Down Regulation with Luteal GnRH Agonist Therapy in Euploid Embryo Transfers Does Not Impact Pregnancy Rates

Introduction : Gonadotropin-releasing hormone (GnRH) agonists have been used during assisted reproductive technology (ART) treatment for pituitary suppression and stimulation. Currently, clinical opinion is divided about whether GnRH agonist therapy improves pregnancy rates when used for luteal down-regulation in a frozen euploid embryo transfer (FET). This study evaluated the clinical utility of GnRH agonist down-regulation in single, euploid FET cycles. Methods : A retrospective analysis was performed, using data from patients who underwent a single, euploid FET cycle from 2012 to 2019. Patients were segregated into two cohorts: Group A: single, euploid FET with down-regulation using GnRH agonist; Group B: single, euploid FET without down-regulation using GnRH agonist. Primary outcomes include pregnancy rates among cohorts. Results : Group A demonstrated a pregnancy rate of 72.92% in 96 cycles. Group B demonstrated a pregnancy rate of 73.27% in 5,668 cycles. There was no difference in pregnancy rates between groups, X2(2, N = 5764) = .0061, p = .94. A subgroup of patients (n=5) with endometriosis in Group A achieved an 80% (4/5) pregnancy rate. Discussion : Single, euploid FET cycle pregnancy rates were not affected by the use of down-regulation with a GnRH agonist. Increased pregnancy rates found with prolonged GnRH agonist use in other studies weren’t seen with short term use for FET cycles. Future research should focus on molecular markers and gene transcription signatures to attempt to define whether there is an ideal population of patients who would benefit from GnRH agonist down-regulation prior to FET

Preferred antiretroviral drugs for the next decade of scale up

Global commitments aim to provide antiretroviral therapy (ART) to 15 million people living with HIV by 2015, and recent studies have demonstrated the potential for widespread ART to prevent HIV transmission. Increasingly, countries are adapting their national guidelines to start ART earlier, for both clinical and preventive benefits. To maximize the benefits of ART in resource-limited settings, six key principles need to guide ART choice: simplicity, tolerability and safety, durability, universal applicability, affordability and heat stability. Currently available drugs, combined with those in late-stage clinical development, hold great promise to simplify treatment in the short term. Over the longer-term, newer technologies, such as long-acting formulations and nanotechnology, could radically alter the treatment paradigm. This commentary reviews recommendations made in an expert consultation on treatment scale up in resource-limited settings

Linguistics

Contains research summary and abstracts for five theses

Linguistics

Contains research summary and abstracts for nine theses

Assessing Communities of Practice in health policy : A conceptual framework as a first step towards empirical research

Peer reviewe

Holistic processing, contact, and the other-race effect in face recognition

Face recognition, holistic processing, and processing of configural and featural facial information are known to be influenced by face race, with better performance for own- than other-race faces. However, whether these various other-race effects (OREs) arise from the same underlying mechanisms or from different processes remains unclear. The present study addressed this question by measuring the OREs in a set of face recognition tasks, and testing whether these OREs are correlated with each other. Participants performed different tasks probing (1) face recognition, (2) holistic processing, (3) processing of configural information, and (4) processing of featural information for both own- and other-race faces. Their contact with other-race people was also assessed with a questionnaire. The results show significant OREs in tasks testing face memory and processing of configural information, but not in tasks testing either holistic processing or processing of featural information. Importantly, there was no cross-task correlation between any of the measured OREs. Moreover, the level of other-race contact predicted only the OREs obtained in tasks testing face memory and processing of configural information. These results indicate that these various cross-race differences originate from different aspects of face processing, in contrary to the view that the ORE in face recognition is due to cross-race differences in terms of holistic processing

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

The phage therapy paradigm: prêt-à-porter or sur-mesure?

The present opinion is the result of discussions on the future of phage therapy (personalized or large-scale uniform therapy?) during the first International Congress on Viruses of Microbes, held at the Institut Pasteur in Paris on June 21–25, 2010

Comparison of clinical rating scales in genetic frontotemporal dementia within the GENFI cohort

Background Therapeutic trials are now underway in genetic forms of frontotemporal dementia (FTD) but clinical outcome measures are limited. The two most commonly used measures, the Clinical Dementia Rating (CDR)+National Alzheimer\u27s Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) and the FTD Rating Scale (FRS), have yet to be compared in detail in the genetic forms of FTD. Methods The CDR+NACC FTLD and FRS were assessed cross-sectionally in 725 consecutively recruited participants from the Genetic FTD Initiative: 457 mutation carriers (77 microtubule-Associated protein tau (MAPT), 187 GRN, 193 C9orf72) and 268 family members without mutations (non-carrier control group). 231 mutation carriers (51 MAPT, 92 GRN, 88 C9orf72) and 145 non-carriers had available longitudinal data at a follow-up time point. Results Cross-sectionally, the mean FRS score was lower in all genetic groups compared with controls: GRN mutation carriers mean 83.4 (SD 27.0), MAPT mutation carriers 78.2 (28.8), C9orf72 mutation carriers 71.0 (34.0), controls 96.2 (7.7), p\u3c0.001 for all comparisons, while the mean CDR+NACC FTLD Sum of Boxes was significantly higher in all genetic groups: GRN mutation carriers mean 2.6 (5.2), MAPT mutation carriers 3.2 (5.6), C9orf72 mutation carriers 4.2 (6.2), controls 0.2 (0.6), p\u3c0.001 for all comparisons. Mean FRS score decreased and CDR+NACC FTLD Sum of Boxes increased with increasing disease severity within each individual genetic group. FRS and CDR+NACC FTLD Sum of Boxes scores were strongly negatively correlated across all mutation carriers (r s =-0.77, p\u3c0.001) and within each genetic group (r s =-0.67 to-0.81, p\u3c0.001 in each group). Nonetheless, discrepancies in disease staging were seen between the scales, and with each scale and clinician-judged symptomatic status. Longitudinally, annualised change in both FRS and CDR+NACC FTLD Sum of Boxes scores initially increased with disease severity level before decreasing in those with the most severe disease: controls-0.1 (6.0) for FRS,-0.1 (0.4) for CDR+NACC FTLD Sum of Boxes, asymptomatic mutation carriers-0.5 (8.2), 0.2 (0.9), prodromal disease-2.3 (9.9), 0.6 (2.7), mild disease-10.2 (18.6), 3.0 (4.1), moderate disease-9.6 (16.6), 4.4 (4.0), severe disease-2.7 (8.3), 1.7 (3.3). Sample sizes were calculated for a trial of prodromal mutation carriers: over 180 participants per arm would be needed to detect a moderate sized effect (30%) for both outcome measures, with sample sizes lower for the FRS. Conclusions Both the FRS and CDR+NACC FTLD measure disease severity in genetic FTD mutation carriers throughout the timeline of their disease, although the FRS may be preferable as an outcome measure. However, neither address a number of key symptoms in the FTD spectrum, for example, motor and neuropsychiatric deficits, which future scales will need to incorporate