Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations. Delandistrogene moxeparvovec is an investigational gene transfer therapy, developed to address the underlying cause of DMD. We report findings from Part 1 (52 weeks) of the two-part EMBARK trial (NCT05096221). Methods: Key inclusion criteria: Ambulatory patients aged ≥4-<8 years with a confirmed DMD mutation within exons 18–79 (inclusive); North Star Ambulatory Assessment (NSAA) score >16 and <29 at screening. Eligible patients were randomized 1:1 to intravenous delandistrogene moxeparvovec (1.33×1014 vg/kg) or placebo. The primary endpoint was change from baseline in NSAA total score to Week 52. Results: At Week 52 (n=125), the primary endpoint did not reach statistical significance, although there was a nominal difference in change from baseline in NSAA total score in the delandistrogene moxeparvovec (2.6, n=63) versus placebo groups (1.9, n=61). Key secondary endpoints (time to rise, micro-dystrophin expression, 10-meter walk/run) demonstrated treatment benefit in both age groups (4-5 and 6-7 years; p<0.05).There were no new safety signals, reinforcing the favorable and manageable safety profile observed to date. Conclusions: Based on the totality of functional assessments including the timed function tests, treatment with delandistrogene moxeparvovec indicates beneficial modification of disease trajectory.

A total of 108 diverse sorghum (Sorghum bicolor) accessions were characterized for quantitative and qualitative fodder-related traits and zonate leaf spot (ZLS) (Gloeocercospora sorghi) disease during two successive wet seasons of 2019 and 2020 in augmented randomized block design. The Shannon's diversity index and analysis of variance showed the existence of significant variability among qualitative and quantitative traits. K-mean clustering showed strong relationship between green fodder yield (GFY) and other yield-contributing traits. The dendrogram constructed based on morphological traits classified accessions into four diverse groups and most of genotype fall under cluster II. The principal component analysis bi-plot analysis showed a total variation of 68.96%, where GFY, stem weight per plant, panicle length and dry matter yield (DMY) contributed significantly. From the experimental results, three sorghum genotypes viz., IG-03-424, IG-01-436 and IG-03-438 were identified as promising for higher GFY (808.66 g/plant) and DMY (238.0 g/plant), respectively. Further, based on disease reactions under natural condition, five genotypes viz., EC-512397, EC512393, EC512394, EC512399 and IG-02-437 were identified as potential donor for resistance to ZLS disease. These selected lines could be used as promising sources for high biomass and disease resistance in forage sorghum breeding programme.

Tight focusing with very small f-numbers is necessary to achieve the highest at-focus irradiances. However, tight focusing imposes strong demands on precise target positioning in-focus to achieve the highest on-target irradiance. We describe several near-infrared, visible, ultraviolet and soft and hard X-ray diagnostics employed in a ∼1022 W/cm2 laser–plasma experiment. We used nearly 10 J total energy femtosecond laser pulses focused into an approximately 1.3-μm focal spot on 5–20 μm thick stainless-steel targets. We discuss the applicability of these diagnostics to determine the best in-focus target position with approximately 5 μm accuracy (i.e., around half of the short Rayleigh length) and show that several diagnostics (in particular, 3$\omega$ reflection and on-axis hard X-rays) can ensure this accuracy. We demonstrated target positioning within several micrometers from the focus, ensuring over 80% of the ideal peak laser intensity on-target. Our approach is relatively fast (it requires 10–20 laser shots) and does not rely on the coincidence of low-power and high-power focal planes.

Himalayan glaciers have been shrinking and losing mass rapidly since 1970s with an enhanced rate after 2000. The shrinkage is, however, quite heterogeneous and it is important to document individual glacier characteristics and their changes at the basin scale. We present an updated glacier inventory of the Upper Alaknanda Basin (UAB), Central Himalaya for the year 2020 and report area, debris cover and length changes for the periods 1994–2006 and 2006–2020 based on remote-sensing data. We identified 198 glaciers, comprising an area of 354.6 ± 8.5 km2, and classified them according to their size and morphology. The glaciers of the basin lost 4.2 ± 2.9% (0.16 ± 0.11% a−1) of their frontal area (from 368.6 ± 9.2 to 353.0 ± 5.3 km2) from 1994 to 2020. The average retreat rate was higher in the period 2006–2020 (13.3 ± 1.8 m a−1) in comparison to 1994–2006 (9.3 ± 1.9 m a−1). However, the area change rate was similar for the two periods (0.14 ± 0.27% a−1 for 1994–2006 and 0.16 ± 0.19% a−1 for 2006–2020). The debris-covered area has increased by 13.4 ± 4.4% from 1994 to 2020. A comparison with previous studies in UAB indicates consistent area loss of ~0.15% a−1 since the 1960s.

Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.

This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.

Childhood adversity and anxiety have been associated with increased risk for internalizing disorders later in life and with a range of brain structural abnormalities. However, few studies have examined the link between harsh parenting practices and brain anatomy, outside of severe maltreatment or psychopathology. Moreover, to our knowledge, there has been no research on parenting and subclinical anxiety symptoms which remain persistent over time during childhood (i.e., between 2.5 and 9 years old). Here, we examined data in 94 youth, divided into four cells based on their levels of coercive parenting (high / low) and of anxiety (high / low) between 2.5 and 9 years old. Anatomical images were analyzed using voxel-based morphometry (VBM) and FreeSurfer. Smaller gray matter volumes in the prefrontal cortex regions and in the amygdala were observed in youth with high versus low levels of harsh parenting over time. In addition, we observed significant interaction effects between parenting practices and subclinical anxiety symptoms in rostral anterior cingulate cortical thickness and in amygdala volume. These youth should be followed further in time to identify which youth will or will not go on to develop an anxiety disorder, and to understand factors associated with the development of sustained anxiety psychopathology.

The onset of magnetic reconnection in space, astrophysical and laboratory plasmas is reviewed discussing results from theory, numerical simulations and observations. After a brief introduction on magnetic reconnection and approach to the question of onset, we first discuss recent theoretical models and numerical simulations, followed by observations of reconnection and its effects in space and astrophysical plasmas from satellites and ground-based detectors, as well as measurements of reconnection in laboratory plasma experiments. Mechanisms allowing reconnection spanning from collisional resistivity to kinetic effects as well as partial ionization are described, providing a description valid over a wide range of plasma parameters, and therefore applicable in principle to many different astrophysical and laboratory environments. Finally, we summarize the implications of reconnection onset physics for plasma dynamics throughout the Universe and illustrate how capturing the dynamics correctly is important to understanding particle acceleration. The goal of this review is to give a view on the present status of this topic and future interesting investigations, offering a unified approach.

A new optimized quasi-helically symmetric configuration is described that has the desirable properties of improved energetic particle confinement, reduced turbulent transport by three-dimensional shaping and non-resonant divertor capabilities. The configuration presented in this paper is explicitly optimized for quasi-helical symmetry, energetic particle confinement, neoclassical confinement and stability near the axis. Post optimization, the configuration was evaluated for its performance with regard to energetic particle transport, ideal magnetohydrodynamic stability at various values of plasma pressure and ion temperature gradient instability induced turbulent transport. The effects of discrete coils on various confinement figures of merit, including energetic particle confinement, are determined by generating single-filament coils for the configuration. Preliminary divertor analysis shows that coils can be created that do not interfere with expansion of the vessel volume near the regions of outgoing heat flux, thus demonstrating the possibility of operating a non-resonant divertor.

Social media influencers (SMI) are gaining interest and many are studying their influence on the online audience, little is known about the role played by them in offline teams. One such attempt to study the effect of influencers in co-design team is presented in this paper, where individuals who are confident in their abilities drive the team process. Thus, self-efficacy is considered for determining influencer behaviour. Results expose the relationship between self-efficacy and influencer status on the design process, besides briefly highlighting the effects on above-average teams.

We present a detailed analysis of the radio galaxy PKS $2250{-}351$ , a giant of 1.2 Mpc projected size, its host galaxy, and its environment. We use radio data from the Murchison Widefield Array, the upgraded Giant Metre-wavelength Radio Telescope, the Australian Square Kilometre Array Pathfinder, and the Australia Telescope Compact Array to model the jet power and age. Optical and IR data come from the Galaxy And Mass Assembly (GAMA) survey and provide information on the host galaxy and environment. GAMA spectroscopy confirms that PKS $2250{-}351$ lies at $z=0.2115$ in the irregular, and likely unrelaxed, cluster Abell 3936. We find its host is a massive, ‘red and dead’ elliptical galaxy with negligible star formation but with a highly obscured active galactic nucleus dominating the mid-IR emission. Assuming it lies on the local M– $\sigma$ relation, it has an Eddington accretion rate of $\lambda_{\rm EDD}\sim 0.014$ . We find that the lobe-derived jet power (a time-averaged measure) is an order of magnitude greater than the hotspot-derived jet power (an instantaneous measure). We propose that over the lifetime of the observed radio emission ( ${\sim} 300\,$ Myr), the accretion has switched from an inefficient advection-dominated mode to a thin disc efficient mode, consistent with the decrease in jet power. We also suggest that the asymmetric radio morphology is due to its environment, with the host of PKS $2250{-}351$ lying to the west of the densest concentration of galaxies in Abell 3936.

This poster presented results from a detailed analysis of observed and theoretical light-curves of classical Cepheid variables in the Galaxy and the Magellanic Clouds. The theoretical light-curves were based on non-linear convective hydrodynamical pulsation models; the observational data were taken from ongoing wide-field variability surveys. The variation which we found in theoretical and observed light-curve parameters as a function of period, wavelength and metallicity was used to constrain the input physics to the pulsation models, such as the mass–luminosity relations obeyed by Cepheid variables. We also accounted for the variation in the convective efficiency as entered into the stellar pulsation models and its impact on the theoretical amplitudes and Period-Luminosity relations for Cepheid variables.

This poster presented results from the Large Magellanic Cloud Near-Infrared Synoptic Survey (LMCNISS) for classical and Type II Cepheid variables that were identified in the Optical Gravitational Lensing Experiment (OGLE-III) catalogue. Multi-wavelength time-series data for classical Cepheid variables are used to study light-curve structures as a function of period and wavelength. We exploited a sample of ∼1400 classical and ∼80 Type II Cepheid variables to derive Period–Wesenheit relations that combine both optical and near-infrared data. The new Period–Luminosity and Wesenheit relations were used to estimate distances to several Local-Group galaxies (using classical Cepheids) and to Galactic globular clusters (using Type II Cepheids). By appealing to a statistical framework, we found that fundamental-mode classical Cepheid Period–Luminosity relations are non-linear around 10–18 days at optical and near-IR wavelengths. We also suggested that a non-linear relation provides a better constraint on the Cepheid Period–Luminosity relation in Type Ia Supernovæ host galaxies, though it has a negligible effect on the systematic uncertainties affecting the local measurement of the Hubble constant.

Temporary confinement during parturition and early postpartum may provide an intermediary step preceding loose housing that offers improvement in sow and piglet welfare. Three experiments were conducted to investigate the implications of replacing farrowing crates (FCs) with an alternative housing system from 3 days postpartum until weaning. In each experiment sows farrowed in FCs and were randomly allocated at day 3 of lactation to either a FC or a pen with increased floor space (lactation pen (LP)) until weaning. In experiment 1, piglet growth and sow and piglet skin injuries were recorded for 32 sows and 128 focal piglets in these litters. Behaviour around nursing and piglet behavioural time budgets were also recorded for 24 of these litters (96 focal piglets for time budgets). In experiment 2, measures of skin injury and behavioural time budgets were conducted on 28 sows and 112 focal piglets. The behavioural response of sows to piglet vocalisation (maternal responsiveness test (MRT)) was also assessed. In experiment 3, piglet mortality from day 3 of lactation until weaning was recorded in 672 litters over 12 months. While housing did not affect piglet weight gain in experiment 1, or piglet skin injuries in experiments 1 or 2, sows in both experiments sustained more injuries in LP than FC (experiment 1, 2.9 v. 1.4; experiment 2, 2.5 v. 0.8 lesions/sow; P<0.05). Sow–piglet interactions were more frequent in LP than FC at days 11 and 18 postpartum in both experiment 1 (day 11, 1.4% v. 1.2%; day 18, 1.7% v. 1.0% of observations; P=0.05) and 2 (day 11, 1.0% v. 0.3%; and at day 18 were 1.0% v. 0.6% of observations; P<0.01), and LP sows were more responsive in the MRT in experiment 2 (2 v. 0 median number of tests in which sows react, P<0.01). In experiment 1 piglets played more (0.7% v. 0.3% of observations, P=0.05) and manipulated others less (0.3% v. 0.7% of observations, P=0.04) in LP, but more piglets missed nursing bouts (0.2 v. 0.1 piglets/bout, P<0.01) compared with FC. There was no effect of housing on piglet mortality from day 3 of lactation until weaning in experiment 3 (0.63 and 0.64 deaths/litter for LP and FC, respectively, P>0.05). Thus, housing sows and litters in LP from day 3 of lactation minimises piglet mortality while improving maternal behaviour in sows and social behaviour in piglets.

The evidence underpinning the developmental origins of health and disease (DOHaD) is overwhelming. As the emphasis shifts more towards interventions and the translational strategies for disease prevention, it is important to capitalize on collaboration and knowledge sharing to maximize opportunities for discovery and replication. DOHaD meetings are facilitating this interaction. However, strategies to perpetuate focussed discussions and collaborations around and between conferences are more likely to facilitate the development of DOHaD research. For this reason, the DOHaD Society of Australia and New Zealand (DOHaD ANZ) has initiated themed Working Groups, which convened at the 2014–2015 conferences. This report introduces the DOHaD ANZ Working Groups and summarizes their plans and activities. One of the first Working Groups to form was the ActEarly birth cohort group, which is moving towards more translational goals. Reflecting growing emphasis on the impact of early life biodiversity – even before birth – we also have a Working Group titled Infection, inflammation and the microbiome. We have several Working Groups exploring other major non-cancerous disease outcomes over the lifespan, including Brain, behaviour and development and Obesity, cardiovascular and metabolic health. The Epigenetics and Animal Models Working Groups cut across all these areas and seeks to ensure interaction between researchers. Finally, we have a group focussed on ‘Translation, policy and communication’ which focusses on how we can best take the evidence we produce into the community to effect change. By coordinating and perpetuating DOHaD discussions in this way we aim to enhance DOHaD research in our region.