bluuebunny/crossref_metadata_2025 huggingface dataset:
Wavefield interpolation in 3D large‐step Fourier wavefield extrapolation
Authors: Chen Gaoxiang , Fu Li‐Yun , Wei Wei , Sun Weijia
Published: March 2017

Extrapolating wavefields and imaging at each depth during three‐dimensional recursive wave‐equation migration is a time‐consuming endeavor. For efficiency, most commercial techniques extrapolate wavefields through thick slabs followed by wavefield interpolation within each thick slab. In this article, we develop this strategy by associating more efficient interpolators with a Fourier‐transform‐related wavefield extrapolation method. First, we formulate a three‐dimensional first‐order separation‐of‐variables screen propagator for large‐step wavefield extrapolation, which allows for wide‐angle propagations in highly contrasting media. This propagator significantly improves the performance of the split‐step Fourier method in dealing with significant lateral heterogeneities at the cost of only one more fast Fourier transform in each thick slab. We then extend the two‐dimensional Kirchhoff and Born–Kirchhoff local wavefield interpolators to three‐dimensional cases for each slab. The three‐dimensional Kirchhoff interpolator is based on the traditional Kirchhoff formula and applies to moderate lateral velocity variations, whereas the three‐dimensional Born–Kirchhoff interpolator is derived from the Lippmann–Schwinger integral equation under the Born approximation and is adapted to highly laterally varying media. Numerical examples on the three‐dimensional salt model of the Society of Exploration Geophysicists/European Association of Geoscientists demonstrate that three‐dimensional first‐order separation‐of‐variables screen propagator Born–Kirchhoff depth migration using thick‐slab wavefield extrapolation plus thin‐slab interpolation tolerates a considerable depth‐step size of up to 72 ms, eventually resulting in an efficiency improvement of nearly 80% without obvious loss of imaging accuracy. Although the proposed three‐dimensional interpolators are presented with one‐way Fourier extrapolation methods, they can be extended for applications to general migration methods.
Tree growth is more sensitive than species distributions to recent changes in climate and acidic deposition in the northeastern United States
Authors: Wason Jay W. , Dovciak Martin , Beier Colin M. , Battles John J.
Published: March 2017

Tree‐growth responses to environmental change could provide early detection of shifts in forest composition and help facilitate ecosystem management and conservation.

We studied forest tree responses to recent trends in climate and acidic deposition using analyses of tree rings and long‐term climate, deposition and forest plot data along an elevational climatic gradient in the northeastern United States. We analysed how (i) individual growth of dominant species (Picea rubens, Abies balsamea) and (ii) spatial distributions of all species, changed with elevation over time due to changing environment.

We observed a mean 220 m upslope shift of temperature envelopes since the 1960s, consistent with regional climate warming, but found no evidence of synchronous upslope shifts in species abundance. Species' ranges were stable although some leaned upslope or downslope, suggesting species‐specific migration lags or controls on species' ranges.

Compared to species distributions, the growth of dominant species was more responsive to environmental change. Although the basal area of P. rubens declined within its range since the 1960s, its growth has increased recently with increasing precipitation pH and to a lesser extent with warming climate. Abies balsamea has gradually increased in both basal area and density since the 1960s, with its growth responding to precipitation pH but not climate. Historically, P. rubens grew better at lower and A. balsamea at higher elevations, but these elevation effects appeared to be mediated primarily by moisture, and have disappeared over time.

Synthesis and applications. Mean tree‐growth responses to changing climate (temperature, moisture) and precipitation chemistry were more consistent and more clearly detectable than shifts in tree species' ranges, suggesting that monitoring tree growth across climatically controlled species' ranges (e.g. along elevational or latitudinal gradients) may provide a powerful tool for early detection of potential future changes in forest composition in a changing environment.
WASPI's Is (Mostly) a Campaign for Inequality
Authors: Pemberton Hugh
Published: March 2017

Women Against State Pension Inequality (WASPI) has mounted a vociferous campaign for full compensation to be given to ‘1950s women’ who, it argues, have suffered severe financial hardship as a result of the rise in their state pension age from age 60. That campaign has gained significant political traction, with much sympathy expressed for the plight of those affected and acceptance (most notably by the Scottish National Party and the Labour Party) that some form of compensation is urgently needed. But WASPI fails to acknowledge the rise in the state pension age's roots in the fight for women's equality, disregards the fact that the problems experienced by this cohort as they near retirement are faced by both women and men and glosses over the fact that the increase in pension age above 65 applies to both genders equally. Its campaign obscures deeper and more important issues in old‐age income replacement.
‘Tomorrow She Will Reign’: Intimate Power and the Making of a Queen Mother in Rwanda, c.1800–1863
Authors: Watkins Sarah E.
Published: March 2017

This article explores the relationship between erotic and institutional power through the political biography of the Queen‐Mother (Umugabekazi) Nyiramongi (r. 1845–1863) in Rwanda. Using historical narratives, genealogies, epic poetry and the translated text of royal rituals, this article argues that Nyiramongi used her status as first an object of desire and then as an erotic partner to her husband to manoeuver herself and her family into positions of institutional power. In contrast to previous literature, this article frames women like Nyiramongi as political actors who consciously cultivated their intimate assets to participate in the construction of systems of power, using their status as daughters, wives, lovers, mothers and sisters to exercise indirect power, often leading to positions of institutional and direct power.
Palynological Investigation of Mummified Human Remains
Authors: Reinhard Karl J. , Amaral Marina Milanello do , Wall Nicole
Published: March 2017

Pollen analysis was applied to a mummified homicide victim in Nebraska, U.S.A., to determine the location of death. A control sample showed the normal ambient pollen in the garage crime scene. Ambient windborne types, common in the air of the region, dominated the control. Internal samples were analyzed from the sacrum, intestine, and diaphragm. Microfossils were recovered from the rehydrated intestine lumen. The intestinal sample was dominated by Brassica (broccoli). The sacrum sample was high in dietary types but with a showing of ambient types. The pollen from the diaphragm was dominated by ambient pollen similar to the control samples. The discovery of diverse pollen spectra from within a single mummy was unexpected. They show that ingested and inhaled pollen mixed in the corpse. The data linked the decedent to a specific crime scene in her Nebraska home in the southern tier of eastern counties on the border with Kansas.
“Tampering to Death”: A Fatal Codeine Intoxication Due to a Homemade Purification of a Medical Formulation
Authors: Fais Paolo , Pigaiani Nicola , Cecchetto Giovanni , Montisci Massimo , Gottardo Rossella , Viel Guido , Pascali Jennifer Paola , Tagliaro Franco
Published: March 2017

Many homemade tamper processes of medical codeine formulations are available on selected “forums” on the Internet, where recreational codeine users claim to be able to purify codeine by removing additives, such as acetaminophen, to avoid or limit adverse effects. In this work, it is reported and discussed a fatal case of codeine intoxication. The findings of objects such as jars, filters, and tablets, and amounts of unknown liquid material at the death scene investigation suggested a fatal codeine intoxication after the tampering procedure called “cold water extraction.” Toxicological results obtained from the analysis of both the nonbiological material and the body fluids of the decedent integrated with the information collected at the death scene investigation confirmed the above‐mentioned hypothesis. This report underlines the importance of a tight interconnection between criminalistics and legal medicine to strengthen the identification of the cause of death and the reconstruction of the event.
Estimation of Glomerular Filtration Rate in Elderly Chronic Kidney Disease Patients: Comparison of Three Novel Sophisticated Equations and Simple Cystatin C Equation
Authors: Bevc Sebastjan , Hojs Nina , Hojs Radovan , Ekart Robert , Gorenjak Maksimiljan , Puklavec Ludvik
Published: March 2017

Estimating glomerular filtration rate (GFR) in elderly patients is a problem, since they are poorly represented in studies developing GFR equations. Serum cystatin C is a better indicator of GFR than serum creatinine in elderly patients. Therefore the aim of our study was to compare frequently used serum cystatin C based GFR equations with a gold standard (51CrEDTA clearance) in elderly chronic kidney disease (CKD) patients. 106 adult Caucasian patients, older than 65 years (58 women, 48 men; mean age 72.5 years), were included. In each patient 51CrEDTA clearance, serum creatinine (IDMS traceable method) and serum cystatin C (immunonephelometric method) were determined. GFR was estimated using the Simple cystatin C, CKD‐EPI cystatin C, CKD‐EPI creatinine‐cystatin C and BIS2 equation. Mean serum creatinine of our patients was 141.4 ± 41.5 μmol/L, mean serum cystatin C 1.79 ± 0.6 mg/L, mean 51CrEDTA clearance was 52.2 ± 15.9 mL/min per 1.73 m2. Statistically significant correlations between 51CrEDTA clearance and all formulas were found (P < 0.0001). In the receiver operating characteristic (ROC) curve analysis (cut‐off for GFR 45 mL/min per 1.73 m2) no significant differences in diagnostic accuracy between all the before mentioned equations were found. Bland‐Altman analysis for the same cut‐off showed that CKD‐EPI creatinine‐cystatin C and BIS2 equation underestimated and CKD‐EPI cystatin C and Simple cystatin C equation overestimated measured GFR. All equations lacked precision. Analysis of ability to correctly predict patient's GFR below or above 45 mL/min per 1.73 m2 showed similar ability for all equations (P = 0.24–0.89). All equations are equally accurate for estimating GFR in elderly Caucasian CKD patients. For daily practice Simple cystatin C equation is most practical.
MicroRNA‐1254 inhibits the migration of colon adenocarcinoma cells by targeting PSMD10
Authors: Chu Yi Min , Peng Hai Xia , Xu Ying , Yang Da Ming , Zhou Feng Li , Li Ji , Kuai Rong , Lin Yong
Published: March 2017

OBJECTIVE

MicroRNA‐1254 (miR‐1254) has not been studied in colorectal cancer (CRC) to date. This study aimed to investigate the inhibitory mechanism of miR‐1254 in CRC tumorigenesis.

METHODS

MiR‐1254 expression was examined using real‐time polymerase chain reaction in CRC and adjacent non‐tumorous tissues. The correlation between miR‐1254 expressions and proliferation and migration of cancer cells was determined using the CCK‐8 and transwell assays. RNA sequencing was used to identify differentially expressed genes downstream from miR‐1254. A luciferase reporter assay was used to confirm the direct interaction between miR‐1254 and its predicted target gene, PSMD10. Moreover, PSMD10 was either overexpressed or silenced in colon carcinoma cells overexpressing miR‐1254 to determine whether their interaction contributed to CRC migration and epithelial‐mesenchymal transition (EMT).

RESULTS

Significantly lower miR‐1254 expressions were observed in CRC tissues than in adjacent non‐tumorous tissues. Exogenous miR‐1254 expression suppressed the migration of colon carcinoma cell lines SW1116 and HCT116. RNA sequencing and luciferase assays revealed that miR‐1254 directly binded to the 3′‐untranslated region of PSMD10, an important regulator of EMT and cell migration. PSMD10 knockdown inhibited EMT and colon cancer cell migration, whereas PSMD10 overexpression reversed the inhibition of EMT and cell migration caused by miR‐1254.

CONCLUSION

MiR‐1254 may act as a tumor suppressor in CRC and may inhibit CRC migration by directly targeting PSMD10 to suppress the EMT process.
Anxiety, Anxiety Sensitivity, and Perceived Stress as Predictors of Recent Drinking, Alcohol Craving, and Social Stress Response in Heavy Drinkers
Authors: McCaul Mary E. , Hutton Heidi E. , Stephens Mary Ann C. , Xu Xiaoqiang , Wand Gary S.
Published: March 2017

Background

Stress and anxiety are widely considered to be causally related to alcohol craving and consumption, as well as development and maintenance of alcohol use disorder (AUD). However, numerous preclinical and human studies examining effects of stress or anxiety on alcohol use and alcohol‐related problems have been equivocal. This study examined relationships between scores on self‐report anxiety, anxiety sensitivity, and stress measures and frequency and intensity of recent drinking, alcohol craving during early withdrawal, as well as laboratory measures of alcohol craving and stress reactivity among heavy drinkers with AUD.

Methods

Media‐recruited, heavy drinkers with AUD (N = 87) were assessed for recent alcohol consumption. Anxiety and stress levels were characterized using paper‐and‐pencil measures, including the Beck Anxiety Inventory (BAI), the Anxiety Sensitivity Index‐3 (ASI‐3), and the Perceived Stress Scale (PSS). Eligible subjects (N = 30) underwent alcohol abstinence on the Clinical Research Unit; twice daily measures of alcohol craving were collected. On day 4, subjects participated in the Trier Social Stress Test; measures of cortisol and alcohol craving were collected.

Results

In multivariate analyses, higher BAI scores were associated with lower drinking frequency and reduced drinks/drinking day; in contrast, higher ASI‐3 scores were associated with higher drinking frequency. BAI anxiety symptom and ASI‐3 scores also were positively related to Alcohol Use Disorders Identification Test total scores and AUD symptom and problem subscale measures. Higher BAI and ASI‐3 scores but not PSS scores were related to greater self‐reported alcohol craving during early alcohol abstinence. Finally, BAI scores were positively related to laboratory stress‐induced cortisol and alcohol craving. In contrast, the PSS showed no relationship with most measures of alcohol craving or stress reactivity.

Conclusions

Overall, clinically oriented measures of anxiety compared with perceived stress were more strongly associated with a variety of alcohol‐related measures in current heavy drinkers with AUD.
Hypomania Checklist‐32 – cross‐validation of shorter versions screening for bipolar disorders in an epidemiological study
Authors: Meyer T. D. , Castelao E. , Gholamrezaee M. , Angst J. , Preisig M.
Published: March 2017

Objective

Self‐reports such as Hypomania Checklist (HCL‐32) can be used to enhance recognition of bipolar disorders, but they are often too long and only validated in clinical samples. The objectives of this study are therefore to test whether (i) the HCL‐32 can be used for screening in the community and (ii) whether two previously suggested shorter versions would do as well.

Method

Data stemmed from the CoLaus|PsyColaus, a prospective cohort study which included randomly selected residents aged 35–66 years from an urban area. Participants underwent semistructured interviews to assess DSM‐IV disorders and 1712 of them completed the HCL‐32.

Results

Forty individuals (2.3%) were diagnosed as having BD. Compared to others, participants with BD scored significantly higher on the HCL‐32. The HCL‐32 had a sensitivity of 0.78 and specificity of 0.68. Very similar figures were found for two previously proposed shorter versions with 16 and 20 items. The results of confirmatory factor analysis and item response theory (IRT) models supported the postulated two‐factor structure for the three HCL versions.

Conclusion

Despite the low base rate of BD in this sample, the screening properties of the HCL‐32 remained almost as good. Importantly, two previously proposed shorter versions performed as well, suggesting that those could be used without losing essential information.
Identification of the interaction between bta‐miR‐370 and OLR1 gene in bovine adipocyte
Authors: Li H. F. , Wang S. H. , Guo Y. , Zhao H. B. , Li X. Y. , Wang X.
Published: March 2017

It has been shown that the oxidized low density lipoprotein receptor 1 (OLR1) gene plays an important role in the degradation of oxidized low density lipoprotein. Previous studies found a SNP in the 3′‐untranslated region (3′‐UTR) of the OLR1 gene associated with milk production traits in different dairy cattle populations and with loin eye area and marbling depth in beef cattle. MicroRNAs can regulate gene expression by binding the 3′‐UTR of target genes to degrade or to repress the translation of target genes. Bioinformatics have shown that there is a binding site of bta‐miR‐370 in the 3′‐UTR of the OLR1 gene, and a previous luciferase reporter assay system showed that the A/C mutation occurring in the 3′‐UTR of this gene caused the binding sites of bta‐miR‐370 to disappear in HEK293 cells. To further validate whether OLR1 was the target gene of bta‐miR‐370, the over‐expression and interference expression of bta‐miR‐370 were determined by transfecting bta‐miR‐370 mimics and inhibitor supplementations into bovine adipocyte. The qRT‐PCR result showed that the relative expression of OLR1 gene significantly decreased in the mimics group compared to the control, whereas the expression level in inhibitor group was higher than its control group. The above results were further verified by a Western blot at the protein level. In addition, lipid formation analysis of bovine adipocytes was performed via oil red O staining, and we found that cytoplasm lipid droplets in the inhibitor group showed a tendency to increase compared to the control group, whereas in the mimics group, we observed an obvious decrease of cytoplasm lipid droplets compared to the control and inhibitor groups. Taken together, our data here suggest that bta‐miR‐370 has a negative regulation role for OLR1 both at the gene expression and protein levels and bovine adipocytes cytoplasm lipid droplets formation, which provides a reference for illustrating how the OLR1 gene affects milk production and beef quality traits in cattle.
Implementing universal cervical length screening in asymptomatic women with singleton pregnancies: challenges and opportunities
Authors: Pedretti Michelle K. , Kazemier Brenda M. , Dickinson Jan E. , Mol Ben W. J.
Published: March 2017

Cervical length (CL) screening has been successfully utilised to identify asymptomatic women, with a singleton pregnancy, at risk of preterm birth (PTB), thereby providing an opportunity to offer interventions that may reduce that risk. Cervical length screening with ultrasound is most effectively performed with a transvaginal approach. Universal cervical length screening, encompassing all singleton pregnancies rather than restricting screening to those considered at increased risk ofPTB, is currently not widely used, despite a growing body of evidence in support of its utility forPTBprevention. There are a number of barriers that may prevent or restrict the implementation of a universalCLscreening program. These include cost, availability of vaginal progesterone and other treatment options, reluctance of women to undergo transvaginal ultrasound and the perceptions and beliefs of medical practitioners. Given that mid‐pregnancyCLmeasurement is a recognised predictor of spontaneousPTB, that most cases ofPTBoccur with no prior maternal history and that there are interventions available that may reduce the risk ofPTB, we believe there is a clear role for routineCLscreening to be adopted as a component of the fetal morphology ultrasound examination. As a strategy to reducePTBrates, discussion and counselling aboutPTBprevention andCLscreening should be adopted as a core element of prenatal care.
Children with atopic dermatitis and frequent emollient use have increased urinary levels of low‐molecular‐weight phthalate metabolites and parabens
Authors: Overgaard L. E. K. , Main K. M. , Frederiksen H. , Stender S. , Szecsi P. B. , Williams H. C. , Thyssen J. P.
Published: March 2017

Background

Parabens may be added to cosmetic and personal care products for preservation purposes. Low‐molecular weight (LMW) phthalate diesters function as plasticizers, fixatives or solvents in such products, but may also be found in small quantities as contaminants from plastic containers.

Objective

To evaluate the association between emollient use, atopic dermatitis and FLG mutations, respectively, with urinary concentrations of phthalate metabolites and parabens in Danish children.

Methods

Eight hundred and forty‐five Danish children 4‐9 years of age were studied. Urinary concentrations of phthalate metabolites and parabens were determined, and children were genotyped for common FLG loss‐of‐function mutations. Information about atopic dermatitis and use of emollients was obtained from questionnaires completed by parents.

Results

The prevalence of atopic dermatitis was 16.1%. Phthalate metabolite and paraben levels were generally higher in children with frequent use of emollients compared to uncommon users, reaching statistical significance for some LMW phthalates and parabens. While there was no association with common FLG mutations, children with atopic dermatitis had significantly higher urinary levels of one LMW phthalate and two parabens, respectively, when compared to children without atopic dermatitis.

Conclusion

Emollient use and atopic dermatitis were associated with modestly increased internal LMW phthalate and paraben exposure in 4‐9 year old children. It is unknown whether the difference is explained by increased use of the specific emollients that are used to treat pruritic and inflamed skin, and/or whether the impaired skin barrier allows chemicals to penetrate more easily. Moreover, the putative toxicological burden is unknown.
An investigation of the potential effect of sperm nuclear vacuoles in human spermatozoa on DNA fragmentation using a neutral and alkaline Comet assay
Authors: Pastuszek E. , Kiewisz J. , Skowronska P. , Liss J. , Lukaszuk M. , Bruszczynska A. , Jakiel G. , Lukaszuk K.
Published: March 2017

Presence of vacuoles and degree of sperm DNA damage are considered to be the basic factors used for the assessment of sperm fertilization capacity. We aimed to investigate the link between these two parameters. According to our knowledge, this is the first study where the Comet assay was used to assess the degree of DNA fragmentation of sperm categorized by Motile Sperm Organelle Morphology Examination (MSOME) Grades. Semen samples from 10 patients were assessed. Spermatozoa were graded into four MSOME groups according to the Vanderzwalmen's criteria. A total of 3930 motile spermatozoa were selected one‐by‐one using an inverted microscope and transferred onto two different slides. The degree of DNA fragmentation was analyzed by alkaline and neutral Comet assay. Results of the neutral Comet assay showed that Grade I spermatozoa (absence of vacuoles) presented significantly lower dsDNA fragmentation level (mean: 3.13 ± 1.17%) than Grade II (maximum of two small vacuoles; mean: 10.34 ± 2.65%), Grade III (more than two small vacuoles or at least one large vacuole; mean: 23.88 ± 8.37%), and Grade IV (large vacuoles associated with abnormal head shapes or other abnormalities; mean: 36.94 ± 7.78%; p < 0.05). Results of the alkaline Comet assay showed that Grade I spermatozoa had significantly lower DNA (ssDNA + dsDNA) fragmentation level (mean: 8.33 ± 3.62%) than Grade III (mean: 25.64 ± 9.15%) and Grade IV (mean: 40.10 ± 9.10%, p < 0.05), but not significantly lower than Grade II (mean: 12.73 ± 5.06%; p > 0.05). Probably, the vacuoles may be responsible for double strand DNA breaks rather than single strand DNA breaks (only 2.39% spermatozoa in MSOME Grade II, 1.76% in III, and 3.16% in IV has single strand breaks). The results demonstrate that lower MSOME grading correlates with lower sperm DNA fragmentation. Therefore, the observation of sperm nuclear vacuoles using real‐time optical microscopy without precise DNA fragmentation examination is not sufficient for optimal sperm selection for intracytoplasmic sperm injection.
DNA methylation imprinting errors in spermatogenic cells from maturation arrest azoospermic patients
Authors: Marques P. I. , Fernandes S. , Carvalho F. , Barros A. , Sousa M. , Marques C. J.
Published: March 2017

Imprinting errors have been described in spermatozoa from infertile patients with oligozoospermia and azoospermia. However, little is known about methylation of imprinted genes in other spermatogenic cells from azoospermic patients. Therefore, we aimed to evaluate the methylation status of single CpGs located in the differentially methylated regions (DMRs) of two imprinted genes, one paternally (H19) and one maternally (MEST) methylated, in primary spermatocytes of azoospermic patients presenting complete (MAc, n = 7) and incomplete (MAi, n = 8) maturation arrest, as well as in other spermatogenic cells from MAi patients that presented focus of complete spermatogenesis in some seminiferous tubules. We observed H19 imprinting errors in primary spermatocytes from one MAi patient and MEST imprinting errors in one MAi and two MAc patients. Additionally, H19 imprinting errors were observed in elongated spermatids/spermatozoa from one MAi patient. Nevertheless, no statistical differences were found for H19 and MEST global methylation levels (percentage of methylated and unmethylated CpGs, respectively) between patients with complete and incomplete MA and also between MA groups and a control group. These results provide further evidence that imprinting errors occur in spermatogenic cells from patients presenting impaired spermatogenesis, as we and others have previously described in ejaculated and testicular spermatozoa. As paternal imprinting errors can be transmitted to the embryo by the sperm cell, they can provide a possible explanation for poor embryo development and/or low pregnancy rates as correct expression of imprinted genes is crucial for embryo and placental development and function. Therefore, in cases with male factor infertility where unsuccessful in vitro fertilization (IVF) treatments are recurrent, analysis of imprinting marks in spermatozoa might be a useful diagnostic tool.
Effect of endocrine disruptors on male reproduction in humans: why the evidence is still lacking?
Authors: Bliatka D. , Lymperi S. , Mastorakos G. , Goulis D. G.
Published: March 2017

The so‐called “endocrine disruption hypothesis” suggests that exposures to endocrine disruption (EDs) during fetal, neonatal and adult life may interfere with the development of reproductive organs and alter semen quality and reproductive hormone production. Even though animal studies provide substantial evidence of adverse effects of EDs on male reproductive system, epidemiological studies in humans arrive at conflicting results. The aim of the present study was to systematically review the literature to locate methodological characteristics of the studies that struggle the formation of an association between EDs and human male reproduction. Such characteristics include: (i) definition of the exposed and the non‐exposed population, (ii) age, (iii) insufficient control for confounders, (iv) ED assay and threshold, (v) time parameters of ED exposure, and (vi) study outcomes. Additional issues are: (i) the late effect of an early exposure, (ii) the multiple exposure effect, and (iii) the fact the same ED may exhibit different modes of action. Unfortunately, the nature of the field precludes the conduction of randomized‐controlled trials, which could result to etiological associations between EDs and human male reproduction. Consequently, there is a great need to conduct well‐designed studies of case–control or cohort type to evaluate EDs effects on human male reproductive health, and apply possible measures that could limit dangerous exposures.
Hypothesis Testing in Functional Linear Models
Authors: Su Yu-Ru , Di Chong-Zhi , Hsu Li
Published: March 2017

Functional data arise frequently in biomedical studies, where it is often of interest to investigate the association between functional predictors and a scalar response variable. While functional linear models (FLM) are widely used to address these questions, hypothesis testing for the functional association in the FLM framework remains challenging. A popular approach to testing the functional effects is through dimension reduction by functional principal component (PC) analysis. However, its power performance depends on the choice of the number of PCs, and is not systematically studied. In this article, we first investigate the power performance of the Wald-type test with varying thresholds in selecting the number of PCs for the functional covariates, and show that the power is sensitive to the choice of thresholds. To circumvent the issue, we propose a new method of ordering and selecting principal components to construct test statistics. The proposed method takes into account both the association with the response and the variation along each eigenfunction. We establish its theoretical properties and assess the finite sample properties through simulations. Our simulation results show that the proposed test is more robust against the choice of threshold while being as powerful as, and often more powerful than, the existing method. We then apply the proposed method to the cerebral white matter tracts data obtained from a diffusion tensor imaging tractography study.
Learning Gene Regulatory Networks from Next Generation Sequencing Data
Authors: Jia Bochao , Xu Suwa , Xiao Guanghua , Lamba Vishal , Liang Faming
Published: March 2017

In recent years, next generation sequencing (NGS) has gradually replaced microarray as the major platform in measuring gene expressions. Compared to microarray, NGS has many advantages, such as less noise and higher throughput. However, the discreteness of NGS data also challenges the existing statistical methodology. In particular, there still lacks an appropriate statistical method for reconstructing gene regulatory networks using NGS data in the literature. The existing local Poisson graphical model method is not consistent and can only infer certain local structures of the network. In this article, we propose a random effect model-based transformation to continuize NGS data and then we transform the continuized data to Gaussian via a semiparametric transformation and apply an equivalent partial correlation selection method to reconstruct gene regulatory networks. The proposed method is consistent. The numerical results indicate that the proposed method can lead to much more accurate inference of gene regulatory networks than the local Poisson graphical model and other existing methods. The proposed data-continuized transformation fills the theoretical gap for how to transform discrete data to continuous data and facilitates NGS data analysis. The proposed data-continuized transformation also makes it feasible to integrate different types of data, such as microarray and RNA-seq data, in reconstruction of gene regulatory networks.
Augmented Estimation for t-Year Survival with Censored Regression Models
Authors: Zheng Yu , Cai Tianxi
Published: March 2017

Reliable and accurate risk prediction is fundamental for successful management of clinical conditions. Estimating comprehensive risk prediction models precisely, however, is a difficult task, especially when the outcome of interest is time to a rare event and the number of candidate predictors, p, is not very small. Another challenge in developing accurate risk models arises from potential model misspecification. Time-specific generalized linear models estimated with inverse censoring probability weighting are robust to model misspecification, but may be inefficient in the rare event setting. To improve the efficiency of such robust estimation procedures, various augmentation methods have been proposed in the literature. These procedures can also leverage auxiliary variables such as intermediate outcomes that are predictive of event risk. However, most existing methods do not perform well in the rare event setting, especially when p is not small. In this article, we propose a two-step, imputation-based augmentation procedure that can improve estimation efficiency and that is robust to model misspecification. We also develop regularized augmentation procedures for settings where p is not small, along with procedures to improve the estimation of individualized treatment effect in risk reduction. Numerical studies suggest that our proposed methods substantially outperform existing methods in efficiency gains. The proposed methods are applied to an AIDS clinical trial for treating HIV-infected patients.
State of the art – how I manage immune thrombocytopenia
Authors: Cooper Nichola
Published: March 2017

The management of patients with immune thrombocytopenia (ITP) is rapidly evolving. Over the last 15 years, a number of novel treatments have improved practice, with many steroid‐sparing agents and a reduction in the progression to splenectomy. Although this has improved clinical care, many therapeutic challenges remain. There is no diagnostic test, no biomarkers to direct treatment and few comparative studies to help management decisions. Development of up to date guidelines is difficult with little high‐grade evidence. First line treatment continues to be steroids and intravenous immunoglobulins (IVIG) although both are often poorly tolerated and not curative. Common second line treatments include rituximab, immunosuppressive agents, such as azathioprine and mycophenolate mofetil, and the thrombopoietin receptor agonists romiplostim and eltrombopag. There are no comparative studies to decide between these agents and treatment is generally individualized, depending on comorbidity. Use of splenectomy has declined and is generally reserved for patients with chronic disease, although the exact position of splenectomy is subject to debate. Further understanding of the cause of disease in individual patients may help guide treatment. Randomized controlled studies of common treatments and novel treatments for refractory patients are urgently needed.
Home and the social worlds beyond: exploring influences in the lives of children of mothers with intellectual disability
Authors: Collings S. , Llewellyn G. , Grace R.
Published: March 2017

Background

Mothers with intellectual disability are likely to raise their children in socially disadvantaged circumstances, and many face social isolation; however, the impact of a potentially restricted home context on children's social worlds has not been examined. This study was conducted to explore influences in the social worlds of children of mothers with intellectual disability from a child's perspective.

Methods

Seven children aged 7 to 11 years took part in at least two semi‐structured interviews over a year. Narrative accounts of each child's social interactions were analysed to ascertain if a pattern was present across the group.

Results

Home was found to influence the children's social interactions elsewhere by providing (or not) predictable routines and rules, and support from a significant adult other than a mother. Home environments were found to influence other social worlds by establishing a foundation for children's expectations about social interactions.

Conclusions

The social worlds of school‐aged children of mothers with intellectual disability are shaped by influences in the home that cannot be attributed exclusively to having a parent with intellectual disability. Significant adults provide an important support role and can be fulfilled by social service workers when a family‐centred approach is applied.
The polymorphic CAG repeat in exon 1 of androgen receptor is associated with level of HDL cholesterol and hypertension in Chinese middle‐aged and elderly men
Authors: Yang Deyu , Tian Jinhai , Zhang Xu , Yu Jingjing , Li Shuya , Wang Zhizhong , Ma Yuying , Liu Lan , Huang Qi , Ma Rong , Wang Jia , Li Xin , Jiang Min
Published: March 2017

Objective

The length of the CAG repeats in exon 1 of the androgen receptor (AR) gene has been shown to be inversely correlated with AR transcriptional activity. This study aimed to investigate the correlations between the length of CAG repeat in AR and serum lipids and hypertension in Chinese men.

Design and patients

The relationship between length of the CAG repeat in exon 1 of AR with prevalence of hypertension and the levels of serum lipids among Chinese men (aged ≥40 years).

Measurements

The physical condition of the subjects was examined and recorded. The concentrations of blood lipids and sex hormones were measured, and the CAG repeat lengths of the AR gene were determined.

Results

The length of the AR CAG repeats was associated with HDL cholesterol (HDL‐C) concentration, and the stepwise multiple regression model showed that this association was independent of body mass index (BMI), triglycerides (TG) and total cholesterol (TC), although these factors influence HDL‐C concentration. Furthermore, men with <22 vs men with ≥22 CAG repeats showed higher blood pressure and higher prevalence of hypertension. Shorter CAG repeat numbers were associated with the increased risk of hypertension in a multivariate logistic regression analysis (odds ratio = 0·715; 95% confidence interval, 0·517–0·989; P = 0·043). No significant correlation of AR CAG repeat polymorphism with sex hormone levels, TG, LDL cholesterol (LDL‐C) or TC was found.

Conclusions

This study provides evidence that men carrying shorter (<22) AR CAG repeats have lower HDL‐C level and increased risk of hypertension. The androgenic activity may differ due to the polymorphic length of CAG repeats of the AR gene.
Inpatient treatment of patients with acute idiopathic peripheral facial palsy: A population‐based healthcare research study
Authors: Plumbaum K. , Volk G.F. , Boeger D. , Buentzel J. , Esser D. , Steinbrecher A. , Hoffmann K. , Jecker P. , Mueller A. , Radtke G. , Witte O.W. , Guntinas‐Lichius O.
Published: March 2017

Objectives

To determine the inpatient management for patients with acute idiopathic facial palsy (IFP) in Thuringia, Germany.

Design

Population‐based study.

Setting

All inpatients with IFP in all hospitals with departments of otolaryngology and neurology in 2012, in the German federal state, Thuringia.

Main outcome measures

Patients’ characteristics and treatment were compared between departments, and the probability of recovery was tested.

Results

A total of 291 patients were mainly treated in departments of otolaryngology (55%) and neurology (36%). Corticosteroid treatment was the predominant therapy (84.5%). The probability to receive a facial nerve grading (odds ratio [OR=12.939; 95% confidence interval [CI]=3.599 to 46.516), gustatory testing (OR=6.878; CI=1.064 to 44.474) and audiometry (OR=32.505; CI=1.485 to 711.257) was significantly higher in otolaryngology departments, but lower for cranial CT (OR=0.192; CI=0.061 to 0.602), cerebrospinal fluid examination (OR=0.024; CI=0.006 to 0.102). A total of 131 patients (45%) showed a recovery to House‐Brackmann grade≤II. A pathological stapedial reflex test (Hazard ratio [HR]=0.416; CI=0.180 to 0.959) was the only independent diagnostic predictor of worse outcome. Prednisolone dose >500 mg (HR=0.579; CI 0.400 to 0.838) and no adjuvant physiotherapy (HR=0.568; CI=0.407 to 0.794) were treatment‐related predictors of worse outcome.

Conclusions

Inpatient treatment of IFP seems to be highly variable in daily practice, partly depending on the treating discipline and despite the availability of evidence‐based guidelines. The population‐based recovery rate was worse than reported in clinical trials.
Efficacy and safety of sitagliptin as compared with glimepiride in Japanese patients with type 2 diabetes mellitus aged ≥ 60 years (START‐J trial)
Authors: Terauchi Yasuo , Yamada Yuichiro , Ishida Hitoshi , Ohsugi Mitsuru , Kitaoka Masafumi , Satoh Jo , Yabe Daisuke , Shihara Nobuyuki , Seino Yutaka
Published: March 2017

The aim of this study was to evaluate the efficacy and safety of sitagliptin administered to elderly patients with type 2 diabetes mellitus (T2DM) for 1 year as compared with glimepiride. Patients aged ≥60 years with T2DM and inadequately controlled blood glucose were randomly assigned to sitagliptin 50 mg once daily or glimepiride 0.5 mg once daily for 52 weeks. The primary efficacy endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 52. Secondary efficacy endpoints included self‐monitored blood glucose and weight. Safety endpoints were adverse events including hypoglycaemia. Administration of sitagliptin or glimepiride to elderly patients with T2DM resulted in a significant decrease in HbA1c change from baseline. At 52 weeks, the least squares mean difference between the treatments was 0.11% (95% confidence interval [CI] −0.02 to 0.24; P = .087) (1.2 mmol/mol [−0.2 to 2.6]). The upper limit of the CI was below the predefined non‐inferiority margin (0.3% [3.3 mmol/mol]), demonstrating non‐inferiority of sitagliptin to glimepiride for the primary endpoint. Sitagliptin resulted in a significantly lower incidence rate of non‐serious hypoglycaemia than glimepiride during the 52 weeks (4.7% vs 16.1%; P = .002); thus, sitagliptin is a useful therapeutic option for elderly patients with T2DM.
Association between diabetes mellitus and incidence of intracerebral haemorrhage and case fatality rates: A retrospective population‐based cohort study
Authors: Boulanger Marion , Al‐Shahi Salman Rustam , Kerssens Jan , Wild Sarah H. ,   on behalf of the Scottish Diabetes Research Network Epidemiology Group
Published: March 2017

We investigated the associations between diabetes (type 1, type 2 or no diabetes) and intracerebral haemorrhage (ICH) incidence as well as case fatality after ICH, in a retrospective cohort study of people aged 40 to 89 years in Scotland during the period 2004 to 2013, using linkage of population‐based records of diagnosed diabetes, hospital discharges and deaths. We calculated ICH incidence and 30‐day case fatality after hospital admission for ICH, along with their relative risks (RR) and 95% confidence intervals (CIs), among people with type 1 or type 2 diabetes compared to people without diabetes, adjusting for age, sex and socio‐economic status (SES). There were 77, 1275 and 9778 incident ICH events and the case‐fatality rate was 44% (95% CI 33, 57), 38% (95% CI 35, 41) and 36% (95% CI 35, 37) in people with type 1, type 2 and without diabetes, respectively. In comparison with absence of diabetes, type 1 diabetes was associated with a higher incidence of ICH (1.74, 95% CI 1.38‐2.21) and higher case fatality after ICH (1.35, 95% CI 1.01‐1.70), after adjustment for age, sex and SES. The small increases in ICH incidence (1.06, 95% CI 0.99‐1.12) and case‐fatality (1.04, 95% CI 0.96‐1.13) in people with type 2 diabetes compared with people without diabetes were not statistically significant.
Residual pyruvate kinase activity in PKLR‐deficient erythroid precursors of a patient suffering from severe haemolytic anaemia
Authors: Klei Thomas R.L. , Kheradmand Kia Sima , Veldthuis Martijn , Beuger Boukje M. , Geissler Judy , Dehbozorgian Javad , Karimi Mehran , van Bruggen Robin , van Zwieten Rob
Published: March 2017

Objective

Here, we present a 7‐year‐old patient suffering from severe haemolytic anaemia. The most common cause of chronic hereditary non‐spherocytic haemolytic anaemia is red blood cell pyruvate kinase (PK‐R) deficiency. Because red blood cells rely solely on glycolysis to generate ATP, PK‐R deficiency can severely impact energy supply and cause reduction in red blood cell lifespan. We determined the underlying cause of the anaemia and investigated how erythroid precursors in the patient survive.

Methods

PK activity assays, Western blot and Sanger sequencing were employed to determine the underlying cause of the anaemia. Patient erythroblasts were cultured and reticulocytes were isolated to determine PK‐R and PKM2 contribution to glycolytic activity during erythrocyte development.

Results

We found a novel homozygous mutation (c.583G>A) in the PK‐R coding gene (PKLR). Although this mutation did not influence PKLR mRNA production, no PK‐R protein could be detected in the red blood cells nor in its precursors. In spite of the absence of PK‐R, the reticulocytes of the patient exhibited 20% PK activity compared with control. Western blotting revealed that patient erythroid precursors, like controls, express residual PKM2.

Conclusions

We conclude that PKM2 rescues glycolysis in PK‐R‐deficient erythroid precursors.
Pathophysiological aspects of red blood cells in end‐stage renal disease patients resistant to recombinant human erythropoietin therapy
Authors: Georgatzakou Hara T. , Tzounakas Vassilis L. , Kriebardis Anastasios G. , Velentzas Athanassios D. , Papageorgiou Effie G. , Voulgaridou Artemis I. , Kokkalis Apostolos C. , Antonelou Marianna H. , Papassideri Issidora S.
Published: March 2017

Objective

Modified, bioreactive red blood cells (RBCs) and RBC‐derived microvesicles (MVs) likely contribute to the hematological and cardiovascular complications in end‐stage renal disease (ESRD). This study assesses the physiological profile of RBCs in patients with ESRD receiving standard or high doses of recombinant human erythropoietin (rhEPO).

Method

Blood samples from twenty‐eight patients under sustained hemodialysis, responsive, or not to standard rhEPO administration were examined for RBC morphology, fragility, hemolysis, redox status, removal signaling, membrane protein composition, and microvesiculation before and after dialysis. Acute effects of uremic plasma on RBC features were examined in vitro through reconstitution experiments.

Results

Overall, the ESRD RBCs were characterized by pathological levels of shape distortions, surface removal signaling, and membrane exovesiculation, but reduced fragility compared to healthy RBCs. Irreversible transformation of RBCs was found to be a function of baseline Hb concentration. The more toxic uremic context in non‐responsive patients compared to rhEPO responders was blunted in part by the antioxidant, antihemolytic, and anti‐apoptotic effects of high rhEPO doses, and probably, of serum uric acid. A selective lower expression of RBC membrane in complement regulators (CD59, clusterin) and of CD47 “marker‐of‐self” was detected in non‐responders and responders, respectively. Evidence for different short‐term dialysis effects and probably for a different erythrocyte vesiculation mechanism in rhEPO responsive compared to non‐responsive patients was also revealed.

Conclusion

Deregulation of RBC homeostasis might involve diverse molecular pathways driving erythrocyte signaling and removal in rhEPO non‐responders compared to responsive patients.