bluuebunny/crossref_metadata_2025 huggingface dataset:
DESEJO DE LUZ: O CRISTIANISMO E O SURGIMENTO DA FILOSOFIA MODERNA EM LUDWIG FEUERBACH
Authors: Figueiredo Chrysantho
Published: April 2015

Este trabalho é uma resenha da introdução do livro de Ludwig Feuerbach Geshichte der Neuern Philosophie von Bacon bis Spinoza. O texto original é em alemão; a resenha, em português. Apresentamos, entretanto, em anexo, a tradução do texto, também inédita e original. Em A Essência do Cristianismo, de 1841, Feuerbach apresenta de maneira mais acabada sua versão do humanismo radical que entusiasmou os jovens hegelianos de sua geração. Entretanto, é entre 1833 e 1838 que Feuerbach formula seu próprio ponto de vista filosófico a partir da crítica sistemática dos principais sistemas filosóficos da modernidade. História da Filosofia Moderna de Bacon a Spinoza, obra de 1833, é a primeira das obras histórico-filosóficas de Feuerbach que, além da crítica aos filósofos apresentados no próprio título da obra, traz também a visão singular feuerbachiana da história como um todo, mostrando como a filosofia moderna surge das contradições inerentes ao espírito religioso cristão.
EXPEDIENTE
Authors: Editorial Team Equipe Editorial /
Published: April 2015

Expediente
Nitrate reductase activity and yield of dry mass and protein content in cucumber seedlings supplied with nitrates and ammonium
Authors: Buczek J. , Burzyński M.
Published: April 2015

The presence of NH4+ ions in a nutrient solution containing NH4NO3 with the K+ ions removed, caused an inhibition of nitrate reductase (NR) activity in cucumber leaves. The lack of K+ in a NaNO3 medium also decreased the NR activity. Addition of K+ to these media suppressed the inhibitory effect of NH4+ and enhanced the NR activity in the leaves of plants growing in NaNO3 nutrient solution. The results suggest that K+ is essential for NO3- reduction, Na+ is less effective in this process, whereas NH4+ ions markedly inhibit NO3- reduction. The protein content and increment of dry mass of cucumber plants grown 10 days with NH4-N as the sole source of nitrogen was significantly lower as compared with NO3-N supplied plants feed with plants feed with both forms of mineral nitrogen (NH4NO3). The results show that cucumber prefers the nitrates, although it can utilize the ammonium form of nitrogen.
Control of shoot growth in Agrostemma githago L. by 4,4-dimethylmorpholinium chloride and related compounds
Authors: Knypl J. S.
Published: April 2015

4,4-Dimethylmorpholinium chloride and (2-chloroethyl)-trimethylammonium chloride retarded shoot growth in Agrostemma githago L. This effect was nullified by gibberellin. 4,4-Dimethyl-2-oxomorpholinium chloride and 4,4-diethyl-2-oxomorpholinium chloride slightly stimulated shoot growth.
Isolation of 'mating fraction' from Chlamydomonas reinhardtii gametic flagellum membranes by affinity chromatography
Authors: Sikorski Aleksander F. , Mejbaum-Katzenellenbogen Wanda
Published: April 2015

Solubilized with Triton X-100 strain 137+ gametic flagellum membrane material was bound to CNBr-activated Sepharose 4B, and used for affinity chromatography of labeled with 125I 89 gametic flagellum membrane soluble in Triton X-100. A single peak containing 2.7-4.7% of total radioactivity was obtained upon pH change of the eluting buffer. Upon re-chromatography 50-70% of this material was adsorbed and eluted. The complex was found to be stable at pH 7.0-8.0 in the presence of divalent cations (Ca+2 and Mg+2).
Methylmalonic Acidemia: Can Treatment be Improved?
Authors: Michals-Matalon Kimberlee , Lombardo Rachel , Bilger Kimberly , Ross Nancy , Fuller Kelly , Freedenberg Debra , Matalon Reuben
Published: April 2015

Methylmalonic acidemia (MMA) is a severe metabolic disorder, particularly with complete deficiency of methylmalonyl-CoA mutase. Dietary restriction has led to overt signs of deficiencies including skin rashes, hair loss, and poor growth. More liberal intake of the restricted amino acids has resulted in better growth and less frequent episodes of illness.
Clicking for supper
Authors: Tyack Peter
Published: April 2015

When close to prey, porpoises actively widen their sonar beam, which may make it harder for the prey to escape.
Distribution of C26 norcholestanes in Ordovician crude oils from Tahe Oilfield and its geological significance
Authors: Li Meijun , Wang Tieguan , Zhang Weibiao
Published: April 2015

A series of C26 norcholestanes was detected in the Ordovician crude oils from the Tahe Oilfield, the Tarim Basin, northwest China. The abundance of 24-norcholestanes in most of the Ordovician crude oils was lower than that of 27-norcholestanes. The oils from well T904 in the eastern Tahe Oilfield and well TD2 in the eastern Tarim Basin, however, were characterized by relatively higher 24-norcholestane abundance. The distribution of C26 norcholestane of the Upper Ordovician marls from the wells LN46 and BD2 resembled that of the most Ordovician crude oils from the Tahe Oilfield. The distribution of C26 norcholestanes in typical Cambrian black shales and gray limestones from the wells TD2, He4 and outcrops from Keping profile resembled that of the crude oils from the wells T904 and TD2. Criteria are proposed relative to C26 norcholestanes that could be used to classify oil families within the Ordovician reservoirs. Oils with NCR (defined as 24/ (24+27)-norcholestanes) >0.50 and NDR (defined as 24/ (24+27)-nordia-cholestanes) >0.35 were thought to be derived from the Cambrian source rocks, and oils with NCR<0.40 and NDR<0.35 were thought to be derived from the Upper Ordovician source rocks. Therefore, C26 norcholestanes were effective molecular markers to classify oil genetic families in the Tahe Oilfield. They could also provide molecular evidence for the origin and evolution of diatoms and dinoflagellates and the plate drift of the Tarim Basin.
Radiochromic Fuchsine‐Gel and Its Possible Use for Low Dosimetry Applications
Authors: Gafar S. M. , El‐Ahdal M. A.
Published: April 2015

A new dyed–gelatin gel shows promise as a stable dosimeter for low‐dose dosimetry processing. Fuchsine acid cyanide (FAC) dye diffuses in gelatin, forming a colorless sample, which developed a color with the increase in absorbed doses. Upon irradiation, the sample turned pink and the color change was measured at 550 nm using UV‐vis spectroscopy. A formulation suitable for dosimetry was investigated by varying the concentrations of FAC. This dosimeter was also evaluated for stability, dose sensitivity, and irradiation effect dependence. On the other hand, it can be used as a dosimeter in a relatively dose range 1 to 170 Gy. The radiation chemical yield (G value) and pre‐ and postirradiation stability were studied.
Application of ICA to realistically simulated 1H‐MRS data
Authors: Kalyanam Ravi , Boutte David , Hutchison Kent E. , Calhoun Vince D.
Published: April 2015

Introduction

1H‐MRS signals from brain tissues capture information on in vivo brain metabolism and neuronal biomarkers. This study aims to advance the use of independent component analysis (ICA) for spectroscopy data by objectively comparing the performance of ICA and LCModel in analyzing realistic data that mimics many of the known properties of in vivo data.

Methods

This work identifies key features of in vivo 1H‐MRS signals and presents methods to simulate realistic data, using a basis set of 12 metabolites typically found in the human brain. The realistic simulations provide a much needed ground truth to evaluate performances of various MRS analysis methods. ICA is applied to collectively analyze multiple realistic spectra and independent components identified with our generative model to obtain ICA estimates. These same data are also analyzed using LCModel and the comparisons between the ground‐truth and the analysis estimates are presented. The study also investigates the potential impact of modeling inaccuracies by incorporating two sets of model resonances in simulations.

Results

The simulated fid signals incorporating line broadening, noise, and residual water signal closely resemble the in vivo signals. Simulation analyses show that the resolution performances of both LCModel and ICA are not consistent across metabolites and that while ICA resolution can be improved for certain resonances, ICA is as effective as, or better than, LCModel in resolving most model resonances.

Conclusion

The results show that ICA can be an effective tool in comparing multiple spectra and complements existing approaches for providing quantified estimates.
Diet quality influences isotopic discrimination among amino acids in an aquatic vertebrate
Authors: Chikaraishi Yoshito , Steffan Shawn A. , Takano Yoshinori , Ohkouchi Naohiko
Published: April 2015

Stable nitrogen isotopic composition of amino acids (δ15NAA) has recently been employed as a powerful tool in ecological food web studies, particularly for estimating the trophic position (TP) of animal species in food webs. However, the validity of these estimates depends on the consistency of the trophic discrimination factor (TDF; = Δδ15NAA at each shift of trophic level) among a suite of amino acids within the tissues of consumer species. In this study, we determined the TDF values of amino acids in tadpoles (the Japanese toad, Bufo japonicus) reared exclusively on one of three diets that differed in nutritional quality. The diets were commercial fish‐food pellets (plant and animal biomass), bloodworms (animal biomass), and boiled white rice (plant carbohydrate), representing a balanced, protein‐rich, and protein‐poor diet, respectively. The TDF values of two “source amino acids” (Src‐AAs), methionine and phenylalanine, were close to zero (0.3–0.5‰) among the three diets, typifying the values reported in the literature (~0.5‰ and ~0.4‰, respectively). However, TDF values of “trophic amino acids” (Tr‐AAs) including alanine, valine, leucine, isoleucine, and glutamic acid varied by diet: for example, the glutamic acid TDF was similar to the standard value (~8.0‰) when tadpoles were fed either the commercial pellets (8.0‰) or bloodworms (7.9‰), but when they were fed boiled rice, the TDF was significantly reduced (0.6‰). These results suggest that a profound lack of dietary protein may alter the TDF values of glutamic acid (and other Tr‐AAs and glycine) within consumer species, but not the two Src‐AAs (i.e., methionine and phenylalanine). Knowledge of how a nutritionally poor diet can influence the TDF of Tr‐ and Src‐AAs will allow amino acid isotopic analyses to better estimate TP among free‐roaming animals.
Differential adaptive responses to 1‐ or 2‐day fasting in various mouse tissues revealed by quantitative PCR analysis
Authors: Yamamoto Junya , Kamata Shotaro , Miura Asumi , Nagata Tomoko , Kainuma Ryo , Ishii Isao
Published: April 2015

Dietary or caloric restriction confers various clinical benefits. Short‐term fasting of mice is a common experimental procedure that may involve systemic metabolic remodeling, which may significantly affect experimental outputs. This study evaluated adaptive cellular responses after 1‐ or 2‐day fasting in 13 mouse tissues by quantitative PCR using 15 marker primer sets for the activation of ubiquitin–proteasome (Atrogin‐1 andMuRF1), autophagy–lysosome (LC3b,p62 andLamp2), amino acid response (Asns,Trib3,Herpud1,xCT, andChop), Nrf2‐mediated antioxidant (HO‐1 andGsta1), and amino acid transport (Slc38a2,Slc7a5, andSlc7a1) systems. Differential activation profiles obtained in seven highly (thymus, liver, spleen, and small intestine) or mildly (stomach, kidney, and colon) atrophied tissues as well as in six non‐atrophied tissues (brain, eye, lung, heart, skeletal muscle, and testis) suggested tissue‐specific active metabolic remodeling.
Study of the serum levels of polyunsaturated fatty acids and the expression of related liver metabolic enzymes in a rat valproate‐induced autism model
Authors: Zhao Gang , Gao Jingquan , Liang Shuang , Wang Xuelai , Sun Caihong , Xia Wei , Hao Yanqiu , Li Xiang , Cao Yonggang , Wu Lijie
Published: April 2015

To investigate whether the decreased level of serum polyunsaturated fatty acids (PUFAs) in patients with autism is associated with the expression of related liver metabolic enzymes, we selected rats that were exposed to valproic acid (VPA) on embryonic day 12.5 (E12.5) as a model of autism. We observed the serum levels of PUFAs and the expression of related liver metabolic enzymes, including Δ5‐desaturase, Δ6‐desaturase and elongase (Elovl2), in VPA‐exposed and control rats on postnatal day 35 (PND35) and conducted sex dimorphic analysis. We found that the levels of serum PUFAs and related liver metabolic enzymes in the VPA rats were significantly reduced, in association with autism‐like behavioral changes, the abnormal expression of apoptosis‐related proteins and hippocampal neuronal injury, compared to the control rats and showed sex difference in VPA group. This finding indicated that rats exposed to VPA at the embryonic stage may exhibit reduced synthesis of serum PUFAs due to the down‐regulation of liver metabolic enzymes, thereby inducing nervous system injury and behavioral changes, which is affected by sex in the meantime.
Systemic physiology and neuroapoptotic profiles in young and adult rats exposed to surgery: A randomized controlled study comprising four different anaesthetic techniques
Authors: Ibrahim Rami Mossad , Krammer Caspar Weel , Hansen Tom Giedsing , Kristensen Bjarne Winther , Vutskits Laszlo , Sørensen Jens Ahm
Published: April 2015

Background

Experimental evidence indicates that general anaesthetics can induce apoptotic neurodegeneration in the developing brain. The majority of these studies have been performed in the absence of surgery and it currently remains unclear how the presence of surgical stimuli would influence neuroapoptosis as well as systemic homeostasis. Here we explored this possibility by performing dorsal skin flap surgery in young and adult rats under four distinct currently used anaesthesia regimens.

Methods

Young (21‐days) and adult (2 months) male Sprague–Dawley rats were randomized to 150 min exposure to one of four anaesthetics regimens: (i) sevoflurane/dexmedetomidine, (ii) sevoflurane/fentanyl; (iii) propofol/dexmedetomidine, and (iv) propofol/fentanyl. Animals underwent a dorsal skin flap procedure while physiologic, metabolic and biochemical parameters were closely monitored. Neuroapoptotic profiles were evaluated in the cortex, thalamus and hippocampus (CA1 and CA3) at the end of the procedure in each experimental group.

Results

Significant perturbations of systemic homeostasis were found under all anaesthetic regimens. Hyperglycemia and decreased heart rate were particularly relevant in experimental groups receiving dexmedetomidine, while propofol administration was associated with increased systemic lactate levels and metabolic acidosis. A substantial difference in anaesthesia/surgery‐induced neuroapoptosis was found between young and adult rats in several brain regions. Combination of sevoflurane and dexmedetomidine resulted in the highest number of caspase‐3 positive cells, although the extent of cell death remained relatively low in all experimental groups.

Conclusion

Combination of anaesthesia and surgery induces significant perturbations of physiological parameters in both young and adult spontaneously breathing rats undergoing surgery. These observations further enlighten the need for detailed physiological monitoring under these experimental conditions. Although some statistically significant differences in activated caspase‐3 profiles were detected between experimental groups, the overall extent of neuronal cell death remained very low under all conditions questioning, thereby, the physiological significance of apoptotic neurodegeneration in the context of anaesthesia and surgery.
Endometriosis and associated symptoms among Nigerian women
Authors: Fawole Adeniran O. , Bello Folasade A. , Ogunbode Olayinka , Odukogbe Akin‐Tunde A. , Nkwocha Gerald C. , Nnoaham Kelechi E. , Zondervan Krina T. , Akintan Adesina , Abdus‐Salam Rukiyat A. , Okunlola Michael A.
Published: April 2015

Objective

To determine the prevalence of endometriosis and identify associated symptoms among Nigerian women.

Methods

A cross‐sectional study was conducted at a center in Ibadan, Nigeria, between October 2008 and December 2010. All women aged 18–45 years scheduled for their first diagnostic laparoscopy for gynecologic indications were enrolled. Participants completed a previously validated self‐administered questionnaire. Endometriosis was diagnosed on the basis of visual evidence.

Results

Among 239 women analyzed, 115 (48.1%) had endometriotic lesions. Endometriosis was more common among women reporting dysmenorrhea and pelvic pain than among those not reporting these symptoms (20/28 [71.4%] vs 95/211 [45.0%]; P = 0.009). Women who reported dysmenorrhea were significantly more likely to have endometriosis than were those without dysmenorrhea (90/171 [52.6%] vs 25/68 [36.8%]; P = 0.027). The risk of endometriosis was not significantly increased in women with one pain symptom (odds ratio [OR]1.69; 95% confidence interval [CI] 0.67–4.27), but was significantly increased in women with two (OR 2.70; 95% CI 1.13–6.52) or three (OR 4.87; 95% CI 1.88–12.82) pain symptoms (χ2trend = 15.5; P < 0.001). In a multivariate logistic regression model, only pain other than dysmenorrhea or dyspareunia independently predicted endometriosis (P = 0.017).

Conclusion

Endometriosis is fairly common among Nigerian women. Efforts to increase the awareness of endometriosis among the public, researchers, and clinicians are needed.
Pregnancy outcomes after laparoscopic sleeve gastrectomy among obese patients
Authors: Ducarme Guillaume , Chesnoy Veronique , Lemarié Philippe , Koumaré Sekou , Krawczykowski Daniel
Published: April 2015

Objective

To analyze pregnancy outcomes after laparoscopic sleeve gastrectomy (LSG) according to body mass index (BMI) at conception and the interval between LSG and pregnancy.

Methods

In a retrospective study, data were obtained for all women who became pregnant after LSG at a center in France between December 2001 and December 2011. Frequencies of perinatal events according to BMI at conception and the interval between LSG and pregnancy were compared.

Results

A total of 63 pregnancies occurring in 54 patients were included, among which 52 (83%) occurred after the first postoperative year and 26 (41%) in women who remained obese. Compared with women who were no longer obese at conception, women who were still obese delivered neonates of significantly lower gestational age at birth (P = 0.02) and birth weight (P = 0.001). Odds of preterm delivery were also increased (odds ratio 4.37, 95% confidence interval 1.17–16.27; P = 0.03). Maternal and neonatal outcomes according to the interval between LSG and pregnancy did not differ significantly.

Conclusion

Women who remain obese following LSG are at increased risk of adverse outcomes, including low gestational age at birth, low birth weight, and preterm delivery, and should be regarded as a risk group.
Syphilis testing in antenatal care: Policies and practices among laboratories in the Americas
Authors: Luu Minh , Ham Cal , Kamb Mary L. , Caffe Sonja , Hoover Karen W. , Perez Freddy
Published: April 2015

Objective

To asses laboratory syphilis testing policies and practices among laboratories in the Americas.

Methods

Laboratory directors or designees from PAHO member countries were invited to participate in a structured, electronically‐delivered survey between March and August, 2014. Data on syphilis tests, algorithms, and quality control (QC) practices were analyzed, focusing on laboratories receiving specimens from antenatal clinics (ANCs).

Results

Surveys were completed by 69 laboratories representing 30 (86%) countries. Participating laboratories included 36 (52%) national or regional reference labs and 33 (48%) lower‐level laboratories. Most (94%) were public sector facilities and 71% reported existence of a national algorithm for syphilis testing in pregnancy, usually involving both treponemal and non‐treponemal testing (72%). Less than half (41%) used rapid syphilis tests (RSTs); and only seven laboratories representing five countries reported RSTs were included in the national algorithm for pregnant women. Most (83%) laboratories serving ANCs reported using some type of QC system; 68% of laboratories reported participation in external QC. Only 36% of laboratories reported data to national/local surveillance. Half of all laboratories serving ANC settings reported a stockout of one or more essential supplies during the previous year (median duration, 30 days).

Conclusion

Updating laboratory algorithms, improving testing standards, integrating data into existing surveillance, and improved procurement and distribution of commodities may be needed to ensure elimination of MTCT of syphilis in the Americas.
Improving global estimates of syphilis in pregnancy by diagnostic test type: A systematic review and meta‐analysis
Authors: Ham D. Cal , Lin Carol , Newman Lori , Wijesooriya N. Saman , Kamb Mary
Published: April 2015

Background

“Probable active syphilis,” is defined as seroreactivity in both non‐treponemal and treponemal tests. A correction factor of 65%, namely the proportion of pregnant women reactive in one syphilis test type that were likely reactive in the second, was applied to reported syphilis seropositivity data reported to WHO for global estimates of syphilis during pregnancy.

Objectives

To identify more accurate correction factors based on test type reported.

Search Strategy

Medline search using: “Syphilis [Mesh] and Pregnancy [Mesh],” “Syphilis [Mesh] and Prenatal Diagnosis [Mesh],” and “Syphilis [Mesh] and Antenatal [Keyword].

Selection Criteria

Eligible studies must have reported results for pregnant or puerperal women for both non‐treponemal and treponemal serology.

Data collection and analysis

We manually calculated the crude percent estimates of subjects with both reactive treponemal and reactive non‐treponemal tests among subjects with reactive treponemal and among subjects with reactive non‐treponemal tests. We summarized the percent estimates using random effects models.

Main results

Countries reporting both reactive non‐treponemal and reactive treponemal testing required no correction factor. Countries reporting non‐treponemal testing or treponemal testing alone required a correction factor of 52.2% and 53.6%, respectively. Countries not reporting test type required a correction factor of 68.6%.

Conclusions

Future estimates should adjust reported maternal syphilis seropositivity by test type to ensure accuracy.
Estimating disease burden of maternal syphilis and associated adverse pregnancy outcomes in India, Nigeria, and Zambia in 2012
Authors: Chen Xiang‐Sheng , Khaparde Sunil , Prasad Turlapati L.N. , Srinivas Vani , Anyaike Chukwuma , Ijaodola Gbenga , Ngige Evelyn , Tembo Mumba Grace , Phiri Carolline , Tambatamba Bushimbwa , Chavan Laxmikant , Seguy Nicole , Oyelade Taiwo A. , Bvulani Malumo Sarai , Newman Lori M.
Published: April 2015

Objective

To estimate maternal syphilis and its associated adverse pregnancy outcomes in India, Nigeria, and Zambia.

Methods

An online estimation tool was used to generate point estimates and uncertainty ranges of maternal syphilis and adverse pregnancy outcomes due to mother‐to‐child transmission (MTCT). The most recent data (2010–2012) on antenatal care coverage, syphilis seroprevalence, and syphilis screening and treatment coverage at the subnational level in India, Nigeria, and Zambia were used to estimate disease burden for 2012. Sensitivity analysis was conducted for three screening and treatment scenarios (current coverages, current coverages minus 20%, and ideal coverages consistent with WHO targets for eliminating MTCT of syphilis).

Results

A total of 103 960, 74 798, and 9072 pregnant women with probable active syphilis were estimated to occur in India, Nigeria, and Zambia, resulting in 53 187, 37 045, and 2973 adverse outcomes, respectively; approximately 1.6%, 4.8%, and 37.0% of these were averted under the current service coverages in India, Nigeria, and Zambia. The disease burden varied significantly in its subnational distribution within India and Nigeria, but was distributed evenly across Zambia.

Conclusions

The obtained results suggest an ongoing, unaverted high burden of maternal syphilis and associated adverse outcomes in India, Nigeria, and Zambia. Screening and treatment for syphilis must be scaled‐up significantly in these countries to achieve elimination of MTCT of syphilis.
Magnitude of maternal and neonatal mortality in Tanzania: A systematic review
Authors: Armstrong Corinne E. , Magoma Moke , Ronsmans Carine
Published: April 2015

Background

Maternal and neonatal mortality remains a serious challenge in Tanzania. Progress is tracked through maternal mortality ratios (MMR) and neonatal mortality rates (NMR), yet robust national data on these outcomes is difficult and expensive to ascertain, and mask wide variation.

Search strategy

We searched EMBASE, MEDLINE, Popline, and EBSCO online databases, basing search terms on (“maternal” OR “neonatal”) AND (“mortality” OR “cause of death”) AND “Tanzania.”

Selection criteria

Nationally representative or population representative from the subnational context were eligible, providing NMR, MMR, or numbers of maternal deaths or early neonatal deaths or neonatal deaths and live births.

Data collection and analysis

Data were extracted on study context, time period, number of deaths and live births, definition of maternal and neonatal death, study design, and completeness and representativeness of data. NMR and MMR were extracted or calculated and study quality was assessed. Nationally representative data were compared with modelled national data from international agencies.

Main results

2107 records were screened yielding 21 maternal mortality and 15 neonatal mortality datasets. There were high mortality levels with wide subnational MMR and NMR variation. National survey data differed from the modelled estimates, with wide uncertainty ranges.

Conclusion

Subnational data quality was generally poor with no observable trends and geographical clustering across several regions. Combined MMR and NMR reporting is uncommon. Modelled national estimates lack precision and are complex to interpret. Results suggest that aggregate national data are inadequate for policy generation and progress monitoring. We recommend strengthening of vital registration and Health Management Information Systems with complementary use of process indicators, for improved monitoring of, and accountability for maternal and newborn health.
Alzheimer's disease first symptoms are age dependent: Evidence from the NACC dataset
Authors: Barnes Josephine , Dickerson Bradford C. , Frost Chris , Jiskoot Lize C. , Wolk David , van der Flier Wiesje M.
Published: April 2015

Introduction

Determining the relationship between age and Alzheimer's disease (AD) presentation is important to improve understanding and provide better patient services.

Methods

We used AD patient data (N = 7815) from the National Alzheimer Coordinating Center database and multinomial logistic regression to investigate presentation age and first cognitive/behavioral symptoms.

Results

The odds of having a nonmemory first cognitive symptom (including impairment in judgment and problem solving, language, and visuospatial function) increased with younger age (P <.001, all tests). Compared with apathy/withdrawal, the odds of having depression and “other” behavioral symptoms increased with younger age (P <.02, both tests), whereas the odds of having psychosis and no behavioral symptom increased with older age (P <.001, both tests).

Discussion

There is considerable heterogeneity in the first cognitive/behavioral symptoms experienced by AD patients. Proportions of these symptoms change with age with patients experiencing increasing nonmemory cognitive symptoms and more behavioral symptoms at younger ages.
Genetic risk of neurodegenerative diseases is associated with mild cognitive impairment and conversion to dementia
Authors: Adams Hieab H.H. , de Bruijn Renée F.A.G. , Hofman Albert , Uitterlinden André G. , van Duijn Cornelia M. , Vernooij Meike W. , Koudstaal Peter J. , Ikram M. Arfan
Published: April 2015

Introduction

Neurodegenerative diseases are a major cause of cognitive impairment and can ultimately lead to dementia. Genome‐wide association studies have uncovered many genetic variants conferring risk of neurodegenerative diseases, but their role in cognitive impairment remains unexplored.

Methods

In the prospective, population‐based Rotterdam Study, 3605 nondemented persons aged ≥55 years were genotyped, screened for mild cognitive impairment (MCI) in 2002 to 2005 and underwent continuous follow‐up for dementia until 2012. Weighted polygenic risk scores of genetic variants for Alzheimer's disease (AD), Parkinson's disease (PD), and the frontotemporal lobar degeneration/amyotrophic lateral sclerosis disease spectrum (FTLD/ALS) were constructed and investigated for association with MCI and the subsequent conversion to dementia.

Results

In total, 360 (10.0%) persons had MCI, of whom 147 (4.1%) were amnestic and 213 (5.9%) nonamnestic. The AD risk score was associated with both MCI subtypes (odds ratio for all MCI 1.15 [95% CI, 1.03–1.28]), whereas PD and FTLD/ALS risk scores were associated only with nonamnestic MCI (odds ratios 1.15 [1.00–1.32] and 1.19 [1.03–1.37], respectively). The AD risk score, but not PD and FTLD/ALS risk scores, was associated with an increased risk of dementia (hazard ratio 1.55 [1.37–1.77]).

Discussion

Genetic evidence supports the view that multiple neurodegenerative pathways lead to MCI and that the subsequent conversion to dementia, primarily of the AD subtype, is mainly due to the AD pathway(s).
Topographic variability of the left atrium and pulmonary veins assessed by 3D‐CT predicts the recurrence of atrial fibrillation after catheter ablation
Authors: Kiuchi Kunihiko , Yoshida Akihiro , Takei Asumi , Fukuzawa Koji , Itoh Mitsuaki , Imamura Kimitake , Fujiwara Ryudo , Suzuki Atsushi , Nakanishi Tomoyuki , Yamashita Soichiro , Hirata Ken‐ichi , Kanda Gaku , Okajima Katsunori , Shimane Akira , Yamada Shinichiro , Taniguchi Yasuyo , Yasaka Yoshinori , Kawai Hiroya
Published: April 2015

Background

Catheter ablation (CA) is an established therapy for atrial fibrillation (AF). However, the assessment of anatomical information and predictors of AF recurrence remain unclear. We investigated the relationship between anatomical information on the left atrium (LA) and pulmonary veins (PVs) from three‐dimensional computed tomography images and the recurrence of AF after CA.

Methods

Sixty‐seven consecutive AF patients (mean age: 62±10 years, median AF history: 42 (12; 60) months, mean LA size: 41±7 mm, paroxysmal: 56%) underwent CA and were followed for 19±10 months. The segmented surface areas (antral, posterior, septal, and lateral) and dimensions (between the anterior and posterior walls, the right inferior PV and mitral annulus [MA], the right superior PV and MA, the left superior PV and MA, and the mitral isthmus) of the LA were evaluated three dimensionally using the NavX system. The cross‐sectional areas of the PVs were also evaluated.

Results

After the follow‐up period, 49 patients (73%) remained free from AF. A multivariate analysis showed that the diameter of the mitral isthmus and cross‐sectional area of the right upper PV were associated with AF recurrence (odds ratio: 1.070, CI: 1.02–1.12, p=0.001; odds ratio: 0.41, CI: 0.21–0.77, p=0.006).

Conclusion

Enlargement of the mitral isthmus and a smaller right superior PV cross‐sectional area were associated with AF recurrence.
Connecting An Open Classroom Climate to Social Movement Citizenship: A Study of 8Th Graders in Europe Using Iea Iccs Data
Authors: Knowles Ryan T. , McCafferty-Wright Jennice
Published: April 2015

Using data from the International Civic and Citizenship Study, this quantitative study explores the potential for open classroom climates to foster political efficacy and civic knowledge among 8th grade students in 14 Western European countries. Findings show that an open classroom climate is associated with increased civic knowledge and political efficacy. In addition, civic knowledge and political efficacy are positively correlated with social movement citizenship. However, the relationships between both political efficacy and civic knowledge on social movement citizenship are strengthened with presence of an open classroom climate. This study demonstrates the importance of an open classroom climate to develop students’ knowledge and efficacy related to active citizenship.
Emerging roles of hypoxia‐inducible factors and reactive oxygen species in cancer and pluripotent stem cells
Authors: Saito Shigeo , Lin Ying‐Chu , Tsai Ming‐Ho , Lin Chang‐Shen , Murayama Yoshinobu , Sato Ryuji , Yokoyama Kazunari K.
Published: April 2015

Eukaryotic organisms require oxygen homeostasis to maintain proper cellular function for survival. During conditions of low oxygen tension (hypoxia), cells activate the transcription of genes that induce an adaptive response, which supplies oxygen to tissues. Hypoxia and hypoxia‐inducible factors (HIFs) may contribute to the maintenance of putative cancer stem cells, which can continue self‐renewal indefinitely and express stemness genes in hypoxic stress environments (stem cell niches). Reactive oxygen species (ROS) have long been recognized as toxic by‐products of aerobic metabolism that are harmful to living cells, leading to DNA damage, senescence, or cell death. HIFs may promote a cancer stem cell state, whereas the loss of HIFs induces the production of cellular ROS and activation of proteins p53 and p16Ink4a, which lead to tumor cell death and senescence. ROS seem to inhibit HIF regulation in cancer cells. By contrast, controversial data have suggested that hypoxia increases the generation of ROS, which prevents hydroxylation of HIF proteins by inducing their transcription as negative feedback. Moreover, hypoxic conditions enhance the generation of induced pluripotent stem cells (iPSCs). During reprogramming of somatic cells into a PSC state, cells attain a metabolic state typically observed in embryonic stem cells (ESCs). ESCs and iPSCs share similar bioenergetic metabolisms, including decreased mitochondrial number and activity, and induced anaerobic glycolysis. This review discusses the current knowledge regarding the emerging roles of ROS homeostasis in cellular reprogramming and the implications of hypoxic regulation in cancer development.
Diphtheria‐toxin based anti‐human CCR4 immunotoxin for targeting human CCR4+ cells in vivo
Authors: Wang Zhaohui , Wei Min , Zhang Huiping , Chen Hongyuan , Germana Sharon , Huang Christene A. , Madsen Joren C. , Sachs David H. , Wang Zhirui
Published: April 2015

CC chemokine receptor 4 (CCR4) has attracted much attention as a promising therapeutic drug target for CCR4+ tumor cells and Tregs. CCR4 is expressed on some tumor cells such as T‐cell acute lymphoblastic leukemia (ALL), adult T‐cell leukemia/lymphoma (ATLL), adult peripheral T cell lymphoma (PTCL) and cutaneous T cell lymphoma (CTCL). CCR4 is also expressed on majority of Tregs, mainly effector Tregs. In this study we have successfully developed three versions of diphtheria‐toxin based anti‐human CCR4 immunotoxins (monovalent, bivalent and single‐chain fold‐back diabody). Binding analysis by flow cytometry showed that all three versions of the anti‐human CCR4 immunotoxins bound to the human CCR4+ tumor cell line as well as CCR4+ human PBMC. The bivalent isoform bound stronger than its monovalent counterpart and the single‐chain foldback diabody isoform was the strongest among the three versions. In vitro efficacy analysis demonstrated that the bivalent isoform was 20 fold more potent in inhibiting cellular proliferation and protein synthesis in human CCR4+ tumor cells compared to the monovalent anti‐human CCR4 immunotoxin. The single‐chain fold‐back diabody isoform was 10 fold more potent than its bivalent counterpart and 200 fold more potent than its monovalent counterpart. The in vivo efficacy was assessed using a human CCR4+ tumor‐bearing mouse model. The immunotoxin significantly prolonged the survival of tumor‐bearing NOD/SCID IL‐2 receptor γ−/− (NSG) mice injected with human CCR4+ acute lymphoblastic leukemia cells compared with the control group. This novel anti‐human CCR4 immunotoxin is a promising drug candidate for targeting human CCR4+ tumor cells and Tregs in vivo.
Should fee-for-service be for all guideline-advocated acute coronary syndrome (ACS) care? Observations from the Snapshot ACS study
Authors: Briffa Thomas G. , Hammett Christopher J. , Cross David B. , Macisaac Andrew I. , Rankin James M. , Board Neville , Carr Bridie , Hyun Karice K. , French John , Brieger David B. , Chew Derek P.
Published: April 2015

Objective
The aim of the present study was to explore the association of health insurance status on the provision of guideline-advocated acute coronary syndrome (ACS) care in Australia.

Methods
Consecutive hospitalisations of suspected ACS from 14 to 27 May 2012 enrolled in the Snapshot study of Australian and New Zealand patients were evaluated. Descriptive and logistic regression analysis was performed to evaluate the association of patient risk and insurance status with the receipt of care.

Results
In all, 3391 patients with suspected ACS from 247 hospitals (23 private) were enrolled in the present study. One-third of patients declared private insurance coverage; of these, 27.9% (304/1088) presented to private facilities. Compared with public patients, privately insured patients were more likely to undergo in-patient echocardiography and receive early angiography; furthermore, in those with a discharge diagnosis of ACS, there was a higher rate of revascularisation (P < 0.001). Each of these attracts potential fee-for-service. In contrast, proportionately fewer privately insured ACS patients were discharged on selected guideline therapies and were referred to a secondary prevention program (P = 0.056), neither of which directly attracts a fee. Typically, as GRACE (the Global Registry of Acute Coronary Events) risk score rose, so did the level of ACS care; however, propensity-adjusted analyses showed lower in-hospital adverse events among the insured group (odds ratio 0.68; 95% confidence interval 0.52–0.88; P = 0.004).

Conclusion
Fee-for-service reimbursement may explain differences in the provision of selected guideline-advocated components of ACS care between privately insured and public patients.

What is known about this topic?
There is variation in the pattern of acute coronary syndrome care across Australia.

What does this paper add?
Clear differences in the provision of selected proven therapies for acute coronary syndrome apply independent of whether a fee is charged or not.

What are the implications for practitioners?
Consideration should be given to the remuneration for proven therapies for acute coronary syndrome care in preference to those not supported by the evidence base.
Australian doctors’ non-clinical activities: results from the Medicine in Australia: Balancing Employment and Life (MABEL) survey of doctors
Authors: Joyce Catherine , Eyre Harris , Wang Wei Chun , Laurence Caroline
Published: April 2015

Objective The aim of the present study was to investigate non-clinical work conducted by Australian doctors. Methods This study was an exploratory descriptive study using data from Wave 5 of the Medicine in Australia: Balancing Employment and Life (MABEL) longitudinal survey, collected in 2012 from Australian medical practitioners (2200 general practitioners (GPs), 3455 specialists, 1270 specialists in training and 1656 hospital non-specialists). The main outcome measure was the number of hours worked per week in non-clinical work. Regression analysis was used to determine associations between non-clinical activities (i.e. education-related, management and administration and other) and personal and professional characteristics, including age, gender, job and life satisfaction, total clinical working hours, sector of practice (public or private) and doctor type. Results Australian doctors spend an average of just under 7 h per week, or 16% of their working time, on non-clinical activities. Doctors who worked more hours on non-clinical activities overall, and in education-related and management and administration specifically, were male, younger, had lower life satisfaction and generally spent fewer hours on clinical work. Lower job satisfaction was associated with longer management and administration hours, but not with time spent in education-related activities. Specialists were more likely to work long non-clinical hours, whereas GPs were more likely to report none. Hospital non-specialists reported relatively high management and administration hours. Conclusions Further work is required to better understand the full range of non-clinical activities doctors are involved in and how this may impact future workforce projections. What is known about the topic? Doctors usually engage in a range of non-clinical activities, such as research, education and administration. Policy documents suggest these activities are expected to comprise 20%–30% of a doctor’s time in public settings. Understanding how engagement in non-clinical activities affects doctors’ time in direct patient care, their career progression and job and life satisfaction is highly important and poorly understood. What does this paper add? This national study provides the first empirical data on doctors’ non-clinical activity, and shows that non-clinical hours are traded off with clinical hours, and are associated with personal and professional characteristics. What are the implications for practitioners? Any changes in doctors’ non-clinical hours may influence doctors’ satisfaction as well as their clinical working hours. Workforce planning needs to take non-clinical hours into account.
Sexual health literacy of the student population of the University of Tasmania: results of the RUSSL Study
Authors: Simpson Steve , Clifford Christine , Ross Kaz , Sefton Neil , Owen Louise , Blizzard Leigh , Turner Richard
Published: April 2015

Background
Evidence suggests a varied level of sexual health literacy (SHL) among university student populations, so we evaluated the SHL among students at the University of Tasmania. Methods: Students were invited to complete an anonymous online questionnaire during August/September 2013. SHL was assessed using the ARCSHS National Survey of Australian Secondary Students & Sexual Health (ARC) and the Sexual Health Questionnaire (SHS). Predictors of literacy scores were evaluated by linear regression. Results: The study recruited 1786 participants (8.2% of 2013 student population), of similar composition to the general university population. Female sex, older age, sexual education, and sexual experience were significant predictors of SHL. As hypothesised, students in medical/nursing disciplines had the highest SHL. Less expected were the significant differences by birthplace and religious affiliation, many of which persisted on adjustment for confounders. Compared with Australian/New Zealander students, overseas-born students had significantly lower ARC (–3.6%, P < 0.001) & SHS (–4.2%, P < 0.001); this was driven by Malaysian, Indian, and Chinese students. Compared with agnostic/atheist-identifying students, those of Buddhist (ARC: –5.4%, P = 0.014; SHS: –6.7%, P = 0.002), Hindu (ARC: –8.8%, P = 0.098; SHS: –12.2%, P = 0.027), Muslim (ARC: –16.5%, P < 0.001; SHS: –13.4%, P = 0.001) and Protestant (ARC: –2.3%, P = 0.023; SHS: –4.4%, P < 0.001) identifications had markedly lower SHL. Conclusions: This study, one of the first among university students in Australia, found a varied SHL by sex, age, sexual education and sexual experience, as well as by birthplace and religious affiliation. These findings have applications in orientation and education programs at Australian universities.
chipPCR: an R package to pre-process raw data of amplification curves
Authors: Rödiger Stefan , Burdukiewicz Michał , Schierack Peter
Published: April 2015

Motivation: Both the quantitative real-time polymerase chain reaction (qPCR) and quantitative isothermal amplification (qIA) are standard methods for nucleic acid quantification. Numerous real-time read-out technologies have been developed. Despite the continuous interest in amplification-based techniques, there are only few tools for pre-processing of amplification data. However, a transparent tool for precise control of raw data is indispensable in several scenarios, for example, during the development of new instruments.

Results:  chipPCR is an R package for the pre-processing and quality analysis of raw data of amplification curves. The package takes advantage of R’s S4 object model and offers an extensible environment. chipPCR contains tools for raw data exploration: normalization, baselining, imputation of missing values, a powerful wrapper for amplification curve smoothing and a function to detect the start and end of an amplification curve. The capabilities of the software are enhanced by the implementation of algorithms unavailable in R, such as a 5-point stencil for derivative interpolation. Simulation tools, statistical tests, plots for data quality management, amplification efficiency/quantification cycle calculation, and datasets from qPCR and qIA experiments are part of the package. Core functionalities are integrated in GUIs (web-based and standalone shiny applications), thus streamlining analysis and report generation.

Availability and implementation:  http://cran.r-project.org/web/packages/chipPCR. Source code: https://github.com/michbur/chipPCR.

Contact: stefan.roediger@b-tu.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Genome-scale strain designs based on regulatory minimal cut sets
Authors: Mahadevan Radhakrishnan , von Kamp Axel , Klamt Steffen
Published: April 2015

Motivation: Stoichiometric and constraint-based methods of computational strain design have become an important tool for rational metabolic engineering. One of those relies on the concept of constrained minimal cut sets (cMCSs). However, as most other techniques, cMCSs may consider only reaction (or gene) knockouts to achieve a desired phenotype.

Results: We generalize the cMCSs approach to constrained regulatory MCSs (cRegMCSs), where up/downregulation of reaction rates can be combined along with reaction deletions. We show that flux up/downregulations can virtually be treated as cuts allowing their direct integration into the algorithmic framework of cMCSs. Because of vastly enlarged search spaces in genome-scale networks, we developed strategies to (optionally) preselect suitable candidates for flux regulation and novel algorithmic techniques to further enhance efficiency and speed of cMCSs calculation. We illustrate the cRegMCSs approach by a simple example network and apply it then by identifying strain designs for ethanol production in a genome-scale metabolic model of Escherichia coli. The results clearly show that cRegMCSs combining reaction deletions and flux regulations provide a much larger number of suitable strain designs, many of which are significantly smaller relative to cMCSs involving only knockouts. Furthermore, with cRegMCSs, one may also enable the fine tuning of desired behaviours in a narrower range. The new cRegMCSs approach may thus accelerate the implementation of model-based strain designs for the bio-based production of fuels and chemicals.

Availability and implementation: MATLAB code and the examples can be downloaded at http://www.mpi-magdeburg.mpg.de/projects/cna/etcdownloads.html.

Contact: krishna.mahadevan@utoronto.ca or klamt@mpi-magdeburg.mpg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.