bluuebunny/crossref_metadata_2025 huggingface dataset:
Christianising a Country: A Genuine Act of Faith or an Exercise in Political Opportunism? On (Questioning) the Authenticity of Medieval Political Conversions — the Case of Poland
Authors: Cebula Adam
Published: March 2019

The most peculiar feature of the majority of historical publications accompanying the anniversary (966–1016) of the adoption of Christianity by Poland’s first historical ruler was a specific treatment of the (possible) motivation behind Mieszko's consequential decision. The so‐called. “baptism of Poland” is generally thought to have been a strategically brilliant move, guaranteeing the country’s long‐lasting political success. The reluctance of Polish researchers to consider some spiritual motives of Mieszko is especially puzzling in the context of a significant (even if slightly provocative) contribution to the debate by American historian Philip E. Steele (2005). Following in the footsteps of Charles Odahl (2004), Steele claims that the conversion of Mieszko — similarly to that of Constantine the Great — must have been principally caused by the prince’s undergoing some sort of religious experience. While endorsing a serious treatment of the religious‐experience‐based motivation of political conversions, I suggest revisiting critically the concept of “empirical religion” underlying this approach.
Private Actions and Preferences for Coordinated Groundwater Conservation in Colorado's Republican River Basin
Authors: Shepler Ryan , Suter Jordan F. , Manning Dale T. , Goemans Chris
Published: March 2019

Conservation of groundwater resources is critical for maintaining the future productivity of irrigated land in the Ogallala Aquifer Region and beyond. This research explores motivations and behavior related to groundwater conservation among agricultural producers in the Colorado portion of the Republican River Basin, which is part of the Ogallala Aquifer. The empirical modeling uses data from a recently conducted survey to analyze how a common set of producer, farm, and resource characteristics influence groundwater values, concern for future groundwater availability, private conservation actions, and support for coordinated conservation efforts. We find two factors, producer age and land owner status, are consistently correlated with the key conservation‐related outcomes we evaluate. More generally, the results suggest considerable similarities in the characteristics that drive private conservation actions and support for coordinated conservation. This knowledge could be used to better target and incentivize future groundwater conservation efforts in the region. Editor's note: This paper is part of the featured series on Optimizing Ogallala Aquifer Water Use to Sustain Food Systems. See the February 2019 issue for the introduction and background to the series.
Employee Movements from Audit Firms to Audit Clients
Authors: Finley Andrew R. , Kim Mindy H. J. , Lamoreaux Phillip T. , Lennox Clive S.
Published: March 2019

Regulators have expressed concerns about the “revolving door” between auditors and clients, whereby audit employees move directly from audit firms to audit clients (i.e., “direct alumni hires”). Regulators are concerned that these direct hires could compromise audit quality, partly because these employees could have previously audited their hiring company's financial statements. In contrast, we examine accounting and finance executives who move indirectly from audit firms to audit clients and who could not have previously audited the hiring company's financial statements (i.e., “indirect alumni hires”). We show that indirect hires occur more often than the direct hires that have concerned regulators. We predict and find that both direct and indirect alumni hires are associated with lower rates of executive turnover and audit firm turnover. However, there is no evidence that the reduced rates of executive turnover are explained by managerial entrenchment or that these hires are associated with lower audit quality. Overall, our findings suggest that direct and indirect employee movements from audit firms to audit clients are beneficial to executives, audit clients, and audit firms because they reduce the incidence of costly turnover.
Comparative analysis of experimental data
Authors: Freckleton Robert P. , Rees Mark
Published: March 2019

We consider the problem of how to analyse data from experiments conducted on multiple species. This seems to have been largely overlooked in the literature, and we highlight that the use of species as experimental units creates issues for both the design and analysis of experiments.

We distinguish fully randomized experiments in which all treatments are applied to all species from those experiments in which the factor of interest varies at the species level, that is, treatments are not randomly allocated to species. In this latter case, the distribution of the experimental factor across species may be random, phylogenetically structured or species may be chosen in order to phylogenetically balance the sample (e.g. through sister‐species comparisons).

We show using simulations that the design of the experiment in terms of the phylogenetic distribution of the treatment can affect power and Type I error, and that commonly used approaches (Linear Mixed Models andANOVAs) may have poor statistical properties (high Type I errors) when both the predictors and response data show strong phylogenetic signal.

We highlight that the true phylogenetic generalized least squares model yield has good statistical properties but show that in some cases the true variance structure may be difficult to identify empirically. Moreover, many current comparative tools do not allow such analyses to be easily applied, and we highlight some of those that do.
Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction
Authors: Walaszczyk Anna , Dookun Emily , Redgrave Rachael , Tual‐Chalot Simon , Victorelli Stella , Spyridopoulos Ioakim , Owens Andrew , Arthur Helen M. , Passos João F. , Richardson Gavin D.
Published: March 2019

Cardiovascular disease is the leading cause of death in individuals over 60 years old. Aging is associated with an increased prevalence of coronary artery disease and a poorer prognosis following acute myocardial infarction (MI). With age, senescent cells accumulate in tissues, including the heart, and contribute to age‐related pathologies. However, the role of senescence in recovery following MI has not been investigated. In this study, we demonstrate that treatment of aged mice with the senolytic drug, navitoclax, eliminates senescent cardiomyocytes and attenuates profibrotic protein expression in aged mice. Importantly, clearance of senescent cells improved myocardial remodelling and diastolic function as well as overall survival following MI. These data provide proof‐of‐concept evidence that senescent cells are major contributors to impaired function and increased mortality following MI and that senolytics are a potential new therapeutic avenue for MI.
Nudging the financial market? A review of the nudge theory
Authors: Cai Cynthia Weiyi
Published: March 2019

A systematic review of the nudge literature and an examination of its applications across different domains reveals that: (i) a nudge, in the sense of using choice architecture to push people to choose desired results, works well; and (ii) a nudge, in the sense of pushing people to choose desired results so that people will be better off, remains questionable. In financial markets, regulators and financial intermediaries currently use nudge theory to: (i) adjust how investment choices are presented to investors; and (ii) provide information in a selective way. Besides nudging investors, it is also possible for regulators to nudge financial intermediaries towards making more ethical decisions.
Inhibitory‐control event‐related potentials correlate with individual differences in alcohol use
Authors: O'Halloran Laura , Rueda‐Delgado Laura M. , Jollans Lee , Cao Zhipeng , Boyle Rory , Vaughan Christina , Coey Phillip , Whelan Robert
Published: March 2019

Impulsivity is a multidimensional construct that is related to different aspects of alcohol use, abuse, and dependence. Inhibitory control, one facet of impulsivity, can be assayed using the stop‐signal task (SST) and quantified behaviorally via the stop‐signal reaction time (SSRT) and electrophysiologically using event‐related potentials (ERPs). Research on the relationship between alcohol use and SSRTs, and between alcohol use and inhibitory‐control ERPs, is mixed. Here, adult alcohol users (n = 79), with a wide range of scores on the Alcohol Use Disorders Identification Test (AUDIT), completed the SST under electroencephalography (EEG) (70% of participants had AUDIT total scores greater than or equal to 8). Other measures, including demographic, self‐report, and task‐based measures of impulsivity, personality, and psychological factors, were also recorded. A machine‐learning method with penalized linear regression was used to correlate individual differences in alcohol use with impulsivity measures. Four separate models were tested, with out‐of‐sample validation used to quantify performance. ERPs alone statistically predicted alcohol use (cross‐validatedr = 0.28), with both early and late ERP components contributing to the model (larger N2, but smaller P3, amplitude). Behavioral data from a wide range of impulsivity measures were also associated with alcohol use (r = 0.37). SSRT was a relatively weak statistical predictor, whereas the Stroop interference effect was relatively strong. The addition of nonimpulsivity behavioral measures did not improve the correlation (r = 0.34) and was similar when ERPs were combined with non‐ERP data (r = 0.29). These findings show that inhibitory control ERPs are robustly correlated individual differences in alcohol use.
The effect of a novel intravenous fluid (Oxsealife®) on recovery from haemorrhagic shock in pigs
Authors: Oller L. , Dyer W. B. , Santamaría L. , Largo C. , Javidroozi M. , Shander A.
Published: March 2019

Blood transfusion is given according to haemoglobin thresholds aimed at restoration of arterial oxygen‐carrying capacity. Patient survival after severe haemorrhagic shock depends on restoration of microvascular perfusion, tissue oxygen delivery, endothelial function and organ integrity. We investigated a novel crystalloid fluid designed for tissue oxygen delivery, Oxsealife®, with components that generate microvascular nitric oxide and scavenge reactive oxygen species generated during ischaemia–reperfusion injury. The amount of dissolved oxygen in blood progressively increased during step‐wise in vitro haemodilution with this fluid, suggesting that the oxygen solubility coefficient of blood is dynamic, not static. We performed a pilot safety and efficacy study to compare resuscitation with this novel crystalloid vs. whole blood transfusion in a swine haemorrhagic shock model with animals bled to an arterial lactate oxygen debt target. Despite contributing no haemoglobin, viscosity nor oncotic potential, resuscitation with Oxsealife after severe haemorrhagic shock restored central haemodynamic parameters comparable to stored allogeneic blood transfusion. Tissue perfusion, oxygenation and metabolic outcomes were equivalent between treatment groups. Increased consumption of bicarbonate in animals given Oxsealife suggested greater capillary recruitment and enhanced clearance of acidic tissue metabolites. Serum markers of organ function, animal activity during recovery and histological analysis of tissue morphology and endothelial glycocalyx integrity confirmed functional recovery from haemorrhagic shock. We conclude that recovery of tissue oxygen delivery and organ function after haemorrhagic shock may not be dependent on treatments that increase haemoglobin levels. Oxsealife shows promise for treatment of severe haemorrhagic shock and may reduce the requirement for allogeneic blood products.
Detection of protamine 2 in bovine spermatozoa and testicles
Authors: Hamilton T. R. S. , Simões R. , Mendes C. M. , Goissis M. D. , Nakajima E. , Martins E. A. L. , Visintin J. A. , Assumpção M. E. O. A.
Published: March 2019

Background

Sperm DNA integrity is crucial for transmission of genetic information to future generations and DNA damage can occur during chromatin packaging. Chromatin packaging involves the replacement of somatic nucleosomal histones by nuclear proteins called protamines. Protamine 1 (PRM1) is transcribed and translated in spermatids of all mammals; however, protamine 2 (PRM2) is transcribed in low levels in spermatids and it is not yet described in bull mature spermatozoa.

Objectives

The aim of this study was to assess gene and protein expression of PRM2 and corroborate gene and protein expression of PRM1 in bull spermatozoa and testis.

Materials and methods

For this purpose, absolute q‐RT‐PCR was performed to calculate the number of copies of PRM1 and PRM2 mRNAs in bovine epididymal spermatozoa and testicular tissue. Western blot and mass spectrometry were performed to identify PRM1 and PRM2 in samples of bovine epididymal spermatozoa. Samples of bovine testicular tissue were collected to identify PRM1 and PRM2 by immunohistochemistry.

Results

We evaluated that the number of PRM1 mRNA copies was about hundred times higher than PRM2 mRNA copies in sperm and testicular samples (p < 0.0001). In addition, we estimated the PRM1: PRM2 ratio based on mRNA number of copies. In spermatozoa, the ratio was 1: 0.014, and in testicle, the ratio was 1: 0.009. We also evaluated the immunolocalization for PRM1 and PRM2 in bovine testis, and both proteins were detected in spermatids. Western blot and mass spectrometry in bovine epididymal spermatozoa confirmed these results.

Conclusion

Our work identifies, for the first time, PRM2 in bovine epididymal spermatozoa and in testis. Further studies are still needed to understand the role of PRM2 on the chromatin of the spermatozoa and to verify how possible changes in PRM2 levels may influence the bull fertility.
Humanin levels in human seminal plasma and spermatozoa are related to sperm quality
Authors: Rao M. , Wu Z. , Wen Y. , Wang R. , Zhao S. , Tang L.
Published: March 2019

Background

Humanin has reportedly been expressed in testis and spermatozoa, but no study has yet reported its presence in human seminal plasma (SP).

Objective

The aim of this study was to investigate the presence of humanin in human SP and to determine the correlation between humanin levels in SP/spermatozoa and sperm quality.

Materials and methods

Semen samples for SP/sperm humanin level measurement were collected from 164 patients who attended our andrology clinic for fertility evaluation. The localization of humanin in spermatozoa was evaluated using an immunofluorescence method, and SP/sperm humanin levels were measured with ELISA. Correlations between SP/sperm humanin levels and sperm parameters were analyzed.

Results

Humanin was expressed in the midpiece of the spermatozoa. Humanin concentrations in the SP ranged from 24.4 to 285.1 pg/mL, with a median of 89.7 pg/mL. The SP humanin concentrations in patients with normospermia were significantly higher than those in patients with oligospermia (p < 0.001), asthenospermia (p = 0.002), and oligoasthenospermia (p < 0.001). Spearman analysis showed a positive and significant correlation between SP humanin concentration and sperm concentration (r = 0.75, p < 0.001), and progressive sperm motility (r = 0.29, p < 0.001). Sperm humanin level was significantly and positively associated with progressive sperm motility (r = 0.70, p < 0.001). In addition, a significantly higher level of humanin was found in swim‐up spermatozoa than in non‐swim‐up spermatozoa (p = 0.03).

Conclusions

Seminal plasma and sperm humanin levels were significantly and positively correlated with sperm quality, especially sperm motility. Further studies of the origin of SP humanin and its role in spermatogenesis should be conducted.
Clinical implications of the genetics of sporadic colorectal cancer
Authors: Fischer Jesse , Walker Logan C. , Robinson Bridget A. , Frizelle Frank A. , Church James M. , Eglinton Tim W.
Published: March 2019

Colorectal cancer (CRC) is common and at least 80% of cases are sporadic, without any significant family history. Prognostication and treatment have been relatively empirical for what has become increasingly identified as a genetically heterogeneous disease. There are three main genetic pathways in sporadic CRC: the chromosomal instability pathway, the microsatellite instability pathway and the CpG island methylator phenotype pathway. There is significant overlap between these complex molecular pathways and this limits the clinical application of CRC genetics. Recent Australian and New Zealand guidelines recommend routine testing of mismatch repair (MMR) status for new cases of CRC and selective KRAS and BRAF testing on the basis of diagnostic, prognostic and therapeutic implications. It is important that all clinicians treating CRC have an understanding of the importance of and basis for identifying key genetic features of CRC. It is likely that in the future better molecular characterization such as that allowed by the consensus molecular subtype classification will allow improved prognostication and targeted therapy in order to deliver more personalized treatment for CRC.
Editorial: biomarker predictors of non‐response to TNFα antagonists—the quest continues
Authors: Shouval Dror S. , Ben‐Horin Shomron
Published: March 2019

Linked Content

This article is linked to Verstockt et al papers. To view these articles,
visit https://doi.org/10.1111/apt.15126, and https://doi.org/10.1111/apt.15212.
Editorial: differences in sex‐based incidence of inflammatory bowel diseases between Asia‐Pacific and Western countries – are these due to differences in environment, access to healthcare, or pathophysiology?
Authors: Chan Simon S. M.
Published: March 2019

Linked Content

This article is linked to Shah et al paper. To view this article, visit
https://doi.org/10.1111/apt.15178.
Editorial: sarcopenia in liver transplantation—our weakest patients may need the strongest push
Authors: Mazumder Nikhilesh , Rinella Mary
Published: March 2019

Linked Content

This article is linked to Bhanji et al paper. To view this article, visit
https://doi.org/10.1111/apt.15161.
Antimicrobial dosing for common equine drugs: a content review and practical advice for veterinarians in Australia
Authors: Hardefeldt LY , Crabb HK , Bailey KE , Gilkerson JR , Billman‐Jacobe H , Browning GF
Published: March 2019

Background

Appropriate dosing with antimicrobial agents is critical for effective treatment and to prevent the development of antimicrobial resistance.

Methods

A review was undertaken of equine journal articles (Equine Veterinary Journal,Equine Veterinary Education,Australian Veterinary Journal,Australian Equine Veterinarian,Journal of Veterinary Internal MedicineandJournal of Equine Veterinary Science) between January 2015 and August 2018. Those with dosing regimens for procaine penicillin G, gentamicin or trimethoprim‐sulfonamide in adult horses were examined and evaluated. Pharmacokinetics and ‐dynamics of these drugs were also reviewed.

Results & Conclusion

The most frequently reported doses for penicillin, gentamicin and trimethoprim‐sulfonamide were 20–25,000 IU/kg, 6.6 mg/kg and 30 mg/kg, respectively. Veterinarians treating equine patients in Australia should be aware of the current recommended doses and inter‐dosing intervals to ensure efficacy in therapy and to preserve the usefulness of these antimicrobials for the future.
Antebrachiometacarpal arthrodesis in five dogs
Authors: Lewis ST , Lewis DD , Cross AR , Radasch RM , Boekhout‐Ta C
Published: March 2019

Case reports

Five dogs (4 with severe carpal contracture, 1 with a chronically infected carpal joint) underwent antebrachiometacarpal arthrodesis. Excision of all carpal bones, except the accessory carpal bone, was done, either because of persistent infection or to allow the manus to be arthrodesed in a functional position. All five dogs developed varying degrees of soft tissue swelling of the surgical site following surgery. All five arthrodeses achieved complete osseous union within 4–67 weeks. The immediate postoperative distal radiometacarpal frontal plane angulation ranged from 1° to 19° (mean ± SD: 7 ± 8°). The immediate postoperative distal radiometacarpal sagittal plane angulation ranged from 6° to 26° (mean ± SD: 17 ± 9°). Plate coverage of the secured metacarpal bone(s) ranged from 75% to 87% (mean ± SD: 80 ± 4%). Infection necessitated plate removal in four dogs, 3–17 (mean ± SD: 8 ± 6) months following surgery and 0–15 (mean ± SD: 5 ± 7) weeks following radiographic documentation of complete osseous union.

Conclusion

Despite one dog having marked elbow incongruency and degenerative joint disease and one dog having an ipsilateral radial nerve deficit, all five dogs improved and had acceptable limb function at the time of the final evaluation, which ranged from 25 to 296 (mean ± SD: 99 ± 111) weeks following surgery.
A randomized double‐blind, placebo‐controlled clinical phase IIa trial on safety, immunomodulatory effects and pharmacokinetics of EA‐230 during experimental human endotoxaemia
Authors: van Groenendael Roger , Kox Matthijs , Leijte Guus , Koeneman Bouke , Gerretsen Jelle , van Eijk Lucas , Pickkers Peter
Published: March 2019

Aims

EA‐230 is a human chorionic gonadotropin hormone‐derived linear tetrapeptide, developed for the treatment of systemic inflammation‐related disorders. EA‐230 has shown promising immunomodulatory and tissue‐protective effects in animals and an excellent safety profile in human phase I studies that we performed. The present phase IIa study follows‐up on these results by investigating the safety, efficacy and pharmacokinetics of EA‐230 under systemic inflammatory conditions induced by experimental human endotoxaemia.

Methods

In this randomized, double blind, placebo‐controlled phase IIa study, systemic inflammation was induced by intravenous administration of Escherichia coli‐derived lipopolysaccharide (LPS). At t = 0 hours, 36 healthy male volunteers received 2 ng/kg LPS, followed by a 2‐hour continuous infusion of EA‐230 (15, 45 and 90 mg/kg/h, n = 8 per group) or placebo (n = 12).

Results

EA‐230 was well tolerated and showed a favourable safety profile. Treatment with the highest dose of EA‐230 resulted in a significant attenuation of the LPS‐induced increase in plasma levels of inflammatory mediators interleukin (IL)‐6, IL‐8, IL‐1 receptor antagonist, monocyte chemoattractant protein‐1, macrophage inflammatory proteins‐1α and ‐1β, and vascular cell adhesion protein‐1 (% reduction of 48, 28, 33, 28, 14, 16 and 19 respectively, p < .01), and reduced fever (peak decrease from 1.8 ± 0.1°C to 1.3 ± 0.2°C, P < .05) and symptom scores (peak decrease from 7.4 ± 1.0 to 4.0 ± 1.2 points, P < .05). EA‐230 exhibited a very short elimination half‐life and a large volume of distribution in the highest dosage group (geometric mean and 95% confidence interval: 0.17 [0.12–0.24] hours and 2.2 [1.3–3.8] L/kg, respectively).

Conclusion

Administration of EA‐230 is safe and results in attenuation of the systemic inflammatory response in humans.
Live cell optical assay for precise characterization of receptors coupling to Gα12
Authors: Masuho Ikuo , Skamangas Nickolas K. , Martemyanov Kirill A.
Published: March 2019

Heterotrimeric G proteins are essential mediators of G protein‐coupled receptors (GPCRs) signalling to intracellular effectors. There is a considerable diversity of G protein subunits that channel signals initiated by GPCRs into specific outcome. In particular, mammalian genomes contain 16 conserved genes encoding G protein α subunits with unique properties. Of four Gα subfamilies (Gi/o, Gq, Gs and G12/13), members of the G12/13 group have received considerable attention for their roles in carcinogenesis. However, our ability to study activation of G12/13 by GPCRs with the power to distinguish between the two subunits is limited. Here, we present an adaptation of the bioluminescence resonance energy transfer (BRET)‐based assay to specifically monitor activity of Gα12 in living cells. In this kinetic assay, agonist‐induced release of Venus‐tagged Gβγ subunits from Gα12 is followed in real time using nano‐luciferase (Nluc)–tagged BRET donor. Using this assay, we characterized bradykinin B2 receptor (BDKRB2) and found that the receptor couples to Gα12 in addition to Gαo, and Gαq, but not to Gαs. We demonstrated the utility of this assay to quantify rates of G protein activation and inactivation as well as performing dose‐response studies while rank ordering signalling via individual Gα subunits. We further showed the utility of this assay to other GPCRs by demonstrating Gα12 coupling of cholecystokinin A receptor (CCKAR). Introduction of the Gα12‐coupling BRET assay is expected to accelerate characterization of GPCR actions on this understudied G protein.
A comparative study of digital informal learning: The effects of digital competence and technology expectancy
Authors: He Tao , Li Shihua
Published: March 2019

The objective of this paper is to investigate the effects of digital competence and technology expectancy and how they interact with cultural differences on digital informal learning (DIL) of university students have different cultural backgrounds. Empirical data collected from a survey conducted both in China and Belgium, the total sample consists of 335 Chinese and 197 Belgians. Partial least square with formative assessment was employed to test the proposed model and multi‐groups comparison analysis was conducted to examine the moderation effects of cultural difference on influential factors related to students’ DIL behaviors. The results highlighted the essential role of digital competence and technology expectancy in DIL. Cultural difference revealed a strong influence on the motive pattern of DIL behaviors. This study raised some major implications for educational researchers and practitioners alike. Specifically, the paper introduced and stressed the role of digital competence in informal learning context which was rarely considered in prior studies in terms of learning ecology. The study expanded current theoretical understanding of technology adoption in informal learning environments across different cultural contexts. The finding has shown both a homogeneous informal learning behavior and motive variance between different two cultural backgrounds. The study also provided a set of practical implications, including the need for digital competence training in today’s digital era, and the need for a satisfactory user interface design globally.
Identity threat and identity multiplicity among minority youth: Longitudinal relations of perceived discrimination with ethnic, religious, and national identification in Germany
Authors: Fleischmann Fenella , Leszczensky Lars , Pink Sebastian
Published: March 2019

The notion that ethnic and religious minority identities are inherently incompatible with the national identities of European immigrant‐receiving societies is popular in public discourse. Although findings documenting such negative associations seemingly support this claim, other research shows that the intergroup context matters for the extent to which minorities’ ethnic and religious identities are conflicting (i.e., negatively associated) or compatible (i.e., positively associated) with European national identities. However, previous research relied on cross‐sectional data and therefore could not capture the dynamic process through which minority youth come to develop compatible or conflicting identification patterns. We extend this work with a longitudinal approach by capturing developmental trajectories of identity multiplicity among ethnic minority early adolescents in Germany over three waves with 9‐month intervals. At each measurement point, participants reported their ethnic, religious, and (German) national identification and their experiences with discriminatory treatment. We estimate a cross‐lagged panel model to study how identification relates to perceived discrimination and how this affects (changes in) associations between ethnic, religious, and national identification of minority youth. Our results show prevalent positive associations between ethnic, religious, and national identification across minority youth in the sample. Those who report more frequent discrimination, however, lower their (German) national identification over time, which in turn predicts increased minority identification. We conclude that identity threat indeed triggers a development of more conflicting identification patterns.
Did humans and natural forests coexist in close proximity? A case study of the Lateglacial and Holocene Mollusca in the Moravian Karst, Czech Republic
Authors: Juřičková Lucie , Horáčková Jitka , Jansová Anna , Škodová Jana , Kosová Tereza , Ložek Vojen
Published: March 2019

Prehistoric settlements are usually perceived as being in opposition to the natural development of the landscape. Indeed, for woodland snail assemblages in anthropogenic landscapes in central Europe, considerable impoverishment is typical. However, it remains unclear whether this has been caused by humans only or also by climate effects. From an archaeological point of view, the Moravian Karst is one of the classic prehistorical locations in central Europe, but with a more humid climate than the previously studied anthropogenic areas. To learn more about coexistence of humans and natural forests during the Lateglacial and Holocene, we analysed 11 mollusc successions covering this entire area, a unique data set for such a relatively small area. These mollusc successions show several specific features compared to the standard development known from other mid‐European areas. One is that although the Moravian Karst is not far from the Western Carpathians, Carpathian species appeared relatively late, only during the second half of the Holocene climatic optimum. Similarly, some western European and Alpine elements appeared later than expected. In contrast to this, however, a number of forest species with central European range appeared relatively early during the Lateglacial or Early Holocene. Two even survived the Last Glacial Maximum in the Moravian Karst. This would suggest an early occurrence of forest patches in a mosaic landscape. Humans have apparently inhabited this area since the Lateglacial amongst islands of forests, which later changed during the Boreal and then the climatic optimum into humid canopy forests. Thus, a mosaic of anthropogenic and natural habitats persisting in close vicinity was possible in rugged and humid landscapes practically until the Industrial Revolution.
Design of diffusion‐controlled drug delivery devices for controlled release of Paclitaxel
Authors: Pramanik Anurag , Garg Sanjeev
Published: March 2019

Controlled drug delivery devices were predicted in a reverse engineering framework for the controlled release of Paclitaxel, an anti‐cancer drug, widely used in the treatment of solid tumors. Using quantitative structure–property relationship models for mutual diffusion coefficients of the drug in biocompatible and biodegradable polymers and partition coefficients of the drug between polymers and blood, a framework was developed to predict optimal drug delivery devices for desired dosage regimens. The validation of the predicted mutual diffusion and partition coefficients using experimental data was reported in previous studies. Optimal design parameters along with selection of most appropriate polymers suitable for different dosage regimens, selected based on current clinical practice, were predicted for maximum bioavailability of the drug while maintaining the released drug concentration in blood within the therapeutic range. Reservoir and monolithic type of diffusion‐controlled drug delivery devices of different shapes and sizes were predicted with different initial drug loadings and bioavailability for different dosage regimens. The effects of the released Paclitaxel from these devices on the tumor growth were also modeled using a previously reported mathematical pharmacokinetic–pharmacodynamic model. The proposed approach can easily be used to design other diffusion‐controlled drug delivery devices.
Socioeconomic Disparities in Language Input Are Associated With Children's Language‐Related Brain Structure and Reading Skills
Authors: Merz Emily C. , Maskus Elaine A. , Melvin Samantha A. , He Xiaofu , Noble Kimberly G.
Published: March 2019

The mechanisms underlying socioeconomic disparities in children's reading skills are not well understood. This study examined associations among socioeconomic background, home linguistic input, brain structure, and reading skills in 5‐to‐9‐year‐old children (N = 94). Naturalistic home audio recordings and high‐resolution, T1‐weighted MRI scans were acquired. Children who experienced more adult–child conversational turns or adult words had greater left perisylvian cortical surface area. Language input mediated the association between parental education and left perisylvian cortical surface area. Language input was indirectly associated with children's reading skills via left perisylvian surface area. Left perisylvian surface area mediated the association between parental education and children's reading skills. Language experience may thus partially explain socioeconomic disparities in language‐supporting brain structure and in turn reading skills.
Early activating somatic PIK3CA mutations promote ectopic muscle development and upper limb overgrowth
Authors: Frisk Sofia , Taylan Fulya , Blaszczyk Izabela , Nennesmo Inger , Annerén Göran , Herm Bettina , Stattin Eva‐Lena , Zachariadis Vasilios , Lindstrand Anna , Tesi Bianca , Laurell Tobias , Nordgren Ann
Published: March 2019

PIK3CA‐related overgrowth spectrum is a group of rare genetic disorders with asymmetric overgrowth caused by somatic mosaic PIK3CA mutations. Here, we report clinical data and molecular findings from two patients with congenital muscular upper limb overgrowth and aberrant anatomy. During debulking surgery, numerous ectopic muscles were found in the upper limbs of the patients. DNA sequencing, followed by digital polymerase chain reaction, was performed on DNA extracted from biopsies from hypertrophic ectopic muscles and identified the somatic mosaic PIK3CA hotspot mutations c.3140A > G, p.(His1047Arg) and c.1624G > A, p.(Glu542Lys) in a male (patient 1) and a female (patient 2) patient, respectively. Patient 1 had four ectopic muscles and unilateral isolated muscular overgrowth while patient 2 had 13 ectopic muscles and bilateral isolated muscular overgrowth of both upper limbs, indicating that her mutation occurred at early pre‐somitic mesoderm state. The finding of PIK3CA mutations in ectopic muscles highlights the importance of PIK3CA in cell fate in early human embryonic development. Moreover, our findings provide evidence that the disease phenotype depends on the timing of PIK3CA mutagenesis during embryogenesis and confirm the diagnostic entity PIK3CA‐related muscular overgrowth with ectopic accessory muscles.
Heterogeneity and overlaps in nucleotide excision repair disorders
Authors: Ferri Debora , Orioli Donata , Botta Elena
Published: March 2019

Nucleotide excision repair (NER) is an essential DNA repair pathway devoted to the removal of bulky lesions such as photoproducts induced by the ultraviolet (UV) component of solar radiation. Deficiencies in NER typically result in a group of heterogeneous distinct disorders ranging from the mild UV sensitive syndrome to the cancer‐prone xeroderma pigmentosum and the neurodevelopmental/progeroid conditions trichothiodystrophy, Cockayne syndrome and cerebro‐oculo‐facio‐skeletal‐syndrome. A complicated genetic scenario underlines these disorders with the same gene linked to different clinical entities as well as different genes associated with the same disease. Overlap syndromes with combined hallmark features of different NER disorders can occur and sporadic presentations showing extra features of the hematological disorder Fanconi Anemia or neurological manifestations mimicking Hungtinton disease‐like syndromes have been described. Here, we discuss the multiple functions of the five major pleiotropic NER genes (ERCC3/XPB, ERCC2/XPD, ERCC5/XPG, ERCC1 and ERCC4/XPF) and their relevance in phenotypic complexity. We provide an update of mutational spectra and examine genotype‐phenotype relationships. Finally, the molecular defects that could explain the puzzling overlap syndromes are discussed.
Impaired glucose tolerance, body mass index and respiratory function in patients with cystic fibrosis: A systematic review
Authors: Iwanicki Courtney , Logomarsino John V.
Published: March 2019

Objectives

This systematic review aims to evaluate body mass index (BMI) and forced expiratory volume in one second (FEV1) in patients with cystic fibrosis (CF) diagnosed with impaired glucose tolerance (IGT) compared to those with normal glucose tolerance (NGT). The significance of this topic stems from concern that individuals with CF and IGT may have an overall worse clinical status as indicated by BMI and FEV1.

Data Source

An exhaustive literature search was completed between July 2017 and September 2017 using PubMed, CINAHL, Web of Science, Dissertations & Theses, PsycINFO, and Open Grey. Studies were limited to human subjects with CF. There were no restrictions on publication date, study design or language.

Study Selection

Included studies examined BMI and FEV1 as outcome measures in individuals with CF and IGT compared to those with NGT. After screening for inclusion criteria, 12 observational studies met the specified conditions.

Results

Two studies showed a significantly worse BMI and FEV1 in subjects with CF and IGT compared to those with NGT. The remaining 10 studies found no significant associations with BMI and FEV1 in subjects with CF and IGT compared to NGT.

Conclusion

Although this review does not prove cause and effect, BMI and FEV1 are important outcome measures in patients with CF. Considering the inconclusive findings, practitioners should individualize care for this patient population. Additional research should focus on clinical status and interventions/treatment for individuals with CF and IGT.
Bacterial sexually transmitted infections
Authors: Buder Susanne , Schöfer Helmut , Meyer Thomas , Bremer Viviane , Kohl Peter K. , Skaletz‐Rorowski Adriane , Brockmeyer Norbert
Published: March 2019

Worldwide, the incidence of bacterial sexually transmitted infections (STIs) has shown a significant increase in recent years. In Germany, this circumstance is reflected by a rise in the number of reported syphilis cases. There has also been an uptick in the incidence of non‐notifiable STIs such as gonorrhea and infections caused by Chlamydia trachomatis and Mycoplasma genitalium. A key factor in the spread of these infections is their varied clinical presentation, which includes urogenital, pharyngeal and rectal involvement as well as a large number of asymptomatic cases. New real‐time multiplex PCR methods allow for rapid and targeted detection of STI pathogens. The most common bacterial STI is urogenital chlamydial infection caused by serovars D–K, which affects young adults in particular. Lymphogranuloma venereum (LGV) caused by L serovars often presents as chlamydial proctitis. In recent years, Neisseria (N.) gonorrhoeae has shown a significant development of resistance, with high‐level monoresistance and multiresistance to antibiotics commonly used for treatment. It is therefore imperative that sensitivity testing of N. gonorrhoeae be performed in addition to nucleic acid amplification tests (NAATs). Increased drug resistance has also been observed for Mycoplasma genitalium, a fact that complicates treatment.
Cheiroarthropathy and tendinopathy in diabetes
Authors: Hill N. E. , Roscoe D. , Stacey M. J. , Chew S.
Published: March 2019

Joint problems commonly occur in people with diabetes. Cheiroarthropathy affects the hands and results in painless limited finger joint extension, appearing to be associated with longer diabetes duration and the presence of microvascular complications. The prevalence of cheiroarthropathy seems to be falling, perhaps as a result of improvements in glycaemic management. Non‐enzymatic glycation of collagen results in abnormally crosslinked protein resistant to degradation with subsequent increased build‐up of collagen in joints. The management of cheiroarthropathy is predominantly conservative, with occupational and hand therapy at the forefront. Tendinopathy is more common in people with diabetes than those without, and is associated with obesity and insulin resistance. As with cheiroarthropathy, the exact causative mechanism of tendinopathy in diabetes is not known, but may be linked to inflammation, apoptosis and increased vascularity of affected tendons, driven by hyperinsulinaemia. Local fat pads have also been suggested to play a role in the pathogenesis of tendinopathy.
Atrial functional tricuspid regurgitation: An underappreciated cause of secondary tricuspid regurgitation
Authors: Silbiger Jeffrey J.
Published: March 2019

Secondary tricuspid regurgitation (TR) caused by right ventricular enlargement in the setting of left heart disease/pulmonary hypertension has been well described. In contrast, that associated with right atrial enlargement—atrial functional TR (AF‐TR)—remains largely underappreciated. AF‐TR most often occurs in the setting of lone atrial fibrillation, although it is also seen in its absence (idiopathic AF‐TR). Several recent studies have found that the prevalence, hemodynamic significance, and prognosis of AF‐TR are not inconsequential, suggesting increased physician awareness of this novel clinical entity is warranted. This article discusses the pathogenesis, echocardiographic findings, and treatment of this underappreciated cause of secondary TR.
Resolving the invasion paradox: pervasive scale and study dependence in the native‐alien species richness relationship
Authors: Tomasetto Federico , Duncan Richard P. , Hulme Philip E.
Published: March 2019

The degree to which plant communities are vulnerable to invasion by alien species has often been assessed using the relationship between native and alien plant species richness (NAR). Variation in the direction and strength of the NAR tends to be negative for small plot sizes and study extents, but positive for large plots and extents. This invasion paradox has been attributed to different processes driving species richness at different spatial scales. However, the focus on plot size has drawn attention away from other factors influencing the NAR, in part because the influence of other factors may be obscured by or interact with plot size. Here, we test whether variation in the NAR can be explained by covariates linked to community susceptibility to invasion and whether these interact with plot size using a quantitative meta‐analysis drawn from 87 field studies that examined 161 NARs. While plot size explained most variation, the NAR was less positive in grassland habitats and in the Australasian region. Other covariates did not show strong relationships with the NAR even after accounting for interactions with plot size. Instead, much of the unexplained variation is associated with article or author specific differences, suggesting the NAR depends strongly on how different authors choose their study system or study design.
“It Tastes Like Order”: Psychotic Evidence for Antipsychotic Efficacy and Medicated Subjectivity
Authors: D'Arcy Michael
Published: March 2019

What counts as evidence in contemporary debates about antipsychotic efficacy? Current research in the fields of psychiatry, public health, and the social sciences continues to cast doubt upon the efficacy of antipsychotic medications, but patient testimonies illuminating the intersection of psychotic experience and the psychiatric injunction to adhere are largely missing from research about psychotropic medications’ intended and actually reported effects. Drawing on ethnographic fieldwork in an inpatient psychiatric ward and the community mental health network of Dublin, Ireland, this article explores the ways in which mental health patients are actively engaged in an ongoing process of experimenting with their psychopharmaceuticals, often in the pursuit of an idiosyncratically medicated subjectivity. Joining larger debates about the epistemologically plural nature of evidentiary claims regarding psychopharmaceutical efficacy, this article seeks to foreground the dialogue between clinicians and patients, the latter of whom offer invaluable insights regarding the experience of living with psychosis.
Hair growth control by innate immunocytes: Perifollicular macrophages revisited
Authors: Muneeb Ferhan , Hardman Jonathan A. , Paus Ralf
Published: March 2019

The role of innate immunocytes such as mast cells, γδ T cells, NK cells and macrophages (MACs) in hair growth control under physiological and pathological conditions has recently begun to be re‐explored. Here, we revisit the role of resident perifollicular macrophages (pfMACs) located in the hair follicle (HF) mesenchyme (CTS). Substantial, stringently timed fluctuations in the number and localization of pfMACs were first observed long ago during murine HF morphogenesis and cycling. This already suggested some involvement of these innate immunocytes, with a recognized role in tissue remodelling and in hair growth control. The relatively recent demonstration of a Wnt signalling‐driven crosstalk between these immunocytes and HF epithelial stem cells in telogen HFs, which promotes anagen induction, has reinvigorated interest in the role that pfMAC plays in hair biology. Besides the apoptosis‐associated secretion of stem cell–activating Wnts and the differential secretion of HF‐targeting growth factors such as FGF‐5 and FGF5s from pfMACs, we also explore how MAC polarization, and thus function, may be influenced by the local metabolic and immune environment. Moreover, we examine how pfMACs may contribute to hair cycle–associated angiogenesis, vascular remodelling, HF immune privilege and immunopathology. On this basis, we discuss why targeting pfMACs may be relevant in the management of hair growth disorders. Finally, we argue that studying pfMACs offers an excellent, clinically relevant model system for characterizing and experimentally manipulating MAC interactions with an easily accessible mammalian, continuously remodelled (mini‐)organ under both physiological and pathological conditions.
Human stratum corneum proteomics reveals cross‐linking of a broad spectrum of proteins in cornified envelopes
Authors: Karim Noreen , Phinney Brett S. , Salemi Michelle , Wu Pei‐Wen , Naeem Muhammad , Rice Robert H.
Published: March 2019

Defects in keratinocyte transglutaminase (TGM1), resulting in an improper protein scaffold for deposition of the lipid barrier, comprise a major source of autosomal recessive congenital ichthyosis. For that reason, the composition and formation of the cornified (cross‐linked) protein envelope of the epidermis have been of considerable interest. Since the isopeptide cross‐linked protein components are not individually isolable once incorporated, purified envelopes were analysed by mass spectrometry after trypsin digestion. Quantitative estimates of the identified components revealed some 170 proteins, each comprising at least 0.001% of the total, of which keratins were major constituents accounting for ≈74% of the total. Some prevalent non‐keratin constituents such as keratinocyte proline‐rich protein, loricrin and late envelope protein‐7 were preferentially incorporated into envelopes. The results suggest a model where, as previously observed in hair shaft and nail plate, a diversity of cellular proteins are incorporated. They also help rationalize the minimal effect on epidermis of ablating genes for specific single envelope structural components. The quantitative profile of constituent proteins provides a foundation for future exploration of envelope perturbations that may occur in pathological conditions.