bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Endobronchial Ultrasound and Computed Tomography With Fluoroscopy in the Guidance of Lung Cancer Biopsies
Authors: DiGiacinto Dora , Bagley Jennifer , Garrison Miranda
Published: September 2012

Open lung biopsy is the gold standard for diagnosing lung cancer, but it is an invasive approach. There have been several noninvasive methods developed to biopsy the lung. This literature review compares the use of endobronchial ultrasound (EBUS) and computed tomography with fluoroscopy (CTF) guidance in the biopsy of lung nodules. Computed tomography with fluoroscopy has a higher diagnostic yield than endobronchial ultrasound but has more postprocedural complications. Endobronchial ultrasound guided lung biopsy is effective when the lesions are located in the right middle lobe of the lung, and overall EBUS has a low rate of complications when compared to CTF.
Influence of host rocks on composition of colloid particles in groundwater at the Karachai Lake site
Authors: Malkovsky V. I. , Dikov YU. P. , Asadulin EN. E. , Krupskaya V. V.
Published: September 2012

The radioactive contaminant plume in groundwater at the Karachai Lake site has been examined further. The source of pollution is the Karachai Lake which was used as a reservoir for liquid radioactive waste (LRW) from the Radiochemical Production Association “Mayak” (South Urals, Russia). Taking into account that colloid-facilitated transport of radionuclides can substantially increase the contaminant migration velocity, the composition and structure of colloid particles from the groundwater within the contaminant plume were studied. Sampling of groundwater was carried out in the observation well within the contaminant plume. Different fractions of colloid particles were extracted from the groundwater samples by sequential filtration through membranes with decreasing pore size. Chemical and mineralogical compositions of the colloid particles were determined by X-ray photoelectron spectroscopy in combination with ion etching of the particle surfaces. The host rocks were studied using characteristic samples from the surface outcrop nearest to the observation well. The analysis showed that the colloid particles consisted of an inorganic core with a discontinuous organic cover. The inorganic core was close in composition to the host rocks along the flow path with a predominance of layered hydrosilicates.
Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation
Authors: Peffault de Latour Régis , Calado Rodrigo T. , Busson Marc , Abrams Jeffrey , Adoui Nadir , Robin Marie , Larghero Jérôme , Dhedin Nathalie , Xhaard Alienor , Clave Emmanuel , Charron Dominique , Toubert Antoine , Loiseau Pascale , Socié Gérard , Young Neal S.
Published: September 2012

Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatment-related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donors after myeloablative conditioning regimens, mainly for hematologic malignancies (n = 153). Blood lymphocytes' telomere length was measured by real-time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere lengths were analyzed for correlation with clinical outcomes. After age adjustment, patients' telomere-length distribution was similar among all 4 quartiles except for disease stage. There was no correlation between telomere length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years (95% confidence interval [CI], 54-70). After a median follow-up of 51 months (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely correlated with telomere length. TRM in patients in the first (lowest telomere length) quartile was significantly higher than in patients with longer telomeres (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI, .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI; 0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age-adjusted recipients' telomere length is an independent biologic marker of TRM after HSCT.
Regulation of plasmacytoid dendritic cell responses by PIR-B
Authors: Mitsuhashi Yoshiya , Nakamura Akira , Endo Shota , Takeda Kazuya , Yabe-Wada Toshiki , Nukiwa Toshihiro , Takai Toshiyuki
Published: September 2012

Plasmacytoid dendritic cells (PDCs) produce type I interferons (IFNs) in response to viral nucleic acids to exert antiviral immunity. However, PDCs are related to the progress and severity of autoimmune diseases, such as systemic lupus erythematosus, because they respond to host DNA. Therefore, the regulation of PDC activation is critical for maintaining adequate immune responses. Here we show that an inhibitory major histocompatibility complex class I receptor, paired immunoglobulin-like receptor B (PIR-B), suppressed Fms-like tyrosine kinase 3 ligand-induced PDC differentiation in BM cells, as well as Toll-like receptor 9-mediated IFN-α production by PDCs, through the dephosphorylation of STAT1/STAT2. In particular, PIR-B inhibited IFN-α–mediated STAT phosphorylation, suggesting that PIR-B negatively regulates the positive feedback mechanism of IFN-α secretion triggered by Toll-like receptor 9. These results demonstrate a novel regulatory role for PIR-B in PDCs.
Oestradiol ameliorates monocrotaline pulmonary hypertensionviaNO, prostacyclin and endothelin-1 pathways
Authors: Yuan Ping , Wu Wen-Hui , Gao Lan , Zheng Ze-Qi , Liu Dong , Mei Han-Ying , Zhang Zhuo-Li , Jing Zhi-Cheng
Published: August 2012

Pulmonary hypertension continues to be a serious clinical problem with high mortality. As oestrogen is a potential vasodilator of the pulmonary circulation, this study examined the mechanisms by which 17β-oestradiol improves monocrotaline (MCT)-induced pulmonary hypertension.

Female Sprague–Dawley rats underwent bilateral ovariectomy or sham operations. The rats received MCT (50 mg·kg−1) and were treated with 17β-oestradiol (1 mg·kg−1per day) for either 5 weeks or only from week 4 to week 5. Plasma 17β-oestradiol concentrations were decreased in sham-operated, MCT-treated rats when compared with sham-operated rats (17.7±4.7versus50.3±15.4 pg·mL−1; p=0.029). The 17β-oestradiol anabolic enzyme cytochrome P450 (CYP)-19 was decreased by MCT treatment, while the catabolic enzymes CYP-1A1 and -1B1 were increased. Ovariectomised and MCT-treated rats had more severe pulmonary hypertension. 17β-oestradiol suppressed pulmonary arterial smooth muscle cell proliferation and macrophage infiltration, and enhanced apoptosis by increasing nitric oxide (NO) and prostacyclin (prostaglandin (PG)I2) levels and reducing endothelin (ET)-1 levels. Phosphoinositide-3-kinase (PI3K) and Akt phosphorylations were markedly increased, but were inhibited by 17β-oestradiol treatment in rats with pulmonary hypertension.

Oestrogen deficiency may aggravate development of pulmonary hypertension. 17β-oestradiol improved pulmonary hypertensionviaactivation of the PI3K/Akt pathway to regulate NO, PGI2and ET-1 expression.
TheTL,NO/TL,COratio in pulmonary function test interpretation
Authors: Hughes J. Michael B. , van der Lee Ivo
Published: August 2012

The transfer factor of the lung for nitric oxide (TL,NO) is a new test for pulmonary gas exchange. The procedure is similar to the already well-established transfer factor of the lung for carbon monoxide (TL,CO). Physiologically,TL,NOpredominantly measures the diffusion pathway from the alveoli to capillary plasma. In the Roughton–Forster equation,TL,NOacts as a surrogate for the membrane diffusing capacity (DM). The red blood cell resistance to carbon monoxide uptake accounts for ∼50% of the total resistance from gas to blood, but it is much less for nitric oxide.

TL,NOandTL,COcan be measured simultaneously with the single breath technique, andDMand pulmonary capillary blood volume (Vc) can be estimated.TL,NO, unlikeTL,CO, is independent of oxygen tension and haematocrit. TheTL,NO/TL,COratio is weighted towards theDM/Vcratio and to α; where α is the ratio of physical diffusivities of NO to CO (α=1.97). TheTL,NO/TL,COratio is increased in heavy smokers, with and without computed tomography evidence of emphysema, and reduced in the voluntary restriction of lung expansion; it is expected to be reduced in chronic heart failure. TheTL,NO/TL,COratio is a new index of gas exchange that may, more than derivations from them ofDMandVcwith their in-built assumptions, give additional insights into pulmonary pathology.
Impact of obesity on outcomes for patients hospitalised with pneumonia
Authors: King Phoebe , Mortensen Eric M. , Bollinger Mary , Restrepo Marcos I. , Copeland Laurel A. , Pugh Mary Jo V. , Nakashima Brandy , Anzueto Antonio , Hitchcock Noël Polly
Published: August 2012

Obesity is an increasing problem in the USA, and research into the association between obesity and pneumonia has yielded conflicting results.

Using Department of Veterans Affairs administrative data from fiscal years 2002–2006, we examined a cohort of patients hospitalised with a discharge diagnosis of pneumonia. Body mass index was categorised as underweight (<18.5 kg·m−2), normal (18.5–24.9 kg·m−2, reference group), overweight (25–29.9 kg·m−2), obese (30–39.9 kg·m−2) and morbidly obese (≥40 kg·m−2). Our primary analyses were multi level regression models with the outcomes of 90-day mortality, intensive care unit (ICU) admission, need for mechanical ventilation and vasopressor utilisation.

The cohort comprised 18 746 subjects: 3% were underweight, 30% were normal, 36% were overweight, 27% were obese and 4% were morbidly obese. In the regression models, after adjusting for potential confounders, morbid obesity was not associated with mortality (OR 0.96, 95% CI 0.72–1.28), but obesity was associated with decreased mortality (OR 0.86, 95% CI 0.74–0.99). Neither obesity nor morbid obesity was associated with ICU admission, use of mechanical ventilation or vasopressor utilisation. Underweight patients had increased 90-day mortality (OR 1.40, 95% CI 1.14–1.73).

Although obesity is a growing health epidemic, it appears to have little impact on clinical outcomes and may reduce mortality for veterans hospitalised with pneumonia.
Transcripts with in silico predicted RNA structure are enriched everywhere in the mouse brain
Authors: Seemann Stefan E , Sunkin Susan M , Hawrylycz Michael J , Ruzzo Walter L , Gorodkin Jan
Published: September 2012

Background

Post-transcriptional control of gene expression is mostly conducted by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration with specific binding proteins and RNAs. In several well characterized cases, these RNA elements are known to form stable secondary structures. RNA secondary structures also may have major functional implications for long noncoding RNAs (lncRNAs). Recent transcriptional data has indicated the importance of lncRNAs in brain development and function. However, no methodical efforts to investigate this have been undertaken. Here, we aim to systematically analyze the potential for RNA structure in brain-expressed transcripts.

Results

By comprehensive spatial expression analysis of the adult mouse in situ hybridization data of the Allen Mouse Brain Atlas, we show that transcripts (coding as well as non-coding) associated with in silico predicted structured probes are highly and significantly enriched in almost all analyzed brain regions. Functional implications of these RNA structures and their role in the brain are discussed in detail along with specific examples. We observe that mRNAs with a structure prediction in their UTRs are enriched for binding, transport and localization gene ontology categories. In addition, after manual examination we observe agreement between RNA binding protein interaction sites near the 3’ UTR structures and correlated expression patterns.

Conclusions

Our results show a potential use for RNA structures in expressed coding as well as noncoding transcripts in the adult mouse brain, and describe the role of structured RNAs in the context of intracellular signaling pathways and regulatory networks. Based on this data we hypothesize that RNA structure is widely involved in transcriptional and translational regulatory mechanisms in the brain and ultimately plays a role in brain function.
Simultaneous copy number gains of NUPR1 and ERBB2 predicting poor prognosis in early-stage breast cancer
Authors: Jung Seung-Hyun , Lee Ahwon , Yim Seon-Hee , Hu Hae-Jin , Choe Chungyoul , Chung Yeun-Jun
Published: August 2012

Background

The full extent of chromosomal alterations and their biological implications in early breast carcinogenesis has not been well examined. In this study, we aimed to identify chromosomal alterations associated with poor prognosis in early-stage breast cancers (EBC).

Methods

A total of 145 EBCs (stage I and II) were examined in this study. We analyzed copy number alterations in a discovery set of 48 EBCs using oligoarray-comparative genomic hybridization. In addition, the recurrently altered regions (RARs) associated with poor prognosis were validated using an independent set of 97 EBCs.

Results

A total of 23 RARs were defined in the discovery set. Six were commonly detected in both stage I and II groups (> 50%), suggesting their connection with early breast tumorigenesis. There were gains on 1q21.2-q21.3, 8q24.13, 8q24.13-21, 8q24.3, and 8q24.3 and a loss on 8p23.1-p22. Among the 23 RARs, copy number gains on 16p11.2 (NUPR1) and 17q12 (ERBB2) showed a significant association with poor survival (P = 0.0186 and P = 0.0186, respectively). The patients simultaneously positive for both gains had a significantly worse prognosis (P = 0.0001). In the independent replication, the patients who were double-positive for NUPR1-ERBB2 gains also had a significantly poorer prognosis on multivariate analysis (HR = 7.31, 95% CI 2.65-20.15, P = 0.0001).

Conclusions

The simultaneous gain of NUPR1 and ERBB2 can be a significant predictor of poor prognosis in EBC. Our study will help to elucidate the molecular mechanisms underlying early-stage breast cancer tumorigenesis. This study also highlights the potential for using combinations of copy number alterations as prognosis predictors for EBC.
An uncommon case of random fire-setting behavior associated with Todd paralysis: A case report
Authors: Kanehisa Masayuki , Morinaga Katsuhiko , Kohno Hisae , Maruyama Yoshihiro , Ninomiya Taiga , Ishitobi Yoshinobu , Tanaka Yoshihiro , Tsuru Jusen , Hanada Hiroaki , Yoshikawa Tomoya , Akiyoshi Jotaro
Published: August 2012

Background

The association between fire-setting behavior and psychiatric or medical disorders remains poorly understood. Although a link between fire-setting behavior and various organic brain disorders has been established, associations between fire setting and focal brain lesions have not yet been reported. Here, we describe the case of a 24-year-old first time arsonist who suffered Todd’s paralysis prior to the onset of a bizarre and random fire-setting behavior.

Case presentation

A case of a 24-year-old man with a sudden onset of a bizarre and random fire-setting behavior is reported. The man, who had been arrested on felony arson charges, complained of difficulties concentrating and of recent memory disturbances with leg weakness. A video-EEG recording demonstrated a close relationship between the focal motor impairment and a clear-cut epileptic ictal discharge involving the bilateral motor cortical areas. The SPECT result was statistically analyzed by comparing with standard SPECT images obtained from our institute (easy Z-score imaging system; eZIS). eZIS revealed hypoperfusion in cingulate cortex, basal ganglia and hyperperfusion in frontal cortex,. A neuropsychological test battery revealed lower than normal scores for executive function, attention, and memory, consistent with frontal lobe dysfunction.

Conclusion

The fire-setting behavior and Todd’s paralysis, together with an unremarkable performance on tests measuring executive function fifteen months prior, suggested a causal relationship between this organic brain lesion and the fire-setting behavior. The case describes a rare and as yet unreported association between random, impulse-driven fire-setting behavior and damage to the brain and suggests a disconnection of frontal lobe structures as a possible pathogenic mechanism.
Unmet need for induction of labor in Africa: secondary analysis from the 2004 - 2005 WHO Global Maternal and Perinatal Health Survey (A cross-sectional survey)
Authors: Bukola Fawole , Idi Nafiou , M’Mimunya Machoki , Jean-Jose Wolomby-Molondo , Kidza Mugerwa , Isilda Neves , Faouzi Amokrane , Archana Shah , Paulo Souza Joao , Matthews Mathai , Metin Gulmezoglu
Published: August 2012

Background

Induction of labor is being increasingly used to prevent adverse outcomes in the mother and the newborn.This study assessed the prevalence of induction of labor and determinants of its use in Africa.

Methods

We performed secondary analysis of the WHO Global Survey of Maternal and Newborn Health of 2004 and 2005. The African database was analyzed to determine the use of induction of labor at the country level and indications for induction of labor. The un-met needs for specific obstetric indications and at country level were assessed. Determinants of use of induction of labor were explored with multivariate regression analysis.

Results

A total of 83,437 deliveries were recorded in the 7 participating countries. Average rate of induction was 4.4% with a range of 1.4 – 6.8%. Pre-labor rupture of membranes was the commonest indication for induction of labor. Two groups of women were identified: 2,776 women with indications had induction of labor while 7,996 women although had indications but labor was not induced.

Induction of labor was associated with reduction of stillbirths and perinatal deaths [OR – 0.34; 95% CI (0.27 – 0.43)].

Unmet need for induction of labor ranged between 66.0% and 80.2% across countries. Determinants of having an induction of labor were place of residence, duration of schooling, type of health facility and level of antenatal care.

Conclusion

Utilization of induction of labor in health facilities in Africa is very low. Improvements in social and health infrastructure are required to reverse the high unmet need for induction of labor.
The effects of extraction of pulpally involved primary teeth on weight, height and BMI in underweight Filipino children. A cluster randomized clinical trial
Authors: Monse Bella , Duijster Denise , Sheiham Aubrey , Grijalva-Eternod Carlos S , van Palenstein Helderman Wim , Hobdell Martin H
Published: August 2012

Background

Severe dental caries and the treatment thereof are reported to affect growth and well-being of young children. The objective of this study was to assess the effects of extraction of severely decayed pulpally involved primary teeth on weight and height in underweight preschool Filipino children.

Methods

Underweight preschool Filipino children with severe dental decay had their pulpally involved primary teeth extracted during a stepped wedge cluster randomized clinical trial. Day care centers were randomly divided into two groups; children from Group A day care centers received treatment as soon as practical, whereas children from Group B day care centers were treated four months after Group A. Clinical oral examinations using WHO criteria and the pufa-index were carried out. Anthropometric measurements were done on both groups immediately before treatment of Group A and at follow-up four months later. Height and weightz-scores were calculated using 2006 and 2007 WHO Growth Standards. Multilevel analysis was used to assess the effect of dental extractions on changes in anthropometric measurements after dental treatment.

Results

Data on 164 children (85 in Group A and 79 in Group B), mean age 59.9 months, were analyzed. Both groups gained weight and height during the trial period. Children in Group A significantly increased their BMI (p < 0.001), and their weight-for-age (p < 0.01) and BMI-for-agez-scores (p < 0.001) after dental treatment, whereas untreated children in Group B did not. Children in Group A had significantly more weight gain (p < 0.01) compared to untreated children in Group B. However, children in Group A had an inverse change in height gain (p < 0.001). Adjustment for the time interval between the two visits had little effect on the results.

Conclusions

The extraction of severely decayed primary teeth resulted in significant weight gain in underweight Filipino children. Untreated dental decay should be considered an important co-factor affecting child growth and should be considered when planning for interventions to improve child growth.

Trial registration

ISRCTN90779069http://www.controlled-trials.com/isrctn/isrctn_loa
Obesity does not aggravate vitrification injury in mouse embryos: a prospective study
Authors: Ma Wenhong , Yang Xing , Liang Xiaoyan
Published: August 2012

Background

Obesity is associated with poor reproductive outcomes, but few reports have examined thawed embryo transfer in obese women. Many studies have shown that increased lipid accumulation aggravates vitrification injury in porcine and bovine embryos, but oocytes of these species have high lipid contents (63 ng and 161 ng, respectively). Almost nothing is known about lipids in human oocytes except that these cells are anecdotally known to be relatively lipid poor. In this regard, human oocytes are considered to be similar to those of the mouse, which contain approximately 4 ng total lipids/oocyte. To date, no available data show the impact of obesity on vitrification in mouse embryos. The aim of this study was to establish a murine model of maternal diet-induced obesity and to characterize the effect of obesity on vitrification by investigating the survival rate and embryo developmental competence after thawing.

Methods

Prospective comparisons were performed between six–eight-cell embryos from obese and normal-weight mice and between fresh and vitrified embryos. Female C57BL/6 mice were fed standard rodent chow (normal-weight group) or a high-fat diet (obese group) for 6 weeks. The mice were mated, zygotes were collected from oviducts and cultured for 3 days, and six–eight-cell embryos were then selected to assess lipid content in fresh embryos and to evaluate differences in apoptosis, survival, and development rates in response to vitrification.

Results

In fresh embryos from obese mice, the lipid content (0.044 vs 0.030, P<0.01) and apoptosis rate (15.1% vs.9.3%, P<0.05)were significantly higher, the survival rate (83.1% vs. 93.1%, P<0.01) on day 5 was significantly lower, and embryo development was notably delayed on days 3–5 compared with the normal-weight group. After vitrification, no significant difference was found between thawed embryos from obese and normal-weight mice in apoptosis, survival, and development rates on days 4 and 5. In both groups, pre- and post-vitrification embryo apoptosis, survival, and development rates were similar.

Conclusions

This study demonstrated that differences in survival and developmental rates between embryos from obese and normal-weight mice were eliminated after vitrification. Thus, maternal obesity does not aggravate vitrification injury, but obesity alone greatly impairs pre-implantation embryo survival and development.
Epigenetic dysregulation of secreted frizzled-related proteins in myeloproliferative neoplasms complements the JAK2V617F-mutation
Authors: Bennemann Karla , Galm Oliver , Wilop Stefan , Schubert Claudia , Brümmendorf Tim H , Jost Edgar
Published: August 2012

Background

Secreted frizzled-related proteins (SFRPs) are antagonists of the Wnt signaling pathway, which plays a central role in stem cell maintenance and differentiation of stem cells and hematopoietic progenitors. Epigenetic downregulation of SFRPs by promoter hypermethylation has been described to be involved in the pathogenesis of hematopoietic malignancies. There is an association between aberrant Wnt signaling and the established cancer stem cell concept. In contrast to BCR-ABL1-positive chronic myeloid leukemia CML, BCR-ABL1-negative myeloproliferative neoplasms (Ph-MPN) are characterized by the frequent occurrence of an autoactivating mutation in the JAK2 tyrosine kinase (JAK2V617F) or other mutations in the JAK-STAT pathway. However, pathogenetic mechanisms of JAK2 mutated or unmutated Ph-MPN remain not completely understood. We determined the promoter methylation status of SFRP-1, -2, -4, and -5 in 57 MPN patient samples by methylation-specific polymerase chain reaction (PCR) (MSP). JAK2V617F was assessed by allele-specific PCR.

Results

Aberrant methylation among primary MPN samples was 4% for SFRP-1, 25% for SFRP-2, 2% for SFRP-4, and 0% for SFRP-5. Hypermethylation of SFRP-2, which was the most frequently hypermethylated gene in our study, could not be correlated to any specific MPN subtype. However, we detected a significant correlation between SFRP-2 methylation and presence of a JAK2V617F mutation (P = 0.008). None of the 10 CML samples showed any SFRP-methylation.

Conclusions

Our data indicate that epigenetic dysregulation of the Wnt signaling pathway is a common event in MPN with aberrant methylation of at least one SFRP being detected in 25% of the primary patient samples and in 30% if only accounting for Ph-MPN. A significant correlation between SFRP-2 methylation and presence of JAK2V617F in our data supports the hypothesis that epigenetic dysregulation may be a complementary mechanism to genetic aberrations. Aberrant methylation of crucial stem cell maintenance genes seems to contribute to disease pathogenesis in Ph-MPN.
The impact of saliva collection and processing methods on CRP, IgE, and Myoglobin immunoassays
Authors: Mohamed Roslinda , Campbell Jennifer‐Leigh , Cooper‐White Justin , Dimeski Goce , Punyadeera Chamindie
Published: September 2012

Background

Owing to its ease of collection, saliva is potentially the sample of choice in diagnosis. Salivary biomolecules have provided a porthole in surveying a person's health and well‐being. Our study aims were (1) to demonstrate the effects of pre‐analytical steps, collection and pre‐processing techniques on salivary protein detection and (2) to establish an indication of salivary reference intervals for 3 biomolecules of clinical interest.

Methods

Saliva samples were collected from participants (n = 25, ages 20–35 years) using the following methods: no stimulation (resting/unstimulated), mechanical, and acid stimulation. The saliva was prepared for analysis by: unprocessed, post standard centrifugation in a container without any additives, and centrifugation using Centrifugal Filter Unit (Amicon® Ultra‐0.5). AlphaLisa® assays were used to measure the levels of C‐Reactive Protein (CRP), Immunoglobin (IgE) and myoglobin in saliva samples.

Results

Saliva flow rates were lowest with the resting/drooling collection method. The lowest total protein concentration was with acid stimulation. Unstimulated and mechanically stimulated collections produced no effect on the CRP and IgE levels while myoglobin levels were highest with the unstimulated collection. Acid stimulation had a negative impact on the measured concentrations of IgE and myoglobin (except for CRP levels).

Conclusion

Mechanical stimulation was the most viable option for collecting saliva without affecting the levels of CRP and myoglobin. The processing methods had an adverse effect on the concentration of total protein as well as on CRP and IgE concentrations.
The GENCODE pseudogene resource
Authors: Pei Baikang , Sisu Cristina , Frankish Adam , Howald Cédric , Habegger Lukas , Mu Xinmeng Jasmine , Harte Rachel , Balasubramanian Suganthi , Tanzer Andrea , Diekhans Mark , Reymond Alexandre , Hubbard Tim J , Harrow Jennifer , Gerstein Mark B
Published: September 2012

Background

Pseudogenes have long been considered as nonfunctional genomic sequences. However, recent evidence suggests that many of them might have some form of biological activity, and the possibility of functionality has increased interest in their accurate annotation and integration with functional genomics data.

Results

As part of the GENCODE annotation of the human genome, we present the first genome-wide pseudogene assignment for protein-coding genes, based on both large-scale manual annotation and in silico pipelines. A key aspect of this coupled approach is that it allows us to identify pseudogenes in an unbiased fashion as well as untangle complex events through manual evaluation. We integrate the pseudogene annotations with the extensive ENCODE functional genomics information. In particular, we determine the expression level, transcription-factor and RNA polymerase II binding, and chromatin marks associated with each pseudogene. Based on their distribution, we develop simple statistical models for each type of activity, which we validate with large-scale RT-PCR-Seq experiments. Finally, we compare our pseudogenes with conservation and variation data from primate alignments and the 1000 Genomes project, producing lists of pseudogenes potentially under selection.

Conclusions

At one extreme, some pseudogenes possess conventional characteristics of functionality; these may represent genes that have recently died. On the other hand, we find interesting patterns of partial activity, which may suggest that dead genes are being resurrected as functioning non-coding RNAs. The activity data of each pseudogene are stored in an associated resource, psiDR, which will be useful for the initial identification of potentially functional pseudogenes.
Bosutinib Versus Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: Results From the BELA Trial
Authors: Cortes Jorge E. , Kim Dong-Wook , Kantarjian Hagop M. , Brümmendorf Tim H. , Dyagil Irina , Griskevicius Laimonas , Malhotra Hemant , Powell Christine , Gogat Karïn , Countouriotis Athena M. , Gambacorti-Passerini Carlo
Published: September 2012

Purpose

Bosutinib is an oral Src/Abl tyrosine kinase inhibitor. The phase III Bosutinib Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia (BELA) trial compared bosutinib with imatinib in newly diagnosed, chronic-phase chronic myeloid leukemia (CML).

Patients and Methods

A total of 502 patients were randomly assigned 1:1 to bosutinib 500 mg per day or imatinib 400 mg per day.

Results

The complete cytogenetic response (CCyR) rate at 12 months was not different for bosutinib (70%; 95% CI, 64% to 76%) versus imatinib (68%; 95% CI, 62% to 74%; two-sided P = .601); therefore, the study did not achieve its primary end point. The major molecular response (MMR) rate at 12 months was higher with bosutinib (41%; 95% CI, 35% to 47%) compared with imatinib (27%; 95% CI, 22% to 33%; two-sided P < .001). Time to CCyR and MMR was faster with bosutinib compared with imatinib (two-sided P < .001 for both). On-treatment transformation to accelerated/blast phase occurred in four patients (2%) on bosutinib compared with 10 patients (4%) on imatinib. A total of three CML-related deaths occurred on the bosutinib arm compared with eight on the imatinib arm. The safety profiles of bosutinib and imatinib were distinct; GI and liver-related events were more frequent with bosutinib, whereas neutropenia, musculoskeletal disorders, and edema were more frequent with imatinib.

Conclusion

This ongoing trial did not meet its primary end point of CCyR at 12 months, despite the observed higher MMR rate at 12 months, faster times to CCyR and MMR, fewer on-treatment transformations to accelerated/blast phase, and fewer CML-related deaths with bosutinib compared with imatinib. Each drug had a distinct safety profile.
Randomized, Phase III Study of Gemcitabine or Erlotinib Maintenance Therapy Versus Observation, With Predefined Second-Line Treatment, After Cisplatin-Gemcitabine Induction Chemotherapy in Advanced Non–Small-Cell Lung Cancer
Authors: Pérol Maurice , Chouaid Christos , Pérol David , Barlési Fabrice , Gervais Radj , Westeel Virginie , Crequit Jacky , Léna Hervé , Vergnenègre Alain , Zalcman Gérard , Monnet Isabelle , Le Caer Hervé , Fournel Pierre , Falchero Lionel , Poudenx Michel , Vaylet Fabien , Ségura-Ferlay Céline , Devouassoux-Shisheboran Mojgan , Taron Miquel , Milleron Bernard
Published: September 2012

Purpose

This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non–small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy.

Patients and Methods

Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m2 days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m2 once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS).

Results

PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P < .001) and erlotinib (median, 2.9 v 1.9 months; HR, 0.69; 95% CI, 0.54 to 0.88; log-rank P = .003) versus observation; this benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events.

Conclusion

Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.
A future for faecal haemoglobin measurements in the medical laboratory
Authors: Fraser Callum G
Published: September 2012

Guaiac-based faecal occult blood tests (gFOBT) are still used in asymptomatic population bowel screening programmes but are being replaced by faecal immunochemical tests (FIT) for haemoglobin. gFOBT have many well-documented disadvantages and there is little evidence for their use in assessment of the symptomatic. Many laboratories have eliminated gFOBT from their approved repertoires by invoking the authoritative published guidelines. Data continue to accumulate that gFOBT are obsolete. FIT are available in two formats, qualitative and quantitative, the latter having advantages that the faecal haemoglobin concentrations are measured and cut-off concentrations that stimulate further investigation can be user-defined. There is growing evidence that FIT would be useful in a spectrum of clinical settings in addition to screening. All laboratories should have FIT in their existing repertoire. For some uses, qualitative FIT would be adequate. However, much evidence has accumulated that measurements of faecal haemoglobin concentrations are beneficial for the assessment of both disease severity and the future risk of colorectal neoplasia. Interpretation requires appreciation that faecal haemoglobin concentrations are higher in men than women and rise with age. It might well be that risk scoring systems that take gender and age into account, possibly with other factors including symptoms, will benefit individuals. Laboratories should consider how quantitative faecal haemoglobin measurements could be brought into routine practice and included in their forward planning. External quality assessment is needed. Specialists in laboratory medicine are urged to play a significant role in the research and development still required to make this a truly mature investigation.
Unusual mediastinal cystic lesions with air fluid level
Authors: Chacko Binita Riya , Irodi Aparna , Jesudason Thomas , Devasahayam Jesudas , Isaac Barney
Published: August 2012

An air-fluid level within an enlarged mediastinal lymph node is unusual. We describe three patients who had mediastinal lymphadenopathy containing air-fluid levels. The differential diagnosis and approach are discussed.
Understanding Change of Direction Performance: A Technical Analysis of a 180° Aerial Catch and Turn Task
Authors: Hewit Jennifer K. , Cronin John B. , Hume Patria A.
Published: September 2012

Prior to improving the strength/power qualities associated with a movement, strength and conditioning coaches need to first understand the mechanics of the movement via some sort of movement analysis. The purpose of this study was to determine the key technical features associated with a 180° aerial change of direction (aCOD) performance. The aCOD task involved catching a suspended ball while turning 180° in the air and was recorded using high-speed video. Thirty seven netball players (5 elite, 32 sub-elite) were grouped into three categories (Superior, Average and Below Average) based on the effectiveness of their landing (a complete 180° rotation with a two-foot landing). Seven key technical features were consistently observed in the superior aCOD performances: 1) sinking into a deep hip and knee flexion (∼135°) through the final ground contact in the approach; 2) rotating about the takeoff leg prior to leaving the ground; 3) driving both arms up towards the ball, no more than shoulder width apart; 4) driving the free leg up towards the ball at takeoff; 5) following possession of the ball, rapidly rotating the head into the new direction; 6) holding the ball close to the body at chest height once possession had been made in preparation for a quick release pass; and, 7) rapid rotation of the lower body throughout the airborne phase to elicit a full 180° turn. This type of analysis provides focus for programming of the appropriate musculature and technical cues for coaching the movement of interest.
Attacking Strategies That Lead to Goal Scoring Opportunities in High Level Women's Football
Authors: Mara Jocelyn K. , Wheeler Keane W. , Lyons Keith
Published: September 2012

This study identified the attacking strategies that lead to goal scoring opportunities in women's football (soccer). All regular season games (n = 34) of the 2010/2011 W-League football competition were coded using performance analysis. Variables described the attacking strategies employed by teams and their association with goal scoring. It was shown that 24% (p < .001) of goals were the result of a cross (a distribution made from a wide area to a central area in front of goal). Further analysis demonstrated that 26% of corner kicks resulted in a shot at goal (p < .001). It was concluded that attacking through the wide areas of the field followed by a cross into a central zone inside the 18-yard box was the most effective strategy for creating goal scoring opportunities in women's football.
Empowering Professional Soccer Players in South Africa: Evaluation of Project Ithuseng
Authors: Draper Catherine E. , Forbes Jared , Taylor Gill , Lambert Mike I.
Published: September 2012

The aim of this study was to evaluate Project Ithuseng, a life skills programme for professional soccer players in South Africa (SA). Prior to implementation, a needs assessment questionnaire was administered to all players, and seven focus groups were conducted with players. A life skills questionnaire was administered to all players pre- and post-implementation (n=123). Post-implementation, seven focus groups and nine key informant interviews were conducted. Priority issues identified in the formative evaluation were planning for the future, leadership, communication, teamwork, self-confidence, taking responsibility and financial skills. Post-implementation focus groups revealed that Project Ithuseng was generally perceived as beneficial for players. The main factor influencing successful implementation was the support of team management. There was a significant difference between pre- and post-implementation scores on the life skills questionnaire (p=0.046). Through encouraging collaboration between soccer stakeholders in SA, Project Ithuseng has created a platform for future work in this area.
Triggering in Thermoacoustics
Authors: Juniper Matthew P.
Published: September 2012

Under certain conditions, the flow in a combustion chamber can sustain large amplitude oscillations even when its steady state is linearly stable. Experimental studies show that these large oscillations can sometimes be triggered by very low levels of background noise. This theoretical paper sets out the conditions that are necessary for triggering to occur. It uses a weakly nonlinear analysis to show when these conditions will be satisfied for cases where the heat release rate is a function of the acoustic velocity. The role played by non-normality is investigated. It is shown that, when a state triggers to sustained oscillations from the lowest possible energy, it exploits transient energy growth around an unstable limit cycle. The positions of these limit cycles in state space is determined by nonlinearity, but the tangled-ness of trajectories in state space is determined by non-normality. When viewed in this dynamical systems framework, triggering in thermoacoustics is seen to be directly analogous to bypass transition to turbulence in pipe flow.
Solving an Infinite Horizon Adverse Selection Model Through Finite Policy Graphs
Authors: Zhang Hao
Published: September 2012

This paper studies an infinite horizon adverse selection model with an underlying Markov information process. It introduces a graphic representation of continuation contracts and continuation payoff frontiers, namely finite policy graph, and provides an algorithm to approximate the optimal policy graph through iterations. The algorithm performs an additional step after each value iteration—replacing dominated points on the previous continuation payoff frontier by points on the new frontier and reevaluating the new frontier. This dominance-free reevaluation step accelerates the convergence of the continuation payoff frontiers. Numerical examples demonstrate the effectiveness of this algorithm and properties of the optimal contracts.
Three Ideas for the Quadratic Assignment Problem
Authors: Fischetti Matteo , Monaci Michele , Salvagnin Domenico
Published: September 2012

We address the exact solution of the famous esc instances of the quadratic assignment problem. These are extremely hard instances that remained unsolved—even allowing for a tremendous computing power—by using all previous techniques from the literature. During this challenging task we found that three ideas were particularly useful and qualified as a breakthrough for our approach. The present paper is about describing these ideas and their impact in solving esc instances. Our method was able to solve, in a matter of seconds or minutes on a single PC, all easy cases (all esc16* plus esc32e and esc32g). The three very hard instances esc32c, esc32d, and esc64a were solved in less than half an hour, in total, on a single PC. We also report the solution, in about five hours, of tai64c. By using a facility-flow splitting procedure, we were also able to solve to proven optimality, for the first time, esc32h (in about two hours) as well as “the big fish” esc128. (To our great surprise, the solution of the latter required just a few seconds on a single PC.)
Cyclophosphamide, Epirubicin, and Fluorouracil (CEF) Regimen for Breast Cancer
Authors: Moller Alexandra G. , Solimando Dominic A. , Waddell J. Aubrey
Published: August 2012

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
Effect of Computerized Provider Order Entry on Rate of Medication Errors in a Community Hospital Setting
Authors: Joy Alexis , Davis Jennifer , Cardona Jason
Published: August 2012

Purpose

Computerized provider order entry (CPOE) has been shown to reduce medication error rates by as much as 55%. The purpose of this study was to examine the effect of CPOE on the rate of medication errors at a not-for-profit community hospital.

Methods

A prospective, observational study was conducted utilizing a pharmacist-driven concurrent data collection tool to evaluate all medication errors intercepted by each pharmacist. The survey was conducted for 3 separate 1-week periods: once prior to CPOE implementation and twice post CPOE implementation. The primary outcome was the rate of medication errors reported via the pharmacist concurrent data collection tool pre and post CPOE. The secondary outcomes included the errors reported through a hospitalwide, self-reported adverse medication event system, the types of errors, and error severity.

Results

A statistically significant 41% reduction ( P < .01) in the rate of errors 3 months following CPOE implementation was observed. The secondary outcome of self-reported medication errors per adjusted patient day decreased significantly with a 25% reduction ( P < .05). The type of errors reported by the pharmacists changed notably pre and post CPOE implementation; however the severity of the reported errors did not change.

Conclusion

CPOE decreased the rate of medication errors at our community hospital 3 months post CPOE implementation. Errors were increased at 1 month post CPOE implementation, but not significantly. The types of errors changed post CPOE implementation, but distribution of error severity was unchanged.
Meaningful Use and Electronic Health Records
Authors: Fox Brent I. , Felkey Bill G.
Published: August 2012

There is rarely a day that passes when we do not see a news report about electronic health records (EHRs) and meaningful use. Of course, our professional home is in the health information technology (IT) sector, so our view may be somewhat biased. In this column, we offer a snapshot overview of EHR efforts from a national thought leader within the governmental office that is driving national health IT efforts.