bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide characterization of PRE-1 reveals a hidden evolutionary relationship between suidae and primates
Authors: Yu Hao , Wu Qingyan , Zhang Jing , Zhang Ying , Lu Chao , Cheng Yunyun , Zhao Zhihui , Windemuth Andreas , Liu Di , Hao Linlin
Published: December 2015

We identified and characterized a free PRE-1 element inserted into the promoter region of the porcineIGFBP7gene whose integration mechanisms into the genome, including copy number, distribution preferences, capacity to exonize and phyloclustering pattern are similar to that of the primate Alu element. 98% of these PRE-1 elements also contain two conserved internal AluI restriction enzyme recognition sites, and the RNA structure of PRE1 can be folded into a two arms model like the Alu RNA structure. It is more surprising that the length of the PRE-1 fragments is nearly the same in 20 chromosomes and positively correlated to its fracture site frequency. All of these fracture sites are close to the mutation hot spots of PRE-1 families, and most of these hot spots are located in the non-complementary fragile regions of the PRE-1 RNA structure. Sequence homology analysis showed that the PRE-1 element seemed to share a common ancestor 7SL RNA with primates but was generated by different evolutionary model, which suggests that the suidae may be the closest relatives to primates in laurasiatheria.
Integrated analysis linksTP53, NOTCH, SLC38Aand 11p with survival in patients with oral tongue squamous cell carcinoma
Authors: Krishnan Neeraja M , Gupta Saurabh , Khyriem Costerwell , Palve Vinayak , Suresh Amritha , Siddappa Gangotri , Kekatpure Vikram , Kuriakose Moni Abraham , Panda Binay
Published: December 2015

Head and neck squamous cell carcinoma (HNSCC) are a heterogeneous group of cancers affecting multiple subsites, including oral cavity. Oral or anterior tongue tumors (OTSCC) are an aggressive group of squamous cell carcinomas, characterized by their early spread to lymph nodes and higher rate of regional failure compared to other oral cavity cancers. There is a rise in the incidence of oral tongue cancer among younger population (<50yrs); many of who lack the typical associated risk factors of alcohol and/or tobacco exposure. In order to carry out an ensemble learning and prediction method with multiple parameters classifying survival, we generated data, on somatic mutations in genes from exome sequencing, immediate upstream and downstream flanking nucleotides of the somatic mutations, DNA methylation, loss of heterozygosity (LOH), copy number variations (CNV), gene expression, significant pathways altered and Human Papilloma Virus (HPV) infection, from 50 OTSCC patients. Results of our analysis identified somatic mutations inNOTCH2and/orTP53, and/or LOH in 11p to associate with better disease free survival in HPV positive patients (P= 0.0254) and not in HPV negative patients (P= 0.414). We validated the latter in patients without HPV infection from TCGA cohort (P= 0.369,N =17 for TCGA_ OralTongue;P= 0.472,N =67 for all TCGA_HNSCC patients). Integrated analysis, including pathways, linked survival with apoptosis and aberrant methylation inSLC38A8(P= 0.0129).

Author Summary

Oral tongue squamous cell carcinomas (OTSCC) are a homogenous group of head and neck tumors characterized with aggressive behavior among younger patients. In this report, we have analysed genetic variants, expression and DNA methylation changes across 50 oral tongue primary tumors along with the Human Papilloma Virus (HPV) infection status in those tumors to identify factors associated with disease free survival. Our data identified somatic mutations in the genesNOTCH2, TP53and LOH in 11p, to be significantly associated with better disease free survival in HPV positive patients (P= 0.0254), but not in HPV negative patients (P= 0.414). We validated the latter using patients without HPV infection from TCGA (P= 0.369,N =17 for TCGA_OralTongue;P= 0.472,N =67 for all TCGA_HNSCC patients). Integrated analysis linked survival with apoptosis and aberrant methylation inSLC38A8(P= 0.0129).
Principles of ipsilateral and contralateral cortico-cortical connectivity in the mouse
Authors: Goulas Alexandros , Uylings Harry BM , Hilgetag Claus C
Published: December 2015

Structural connectivity among cortical areas provides the substrate for information exchange in the brain and is characterized by the presence or absence of connections between specific areas. What principles govern this cortical wiring diagram? Here, we investigate the relation of physical distance and cytoarchitecture with the connectional architecture of the mouse cortex. Moreover, we examine the relation between patterns of ipsilateral and contralateral connections. Our analysis reveals a mirrored and attenuated organization of contralateral connections when compared to ipsilateral connections. Both spatial proximity and cytoarchitectonic similarity of cortical areas are related to the presence or absence of connections. Notably, our analysis demonstrated that these factors conjointly relate better to cortico-cortical connectivity than each factor in isolation, and that the two factors contribute differently to ipsilateral and contralateral connectivity. Distance is more tightly related to the presence or absence of ipsilateral connections, but its contribution greatly diminishes for contralateral connections, while the contribution of cytoarchitectonic similarity remains stable. Our results, conjointly with similar findings in the cat and macaque cortex, suggest that a common set of principles underlies the macroscale wiring of mammalian brains.
Archaic adaptive introgression inTBX15/WARS2
Authors: Racimo Fernando , Gokhman David , Fumagalli Matteo , Ko Amy , Hansen Torben , Moltke Ida , Albrechtsen Anders , Carmel Liran , Huerta-Sánchez Emilia , Nielsen Rasmus
Published: December 2015

A recent study conducted the first genome-wide scan for selection in Inuit from Greenland using SNP chip data. Here, we report that selection in the region with the second most extreme signal of positive selection in Greenlandic Inuit favored a deeply divergent haplotype that is closely related to the sequence in the Denisovan genome, and was likely introgressed from an archaic population. The region contains two genes,WARS2andTBX15, and has previously been associated with adipose tissue differentiation and body-fat distribution in humans. We show that the adaptively introgressed allele has been under selection in a much larger geographic region than just Greenland. Furthermore, it is associated with changes in expression ofWARS2andTBX15in multiple tissues including the adrenal gland and subcutaneous adipose tissue, and with regional DNA methylation changes inTBX15.
A webometric analysis of major keywords and expressions in biochemistry using LexiURL Searcher
Authors: Taram Kobra , Doulani Abbas
Published: December 2015

Purpose

– The purpose of this paper is to explore webometric analysis of keywords and expressions of the biochemistry field of study via LexiURL Searcher.

Design/methodology/approach

– Interfaces for assisting users with information access have received considerable attention. Along with the extraction of data on Web sites for webometric purposes (e.g. link analysis, ranking of Web sites, etc.), LexiURL Searcher presents some information on the arrangement of links among different Web sites. Such capability enables users to identify one or more Web sites around their intended subject and, accordingly, explore all Web sites linked with their identified Web site(s). LexiURL Searcher has preceded webometric analysis by considering the main expressions and keywords derived from the MeSH database.

Findings

– The worldwide survey indicated that links from countries such as England, Japan, Germany, Australia and Canada were among the Web sites that are most used in biochemistry. Alternatively, other countries such as Singapore, Thailand and Poland had the most advantageous links to the outside world, whereas South Africa, New Zealand and The Netherlands had the least link effect. Biochemistry, being a specialized domain, would benefit greatly from site linking and would provide users the most assistance in information processing.

Originality/value

– Most webometric studies remain on the level of link analysis and Web site statuses; however, this paper gives information on the common thread Web sites based on a standard thesaurus.
An adhesin from hydrogen‐utilizing rumen methanogen Methanobrevibacter ruminantium M1 binds a broad range of hydrogen‐producing microorganisms
Authors: Ng Filomena , Kittelmann Sandra , Patchett Mark L. , Attwood Graeme T. , Janssen Peter H. , Rakonjac Jasna , Gagic Dragana
Published: December 2015

Symbiotic associations are ubiquitous in the microbial world and have a major role in shaping the evolution of both partners. One of the most interesting mutualistic relationships exists between protozoa and methanogenic archaea in the fermentative forestomach (rumen) of ruminant animals. Methanogens reside within and on the surface of protozoa as symbionts, and interspecies hydrogen transfer is speculated to be the main driver for physical associations observed between the two groups. In silico analyses of several rumen methanogen genomes have previously shown that up to 5% of genes encode adhesin‐like proteins, which may be central to rumen interspecies attachment. We hypothesized that adhesin‐like proteins on methanogen cell surfaces facilitate attachment to protozoal hosts. Using phage display technology, we have identified a protein (Mru_1499) from Methanobrevibacter ruminantium M1 as an adhesin that binds to a broad range of rumen protozoa (including the genera Epidinium and Entodinium). This unique adhesin also binds the cell surface of the bacterium Butyrivibrio proteoclasticus, suggesting a broad adhesion spectrum for this protein.
Prediction of small‐for‐gestational‐age status by symphysis–fundus height: a registry‐based population cohort study
Authors: Pay ASD , Frøen JF , Staff AC , Jacobsson B , Gjessing HK
Published: December 2015

Objective

To develop a chart for risk of small‐for‐gestational‐age (SGA) at birth depending on deviations in symphysis–fundus (SF) height values for gestational age during pregnancy weeks 24–42.

Design

Registry‐based population cohort study.

Setting

Antenatal clinics, Västra Götaland County, Sweden, 2005–2010.

Population

The study included 42 018 women with ultrasound‐dated singleton pregnancies who delivered at Sahlgrenska University Hospital. Data (including 282 713 SF height measurements) were extracted from the hospital's computerised obstetric database.

Methods

Linear and binary regression analyses were used to derive prediction models with deviations in birthweight (BW) and SF height by gestational age as dependent and independent variables, respectively. Receiver operating characteristic curves were generated to evaluate the predictive value of the model in detecting SGA.

Main outcome measures

Birthweight and small‐for‐gestational‐age.

Results

Symphysis–fundus height accounted for 3% of individual BW variance at 24 weeks, increasing gradually to 20% at 40 weeks. Maternal factors explained an additional 10 percentage points of BW variance. Receiver operating characteristic curves confirmed that SF height was a stronger SGA predictor in late than in early pregnancy. Using an SGA relative risk cut‐off limit of ≥2‐fold, the overall sensitivity was 50% and the overall specificity 80%. Only the most recent SF measurement was useful in predicting BW deviation; previous measurements added nothing to the predictive value.

Conclusions

The ability of SF measurements to detect SGA status at birth increases with gestational age. Only the most recent SF measurement has predictive value; a static or falling pattern of SF values did not increase SGA likelihood.

Tweetable abstract

New SF curves predict SGA best in late pregnancy; only the most recent SF measurement has predictive value.
Characterization and Quantitation of Triterpenoid Saponins in Raw and Sprouted Chenopodium berlandieri spp. (Huauzontle) Grains Subjected to Germination with or without Selenium Stress Conditions
Authors: Lazo‐Vélez Marco A. , Guajardo‐Flores Daniel , Mata‐Ramírez Daniel , Gutiérrez‐Uribe Janet A. , Serna‐Saldivar Sergio O.
Published: December 2015

Pseudocereal Chenopodium berlandieri spp. (huauzontle) was evaluated to determine saponin composition. Saponins were evaluated in raw and germinated grains subjected to chemical stress induced by sodium selenite. Analysis by liquid chromatography coupled with ELSD detector revealed the presence of 12 saponins, identified according to compounds previously assayed in Chenopodium quinoa. Saponins found at the highest concentrations in raw grains were derived from oleanolic and phytolaccagenic acids. Total saponin concentration significantly decreased in germinated compared to raw grains due to the significant loss of 90.1% and 95.7% of the phytolaccagenic acid without and with chemical selenium stress, respectively. The most abundant saponin in germinated sprouts decreased during normal germination. Interestingly, the concentration of this particular saponin significantly increased during the Se‐induced stress germination. Chemical stress with selenium salts proved to change the saponin composition in geminated Chenopodium berlandieri spp. grains, therefore affecting their potential use as ingredient in the food industry.
Characterization of the transcriptome and gene expression of four different tissues in the ecologically relevant sea urchin Arbacia lixula using RNA‐seq
Authors: Pérez‐Portela R. , Turon X. , Riesgo A.
Published: December 2015

The sea urchin Arbacia lixula is a keystone species in Mediterranean ecosystems that drive landscape changes in littoral communities. However, genomic information available for the whole order Arbacioida is very limited. Using RNA‐seq techniques, we have characterized the transcriptome of four different tissue types in A. lixula: the ‘somatic’ tissues (coelomocytes and digestive tissue) and the ‘reproductive’ tissues (ovary and testis), from two replicated cDNA libraries for each sample. Additionally, we performed a de novo assembly to build the ‘reference’ transcriptome, pooling reads of the four tissues, to analyse the differential expression (DE) in pairwise comparisons between tissues. The complete de novo assembly yielded 186 084 transcripts, with a sequence size limit of 100 nt, being 31% of them spliced isoforms. Approximately 21% of the transcripts had blast hits against proteins of metazoans (E < 10−5), being less than 2.2% functionally annotated. Between coelomocytes and digestive, 30 794 transcripts showed DE (~11.8% of them with blast hit), and 19 567 transcripts did so between testis and ovary (~28.5% of them with blast hit). Major GO‐term categories upregulated in somatic tissues were those related to muscle contraction and energy generation in digestive, and lipid metabolism associated with immune response in coelomocytes. Between reproductive tissues, the major upregulated GO categories were related to energy generation in testis, and negative regulation of nucleotide metabolism in ovary. We particularly screened for a collection of target genes in each tissue because of their relevance for further studies on evolution and adaptation of echinoids.
Excessive alcohol consumption increases mortality in later life: a genetic analysis of the health in men cohort study
Authors: Almeida Osvaldo P. , McCaul Kieran , Hankey Graeme J. , Yeap Bu B. , Golledge Jonathan , Flicker Leon
Published: December 2015

We designed this cohort study of men aged 70–89 years to determine if excessive alcohol use increases mortality. They reported history of alcohol use (never, past, ≤ two daily drinks, two to four daily drinks, four to six daily drinks, > six daily drinks) and donated a blood sample in 2001–2004. We determined the ADH1B rs1229984 G>A polymorphism and retrieved mortality data from the Western Australian Data Linkage System. Other study measures included age, education, body mass index, smoking, and history of hypertension, diabetes, chronic respiratory diseases, coronary heart disease and stroke. Of the 3496 participants, 225 (6.4 percent) carried the ADH1B rs1229984 G>A polymorphism. Carriers consumed significantly less alcohol than non‐carriers. The adjusted mortality hazard ratio (MHR, 95 percent confidence interval—95%CI) over 8.0 years (range: 10 weeks to 11.2 years) relative to never drinkers was 1.15 (95%CI = 0.86, 1.55) for past drinkers, 0.98 (95%CI = 0.76, 1.25) for men consuming ≤ two daily drinks, 1.13 (95%CI = 0.85, 1.49) for two to four drinks, 1.18 (95%CI = 0.81, 1.71) for four to six drinks and 1.87 (95%CI = 1.11, 3.12) for those consuming more than six daily drinks on a regular basis. The MHR associated with the ADH1B rs1229984 G>A polymorphism was 0.68 (95%CI = 0.54, 0.87). Excessive alcohol use in later life is associated with increased mortality, and this association is likely to be causal. We found no evidence that light to moderate alcohol use decreases the mortality of older men. Health messages regarding the safe use of alcohol in older age may benefit from taking these findings into account.
Twenty years of artificial directional selection have shaped the genome of the Italian Large White pig breed
Authors: Schiavo G. , Galimberti G. , Calò D. G. , Samorè A. B. , Bertolini F. , Russo V. , Gallo M. , Buttazzoni L. , Fontanesi L.
Published: December 2015

In this study, we investigated at the genome‐wide level if 20 years of artificial directional selection based on boar genetic evaluation obtained with a classical BLUP animal model shaped the genome of the Italian Large White pig breed. The most influential boars of this breed (n = 192), born from 1992 (the beginning of the selection program of this breed) to 2012, with an estimated breeding value reliability of >0.85, were genotyped with the Illumina Porcine SNP60 BeadChip. After grouping the boars in eight classes according to their year of birth, filtered single nucleotide polymorphisms (SNPs) were used to evaluate the effects of time on genotype frequency changes using multinomial logistic regression models. Of these markers, 493 had a PBonferroni < 0.10. However, there was an increasing number of SNPs with a decreasing level of allele frequency changes over time, representing a continuous profile across the genome. The largest proportion of the 493 SNPs was on porcine chromosome (SSC) 7, SSC2, SSC8 and SSC18 for a total of 204 haploblocks. Functional annotations of genomic regions, including the 493 shifted SNPs, reported a few Gene Ontology terms that might underly the biological processes that contributed to increase performances of the pigs over the 20 years of the selection program. The obtained results indicated that the genome of the Italian Large White pigs was shaped by a directional selection program derived by the application of methodologies assuming the infinitesimal model that captured a continuous trend of allele frequency changes in the boar population.
Innovation and Consumer Directed Care: Identifying the challenges
Authors: Gill Liz , Cameron Ian D
Published: December 2015

Our aim was to report clinician and researcher observations about the practical difficulties with achieving the articulated objectives of Consumer Directed Care (CDC). The methods used were as follows: identification of key client community services issues through analysis of qualitative data related to a PhD project; review of the summary of these issues by the supervising academic; presentation of the issues to five clinicians involved with a community service clinical trial; verification of the findings through discussions with a senior community service provider. There is anecdotal evidence that the current overlay of CDC in the existing community‐based home services sector for people who are older will continue to prevent its effective implementation. The existing culture and underlying philosophies related to this sector maybe unable to support the level of innovative change required. Research is needed into how the stated objectives of CDC can be achieved in Australia and how this can best be managed.
A randomised comparison of the Ambu® AuraGain™ and the LMA® supreme in infants and children
Authors: Jagannathan N. , Hajduk J. , Sohn L. , Huang A. , Sawardekar A. , Gebhardt E. R. , Johnson K. , De Oliveira G. S.
Published: December 2015

We conducted a randomised trial in 100 children in order to compare the clinical performance of the Ambu® AuraGain™ and the LMA® Supreme* for airway maintenance during mechanical ventilation. The primary outcomes were initial and 10‐min airway leak pressures. Ease, time and success rates for device and gastric tube insertion, fibreoptic grades of view, airway quality during anaesthetic maintenance, and complications were also assessed. There were no differences in the initial and ten min airway leak pressures between the Ambu AuraGain and LMA Supreme, median (IQR [range]) initial: 19 (16–22 [10–34]) vs 18 (14–24 [8–40]) cmH2O, p = 0.4; and ten min: 22 (18–26 [11–40]) vs 20 (16–26 [12–40]) cmH2O, p = 0.08, respectively. Ease, time and success rates for device placement, gastric tube insertion and complications were also not significantly different. Children receiving the LMA Supreme required more airway manouevers (7 vs 1 patient, p = 0.06) to maintain a patent airway. Our results suggest that the Ambu AuraGain may be a useful alternative to the LMA Supreme, as demonstrated by comparable overall clinical performance in children.
Use of vaginal estrogen in Danish women: a nationwide cross‐sectional study
Authors: Meaidi Amani , Goukasian Irina , Lidegaard Oejvind
Published: December 2015

Introduction

We know little about the use of vaginal estrogen in perimenopausal and postmenopausal women. We aimed to assess the prevalence of vaginal estrogen use in Denmark.

Material and methods

The study was designed as a nationwide cross‐sectional study of all Danish women aged 40–79 years, living in Denmark during the period 2007–2013. The Danish Prescription Register delivered data permitting us to assess the prevalence, age and regional geographical belonging of women purchasing prescribed vaginal estradiol. The number of women using over‐the‐counter vaginal estriol products was estimated from sale statistics from the same register.

Results

In 2013, 10.2% of all Danish women between 40 and 79 years of age used vaginal estradiol. The prevalence of women using this type of vaginal estrogen increased from 8.5% in year 2007 to 10.2% in 2013. The use peaked at 16.5% in women aged 60–74 years. The vaginal tablet was purchased more than the vaginal ring. We found no relevant difference in use between the five regions of Denmark. Taking the sale of vaginal estriol into account, the prevalence of vaginal estrogen use in 2013 could be estimated to a total of 12.1%.

Conclusions

Comparing our result to the prevalence of urogenital atrophy‐related symptoms reported in the literature, our study suggests an under‐diagnosis and under‐treatment of this condition. Teaching women and primary‐care physicians about symptomatic urogenital atrophy and its treatment options may increase the quality of life for many women.
The efficacy and complications of black diaphragm intra‐ocular lens implantation in patients with congenital aniridia
Authors: Qiu Xiaodi , Ji Yinghong , Zheng Tianyu , Lu Yi
Published: December 2015

Purpose

To evaluate the efficacy and complications of black diaphragm intra‐ocular (BDI) lens implantation in patients with congenital aniridia.

Methods

Twenty patients underwent BDI lens implantation for the treatment of congenital aniridia from January 1999 to December 2012. Fifteen patients (23 eyes) were enrolled in our study, and the mean follow‐up period was 26 months. Patient demographics, clinical evaluations [visual acuity (VA), best‐corrected visual acuity (BCVA), intra‐ocular pressure measurement (IOP), corneal endothelial cell density (ECD) and ultrasound biomicroscopy (UBM)], complications and treatments were analysed for each patient.

Results

Sixteen eyes (70.1%) had a BCVA better than 20/200 after BDI lens implantation, and photophobia obviously decreased in all patients. Six eyes (26.09%) developed secondary glaucoma after BDI lens implantation, and one eye underwent glaucoma surgery. Corneal decompensation occurred in two eyes (8.70%), one of which was complicated by glaucoma. Two eyes (8.70%) developed visual axis opacity (VAO) after surgery. One patient (4.35%) had limbal stem cell failure, and another patient (4.35%) had an eccentric BDI lens. Intra‐ocular pressure measurement elevation and ECD reduction were found after BDI lens implantation.

Conclusions

Black diaphragm intra‐ocular lens implantation can effectively improve VA, decrease photophobia and resolve cosmetic issues in most congenital aniridia eyes. Glaucoma, corneal decompensation and VAO were the major long‐term complications of BDI lens implantation in patients with congenital aniridia. All patients should be managed attentively because of high risk of complications and followed long term to achieve favourable outcomes.
Pharmacokinetics and safety of single doses of tabalumab in subjects with rheumatoid arthritis or systemic lupus erythematosus
Authors: Witcher Jennifer , Fleischmann Roy , Chindalore Vishala L. , Hansen Ryan J. , Hu Leijun , Radtke David , Voelker James , Gomez Elisa , McColm Juliet
Published: December 2015

Aims

Two phase 1 studies evaluated the pharmacokinetics (PK), safety and biological activity of tabalumab, a human monoclonal antibody against B‐cell activating factor (BAFF), administered intravenously (i.v.) or subcutaneously (s.c.) in subjects with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).

Methods

In study A, subjects with RA (n = 23) or SLE (n = 6) received a single i.v. dose of tabalumab (RA 0.01, 0.04, 0.125, 0.5, 2.0, and 8.0 mg kg–1 and SLE 0.125 or 2.0 mg kg–1) or placebo. In study B, subjects with RA received a single tabalumab dose i.v. (10 mg) (n = 12) or s.c. (20 mg) (n = 12). Serum tabalumab and CD20+ B cells were evaluated and safety was assessed throughout both studies.

Results

Tabalumab PK were non‐linear across the 0.01 to 8.0 mg kg–1 dose range. Clearance (CL) decreased from 2.9 to 0.1 l day–1 and terminal half‐life (t1/2) increased from about 1.6 to 25 days. Subjects with RA or SLE had similar PK. After s.c. dosing, tabalumab time to maximal concentration (tmax) was 5.5 days. Absolute bioavailability (F) was approximately 62%. Following tabalumab dosing, CD20+ B cells transiently increased from baseline followed by a progressive decrease below baseline.

Conclusion

A single tabalumab dose administered i.v. or s.c. was well tolerated and had non‐linear CL over the dose range investigated in subjects with RA and SLE. The non‐linearity likely reflects target‐mediated CL due to binding to BAFF. Tabalumab showed biological activity based on changes in peripheral CD20+ lymphocyte numbers in both subjects with RA and SLE.
Integrative Bioethics: A Conceptually Inconsistent Project
Authors: Ivanković Viktor , Savić Lovro
Published: December 2015

This article provides a critical evaluation of the central components of Integrative Bioethics, a project aiming at a bioethical framework reconceptualization. Its proponents claim that this new system of thought has developed a better bioethical methodology than mainstream Western bioethics, a claim that we criticize here. We deal especially with the buzz words of Integrative Bioethics – pluriperspectivism, integrativity, orientational knowledge, as well as with its underlying theory of moral truth. The first part of the paper looks at what the claims of a superior methodology consist in. The second reveals pluriperspectivism and integrativity to be underdeveloped, hazy terms, but which seem to be underpinned by two theses – the incommensurability and the inclusiveness theses. These theses we critically scrutinize. We then consider strategies the project's proponents might apply to curb these theses in order to acquire minimal consistency for their framework. This part of the article also deals with the conception of moral truth that drives the theory, a position equally burdened with inconsistencies. In the last part of the article, we observe the concept of orientational knowledge, and develop two interpretations of its possible meaning. We claim that, following the first interpretation, Integrative Bioethics is completely descriptive, in which case it is informative and important, but hardly bioethics; if it is normative, following the second interpretation, it is bioethics as we already know it, but merely clad in rhetorical embellishments. We conclude that there is nothing new about this project, and that its inconsistencies are reason enough for its abandonment.
Pregnancy Outcome in Women with Decreased Sensation of Fetal Movements at Term According to Parity
Authors: Aviram Amir , Shmueli Anat , Hiersch Liran , Ashwal Eran , Wiznitzer Arnon , Yogev Yariv , Hadar Eran
Published: December 2015

Background

Decreased sensation of fetal movements (DFM) is a common maternal complaint. Thus, we aimed to evaluate the association between DFM and pregnancy outcome in singleton gestation at term according to parity.

Methods

A retrospective cohort study of singleton pregnancies at term between 2008 and 2013. Eligibility was limited to women carrying a fetus with no known structural or chromosomal anomalies, at 37+0/7 to 42+0/7 weeks of gestation. Women presenting to the delivery ward with DFM were compared with women without similar complaints.

Results

Overall, 12,564 nulliparous women and 25,292 multiparous women gave birth during the study period; of them, 300 nulliparous women (2.4%) and 525 multiparous women (2.1%) complained of DFM. For nulliparous women, after adjusting for potential confounders, DFM was associated with antepartum fetal death (aOR 4.6 [95% CI 1.1–19.8]), cesarean delivery (CD) (aOR 1.3 [95% CI 1.01–1.8]), 1‐minute Apgar score less than 7 (aOR 2.3 [95% CI 1.5–3.5]) and neonatal seizures (aOR 3.2 [95% CI 1.3–8.2]). For multiparous women, DFM was associated with unscheduled CD (aOR 2.7 [95% CI 1.6–4.6]) and CD indicated by intermediate/abnormal fetal heart rate tracing (aOR 4.8 [95% CI 2.8–8.4]).

Conclusions

DFM carries different outcomes according to parity. Although for nulliparous women, DFM is associated with increased risk of CD and immediate adverse perinatal outcome, for multiparous women it is associated with increased risk for CD, with no immediate increased risk for adverse perinatal outcome.
Dynamic sentinel lymph node biopsy for penile cancer: a comparison between 1‐ and 2‐day protocols
Authors: Dimopoulos Panagiotis , Christopoulos Panagiotis , Shilito Sam , Gall Zara , Murby Brian , Ashworth David , Taylor Ben , Carrington Bernadette , Shanks Jonathan , Clarke Noel , Ramani Vijay , Parr Nigel , Lau Maurice , Sangar Vijay
Published: December 2015

Objective

To determine the outcome of clinically negative node (cN0) patients with penile cancer undergoing dynamic sentinel node biopsy (DSNB), comparing the results of a 1‐ and 2‐day protocol that can be used as a minimal invasive procedure for staging of penile cancer.

Patients and Methods

This is a retrospective analysis of 151 cN0 patients who underwent DSNB from 2008 to 2013 for newly diagnosed penile cancer. Data were analysed per groin and separated into groups according to the protocol followed. The comparison of the two protocols involved the number of nodes excised, γ‐counts, false‐negative rates (FNR), and complication rates (Clavien–Dindo grading system).

Results

In all, 280 groins from 151 patients underwent DSNB after a negative ultrasound ± fine‐needle aspiration cytology. The 1‐day protocol was performed in 65 groins and the 2‐day protocol in 215. Statistically significantly more nodes were harvested with the 1‐day protocol (1.92/groin) compared with the 2‐day protocol (1.60/groin). The FNRs were 0%, 6.8% and 5.1%, for the 1‐day protocol, 2‐day protocol, and overall, respectively. Morbidity of the DSNB was 21.4% for all groins, and 26.2% and 20.1% for the 1‐day and 2‐day protocols, respectively. Most of the complications were of Clavien–Dindo Grade 1–2.

Conclusions

DSNB is safe for staging patients with penile cancer. There is a trend towards a 1‐day protocol having a lower FNR than a 2‐day protocol, albeit at the expense of a slightly higher complication rate.
Substituent Effects on Cytotoxic Activity, Spectroscopic Property, and DNA Binding Property of Naphthalimide Derivatives
Authors: Wang Ke‐Rang , Qian Feng , Sun Qian , Ma Cui‐Lan , Rong Rui‐Xue , Cao Zhi‐Ran , Wang Xiao‐Man , Li Xiao‐Liu
Published: December 2015

A series of novel naphthalimide derivatives NI1‐5 containing piperazine moieties (N‐(2‐hydroxyethyl)piperazine and 1‐piperazinepropanol) and piperidine moieties (4‐piperidinemethanol, 4‐hydroxypiperidine and 4‐piperidineethanol) have been synthesized and evaluated for their cytotoxic activity, spectroscopic property, and DNA binding behaviors. It was found that substituents at the 4‐position remarkably influence the various activities of this series of compound. Compounds NI3‐5 modified with piperidines exhibited potent cytotoxic activities against Hela, SGC‐7901, and A549 cells with the IC50 values from 0.73 μm to 6.80 μm, which are better than NI1‐2 functionalized with piperazines. Compounds NI1‐2 showed higher binding capacity with Ct‐DNA than compounds NI3‐5 based on studies of UV–vis, fluorescence and CD spectra. Furthermore, compounds NI3‐5, as DNA intercalators, showed fluorescence enhancement upon binding with Ct‐DNA. More interestingly, fluorescence imaging studies of compound NI4 with A549 cells showed that the fluorescence predominantly appeared in the cytoplasm. These results provided a potential application of NI3‐5 as anticancer therapeutic and cancer cell imaging agents.
Design, Synthesis, and Biological Evaluation of Pyrazole Derivatives
Authors: Hu Chunqi , Gao Yali , Du Wenting
Published: December 2015

In this in vitro study, a series of novel pyrazole derivatives were designed, synthesized, and evaluated against five human cancer cell lines (PC3, A549, HL60, HCT116, and SW620) for their antiproliferative and p53‐MDM2 binding inhibitory activities. Although biological evaluations showed that this series of compounds possessed weak p53‐MDM2 inhibitory activities, most of them displayed moderate to potent antiproliferative activities against the tested cells lines. Compound 11c exhibited the best potency for MDM2 (FP‐IC50 = 29.22 μm) and demonstrated antiproliferative activities in response to the five tested cell lines (IC50 = 4.09–16.82 μm). Compared with the positive control Nutlin‐1, there was enhanced antiproliferative activity to p53‐mutated or p53‐deficient cell lines (SW620, HL60, and PC3).
Perceptions of family‐centred services in a paediatric rehabilitation programme: strengths and complexities from multiple stakeholders
Authors: Arcuri G. G. , McMullan A. E. , Murray A. E. , Silver L. K. , Bergthorson M. , Dahan‐Oliel N. , Coutinho F.
Published: December 2015

Background

Family‐centred services (FCS) are best practice in paediatric rehabilitation and describe philosophies and approaches to medical care that emphasize the partnership and involvement of parents. While evidence supports FCS, there are complexities to its successful implementation. This mixed‐methods study aimed to measure the extent to which parents and the healthcare provider (HCP) perceive service provision as being family centred, and to describe barriers and facilitators to the delivery of FCS.

Methods

Parents of children participating in a rehabilitation programme and HCPs providing services participated in this study. Parents completed the measure of processes of care‐20 and participated in interviews, while HCPs completed the measure of processes of care–service providers and participated in a focus group.

Results

Quantitative analysis revealed that parents were mostly satisfied with features of FCS, which included communication and support between parents and HCPs, respect of diversity and parental collaboration and participation. Parents identified communication methods and psychosocial needs as areas that facilitated but sometimes detracted from FCS. Institutional barriers led to the identification of areas for improvement identified by multiple stakeholders. HCPs identified more areas for improvement than parents.

Conclusion

When considering these barriers, it is evident that implementation is a complex process, impacted by institutional barriers. FCS needs to be investigated further, and systemic interventions should be used to facilitate its implementation.
Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross-sectional study
Authors: Mensah F , Bansal A , Berkovitz S , Sharma A , Reddy V , Leandro M J , Cambridge G
Published: December 2015

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a heterogeneous condition of unknown aetiology characterized by multiple symptoms including fatigue, post-exertional malaise and cognitive impairment, lasting for at least 6 months. Recently, two clinical trials of B cell depletion therapy with rituximab (anti-CD20) reported convincing improvement in symptoms. A possible but undefined role for B cells has therefore been proposed. Studies of the relative percentages of B cell subsets in patients with ME/CFS have not revealed any reproducible differences from healthy controls (HC). In order to explore whether more subtle alterations in B cell subsets related to B cell differentiation exist in ME/CFS patients we used flow cytometry to immunophenotype CD19+ B cells. The panel utilized immunoglobulin (Ig)D, CD27 and CD38 (classical B cell subsets) together with additional markers. A total of 38 patients fulfilling Canadian, Centre for Disease Control and Fukuda ME/CFS criteria and 32 age- and sex-matched HC were included. We found no difference in percentages of classical subsets between ME/CFS patients and HC. However, we observed an increase in frequency (P < 0·01) and expression (MFI; P = 0·03) of CD24 on total B cells, confined to IgD+ subsets. Within memory subsets, a higher frequency of CD21+CD38– B cells (>20%) was associated with the presence of ME/CFS [odds ratio: 3·47 (1·15–10·46); P = 0·03] compared with HC, and there was a negative correlation with disease duration. In conclusion, we identified possible changes in B cell phenotype in patients with ME/CFS. These may reflect altered B cell function and, if confirmed in other patient cohorts, could provide a platform for studies based on clinical course or responsiveness to rituximab therapy.
Interleukin-21 induces migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis
Authors: Xing R , Jin Y , Sun L , Yang L , Li C , Li Z , Liu X , Zhao J
Published: December 2015

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial fibroblast hyperplasia and bone erosion. Fibroblast-like synoviocytes (FLS) play a pivotal role in RA pathogenesis through aggressive migration and matrix invasion, and certain proinflammatory cytokines may affect synoviocyte invasion. Whether interleukin (IL)-21 influences this process remains controversial. Here, we evaluated the potential regulatory effect of IL-21 on the migration, invasion and matrix metalloproteinase (MMP) expression in RA-FLS. We found that IL-21 promoted the migration, invasion and MMP (MMP-2, MMP-3, MMP-9, MMP-13) production in RA-FLS. Moreover, IL-21 induced activation of the phosphoinositide 3-kinase (PI3K), signal transducer and activator of transcription-3 (STAT-3) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathways, and blockage of these pathways [PI3K/protein kinase B (AKT) inhibitor LY294002, STAT-3 inhibitor STA-21 and ERK1/2 inhibitor PD98059] attenuated IL-21-induced migration and secretion of MMP-3 and MMP-9. In conclusion, our results suggest that IL-21 promotes migration and invasion of RA-FLS. Therefore, therapeutic strategies targeting IL-21 might be effective for the treatment of RA.
Interactions Between Biodiversity Offsets and Protected Area Commitments: Avoiding Perverse Outcomes
Authors: Maron Martine , Gordon Ascelin , Mackey Brendan G. , Possingham Hugh P. , Watson James E. M.
Published: December 2015

Economic growth is often in conflict with environmental goals. Biodiversity offsetting attempts to resolve this conflict by requiring industries to compensate for the biodiversity loss they cause, by generating an equivalent biodiversity gain elsewhere. Offsets for environmental impacts are increasingly being seen as a way to help meet preexisting conservation targets, such as those relating to the establishment and management of protected areas. We examine how using offsets to meet a state or organization's genuine commitments, which are not contingent on the offsets, results in no additional conservation benefit. In this case, either the offset or the preexisting commitment is invalid. For example, the use of offsets to meet commitments under the Convention on Biological Diversity requires an admission that those commitments would otherwise not be met. This interaction between international agreements around protected areas and offset policy can generate perverse incentives, which must be carefully managed to avoid poor conservation outcomes. We propose separate accounting for conservation gains generated using offsets, and that future conservation agreements and targets should explicitly separate commitments met using offset gains from those which are not reliant on equivalent losses.
Serum Iron Level Is Associated with Time to Antibiotics in Cystic Fibrosis
Authors: Gifford Alex H. , Dorman Dana B. , Moulton Lisa A. , Helm Jennifer E. , Griffin Mary M. , MacKenzie Todd A.
Published: December 2015

Background

Serum levels of hepcidin‐25, a peptide hormone that reduces blood iron content, are elevated when patients with cystic fibrosis (CF) develop pulmonary exacerbation (PEx). Because hepcidin‐25 is unavailable as a clinical laboratory test, we questioned whether a one‐time serum iron level was associated with the subsequent number of days until PEx, as defined by the need to receive systemic antibiotics (ABX) for health deterioration.

Methods

Clinical, biochemical, and microbiological parameters were simultaneously checked in 54 adults with CF. Charts were reviewed to determine when they first experienced a PEx after these parameters were assessed. Time to ABX was compared in subgroups with and without specific attributes. Multivariate linear regression was used to identify parameters that significantly explained variation in time to ABX.

Results

In univariate analyses, time to ABX was significantly shorter in subjects with Aspergillus‐positive sputum cultures and CF‐related diabetes. Multivariate linear regression models demonstrated that shorter time to ABX was associated with younger age, lower serum iron level, and Aspergillus sputum culture positivity.

Conclusions

Serum iron, age, and Aspergillus sputum culture positivity are factors associated with shorter time to subsequent PEx in CF adults.
Do performance and image enhancing drug users in regional Queensland experience difficulty accessing health services?
Authors: Dunn Matthew , Henshaw Richard , McKay Fiona H.
Published: December 2015

Introduction and Aim

To understand health service access and needs of people who use performance and image enhancing drugs (PIED) in regional Queensland.

Design and Methods

Semi‐structured interviews were conducted with 21 people (n = 19 men) who reported the use of a range of PIEDs, including anabolic‐androgenic steroids, human chorionic gonadotropin, growth hormone, clenbuterol, tamoxifen, insulin and peptides.

Results

Participants reported accessing a range of services, including needle and syringe programs and pharmacies, for sterile injecting equipment. While PIEDs users attributed some stigma to needle and syringe programs, they were seen as an important service for injecting equipment. Participants reported receiving either positive care from health‐care providers, such as general practitioners (GP), or having negative experiences due to the stigma attached with PIED use. Few participants reported disclosing their PIED use to their GP not only because of the concerns that their GP would no longer see them but also because they felt their GP was not knowledgeable about these substances.

Discussion and Conclusion

Participants in the study reported no difficulty in accessing health services based on living in a regional area, with their concern focused more upon how they were viewed and treated by service staff. [Dunn M, Henshaw R, Mckay F. H. Do performance and image enhancing drug users in regional Queensland experience difficulty accessing health services? Drug Alcohol Rev 2016;35:377–382]
Mortality risk in a cohort of Italian alcoholic individuals treated for alcohol dependence
Authors: Pavarin Raimondo Maria , Caputo Fabio , Zoli Giorgio , Domenicali Marco , Bernardi Mauro , Gambini Daniele
Published: December 2015

Introduction and Aims

The aim of this study was to investigate the mortality risk and to explore the presence of subjects more at risk of dying in a cohort of alcoholic individuals treated for alcohol dependence over a lengthy follow‐up period.

Design and Methods

A total of 2363 subjects attending 10 centres for addiction treatment for alcohol dependence were recruited.

Results

During the 17 year follow‐up period, 14.7% of the entire cohort died. Total standardised mortality rates (SMR) were higher in women (SMR = 5.94) as compared with men (SMR = 4.65). Higher SMRs were found for several diseases, for traumatic episodes (SMR = 6.65) and in younger patients (18–44 age group) (SMR = 8.16). Alcoholic women showed a higher survival rate as compared with men. In addition, a higher risk of death for men and unemployed subjects, with a progressive increase of risk in line with the increase of the age of admission to treatment, and with a progressive decrease of risk after 1 year from the beginning of the treatment, was also found.

Discussion and Conclusions

This study confirms that mortality risk in alcoholic individuals in treatment is higher in comparison with the general population. Moreover, alcoholics men, unemployed, >40 years at time of admission and during the first year of treatment are more at risk to die. Thus, much more attention to patients with these characteristics should be planned by the professional staff working in centres for addiction treatment. [ Pavarin R M, Caputo F, Zoli G, Domenicali M, Bernardi M, Gambini D. Mortality risk in a cohort of Italian alcoholic individuals treated for alcohol dependence Drug Alcohol Rev 2017;36:186–191]
RETIREMENT, PERSONALITY, AND WELL‐BEING
Authors: Kesavayuth Dusanee , Rosenman Robert E. , Zikos Vasileios
Published: December 2015

This study investigates how two sources of individual heterogeneity—personality and gender—impact the well‐being effects of retirement. Using data on older men and women from the British Household Panel Survey and its continuation, Understanding Society, we estimate the causal effect of retirement on satisfaction with overall life and domains of life in the presence of personality characteristics. As retirement is often considered to be a choice and thus may be endogenous to individual‐level characteristics, we use the eligibility ages for basic state pension in the United Kingdom as instruments for retirement. We find that retirement increases leisure satisfaction of both males and females but not necessarily life satisfaction and income satisfaction. We further show that certain personality characteristics affect the well‐being of female retirees. For males, however, personality does not seem to matter in how they cope with retirement. (JEL I31, J26, A12, C23)