bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary hypertension in HIV infection: a prospective echocardiographic study
Authors: Schwarze‐Zander C , Pabst S , Hammerstingl C , Ohlig J , Wasmuth JC , Boesecke C , Stoffel‐Wagner B , Carstensen A , Nickenig G , Strassburg CP , Rockstroh JK , Skowasch D , Schueler R
Published: May 2015

Objectives

While idiopathic pulmonary arterial hypertension (PAH) is a rare disease, it is seen more frequently in patients with HIV infection. The aim of this study was to evaluate the prevalence of pulmonary hypertension (PH) in patients with HIV infection by echocardiographic screening.

Methods

Echocardiography and N‐terminal of the prohormone brain natriuretic peptide measurement were used to examine the prevalence of PH prospectively in HIV‐positive patients (n = 374) during routine follow‐up visits for HIV disease.

Results

In echocardiographic screening, PH was detected in a total of 23 of 374 HIV‐infected patients (6.1%). Of these, three patients (13%) presented with symptoms of dyspnoea and fatigue, and diagnosis of PAH was confirmed by right heart catheterization. Patients with systolic pulmonary artery pressure (sPAP) > 30 mmHg were more likely to be female, to have a history of injecting drug use and to originate from high‐prevalence countries (HPCs).

Conclusions

Echocardiographic screening detected PH in a substantial proportion of HIV‐positive patients. Female gender, a history of injecting drug use and HPC origin were associated with a higher prevalence of HIV‐associated PH. The relevance and long‐term outcome of these findings need to be validated in follow‐up studies, which are ongoing.
On the Fishburn social choice function
Authors: Kamwa Eric
Published: May 2015

A Condorcet social choice function is a voting rule that always elects the Condorcet winner when he exists. The Condorcet winner is a candidate who beats all the others in pairwise comparisons. Fishburn proposed a Condorcet social choice function, now referred to as the Fishburn function, and on the basis of some properties he concludes that his rule appears to hold an advantage over the other Condorcet social choice functions. This note uses other properties to reach the same conclusion with a more extended set of Condorcet social choice functions.
JAK2 46/1 haplotype is associated with JAK2 V617F – positive myeloproliferative neoplasms in Brazilian patients
Authors: Macedo L. C. , Santos B. C. , Pagliarini‐e‐Silva S. , Pagnano K. B. B. , Rodrigues C. , Quintero F. C. , Ferreira M. E. , Baraldi E. C. , Ambrosio‐Albuquerque E. P. , Sell A. M. , Visentainer J. E. L.
Published: May 2015

Introduction

This study aimed to verify the association between the JAK2 46/1 haplotype (V617F positive) and some hematological parameters in BCR‐ABL‐negative chronic myeloproliferative neoplasms (cMPNs) in our population.

Methods

The blood samples obtained from the patients with cMPN were genotyped for the JAK2 V617F mutation and JAK2 rs10974944 SNP screening using a PCR‐RFLP assay.

Results

The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of rs10974944 was more frequent in all MPNs, especially those that were JAK2 V617F positive, than in the control population. We also compared the 46/1 haplotype status in each MPN disease entity, polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), and MPNu with controls. The G allele frequency relative to controls was significantly enriched in patients with PV and ET, but not in those with PMF and MPNu. PV and ET patients especially, all of whom had the JAK2 V617F mutation, showed significant excess of the G allele. The frequency of JAK2 V617F mutation was associated with elevated hematological parameters, but when we analyze the occurrence of the mutation and the presence of the G allele, just the high hemoglobin was significantly.

Conclusion

In agreement with previous reports, JAK2 46/1 haplotype for JAK2 V617F was associated with cMPN positive in Brazilian patients.
The Close Relationships of People with Intellectual Disabilities: A Qualitative Study
Authors: Sullivan Faye , Bowden Keith , McKenzie Karen , Quayle Ethel
Published: May 2015

Background

Positive interpersonal relationships have been found to enhance an individual's quality of life. However, people with intellectual disabilities (PWID) often have restricted social networks, and little is known about their views on close social relationships. The study aimed to explore how this group perceives and experiences close relationships.

Materials and Methods

Ten (6 = men 4 = women) PWID participated. Data were collected using semi‐structured interviews, and analysed using interpretive phenomenological analysis.

Results

The results report on three of five themes drawn from a larger qualitative study: ‘Relationships feeling safe and being useful’; ‘Who's in charge?’ and ‘Struggling for an ordinary life’.

Conclusions

Close relationships are valued and desired by PWID, but a variety of barriers inhibit their development and maintenance. This includes the failure of others to value, accept and appropriately support the independence and relationships of PWID. Potential ways of addressing these issues are discussed.
Retrospective analysis of routine use of a double heat cycle (DHC) during radiofrequency segmental ablation (ClosureFAST™) of saphenous veins
Authors: Schuller‐Petrović S. , Pavlović M.D. , Schuller‐Lukić B. , Schuller S.
Published: May 2015

Background

Recent experimental evidence suggests that increasing energy delivered during radiofrequency segmental ablation (RFSA) of varicose veins might further improve outcomes.

Objectives

To evaluate occlusion rates and safety of the routine use of double heat cycle (DHC) during RFSA of incompetent saphenous veins up to 3 years after the initial treatment.

Methods

Retrospective review of prospectively collected duplex ultrasound (DUS) and complication rate data of successive patients from the Viennese, Lower Austrian and Slovenian regions treated for incompetent saphenous veins, followed up on a yearly basis for up to 3 years after the procedure.

Results

Between 2007 and 2011, 258 patients (389 veins; 322 great saphenous veins (GSV)] had been treated with DHC ClosureFast. Patients’ return was 46% (122 subjects) 3 years after RFSA [140 GSV and 31 small saphenous veins (SSV)] with a mean follow‐up time of 24.93 ± 11.77 months. At 36 months Kaplan–Meier survival analysis showed the occlusion probability of 98.6% (95% CI: 1.005–0.966). All SSV were closed. Except for three cases of dysaesthesia which disappeared within a year, there have not been major side‐effects.

Conclusions

Results of the retrospective analysis indicate that the routine use of DHC during RFSA for incompetent saphenous veins is equally safe but potentially more efficacious considering mid‐term venous closure rates.
Lean Six Sigma: a new approach to the management of patients undergoing prosthetic hip replacement surgery
Authors: Improta Giovanni , Balato Giovanni , Romano Maria , Carpentieri Francesco , Bifulco Paolo , Alessandro Russo Mario , Rosa Donato , Triassi Maria , Cesarelli Mario
Published: May 2015

Rationale, aims and objectives

In 2012, health care spending in Italy reached €114.5 billion, accounting for 7.2% of the Gross Domestic Product (GDP) and 14.2% of total public spending. Therefore, reducing waste in health facilities could generate substantial cost savings. The objective of this study is to show that Lean Six Sigma represents an appropriate methodology for the development of a clinical pathway which allows to improve quality and to reduce costs in prosthetic hip replacement surgery.

Methods

The methodology used for the development of a new clinical pathway was Lean Six Sigma. Problem solving in Lean Six Sigma is the DMAIC (Define, Measure, Analyse, Improve, Control) roadmap, characterized by five operational phases which make possible to reach fixed goals through a rigorous process of defining, measuring, analysing, improving and controlling business problems.

Results

The following project indicated several variables influencing the inappropriate prolongation of the length of stay for inpatient treatment and corrective actions were performed to improve the effectiveness and efficiency of the process of care. The average length of stay was reduced from 18.9 to 10.6 days (−44%).

Conclusion

This article shows there is no trade‐off between quality and costs: Lean Six Sigma improves quality and, at the same time, reduces costs.
Can nurses be key players in assessing early motor development using a structured method in the child health setting?
Authors: Johansen Kine , Persson Kristina , Sarkadi Anna , Sonnander Karin , Magnusson Margaretha , Lucas Steven
Published: May 2015

Rational, aims and objectives

Increasing evidence highlights the importance of early interventions for motor disorders in children. Given the key medical role of the nurse within the Swedish Child Health Service (CHS), we aimed to examine if nurses could apply a structured assessment of early motor development at the child health centre to enable early identification of children at risk.

Methods

Structured Observation of Motor Performance in Infants (SOMP‐I) assesses infant's level of motor development and quality of motor performance using subscales converted to total scores. The total score for both level and quality can then be plotted within the SOMP‐I percentile distribution at the child's age for comparison with a reference population. Fifty‐five infants (girls: 30) were assessed according to SOMP‐I at three child health centres. Assessments were performed by nurses (n = 10) in a clinical setting; one nurse performed the assessment while another nurse and a physiotherapist observed.

Results

Agreement for the assessment of level as a continuous variable was excellent [intraclass correlation coefficient (ICC) 0.97–0.98], but was lower for quality (ICC 0.02–0.46). When the children were categorized according to the percentile range categories, the assessors were in agreement for the majority of the children, with respect to both level (78–82%) and quality (78–87%).

Conclusion

Despite brief experience with SOMP‐I, the agreement was excellent when assessing the level of motor development, but was less satisfactory for the assessment of quality of motor performance. More extensive education and training may be necessary to improve the nurses' ability to assess quality, as this domain was an entirely new concept to the nurses. Further research is warranted to determine the applicability of SOMP‐I as a standardized method for nurses to assess motor development within the CHS.
Isolation and Molecular Characterization of Acanthamoeba Strains from Dental Units in Costa Rica
Authors: Retana‐Moreira Lissette , Abrahams‐Sandí Elizabeth , Castro‐Artavia Esteban , Fernández‐Sánchez Ana , Castro‐Castillo Alfredo , Reyes‐Batlle María , Lorenzo‐Morales Jacob
Published: May 2015

Free‐living amoebae are protozoa widely distributed in nature, which can be found in a variety of environments. Four genera are recognized as causal agents of infections in humans and animals: Acanthamoeba, Naegleria, Balamuthia, and Sappinia. In this study, the presence of Acanthamoeba in dental units was determined and the isolates obtained were molecularly characterized; osmotolerance and thermotolerance assays were also performed to evaluate multiplication under these conditions, frequently associated with pathogenicity. The morphological analysis and partial sequencing of the 18S rDNA gene revealed the presence of Acanthamoeba genotype T4 in 14% of the units sampled. Osmotolerance and thermotolerance tests were positive for more than 80% of the isolates. Up to date, this is the first study that reports the detection, identification, and genotyping of Acanthamoeba isolated from dental units in Costa Rica and even in Latin‐America. Further assays to determine the potential pathogenicity of these Acanthamoeba isolates are underway.
The role as moderator and mediator in parent education groups – a leadership and teaching approach model from a parent perspective
Authors: Forslund Frykedal Karin , Rosander Michael
Published: May 2015

Aims and objectives

To investigate the didactic and social leadership in parent education groups based on a parent perspective, and to conceptualise parent experiences of the leader roles in these groups.

Background

Leadership in parent education groups has been associated with a lack of confidence in one's ability to function in that role. Research on how it can be delivered to produce a favourable outcome is scarce. It can be difficult to abandon the role of expert and let participants set their own learning agenda. To facilitate these processes requires leadership skills, knowledge of group dynamics as well as pedagogical skills.

Design

Qualitative interview study.

Methods

Semi‐structured interviews with parents (25 participants, 21 interviews). Transcripts were analysed using, first, thematic analysis, then comparative analysis.

Results

The study resulted in a four‐field model, The Leadership – Teaching Approach model. It consists of the dimensions ‘Teaching approaches’ (‘Knowledge is imparted’ and ‘Knowledge is jointly constructed’), and ‘Leadership approaches’ (‘Instrumental approach’ and ‘Investigative approach’).

Conclusions

Using an investigative approach is necessary to get a well‐functioning group that can help the expectant and new parents in the transition to parenthood. Supervision can help develop an awareness of one's professional role as a nurse and leader of a parent education group.

Relevance to clinical practice

The actions and choices of nurses as leaders of parent groups have an impact on how the participants perceive and take in the content and purpose of the group, and whether they perceive it as meaningful. Getting support in reflecting about one's role as a leader in this context can help create a learning environment in which the participants can become engaged in the activities and be strengthened by the experience.
Carprofen pharmacokinetics in plasma and in control and inflamed canine tissue fluid using in vivo ultrafiltration
Authors: Messenger K. M. , Wofford J. A. , Papich M. G.
Published: May 2015

Measurement of unbound drug concentrations at their sites of action is necessary for accurate PK/PD modeling. The objective of this study was to determine the unbound concentration of carprofen in canine interstitial fluid (ISF) using in vivo ultrafiltration and to compare pharmacokinetic parameters of free carprofen concentrations between inflamed and control tissue sites. We hypothesized that active concentrations of carprofen would exhibit different dispositions in ISF between inflamed vs. normal tissues. Bilateral ultrafiltration probes were placed subcutaneously in six healthy Beagle dogs 12 h prior to induction of inflammation. Two milliliters of either 2% carrageenan or saline control was injected subcutaneously at each probe site, 12 h prior to intravenous carprofen (4 mg/kg) administration. Plasma and ISF samples were collected at regular intervals for 72 h, and carprofen concentrations were determined using HPLC. Prostaglandin E2 (PGE2) concentrations were quantified in ISF using ELISA. Unbound carprofen concentrations were higher in ISF compared with predicted unbound plasma drug concentrations. Concentrations were not significantly higher in inflamed ISF compared with control ISF. Compartmental modeling was used to generate pharmacokinetic parameter estimates, which were not significantly different between sites. Terminal half‐life (T½) was longer in the ISF compared with plasma. PGE2 in ISF decreased following administration of carprofen. In vivo ultrafiltration is a reliable method to determine unbound carprofen in ISF, and that disposition of unbound drug into tissue is much higher than predicted from unbound drug concentration in plasma. However, concentrations and pharmacokinetic parameter estimates are not significantly different in inflamed vs. un‐inflamed tissues.
Risks for mortality and renal replacement therapy in atherosclerotic renovascular disease compared with other causes of chronic kidney disease
Authors: Ritchie James , Green Darren , Alderson Helen V , Chiu Diana , Sinha Smeeta , Kalra Philip A
Published: May 2015

Aim

Patients with atherosclerotic renovascular disease (ARVD) have an increased risk for death and likelihood of initiating renal replacement therapy (RRT) compared with the general population. No data exist to describe prognosis in ARVD compared with other causes of chronic kidney disease (CKD). We compare patient outcomes between ARVD and other causes of CKD.

Methods

Patients were selected from two prospective observational cohort studies of outcome in ARVD and CKD. Multivariate Cox regression was used to compare risk for RRT and death (both prior to and following initiation of RRT) between patients with ARVD and other causes of CKD.

Results

Of 1472 patients (563 (38%) ARVD, 909 (62%) non‐ARVD), 242 (16%) progressed to RRT and 640 (44%) died over a median follow‐up period of 4.1 (2.4–5.6) years. Patients with ARVD had an increased risk for death (HR 1.5 (1.2–1.8), P < 0.001) but not for RRT (HR 1.0 (0.7–1.4), P = 0.9). The largest increase in risk for death was observed relative to renal limited diseases, e.g. pyelonephritis (HR 2.4 (1.3–4.5), P = 0.004) and interstitial/infiltrative disease (HR 2.2 (1.3–4.5), P = 0.02). Following initiation of RRT, patients with ARVD had a significantly increased risk for death compared with patients without ARVD (HR 3.3 (2.2–5.0), P < 0.001).

Conclusions

Patients with ARVD as a cause of CKD have an increased risk for death both prior to and following initiation of RRT. Further work should seek to identify modifiable risk factors relevant to prognosis.
Quality and safety: reflection on the implications for critical care nursing education
Authors: Baid Heather , Hargreaves Jessica
Published: May 2015

ABSTRACT

Background

Safe and high quality health care is underpinned by health care professionals possessing the knowledge, skills and professional attributes which are necessary for their specific clinical speciality and area of practice. Education is crucial as it enables clinicians to learn and put into practice their specialist knowledge, skills and attributes. These elements will be based on clinical standards, which set the agenda for quality and safety in health care.

Aim

The purpose of this paper is to reflect upon how a post‐registration, degree‐level critical care nursing course provided by an English university facilitates nurses to deliver high quality, safe nursing care for critically ill patients and their families.

Methods

As a reflective analysis, the process of reflection will be guided and structured according to Rolfe's framework for reflective practice. The reflection is based upon the personal observations and teaching experiences of two university lecturers involved in the delivery of the critical care course.

Conclusions

Critical care nursing education can incorporate informed practice, simulation and non‐technical skills into post‐registration critical‐care nursing courses as a way of promoting high‐quality, safe clinical practice in the critical care setting. This article provides examples from one course's experience with doing this and ends with specific recommendations for how critical care nursing courses can enhance further the promotion of quality and safety.

Relevance to clinical practice

Educators, mentors and students of post‐registration critical care nursing courses are encouraged to explore the relevance of nursing education in promoting safe and high‐quality clinical practice.
BAFF receptor and TACI in B‐1b cell maintenance and antibacterial responses
Authors: Dickinson Gregory S. , Akkoyunlu Mustafa , Bram Richard J. , Alugupalli Kishore R.
Published: May 2015

Although evidence of the protective immunity conferred by B‐1b cells (CD19+B220+IgMhiMac1+CD5−) has been established, the mechanisms governing the maintenance and activation of B‐1b cells following pathogen encounter remain unclear. B cell–activating factor (BAFF) and a proliferation‐inducing ligand (APRIL) mediate their function in mature B cells through the BAFF receptor (BAFFR) and transmembrane activator and CAML interactor (TACI). BAFFR‐deficient mice have lower numbers of B‐1b cells, and this reduction is directly proportional to BAFFR levels. The generation of B‐1b cells is also dependent on the strength of B cell receptor (BCR) signaling. Mice with impaired BCR signaling, such as X‐linked immunodeficient (xid) mice, have B‐1b cell deficiency, indicating that both BCR‐ and BAFFR‐mediated signaling are critical for B‐1b cell homeostasis. Borrelia hermsii induces expansion and persistence of B‐1b cells in xid mice, and these B‐1b cells provide a heightened protective response. Toll‐like receptor (TLR)–mediated stimulation of xid B cells results in a significant increase in TACI expression and restoration of TACI‐mediated functions. The activation of TLR signaling by B. hermsii and BCR/TLR costimulation–mediated upregulation of BAFFR and TACI on B‐1b cells suggests that B‐1b cell maintenance and function following bacterial exposure may depend on BAFFR‐ and TACI‐mediated signaling. In fact, the loss of both BAFFR and TACI results in a greater impairment in anti‐B. hermsii responses compared to deficiency of BAFFR or TACI alone.
Development of maraviroc, a CCR5 antagonist for treatment of HIV, using a novel tropism assay
Authors: van der Ryst Elna , Heera Jayvant , Demarest James , Knirsch Charles
Published: May 2015

Assays to identify infectious organisms are critical for diagnosis and enabling the development of therapeutic agents. The demonstration that individuals with a 32‐bp deletion within the CCR5 locus were resistant to human immunodeficiency virus (HIV) infection, while those heterozygous for the mutation progressed more slowly, led to the discovery of maraviroc (MVC), a CCR5 antagonist. As MVC is only active against CCR5‐tropic strains of HIV, it was critical to develop a diagnostic assay to identify appropriate patients. Trofile™, a novel phenotypic tropism assay, was used to identify patients with CCR5‐tropic virus for the MVC development program. Results of these clinical studies demonstrated that the assay correctly identified patients likely to respond to MVC. Over time, the performance characteristics of the phenotypic assay were enhanced, necessitating retesting of study samples. Genotypic tropism tests that have the potential to allow for local use and more rapid turnaround times are also being developed.
A call for applying trophic structure in ecological restoration
Authors: Fraser Lauchlan H. , Harrower William L. , Garris Heath W. , Davidson Scott , Hebert Paul D. N. , Howie Rick , Moody Anne , Polster David , Schmitz Oswald J. , Sinclair Anthony R. E. , Starzomski Brian M. , Sullivan Thomas P. , Turkington Roy , Wilson Dennis
Published: May 2015

Ecological restoration projects have traditionally focused on vegetation as both a means (seeding, planting, and substrate amendments) and ends (success based upon primary productivity and vegetation diversity). This vegetation‐centric approach to ecological restoration stems from an historic emphasis on esthetics and cost but provides a limited measure of total ecosystem functioning and overlooks alternative ways to achieve current and future restoration targets. We advocate a shift to planning beyond the plant community and toward the physical and biological components necessary to initiate autogenic recovery, then guiding this process through the timely introduction of top predators and environmental modifications such as soil amendments and physical structures for animal nesting and refugia.
Determination of optimal storage temperature and duration for analysis of total and isoenzyme lactate dehydrogenase activities in canine serum and cerebrospinal fluid
Authors: Houle Jennifer C. , Chen Annie V. , Brenna Amanda C. , Mealey Katrina L. , Kiszonas Alecia M.
Published: May 2015

Background

Lactate dehydrogenase (LDH) exists as 5 isoenzymes in both serum and cerebrospinal fluid (CSF). Human studies have demonstrated that changes inLDHactivity can be correlated with a particular disease.

Objectives

Conflicting reports regarding the stability ofLDHmade it necessary to determine storage conditions before further study of the diagnostic power of this enzyme's activity can be pursued in dogs. The purpose of this study was to optimize measurement ofLDHactivity and analysis of its isoenzyme profile in canine serum andCSFthrough proper storage.

Methods

Serum andCSFwere collected from 5 healthy dogs. Samples were stored at 22°C, 4°C, or −20°C for up to 2 months. TotalLDHactivity was measured spectrophotometrically. Isoenzyme profiles were determined using the QuickGelLDHIsoenzyme technique and densitometric scanning. Retention of > 70%LDHactivity in stored samples was considered clinically acceptable.

Results

Serum andCSFstored at −20°C retained > 85% of the totalLDHactivity for 4 weeks, althoughCSFtotalLDHactivity degraded by > 10% within 24 hours of storage. All serumLDHisoenzymes retained > 85% activity for up to 4 weeks at −20°C.CSF LDHisoenzyme activity degraded rapidly, thereforeCSF LDHshould be evaluated within 72 hours to assure > 75% ofLDHisoenzyme activity.

Conclusions

Proper storage at −20°C can optimize detection of totalLDHactivity and theLDHisoenzyme profile in canine serum andCSF. This information is important for evaluating the potential usefulness ofLDHin veterinary medicine.
Nonlinear Finite Element Analysis of Frames Under Interval Material and Load Uncertainty
Authors: Muhanna Rafi L. , Mullen Robert L. , Rama Rao M. V.
Published: May 2015

The present study focuses on the development of nonlinear interval finite elements (NIFEM) for beam and frame problems. Three constitutive models have been used in the present study, viz., bilinear, Ramberg–Osgood, and cubic models, to illustrate the development of NIFEM. An interval finite element method (IFEM) has been developed to handle load, material, and geometric uncertainties that are introduced in a form of interval numbers defined by their lower and upper bounds. However, the scope of the previous methods was limited to linear problems. The present work introduces an IFEM formulation for problems involving material nonlinearity under interval material parameters and loads. The algorithm is based on the previously developed high-accuracy interval solutions. An iterative method that generates successive approximations to the secant stiffness is introduced. Examples are presented to illustrate the behavior of the formulation. It is shown that bounding the response of nonlinear structures for a large number of load combinations under uncertain yield stress can be computed at a reasonable computational cost.
Altered Micafungin Pharmacokinetics in Intensive Care Unit Patients
Authors: Lempers Vincent J. , Schouten Jeroen A. , Hunfeld Nicole G. , Colbers Angela , van Leeuwen Henk J. , Burger David M. , Verweij Paul E. , Pickkers Peter , Brüggemann Roger J.
Published: May 2015

Micafungin is considered an important agent for the treatment of invasive fungal infections in the intensive care unit (ICU). Little is known on the pharmacokinetics of micafungin. We investigated micafungin pharmacokinetics (PK) in ICU patients and set out to explore the parameters that influence micafungin plasma concentrations. ICU patients receiving 100 mg of intravenous micafungin once daily for suspected or proven fungal infection or as prophylaxis were eligible. Daily trough concentrations and PK curves (days 3 and 7) were collected. Pharmacokinetic analysis was performed using a standard two-stage approach. Twenty patients from the ICUs of four hospitals were evaluated. On day 3 (
n
= 20), the median (interquartile range [IQR]) area under the concentration-time curve from 0 to 24 h (AUC
0–24
) was 78.6 (65.3 to 94.1) mg · h/liter, the maximum concentration of drug in serum (
C
max
) was 7.2 (5.4 to 9.2) mg/liter, the concentration 24 h after dosing (
C
24
) was 1.55 (1.4 to 3.1) mg/liter, the volume of distribution (
V
) was 25.6 (21.3 to 29.1) liters, the clearance (CL) was 1.3 (1.1 to 1.5) liters/h, and the elimination half-life (
t
1/2
) was 13.7 (12.2 to 15.5) h. The pharmacokinetic parameters on day 7 (
n
= 12) were not significantly different from those on day 3. Daily trough concentrations (day 3 to the end of therapy) showed moderate interindividual (57.9%) and limited intraindividual variability (12.9%). No covariates of the influence on micafungin exposure were identified. Micafungin was considered safe and well tolerated. We performed the first PK study with very intensive sampling on multiple occasions in ICU patients, which aided in resolving micafungin PK. Strikingly, micafungin exposure in our cohort of ICU patients was lower than that in healthy volunteers but not significantly different from that of other reference populations. The clinical consequence of these findings must be investigated in a pharmacokinetic-pharmacodynamic (PK-PD) study incorporating outcome in a larger cohort. (This study is registered at ClinicalTrials.gov under registration no. NCT01783379.)
Error estimates for forward Euler shock capturing finite element approximations of the one-dimensional Burgers' equation
Authors: Burman Erik
Published: May 2015

We propose an error analysis for a shock capturing finite element method for the Burgers' equation using the duality theory due to Tadmor. The estimates use a one-sided Lipschitz stability (Lip+-stability) estimate on the discrete solution and are obtained in a weak norm, but thanks to a total variation a priori bound on the discrete solution and an interpolation inequality, error estimates in Lp-norms (1 ≤ p < ∞) are deduced. Both first-order artificial viscosity and a nonlinear shock capturing term that formally is of second order are considered. For the discretization in time we use the forward Euler method. In the numerical section we verify the convergence order of the nonlinear scheme using the forward Euler method and a second-order strong stability preserving Runge–Kutta method. We also study the Lip+-stability property numerically and give some examples of when it holds strictly and when it is violated.
Darcy's law and diffusion for a two-fluid Euler–Maxwell system with dissipation
Authors: Duan Renjun , Liu Qingqing , Zhu Changjiang
Published: May 2015

This paper is concerned with the large-time behavior of solutions to the Cauchy problem on the two-fluid Euler–Maxwell system with dissipation when initial data are around a constant equilibrium state. The main goal is the rigorous justification of diffusion phenomena in fluid plasma at the linear level. Precisely, motivated by the classical Darcy's law for the nonconductive fluid, we first give a heuristic derivation of the asymptotic equations of the Euler–Maxwell system in large time. It turns out that both the density and the magnetic field tend time-asymptotically to the diffusion equations with diffusive coefficients explicitly determined by given physical parameters. Then, in terms of the Fourier energy method, we analyze the linear dissipative structure of the system, which implies the almost exponential time-decay property of solutions over the high-frequency domain. The key part of the paper is the spectral analysis of the linearized system, exactly capturing the diffusive feature of solutions over the low-frequency domain. Finally, under some conditions on initial data, we show the convergence of the densities and the magnetic field to the corresponding linear diffusion waves with the rate [Formula: see text] in L2-norm and also the convergence of the velocities and the electric field to the corresponding asymptotic profiles given in the sense of the generalized Darcy's law with the faster rate [Formula: see text] in L2-norm. Thus, this work can be also regarded as the mathematical proof of the Darcy's law in the context of collisional fluid plasma.
CO-WORKING SPACES AND THE LOCALISED DYNAMICS OF INNOVATION IN BARCELONA
Authors: CAPDEVILA IGNASI
Published: May 2015

This paper considers a multi-level perspective to analyse the crucial role of individuals and communities outside firms in the localised dynamics of innovation. Through a qualitative study of the communities emerging in co-working spaces (CWSs) in Barcelona, we disentangle the different dynamics of innovation involving community insiders and local actors (firms, citizens and governmental bodies). We argue that CWSs act as intermediaries between creative individuals ("the underground") and innovative firms ("the upper-ground"), contributing to the interaction between co-located actors through the articulation of places, spaces, projects and events. The results lead to suggestions for policies to contribute to the emergence and development of innovation by fostering innovative processes outside firms.
Resampled Regenerative Estimators
Authors: Calvin James M. , Nakayama Marvin K.
Published: May 2015

We discuss some estimators for simulations of processes having multiple regenerative sequences. The estimators are obtained by resampling trajectories without and with replacement, which correspond to a type of
U
-statistic and a type of
V
-statistic, respectively. The
U
-statistic estimator turns out to be equivalent to the permuted regenerative estimator, which we previously proposed, but the
V
-statistic estimator is new. We compare analytically some properties of these estimators and the semiregenerative estimator. We show that when estimating the second moment of a cycle reward, the semiregenerative estimator has positive bias, which is strictly larger than the (positive) bias of the
V
-statistic estimator. The permuted estimator is unbiased. All of the estimators have the same asymptotic central limit behavior, with reduced asymptotic variance compared to the standard regenerative estimator. Some numerical results are included.
On Transience and Recurrence in Irreducible Finite-State Stochastic Systems
Authors: Glynn Peter W. , Haas Peter J.
Published: May 2015

Long-run stochastic stability is a precondition for applying steady-state simulation output analysis methods to a discrete-event stochastic system, and is of interest in its own right. We focus on systems whose underlying stochastic process can be represented as a Generalized Semi-Markov Process (GSMP); a wide variety of stochastic systems fall within this framework. A fundamental stability requirement for an irreducible GSMP is that the states be “recurrent” in that the GSMP visits each state infinitely often with probability 1. We study recurrence properties of irreducible GSMPs with finite state space. Our focus is on the “clocks” that govern the occurrence of events, and we consider GSMPs in which zero, one, or at least two simultaneously active events can have clock-setting distributions that are “heavy tailed” in the sense that they have infinite mean. We establish positive recurrence, null recurrence, and, perhaps surprisingly, possible transience of states for these respective regimes. The transience result stands in strong contrast to Markovian or semi-Markovian GSMPs, where irreducibility and finiteness of the state space guarantee positive recurrence.
Hyperspectral Modeling of Skin Appearance
Authors: Chen Tenn F. , Baranoski Gladimir V. G. , Kimmel Bradley W. , Miranda Erik
Published: May 2015

Exploration of the hyperspectral domain offers a host of new research and application possibilities involving material appearance modeling. In this article, we address these prospects with respect to human skin, one of the most ubiquitous materials portrayed in synthetic imaging. We present the first hyperspectral model designed for the predictive rendering of skin appearance attributes in the ultraviolet, visible, and infrared domains. The proposed model incorporates the intrinsic bio-optical properties of human skin affecting light transport in these spectral regions, including the particle nature and distribution patterns of the main light attenuation agents found within the cutaneous tissues. Accordingly, it accounts for phenomena that significantly affect skin spectral signatures, both within and outside the visible domain, such as detour and sieve effects, that are overlooked by existing skin appearance models. Using a first-principles approach, the proposed model computes the surface and subsurface scattering components of skin reflectance taking into account not only the wavelength and the illumination geometry, but also the positional dependence of the reflected light. Hence, the spectral and spatial distributions of light interacting with human skin can be comprehensively represented in terms of hyperspectral reflectance and BSSRDF, respectively.
Truthful Mechanisms with Implicit Payment Computation
Authors: Babaioff Moshe , Kleinberg Robert D. , Slivkins Aleksandrs
Published: May 2015

It is widely believed that computing payments needed to induce truthful bidding is somehow harder than simply computing the allocation. We show that the opposite is true: creating a randomized truthful mechanism is essentially as easy as a
single
call to a monotone allocation rule. Our main result is a general procedure to take a monotone allocation rule for a single-parameter domain and transform it (via a black-box reduction) into a randomized mechanism that is truthful in expectation and individually rational for every realization. The mechanism implements the same outcome as the original allocation rule with probability arbitrarily close to 1, and requires evaluating that allocation rule only once. We also provide an extension of this result to multiparameter domains and cycle-monotone allocation rules, under mild star-convexity and nonnegativity hypotheses on the type space and allocation rule, respectively.

Because our reduction is simple, versatile, and general, it has many applications to mechanism design problems in which re-evaluating the allocation rule is either burdensome or informationally impossible. Applying our result to the multiarmed bandit problem, we obtain truthful randomized mechanisms whose regret matches the information-theoretic lower bound up to logarithmic factors, even though prior work showed this is impossible for truthful deterministic mechanisms. We also present applications to offline mechanism design, showing that randomization can circumvent a communication complexity lower bound for deterministic payments computation, and that it can also be used to create truthful shortest path auctions that approximate the welfare of the VCG allocation arbitrarily well, while having the same running time complexity as Dijkstra's algorithm.
Finding Correlations in Subquadratic Time, with Applications to Learning Parities and the Closest Pair Problem
Authors: Valiant Gregory
Published: May 2015

Given a set of
n
d
-dimensional Boolean vectors with the promise that the vectors are chosen uniformly at random with the exception of two vectors that have Pearson correlation coefficient ρ (Hamming distance
d
· 1-ρ/ 2), how quickly can one find the two correlated vectors? We present an algorithm which, for any constant ϵ>0, and constant ρ>0, runs in expected time
O
(n
5-ω / 4-ω+ϵ
+nd) <
O
(n
1.62
+nd), where ω < 2.4 is the exponent of matrix multiplication. This is the first subquadratic--time algorithm for this problem for which ρ does not appear in the exponent of
n
, and improves upon
O
(n
2-O(ρ)
), given by Paturi et al. [1989], the Locality Sensitive Hashing approach of Motwani [1998] and the Bucketing Codes approach of Dubiner [2008].

Applications and extensions of this basic algorithm yield significantly improved algorithms for several other problems.

Approximate Closest Pair.
For any sufficiently small constant ϵ>0, given
n
d
-dimensional vectors, there exists an algorithm that returns a pair of vectors whose Euclidean (or Hamming) distance differs from that of the closest pair by a factor of at most 1+ϵ, and runs in time
O
(n
2-Θ(√ϵ
)). The best previous algorithms (including Locality Sensitive Hashing) have runtime
O
(n
2-O(ϵ)
).

Learning Sparse Parities with Noise.
Given samples from an instance of the learning parities with noise problem where each example has length
n
, the true parity set has size at most
k
«
n
, and the noise rate is η, there exists an algorithm that identifies the set of
k
indices in time
n
ω+ϵ/3 k
poly(1/1-2η)
<
n
0.8k
poly(1/1-2 η). This is the first algorithm with no dependence on η in the exponent of
n
, aside from the trivial
O
((
n
k
)) ≈
O
(
n
k
) brute-force algorithm, and for large noise rates (η > 0.4), improves upon the results of Grigorescu et al. [2011] that give a runtime of
n
(1+(2 η)
2
+
o
(1))k/2
poly
(1/1-2η).

Learning
k
-Juntas with Noise.

Given uniformly random length
n
Boolean vectors, together with a label, which is some function of just
k
«
n
of the bits, perturbed by noise rate η, return the set of relevant indices. Leveraging the reduction of Feldman et al. [2009], our result for learning
k
-parities implies an algorithm for this problem with runtime
n
ω+ϵ/3 k
poly
(1/1-2η) <
n
0.8k
poly
(1/1-2 η), which is the first runtime for this problem of the form
n
ck
with an absolute constant
c
< 1.

Learning
k
-Juntas without Noise.

Given uniformly random length
n
Boolean vectors, together with a label, which is some function of
k
«
n
of the bits, return the set of relevant indices. Using a modification of the algorithm of Mossel et al. [2004], and employing our algorithm for learning sparse parities with noise via the reduction of Feldman et al. [2009], we obtain an algorithm for this problem with runtime
n
ω+ ϵ/4 k
poly(n)
<
n
0.6k
poly(n)
, which improves on the previous best of
n
ω+1/ωk
≈
n
0.7k
poly(n)
of Mossel et al. [2004].
Securing Android
Authors: Sufatrio  , Tan Darell J. J. , Chua Tong-Wei , Thing Vrizlynn L. L.
Published: May 2015

Recent years have seen a global adoption of smart mobile devices, particularly those based on Android. However, Android’s widespread adoption is marred with increasingly rampant malware threats. This article gives a survey and taxonomy of existing works that secure Android devices. Based on Android app deployment stages, the taxonomy enables us to analyze schemes that share similar objective and approach and to inspect their key differences. Additionally, this article highlights the limitations of existing works and current challenges. It thus distills the state of the art in Android security research and identifies potential research directions for safeguarding billions (and keep counting) of Android-run devices.
A New Memory-Disk Integrated System with HW Optimizer
Authors: Lee Do-Heon , Yoon Su-Kyung , Kim Jung-Geun , Weems Charles C. , Kim Shin-Dug
Published: May 2015

Current high-performance computer systems utilize a memory hierarchy of on-chip cache, main memory, and secondary storage due to differences in device characteristics. Limiting the amount of main memory causes page swap operations and duplicates data between the main memory and the storage device. The characteristics of next-generation memory, such as nonvolatility, byte addressability, and scaling to greater capacity, can be used to solve these problems. Simple replacement of secondary storage with new forms of nonvolatile memory in a traditional memory hierarchy still causes typical problems, such as memory bottleneck, page swaps, and write overhead. Thus, we suggest a single architecture that merges the main memory and secondary storage into a system called a Memory-Disk Integrated System (MDIS). The MDIS architecture is composed of a virtually decoupled NVRAM and a nonvolatile memory performance optimizer combining hardware and software to support this system. The virtually decoupled NVRAM module can support conventional main memory and disk storage operations logically without data duplication and can reduce write operations to the NVRAM. To increase the lifetime and optimize the performance of this NVRAM, another hardware module called a Nonvolatile Performance Optimizer (NVPO) is used that is composed of four small buffers. The NVPO exploits spatial and temporal characteristics of static/dynamic data based on program execution characteristics. Enhanced virtual memory management and address translation modules in the operating system can support these hardware components to achieve a seamless memory-storage environment. Our experimental results show that the proposed architecture can improve execution time by about 89% over a conventional DRAM main memory/HDD storage system, and 77% over a state-of-the-art PRAM main memory/HDD disk system with DRAM buffer. Also, the lifetime of the virtually decoupled NVRAM is estimated to be 40% longer than that of a traditional hierarchy based on the same device technology.
Buddy SM
Authors: Zhang Tao , Jing Naifeng , Jiang Kaiming , Shu Wei , Wu Min-You , Liang Xiaoyao
Published: May 2015

A modern general-purpose graphics processing unit (GPGPU) usually consists of multiple streaming multiprocessors (SMs), each having a pipeline that incorporates a group of threads executing a common instruction flow. Although SMs are designed to work independently, we observe that they tend to exhibit very similar behavior for many workloads. If multiple SMs can be grouped and work in the lock-step manner, it is possible to save energy by sharing the front-end units among multiple SMs, including the instruction fetch, decode, and schedule components. However, such sharing brings architectural challenges and sometime causes performance degradation. In this article, we show our design, implementation, and evaluation for such an architecture, which we call
Buddy SM
. Specifically, multiple SMs can be opportunistically grouped into a buddy cluster. One SM becomes the master, and the rest become the slaves. The front-end unit of the master works actively for itself as well as for the slaves, whereas the front-end logics of the slaves are power gated. For efficient flow control and program correctness, the proposed architecture can identify unfavorable conditions and ungroup the buddy cluster when necessary. We analyze various techniques to improve the performance and energy efficiency of Buddy SM. Detailed experiments manifest that 37.2% front-end and 7.5% total GPU energy reduction can be achieved.
Push-pull constraint graph for efficient points-to analysis
Authors: Ratnakar Bollu , Nasre. Rupesh
Published: May 2015

We present techniques for efficient computation of points-to information for C programs. Pointer analysis is an important phase in the compilation process. The computed points-to information and the alias information is useful for client analyses from varied domains such as bug finding, data-flow analysis, identifying security vulnerabilities, and parallelization, to name a few. Former research on pointer analysis has indicated that the main bottleneck towards scalability is manifested by the presence of complex constraints (load p = *q and store *p = q constraints) in the program. Complex constraints add edges to the constraint graph in an unpredictable manner and are responsible for initiating propagation of large amounts of points-to information across edges. We identify that the root cause to this issue is in the homogeneous structure in the constraint graph, due to which existing analyses treat loads and stores in a uniform manner. To address these issues, we present two techniques. First, we represent a constraint graph in a non-homogeneous manner, treat loads and stores in different ways, and employ a push-pull model for non-uniform propagation. Second, we propose lazy propagation which propagates information in the constraint graph only when necessary. We illustrate the effectiveness of our techniques using six large open-source programs and show that they improve the analysis time over a state-of-the-art BDD-based analysis by 33% and over Deep Propagation by 21%.