bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying comorbidity in individuals with COPD: a population study
Authors: Gershon Andrea S. , Mecredy Graham C. , Guan Jun , Victor J. Charles , Goldstein Roger , To Teresa
Published: August 2014

Chronic obstructive pulmonary disease (COPD) has been associated with many types of comorbidity. We aimed to quantify the real world impact of COPD on lower respiratory tract infection, cardiovascular disease, diabetes, psychiatric disease, musculoskeletal disease and cancer, and their impact on COPD through health services.

A population study using health administrative data from Ontario, Canada, in 2008–2012 was conducted. Absolute and adjusted relative rates of ambulatory care visits, emergency department visits and hospitalisations for the comorbidities of interest in people with and without COPD were determined and compared.

Among 7 241 591 adults, 909 948 (12.6%) had COPD. Over half of all lung cancer, a third of all lower respiratory tract infection and cardiovascular disease, a quarter of all low trauma fracture, and a fifth of all psychiatric, musculoskeletal, non-lung cancer and diabetes ambulatory care visits, emergency department visits and hospitalisations in Ontario were used by people with COPD. Individuals with COPD used about five times more health services for lung cancer, and two times more health services for lower respiratory tract infections and cardiovascular disease than people without COPD.

Individuals with COPD use a disproportionate amount of health services for comorbid disease, placing significant burden on the healthcare system.
The chemokine CCL18 characterisesPseudomonasinfections in cystic fibrosis lung disease
Authors: Hector Andreas , Kröner Carolin , Carevic Melanie , Bakele Martina , Rieber Nikolaus , Riethmüller Joachim , Griese Matthias , Zissel Gernot , Hartl Dominik
Published: August 2014

Cystic fibrosis (CF) lung disease is characterised by chronicPseudomonas aeruginosainfection and leukocyte infiltration. Chemokines recruit leukocytes to sites of infection. Gene expression analysis identified the chemokine CCL18 as upregulated in CF leukocytes. We hypothesised that CCL18 characterises infection and inflammation in patients with CF lung disease.

Therefore, we quantified CCL18 protein levels in the serum and airway fluids of CF patients and healthy controls, and studied CCL18 protein production by airway cellsex vivo.

These studies demonstrated that CCL18 levels were increased in the serum and airway fluids from CF patients compared with healthy controls. Within CF patients, CCL18 levels were increased inP. aeruginosa-infected CF patients. CCL18 levels in the airways, but not in serum, correlated with severity of pulmonary obstruction in CF. Airway cells isolated fromP. aeruginosa-infected CF patients produced significantly higher amounts of CCL18 protein compared with airway cells from CF patients withoutP. aeruginosainfection or healthy controls.

Collectively, these studies show that CCL18 levels characterise chronicP. aeruginosainfection and pulmonary obstruction in patients with CF. CCL18 may, thus, serve as a potential biomarker and therapeutic target in CF lung disease.
Immobilization of peroxidase enzyme onto the porous silicon structure for enhancing its activity and stability
Authors: Sahare Padmavati , Ayala Marcela , Vazquez-Duhalt Rafael , Agrawal Vivechana
Published: August 2014

In this work, a commercial peroxidase was immobilized onto porous silicon (PS) support functionalized with 3-aminopropyldiethoxysilane (APDES) and the performance of the obtained catalytic microreactor was studied. The immobilization steps were monitored and the activity of the immobilized enzyme in the PS pores was spectrophotometrically determined. The enzyme immobilization in porous silicon has demonstrated its potential as highly efficient enzymatic reactor. The effect of a polar organic solvent (acetonitrile) and the temperature (up to 50°C) on the activity and stability of the biocatalytic microreactor were studied. After 2-h incubation in organic solvent, the microreactor retained 80% of its initial activity in contrast to the system with free soluble peroxidase that lost 95% of its activity in the same period of time. Peroxidase immobilized into the spaces of the porous silicon support would be perspective for applications in treatments for environmental security such as removal of leached dye in textile industry or in treatment of different industrial effluents. The system can be also applied in the field of biomedicine.
Intra‐observer reliability for measuring first and second toe and metatarsal protrusion distance using palpation‐based tests: a test‐retest study
Authors: Martínez‐Cepa Carmen‐Belén , Zuil‐Escobar Juan‐Carlos , Chillón‐Martínez Raquel , Jiménez‐Rejano José‐Jesús , Palomo‐Toucedo Inmaculada‐Concepción
Published: August 2014

Background

Measurement of first and second metatarsal and toe protrusion is frequently used to explain foot problems using x‐rays, osteological measurements or palpation‐based tests. Length differences could be related to the appearance of problems in the foot. A test‐retest design was conducted in order to establish the intra‐rater reliability of three palpation‐based tests.

Methods

202 feet of physical therapy students and teachers of the CEU San Pablo University of Madrid, 39 men and 62 women, were measured using three different tests. Data were analysed using SPSS version 15.0. Mean, SD and 95% CI were calculated for each variable. A normal distribution of quantitative data was assessed using the Kolmogorov‐Smirnov test. The test‐retest intra‐rater reliability was assessed using an Intraclass Correlation Coefficient (ICC). The Standard Error Mean (SEM) and the Minimal Detectable Change (MDC) were also obtained.

Results

All the ICC values showed a high degree of reliability (Test 1 = 0.97, Test 2 = 0.86 and Test 3 = 0.88) as did the SEM (Test 1 = 0.07, Test 2 = 0.10 and Test 3 = 0.11) and the MDC (Test 1 = 0.21, Test 2 = 0.30 and Test 3 = 0.31).

Conclusions

Reliability of measuring first and second metatarsal and toe protrusion using the three palpation‐based tests showed a high degree of reliability.
Risk factors for self-reported arm lymphedema among female breast cancer survivors: a prospective cohort study
Authors: Togawa Kayo , Ma Huiyan , Sullivan-Halley Jane , Neuhouser Marian L , Imayama Ikuyo , Baumgartner Kathy B , Smith Ashley Wilder , Alfano Catherine M , McTiernan Anne , Ballard-Barbash Rachel , Bernstein Leslie
Published: August 2014

Introduction

Lymphedema is a potentially debilitating condition that occurs among breast cancer survivors. This study examines the incidence of self-reported lymphedema, timing of lymphedema onset, and associations between sociodemographic, clinical and lifestyle factors and lymphedema risk across racial-ethnic groups using data from a multicenter, multiethnic prospective cohort study of breast cancer survivors, the Health, Eating, Activity and Lifestyle Study.

Methods

A total of 666 women diagnosed with breast cancer staged as in situ, localized or regional disease at ages 35 to 64 years were recruited through the Surveillance, Epidemiology, and End Results registries in New Mexico (non-Hispanic white and Hispanic white), Los Angeles County (black), and Western Washington (non-Hispanic white) and followed for a median of 10.2 years. We evaluated sociodemographic factors, breast cancer- and treatment-related factors, comorbidities, body mass index (BMI), hormonal factors, and lifestyle factors in relation to self-reported lymphedema by fitting Cox proportional hazards models, estimating hazard ratios (HR) and 95% confidence intervals (CI).

Results

Over the follow-up period, 190 women (29%) reported lymphedema. The median time from breast cancer diagnosis to onset of lymphedema was 10.5 months (range: 0.5 to 134.9 months). Factors independently associated with lymphedema were total/modified radical mastectomy (versus partial/less than total mastectomy; HR = 1.37, 95% CI: 1.01 to 1.85), chemotherapy (versus no chemotherapy; HR = 1.48, 95% CI: 1.09 to 2.02), no lymph nodes removed (versus ≥10 lymph nodes removed; HR = 0.17, 95% CI: 0.08 to 0.33), pre-diagnostic BMI ≥30 kg/m2 (versus BMI <25 kg/m2; HR = 1.59, 95% CI: 1.09 to 2.31), and hypertension (versus no hypertension; HR = 1.49, 95% CI: 1.06 to 2.10). After adjusting for demographics and breast cancer- and treatment-related factors, no significant difference in lymphedema risk was observed across racial/ethnic groups. Analyses stratified by race/ethnicity showed that hypertension and chemotherapy were lymphedema risk factors only for black women.

Conclusions

Breast cancer patients who have undergone extensive surgery or extensive lymph node dissection, or who have a higher BMI should be closely monitored for detection and treatment of lymphedema. Further studies are needed to understand the roles of chemotherapy and hypertension in the development of lymphedema.
Heterogeneity in the inter-tumor transcriptome of high risk prostate cancer
Authors: Wyatt Alexander W , Mo Fan , Wang Kendric , McConeghy Brian , Brahmbhatt Sonal , Jong Lina , Mitchell Devon M , Johnston Rebecca L , Haegert Anne , Li Estelle , Liew Janet , Yeung Jake , Shrestha Raunak , Lapuk Anna V , McPherson Andrew , Shukin Robert , Bell Robert H , Anderson Shawn , Bishop Jennifer , Hurtado-Coll Antonio , Xiao Hong , Chinnaiyan Arul M , Mehra Rohit , Lin Dong , Wang Yuzhuo , Fazli Ladan , Gleave Martin E , Volik Stanislav V , Collins Colin C
Published: August 2014

Background

Genomic analyses of hundreds of prostate tumors have defined a diverse landscape of mutations and genome rearrangements, but the transcriptomic effect of this complexity is less well understood, particularly at the individual tumor level. We selected a cohort of 25 high-risk prostate tumors, representing the lethal phenotype, and applied deep RNA-sequencing and matched whole genome sequencing, followed by detailed molecular characterization.

Results

Ten tumors were exposed to neo-adjuvant hormone therapy and expressed marked evidence of therapy response in all except one extreme case, which demonstrated early resistance via apparent neuroendocrine transdifferentiation. We observe high inter-tumor heterogeneity, including unique sets of outlier transcripts in each tumor. Interestingly, outlier expression converged on druggable cellular pathways associated with cell cycle progression, translational control or immune regulation, suggesting distinct contemporary pathway affinity and a mechanism of tumor stratification. We characterize hundreds of novel fusion transcripts, including a high frequency of ETS fusions associated with complex genome rearrangements and the disruption of tumor suppressors. Remarkably, several tumors express unique but potentially-oncogenic non-ETS fusions, which may contribute to the phenotype of individual tumors, and have significance for disease progression. Finally, one ETS-negative tumor has a striking tandem duplication genotype which appears to be highly aggressive and present at low recurrence in ETS-negative prostate cancer, suggestive of a novel molecular subtype.

Conclusions

The multitude of rare genomic and transcriptomic events detected in a high-risk tumor cohort offer novel opportunities for personalized oncology and their convergence on key pathways and functions has broad implications for precision medicine.
Evaluation of solvent effect on the extraction of phenolic compounds and antioxidant capacities from the berries: application of principal component analysis
Authors: Boeing Joana Schuelter , Barizão Érica Oliveira , e Silva Beatriz Costa , Montanher Paula Fernandes , de Cinque Almeida Vitor , Visentainer Jesuí Vergilio
Published: August 2014

Background

This study evaluated the effect of the solvent on the extraction of antioxidant compounds from black mulberry (Morus nigra), blackberry (Rubus ulmifolius) and strawberry (Fragariaxananassa). Different extracts of each berry were evaluated from the determination of total phenolic content, anthocyanin content and antioxidant capacity, and data were applied to the principal component analysis (PCA) to gain an overview of the effect of the solvent in extraction method.

Results

For all the berries analyzed, acetone/water (70/30, v/v) solvent mixture was more efficient solvent in the extracting of phenolic compounds, and methanol/water/acetic acid (70/29.5/0.5, v/v/v) showed the best values for anthocyanin content. Mixtures of ethanol/water (50/50, v/v), acetone water/acetic acid (70/29.5/0.5, v/v/v) and acetone/water (50/50, v/v) presented the highest antioxidant capacities for black mulberries, blackberries and strawberries, respectively.

Conclusion

Antioxidants extractions are extremely affected by the solvent combination used. In addition, the obtained extracts with the organic solvent-water mixtures were distinguished from the extracts obtained with pure organic solvents, through the PCA analysis.
Treatment patterns in psoriatic arthritis patients newly initiated on oral nonbiologic or biologic disease-modifying antirheumatic drugs
Authors: Zhang Huabin F , Gauthier Geneviève , Hiscock Robert , Curtis Jeffrey R
Published: August 2014

Introduction

This study aimed to describe treatment changes (discontinuation, switching, and therapy add-on) following the initiation of biologic or nonbiologic oral disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis (PsA) patients.

Methods

Adult patients with ≥2 PsA diagnoses from physician office visits, initiated on a biologic or nonbiologic oral DMARD, were selected from the Truven Health Analytics MarketScan® Research Database (2005 to 2009). Patients were required to have continuous insurance coverage ≥6 months prior to and ≥12 months post index date (first prescription fill date). Treatment discontinuation, treatment switch, and therapy add-on were captured over the 1 year period following the index date. Treatment changes were described separately for patients initiated on nonbiologic and biologic DMARDs.

Results

A total of 1,698 and 3,263 patients were initiated on an oral nonbiologic DMARD and biologic DMARD respectively. For patients initiated on nonbiologic DMARDs, 69% had ≥1 therapy change over the 12 month study period (median time 85 days). Among patients who had a therapy change, 83% discontinued, 29% switched therapy (64% switched to a biologic DMARD), and 25% had a therapy add-on (76% added-on with a biologic DMARD). For patients initiated on a biologic DMARD, 46% had ≥1 therapy change (median time 110 days). Among patients who had a therapy change, 100% discontinued, 25% switched therapy (92% switched to another biologic DMARD), and 7% had a therapy add-on with a nonbiologic DMARD.

Conclusion

This study suggests that PsA patients newly initiated on a nonbiologic/biologic DMARD do not remain on the index treatment for a long period of time. A better understanding of factors related to these early treatment changes in PsA patients is needed.
Clinical value of whole-body PET/CT in patients with active rheumatic diseases
Authors: Yamashita Hiroyuki , Kubota Kazuo , Mimori Akio
Published: August 2014

Advanced imaging techniques may enable early diagnosis and monitoring of therapy in various rheumatic diseases. To prevent irreversible tissue damage, inflammatory rheumatic disease must be diagnosed and treated in pre-clinical stages, requiring highly sensitive detection techniques. Positron emission tomography (PET) provides highly sensitive, quantitative imaging at a molecular level, revealing the important pathophysiological processes underlying inflammation. This review provides an overview of the current utility of 18 F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in patients with active rheumatic diseases such as rheumatoid arthritis, spondyloarthritis, polymyalgia rheumatica, adult-onset Still's disease, relapsing polychondritis, immunoglobulin G4-related disease, large-vessel vasculitis, Wegener's granulomatosis, polymyositis, and dermatomyositis. We also discuss the role of FDG-PET/CT in the diagnosis and monitoring of these diseases.
Application of insect songs in monitoring population density level of Locusta migratoria migratoria (Orthoptera: Acrididae)
Authors: Wang Yinliang , Huang Qiuchen , Zhang Xue , Ren Bingzhong
Published: August 2014

Background

The locustsLocusta migratoria migratoria(Orthoptera: Acrididae) is the most destructive agricultural pests worldwide, the population and distribution ofL. migratoria migratoriagrowing rapidly in recent years. It is crucial to find a green, economical way to monitor this insect's population for effective control tactics. In this study, acoustic samples were recorded and analyzed under three different density levels of Asian migratory locustL. migratoria migratoria.

Results

The results showed that the songs ofL. migratoria migratoriahad a very stable acoustic feature in time domains; then, we used duration of pulse as a tool for identifying and counting the numbers of pulse to classify the population size. After removing the background noises, an automatic density classification and monitoring system was established based on the backpropagation (BP) neural network. The field sample test showed that the accuracy of the density level recognition reached 96.67%.

Conclusions

The results indicated that the calling songs of insects could be an effective character to distinguish population density level of locust plagues, and it could be potentially used as a green and environmental protection solution in monitoring the dynamics of locust plagues and other acoustic agriculture pests.
Dynamic time warping — An improved method for 4D and tomography time shift estimation?
Authors: Venstad Jon Marius
Published: August 2014

Time shift estimation is a key issue in many areas of seismic exploration such as time-lapse studies and traveltime tomography. Automated estimation is useful because it enables applications such as time strain analysis and automated velocity model building. A commonly used automated estimation algorithm is the windowed crosscorrelation. Unfortunately, this method can be inaccurate in areas where time shifts vary significantly over short intervals. Algorithms based on mismatch minimization have been proposed to remedy this problem. All the mentioned methods suffer from cycle skipping in the face of large time shifts. I, therefore, used the dynamic time warping (DTW) algorithm as an alternative method to estimate time shifts. I claimed the time shift estimates produced by DTW are of higher quality than those produced by the previous methods, especially with regard to the cycle-skipping problem. I found that DTW always is able to perfectly restore time shifts applied to traces when the changes are purely temporal. I investigated its accuracy when amplitude changes are present, and found that the algorithm is well suited for time-lapse analysis. Finally, we determined that DTW is resilient against cycle-skipping errors, in the presence of large time shifts and with significant changes in the data, and thus a candidate for use in automated velocity model-building methods, such as waveform tomography or full-waveform inversion.
Migration of primaries and multiples using an imaging condition for amplitude-normalized separated wavefields
Authors: Ordoñez Alba , Söllner Walter , Klüver Tilman , Gelius Leiv J.
Published: August 2014

Migration of primary and multiple reflections leads to enhanced subsurface illumination and to increased image resolution. A joint migration approach using the complete wavefield requires properly imaged primaries and multiples of all orders. In recent works, primaries and multiples have therefore been imaged separately, using the upgoing and downgoing pressure wavefields obtained by decomposing dual-sensor streamer data. The matches between the corresponding depth images are still not found to be sufficiently accurate, so new and more appropriate imaging conditions need to be found. We reviewed the classical imaging approach used in one-way wave-equation migration, with the aim of extending it for simultaneous migration of primaries and all orders of multiples. Based on Rayleigh’s reciprocity theorem and well-known theoretical developments, we derived a new imaging condition described in terms of the upgoing pressure wavefield and a filtered version of the downgoing vertical-velocity wavefield. To evaluate the efficiency of this new imaging approach, primaries and multiples were separately migrated using synthetic and real data examples. These results were compared to those obtained using a conventional imaging condition. We found that the use of the new imaging condition led to a better match between the depth images and spectra of the migrated primaries and migrated multiples.
Childhood family income, adolescent violent criminality and substance misuse: quasi-experimental total population study
Authors: Sariaslan Amir , Larsson Henrik , D'Onofrio Brian , Långström Niklas , Lichtenstein Paul
Published: August 2014

Background

Low socioeconomic status in childhood is a well-known predictor of subsequent criminal and substance misuse behaviours but the causal mechanisms are questioned.

Aims

To investigate whether childhood family income predicts subsequent violent criminality and substance misuse and whether the associations are in turn explained by unobserved familial risk factors.

Method

Nationwide Swedish quasi-experimental, family-based study following cohorts born 1989–1993 (ntotal = 526 167, ncousins = 262 267, nsiblings = 216 424) between the ages of 15 and 21 years.

Results

Children of parents in the lowest income quintile experienced a seven-fold increased hazard rate (HR) of being convicted of violent criminality compared with peers in the highest quintile (HR = 6.78, 95% CI 6.23–7.38). This association was entirely accounted for by unobserved familial risk factors (HR = 0.95, 95% CI 0.44–2.03). Similar pattern of effects was found for substance misuse.

Conclusions

There were no associations between childhood family income and subsequent violent criminality and substance misuse once we had adjusted for unobserved familial risk factors.
White matter integrity and late-life depression in community-dwelling individuals: diffusion tensor imaging study using tract-based spatial statistics
Authors: Reppermund Simone , Zhuang Lin , Wen Wei , Slavin Melissa J. , Trollor Julian N. , Brodaty Henry , Sachdev Perminder S.
Published: August 2014

Background

Late-life depression has been associated with white matter changes in studies using the regions of interest approach.

Aims

To investigate the cross-sectional and longitudinal relationship between white matter integrity and depression in community-dwelling individuals using diffusion tensor imaging with tract-based spatial statistics.

Method

The sample comprised 381 participants aged between 72 and 92 years who were assessed twice within 2 years. Depressive symptoms were measured with the Geriatric Depression Scale. Tract-based spatial statistics were applied to investigate white matter integrity in currently depressed v. non-depressed elderly people and in those with a history of depression v. no history of depression. The relationship between white matter integrity and development of depressive symptoms after 2 years were analysed with logistic regression.

Results

Individuals with current depression had widespread white matter integrity reduction compared with non-depressed elderly people. Significant fractional anisotropy reductions were found in 45 brain areas with the most notable findings in the frontal lobe, association and projection fibres. A history of depression was not associated with reduced fractional anisotropy. White matter changes in the superior frontal gyrus, posterior thalamic radiation, superior longitudinal fasciculus and in the body of corpus callosum predicted depression at follow-up.

Conclusions

Reduced white matter integrity is associated with late-life depression and predicts future depressive symptoms whereas a history of depression is not related to white matter changes. Disruption to white matter integrity may be a biomarker to predict late-life depression.
Prostaglandin D2 acts through the Dp2 receptor to influence male germ cell differentiation in the foetal mouse testis
Authors: Moniot Brigitte , Ujjan Safdar , Champagne Julien , Hirai Hiroyuki , Aritake Kosuke , Nagata Kinya , Dubois Emeric , Nidelet Sabine , Nakamura Masataka , Urade Yoshihiro , Poulat Francis , Boizet-Bonhoure Brigitte
Published: August 2014

Through intercellular signalling, the somatic compartment of the foetal testis is able to program primordial germ cells to undergo spermatogenesis. Fibroblast growth factor 9 and several members of the transforming growth factor β superfamily are involved in this process in the foetal testis, counteracting the induction of meiosis by retinoic acid and activating germinal mitotic arrest. Here, using in vitro and in vivo approaches, we show that prostaglandin D2 (PGD2), which is produced through both L-Pgds and H-Pgds enzymatic activities in the somatic and germ cell compartments of the foetal testis, plays a role in mitotic arrest in male germ cells by activating the expression and nuclear localization of the CDK inhibitor p21Cip1 and by repressing pluripotency markers. We show that PGD2 acts through its Dp2 receptor, at least in part through direct effects in germ cells, and contributes to the proper differentiation of male germ cells through the upregulation of the master gene Nanos2. Our data identify PGD2 signalling as an early pathway that acts in both paracrine and autocrine manners, and contributes to the differentiation of germ cells in the foetal testis.
Indispensable pre-mitotic endocycles promote aneuploidy in the Drosophila rectum
Authors: Schoenfelder Kevin P. , Montague Ruth A. , Paramore Sarah V. , Lennox Ashley L. , Mahowald Anthony P. , Fox Donald T.
Published: August 2014

The endocycle is a modified cell cycle that lacks M phase. Endocycles are well known for enabling continued growth of post-mitotic tissues. By contrast, we discovered pre-mitotic endocycles in precursors of Drosophila rectal papillae (papillar cells). Unlike all known proliferative Drosophila adult precursors, papillar cells endocycle before dividing. Furthermore, unlike diploid mitotic divisions, these polyploid papillar divisions are frequently error prone, suggesting papillar structures may accumulate long-term aneuploidy. Here, we demonstrate an indispensable requirement for pre-mitotic endocycles during papillar development and also demonstrate that such cycles seed papillar aneuploidy. We find blocking pre-mitotic endocycles disrupts papillar morphogenesis and causes organismal lethality under high-salt dietary stress. We further show that pre-mitotic endocycles differ from post-mitotic endocycles, as we find only the M-phase-capable polyploid cells of the papillae and female germline can retain centrioles. In papillae, this centriole retention contributes to aneuploidy, as centrioles amplify during papillar endocycles, causing multipolar anaphase. Such aneuploidy is well tolerated in papillae, as it does not significantly impair cell viability, organ formation or organ function. Together, our results demonstrate that pre-mitotic endocycles can enable specific organ construction and are a mechanism that promotes highly tolerated aneuploidy.
SirT1 is required in the male germ cell for differentiation and fecundity in mice
Authors: Bell Eric L. , Nagamori Ippei , Williams Eric O. , Del Rosario Amanda M. , Bryson Bryan D. , Watson Nicki , White Forest M. , Sassone-Corsi Paolo , Guarente Leonard
Published: August 2014

Sirtuins are NAD+-dependent deacylases that regulate numerous biological processes in response to the environment. SirT1 is the mammalian ortholog of yeast Sir2, and is involved in many metabolic pathways in somatic tissues. Whole body deletion of SirT1 alters reproductive function in oocytes and the testes, in part caused by defects in central neuro-endocrine control. To study the function of SirT1 specifically in the male germ line, we deleted this sirtuin in male germ cells and found that mutant mice had smaller testes, a delay in differentiation of pre-meiotic germ cells, decreased spermatozoa number, an increased proportion of abnormal spermatozoa and reduced fertility. At the molecular level, mutants do not have the characteristic increase in acetylation of histone H4 at residues K5, K8 and K12 during spermiogenesis and demonstrate corresponding defects in the histone to protamine transition. Our findings thus reveal a germ cell-autonomous role of SirT1 in spermatogenesis.
Development of hepatocellular adenomas and carcinomas in mice with liver-specific G6Pase-α deficiency
Authors: Resaz Roberta , Vanni Cristina , Segalerba Daniela , Sementa Angela R. , Mastracci Luca , Grillo Federica , Murgia Daniele , Bosco Maria Carla , Chou Janice Y. , Barbieri Ottavia , Varesio Luigi , Eva Alessandra
Published: August 2014

Glycogen storage disease type 1a (GSD-1a) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α), and is characterized by impaired glucose homeostasis and a high risk of developing hepatocellular adenomas (HCAs). A globally G6Pase-α-deficient (G6pc−/−) mouse model that shows pathological features similar to those of humans with GSD-1a has been developed. These mice show a very severe phenotype of disturbed glucose homeostasis and rarely live beyond weaning. We generated liver-specific G6Pase-α-deficient (LS‑G6pc−/−) mice as an alternative animal model for studying the long-term pathophysiology of the liver and the potential treatment strategies, such as cell therapy. LS‑G6pc−/− mice were viable and exhibited normal glucose profiles in the fed state, but showed significantly lower blood glucose levels than their control littermates after 6 hours of fasting. LS‑G6pc−/− mice developed hepatomegaly with glycogen accumulation and hepatic steatosis, and progressive hepatic degeneration. Ninety percent of the mice analyzed developed amyloidosis by 12 months of age. Finally, 25% of the mice sacrificed at age 10–20 months showed the presence of multiple HCAs and in one case late development of hepatocellular carcinoma (HCC). In conclusion, LS‑G6pc−/− mice manifest hepatic symptoms similar to those of human GSD-1a and, therefore, represent a valid model to evaluate long-term liver pathogenesis of GSD-1a.
Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus
Authors: Crampton Steve P. , Morawski Peter A. , Bolland Silvia
Published: August 2014

Systemic lupus erythematosus (SLE) represents a challenging autoimmune disease from a clinical perspective because of its varied forms of presentation. Although broad-spectrum steroids remain the standard treatment for SLE, they have many side effects and only provide temporary relief from the symptoms of the disease. Thus, gaining a deeper understanding of the genetic traits and biological pathways that confer susceptibility to SLE will help in the design of more targeted and effective therapeutics. Both human genome-wide association studies (GWAS) and investigations using a variety of mouse models of SLE have been valuable for the identification of the genes and pathways involved in pathogenesis. In this Review, we link human susceptibility genes for SLE with biological pathways characterized in mouse models of lupus, and discuss how the mechanistic insights gained could advance drug discovery for the disease.
Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo
Authors: Vlaming Hanneke , van Welsem Tibor , de Graaf Erik L , Ontoso David , Altelaar AF Maarten , San‐Segundo Pedro A , Heck Albert JR , van Leeuwen Fred
Published: August 2014

Histone H2B ubiquitination is a dynamic modification that promotes methylation of histone H3K79 and H3K4. This crosstalk is important for the DNA damage response and has been implicated in cancer. Here, we show that in engineered yeast strains, ubiquitins tethered to every nucleosome promote H3K79 and H3K4 methylation from a proximal as well as a more distal site, but only if in a correct orientation. This plasticity indicates that the exact location of the attachment site, the native ubiquitin‐lysine linkage and ubiquitination cycles are not critical for trans‐histone crosstalk in vivo. The flexibility in crosstalk also indicates that other ubiquitination events may promote H3 methylation.
Age-Specific Changes in Intrinsic Breast Cancer Subtypes: A Focus on Older Women
Authors: Jenkins Emily O. , Deal Allison M. , Anders Carey K. , Prat Aleix , Perou Charles M. , Carey Lisa A. , Muss Hyman B.
Published: August 2014

Purpose.

Breast cancer (BC) is a disease of aging and the number of older BC patients in the U.S. is rising. Immunohistochemical data show that with increasing age, the incidence of hormone receptor-positive tumors increases, whereas the incidence of triple-negative tumors decreases. Few data exist on the frequency of molecular subtypes in older women. Here, we characterize the incidence and outcomes of BC patients by molecular subtypes and age.

Patients and Methods.

Data from 3,947 patients were pooled from publicly available clinical and gene expression microarray data sets. The PAM50 algorithm was used to classify tumors into five BC intrinsic subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like. The association of age and subtype with recurrence-free survival (RFS), overall survival, and disease-specific survival (DSS) was assessed.

Results.

The incidence of luminal (A, B, and A+B) tumors increased with age (p < .01, p < .0001, and p < .0001, respectively), whereas the percentage of basal-like tumors decreased (p < .0001). Among patients 70 years and older, luminal B, HER2-enriched, and basal-like tumors were found at a frequency of 32%, 11%, and 9%, respectively. In older women, luminal subtypes had better outcomes than basal-like and HER2-enriched subtypes. After controlling for subtype, treatment, tumor size, nodal status, and grade, increasing age had no impact on RFS or DSS.

Conclusion.

More favorable BC subtypes increase with age, but older patients still have a substantial percentage of high-risk tumor subtypes. After accounting for tumor subtypes, age at diagnosis is not an independent prognostic factor for outcome.
Modeling elephant‐mediated cascading effects of water point closure
Authors: Hilbers Jelle P. , van Langevelde Frank , Prins Herbert H. T. , Grant C. C. , Peel Mike J. S. , Coughenour Michael B. , de Knegt Henrik J. , Slotow Rob , Smit Izak P. J. , Kiker Greg A. , Boer Willem F. de
Published: August 2014

Wildlife management to reduce the impact of wildlife on their habitat can be done in several ways, among which removing animals (by either culling or translocation) is most often used. There are, however, alternative ways to control wildlife densities, such as opening or closing water points. The effects of these alternatives are poorly studied. In this paper, we focus on manipulating large herbivores through the closure of water points (WPs). Removal of artificial WPs has been suggested in order to change the distribution of African elephants, which occur in high densities in national parks in Southern Africa and are thought to have a destructive effect on the vegetation. Here, we modeled the long‐term effects of different scenarios of WP closure on the spatial distribution of elephants, and consequential effects on the vegetation and other herbivores in Kruger National Park, South Africa. Using a dynamic ecosystem model, SAVANNA, scenarios were evaluated that varied in availability of artificial WPs; levels of natural water; and elephant densities. Our modeling results showed that elephants can indirectly negatively affect the distributions of meso‐mixed feeders, meso‐browsers, and some meso‐grazers under wet conditions. The closure of artificial WPs hardly had any effect during these natural wet conditions. Under dry conditions, the spatial distribution of both elephant bulls and cows changed when the availability of artificial water was severely reduced in the model. These changes in spatial distribution triggered changes in the spatial availability of woody biomass over the simulation period of 80 years, and this led to changes in the rest of the herbivore community, resulting in increased densities of all herbivores, except for giraffe and steenbok, in areas close to rivers. The spatial distributions of elephant bulls and cows showed to be less affected by the closure of WPs than most of the other herbivore species. Our study contributes to ecologically informed decisions in wildlife management. The results from this modeling exercise imply that long‐term effects of this intervention strategy should always be investigated at an ecosystem scale.
Determining Ground Penetrating Radar Amplitude Thresholds for the Corrosion State of Reinforced Concrete Bridge Decks
Authors: Martino Nicole , Maser Ken , Birken Ralf , Wang Ming
Published: August 2014

The most expensive part to maintain throughout the lifespan of a reinforced concrete bridge is the deck, largely because rehabilitation occurs after degradation is visible on a surface. However, the mechanisms that are the cause of deterioration, such as reinforcing bar corrosion, are initiated long before damage is detected via visual inspection. If rebar corrosion can be detected in its early stages, before severe deterioration has resulted, maintenance costs can be significantly reduced and the life cycle extended.

Recent studies have shown that ground penetrating radar (GPR) rebar reflection amplitude attenuation correlates with active corrosion in reinforced concrete bridge decks. A significant advantage of GPR over other non-destructive evaluation (NDE) methods is its ability to be operated at highway speeds so that traffic is not disrupted. However, a well-defined GPR amplitude threshold allowing the operator to distinguish non-corroded from corroded areas of the deck has yet to be established. Because reinforcing steel corrosion is the most predominant cause of bridge deck deterioration, this research seeks to quantify the thresholds relating GPR signal amplitudes and rebar corrosion.

One bridge deck removed from service, seventeen artificially corroded slabs, and one in-service bridge deck were analyzed using GPR and half-cell potential (HCP), which measures the amount of active corrosion and is currently considered the standard NDE method. A significant correlation between these two methods was found for each case. To systematically determine a threshold for the GPR so that deteriorated areas of the deck can be identified, receiver operating characteristic (ROC) curves were utilized. With an accuracy of over 87% for each scenario, this method clearly demonstrates the use of GPR for distinguishing corrosion in bridge decks.
Comparison of Reduced and Conventional Two-Phase Flash Calculations
Authors: Gorucu S.E.. E. , Johns R.T.. T.
Published: August 2014

Phase-equilibrium calculations become computationally intensive in compositional simulation as the number of components and phases increases. Reduced methods were developed to address this problem, where the binary-interaction-parameter (BIP) matrix is approximated either by spectral decomposition (SD), as performed by Hendriks and van Bergen (1992), or with the two-parameter BIP formula of Li and Johns (2006). Several authors have recently stated that the SD method—and by reference all reduced methods—is not as fast as previously reported in the literature. In this paper we present the first study that compares all eight reduced and conventional methods published to date by use of optimized code and compilers.

The results show that the SD method and its variants are not as fast as other reduced methods, and can be slower than the conventional approach when fewer than 10 components are used. These conclusions confirm the findings of recently published papers. The reason for the slow speed is the requirement that the code must allow for a variable number of eigenvalues. We show that the reduced method of Li and Johns (2006) and its variants, however, are faster because the number of reduced parameters is fixed to six, which is independent of the number of components. Speed up in flash calculations for their formula is achieved for all fluids studied when more than six components are used. For example, for 10-component fluids, a speed up of 2–3 in the computational time for Newton-Raphson (NR) iterations is obtained compared with the conventional method modeled after minimization of Gibbs energy. The reduced method modeled after the linearized approach of Nichita and Graciaa (2011), which uses the two-parameter BIP formula of Li and Johns (2006), is also demonstrated to have a significantly larger radius of convergence than other reduced and conventional methods for five fluids studied.
The Lifetime Cost of Diabetes and Its Implications for Diabetes Prevention
Authors: Zhuo Xiaohui , Zhang Ping , Barker Lawrence , Albright Ann , Thompson Theodore J. , Gregg Edward
Published: August 2014

OBJECTIVE

To assess the cost implications of diabetes prevention, it is important to know the lifetime medical cost of people with diabetes relative to those without. We derived such estimates using data representative of the U.S. national population.

RESEARCH DESIGN AND METHODS

We aggregated annual medical expenditures from the age of diabetes diagnosis to death to determine lifetime medical expenditure. Annual medical expenditures were estimated by sex, age at diagnosis, and diabetes duration using data from 2006–2009 Medical Expenditure Panel Surveys, which were linked to data from 2005–2008 National Health Interview Surveys. We combined survival data from published studies with the estimated annual expenditures to calculate lifetime spending. We then compared lifetime spending for people with diabetes with that for those without diabetes. Future spending was discounted at 3% annually.

RESULTS

The discounted excess lifetime medical spending for people with diabetes was $124,600 ($211,400 if not discounted), $91,200 ($135,600), $53,800 ($70,200), and $35,900 ($43,900) when diagnosed with diabetes at ages 40, 50, 60, and 65 years, respectively. Younger age at diagnosis and female sex were associated with higher levels of lifetime excess medical spending attributed to diabetes.

CONCLUSIONS

Having diabetes is associated with substantially higher lifetime medical expenditures despite being associated with reduced life expectancy. If prevention costs can be kept sufficiently low, diabetes prevention may lead to a reduction in long-term medical costs.
“I’m Not Going to Be, Like, for the AP”
Authors: Kanno Yasuko , Kangas Sara E. N.
Published: August 2014

Advancement to postsecondary education for English language learners (ELLs) can be seriously constrained by a lack of academic preparation during high school. Currently, ELLs lag behind their non-ELL peers in their level of access to advanced college-preparatory courses. Through a qualitative case study of ELL education at a large public high school, we examine the educational practices that result in ELLs’ restricted curricular choices. The findings expose the way in which ELLs’ chances for rigorous academic preparation are systematically reduced and point to the importance of providing ELLs with high-level academic curriculum while also supplying linguistic scaffolding that makes such learning possible.
Improved representation of East Antarctic surface mass balance in a regional atmospheric climate model
Authors: Van Wessem J.M. , Reijmer C.H. , Morlighem M. , Mouginot J. , Rignot E. , Medley B. , Joughin I. , Wouters B. , Depoorter M.A. , Bamber J.L. , Lenaerts J.T.M. , Van De Berg W.J. , Van Den Broeke M.R. , Van Meijgaard E.
Published: August 2014

This study evaluates the impact of a recent upgrade in the physics package of the regional atmospheric climate model RACMO2 on the simulated surface mass balance (SMB) of the Antarctic ice sheet. The modelled SMB increases, in particular over the grounded ice sheet of East Antarctica (+44 Gt a–1), with a small change in West Antarctica. This mainly results from an increase in precipitation, which is explained by changes in the cloud microphysics, including a new parameterization for ice cloud supersaturation, and changes in large-scale circulation patterns, which alter topographically forced precipitation. The spatial changes in SMB are evaluated using 3234 in situ SMB observations and ice-balance velocities, and the temporal variability using GRACE satellite retrievals. The in situ observations and balance velocities show a clear improvement of the spatial representation of the SMB in the interior of East Antarctica, which has become considerably wetter. No improvements are seen for West Antarctica and the coastal regions. A comparison of model SMB temporal variability with GRACE satellite retrievals shows no significant change in performance.
High level gentamicin resistance and susceptibility to Vancomycin in enterococci in a tertiary care hospital of Dhaka City
Authors: Tamanna Shakila , Barai Lovely , Ahmed AA , Haq J Ashraful
Published: August 2014

Vancomycin and high level gentamicin resistant enterococci detection is important for effective treatment and control of nosocomial infection. The present study was undertaken to determine the species distribution of Enterococcus and the rate of vancomycin and high level gentamicin resistant enterococci (HLGRE) in clinical samples in a tertiary care hospital of Dhaka city. Enterococci were identified to species level by standard biochemical and serological methods. Their susceptibilities to antibiotics were determined by disc diffusion method according to CLSI guideline. Minimum inhibitory concentration (MIC) of vancomycin and gentamicin were determined by agar dilution method. The study was conducted from July 2009 to February 2010. Among 80 isolates, 95% and 5% were identified as Enterococcus faecalis and Enterococcus faecium respectively. Out of 80 isolates 72 (90%) were sensitive and 8 (10%) were intermediate resistant to vancomycin (30?g) by disc diffusion method, but all isolates were susceptible by agar dilution MIC method. Out of 80 enterococci, 37 (46.25%) showed high level resistance to gentamicin (MIC: > 500 ?g/ml) by MIC method but, initially six of which showed sensitive result to gentamicin by disc diffusion method using 120 ?g disc. The study indicated high prevalence of HLGRE in our hospital population. MIC method was more accurate in detecting high level gentamycin resistant enterococci compared to disc diffusion method with 120 ?g gentamicin disc. However, none of the enterococcal strains showed resistance to vancomycin. HLGRE should be monitored regularly in clinical samples as it is difficult to treat. DOI: http://dx.doi.org/10.3329/imcj.v7i2.20103 Ibrahim Med. Coll. J. 2013; 7(2): 28-31