bluuebunny/crossref_metadata_2025 huggingface dataset:
A Two-State Epistasis Model Reduces Missing Heritability of Complex Traits
Authors: Bubb Kerry L. , Queitsch Christine
Published: April 2015

Despite decade-long efforts, the genetic underpinnings of many complex traits and diseases remain largely elusive. It is increasingly recognized that a purely additive model, upon which most genome-wide association studies (GWAS) rely, is insufficient. Although thousands of significant trait-associated loci have been identified, purely additive models leave much of the inferred genetic variance unexplained. Several factors have been invoked to explain the ‘missing heritability’, including epistasis. Accounting for all possible epistatic interactions is computationally complex and requires very large samples. Here, we propose a simple two-state epistasis model, in which individuals show either high or low variant penetrance with respect to a certain trait. The use of this model increases the power to detect additive trait-associated loci. We show that this model is consistent with current GWAS results and improves fit with heritability observations based on twin studies. We suggest that accounting for variant penetrance will significantly increase our power to identify underlying additive loci.
Phylogenetic tree inference from local gene content
Authors: Glazko Galina , Gensheimer Michael , Mushegian Arcady
Published: April 2015

Background

Complete genome sequences provide many new characters suitable for studying phylogenetic relationships. The limitations of the single sequence-based phylogenetic reconstruction prompted the efforts to build trees based on genome-wide properties, such as the fraction of shared orthologous genes or conservation of adjoining gene pairs. Gene content-based phylogenies, however, have their own biases: most notably, differential losses and horizontal transfers of genes interfere with phylogenetic signal, each in their own way, and special measures need to be taken to eliminate these types of noise.

Results

We expand the repertoire of genome-wide traits available for phylogeny building, by developing a practical approach for measuring local gene conservation in two genomes. We counted the number of orthologous genes shared by chromosomal neighborhoods (“bins”), and built the phylogeny of 63 prokaryotic genomes on this basis. The tree correctly resolved all well-established clades, and also suggested the monophily of firmicutes, which tend to be split in other genome-based trees.

Conclusions

Our measure of local gene order conservation extracts strong phylogenetic signal. This new measure appears to be substantially resistant to the observed instances of gene loss and horizontal transfer, two evolutionary forces which can cause systematic biases in the genome-based phylogenies.
An empirical survey of the perceived benefits of implementing the Mandatory Building Inspection Scheme (MBIS) in Hong Kong
Authors: CHAN Dr Daniel W.M. , Hung Henry T.W.
Published: April 2015

Purpose

– This paper aims to review the current state of building decay in Hong Kong, and attempts to identify and analyze the perceived benefits of implementing the Mandatory Building Inspection Scheme (MBIS) via an industry-wide empirical questionnaire survey.

Design/methodology/approach

– A total of 340 professional respondents who have gained hands-on experience in either new building works or building management or building repair/maintenance were requested to complete a survey questionnaire to indicate the relative importance of those benefits identified in relation to MBIS. The perceived benefits were measured, ranked and compared according to the different roles of industrial practitioners, and between the residents in private premises and those in public estates.

Findings

– The survey findings suggested the most significant benefits derived from implementing MBIS to be: raise the overall building safety toward residents and the general public; create more job openings and business opportunities in building repair and maintenance services; and MBIS is an effective solution to address the problems with building decay (e.g. dilapidation and control over the existing unauthorized building works). The results of factor analysis indicated that the 13 perceived benefits of implementing MBIS were consolidated under three underlying factors: addressing building dilapidation and assuring building safety; improving the living environment and upgrading property values; and creating more job openings and business opportunities.

Social implications

– As MBIS was officially launched on June 30, 2012, it is expected to be one of the proposed effective measures in resolving the long-standing problems of building neglect and deterioration in Hong Kong and overseas, especially to those existing old private premises.

Originality/value

– In the long run, the number of prematurely ageing buildings would be reduced, and the service life span of existing private premises would be prolonged. This is in line with the sustainability principle of providing a better living and the working environment within the community as a whole.
Clinical studies of the treatment of facial atrophic acne scars and acne with a bipolar fractional radiofrequency system
Authors: Kaminaka Chikako , Uede Mikiko , Matsunaka Hiroshi , Furukawa Fukumi , Yamamoto Yuki
Published: April 2015

Few clinical studies have examined the utility of bipolar fractional radiofrequency (FRF) therapy as a treatment for atrophic acne scars and active acne in people with darker skin. This study was designed to compare the safety and efficacy of bipolarFRFtherapy as a treatment for atrophic acne scars and acne vulgaris. Twenty‐three Japanese patients with atrophic acne scars and mild to severe acne on both cheeks were treated with a bipolarFRFsystem (eMatrix; Syneron, Yokneam Illit, Israel). Five treatment sessions were carried out at 1‐month intervals, and the patients were followed up for 3 months after the final treatment. Assessments of scar severity and the number of acne lesions and 3‐Din vivoimaging analysis were performed. Evaluations of the treatment outcomes and their effects on the patients’ quality of life (QOL) were also carried out. We demonstrated that the improvement in scar volume was marked in the patients with mild scars and was at least moderate in 23 (57.5%) of the treated areas. With regard to the number of acne lesions, the treated areas exhibited significantly fewer lesions compared with the baseline at each time point (P < 0.05). The patients’ assessments of the treatment outcomes and theirQOLindicated that both had improved significantly by the end of the study. Furthermore, significant reductions in the patients’ sebum levels, skin roughness and scar depth were observed. BipolarFRFtreatment significantly improved the atrophic acne scars and acne of Japanese patients and had minimal side‐effects.
Melting glacier impacts community structure of Bacteria, Archaea and Fungi in a Chilean Patagonia fjord
Authors: Gutiérrez Marcelo H. , Galand Pierre E. , Moffat Carlos , Pantoja Silvio
Published: April 2015

Jorge Montt glacier, located in the Patagonian Ice Fields, has undergone an unprecedented retreat during the past century. To study the impact of the meltwater discharge on the microbial community of the downstream fjord, we targeted Bacteria, Archaea and Fungi communities during austral autumn and winter. Our results showed a singular microbial community present in cold and low salinity surface waters during autumn, when a thicker meltwater layer was observed. Meltwater bacterial sequences were related to Cyanobacteria, Proteobacteria, Actinobacteria and Bacteriodetes previously identified in freshwater and cold ecosystems, suggesting the occurrence of microorganisms adapted to live in the extreme conditions of meltwater. For Fungi, representative sequences related to terrestrial and airborne fungal taxa indicated transport of allochthonous Fungi by the meltwater discharge. In contrast, bottom fjord waters from autumn and winter showed representative Operational Taxonomic Units (OTUs) related to sequences of marine microorganisms, which is consistent with current models of fjord circulation. We conclude that meltwater can significantly modify the structure of microbial communities and support the development of a major fraction of microorganisms in surface waters of Patagonian fjords.
Is the increased risk of preterm birth following excision for cervical intraepithelial neoplasia restricted to the first birth post treatment?
Authors: Castañon A , Landy R , Brocklehurst P , Evans H , Peebles D , Singh N , Walker P , Patnick J , Sasieni P ,   the PaCT Study Group
Published: April 2015

Objective

To explore whether the increased risk of preterm birth following treatment for cervical disease is limited to the first birth following colposcopy.

Design

Nested case–control study.

Setting

Twelve NHS hospitals in England.

Population

All nonmultiple births from women selected as cases or controls from a cohort of women with both colposcopy and a hospital birth. Cases had a preterm (20–36 weeks of gestation) birth. Controls had a term birth (38–42 weeks) and no preterm.

Methods

Obstetric, colposcopy and pathology details were obtained.

Main outcome measures

Adjusted odds ratio of preterm birth in first and second or subsequent births following treatment for cervical disease.

Results

A total of 2798 births (1021 preterm) from 2001 women were included in the analysis. The risk of preterm birth increased with increasing depth of treatment among first births post treatment [trend per category increase in depth, categories <10 mm, 10–14 mm, 15–19 mm, ≥20 mm: odds ratio (OR) 1.23, 95% confidence interval (95% CI) 1.12–1.36, P < 0.001] and among second and subsequent births post treatment (trend OR 1.34, 95% CI 1.15–1.56, P < 0.001). No trend was observed among births before colposcopy (OR 0.98, 95% CI 0.83–1.16, P = 0.855). The absolute risk of a preterm birth following deep treatments (≥15 mm) was 6.5% among births before colposcopy, 18.9% among first births and 17.2% among second and subsequent births post treatment. Risk of preterm birth (once depth was accounted for) did not differ when comparing first births post colposcopy with second and subsequent births post colposcopy (adjusted OR 1.15, 95% CI 0.89–1.49).

Conclusions

The increased risk of preterm birth following treatment for cervical disease is not restricted to the first birth post colposcopy; it remains for second and subsequent births. These results suggest that once a woman has a deep treatment she remains at higher risk of a preterm birth throughout her reproductive life.

Tweetable abstract

Risk of preterm birth following large treatments for cervical disease remains for second and subsequent births.
Mandatory Disclosure, Generation of Decision‐Relevant Information, and Market Entry
Authors: Schneider Georg T. , Scholze Andreas
Published: April 2015

We investigate the interaction of mandatory disclosure and the gathering of decision‐relevant information in a setting in which a competitor may enter the market. Gathering detailed information allows for an efficient allocation of resources, but eventually attracts competition by revealing beneficial information to competitors. In contrast, refraining from generating detailed information implies inefficient decisions, but eventually prevents competitors from entering the market. Our results show that an incentive not to generate internal information arises for two reasons: If the incumbent's cost advantage is sufficiently large, disclosing aggregated information can be an instrument to avoid competition by reducing the likelihood of market entry. If the incumbent's cost advantage is small, disclosing aggregated information attracts competition by increasing the likelihood of market entry. In this case, imprecise cost information serves as a commitment device to reduce the intensity of competition by forcing the competitor to take into account his efficiency disadvantage in making his production decision.
Psychosocial correlates of alcohol use and heavy episodic drinking among Italian adolescents: Data from the second International Self‐Reported Delinquency study
Authors: Innamorati Marco , Maniglio Roberto
Published: April 2015

Background and Objectives

To provide a comprehensive picture of the wide spectrum of psychosocial factors potentially associated with alcohol consumption and problematic drinking among Italian adolescents in order to encourage debate on the context‐specificity or universality of psychosocial correlates of adolescent alcohol use and misuse across countries and cultures.

Methods

The International Self‐Report Delinquency survey questionnaire was used to assess several variables concerning sociodemographic background, family relationships and problems, school performance and climate, life events, victimization experiences, neighborhood climate, personality traits, and attitudes, delinquent behavior, drug use, and peers behavior in a city‐based sample of 6,363 seventh to ninth grade Italian students.

Results

Generalized linear regression models showed that recent alcohol consumption and heavy episodic drinking were associated with multiple factors pertaining to different levels and domains reflecting the adolescent's personality and behavior as well as the different social and cultural contexts in which adolescents spend most of their time. Poor relations with parents, parental divorce, positive attitudes toward violence, and low self‐control appeared to precede recent alcohol use and misuse and might be potential risk factors for alcohol use and/or misuse, while the association between problematic drinking and deviant attitudes (ie, violent behavior, drug use, and affiliation with deviant peers) might be explained through reciprocal influences.

Discussion and Conclusions

Some psychosocial correlates of adolescent alcohol use and misuse might be universal across countries and cultures. Additionally, certain family, school, personality, behavioral, and peer‐related factors might be more important than other correlates of youth alcohol use. (Am J Addict 2015;24:507–514)
Clinical perspectives: Practical insights from clinical experience with cabazitaxel in Australia
Authors: Parente Phillip , Gurney Howard , Ng Siobhan , Bahre Martina
Published: April 2015

Prostate cancer, and in particular the management options for patients with metastatic castration‐resistant prostate cancer (mCRPC), remains an important health issue. The approval of cabazitaxel provides a new treatment option for patients who have progressed despite docetaxel therapy. Clinical use of cabazitaxel in mCRPC is based on the results of the TROPIC study, which demonstrated an approximately 30% reduction in the risk of death compared with mitoxantrone. In this paper, we draw on accumulating clinical experience with cabazitaxel in Australia to discuss important questions such as how to select the right patient for treatment and how to proactively prevent and manage toxicities associated with this therapy. Recognizing the need for a multidisciplinary approach to patient care, opinion and insight has been sought from medical oncologists, nurses and pharmacists. While lack of trial data means that a number of questions remain unanswered, local clinical experience has helped to guide treatment decisions and refine management protocols. Appropriate patient selection, careful ongoing monitoring and proactive management of adverse events will ensure optimal treatment of patients. Nurses in particular play an important role in educating patients and identifying patients at increased risk of developing adverse events with cabazitaxel. The oncology team must work together to educate patients; taking a proactive approach to issues such as adverse events will help maximize the clinical outcome of cabazitaxel treatment and impact positively on the patient's quality of life.
Psychosocial concerns of cancer patients in Singapore
Authors: Mahendran Rathi , Lim Haikel A , Chua Joanne , Lim Siew Eng , Kua Ee Heok
Published: April 2015

Aims

Psychosocial needs are high among cancer patients, and screening for these is recognized as integral to quality cancer care. This study identified the psychosocial needs of cancer patients at their first visit at a hematology‐oncology clinic.

Methods

Fifty‐four new consecutive patients completed the Distress Thermometer and the Problem List, the Hospital Anxiety and Depression Scale, and the EuroQol Quality of Life Scale at their first visit to plan for chemotherapy. Data were analyzed with SPSS.

Results

Analyses revealed that participants had an average of 2.8 ± 2.3 problems, with 82% having psychosocial needs. Emotional concerns formed the top four psychosocial needs of the cohort (worry 46%, fears 26%, nervousness 26%, sadness 24%), with the fifth being a practical concern (insurance/finance 22%). The former were more frequent among 41‐ to 50‐year‐olds and significantly correlated with distress scores. Practical concerns were significantly correlated with depressive symptoms. Family concerns were more significant in women. The overall score on the Problem List correlated with distress, anxious symptomatology and poorer quality of life scores.

Conclusions

Distress and psychosocial needs are high in cancer patients even at an early stage prior to chemotherapy. Attention to these needs is crucial as they cause significant distress and affect the patient's quality of life.
Catecholamine pathway polymorphisms and antidepressant response
Authors: Yin Li , Zhang Xu , Huang Yi , Sun XueLi
Published: April 2015

Introduction

Genes that regulate the catecholamine metabolism pathways are potential targets for research in the antidepressant treatment response. This study was intended to determine whether antidepressant responses to selective serotonin reuptake inhibitors (SSRIs) are associated with genetic polymorphisms of the tyrosine or tryptophan gene in Chinese major depressive disorder (MDD) patients.

Methods

A total of 290 MDD patients were recruited and received a 6‐week SSRIs randomized double‐blinded treatment. Allele, genotype, and haplotype frequencies were compared between responders and nonresponders in catecholamine genes.

Results

Genotype frequency of the rs1800544 polymorphism in the DRD4 gene was significantly different between responders and nonresponders after false discovery rate correction (P = 0.042). The frequency of the DRD4 rs1800544 CG genotype was significantly higher (P = 0.003) in responders (51.4%) than in nonresponders (35.8%), and patients with the CG genotype showed an 81.7% response rate. In comparison, the response rates were 73.9% and 52.2% in patients with the GG genotype and the CC genotype, respectively. The frequencies of the DRD4 rs1800544 CC and GG genotypes were significantly lower (P = 0.003) in responders (7.7%, 40.9%) than in the nonresponders (19.4%, 44.8%). No significant difference was found between two groups either in genotype or allele frequencies of single nucleotide polymorphisms in the TPH, SLC6A2, SLC6A3, or DRD2 genes. No significant difference was found between two groups in TPH, SLC6A2, SLC6A3, DRD2, orDRD4 gene haplotypes.

Discussion

Polymorphisms of the DRD4 gene appear to be associated with SSRI treatment response in Chinese MDD patients.
A phase‐II sequential case‐series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab
Authors: Clark William F. , Rock Gail , Barth David , Arnold Donald M. , Webert Kathyrn E. , Yenson Paul R. , Kelton John G. , Li Lihua , Foley Steven R. ,   members of the Canadian Apheresis Group
Published: April 2015

The primary objective of this phase II study was to evaluate the efficacy of rituximab in the management of adult patients with physician‐diagnosed presumed thrombotic thrombocytopenic purpura (TTP); relapsed or refractory. We conducted a multicentre study in four Canadian hospital‐based apheresis units. Forty patients with presumed TTP (20 refractory and 20 relapsing) were sequentially enrolled and all received rituximab in a standardized manner. A complete response was documented in 14 of 19 refractory patients by week 8 and 15/16 were alive and in remission at 52 weeks (one patient was lost to follow‐up, one was a non‐responder, and three died). Among relapsing patients, 16/18 had a complete response at week 8 and 18/18 at week 52 (one patient lost to follow‐up and one withdrew). At 1 year, all relapsing and 85% of refractory patients survived. Of 38/40 patients who had ADMATS13 testing at study entry, 13/19 refractory and 10/19 relapsing patients had ADAMTS13 < 10% (typical TTP); whereas 6/19 refractory and 9/19 relapsing cases had ADAMTS13 > 10% (other thrombotic microangiopathy; TMA). Refractory‐typical TTP in contrast to refractory‐other TMA and all relapsing patients treated with plasma exchange and rituximab, were less likely to be responsive and more likely to die or relapse.
Impact of persistent minimal residual disease post‐consolidation therapy in children and adolescents with advanced Burkitt leukaemia: a Children's Oncology Group Pilot Study Report
Authors: Shiramizu Bruce , Goldman Stanton , Smith Lynette , Agsalda‐Garcia Melissa , Galardy Paul , Perkins Sherrie L. , Frazer J. Kimble , Sanger Warren , Anderson James R. , Gross Thomas G. , Weinstein Howard , Harrison Lauren , Barth Matthew J. , Mussolin Lara , Cairo Mitchell S.
Published: April 2015

Patient‐specific primers from 10 children/adolescents with Burkitt leukaemia (BL) ± central nervous system disease who were treated with French‐British‐American/Lymphome Malins de Burkitt 96 C1 plus rituximab were developed from diagnostic blood/bone marrow. Minimal residual disease (MRD) was assessed by real‐time polymerase chain reaction at the end of induction (EOI) and consolidation (EOC). Seventy per cent (7/10) and 71% (5/7) were MRD‐positive at EOI and EOC, respectively, with no disease recurrences. MRD after induction and consolidation did not predict relapse and subsequent therapy appeared to eliminate MRD. Thus, assessing MRD at a later time point is warranted in future trials to determine its clinical significance.
The dynamics of adult haematopoiesis in the bone and bone marrow environment
Authors: Ho Miriel S. H. , Medcalf Robert L. , Livesey Stephen A. , Traianedes Kathy
Published: April 2015

This review explores the dynamic relationship between bone and bone marrow in the genesis and regulation of adult haematopoiesis and will provide an overview of the haematopoietic hierarchical system. This will include the haematopoietic stem cell (HSC) and its niches, as well as discuss emerging evidence of the reciprocal interplay between bone and bone marrow, and support of the pleiotropic role played by bone cells in the regulation of HSC proliferation, differentiation and function. In addition, this review will present demineralized bone matrix as a unique acellular matrix platform that permits the generation of ectopic de novo bone and bone marrow and provides a means of investigating the temporal sequence of bone and bone marrow regeneration. It is anticipated that the utilization of this matrix‐based approach will help researchers in gaining deeper insights into the major events leading to adult haematopoiesis in the bone marrow. Furthermore, this model may potentially offer new avenues to manipulate the HSC niche and hence influence the functional output of the haematopoietic system.
Antitumor activity of the MEK inhibitor trametinib on intestinal polyp formation in ApcΔ716 mice involves stromal COX‐2
Authors: Fujishita Teruaki , Kajino‐Sakamoto Rie , Kojima Yasushi , Taketo Makoto Mark , Aoki Masahiro
Published: April 2015

Extracellular signal‐regulated kinase is an MAPK that is most closely associated with cell proliferation, and the MEK/ERK signaling pathway is implicated in various human cancers. Although epidermal growth factor receptor, KRAS, and BRAF are considered major targets for colon cancer treatment, the precise roles of the MEK/ERK pathway, one of their major downstream effectors, during colon cancer development remain to be determined. Using ApcΔ716 mice, a mouse model of familial adenomatous polyposis and early‐stage sporadic colon cancer formation, we show that MEK/ERK signaling is activated not only in adenoma epithelial cells, but also in tumor stromal cells including fibroblasts and vascular endothelial cells. Eight‐week treatment of ApcΔ716 mice with trametinib, a small‐molecule MEK inhibitor, significantly reduced the number of polyps in the large size class, accompanied by reduced angiogenesis and tumor cell proliferation. Trametinib treatment reduced the COX‐2 level in ApcΔ716 tumors in vivo and in primary culture of intestinal fibroblasts in vitro. Antibody array analysis revealed that trametinib and the COX‐2 inhibitor rofecoxib both reduced the level of CCL2, a chemokine known to be essential for the growth of Apc mutant polyps, in intestinal fibroblasts in vitro. Consistently, trametinib treatment reduced the Ccl2 mRNA level in ApcΔ716 tumors in vivo. These results suggest that MEK/ERK signaling plays key roles in intestinal adenoma formation in ApcΔ716 mice, at least in part, through COX‐2 induction in tumor stromal cells.
Synthesis and Evaluation of Trehalose‐Based Compounds as Novel Inhibitors of Cancer Cell Migration and Invasion
Authors: Jiang Yong‐Li , Li Shui‐Xian , Liu Yu‐Jing , Ge Lian‐Ping , Han Xiu‐Zhen , Liu Zhao‐Peng
Published: April 2015

As a continuous research for the discovery of trehalose‐based anti‐invasive agents, we developed a convenient synthetic approach for the preparation of 6,6′‐dideoxy‐6,6′‐bis(acylamino)‐α,α‐D‐trehaloses. A series of trehalose‐based amides were prepared through the trityl protection of the two primary hydroxyls of α,α‐D‐trehalose, benzoylation, the removal of the trityl protective group, mesylation, azidation, catalytic hydrogenation in the presence of hydrochloride, coupling reaction with a variety of acids, and subsequent debenzoylation and deacetylation in some cases. Compound 8b, 6,6′‐dideoxy‐6,6′‐bis(2‐hydroxybenzamide)‐α,α‐D‐trehalose, was just as potent as the natural brartemicin against the invasion of murine colon 26‐L5 cells. It exhibited no cytotoxicity on human breast adenocarcinoma MDA‐MB‐231 and murine colon 26‐L5 cells. It can significantly inhibit the migration and invasion of the MDA‐MB‐231 cells. The anti‐invasive effect of 8b was possibly related to its inhibitory activity on MMP‐9, its suppression on the expression of MMP‐9 and VEGF, and its deactivation of Akt.
Influence of blinded wound closure on the volume stability of different GBR materials: an in vitro cone‐beam computed tomographic examination
Authors: Mir‐Mari Javier , Wui Hu , Jung Ronald E. , Hämmerle Christoph H. F. , Benic Goran I.
Published: April 2015

Objective

To test whether the use of (i) particulated bone substitute + collagen membrane used for guided bone regeneration (GBR) of peri‐implant bone defects renders different results from (ii) particulated bone substitute + collagen membrane + fixation pins and from (iii) block bone substitute + collagen membrane with respect to the volume stability of the augmented region during suturing of mucosal flaps.

Material and methods

Twenty peri‐implant box‐shaped bone defects were created in 10 pig mandibles. Every bone defect was augmented once with each of the following GBR procedures: Granulate (particulated xenograft + collagen membrane), Granulate + Pins (particulated xenograft + collagen membrane + fixation pins), and Block (block xenograft + collagen membrane). Cone‐beam computed tomography scans were obtained prior and after blinded wound closure. The horizontal thickness (HT) of the augmented region (bone substitute + membrane) was assessed at the implant shoulder (HT0 mm) and at 1–5 mm apical to the implant shoulder (HT1 mm–HT5 mm). The changes of HT during flap suturing were calculated as absolute (mm) and relative values (%). Repeated‐measures ANOVA was used for statistical analysis.

Results

Wound closure induced a statistically significant change of HT0 mm and of HT1 mm in all the treatment groups (P ≤ 0.05). The change in HT0 mm measured −42.8 ± 17.9% (SD) for Granulate, −22.9 ± 21.2% (SD) for Granulate + Pins, and −20.2 ± 18.9% (SD) for Block. The reduction in HT0 mm, HT1 mm, HT2 mm, and HT3 mm for the Granulate procedure was significantly higher as compared to the Granulate + Pins and the Block procedures (P ≤ 0.05). There were no statistically significant differences in the change of HT between the Granulate + Pins and the Block procedures (P > 0.05).

Conclusion

Wound closure induced displacement of the bone substitute resulting in a partial collapse of the collagen membrane in the coronal portion of the augmented site. The stability of the bone substitute and collagen membrane was enhanced by the application of fixation pins and by the use of block bone substitute instead of particulated bone substitute.
Long‐term retrospective follow‐up of turned and moderately rough implants in the edentulous jaw
Authors: Vandeweghe Stefan , Ferreira Deon , Vermeersch Louis , Mariën Margot , De Bruyn Hugo
Published: April 2015

Aim

To compare the long‐term clinical outcome of turned vs. moderately rough implants.

Materials and methods

Patients treated with implants in the edentulous mandible and/or maxilla were invited for a clinical examination. After prosthesis removal, the pocket depth was measured and the bleeding scored. Also, a new radiograph was taken for bone loss evaluation. Patients were also requested to rate their satisfaction with the treatment.

Results

One hundred and ninety‐seven implants in 33 patients were evaluated. After a mean follow‐up of 172 months (SD42, range 120–252), the mean loss was 1.61 mm (SD1.35, range 0.00–8.25). Bone loss was higher in the maxilla compared to the mandible (P < 0.001), and at implants, that was restored on implant level (P = 0.003). Multivariate analyses demonstrated a significant effect of implant surface roughness and time of loading on bone loss. Smoking, on the other hand, did not affect the outcome. Mean pocket probing depth was 3.64 mm (SD0.96, range 1.25–7.25). A total of 4.1% of the implants demonstrated signs of peri‐implantitis. The overall patient satisfaction rate was 98.5%.

Conclusion

Implant treatment in the edentulous jaw has a predictable long‐term outcome with limited complications.
Conservation of biodiversity through taxonomy, data publication, and collaborative infrastructures
Authors: Costello Mark J. , Vanhoorne Bart , Appeltans Ward
Published: April 2015

Taxonomy is the foundation of biodiversity science because it furthers discovery of new species. Globally, there have never been so many people involved in naming species new to science. The number of new marine species described per decade has never been greater. Nevertheless, it is estimated that tens of thousands of marine species, and hundreds of thousands of terrestrial species, are yet to be discovered; many of which may already be in specimen collections. However, naming species is only a first step in documenting knowledge about their biology, biogeography, and ecology. Considering the threats to biodiversity, new knowledge of existing species and discovery of undescribed species and their subsequent study are urgently required. To accelerate this research, we recommend, and cite examples of, more and better communication: use of collaborative online databases; easier access to knowledge and specimens; production of taxonomic revisions and species identification guides; engagement of nonspecialists; and international collaboration. “Data‐sharing” should be abandoned in favor of mandated data publication by the conservation science community. Such a step requires support from peer reviewers, editors, journals, and conservation organizations. Online data publication infrastructures (e.g., Global Biodiversity Information Facility, Ocean Biogeographic Information System) illustrate gaps in biodiversity sampling and may provide common ground for long‐term international collaboration between scientists and conservation organizations.
Predictors for early diagnosis of cerebral palsy from national registry data
Authors: Granild‐Jensen Jakob Bie , Rackauskaite Gija , Flachs Esben Meulengracht , Uldall Peter
Published: April 2015

Aim

As early intervention is important in cerebral palsy (CP), an early diagnosis is desirable. The aim of this study was to establish the median diagnostic age of CP and to identify predictors of an early diagnosis in a population‐based cohort.

Method

Using the Danish National Cerebral Palsy Registry (NCPR), we identified 1291 children with CP (764 males, 527 females) born between 1995 and 2003. The date of diagnosis was defined as the day the parents were told that their child was spastic or had CP. We calculated the age of diagnosis and analysed the following predictors: type of CP, degree of motor disability, cerebral ultrasonography results, epilepsy, gestational age, and degree of cognitive impairment.

Results

We found the overall median corrected diagnostic age of CP to be 11 months. Early diagnosis was associated with the type of CP, presence of epilepsy, a high degree of motor disability, and abnormalities in the cerebral ultrasonography. The gestational age was not associated with the diagnostic age.

Interpretation

The median diagnostic age implies that half of the Danish children with CP will be able to enter an early intervention program before 1 year of age. A late diagnosis was associated with less severe symptoms, and gestational age did not influence the diagnostic age.
Adaptive seating systems in children with severe cerebral palsy across International Classification of Functioning, Disability and Health for Children and Youth version domains: a systematic review
Authors: Angsupaisal Mattana , Maathuis Carel G B , Hadders‐Algra Mijna
Published: April 2015

Aim

The aim of this study was to systematically review the effect of adaptive seating systems (AdSSs) in young people less than 19 years of age with severe cerebral palsy (CP), with particular focus on child‐related outcomes across all components of the functioning and disability domains of the International Classification of Functioning, Disability, and Health for Children and Youth version (ICF‐CY).

Method

Literature searches of studies published from 1975 to October 2014 were performed. Methodological quality and the risk of bias were analysed using Sackett's level of evidence, the American Academy for Cerebral Palsy and Developmental Medicine guidelines, and Mallen criteria for observational studies.

Results

Nine studies fulfilled the selection criteria. All studies had level IV evidence and were of moderate methodological quality. The results focused on the effects of AdSSs on postural control and on upper extremity function and on additional child‐related outcomes. The results suggested that AdSSs that include trunk and hip support devices may improve postural control outcomes, and that special‐purpose AdSSs may improve self‐care and play behaviour at home.

Interpretation

Because of a low level of evidence and the moderate methodological quality of the studies available, no robust conclusions can be drawn. Nevertheless, the data suggest that AdSSs may be able to improve activity and participation at home among children with severe CP. More studies of high methodological quality addressing the effect of AdSSs on activity and participation are urgently needed. Suggestions for future research are provided.
Prenatal ethanol increases ethanol intake throughout adolescence, alters ethanol‐mediated aversive learning, and affects μ but not δ or κ opioid receptor mRNA expression
Authors: Fabio María Carolina , Macchione Ana Fabiola , Nizhnikov Michael E. , Pautassi Ricardo Marcos
Published: April 2015

Animal models of prenatal ethanol exposure (PEE) have indicated a facilitatory effect of PEE on adolescent ethanol intake, but few studies have assessed the effects of moderate PEE throughout adolescence. The mechanisms underlying this facilitatory effect remain largely unknown. In the present study, we analysed ethanol intake in male and female Wistar rats with or without PEE (2.0 g/kg, gestational days 17–20) from postnatal days 37 to 62. The results revealed greater ethanol consumption in PEE rats than in controls, which persisted throughout adolescence. By the end of testing, ethanol ingestion in PEE rats was nearly 6.0 g/kg. PEE was associated with insensitivity to ethanol‐induced aversion. PEE and control rats were further analysed for levels of μ, δ and κ opioid receptor mRNA in the infralimbic cortex, nucleus accumbens shell, and ventral tegmental area. Similar levels of mRNA were observed across most areas and opioid receptors, but μ receptor mRNA in the ventral tegmental area was significantly increased by PEE. Unlike previous studies that assessed the effects of PEE on ethanol intake close to birth, or in only a few sessions during adolescence, the present study observed a facilitatory effect of PEE that lasted throughout adolescence. PEE was associated with insensitivity to the aversive effect of ethanol, and increased levels of μ opioid receptor transcripts. PEE is a prominent vulnerability factor that probably favors the engagement of adolescents in risky trajectories of ethanol use.
Sustained Impact of UK Fast-Test Public Education on Response to Stroke: A Population-Based Time-Series Study
Authors: Wolters Frank J. , Paul Nicola L. M. , Li Linxin , Rothwell Peter M.
Published: April 2015

Background

Urgent assessment is essential after stroke. Several countries have had public education campaigns, based on the FAST (Face-Arm-Speech-Time) test to reduce delays in seeking attention. However, the impact of these campaigns on patient behavior is uncertain.

Methods

We prospectively determined patient behavior after incident major stroke (NIHSS > 3) in a UK population based study (Oxford Vascular Study) before (2002–2008) and after (2009–2013) introduction of the FAST TV-campaign and assessed any sustained impact of campaign continuation.

Results

Among 668 consecutive patients with major stroke, medical attention was sought by a bystander in 553 (89·6%). Patients were more likely to present directly to emergency services (OR = 2·18, 95%CI:1·54–3·09, P < 0·0001) after the campaign and to arrive at hospital within 3 h (OR = 2·18, 1·55–3·06, P < 0·0001). Median [IQR] time to seeking attention fell from 53 [15–265] to 31 [7–120] minutes ( P = 0·005) and median time to hospital arrival from 185 [88–885] to 119 [78–256] minutes ( P < 0·0001). On time-series analysis improvements in hospital arrival within 3 h and use of emergency medical services were significantly associated to initiation of the campaign (aOR = 3·11, 1·53–6·29, P = 0·002; and 2·22, 1·05–4·67, P = 0·036, respectively), independent of trend, age, sex, ethnicity, educational level, social class, prior stroke and stroke severity, and have been sustained to 2013.

Conclusion

Delays to seeking and receiving medical attention after major stroke in the UK. fell strikingly in 2009, coinciding with the start of the FAST TV campaign. That medical attention was sought by a bystander in nearly 90% of cases illustrates the importance of mass-media public education rather than focused programs in high-risk groups for major stroke.
Efficacy and safety of 40 mg or 60 mg duloxetine in Japanese adults with diabetic neuropathic pain: Results from a randomized, 52‐week, open‐label study
Authors: Yasuda Hitoshi , Hotta Nigishi , Kasuga Masato , Kashiwagi Atsunori , Kawamori Ryuzo , Yamada Tadaaki , Baba Yuko , Alev Levent , Nakajo Ko
Published: April 2015

Introduction

To examine the long‐term efficacy and safety of duloxetine in the treatment of Japanese patients with diabetic neuropathic pain, we carried out a 52‐week, randomized, open‐label extension of a 12‐week, double‐blind, placebo‐controlled study.

Materials and Methods

Japanese adults with diabetic neuropathic pain who completed the double‐blind study were eligible for this long‐term study, carried out at 71 sites in Japan (March 2008 to March 2010). Participants (n = 258) were re‐randomized (1:1) to 40 mg/day or 60 mg/day duloxetine. Pain (Brief Pain Inventory severity and interference), quality of life (Patient's Global Impression of Improvement), and safety (primary outcome; adverse events, vital signs, metabolic measures) were measured.

Results

Significant (P < 0.0001) and sustained improvements (change ± standard deviation; n = 257) were observed in Brief Pain Inventory severity (average pain score −2.1 ± 1.7). Improvements were also seen in Brief Pain Inventory interference (mean of subscores −0.96 ± 1.52) and Patient's Global Impression of Improvement (−0.9 ± 1.1) scores; these scores decreased significantly (P < 0.0001) during the long‐term study. Frequently reported adverse events included somnolence (13.6%), constipation (13.2%) and nausea (10.5%). Increases were observed in plasma glucose, glycosylated hemoglobin and total cholesterol levels, and in bodyweight and heart rate; however, none of these were clinically meaningful. Overall, there were no clinically significant safety concerns.

Conclusions

This is the first publication of a long‐term study carried out in Asia with an entirely Japanese patient population to suggest that long‐term duloxetine therapy for diabetic neuropathic pain is effective and has an acceptable safety profile.
Human epithelial cells exposed to functionalized multiwalled carbon nanotubes: interactions and cell surface modifications
Authors: FANIZZA C. , CASCIARDI S. , INCORONATO F. , CAVALLO D. , URSINI C.L. , CIERVO A. , MAIELLO R. , FRESEGNA A.M. , MARCELLONI A.M. , LEGA D. , ALVINO A. , BAIGUERA S.
Published: April 2015

With the expansion of the production and applications of multiwalled carbon nanotubes (MWCNTs) in several industrial and science branches, the potential adverse effects on human health have attracted attention. Numerous studies have been conducted to evaluate how chemical functionalization may affect MWCNT effects; however, controversial data have been reported, showing either increased or reduced toxicity. In particular, the impact of carboxylation on MWCNT cytotoxicity is far from being completely understood. The aim of this work was the evaluation of the modifications induced by carboxylated‐MWCNTs (MWCNTs‐COOH) on cell surface and the study of cell–MWCNT‐COOH interactions by means of field emission scanning electron microscope (FESEM). Human pulmonary epithelial cells (A549) were incubated with MWCNTs‐COOH for different exposure times and concentrations (10 μg/mL for 1, 2, 4 h; 5, 10, 20 μg/mL for 24 h). At short incubation time, MWCNTs‐COOH were easily observed associated with plasma membrane and in contact with microvilli. After 24 h exposure, FESEM analysis revealed that MWCNTs‐COOH induced evident changes in the cellular surface in comparison to control cells: treated cells showed blebs, holes and a depletion of the microvilli density in association with structure modifications, such as widening and/or lengthening. In particular, an increase of cells showing holes and microvilli structure alterations was observed at 20 μg/mL concentration. FESEM analysis showed nanotube agglomerates, of different sizes, entering into the cell with two different mechanisms: inward bending of the membrane followed by nanotube sinking, and nanotube internalization directly through holes. The observed morphological microvilli modifications, induced by MWCNTs‐COOH, could affect epithelial functions, such as the control of surfactant production and secretion, leading to pathological conditions, such as alveolar proteinosis. More detailed studies will be, however, necessary to examine in depth the effects induced by MWCNTs‐COOH and, in particular, the timing of the MWCNT‐COOH–cell interaction.
An In Vitro Comparison of Fracture Load of Zirconia Custom Abutments with Internal Connection and Different Angulations and Thicknesses: Part II
Authors: Zandparsa Roya , Albosefi Abdalah
Published: April 2015

Purpose

The purpose of part II of this in vitro study was to compare the fracture load of two‐piece zirconia custom abutments with different thicknesses and angulations.

Materials and Methods

Forty zirconia custom abutments were divided into four groups as follows: group A1: 0.7 mm thickness and 0° angulations; group A2: 0.7 mm thickness and 15° angulations; group B1: 1 mm thickness and 0° angulations; group B2: 1 mm thickness and 15° angulations. As in part I, in all groups, implant replicas were mounted in self‐cure acrylic jigs to support the abutments. The zirconia custom abutments were engaged in the implant replicas using a manual torque wrench. All jigs were secured and mounted in a metallic vice and subjected to shear stress till failure using a universal testing machine with a 0.5 mm/min crosshead speed with the force transferred to the lingual surface of the zirconia custom abutments 2 mm below the incisal edge. The test specimens used in this study did not include a crown. The universal testing machine was controlled via a computer software system, which also completed the stress‐strain diagram and recorded the breaking fracture load. The fracture loads were recorded for comparison among the groups and subjected to statistical analysis (two‐way ANOVA and Kolmogorov‐Smirnov).

Results

The mean fracture load of zirconia custom abutments across the groups (A1 to B2) ranged from 432 ± 97 N to 746 ± 275 N. The angulated zirconia custom abutment exhibited the highest fracture load, which was statistically significant (p = 0.045). The thickness of the zirconia custom abutment also had a positive influence on the strength of the specimens (p = 0.005).

Conclusions

In this study, the 15° angulated zirconia custom abutments showed the highest fracture load of those investigated. The 1 mm thick zirconia custom abutments also exhibited significantly higher fracture load compared to 0.7 mm abutments.

Clinical Implications

The results of this in vitro study will help dental practitioners with their decision‐making process in selecting the type of custom abutment to be used clinically.