Reproducibility of corpus cavernosum electromyography in healthy young man

Research on reproducibility of corpus cavernosum electromyography (CC-EMG) is relevant because reproducible signals indicate a biological phenomenon and not an artefact. Reproducible signals are also required to use CC-EMG as a diagnostic tool for erectile dysfunction. The aim of this study was to assess the reproducibility of CC-EMG in healthy young men under well-controlled conditions.\u

Modeling group-specific interviewer effects on survey participation using separate coding for random slopes in multilevel models

Despite its importance in terms of survey participation, the literature is sparse on how face-to-face interviewers differentially affect specific groups of sample units. In this paper, we demonstrate how an alternative parametrization of the random components in multilevel models, so-called separate coding, delivers valuable insights into differential interviewer effects for specific groups of sample members. At the example of a face-to-face recruitment interview for a probability-based online panel, we detect small interviewer effects regarding survey participation for non-Internet households, whereas we find sizable interviewer effects for Internet households. Based on the proposed variance decomposition, we derive practical guidance for survey practitioners to address such differential interviewer effects

Modelling Group-Specific Interviewer Effects on Nonresponse Using Separate Coding for Random Slopes in Multilevel Models

To enhance response among underrepresented groups and hence, to increase response rates and to decrease potential nonresponse bias survey practitioners often use interviewers in population surveys (Heerwegh, 2009). While interviewers tend to increase overall response rates in surveys (see Heerwegh, 2009), research on the determinants of nonresponse have also identified human interviewers as one reason for variations in response rates (see for examples Couper & Groves, 1992; Durrant, Groves, Staetsky, & Steele, 2010; Durrant & Steele, 2009; Hox & de Leeuw, 2002; Loosveldt & Beullens, 2014; West & Blom, 2016). In addition, research on interviewer effects indicates that interviewers introduce nonresponse bias, if interviewers systematically differ in their success in obtaining response from specific respondent groups (see West, Kreuter, & Jaenichen, 2013; West & Olson, 2010). Therefore, interviewers might be a source of selective nonresponse in surveys. Interviewers might also differentially contribute to selective nonresponse in surveys and hence, potential nonresponse bias, when interviewer effects are correlated with characteristics of the approached sample units (for an example see Loosveldt & Beullens, 2014). Multilevel models including dummies in the random part of the model to distinguish between respondent groups are commonly used to investigate whether interviewer effects on nonresponse differ across specific respondent groups (see Loosveldt & Beullens, 2014). When dummy coding, which is also referred to as contrast coding (Jones, 2013), are included as random components in multilevel models for interviewers effects, the obtained variance estimates indicate to what extent the contrast between respondent groups varies across interviewers. Yet, such parameterization does not directly yield insight on the size of interviewer effects for specific respondent groups. Surveys with large imbalances among respondent groups gain from an investigation of the variation of interviewer effect sizes on nonresponse, as one gains insights on whether the interviewer effect size is the same for specific respondent groups. The importance of the interviewer effect size for specific groups of respondents lies in its prediction of the effectiveness of interviewer-related fieldwork strategies (for examples on liking, matching, or prioritizing respondents with interviewers see Durrant et al., 2010; Peytchev, Riley, Rosen, Murphy, & Lindblad, 2010; Pickery & Loosveldt, 2002, 2004) and thus, a effective mitigation of potential nonresponse bias. Consequently, understanding group-specific interviewer effect sizes can aide the efficiency of respondent recruitment, because we then understand why some interviewer-related fieldwork strategies have great impact on some respondent group’s participation while other strategies have little effect. To obtain information on differences in interviewer effect size, we propose to use an alternative coding strategy, so-called separate coding in multilevel models with random slopes (for examples see Jones, 2013; Verbeke & Molenberghs, 2000, ch. 12.1). In case of separate coding, every variable represents a direct estimate of the interviewer effects for specific respondent groups (rather than the contrast with a reference category). Investigating nonresponse during the recruitment of a probability-based online panel separately for persons with and without prior internet access (data used from the German Internet Panel, see Blom et al., 2017), we detect that the size of the interviewer effect differs between the two respondent groups. While we discover no interviewer effects on nonresponse for persons without internet access (offliners), we find sizable interviewer effects for persons with internet access (onliners). In addition, we identify interviewer characteristics that explain this group-specific nonresponse. Our results demonstrate that the implementation of interviewer-related fieldwork strategies might help to increase response rates among onliners, as for onliners the interviewer effect size was relatively large compared to the interviewer effect size for offliners

Flexible operation of CSIRO's post-combustion CO2 capture pilot plant at the AGL Loy Yang power station

Flexible operation has the potential to significantly improve the economic viability of post-combustion CO2 capture (PCC). However, the impact of disturbances from flexible operation of the PCC process is unclear. The purpose of this study was to investigate the effects of flexible operation in a PCC pilot plant by implementing step-changes for improved dynamic data reliability. The flexible operation campaign was conducted at the CSIRO PCC pilot plant at AGL Loy Yang using monoethanolamine (MEA) absorbent. The pilot plant was operated under a broad range of transient conditions (changing flue gas flow, liquid absorbent flow and steam pressure) to capture the dynamics of a PCC process during flexible operation. The study demonstrated that the dynamics of flue gas flow rate was faster than absorbent flow rate. The greatest CO2 removal% was achieved at the lowest flue gas flow rate or at the highest absorbent flow rate; however, the latter provided improved energy efficiency. The steam pressure parameter could adjust the temperature of all columns simultaneously which can be used to compensate for effects from ambient conditions or heat losses. These results verify the technical feasibility of flexible PCC operation and provide a suitable dataset for dynamic model validation

Challenge pools of hepatitis C virus genotypes 1-6 prototype strains: replication fitness and pathogenicity in chimpanzees and human liver-chimeric mouse models

Chimpanzees represent the only animal model for studies of the natural history of hepatitis C virus (HCV). To generate virus stocks of important HCV variants, we infected chimpanzees with HCV strains of genotypes 1-6 and determined the infectivity titer of acute-phase plasma pools in additional animals. The courses of first- and second-passage infections were similar, with early appearance of viremia, HCV RNA titers of >10(4.7) IU/mL, and development of acute hepatitis; the chronicity rate was 56%. The challenge pools had titers of 10(3)-10(5) chimpanzee infectious doses/mL. Human liver-chimeric mice developed high-titer infections after inoculation with the challenge viruses of genotypes 1-6. Inoculation studies with different doses of the genotype 1b pool suggested that a relatively high virus dose is required to consistently infect chimeric mice. The challenge pools represent a unique resource for studies of HCV molecular virology and for studies of pathogenesis, protective immunity, and vaccine efficacy in vivo

HLA-C antibodies in women with recurrent miscarriage suggests that antibody mediated rejection is one of the mechanisms leading to recurrent miscarriage

AbstractHLA-C is the only polymorphic classical HLA I antigen expressed on trophoblast cells. It is known that higher incidence of C4d deposition on trophoblast cells is present in women with recurrent miscarriage. C4d is a footprint of antibody-mediated classical complement activation. Therefore, this study hypothesize that antibodies against HLA-C may play a role in the occurrence of unexplained consecutive recurrent miscarriage.Present case control study compared the incidence of HLA-C specific antibodies in 95 women with at least three consecutive miscarriages and 105 women with uneventful pregnancy. In the first trimester of the next pregnancy, presence and specificity of HLA antibodies were determined and their complement fixing ability. The incidence of HLA antibodies was compared with uni- and multivariate logistic regression models adjusting for possible confounders.Although in general a higher incidence of HLA antibodies was found in women with recurrent miscarriage 31.6% vs. in control subjects 9.5% (adjusted OR 4.3, 95% CI 2.0–9.5), the contribution of antibodies against HLA-C was significantly higher in women with recurrent miscarriage (9.5%) compared to women with uneventful pregnancy (1%) (adjusted OR 11.0, 95% CI 1.3–89.0). In contrast to the control group, HLA-C antibodies in the recurrent miscarriage group were more often able to bind complement.The higher incidence of antibodies specific for HLA-C in women with recurrent miscarriage suggests that HLA-C antibodies may be involved in the aetiology of unexplained consecutive recurrent miscarriage

Protein processing characterized by a gel-free proteomics approach

We describe a method for the specific isolation of representative N-terminal peptides of proteins and their proteolytic fragments. Their isolation is based on a gel-free, peptidecentric proteomics approach using the principle of diagonal chromatography. We will indicate that the introduction of an altered chemical property to internal peptides holding a free α-N-terminus results in altered column retention of these peptides, thereby enabling the isolation and further characterization by mass spectrometry of N-terminal peptides. Besides pointing to changes in protein expression levels when performing such proteome surveys in a differential modus, protease specificity and substrate repertoires can be allocated since both are specified by neo-N-termini generated after a protease cleavage event. As such, our gel-free proteomics technology is widely applicable and amenable for a variety of proteome-driven protease degradomics research

Principles guiding embryo selection following genome-wide haplotyping of preimplantation embryos.

STUDY QUESTION How to select and prioritize embryos during PGD following genome-wide haplotyping? SUMMARY ANSWER In addition to genetic disease-specific information, the embryo selected for transfer is based on ranking criteria including the existence of mitotic and/or meiotic aneuploidies, but not carriership of mutations causing recessive disorders. WHAT IS KNOWN ALREADY Embryo selection for monogenic diseases has been mainly performed using targeted disease-specific assays. Recently, these targeted approaches are being complemented by generic genome-wide genetic analysis methods such as karyomapping or haplarithmisis, which are based on genomic haplotype reconstruction of cell(s) biopsied from embryos. This provides not only information about the inheritance of Mendelian disease alleles but also about numerical and structural chromosome anomalies and haplotypes genome-wide. Reflections on how to use this information in the diagnostic laboratory are lacking. STUDY DESIGN, SIZE, DURATION We present the results of the first 101 PGD cycles (373 embryos) using haplarithmisis, performed in the Centre for Human Genetics, UZ Leuven. The questions raised were addressed by a multidisciplinary team of clinical geneticist, fertility specialists and ethicists. PARTICIPANTS/MATERIALS, SETTING, METHODS Sixty-three couples enrolled in the genome-wide haplotyping-based PGD program. Families presented with either inherited genetic variants causing known disorders and/or chromosomal rearrangements that could lead to unbalanced translocations in the offspring. MAIN RESULTS AND THE ROLE OF CHANCE Embryos were selected based on the absence or presence of the disease allele, a trisomy or other chromosomal abnormality leading to known developmental disorders. In addition, morphologically normal Day 5 embryos were prioritized for transfer based on the presence of other chromosomal imbalances and/or carrier information. LIMITATIONS, REASONS FOR CAUTION Some of the choices made and principles put forward are specific for cleavage-stage-based genetic testing. The proposed guidelines are subject to continuous update based on the accumulating knowledge from the implementation of genome-wide methods for PGD in many different centers world-wide as well as the results of ongoing scientific research. WIDER IMPLICATIONS OF THE FINDINGS Our embryo selection principles have a profound impact on the organization of PGD operations and on the information that is transferred among the genetic unit, the fertility clinic and the patients. These principles are also important for the organization of pre- and post-counseling and influence the interpretation and reporting of preimplantation genotyping results. As novel genome-wide approaches for embryo selection are revolutionizing the field of reproductive genetics, national and international discussions to set general guidelines are warranted. STUDY FUNDING/COMPETING INTEREST(S) The European Union's Research and Innovation funding programs FP7-PEOPLE-2012-IAPP SARM: 324509 and Horizon 2020 WIDENLIFE: 692065 to J.R.V., T.V., E.D. and M.Z.E. J.R.V., T.V. and M.Z.E. have patents ZL910050-PCT/EP2011/060211-WO/2011/157846 (‘Methods for haplotyping single cells’) with royalties paid and ZL913096-PCT/EP2014/068315-WO/2015/028576 (‘Haplotyping and copy-number typing using polymorphic variant allelic frequencies’) with royalties paid, licensed to Cartagenia (Agilent technologies). J.R.V. also has a patent ZL91 2076-PCT/EP20 one 3/070858 (‘High throughout genotyping by sequencing’) with royalties paid

Definition and criteria for diagnosing cesarean scar disorder.

IMPORTANCE: Approximately 60% of women develop a uterine niche after a cesarean delivery (CD). A niche is associated with various gynecological symptoms including abnormal uterine bleeding, pain, and infertility, but there is little consensus in the literature on the distinction between the sonographic finding of a niche and the constellation of associated symptoms. OBJECTIVE: To achieve consensus on defining the clinical condition that constitutes a symptomatic uterine niche and agree upon diagnostic criteria and uniform nomenclature for this condition. DESIGN, SETTING, AND PARTICIPANTS: A consensus based modified electronic Delphi (eDelphi) study, with a predefined Rate of Agreement (RoA) of 70% or higher. Experts were selected according to their expertise with niche-related consultations, publications, and participation in expert groups and received online questionnaires between November 2021 and May 2022. MAIN OUTCOMES AND MEASURES: Definition, nomenclature, symptoms, conditions to exclude, and diagnostic criteria of an illness caused by a symptomatic uterine niche. RESULTS: In total, 31 of the 60 invited experts (51.7%) participated, of whom the majority worked in university-affiliated hospitals (28 of 31 [90.3%]), specialized in benign gynecology (20 of 31 [64.5%]), and worked in Europe (24 of 31 [77.4%]). Three rounds were required to achieve consensus on all items. All participants underlined the relevance of a new term for a condition caused by a symptomatic niche and its differentiation from a sonographic finding only. Experts agreed to name this condition cesarean scar disorder, defined as a uterine niche in combination with at least 1 primary or 2 secondary symptoms (RoA, 77.8%). Defined primary symptoms were postmenstrual spotting, pain during uterine bleeding, technical issues with catheter insertion during embryo transfer, and secondary unexplained infertility combined with intrauterine fluid. Secondary symptoms were dyspareunia, abnormal vaginal discharge, chronic pelvic pain, avoiding sexual intercourse, odor associated with abnormal blood loss, secondary unexplained infertility, secondary infertility despite assisted reproductive technology, negative self-image, and discomfort during participation in leisure activities. Consensus was also achieved on certain criteria that should be met and conditions that should be excluded before making the diagnosis. CONCLUSIONS AND RELEVANCE: In this modified Delphi study, a panel of 31 international niche experts reached consensus for the constellation of symptoms secondary to a uterine niche and named it cesarean scar disorder