bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative study of quantitative immunohistochemistry and quantum dot immunohistochemistry for mutation carrier identification in Lynch syndrome
Authors: Barrow Emma , Evans D Gareth , McMahon Ray , Hill James , Byers Richard 
Published: December 2010

AimsLynch Syndrome is caused by mutations in DNA mismatch repair (MMR) genes. Mutation carrier identification is facilitated by immunohistochemical detection of the MMR proteins MHL1 and MSH2 in tumour tissue and is desirable as colonoscopic screening reduces mortality. However, protein detection by conventional immunohistochemistry (IHC) is subjective, and quantitative techniques are required. Quantum dots (QDs) are novel fluorescent labels that enable quantitative multiplex staining. This study compared their use with quantitative 3,3′-diaminobenzidine (DAB) IHC for the diagnosis of Lynch Syndrome.MethodsTumour sections from 36 mutation carriers and six controls were obtained. These were stained with DAB on an automated platform using antibodies against MLH1 and MSH2. Multiplex QD immunofluorescent staining of the sections was performed using antibodies against MLH1, MSH2 and smooth muscle actin (SMA). Multispectral analysis of the slides was performed. The staining intensity of DAB and QDs was measured in multiple colonic crypts, and the mean intensity scores calculated. Receiver operating characteristic (ROC) curves of staining performance for the identification of mutation carriers were evaluated.ResultsFor quantitative DAB IHC, the area under the MLH1 ROC curve was 0.872 (95% CI 0.763 to 0.981), and the area under the MSH2 ROC curve was 0.832 (95% CI 0.704 to 0.960). For quantitative QD IHC, the area under the MLH1 ROC curve was 0.812 (95% CI 0.681 to 0.943), and the area under the MSH2 ROC curve was 0.598 (95% CI 0.418 to 0.777).ConclusionsDespite the advantage of QD staining to enable several markers to be measured simultaneously, it is of lower utility than DAB IHC for the identification of MMR mutation carriers. Automated DAB IHC staining and quantitative slide analysis may enable high-throughput IHC.
Relationship between pathological features, HER2 protein expression andHER2and CEP17 copy number in breast cancer: biological and methodological considerations
Authors: Lambein Kathleen , Praet Marleen , Forsyth Ramses , Van den Broecke Rudy , Braems Geert , Matthys Bart , Cocquyt Veronique , Denys Hannelore , Pauwels Patrick , Libbrecht Louis 
Published: December 2010

AimsA few reports have assessed HER2 status in breast cancer by both dual-probe fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in an unselected and consecutive fashion, but CEP17 andHER2copy number were not evaluated separately in these studies. Therefore, the aim of this study was to perform FISH testing forHER2in a large number of breast tumours, irrespective of the IHC scores, which were also determined in all cases.MethodsBoth FISH and IHC were applied to 200 tumours from 196 consecutive patients who underwent resection of primary breast cancer with the sentinel procedure and/or axillary dissection. Not only the ratio, but also meanHER2and CEP17 copy number were determined and used in statistical analyses to evaluate relationships between FISH, IHC and clinicopathological features.ResultsThe amplification status based solely on HER2 signals was 98% concordant with results of dual-probe FISH. In non-amplified tumours, the mean CEP17 andHER2copy number correlated, possibly because of cell cycling. Amplified tumours were histopathologically more aggressive than non-amplified tumours, and features of aggressiveness increased with the meanHER2copy number. In both amplified and non-amplified tumours, a gene dosage effect was observed: an increase in the meanHER2copy number was associated with a higher IHC score.ConclusionsThis working method and analysis enabled new insights to be obtained into the pathobiology of HER2 in breast cancer. The findings may be helpful in optimising the methodology of HER2 testing.
Digital mammography in a screening programme and its implications for pathology: a comparative study
Authors: Feeley Linda , Kiernan Donal , Mooney Therese , Flanagan Fidelma , Hargaden Gormlaith , Kell Malcolm , Stokes Maurice , Kennedy Margaret 
Published: December 2010

AimsMost studies comparing full-field digital mammography (FFDM) with conventional screen-film mammography (SFM) have been radiology-based. The pathological implications of FFDM have received little attention in the literature, especially in the context of screening programmes. The primary objective of this retrospective study is to compare FFDM with SFM in a population-based screening programme with regard to a number of pathological parameters.MethodsDuring the study period, 107 818 women underwent screening mammograms with almost equal numbers obtained with each technique (49.9% with SFM vs 50.1% with FFDM). We compared SFM with FFDM using the following parameters: recall rate, diagnostic core biopsy rate, cancer detection rates, B3 rate, B4 rate, preoperative diagnostic rate for malignancy, positive predictive values and tumour characteristics.ResultsThe recall rate was significantly higher with FFDM (4.21% vs 3.52%, p<0.0001). The overall cancer detection rate of 7.2 per 1000 women screened with FFDM was also significantly higher than the rate of 6.2 per 1000 women screened with SFM (p=0.04). The B3 rate in the SFM group was 1.3 per 1000 women screened versus 2.5 per 1000 women screened in the FFDM group (p<0.001). The recall rate and cancer detection rates (overall, invasive and pure ductal carcinoma in situ) were all significantly higher with FFDM for lesions presenting as microcalcifications.ConclusionsThe higher cancer detection rate with FFDM in this study was due to improved detection of microcalcifications. However, this was achieved at the cost of a higher recall rate and a higher B3 rate, indicating that overtreatment may be problematic with digital mammography.
Participatory ergonomics to reduce exposure to psychosocial and physical risk factors for low back pain and neck pain: results of a cluster randomised controlled trial
Authors: Driessen Maurice T , Proper Karin I , Anema Johannes R , Knol Dirk L , Bongers Paulien M , van der Beek Allard J 
Published: December 2010

ObjectivesThis study investigated the effectiveness of the Stay@Work participatory ergonomics programme to reduce workers′ exposure to psychosocial and physical risk factors.Methods37 departments (n=3047 workers) from four Dutch companies participated in this cluster randomised controlled trial; 19 (n=1472 workers) were randomised to an intervention group (participatory ergonomics) and 18 (n=1575 workers) to a control group (no participatory ergonomics). During a 6 h meeting guided by an ergonomist, working groups devised ergonomic measures to reduce psychosocial and physical workload and implemented them within 3 months in their departments. Data on psychosocial and physical risk factors for low back pain and neck pain were collected at baseline and after 6 months. Psychosocial risk factors were measured using the Job Content Questionnaire and physical risk factors using the Dutch Musculoskeletal Questionnaire. Intervention effects were studied using multilevel analysis.ResultsIntervention group workers significantly increased on decision latitude (0.29 points; 95% CI 0.07 to 0.52) and decision authority (0.16 points; 95% CI 0.04 to 0.28) compared to control workers. However, exposure to awkward trunk working postures significantly increased in the intervention group (OR 1.86; 95% CI 1.15 to 3.01) compared to the control group. No significant differences between the intervention and control group were found for the remaining risk factors. After 6 months, loss to follow-up was 35% in the intervention group and 29% in the control group.ConclusionParticipatory ergonomics was not effective in reducing exposure to psychosocial and physical risk factors for low back pain and neck pain among a large group of workers.Trial registrationISRCTN27472278.
Not just ‘a few wisps’: real-time measurement of tobacco smoke at entrances to office buildings
Authors: Kaufman Pamela , Zhang Bo , Bondy Susan J , Klepeis Neil , Ferrence Roberta 
Published: December 2010

IntroductionAn unintended consequence of indoor smoking restrictions is the relocation of smoking to building entrances, where non-smokers may be exposed to secondhand smoke, and smoke from outdoor areas may drift through entrances, exposing people inside. Tobacco smoke has been linked to numerous health effects in non-smokers and there is no safe level of secondhand smoke (SHS) exposure. This paper presents data on levels of tobacco smoke inside and outside entrances to office buildings.MethodsReal-time air quality monitors were used to simultaneously measure respirable particulate matter (PM2.5; air pollutant particles with a diameter of 2.5 μm or less) as a marker for tobacco smoke, outside and inside 28 entrances to office buildings in downtown Toronto, Ontario, in May and June 2008. Measurements were taken when smoking was and was not present within 9 m of entrances. Background levels of PM2.5were also measured for each session. A mixed model analysis was used to estimate levels of PM2.5, taking into account repeated measurement errors.ResultsPeak levels (10 s averages) of PM2.5were as high as 496 μg/m3when smoking was present. Mixed model analysis shows that the average outdoor PM2.5with smoking was significantly higher than the background level (p<0.0001), and significantly and positively associated with the number of lit cigarettes (p<0.0001). The average level of PM2.5with ≥5 lit cigarettes was 2.5 times greater than the average background level.ConclusionsThese findings support smoke-free policies at entrances to buildings to protect non-smokers from exposure to tobacco smoke.
Influence of modified open lung concept ventilation on the cardiovascular and pulmonary function of horses during total intravenous anaesthesia
Authors: Bringewatt T. , Hopster K. , Kästner S. B. R. , Rohn K. , Ohnesorge B. 
Published: December 2010

The influence of a modified open lung concept (mOLC) on pulmonary and cardiovascular function during total intravenous anaesthesia (TIVA) in horses was evaluated. Forty‐two warmblood horses (American Society of Anesthesiologists class 1 to 2), scheduled for elective surgery (mean [sd] weight 526 [65] kg, age 6.4 [5.4] years) were randomly divided into three groups: ventilation with mOLC, intermittent positive‐pressure ventilation (IPPV), and spontaneous breathing. Premedication (0.8 mg/kg xylazine), induction (2.2 mg/kg ketamine and 0.05 mg/kg diazepam) and maintenance of anaesthesia with TIVA (1.4 mg/kg/hour xylazine, 5.6 mg/kg/hour ketamine and 131.1 mg/kg/hour guaifenesin), with inhalation of 35 per cent oxygen in air, were identical in all horses. Heart rate, respiratory rate, mean arterial blood pressure (MAP), pH, and arterial partial pressure of oxygen (paO2) and carbon dioxide (paCO2) were evaluated. Data were collected every 10 minutes from 20 to 90 minutes anaesthesia time. Factorial analysis of variance and Tukey's post hoc test were used for statistical analysis (a=5 per cent). Horses in the mOLC‐ventilated group had an overall significantly higher paO2(16.9 [1.0] v 11.7 [1.34] v 10.5 [0.57] kPa) and lower MAP (93.1 [5.47] v 107.1 [6.99] v 101.2 [5.45] mmHg) than the IPPV and spontaneously breathing groups, respectively.
Selection on size and secondary sexual characters of the damselfly Calopteryx splendens when sympatric with the congener Calopteryx virgo
Authors: Kuitunen Katja , Kotiaho Janne S. , Luojumäki Mari , Suhonen Jukka 
Published: December 2010

Male mating success is often determined by body size or secondary sexual characters because of female mate choice or competition for females. In addition to intraspecific interactions, interspecific interactions may interfere with intraspecific selection. In this study, we investigated sexual selection on size and sexual characters of male banded demoiselle ( Calopteryx splendens (Harris, 1780)) in wild populations sympatric with the beautiful demoiselle ( Calopteryx virgo (L., 1758)). As secondary sexual characters, male C. splendens have pigmented wing spots whose size appears to be under positive selection. Male C. virgo resemble male C. splendens that have the largest wing spots, leading to interspecific male–male aggression and possibly also to heterospecific matings via mistaken species recognition. If interspecific interactions interfere with intraspecific sexual selection on wing-spot size of C. splendens, their effects should increase with the increasing relative abundance of C. virgo. Our results did not show the expected positive selection on wing-spot size in C. splendens, suggesting that interspecific interactions might interfere with sexual selection. Also, we observed no relationship between the strength of interspecific sexual selection and the relative abundance of C. virgo. However, there was a positive intraspecific density-dependent sexual selection for larger size. Although the present results are tentative, we suggest that interspecific interactions should be considered along with intraspecific selection when studies of sexual selection are performed in the wild.
Reproductive phase dependent variation in lung-associated immune system (LAIS) and expression of melatonin receptors (Mel1a and Mel1b) in the lung of the Jungle-Bush Quail (Perdicula asiatica)
Authors: Kharwar R. K. , Haldar C. 
Published: December 2010

The present study was performed to assess the variation of the lung-associated immune system (LAIS) in the Jungle-Bush Quail ( Perdicula asiatica (Latham, 1790)) during two different reproductive phases when differences in the circulatory level of hormones (melatonin and gonadal steroid) and environmental conditions were maximum. We noted high significant variation in size and number of bronchus-associated lymphoid tissue (BALT) nodules, as well as in the size and number of non-BALT nodules, during the reproductively inactive phase (RIP; December) compared with the active phase (RAP; June). We also noted high significant variation in the percent stimulation ratio of lung lymphocyte, as well as in the concentrations of plasma melatonin and melatonin receptors, during RIP compared with RAP. Testosterone level and number of macrophages in lungs were high during RAP. Thus, we suggest that the LAIS had reproductive phase dependent variation, which could be due to (i) variation in environmental factors (photoperiod, temperature, and humidity) and (ii) circulatory level of hormones (melatonin and testosterone). Because of the importance of melatonin in avian immune regulation, we assess and document the expression of melatonin receptor types Mel1a and Mel1b in the avian lung, which suggest that the lung is a target organ for melatonin and that melatonin is an immunomodulator for lung-associated immunity in birds.
Thermal ecology of Massasauga Rattlesnakes (Sistrurus catenatus) near their northern range limit
Authors: Harvey Daniel S. , Weatherhead Patrick J. 
Published: December 2010

Using populations at their northern range limits, we compared the thermoregulatory behaviour of Massasauga Rattlesnakes ( Sistrurus catenatus (Rafinesque, 1818)) to published results for Ratsnakes ( Elaphe obsoleta (Say in James, 1823)) and Northern Watersnakes ( Nerodia sipedon (L., 1758)) to test the hypothesis that given similar benefits of thermoregulation, costs associated with foraging ecology should shape thermoregulatory behaviour. More than 32 000 body temperature measurements from 34 individual snakes over 4 years were used to quantify thermoregulation by Massasauga Rattlesnakes using standard indices and a new index (%MaxE) that describes how much of the thermoregulatory potential available to a snake is realized. On average, Massasaugas were much cooler (db = 6.9 °C) than their preferred body temperature range (30–33.6 °C) but warmer (de – db = 3.3 °C) than were they not thermoregulating. Massasaugas realized more than half of their environmental potential for effective thermoregulation (%MaxE = 64%). Consistent with there being less conflict between foraging and thermoregulation for ambush predators than active foragers, Massasaugas were more effective thermoregulators than Ratsnakes or Watersnakes during the day. All three species were effective thermoregulators at night, supporting the assumption that species in a cool environment will thermoregulate when there are few competing interests.
High IGF-IR Activity in Triple-Negative Breast Cancer Cell Lines and Tumorgrafts Correlates with Sensitivity to Anti–IGF-IR Therapy
Authors: Litzenburger Beate C. , Creighton Chad J. , Tsimelzon Anna , Chan Bonita T. , Hilsenbeck Susan G. , Wang Tao , Carboni Joan M. , Gottardis Marco M. , Huang Fei , Chang Jenny C. , Lewis Michael T. , Rimawi Mothaffar F. , Lee Adrian V. 
Published: December 2010

AbstractPurpose: We previously reported an insulin-like growth factor (IGF) gene expression signature, based on genes induced or repressed by IGF-I, which correlated with poor prognosis in breast cancer. We tested whether the IGF signature was affected by anti–IGF-I receptor (IGF-IR) inhibitors and whether the IGF signature correlated with response to a dual anti–IGF-IR/insulin receptor (InsR) inhibitor, BMS-754807.Experimental Design: An IGF gene expression signature was examined in human breast tumors and cell lines and changes were noted following treatment of cell lines or xenografts with anti–IGF-IR antibodies or tyrosine kinase inhibitors. Sensitivity of cells to BMS-754807 was correlated with levels of the IGF signature. Human primary tumorgrafts were analyzed for the IGF signature and IGF-IR levels and activity, and MC1 tumorgrafts were treated with BMS-754807 and chemotherapy.Results: The IGF gene expression signature was reversed in three different models (cancer cell lines or xenografts) treated with three different anti–IGF-IR therapies. The IGF signature was present in triple-negative breast cancers (TNBC) and TNBC cell lines, which were especially sensitive to BMS-754807, and sensitivity was significantly correlated to the expression of the IGF gene signature. The TNBC primary human tumorgraft MC1 showed high levels of both expression and activity of IGF-IR and IGF gene signature score. Treatment of MC1 with BMS-754807 showed growth inhibition and, in combination with docetaxel, tumor regression occurred until no tumor was palpable. Regression was associated with reduced proliferation, increased apoptosis, and mitotic catastrophe.Conclusions: These studies provide a clear biological rationale to test anti–IGF-IR/InsR therapy in combination with chemotherapy in patients with TNBC. Clin Cancer Res; 17(8); 2314–27. ©2011 AACR.
Race, Sex, and Age Differences in Heart Failure-Related Hospitalizations in a Southern State
Authors: Husaini Baqar A. , Mensah George A. , Sawyer Douglas , Cain Van A. , Samad Zahid , Hull Pamela C. , Levine Robert S. , Sampson Uchechukwu K.A. 
Published: December 2010

Background—
Because heart failure (HF) is the final common pathway for most heart diseases, we examined its 10-year prevalence trend by race, sex, and age in Tennessee.

Methods and Results—
HF hospitalization data from the Tennessee Hospital Discharge Data System were analyzed by race, sex, and age. Rates were directly age-adjusted using the Year 2000 standard population. Adult (age 20+ years) inpatient hospitalization for primary diagnosis of HF (HFPD) increased from 4.2% in 1997 to 4.5% in 2006. Age-adjusted hospitalization for HF (per 10 000 population) rose by 11.3% (from 29.3 in 1997 to 32.6 in 2006). Parallel changes in secondary HF admissions were also noted. Age-adjusted rates were higher among blacks than whites and higher among men than women. The ratios of black to white by sex admitted with HFPD in 2006 were highest (9:1) among the youngest age categories (20 to 34 and 35 to 44 years). Furthermore, for each age category of black men below 65 years, there were higher HF admission rates than for white men in the immediate older age category. In 2006, the adjusted rate ratios for HFPD in black to white men ages 20 to 34 and 35 to 44 years were odds ratio, 4.75; 95% confidence interval, 3.29 to 6.86 and odds ratio, 5.10; 95% confidence interval, 4.15 to 6.25, respectively. Hypertension was the independent predictor of HF admissions in black men ages 20 to 34 years.

Conclusions—
The higher occurrence of HF among young adults in general, particularly among young black men, highlights the need for prevention by identifying modifiable biological and social determinants to reduce cardiovascular health disparities in this vulnerable group.
Personality disorders: Prevalence and demography at a psychiatric outpatient in North India
Authors: Gupta Swapnil , Mattoo Surendra Kumar 
Published: December 2010

Background: Even though personality disorders are common among psychiatric populations, the data from India on their prevalence and demography are sparse. Aim: To profile the prevalence and demography of personality disorders in North India. Methods: The retrospective study was based on patients attending the outpatient of a general hospital psychiatric centre in North India between June 1996 and June 2006. The specified data were collected from the case records of those receiving a primary or comorbid ICD-10 diagnosis of a personality disorder. Results: Personality disorders had a prevalence of 1.07%, with a preponderance of those aged 21–40 years (69.4%), men (64.9%), employed and students (37.3% and 32.8% respectively), unmarried (56%), graduates and undergraduates (27.6% each), and referred by the family (68.7%). The most common personality disorders were anxious-avoidant and borderline. Compared with the anxious-avoidant group, the borderline group was younger (mean age 24.44 vs 29.66 years) and had a preponderance of females (60% vs 27.1%). Conclusion: The prevalence of personality disorders among the psychiatric outpatients was low compared to most of the research literature reporting clinically diagnosed personality disorders. The differences between the borderline and anxious-avoidant personality disorder subjects were largely explained by interrelated demographic variables.
The impact of balanced hydroxylethyl starch cardiopulmonary bypass priming solution on the fibrin part of clot formation: ex vivo rotation thromboelastometry
Authors: Appelman Marly H , van Barneveld Lerau J M , Romijn Johannes W A , Vonk Alexander B A , Boer Christa 
Published: December 2010

Introduction: Balanced colloidal priming solutions are supposed to further minimize the effects of cardiopulmonary bypass (CPB) on haemostasis as compared to gelatin-based preparations. This exploratory study investigated whether clot formation, in particular the fibrin part of the clot, is less altered by a modern balanced HES solution as compared to a gelatin-based priming solution. Methods: CPB priming solutions containing 60% gelatin (Gelofusin®) or balanced HES starch (100% or 60% Tetraspan®) were mixed with blood samples from healthy volunteers and compared with respect to their impact on clotting time (CT), alpha angle, maximum clot firmness (MCF), and fibrinogen, using thromboelastometry. Results: The 100% and 60% HES priming solutions significantly increased the EXTEM CT from 66 ± 9 s to 82 ± 19 and 83 ± 13, respectively (both P<0.05 vs. baseline). The speed of solid clot formation decreased significantly for all priming solutions compared with baseline values. The INTEM MCF decreased from 59 ± 4 mm to 47 ± 4, 44 ± 4 and 43 ± 3 mm, whereas the EXTEM MCF decreased from 57 ± 4 mm to 51 ± 4, 51 ± 4 and 50 ± 4 mm after dilution with 60% gelatin, 100% HES or 60% HES priming solution, respectively (all P<0.01 vs. baseline). The priming solutions containing HES induced the largest decrease in MCF attributed to fibrinogen from 12 ± 3 mm to 4 ± 4 mm and 3 ± 2 mm (both P<0.05) for the 100% and mixed priming solution, respectively. Conclusions: Ex vivo rotation thromboelastometry did not reveal the expected preservation of coagulation parameters, in particular the fibrin part of clot formation, by a balanced HES priming solution.