bluuebunny/crossref_metadata_2025 huggingface dataset:
A Value-Based Framework for Software Evolutionary Testing
Authors: Zhang Du
Published: November 2012

The fundamental objective in value-based software engineering is to integrate consistent stakeholder value propositions into the full extent of software engineering principles and practices so as to increase the value for software assets. In such a value-based setting, artifacts in software development such as requirement specifications, use cases, test cases, or defects, are not treated as equally important during the development process. Instead, they will be differentiated according to how much they are contributing, directly or indirectly, to the stakeholder value propositions. The higher the contributions, the more important the artifacts become. In turn, development activities involving more important artifacts should be given higher priorities and greater considerations in the development process. In this paper, a value-based framework is proposed for carrying out software evolutionary testing with a focus on test data generation through genetic algorithms. The proposed framework incorporates general principles in value-based software testing and makes it possible to prioritize testing decisions that are rooted in the stakeholder value propositions. It allows for a cost-effective way to fulfill most valuable testing objectives first and a graceful degradation when planned testing process has to be shortened.
Indoor Surveillance Application using Wireless Robots and Sensor Networks
Authors: Koubaa Anis , Trigui Sahar , Chaari Imen
Published: November 2012

Mobile robots and Wireless Sensor Networks (WSNs) are enabling technologies of ubiquitous and pervasive applications. Surveillance is one typical example of such applications for which the literature proposes several solutions using mobile robots and/or WSNs. However, robotics and WSNs have mostly been considered as separate research fields, and little work has investigated the marriage of these two technologies. In this chapter, the authors propose an indoor surveillance application, SURV-TRACK, which controls a team of multiple cooperative robots supported by a WSN infrastructure. They propose a system model for SURV-TRACK to demonstrate how robots and WSNs can complement each other to efficiently accomplish the surveillance task in a distributed manner. Furthermore, the authors investigate two typical underlying problems: (1) Multi-Robot Task Allocation (MRTA) for target tracking and capturing and (2) robot path planning. The novelty of the solutions lies in incorporating a WSN in the problems’ models. The authors believe that this work advances the literature by demonstrating a concrete ubiquitous application that couples robotic and WSNs and proposes new solutions for path planning and MRTA problems.
Control Architecture Model in Mobile Robots for the Development of Navigation Routes in Structured Environments
Authors: Hossian Alejandro , Monte Gustavo , Olivera Verónica
Published: November 2012

Robotic navigation applies to multiple disciplines and industrial environments. Coupled with the application of Artificial Intelligence (AI) with intelligent technologies, it has become significant in the field of cognitive robotics. The capacity of reaction of a robot in unexpected situations is one of the main qualities needed to function effectively in the environment where it should operate, indicating its degree of autonomy. This leads to improved performance in structured environments with obstacles identified by evaluating the performance of the reactive paradigm under the application of the technology of neural networks with supervised learning. The methodology implemented a simulation environment to train different robot trajectories and analyze its behavior in navigation and performance in the operation phase, highlighting the characteristics of the trajectories of training used and its operating environment, the scope and limitations of paradigm applied, and future research.
A Hierarchically Structured Collective of Coordinating Mobile Robots Supervised by a Single Human
Authors: Wong Choon Yue , Seet Gerald , Sim Siang Kok , Pang Wee Ching
Published: November 2012

Using a Single-Human Multiple-Robot System (SHMRS) to deploy rescue robots in Urban Search and Rescue (USAR) can induce high levels of cognitive workload and poor situation awareness. Yet, the provision of autonomous coordination between robots to alleviate cognitive workload and promote situation awareness must be made with careful management of limited robot computational and communication resources. Therefore, a technique for autonomous coordination using a hierarchically structured collective of robots has been devised to address these concerns. The technique calls for an Apex robot to perform most of the computation required for coordination, allowing Subordinate robots to be simpler computationally and to communicate with only the Apex robot instead of with many robots. This method has been integrated into a physical implementation of the SHMRS. As such, this chapter also presents practical components of the SHMRS including the robots used, the control station, and the graphical user interface.
RobotBASIC
Authors: Blankenship John , Mishal Samuel
Published: November 2012

Unlike most chapters in this book, this chapter does not introduce new methods or algorithms related to robotic navigation systems. Instead, it provides an overview of a simulation tool that, in some situations, can be useful for quickly evaluating the overall appropriateness of a wide variety of alternatives before focusing more advanced development activities on a chosen design. In addition, since the tool described herein is totally free, it can be used to help students and others new to robotics understand the value of utilizing a design-simulate-deploy approach to developing robotic behaviors. Robot Simulators can emulate nearly all aspects of a robot’s functionality. Unfortunately, many programming environments that support simulation have steep learning curves and are difficult to use because of their ability to handle complex attributes such as 3D renderings and bearing friction. Fortunately, there are many situations where advanced attributes are unnecessary. When the primary goal is to quickly test the feasibility of a variety of algorithms for robotic behaviors, RobotBASIC provides an easy-to-use, economical alternative to more complex systems without sacrificing the features necessary to implement a complete design-simulate-deploy cycle. RobotBASIC’s ability to simulate a variety of sensors makes it easy to quickly test the performance of various configurations in an assortment of environments. Once algorithm development is complete, the same programs used during the simulation phase of development can immediately control a real robot.
Design and Optimization of Microwave Circuits and Devices with the Particle Swarm Optimizer
Authors: Donelli Massimo
Published: November 2012

In this chapter, a methodology for the unsupervised design of microwave devices, circuits, and systems is considered. More specifically, the application of the Particle Swarm Optimizer and its integration with electromagnetic simulators is discussed in the framework of the microwave circuits and devices design and optimization. The idea is to automatically modify the characteristics of the device in an unsupervised way, with the goal of improve the device performances. Such kind of CAD tool could be the solution to reduce the time to market and keep the commercial predominance, since they do not require expert microwave engineers and it can reduce the computational time typical of the standard design methodologies. To assess the potentialities of the proposed method, a selected set of examples concerning the design of microwave planar devices such as filters, splitters, and other microwave devices under various operative conditions and frequency bands are reported and discussed. The chapter also includes a brief discussion concerning different strategies, such as parallel computation, to reduce the computational burden and the elaboration time. The obtained results seem to confirm the capabilities of the proposed method as effectiveness microwave CAD tool for the unsupervised design of microwave devices, circuits, and systems. The chapter ends with some conclusions and considerations related to ideas for future works.
The Influences of Employees’ Emotions and Cognition on IT Adoption
Authors: Kashefi Armin , Abbott Pamela , Bell David
Published: November 2012

This paper presents an extended model of individuals’ reactions to IT implementation initiatives. The aim is to explore the relationship between an employee’s cognitive appraisal of an IT initiative, their emotional response, and the processes they undergo when faced with difficulties in accepting IT adoption and change in an organizational setting. The paper presents the results of an interpretive case study based in Iran. According to the findings of the study, employees’ evaluations of a new IT initiative can become an obstacle to change. The paper’s first contribution is to provide a deeper understanding of the effects of an IT implementation on individuals’ emotions and cognition. The second contribution is the use of the extended model in a real organizational setting in Iran, a country in which the importance of employee’s reactions to technology change has never been considered as crucial.
Proposing an Intelligent Cloud-Based Electronic Health Record System
Authors: Khansa Lara , Forcade Jonathan , Nambari Girivaraprasad , Parasuraman Saravanan , Cox Patrick
Published: November 2012

With the aging United States population, healthcare costs have considerably increased and are expected to keep rising in the foreseeable future. In this paper, the authors propose an intelligent cloud-based electronic health record (ICEHR) system that has the potential to reduce medical errors and improve patients’ quality of life, in addition to reducing costs and increasing the productivity of healthcare organizations. They developed a set of best practices that encompass end-user policies and regulations, identity and access management, network resilience and service level agreements, advanced computational power, “Big Data” mining abilities, and other operational/managerial controls that are meant to improve the privacy and security of the ICEHR, and make it inherently compliant to healthcare regulations. These best practices serve as a framework that offers a single interconnection agreement between the cloud host and healthcare entities, and streamlines access to private patient information based on a unified set of access principles.
Towards HIPAA-Compliant Healthcare Systems in Cloud Computing
Authors: Wu Ruoyu , Ahn Gail-Joon , Hu Hongxin
Published: November 2012

In modern healthcare environments, there is a strong need to create an infrastructure that reduces time-consuming efforts and costly operations to obtain a patient’s complete medical record and uniformly integrates this heterogeneous collection of medical data to deliver it to the healthcare professionals. As a result, healthcare providers are more willing to shift their electronic medical record (EMR) systems to clouds that can remove the geographical distance barriers among providers and patients. Since a shared electronic health record (EHR) essentially represents a virtualized aggregation of distributed clinical records from multiple healthcare providers, sharing of such integrated EHRs should comply with various authorization policies from these data providers. In previous work, the authors present and implement a secure medical data sharing system to support selective sharing of composite EHRs aggregated from various healthcare providers in cloud computing environments. In this paper, the authors point out that when EMR systems are migrated to clouds, it is also critical to ensure that EMR systems are compliant with government regulations such as the Health Insurance Portability and Accountability Act (HIPAA). Also, the authors propose a HIPAA compliance management approach by leveraging logic-based techniques and apply it to the cloud-based EHRs sharing system. The authors also describe evaluation results to demonstrate the feasibility and effectiveness of the approach.
Deep Vein Thrombosis, Ecythyma Gangrenosum and Heparin-Induced Thrombocytopenia Occurring in a Man with a Heterozygous Factor V Leiden Mutation
Authors: Apostolova Mariya , Weng Baoying , Pote Harry , Ashcraft Harold , Goldblatt Curtis , Woolley Paul
Published: November 2012

Skin necrosis and limb gangrene are occasional thrombotic manifestations of anticoagulation therapy. We report a man heterozygous for the Factor V Leiden (FVL) mutation, and with a history of recurrent deep venous thrombosis, who initially presented with a necrotic skin lesion of the right flank while on warfarin therapy with a therapeutic international normalized ratio. Warfarin was discontinued and he received intravenous heparin. Thereafter he developed thrombocytopenia and pedal erythema and was diagnosed with heparin-induced thrombocytopenia (HIT). Heparin was replaced with argatroban. He ultimately underwent bilateral below-knee amputations for the thrombotic complications of the HIT. The initial necrotic lesion healed with antibiotics and wound care. Pathologic examination of multiple biopsy specimens revealed two separate lesions. One was necrotic tissue infiltrated with methicillin resistant Staphylococcus aureus having features of ecthyma gangrenosum. The second showed thrombotic changes consistent with HIT. The case illustrates the differential diagnosis of skin necrosis and limb gangrene in patients on warfarin and heparin, and also the clinical complexities that can occur in a FVL heterozygote.
The biology of human sexuality: evolution, ecology and physiology
Authors: Bateman PW , Bennett NC
Published: November 2012

Many evolutionary biologists argue that human sexual behaviour can be studied in exactly the same way as that of other species. Many sociologists argue that social influences effectively obscure, and are more important than, a reductionist biological approach to human sexual behaviour. Here,we authors attempt to provide a broad introduction to human sexual behaviour from a biological standpoint and to indicate where the ambiguous areas are. We outline the evolutionary selective pressures that are likely to have influenced human behaviour and mate choice in the past and in the present; ecological features that influence such things as degree of parental care and polygamy; and the associated physiology of human sexuality. Then they end with a discussion of ‘abnormal’ sexuality.
Der wahre Große im Dienst seiner Seele: "Mýthos" und "bìos" in Carl Spittelers
Authors: Hauser Jeannine
Published: November 2012

Carl Spittelers Prometheus-Dichtungen von 1881 und 1924, beide dem hohen Stil des Epos verpflichtet, übertragen den antiken Prometheus-Stoff in eine phantastische Welt, in der sich religiöse Vorstellungen mit märchenhaften Elementen vermischen, und zeigen an Prometheus und dessen Bruder Epimetheus exemplarisch die Diskrepanz zwischen dem Ausnahmemenschen und dem Mitläufer, zwischen dem wahren und falschen Großen, wobei sich diese wahre „Größe“ in ihrer Treue zu einer Seelenfigur manifestiert. Beide Fassungen weisen starke Bezüge sowohl zum zeitgenössischen Kontext als auch zur Biographie des Verfassers auf, der in seinen epischen Monumentalwerken nicht nur Stellung zur zeitgeschichtlichen Situation der Jahrhundertwende bezieht, sondern auch seine Dichterwerdung verarbeitet und das Künstlerdasein problematisiert.
Leopoldo Lugones contra los dioses: la configuración prometeica del arquetipo del gaucho en "El payador" (1916)
Authors: Polotto Sabaté María Lydia
Published: November 2012

En este artículo nos proponemos demostrar cómo Leopoldo Lugones configura el arquetipo del gaucho en su obra El payador (1916) como un personaje prometeico. En primer lugar, veremos que tanto Prometeo como el gaucho cumplen la función de agentes civilizadores y llevan adelante su actividad a partir de un acto de rebeldía contra la autoridad. En segundo lugar, analizaremos por qué es importante el “castigo” de ambos personajes como elemento esencial para que dicha función civilizadora pueda ser culminada con éxito.
Clinical Diagnostic Clues in Crohn's Disease: A 41-Year Experience
Authors: Quintana C. , Galleguillos L. , Benavides E. , Quintana J. C. , Zúñiga A. , Duarte I. , Klaassen J. , Kolbach M. , Soto R. M. , Iacobelli S. , Álvarez M. , O'Brien A.
Published: November 2012

Determining the diagnosis of Crohn’s disease has been highly difficult mainly during the first years of this study carried out at the Pontificia Universidad Catolica (PUC) Clinical Hospital. For instance, it has been frequently confused with Irritable bowel syndrome and sometimes misdiagnosed as ulcerative colitis, infectious colitis or enterocolitis, intestinal lymphoma, or coeliac disease. Consequently, it seems advisable to characterize what the most relevant clinical features are, in order to establish a clear concept of Crohn's disease. This difficulty may still be a problem at other medical centers in developing countries. Thus, sharing this information may contribute to a better understanding of this disease. Based on the clinical experience gained between 1963 and 2004 and reported herein, the main clinical characteristics of the disease are long-lasting day and night abdominal pain, which becomes more intense after eating and diarrhoea, sometimes associated to a mass in the abdomen, anal lesions, and other additional digestive and nondigestive clinical features. Nevertheless, the main aim of this work has been the following: is it possible to make, in an early stage, the diagnosis of Crohn's disease with a high degree of certainty exclusively with clinical data?
Comparative Analysis of Motorized and Manually Propelled Technologies of Artisanal Fisheries in Ijebu Waterside of Ogun State
Authors: R O Kareem , E O Idowu , S B Williams , I A Ayinde , N O Bashir
Published: November 2012

This study was carried out to analyze the comparative analysis of efficiencies of artisanal fisheries in Ijebu Waterside of Ogun State. The objectives determined gross margin analysis; estimate the technical efficiencies of both the manually propelled technology (MPT) and motorized technology (MT) of artisanal fishery systems and determining the factors influencing the technical efficiencies of artisanal fisheries in the study area. A multistage sampling technique was used to select a total of 400 Artisans from the study area. Primary data were collected using structured questionnaire as interview guide, on the socio-economic characteristics, production inputs and output prices. The data collected were analyzed using both descriptive and inferential statistics. Stochastic production frontier model was used to estimate the technical, efficiencies of both motorized and manually propelled technologies in artisanal fishery system as well as the factors influencing the technical, efficiencies of the artisans.

The results of the comparison of the MPT and (MT) revealed that the average income per month for MPT was N361,847.48 and the amount accruable per month for the MT was N560,755.57. The results of the comparison of catch efficiency and inefficiency function showed that in MPT, fishing gear, vessel length, number of crew/skippers, quantity of bait and battery were all significant at 5 percent probability level while for MT, fishing gear, outboard engine, battery and miscellaneous quantity were the significant factors. The mean catch efficiency of MPT was 0.92 compared to MT with 0.98. However, the comparison of the inefficiency shows that education, age, and household size are significant factors while education is significant factors in both MPT and MT respectively. The results of the returns-to-scale revealed that the parameters estimate of the MT was higher with 4.35 compared to MPT with 2.56.
“Connecting Cultures“: The Mekong River at the Smithsonian Folklife Festival, 2007
Authors: Rees Helen
Published: November 2012

Each summer, the world-renowned Smithsonian Institution in Washington, DC, mounts a huge, ten-day-long festival on the National Mall, showcasing the folk arts of selected US states, communities, occupational groups, foreign countries, and/or transnational regions. The Smithsonian Folklife Festival has run every year since 1967, organized as “an annual display of living cultural heritage” (Kurin 1997:111) that typically features musicians, dancers, ritual specialists, craftspeople, storytellers, food preparers, specialized workers, learning opportunities, and discussion sessions. The emphasis is very much on “grassroots” culture, and on “foreground[ing] the voices of tradition bearers as they demonstrate, discuss, and present their cultures” (ibid.: 113). The festival is simultaneously an opportunity for the chosen locales and communities to raise their profile on an international stage, and for hundreds of thousands of Americans and overseas tourists to learn about places and cultures they might never otherwise encounter. Entrance to all events is free of charge, and annual attendance averages over one million.
The Efficacy and Safety of Platelet-Rich Plasma and Adipose-Derived Stem Cells: An Update
Authors: Choi Jaehoon , Minn Kyung Won , Chang Hak
Published: November 2012

During the past decade, many studies using platelet-rich plasma (PRP) or adipose-derived stem cells (ASCs) have been conducted in various medical fields, from cardiovascular research to applications for corneal diseases. Nonetheless, there are several limitations of practical applications of PRP and ASCs. Most reports of PRP are anecdotal and few include controls to determine the specific role of PRP. There is little consensus regarding PRP production and characterization. Some have reported the development of an antibody to bovine thrombin, which was the initiator of platelet activation. In the case of ASCs, good manufacturing practices are needed for the production of clinical-grade human stem cells, and in vitro expansion of ASCs requires approval of the Korea Food and Drug Administration, such that considerable expense and time are required. Additionally, some have reported that ASCs could have a potential risk of transformation to malignant cells. Therefore, the authors tried to investigate the latest research on the efficacy and safety of PRP and ASCs and report on the current state and regulation of these stem cell-based therapies.
Soft Palate Reconstruction Using Bilateral Palatal Mucomuscular Flap and Pharyngeal Flap after Resection of Squamous Cell Carcinoma
Authors: Kim Jun Sik , Jo Hyeon Jong , Kim Nam Gyun , Lee Kyung Suk
Published: November 2012

Squamous cell carcinoma infrequently occurs at the soft palate. Although various methods can be used for reconstruction of soft palate defects that occur after resecting squamous cell carcinoma, it is difficult to obtain satisfactory results from the perspective of the functional restoration of the soft palate. A combination of bilateral palatal mucomuscular flap for the oral side and superiorly based posterior pharyngeal flap for the nasal side were performed on two patients who were diagnosed with squamous cell carcinoma of the soft palate in order to reconstruct the soft palate defects after surgical resection. After surgery, the patients were followed-up for a mean period of 11 months. The flaps were well maintained in both patients. The donor site defects were epithelialized and completely recovered. Additionally, no recurrence of the primary sites was shown. Slight hyponasality was observed in the voice assessments that were conducted 6 months after surgery. No food regurgitation or aspiration was observed in the swallowing tests. We used a combination of bilateral palatal mucomuscular flap and superiorly based posterior pharyngeal flap to reconstruct the soft palate defects that occurred after resecting the squamous cell carcinomas. We reduced the donor site complications and achieved functionally satisfactory outcomes.
Cell-Assisted Lipotransfer for the Treatment of Parry-Romberg Syndrome
Authors: Castro-Govea Yanko , De La Garza-Pineda Oscar , Lara-Arias Jorge , Chacón-Martínez Hernán , Mecott-Rivera Gabriel , Salazar-Lozano Abel , Valdes-Flores Everardo
Published: November 2012

Progressive facial hemiatrophy, also known as Parry-Romberg syndrome, is a progressive and self-limited deformation of the subcutaneous tissue volume on one side of the face that creates craniofacial asymmetry. We present the case of a patient with a five-year history of progressive right facial hemiatrophy, who underwent facial volumetric restoration using cell-assisted lipotransfer (CAL), which consists of an autologous fat graft enriched with adipose-derived stem cells (ASCs) extracted from the same patient. ASCs have the capacity to differentiate into adipocytes. They also promote angiogenesis, release angiogenic growth factors, and some can survive as stem cells. The use of autologous fat as a filler in soft tissue atrophy has been satisfactory in patients with mild and moderate Parry-Romberg syndrome. Currently, CAL has showed promising results in the long term by decreasing the rate of fat reabsorption. The permanence and stability of the graft in all the injected areas has showed that autologous fat grafts enriched with stem cells could be a promising technique for the correction of defects caused by this syndrome.
Secondary hyperparathyroidism in HIV‐infected patients: relationship with bone remodeling and response to vitamin D supplementation
Authors: Bañon S , Del Palacio M , Pérez Elías M , Moreno A , Moreno S , Dronda F , Casado J
Published: November 2012

Purpose of the study

Secondary hyperparathyroidism (SH) is frequent in HIV‐infected patients. However, the causes and consequences are not well established. The aim of our study was to determine the relationship between parathyroid hormone (PTH), vitamin D and bone mineral density (BMD) in HIV‐infected patients, and the effect of vitamin D replacement on PTH levels.

Methods

Prospective study of 506 patients with at least two sequential serum determinations of PTH and 25‐hydroxyvitamin D levels. In all cases, a bone dual X‐ray absorptiometry (DEXA) was performed at inclusion. Hyperparathyroidism was defined as a PTH level above 65 pg/ml.

Summary of results

Mean age was 44 yrs (24–78), and 75% were male. Mean BMI was 23.7 (17.97–33.11), and only 3% were of black race. Median nadir CD4+ was 200 cells/µL (9–499), and median time of HIV infection was 15.3 yrs (1.7–25.2). At inclusion, 488 patients (86%) were on HAART (31% TDF+PI, 44% TDF+NNRTI, 25% non‐TDF based regimen) for a median of 929.5 days (154–1969), and 40% were HCV‐coinfected. Median eGFR was 97.9 ml/min (62.14–134.08). Overall, mean serum PTH was 56.3 pg/mL (27.2–95.07). SH was observed in 27% of cases, with a marked influence of seasonality (from 44% in January to 10% in August). Mean levels of vitamin D were 17.45 ng/mL (7.6–40.78), with 16% below 10 ng/ml, 59%<20 ng/ml (deficiency), 85%<30 ng/ml (insufficiency). SH was related to vitamin D deficiency (relative risk, RR, 2.44), age (RR 1.04 per year), and a higher decrease in eGFR (RR 1.03 per ml/min), after adjustment by season, antiretroviral therapy, GFR at baseline, and HCV coinfection. DEXA scan showed 18% osteoporosis and 54% osteopenia, and there was an inverse correlation between PTH levels and T and Z score in femoral neck (r=−0.14, p<0.01), higher in those patients below 40 yrs. Vitamin D supplementation in 181 patients produced a significant decrease in serum PTH (57.2 if not treated vs 50.5 pg/ml, p=0.02, 23% continues with SH) and the only factor associated with lack of response was persistent vitamin D deficiency.

Conclusion

SH is relatively frequent in HIV patients, in close relation with vitamin D deficiency. It is associated with bone resorption, especially in the femoral neck. The use of vitamin D supplementation improves SH when levels above 20 ng/ml are achieved.
Bone turnover markers in HIV‐infected patients before starting antiretroviral therapy
Authors: Martín‐Morales R , Ruiz J , Nuño E , Márquez M , Santos J , Palacios R
Published: November 2012

Purpose

Bone turnover markers (BTM) ‐ aminoterminal propeptide of type 1 collagen (P1NP) and C‐terminal telopeptide of type 1 collagen (β‐CTX) ‐ are related to bone density and fracture risk. A high prevalence of osteopenia/osteoporosis and hypovitaminosis D has been reported in HIV patients, however there are few data about BTM in this population. Our aim was to analyse the prevalence of elevated serum levels of BTM in HIV patients before starting antiretroviral therapy (ART), and related factors.

Methods

Cross‐sectional study of a series of HIV‐patients who started ART during June/11–June/12 in our hospital. Patients with presence of diseases or treatments known to affect bone metabolism were excluded. Epidemiological, clinical, and immunovirological data in addition to serum fasting levels of glucose, lipid profile, calcium, phosphate, alkaline phosphatase, 25‐hydroxyvitamin D3 (25OHD), parathyroid hormone (PTH), P1NP, and β‐CTX were collected. Definitions: hypovitaminosis D if 25OHD<30 ng/ml, vitamin D deficiency if 25OHD<20 ng/ml; elevated levels of BTM if β‐CTX (ng/ml) >0.64 (men<70 years),>0.85 (men >70 years),>0.58 (pre‐menopause women), >0.99 (post‐menopause women), or P1NP (ng/mL)>69.4 (men <60 years), >71.1 (men>60 years), >55.7 (pre‐menopause women), >61.2 (post‐menopause women).

Results

47 patients were included, 91.5% men, median age 37.1 years (30.0–44.3), and 93.6% sexual transmission of HIV (34 HMX, 10 HTX). Median time since the diagnosis of HIV was 3.4 months (1.4–31.7); there were 7 (14.9%) Aids cases, median CD4 count was 277/mm3 (155–433), and HIV‐VL 4.8 log10 (4.1–5.2). Median serum 25OHD was 29 µg/L (21.9–41.1), with a prevalence of hypovitaminosis of 52.2%, and deficiency of 17.4%. PTH was in range in all cases. Median serum P1NP was 33.3 ng/mL (24.5–52.5) and β‐CTX 0.25 ng/mL (0.20–0.45); five (11.4%) patients presented high levels of BTM: 4 men, median age 37.1 years, median CD4 count 247/mm3, median HIV‐VL 5.18 log10, and one with hypovitaminosis D. Elevated BTM were related with no clinical, analytical, immunovirological parameters nor with serum levels of 25OHD nor PTH.

Conclusions

The prevalence of elevated BTM was high in this series of HIV‐patients, mostly young men, with short time of HIV infection and with no immunovirologic control. BTM were related with no clinical nor analytical data.
Densitometric disorders in children infected with HIV
Authors: Marczyñska M , Oldakowska A , Szczepañska‐Putz M , Dobosz S , Coupland U , Popielska J
Published: November 2012

The aim of study was to assess the prevalence of densitometric disorders and deficiencies of vitamin D3 in children vertically HIV‐infected, treated with cART. In 34 children vertically HIV‐infected aged 10–16 years (mean 13 years), receiving cART≥5, bone densitometry and the titer of 25‐OHD3 was done. We analyzed at the time of diagnosis of HIV infection and at the time of the study: age, clinical and immunological classification, the length, effectiveness of cART, the lowest immunological classification. 15/34 (44%) children had abnormal dual‐energy X‐ray absorptiometry examination (DEXA) of the lumbar aged‐matched mean Z‐score −2.1 (range −1.2 to −3.5), of which 8 also had abnormal DEXA whole spine aged‐matched mean Z‐score −1.6 (range −1.1 to−2.2). Level of 25‐OHD3 was abnormal (<20 ng/ml) in 29/34 (85%), in 7 of them the level was very low (<4.0 ng /ml). 4/5 children with normal values of 25‐OHD3 parallel had correct densitometry; 1/5 with a normal value of 25‐OHD3 had significant abnormalities of bone density, visible in radiographs of the hand. Clinical classification at diagnosis was: N/A in 17, B in 12, C in 5 and immunological classification: 1 in 11, 2 in 9, 3 in 13 cases. The lowest classification was AIDS in 9 children, 15 had moderate signs of infection, and 10 mild signs; deep immune deficiency occurred in 17 children, 15 had moderate and 2 have never had immunodeficiency. The regimens based on PI received 9 children, NNTRI −6, all 3 classes received 19. At the time of the study 31 children were successfully treated, 32 had no immunodeficiency, two had moderate deficiency. 32 children were qualified to N/A group, one was in the classification of B and one in C. All children unsuccessfully treated (3) had low levels of 25‐OHD3. In a significant percentage of older children receiving antiretroviral treatment≥5 years, had abnormal results of densytometry examination. There was no correlation between age, duration of the cART, the severity of the clinical, immunological classification, viral load and bone density disorders. Level of 25‐OHD3 was abnormal in the majority of children. Disorders were also found in children successfully treated.
Temporal changes of sleep disturbances and their associations with CYP450 2B6 polymorphism and plasma drug level in HIV patients on efavirenz
Authors: To K , Lee M , Lee C , Lee S
Published: November 2012

Neurological and sleep disturbances were commonly reported among HIV patients on efavirenz (EFV), the pharmacokinetic pattern varies with different CYP450 2B6 G516T genotypes. This prospective study aims to detect temporal changes and differences in the profile of these adverse reactions and their relation to plasma EFV level and host genotypes. HIV patients of Chinese ethnicity on an EFV‐containing HAART regimen were recruited from a specialist clinic. Blood for CYP2B6 G516T genotypes was taken. A questionnaire assessing adverse neurological problems and sleep disturbance was administered, alongside testing for plasma EFV levels at baseline, 4 weeks, 8 months and 1 year intervals after treatment. Analysis was performed using χ2 and t‐test. A total of 64 patients (31 GG, 27 GT, 6 TT genotypes, 59 male, and 5 female, mean age of 41±9.9) were recruited. At 4 weeks after EFV, 49 (76%) gave a history of any one of the neurological side effects: dizziness, headache and drunk feeling. Sleep disturbances were common: bizarre dream (45%), nightmares (35%), waking at night (73%), poor sleep quality (31%), nocturia (84%) and difficulty in falling asleep (67%). The mean plasma EFV level of GG genotype was 2.8 µg/ml and 3 µg/ml, GT genotype was 3.8 µg/ml and 3.9 µg/ml, at 4 weeks and 1 year respectively. The mean plasma EFV level of TT genotype was 11.9 µg/ml and 9.7 µg/ml at 4 weeks and 1 year respectively. There was no significant variation of drug level within each genotype over time (p>0.08), while EFV level of TT was significantly higher at all time points (p<0.01). Overall, nightmares and difficulty to fall asleep were significantly related to the plasma EFV level (p=0.021 and 0.017 respectively). However, the sleep quality, nocturnal awakening, nocturia or requirement of sleeping pills was not significantly associated with EFV level (p=0.28, 0.06, 0.1 and 0.5 respectively). When the side effects were separately evaluated according to time points, they all became insignificantly related to plasma EFV level at 12 weeks. In conclusion, very high plasma EFV level was observed in TT genotype (9.4% of patients). There was no relationship between genotype GG/GT and the occurrence of neurological side effects. While selected sleep disturbances like nightmares and difficulty to fall asleep were associated with plasma EFV levels, the general sleep quality was not significantly affected. The influence of plasma EFV levels on side effects diminished over time.
Lack of correlation between UGT1A1*6, *28 genotypes, and plasma raltegravir concentrations in Japanese HIV‐1‐infected patients
Authors: Takahashi M , Hirano A , Oishi Y , Sato M , Yoshino M , Ikemura K , Shibata M , Fukushima N , Amioka K , Nomura T , Yokomaku Y , Sugiura W
Published: November 2012

Background

Raltegravir is metabolized by glucuronidation via UGT1A1. Among the genetic polymorphisms of UGT1A1, the *6, *27 and *28 alleles are associated with reduced levels of UGT1A1. In particular, the *28 allele accounts for most of the UGT1A1 polymorphisms, and the level of UGT1A1 activity has been the focus of most studies. On the other hand, among Asians, the *6 and *27 alleles are more commonly found in comparison with white populations. In this study, we aimed to clarify the contribution of UGT1A1 polymorphisms (*6, *27) to plasma raltegravir concentrations in Japanese HIV‐1‐infected patients.

Materials & Methods

We analyzed the presence of genotypic variants (*6, *27 and *28) among the 74 patients recruited at the National Hospital Organization Nagoya Medical Center. Genotyping of *6 and *27 in UGT1A1 was performed using the TaqMan drug metabolism genotyping assay. Genotyping of *28 in UGT1A1 was performed using the primers described by Ehmer et al. Plasma raltegravir concentrations were determined by a LC‐MS method.

Results

Among the 74 patients, the UGT1A1 genotype in 3 patients (two male, one female) was *6 homozygote. Heterozygous variants were found in 20 patients for *6, and in 14 patients for *28, while all of the patients were found to carry wild‐type sequences at the position corresponding to the *27 allele. The male *6 homozygote patient had modestly higher plasma raltegravir concentration (0.53 µg/ml) than other patients who were wild type (0.12 µg/ml) or heterozygous (0.16 µg/ml) for the *6 polymorphism. The other two UGT1A1*6 homozygote patients had a lower plasma raltegravir concentration (0.03 and 0.05 µg/ml). On the other hand, plasma raltegravir concentrations were 0.12 µg/ml (*6−/− *28−/−; n=37), 0.11 µg/ml (*6−/− *28−/+; n=14), 0.16 µg/ml (*6−/+ *28−/−; n=20). There were no statistically significant differences in the plasma raltegravir concentrations between patients carrying wild‐type alleles and those heterozygous for *6 or *28.

Conclusions

Patients heterozygous for the *6 or *28 allele did not display significantly different plasma raltegravir concentrations compared to patients homozygous for the respective wild‐type allele. In this study, we showed that heterozygosity for the reduced‐function *6 and *28 alleles had no significant effect on plasma raltegravir concentrations in Japanese HIV‐1‐infected patients.
Use of antacid preparations with HAART
Authors: Vekeria S , Nelson M
Published: November 2012

Background

Concurrent prescription and consumption of antacid and ulcer healing preparations can affect the absorption of some antiretrovirals (ARV) due to increases in intra‐gastric pH and should therefore be avoided in drugs dependent on gastric pH for absorption.

Methods

Questionnaires were given to consecutive consenting patients presenting to outpatient pharmacy who were receiving antiretroviral therapy (ART) which consisted of either atazanavir (TAZ), darunavir (DRV) or efavirenz (EFV) for greater than 1 year. All patients receiving TAZ are routinely advised on the need for caution with co‐administration of antacid preparations when they commence the drug. Information was gathered on the awareness of potential interactions between ARVs and antacid/ulcer healing medication and the use of such preparations over the past year. Viral load (VL) data was observed for each patient and any VL blips in the preceding year recorded.

Results

A total of 215 patients were questioned, of whom 30% were aware of interactions between ART and antacids/ulcer healing medication; 38% of patients receiving TAZ, 30% on DRV and 25% and on EFV were aware of the drug interaction. 62% of individuals receiving TAZ were therefore unaware of the need not to receive antacid preparations with this drug. 30% (n=66) of patients had either been prescribed or bought antacid/ulcer healing medication in the previous year. 16 out of the 215 patients were recorded as having at least one VL blip in the last year; 9 on TAZ, 6 on DRV and 1 on EFV. 7 of these patients had either bought or been prescribed antacids in the previous year. Four of the patients with viral blips on TAZ had taken antacid preparations.

TAZ
DRV
EFV

n
63
53
99

Aware of interactions with ART
24
16
25

Prescribed PPI/antacid
5
13
9

Bought PPI/antacid
15
15
19

Conclusion

The majority of patients are unaware of potential interactions between ARVs and antacids. However, few patients developed a positive viral load during the period studied. Patients receiving TAZ were not more aware of the potential drug interaction than those receiving other agents. It is essential that information is given to patients at each clinic visit to reinforce interactions between antacids and HAART.
No change of plasma darunavir concentrations by switching from ritonavir soft capsule to tablet
Authors: Shibata M , Takahashi M , Fukushima N , Yamaguchi F , Nomura T , Yokomaku Y , Sugiura W
Published: November 2012

Background

Darunavir, a second‐generation protease inihibitor, is used with a low boosting dose of ritonavir to improve its clinical efficacy. The boosting dose of ritonavir acts as an inhibitor of CYP3A4, thereby increasing darunavir bioavailability. Recently, ritonavir tablet has been on sale in place of soft capsule. However, pharmacokinetic study of darunavir by changing ritonavir form is still not clear. In this study, we aimed to compare with plasma darunavir concentrations by switching ritinavir soft capsule to tablet in Japanese HIV‐1 infected patients.

Methods

We analyzed 34 Japanese HIV‐1 infected patients (32 males: 2 females) recruited at the National Hospital Organization Nagoya Medical Center. All patients had been administered with 800/100 mg darunavir/ritonavir once daily in combination with other antiretrovirals. Plasma darunavir concentrations were determined by an HPLC method. A pared t‐test was used to compare with their concentrations by switching from ritonavir soft capsule to tablet.

Results

The mean of age, body weight, and duration of antiretroviral therapy for 34 patients were 41.9 (range: 24–62) years, 66.3 (range: 51.4–90.0) kg, and 436 (range: 182–739) days, respectively. The mean±SD darunavir concentration was 3.44±1.78 µg/ml when ritonavir soft capsule was co‐administered. After switching to ritonavir tablet, the mean±SD darunavir concentration was 3.30±2.02 µg/ml. Statistical difference was not found in plasma trough darunavir concentration between ritonavir soft capsule and tablet (P=0.826). On the other hand, the mean of viral load was 78 copies/ml when ritonavir soft capsule was administered. After switching to ritonavir tablet, the mean viral load was 33 copies/ml.

Conclusion

Recruited all patients have been sustained an ndetectable viral load (less than 40 copies/ml) after switching to ritonavir tablet. In this study, switching to ritonavir tablet had no significant difference on plasma darunavir concentrations in Japanese HIV‐1 infected patients.
Cost of switching darunavir+ritonavir (DRV+RTV) to lopinavir/ritonavir (LPV/r) in HIV‐1‐infected treatment‐naïve women of child‐bearing age (WOCBA)
Authors: Baran R , Moller J , Desai K , Simpson K , Van de Steen O , Dietz B , Gooch K
Published: November 2012

Guidelines consider LPV/r a preferred protease inhibitor for use during pregnancy. When an HIV‐infected woman receiving DRV+RTV becomes pregnant, a switch to LPV/r may be warranted. The budget implications of proactively initiating LPV/r versus initiating DRV+RTV and then switching has not been examined. A cost‐minimization analysis was performed from the US healthcare perspective for HIV‐1‐infected, treatment‐naïve WOCBA comparing: initiating LPV/r in all patients versus initiating DRV+RTV and switching to LPV/r when pregnant. A discrete event simulation was employed to represent antiretroviral (ARV) therapy management. Healthcare utilization and clinical trial data [1] were used to model pregnancy rates [2], ARV regimen switch rates, and impact of treatment as a function of CD4‐cell count and viral load, adherence, treatment response, acquired resistance mutations, and ensuing treatment changes. Five‐ and 10‐year costs incurred due to ARV therapy, clinician visits and management of AIDS‐related, non‐AIDS related, and cardiovascular events were estimated. Base‐case analysis assumptions: switching to LPV/r can occur only once at first pregnancy, 30% of WOBCA switch to LPV/r circa time of pregnancy, and women's adherence to medication improves by 15% when becoming pregnant. Sensitivity analyses varied the rate of switching to LPV/r at time of pregnancy, pregnancy rates, adherence improvement, and healthcare costs. Daily drug cost of LPV/r + TDF/FTC was $56.59 while DRV+RTV+TDF/FTC was $73.89. Costs were discounted at 3% per annum. Survival was similar in both groups. Five‐ and 10‐year total healthcare costs of ARV‐naïve HIV‐positive WOCBA who initiate LPV/r were $108,200 and $192,600 per patient, respectively, compared to $132,200 and $234,400 when women initiated DRV+RTV and then 30% switched to LPV/r. Initiating with LPV/r resulted in 5‐ and 10‐year savings of $24,000 and $41,800 per patient, respectively. If 100% of patients who initiated with DRV+RTV switched to LPV/r upon pregnancy, the savings per patient were $21,300 at 5 years or $33,140 at 10 years, since a greater number of patients switch to the less expensive LPV/r. Sensitivity analyses showed that initiating with LPV/r was always cost‐saving relative to DRV+RTV. Initiating HIV‐infected, treatment‐naïve WOCBA on LPV/r was cost‐saving compared to initiating DRV+RTV. Limitations of the analysis include the uncertainty of long‐term outcomes projections driven by short‐term clinical trial endpoints.
Budget impact analysis of switch to darunavir/ritonavir monotherapy in Greece
Authors: Lazanas M , Hill A , Sawyer A , Paparouni K
Published: November 2012

Background

In virologically suppressed patients, simplifying to darunavir/ ritonavir (DRV/r) monotherapy maintains HIV RNA suppression and could lower treatment costs. Monotherapy is mentioned as an alternative treatment option in the Greek therapeutic guidelines (posted in the Greek Health Authority website), even though it is not included in the label of darunavir or any other PI.

Methods

In the MONET trial 256 patients with HIV RNA<50 copies/mL and no history of virological failure on HAART were switched to DRV/r 800/100 mg once daily, either as monotherapy (n=127) or with 2NRTI (n=129). The three‐year analysis of the MONET trial was used to calculate the overall nationwide cost of switching to DRV/r monotherapy in Greek patients. We used a ‘switch included’ analysis at Week 144 to account for additional antiretrovirals taken after initial treatment failure. Published Greek hospital prices of antiretrovirals were used in this analysis. Data from a local expert panel were used to estimate the number of patients currently receiving NNRTI versus PI‐based treatment in Greece, and the number of patients eligible for DRV/r monotherapy.

Results

In the ITT switch included analysis, HIV RNA<50 copies/mL by Week 144 was 86.1% versus 84.3% in the DRV/r monotherapy and control arms. No patients developed resistance to DRV as measured by virtual phenotype. Before the trial, the mean annual cost of antiretrovirals was €5,625 for patients on NNRTI‐based HAART, and €6,935 for patients on PI‐based HAART. The mean per‐patient cost in the monotherapy arm was €4,514 in the MONET trial (including the cost of intensification with NRTIs where needed): this annual cost of antiretrovirals was €1,111 lower (20%) than NNRTI‐based treatment, and €2,421 (35%) lower than PI‐based treatment taken before the trial, respectively. According to the local expert panel feedback 5,230 people are treated with antiretrovirals in Greece (40% NNRTI‐based, 60% PI‐based) and 20% of patients (n=1,046) are eligible for PI monotherapy. Based on the MONET results, a switch to DRV/r monotherapy in 20% of patients could reduce the three‐year cost of antiretroviral treatment for these patients, from €20.11 million to €14.26 million.

Conclusions

Based on the MONET trial results, if the 1,046 eligible patients were to switch to PI monotherapy the lower cost of DRV/r monotherapy versus triple therapy in Greece would allow a potential saving of up to €5.85 million over three years.