The JAK2 V617F and Calreticulin mutations (CALR) are frequent driver mutations within the myeloproliferative neoplasms (MPN). JAK2 V617F has been detected in the general population but no studies have previously investigated the prevalence of CALR. Thus, we aimed to determine the CALR and JAK2 V617F population prevalence and to assess the biochemical profile and lifestyle risk factors in mutation positives with and without MPN. 19,958 eligible participants, enrolled from 2010-2013, from the Danish General Suburban Population Study including DNA, blood tests, and questionnaires were screened for JAK2 V617F and CALR by droplet digital PCR. 645 participants were mutation positive (3.5%) and 16 of these (2.5%) had MPN at baseline. 613 participants were JAK2 V617F positive (allele burden (mean(SE)):2.1(0.34)%) and 32 participants were CALR positive (allele burden:7.5(2.2)%), corresponding to a population prevalence of 3.1% (CI 2.8-3.3%) and 0.16% (CI 0.11-0.23%), respectively. Increasing age, smoking, and alcohol were risk factors for the mutations. JAK2 V617F positives with and without MPN presented elevated odds for prevalent venous thromboembolism. The odds ratio for a diagnosis of MPN per percentage allele burden was 1.14 (95% CI 1.09-1.18, p=1.6x10^-10). Mutation positives displayed higher blood cell counts compared to non-mutated, and 40% of mutation positives without MPN presented elevation of {greater than or equal to}1 blood cell counts. In conclusion, we present a novel population prevalence of CALR and a JAK2 V617F prevalence that is 3-30 times higher compared to less sensitive methods. Mutation positive non-MPNs have elevated blood cell counts which raises concerns of underdiagnosis of MPN in the population. Key Points CALR mutations are prevalent in the general population but are much less frequent compared to the estimated JAK2 V617F prevalence JAK2 V617F and CALR mutations in the general population are linked to a distinct blood count profile, also in the absence of MPN diagnosis

Background: Evidence for the relationship between maternal and perinatal factors and the success of vaginal birth after cesarean section (VBAC) is conflicting. We aimed to systematically analyze published data on maternal and fetal factors for successful VBAC. Methods: A comprehensive search of Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature, from each database’s inception to March 16, 2018. Observational studies, identifying women with a trial of labor after one previous low-transverse cesarean section were included. Two reviewers independently abstracted the data. Meta-analysis was performed using the random-effects model. Risk of bias was assessed by the Newcastle-Ottawa Scale. Results: We included 94 eligible observational studies (239,006 pregnant women with 163,502 VBAC). Factors were associated with successful VBAC with the following odds ratios (OR;95%CI): age (0.92;0.86–0.98), obesity (0.50;0.39–0.64), diabetes (0.50;0.42–0.60), hypertensive disorders complicating pregnancy (HDCP) (0.54;0.44–0.67), Bishop score (3.77;2.17–6.53), labor induction (0.58;0.50–0.67), macrosomia (0.56;0.50–0.64), white race (1.39;1.26–1.54), previous vaginal birth before cesarean section (3.14;2.62–3.77), previous VBAC (4.71;4.33–5.12), the indications for the previous cesarean section (cephalopelvic disproportion (0.54;0.36–0.80), dystocia or failure to progress (0.54;0.41–0.70), failed induction (0.56;0.37–0.85), and fetal malpresentation (1.66;1.38–2.01)). Adjusted ORs were similar. Conclusions: Diabetes, HDCP, Bishop score, labor induction, macrosomia, age, obesity, previous vaginal birth, and the indications for the previous CS should be considered as the factors affecting the success of VBAC.

Background Most errors in a clinical chemistry laboratory are due to preanalytical errors. Preanalytical variability of biospecimens can have significant effects on downstream analyses, and controlling such variables is therefore fundamental for the future use of biospecimens in personalized medicine for diagnostic or prognostic purposes. Content The focus of this review is to examine the preanalytical variables that affect human biospecimen integrity in biobanking, with a special focus on blood, saliva, and urine. Cost efficiency is discussed in relation to these issues. Summary The quality of a study will depend on the integrity of the biospecimens. Preanalytical preparations should be planned with consideration of the effect on downstream analyses. Currently such preanalytical variables are not routinely documented in the biospecimen research literature. Future studies using biobanked biospecimens should describe in detail the preanalytical handling of biospecimens and analyze and interpret the results with regard to the effects of these variables.

A meta-analysis can help inform the debate about the epidemiological evidence on dairy intake and development of acne. A systematic literature search of PubMed from inception to 11 December 2017 was performed to estimate the association of dairy intake and acne in children, adolescents, and young adults in observational studies. We estimated the pooled random effects odds ratio (OR) (95% CI), heterogeneity (I²-statistics, Q-statistics), and publication bias. We included 14 studies (n = 78,529; 23,046 acne-cases/55,483 controls) aged 7–30 years. ORs for acne were 1.25 (95% CI: 1.15–1.36; p = 6.13 × 10⁻⁸) for any dairy, 1.22 (1.08–1.38; p = 1.62 × 10⁻³) for full-fat dairy, 1.28 (1.13–1.44; p = 8.23 × 10⁻⁵) for any milk, 1.22 (1.06–1.41; p = 6.66 × 10⁻³) for whole milk, 1.32 (1.16–1.52; p = 4.33 × 10⁻⁵) for low-fat/skim milk, 1.22 (1.00–1.50; p = 5.21 × 10⁻²) for cheese, and 1.36 (1.05–1.77; p = 2.21 × 10⁻²) for yogurt compared to no intake. ORs per frequency of any milk intake were 1.24 (0.95–1.62) by 2–6 glasses per week, 1.41 (1.05–1.90) by 1 glass per day, and 1.43 (1.09–1.88) by ≥2 glasses per day compared to intake less than weekly. Adjusted results were attenuated and compared unadjusted. There was publication bias (p = 4.71 × 10⁻³), and heterogeneity in the meta-analyses were explained by dairy and study characteristics. In conclusion, any dairy, such as milk, yogurt, and cheese, was associated with an increased OR for acne in individuals aged 7–30 years. However, results should be interpreted with caution due to heterogeneity and bias across studies.

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.