bluuebunny/crossref_metadata_2025 huggingface dataset:
Corrigendum to: 131 CHROMOSOMAL ABNORMALITIES IN IN VITRO-PRODUCED 4-DAY-OLD CATTLE EMBRYOS: INFLUENCE OF THE OOCYTE MATURATION MEDIA
Authors: Demyda Peyrás S. , Moreno Millán M.
Published: January 2015

Chromosomal abnormalities were related to embryo developmental failures in cattle, being highly increased in IVF-produced compared with multiple-ovulation embryo transfer-produced embryos. The origin of this difference remains unclear, but they were related to the suboptimal environmental culture laboratory conditions. We studied the influence of 3 different maturation media in the appearance of chromosomal abnormalities in early in vitro-produced embryos. A total of 562 oocytes classified as Class A were collected by follicular aspiration in slaughterhouse ovaries and matured by 20 h in 3 different culture media supplemented with 10% FCS and antibiotics as follows: TCM-199 (T, 193 oocytes); DME (D, 178 oocytes); and RPMI-1640 (R, 191 oocytes). Matured oocytes were fertilized by 16 h with 1 × 106 spz mL–1 in IVF-TALP media and cultured by 72 h in SOF media. Later, 48 h after fertilization, 562 presumptive embryos were evaluated showing a normal cleavage rate of 64.7, 55.2, and 54.9% in T, D, and R groups, respectively. After culture, only 181 early embryos (90 hpi) showing normal development were correctly karyotyped following our standard laboratory techniques. Individual blastomeres were stained with Giemsa and assessed by direct observation at ×1250 magnification in a brightfield microscope. The percentage of normal diploid embryos (D) and abnormal haploid (H), polyploid (P), or aneuploid (A) embryos were determined. Only embryos showing almost 2 different blastomeres correctly karyotyped were included in this study. Cleavage rates were statistically higher (P < 0.05) in the oocytes matured in T media in comparison with the oocytes matured in D or R media. The percentage of diploid embryos were almost equals in the 3 groups evaluated (Table 1). There was some variation when each kind of chromosomal abnormality was assessed individually, but no statistical differences were observed. These results are in consonance with our previous studies in which we demonstrated the maturation time and morphological quality are the 2 main oocyte-derived factors influencing the ploidy of early embryos. It was also demonstrated that chromosomal complements were affected, in a much lesser extent, by the maturation media supplementation. However, in the present study, the maturation media did not statistically affected embryo ploidy. However, the higher percentage of cleaved embryos using TCM-199 observed agree with fact that this maturation media is one of the most widely used in IVF procedures in cattle. Based on our data, we suggest that oocyte maturation, a well established technique in cattle, could be performed using different maturation media without expecting major differences in the embryo ploidy, and therefore, the differences observed in cleavage rate must be originated in other physiological factors.
Table 1.Results
Assessing interactions between dolphins and small pelagic fish on branchline to design a depredation mitigation device in pelagic longline fisheries
Authors: Rabearisoa Njaratiana , Bach Pascal , Marsac Francis
Published: January 2015

Depredation by false killer whales (Pseudorca crassidens) and short-finned pilot whales (Globicephala macrorhynchus) in pelagic longlining is an issue leading to negative impacts on the economics of the fishery and on odontocetes themselves. We investigated the efficacy of a new depredation mitigation device called “DEPRED” in the interaction between bottlenose dolphins (Tursiops aduncus), spinner dolphins (Stenella longirostris), and small pelagic fish (SPF) attached to branchlines to simulate caught fish. We suggest implications for DEPRED efficacy with larger toothed whales interacting with pelagic longline capture in the open ocean. The design of the device uses streamers to both deter cetaceans and protect fish from predation. In controlled experiments, we tested its efficacy by observing changes in the dolphin's behaviour brought on by the presence or absence of the device on branchlines. First, dolphin–SPF interactions were observed at the small scale using video footage recorded with an underwater camcorder. Second, the efficacy of the device was quantified from interactions between dolphins and 80 branchlines deployed on a longline 500 m long baited with SPF. One half of the SPF on successive branchlines was protected by DEPRED and the other half was not. A total of 707 branchlines were set when dolphins interacted with SPF, and among them, 355 were equipped with DEPRED. Encouraging results were obtained: over the short term, the number of damaged unprotected SPF was on average more than twice the number of protected ones. Nevertheless, habituation behaviour was observed for a resident group of T. aduncus in the experimental area. The relation between the deterrent effect of the device and constraints related to the design of such a device to be used at a commercial operational level are discussed.
An evaluation of the association between an antimicrobial stewardship score and antimicrobial usage
Authors: Pakyz Amy L. , Moczygemba Leticia R. , Wang Hui , Stevens Michael P. , Edmond Michael B.
Published: January 2015

Objectives

To determine whether an antimicrobial stewardship ‘intensity’ score predicts hospital antimicrobial usage.

Methods

An antimicrobial stewardship score for 44 academic medical centres was developed that comprised two main categories: resources (antimicrobial stewardship programme personnel and automated surveillance software) and strategies (preauthorization, audit with intervention and feedback, education, guidelines and clinical pathways, parenteral to oral therapy programmes, de-escalation of therapy, antimicrobial order forms and dose optimization). Multiple regression analyses were used to assess whether the composite score and also the categories were associated with either total or antimicrobial stewardship programme-target antimicrobial use as measured in days of therapy.

Results

The mean antimicrobial stewardship programme score was 55 (SD 21); the total composite score was not significantly associated with total or target antimicrobial use [estimate –0.49 (95% CI –2.30 to 0.89)], while the category strategies was significantly and negatively associated with target antimicrobial use [–5.91 (95% CI –9.51 to –2.31)].

Conclusions

The strategy component of a score developed to measure the intensity of antimicrobial stewardship was associated with the amount of antimicrobials used. Thus, the number and types of strategies employed by antimicrobial stewardship programmes may be of particular importance in programme effectiveness.
Detection of Francisella tularensis in Alaskan Mosquitoes (Diptera: Culicidae) and Assessment of a Laboratory Model for Transmission
Authors: Triebenbach Alison N. , Vogl Sigrid J. , Lotspeich-Cole Leda , Sikes Derek S. , Happ George M. , Hueffer Karsten
Published: January 2015

Tularemia is a zoonotic disease caused by the Category A bioterrorism agent Francisella tularensis. In Scandinavia, tularemia transmission by mosquitoes has been widely cited in the literature. We tested >2,500 mosquitoes captured in Alaska and found Francisella DNA in 30% of pooled samples. To examine the potential for transmission of Francisella by mosquitoes, we developed a mosquito model of Francisella infection. Larvae of Anopheles gambiae Giles and Aedes aegypti (L.) readily ingest F. tularensis but do not efficiently transfer infective doses of the bacterium to the pupal or adult stage. After a bloodmeal containing Francisella, adult female An. gambiae and Ae. aegypti retained detectable levels of Francisella DNA for 3 d, but when they took a second bloodmeal, the mammalian host was not infected. This study suggests that although Francisella DNA can be detected in a significant portion of wild-caught mosquitoes, transmission of Francisella is either very inefficient or is species dependent for the Francisella strain or the arthropod vector.
Evaluation of BG-Sentinel Trap Trapping Efficacy for Aedes aegypti (Diptera: Culicidae) in a Visually Competitive Environment
Authors: Ball Tamara S. , Ritchie Scott R.
Published: January 2015

The BG-Sentinel (BGS) trap uses visual and olfactory cues as well as convection currents to attract Aedes aegypti (L.). The impact of the visual environment on trapping efficacy of the BGS trap for Ae. aegypti was investigated. Four- to 5-d nulliparous female and male Ae. aegypti were released into a semicontrolled room to evaluate the effect of the presence, reflectance, and distribution of surrounding harborage sites on BGS trapping efficacy. Low-reflective (dark) harborage sites near the BGS had a negative effect on both male and nulliparous female recapture rates; however, a more pronounced effect was observed in males. The distribution (clustered versus scattered) of dark harborage sites did not significantly affect recapture rates in either sex. In a subsequent experiment, the impact of oviposition sites on the recapture rate of gravid females was investigated. Although gravid females went to the oviposition sites and deposited eggs, the efficacy of the BGS in recapturing gravid females was not compromised. Ae. aegypti sampling in the field will mostly occur in the urban environment, whereby the BGS will be among oviposition sites and dark harborage areas in the form of household items and outdoor clutter. In addition to understanding sampling biases of the BGS, estimations of the adult population size and structure can be further adjusted based on an understanding of the impact of dark harborage sites on trap captures. Outcomes from this suite of experiments provide us with important considerations for trap deployment and interpretation of Ae. aegypti samples from the BGS trap.
Trial of a Minimal-Risk Botanical Compound to Control the Vector Tick of Lyme Disease
Authors: Rand Peter W. , Lacombe Eleanor H. , Elias Susan P. , Lubelczyk Charles B. , Amand Theodore St. , Smith Robert P.
Published: January 2015

We compared the application of IC2, a minimal-risk (25B) botanical compound containing 10% rosemary oil, with bifenthrin, a commonly used synthetic compound, and with water for the control of Ixodes scapularis Say (=Ixodes dammini Spielman, Clifford, Piesman & Corwin), on tick-infested grids in Maine, in an area where Lyme disease is established and other tick-borne diseases are emerging. High-pressure sprays of IC2, bifenthrin, and water were applied during the peak nymphal (July) and adult (October) seasons of the vector tick. No ticks could be dragged on the IC2 grids within 2 wk of the July spray, and few adult ticks were found in October or the following April. Similarly, no adult ticks could be dragged 1.5 wk after the October IC2 spray, and few the following April. No ticks were found on the bifenthrin grids after either spray through the following April, whereas substantial numbers of ticks remained throughout on the grids sprayed with water. Thus, IC2 appears to be an effective, minimum-risk acaricide to control the vector tick of Lyme disease.
Genome-wide analyses of LINE–LINE-mediated nonallelic homologous recombination
Authors: Startek Michał , Szafranski Przemyslaw , Gambin Tomasz , Campbell Ian M. , Hixson Patricia , Shaw Chad A. , Stankiewicz Paweł , Gambin Anna
Published: January 2015

Nonallelic homologous recombination (NAHR), occurring between low-copy repeats (LCRs) >10 kb in size and sharing >97% DNA sequence identity, is responsible for the majority of recurrent genomic rearrangements in the human genome. Recent studies have shown that transposable elements (TEs) can also mediate recurrent deletions and translocations, indicating the features of substrates that mediate NAHR may be significantly less stringent than previously believed. Using >4 kb length and >95% sequence identity criteria, we analyzed of the genome-wide distribution of long interspersed element (LINE) retrotransposon and their potential to mediate NAHR. We identified 17 005 directly oriented LINE pairs located <10 Mbp from each other as potential NAHR substrates, placing 82.8% of the human genome at risk of LINE–LINE-mediated instability. Cross-referencing these regions with CNVs in the Baylor College of Medicine clinical chromosomal microarray database of 36 285 patients, we identified 516 CNVs potentially mediated by LINEs. Using long-range PCR of five different genomic regions in a total of 44 patients, we confirmed that the CNV breakpoints in each patient map within the LINE elements. To additionally assess the scale of LINE–LINE/NAHR phenomenon in the human genome, we tested DNA samples from six healthy individuals on a custom aCGH microarray targeting LINE elements predicted to mediate CNVs and identified 25 LINE–LINE rearrangements. Our data indicate that LINE–LINE-mediated NAHR is widespread and under-recognized, and is an important mechanism of structural rearrangement contributing to human genomic variability.
Exposures of Lateral and Inferior Cardiac Surface for Coronary Anastomosis during Minimally Invasive Coronary Artery Bypass Grafting
Authors: Pande Shantanu , Gupta Devendra , Siddartha CR , Bansal Anubhav , Agarwal Surendra K.
Published: January 2015

Exposure of the lateral and inferior surface of the heart during off-pump coronary artery bypass grafting is associated with some degree of cardiac instability during recovery with completion of grafting. Exposure of lateral and posterior surfaces by currently available equipment is difficult in minimally invasive coronary artery bypass grafting (MICABG) owing to limited exposure. We describe an effective variation of often-used technique of pericardial stitch in exposure of cardiac surfaces during MICABG. This technique was used in 24 patients undergoing multivessel MICABG. Deep pericardial sutures were used to manipulate the exposure of cardiac surfaces. Left anterior descending artery was grafted in all 24 cases. Obtuse marginal artery was grafted in 20 cases and posterior descending artery in 12 cases. Average grafts were 2.3 per patient. There was no conversion to median sternotomy. Use of deep pericardial suture is simple technique for exposure of lateral and inferior surface during multivessel MICABG. This offers adequate exposure and operating space for easy maneuverability.
A Video-Assisted Thoracoscopic Approach to Transaxillary First Rib Resection
Authors: Soukiasian Harmik J. , Shouhed Daniel , Serna-Gallgos Derek , McKenna Robert , Bairamian Vahak J. , McKenna Robert J.
Published: January 2015

Objective

Thoracic outlet syndrome (TOS) can be associated with neurologic, arterial, or venous deficiencies. When nonsurgical treatment has failed to adequately palliate TOS, surgical intervention is indicated. The supraclavicular and transaxillary approaches are currently the most commonly used approaches for first rib resection, yet little has been reported to date on outcomes of minimally invasive procedures, such as video-assisted thoracoscopic surgery (VATS). The purpose of this article was to describe a minimally invasive approach to TOS and the associated outcomes.

Methods

This study is a retrospective analysis of a prospectively maintained database. Patients who failed nonsurgical therapy for TOS were referred to our practice for evaluation of surgery with a VATS minimally invasive first rib resection. Between 2001 and 2010, 66 VATS procedures were performed on 58 patients (41 women, 17 men). Patients were followed postoperatively for a mean time of 13.5 months.

Results

Forty-one patients were women (70.7%), and the mean age was 40.5 years, with a patient age range of 17 to 59 years. The mean length of hospital stay was 2.47 days; median length of stay was 2 days. There were a total of eight complications (12.1%). There were no mortalities.

Conclusions

Video-assisted thoracoscopic surgery first rib resection for TOS is another feasible option for TOS, which can be added to the armamentarium of the thoracic surgeon. The outcomes associated with our technique are comparable with the outcomes related to other current standards of care.
The experiences of students studying higher education on a part time basis in English further education colleges
Authors: King Madeleine , Saraswat Arti , Widdowson John
Published: January 2015

Purpose

– The purpose of this paper is to report research carried out by the Mixed Economy Group of colleges into the student experience of part time (PT) higher education (HE) delivered in English further education (FE) colleges.

Design/methodology/approach

– An online survey was completed by 352 PT students. Their responses, including free comments, formed the basis of the report. The authors provide a context for the work by referring to research carried out by other national agencies.

Findings

– The research illustrates the strengths of college-based HE, which largely derives from delivery by staff who are qualified teachers and, often, professionally active in their field of expertise. Whilst valuing this, students also seek recognition of the demands of work and family on their study time, as well as an identity as HE students within the greater FE environment.

Social implications

– PT HE can drive regional economic growth. By addressing the issues raised by students in the research, local colleges, partner universities, employers and national government can re-build local skill bases. Promoting PT HE develops a vocational ladder to HE, thus widening participation.

Originality/value

– Relatively little publically available research exists into the experiences of students pursuing PT HE in colleges. This primary research begins an evidence-based debate about how colleges can improve their offer but also reminds Government of the need to give equal weight to the needs of PT students in future changes to the delivery of HE.
Do Finnish young people support the Nordic welfare state?
Authors: Rantanen Teemu , McLaughlin Thomas Chalmers , Toikko Timo
Published: January 2015

Purpose

– The purpose of this paper is to examine young people’s attitudes toward social welfare and their perceptions of who is responsible for providing social welfare benefits.

Design/methodology/approach

– Social welfare attitudes were examined related to three themes: government responsibility, trust in society, and individual responsibility. A sample of 725 students from 12 high and vocational schools in south Finland was used for analysis.

Findings

– The data suggest that young people have a high regard for the importance of the government’s role as a social support and a mechanism of social welfare for all citizens. In addition, the results show that women highlight government responsibility more than men, and that men highlight the individual’s own responsibility for social issues. According to the results, there is a weak relationship between cultural values and social welfare attitudes. Collective values relate positively to an emphasis on trust in government and government responsibility for social problems, and relate negatively to an emphasis on individuals’ personal responsibility.

Originality/value

– The study shows that the main principles of the welfare state are still accepted by the Finnish youth, although recent speculations about the future of welfare states.
The role of external customer mind-set among service employees
Authors: Iyer Rajesh , Johlke Mark C
Published: January 2015

Purpose

– The purpose of this study is to develop and test a model of the antecedents and outcomes of one aspect of customer mind-set (CMS) – external CMS (ECMS) — among front-line employees. The goal of this paper is to help managers address customer-level orientation by further investigating the external dimension of CMS (referred to as ECMS).

Design/methodology/approach

– Data were gathered from a sample of front-line employees of a variety of firms located in a mid-sized southeastern US city.

Findings

– The results indicate that greater amounts of job autonomy and job satisfaction are positively associated with front-line employee ECMS, while the employee’s global role ambiguity, customer-specific ambiguity and role conflict are negatively associated with ECMS. In turn, front-line employee ECMS is associated with increased work motivation and sales performance.

Research limitations/implications

– The data are cross-sectional in nature; so, strictly causal relations cannot be inferred from these results. Also, the sample primarily consists of younger females with less work experience and who are employed at smaller organizations. Therefore, future research should further test these relations in different samples to increase the robustness of the results.

Practical implications

– This research utilizes a rich description of the front-line employee’s job attitudes and work characteristics to build a model describing their association with the extent to which the ideas of market orientation have taken hold at the operational level and their relationship with the employee’s motivation and subsequent performance. It shows that both internal and external characteristics are associated with front-line employee ECMS, which itself is very strongly related to desirable job outcomes.

Originality/value

– The firm’s financial performance is most directly affected by how well it serves its external customers. However, there has been no research on the role and the consequences of employee ECMS. There are only a few studies (less than five) that have empirically explored the CMS. Therefore, the many potential benefits from a deeper understanding of a market orientation culture and behaviors at the level of the front-line employee remain unclear, particularly in regards to its ECMS dimension.
Accounting conservatism, capital structure, and global diversification
Authors: Salama Feras M , Putnam Karl
Published: January 2015

Purpose

– The purpose of this paper is to investigate the effect of accounting conservatism (as a proxy for financial reporting quality) on the degree of financial leverage. In addition, this paper examines the impact of global diversification (as a proxy for operational complexity) on the relationship between conservatism and financial leverage.

Design/methodology/approach

– A panel data regression analysis is conducted for the period 2000-2006. The authors utilized a two-way fixed-effects model to control for unobservable firm characteristics and time effects that may influence the firm’s decision to report conservatively.

Findings

– This paper provides empirical evidence that conservatism is positively associated with the degree of financial leverage, and the influence of conservatism on financial leverage is enhanced by the degree of global diversification.

Originality/value

– A major issue in corporate finance is the identification of variables that influence corporate capital structure choices. The evidence presented in this paper reveals that more conservative financial reporting is associated with a higher degree of financial leverage in the firm’s capital structure. This effect increases with the extent of global diversification, indicating that bondholders place a higher value on conservatism when there is more information asymmetry between stakeholders and managers caused by global diversification.
The detection of Propionibacterium acnes signatures in granulomas of lupus miliaris disseminatus faciei
Authors: Nishimoto Junko , Amano Masahiro , Setoyama Mitsuru
Published: January 2015

Lupus miliaris disseminatus faciei (LMDF) is a papular eruption that occurs on adults' faces, predominantly on the lower eyelids. Histologically, the granulomatous lesions are primarily situated around the hair follicles, particularly the superficial region/infundibula. Its etiology remains to be elucidated. Recently, Propionibacterium acnes (P. acnes) has been suspected as a cause of sarcoidosis. In light of the sarcoid‐like reactions that are present in LMDF, we hypothesized that P. acnes may also be implicated in granulomas associated with the disease. We evaluated nine DNA samples from granulomatous lesions from the skin of patients with LMDF. We used laser capture microdissection to extract DNA from these regions. Polymerase chain reaction was performed to amplify segments of the 16S ribosomal RNA of P. acnes, and the P. acnes gene was clearly detectable in all nine DNA samples. The gene was also detected in samples from normal‐appearing skin, but these bands were faint in all samples. The results of the present study suggest that P. acnes plays a pathogenetic roles in LMDF.
Case series of patients with chronic foot ulcers treated with autologous platelet‐rich plasma
Authors: Yotsu Rie R. , Hagiwara Shotaro , Okochi Hitoshi , Tamaki Takeshi
Published: January 2015

Treatment for patients with chronic wounds is entering a new era, and autologous platelet‐rich plasma (PRP) is among the most promising treatments. PRP contains a concentration of platelets obtained by centrifuging the patient's blood. Because it contains fibrin and high concentrations of growth factors, PRP is known to promote wound healing. In this study, we present five patients with chronic foot ulcers successfully treated with PRP in our institution. The patients had various underlying diseases: diabetes (n = 2), peripheral arterial disease (n = 1), both diabetes and peripheral arterial disease (n = 1), and cutaneous polyarteritis nodosa (n = 1). Also, we provide a description of PRP's mechanisms, advantages, and limitations.
Diabetic macular ischaemia is associated with narrower retinal arterioles in patients with type 2 diabetes
Authors: Liew Gerald , Sim Dawn A. , Keane Pearse A. , Tan Ava G. , Mitchell Paul , Wang Jie Jin , Wong Tien Y. , Fruttiger Marcus , Tufail Adnan , Egan Catherine A.
Published: January 2015

Purpose

Diabetic macular ischaemia (DMI) is an important cause of visual loss in patients with diabetes, but its relationship to the larger retinal vessels is unknown. We examined whether retinal vessel calibre is related to DMI.

Methods

Clinic‐based case–control study of patients with type 2 diabetes. The presence and severity of DMI was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) protocols from fundus fluorescein angiographic (FFA) images. Custom software was used to quantify the greatest linear dimension and area of the foveal avascular zone (FAZ). Retinal vessel calibre was measured using a semi‐automated software on fundus fluorescein images.

Results

Of 53 patients examined, 18 (34%), 18 (34%) and 17 (32%) had no/mild, moderate and severe DMI, respectively. Persons with moderate or severe DMI had narrower mean retinal arteriolar calibre than persons with no/mild DMI (140.6 μm 95% confidence interval (CI) 134.7, 146.4 versus 150.7 μm, 95% CI 142.5, 158, p = 0.04). The association remained after multivariate adjustment for age, gender, previous panretinal photocoagulation, neovascularization at the disc and elsewhere and diabetic retinopathy severity. Increased FAZ size was also associated with narrower arteriolar calibre. Retinal venular calibre and arteriole to venule ratio (AVR) were not associated with DMI.

Conclusions

Retinal arteriolar narrowing was associated with moderate‐to‐severe macular ischaemia in eyes with diabetic retinopathy. This suggests that larger vessels other than capillaries may also be associated with DMI.
Therapeutic antibodies against CGRP or its receptor
Authors: Bigal Marcelo E. , Walter Sarah , Rapoport Alan M.
Published: January 2015

CGRP is an extensively studied neuropeptide that has been implicated in the pathophysiology of migraine. While a number of small molecule antagonists against the CGRP receptor have demonstrated that targeting this pathway is a valid and effective way of treating migraine, off‐target hepatoxicity and formulation issues have hampered the development for regulatory approval of any therapeutic in this class. The development of monoclonal antibodies to CGRP or its receptor as therapeutic agents has allowed this pathway to be re‐investigated. Herein we review why CGRP is an ideal target for the prevention of migraine and describe four monoclonal antibodies against either CGRP or its receptor that are in clinical development for the treatment of both episodic and chronic migraine. We describe what has been publically disclosed about their clinical trials and future clinical development plans.
A Gelatinases‐targeting scFv‐based Fusion Protein Shows Enhanced Antitumour Activity with Endostar against Hepatoma
Authors: Gao Ruijuan , Li Liang , Shang Boyang , Zhao Chunyan , Sheng Weijin , Li Diandong
Published: January 2015

Gelatinases play important roles in tumour invasion and metastasis and are thus considered promising targets for cancer therapy. In this study, a new single‐chain variable fragment (scFv)‐based fusion protein Fv‐LDP, composed of the anti‐gelatinases scFv and lidamycin apoprotein (LDP), was prepared, and its combination with angiogenesis inhibitor Endostar was then investigated. The fusion protein Fv‐LDP specifically bound to various tumour cells, and its binding capability to human pulmonary giant cell carcinoma (PG) cells was higher than that of LDP. Fv‐LDP inhibited the expression and secretion of gelatinases and could be internalized into tumour cells via endocytosis. Fv‐LDP also suppressed the growth of human hepatoma cells and murine hepatoma 22 transplanted in Kunming mice in various degrees. In addition, Endostar could enhance the synergistic or additive inhibition of Fv‐LDP on the growth, migration or invasion of human hepatoma cells shown by a colony formation assay and a transwell‐based migration or invasion assay, respectively. In vivo, Fv‐LDP/Endostar combination showed a significantly synergistic effect on the growth of a human hepatoma xenograft, with an inhibition rate of 80.8% compared with the Fv‐LDP (44.1%) or Endostar (8.9%)‐treated group. The above‐mentioned results indicate that the fusion protein Fv‐LDP is effective against transplantable hepatoma in mice and human hepatoma xenografts in athymic mice. Moreover, Endostar can potentiate the inhibition effect of Fv‐LDP on the growth of human hepatoma cells and xenografts. These data will provide a new combined strategy for improving the therapeutic efficacy of treatments for hepatoma or other gelatinase‐overexpressing tumours.
Spread of tumor microenvironment contributes to colonic obstruction through subperitoneal fibroblast activation in colon cancer
Authors: Yokota Mitsuru , Kojima Motohiro , Higuchi Youichi , Nishizawa Yuji , Kobayashi Akihiro , Ito Masaaki , Saito Norio , Ochiai Atsushi
Published: January 2015

We evaluated the influence of the cancer microenvironment formed by peritoneal invasion (CMPI) on clinical findings in colon cancer patients. In addition to the association with poor prognosis, we discovered a relationship with bowel obstruction. Detailed analysis revealed that clinical findings related to bowel obstruction occurred more frequently in patients with an elevated type tumor, which had peritoneal elastic laminal elevation to the tumor surface, compared to those with non‐elevated type tumors among those with elastic laminal invasion (ELI). Lateral tumor spread and increase of tumor annularity rate in ELI‐positive elevated type cases suggested the morphological progression from ELI‐positive non‐elevated type to elevated type. In addition, α‐smooth muscle actin expression was the highest in ELI‐positive elevated type, and prominent expressions were found not only in the deep tumor area but also in the shallow tumor area. Furthermore, contraction assays revealed the robust contractile ability of subperitoneal fibroblasts stimulated by cancer cell‐conditioned medium. Our findings suggest that CMPI spread into the luminal side of the colonic wall along with tumor progression, which caused bowel obstruction through the activation of subperitoneal fibroblasts. However, although the clinical outcome was not different between the two types, the clinical findings were affected by the spread of CMPI. We are the first to explore how the alteration of the tumor‐promoting microenvironment, along with tumor progression, contributes to the development of clinical findings.
Design and Biological Evaluation of Furan/Pyrrole/Thiophene‐2‐carboxamide Derivatives as EfficientDNAGyraseB Inhibitors ofStaphylococcus aureus
Authors: Janupally Renuka , Medepi Bhramam , Brindha Devi Parthiban , Suryadevara Priyanka , Jeankumar Variam Ullas , Kulkarni Pushkar , Yogeeswari Perumal , Sriram Dharmarajan
Published: January 2015

DNAtopoisomerases are well‐validated targets in micro‐organisms.DNAgyraseB is one of the most important enzymes among them as per their clinical importance. In earlier study, a novel lead 4‐((4‐(furan‐2‐carboxamido)phenyl)amino)‐4‐oxobutanoic acid was identified as inhibitor againstDNAgyraseB with anIC50of 12.88 ± 1.39 μm. Subsequently, analogues of this lead were developed and evaluated throughin vitroassays andin vivostudies. Among the 24 analogues, compound22was found to be the top hit with an improvedDNAgyraseB activity of 5.35 ± 0.61 μm, and the binding affinity of this compound was further ascertained biophysically through differential scanning fluorimetry. The most potent ligand did not show any signs of cardiotoxicity in zebra fish ether‐ago‐go‐related gene, ascertaining the safety profile of this series a breakthrough among the previously reported cardiotoxic gyraseB inhibitors.
ST13 polymorphisms and their effect on exacerbations in steroid‐treated asthmatic children and young adults
Authors: Vijverberg S. J. H. , Koster E. S. , Tavendale R. , Leusink M. , Koenderman L. , Raaijmakers J. A. M. , Postma D. S. , Koppelman G. H. , Turner S. W. , Mukhopadhyay S. , Tse S. M. , Tantisira K. G. , Hawcutt D. B. , Francis B. , Pirmohamed M. , Pino‐Yanes M. , Eng C. , Burchard E. G. , Palmer C. N. A. , Maitland‐van der Zee A. H.
Published: January 2015

Background

The clinical response to inhaled corticosteroids (ICS) is associated with single nucleotide polymorphisms (SNPs) in various genes. This study aimed to relate variations in genes in the steroid pathway and asthma susceptibility genes to exacerbations in children and young adults treated with ICS.

Methods

We performed a meta‐analysis of three cohort studies: Pharmacogenetics of Asthma Medication in Children: Medication with Anti‐Inflammatory effects (n = 357, age: 4–12 years, the Netherlands), BREATHE (n = 820, age: 3–22 years, UK) and Paediatric Asthma Gene Environment Study (n = 391, age: 2–16 years, UK). Seventeen genes were selected based on a role in the glucocorticoid signalling pathway or a reported association with asthma. Two outcome parameters were used to reflect exacerbations: hospital visits and oral corticosteroid (OCS) use in the previous year. The most significant associations were tested in three independent validation cohorts; the Childhood Asthma Management Programme (clinical trial, n = 172, age: 5–12 years, USA), the Genes‐ environment and Mixture in Latino Americans II‐ study (n = 745, age: 8–21, USA) and the Pharmacogenetics of adrenal suppression cohort (n = 391, age: 5–18, UK) to test the robustness of the findings. Finally, all results were meta‐analysed.

Results

Two SNPs in ST13 (rs138335 and rs138337), but not in the other genes, were associated at a nominal level with an increased risk of exacerbations in asthmatics using ICS in the three cohorts studied. In a meta‐analysis of all six studies, ST13 rs138335 remained associated with an increased risk of asthma‐related hospital visits and OCS use in the previous year; OR = 1.22 (P = 0.013) and OR = 1.22 (P = 0.0017), respectively.

Conclusion and clinical relevance

A novel susceptibility gene, ST13, coding for a cochaperone of the glucocorticoid receptor, is associated with exacerbations in asthmatic children and young adults despite their ICS use. Genetic variation in the glucocorticoid signalling pathway may contribute to the interindividual variability in clinical response to ICS treatment in children and young adults.
X‐chromosomal inactivation directly influences the phenotypic manifestation of X‐linked protoporphyria
Authors: Brancaleoni V. , Balwani M. , Granata F. , Graziadei G. , Missineo P. , Fiorentino V. , Fustinoni S. , Cappellini M.D. , Naik H. , Desnick R.J. , Di Pierro E.
Published: January 2015

X‐linked protoporphyria (XLP), a rare erythropoietic porphyria, results from terminal exon gain‐of‐function mutations in the ALAS2 gene causing increased ALAS2 activity and markedly increased erythrocyte protoporphyrin levels. Patients present with severe cutaneous photosensitivity and may develop liver dysfunction. XLP was originally reported as X‐linked dominant with 100% penetrance in males and females. We characterized 11 heterozygous females from six unrelated XLP families and show markedly varying phenotypic and biochemical heterogeneity, reflecting the degree of X‐chromsomal inactivation of the mutant gene. ALAS2 sequencing identified the specific mutation and confirmed heterozygosity among the females. Clinical history, plasma and erythrocyte protoporphyrin levels were determined. Methylation assays of the androgen receptor and zinc‐finger MYM type 3 short tandem repeat polymorphisms estimated each heterozygotes X‐chromosomal inactivation pattern. Heterozygotes with equal or increased skewing, favoring expression of the wild‐type allele had no clinical symptoms and only slightly increased erythrocyte protoporphyrin concentrations and/or frequency of protoporphyrin‐containing peripheral blood fluorocytes. When the wild‐type allele was preferentially inactivated, heterozygous females manifested the disease phenotype and had both higher erythrocyte protoporphyrin levels and circulating fluorocytes. These findings confirm that the previous dominant classification of XLP is inappropriate and genetically misleading, as the disorder is more appropriately designated XLP.
Measuring the Competitiveness of China's Processed Exports
Authors: Thorbecke Willem
Published: January 2015

China's surplus in processing trade remains large. Processed exports are final goods produced using parts and components that are imported duty free. Because much of the value‐added of these exports comes from East Asia, exchange rates throughout the region should affect their foreign currency prices. This paper presents data on value‐added exchange rates for processed exports over the 1993–2013 period and reports that they significantly affect exports. While the renminbi appreciated 36 percent between the beginning of 2005 and the end of 2013, exchange rates in supply chain countries depreciated. This has mitigated the effect of the RMB appreciation on the price competitiveness of processed exports.
Impact of an integrated model of care on potentially preventable hospitalizations for people with Type 2 diabetes mellitus
Authors: Zhang J. , Donald M. , Baxter K. A. , Ware R. S. , Burridge L. , Russell A. W. , Jackson C. L.
Published: January 2015

Aims

To evaluate the impact of an integrated model of care for patients with complex Type 2 diabetes mellitus on potentially preventable hospitalizations.

Methods

A prospective controlled trial was conducted comparing a multidisciplinary, community‐based, integrated primary–secondary care diabetes service with usual care at a hospital diabetes outpatient clinic. Study and hospital admissions data were linked for the period from 12 months before to 24 months after commencement of the trial. The primary outcome was the number of potentially preventable hospitalizations with diabetes‐related principal diagnoses. Length of stay once hospitalized was also reported.

Results

Of 327 adult participants, 206 were hospitalized and accounted for 667 admissions during the study period. Compared with the usual care group, patients in the integrated model of care group were nearly half as likely to be hospitalized for a potentially preventable diabetes‐related principal diagnosis in the 24 months after study commencement (incidence rate ratio 0.53, 95% CI 0.29, 0.96; P = 0.04). The magnitude of the result remained similar after adjusting for age, sex, education and baseline HbA1c concentration (incidence rate ratio 0.54, 95% CI 0.29, 1.01; P = 0.05).When hospitalized, patients in the integrated care group had a similar length of stay compared with those in the usual care group (median difference ‐2 days, 95%CI ‐6.5, 2.3; P = 0.33).

Conclusions

Patients receiving the integrated model of care had a reduction in the number of hospitalizations when the principal diagnosis for admission was a diabetes‐related complication. Integrated models of care for people with complex diabetes can reduce hospitalizations and help attempts to curtail increasing demand on finite health services.
The Sound of Bedrock: Lines of Grammar between Kant, Wittgenstein, and Cavell
Authors: Baz Avner
Published: January 2015

In ‘Aesthetics Problems of Modern Philosophy’ Stanley Cavell proposes, first, that Kant's characterization of judgments of beauty may be read as a Wittgensteinian grammatical characterization, and, second, that the philosophical appeal to ‘what we say and mean’ partakes of the grammar of judgment of beauty. I argue first that the expression of the dawning of an aspect partakes of the grammar of judgments of beauty as characterized by Kant, and may also be seen—on a prevailing way of thinking about concepts and how they relate to their instances—to have the same kind of significance that judgments of beauty have according to Kant. And then I argue that there are good (Wittgensteinian) reasons for being suspicious of the prevailing conception of concepts, and therefore good reasons for being suspicious of the proposed understanding of the significance of aspect perception—an understanding that has attracted many readers of Wittgenstein's remarks on aspects. This leads me to suggest that it is actually the philosophical appeal to ordinary language that has the kind of significance that the Kantian picture attributes to judgments of beauty and to the seeing of aspects. In this way, I offer a way to vindicate Cavell's second proposal.
Preaching, politics and episcopal reform in Wulfstan's early writings
Authors: Gates Jay Paul
Published: January 2015

Putting Wulfstan's earliest legal texts – the Canons of Edgar and the so‐called Peace of Edward and Guthrum – in dialogue with his homilies on the role of the bishop, this article argues that, from his earliest writings, Wulfstan adapted approaches from Kings Alfred and Edgar as well as from the Benedictine reform to make ambitious claims concerning the role of the bishop in the secular sphere. These claims went beyond the contemporary understanding of the relationship between bishop and king both in England and on the Continent, to frame the bishop as the primary authority in the nation because he is the teacher of teachers.
Longitudinal Associations among Parental Acceptance, Familism Values, and Sibling Intimacy in Mexican‐Origin Families
Authors: Killoren Sarah E. , Wheeler Lorey A. , Updegraff Kimberly A. , Rodríguez de Jésus Sue A. , McHale Susan M.
Published: January 2015

Prospective associations among parent–adolescent acceptance and familism values in early and middle adolescence and sibling intimacy in late adolescence and young adulthood were assessed in 246 Mexican‐origin families. Older sibling gender and sibling gender constellation were investigated as moderators of these associations. Sibling intimacy was stable over time and younger siblings with older sisters reported higher levels of sibling intimacy than those with older brothers. As predicted, stronger familism values were associated with greater sibling intimacy, but this link was evident only for older sisters and for girl‐girl dyads. The links from mother‐ and father‐acceptance to sibling intimacy also depended on the gender constellation of the sibling dyad: Higher levels of maternal warmth were associated with greater sibling intimacy for older sisters and girl‐girl sibling pairs but higher levels of paternal warmth were linked to greater sibling intimacy only for older siblings in mixed‐gender sibling dyads. Findings are consistent with prior research on the role of gender in family relationships but extend this work to encompass the effects of both parents' and siblings' gender, as well as the role of sociocultural values in parents' socialization influences.
Seasonal dynamics of bioenergy characteristics in grassland functional groups
Authors: Melts I. , Heinsoo K.
Published: January 2015

Semi‐natural grasslands (SNG) are considered as bioenergy resources, either for combustion or for biogas production. To provide information on the seasonal (June–August) dynamics of herbage quantity and chemical composition, we studied the effects of factors on the proportions of four plant functional groups, chemical composition and total biomass yield at twelve sites representing three Estonian SNG types. Biomass yield increased only in alluvial meadows with the largest contribution of sedges/rushes (39%). Grasses dominated in dry‐to‐mesic meadows (62%) and other forbs in wooded meadows (55%). Concentration of fibre was highest in grasses and sedges/rushes (682 and 645 g NDF kg−1), and lignin was highest in legumes and other forbs (103 and 113 g kg−1). Legumes contained more C and N (447 and 25 g kg−1) and grasses more Cl (1 g kg−1). The highest concentrations of Mg, K and ash were in other forbs (4, 18 and 80 g kg−1), and Ca in legumes (16 g kg−1). The results are discussed in the context of suitability of different functional groups and SNG types for bioenergy conversion. Grasses and sedge‐/rush‐rich biomass are considered suitable for methane production. Biomass harvesting in July and minimizing the problems with N and Cl during combustion need to be considered. Forb‐rich biomass should be pre‐treated before direct combustion.
Planet formation processes revealed by meteorites
Authors: Day James M.D.
Published: January 2015

The history of the solar system is locked within the planets, asteroids and other objects that orbit the Sun. While remote observations of these celestial bodies are essential for understanding planetary processes, much of the geological and geochemical information regarding solar system heritage comes directly from the study of rocks and other materials originating from them. The diversity of materials available for study from planetary bodies largely comes from meteorites; fragments of rock that fall through Earth's atmosphere after impact‐extraction from their parent planet or asteroid. These extra‐terrestrial objects are fundamental scientific materials, providing information on past conditions within planets, and on their surfaces, and revealing the timing of key events that affected a planet's evolution. Meteorites can be sub‐divided into four main groups: (1) chondrites, which are unmelted and variably metamorphosed ‘cosmic sediments’ composed of particles that made up the early solar nebula; (2) achondrites, which represent predominantly silicate materials from asteroids and planets that have partially to fully melted, from a broadly chondritic initial composition; (3) iron meteorites, which represent Fe‐Ni samples from the cores of asteroids and planetesimals; and (4) stony‐iron meteorites such as pallasites and mesosiderites, which are mixtures of metal and dominantly basaltic materials. Meteorite studies are rapidly expanding our understanding of how the solar system formed and when and how key events such as planetary accretion and differentiation occurred. Together with a burgeoning collection of classified meteorites, these scientific advances herald an unprecedented period of further scientific challenges and discoveries, an exciting prospect for understanding our origins.