Marcos Cruz

Recent observations have indicated a Cosmic Microwave Background (CMB) temperature decrement in the direction of local galaxies within the 2MASS Redshift Survey. We investigate this detection by analyzing its frequency dependence and sensitivity to component separation methods, suggesting that Galactic foregrounds are unlikely to be the cause. Contrary to previous studies, we find that the decrement is independent of galaxy type, indicating a possible correlation between the CMB and the overall matter density field. To test this hypothesis, we employ three analytical approaches: cross-correlation analysis, template fitting, and Bayes Factor calculation. Our analyses consistently reveal a moderate correlation (with significance levels in the 1% – 5% range) between the CMB and the 2MASS Redshift Survey projected matter density at distances below 50 Mpc/h. Importantly, we do not detect this signal beyond 50 Mpc/h, which constrains potential physical interpretations and suggests caution regarding possible look-elsewhere effects in our analysis. We discuss that the physical origin of this correlation could potentially be linked to the dark matter distribution in the halos of galaxies. Further investigation is required to confirm and understand this intriguing connection between the CMB and local matter distribution.

Recent observations have indicated a Cosmic Microwave Background (CMB) temperature decrement in the direction of local galaxies within the 2MASS Redshift Survey. We investigate this detection by analyzing its frequency dependence and sensitivity to component separation methods, suggesting that Galactic foregrounds are unlikely to be the cause. Contrary to previous studies, we find that the decrement is independent of galaxy type, indicating a possible correlation between the CMB and the overall matter density field. To test this hypothesis, we employ three analytical approaches: cross-correlation analysis, template fitting, and Bayes Factor calculation. Our cross-correlation analysis shows a significant correlation (p < 0.7%) between the CMB and the 2MASS Redshift Survey projected matter density at distances below 50 Mpc/h. Template fitting and Bayes Factor analyses support this finding, albeit with lower significance levels (1% - 5%). Importantly, we do not detect this signal beyond 50 Mpc/h, which constrains potential physical interpretations. We discuss that the physical origin of this correlation could potentially be linked to the dark matter distribution in the halos of galaxies. Further investigation is required to confirm and understand this intriguing connection between the CMB and local matter distribution.

Background: Heavy menstrual bleeding affects one in four women and negatively impacts quality of life. The levonorgestrel-releasing intrauterine system is an effective long-term treatment but is discontinued by many due to unpredictable bleeding, or adverse effects. The selective progesterone receptor modulator ulipristal acetate is used to treat symptomatic fibroids but long-term efficacy for the symptom of heavy menstrual bleeding, irrespective of presence of fibroids, is unknown. Objectives: To determine whether ulipristal acetate is more effective at reducing the burden of heavy menstrual bleeding than levonorgestrel-releasing intrauterine system after 12 months of treatment in women with and without fibroids. We investigated mechanism of action of ulipristal acetate in a subset of 20 women. Design: Randomised, open-label, parallel group, multicentre trial with embedded mechanistic study. Setting: Ten UK hospitals. Participants: Women with heavy menstrual bleeding aged 18 and over with no contraindications to levonorgestrel-releasing intrauterine system or ulipristal acetate. Interventions: Three 12-week treatment cycles of 5 mg ulipristal acetate daily, separated by 4-week treatment-free intervals, or continuous levonorgestrel-releasing intrauterine system following allocation in a 1 : 1 ratio using a web-based minimisation procedure. Main trial outcome measures: Primary outcome was quality-of-life measured by menorrhagia multi-attribute scale at 12 months. Secondary outcomes included menstrual bleeding and patient satisfaction. Impact on fibroid size, endometrial appearance and liver function was also collected. Mechanistic study outcome: Cellular markers for endometrial cell structure and function, determined from endometrial biopsies; volume of uterus and fibroids and microcirculation parameters were determined from magnetic resonance images. Results: Sample size was increased from 220 to 302 as a result of temporary halt to recruitment due to concerns of ulipristal acetate hepatoxicity. Subsequent withdrawal of ulipristal acetate and the COVID-19 pandemic led to a premature closure of recruitment, with 118 women randomised to each treatment and 103 women completing 12-month menorrhagia multi-attribute scale scores prior to this point. Primary outcome scores substantially improved in both arms, but at 12 months there was no evidence of a difference between those receiving three cycles of ulipristal acetate [median score category: 76–99, interquartile range (51–75 to 100), n = 53] and levonorgestrel-releasing intrauterine system [median score category: 76–99, interquartile range (51–75 to 100), n = 50; adjusted odds ratio 0.55, 95% confidence interval 0.26 to 1.17; p = 0.12]. Rates of amenorrhoea were much higher in those allocated ulipristal acetate compared with the levonorgestrel-releasing intrauterine system (12 months: 64% vs. 25%, adjusted odds ratio 7.12, 95% confidence interval 2.29 to 22.2). There was no evidence of a difference in other participant-reported outcomes. There were no cases of endometrial malignancy and no hepatotoxicity due to ulipristal acetate use. Mechanistic study results: Ulipristal acetate produced a reversible reduction in endometrial cell proliferation, as well as reversible alteration of other endometrial cellular markers. Ulipristal acetate did not produce a reduction in the volume of the uterus irrespective of coexisting fibroids, nor an effect on uterine microvascular blood flow. Limitations: The urgent safety measures and premature closure of recruitment impacted final sample size. Conclusions: We found no evidence of a difference in quality of life between the two treatments, but ulipristal acetate was superior to levonorgestrel-releasing intrauterine system at inducing amenorrhoea. Ulipristal acetate currently has restricted availability due to concerns regarding hepatotoxicity. Future work: There is a need to develop new, safe, effective and fertility-sparing medical treatments for heavy menstrual bleeding. The observed acceptability and effectiveness of ulipristal acetate warrants further research into the selective progesterone receptor modulator class of pharmacological agents. Study registration: This trial is registered as ISRCTN 20426843.

STUDY QUESTION: Does application of an unbiased method for analysis of magnetic resonance (MR) images reveal any effect on uterine or fibroid volume from treatment of heavy menstrual bleeding (HMB) with three 12-week courses of the selective progesterone receptor modulator ulipristal acetate (SPRM-UPA)? SUMMARY ANSWER: Application of an unbiased method for analysis of MR images showed that treatment of HMB with SPRM-UPA was not associated with a significant reduction in the volume of the uterus or in the volume of uterine fibroids. WHAT IS KNOWN ALREADY: SPRM-UPA shows therapeutic efficacy for treating HMB. However, the mechanism of action (MoA) is not well understood and there have been mixed reports, using potentially biased methodology, regarding whether SPRM-UPA has an effect on the volume of the uterus and fibroids. STUDY DESIGN, SIZE, DURATION: In a prospective clinical study (with no comparator), 19 women with HMB were treated over a period of 12 months with SPRM-UPA and uterine and fibroid size were assessed with high resolution structural MRI and stereology. PARTICIPANTS/MATERIALS, SETTING, METHODS: A cohort of 19 women aged 38–52 years (8 with and 11 without fibroids) were treated with three 12-week courses of 5 mg SPRM-UPA given daily, with four weeks off medication in-between treatment courses. Unbiased estimates of the volume of uterus and total volume of fibroids were obtained at baseline, and after 6 and 12 months of treatment, by using the Cavalieri method of modern design-based stereology in combination with magnetic resonance imaging (MRI). MAIN RESULTS AND THE ROLE OF CHANCE: Bland–Altman plots showed good intra-rater repeatability and good inter-rater reproducibility for measurement of the volume of both fibroids and the uterus. For the total patient cohort, two-way ANOVA did not show a significant reduction in the volume of the uterus after two or three treatment courses of SPRM-UPA (P = 0.51), which was also the case when the groups of women with and without fibroids were considered separately (P = 0.63). One-way ANOVA did not show a significant reduction in total fibroid volume in the eight patients with fibroids (P = 0.17). LIMITATIONS, REASONS FOR CAUTION: The study has been performed in a relatively small cohort of women and simulations that have subsequently been performed using the acquired data have shown that for three time points and a group size of up to 50, with alpha (Type I Error) and beta (Type II Error) set to 95% significance and 80% power, respectively, at least 35 patients would need to be recruited in order for the null hypothesis (that there is no significant reduction in total fibroid volume) to be potentially rejected. WIDER IMPLICATIONS OF THE FINDINGS: The imaging protocol that we have developed represents a generic paradigm for measuring the volume of the uterus and uterine fibroids that can be readily incorporated in future studies of medical treatments of HMB. In the present study, SPRM-UPA failed to produce a significant reduction in the volume of the uterus or the total volume of fibroids (which were present in approximately half of the patients) after either two or three 12-week courses of treatment. This finding represents a new insight in respect of the management of HMB using treatment strategies that target hormone-dependence. STUDY FUNDING/COMPETING INTEREST(S): The UPA Versus Conventional Management of HMB (UCON) trial was funded by the EME Programme (Medical Research Council (MRC) and National Institutes of Health Research (NIHR)) (12/206/52). The views expressed in this publication are those of the authors and not necessarily those of the Medical Research Council, National Institute for Health Research, or Department of Health and Social Care. Medical Research Council (MRC) Centre grants to the Centre for Reproductive Health (CRH) (G1002033 and MR/N022556/1) are also gratefully acknowledged. H.C. has clinical research support for laboratory consumables and staff from Bayer AG and provides consultancy advice (All paid to Institution) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc., and Myovant Sciences GmbH. H.C. has received royalties from UpToDate for an article on abnormal uterine bleeding. L.W. has received grant funding from Roche Diagnostics (Paid to Institution). All other authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: The study reported here is an embedded mechanism of action study (no comparator) within the UCON clinical trial (registration ISRCTN: 20426843).

Many of the methods used for estimating population size from ecological surveys have limitations on precision, cost, and/or applicability. The CountEm method was proposed recently for estimating the number of individuals in large groups from single images. It is simple and efficient, and can be applied to any species. Here we present a case study by applying CountEm to a real ecological survey with 278 images of Greater Snow Geese (Anser caerulescens atlanticus) and Common Eiders (Somateria mollissima) flocks taken from fixed‐wing aircraft in Eastern Canada. First, we evaluated the precision and counting time of CountEm on single images. Second, we developed and tested a new multi‐image version of the CountEm software. We show that flock sizes of N > 35,000 can be estimated on single images in ∼5 min, from counting a sample of ∼200 birds, yielding relative SEs in the 5%−10% range. Processing times increased to 10–20 min when simultaneously processing large numbers of images that contained over half a million birds with only modest increases in relative SE (range: 10%−15%). Our results suggest that CountEm may be used to save time and resources if incorporated into monitoring programs that utilize imagery in the abundance estimates.

Is there any difference in the time to obtain euploid embryos from poor prognosis patients who performed two conventional cycles versus double stimulation (DuoStim) in the same cycle? DuoStim showed similar ovarian response and in vitro fertilization (IVF) laboratory outcomes while shortening the time to obtain an euploid embryo in poor prognosis patients. Several waves of cyclic development of antral follicles within the same menstrual cycle have been demonstrated. Likewise, it has been shown that oocytes obtained from luteal phase ovarian stimulation (OS) have similar competence than those obtained in the follicular phase OS. Often, some patients require sequential OS in order to obtain more oocytes and increase their chances to reach embryo transfer. Thus, the DuoStim strategy could be an attractive alternative to reduce the time-to-pregnancy. However, prospective data and randomized trials that validate this strategy are lacking. We conducted a prospective, randomized controlled trial at our institution from[MCM1] [JAGV2] January 2017 to December 2020. A total of 80 poor prognosis patients aged over 38 years undergoing PGT-A were enrolled in two groups: 39 patients did two OS in consecutive cycles (control) whereas 41 women underwent two OS in the same menstrual cycle (DuoStim). Poor prognosis was defined as suboptimal responders. The primary outcome was the time needed to obtain an euploid embryo. The secondary outcomes were duration of stimulation, dose of gonadotropins, oocyte maturity rate, fertilization and blastocyst formation rates. Variables were expressed as mean ± standard deviation. Statistical analyses was performed by ANOVA and Chi-square tests, as appropriate. Differences were considered significant when p-value < 0.05. The patients’ baseline characteristics were similar between groups. We did not find any difference in the mean days of stimulation between the control and the DuoStim group (21.3 ± 1.6 vs. 23 ± 1.4, p = 0.105), nor in the amount of gonadotropin required (4005 ± 450 vs. 4245 ± 430, p = 0.43), number of MII oocyte (8.7 ± 1.8 vs. 6.8 ± 1.7, p = 0.159), blastocyst rate (51.4% vs. 34.8%, p = 0.113) and the number of euploid embryos (0.8 ± 0.4 vs. 0.6 ± 0.4, p = 0.45). However, there was a significant difference in the average number of days until reaching an euploid blastocyst, favoring the DuoStim group (44.1 ± 2 vs. 23.3 ± 2.8, p < 0.001). Comparing the follicular versus the luteal phase within the DuoStim group, the only difference detected concerns to the mean days of stimulation (10.3 ± 0.8 vs. 12.7 ± 0.9, p < 0.001). We also observed a trend towards a higher fertilization (38.1% vs. 61.8%, p = 0.02) and blastulation rate (23% vs. 53%, p = 0.03) in the luteal phase of the DuoStim cycle. The major limitation is related to the limited sample size, as it limits our power analysis (70%). On the other hand, it is one of the first randomized prospective pilot trial that compared the efficiency of performing two consecutive ovarian stimulation in different menstrual cycles with the DuoStim strategy. This study clearly showed that the DuoStim protocol is not inferior to the conventional stimulation in terms of ovarian response and laboratory outcomes. Moreover, the DuoStim reduces the time to obtain an euploid embryo in poor prognosis patients, which is of great clinical utility. NCT03291821

The Eastern Canada (ECA) Flocks data set consists of manually annotated images from the Common Eider (COEI, Somateria mollissima) Winter Survey and the Greater Snow Geese (GSGO, Anser caerulescens atlanticus) Spring Survey. The images were taken in eastern Canada using fixed‐wing aircraft and manually annotated with ImageJ’s Cell counter plugins. We selected and annotated the ECA Flocks images in order to test the precision of the CountEm flock size estimation method. ECA Flocks includes 179 COEI and 99 GSGO single flock images. We cut each image manually to a rectangle that excluded large parts of the image with no birds. Both versions (original and cut) of each image are available in the data set. We manually annotated 637,555 (124,309 COEI and 514,235 GSGO) bird positions in the cut images from both surveys. Each bird has an associated “Type,” which refers to species and/or sex. Sex identification was only possible for adult common eiders, because females and immature males are brown birds, whereas adult males have mainly white plumage. In the COEI images 64,484 males and 58,029 females, as well as 1,796 birds of other species, were identified. In the GSGO images 504,891 Snow Geese and 9,344 birds of other species were labeled. A .csv file including all annotated bird positions and types is available for each image. The COEI and GSGO photos of the ECA Flocks data set were taken in the years 2006 and 2018 and 2016–2018, respectively. We selected these photos in order to include images with different quality and resolution. COEI and GSGO flock sizes range from 6 to 4,154 and from 43 to 36,241 respectively. There is high variability in light conditions, backgrounds, and number and spatial arrangement of birds across the images. The data set is therefore potentially useful to test the precision of methods for analyzing imagery to estimate the abundance of animals by directly detecting, identifying, and counting individuals. We release these data into the public domain under a Creative Commons Zero license waiver. When you use the data in your publication, cite this data paper. Should ECA Flocks be a major part of the data analyzed in your study, you should consider inviting the ECA Flocks originators as collaborators. If you plan to use the ECA Flocks data set, we request that you contact the ECA Flocks core team to learn whether updates are available, and whether similar analyses are already ongoing.

The direct superimposition of a standard test grid of congruent quadrats onto an image bearing a population of particles exhibiting perspective artifacts, tends to increase the variance of the population size estimator, because the quadrat contents become unbalanced. If the quadrats are transformed according to the same projection mechanism affecting the particles, however, then the variance is restored into moderate values. Our purpose was to provide exact, easily programmable equations for the relevant transform.

Population size estimation is essential in ecology and conservation studies. Aerial photography can facilitate this laborious task with high resolution images. However, in images with thousands of individuals exhaustive manual counting is tedious, slow and difficult to verify. Computer vision software may work under some particular conditions but they are generally biased and known to fail in several situations. The CountEm software is a simple alternative based on geometric sampling. It provides a fast and unbiased size estimation for all sorts of populations. The only requirement is that the discrete objects (e.g. animals) in the target population are unambiguously distinguishable for counting in a still image. Typical relative standard errors in the 5–10% range are obtained after counting ~200 properly sampled animals in about 5 min irrespective of population size. The CountEm ver. 1.4.1 is presented here, which includes a guided mode with a simple software interface.

Design unbiased estimation of population size by stereological methods is an efficient alternative to automatic computer vision methods, which are generally biased. Moreover, stereological methods offer the possibility of predicting the error variance from a single sample. Here we explore the statistical performance of two alternative variance estimators on a dataset of 26 labelled crowd pictures. The empirical mean square errors of the variance predictors are compared by means of Monte Carlo resampling.