bluuebunny/crossref_metadata_2025 huggingface dataset:
Universal extraction method for gastrointestinal pathogens
Authors: Halstead Fenella D. , Lee Adele V. , Couto-Parada Xose , Polley Spencer D. , Ling Clare , Jenkins Claire , Chalmers Rachel M. , Elwin Kristin , Gray Jim J. , Iturriza-Gómara Miren , Wain John , Clark Duncan A. , Bolton Frederick J. , Manuel Rohini J. ,   the Olympics GI Group
Published: July 2013

A universal stool extraction method for recovery of nucleic acids (NAs) from gastrointestinal pathogens was developed to support rapid diagnostics for the London 2012 Olympics. The method involved mechanical disruption (bead beating) of the stools, followed by automated extraction and detection using real-time PCR. This method had been used extensively in the Second Infectious Intestinal Disease Study (IID2) for the isolation of NA from bacteria and parasites (and was effective for the robust recovery of Cryptosporidium spp.) but had not been used for enteric viruses. To ensure this method was universally suitable, panels of samples known to contain target bacteria, viruses or parasites were processed in triplicate using the pre-treatment method routinely used for each target and the new extraction method (bead beating). The extracts were tested using real-time PCR and the cycle threshold values were compared. The results from this study showed that bead beating improved yields for the bacterial and parasitic targets and was suitable for the viral targets. The implementation of this universal method should confer cost- and time-saving benefits and streamline the processes required for the characterization of an array of pathogens from faecal samples.
Emergence of Pseudomonas aeruginosa with KPC-type carbapenemase in a teaching hospital: an 8-year study
Authors: Ramírez Dolores García , Nicola Federico , Zarate Soledad , Relloso Silvia , Smayevsky Jorgelina , Arduino Sonia
Published: July 2013

An outbreak of Klebsiella pneumoniae carbapenamase (KPC)-producing K. pneumoniae occurred at our institution. Multiresistant Pseudomonas aeruginosa could have acquired this transmissible resistance mechanism, going unnoticed because its phenotypic detection in this species is difficult. We compared P. aeruginosa isolates obtained before and after the KPC-producing K. pneumoniae outbreak. No bla
KPC genes were detected in the isolates obtained before the outbreak, whereas 33/76 (43 %) of the isolates obtained after the outbreak harboured the bla
KPC gene. P. aeruginosa may thus become a reservoir of this transmissible resistance mechanism. It is very important to understand the epidemiology of these multiresistant isolates, in order to achieve early implementation of adequate control measures to contain and reduce their dissemination in the hospital environment.
Trans-Golgi Network Localized ECHIDNA/Ypt Interacting Protein Complex Is Required for the Secretion of Cell Wall Polysaccharides inArabidopsis
Authors: Gendre Delphine , McFarlane Heather E. , Johnson Errin , Mouille Gregory , Sjödin Andreas , Oh Jaesung , Levesque-Tremblay Gabriel , Watanabe Yoichiro , Samuels Lacey , Bhalerao Rishikesh P.
Published: July 2013

The secretion of cell wall polysaccharides through the trans-Golgi network (TGN) is required for plant cell elongation. However, the components mediating the post-Golgi secretion of pectin and hemicellulose, the two major cell wall polysaccharides, are largely unknown. We identified evolutionarily conserved YPT/RAB GTPase Interacting Protein 4a (YIP4a) and YIP4b (formerly YIP2), which form a TGN-localized complex with ECHIDNA (ECH) in Arabidopsis thaliana. The localization of YIP4 and ECH proteins at the TGN is interdependent and influences the localization of VHA-a1 and SYP61, which are key components of the TGN. YIP4a and YIP4b act redundantly, and the yip4a yip4b double mutants have a cell elongation defect. Genetic, biochemical, and cell biological analyses demonstrate that the ECH/YIP4 complex plays a key role in TGN-mediated secretion of pectin and hemicellulose to the cell wall in dark-grown hypocotyls and in secretory cells of the seed coat. In keeping with these observations, Fourier transform infrared microspectroscopy analysis revealed that the ech and yip4a yip4b mutants exhibit changes in their cell wall composition. Overall, our results reveal a TGN subdomain defined by ECH/YIP4 that is required for the secretion of pectin and hemicellulose and distinguishes the role of the TGN in secretion from its roles in endocytic and vacuolar trafficking.
Structure of the Arabidopsis Glucan Phosphatase LIKE SEX FOUR2 Reveals a Unique Mechanism for Starch Dephosphorylation
Authors: Meekins David A. , Guo Hou-Fu , Husodo Satrio , Paasch Bradley C. , Bridges Travis M. , Santelia Diana , Kötting Oliver , Vander Kooi Craig W. , Gentry Matthew S.
Published: July 2013

Starch is a water-insoluble, Glc-based biopolymer that is used for energy storage and is synthesized and degraded in a diurnal manner in plant leaves. Reversible phosphorylation is the only known natural starch modification and is required for starch degradation in planta. Critical to starch energy release is the activity of glucan phosphatases; however, the structural basis of dephosphorylation by glucan phosphatases is unknown. Here, we describe the structure of the Arabidopsis thaliana starch glucan phosphatase LIKE SEX FOUR2 (LSF2) both with and without phospho-glucan product bound at 2.3Å and 1.65Å, respectively. LSF2 binds maltohexaose-phosphate using an aromatic channel within an extended phosphatase active site and positions maltohexaose in a C3-specific orientation, which we show is critical for the specific glucan phosphatase activity of LSF2 toward native Arabidopsis starch. However, unlike other starch binding enzymes, LSF2 does not possess a carbohydrate binding module domain. Instead we identify two additional glucan binding sites located within the core LSF2 phosphatase domain. This structure is the first of a glucan-bound glucan phosphatase and provides new insights into the molecular basis of this agriculturally and industrially relevant enzyme family as well as the unique mechanism of LSF2 catalysis, substrate specificity, and interaction with starch granules.
The impact of foreign parent control mechanisms upon measurements of performance in IJVs in South Korea
Authors: Ghauri Pervez N. , Cave Adam H. , Il Park Byung
Published: July 2013

Purpose

The purpose of this paper is to generate an observable relationship between five control mechanisms used by parent firms to direct international joint ventures (IJVs) with three distinct performance measurements. By observing relationships with different performance measures it serves to enhance the debate on IJV creation and control functions.

Design/methodology/approach

This paper looks at IJVs and analyzes the application of control mechanisms through a survey of IJVs in South Korea, then a further review of the different performance measurements is provided to expound upon the increasing reasons of IJV creation.

Findings

The paper determines different impacts upon performance measures through the use of either personnel or policy measures. Parents' use of personnel shows a direct relationship with satisfaction levels of IJV performance, while policy measures show significant relationships to both financial and growth measurements. The paper finds that through the use of multiple performance measurements there is a greater understanding of the implications of control of different aspects of an IJV.

Research limitations/implications

The paper is concentrated solely on IJVs in South Korea; and further, measurements based on perception are consistently subject to accuracy concerns in statistical analysis.

Practical implications

IJVs are set up with different goals. Utilizing control mechanisms that enhance the performance goal of a parent can provide support during the creation and negotiation process.

Originality/value

The value provided by this paper is the critical analysis of control mechanisms on more than one performance measurement and a quantifiable statistical analysis that shows significant impact of certain mechanisms.
Research note: the development of an Arabic cross‐cultural adjustment scale
Authors: Al‐Rajhi Ibrahim , Bartlett Dean , Altman Yochanan
Published: July 2013

Purpose

The purpose of this paper is to report on the development of an Arabic language scale for measuring cross‐cultural adjustment in the Arab world, predominately the Middle East. It also comments on aspects of psychometric tools and their appropriateness for use in cross‐cultural management research.

Design/methodology/approach

Black and Stephen's Cross‐Cultural Adjustment Scale was translated into Arabic using the method of back‐translation and a pilot item‐by‐item debriefing. It was then administered to 111 Arabic‐speaking employees of a single firm.

Findings

The Arabic language version yielded high alpha coefficients and a subsequent factor analysis revealed three primary factors of cross‐cultural adjustment, namely, Work Adjustment, Interaction Adjustment and General Adjustment, which corresponded closely to the original English version of the scale, with two minor exceptions.

Research limitations/implications

The research is confined to the cultural‐linguistic context in which it was executed.

Practical implications

The findings suggest that an Arabic version of the three‐factor scale is useful for measuring adjustment in Arabic‐speaking samples and implies the wider generalizability of the cross‐cultural adjustment construct. The development of this scale in an important region for migrant labor is highly relevant to practice.

Originality/value

An Arabic version of the most widely used cross‐cultural adjustment scale is of value to researchers and practitioners. The Muslim sample drawn from the Middle East region also makes the paper highly original.
Opening the door to tomorrow's top talent
Authors: Stephens Nick
Published: July 2013

Purpose

The purpose of this paper is to use new research in the life‐sciences sector to explain how the active management of high‐potential individuals and leadership development will be the key to success.

Design/methodology/approach

It draws on research conducted among 203 senior executives and HR directors working in the global life‐sciences industry. Some 70 per cent of respondents are either chief executives or senior members of their organization's leadership team.

Findings

The paper reveals that more than 90 per cent of interviewees identified talent management as a key priority, but 72 per cent of their organizations are failing to deliver this in practice, operating without an active strategy in place.

Practical implications

The paper highlights a trend, over the past three years, for talent management to be less well planned and more ad hoc, mainly because of the continuing impact of market change and the double‐dip recession.

Social implications

It argues that the current economic conditions are ideal for organizations to execute effective talent‐management strategies, as most organizations are looking to optimize the performance of existing talent, generate efficiencies and reduce costs.

Originality/value

This paper advances the view that companies most able to attract, retain and develop top talent will be the most likely to achieve success.
Correlation of interleukin‐6 and monocyte chemotactic protein‐1 concentrations with crescent formation and myeloperoxidase‐specific anti‐neutrophil cytoplasmic antibody titer in SCG/Kj mice by treatment with anti‐interleukin‐6 receptor antibody or mizoribine
Authors: Nagao Tomokazu , Kusunoki Reina , Iwamura Chiaki , Kobayashi Shigeto , Yumura Wako , Kameoka Yosuke , Nakayama Toshinori , Suzuki Kazuo
Published: July 2013

Myeloperoxidase‐specific anti‐neutrophil cytoplasmic antibody (MPO–ANCA) is associated with rapidly progressive glomerulonephritis (RPGN) and glomerular crescent formation. Pathogenic factors in RPGN were analyzed by using SCG/Kj mice, which spontaneously develop MPO–ANCA‐associated RPGN. The serum concentration of soluble IL‐6R was determined by using ELISA and those of another 23 cytokines and chemokines by Bio‐Plex analysis. Sections of frozen kidney tissue were examined by fluorescence microscopy and the CD3+B220+ T cell subset in the spleen determined by a flow cytometry. Concentrations of IL‐6 and monocyte chemotactic protein‐1 were significantly correlated with the percentages of crescent formation. Anti‐IL‐6R antibody, which has been effective in patients with rheumatoid arthritis, was administered to SCG/Kj mice to elucidate the role of IL‐6 in the development of RPGN. MPO–ANCA titers decreased after administration of anti‐IL‐6R antibody, but not titers of mizoribine, which is effective in Kawasaki disease model mice. These results suggest that IL‐6‐mediated signaling is involved in the production of MPO–ANCA.
Foraging strategy of a neotropical primate: how intrinsic and extrinsic factors influence destination and residence time
Authors: Plante Sabrina , Colchero Fernando , Calmé Sophie
Published: July 2013

Most animals need to actively search for food to meet energetic requirements and live in heterogeneous environments where food resources have complex spatio‐temporal patterns of availability. Consequently, foraging animals need to find a balance between effort and resource allocation while accounting for intrinsic and extrinsic factors, which are often overlooked when modelling foraging behaviour.

We identified the decision rules for foraging in black howler monkeys (Alouatta pigra), according to food preferences, locations of high‐quality patches and previously eaten trees, phenology of food resources and hunger state. We depicted foraging in two stages: (i) the choice of the immediate next tree and (ii) the time spent on this tree. We used a recently developed model for inference of movement processes, incorporating resource selection functions into a Markov chain framework.

We found that monkeys tend to move to preferred tree species at each step. However, we did not find conclusively that, at each step, monkeys direct their movements to reach high‐quality patches. In fact, they were using these patches intensively, thus limiting the possibility to move towards other high‐quality patches. Time spent on a tree was positively and strongly affected by the presence of preferred food items, but not by its species. We also showed that time spent on trees increased as a function of satiation state. We suggest that the strategy adopted by black howlers tends to be efficient because choosing preferred trees at each step and spending spend more time where preferred resources are available should favour energy intake and restrain movement costs.

This study showcases a modelling framework that can be widely used in ecology to describe movements as a combination of multiple attraction and repulsion sources, such as mates and competitors.
Efficacy of interventions to combat tobacco addiction: Cochrane update of 2012 reviews
Authors: Hartmann‐Boyce Jamie , Stead Lindsay F. , Cahill Kate , Lancaster Tim
Published: July 2013

Background and aims

The Cochrane Collaboration is an international not‐for‐profit organization which produces and disseminates systematic reviews of health‐care interventions. This paper is the first in a series of annual updates of Cochrane reviews on tobacco addiction interventions. It also provides an up‐to‐date overview of review findings in this area to date and summary statistics for cessation reviews in which meta‐analyses were conducted.

Methods

In 2012, the Group published seven new reviews and updated 13 others. This update summarizes and comments on these reviews. It also summarizes key findings from all the other reviews in this area.

Results

New reviews in 2012 found that in smokers using pharmacotherapy, behavioural support improves success rates [risk ratio (RR) 1.16, 95% confidence interval (CI) = 1.09–1.24], and that combining behavioural support and pharmacotherapy aids cessation (RR 1.82, 95% CI = 1.66–2.00). Updated reviews established mobile phones as potentially helpful in aiding cessation (RR 1.71, 95% CI = 1.47–1.99), found that cytisine (RR 3.98, 95% CI = 2.01–7.87) and low‐dose varenicline (RR 2.09, 95% CI = 1.56–2.78) aid smoking cessation, and found that training health professionals in smoking cessation improves patient cessation rates (RR 1.60, 95% CI = 1.26–2.03). The updated reviews confirmed the benefits of nicotine replacement therapy, standard dose varenicline and providing cessation treatment free of charge. Lack of demonstrated efficacy remained for partner support, expired‐air carbon monoxide feedback and lung function feedback.

Conclusions

Cochrane systematic review evidence for the first time establishes the efficacy of behavioural support over and above pharmacotherapy, as well as the efficacy of cytisine, mobile phone technology, low‐dose varenicline and health professional training in promoting smoking cessation.
A contemporary review of uterine cancer management
Authors: Carter Jonathan
Published: July 2013

Cancer of the uterine corpus is the most common of all the gynaecological cancers. Whilst most are sporadic, a small proportion may develop as a consequence of genetic predisposition, most commonly hereditary nonpolyposis colon cancer. The surgical management remains resection of the uterus with some short‐term advantages for a minimally invasive approach. Surgical staging to define the extent of disease may be advocated but its ability to affect survival has not been demonstrated. If surgical staging is undertaken, the routine performance of a para‐aortic lymph node dissection must be questioned. Adjuvant radiation therapy whilst reducing locoregional recurrence has not been shown to improve survival. Whilst the definitions of risk vary, grade 1 and 2 tumours, invading <50% into the myometrium, are considered low risk and should not be offered adjuvant therapy. Women with grade 3 tumours invading >50% into the myometrium have an increased risk of regional nodal spread and distant spread and recurrence. In these high‐risk cases, pelvic radiation therapy will reduce local and regional recurrence but will not impact upon survival. The addition of systemic therapy in this group is an attractive proposition with limited supportive evidence. All other patients are of intermediate risk of recurrence, and the addition of vaginal vault brachytherapy will reduce vaginal vault recurrences. Whilst there is no evidence to support a role for adjuvant hormonal therapy in apparent early‐stage disease, progestin therapy does have a role in nonlocalised advanced or recurrent disease.
Perceived changes in the knowledge and confidence of doctors and midwives to manage obstetric emergencies following completion of an Advanced Life Support in Obstetrics course in Australia
Authors: Walker Laura J.M. , Fetherston Catherine M. , McMurray Anne
Published: July 2013

Background

The Advanced Life Support in Obstetrics (ALSO) course is an internationally recognised interprofessional course to support health professionals to develop and maintain the knowledge and skills to manage obstetric emergencies.

Aims

This study investigated changes in confidence and perceived changes in the knowledge of doctors and midwives to manage specific obstetric emergency situations following completion of an ALSO course in Australia.

Methods

A prospective repeated‐measures survey design was used to survey 165 course attendees from four Australian states pre‐ and postcourse and at six weeks (n = 101). Data were analysed using a Friedman two‐way repeated‐measures analysis of variance and the Wilcoxon signed rank test.

Results

There was a significant improvement in confidence and perceived knowledge of the recommended management of all 17 emergency situations immediately postcourse (P < 0.001) and at six weeks postcourse (P < 0.001) when compared to precourse levels for both groups of health professionals. However, a significant decrease in knowledge and confidence for many emergency situations from immediately postcourse to six weeks postcourse (P < 0.05) was also observed in both groups.

Conclusions

Completion of the Australian ALSO course in Australia has a positive effect on the confidence and perceived knowledge of doctors and midwives to manage obstetric emergencies. However, there needs to be some means of reinforcing the effects of the course for longer term maintenance of knowledge and confidence.
Low‐dose anti‐CD20 veltuzumab given intravenously or subcutaneously is active in relapsed immune thrombocytopenia: a phase I study
Authors: Liebman Howard A. , Saleh Mansoor N. , Bussel James B. , Negrea Ovidiu George , Horne Heather , Wegener William A. , Goldenberg David M.
Published: July 2013

Low doses of the humanized anti‐CD20 monoclonal antibody, veltuzumab, were evaluated in 41 patients with immune thrombocytopenia (ITP), including 9 with ITP ≤1 year duration previously treated with steroids and/or immunoglobulins, and 32 with ITP >1 year and additional prior therapies. They received two doses of 80–320 mg veltuzumab 2 weeks apart, initially by intravenous (IV) infusion (N = 7), or later by subcutaneous (SC) injections (N = 34), with only one Grade 3 infusion reaction and no other safety issues. Thirty‐eight response‐assessable patients had 21 (55%) objective responses (platelet count ≥30 × 109/l and ≥2 × baseline), including 11 (29%) complete responses (CRs) (platelet count ≥100 × 109/l). Responses (including CRs) occurred with both IV and SC administration, at all veltuzumab dose levels, and regardless of ITP duration. Responders with ITP ≤1 year had a longer median time to relapse (14·4 months) than those with ITP >1 year (5·8 months). Three patients have maintained a response for up to 4·3 years. SC injections resulted in delayed and lower peak serum levels of veltuzumab, but B‐cell depletion occurred after first administration even at the lowest doses. Eight patients, including 6 responders, developed anti‐veltuzumab antibodies following treatment (human anti‐veltuzumab antibody, 19·5%). Low‐dose SC veltuzumab appears convenient, well‐tolerated, and with promising clinical activity in relapsed ITP.(Clinicaltrials.gov identifier: NCT00547066.)
Autologous haematopoietic cell transplantation for non‐Hodgkin lymphoma with secondary CNS involvement
Authors: Maziarz Richard T. , Wang Zhiwei , Zhang Mei‐Jie , Bolwell Brian J. , Chen Andy I. , Fenske Timothy S. , Freytes Cesar O. , Gale Robert P. , Gibson John , Hayes‐Lattin Brandon M. , Holmberg Leona , Inwards David J. , Isola Luis M. , Khoury Hanna J. , Lewis Victor A. , Maharaj Dipnarine , Munker Reinhold , Phillips Gordon L. , Rizzieri David A. , Rowlings Philip A. , Saber Wael , Satwani Prakash , Waller Edmund K. , Maloney David G. , Montoto Silvia , Laport Ginna G. , Vose Julie M. , Lazarus Hillard M. , Hari Parameswaran N.
Published: July 2013

Pre‐existing central nervous system (CNS) involvement may influence referral for autologous haematopoietic cell transplantation (AHCT) for patients with non‐Hodgkin lymphoma (NHL). The outcomes of 151 adult patients with NHL with prior secondary CNS involvement (CNS+) receiving an AHCT were compared to 4688 patients without prior CNS lymphoma (CNS−). There were significant baseline differences between the cohorts. CNS+ patients were more likely to be younger, have lower performance scores, higher age‐adjusted international prognostic index scores, more advanced disease stage at diagnosis, more aggressive histology, more sites of extranodal disease, and a shorter interval between diagnosis and AHCT. However, no statistically significant differences were identified between the two groups by analysis of progression‐free survival (PFS) and overall survival (OS) at 5 years. A matched pair comparison of the CNS+ group with a subset of CNS− patients matched on propensity score also showed no differences in outcomes. Patients with active CNS lymphoma at the time of AHCT (n = 55) had a higher relapse rate and diminished PFS and OS compared with patients whose CNS lymphoma was in remission (n = 96) at the time of AHCT. CNS+ patients can achieve excellent long‐term outcomes with AHCT. Active CNS lymphoma at transplant confers a worse prognosis.
Longitudinal study of echocardiography‐derived tricuspid regurgitant jet velocity in sickle cell disease
Authors: Desai Payal C. , May Ryan C. , Jones Susan K. , Strayhorn Dell , Caughey Melissa , Hinderliter Alan , Ataga Kenneth I.
Published: July 2013

Although echocardiography‐derived tricuspid regurgitant jet velocity (TRV) is associated with increased mortality in sickle cell disease (SCD), its rate of increase and predictive markers of its progression are unknown. We evaluated 55 subjects (median age: 38 years, range: 20–65 years) with at least two measurable TRVs, followed for a median of 4·5 years (range: 1·0–10·5 years) in a single‐centre, prospective study. Thirty‐one subjects (56%) showed an increase in TRV, while 24 subjects (44%) showed no change or a decrease in TRV. A linear mixed effects model indicated an overall rate of increase in the TRV of 0·02 m/s per year (P = 0·023). The model showed that treatment with hydroxycarbamide was associated with an initial TRV that was 0·20 m/s lower than no such treatment (P = 0·033), while treatment with angiotensin converting enzyme inhibitors and angiotensin receptor blockers was associated with an increase in the TRV (P = 0·006). In summary, although some patients have clinically meaningful increases, the overall rate of TRV increase is slow. Treatment with hydroxycarbamide may decrease the progression of TRV. Additional studies are required to determine the optimal frequency of screening echocardiography and the effect of therapeutic interventions on the progression of TRV in SCD.
Anti‐leukaemic activity of a novel haploidentical‐transplantation approach employing unmanipulated bone marrow followed by CD6‐depleted peripheral blood stem cells in children with refractory/relapsed acute leukaemia
Authors: Schuster Friedhelm R. , Meisel Roland , Führer Monika , Reuther Susanne , Hauer Julia , Tischer Johanna , Feuchtinger Tobias , Laws Hans‐Jürgen , Kolb Hans‐Jochem , Borkhardt Arndt
Published: July 2013

The treatment outcome of children with refractory acute leukaemia or relapse post‐stem cell transplantation is dismal. We report 10 children (non‐remission n = 7) who underwent a new haploidentical transplant approach utilizing unmanipulated bone marrow followed by CD6‐depleted peripheral blood stem cells. Nine patients had successful engraftment and no evidence of leukaemia. Acute and chronic graft‐versus‐host‐disease was observed in five and three patients, respectively; two patients died of treatment‐related toxicity. Seven patients relapsed after 7 (range 3–34) months, however two patients are alive at 6·5 and 7·0 years. This approach provides anti‐leukaemic activity even in heavily pre‐treated children but long‐term disease control requires further intervention.
Phase II study of personalized peptide vaccination for refractory bone and soft tissue sarcoma patients
Authors: Takahashi Ryuji , Ishibashi Yukinao , Hiraoka Koji , Matsueda Satoko , Kawano Kouichirou , Kawahara Akihiko , Kage Masayoshi , Ohshima Koichi , Yamanaka Ryuya , Shichijo Shigeki , Shirouzu Kazuo , Itoh Kyogo , Sasada Tetsuro
Published: July 2013

Refractory bone and soft tissue sarcomas are challenging diseases to treat because of their robustness to chemotherapy. Although cancer vaccines have the potential to become an attractive treatment modality, their progress has been hampered by the presence of many subtypes of sarcomas and different human leukocyte antigen (HLA)‐types. We investigated whether personalized peptide vaccination (PPV) would be feasible for the vast majority of sarcoma patients. Twenty refractory bone and soft tissue sarcoma patients with nine different subtypes and 11 different HLA‐class IA phenotypes were enrolled in this study. A maximum of four HLA‐matched peptides showing higher peptide‐specific IgG responses in pre‐vaccination plasma were selected from 31 pooled peptide candidates applicable for the HLA‐A2, ‐A3, ‐A11, ‐A24, ‐A26, ‐A31, and ‐A33 types, and were subcutaneously administered weekly for 6 weeks and bi‐weekly thereafter. Measurement of peptide‐specific CTL and IgG responses along with other laboratory analyses were conducted before and after vaccination. No patients were excluded by either sarcoma subtypes or different HLA‐types. No severe adverse events associated with PPV were observed in any patients. Peptide‐specific immunological boosting was observed in the post‐vaccination samples from the majority of patients. Tumor reduction of the lung metastasis and a long stable disease was observed in each case, and the median overall survival time of the 20 cases was 9.6 months. Taken together, PPV could be feasible for the vast majority of refractory sarcoma patients because of the safety and higher rates of immunological responses regardless of the presence of different sarcoma subtypes and various HLA‐types.
Retrospective study of the medium‐chain acyl‐CoA dehydrogenase deficiency in Portugal
Authors: Ventura F.V. , Leandro P. , Luz A. , Rivera I.A. , Silva M.F.B. , Ramos R. , Rocha H. , Lopes A. , Fonseca H. , Gaspar A. , Diogo L. , Martins E. , Leão‐Teles E. , Vilarinho L. , Tavares de Almeida I.
Published: July 2013

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) is the commonest genetic defect of mitochondrial fatty acid β‐oxidation. About 60% of MCADD patients are homozygous for the c.985A>G (p.Lys329Glu) mutation in the ACADM gene (G985 allele). Herein, we present the first report on the molecular and biochemical spectrum of Portuguese MCADD population. From the 109 patients studied, 83 were diagnosed after inclusion of MCADD in the national newborn screening, 8 following the onset of symptoms and 18 through segregation studies. Gypsy ancestry was identified in 85/109 patients. The G985 allele was found in homozygosity in 102/109 patients, in compound heterozygosity in 6/109 and was absent in one patient. Segregation studies in the Gypsy families showed that 93/123 relatives were carriers of the G985 allele, suggesting its high prevalence in this ethnic group. Additionally, three new substitutions—c.218A>G (p.Tyr73Cys), c.503A>T (p.Asp168Val) and c.1205G>T (p.Gly402Val)—were identified. Despite the particularity of the MCADD population investigated, the G985 allele was found in linkage disequilibrium with H1(112) haplotype. Furthermore, two novel haplotypes, H5(212) and H6(122) were revealed.
Molecular cytogenetics: recent developments and applications in cancer
Authors: Das K , Tan P
Published: July 2013

Aneuploidy or alteration in chromosome numbers is a characteristic feature in cancer that is generally a consequence of defective chromosome segregation during cell division. Molecular cytogenetic analyses have conferred substantial evidence with regards to the chromosomal architectures in cancer. Most importantly, the fluorescence in situ hybridization (FISH) technique that plays a leading role in diagnostic pathology for its single‐cell analysis has provided crucial information regarding genomic variations in malignant cells. Further development of molecular cytogenetic methodologies such as chromosome specific FISH karyotyping and comparative genomic hybridization have also helped in the detection of cryptic genetic changes in cancer. But, the recent advancement of high throughput sequencing technologies have provided a more comprehensive genomic analyses resulting in novel chromosome rearrangements, somatic mutations as well as identification of fusion genes leading to new therapeutic targets. This review highlights the application of early molecular cytogenetics and the recent high throughput genomic approaches in characterizing various cancers and their invaluable support in cancer therapeutics.
Using Excel for White's Test—An Important Technique for Evaluating the Equality of Variance Assumption and Model Specification in a Regression Analysis
Authors: Berenson Mark L.
Published: July 2013

There is consensus in the statistical literature that severe departures from its assumptions invalidate the use of regression modeling for purposes of inference. The assumptions of regression modeling are usually evaluated subjectively through visual, graphic displays in a residual analysis but such an approach, taken alone, may be insufficient for assessing the appropriateness of the fitted model. Here, an easy‐to‐use test of the assumption of equal variance (i.e., homoscedasticity) as well as model specification is provided. Given the importance of the equal‐variance assumption (i.e., if uncorrected, severe violations preclude the use of statistical inference and moderate violations result in a loss of statistical power) and given the fact that, if uncorrected, a misspecified or underspecified model could invalidate an entire study, the test developed by Halbert White in 1980 is recommended for supplementing a graphic residual analysis when teaching regression modeling to business students at both the undergraduate and graduate levels. Using this confirmatory approach to supplement a traditional residual analysis has value because students often find that graphic displays are too subjective for determining what constitutes severe from moderate departures from the equal variance assumption or for assessing patterns in plots that might indicate model misspecification or underspecification.
Clinical trial of tooth desensitization prior to in‐office bleaching
Authors: Mehta Deepak , Venkata Suresh , Naganath Meena , LingaReddy Usha , Ishihata Hiroshi , Finger Werner J.
Published: July 2013

The aim of this clinical trial was to compare tooth sensitivity during and after bleaching with hydrogen peroxide gel following application of GLUMA Desensitizer PowerGel or placebo. Forty‐six subjects with sound maxillary incisors and canines were enrolled. Tooth shades were determined by comparison with a Vitapan Classic Shade guide. GLUMA Desensitizer PowerGel and placebo were randomly applied to the labial surfaces of the left or right anterior teeth for 1 min, which were then rinsed and dried. Then, Opalescence Boost PF 40% gel was applied onto labial enamel for 15 min. Sensitivity scores [recorded on a 10‐point visual‐analog scale (VAS)] were determined before, at 5, 10, and 15 min during, and 1, 24, 48 h and 1 wk after, the bleaching treatment. Shades were determined postbleaching and after 1 wk. Prebleaching application of GLUMA Desensitizer PowerGel significantly reduced tooth sensitivity during and after bleaching when compared with treatment with placebo. The whitening effects immediately and 1 wk after bleaching were significant when compared with the prebleaching shades. In conclusion, tooth pretreatment with GLUMA Desensitizer PowerGel for 1 min prior to 15 min of in‐office bleaching with 40% hydrogen peroxide gel was highly effective in reducing tooth sensitivity during and after bleaching.
Observations on the crystallization of spodumene from aqueous solutions in a hydrothermal diamond‐anvil cell
Authors: Li J. , Chou I.‐M. , Yuan S. , Burruss R. C.
Published: July 2013

Crystallization experiments were conducted in a new type of hydrothermal diamond‐anvil cell (HDAC; type V) using LiAlSi2O6 (S) gel and H2O (W) as starting materials. A total of 21 experiments were performed at temperatures up to 950°C and pressures up to 788 MPa. In the samples with relatively low W/S ratios, many small crystals formed in the melt phase during cooling. In those with high W/S ratios, only a few crystals with smooth surfaces crystallized from the aqueous fluid in the presence of melt droplets, which were gradually consumed during crystal growth, indicating rapid transfer of material from the melt to the crystals through the aqueous fluid. The nucleation of crystals started at 710 (±70)°C and 520 (±80) MPa, and crystal growth ended at 570 (±40)°C and 320 (±90) MPa, with the cooling P‐T path within the stability field of spodumene + quartz in the S‐W system. The observed linear crystal growth rates in the aqueous phase, calculated by dividing the maximum length of a single crystal by the duration of the entire growth step, were 4.7 × 10−6 and 5.7 × 10−6 cm s−1 for the cooling rates of 0.5 and 1°C min−1, respectively. However, a rapid crystal growth rate of 3.6 × 10−5 cm s−1 in the aqueous fluid was observed when the components were supplied by nearby melt droplets. Our results show that when crystals nucleate in the aqueous fluid instead of the melt phase, there are fewer nuclei formed, and they grow much faster due to the low viscosity of the aqueous fluid, which accelerates diffusion of components for the growth of crystals. Therefore, the large crystals in granitic pegmatite can crystallize directly from aqueous fluids rather than hydrosilicate melt.
Effects of bacterial products on the activity of odontoblast‐like cells and their formation of type 1 collagen
Authors: Fransson H. , Petersson K. , Davies J. R.
Published: July 2013

Aim

To study how products released from different bacteria in a deep carious lesion affect the metabolic activity of odontoblast‐like cells and their ability to produce the major organic component of dentine, collagen 1.

Methodology

MDPC‐23 cells were exposed to supernatants from biofilm cultures of strains isolated from the deepest part of a carious lesion as well as from a clinical isolate of Enterococcus faecalis. Lipoteichoic acid (LTA) and lipopolysaccharide (LPS) were used for comparison. Cell activity was assessed using an methyl‐thiazolyl‐diphenyl tetrazolium bromide (MTT) assay, and collagen 1 levels were determined by ELISA.

Results

The lesion microflora was dominated by Lactobacillus spp. Neither extracellular products from the isolates nor LPS affected the activity of the MDPC‐23 cells, whereas extracellular products from E. faecalis and LTA significantly reduced total cell activity (P < 0.01). Enterococcus faecalis had an inhibitory effect upon collagen 1 production by the cells, whereas no such effect or even a slight stimulatory effect was seen for the isolates from the deep carious lesion.

Conclusions

These studies indicate that culture supernatants from E. faecalis reduced the metabolic activity of odontoblast‐like cells as shown using the MTT assay. No effect was seen for supernatants from biofilms of bacteria recovered from a deep carious lesion. Different bacteria varied in their effects upon collagen 1 production suggesting that the nature of the bacterial species in a carious lesion may have a direct influence upon the ability of the odontoblasts to produce tertiary dentine.
Evaluation of an improved endodontic teaching model: do preclinical exercises have an influence on the technical quality of root canal treatments?
Authors: Tchorz J. P. , Ganter P. A. , Woelber J. P. , Stampf S. , Hellwig E. , Altenburger M. J.
Published: July 2013

Aim

To investigate whether the preclinical application of an electronic root canal length measurement device (ERCLMD) leads to more accurate working length (WL) determinations in a preclinical endodontic course and if this exercise effects the technical quality of root canal procedures when treatments are performed on patients for the first time.

Methodology

Root canal treatments performed by two consecutive groups of third year students (group 1: n = 39, group 2: n = 44) were compared in the preclinical course and when root canal treatments were performed on patients in the following term. Two different teaching models were applied in the preclinical endodontic course. WL in group 1 was determined with radiographs only. The teaching model applied in group 2 allowed the application of an ERCLMD. When treatments were performed on patients, both groups used the same technique to determine WL. It was first determined using an ERCLMD and verified radiographically. Master cone and root filling lengths were evaluated using radiographs, and comparisons between both groups were made using Fischer's exact test.

Results

Root fillings performed by students of group 2 were more often classified as acceptable. This observation was made in the preclinical endodontic course and when treatments were performed on patients.

Conclusions

The application of an ERCLMD in combination with radiographs is more accurate to determine WL than radiographs alone. Students practiced the use of ERCLMDs with the new model and benefited from this experience when performing their first root canal treatments on patients.
Synthesis and characterization of zinc oxide nanocrystals and histologic evaluation of their biocompatibility by means of intraosseous implants
Authors: Sousa C. J. A. , Pereira M. C. , Almeida R. J. , Loyola A. M. , Silva A. C. A. , Dantas N. O.
Published: July 2013

Aim

To synthesize and characterize zinc oxide (ZnO) nanocrystals and assess their biological properties for applications in dentistry, particularly in endodontics, by means of intraosseous implants.

Methodology

ZnO nanocrystals were synthesized and characterized by micro‐Raman spectroscopy and X‐ray Diffraction. Ten guinea pigs were divided into two groups representing experimental periods of 4 and 12 weeks and received implants on both sides of the mandible in the region of the symphysis. The connective tissue response along the lateral wall outside the cup served as the negative control. The animals were euthanized at the end of each observation period and prepared for routine histological examinations which evaluated inflammatory response and material biocompatibility.

Results

ZnO nanocrystals were highly pure, crystalline, and averaged 21 nm in size. After 12 weeks, tissue analysis revealed the presence of a thin layer of connective tissue with some giant cells between the implanted material and underlying bone tissue. While signs of mild inflammation could be seen, bone resorption and remodeling were not apparent.

Conclusion

ZnO nanocrystals were biocompatible, well tolerated and allowed new bone formation and bone remodelling.
Caprine Toll‐like receptor 8 gene sequence characterization reveals close relationships among ruminant species
Authors: Goyal S. , Dubey P. K. , Kumari N. , Niranjan S. K. , Kathiravan P. , Mishra B. P. , Mahajan R. , Kataria R. S.
Published: July 2013

TLR8 mediates antiviral immunity by recognizing ssRNA viruses and triggers potent antiviral and antitumor immune responses. In this study, approximately 3.5 Kb nucleotide sequence data of caprine TLR8 gene were generated from one sample each of twelve different Indian goat breeds belonging to different geographical regions. Cloning and characterization of cDNA synthesized from RNA purified from goat spleen revealed TLR8 ORF to be of 3102 nucleotides long coding for 1033 amino acids similar to other ruminant species, that is sheep, buffalo and cattle. The sequence analysis at nucleotide level revealed goat TLR8 to be closer to buffalo sharing 99.6% homology, followed by cattle and sheep. Simple Modular Architecture Research Tool (SMART) used for the structural analysis of goat TLR8 showed the presence of 16 leucine‐rich repeats (LRRs) along with single Toll/interleukin‐1 receptor (TIR) domain. TIR domain when compared with other livestock species was found to be conserved in ruminant species goat, sheep, cattle and buffalo. The phylogenetic analysis also revealed grouping of all ruminant species together, goat being closer to buffalo followed by cattle and sheep. Total 4 polymorphic sites were observed in TLR8 gene of one specimen goat representing each of 12 different breeds studied, all of which were synonymous and present within the coding region. Of these 4 SNPs, two were in ectodomains, one in TIR domain and one was found to be present in transmembrane domain. PCR‐RFLP genotyping of two of the SNPs indicated variations in allele frequencies among different goat breeds. The expression profiling in 13 tissues of goat showed maximum expression of TLR8 gene in kidney followed by spleen, lung and lymph node. Overall, our results indicate conservation of TLR8 gene among the ruminant species and low variation within Indian goat breeds.
Combining Magnetic Resonance Imaging within Six-Hours of Symptom Onset with Clinical Follow-Up at 24 h Improves Prediction of ‘malignant’ Middle Cerebral Artery Infarction
Authors: Kruetzelmann Anna , Hartmann Frank , Beck Christoph , Juettler Eric , Singer Oliver C. , Köhrmann Martin , Kersten Jan F. , Sobesky Jan , Gerloff Christian , Villringer Arno , Fiehler Jens , Neumann-Haefelin Tobias , Schellinger Peter D. , Röther Joachim , Thomalla Götz ,   for the Clinical Trial Net of the German Competence Network Stroke
Published: July 2013

Background

A large diffusion-weighted imaging lesion ⩽six-hours of symptom onset was found to predict the development of ‘malignant’ middle cerebral artery infarction with high specificity, positive predictive value, and negative predictive value, but sensitivity was low.

Hypothesis

We tested the hypothesis that sensitivity can be improved by adding information from clinical follow-up examination after 24 h.

Methods

We analyzed data from a prospective, multicenter, observational cohort study of patients with acute ischemic stroke and middle cerebral artery occlusion studied by stroke magnetic resonance imaging ⩽six-hours of symptom onset. We used the National Institutes of Health Stroke Scale to assess severity of symptoms after 24 h. We used the Classification and Regression Trees analysis to define the optimal thresholds of diffusion-weighted imaging lesion volume and the National Institutes of Health Stroke Scale after 24 h in patients developing ‘malignant’ middle cerebral artery infarction. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for two simple predictive models based on acute diffusion-weighted imaging lesion volume alone and acute diffusion-weighted imaging lesion volume together with the National Institutes of Health Stroke Scale after 24 h.

Results

Of 135 patients, 27 (20%) developed a ‘malignant’ middle cerebral artery infarction. The Classification and Regression Trees analysis identified acute diffusion-weighted imaging lesion ⩾78 ml and the National Institutes of Health Stroke Scale score after 24 h ⩾22 as optimal cut-offs. Inclusion of the National Institutes of Health Stroke Scale score after 24 h in a simple two-step decision tree increased sensitivity from 0·59 to 0·79, while specificity, positive predictive value, and negative predictive value remained largely unchanged.

Conclusion

Clinical follow-up examination after 24 h helps identify patients at risk of ‘malignant’ middle cerebral artery infarction that are missed by predictive algorithms based on early diffusion-weighted imaging lesion volume alone.