Automated identification of abnormal infant movements from smart phone videos.

Cerebral palsy (CP) is the most common cause of physical disability during childhood, occurring at a rate of 2.1 per 1000 live births. Early diagnosis is key to improving functional outcomes for children with CP. The General Movements (GMs) Assessment has high predictive validity for the detection of CP and is routinely used in high-risk infants but only 50% of infants with CP have overt risk factors when they are born. The implementation of CP screening programs represents an important endeavour, but feasibility is limited by access to trained GMs assessors. To facilitate progress towards this goal, we report a deep-learning framework for automating the GMs Assessment. We acquired 503 videos captured by parents and caregivers at home of infants aged between 12- and 18-weeks term-corrected age using a dedicated smartphone app. Using a deep learning algorithm, we automatically labelled and tracked 18 key body points in each video. We designed a custom pipeline to adjust for camera movement and infant size and trained a second machine learning algorithm to predict GMs classification from body point movement. Our automated body point labelling approach achieved human-level accuracy (mean ± SD error of 3.7 ± 5.2% of infant length) compared to gold-standard human annotation. Using body point tracking data, our prediction model achieved a cross-validated area under the curve (mean ± S.D.) of 0.80 ± 0.08 in unseen test data for predicting expert GMs classification with a sensitivity of 76% ± 15% for abnormal GMs and a negative predictive value of 94% ± 3%. This work highlights the potential for automated GMs screening programs to detect abnormal movements in infants as early as three months term-corrected age using digital technologies.

Molecular signatures of cortical expansion in the human fetal brain.

The third trimester of human gestation is characterised by rapid increases in brain volume and cortical surface area. A growing catalogue of cells in the prenatal brain has revealed remarkable molecular diversity across cortical areas.1,2 Despite this, little is known about how this translates into the patterns of differential cortical expansion observed in humans during the latter stages of gestation. Here we present a new resource, µBrain, to facilitate knowledge translation between molecular and anatomical descriptions of the prenatal developing brain. Built using generative artificial intelligence, µBrain is a three-dimensional cellular-resolution digital atlas combining publicly-available serial sections of the postmortem human brain at 21 weeks gestation3 with bulk tissue microarray data, sampled across 29 cortical regions and 5 transient tissue zones.4 Using µBrain, we evaluate the molecular signatures of preferentially-expanded cortical regions during human gestation, quantified in utero using magnetic resonance imaging (MRI). We find that differences in the rates of expansion across cortical areas during gestation respect anatomical and evolutionary boundaries between cortical types5 and are founded upon extended periods of upper-layer cortical neuron migration that continue beyond mid-gestation. We identify a set of genes that are upregulated from mid-gestation and highly expressed in rapidly expanding neocortex, which are implicated in genetic disorders with cognitive sequelae. Our findings demonstrate a spatial coupling between areal differences in the timing of neurogenesis and rates of expansion across the neocortical sheet during the prenatal epoch. The µBrain atlas is available from: https://garedaba.github.io/micro-brain/ and provides a new tool to comprehensively map early brain development across domains, model systems and resolution scales.

Fine-tuning the dose of recombinant human follicle-stimulating hormone alfa to individualize treatment in ovulation induction and ovarian stimulation cycles: a real-world database analysis.

Introduction: Fine-tuning of injectable gonadotropin doses during ovulation induction (OI) or ovarian stimulation (OS) treatment cycles with the aim of using doses low enough to minimize the risk of excessive ovarian response while maintaining optimal efficacy may be facilitated by using an adjustable-dose pen injector. We examined the incidence and magnitude of individualized gonadotropin dose adjustments made during cycles of OI or OS, followed by either timed intercourse or intrauterine insemination, with or without oral medications, and assessed the relationship between patient characteristics and dosing changes using real-world evidence. Methods: This was an observational, retrospective cohort study using electronic medical records from a large US database of fertility centers. Data from patients who had undergone a first recombinant human follicle stimulating hormone alfa (r-hFSH-alfa/follitropin alfa) treated OI/OS cycle followed by timed intercourse or intrauterine insemination between 2015 and 2016 were included. Percentages of OI/OS cycles involving r-hFSH-alfa dose adjustments (in increments of ±12.5 IU or greater) with or without oral medications (clomiphene citrate or letrozole) were analyzed. Results: Of 2,832 OI/OS cycles involving r-hFSH-alfa administration, 74.6% included combination treatment with orals; 25.4% involved r-hFSH-alfa alone. As expected, the starting dose of r-hFSH-alfa was lower for cycles that used r-hFSH-alfa with orals than r-hFSH-alfa only cycles (mean [SD]: 74.2 [39.31] vs 139.3 [115.10] IU). Dose changes occurred in 13.7% of r-hFSH-alfa with orals versus 43.9% of r-hFSH-alfa only cycles. Dose adjustment magnitudes ranged from ±12.5 IU to ±450 IU. The smallest adjustment magnitudes (±12.5 IU and ±25 IU) were used frequently and more often for dose increases than for dose decreases. For r-hFSH-alfa with orals and r-hFSH-alfa only cycles, the smallest adjustments were used in 53.5% and 64.5% of cycles with dose increases and in 35.7% and 46.8% of cycles with dose decreases, respectively. Discussion: In OI/OS cycles followed by timed intercourse or intrauterine insemination, r-hFSH-alfa dose adjustments were frequent. In cycles that included orals, r-hFSH-alfa starting doses were lower and dose changes were fewer than with r-hFSH-alfa alone. Smaller dose adjustments facilitate individualized treatment with the goal of reducing the risks of multiple gestation, cycle cancellation, and ovarian hyperstimulation syndrome.

First Evidence of Axial Shape Asymmetry and Configuration Coexistence in

The excited states of N=44 ^{74}Zn were investigated via γ-ray spectroscopy following ^{74}Cu ß decay. By exploiting γ-γ angular correlation analysis, the 2_{2}^{+}, 3_{1}^{+}, 0_{2}^{+}, and 2_{3}^{+} states in ^{74}Zn were firmly established. The γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2_{2}^{+}, 3_{1}^{+}, and 2_{3}^{+} states were measured, allowing for the extraction of relative B(E2) values. In particular, the 2_{3}^{+}→0_{2}^{+} and 2_{3}^{+}→4_{1}^{+} transitions were observed for the first time. The results show excellent agreement with new microscopic large-scale shell-model calculations, and are discussed in terms of underlying shapes, as well as the role of neutron excitations across the N=40 gap. Enhanced axial shape asymmetry (triaxiality) is suggested to characterize ^{74}Zn in its ground state. Furthermore, an excited K=0 band with a significantly larger softness in its shape is identified. A shore of the N=40 "island of inversion" appears to manifest above Z=26, previously thought as its northern limit in the chart of the nuclides.

PGT-A is associated with reduced cumulative live birth rate in first reported IVF stimulation cycles age ≤ 40: an analysis of 133,494 autologous cycles reported to SART CORS.

PURPOSE: To evaluate the impact of preimplantation genetic testing for aneuploidy (PGT-A) on cumulative live birth rate (CLBR) in IVF cycles. METHODS: Retrospective cohort study of the SART CORS database, comparing CLBR for patients using autologous oocytes, with or without PGT-A. The first reported autologous ovarian stimulation cycle per patient between January 1, 2014, and December 31, 2015, and all linked embryo transfer cycles between January 1, 2014, and December 31, 2016, were included in the study. Exclusion criteria were donor oocyte cycles, donor embryo cycles, gestational carrier cycles, cycles which included both a fresh embryo transfer (ET) combined with a thawed embryo previously frozen (ET plus FET), or cycles with a fresh ET after PGT-A. RESULTS: A total of 133,494 autologous IVF cycles were analyzed. Amongst patients who had blastocysts available for either ET or PGT-A, including those without transferrable embryos, decreased CLBR was noted in the PGT-A group at all ages, except ages > 40 (p < 0.01). A subgroup analysis of only those patients who had PGT-A and a subsequent FET, excluding those without transferrable embryos, demonstrated a very high CLBR, ranging from 71.2% at age < 35 to 50.2% at age > 42. Rates of multiple gestations, preterm birth, early pregnancy loss, and low birth weight were all greater in the non-PGT-A group. CONCLUSIONS: PGT-A was associated with decreased CLBR amongst all patients who had blastocysts available for ET or PGT-A, except those aged > 40. The negative association of PGT-A use and CLBR per cycle start was especially pronounced at age < 35.

Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Fresh embryo transfer after in vitro insemination of fresh vs. cryopreserved anonymous donor oocytes: which has a better live birth rate? A Society for Assisted Reproductive Technology Clinic Outcome Reporting System analysis.

OBJECTIVE: To determine if transfer of fresh embryos derived from fresh or cryopreserved donor oocytes yields a higher live birth rate. DESIGN: Historical cohort study. SETTING: Society for Assisted Reproductive Technology Clinic Outcome Reporting System database. PATIENT(S): A total of 24,663 fresh embryo transfer cycles of donor oocytes. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome was live births per number of embryos transferred on day 5. The secondary outcomes included number of infants per embryo transfer, surplus embryos cryopreserved, and characterization of US oocyte recipients. RESULT(S): A total of 16,073 embryo transfers were from fresh oocytes and 8,590 were from cryopreserved oocytes. Recipient age, body mass index (BMI), gravidity, and parity were similar between the groups. Most recipients were of White non-Hispanic race (66.9%), followed by Asian (13.7%), Black non-Hispanic (9.3%), and Hispanic (7.2%). Fresh oocyte cycles were more likely to use elective single embryo transfer (42.5% vs. 37.8%) or double embryo transfer (53.2% vs. 50.4%) and resulted in more surplus embryos for cryopreservation (4.6 vs. 1.2). The live birth rate from fresh oocytes was 57.5% vs. 49.7% from cryopreserved oocytes. Negative predictors of live birth included the use of cryopreserved oocytes (odds ratio [OR] 0.731, 95% confidence interval [CI] 0.665-0.804), Black non-Hispanic race (OR 0.603, 95% CI 0.517-0.703), Asian race (OR 0.756, 95% CI 0.660-0.867), and increasing recipient BMI (OR 0.982, 95% CI 0.977-0.994) after controlling for recipient age, number of embryos transferred on day 5, and unexplained infertility diagnosis. The proportion of multifetal deliveries was greater in cycles utilizing fresh (26.4%) vs. cryopreserved (20.6%) oocytes. CONCLUSION(S): The live birth rate is higher with use of fresh oocytes vs. cryopreserved oocytes in fresh embryo transfer cycles. Negative live birth predictors include recipient Black non-Hispanic or Asian race and increasing BMI.

Recombinant Human Follicle-Stimulating Hormone Alfa Dose Adjustment in US Clinical Practice: An Observational, Retrospective Analysis of a Real-World Electronic Medical Records Database.

Purpose: To determine the pattern of dose adjustment of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) during ovarian stimulation (OS) for assisted reproductive technology (ART) in a real-world setting. Methods: This was an observational, retrospective analysis of data from an electronic de-identified medical records database including 39 clinics in the USA. Women undergoing OS for ART (initiated 2009-2016) with r-hFSH-alfa (Gonal-f® or Gonal-f RFF Redi-ject®) were included. Assessed outcomes were patients' baseline characteristics and dosing characteristics/cycle. Results: Of 33,962 ART cycles, 13,823 (40.7%) underwent dose adjustments: 23.4% with ≥1 dose increase, 25.4% with ≥1 dose decrease, and 8.1% with ≥1 increase and ≥1 decrease. Patients who received dose adjustments were younger (mean [SD] age 34.8 [4.58] years versus 35.9 [4.60] years, p<0.0001) and had lower BMI (25.1 [5.45] kg/m2 versus 25.5 [5.45] kg/m2, p<0.0001) than those who received a constant dose. The proportion of patients with non-normal ovarian reserve was 38.4% for those receiving dose adjustment versus 51.9% for those with a constant dose. The mean (SD) number of dose changes/cycle was 1.61 (0.92) for cycles with any dose adjustment, 1.72 (1.03) for cycles with ≥1 dose increase, 2.77 (1.00) for cycles with ≥1 dose increase and ≥1 decrease (n=2,755), and 1.88 (1.03) for cycles with ≥1 dose decrease. Conclusions: Dose adjustment during OS is common in clinical practice in the USA and occurred more often in younger versus older patients, those with a high versus non-normal ovarian reserve or those with ovulation disorders/polycystic ovary syndrome versus other primary diagnoses of infertility.

First Direct Measurement of an Astrophysical p-Process Reaction Cross Section Using a Radioactive Ion Beam.

We have performed the first direct measurement of the ^{83}Rb(p,γ) radiative capture reaction cross section in inverse kinematics using a radioactive beam of ^{83}Rb at incident energies of 2.4 and 2.7A MeV. The measured cross section at an effective relative kinetic energy of E_{cm}=2.393 MeV, which lies within the relevant energy window for core collapse supernovae, is smaller than the prediction of statistical model calculations. This leads to the abundance of ^{84}Sr produced in the astrophysical p process being higher than previously calculated. Moreover, the discrepancy of the present data with theoretical predictions indicates that further experimental investigation of p-process reactions involving unstable projectiles is clearly warranted.

Absence of Low-Energy Shape Coexistence in

The ^{80}Ge structure was investigated in a high-statistics ß-decay experiment of ^{80}Ga using the GRIFFIN spectrometer at TRIUMF-ISAC through γ, ß-e, e-γ, and γ-γ spectroscopy. No evidence was found for the recently reported 0_{2}^{+} 639-keV level suggested as evidence for low-energy shape coexistence in ^{80}Ge. Large-scale shell model calculations performed in ^{78,80,82}Ge place the 0_{2}^{+} level in ^{80}Ge at 2 MeV. The new experimental evidence combined with shell model predictions indicate that low-energy shape coexistence is not present in ^{80}Ge.

Health care providers' weight management practices for adolescent obesity and alignment with clinical practice guidelines: a multi-centre, qualitative study.

BACKGROUND: Clinical practice guidelines (CPGs) include evidence-based recommendations for managing obesity in adolescents. However, information on how health care providers (HCPs) implement these recommendations in day-to-day practice is limited. Our objectives were to explore how HCPs deliver weight management health services to adolescents with obesity and describe the extent to which their reported practices align with recent CPGs for managing pediatric obesity. METHODS: From July 2017 to January 2018, we conducted a qualitative study that used purposeful sampling to recruit HCPs with experience in adolescent weight management from multidisciplinary, pediatric weight management clinics in Edmonton and Ottawa, Canada. Data were collected using audio-recorded focus groups (4-6 participants/group; 60-90 min in length). We applied inductive, semantic thematic analysis and the congruent methodological approach to analyze our data, which included transcripts, field notes, and memos. Qualitative data were compared to recent CPGs for pediatric obesity that were published by the Endocrine Society in 2017. Of the 12 obesity 'treatment-related' recommendations, four were directly relevant to the current study. RESULTS: Data were collected through three focus groups with 16 HCPs (n = 10 Edmonton; n = 6 Ottawa; 94% female; 100% Caucasian), including dietitians, exercise specialists, nurses, pediatricians, psychologists, and social workers. We identified three main themes that we later compared with CPG recommendations, including: (i) discuss realistic expectations regarding weight management (e.g., shift focus from weight to health; explore family cohesiveness; foster delayed vs instant gratification), (ii) personalize weight management (e.g., address personal barriers to change; consider developmental readiness), and (iii) exhibit non-biased attitudes and practices (e.g., de-emphasize individual causes of obesity; avoid making assumptions about lifestyle behaviors based on weight). Based on these qualitative findings, HCPs applied all four CPG recommendations in their practices. CONCLUSIONS: HCPs provided practical insights into what and how they delivered weight management for adolescents, which included operationalizing relevant CPG recommendations in their practices.

Cortical remodelling in childhood is associated with genes enriched for neurodevelopmental disorders.

Cortical development during childhood and adolescence has been characterised in recent years using metrics derived from Magnetic Resonance Imaging (MRI). Changes in cortical thickness are greatest in the first two decades of life and recapitulate the genetic organisation of the cortex, highlighting the potential early impact of gene expression on differences in cortical architecture over the lifespan. It is important to further our understanding of the possible neurobiological mechanisms that underlie these changes as cortical thickness may be altered in several common neurodevelopmental and psychiatric disorders. In this study, we combine MRI acquired from a large typically-developing childhood population (n â€‹= â€‹768) with comprehensive human gene expression databases to test the hypothesis that disrupted mechanisms common to neurodevelopmental disorders are encoded by genes expressed early in development and nested within those associated with typical cortical remodelling in childhood. We find that differential rates of thinning across the developing cortex are associated with spatially-varying gradients of gene expression. Genes that are expressed highly in regions of accelerated thinning are expressed predominantly in cortical neurons, involved in synaptic remodelling, and associated with common cognitive and neurodevelopmental disorders. Further, we identify subsets of genes that are highly expressed in the prenatal period and jointly associated with both developmental cortical morphology and neurodevelopmental disorders.

Multiple Shape Coexistence in

From detailed spectroscopy of ^{110}Cd and ^{112}Cd following the ß^{+}/electron-capture decay of ^{110,112}In and the ß^{-} decay of ^{112}Ag, very weak decay branches from nonyrast states are observed. The transition rates determined from the measured branching ratios and level lifetimes obtained with the Doppler-shift attenuation method following inelastic neutron scattering reveal collective enhancements that are suggestive of a series of rotational bands. In ^{110}Cd, a γ band built on the shape-coexisting intruder configuration is suggested. For ^{112}Cd, the 2^{+} and 3^{+} intruder γ-band members are suggested, the 0_{3}^{+} band is extended to spin 4^{+}, and the 0_{4}^{+} band is identified. The results are interpreted using beyond-mean-field calculations employing the symmetry conserving configuration mixing method with the Gogny D1S energy density functional and with the suggestion that the Cd isotopes exhibit multiple shape coexistence.

End-user perspectives to inform policy and program decisions: a qualitative and quantitative content analysis of lifestyle treatment recommendations by adolescents with obesity.

BACKGROUND: Lifestyle modifications represent the first line of treatment in obesity management; however, many adolescents with obesity do not meet lifestyle recommendations. Given that adolescents are rarely consulted during health policy development and in the design of lifestyle interventions, their first-hand experiences, preferences, and priorities may not be represented. Accordingly, our purpose was to explore adolescents' lifestyle treatment recommendations to inform policy and program decisions. METHODS: Conducted from July 2017 to January 2018, this study adhered to a qualitative, crosslanguage, patient-oriented design. We recruited 19 13-17-year-old adolescents (body mass index [BMI] ≥85th percentile) seeking multidisciplinary treatment for obesity in geographically and culturally diverse regions of Canada. Adolescents participated in one-on-one, in-person, semi-structured interviews in English or French. Interviews were audio-recorded, transcribed verbatim, managed using NVivo 11, and analyzed using quantitative and qualitative content analysis by two independent researchers. RESULTS: Adolescents' recommendations were organized into five categories, each of which denotes health as a collective responsibility: (i) establish parental support within limits, (ii) improve accessibility and availability of 'healthy foods', (iii) limit deceptive practices in food marketing, (iv) improve accessibility and availability of varied physical activity opportunities, and (v) delay school start times. Respect for individual autonomy and decision-making capacity were identified as particularly important, however these were confronted with adolescents' partial knowledge on nutrition and food literacy. CONCLUSIONS: Adolescents' recommendations highlighted multi-level, multi-component factors that influenced their ability to lead healthy lifestyles. Uptake of these recommendations by policy-makers and program developers may be of added value for lifestyle treatment targeting adolescents with obesity.

30 years of data: impact of the United States in vitro fertilization data registry on advancing fertility care.

OBJECTIVE: To summarize and assess the impact of key research generated through the Society of Assisted Reproductive Technology (SART)-initiated United States IVF registry and annual reporting system. DESIGN: Review. SETTING: Eligible studies included those that analyzed data generated by the National IVF data collection program (through SART or Centers for Disease Control and Prevention). PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Summarize and report outcomes of research using National IVF registry data. RESULT(S): The Society of Assisted Reproductive Technology was founded in 1985 and published the first annual US IVF data report 30 years ago in 1988 in Fertility and Sterility. In 1995, the Centers for Disease Control and Prevention subsequently began collecting data from IVF programs and published their first report in 1997. This annual National IVF data collection and reporting is a significant responsibility and effort for IVF programs. Using these data sources, 199 articles have been published by clinicians and researchers from across the country. This research has guided the development of evidence-based assisted reproductive technology (ART) practice guidelines during the past 30 years, which have ultimately led to improved quality and patient care. CONCLUSION(S): Since the first SART National IVF data report publication 30 years ago, SART has achieved its original goals of creating a national IVF registry that successfully assesses clinical effectiveness, quality of care, and safety.

Individual variation in longitudinal postnatal development of the primate brain.

Quantifying individual variation in postnatal brain development can provide insight into cognitive diversity within a population and the aetiology of common neuropsychiatric and neurodevelopmental disorders. Non-invasive studies of the non-human primate can aid understanding of human brain development, facilitating longitudinal analysis during early postnatal development when comparative human populations are difficult to sample. In this study, we perform analysis of a longitudinal MRI dataset of 32 macaques, each with up to five magnetic resonance imaging (MRI) scans acquired between 3 and 36 months of age. Using nonlinear mixed effects model we derive growth trajectories for whole brain, cortical and subcortical grey matter, cerebral white matter and cerebellar volume. We then test the association between individual variation in postnatal tissue volumes and birth weight. We report nonlinear growth models for all tissue compartments, as well as significant variation in total intracranial volume between individuals. We also demonstrate that regional subcortical grey matter varies both in total volume and rate of change between individuals and is associated with differences in birth weight. This supports evidence that birth weight may act as a marker of subsequent brain development and highlights the importance of longitudinal MRI analysis in developmental studies.

Feasibility, user experiences, and preliminary effect of Conversation Cards for Adolescents© on collaborative goal-setting and behavior change: protocol for a pilot randomized controlled trial.

BACKGROUND: Adolescents and providers can benefit from practical tools targeting lifestyle modification for obesity prevention and management. We created Conversation Cards for Adolescents© (CCAs), a patient-centered communication and behavior change tool for adolescents and providers to use in clinical practice. The purpose of our study is to (i) assess the feasibility of CCAs in a real-world, practice setting to inform full-scale trial procedures, (ii) assess user experiences of CCAs, and (iii) determine the preliminary effect of CCAs on changing behavioral and affective-cognitive outcomes among adolescents. METHODS: Starting in early 2019, this prospective study is a nested mixed-methods, theory-driven, and pragmatic pilot randomized controlled trial with a goal to enroll 50 adolescents (13-17 years old) and 9 physicians practicing at the Northeast Community Health Centre in Edmonton, Alberta, Canada. Adolescents will collaboratively set one S.M.A.R.T. (specific, measurable, attainable, realistic, timely) goal with their physician to implement over a 3-week period; however, only those randomized to the experimental group will use CCAs to inform their goal. Outcome assessments at baseline and follow-up (3 weeks post-baseline) will include behavioral, affective-cognitive, and process-related outcomes. DISCUSSION: In examining the feasibility, user experiences, and preliminary effect of CCAs, our study will add contributions to the obesity literature on lifestyle modifications among adolescents in a real-world, practice setting as well as inform the scalability of our approach for a full-scale effectiveness randomized controlled trial on behavior change. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03821896.