bluuebunny/crossref_metadata_2025 huggingface dataset:
The Incidence of Injury Among Male and Female Intercollegiate Rugby Players
Authors: Peck Karen Y. , Johnston Dana A. , Owens Brett D. , Cameron Kenneth L.
Published: May 2013

Background:

The National Collegiate Athletic Association classifies women’s rugby as an emerging sport. Few studies have examined the injury rates in women’s collegiate rugby or compared injury rates between sexes.

Hypothesis:

Injury rates will differ between female and male intercollegiate club rugby players.

Study Design:

Descriptive epidemiological study.

Methods:

Five years of injury data were collected from the men’s and women’s rugby teams at a US service academy using the institution’s injury surveillance system. The primary outcome of interest was the incidence rate of injury during the study period per 10,000 athlete exposures. Incidence rate ratios (IRRs) were calculated using a Poisson distribution to compare the rates by sex.

Results:

During the study period, the overall incidence rate for injury was 30% higher (IRR = 1.30, 95% CI: 1.09, 1.54) among men when compared with women; however, the distribution of injuries varied by sex. The incidence rate for ACL injury among women was 5.3 times (IRR = 5.32, 95% CI: 1.33, 30.53) higher compared with that among men. Men were 2.5 times (IRR = 2.54, 95% CI: 1.03, 7.52) more likely to sustain a fracture. The rate of acromioclavicular joint injury was 2.2 times (IRR = 2.19, 95% CI: 1.03, 5.19) higher among men when compared with women. Men were 6.6 times (IRR = 6.55, 95% CI: 2.65, 20.91) more likely to have an open wound than women.

Conclusion:

There are differences in injury rates and patterns between female and male American rugby players.

Clinical Relevance:

The differences in injury patterns may reflect distinct playing styles, which could be the result of the American football background common among many of the male players.
The first five years: a mixed methods study investigating reflections on working as a hospital consultant
Authors: Brown Jeremy M , Shaw Nigel J , Graham David R
Published: May 2013

Objectives

This paper revisits the same cohort of hospital consultants approximately five years after they were first appointed to investigate their reflections on establishing themselves in their role.

Design

Mixed methods using a short survey and in-depth semistructured interviews.

Setting

The study was conducted within one Deanery in the North of England.

Participants

The same 45 hospital consultants who were invited to participate in the study in 2007 were asked to take part in the second stage of the project in February 2011. These 45 consultants started their appointments no earlier than May 2006 within 12 National Health Service (NHS) Trusts in one Deanery. A total of 16 consultants participated. Six consultants who took part in semistructured interviews in 2007–2008 were invited to be interviewed again. Four consented and participated in a further interview in 2011.

Main outcome measures

Do consultants feel they have completed their transition into their senior clinical posts? Yes, although the ever changing nature of the consultant role means new challenges are always having to be being addressed. What support mechanisms are valued by consultants? Informal support mechanisms are greatly valued by consultants and these are built up over time. Are consultants satisfied that they made the correct specialty choice? Yes, all respondents reported satisfaction in their specialty choice.

Results

After reflecting on five years in post, all agreed that Specialist training prepared them well for the clinical aspects of their role. Ten (62%) felt they were not prepared for dealing with Trust Management issues and 13 (81%) felt unprepared for financial management.

Conclusions

consultants learn on the job and eventually fulfil their potential in the role over time. However, the role is regularly changing so informal support mechanisms are valued to help deal with a highly complex role.
Injuries associated with recreational horse riding and changes over the last 20 years: a review
Authors: Sandiford Nemandra , Buckle Christopher , Alao Uthman , Davidson Jerome , Ritchie James
Published: May 2013

Objective

To assess the incidence and distribution of recreational equestrian injuries seen in the Kent and Sussex region and review the available literature on this subject.

Design

This is a retrospective case series with historical controls.

Setting

Kent and Sussex region, England.

Main outcome measurement

Injuries related to horses in the recreational setting.

Methods

Subjects were selected from our acute injury database. Notes of all patients presenting with horse riding-related injuries between January and December 2010 were reviewed. Skeletal injuries were confirmed using our Picture Archiving and Communications Systems (PACS) system. Data were tabulated and grouped using Microsoft Excel software. Statistics were calculated using Graph Pad software.

Results

During the study period, 155 patients presented with a total of 199 injuries related to horses, accounting for 0.3% of all presentations; 69% were soft tissue injuries. The most commonly affected areas were the extremities (77 patients, 49.7%) followed by injuries to the head (38 patients, 24.5%) and trunk (36 patients, 23.2%). Seventeen patients (11%) were admitted. Patients presenting with head injuries suffered significantly more injuries compared to other groups (1.65 compared to 1.4 injuries, p < 0.0002).

Conclusion

A larger number of persons were riding for a longer period of the year compared to previous studies in the United Kingdom. There was also a shift in the patterns of injury seen in this population over the last two to three decades.
From gold-medal glory to prohibition: the early evolution of cocaine in the United Kingdom and the United States
Authors: Wielenga Vicki , Gilchrist Dawna
Published: May 2013

As reported in the 2011 World Drug Report, cocaine is likely to be the most problematic drug worldwide in terms of trafficking-related violence and second only to heroin in terms of negative health consequences and drug deaths. Over a period of 60 years, cocaine evolved from the celebrated panacea of the 1860s to outlawed street drug of the 1920s. As demonstrated by the evolution of cocaine use and abuse in the United Kingdom and United States during this time period, cultural attitudes influenced both the acceptance of cocaine into the medical field and the reaction to the harmful effects of cocaine. Our review of articles on cocaine use in the United Kingdom and the United States from 1860 to 1920 reveals an attitude of caution in the United Kingdom compared with an attitude of progressivism in the United States. When the trends in medical literature are viewed in the context of the development of drug regulations, our analysis provides insight into the relationship between cultural attitudes and drug policy, supporting the premise that it is cultural and social factors which shape drug policy, rather than drug regulations changing culture.
Food Allergy Management in Elementary School
Authors: Russell Anne F. , Huber Mary M.
Published: May 2013

The prevalence of food allergies, with associated risk for anaphylaxis, has increasingly become a significant public health concern with copious and pervasive implications for patients, families, clinical health care professionals, researchers, and society at large. While potential treatments for food allergy are being explored through clinical research trials, there is currently no widespread scientifically proven cure available. Daily management of this atopic disorder consists of strict avoidance of the offending allergen. Subsequently, many families make concerted, burdensome efforts to create an allergen-controlled home environment. When children with food allergies start elementary school, this transition can be quite anxiety provoking for parents/caregivers. Schools may be perceived as allergen ubiquitous settings coupled with staff having varying awareness and training regarding food allergy and anaphylaxis. Clinical nurse educators, clinical nurse case managers, and other members of the primary care and/or specialty clinic teams can play a critical role in spanning the informational gap between clinic and school community. Ongoing collaboration between clinic team members with school nurse coordinators, school administrators, and other members of the school health services team may serve to minimize fragmentation of patient care, maximize ease of the child’s school entry transition, expand food allergy/anaphylaxis educational opportunities, and provide support to school nurse colleagues.
Enhancing torsion fatigue behaviour of a martensitic stainless steel by generating gradient nanograined layer via surface mechanical grinding treatment
Authors: Huang H. W. , Wang Z. B. , Yong X. P. , Lu K.
Published: May 2013

A gradient nanograined (GNG) surface layer was formed on a martensitic stainless steel bar sample by means of the surface mechanical grinding treatment (SMGT). The average grain size is ∼25 nm on the topmost surface layer and increases gradually with increasing depth. The torsion fatigue strength is elevated by 38 with the GNG surface layer compared with the original material. An additional 8 increment in fatigue strength is achieved after a post-annealing treatment of the SMGT sample. By analysing the microstructure, hardness, surface roughness and residual stress distribution in the SMGT samples, we believe that the enhanced fatigue resistances originate from the GNG structure with a hard surface layer and a high structural homogeneity.
Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity, and outcome in childhood acute lymphoblastic leukemia
Authors: Radtke Susanne , Zolk Oliver , Renner Bertold , Paulides Marios , Zimmermann Martin , Möricke Anja , Stanulla Martin , Schrappe Martin , Langer Thorsten
Published: May 2013

Key Points

Polymorphisms in the MTX pathway genes substantially influence the kinetics and response to high-dose MTX therapy in childhood ALL. Germline variants in SLCO1B1, thymidylate synthase, and methylenetetrahydrofolate reductase are significantly associated with kinetics, toxicity, and outcome.
The microenvironment of AIDS-related diffuse large B-cell lymphoma provides insight into the pathophysiology and indicates possible therapeutic strategies
Authors: Liapis Konstantinos , Clear Andrew , Owen Andrew , Coutinho Rita , Greaves Paul , Lee Abigail M. , Montoto Silvia , Calaminici Maria , Gribben John G.
Published: May 2013

Key Points

AIDS-related DLBCL is highly angiogenic with markedly higher blood-vessel density than sporadic cases. Infiltration by activated cytotoxic cells in AIDS-related DLBCL is determined by the presence of LMP1 and/or p24 viral antigens.
Some new generalized Gronwall-Bellman-type integral inequalities in two independent variables on time scales
Authors: Wang Yulu , Feng Qinghua , Zhou Shixiang , Xu Feng
Published: May 2013

In this paper, some new Gronwall-Bellman-type integral inequalities in two independent variables on time scales are established, which can be used as a handy tool in the research of qualitative and quantitative properties of solutions of dynamic equations on time scales. The inequalities established unify some of the integral inequalities for continuous functions in (Meng and Li in Appl. Math. Comput. 148:381-392, 2004) and their discrete analysis in (Meng and Li in J. Comput. Appl. Math. 158:407-417, 2003).

MSC:26E70, 26D15, 26D10.
Discovering chromatin motifs using FAIRE sequencing and the human diploid genome
Authors: Yang Chia-Chun , Buck Michael J , Chen Min-Hsuan , Chen Yun-Fan , Lan Hsin-Chi , Chen Jeremy JW , Cheng Chao , Liu Chun-Chi
Published: May 2013

Background

Specific chromatin structures are associated with active or inactive gene transcription. The gene regulatory elements are intrinsically dynamic and alternate between inactive and active states through the recruitment of DNA binding proteins, such as chromatin-remodeling proteins.

Results

We developed a unique genome-wide method to discover DNA motifs associated with chromatin accessibility using formaldehyde-assisted isolation of regulatory elements with high-throughput sequencing (FAIRE-seq). We aligned the FAIRE-seq reads to the GM12878 diploid genome and subsequently identified differential chromatin-state regions (DCSRs) using heterozygous SNPs. The DCSR pairs represent the locations of imbalances of chromatin accessibility between alleles and are ideal to reveal chromatin motifs that may directly modulate chromatin accessibility. In this study, we used DNA 6-10mer sequences to interrogate all DCSRs, and subsequently discovered conserved chromatin motifs with significant changes in the occurrence frequency. To investigate their likely roles in biology, we studied the annotated protein associated with each of the top ten chromatin motifs genome-wide, in the intergenic regions and in genes, respectively. As a result, we found that most of these annotated motifs are associated with chromatin remodeling, reflecting their significance in biology.

Conclusions

Our method is the first one using fully phased diploid genome and FAIRE-seq to discover motifs associated with chromatin accessibility. Our results were collected to construct the first chromatin motif database (CMD), providing the potential DNA motifs recognized by chromatin-remodeling proteins and is freely available at http://syslab.nchu.edu.tw/chromatin.
The impact of polymorphisms in STAT6 on treatment outcome in HCV infected Taiwanese Chinese
Authors: Lim Yun-Ping , Hsu Yu-An , Tsai Kun-Hsi , Tsai Fuu-Jen , Peng Cheng-Yuan , Liao Wen-Ling , Hung Dong-Zong , Tien Ni , Lin Chien-Yih , Wan Lei
Published: May 2013

Genetic polymorphisms observed in various disease states associated with sensitivity or resistance to specific treatments have been a robust area of investigation for decades, with the potential to allow clinicians to make evidence-based decisions on the appropriate course of treatment. This study aimed to evaluate whether genetic polymorphisms of the signal transducer and activator of transcription 6 gene (STAT6) could be associated with a sustained virological response (SVR) among patients infected with hepatitis C virus genotypes 1 and 2 (HCV-1 and HCV-2) who were treated with peginterferon plus ribavirin (PEG-IFNα-RBV). We analyzed the associations between SVR to PEG-IFNα-RBV therapy and 4 single nucleotide polymorphisms (SNPs) in STAT6. This study included Taiwanese Chinese patients infected with either HCV-1 (n = 265) or HCV-2 (n = 195) in the presence or absence of an SVR. Among the STAT6 SNPs examined, the dosage effect of the A allele and allele frequency in rs1059513 were inversely correlated with SVR in patients infected with HCV-1 (P = 0.0179 and P = 0.0235, respectively). This effect was not observed in patients infected with HCV-2. The GG, GGG, and GGGC STAT6 haplotypes comprising 2, 3, and 4 SNPs (rs1059513, rs703817, rs324015, and rs3024974) were found to be associated with SVR, and their presence may increase the probability of a successful treatment outcome in patients infected with HCV-1 (P = 0.0273, 0.0352, and 0.0368, respectively). Moreover, a multivariate logistic regression model for predicting an SVR revealed that the presence of the GGGC haplotype carriers mutually affected the outcome of PEG-IFNα-RBV treatment. The presence of STAT6 SNPs and the association with SVR demonstrated that STAT6 polymorphisms might influence the therapeutic outcomes of patients infected with HCV-1 under standard-of-care (SOC) treatment.
The outcomes of hip resurfacing compared to standard primary total hip arthroplasty in Men
Authors: Issa Kimona , Palich Amanda , Tatevossian Tiffany , Kapadia Bhaveen H , Naziri Qais , Mont Michael A
Published: May 2013

Background

The purpose of this study was to evaluate the clinical and radiographic outcomes of hip resurfacing patients and compare them to standard primary total hip arthroplasty procedures performed during the same period of time.

Methods

One hundred and fourteen consecutive men who had a mean age of 50 years (range, 20 to 85 years) and who had undergone 120 hip resurfacing arthroplasties between 2007 and 2009 were compared to 117 consecutive men (120 hips) who had undergone a standard total hip arthroplasty during the same time period. The mean follow-up was 42 months (range, 24 to 55 months) for both groups. Outcomes evaluated included implant survivorship, hip scores, activity levels, and complication rates.

Results

In the resurfacing hip arthroplasty cohort, implant survivorship was 98% with two patients requiring a revision surgery one for femoral neck fracture and another for femoral head loosening. In comparison, implant survivorship was 99% in the standard total hip arthroplasty cohort, with 1 revision due to peri-prosthetic fracture which was successfully treated with a femoral component revision. In the resurfacing and standard hip arthroplasty cohorts, the mean post-operative Harris hip scores had improved to 96 and 94 points, respectively and were statistically similar. The resurfacing cohort had achieved a significantly higher mean post-operative University of California Activity Score (6.7 versus 5 points). There were no differences in the complication rates between the two cohorts.

Conclusion

When patients meet the appropriate selection criteria in the hands of experienced and high-volume arthroplasty surgeons, hip resurfacing provides excellent results at short- to mid-term follow-up.
A Case of simultaneous occurrence of Marine – Lenhart syndrome and a papillary thyroid microcarcinoma
Authors: Scherer Thomas , Wohlschlaeger-Krenn Evelyne , Bayerle-Eder Michaela , Passler Christian , Reiner-Concin Angelika , Krebs Michael , Gessl Alois
Published: May 2013

Background

Marine-Lenhart syndrome is defined as the co-occurrence of Graves’ disease and functional nodules. The vast majority of autonomous adenomas are benign, whereas functional thyroid carcinomas are considered to be rare. Here, we describe a case of simultaneous occurrence of Marine-Lenhart syndrome and a papillary microcarcinoma embedded in a functional nodule.

Case presentation

A 55 year-old, caucasian man presented with overt hyperthyroidism (thyrotropin (TSH) <0.01 μIU/L; free thyroxine (FT4) 3.03 ng/dL), negative thyroid peroxidase and thyroglobulin autoantibodies, but elevated thyroid stimulating hormone receptor antibodies (TSH-RAb 2.6 IU/L). Ultrasound showed a highly vascularized hypoechoic nodule (1.1 × 0.9 × 2 cm) in the right lobe, which projected onto a hot area detected in the 99mtechnetium thyroid nuclear scan. Overall uptake was increased (4.29%), while the left lobe showed lower tracer uptake with no visible background-activity, supporting the notion that both Graves’ disease and a toxic adenoma were present. After normal thyroid function was reinstalled with methimazole, the patient underwent thyroidectomy. Histological work up revealed a unifocal papillary microcarcinoma (9 mm, pT1a, R0), positively tested for the BRAF V600E mutation, embedded into the hyperfunctional nodular goiter.

Conclusions

Neither the finding of an autonomously functioning thyroid nodule nor the presence of Graves’ disease rule out papillary thyroid carcinoma.
Psychometric evaluation of a Swedish version of Minneapolis-Manchester quality of life-youth form and adolescent form
Authors: Einberg Eva-Lena , Kadrija Ibadete , Brunt David , Nygren Jens M , Svedberg Petra
Published: May 2013

Background

It has become important to measure long-term effects and quality of life in survivors of childhood cancer. The Minneapolis- Manchester Quality of Life (MMQL) instrument has been proven to better capture the quality of life (QoL) perspective of health than other instruments. The instrument has age appropriate versions and is therefore favourable for longitudinal studies of QoL of children surviving from cancer. The aim of this study was to evaluate the psychometric properties of the Swedish version of MMQL-Youth Form and the Adolescent Form focusing on: 1) face and content validity 2) the internal consistency and 3) the test-retest reliability.

Methods

The sample consisted of 950 pupils (11–16 years old) from 7 schools in the western Sweden who completed the questionnaire. For the test-retest evaluation 230 respondents completed the questionnaire two weeks later.

Results

Face and content validity was supported and internal consistency was found to be acceptable for the total scale for both the MMQL-Youth Form (8–12 years of age) and the Adolescent Form (13–20 years of age). Test-retest reliability for the MMQL-Youth Form was moderate for 50% of the items and good for the remaining. For the MMQL-Adolescent Form the test-retest showed moderate or good agreement for 80% of the items and fair for 20%.

Conclusions

The result indicated that the Swedish version of the MMQLYouth Form and Adolescent Form was valid and reliable in a sample of healthy children in a Swedish context. It is recommended to test the instrument among diverse samples of children such as survivors of childhood cancer in order to validate its usefulness in research and clinical settings.
The role of globular heads of the C1q receptor in HPV 16 E2-induced human cervical squamous carcinoma cell apoptosis is associated with p38 MAPK/JNK activation
Authors: Gao Ling-juan , Gu Ping-qing , Zhao Wei , Ding Wen-yan , Zhao Xue-qing , Guo Shu-yu , Zhong Tian-ying
Published: May 2013

Background

Human papillomavirus type 16 (HPV 16) E2 protein is a multifunctional DNA-binding protein. HPV 16 E2 regulates many biological responses, including DNA replication, gene expression, and apoptosis. The purpose of this study was to investigate the relationship among the receptor for globular heads of the human C1q (gC1qR) gene expression, HPV 16 E2 transfection and apoptosis regulation in human cervical squamous carcinoma cells (C33a and SiHa).

Methods

gC1qR expression was examined in C33a and SiHa cells using real-time PCR and Western blot analysis. Apoptosis of C33a and SiHa cells was assessed by flow cytometry. C33a and SiHa cell viability, migration and proliferation were detected using the water-soluble tetrazolium salt (WST-1) assay, a transwell assay and 3H-thymidine incorporation into DNA (3H-TdR), respectively.

Results

C33a and SiHa cells that were transfected with a vector encoding HPV 16 E2 displayed significantly increased gC1qR gene expression and p38 mitogen-activated protein kinase (p38 MAPK)/ c-jun N-terminal kinase (JNK) activation as well as up-regulation of cellular apoptosis, which was abrogated by the addition of gC1qR small interfering RNA (siRNA). Furthermore, the changes in C33a and SiHa cell viability, migration and proliferation that were observed upon HPV 16 E2 transfection were abrogated by SB203580 (a p38 MAPK inhibitor) or SP600125 (a JNK inhibitor) treatment.

Conclusion

These data support a mechanism whereby HPV 16 E2 induces apoptosis by silencing the gC1qR gene or inhibiting p38 MAPK/JNK signalling in cervical squamous cell carcinoma.
Resistive switching memory characteristics of Ge/GeO
x
nanowires and evidence of oxygen ion migration
Authors: Prakash Amit , Maikap Siddheswar , Rahaman Sheikh Ziaur , Majumdar Sandip , Manna Santanu , Ray Samit K
Published: May 2013

The resistive switching memory of Ge nanowires (NWs) in an IrO
x
/Al2O3/Ge NWs/SiO2/p-Si structure is investigated. Ge NWs with an average diameter of approximately 100 nm are grown by the vapor–liquid-solid technique. The core-shell structure of the Ge/GeO
x
NWs is confirmed by both scanning electron microscopy and high-resolution transmission electron microscopy. Defects in the Ge/GeO
x
NWs are observed by X-ray photoelectron spectroscopy. Broad photoluminescence spectra from 10 to 300 K are observed because of defects in the Ge/GeO
x
NWs, which are also useful for nanoscale resistive switching memory. The resistive switching mechanism in an IrO
x
/GeO
x
/W structure involves migration of oxygen ions under external bias, which is also confirmed by real-time observation of the surface of the device. The porous IrO
x
top electrode readily allows the evolved O2 gas to escape from the device. The annealed device has a low operating voltage (<4 V), low RESET current (approximately 22 μA), large resistance ratio (>103), long pulse read endurance of >105 cycles, and good data retention of >104 s. Its performance is better than that of the as-deposited device because the GeO
x
film in the annealed device contains more oxygen vacancies. Under SET operation, Ge/GeO
x
nanofilaments (or NWs) form in the GeO
x
film. The diameter of the conducting nanofilament is approximately 40 nm, which is calculated using a new method.
Fault diagnosis of induction motors utilizing local binary pattern-based texture analysis
Authors: Shahriar Md Rifat , Ahsan Tanveer , Chong UiPil
Published: May 2013

Fault diagnosis of induction motors in the practical industrial fields is always a challenging task due to the difficulty that lies in exact identification of fault signatures at various motor operating conditions in the presence of background noise produced by other mechanical subsystems. Several signal processing approaches have been adopted so far to mitigate the effect of this background noise in the acquired sensor signal so that fault-related features can be extracted effectively. Addressing this issue, this paper proposes a new approach for fault diagnosis of induction motors utilizing two-dimensional texture analysis based on local binary patterns (LBPs). Firstly, time domain vibration signals acquired from the operating motor are converted into two-dimensional gray-scale images. Then, discriminating texture features are extracted from these images employing LBP operator. These local feature descriptors are later utilized by multi-class support vector machine to identify faults of induction motors. The efficient texture analysis capability as well as the gray-scale invariance property of the LBP operators enables the proposed system to achieve impressive diagnostic performance even in the presence of high background noise. Comparative analysis reveals that LBP8,1 is the most suitable texture analysis operator for the proposed system due to its perfect classification performance along with the lowest degree of computational complexity.
An innovative pay-for-performance (P4P) strategy for improving malaria management in rural Kenya: protocol for a cluster randomized controlled trial
Authors: Menya Diana , Logedi John , Manji Imran , Armstrong Janice , Neelon Brian , O’Meara Wendy Prudhomme
Published: May 2013

Background

In high-resource settings, ‘pay-for-performance’ (P4P) programs have generated interest as a potential mechanism to improve health service delivery and accountability. However, there has been little or no experimental evidence to guide the development or assess the effectiveness of P4P incentive programs in developing countries. In the developing world, P4P programs are likely to rely, at least initially, on external funding from donors. Under these circumstances, the sustainability of such programs is in doubt and needs assessment.

Methods/design

We describe a cluster-randomized controlled trial underway in 18 health centers in western Kenya that is testing an innovative incentive strategy to improve management of an epidemiologically and economically important problem—diagnosis and treatment of malaria. The incentive scheme in this trial promotes adherence to Ministry of Health guidelines for laboratory confirmation of malaria before treatment, a priority area for the Ministry of Health. There are three important innovations that are unique to this study among those from other resource-constrained settings: the behavior being incentivized is quality of care rather than volume of service delivery; the incentives are applied at the facility-level rather than the individual level, thus benefiting facility infrastructure and performance overall; and the incentives are designed to be budget-neutral if effective.

Discussion

Linking appropriate case management for malaria to financial incentives has the potential to improve patient care and reduce wastage of expensive antimalarials. In our study facilities, on average only 25% of reported malaria cases were confirmed by laboratory diagnosis prior to the intervention, and the total treatment courses of antimalarials dispensed did not correspond to the number of cases reported. This study will demonstrate whether facility rather than individual incentives are compelling enough to improve case management, and whether these incentives lead to offsetting cost-savings as a result of reduced drug consumption.

Trial registration

ClinicalTrials.gov Registration Number NCT01809873
Comparative transcriptome analysis to investigate the high starch accumulation of duckweed (Landoltia punctata) under nutrient starvation
Authors: Tao Xiang , Fang Yang , Xiao Yao , Jin Yan-ling , Ma Xin-rong , Zhao Yun , He Kai-ze , Zhao Hai , Wang Hai-yan
Published: May 2013

Background

Duckweed can thrive on anthropogenic wastewater and produce tremendous biomass production. Due to its relatively high starch and low lignin percentage, duckweed is a good candidate for bioethanol fermentation. Previous studies have observed that water devoid of nutrients is good for starch accumulation, but its molecular mechanism remains unrevealed.

Results

This study globally analyzed the response to nutrient starvation in order to investigate the starch accumulation in duckweed (Landoltia punctata). L. punctata was transferred from nutrient-rich solution to distilled water and sampled at different time points. Physiological measurements demonstrated that the activity of ADP-glucose pyrophosphorylase, the key enzyme of starch synthesis, as well as the starch percentage in duckweed, increased continuously under nutrient starvation. Samples collected at 0 h, 2 h and 24 h time points respectively were used for comparative gene expression analysis using RNA-Seq. A comprehensive transcriptome, comprising of 74,797 contigs, was constructed by a de novo assembly of the RNA-Seq reads. Gene expression profiling results showed that the expression of some transcripts encoding key enzymes involved in starch biosynthesis was up-regulated, while the expression of transcripts encoding enzymes involved in starch consumption were down-regulated, the expression of some photosynthesis-related transcripts were down-regulated during the first 24 h, and the expression of some transporter transcripts were up-regulated within the first 2 h. Very interestingly, most transcripts encoding key enzymes involved in flavonoid biosynthesis were highly expressed regardless of starvation, while transcripts encoding laccase, the last rate-limiting enzyme of lignifications, exhibited very low expression abundance in all three samples.

Conclusion

Our study provides a comprehensive expression profiling of L. punctata under nutrient starvation, which indicates that nutrient starvation down-regulated the global metabolic status, redirects metabolic flux of fixed CO2 into starch synthesis branch resulting in starch accumulation in L. punctata.
Bio-oil based biorefinery strategy for the production of succinic acid
Authors: Wang Caixia , Thygesen Anders , Liu Yilan , Li Qiang , Yang Maohua , Dang Dan , Wang Ze , Wan Yinhua , Lin Weigang , Xing Jianmin
Published: May 2013

Background

Succinic acid is one of the key platform chemicals which can be produced via biotechnology process instead of petrochemical process. Biomass derived bio-oil have been investigated intensively as an alternative of diesel and gasoline fuels. Bio-oil could be fractionized into organic phase and aqueous phase parts. The organic phase bio-oil can be easily upgraded to transport fuel. The aqueous phase bio-oil (AP-bio-oil) is of low value. There is no report for its usage or upgrading via biological methods. In this paper, the use of AP-bio-oil for the production of succinic acid was investigated.

Results

The transgenic E. coli strain could grow in modified M9 medium containing 20 v/v% AP-bio-oil with an increase in OD from 0.25 to 1.09. And 0.38 g/L succinic acid was produced. With the presence of 4 g/L glucose in the medium, succinic acid concentration increased from 1.4 to 2.4 g/L by addition of 20 v/v% AP-bio-oil. When enzymatic hydrolysate of corn stover was used as carbon source, 10.3 g/L succinic acid was produced. The obtained succinic acid concentration increased to 11.5 g/L when 12.5 v/v% AP-bio-oil was added. However, it decreased to 8 g/L when 50 v/v% AP-bio-oil was added. GC-MS analysis revealed that some low molecular carbon compounds in the AP-bio-oil were utilized by E. coli.

Conclusions

The results indicate that AP-bio-oil can be used by E. coli for cell growth and succinic acid production.
Nucleosomal DNA binding drives the recognition of H3K36-methylated nucleosomes by the PSIP1-PWWP domain
Authors: van Nuland Rick , van Schaik Frederik MA , Simonis Marieke , van Heesch Sebastiaan , Cuppen Edwin , Boelens Rolf , Timmers HT Marc , van Ingen Hugo
Published: May 2013

Background

Recognition of histone modifications by specialized protein domains is a key step in the regulation of DNA-mediated processes like gene transcription. The structural basis of these interactions is usually studied using histone peptide models, neglecting the nucleosomal context. Here, we provide the structural and thermodynamic basis for the recognition of H3K36-methylated (H3K36me) nucleosomes by the PSIP1-PWWP domain, based on extensive mutational analysis, advanced nuclear magnetic resonance (NMR), and computational approaches.

Results

The PSIP1-PWWP domain binds H3K36me3 peptide and DNA with low affinity, through distinct, adjacent binding surfaces. PWWP binding to H3K36me nucleosomes is enhanced approximately 10,000-fold compared to a methylated peptide. Based on mutational analyses and NMR data, we derive a structure of the complex showing that the PWWP domain is bound to H3K36me nucleosomes through simultaneous interactions with both methylated histone tail and nucleosomal DNA.

Conclusion

Concerted binding to the methylated histone tail and nucleosomal DNA underlies the high- affinity, specific recognition of H3K36me nucleosomes by the PSIP1-PWWP domain. We propose that this bipartite binding mechanism is a distinctive and general property in the recognition of histone modifications close to the nucleosome core.
Open‐label parallel dose tolerability study of three subcutaneous immunotherapy regimens in house dust mite allergic patients
Authors: Rieker‐Schwienbacher Juliane , Nell Marja J , Diamant Zuzana , van Ree Ronald , Distler Andreas , Boot Johan D , Kleine‐Tebbe Jörg
Published: May 2013

Background

The current maintenance dose (10,000 AUeq/monthly) of a subcutaneous allergoid for house dust mite (HDM) immunotherapy has previously shown significant clinical efficacy in patients with HDM induced allergic rhinitis or rhinoconjunctivitis. In order to comply with the 2009 EMA guidelines on immunotherapy products, a study was conducted to evaluate the safety, tolerability and short‐term treatment effects of up‐dosing regimens with high doses (up to 40,000 AUeq) of allergoid HDM immunotherapy.

Methods

In total 48 patients with HDM‐allergic rhinitis or rhinoconjunctivitis (29 M/19 F; 18–53 years) were included and enrolled into one of three up‐dosing regimens (1:4:4): 1) a regular regimen with up‐dosing to 40,000 AUeq followed by two maintenance doses (total duration 17 weeks), 2) an intermediate regimen (14 weeks) or 3) a fast regimen (11 weeks). Safety and tolerability were evaluated by monitoring of early and late local reactions and systemic reactions. In addition, short‐term effects were assessed by conjunctival provocation test (CPT) and levels of serum allergen‐specific IgE, IgG and IgG4.

Results

Thirty‐nine patients completed the study according to protocol. No early local reactions occurred. Late local reactions (LLR) were observed in 12% of the injections. In total, 31 systemic reactions, all grade 1, were reported of which two needed oral antihistamine treatment. No grade 2 or higher systemic reactions were observed. Six patients (15%) did not reach the highest dose due to LLR and/or systemic reactions needing antihistamines (20% in the regular regimen, 16% in the intermediate regimen and 13% in the fast regimen). At the end of the study, an improvement in the CPT was observed in 82.1% of patients, indirectly indicating an early treatment effect at the current dose and higher doses. In addition, IgG4 immunoglobulin levels were significantly increased in all groups following treatment.

Conclusions

In this open‐label study, allergoid HDM immunotherapy in doses up to 40,000 AUeq was generally well tolerated and no clinically relevant safety issues were identified. In the safety aspects of the three up‐dosing regimens no clinically relevant differences were encountered. Therefore, these dose ranges and up‐dosing regimens can be safely included in future dose‐finding efficacy studies.
The influence of DNA repair on neurological degeneration, cachexia, skin cancer and internal neoplasms: autopsy report of four xeroderma pigmentosum patients (XP-A, XP-C and XP-D)
Authors: Lai Jin-Ping , Liu Yen-Chun , Alimchandani Meghna , Liu Qingyan , Aung Phyu Phyu , Matsuda Kant , Lee Chyi-Chia R , Tsokos Maria , Hewitt Stephen , Rushing Elisabeth J , Tamura Deborah , Levens David L , DiGiovanna John J , Fine Howard A , Patronas Nicholas , Khan Sikandar G , Kleiner David E , Oberholtzer J Carl , Quezado Martha M , Kraemer Kenneth H
Published: May 2013

Background

To investigate the association of DNA nucleotide excision repair (NER) defects with neurological degeneration, cachexia and cancer, we performed autopsies on 4 adult xeroderma pigmentosum (XP) patients with different clinical features and defects in NER complementation groups XP-A, XP-C or XP-D.

Results

The XP-A (XP12BE) and XP-D (XP18BE) patients exhibited progressive neurological deterioration with sensorineural hearing loss. The clinical spectrum encompassed severe cachexia in the XP-A (XP12BE) patient, numerous skin cancers in the XP-A and two XP-C (XP24BE and XP1BE) patients and only few skin cancers in the XP-D patient. Two XP-C patients developed internal neoplasms including glioblastoma in XP24BE and uterine adenocarcinoma in XP1BE. At autopsy, the brains of the 44 yr XP-A and the 45 yr XP-D patients were profoundly atrophic and characterized microscopically by diffuse neuronal loss, myelin pallor and gliosis. Unlike the XP-A patient, the XP-D patient had a thickened calvarium, and the brain showed vacuolization of the neuropil in the cerebrum, cerebellum and brainstem, and patchy Purkinje cell loss. Axonal neuropathy and chronic denervation atrophy of the skeletal muscles were observed in the XP-A patient, but not in the XP-D patient.

Conclusions

These clinical manifestations and autopsy findings indicate advanced involvement of the central and peripheral nervous system. Despite similar defects in DNA repair, different clinicopathological phenotypes are seen in the four cases, and therefore distinct patterns of neurodegeneration characterize XP-D, XP-A and XP-C patients.
Intrastriatal injection of interleukin-1 beta triggers the formation of neuromyelitis optica-like lesions in NMO-IgG seropositive rats
Authors: Kitic Maja , Hochmeister Sonja , Wimmer Isabella , Bauer Jan , Misu Tatsuro , Mader Simone , Reindl Markus , Fujihara Kazuo , Lassmann Hans , Bradl Monika
Published: May 2013

Background

Neuromyelitis optica (NMO) is a severe, disabling disease of the central nervous system (CNS) characterized by the formation of astrocyte-destructive, neutrophil-dominated inflammatory lesions in the spinal cord and optic nerves. These lesions are initiated by the binding of pathogenic aquaporin 4 (AQP4)-specific autoantibodies to astrocytes and subsequent complement-mediated lysis of these cells. Typically, these lesions form in a setting of CNS inflammation, where the blood–brain barrier is open for the entry of antibodies and complement. However, it remained unclear to which extent pro-inflammatory cytokines and chemokines contribute to the formation of NMO lesions. To specifically address this question, we injected the cytokines interleukin-1 beta, tumor necrosis factor alpha, interleukin-6, interferon gamma and the chemokine CXCL2 into the striatum of NMO-IgG seropositive rats and analyzed the tissue 24 hours later by immunohistochemistry.

Results

All injected cytokines and chemokines led to profound leakage of immunoglobulins into the injected hemisphere, but only interleukin-1 beta induced the formation of perivascular, neutrophil-infiltrated lesions with AQP4 loss and complement-mediated astrocyte destruction distant from the needle tract. Treatment of rat brain endothelial cells with interleukin-1 beta, but not with any other cytokine or chemokine applied at the same concentration and over the same period of time, caused profound upregulation of granulocyte-recruiting and supporting molecules. Injection of interleukin-1 beta caused higher numbers of blood vessels with perivascular, cellular C1q reactivity than any other cytokine tested. Finally, the screening of a large sample of CNS lesions from NMO and multiple sclerosis patients revealed large numbers of interleukin-1 beta-reactive macrophages/activated microglial cells in active NMO lesions but not in MS lesions with comparable lesion activity and location.

Conclusions

Our data strongly suggest that interleukin-1 beta released in NMO lesions and interleukin-1 beta-induced production/accumulation of complement factors (like C1q) facilitate neutrophil entry and BBB breakdown in the vicinity of NMO lesions, and might thus be an important secondary factor for lesion formation, possibly by paving the ground for rapid lesion growth and amplified immune cell recruitment to this site.
Study on Synergistic Interligand Interactions of Thermally Stable Gold Nanoparticles
Authors: Okumura Atsushi , Yamada Kou , Todori Kenji , Machida Shigeru
Published: May 2013

In order to apply gold nanoparticles to the materials for electronic and optical devices, they are required to be tolerant of heat applied in the fabrication processes. In our previous study, novel gold nanoparticles with excellent thermal stability were developed by introducing an amide bond and a condensed ring into the ligand molecules. On the other hand, particle size is a key factor in determining device performance, gaining control over the size is highly advantageous. In this study, a size-increase reaction of the pyrene-containing gold nanoparticle was carried out. The particle size was successfully increased from 2 to ca. 10 nm, without lowering the thermal stability. Furthermore, their interligand interactions could be probed using fluorescence measurements based on the characteristic excimer emission of pyrene. It is suggested that strong π–π stacking occurred around the particles, even after the size-increase reaction, contributing to maintaining the thermal stability.
Direct evidence for RNA–RNA interactions at the 3′ end of the Hepatitis C virus genome using surface plasmon resonance
Authors: Palau William , Masante Cyril , Ventura Michel , Di Primo Carmelo
Published: May 2013

Surface plasmon resonance was used to investigate two previously described interactions analyzed by reverse genetics and complementation mutation experiments, involving 5BSL3.2, a stem–loop located in the NS5B coding region of HCV. 5BSL3.2 was immobilized on a sensor chip by streptavidin-biotin coupling, and its interaction either with the SL2 stem–loop of the 3′ end or with an upstream sequence centered on nucleotide 9110 (referred to as Seq9110) was monitored in real-time. In contrast with previous results obtained by NMR assays with the same short RNA sequences that we used or SHAPE analysis with longer RNAs, we demonstrate that recognition between 5BSL3.2 and SL2 can occur in solution through a kissing-loop interaction. We show that recognition between Seq9110 and the internal loop of 5BSL3.2 does not prevent binding of SL2 on the apical loop of 5BSL3.2 and does not influence the rate constants of the SL2-5BSL3.2 complex. Therefore, the two binding sites of 5BSL3.2, the apical and internal loops, are structurally independent and both interactions can coexist. We finally show that the stem–loop SL2 is a highly dynamic RNA motif that fluctuates between at least two conformations: One is able to hybridize with 5BSL3.2 through loop–loop interaction, and the other one is capable of self-associating in the absence of protein, reinforcing the hypothesis of SL2 being a dimerization sequence. This result suggests also that the conformational dynamics of SL2 could play a crucial role for controlling the destiny of the genomic RNA.
Overconfidence in Newsvendor Orders: An Experimental Study
Authors: Ren Yufei , Croson Rachel
Published: May 2013

Previous studies have shown that individuals make suboptimal decisions in a variety of supply chain and inventory settings. We hypothesize that one cause is that individuals are overconfident (in particular, overprecise) in their estimation of order variation. Previous work has shown theoretically that underestimating the variance of demand causes orders to deviate from optimal in predictable ways. We provide two experiments supporting this theoretical link. In the first, we elicit the precision of each individual's beliefs and demonstrate that overprecision significantly correlates with order bias. We find that overprecision explains almost one-third of the observed ordering mistakes and that the effect of overprecision is robust to learning and other dynamic considerations. In the second, we introduce a new technique to exogenously reduce overprecision. We find that participants randomly assigned to this treatment demonstrate less overprecision and less biased orders than do those in a control group.

This paper was accepted by Peter Wakker, decision analysis.
Price Competition with Consumer Confusion
Authors: Chioveanu Ioana , Zhou Jidong
Published: May 2013

This paper proposes a model in which identical sellers of a homogeneous product compete in both prices and price frames (i.e., ways to present price information). Frame choices affect the comparability of price offers and may cause consumer confusion and lower price sensitivity. In equilibrium, firms randomize their frame choices to obfuscate price comparisons and sustain positive profits. The nature of the equilibrium depends on whether frame differentiation or frame complexity is more confusing. Moreover, an increase in the number of competitors induces firms to rely more on frame complexity, and this may boost industry profits and lower consumer surplus.

This paper was accepted by J. Miguel Villas-Boas, marketing.
O PARADIGMA SUSTENTÁVEL E A FORMULAÇÃO DE ESTRATÉGIAS EMPRESARIAIS PARA A COMPETITIVIDADE
Authors: Menezes Uiara Gonçalves de , Dias Valéria da Veiga , Gomes Clandia Maffini
Published: May 2013

O artigo objetiva analisar o entendimento de gestores da empresa estudada a respeito de RSE e de que forma suas práticas influenciam as estratégias, tendo como pano de fundo o ambiente complexo. A revisão da literatura destacou os conceitos do cartesianismo, da Teoria Geral dos Sistemas e Teoria da Complexidade, analisando a forma como estes impactam as organizações. Essa discussão abordou a importância da estratégia para o posicionamento da organização, considerando tanto o ambiente complexo e inconstante quanto a inclusão de práticas socioambientais para a formação dos valores da sociedade. Os resultados do estudo, de caráter qualitativo e descritivo, foram obtidos a partir da realização de entrevistas semi-estruturadas, com os principais gestores da organização, e análise de dados secundários. A análise das inter-relações correntes evidenciou a falta de existência de uma percepção clara dos conceitos sobre RSE, resultando na falta de alinhamento das práticas socioambientais com as estratégias corporativas.