Validation of a Dutch version of the Tinnitus Functional Index in a tertiary referral tinnitus clinic

Introduction: Tinnitus is a condition with a subjective nature that requires self-report questionnaires for its assessment. Aspects such as quality of life, sleep or intrusiveness have been addressed by multiple tinnitus questionnaires, but the high responsiveness to treatment effects of the Tinnitus Functional Index (TFI) makes this questionnaire part of the standard practice in tinnitus screening. To date, the TFI has been translated to more than 20 languages and used in more than 22 countries. In this study, the TFI was translated to Dutch and validated through a clinical population in the Netherlands. Methods: After a back-translation procedure, the Dutch TFI was filled-out by 377 patients in the tinnitus outpatient clinic at the Ear, Nose and Throat (ENT) department of the University Medical Center Groningen, in the Netherlands. Reliability and construct validity of the questionnaire were assessed by correlations with one other tinnitus questionnaire (Tinnitus Handicap Inventory, THI) and with three psychological functioning questionnaires (Rand-36, Cantril's ladder and the Hospital Anxiety and Depression Scale (HADS)). The eight-factor structure of the Dutch TFI was tested by means of exploratory factor analysis using three different models (ICM-CFA, ESEM and ESEM-CFA). Results: The Dutch TFI showed a high internal consistency (α = 0.95), and construct validity was proven by moderate-to high-convergent correlations with the THI (r = 0.47–0.79) and by moderate convergent (r = 0.55–0.67) and good-to moderate-divergent (r = 0.12–0.47) correlations with the psychological functioning questionnaires. The eight-factor structure of the TFI was confirmed for the Dutch version by the three models. Conclusion: The Dutch version of the TFI is a reliable instrument for screening tinnitus impact in a clinical population, and its psychometric properties are comparable to the original TFI and other validated tinnitus questionnaires

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

Large Momentum Transfer Measurements of the Deuteron Elastic Structure Function A(Q^2) at Jefferson Laboratory

The deuteron elastic structure function A(Q^2) has been extracted in the Q^2 range 0.7 to 6.0 (GeV/c)^2 from cross section measurements of elastic electron-deuteron scattering in coincidence using the Hall A Facility of Jefferson Laboratory. The data are compared to theoretical models based on the impulse approximation with inclusion of meson-exchange currents, and to predictions of quark dimensional scaling and perturbative quantum chromodynamicsComment: Submitted to Physical Review Letter

Cyclostratigraphy and eccentricity tuning of the early Oligocene through early Miocene (30.1–17.1 Ma): Cibicides mundulus stable oxygen and carbon isotope records from Walvis Ridge Site 1264

Few astronomically calibrated high-resolution (≤5 kyr) climate records exist that span the Oligocene–Miocene time interval. Notably, available proxy records show responses varying in amplitude at frequencies related to astronomical forcing, and the main pacemakers of global change on astronomical time-scales remain debated. Here we present newly generated X-ray fluorescence core scanning and benthic foraminiferal stable oxygen and carbon isotope records from Ocean Drilling Program Site 1264 (Walvis Ridge, southeastern Atlantic Ocean). Complemented by data from nearby Site 1265, the Site 1264 benthic stable isotope records span a continuous ∼13-Myr interval of the Oligo-Miocene (30.1–17.1 Ma) at high resolution (∼3.0 kyr). Spectral analyses in the stratigraphic depth domain indicate that the largest amplitude variability of all proxy records is associated with periods of ∼3.4 m and ∼0.9 m, which correspond to 405- and ∼110-kyr eccentricity, using a magnetobiostratigraphic age model. Maxima in CaCO3 content, δ18O and δ13C are interpreted to coincide with ∼110 kyr eccentricity minima. The strong expression of these cycles in combination with the weakness of the precession- and obliquity-related signals allow construction of an astronomical age model that is solely based on tuning the CaCO3 content to the nominal (La2011_ecc3L) eccentricity solution. Very long-period eccentricity maxima (∼2.4-Myr) are marked by recurrent episodes of high-amplitude ∼110-kyr δ18O cycles at Walvis Ridge, indicating greater sensitivity of the climate/cryosphere system to short eccentricity modulation of climatic precession. In contrast, the responses of the global (high-latitude) climate system, cryosphere, and carbon cycle to the 405-kyr cycle, as expressed in benthic δ18O and especially δ13C signals, are more pronounced during ∼2.4-Myr minima. The relationship between the recurrent episodes of high-amplitude ∼110-kyr δ18O cycles and the ∼1.2-Myr amplitude modulation of obliquity is not consistent through the Oligo-Miocene. Identification of these recurrent episodes at Walvis Ridge, and their pacing by the ∼2.4-Myr eccentricity cycle, revises the current understanding of the main climate events of the Oligo-Miocene

Posttranscriptional Regulation of the Human LDL Receptor by the U2-Spliceosome

Background: The low-density lipoprotein receptor (LDLR) in the liver is the major determinant of LDL-cholesterol levels in human plasma. The discovery of genes that regulate the activity of LDLR helps to identify pathomechanisms of hypercholesterolemia and novel therapeutic targets against atherosclerotic cardiovascular disease.Methods: We performed a genome-wide RNA interference screen for genes limiting the uptake of fluorescent LDL into Huh-7 hepatocarcinoma cells. Top hit genes were validated by in vitro experiments as well as analyses of datasets on gene expression and variants in human populations.Results: The knockdown of 54 genes significantly inhibited LDL uptake. Fifteen of them encode for components or interactors of the U2-spliceosome. Knocking down any one of 11 out of 15 genes resulted in the selective retention of intron 3 of LDLR. The translated LDLR fragment lacks 88% of the full length LDLR and is detectable neither in non-transfected cells nor in human plasma. The hepatic expression of the intron 3 retention transcript is increased in non-alcoholic fatty liver disease as well as after bariatric surgery. Its expression in blood cells correlates with LDL-cholesterol and age. Single nucleotide polymorphisms and three rare variants of one spliceosome gene, RBM25, are associated with LDL-cholesterol in the population and familial hypercholesterolemia, respectively. Compared to overexpression of wild type RBM25, overexpression of the three rare RBM25 mutants in Huh-7 cells led to lower LDL uptake.Conclusions: We identified a novel mechanism of post-transcriptional regulation of LDLR activity in humans and associations of genetic variants of RBM25 with LDL-cholesterol levels.</p

Malaria rapid diagnostic kits: quality of packaging, design and labelling of boxes and components and readability and accuracy of information inserts

<p>Abstract</p> <p>Background</p> <p>The present study assessed malaria RDT kits for adequate and correct packaging, design and labelling of boxes and components. Information inserts were studied for readability and accuracy of information.</p> <p>Methods</p> <p>Criteria for packaging, design, labelling and information were compiled from Directive 98/79 of the European Community (EC), relevant World Health Organization (WHO) documents and studies on end-users' performance of RDTs. Typography and readability level (Flesch-Kincaid grade level) were assessed.</p> <p>Results</p> <p>Forty-two RDT kits from 22 manufacturers were assessed, 35 of which had evidence of good manufacturing practice according to available information (<it>i.e</it>. CE-label affixed or inclusion in the WHO list of ISO13485:2003 certified manufacturers). Shortcomings in devices were (i) insufficient place for writing sample identification (n = 40) and (ii) ambiguous labelling of the reading window (n = 6). Buffer vial labels were lacking essential information (n = 24) or were of poor quality (n = 16). Information inserts had elevated readability levels (median Flesch Kincaid grade 8.9, range 7.1 - 12.9) and user-unfriendly typography (median font size 8, range 5 - 10). Inadequacies included (i) no referral to biosafety (n = 18), (ii) critical differences between depicted and real devices (n = 8), (iii) figures with unrealistic colours (n = 4), (iv) incomplete information about RDT line interpretations (n = 31) and no data on test characteristics (n = 8). Other problems included (i) kit names that referred to <it>Plasmodium vivax </it>although targeting a pan-species <it>Plasmodium </it>antigen (n = 4), (ii) not stating the identity of the pan-species antigen (n = 2) and (iii) slight but numerous differences in names displayed on boxes, device packages and information inserts. Three CE labelled RDT kits produced outside the EC had no authorized representative affixed and the shape and relative dimensions of the CE symbol affixed did not comply with the Directive 98/79/EC. Overall, RDTs with evidence of GMP scored better compared to those without but inadequacies were observed in both groups.</p> <p>Conclusion</p> <p>Overall, malaria RDTs showed shortcomings in quality of construction, design and labelling of boxes, device packages, devices and buffers. Information inserts were difficult to read and lacked relevant information.</p

Geographic variation in breeding system and environment predicts melanin-based plumage ornamentation of male and female Kentish plovers

Sexual selection determines the elaboration of morphological and behavioural traits and thus drives the evolution of phenotypes. Sexual selection on males and females can differ between populations, especially when populations exhibit different breeding systems. A substantial body of literature describes how breeding systems shape ornamentation across species, with a strong emphasis on male ornamentation and female preference. However, whether breeding system predicts ornamentation within species and whether similar mechanisms as in males also shape the phenotype of females remains unclear. Here, we investigate how different breeding systems are associated with male and female ornamentation in five geographically distinct populations of Kentish plovers Charadrius alexandrinus. We predicted that polygamous populations would exhibit more elaborate ornaments and stronger sexual dimorphism than monogamous populations. By estimating the size and intensity of male (n = 162) and female (n = 174) melanin-based plumage ornaments, i.e. breast bands and ear coverts, we show that plumage ornamentation is predicted by breeding system in both sexes. A difference in especially male ornamentation between polygamous (darker and smaller ornaments) and monogamous (lighter and larger) populations causes the greatest sexual dimorphism to be associated with polygamy. The non-social environment, however, may also influence the degree of ornamentation, for instance through availability of food. We found that, in addition to breeding system, a key environmental parameter, rainfall, predicted a seasonal change of ornamentation in a sex-specific manner. Our results emphasise that to understand the phenotype of animals, it is important to consider both natural and sexual selection acting on both males and females

A Systematic Review Comparing the Acceptability, Validity and Concordance of Discrete Choice Experiments and Best–Worst Scaling for Eliciting Preferences in Healthcare

Objective: The aim of this study was to compare the acceptability, validity and concordance of discrete choice experiment (DCE) and best–worst scaling (BWS) stated preference approaches in health. Methods: A systematic search of EMBASE, Medline, AMED, PubMed, CINAHL, Cochrane Library and EconLit databases was undertaken in October to December 2016 without date restriction. Studies were included if they were published in English, presented empirical data related to the administration or findings of traditional format DCE and object-, profile- or multiprofile-case BWS, and were related to health. Study quality was assessed using the PREFS checklist. Results: Fourteen articles describing 12 studies were included, comparing DCE with profile-case BWS (9 studies), DCE and multiprofile-case BWS (1 study), and profile- and multiprofile-case BWS (2 studies). Although limited and inconsistent, the balance of evidence suggests that preferences derived from DCE and profile-case BWS may not be concordant, regardless of the decision context. Preferences estimated from DCE and multiprofile-case BWS may be concordant (single study). Profile- and multiprofile-case BWS appear more statistically efficient than DCE, but no evidence is available to suggest they have a greater response efficiency. Little evidence suggests superior validity for one format over another. Participant acceptability may favour DCE, which had a lower self-reported task difficulty and was preferred over profile-case BWS in a priority setting but not necessarily in other decision contexts. Conclusion: DCE and profile-case BWS may be of equal validity but give different preference estimates regardless of the health context; thus, they may be measuring different constructs. Therefore, choice between methods is likely to be based on normative considerations related to coherence with theoretical frameworks and on pragmatic considerations related to ease of data collection

Nest desertion is not predicted by cuckoldry in the Eurasian penduline tit

Engagement in extra-pair copulations is an example of the abundant conflicting interests between males and females over reproduction. Potential benefits for females and the risk of cuckoldry for males are expected to have important implications on the evolution of parental care. However, whether parents adjust parental care in response to parentage remains unclear. In Eurasian penduline tits Remiz pendulinus, which are small polygamous songbirds, parental care is carried out either by the male or by the female. In addition, one third of clutches is deserted by both male and female. Desertion takes place during the egg-laying phase. Using genotypes of nine microsatellite loci of 443 offspring and 211 adults, we test whether extra-pair paternity predicts parental care. We expect males to be more likely to desert cuckolded broods, whereas we expect females, if they obtain benefits from having multiple sires, to be more likely to care for broods with multiple paternity. Our results suggest that parental care is not adjusted to parentage on an ecological timescale. Furthermore, we found that male attractiveness does not predict cuckoldry, and we found no evidence for indirect benefits for females (i.e., increased growth rates or heterozygosity of extra-pair offspring). We argue that male Eurasian penduline tits may not be able to assess the risk of cuckoldry; thus, a direct association with parental care is unlikely to evolve. However, timing of desertion (i.e., when to desert during the egg-laying phase) may be influenced by the risk of cuckoldry. Future work applying extensive gene sequencing and quantitative genetics is likely to further our understanding of how selection may influence the association between parentage and parental care