Double cervical cerclage for cervical insufficiency: Case report.

Recurrent pregnancy loss devastates parents and frustrates doctors, especially when the pregnancy progresses to the second trimester. Cervical insufficiency is the most common cause of second-trimester pregnancy loss. Abdominal cerclage is the treatment option for women with failed vaginally applied cervical cerclage. We report a 33-year-old para 0 with a history of nine second-trimester pregnancy losses. She had six failed transvaginal cerclages using McDonald's procedure. A vaginal double cervical cerclage was placed in her index pregnancy. Two mersilene tape purse-string sutures were placed in the submucosal layer of the cervix; the first 1cm below and the second at the level of the internal os. Both sutures were knotted at the 12 O'Clock position on the cervix. She carried her pregnancy to almost term and delivered a healthy baby girl weighing 2.5kg. We recommend a transvaginal double cervical cerclage with mersilene tape using a modified McDonald's technique as a viable alternative to abdominal cervical cerclage. (Afr J Reprod Health 2024; 28 [6]: 117-125).

Les fausses couches récurrentes sont dévastatrices pour les parents et frustrent les médecins, surtout lorsque la grossesse progresse jusqu'au deuxième trimestre. L'insuffisance cervicale est la cause la plus fréquente de fausse couche au deuxième trimestre. Le cerclage abdominal est l'option de traitement pour les femmes dont le cerclage cervical appliqué par voie vaginale a échoué. Nous rapportons une para 0 de 33 ans avec des antécédents de neuf fausses couches au deuxième trimestre. Elle a eu six cerclages transvaginaux selon la procédure McDonald's qui ont échoué. Un double cerclage vaginal vaginal a été placé lors de sa grossesse index. Deux fils de suture en bourse en ruban de mersilène ont été placés dans la couche sous-muqueuse du col de l'utérus ; le premier 1cm en dessous et le second au niveau de l'os interne. Les deux sutures ont été nouées à la position 12 heures sur le col. Elle a mené sa grossesse presque à terme et a donné naissance à une petite fille en bonne santé pesant 2,5 kg. Nous recommandons un double cerclage cervical transvaginal avec du ruban de mersilène en utilisant une technique McDonald's modifiée comme alternative viable au cerclage cervical abdominal. (Afr J Reprod Health 2024; 28 [6]: 117-125).

The association between the degree of cervical dilatation before ultrasound and physical examination indicated cerclage and subsequent neonatal outcomes.

INTRODUCTION: Preterm identification of cervical dilation in pregnant women leads to the application of emergency cervical cerclage with an expectation of achieving term delivery. However, this is not always feasible. Short- and long-term neonatal complications post-preterm birth pose a significant challenge. It is crucial to anticipate potential complications and understand the possibilities of postpartum development as they can be encountered. We aimed to evaluate the effect of the degree of cervical dilatation before ultrasound and physical examination-indicated cerclage in singleton pregnancies presenting with premature cervical dilatation with bulging fetal membranes (rescue cerclage) on subsequent neonatal outcomes. MATERIALS AND METHODS: In this retrospective clinical study, over a 10-year period between January 2009 and January 2019, 72 singleton pregnancies undergoing rescue cerclage were included and divided into two groups according to pre-cerclage cervical dilatation: Group 1 (n = 33) and Group 2 (n = 39) with cervical dilatation ≤3 cm and >3 cm, respectively. Latency period for pregnancy prolongation, gestational age at delivery, birth weight, and neonatal morbidity and mortality were compared across the groups. Logistic regression was used to delineate the independent effect of cervical dilatation at cerclage placement on neonatal mortality. RESULTS: Group 2 had a higher delivery rate at ≤28 weeks' gestation (p = 0.007) and lower birth weight (p = 0.002) compared to Group 1, with an increased mean latency period in Group 2 (90 ± 55 days versus 52 ± 54 days, p = 0.005). The newborn intensive care unit (NICU) requirement, respiratory distress syndrome (RDS), neonatal jaundice and sepsis, and retinopathy of prematurity (ROP) were more frequent in Group 2. Neonatal mortality rate was higher (52.6% versus 24.2%, p = 0.015) and intact survival was lower (23.1% versus 48.4%, p = 0.013) in Group 2, whereas rates of cerebral palsy (8% and 9%, respectively) were similar between the groups (p = 0.64). CONCLUSION: Advanced cervical dilatation (>3 cm) during physical examination-indicated cerclage in singleton pregnancies is associated with earlier delivery, leading to increased neonatal morbidity and mortality when compared with pregnancies having lesser degrees of cervical dilatation at cerclage. However, short-term poor neurological outcomes seem comparable.

Dissecting Genomic Determinants of Positive Selection with an Evolution-Guided Regression Model.

In evolutionary genomics, it is fundamentally important to understand how characteristics of genomic sequences, such as gene expression level, determine the rate of adaptive evolution. While numerous statistical methods, such as the McDonald-Kreitman (MK) test, are available to examine the association between genomic features and the rate of adaptation, we currently lack a statistical approach to disentangle the independent effect of a genomic feature from the effects of other correlated genomic features. To address this problem, I present a novel statistical model, the MK regression, which augments the MK test with a generalized linear model. Analogous to the classical multiple regression model, the MK regression can analyze multiple genomic features simultaneously to infer the independent effect of a genomic feature, holding constant all other genomic features. Using the MK regression, I identify numerous genomic features driving positive selection in chimpanzees. These features include well-known ones, such as local mutation rate, residue exposure level, tissue specificity, and immune genes, as well as new features not previously reported, such as gene expression level and metabolic genes. In particular, I show that highly expressed genes may have a higher adaptation rate than their weakly expressed counterparts, even though a higher expression level may impose stronger negative selection. Also, I show that metabolic genes may have a higher adaptation rate than their nonmetabolic counterparts, possibly due to recent changes in diet in primate evolution. Overall, the MK regression is a powerful approach to elucidate the genomic basis of adaptation.

Population-Genomic Analysis Identifies a Low Rate of Global Adaptive Fixation in the Proteins of the Cyclical Parthenogen Daphnia magna.

Daphnia are well-established ecological and evolutionary models, and the interaction between D. magna and its microparasites is widely considered a paragon of the host-parasite coevolutionary process. Like other well-studied arthropods such as Drosophila melanogaster and Anopheles gambiae, D. magna is a small, widespread, and abundant species that is therefore expected to display a large long-term population size and high rates of adaptive protein evolution. However, unlike these other species, D. magna is cyclically asexual and lives in a highly structured environment (ponds and lakes) with moderate levels of dispersal, both of which are predicted to impact upon long-term effective population size and adaptive protein evolution. To investigate patterns of adaptive protein fixation, we produced the complete coding genomes of 36 D. magna clones sampled from across the European range (Western Palaearctic), along with draft sequences for the close relatives D. similis and D. lumholtzi, used as outgroups. We analyzed genome-wide patterns of adaptive fixation, with a particular focus on genes that have an a priori expectation of high rates, such as those likely to mediate immune responses, RNA interference against viruses and transposable elements, and those with a strongly male-biased expression pattern. We find that, as expected, D. magna displays high levels of diversity and that this is highly structured among populations. However, compared with Drosophila, we find that D. magna proteins appear to have a high proportion of weakly deleterious variants and do not show evidence of pervasive adaptive fixation across its entire range. This is true of the genome as a whole, and also of putative 'arms race' genes that often show elevated levels of adaptive substitution in other species. In addition to the likely impact of extensive, and previously documented, local adaptation, we speculate that these findings may reflect reduced efficacy of selection associated with cyclical asexual reproduction.

Inclusion of optic neuritis in dissemination in space improves the performance of McDonald 2017 criteria in Hispanic people with suspected multiple sclerosis.

BACKGROUND: Hispanic people compared to White people with multiple sclerosis (MS) are two times more likely to present with optic neuritis (ON). ON in dissemination in space (DIS) after a single attack is not part of the current McDonald 2017 criteria. OBJECTIVE: To evaluate if adding ON in DIS (ON-modified criteria) improves the performance of the McDonald 2017 criteria in the diagnosis of MS after a single attack of ON. METHODS: Retrospective study of 102 patients of Hispanic background. Cases were reviewed between 2017 and 2021. Clinical ON was reported for 35 cases. ON in DIS was verified for 28 patients via MRI, optical coherence tomography, and/or visual evoked potential. We investigated the performance of the McDonald 2017 criteria and ON-modified criteria and calculated sensitivity, specificity, positive and negative predictive values, and accuracy. RESULTS: The ON-modified criteria significantly improved the performance of the McDonald 2017 criteria (p = 0.003) and identified an additional nine patients. Both sensitivity and accuracy increased from 64% to 74% and 62% to 71%, respectively, while specificity remained unchanged (40% (95% confidence interval (CI): 0.10, 0.70)). CONCLUSION: This study provides evidence that the inclusion of ON in DIS improved the overall performance of the McDonald 2017 criteria among Hispanic people.

Real-world challenges in the diagnosis of primary progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Despite the 2017 revisions to the McDonald criteria, diagnosing primary progressive multiple sclerosis (PPMS) remains challenging. To improve clinical practice, the aim was to identify frequent diagnostic challenges in a real-world setting and associate these with the performance of the 2010 and 2017 PPMS diagnostic McDonald criteria. METHODS: Clinical, radiological and laboratory characteristics at the time of diagnosis were retrospectively recorded from designated PPMS patient files. Possible complicating factors were recorded such as confounding comorbidity, signs indicative of alternative diagnoses, possible earlier relapses and/or incomplete diagnostic work-up (no cerebrospinal fluid examination and/or magnetic resonance imaging brain and spinal cord). The percentages of patients fulfilling the 2010 and 2017 McDonald criteria were calculated after censoring patients with these complicating factors. RESULTS: A total of 322 designated PPMS patients were included. Of all participants, it was found that n = 28/322 had confounding comorbidity and/or signs indicative of alternative diagnoses, n = 103/294 had possible initial relapsing and/or uncertainly progressive phenotypes and n = 73/191 received an incomplete diagnostic work-up. When applying the 2010 and 2017 diagnostic PPMS McDonald criteria on n = 118 cases with a full diagnostic work-up and a primary progressive disease course without a better alternative explanation, these were met by 104/118 (88.1%) and 98/118 remaining patients (83.1%), respectively (p = 0.15). CONCLUSION: Accurate interpretation of the initial clinical course, consideration of alternative diagnoses and a full diagnostic work-up are the cornerstones of a PPMS diagnosis. When these conditions are met, the 2010 and 2017 McDonald criteria for PPMS perform similarly, emphasizing the importance of their appropriate application in clinical practice.

McDonald versus Shirodkar cerclage technique in the prevention of preterm birth: A systematic review and meta-analysis.

BACKGROUND: Cervical cerclage has been used for decades to reduce preterm birth. The Shirodkar and McDonald cerclage are the most commonly used techniques with no current consensus on the preferred technique. OBJECTIVE: To compare the efficacy of the Shirodkar and McDonald cerclage techniques in preventing preterm birth. SEARCH STRATEGY: Studies were sourced from six electronic databases and reference lists. SELECTION CRITERIA: Studies including women with a singleton pregnancy, requiring a cervical cerclage, using either the Shirodkar or McDonald technique that ran comparative analyses between the two techniques. DATA COLLECTION AND ANALYSIS: The primary outcome was preterm birth before 37 weeks, with analyses at 28, 32, 34 and 35 weeks. Secondary data were also collected on neonatal, maternal and obstetric outcomes. MAIN RESULTS: Seventeen papers were included: 16 were retrospective cohort studies and one was a randomised controlled trial. The Shirodkar technique was significantly less likely to result in preterm birth before 37 weeks than the McDonald technique (relative risk [RR] 0.91, 95% CI 0.85-0.98). This finding was supported by a statistically significant reduction in rates of preterm birth before 35, 34 and 32 weeks, PPROM, difference in cervical length, cerclage to delivery interval, and an increase in birthweight in the Shirodkar group. No difference was seen in preterm birth rates <28 weeks, neonatal mortality, chorioamnionitis, cervical laceration or caesarean section rates. The RR for preterm birth prior to 37 weeks was no longer significant when sensitivity analyses were performed removing studies with a serious risk of bias. However, similar analyses removing studies that utilised adjunctive progesterone strengthened the primary outcome (RR 0.83, 95% CI 0.74-0.93). CONCLUSION: Shirodkar cerclage reduces the rate of preterm birth prior to 35, 34 and 32 weeks' gestation when compared with McDonald cerclage; however, the overall quality of the studies in this review is low. Further, large, well-designed randomised controlled trials are required to address this important question to optimise care for women who may benefit from cervical cerclage.

The kappa free light chain index and oligoclonal bands have a similar role in the McDonald criteria.

Intrathecal production of kappa free light chains occurs in multiple sclerosis and can be measured using the kappa free light chain index. Kappa free light chain index values can be determined more easily than oligoclonal bands detection and seem more sensitive than the immunoglobulin (Ig)G index to diagnose multiple sclerosis. We assessed the value of oligoclonal bands, kappa free light chain index cut-offs 5.9, 6.6 and 10.61, and IgG index to diagnose multiple sclerosis with prospectively acquired data from a clinically isolated syndrome inception cohort. We selected patients with sufficient data to determine oligoclonal bands positivity, MRI dissemination in space and time, IgG index and sufficient quantities of paired CSF and blood samples to determine kappa free light chain indexes (n = 214). We used Kendall's Tau coefficient to estimate concordance, calculated the number of additional diagnoses when adding each positive index to dissemination in space and positive oligoclonal bands, performed survival analyses for oligoclonal bands and each index with the outcomes second attack and 2017 MRI dissemination in space and time and estimated the diagnostic properties of oligoclonal bands and the different indexes for the previously mentioned outcomes at 5 years. Oligoclonal bands were positive in 138 patients (64.5%), kappa free light chain-5.9 in 136 (63.6%), kappa free light chain-6.6 in 135 (63.1%), kappa free light chain-10.61 in 126 (58.9%) and IgG index in 101 (47.2%). The highest concordance was between oligoclonal bands and kappa free light chain-6.6 (τ = 0.727) followed by oligoclonal bands and kappa free light chain-5.9 (τ = 0.716). Combining dissemination in space plus oligoclonal bands or kappa free light chain-5.9 increased the number of diagnosed patients by 11 (5.1%), with kappa free light chain-6.6 by 10 (4.7%), with kappa free light chain-10.61 by 9 (4.2%) and with IgG index by 3 (1.4%). Patients with positive oligoclonal bands or indexes reached second attack and MRI dissemination in space and time faster than patients with negative results (P < 0.0001 except IgG index in second attack: P = 0.016). In multivariable Cox models [adjusted hazard ratio (95% confidence interval)], the risk for second attack was very similar between kappa free light chain-5.9 [2.0 (0.9-4.3), P = 0.068] and kappa free light chain-6.6 [2.1 (1.1-4.2), P = 0.035]. The highest risk for MRI dissemination in space and time was demonstrated with kappa free light chain-5.9 [4.9 (2.5-9.6), P < 0.0001], followed by kappa free light chain-6.6 [3.4 (1.9-6.3), P < 0.0001]. Kappa free light chains-5.9 and -6.6 had a slightly higher diagnostic accuracy than oligoclonal bands for second attack (70.5, 71.1 and 67.8) and MRI dissemination in space and time (85.7, 85.1 and 81.0). Kappa free light chain indexes 5.9 and 6.6 performed slightly better than oligoclonal bands to assess multiple sclerosis risk and in terms of diagnostic accuracy. Given the concordance between oligoclonal bands and these indexes, we suggest using dissemination in space plus positive oligoclonal bands or positive kappa free light chain index as a modified criterion to diagnose multiple sclerosis.

Should it really be called a heroic cerclage? The obstetrical results of emergency late second-trimester cerclage compared with early history-indicated elective cerclage: a retrospective trial.

PURPOSE: Women diagnosed with mid-trimester cervical insufficiency and dilatation are offered interventions to salvage and support the cervix, where the mainstay of therapy is emergency cervical cerclage. However, considering the significant morbidity associated with delivery in the extreme prematurity period, some women may opt for pregnancy termination. In addition, it is expected that elective cerclage in a subsequent pregnancy may yield better obstetrical results. The objective of this study was, therefore, to compare the obstetrical outcomes of emergency cerclage versus elective cerclage. METHODS: This is a retrospective cohort study of the pregnancy outcomes of women with a singleton pregnancy who underwent cervical cerclage at our institution between December 2008 and November 2021. Women who underwent emergency cervical cerclage due to painless dilatation in the second trimester were compared with women who underwent elective cerclage. RESULTS: Overall, 32 women who underwent emergency cerclage and 183 women who underwent elective cerclage were included. No cases of iatrogenic membrane rupture were noted during the cerclage procedure. There was no statistical difference between the emergency cerclage group and the elective cerclage group in the primary outcomes: gestational age at delivery (35.8 + 4.7 vs 36.3 + 4.9, p = 0.58, respectively), delivery in the extreme prematurity period (between 24 and 28 gestational weeks, 6.5% vs 2.3%, p = 0.21, respectively), and fetal or neonatal death (6.9% vs 6.3%, p = 0.91, respectively). CONCLUSION: Although there are much less favourable circumstances, emergency cerclage is a safe procedure with comparable obstetrical outcomes to elective cerclage. Patient selection and experienced medical team may play a significant role in those cases.

Identification of demyelinating lesions and application of McDonald criteria when confronted with white matter lesions on brain MRI.

INTRODUCTION: White matter lesions (WML) on magnetic resonance imaging (MRI) are common in clinical practice. When analyzing WML, radiologists sometimes propose a pathophysiological mechanism to explain the observed MRI abnormalities, which can be a source of anxiety for patients. In some cases, discordance may appear between the patient's clinical symptoms and the identification of the MRI-appearing WML, leading to extensive diagnostic work-up. To avoid misdiagnosis, the analysis of WML should be standardized, and a consensual MRI reading approach is needed. OBJECTIVE: To analyze the MRI WML identification process, associated diagnosis approach, and misinterpretations in physicians involved in WML routine practice. METHODS: Through a survey distributed online to practitioners involved in WML diagnostic work-up, we described the leading causes of MRI expertise misdiagnosis and associated factors: clinical experience, physicians' subspecialty and location of practice, and type of device used to complete the survey. The survey consisted of sixteen T2-weighted images MRI analysis, from which ten were guided (binary response to lesion location identification), four were not shown (multiple possible answers), and two were associated with dissemination in space (DIS) McDonald criteria application. Two independent, experienced practitioners determined the correct answers before the participants' completion. RESULTS: In total, 364 participants from the French Neuro Radiological (SFNR), French Neurological (SFN), and French Multiple Sclerosis (SFSEP) societies completed the survey entirely. According to lesion identification, 34.3% and 16.9% of the participants correctly identified juxtacortical and periventricular lesions, respectively, whereas 56.3% correctly identified non-guided lesions. Application of the 2017 McDonald's DIS criteria was correct for 35.3% of the participants. According to the global survey scoring, factors independently associated with correct answers in multivariate analysis were MS-expert subspecialty (P<0.001), young clinical practitioners (P=0.02), and the use of a computer instead of a smartphone to perform WML analysis (P=0.03). CONCLUSION: Our results highlight the difficulties regarding WML analysis in clinical practice and suggest that radiologists and neurologists should rely on each other to ensure the diagnosis of multiple sclerosis and related disorders and limit misdiagnoses.

A tutorial on Bayesian single-test reliability analysis with JASP.

The current practice of reliability analysis is both uniform and troublesome: most reports consider only Cronbach's α, and almost all reports focus exclusively on a point estimate, disregarding the impact of sampling error. In an attempt to improve the status quo we have implemented Bayesian estimation routines for five popular single-test reliability coefficients in the open-source statistical software program JASP. Using JASP, researchers can easily obtain Bayesian credible intervals to indicate a range of plausible values and thereby quantify the precision of the point estimate. In addition, researchers may use the posterior distribution of the reliability coefficients to address practically relevant questions such as "What is the probability that the reliability of my test is larger than a threshold value of .80?". In this tutorial article, we outline how to conduct a Bayesian reliability analysis in JASP and correctly interpret the results. By making available a computationally complex procedure in an easy-to-use software package, we hope to motivate researchers to include uncertainty estimates whenever reporting the results of a single-test reliability analysis.

Comparison of pregnancy outcomes of triangular 3-bites and mcdonald techniques of cervical cerclage in women with cervical insufficiency: A pilot study.

Background: Cervical cerclage is the procedure of choice for preventing preterm birth due to cervical insufficiency. Despite the simplicity of the McDonald's method of cerclage application, it is still technically difficult to take four bites around the cervix before knotting. There is a need to develop a simpler method of cervical cerclage application with similar or improved pregnancy outcomes. Aim: This is to compare the ease/duration of application and pregnancy outcomes of the new triangular three-bite cervical cerclage technique and McDonald's technique in women with cervical insufficiency. Patients and Methods: This is a pilot study with 20 participants that met the inclusion criteria. They were randomly grouped into triangular three-bite method (n = 10) and McDonald's method (n = 10). The pregnancy outcomes were compared between the groups with the Chi-square test and student's t-test. A P value of <.05 was set as level of significance. Results: The sociodemographic characteristics of the two groups were similar. There was no statistically significant difference between the two groups regarding the pregnancy outcome (spontaneous miscarriage P = 1.00, preterm delivery P = 0.61, and neonatal birthweight P = 0.96). However, the duration of cerclage application (5.98 ± 1.79 minutes vs. 14.25 ± 7.5 minutes; P <.002) and estimated blood loss (29 ± 9.94 mls vs. 48.5 ± 25.82 mls; P = .04) were significantly lower in the triangular three-bite arm than in the McDonald's arm. Conclusion: The new triangular three-bite technique has similar pregnancy outcomes with the conventional McDonald's technique and has shown a lower duration of procedure and blood loss. Since this is a pilot study, a well-structured randomized control trial to compare the two methods is recommended.

[Diagnostic imaging in multiple sclerosis]. / Bildgebende Diagnostik bei multipler Sklerose.

Multiple sclerosis (MS) is an inflammatory autoimmune disease that leads to the development of demyelination foci in the central nervous system and can affect any neurological function. In the developed world, it represents the most common chronic neurological (nontraumatic) disease in young and middle-aged patients. Magnetic resonance imaging (MRI) is the first-line imaging modality for the diagnosis and follow-up of MS. The currently valid McDonald criteria, updated in 2017, define the exact morphological imaging criteria for diagnosing MS. In addition to the detection of typical MS plaques, the determination of spatial and temporal dissemination is essential for the initial diagnosis. A standardized MRI protocol consisting of mandatory and optional sequences is recommended for reliable diagnosis and differentiation from a broad spectrum of differential diagnoses.

Bayesian Estimation of Single-Test Reliability Coefficients.

Popular measures of reliability for a single-test administration include coefficient α, coefficient λ2, the greatest lower bound (glb), and coefficient ω. First, we show how these measures can be easily estimated within a Bayesian framework. Specifically, the posterior distribution for these measures can be obtained through Gibbs sampling - for coefficients α, λ2, and the glb one can sample the covariance matrix from an inverse Wishart distribution; for coefficient ω one samples the conditional posterior distributions from a single-factor CFA-model. Simulations show that - under relatively uninformative priors - the 95% Bayesian credible intervals are highly similar to the 95% frequentist bootstrap confidence intervals. In addition, the posterior distribution can be used to address practically relevant questions, such as "what is the probability that the reliability of this test is between .70 and .90?", or, "how likely is it that the reliability of this test is higher than .80?" In general, the use of a posterior distribution highlights the inherent uncertainty with respect to the estimation of reliability measures.

Cervical cerclage for prevention of preterm birth: the results from A 20-year cohort.

Cerclages can be used to prevent preterm birth, although their effectiveness and safety is disputed. We aimed to describe obstetric outcomes after cerclage procedures. We included 156 singleton pregnancies and six multiple pregnancies. In singleton pregnancies with history-indicated, short cervix-indicated and emergency cerclages, respectively 84.6, 76.5 and 43.8% resulted in late preterm or term deliveries. In singletons, the following complications were reported: excessive bleeding in one emergency cerclage procedure and three re-cerclage procedures in the history-indicated cerclage group. No perioperative rupture of membranes occurred in singletons. When comparing results of experienced and less-experienced gynaecologists, a remarkably smaller take home child rate was observed for singletons treated by less-experienced gynaecologists: 90.7% and 94.4% for the two experienced gynaecologist as compared to 85.0% for the group of less-experienced gynaecologists. In conclusion, cerclages in singletons result in few cerclage-associated complications and a high take home child rate, when performed by experienced gynaecologists. Impact statementWhat is already known on this subject? Prematurity is the leading cause of perinatal and neonatal mortality and morbidity worldwide. Cervical cerclages can be used to prevent preterm birth, although their effectiveness and safety is disputed.What the results of this study add? In our cohort study, singleton pregnancies with cerclages seem to have satisfactory obstetric outcomes. We found a very low prevalence of cerclage-associated complications in singleton pregnancies, for both history-indicated, short cervix-indicated and emergency cerclages. Additionally, take home child rates in singleton pregnancies were remarkably higher when cerclage procedures were performed by experienced gynaecologists, compared to less experienced gynaecologists.What the implications are of these findings for clinical practice and/or further research? Based on the observed difference in take home child rates, we advise all cerclage procedures to be performed by experienced gynaecologists only. This may mean that women with an indication for cerclage will be referred to a more experienced colleague, either in the same, or in another hospital. To ensure treatment by an experienced gynaecologist, simulation-based training could also provide a solution.

A nearly-neutral biallelic Moran model with biased mutation and linear and quadratic selection.

In this article, a biallelic reversible mutation model with linear and quadratic selection is analysed. The approach reconnects to one proposed by Kimura (1979), who starts from a diffusion model and derives its equilibrium distribution up to a constant. We use a boundary-mutation Moran model, which approximates a general mutation model for small effective mutation rates, and derive its equilibrium distribution for polymorphic and monomorphic variants in small to moderately sized populations. Using this model, we show that biased mutation rates and linear selection alone can cause patterns of polymorphism within and substitution rates between populations that are usually ascribed to balancing or overdominant selection. We illustrate this using a data set of short introns and fourfold degenerate sites from Drosophila simulans and Drosophila melanogaster.

Challenges in multiple sclerosis diagnosis: Misunderstanding and misapplication of the McDonald criteria.

OBJECTIVE: To assess comprehension and application of the McDonald criteria. BACKGROUND: Studies suggest that knowledge gaps for specific core elements of the McDonald criteria may contribute to multiple sclerosis (MS) misdiagnosis. METHODS: Neurology residents (NR) and multiple sclerosis specialists (MSS) in North America completed a web-based survey. RESULTS: A total of 160 participants were included: 72 NR and 88 MSS. Syndromes incorrectly identified as typical of MS included: complete transverse myelopathy (35% NR and 15% MSS), intractable vomiting/nausea/hiccoughs (20% NR and 5% MSS), and bilateral optic neuritis/unilateral optic neuritis with poor visual recovery (17% NR and 10% MSS). Periventricular magnetic resonance imaging (MRI) lesions were correctly identified by 39% NR and 52% MSS, and juxtacortical lesions were correctly identified by 28% NR and 53% MSS. The correct definition of "periventricular" was chosen by 38% NR and 61% MSS, and that of "juxtacortical" was chosen by 19% NR and 54% MSS. Regions incorrectly identified for MRI dissemination in space fulfillment included the optic nerve (31% NR and 26% MSS) and the subcortical white matter (11% NR and 18% MSS). The majority of participants assessed previous non-specific neurological symptoms without objective evidence of a central nervous system (CNS) lesion as sufficient for clinical dissemination in time. CONCLUSION: The McDonald criteria are often misunderstood and misapplied. Concerted educational efforts may prevent MS misdiagnosis.

Primary progressive multiple sclerosis presenting under the age of 18 years: Fact or fiction?

Previous cohort studies on paediatric multiple sclerosis (MS) have reported very low frequencies for a primary progressive MS (PPMS) course ranging from 0% to 7%. We identified six patients presenting prior to the age of 18 years and fulfilling the 2017 McDonald Criteria for PPMS. Presentation with progressive neurological symptoms and signs in young people should prompt evaluation for genetic causes such as leukodystrophies, hereditary spastic paraparesis and mitochondrial diseases given the rarity of primary progressive course in paediatric MS. In the absence of an alternative diagnosis, with new therapeutic options becoming available for PPMS, this diagnosis should then be considered.

Migraine screen questionnaire: further psychometric evidence from categorical data methods.

BACKGROUND: Psychometric investigations of tools used in the screening of migraine including the migraine screen questionnaire (MS-Q), using an adequate statistical approach is needed. We assessed the psychometric properties of the migraine screen questionnaire (MS-Q) using categorical data methods. MATERIAL AND METHODS: A total of 343 students at Mizan-Tepi University, Ethiopia, age range = 18-35 years were selected by a simple random sampling method to participate in a cross-sectional study. The respondents completed the MS-Q, a semi-structured socio-demographic questionnaire, and a visual analog scale for attention (VAS-A). RESULTS: The cumulative variance rule (> 40%), the Kaiser's criteria (Eigenvalue> 1), the Scree test and, the parallel analysis (minimum rank) identified a 1-factor model for the MS-Q with the factor loadings in the range of 0.78 to 0.84. Fit indices favored a 1-factor model of the MS-Q as indicated by comparative fit index (0.993), weighted root mean square residual (0.048), root mean square error of approximation (0.067), the goodness of fit index (1.00), and non-normed fit index (0.987). The values of the Factor Determinacy Index (0.953), marginal reliability (0.909), H-latent (0.909), H-observed (0.727), explained common variance (0.906) and the mean item residual absolute loadings (0.225) further complimented finding of the 1-Factor model. McDonald's Omega (0.903) suggested adequate internal consistency. Discriminative validity was supported by significantly higher scores for the total and all the MS-Q items except one among those with complaints of attention. CONCLUSION: The categorical methods support the psychometric validity of the MS-Q in the study population.

Demographic and clinical profile of patients with multiple sclerosis diagnosed over the last 30 years according to different diagnostic criteria.

The aim of this study was to investigate the demographic and clinical characteristics of patients with multiple sclerosis (MS) diagnosed between 1986 and 2015. 333 patients with definite MS were divided into four subgroups according to the following diagnostic criteria: Group A) Poser (n = 145), Group B) McDonald 2000 (n = 66), Group C) McDonald 2005 (n = 62), and Group D) McDonald 2010 (n = 60). We investigated: 1) patient sex and age at diagnosis, 2) symptoms and number of relapses that prompted MS diagnosis, 3) time between first symptoms suggestive of MS and confirmed diagnosis, and 5) Expanded Disability Status Scale (EDSS) score at disease onset. The overall female-to-male ratio was 2.3:1, but in the subgroups it differed significantly (A - 1.9; B - 1.6; C - 4.7; D - 3.6). The mean age at diagnosis (in years) decreased from 39.6 ± 13.3 in Group A to 29.9 ± 9.3 in Group D, p < 0.001. Pyramidal signs remained the most common manifestation regardless of the diagnostic criteria, although an increased trend of visual dysfunction was observed (A - 16%, B - 14%, C - 19%, D - 23,3%; A vs D, p < 0.001). The number of relapses before diagnosis decreased from median 4.0 to 2.5 in Group A and Group D, p < 0.001. Time from the first symptom to diagnosis shortened from 88.9 ± 80.2 months (Group A) to 33.6 ± 68.2 months (Group D), p < 0.0001. Mean EDSS score at diagnosis also decreased: A - 4.4 ± 2.3; B - 3.1 ± 1.7; C - 2.7 ± 1.3; D - 2.8 ± 1.4, p < 0.001. Our study indicates significant differences in demographic and clinical characteristics of MS diagnosed according to the changing criteria.