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Herbivores affect plants via direct consumption, but also indirectly via changes in the vegetation. These indirect effects may only manifest after decades of exposure and, as a result, their impact is rarely accounted for. To better understand the direct and indirect impacts of a large herbivore, moose ( Alces alces), on forests, we measured tree growth in areas that were both subjected to and excluded from herbivory for over 80 years. Growth data were gathered from five tree species, ranging from low to high palatability. We found that at small sizes, Betula papyrifera, a preferred species, benefited from herbivore exclusion. However, larger individuals grew more when exposed to herbivory, a response we attribute to lower competition in heavily browsed conditions. Populus tremuloides, a highly preferred tree, did not show any differences between levels of herbivory. Abies balsamea, a preferred winter browsed, was only marginally affected by browsing at smaller sizes. The two non-preferred species, Picea glauca and Picea mariana, did not show differential growth between herbivory levels. We conclude that herbivores can impact forests through both direct and indirect effects, that these effects are size specific, and that effects vary among species in ways not always predicted by consumption patterns.

A novel degradable microgel based on poly(N-isopropylacrylamide) (pNIPA) cross-linked with N,N’-bisacryloylcystine (BISS) and containing superparamagnetic iron oxide nanoparticles (SPION@CA) was synthesized by semi-batch precipitation polymerization and examined as a potential hyperthermia-enhanced drug carrier. The pNIPA provided the microgel with temperature sensitivity, the BISS was responsible for degradation in the presence of glutathione (GSH) (an –S–S–bond reductor naturally present in cells), while the SPION@CA permitted remote control of temperature to improve drug release. The microgels exhibited volume phase transition temperature at ca. 34 °C, which is near the human body temperature, and were stable across a wide range of temperatures and ionic strengths, as well as in the blood plasma at 37 °C. It was found that the presence of SPION@CA in the polymer network of the microgels enabled the temperature to be increased up to 42 °C by an alternating magnetic field, and that increasing the temperature from 37 to 42 °C significantly enhanced the releasing of the anticancer drug doxorubicin (DOX). The highest DOX release (82%) was observed at pH 5, 42 °C, and in the presence of GSH, and the lowest (20%) at pH 7.4, 37 °C, and in the absence of GSH. MTT assay indicated that compared to free doxorubicin, the microgel particles loaded with doxorubicin have comparable cytotoxicity against MCF-7 cancer cells while being significantly less toxic to MCF-10A healthy cells. Graphical abstract

To determine the ongoing pregnancy rate among patients with infertility with a low antimüllerian (AMH) level compared with those with a normal AMH level after oral and injectable ovulation induction (OI)/intrauterine insemination (IUI).Retrospective cohort.Academic center.Patients completing ≥1 medicated OI/IUI cycle at our center between 2015 and 2019 were included. The AMH levels were measured within 12 months of treatment initiation. The cohort was stratified into low AMH (AMH level,1.0 ng/mL) and normal AMH (AMH level, ≥1.0 ng/mL) groups. All subsequent medicated OI/IUI cycles occurring within 1 year of initial cycle start date were included up to the third completed cycle or until an ongoing pregnancy was recorded. Patients were stratified by age (35, 35-40, and40 years), and the relationship between the low and normal AMH groups and each binary endpoint were quantified as risk ratios using the age-adjusted Poisson models.None.Ongoing pregnancy.A total of 3,122 patients completed 5,539 oral antiestrogen cycles, and 1,060 completed 1,630 injectable gonadotropin cycles. For oral antiestrogen treatment, pregnancy outcomes, including ongoing pregnancy rate per cycle, for patients with a low AMH level were comparable with those for patients with a normal AMH level (35 years, 15.4% vs. 14.9%; 35-40 years, 10.0% vs. 11.0%; and40 years, 2.8% vs. 3.3%). For injectable gonadotropin treatment, the ongoing pregnancy rate was lower in the low AMH group than in the normal AMH group for the ages of35 (12.1% vs. 23.5%; relative risk [RR], 0.52 [95% confidence interval {CI}, 0.28-0.97]) and 35-40 (12.5% vs. 18.5%; RR, 0.70 [95% CI, 0.49-0.99]) years but comparable with that for patients aged40 years (3.0% vs. 4.0%; RR, 0.86 [95% CI, 0.31-2.35]). The proportion of multifetal gestations was similar between the low and normal AMH groups treated with oral antiestrogens (13.1% vs. 10.8%); however, for injectable gonadotropin treatment, patients with a normal AMH level had a higher proportion of multifetal gestations (18.6% vs. 31.1%).Compared with normal ovarian reserve, treatment with oral antiestrogens for OI/IUI for patients with low ovarian reserve results in comparable follicular development and ongoing pregnancy rates for all age groups. When patients with low ovarian reserve are treated with gonadotropins for OI/IUI, multifollicular recruitment is less likely resulting in a significantly decreased ongoing pregnancy rate for patients aged35 and 35-40 years but also a decrease in multifetal gestations. Overall, the ongoing pregnancy rates of 8.7% per oral antiestrogen cycle and 8.1% per injectable gonadotropin cycle in patients with low ovarian reserve are comparable with the expected rates in the general infertility population.

To estimate the live-birth rate per in vitro fertilization (IVF) cycle and after cumulative infertility treatment among patients with anti-müllerian hormone (AMH) levels of 0.3 ng/mL or lower.We conducted a retrospective cohort study at a single academic center of patients with infertility and AMH levels of 0.3 ng/mL or lower who initiated one or more IVF cycles (2013-2019). Exclusion criteria included prior chemotherapy, hormonal contraceptive use within 3 months of AMH level measurement, and severe male factor infertility. Patients were stratified by Society for Assisted Reproductive Technology (SART) age group. The primary outcome was live-birth rate per IVF cycle. Live-birth outcomes were compared with the 2018 SART National Summary Report for live births per single intended oocyte retrieval, with proportion difference (PD) and 95% CI reported.A total of 978 patients were included. The median (interquartile range) number of cycles initiated was 2 (1-3). With the first initiated cycle, the live-birth rate for those with AMH levels of 0.3 ng/mL or lower was significantly lower in each age category compared with the SART live-birth rate per single initiated cycle (younger than 35 years: 26.2% vs 55.6%, PD 29.4%, 95% CI 20.9-37.9%; 35-37 years: 15.9% vs 40.8%, PD 24.9%, 95% CI 19.0-30.9%; 38-40 years: 12.6% vs 26.8%, PD 14.3%, 95% CI 10.2-18.3%; 41-42 years: 4.7% vs 13.4%, PD 8.7%, 95% CI 5.9-11.6%; older than 42 years: 1.2% vs 4.1%, PD 2.9%, 95% CI 1.5-4.3%). In patients aged 35-37, 38-40, 41-42, and older than 42 years, the cumulative live-birth rate after up to three initiated cycles was comparable with the SART live-birth rate per single initiated cycle but remained significantly lower in patients younger than age 35 years (PD 16.8%, 95% CI 7.3-26.2%). After all treatments were included (cumulative IVF, ovulation induction, and unassisted cycles), live-birth rates were similar to SART live-birth rates per single initiated cycle in all age groups.Compared with national outcomes, patients with AMH levels of 0.3 ng/mL or lower had a significantly lower chance of live birth after their first initiated cycle. However, the cumulative live-birth rate after up to three initiated cycles was comparable with national live-birth outcomes per single initiated cycle in patients aged 35 years or older. In patients younger than age 35 years, only when all IVF and non-IVF treatment cycles were included did the cumulative live-birth rate become comparable with the national rate per single IVF cycle.

What is the impact of advancing paternal age, stratifying for maternal age, on fresh embryo transfer cycle outcomes?All first autologous fresh embryo transfer cycles between 2013 and 2019 at a single high-volume academic institution were retrospectively reviewed. Female age was dichotomized along the cohort median of (37 years) (Female-Young [F-Y]:37 years; Female-Old [F-O]: ≥37 years). Male age was stratified along the cohort median (38 years) and 90th centile (48 years) (Male-Young [M-Y]:38 years; Male-Intermediate [M-I]: ≤38 and48 years; Male-Old [M-O]: ≥48 years). The primary outcome of interest was the odds of live birth using logistic regression. Secondary outcomes included odds of implantation, clinical intrauterine pregnancy and pregnancy loss. All models were adjusted for continuous female age, use of surgically retrieved testicular spermatozoa, severe oligozoospermia and cleavage- versus blastocyst-stage embryo transfer.A total of 6704 couples were included and were divided into six groups based on paternal/maternal age groups (F-Y/M-Y: 2288; F-Y/M-I: 750; F-Y/M-O: 97; F-O/M-Y: 679; F-O/M-I: 2310; F-O/M-O: 580). While some associations were seen on univariable logistic regression, none of the groups with increasing paternal age showed any statistically significant differences on multivariable logistic regression with respect to implantation, clinical intrauterine pregnancy, pregnancy loss or live birth.Advanced paternal age does not impact clinical outcomes in fresh transfer cycles. The authors postulate that IVF with or without intracytoplasmic sperm injection is able to overcome the deleterious effects of advancing paternal age on sperm quality and subsequent embryo performance.

Two widely applied enabling drug delivery approaches, self-nanoemulsifying drug delivery systems (SNEDDS) and amorphous solid dispersions (ASD), were combined, with the aim of enhancing physical stability, solubilization and absorption of the model drug ritonavir. Ritonavir was loaded at a concentration above its saturation solubility (Seq) in the SNEDDS (superSNEDDS, 250% of Seq). An ASD of ritonavir with polyvinylpyrrolidone-vinyl acetate copolymers (Kollidon® VA64) was prepared by ball milling. Relevant control formulations, which include conventional SNEDDS (90% of Seq), superSNEDDS with a physical mix of Kollidon® VA64 and ritonavir (superSNEDDS+PM) and an aqueous suspension of ritonavir were used. A pharmacokinetic (PK) study in rats was performed to assess the relative bioavailability of ritonavir after oral administration. This was followed by evaluating the formulations in a novel two-step in vitro lipolysis model simulating rat gastric and intestinal conditions. The addition of a ritonavir containing ASD to superSNEDDS increased the degree of supersaturation from 250% to 275% Seq in the superSNEDDS and the physical stability (absence of drug recrystallization) of the system from 48 h to 1 month under ambient conditions. The PK study in rats displayed significantly higher Cmax and AUC0-7h (3-fold increase) and faster Tmax for superSNEDDS+ASD compared to the conventional SNEDDS whilst containing 3 times less lipid than the latter. Furthermore, superSNEDDS+ASD were able to keep the drug solubilised during in vitro lipolysis to the same degree as the conventional SNEDDS. These findings suggest that dissolving an ASD in a superSNEDDS can contribute to the development of novel oral delivery systems with increased bioavailability for poorly water-soluble drugs.

What is the blastocyst conversion rate in embryo cryopreservation cycles, per year of female age?Retrospective cohort study including patients undergoing their first ovarian stimulation cycle at our center with planned freeze-all strategy January 1st, 2014-June 30th, 2020. Primary outcome was blastocyst conversion rate. Secondary outcomes included mature oocyte and fertilization rates. Patients were stratified by year of age to assess oocyte yield and embryo development outcomes.3,362 patients were included. The median blastocyst conversion rate in patients ≤30 was 66.7% (interquartile range 50.0-86.6) and remained statistically comparable through age 40 with a significant decline among ages ≥41 (41-years: marginal effect (ME) -5.2% (-9.7 to -0.7); 42-years: ME -9.6% (-14.3 to -4.8); 43-years: ME -7.7% (-12.8 to -2.6); ≥44-years: ME -20.8% (-26.5 to -15.1)). For the entire cohort, the median mature oocyte rate was 81.8% and the median fertilization rate was 81.8%. The mature oocyte and fertilization rates remained statistically comparable for each year of age except age ≥44 which had a statistically significantly increased mature oocyte rate (ME 4.4% (1.3 to 7.5)) and statistically significantly decreased fertilization rate (ME -5.8% (-9.8 to -1.9)) CONCLUSIONS: In embryo cryopreservation cycles, the blastocyst conversion rate remained statistically comparable through age 40 followed by a statistically significant decline for patients ≥41; however, the mature oocyte and fertilization rates were not impacted by increasing age until age ≥44. Even in women ≥44, over 40% of fertilized oocytes developed to blastocyst. Overall, this information is useful when counseling patients during the embryo culture stage regarding predicted blastocyst yield.

PURPOSE: To compare the reproductive outcomes of fresh embryo transfer (ET) cycles utilizing fresh versus frozen ejaculated sperm. METHODS: First autologous fresh embryo transfer cycles at a single high-volume academic institution between 2013 and 2019 were retrospectively reviewed. IVF cycles using ejaculated sperm were included, and cycles using donor or surgically retrieved sperm were excluded. Sperm concentration was stratified as ≥ 5 and

We study the temporal variability of the wintertime Labrador Sea ice area. The driving factors of these intraseasonal and interannual variations are related to large scale atmospheric variability and cyclone variability both of which can be characterized by the Arctic Oscillation (AO) index. We observe negative trends in the maximum sea-ice area over the past 40 years, and a positive correlation between the AO index and Labrador Sea ice area. Using satellite-derived daily ice area along with reanalysis-derived cyclones, turbulent flux, wind, humidity, air and sea temperature fields, we delve into the physical coupling mechanisms by which cyclones influence the position of the ice edge in the Labrador Sea throughout the winter.

With higher levels of automation in vehicles, the need for robust driver monitoring systems increases, since it must be ensured that the driver can intervene at any moment. Drowsiness, stress and alcohol are still the main sources of driver distraction. However, physiological problems such as heart attacks and strokes also exhibit a significant risk for driver safety, especially with respect to the ageing population. In this paper, a portable cushion with four sensor units with multiple measurement modalities is presented. Capacitive electrocardiography, reflective photophlethysmography, magnetic induction measurement and seismocardiography are performed with the embedded sensors. The device can monitor the heart and respiratory rates of a vehicle driver. The promising results of the first proof-of-concept study with twenty participants in a driving simulator not only demonstrate the accuracy of the heart (above 70% of medical-grade heart rate estimations according to IEC 60601-2-27) and respiratory rate measurements (around 30% with errors below 2 BPM), but also that the cushion might be useful to monitor morphological changes in the capacitive electrocardiogram in some cases. The measurements can potentially be used to detect drowsiness and stress and thus the fitness of the driver, since heart rate variability and breathing rate variability can be captured. They are also useful for the early prediction of cardiovascular diseases, one of the main reasons for premature death. The data are publicly available in the UnoVis dataset.

We successfully synthesized a novel hydrogel based on derivatives of natural α-amino acids: ornithine and cystine. To make ornithine attachable to the polymer chain, the δ-amino group was modified with an acryloyl group and the main monomer was obtained. From cystine, the cross-linker

A survey of epiphytic bryophytes and a study of microclimatic variation within a tree crown were conducted in lower montane rainforest at 2400 m in the Peruvian Yungas. A total of 129 species (87 hepatics, 1 hornwort and 41 mosses) were collected on 3 trees, using different methodologies. A single Weinmannia sp. host supported 110 species (77 hepatics, 1 hornwort and 32 mosses). Species with a wide distribution on the hosts made up 47% of the epiphytic assemblage, 22% were limited to the trunks and 31% occurred only in the crowns. The overall hepatic to moss ratio was 2.15:1. Mosses exhibited a narrower distributional range than hepatics. The greatest species richness and abundance was found on the large branches in the mid-crown. Species found in the mid-crown generally had a broader distribution on hosts than those found on the lower trunk or the outer crown. Classification and ordination analyses of the species and environmental data indicated the presence of 4 communities: an outer crown, a mid to mid-outer crown, an upper trunk and a lower trunk community. Species distribution on hosts in the present study appeared to be influenced by the intensity of radiation, particularly diffuse radiation, and relative humidity related to a moisture availability gradient. Temperature appeared least important. Six species were selected as potential microclimate change indicators. Variation in temperature, relative humidity, visible sky fraction, leaf area index and radiation intensity were measured throughout a single canopy a co-dominant Weinmannia sp. The opposing gradients of temperature and relative humidity displayed similar fluctuation patterns as found in lowland rainforest, although the range of the gradients was smaller, possibly due to greater atmospheric mixing facilitated by the more permeable canopy at the montane rainforest study site. Microclimate stability decreased with distance above the ground. The lower trunk micro-habitat was the most humid, coolest and least illuminated. The highest temperature and lowest relative humidity were recorded in the mid-outer crown, closely followed by the most irradiated crown periphery. The above canopy temperature remained cooler during the day than the tree crown. The lowest mean hourly temperature was recorded in the mid-crown, induced by rapid radiative cooling in the evening. The air above the canopy was warmer at night than any micro-habitat on the tree host. The study found 27 bryophytes species (5 mosses, 22 hepatics) not previously recorded for Peru. Recommendations for methodology in future bryophyte surveys in Peruvian lower montane rainforest are presented. Future studies must parallel more concerted efforts to raise the awareness of the local population about the ecological importance of bryophytes, particularly in cloud forests. Resumen Un estudio de briofitas epifitas y de la variaci‚àö‚â•n microclim‚àö¬8tica dentro de la copa de un ‚àö¬8rbol fueron conducidos en los bosques mas bajos de monta‚àö¬±a a 2400 m. en las Yungas peruanas. Un total de 129 especies (87 hep‚àö¬8ticas, 1 antocerota y 41 musgos) fueron recolectadas en 3 ‚àö¬8rboles, usando diferentes metodolog‚àö‚â†as. En un solo Weinmannia sp. se encontr‚àö‚â• 110 especies (77 hep‚àö¬8ticas, 1 antocerota y 32 musgos). Especies con una amplia distribuci‚àö‚â•n en los ‚àö¬8rboles contribuyeron 47% de epifitas, 22% fueron limitados a los troncos y 31% ocurrieron solo en las copas. La totalidad de tasa de hep‚àö¬8ticas a musgos fue 2.15:1. Los musgos mostraron un rango de distribuci‚àö‚â•n mas estrecho que las hep‚àö¬8ticas. La m‚àö¬8s grande riqueza y abundancia de especies fue encontrada en las ramas grandes de la media copa. Las especies encontradas en la media copa generalmente tuvieron una distribuci‚àö‚â•n mas ancha en los ‚àö¬8rboles que aquellos encontrados en el tronco bajo o en la copa exterior. Los an‚àö¬8lisis de clasificaci‚àö‚â•n y ordenaci‚àö‚â•n de las especies y data de medio ambiente indicaron la presencia de 4 comunidades: Copa exterior, de media copa a media copa exterior, parte superior del tronco y la comunidad de la parte baja del tronco. La distribuci‚àö‚â•n en los ‚àö¬8rboles del presente estudio pareci‚àö‚â• ser influenciada por la intensidad de radiaci‚àö‚â•n, particularmente radiaci‚àö‚â•n difusa y relativa humedad relacionada a la escala de disponibilidad de agua. La temperatura pareci‚àö‚â• menos importante. Seis especies fueron seleccionadas como indicadores potenciales del cambio de microclima. La variaci‚àö‚â•n de la temperatura, humedad relativa, fracci‚àö‚â•n visible de cielo, ‚àö‚â†ndice de la ‚àö¬8rea foliar e intensidad de radiaci‚àö‚â•n fueron medidos en todas partes de un co-dominante Weinmannia sp. Las escalas opuestas de temperatura y humedad relativa mostraron similar fluctuaci‚àö‚â•n como los encontrados en Selva Baja; sin embargo, el rango de las escalas fue m‚àö¬8s peque‚àö¬±o, posiblemente a causa de mejor combinaci‚àö‚â•n atmosferica facilitada por el dosel m‚àö¬8s abierto en bosque de monta‚àö¬±a elegido para el presente estudio. La estabilidad microclim‚àö¬8tica disminuyo con la distancia del suelo. El micro h‚àö¬8bitat en la parte baja del tronco fue el m‚àö¬8s h‚àö‚à´medo, m‚àö¬8s fresco y menos iluminado. La temperatura m‚àö¬8s alta y humedad relativa mas baja fueron registradas en la media copa exterior, cercanamente seguido por la periferia de la copa mas irradiada. La temperatura sobre el dosel permaneci‚àö‚â• m‚àö¬8s fresco durante el d‚àö‚â†a que la misma copa del ‚àö¬8rbol. El promedio de horario de la temperatura mas bajo fue registrado en la media copa, causado por el r‚àö¬8pido enfriamiento radiativo en la noche. El aire sobre el dosel fue mas caliente en la noche como en cualquier micro-h‚àö¬8bitat en el ‚àö¬8rbol. En el estudio se encontr‚àö‚â• 27 especies de briofitas (5 musgos, 22 hep‚àö¬8ticas) que no eran citados en el Per‚àö‚à´. Las recomendaciones para metodolog‚àö‚â†a en estudios futuros de briofitas en los bosques de monta‚àö¬±a baja peruana, son incluidas en el presente informe. Futuros estudios deben suceder paralelos a los esfuerzos concertados para la concientizaci‚àö‚â•n de la poblaci‚àö‚â•n sobre la importancia ecol‚àö‚â•gica de las briofitas, particularmente en los bosques nublados.

Background To describe the psychosocial response of the infertile population whose care was curtailed due to the COVID-19 pandemic. Methods A web-based cross-sectional survey was administered to 117 infertile patients at our center who had their infertility treatment delayed due to suspension of care at our hospital during the COVID-19 pandemic. The survey consisted of 52-question multiple-choice questions including the Life Orientation Test-Revised (LOT-R) and the Hospital Anxiety and Depression Scale (HADS) instruments. Characteristics of respondents who "agreed" (strongly agree and agree) that "delaying treatment has permanently impacted my chances at future conception" were compared with participants who "disagreed" (neutral, disagree, and strongly disagree) using Fischer's exact test. Results In total, 79.5% agreed that delaying treatment has permanently impacted their chances at future conception. There were no discernible demographic differences between patients who "agreed" versus "disagreed" with the above statement. The mean LOT-R score was 14.1 (5.1) with an optimism score of 6.8 (2.6) and a pessimism score of 7.3 (2.9). The mean HADS depression score was 5.4 (3.4) with 28.2% reporting scores in the borderline-abnormal to abnormal range. The mean HADS anxiety score was 9.0 (3.9) with 64.6% reporting scores in the borderline-abnormal to abnormal range. Nearly one third of respondents (36.8%) reported wanting to "expedite/be more aggressive with treatment," whereas only 5.1% wanted to postpone treatment. Conclusions Women undergoing ART during the COVID-19 pandemic express significant concern and signs of distress about how delays in care affect their future reproductive potential.

Background Obstructed Mullerian anomalies in adolescents can be grouped into complete outflow obstruction or unilateral outflow obstruction. The challenge with unilateral obstructions is that diagnosis can be delayed for weeks to years, as menstruation occurs normally through the patent side and thus obstruction is often not initially considered in the differential diagnosis. Cases In this case series, we present 3 unusual and challenging cases of unilateral Mullerian obstructions in adolescent female patients, along with strategies for diagnosis and management. Each case involves a unique variation of a recognized Mullerian anomaly that was initially misdiagnosed, leading to a significant delay in definitive diagnosis and treatment. Summary and Conclusion These cases highlight that even among the well-described Mullerian anomalies, there can be unusual variations. Patients who do not respond to initial management or who develop new symptoms should be further evaluated to confirm the correct diagnosis Tools that may be helpful in making the correct diagnosis include imaging studies that use contrast dye to better delineate cavities and their connections, magnetic resonance imaging with a radiologist experienced in Mullerian anomalies, and an examination under anesthesia. A definitive diagnosis is critical to the successful management of these conditions, and individualized management plans are required for each patient depending on their specific anomaly and their preferences for treatment.

With the rise of efficient and highly effective embryo cryopreservation techniques, the modern in vitro fertilization laboratory has unintentionally become a long-term storage facility for embryos and gametes. One challenge posed by long-term storage is the issue of unclaimed, effectively abandoned, cryopreserved embryos whose owners cannot be identified or are unable to provide a dispositional decision. Given the nuanced nature of dealing with human tissue, no straightforward solutions for managing this novel scenario have prevailed. In this article, we discuss the problem faced by physicians, clinics, and patients alike when faced with unclaimed cryopreserved embryos. We also review strategies for proactive prevention and resolution of conflicts that may arise when making dispositional decisions.

STUDY QUESTION Do the length of follicular phase estradiol exposure and the total length of the follicular phase affect pregnancy and live birth outcomes in natural frozen embryo transfer (FET) cycles? SUMMARY ANSWER An estradiol level >100 pg/ml for ≤4 days including the LH surge day is associated with worse pregnancy and live birth outcomes; however, the total length of the follicular phase is not associated with pregnancy and live birth outcomes. WHAT IS KNOWN ALREADY An estradiol level that increases above 100 pg/ml and continues to increase is indicative of the selection and development of a dominant follicle. In programmed FET cycles, a limited duration of follicular phase estradiol of STUDY DESIGN, SIZE, DURATION This retrospective cohort study included infertile patients in an academic hospital setting who underwent their first natural frozen autologous Day-5 embryo transfer cycle in our IVF clinic between 01 January 2013 and 31 December 2018. Donor oocyte and gestational carrier cycles were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS The primary outcomes of this study were pregnancy and live birth rates. Patients were stratified into two groups based on the cohorts’ median number of days from the estradiol level of >100 pg/ml before the LH surge: Group 1 (≤4 days; n = 1052 patients) and Group 2 (>4 days; n = 839 patients). Additionally, patients were stratified into two groups based on the cohorts’ median cycle day of LH surge: Group 1 (follicular length ≤15 days; n = 1287 patients) and Group 2 (follicular length >15 days; n = 1071 patients). A subgroup analysis of preimplantation genetic testing for aneuploidies (PGT-A) embryo transfer cycles was performed. Logistic regression analysis, adjusted a priori for patient age, number of embryos transferred, and use of PGT-A, was used to estimate the odds ratio (OR) with a 95% CI. MAIN RESULTS AND THE ROLE OF CHANCE In the length of elevated estradiol analysis, the pregnancy rate per embryo transfer was statistically significantly lower in patients with an elevated estradiol to surge of ≤4 days (65.6%) compared to patients with an elevated estradiol to surge of >4 days (70.9%; OR 1.30 (95% CI 1.06–1.58)). The live birth rate per embryo transfer was also statistically significantly lower in patients with an elevated estradiol to surge of ≤4 days (46.6%) compared to patients with an elevated estradiol to surge of >4 days (52.0%; OR 1.23 (95% CI 1.02–1.48)). In the follicular phase length analysis, the pregnancy rate per embryo transfer was similar between patients with a follicular length of ≤15 days (65.4%) and patients with a follicular length of >15 days (69.0%; OR 1.12 (95% CI 0.94–1.33)): the live birth rate was also similar between groups (45.5% vs 51.5%, respectively; OR 1.14 (95% CI 0.97–1.35)). In all analyses, once a pregnancy was achieved, the length of the follicular phase or the length of elevated oestradiol >100 pg/ml no longer affected the pregnancy outcomes. LIMITATIONS, REASONS FOR CAUTION The retrospective design of this study is subject to possible selection bias in regard to which patients at our clinic were recommended to undergo a natural FET compared to a fresh embryo transfer or programmed FET. To decrease the heterogeneity of our study population, we only included patients who had blastocyst embryo transfers; therefore, it is unknown whether similar results would be observed in patients with cleavage-stage embryo transfers. The retrospective nature of the study design did not allow randomized to a specific ovarian stimulation or ovulation trigger protocol. However, all patients were managed with the standardized protocols at a single center, which strengthens the external validity of our results when compared to a study that only evaluates one specific stimulation protocol. WIDER IMPLICATIONS OF THE FINDINGS Our observations provide cycle-level characteristics that can be applied during a natural FET cycle to help optimize embryo transfer success rates. Physicians should consider the parameter of number of days that oestradiol is >100 pg/ml prior to the LH surge when determining whether to proceed with embryo transfer in a natural cycle. This cycle-specific characteristic may also help to provide an explanation for some failed transfer cycles. Importantly, our findings should not be used to determine whether to recommend a natural or a programmed FET cycle for a patient, but rather, to identify natural FET cycles that are not optimal to proceed with embryo transfer STUDY FUNDING/COMPETING INTEREST(S) No financial support, funding, or services were obtained for this study. The authors do not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Do women of racial minorities aged 40 years or older have similar reproductive and obstetric outcomes as white women undergoing IVF?A retrospective cohort study conducted at a single academic university-affiliated centre. The study population included women aged 40 years or older undergoing their first IVF cycle with fresh cleavage-stage embryo transfer stratified by racial minority status: minority (black or Asian) versus white. Clinical intrauterine pregnancy and live birth rate were the primary outcomes. Preterm delivery (37 weeks) and small for gestational age were the secondary outcomes. Odds ratios with 95% confidence intervals were estimated. P0.05 was considered to be statistically significant.A total of 2050 cycles in women over the age of 40 years were analysed, 561 (27.4%) of which were undertaken by minority women and 1489 (72.6%) by white women. Minority women were 30% less likely to achieve a pregnancy compared with their white (non-Hispanic) counterparts (adjusted OR 0.68, CI 0.54 to 0.87). Once pregnant, however, the odds of live birth were similar (adjusted OR 1.23, CI 0.91 to 1.67). Minority women were significantly more likely to have lower gestational ages at time of delivery (38.5 versus 39.2 weeks, P = 0.009) and were more likely to have extreme preterm birth delivery 24-28 weeks (5.5 versus 1.0%, P = 0.021).Minority women of advanced reproductive age are less likely to achieve a pregnancy compared with white (non-Hispanic) women. Once pregnancy is achieved, however, live birth rates are similar albeit with minority women experiencing higher rates of preterm delivery.

Objective To describe the incidence of first trimester clinical pregnancy loss in the infertile population during the first wave of the COVID-19 pandemic in New York City. Design Web-based cross-sectional survey. Setting New York City-based academic reproductive medicine practice. Patient(s) A total of 305 infertile patients with a confirmed intrauterine pregnancy in their first trimester between December 1, 2019, and April 1, 2020, were matched by age and treatment type to pregnant patients from the year prior. Intervention(s) None. Main Outcome Measure(s) First trimester clinical pregnancy loss rate. Result(s) In total, the first trimester pregnancy loss rate was lower in the COVID-19 era cohort compared with that in the pre-COVID-19 era cohort (11.9% vs. 20.1%). There was no difference between cohorts in the pregnancy loss rate of women conceiving via fresh embryo transfer (19.6% vs. 24.4%) or via frozen embryo transfer with preimplantation genetic testing (5.4% vs. 9.5%,). In women conceiving via frozen embryo transfer without preimplantation genetic testing, the pregnancy loss rate was statistically lower in the COVID-19 group (12.5% vs. 24.5%). There was no difference in the pregnancy loss rate by treatment type when stratifying by COVID-19 testing or symptom status. Of the 40 (13.1%) patients with a pregnancy loss, there was no difference in self-reported COVID-19 symptoms or symptom type compared with results in those who did not experience a pregnancy loss. Conclusion Despite patients expressing significant worry about COVID-19 and pregnancy, our data provides reassuring information that the first trimester pregnancy loss rate is not elevated for women conceiving via assisted reproductive technology during the global COVID-19 pandemic.

The gray wolf (Canis lupus) population of Isle Royale National Park suffered an extreme population decline where by 2017 only two wolves that were both half-siblings and a father-daughter pair remained with low probability of producing viable young. This precipitous decline was in part due to the negative fitness consequences associated with inbreeding. To restore the Isle Royale ecosystem 19 gray wolves were translocated in 2018 and 2019. The founders were translocated from Grand Portage, MN (n = 4), western Upper Peninsula, MI (n = 4), Jostle Lake, ON (n = 3), and Michipicoten Island, ON (n = 8), and genotyped using 18 microsatellite loci. Allelic richness and heterozygosity of translocated Isle Royale founders was similar to reference populations. Population structure assigned the Isle Royale founders to gray wolves with little evidence of admixture from eastern wolves (Canis lycaon cf). In addition, we confirmed wolves translocated from Michipicoten Island were a single family-group. Through simulation and empirical analysis of the new Isle Royale founders we projected a loss in genetic variation over the next 50 years and an increase in inbreeding. However, varying levels of immigration may allow the retention of some genetic variation. Our findings indicate Isle Royale founders are genetically diverse and representative of the Great Lakes region, but the numerical dominance of a single family group may have negative implications for retaining genetic diversity and success of establishment for specific wolves, reinforcing the importance of continued monitoring of genetic fitness.

Objective To determine if the time from oocyte retrieval to frozen embryo transfer (FET) in the natural cycle affects reproductive or neonatal outcomes. Design Retrospective cohort. Setting Not applicable. Patient(s) Five hundred and seventy-six consecutive freeze-all cycles from January 2011 to December 2018 followed by natural cycle FET of a single blastocyst. Intervention(s) None. Main Outcome Measure(s) Primary outcome of live birth; secondary outcomes of preterm delivery (24–37 weeks) and small for gestational age (SGA) with a multivariable logistic regression performed with adjustment for age, infertility diagnosis, ovulatory trigger type, and preimplantation genetic testing (PGT). Result(s) Before adjustment for confounding, we found a statistically significantly different live-birth rate (57.7% vs. 48.6%) for natural cycle FET occurring in the first versus second menstrual cycle, respectively. In a multivariate analysis, performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle did not statistically significantly impact the odds of live-birth rate. After adjustment for age, diagnosis, and ovulatory trigger type, only PGT was associated with statistically significantly increased odds of live birth compared with no PGT. There were no differences in the incidence of SGA (male, 6.6% vs. 2.3%; female, 9.8% vs. 11.1%) or preterm delivery (1.6% vs. 5.6%) between both groups. Conclusion(s) Performing a natural cycle FET of a single blastocyst in the second compared with the first menstrual cycle after ovarian stimulation did not statistically significantly impact the odds of live birth or neonatal outcomes.

Wolves (Canis lupus) can exert top-down pressure and shape ecological communities through selective predation of ungulates and beavers (Castor Canadensis). Considering their ability to shape communities through predation, understanding wolf foraging decisions is critical to predicting their ecosystem level effects. Specifically, if wolves are optimal foragers, consumers that optimize tradeoffs between cost and benefits of prey acquisition, changes in these factors may lead to prey switching or negative-density dependent selection with potential consequences for community stability. For wolves, factors affecting cost and benefits include prey vulnerability, risk, reward, and availability which can vary temporally. We described wolf diet in by frequency of occurrence and percent biomass and characterized diet in relation to optimal foraging using prey remains found in wolf scats on Isle Royale National Park, Michigan, USA during May–October 2019–2020. We used logistic regression to estimate prey consumption over time. We predicted prey with temporal variation in cost (vulnerability and/or availability) such as adult and calf moose (Alces alces) and beaver to vary in wolves’ diet. We analyzed 206 scats and identified 62% of remains as beaver, 26% as and moose, and 12% as other (birds, smaller mammals, and wolves). Adult moose were more likely to occur in wolf scat in May, when moose are in poor condition following winter. Similarly, the occurrence of moose calves peaked June–mid July following parturition but before their vulnerability declined as they matured. In contrast, beaver occurrence in wolf scat did not change over time, possibly reflecting the importance of low handling cost prey items for recently introduced lone or paired wolves. Our results demonstrate that wolf diet is plastic and responsive to temporal changes in prey acquisition cost as predicted by optimal foraging theory. Temporal fluctuation in diet may influence wolves’ ecological role if prey respond to increased predation risk by altering their foraging or breeding behavior.

The ventrolateral prefrontal cortex (VLPFC) shows robust activation during the perception of faces and voices. However, little is known about what categorical features of social stimuli drive neural activity in this region. Since perception of identity and expression are critical social functions, we examined whether neural responses to naturalistic stimuli were driven by these two categorial features in the prefrontal cortex. We recorded single neurons in the VLPFC, while two macaques viewed short audiovisual videos of unfamiliar conspecifics making expressions of aggressive, affiliative, and neutral valence. Of the 285 neurons responsive to the audiovisual stimuli, 111 neurons had a main effect (two-way ANOVA) of identity, expression or their interaction in their stimulus related firing rates; however, decoding of expression and identity using single unit firing rates rendered poor accuracy. Interestingly, when decoding from pseudopopulations of recorded neurons, the accuracy for both expression and identity increased with population size, suggesting that the population transmitted information relevant to both variables. Principal components analysis of mean population activity across time revealed that population responses to the same identity followed similar trajectories in the response space, facilitating segregation from other identities. Our results suggest that identity is a critical feature of social stimuli that dictates the structure of population activity in the VLPFC, during the perception of vocalizations and their corresponding facial expressions. These findings enhance our understanding of social behavior beyond the temporal lobe in macaques and humans.Significance StatementPrimates are unique in their ability to process and utilize complex, multisensory social information. The brain networks that support this are distributed across the temporal and frontal lobes. In this study, we characterize how social variables like identity and expression are encoded in the neural activity of the ventrolateral prefrontal cortex (VLPFC), a prefrontal region of the macaque brain. We found that single neurons do not appear to encode these variables, but populations of neurons display similar activity patterns that are primarily differentiated by the identity of the conspecific that a macaque is attending to. Furthermore, by employing dynamic, multisensory stimuli, our experiment better approximates real world conditions, making our findings more generalizable.

Study question Is a low anti-Müllerian hormone (AMH) level ( Summary answer Clinical pregnancy, spontaneous abortion, and ongoing pregnancy rates are comparable between patients with AMH levels What is known already Before ovarian stimulation for IVF treatment is recommended, many patients will first be treated with ovulation induction and IUI. Compared to IVF, intrauterine insemination has acceptable success rates, fewer risks, and is less expensive. However, in patients with diminished ovarian reserve, clinicians may be inclined to recommend that a patient proceed straight to IVF due to a concern that IUI cycles may yield unacceptable pregnancy and live birth rates, and that these cycles may waste valuable time for the patient. Study design, size, duration This was a retrospective cohort study of infertile patients at an academic center. The first ovulation induction/IUI cycle with oral medication (clomiphene or letrozole) between 2015-2019 was included. Patients that did not have an AMH level within 12 months of the treatment cycle were excluded. Spontaneous abortion was defined as the spontaneous demise of an intrauterine fetus before 8 weeks’ gestation. Ongoing pregnancy was defined as a viable intrauterine fetus at 8 weeks’ gestation. Participants/materials, setting, methods The primary outcome was ongoing pregnancy. Patients were stratified into two groups based on their AMH level: Group 1 (AMH 40 years). Modified Poisson regression model with robust error variance adjusted a priori for patient age was used to estimate the RR (95% CI). Main results and the role of chance The mean age of patients with an AMH 40 years (3.3% versus 4.5%; RR 0.89 (0.32-2.45). Limitations, reasons for caution As this was a retrospective study, selection bias is possible given that treatment decisions could not be prospectively controlled. However, we attempted to control for this in the study design by restricting our analysis to the first initiated cycle per patient and by excluding natural cycle and gonadotropin treatment cycles. Wider implications of the findings Our observations provide reassurance that a low AMH level is not associated with the chance of success or failure in an ovulation induction/IUI. Ovulation induction/IUI is, therefore, a reasonable option to consider before proceeding to IVF in patients with an AMH level Trial registration number not applicable

The landscape of higher education is moving in a direction of greater variation, leaving traditional academic institutions at risk of obsolescence amidst the myriad of accessible, responsive, flexible learning opportunities increasingly represented in the global learning market. Declining confidence in the value of a college degree forces the higher education industry to open to expanded audiences and diversification of learning opportunities—including embracing the value of alternative credential programming as an institutional priority. This chapter depicts a streamlined model for generating high-quality skills-based microcredentials and professional development offerings with limited resources. To do so, a step-by-step process for identifying opportunities to leverage existing academic content to create more flexible, skills-based learning experiences will be described. The chapter will provide a framework for unbundling credit to non-credit offerings that can be adapted and replicated by other institutions seeking the same outcomes.

To assess the association between anti-müllerian hormone (AMH) and embryo ploidy rates in two cohorts of patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy for preimplantation genetic testing for aneuploidy (PGT-A): (1) the general population of women pursuing IVF with PGT-A (Infertile cohort) and (2) women pursuing IVF with preimplantation genetic testing for monogenic disorders (PGT-M) due to risk for hereditary monogenic diseases (Non-infertile cohort).Retrospective cohort study.Academic center.Patients undergoing their first cycle of IVF with trophectoderm biopsy and PGT-A or PGT-A and PGT-M in our center between 03/2012 and 06/2020. Patients of advanced maternal age according to Bologna criteria (age ≥40) and patients who underwent fresh embryo transfers were excluded.None.Proportion of euploid, mosaic, and aneuploid embryos per cycle."Infertile" (n= 926) and "Non-infertile" (n= 214) patients were stratified based on AMH levels, with low AMH defined as1.1 ng/ml in accordance with the Bologna criteria. Age-adjusted regression models showed no relationship between AMH classification and proportion of euploid, mosaic, and aneuploid embryos in the Infertile or Non-infertile cohorts. In the Infertile cohort, no association between AMH classification and embryo ploidy rates was identified in a subgroup analysis of patients less than 35 years, patients 35-37, and patients 38-39 years old. These findings persisted in a sensitivity analysis of Infertile patients stratified into AMH (ng/ml) quartile categories.AMH is not associated with proportion of euploid, mosaic, or aneuploid embryos in two large cohorts of patients undergoing IVF with PGT-A (Infertile patients) or PGT-A and PGT-M (Non-infertile patients), suggesting that a quantitative depletion of ovarian reserve does not predict the ploidy status of the embryo cohort.

This is a Bachelor thesis on the Diversity Trumps Ability Debate. I have recreated and modified earlier computational models and analysed the results using Python. Supervision and friendliest guidance/feedback: Dr. Ofer Engel

In clinical radiotherapy, the most important aspects are the dose distribution in the target volume and healthy organs, including out-of-field doses in the body. Compared to photon beam radiation, dose distribution in electron beam radiotherapy has received much less attention, mainly due to the limited range of electrons in tissues. However, given the growing use of electron intraoperative radiotherapy and FLASH, further study is needed. Therefore, in this study, we determined out-of-field doses from an electron beam in a phantom model using two dosimetric detectors (diode E and cylindrical Farmer-type ionizing chamber) for electron energies of 6 MeV, 9 MeV and 12 MeV. We found a clear decrease in out-of-field doses as the distance from the field edge and depth increased. The out-of-field doses measured with the diode E were lower than those measured with the Farmer-type ionization chamber at each depth and for each electron energy level. The out-of-field doses increased when higher energy megavoltage electron beams were used (except for 9 MeV). The out-of-field doses at shallow depths (1 or 2 cm) declined rapidly up to a distance of 3 cm from the field edge. This study provides valuable data on the deposition of radiation energy from electron beams outside the irradiation field.

INTRODUCTION: Posthemorrhagic hydrocephalus (PHH) is a common disease process encountered in neonates. Management often includes cerebrospinal fluid (CSF) aspiration through ventricular access devices (VADs). However, a common concern surrounding serial access of implanted subcutaneous reservoirs includes introduction of infection. In addition, there is great variability in aseptic technique. Therefore, the authors sought to evaluate the incidence of VAD access-associated infections in the literature and compare them with the rate of infection found at our institution. We also highlight the use of a preassembled VAD access kit and standardized access protocol, as well as the role of provider education, in maintaining safety and sterility during serial VAD access. METHODS: A single-institution retrospective review was performed for PHH patients younger than 1 year old undergoing serial CSF aspirations via implanted VADs (2009-2019). Patients were excluded if they had a ventriculoperitoneal shunt placed as primary intervention. MEDLINE search for reports of serial VAD access in PHH was also performed. Reports were excluded if they did not include full-text articles in the English literature. RESULTS: At our institution, subcutaneous reservoirs were placed in 37 neonates with PHH for serial CSF aspiration. No infections occurred after a total of 630 taps (average, 17 taps per reservoir; range, 0-83) and 10 420 collective reservoir days (average, 282 per patient; range, 6-3700). Only 2 reservoirs required revision for malfunction. Serial VAD taps for PHH were described in 14 articles in the medical literature, with 7.9% (n = 47/592) of patients reported with tap-related infectious complications. CONCLUSION: A standardized VAD access kit, along with stringent adherence to access protocol, can significantly minimize risk of infection associated with serial VAD access. These principles can be generalized to percutaneous aspiration of CSF from subcutaneous reservoirs placed for other indications to promote safety and sterility of this common procedure.

What is the impact of low body mass index (BMI) on live birth rates and obstetric outcomes in infertile women treated with IVF and fresh embryo transfer?This was a retrospective cohort study of infertile patients in an academic hospital setting who underwent their first oocyte retrieval with planned autologous fresh embryo transfer between 1 January 2012 and 31 December 2018. The primary study outcome was live birth rate. Secondary outcomes were IVF treatment and delivery outcomes. Underweight patients were stratified into a significantly underweight group (body mass index [BMI]17.5 kg/mA total of 5229 patients were included (significantly underweight, 76; mildly underweight, 231; normal weight, 4922), resulting in 4798 embryo transfers. After oocyte retrieval, there were no significant differences between groups for total oocytes, mature oocyte yield and number of supernumerary blastocysts cryopreserved. Among women who had an embryo transfer, there were no significant differences in the live birth rates in significantly (31.0%, odds ratio [OR] 0.67, confidence interval [0.95, CI] 0.40-1.13) and mildly (37.7%, OR 0.95, CI 0.73-1.33) underweight patients compared with normal-weight patients (35.9%). Additionally, there were no statistically significant increased risks of preterm delivery, Caesarean delivery or a low birthweight (2500 g) neonate.Mildly and significantly underweight infertile women have similar pregnancy and live birth rates to normal-weight patients after IVF treatment. In addition, underweight patients do not have an increased risk of preterm delivery (37 weeks), Caesarean delivery or a low birthweight neonate.

We present a case of a tubal ectopic pregnancy (EP) in a patient with an initially undetectable serum β-human chorionic gonadotropin (β-hCG) level. A 33-year-old woman in a same-sex relationship underwent timed donor intrauterine insemination. Her serum β-hCG level was

OBJECTIVE: Assess the effect of class III (body mass index [BMI, kg/m(2)] 40–49.9) and class IV obesity (≥ 50) on clinical pregnancy and live birth outcomes after first oocyte retrieval and fresh embryo transfer cycle. DESIGN: Cohort study SETTING: Academic center PATIENTS: Patients undergoing their first oocyte retrieval with planned fresh embryo transfer in our clinic between 01/01/2012 and 12/31/2018. Patients were stratified by BMI: 18.5–24.9 (n = 4913), 25–29.9 (n = 1566) 30–34.9 (n = 559), 35–39.9 (n = 218), and ≥ 40 (n = 114). INTERVENTION: None MAIN OUTCOME MEASURE: Live birth rate RESULTS: Following embryo transfer, there were no differences in pregnancy rates across all BMI groups (p value, linear trend = 0.86). However among pregnant patients, as BMI increased, a significant trend of a decreased live birth rate was observed (p value, test for linear trend = 0.004). Additionally, as BMI increased, a significant trend of an increased miscarriage rate was observed (p value, linear trend = < 0.001). Compared to the normal-weight cohort, women with a BMI ≥ 40 had a significantly higher rate of cancelled fresh transfers after retrieval (18.4% vs. 8.2%, OR 2.51; 95%CI 1.55–4.08). Among singleton deliveries, a significant trend of an increased c-section rate was identified as the BMI increased (p value, linear trend = 40 have worse IVF treatment outcomes compared to normal-weight patients. After embryo transfer, their pregnancy rate is comparable to normal-weight women; however, their miscarriage rate is higher, leading to a lower live birth rate for pregnant women in this population. Patients with a BMI > 40 have a c-section rate that is 50% higher than normal-weight patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-020-02011-1.

The mistreatment of trainees is known to lead to burnout, loss of empathy, and career changes. Medical students in particular are vulnerable to mistreatment due to their lack of seniority and frequent transitions to new teams. Traditionally, initiatives to eliminate medical student mistreatment have focused on preventing their victimization surrounding verbal, physical, and sexual misconduct. While initiatives to eliminate these types of behaviors are exceedingly important, the most common form of mistreatment that is reported by medical students is not these active forms of abuse. Instead, students on their clinical rotations more frequently report the covert "obstruction of learning" or "exclusion from the medical team" as the most common form of mistreatment experienced. Though the passive neglect of a medical student is not seemingly as serious an offense as active abuse, it can certainly have an impactful, lasting negative effect on student development, morale, and career choice. In this perspective, we recognize the importance of observational learning as a component of medical education, but state that the neglect or exclusion of a medical student should not be considered acceptable and should be labeled what it is-a form of mistreatment. We additionally provide examples for how to prevent medical student neglect by establishing a supportive and inclusive teaching environment.

STUDY QUESTIONWill a delay in initiating IVF treatment affect pregnancy outcomes in infertile women with diminished ovarian reserve?SUMMARY ANSWERA delay in IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation.WHAT IS KNOWN ALREADYIn clinical practice, treatment delays can occur due to medical, logistical or financial reasons. Over a period of years, a gradual decline in ovarian reserve occurs which can result in declining outcomes in response to IVF treatment over time. There is disagreement among reproductive endocrinologists about whether delaying IVF treatment for a few months can negatively affect patient outcomes.STUDY DESIGN, SIZE, DURATIONA retrospective cohort study of infertile patients in an academic hospital setting with diminished ovarian reserve who started an IVF cycle within 180 days of their initial consultation and underwent an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018.PARTICIPANTS/MATERIALS, SETTING, METHODSDiminished ovarian reserve was defined as an anti-Müllerian hormone (AMH) 40 years old with an AMH MAIN RESULTS AND THE ROLE OF CHANCEThe mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85–1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH 40 years old with an AMH LIMITATIONS, REASONS FOR CAUTIONThere is the potential for selection bias with regard to the patients who started their IVF cycle within 90 days compared to 91–180 days after initial consultation. In addition, we did not include patients who were seen for initial evaluation but did not progress to IVF treatment with oocyte retrieval; therefore, our results should only be applied to patients with diminished ovarian reserve who complete an IVF cycle. Finally, since we excluded patients who started their IVF cycle greater than 180 days from their first visit, it is not known how such a delay in treatment affects pregnancy outcomes in IVF cycles.WIDER IMPLICATIONS OF THE FINDINGSA delay in initiating IVF treatment in patients with diminished ovarian reserve up to 180 days from the initial visit does not affect pregnancy outcomes. This observation remains true for patients who are in the high-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistic or financial reasons, treatment outcomes will not be affected.STUDY FUNDING/COMPETING INTEREST(S)No financial support, funding or services were obtained for this study. The authors do not report any potential conflicts of interest.TRIAL REGISTRATION NUMBERNot applicable.

Background Despite the common practice of involving in-patients in the teaching of medical students little is known about the experience for patients. This study investigated inpatients' willingness, motivations and experience with participation in medical student bedside teaching. Methods In-patients at a tertiary hospital who participated in medical student teaching answered a 22 question survey. The survey examined the motivations, impact and overall experience for these patients. Results During July and August of 2019, 111 patients aged 19–93 years completed the survey. Most patients who were approached by preceptors to participate in teaching agreed to participate (74%). Ninety-six percent of patients felt like they could have said no if they had not wanted to participate in medical student teaching. Ninety percent of patients valued the time they spent with students. Conclusions Most hospital inpatients are willing to participate in medical student teaching in order to be helpful, and most have a positive experience. Preceptors in undergraduate medical education should prioritize a quality informed consent process and understand that the teaching experience can be mutually productive for patients and students.

Introduction Immune-related hepatitis (ir-hepatitis) is a common side-effect of checkpoint inhibitors (CPIs). Here, we characterise ir-hepatitis in a large cohort of patients with metastatic melanoma (MM) treated with CPIs and describe potential risk factors and efficacy of medical management. Methods The retrospective study included a large cohort of patients with MM treated with CPIs between 2010 and 2019. Patients were retrieved from the national Danish Metastatic Melanoma Database. Results Five hundred twenty one patients were included. Ir-hepatitis was found in 6.8% of patients. Combination therapy was associated with a significantly greater risk than monotherapy. Of all patients, 34.9% with hepatitis had a different hepatitis grading, when based on either alanine transaminase (ALT) or aspartate transaminase (AST) levels. Of all patients, 72.1% with hepatitis received steroid treatment, and two patients received additional second-line immunosuppressants. Of all patients, 35.5% experienced hepatitis relapse during steroid tapering. Of all patients, 18.6% and 25% of patients with grade ≥2 and ≥ III3, respectively, developed hepatitis within 7 days after finishing an antibiotic treatment for infection. Patients (62.5%) who received a cumulative dose of >4000 mg steroid experienced cancer progression, compared with 22.7% of patients treated with Conclusion Several observations of clinical importance were made. Infection and antibiotic treatment during CPIs could be a possible risk factor for developing ir-hepatitis. Severity of ir-hepatitis is potentially underestimated in a significant number of patients, if only one liver enzyme is measured. The role of second-line immunosuppressants needs to be further investigated because of the high risk of hepatitis relapse during steroid tapering and the potential negative impact of cumulative steroid dose on response to CPIs.

The aim of the study was to determine the influence of a key treatment plan and beam parameters on overall dose distribution and on doses in organs laying in further distance from the target during prostate SBRT. Multiple representative treatment plans (n = 12) for TrueBeam and CyberKnife were prepared and evaluated. Nontarget doses were measured with anionization chamber, in a quasi-humanoid phantom at four sites corresponding to the intestines, right lung, thyroid, and head. The following parameters were modified: radiotherapy technique, presence or not of a flattening filter, degree of modulation, and use or not of jaw tracking function for TrueBeam and beam orientation set-up, optimization techniques, and number of MUs for CyberKnife. After usual optimization doses in intestines (near the target) were 0.73% and 0.76%, in head (farthest from target) 0.05% and 0.19% for TrueBeam and CyberKnife, respectively. For TrueBeam the highest peripheral (head, thyroid, lung) doses occurred for the VMAT with the flattening filter while the lowest for 3DCRT. For CyberKnife the highest doses were for gantry with caudal direction beams blocked (gantry close to OARs) while the lowest was the low modulated VOLO optimization technique. The easiest method to reduce peripheral doses was to combine FFF with jaw tracking and reducing monitor units at TrueBeam and to avoid gantry position close to OARs together with reduction of monitor units at CyberKnife, respectively. The presented strategies allowed to significantly reduce out-of-field and nontarget doses during prostate radiotherapy delivered with TrueBeam and CyberKnife. A different approach was required to reduce peripheral doses because of the difference in dose delivery techniques: non-coplanar using CyberKnife and coplanar using TrueBeam, respectively.