bluuebunny/crossref_metadata_2025 huggingface dataset:
Ionizing radiation induced parametric variations in P3HT:PCBM organic photovoltaic cells
Authors: Kouhestani Camron , Nguyen Duc D. , Kambour Kenneth E. , Devine Roderick A. B. , Chen Johnny , Li Gang , Yang Yang
Published: April 2015

The authors have examined ionizing radiation effects in the organic photovoltaic material poly(3-hexylthiophene):([6, 6]-phenyl C61 butyric acid methyl ester) for total accumulated doses up to 300 krad(SiO2). The authors find that the open circuit voltage varies with the accumulation of irradiation; however, the other parameters such as relaxation time, short circuit current, and charge carrier density remain to first order constant. This behavior is inconsistent with observations on preirradiation devices in which all depend directly on the open circuit voltage.
Dynamic trajectory‐based couch motion for improvement of radiation therapy trajectories in cranial SRT
Authors: Lee MacDonald R. , Thomas Christopher G.
Published: April 2015

Purpose:

To investigate potential improvement in external beam stereotactic radiation therapy plan quality for cranial cases using an optimized dynamic gantry and patient support couch motion trajectory, which could minimize exposure to sensitive healthy tissue.

Methods:

Anonymized patient anatomy and treatment plans of cranial cancer patients were used to quantify the geometric overlap between planning target volumes and organs‐at‐risk (OARs) based on their two‐dimensional projection from source to a plane at isocenter as a function of gantry and couch angle. Published dose constraints were then used as weighting factors for the OARs to generate a map of couch‐gantry coordinate space, indicating degree of overlap at each point in space. A couch‐gantry collision space was generated by direct measurement on a linear accelerator and couch using an anthropomorphic solid‐water phantom. A dynamic, fully customizable algorithm was written to generate a navigable ideal trajectory for the patient specific couch‐gantry space. The advanced algorithm can be used to balance the implementation of absolute minimum values of overlap with the clinical practicality of large‐scale couch motion and delivery time. Optimized cranial cancer treatment trajectories were compared to conventional treatment trajectories.

Results:

Comparison of optimized treatment trajectories with conventional treatment trajectories indicated an average decrease in mean dose to the OARs of 19% and an average decrease in maximum dose to the OARs of 12%. Degradation was seen for homogeneity index (6.14% ± 0.67%–5.48% ± 0.76%) and conformation number (0.82 ± 0.02–0.79 ± 0.02), but neither was statistically significant. Removal of OAR constraints from volumetric modulated arc therapy optimization reveals that reduction in dose to OARs is almost exclusively due to the optimized trajectory and not the OAR constraints.

Conclusions:

The authors’ study indicated that simultaneous couch and gantry motion during radiation therapy to minimize the geometrical overlap in the beams‐eye‐view of target volumes and the organs‐at‐risk can have an appreciable dose reduction to organs‐at‐risk.
Technical Note: Experimental carbon ion range verification in inhomogeneous phantoms using prompt gammas
Authors: Pinto M. , De Rydt M. , Dauvergne D. , Dedes G. , Freud N. , Krimmer J. , Létang J. M. , Ray C. , Testa E. , Testa M.
Published: April 2015

Purpose:

The purpose of this study was to experimentally assess the possibility to monitor carbon ion range variations—due to tumor shift and/or elongation or shrinking—using prompt‐gamma (PG) emission with inhomogeneous phantoms. Such a study is related to the development of PG monitoring techniques to be used in a carbon ion therapy context.

Methods:

A 95 MeV/u carbon ion beam was used to irradiate phantoms with a variable density along the ion path to mimic the presence of bone and lung in homogeneous humanlike tissue. PG profiles were obtained after a longitudinal scan of the phantoms. A setup comprising a narrow single‐slit collimator and two detectors placed at 90° with respect to the beam axis was used. The time of flight technique was applied to allow the selection between PG and background events.

Results:

Using the positions at 50% entrance and 50% falloff of the PG profiles, a quantity called prompt‐gamma profile length (PGPL) is defined. It is possible to observe shifts in the PGPL when there are absolute ion range shifts as small as 1–2 mm. Quantitatively, for an ion range shift of −1.33 ± 0.46 mm (insertion of a Teflon slab), a PGPL difference of −1.93 ± 0.58 mm and −1.84 ± 1.27 mm is obtained using a BaF2 and a NaI(Tl) detector, respectively. In turn, when an ion range shift of 4.59 ± 0.42 mm (insertion of a lung‐equivalent material slab) is considered, the difference is of 4.10 ± 0.54 and 4.39 ± 0.80 mm for the same detectors.

Conclusions:

Herein, experimental evidence of the usefulness of employing PG to monitor carbon ion range using inhomogeneous phantoms is presented. Considering the homogeneous phantom as reference, the results show that the information provided by the PG emission allows for detecting ion range shifts as small as 1–2 mm. When considering the expected PG emission from an energy slice in a carbon ion therapy scenario, the experimental setup would allow to retrieve the same PGPL as the high statistics of the full experimental dataset in 58% of the times. However, this success rate increases to 93% when using a better optimized setup by means of Monte Carlo simulations.
Toe-Out Gait Decreases the Second Peak of the Medial Knee Contact Force
Authors: Ogaya Shinya , Naito Hisashi , Iwata Akira , Higuchi Yumi , Fuchioka Satoshi , Tanaka Masao
Published: April 2015

Toe-out angle alternation is a potential tactic for decreasing the knee adduction moment during walking. Published reports have not examined the medial knee contact force during the toe-out gait, although it is a factor affecting knee articular cartilage damage. This study investigated the effects of increased toe-out angle on the medial knee contact force, using musculoskeletal simulation analysis. For normal and toe-out gaits in 18 healthy subjects, the muscle tension forces were simulated based on the joint moments and ground reaction forces with optimization process. The medial knee contact force during stance phase was determined using the sum of the muscle force and joint reaction force components. The first and second peaks of the medial knee contact force were compared between the gaits. The toe-out gait showed a significant decrease in the medial knee contact force at the second peak, compared with the normal gait. In contrast, the medial knee contact forces at the first peak were not significantly different between the gaits. These results suggest that the toe-out gait is beneficial for decreasing the second peak of the medial knee contact force.
Comment on “Local reorganization of xanthophores fine-tunes and colors the striped pattern of zebrafish”
Authors: Watanabe Masakatsu , Kondo Shigeru
Published: April 2015

Mahalwar
et al
. (Reports, 12 September 2014, p. 1362) observed the onset of pigment pattern formation in zebrafish. They concluded that their data do not support our Turing mechanism–based model and presented an essentially different mechanism. Here, we clarify their misunderstanding that may have caused their conclusion and explain past experimental data that do not support their proposed mechanism.
Japan accelerator poised to go fully operational
Authors: Normile Dennis
Published: April 2015

Closure after radiation leak ended up hampering some teams more than others.
Improved Standardization of the Bio-Rad Platelia Aspergillus Galactomannan Antigen Sandwich Enzyme Immunoassay Using the DS2 (Dynex) Enzyme-Linked Immunosorbent Assay (ELISA) Processing System
Authors: Gorton R. L. , White P. L. , Bagkeris E. , Cotterall D. , Desai R. , McHugh T. , Kibbler C. C.
Published: April 2015

The galactomannan enzyme immunoassay (GM-EIA) is widely utilized for the diagnosis of invasive aspergillosis (IA). There is inconsistent reproducibility of results between centers when the assay is processed manually. Automation of EIAs can reduce variation. This study investigated the semiautomation of the GM-EIA on the DS2 (Dynex) platform in the following three stages: (i) DS2 GM-EIA method validation with experimental samples, (ii) DS2 retesting of case-defined clinical samples, and (iii) a 12-month audit of DS2 GM-EIA performance. In stage i, Bland-Altman analysis demonstrated a reduced variance between optical density index (ODI) values for samples processed on two DS2 platforms (mean difference, −0.02; limits of agreement [LOA], −0.19 to 0.14) compared with the variance between samples processed manually and on a DS2 platform (mean difference, 0.02; LOA, −0.25 to 0.3). In stage ii, 100% (14/14 samples) qualitative agreement was observed for serum samples from patients with IA, with no significant change in the ODI values when samples were processed on the DS2 platform. A significant decrease in ODI values was observed for control serum samples on the DS2 platform (difference, 0.01;
P
= 0.042). In stage iii, a significant reduction in the frequency of equivocal results, from 5.56% (136/2,443 samples) to 1.56% (15/961 samples), was observed after DS2 automation (difference, 4.0%; 95% confidence interval [CI], 2.7 to 5.2%;
P
< 0.01), with an equivalent increase in negative results. This study demonstrates that GM-EIA automation may reduce intersite variability. Automation does not have an impact on the repeatability of truly positive results but contributes to a reduction in false-positive (equivocal) GM-EIA results, reducing the need to retest a significant proportion of samples.
Genotype- and Subtype-Independent Full-Genome Sequencing Assay for Hepatitis C Virus
Authors: Hedskog Charlotte , Chodavarapu Krishna , Ku Karin S. , Xu Simin , Martin Ross , Miller Michael D. , Mo Hongmei , Svarovskaia Evguenia
Published: April 2015

Hepatitis C virus (HCV) exhibits a high genetic diversity and is classified into 6 genotypes, which are further divided into 66 subtypes. Current sequencing strategies require prior knowledge of the HCV genotype and subtype for efficient amplification, making it difficult to sequence samples with a rare or unknown genotype and/or subtype. Here, we describe a subtype-independent full-genome sequencing assay based on a random amplification strategy coupled with next-generation sequencing. HCV genomes from 17 patient samples with both common subtypes (1a, 1b, 2a, 2b, and 3a) and rare subtypes (2c, 2j, 3i, 4a, 4d, 5a, 6a, 6e, and 6j) were successfully sequenced. On average, 3.7 million reads were generated per sample, with 15% showing HCV specificity. The assembled consensus sequences covered 99.3% to 100% of the HCV coding region, and the average coverage was 6,070 reads/position. The accuracy of the generated consensus sequence was estimated to be >99% based on results from
in vitro
HCV replicon amplification, with the same extrapolated amount of input RNA molecules as that for the patient samples. Taken together, the HCV genomes from 17 patient samples were successfully sequenced, including samples with subtypes that have limited sequence information. This method has the potential to sequence any HCV patient sample, independent of genotype or subtype. It may be especially useful in confounding cases, like those with rare subtypes, intergenotypic recombination, or multiple genotype infections, and may allow greater insight into HCV evolution, its genetic diversity, and drug resistance development.
Human Cytomegalovirus
UL135
and
UL136
Genes Are Required for Postentry Tropism in Endothelial Cells
Authors: Bughio Farah , Umashankar Mahadevaiah , Wilson Jean , Goodrum Felicia
Published: April 2015

Endothelial cells (ECs) are a critical target of viruses, and infection of the endothelium represents a defining point in viral pathogenesis. Human cytomegalovirus (HCMV), the prototypical betaherpesvirus, encodes proteins specialized for entry into ECs and delivery of the genome to the nuclei of ECs. Virus strains competent to enter ECs replicate with differing efficiencies, suggesting that the virus encodes genes for postentry tropism in ECs. We previously reported a specific requirement for the
UL133/8
locus of HCMV for replication in ECs. The
UL133/8
locus harbors four genes:
UL133
,
UL135
,
UL136
, and
UL138
. In this study, we find that while
UL133
and
UL138
are dispensable for replication in ECs, both
UL135
and
UL136
are important. These genes are not required for virus entry or the expression of viral genes. The phenotypes associated with disruption of either gene reflect phenotypes observed for the
UL133/8
NULL
virus, which lacks the entire
UL133/8
locus, but are largely distinct from one another. Viruses lacking
UL135
fail to properly envelop capsids in the cytoplasm, produce fewer dense bodies (DB) than the wild-type (WT) virus, and are unable to incorporate viral products into multivesicular bodies (MVB). Viruses lacking
UL136
also fail to properly envelop virions and produce larger dense bodies than the WT virus. Our results indicate roles for the
UL135
and
UL136
proteins in commandeering host membrane-trafficking pathways for virus maturation.
UL135
and
UL136
represent the first HCMV genes crucial for early- to late-stage tropism in ECs.

IMPORTANCE
Human cytomegalovirus (HCMV) persists in the majority of the world's population. While typically asymptomatic in healthy hosts, HCMV can cause significant morbidity and mortality in immunocompromised or naïve individuals, particularly transplant patients and patients with congenital infections, respectively. Lifelong persistence of the virus may also contribute to age-related pathologies, such as vascular disease. One aspect of HCMV infection contributing to complex and varied pathogenesis is the diverse array of cell types that this virus infects in the host. The vascular endothelium is a particularly important target of infection, contributing to viral dissemination and likely leading to CMV complications following transplantation. In this work, we identify two viral gene products required for postentry tropism in endothelial cells. Identifying tropism factors required for replication in critical cell targets of infection is important for the development of strategies to restrict virus replication.
Novel CD4-Based Bispecific Chimeric Antigen Receptor Designed for Enhanced Anti-HIV Potency and Absence of HIV Entry Receptor Activity
Authors: Liu Li , Patel Bhavik , Ghanem Mustafa H. , Bundoc Virgilio , Zheng Zhili , Morgan Richard A. , Rosenberg Steven A. , Dey Barna , Berger Edward A.
Published: April 2015

Adoptive transfer of CD8 T cells genetically engineered to express “chimeric antigen receptors” (CARs) represents a potential approach toward an HIV infection “functional cure” whereby durable virologic suppression is sustained after discontinuation of antiretroviral therapy. We describe a novel bispecific CAR in which a CD4 segment is linked to a single-chain variable fragment of the 17b human monoclonal antibody recognizing a highly conserved CD4-induced epitope on gp120 involved in coreceptor binding. We compared a standard CD4 CAR with CD4-17b CARs where the polypeptide linker between the CD4 and 17b moieties is sufficiently long (CD4-35-17b CAR) versus too short (CD4-10-17b) to permit simultaneous binding of the two moieties to a single gp120 subunit. When transduced into a peripheral blood mononuclear cell (PBMC) or T cells thereof, all three CD4-based CARs displayed specific functional activities against HIV-1 Env-expressing target cells, including stimulation of gamma interferon (IFN-γ) release, specific target cell killing, and suppression of HIV-1 pseudovirus production. In assays of spreading infection of PBMCs with genetically diverse HIV-1 primary isolates, the CD4-10-17b CAR displayed enhanced potency compared to the CD4 CAR whereas the CD4-35-17b CAR displayed diminished potency. Importantly, both CD4-17b CARs were devoid of a major undesired activity observed with the CD4 CAR, namely, rendering the transduced CD8
+
T cells susceptible to HIV-1 infection. Likely mechanisms for the superior potency of the CD4-10-17b CAR over the CD4-35-17b CAR include the greater potential of the former to engage in the serial antigen binding required for efficient T cell activation and the ability of two CD4-10-17b molecules to simultaneously bind a single gp120 subunit.

IMPORTANCE
HIV research has been energized by prospects for a cure for HIV infection or, at least, for a “functional cure” whereby antiretroviral therapy can be discontinued without virus rebound. This report describes a novel CD4-based “chimeric antigen receptor” (CAR) which, when genetically engineered into T cells, gives them the capability to selectively respond to and kill HIV-infected cells. This CAR displays enhanced features compared to previously described CD4-based CARs, namely, increased potency and avoidance of the undesired rendering of the genetically modified CD8 T cells susceptible to HIV infection. When adoptively transferred back to the individual, the genetically modified T cells will hopefully provide durable killing of infected cells and sustained virus suppression without continued antiretroviral therapy, i.e., a functional cure.
The Vesicle-Forming 6K
2
Protein of Turnip Mosaic Virus Interacts with the COPII Coatomer Sec24a for Viral Systemic Infection
Authors: Jiang Jun , Patarroyo Camilo , Garcia Cabanillas Daniel , Zheng Huanquan , Laliberté Jean-François
Published: April 2015

Positive-sense RNA viruses remodel host cell endomembranes to generate quasi-organelles known as “viral factories” to coordinate diverse viral processes, such as genome translation and replication. It is also becoming clear that enclosing viral RNA (vRNA) complexes within membranous structures is important for virus cell-to-cell spread throughout the host. In plant cells infected by turnip mosaic virus (TuMV), a member of the family
Potyviridae
, peripheral motile endoplasmic reticulum (ER)-derived viral vesicles are produced that carry the vRNA to plasmodesmata for delivery into adjacent noninfected cells. The viral protein 6K
2
is responsible for the formation of these vesicles, but how 6K
2
is involved in their biogenesis is unknown. We show here that 6K
2
is associated with cellular membranes. Deletion mapping and site-directed mutagenesis experiments defined a soluble N-terminal 12-amino-acid stretch, in particular a potyviral highly conserved tryptophan residue and two lysine residues that were important for vesicle formation. When the tryptophan residue was changed into an alanine in the viral polyprotein, virus replication still took place, albeit at a reduced level, but cell-to-cell movement of the virus was abolished. Yeast (
Saccharomyces cerevisiae
) two-hybrid and coimmunoprecipitation experiments showed that 6K
2
interacted with Sec24a, a COPII coatomer component. Appropriately, TuMV systemic movement was delayed in an
Arabidopsis thaliana
mutant line defective in Sec24a. Intercellular movement of TuMV replication vesicles thus requires ER export of 6K
2
, which is mediated by the interaction of the N-terminal domain of the viral protein with Sec24a.

IMPORTANCE
Many plant viruses remodel the endoplasmic reticulum (ER) to generate vesicles that are associated with the virus replication complex. The viral protein 6K
2
of turnip mosaic virus (TuMV) is known to induce ER-derived vesicles that contain vRNA as well as viral and host proteins required for vRNA synthesis. These vesicles not only sustain vRNA synthesis, they are also involved in the intercellular trafficking of vRNA. In this investigation, we found that the N-terminal soluble domain of 6K
2
is required for ER export of the protein and for the formation of vesicles. ER export is not absolutely required for vRNA replication but is necessary for virus cell-to-cell movement. Furthermore, we found that 6K
2
physically interacts with the COPII coatomer Sec24a and that an
Arabidopsis thaliana
mutant line with a defective Sec24a shows a delay in the systemic infection by TuMV.
Immunogenic Display of Purified Chemically Cross-Linked HIV-1 Spikes
Authors: Leaman Daniel P. , Lee Jeong Hyun , Ward Andrew B. , Zwick Michael B.
Published: April 2015

HIV-1 envelope glycoprotein (Env) spikes are prime vaccine candidates, at least in principle, but suffer from instability, molecular heterogeneity and a low copy number on virions. We anticipated that chemical cross-linking of HIV-1 would allow purification and molecular characterization of trimeric Env spikes, as well as high copy number immunization. Broadly neutralizing antibodies bound tightly to all major quaternary epitopes on cross-linked spikes. Covalent cross-linking of the trimer also stabilized broadly neutralizing epitopes, although surprisingly some individual epitopes were still somewhat sensitive to heat or reducing agent. Immunodepletion using non-neutralizing antibodies to gp120 and gp41 was an effective method for removing non-native-like Env. Cross-linked spikes, purified via an engineered C-terminal tag, were shown by negative stain EM to have well-ordered, trilobed structure. An immunization was performed comparing a boost with Env spikes on virions to spikes cross-linked and captured onto nanoparticles, each following a gp160 DNA prime. Although differences in neutralization did not reach statistical significance, cross-linked Env spikes elicited a more diverse and sporadically neutralizing antibody response against Tier 1b and 2 isolates when displayed on nanoparticles, despite attenuated binding titers to gp120 and V3 crown peptides. Our study demonstrates display of cross-linked trimeric Env spikes on nanoparticles, while showing a level of control over antigenicity, purity and density of virion-associated Env, which may have relevance for Env based vaccine strategies for HIV-1.

IMPORTANCE
The envelope spike (Env) is the target of HIV-1 neutralizing antibodies, which a successful vaccine will need to elicit. However, native Env on virions is innately labile, as well as heterogeneously and sparsely displayed. We therefore stabilized Env spikes using a chemical cross-linker and removed non-native Env by immunodepletion with non-neutralizing antibodies. Fixed native spikes were recognized by all classes of known broadly neutralizing antibodies but not by non-neutralizing antibodies and displayed on nanoparticles in high copy number. An immunization experiment in rabbits revealed that cross-linking Env reduced its overall immunogenicity; however, high-copy display on nanoparticles enabled boosting of antibodies that sporadically neutralized some relatively resistant HIV-1 isolates, albeit at a low titer. This study describes the purification of stable and antigenically correct Env spikes from virions that can be used as immunogens.
Chronic comorbidities in children with type 1 diabetes: a population-based cohort study
Authors: Fazeli Farsani Soulmaz , Souverein Patrick C , van der Vorst Marja M J , Knibbe Catherijne A J , de Boer Anthonius , Mantel-Teeuwisse Aukje K
Published: April 2015

Objective

To determine the incidence of chronic comorbidities among children with type 1 diabetes (T1D) and to compare incidences with a group of children without diabetes.

Design

Population-based cohort study.

Setting

Dutch PHARMO database (1998–2010).

Patients

All patients (<19 years old) with T1D between 1999 and 2009 (T1D cohort) and a group of age- and sex-matched (ratio: 1–4) children without diabetes (reference cohort).

Main outcome measure

The incidence of nine common chronic comorbidities was assessed on the basis that they were treated pharmacologically and/or resulted in hospital admission. Cox proportional hazard analysis was used to estimate the strength of the association between T1D and comorbidities, expressed as HRs and 95% CIs.

Results

A total of 915 patients with T1D and 3590 children in the reference cohort (51% boys, mean age of 10.1 (SD 4.5) years) were included. T1D was associated with an increased risk (HR; 95% CI) of hospitalisation for any comorbidity (3.7; 2.5 to 5.5), thyroid disease (14.2; 6.7 to 31.0), non-infectious enteritis and colitis (5.9; 3.0 to 11.5), cardiovascular disorders (3.1; 2.3 to 4.2), mental disorders (2.0; 1.4 to 3.1), epilepsy (2.0; 1.1 to 3.7) and (obstructive) pulmonary disease (1.5; 1.2 to 2.0). There was no significant difference in the incidences of other comorbidities (malignant disorders, anaemia and migraine) between the two cohorts.

Conclusions

Our longitudinal study showed that incidences of six chronic diseases were significantly higher in T1D children during the early years of developing this disease compared with the reference children.
Clarifying life lost due to cold and heat: a new approach using annual time series
Authors: Rehill Nirandeep , Armstrong Ben , Wilkinson Paul
Published: April 2015

Objective

To clarify whether deaths associated with hot and cold days are among the frail who would have died anyway in the next few weeks or months.

Design

Time series regression analysis of annual deaths in relation to annual summaries of cold and heat.

Setting

London, UK.

Participants

3 530 280 deaths from all natural causes among London residents between October 1949 and September 2006.

Main outcome measures

Change in annual risk of death (all natural cause, cardiovascular and respiratory) associated with each additional 1°C of average cold (or heat) below (above) the threshold (18°C) across each year.

Results

Cold years were associated with increased deaths from all causes. For each additional 1° of cold across the year, all-cause mortality increased by 2.3% (95% CI 0.7% to 3.8%), after adjustment for influenza and secular trends. The estimated association between hot years and all-cause mortality was very imprecise and thus inconclusive (effect estimate 1.7%, −2.9% to 6.5%). These estimates were broadly robust to changes in the way temperature and trend were modelled. Estimated risk increments using weekly data but otherwise comparable were cold: 2.0% (2.0% to 2.1%) and heat: 3.9% (3.4% to 3.8%).

Conclusions

In this London annual series, we saw an association of cold with mortality which was broadly similar in magnitude to that found in published daily studies and our own weekly analysis, suggesting that most deaths due to cold were among individuals who would not have died in the next 6 months. The estimated association with heat was imprecise, with the CI including magnitudes found in daily studies but also including zero.
Experts’ consensus on use of electronic cigarettes: a Delphi survey from Switzerland
Authors: Blaser Jeremie , Cornuz Jacques
Published: April 2015

Objectives

In some countries, nicotine-containing electronic cigarettes (e-cigarettes) are considered a consumer product without specific regulations. In others (eg, Switzerland), the sale of e-cigarettes containing nicotine is forbidden, despite the eagerness of many smokers to obtain them. As scientific data about efficacy and long-term safety of these products are scarce, tobacco control experts are divided on how to regulate them. In order to gain consensus among experts to provide recommendations to health authorities, we performed a national consensus study.

Setting

We used a Delphi method with electronic questionnaires to bring together the opinion of Swiss experts on e-cigarettes.

Participants

40 Swiss experts from across the country.

Outcome measures

We measured the degree of consensus between experts on recommendations regarding regulation, sale, use of and general opinion about e-cigarettes containing nicotine. New recommendations and statements were added following the experts’ answers and comments.

Results

There was consensus that e-cigarettes containing nicotine should be made available, but only under specific conditions. Sale should be restricted to adults, using quality standards, a maximum level of nicotine and with an accompanying list of authorised ingredients. Advertisement should be restricted and use in public places should be forbidden.

Conclusions

These recommendations encompass three principles: (1) the reality principle, as the product is already on the market; (2) the prevention principle, as e-cigarettes provide an alternative to tobacco for actual smokers, and (3) the precautionary principle, to protect minors and non-smokers, since long-term effects are not yet known. Swiss authorities should design specific regulations to sell nicotine-containing e-cigarettes.
Patient and caregiver preferences for home dialysis—the home first study: a protocol for qualitative interviews and discrete choice experiments
Authors: Walker Rachael C , Morton Rachael L , Tong Allison , Marshall Mark R , Palmer Suetonia , Howard Kirsten
Published: April 2015

Introduction

The number of patients requiring dialysis continues to increase worldwide imposing a substantial social and economic burden on patients, their families and healthcare systems. Compared with facility-based dialysis, dialysis performed by the patient at home is associated with higher quality of life, freedom, survival and reduced healthcare costs. International guidelines recommend suitable patients are offered a choice of dialysis modality, including home-based dialysis. Predialysis education and offering patients choice increase home dialysis uptake, yet the factors that patients and families are willing to trade off in making decisions about dialysis location are not well understood. The Home First study will explore patients’ and caregivers’ beliefs, attitudes and preferences regarding dialysis education and decision-making with regards to dialysis options; to identify key attributes which influence their decision-making, and to quantify the relative value of these attributes.

Methods and analysis

This study will use a mixed-methods approach to describe patient and caregiver preferences and views about the factors that influence their choice of home or facility-based dialysis. Face-to-face, semistructured interviews will be conducted with 30–40 patients and 10–15 caregivers. Thematic analysis of interview transcripts will be conducted. Additional to providing information on the perspectives and experiences of patients and caregivers, these analyses will also inform the design of discrete choice experiments (DCEs). We will undertake DCEs with approximately 150 patients and 150 caregivers to quantify preferences for home and facility dialysis.

Ethics and dissemination

The Hawke's Bay, Counties Manukau, and Capital Coast District Health Board Research Ethics Committees approved the study. Findings will be presented in national/international conferences and peer-reviewed journals. Dissemination to patients will take the form of presentations, newsletters and reports to support and community groups. Reports will be disseminated to funders and participating renal units and to the New Zealand Ministry of Health.

Trial registration number

ACTRN12615000314527.
A cross-sectional study on person-centred communication in the care of older people: the COMHOME study protocol
Authors: Hafskjold Linda , Sundler Annelie J , Holmström Inger K , Sundling Vibeke , van Dulmen Sandra , Eide Hilde
Published: April 2015

Introduction

This paper presents an international cross-sectional study on person-centred communication with older people receiving healthcare (COMHOME). Person-centred care relies on effective communication, but few studies have explored this with a specific focus on older people. The main aim of the COMHOME study is to generate knowledge on person-centred communication with older people (>65 years) in home healthcare services, radiographic and optometric practice.

Methods and analysis

This study will explore the communication between care providers and older persons in home care services. Home healthcare visits will be audiorecorded (n=500) in Norway, the Netherlands and Sweden. Analyses will be performed with the Verona Coding Definitions for Emotional Sequences (VR-CoDES), the Roter Interaction Analysis System (RIAS) and qualitative methods. The content of the communication, communicative challenging situations as well as empathy, power distance, decision-making, preservation of dignity and respect will be explored. In Norway, an additional 100 encounters, 50 in optometric practice (video recorded) and 50 in radiographic practice (audiorecorded), will be analysed. Furthermore, healthcare providers’ self-reported communication skills, empathy, mindfulness and emotional intelligence in relation to observed person-centred communication skills will be assessed using well-established standardised instruments.

Ethics and dissemination

Depending on national legislation, approval of either the central ethical committees (eg, nation or university), the national data protection officials or the local ethical committees (eg, units of home healthcare) was obtained. Study findings will be disseminated widely through peer-reviewed publications and conference presentations. The research findings will add knowledge to improve services provided to this vulnerable group of patients. Additionally, the findings will underpin a training programme for healthcare students and care providers focusing on communication with older people.
Intended and unintended effects of large-scale adverse event disclosure: a controlled before-after analysis of five large-scale notifications
Authors: Wagner Todd H , Taylor Thomas , Cowgill Elizabeth , Asch Steven M , Su Pon , Bokhour Barbara , Durfee Janet , Martinello Richard A , Maguire Elizabeth , Elwy A Rani
Published: April 2015

Background and objective

How patients respond to being notified of a large-scale adverse event (LSAE), such as improper sterilisation of medical equipment that exposes them to bloodborne pathogens, is not well known. The objective of this study was to determine, using administrative data, the intended and unintended consequences of patient notification following a LSAE.

Methods

We examined five LSAEs where patients may have been inadvertently exposed to hepatitis C virus (HCV), HIV, and hepatitis B virus (HBV). A total of 9638 cases were identified at five Department of Veteran Affairs (VA) medical facilities between 2009 and 2012. We identified controls at the same facility prior to the exposure period and at neighbouring facilities (n=45 274). Difference-in-differences models were used with Veterans Health Administration (VHA) and Medicare data to examine infectious disease testing rates and subsequent utilisation patterns.

Results

Receipt of a LSAE notification was associated with a 73.2, 76.8 and 77.1 adjusted percentage point increase for HCV, HIV and HBV testing, respectively (all p<0.001). Compared with white patients, African–American patients were significantly less likely to return to VHA for follow-up testing. Patients exposed to a dental LSAE reduced their use of preventive and restorative dental care over the subsequent year, but they eventually came back to VHA for dental services 18-months post exposure.

Conclusions

The majority of patients notified of a LSAE responded by getting tested for HCV, HIV and HBV, although there remains room for improvement. Potential exposure to a LSAE was associated with increased odds of subsequently using non-VA facilities, but the size and timing of the shift depended on the type of care.
Review of in situ and invasive penile squamous cell carcinoma and associated non-neoplastic dermatological conditions
Authors: Downes Michelle R
Published: April 2015

Penile carcinoma is a rare genitourinary malignancy in North America and Europe with highest rates recorded in South America, Africa and Asia. Recent classifications have refined the terminology used in classifying intraepithelial/in situ lesions and additionally newer entities have been recognised in the invasive category. While increasing recognition of a bimodal pathway of penile carcinogenesis has facilitated understanding and classification of these tumours, handling and subtyping of penile malignancies presents a challenge to the reporting pathologist, in part due to their rarity. This article reviews the terminology and classification of in situ and invasive carcinomas and their relationship to human papilloma virus status. In addition, associated non-neoplastic dermatological conditions of relevance and appropriate ancillary investigations will be addressed.
Discordant pattern ofBRCA1gene epimutation in blood between mothers and daughters
Authors: Wojdacz Tomasz K , Harari Florencia , Vahter Marie , Broberg Karin
Published: April 2015

Methylation of the promoter ofBRCA1gene in peripheral blood (epimutation) has been associated with increased risk for breast cancer. Some studies have indicated that this epimutation is of constitutional origin and hence it could potentially be transmitted across generations. We used methylation sensitive high resolution melting technique to measure methylation ofBRCA1promoter in blood samples from 226 healthy women from the Andean region in Salta province, northern Argentina. In total 29 (13%) of the women showed detectable methylation of this gene. The analyses of mother-daughter pairs in this study, showed discordant methylation ofBRCA1between generations, with mothers tested positive forBRCA1methylation in blood having daughters without signs ofBRCA1methylation, and vice versa. Our results show that theBRCA1epimutation is unlikely transmitted from mother to daughters and hence may be a consequence of environmental exposure.
Evaluation of select warm mix additives with polymer and rubber modified asphalt mixtures
Authors: Chamoun Zahi , Souliman Mena I. , Hajj Elie Y. , Sebaaly Peter
Published: April 2015

Warm mix technologies are being increasingly investigated in an effort to conserve energy, reduce emissions, and extend paving season. Most of the laboratory research conducted to date on warm mix technologies has been concentrated on studying the impact of warm mix technologies on unmodified asphalt binders. This research effort evaluates the use of select warm mix additives with unmodified, polymer-modified, and terminal blend tire rubber asphalt mixtures from Nevada and California. The study evaluated two different warm mix asphalt (WMA) technologies: Sasobit and Advera. The experimental program evaluated the resistance to moisture damage and rutting of different mixtures with and without liquid anti-strip and lime. Additionally, fatigue resistance of modified and unmodified asphalt mixtures without anti-strip was conducted. In this research effort, the unmodified WMA mixtures were able to achieve mixing temperature reductions of 26.7 to 29.4 °C while the modified WMA mixtures were able to achieve mixing temperature reductions of 16.7 to 25.0 °C compared to their corresponding HMA control mixtures. The results showed that the use of modified binders with WMA technologies and anti-strip additives can result in mixtures with a better resistance to moisture damage compared to unmodified mixtures. Additionally, the combination of modified asphalt binders with lime will eventually generate better resisting mixtures to permanent deformation. Moreover, the resistance to fatigue cracking of HMA and WMA mixtures was also enhanced using modified asphalt binders. Furthermore, a mechanistic fatigue analysis using 3D-Move software confirmed the outcomes of fatigue testing.
On the detection of point sources in Planck LFI 70 GHz CMB maps based on cleaned K-map
Authors: Khachatryan H. G. , Kashin A. L. , Poghosyan E. , Yegoryan G.
Published: April 2015

We use the Planck LFI 70 GHz data to further probe point source detection technique in the sky maps of the cosmic microwave background (CMB) radiation. The method developed by Tegmark et al. for foreground reduced maps and the Kolmogorov parameter as the descriptor are adopted for the analysis of Planck satellite CMB temperature data. Most of the detected points coincide with point sources already revealed by other methods. However, we have also found nine source candidates for which still no counterparts are known.
Tubular cross talk in acute kidney injury: a story of sense and sensibility
Authors: El-Achkar Tarek M. , Dagher Pierre C.
Published: April 2015

The mammalian kidney is an organ composed of numerous functional units or nephrons. Beyond the filtering glomerulus of each nephron, various tubular segments with distinct populations of epithelial cells sequentially span the kidney from cortex to medulla. The highly organized folding of the tubules results in a spatial distribution that allows intimate contact between various tubular subsegments. This unique arrangement can promote a newly recognized type of horizontal epithelial-to-epithelial cross talk. In this review, we discuss the importance of this tubular cross talk in shaping the response of the kidney to acute injury in a sense and sensibility model. We propose that injury-resistant tubules such as S1 proximal segments and thick ascending limbs (TAL) can act as “sensors” and thus modulate the responsiveness or “sensibility” of the S2-S3 proximal segments to injury. We also discuss new findings that highlight the importance of tubular cross talk in regulating homeostasis and inflammation not only in the kidney, but also systemically.
Classification of pallidal oscillations with increasing parkinsonian severity
Authors: Connolly Allison T. , Jensen Alicia L. , Baker Kenneth B. , Vitek Jerrold L. , Johnson Matthew D.
Published: April 2015

The firing patterns of neurons in the basal ganglia are known to become more oscillatory and synchronized from healthy to parkinsonian conditions. Similar changes have been observed with local field potentials (LFPs). In this study, we used an unbiased machine learning approach to investigate the utility of pallidal LFPs for discriminating the stages of a progressive parkinsonian model. A feature selection algorithm was used to identify subsets of LFP features that provided the most discriminatory information for severity of parkinsonian motor signs. Prediction errors <20% were achievable using 28 of the possible 206 features tested. For all subjects, a spectral feature within the beta band was chosen through the feature selection algorithm, but a combination of features, including alpha-band power and phase-amplitude coupling, was necessary to achieve minimal prediction errors. There was large variability between the discriminatory features for individual subjects, and testing of classifiers between subjects yielded prediction errors >50%. These results suggest that pallidal oscillations can be predictive biomarkers of parkinsonian severity, but the features are more complex than spectral power in individual frequency bands, such as the beta band. Additionally, the best feature set was subject specific, which highlights the pathophysiological heterogeneity of parkinsonism and the importance of subject specificity when designing closed-loop system controllers dependent on such features.
Reliable Control for Uncertain Singular Systems with Randomly Occurring Time-Varying Delay and Actuator Faults
Authors: Li Yu-Lin , Li Lin-Sheng , Zhao Zhi-Cheng , Zhang Jing-Gang
Published: April 2015

The problem of reliable control is investigated for uncertain continuous singular systems with randomly occurring time-varying delay and actuator faults in this work. The delay occurs in a random way, and such randomly occurring delay obeys certain mutually uncorrelated Bernoulli distributed white noise sequences. The uncertainties under consideration are norm-bounded, and may vary with time. Then, with the constructed Lyapunov function, a sufficient condition is given to ensure the unforced system is mean-square exponentially stable and the corresponding controller can be derived from such condition, and the actuator faults problem is guaranteed. A numerical example is provided to show the effectiveness of the methods.
Induction of Ankrd1 in Dilated Cardiomyopathy Correlates with the Heart Failure Progression
Authors: Bogomolovas Julius , Brohm Kathrin , Čelutkienė Jelena , Balčiūnaitė Giedrė , Bironaitė Daiva , Bukelskienė Virginija , Daunoravičus Dainius , Witt Christian C. , Fielitz Jens , Grabauskienė Virginija , Labeit Siegfried
Published: April 2015

Progression of idiopathic dilated cardiomyopathy (IDCM) is marked with extensive left ventricular remodeling whose clinical manifestations and molecular basis are poorly understood. We aimed to evaluate the clinical potential of titin ligands in monitoring progression of cardiac remodeling associated with end-stage IDCM. Expression patterns of 8 mechanoptotic machinery-associated titin ligands (ANKRD1,ANKRD2,TRIM63,TRIM55,NBR1,MLP,FHL2, andTCAP) were quantitated in endomyocardial biopsies from 25 patients with advanced IDCM. When comparing NYHA disease stages, elevatedANKRD1expression levels marked transition from NYHA < IV to NYHA IV.ANKRD1expression levels closely correlated with systolic strain depression and short E wave deceleration time, as determined by echocardiography. On molecular level, myocardialANKRD1and serum adiponectin correlated with lowBAX/BCL-2ratios, indicative of antiapoptotic tissue propensity observed during the worsening of heart failure. ANKRD1 is a potential marker for cardiac remodeling and disease progression in IDCM.ANKRD1expression correlated with reduced cardiac contractility and compliance. The association ofANKRD1with antiapoptotic response suggests its role as myocyte survival factor during late stage heart disease, warranting further studies on ANKRD1 during end-stage heart failure.
NT-proBNP as Early Marker of Subclinical Late Cardiotoxicity after Doxorubicin Therapy and Mediastinal Irradiation in Childhood Cancer Survivors
Authors: Zidan Amal , Sherief Laila M. , El-sheikh Amera , Saleh Safaa H. , Shahbah Doaa A. , Kamal Naglaa M. , Sherbiny Hanan S. , Ahmad Heba
Published: April 2015

Background. Childhood cancer survivors treated with anthracyclines and mediastinal irradiation are at risk for late onset cardiotoxicity.Aims of the Study. To assess the role of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tissue Doppler imaging (TDI) as early predictors of late onset cardiotoxicity in asymptomatic survivors of childhood cancer treated with doxorubicin with or without mediastinal irradiation.Methods. A cross-sectional study on 58 asymptomatic survivors of childhood cancer who received doxorubicin in their treatment protocols and 32 asymptomatic Hodgkin’s lymphoma survivors who received anthracycline and mediastinal irradiation. Levels of NT-proBNP, TDI, and conventional echocardiography were determined. Results. Thirty percent of survivors had abnormal NT-proBNP levels. It was significantly related to age at diagnosis, duration of follow-up, and cumulative dose of doxorubicin. TDI detected myocardial affection in 20% more than conventional echocardiography. Furthermore, abnormalities in TDI and NT-pro-BNP levels were more common in Hodgkin lymphoma survivors receiving both chemotherapy and radiotherapy.Conclusions. TDI could detect early cardiac dysfunction even in those with normal conventional echocardiography. Measurement of NT-proBNP represents an interesting strategy for detecting subclinical cardiotoxicity. We recommend prospective and multicenter studies to validate the role of NT-proBNP as an early marker for late onset doxorubicin-induced cardiotoxicity.
Dialysis Arteriovenous Fistula Causing Subclavian Steal Syndrome in the Absence of Subclavian Artery Stenosis
Authors: Maiodna Eesha , Ambekar Sudheer , Johnson Jeremiah N. , Elhammady Mohamed Samy
Published: April 2015

We present a rare cause of subclavian steal syndrome secondary to a dialysis arteriovenous fistula (AVF). A 69-year-old female with end-stage renal disease presented with ataxia and recurrent fainting spells. Angiography revealed normal subclavian arteries bilaterally, a right VA origin occlusion, and an apparent left VA origin occlusion. However, carotid artery angiography demonstrated flow through the posterior communicating artery with retrograde filling of the basilar artery and left VA to its subclavian origin. Repeat left subclavian arteriography during external compression of the AVF demonstrated normal antegrade left VA flow. The AVF was subsequently ligated resulting in complete symptom resolution.