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This study aimed to discover whether egg sharing compromises the chance of donors or recipients achieving a live birth. A descriptive cohort study was performed of 4,545 fertility patients and 5,316 stimulation cycles at a London based fertility clinic between 2010 and 2019. There was no significant difference in clinical pregnancy rate (CPR) or live birth rate (LBR) between egg sharers and standard IVF patients or between egg sharing recipients and non-egg sharing recipients. Both egg sharers and their recipients had fewer oocytes and fewer day 3 embryos available for fresh embryo transfer or cryopreservation than standard IVF patients or non-egg sharing recipients. The cumulative LBR were significantly lower amongst egg sharers than standard IVF patients (

Large amounts of carbon (C) are transported through Earth’s aquatic conduit every year. While the C transported to freshwater systems as dissolved organic C (DOC) and dissolved inorganic C (DIC) has been investigated for some time, the dynamics controlling how much DIC gets evaded to the atmosphere (as CO2) remains uncertain and an area of active investigation. Recent technological advancement using in-situ dissolved CO2 (pCO2) sensors increased previously established global C evasion estimates but sensor networks that inform this estimate have an inherent spatial bias towards major tributaries. Contributions from headwater streams where pCO2 values tend to be higher are less well constrained and tend to be biased towards daytime measurements. This research seeks to highlight how much C (as DOC and pCO2) is transported at multiple locations along a headwater to 2nd order stream system, along with an investigation of local dynamics controlling DOC and DIC transformation within the stream network.Headwater monitoring stations were installed in University of British Columbia’s Malcolm Knapp Research Forest in the North American Pacific Coastal temperate rainforest (PCTR) region - an aquatic C hotspot due to its high productivity rainforest ecosystems and steep elevation gradient. This research reports trends of aquatic DOC dynamics and CO2 evasion fluxes where continuous DOC measurements [s::can UV-Vis Spectrolyzer] are validated monthly with the Shimadzu Total Organic Carbon analyzer and time series data obtained from dissolved CO2 probes [Vaisala GMP221] are corrected using gas chromatography [Agilent 7890A]. Monitoring stations (DOC and pCO2) installed over several kilometers in the same stream permitted an investigation into how aquatic carbon evolves between organic and inorganic phases, as well as CO2 transfer between the dissolved phase and the atmosphere.Preliminary data indicates that over the 2 km reach, pCO2 decreased by an average of 22.8%, while DOC declined by 2.35 mg/L between upstream and downstream sites - a 74.9% reduction in DOC concentration over this distance. Ongoing research seeks to disentangle dilusion vs. aquatic metabolism as controlling factors of the observed DOC concentration reduction. In this presentation I will also discuss temporal dynamics (e.g., high flow vs. low flow conditions and hysteresis behaviour), DOC characterization (as SUVA254 and spectral slopes), and evasion flux calculations at the two locations. Results from this study will help establish transformation pathways that connect DOC and DIC with contributions to biogeochemical understanding of catchment carbon cycle and aid in identifying the role of PCTR headwater streams in the global evasion estimate context.

Background: Mortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome domains. Definitions of these measures are highly variable, and validity is often unclear. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid measures of mortality, morbidity, and organ failure for use in perioperative clinical trials. Methods: Three domains of endpoints (mortality, morbidity, and organ failure) were explored through systematic literature review and a three-stage Delphi consensus process using methods consistently applied across the StEP initiative. Reliability, feasibility, and patient-centredness were assessed in round 3 of the consensus process. Results: A high level of consensus was achieved for two mortality time points, 30-day and 1-yr mortality, and these two measures are recommended. No organ failure endpoints achieved threshold criteria for consensus recommendation. The Clavien–Dindo classification of complications achieved threshold criteria for consensus in round 2 of the Delphi process but did not achieve the threshold criteria in round 3 where it scored equivalently to the Post Operative Morbidity Survey. Clavien–Dindo therefore received conditional endorsement as the most widely used measure. No composite measures of organ failure achieved an acceptable level of consensus. Conclusions: Both 30-day and 1-yr mortality measures are recommended. No measure is recommended for organ failure. One measure (Clavien–Dindo) is conditionally endorsed for postoperative morbidity, but our findings suggest that no single endpoint offers a reliable and valid measure to describe perioperative morbidity that is not dependent on the quality of deli-vered care. Further refinement of current measures, or development of novel measures, of postoperative morbidity might improve consensus in this area.

Osteosarcoma is the most common malignant bone tumor in children. After initial diagnosis is made with a biopsy, treatment consists of preoperative chemotherapy followed by definitive surgery and postoperative chemotherapy. The degree of tumor necrosis in response to preoperative chemotherapy is a reliable prognostic factor and is used to guide the choice of postoperative chemotherapy. Patients with tumors, which reveal ≥90% necrosis (good responders), have a much better prognosis than those with t test, we identified 45 genes that discriminate between good and poor responders (P < 0.005) in 20 definitive surgery samples. A support vector machine classifier was built using these predictor genes and was tested for its ability to classify initial biopsy samples. Five of six initial biopsy samples that had corresponding definitive surgery samples in the training set were classified correctly (83%; confidence interval, 36%, 100%). When this classifier was used to predict eight independent initial biopsy samples, there was 100% accuracy (confidence interval, 63%, 100%). Many of the predictor genes are implicated in bone development, drug resistance, and tumorigenesis.

Supplementary Figure S1 & Table S1 from Expression Profiles of Osteosarcoma That Can Predict Response to Chemotherapy

Infants born before 32 weeks’ postmenstrual age are at a high risk of growth failure. International guidelines have long recommended that they match the growth of an equivalent fetus, despite the challenges posed by ex utero life and comorbidities of prematurity. Several groups have recently questioned the necessity or desirability of this target, shifting attention to aiming for growth which optimises important long-term outcomes. Specifically, recent research has identified the neurodevelopmental benefits of enhanced growth during the neonatal period, but work in term infant suggests that rapid growth may promote the metabolic syndrome in later life. In this context, defining a pattern of growth which optimises outcomes is complex, controversial and contested. Even if an optimal pattern of growth can be defined, determining the nutritional requirements to achieve such growth is not straightforward, and investigations into the nutritional needs of the very preterm infant continue. Furthermore, each infant has individual nutritional needs and may encounter a number of barriers to achieving good nutrition. This article offers a narrative review of recent evidence for the competing definitions of optimal growth in this cohort. It examines recent advances in the determination of macronutrient and micronutrient intake targets along with common barriers to achieving good nutrition and growth. Finally, key implications for clinical practice are set out and a recommendation for structured multidisciplinary management of nutrition and growth is illustrated.

To reduce treatment burden and optimise patient outcomes in diabetic macular oedema, we present 1-year results from two phase 3 trials of faricimab, a novel angiopoietin-2 and vascular endothelial growth factor-A bispecific antibody.YOSEMITE and RHINE were randomised, double-masked, non-inferiority trials across 353 sites worldwide. Adults with vision loss due to centre-involving diabetic macular oedema were randomly assigned (1:1:1) to intravitreal faricimab 6·0 mg every 8 weeks, faricimab 6·0 mg per personalised treatment interval (PTI), or aflibercept 2·0 mg every 8 weeks up to week 100. PTI dosing intervals were extended, maintained, or reduced (every 4 weeks up to every 16 weeks) based on disease activity at active dosing visits. The primary endpoint was mean change in best-corrected visual acuity at 1 year, averaged over weeks 48, 52, and 56. Efficacy analyses included the intention-to-treat population (non-inferiority margin 4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters); safety analyses included patients with at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (YOSEMITE NCT03622580 and RHINE NCT03622593).3247 patients were screened for eligibility in YOSEMITE (n=1532) and RHINE (n=1715). After exclusions, 940 patients were enrolled into YOSEMITE between Sept 5, 2018, and Sept 19, 2019, and 951 patients were enrolled into RHINE between Oct 9, 2018, and Sept 20, 2019. These 1891 patients were randomly assigned to faricimab every 8 weeks (YOSEMITE n=315, RHINE n=317), faricimab PTI (n=313, n=319), or aflibercept every 8 weeks (n=312, n=315). Non-inferiority for the primary endpoint was achieved with faricimab every 8 weeks (adjusted mean vs aflibercept every 8 weeks in YOSEMITE 10·7 ETDRS letters [97·52% CI 9·4 to 12·0] vs 10·9 ETDRS letters [9·6 to 12·2], difference -0·2 ETDRS letters [-2·0 to 1·6]; RHINE 11·8 ETDRS letters [10·6 to 13·0] vs 10·3 ETDRS letters [9·1 to 11·4] letters, difference 1·5 ETDRS letters [-0·1 to 3·2]) and faricimab PTI (YOSEMITE 11·6 ETDRS letters [10·3 to 12·9], difference 0·7 ETDRS letters [-1·1 to 2·5]; RHINE 10·8 ETDRS letters [9·6 to 11·9], difference 0·5 ETDRS letters [-1·1 to 2·1]). Incidence of ocular adverse events was comparable between faricimab every 8 weeks (YOSEMITE n=98 [31%], RHINE n=137 [43%]), faricimab PTI (n=106 [34%], n=119 [37%]), and aflibercept every 8 weeks (n=102 [33%], n=113 [36%]).Robust vision gains and anatomical improvements with faricimab were achieved with adjustable dosing up to every 16 weeks, demonstrating the potential for faricimab to extend the durability of treatment for patients with diabetic macular oedema.F Hoffmann-La Roche.

The application of wide-band gap semiconductors and their integration with other power electronics components (e.g., passives, gate drivers, sensing, thermal management) can meet the growing demand for volume reduction in power electronics systems. The design of such an integrated system is a complex multiphysics problem given the high number of variables to identify, objectives to optimize, and constraints to satisfy. Traditionally, this complex problem is approached subdividing the design in different steps, where in each step, the single components are designed and optimized independently from the others. This might clearly overlook the effect that the design choices of a single subsystem has on other subsystems, leading to suboptimal solutions. In this article, an automated design approach is proposed with the aim of maximizing power density whilst minimizing total losses. As a vessel to investigate the presented optimization workflow, the magnetically coupled interleaved H-bridge topology is chosen as an emblematic example of multivariable design problem. The first step of this approach consists of developing a loss model of the converter, which takes into account components physical dimensions, the temperature dependence, and the circuit parasitics. In the second step, these models are used within a nested optimization procedure in order to estimate the losses for multiple points of load. With the aim of validating both design approach and optimization results, three different optimal solutions have been deeply analyzed with commercial suit, prototyped, and tested. The showed experimental results endorse the adopted design approach confirming the optimality/validity of the manufactured solutions.

BACKGROUND: The development of motor skills in infancy is a vital neurodevelopmental milestone. Although previous studies have explored the neurotoxic effects of agricultural pesticides on infants’ motor development, limited research has examined early postnatal household pesticide use on infants’ motor development, particularly among urban communities. OBJECTIVE: This study examined the association between early postnatal household pesticide use and infants’ gross and fine motor development at 6 months of age. METHODS: Questionnaires were administered via telephone to 296 mother-infant dyads in the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort. Early life household pesticide use was assessed via questionnaire administered when infants turned 3 months old and gross and fine motor development was assessed by the Ages and Stages Questionnaire (ASQ3) at 6 months old. Infant gross motor scores were reverse coded so that higher scores indicated lower gross motor performance. Negative binomial regressions were performed to assess the relationship between household pesticide use and infant gross motor development. RESULTS: Infants were predominantly Hispanic (78.7%) and full term (gestational age at birth: 39.0 ±1.9 weeks), with 22.3% of maternal participants reporting household use of rodent and insect pesticides. Adjusting for recruitment site, maternal age, ethnicity, household income, education, infant corrected age, infant sex, and home type, infants with maternal reported household use of rodent and insect pesticides had 1.30 times higher expected gross motor scores (95% CI: 1.05,1.61) than infants with no reported use of household pesticides, with higher scores indicating reduced gross motor performance. CONCLUSIONS: Our results suggest household use of rodent and insect pesticides may harm infants’ gross motor development in early childhood. Future research should evaluate the impact of specific household chemicals in infant biospecimens and their associations with infant motor development to confirm these findings.

This study investigates the power cycling reliability of nanosilver sintered joints formed by a time-reduced sintering process, designed for use on a die bonder. A range of sintering parameters, reflecting different levels of manufacturability, were used to produce sintered joints in respect of shear strength and porosity, within a process cycle time of a few seconds. The reliability of the sintered attachments were evaluated against Pb5Sn solder joints under constant temperature swing power cycling conditions over the range 50 to 200 °C. The thermal performance and microstructural changes of the sintered joints were monitored and evaluated non-destructively at regular intervals using transient thermal impedance and X-ray computed tomography. The results show that sintered joints with higher shear strengths (>50 MPa) and lower porosities (

Most research on the evolution of damage after traumatic brain injury (TBI) focuses on cellular effects, but the analysis of human tissue slices and animal research have shown that TBI causes concomitant damage in the extracellular matrix, which can play a significant role in both short-term consequences such as edema, and late effects such as post-traumatic epilepsy (PTE). To test the hypothesis that traumatic brain injury (TBI) in human patients causes disruption of sulfated glycosaminoglycan (sGAG) in the extracellular matrix, we measured levels of these substances in the ventricular cerebrospinal fluid (CSF) in patients with severe TBI in the acute post-injury period, along with concomitant levels in blood and urine. We assessed whether levels corresponded to parenchymal injury load, distance of traumatic brain lesions from the ventricle, presence of polytrauma, or host demographic factors.MethodsSamples of CSF, blood, and urine were obtained within 72 hours of injury in patients who received external ventricular drains as part of their treatment of severe TBI, and levels of chondroitin and heparan sGAGs were measured, along with their disaccharide constituents. Basic demographic information, presence and severity of polytrauma, brain injury load based on imaging findings, and distance of radiologically visible parenchymal injury from the ventricle were analyzed for correlation with total subtype sGAG levels in each patient.ResultsLevels were measured in 14 patients ranging in age from 17-90 years. CSF sGAG levels were variable among patients, and sGAG levels were higher in plasma than in CSF and variable in urine. Patients with polytrauma had non-significantly higher blood sGAG compared to patients with isolated head injury. Subcategories of CSF sGAG levels correlated with distance from the ventricle of parenchymal injury but not with brain injury load, which may reflect rapid metabolism in the parenchyma, contamination by blood, or bulk directional CSF flow from the ventricle to the subarachnoid space.ConclusionThis study is the first to measure sGAG levels in ventricular CSF and also provides the first measurements in patients with TBI. Damage to the extracellular matrix may play a major role in acute and chronic injury sequelae, and these data demonstrate elevation locally of intracranial sGAGS after severe TBI and also suggest rapid local metabolism of these breakdown products. The consequences of extracellular matrix breakdown may provide unique therapeutic and preventive avenues to mitigate post-injury sequelae.

Genetic changes in the ERBB family of receptor tyrosine kinases serve as oncogenic driver events and predictive biomarkers for ERBB inhibitor drugs. ERBB3 is a pseudokinase member of the family that, although lacking a fully active kinase domain, is well known for its potent signaling activity as a heterodimeric complex with ERBB2. Previous studies have identified few transforming ERBB3 mutations while the great majority of the hundreds of different somatic ERBB3 variants observed in different cancer types remain of unknown significance. Here, we describe an unbiased functional genetics screen of the transforming potential of thousands of ERBB3 mutations in parallel. The screen based on a previously described iSCREAM (in vitro screen of activating mutations) platform, and addressing ERBB3 pseudokinase signaling in a context of ERBB3/ERBB2 heterodimers, identified 18 hit mutations. Validation experiments in Ba/F3, NIH 3T3, and MCF10A cell backgrounds demonstrated the presence of both previously known and unknown transforming ERBB3 missense mutations functioning either as single variants or in cis as a pairwise combination. Drug sensitivity assays with trastuzumab, pertuzumab and neratinib indicated actionability of the transforming ERBB3 variants.

While it is well established that humans develop stronger relationship bonds when they share stressful experiences, there is little known on how shared stressful experiences may influence relationship bonding in animals. Here, we present a study looking at social proximity between individuals in small groups of Merino ewes following a shared stressful experience compared with control sheep that were not exposed to stress. Some sheep were familiar to each other. Analyses of social proximity using real-time-kinematic Global Navigation Satellite System (GNSS) on-animal devices showed sheep preferred to be closest to familiar individuals, but across the study duration they also developed a preference for the individuals they shared the stressful experience with, relative to their proximity to control individuals. These results contribute to limited research on what factors may instigate the development of bonds between unfamiliar sheep. Between-individual bonds may develop as a means of socially mediated stress buffering. Social bonding following a shared stressful experience aligns with human social relationships and increases our understanding of how animals perceive their conspecifics in relation to stressful environmental change.

This study aimed to characterise selected lower-limb muscle contractile properties in a sample of male professional soccer players, and to investigate if muscle contractile properties differed according to playing position or limb dominance. One hundred and ninety-three male professional soccer players (mean ± SD: age=21.6yrs±4.4; height=181.1cm±10.0; body mass=77.4kg±8.5) had bilateral measurements of muscle contractile properties taken during the pre-season period (June-July) of the 2016-17, 2017-18 and 2018-19 seasons using Tensiomyography. The following muscles were measured: Adductor Magnus (AM), Bicep Femoris (BF), Gastrocnemius Lateralis (GL), Gastrocnemius Medialis (GM), Gluteus Maximus (GT) and Rectus Femoris (RF). Participants were sub-categorised by playing position and limb dominance. Data were analysed using Kruskal Wallis H tests or Mann-Whitney U tests. The left GM muscle produced the shortest delay time (Td) (19.5 ms ± 1.9) and contraction time (Tc) (21.3 ms±14.3) whilst the right BF had the longest sustain time (Ts) (196.9ms±83.9). Relaxation time (Tr) was shortest in the right GL (39.3ms±22.7) and the right GT the largest maximal displacement (Dm) value (10.2mm±3.6). Small differences were present between the left AM Td in Forwards (p=0.005, η2=0.05) and Midfielders and in the left GM Ts between Forwards and Goalkeepers (p=0.04, η2=0.02). The right RF Tc measurement was lower in the right dominant participants (p=0.04, η2=0.35). No other differences were detected between playing positions or limb dominance (p>0.05). The findings from this study provide a profile of lower limb muscle contractile properties in a sample of male professional soccer players. The lack of consistent differences reported between sub-categories suggest that soccer players are homogeneous, regardless of playing position or limb dominance. The data generated from this study may be used to monitor soccer players following periods of inactivity, fixture congestion, long-term injury or acute changes in professional status.