. The polyclonal antibodies neutralized both MV and EV in cell culture. The ability of antibody cocktails consisting of anti-MV, anti-EV, or a combination of anti-MV/EV to protect BALB/c mice was evaluated as was the efficacy of the anti-MV/EV mixture in a mouse model of progressive vaccinia. In addition to evaluating weight loss and lethality, bioimaging technology was used to characterize the spread of the VACV infections in mice. We found that the anti-EV cocktail, but not the anti-MV cocktail, limited virus spread and lethality.

Conclusions

A combination of anti-MV/EV antibodies was significantly more protective than anti-EV antibodies alone. These data suggest that DNA vaccine technology could be used to produce a polyclonal antibody cocktail as a possible product to replace vaccinia immune globulin.
An open pilot study of zonisamide augmentation in major depressive patients not responding to a low dose trial with duloxetine: preliminary results on tolerability and clinical effects
Authors: Fornaro Michele , Martino Matteo , Dalmasso Bruna , Colicchio Salvatore , Benvenuti Marzia , Rocchi Giulio , Escelsior Andrea , Perugi Giulio
Published: September 2011

Background

Despite multiple antidepressant options, major depressive disorder (MDD) still faces high non-response rates, eventually requiring anticonvulsant augmentation strategies too. The aim of this study was to explore such a potential role for zonisamide.

Methods

A total of 40 MDD outpatients diagnosed using the Diagnostic and Statistical Manual for Mental Disorders, fourth edition criteria entered a 24 week open trial receiving duloxetine 60 mg/day for the first 12 weeks and subsequently (weeks 12 to 24) augmentation with zonisamide 75 mg/day if they did not respond to the initial monotherapy. Efficacy and tolerability were assessed using the Hamilton Scales for Anxiety and Depression (a 12 week score ≥50% vs baseline defined 'non-response'), the Arizona Sexual Experience Scale, the Patient Rated Inventory of Side Effects and the Young Mania Rating Scale.

Results

At week 12, 15 patients out of 39 (38.5%) were responders, and 1 had dropped out; remarkably, 14 patients out of 24 (58.3%) had achieved response by week 24. Poor concentration and general malaise were associated with non-response both at week 12 and 24 (P = 0.001), while loss of libido and reduced energy were prominent among final timepoint non-responders. Patients receiving zonisamide also experienced weight reduction (2.09 ± 12.14 kg; P = 0.001) independently of the outcome.

Conclusions

Although only a preliminary study due to strong methodological limitations, and thus requiring confirmation by further controlled investigations, the current results indicate zonisamide may be a potential augmentation option for some depressed patients receiving low doses of duloxetine.
Pilot proof of concept clinical trials of Stochastic Targeted (STAR) glycemic control
Authors: Evans Alicia , Shaw Geoffrey M , Le Compte Aaron , Tan Chia-Siong , Ward Logan , Steel James , Pretty Christopher G , Pfeifer Leesa , Penning Sophie , Suhaimi Fatanah , Signal Matthew , Desaive Thomas , Chase J Geoffrey
Published: September 2011

Introduction

Tight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. STAR (Stochastic TARgeted) is a flexible, model-based TGC approach directly accounting for intra- and inter- patient variability with a stochastically derived maximum 5% risk of blood glucose (BG) < 4.0 mmol/L. This research assesses the safety, efficacy, and clinical burden of a STAR TGC controller modulating both insulin and nutrition inputs in pilot trials.

Methods

Seven patients covering 660 hours. Insulin and nutrition interventions are given 1-3 hourly as chosen by the nurse to allow them to manage workload. Interventions are calculated by using clinically validated computer models of human metabolism and its variability in critical illness to maximize the overlap of the model-predicted (5-95th percentile) range of BG outcomes with the 4.0-6.5 mmol/L band while ensuring a maximum 5% risk of BG < 4.0 mmol/L. Carbohydrate intake (all sources) was selected to maximize intake up to 100% of SCCM/ACCP goal (25 kg/kcal/h). Maximum insulin doses and dose changes were limited for safety. Measurements were made with glucometers. Results are compared to those for the SPRINT study, which reduced mortality 25-40% for length of stay ≥3 days. Written informed consent was obtained for all patients, and approval was granted by the NZ Upper South A Regional Ethics Committee.

Results

A total of 402 measurements were taken over 660 hours (~14/day), because nurses showed a preference for 2-hourly measurements. Median [interquartile range, (IQR)] cohort BG was 5.9 mmol/L [5.2-6.8]. Overall, 63.2%, 75.9%, and 89.8% of measurements were in the 4.0-6.5, 4.0-7.0, and 4.0-8.0 mmol/L bands. There were no hypoglycemic events (BG < 2.2 mmol/L), and the minimum BG was 3.5 mmol/L with 4.5% < 4.4 mmol/L. Per patient, the median [IQR] hours of TGC was 92 h [29-113] using 53 [19-62] measurements (median, ~13/day). Median [IQR] results: BG, 5.9 mmol/L [5.8-6.3]; carbohydrate nutrition, 6.8 g/h [5.5-8.7] (~70% goal feed median); insulin, 2.5 U/h [0.1-5.1]. All patients achieved BG < 6.1 mmol/L. These results match or exceed SPRINT and clinical workload is reduced more than 20%.

Conclusions

STAR TGC modulating insulin and nutrition inputs provided very tight control with minimal variability by managing intra- and inter- patient variability. Performance and safety exceed that of SPRINT, which reduced mortality and cost in the Christchurch ICU. The use of glucometers did not appear to impact the quality of TGC. Finally, clinical workload was self-managed and reduced 20% compared with SPRINT.
In vitro microbiological evaluation of 1,1'-(5,5'-(1,4-phenylene)bis(3-aryl-1H-pyrazole-5,1-(4H,5H)-diyl))diethanones, novel bis acetylated pyrazoles
Authors: Kanagarajan Vijayakumar , Ezhilarasi Muthuvel Ramanathan , Gopalakrishnan Mannathusamy
Published: September 2011

Novel 1,1'-(5,5'-(1,4-phenylene)bis(3-aryl-1H-pyrazole-5,1-(4H,5H)-diyl))diethanones7-12were tested for their antimicrobial activity by disc diffusion and twofold serial dilution method against the tested bacterial and fungal strains. Compounds7againstMicrococcus luteus,8againstβ-Heamolytic streptococcus, M. luteus, Klebsiella pneumonia, Microsporum gypseum,9againstStaphylococcus aureus, Shigella flexneri, Vibreo cholerae, Pseudomonas aeruginosa, Aspergillus flavus, Mucor indicus,10againstSalmonella typhii, S. flexneri, M. gypseum,11againstK. pneumonia, M. gypseum,12againstK. pneumonia, andM. gypseumshow superior zone of inhibitions and exhibited excellent antibacterial and antifungal activities at a MIC value of 6.25 μg/mL. Moreover, all the tested compounds7-12revealed promising antitubercular activity againstMycobacterium tuberculosisH37Rv and INH-resistantM. tuberculosis. Compounds8againstM. tuberculosisand11against INH-resistantM. tuberculosisexhibited the percentage of reduction in RLU at 89 and 85%, respectively.
A targeted lipidomics approach to the study of eicosanoid release in synovial joints
Authors: de Grauw Janny C , van de Lest Chris HA , van Weeren Paul René
Published: September 2011

Introduction

Articular tissues are capable of producing a range of eicosanoid mediators, each of which has individual biological effects and may be affected by anti-inflammatory treatment. We set out to develop and evaluate a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) approach for the simultaneous analysis of multiple eicosanoid lipid mediators in equine synovial fluid (SF), and to illustrate its use for investigation of the in vivo effects of non-steroidal anti-inflammatory drug (NSAID) treatment.

Methods

Synovial fluid samples were obtained from normal joints of 6 adult horses at baseline (0 hr) and at 8, 24 and 168 hours after experimental induction of transient acute synovitis, with horses treated once daily with oral NSAID (meloxicam, 0.6 mg/kg) or placebo. Following solid-phase extraction, SF lipid mediator quantitation was based on liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis, and results were compared between disease states using linear discriminant analysis (LDA) and analysis of variance (ANOVA) with multiple comparisons corrections.

Results

Of a total of 23 mediators targeted, 14 could be reliably identified and quantified in SF samples based on detection of characteristic fragment ions at retention times similar to those of commercial standards. LDA analysis of baseline, 8, 24 and 168 hour synovial fluid samples revealed a separation of these groups into discrete clusters, reflecting dynamic changes in eicosanoid release over the course of synovitis. Prostaglandin (PG) E2 was significantly lower in NSAID vs. placebo treated samples at all time points; PGE1, 11-hydroxyeicosatetraenoic acid (11-HETE) and 13,14-dihydro-15keto PGF2α were reduced at 8 and 24 hours by NSAID treatment; while 15-HETE, 6-keto PGF1α, PGF2α, 13,14-dihydro-15keto PGE2 and thromboxane B2 (TXB2) were reduced at the 8 hour time point only. An interesting pattern was seen for Leukotriene B4 (LTB4), NSAID treatment causing an initial increase at 8 hours, but a significant reduction by 168 hours.

Conclusions

The described method allows a comprehensive analysis of synovial fluid eicosanoid profiles. Eicosanoid release in inflamed joints as well as differences between NSAID treated and placebo treated individuals are not limited to PGE2 or to the early inflammatory phase.