Nevin Manimala

Hum Reprod. 2021 Mar 4:deab031. doi: 10.1093/humrep/deab031. Online ahead of print.

ABSTRACT

STUDY QUESTION: Does an individualised luteal phase support (iLPS), according to serum progesterone (P4) level the day prior to euploid frozen embryo transfer (FET), improve pregnancy outcomes when started on the day previous to embryo transfer?

SUMMARY ANSWER: Patients with low serum P4 the day prior to euploid FET can benefit from the addition of daily subcutaneous P4 injections (Psc), when started the day prior to FET, and achieve similar reproductive outcomes compared to those with initial adequate P4 levels.

WHAT IS KNOWN ALREADY: The ratio between FET/IVF has spectacularly increased in the last years mainly thanks to the pursuit of an ovarian hyperstimulation syndrome free clinic and the development of preimplantation genetic testing (PGT). There is currently a big concern regarding the endometrial preparation for FET, especially in relation to serum P4 levels around the time of embryo transfer. Several studies have described impaired pregnancy outcomes in those patients with low P4 levels around the time of FET, considering 10 ng/ml as one of the most accepted reference values. To date, no prospective study has been designed to compare the reproductive outcomes between patients with adequate P4 the day previous to euploid FET and those with low, but restored P4 levels on the transfer day after iLPS through daily Psc started on the day previous to FET.

STUDY DESIGN, SIZE, DURATION: A prospective observational study was conducted at a university-affiliated fertility centre between November 2018 and January 2020 in patients undergoing PGT for aneuploidies (PGT-A) IVF cycles and a subsequent FET under hormone replacement treatment (HRT). A total of 574 cycles (453 patients) were analysed: 348 cycles (leading to 342 euploid FET) with adequate P4 on the day previous to FET, and 226 cycles (leading to 220 euploid FET) under iLPS after low P4 on the previous day to FET, but restored P4 levels on the transfer day.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall we included 574 HRT FET cycles (453 patients). Standard HRT was used for endometrial preparation. P4 levels were measured the day previous to euploid FET. P4 > 10.6 ng/ml was considered as adequate and euploid FET was performed on the following day (FET Group 1). P4 < 10.6 ng/ml was considered as low, iLPS was added in the form of daily Psc injections, and a new P4 analysis was performed on the following day. FET was only performed on the same day when a restored P4 > 10.6 ng/ml was achieved (98.2% of cases) (FET Group 2).

MAIN RESULTS AND THE ROLE OF CHANCE: Patient’s demographics and cycle parameters were comparable between both euploid FET groups (FET Group 1 and FET Group 2) in terms of age, weight, oestradiol and P4 levels and number of embryos transferred. No statistically significant differences were found in terms of clinical pregnancy rate (56.4% vs 59.1%: rate difference (RD) -2.7%, 95% CI [-11.4; 6.0]), ongoing pregnancy rate (49.4% vs 53.6%: RD -4.2%, 95% CI [-13.1; 4.7]) or live birth rate (49.1% vs 52.3%: RD -3.2%, 95% CI [-12; 5.7]). No significant differences were also found according to miscarriage rate (12.4% vs 9.2%: RD 3.2%, 95% CI [-4.3; 10.7]).

LIMITATIONS, REASONS FOR CAUTION: Only iLPS through daily Psc was evaluated. The time for Psc injection was not stated and no serum P4 determinations were performed once the pregnancy was achieved.

WIDER IMPLICATIONS OF THE FINDINGS: Our study provides information regarding an ‘opportunity window’ for improved ongoing pregnancy rates and miscarriage rates through a daily Psc injection in cases of inadequate P4 levels the day previous to FET (P4 < 10.6 ng/ml) and restored values the day of FET (P4 > 10.6 ng/ml). Only euploid FET under HRT were considered, avoiding one of the main reasons of miscarriage and implantation failure and overcoming confounding factors such as female age, embryo quality or ovarian stimulation protocols.

STUDY FUNDING/COMPETING INTEREST(S): No external funding was received. B.C. reports personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, IBSA and Gedeon Richter outside the submitted work. N.P. reports grants and personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, Theramex and Besins International and personal fees from IBSA and Gedeon Richter outside the submitted work. The remaining authors have no conflicts of interest to declare.

TRIAL REGISTRATION NUMBER: NCT03740568.

PMID:33686413 | DOI:10.1093/humrep/deab031

Interact Cardiovasc Thorac Surg. 2021 Mar 4:ivab052. doi: 10.1093/icvts/ivab052. Online ahead of print.

ABSTRACT

OBJECTIVES: Minimally invasive repair of pectus excavatum (MIRPE) is the most popular surgical approach for paediatric patients with pectus excavatum. A substernal stainless still bar is inserted and left in place for 3 years and then removed. Our goal was to investigate blood metal levels after MIRPE and to correlate them with surgical details, such as the numbers of bars and stabilizers and the length of time the bar was in place.

METHODS: Blood levels of iron, chromium, manganese, molybdenum and nickel were analysed in 130 teenagers (108 boys and 22 girls) who had MIRPE using inductively coupled plasma mass spectrometry. A total of 62 patients were operated on using MIRPE (study group) and 68 patients were evaluated at implant time (control group). Differences between the numbers of bars implanted and the presence or absence of stabilizers were also considered.

RESULTS: Significant increases in the levels of abnormal chromium were found in patients in the study group compared with the controls (P = 0.02). When we compared the group of patients with 2 or more bars with the group with 1 bar, the percentage of patients with a value above the threshold increased by 29 (P = 0.05). A significant increase in chromium levels was observed in patients with stabilizers (P = 0.03). Above-threshold levels of molybdenum were found in 5.1% of patients in the control group, but the number was not statistically significant (P = 0.09).

CONCLUSIONS: We demonstrated that stainless steel devices used in MIRPE can elevate blood metal levels in paediatric patients. Moreover, we demonstrated that the use of metal stabilizers is associated with higher metal levels, probably due to increased dispersion.

PMID:33686408 | DOI:10.1093/icvts/ivab052

Z Erziehwiss. 2021 Mar 3:1-17. doi: 10.1007/s11618-021-01001-y. Online ahead of print.

ABSTRACT

Keeping schools open was an active strategy in Sweden to meet the threats of the COVID-19 pandemic. In this article we analyze how a collection of welfare state agents with different tasks, resources and interests in interaction formed an assemblage in their responses to the pandemic and how education thereby became part of a strategy to keep the society going. The inquiries concern what this tells us about education as framed and constrained as a part of society. Our observations are based on statements presented by the government and public agencies, mass media and websites. We identified an assemblage of interwoven agents such as institutions, laws, regulations and recommendations, pandemic manuals, statistics and media. All these were brought together by actions and ideas to handle a pandemic when there were no preventive vaccines. The overarching principle was to educate the population to competent actions in dealing with the pandemic. To keep schools open was part of that principle combined with caretaking ambitions. This assemblage looked like a centralistic machine but it was not; risks were pushed back to local authorities and schools. In conclusion, we note that education is vital in the overarching strategy to deal with the pandemic in Sweden in terms of trust in people and governmentality.

PMID:33686342 | PMC:PMC7927774 | DOI:10.1007/s11618-021-01001-y

Nat Genet. 2021 Mar 8. doi: 10.1038/s41588-021-00787-1. Online ahead of print.

ABSTRACT

Psychiatric disorders are highly genetically correlated, but little research has been conducted on the genetic differences between disorders. We developed a new method (case-case genome-wide association study; CC-GWAS) to test for differences in allele frequency between cases of two disorders using summary statistics from the respective case-control GWAS, transcending current methods that require individual-level data. Simulations and analytical computations confirm that CC-GWAS is well powered with effective control of type I error. We applied CC-GWAS to publicly available summary statistics for schizophrenia, bipolar disorder, major depressive disorder and five other psychiatric disorders. CC-GWAS identified 196 independent case-case loci, including 72 CC-GWAS-specific loci that were not significant at the genome-wide level in the input case-control summary statistics; two of the CC-GWAS-specific loci implicate the genes KLF6 and KLF16 (from the Krüppel-like family of transcription factors), which have been linked to neurite outgrowth and axon regeneration. CC-GWAS loci replicated convincingly in applications to datasets with independent replication data.

PMID:33686288 | DOI:10.1038/s41588-021-00787-1

Eye (Lond). 2021 Mar 8. doi: 10.1038/s41433-021-01490-5. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the inter-rater reliability for identification of complete retinal pigment epithelium and outer retinal atrophy (cRORA) on SD-OCT images as defined by the Classification of Atrophy Meetings (CAM) group.

METHODS: Fifty images of anonymized SD-OCT line scans of eyes with cRORA due to AMD were selected. Each .tiff image was saved in both black-on-white (BW) and white-on-black (WB) format. Five retina-trained clinicians graded both sets of images twice for the diagnosis of cRORA based on the CAM group definition. Fleiss kappa statistic was calculated for inter-rater reliability and Cohen’s kappa statistic for intra-grader and inter-grader reliability between any two graders.

RESULTS: The inter-grader reliability varied from as low as 0.28 to 0.92 for WB images and 0.34 to 0.86 for BW images. However, the inter-grader and intra-grader agreement was ĸ WB 0.92; ĸ BW 0.86 and ĸ 0.92 respectively, for graders accustomed to the CAM criteria. Fleiss kappa was ĸ 0.49 (p value < 0.0001) for WB images and ĸ 0.34 (p value < 0.0001 for BW images. Overall, the agreement was better using WB images for all parameters except RPE attenuation/loss.

CONCLUSION: There is significant variability in diagnosis of cRORA on SD-OCT by retina-trained ophthalmologists in the real world. The study highlights the need for training to recognise the different features of cRORA prior to its implementation in clinical practice.

PMID:33686233 | DOI:10.1038/s41433-021-01490-5

Nat Hum Behav. 2021 Mar 8. doi: 10.1038/s41562-021-01065-0. Online ahead of print.

ABSTRACT

How do we evaluate a group of people after a few negative experiences with some members but mostly positive experiences otherwise? How do rare experiences influence our overall impression? We show that rare events may be overweighted due to normative inference of the hidden causes that are believed to generate the observed events. We propose a Bayesian inference model that organizes environmental statistics by combining similar events and separating outlying observations. Relying on the model’s inferred latent causes for group evaluation overweights rare or variable events. We tested the model’s predictions in eight experiments where participants observed a sequence of social or non-social behaviours and estimated their average. As predicted, estimates were biased toward sparse events when estimating after seeing all observations, but not when tracking a summary value as observations accrued. Our results suggest that biases in evaluation may arise from inferring the hidden causes of group members’ behaviours.

PMID:33686201 | DOI:10.1038/s41562-021-01065-0

Nat Hum Behav. 2021 Mar 8. doi: 10.1038/s41562-021-01053-4. Online ahead of print.

ABSTRACT

Epidemiological studies show high comorbidity between different mental health problems, indicating that individuals with a diagnosis of one disorder are more likely to develop other mental health problems. Genetic studies reveal substantial sharing of genetic factors across mental health traits. However, mental health is also genetically correlated with socio-economic status (SES), and it is therefore important to investigate and disentangle the genetic relationship between mental health and SES. We used summary statistics from large genome-wide association studies (average N ~ 160,000) to estimate the genetic overlap across nine psychiatric disorders and seven substance use traits and explored the genetic influence of three different indicators of SES. Using genomic structural equation modelling, we show significant changes in patterns of genetic correlations after partialling out SES-associated genetic variation. Our approach allows the separation of disease-specific genetic variation and genetic variation shared with SES, thereby improving our understanding of the genetic architecture of mental health.

PMID:33686200 | DOI:10.1038/s41562-021-01053-4

Sci Rep. 2021 Mar 8;11(1):5440. doi: 10.1038/s41598-021-84844-z.

ABSTRACT

In grasses, leaf expansion and central rib growth occur in a non-proportional manner, with potential implications to the nutritive value of leaves. The objective of this study was to evaluate the relationship among blade length, percentage of central rib, anatomical characteristics and the nutritive value along the length of leaf blades of different sizes and hierarchical order of insertion on the tiller axis of Napier elephant grass (Pennisetum purpureum Schum. cv. Napier). Two experiments were carried out with isolated growing plants during the summer of 2017 (January to March). Central rib mass increased linearly with the increase in leaf blade mass and its percentage relative to blade mass decreased from the base to the tip of the leaf. There were no significant variations in anatomical characteristics along the length of leaf blades when central rib was not taken into account. The central rib showed negative relationship with nutritive value. The apical portions of long leaves showed similar digestibility to short leaves. The multivariate analysis of Cluster and Principal Components grouped the response variables according to leaf hierarchical order, final blade length and percentage of structural tissues, highlighting the relationship between leaf size, structural tissues and nutritive value.

PMID:33686178 | DOI:10.1038/s41598-021-84844-z

Sci Rep. 2021 Mar 8;11(1):5355. doi: 10.1038/s41598-021-84486-1.

ABSTRACT

The homological scaffold leverages persistent homology to construct a topologically sound summary of a weighted network. However, its crucial dependency on the choice of representative cycles hinders the ability to trace back global features onto individual network components, unless one provides a principled way to make such a choice. In this paper, we apply recent advances in the computation of minimal homology bases to introduce a quasi-canonical version of the scaffold, called minimal, and employ it to analyze data both real and in silico. At the same time, we verify that, statistically, the standard scaffold is a good proxy of the minimal one for sufficiently complex networks.

PMID:33686171 | DOI:10.1038/s41598-021-84486-1

Sci Rep. 2021 Mar 8;11(1):5397. doi: 10.1038/s41598-021-84868-5.

ABSTRACT

This study analyzed the association between medication adherence and the intrapatient variability (IPV) of tacrolimus concentrations among kidney transplant recipients through a post hoc analysis of the dataset from a recently conducted randomized controlled trial. Among 138 patients enrolled in the original trial, 92 patients with ≥ 5 months of medication event monitoring system (MEMS) use and ≥ 4 tacrolimus trough values were included in this post hoc analysis. The variability of tacrolimus trough levels was calculated using coefficient variation (CV) and mean absolute deviation. Adherence was assessed using MEMS and self-report via the Basal Assessment of Adherence to Immunosuppressive Medication Scale. There were no statistically significant differences in the CV [median 16.5% [interquartile range 11.6-25.5%] and 16.0% [11.5-23.5%], respectively, P = .602] between the nonadherent (n = 59) and adherent groups (n = 33). There was also no significant correlation between the CV and adherence detected by MEMS (taking adherence, ρ = – 0.067, P = .527; dosing adherence, ρ = – 0.098, P = .352; timing adherence, ρ = – 0.113, P = .284). Similarly, adherence measured by self-report did not significantly affect the IPV (P = .452). In this post hoc analysis, nonadherent behavior, measured through electronic monitoring or self-report, did not affect the IPV.

PMID:33686160 | DOI:10.1038/s41598-021-84868-5