The Scientific Advisory Committee on Nutrition (SACN) provides independent advice on nutrition and related health matters to UK government organisations. In keeping with its commitment to openness and transparency, SACN follows a set ‘Framework’ to ensure a prescribed and consistent approach is taken in all its evidence evaluations. Following an update of the SACN Framework in 2020, which addressed some straightforward issues, the SACN Framework subgroup was established in 2021 to consider more complex matters that were not addressed in the 2020 update. The SACN Framework subgroup considered 4 main topics for update: 1) the different types of evidence evaluations produced by SACN, 2) interpretation of statistical data, 3) tools for assessment of study quality, 4) tools to assess the certainty of a body of evidence for exposure-outcome relationships. The Framework subgroup agreed clear definitions and processes for the different types of evidence evaluations produced by SACN and agreed that interpretation of p values should be informed by consideration of study size, power and methodological quality. The subgroup recommended use of the AMSTAR 2 tool for quality assessment of evidence from systematic reviews and use of the GRADE approach to assess the certainty of evidence. The updated Framework was published in January 2023. This was followed by publication of a further update in October 2024. As a ‘living’ document, the Framework will be subject to regular review by the Framework subgroup and continue to evolve in line with best practice.

We provide an assessment of the Infinity Two fusion pilot plant (FPP) baseline plasma physics design. Infinity Two is a four-field period, aspect ratio $A = 10$, quasi-isodynamic stellarator with improved confinement appealing to a max-$J$ approach, elevated plasma density and high magnetic fields ($ \langle B\rangle = 9$ T). Here $J$ denotes the second adiabatic invariant. At the envisioned operating point ($800$ MW deuterium-tritium (DT) fusion), the configuration has robust magnetic surfaces based on magnetohydrodynamic (MHD) equilibrium calculations and is stable to both local and global MHD instabilities. The configuration has excellent confinement properties with small neoclassical transport and low bootstrap current ($|I_{bootstrap}| \sim 2$ kA). Calculations of collisional alpha-particle confinement in a DT FPP scenario show small energy losses to the first wall (${\lt}1.5 \,\%$) and stable energetic particle/Alfvén eigenmodes at high ion density. Low turbulent transport is produced using a combination of density profile control consistent with pellet fueling and reduced stiffness to turbulent transport via three-dimensional shaping. Transport simulations with the T3D-GX-SFINCS code suite with self-consistent turbulent and neoclassical transport predict that the DT fusion power$P_{{fus}}=800$ MW operating point is attainable with high fusion gain ($Q=40$) at volume-averaged electron densities $n_e\approx 2 \times 10^{20}$ m$^{-3}$, below the Sudo density limit. Additional transport calculations show that an ignited ($Q=\infty$) solution is available at slightly higher density ($2.2 \times 10^{20}$ m$^{-3}$) with $P_{{fus}}=1.5$ GW. The magnetic configuration is defined by a magnetic coil set with sufficient room for an island divertor, shielding and blanket solutions with tritium breeding ratios (TBR) above unity. An optimistic estimate for the gas-cooled solid breeder designed helium-cooled pebble bed is TBR $\sim 1.3$. Infinity Two satisfies the physics requirements of a stellarator fusion pilot plant.

Transport characteristics and predicted confinement are shown for the Infinity Two fusion pilot plant baseline plasma physics design, a high field stellarator concept developed using modern optimization techniques. Transport predictions are made using high-fidelity nonlinear gyrokinetic turbulence simulations along with drift kinetic neoclassical simulations. A pellet-fuelled scenario is proposed that enables supporting an edge density gradient to substantially reduce ion temperature gradient turbulence. Trapped electron mode turbulence is minimized through the quasi-isodynamic configuration that has been optimized with maximum-J. A baseline operating point with deuterium–tritium fusion power of $P_{{fus,DT}}=800$ MW with high fusion gain $Q_{{fus}}=40$ is demonstrated, respecting the Sudo density limit and magnetohydrodynamic stability limits. Additional higher power operating points are also predicted, including a fully ignited ($Q_{{fus}}=\infty$) case with $P_{{fus,DT}}=1.5$ GW. Pellet ablation calculations indicate it is plausible to fuel and sustain the desired density profile. Impurity transport calculations indicate that turbulent fluxes dominate neoclassical fluxes deep into the core, and it is predicted that impurity peaking will be smaller than assumed in the transport simulations. A path to access the large radiation fraction needed to satisfy exhaust requirements while sustaining core performance is also discussed.

The selection, design and optimization of a suitable blanket configuration for an advanced high-field stellarator concept is seen as a key feasibility issue and has been incorporated as a vital and necessary part of the Infinity Two fusion pilot plant physics basis. The focus of this work was to identify a baseline blanket which can be rapidly deployed for Infinity Two while also maintaining flexibility and opportunities for higher performing concepts later in development. Results from this analysis indicate that gas-cooled solid breeder designs such as the helium-cooled pebble bed (HCPB) are the most promising concepts, primarily motivated by the neutronics performance at applicable blanket build depths, and the relatively mature technology basis. The lithium lead (PbLi) family of concepts, particularly the dual-cooled lithium lead, offer a compelling alternative to solid blanket concepts as they have synergistic developmental pathways while simultaneously mitigating much of the technical risk of those designs. Homogenized three-dimensional neutronics analysis of the Infinity Two configuration indicates that the HCPB achieves an adequate tritium breeding ratio (TBR) (1.30 which enables sufficient margin at low engineering fidelity), and near appropriate shielding of the magnets (average fast fluence of 1.3 ${\times}$ 10$^{18}$ n cm$^{-2}$ per full-power year). The thermal analysis indicates that reasonably high thermal efficiencies (greater than 30 %) are readily achievable with the HCPB paired with a simple Rankine cycle using reheat. Finally, the tritium fuel cycle analysis for Infinity Two shows viability, with anticipated operational inventories of less than one kilogram (approximately 675 g) and a required TBR (TBR$_{\textrm {req}}$) of less than 1.05 to maintain fuel self-sufficiency (approximately 1.023 for a driver blanket with no inventory doubling). Although further optimization and engineering design are still required, at the physics basis stage all initial targets have been met for the Infinity Two configuration.

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.

This contribution focuses on the abatement with hydrogen of CO2 and non-CO2 emissions. It is agenda-setting in two respects. Firstly, it challenges the globally accepted hydrocarbon sustainable aviation fuel (SAF) pathway to sustainability and recommends that our industry accelerates along the hydrogen pathway to ‘green’ aviation. Secondly, it reports a philosophical and analytical investigation of appropriate accuracy on abatement strategies for nitrogen oxides and contrails of large hydrogen airliners. For the second contribution, a comparison is made of nitrogen oxide emissions and contrail avoidance options of two hydrogen airliners and a conventional airliner of similar passenger capacity. The hydrogen aircraft are representative of the first and second innovation waves where the main difference is the weight of the hydrogen tanks. Flights of 1000, 2000, 4000 and 8000 nautical miles are explored. Cranfield’s state of the art simulators for propulsion system integration and gas turbine performance (Orion and Turbomatch) were used for this. There are two primary contributions to knowledge. The first is a new set of questions to be asked of SAF and hydrogen decarbonising features. The second is the quantification of the benefits from hydrogen on non-CO2 emissions. For the second generation of long-range hydrogen-fuelled aircraft having gas turbine propulsion, lighter tanks (needing less thrust and lower gas temperatures) are anticipated to reduce NOx emissions by over 20%; in the case of contrails, the preliminary findings indicate that regardless of the fuel, contrails could largely be avoided with fuel-burn penalties of a few per cent. Mitigating action is only needed for a small fraction of flights. For conventional aircraft this penalty results in more CO2, while for hydrogen aircraft the additional emission is water vapour. The conclusion is that our research community should continue to consider hydrogen as the key ‘greening’ option for aviation, notwithstanding the very significant costs of transition.

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.

Silcretes developed within the in situ regolith in the Barr Smith Range, Western Australia, were investigated using optical and electron-beam techniques. One of the cementing agents in these silcretes showed gel-like optical properties and had a variable aluminosilicate chemical composition at the scale of electron microprobe analysis so that it might be considered as allophane-like material. High resolution transmission electron microscopy demonstrated that the material consists of a fine-grained and poorly ordered kaolinite embedded in a matrix of amorphous silica.

Diagnostic stewardship seeks to improve ordering, collection, performance, and reporting of tests. Test results play an important role in reportable HAIs. The inclusion of HAIs in public reporting and pay for performance programs has highlighted the value of diagnostic stewardship as part of infection prevention initiatives. Inappropriate testing should be discouraged, and approaches that seek to alter testing solely to impact a reportable metric should be avoided. HAI definitions should be further adapted to new testing technologies, with focus on actionable and clinically relevant test results that will improve patient care.

We have employed the VULCAN laser facility to generate a laser plasma X-ray source for use in photoionization experiments. A nanosecond laser pulse with an intensity of order 1015 Wcm−2 was used to irradiate thin Ag or Sn foil targets coated onto a parylene substrate, and the L-shell emission in the 3.3–4.4 keV range was recorded for both the laser-irradiated and nonirradiated sides. Both the experimental and simulation results show higher laser to X-ray conversion yields for Ag compared with Sn, with our simulations indicating yields approximately a factor of two higher than those found in the experiments. Although detailed angular data were not available experimentally, the simulations indicate that the emission is quite isotropic on the laser-irradiated side but shows close to a cosine variation on the nonirradiated side of the target as seen experimentally in the previous work.

Twenty-nine exotic common bean germplasms and three elite cultivars were examined for phenotypic diversity in two bean-producing environments (Kanpur and Shimla) across three winter seasons and one rainy season. The estimate of genetic variability parameters revealed that the exotic bean germplasm has enough diversity for all the evaluated features. The highest genotypic and phenotypic coefficients of variation were found in seed yield, followed by 100-seed weight, pods per plant and pod length. Furthermore, seed yield was the most heritable and genetically advanced quantitative feature, followed by 100-seed weight, pod length and pods per plant. According to a trait association study, the days to maturity of phenological traits have a strong positive correlation with the days to initial flowering and the days to 50% flowering. Pods per plant and seeds per pod most strongly influence increased grain yield. The first two principal components accounted for 63.3% of the variation and demonstrated significant diversity among exotic bean lines for the traits studied, according to the principal component analysis. According to the hierarchical clustering analysis, 29 accessions and three cultivars were divided into three groups. Cluster I contains early flowering and maturing accessions, while cluster III contains high pods per plant and an increased grain yield of germplasms. The fundamental source of phenological fluctuations in both environmental circumstances is temperature. This study found four genetically divergent and stable performance accessions, including EC932021, EC932189 (earliness), and EC931452, EC931971 (high grain yield), which may aid in the establishment of a bean breeding programme.

In Denmark and Sweden, surveys were undertaken to estimate the prevalence of leg problems in conventional broiler production. The Danish survey included 28 Ross 208 flocks, and the Swedish survey included 15 Ross 208 and 16 Cobb flocks. Leg problems included reduced walking ability (gait), tibial dyschondroplasia (TD), varus/valgus deformations (VV) and foot-pad dermatitis (FPD). Danish Ross chicks showed a significantly higher prevalence of gait score > 0, gait score > 2 and TD, but a lower prevalence of VV, than Swedish Ross chicks. Cobb chicks showed a significantly higher prevalence of gait score > 0, gait score > 2 and TD than Swedish Ross chicks, a significantly higher prevalence of VV than Danish Ross chicks, and a significantly lower prevalence of FPD than both Danish and Swedish Ross chicks. The two genotypes of Swedish chicks showed similar relationships between body weight and probability of gait score > 0, TD and VV, indicating that the difference in prevalence of these leg problems may be due to the difference in mean body weight at slaughter age. At body weights below 2300 g, Danish chicks showed a higher probability of gait score > 2 than Swedish chicks. Furthermore, at body weights below 1900 g, Danish chicks had a higher probability of TD than Swedish chicks, whereas at body weights above 2200 g they had a lower probability of TD. This indicates that the difference in prevalence of TD between Danish and Swedish chicks was due to differences in mean body weight at slaughter age as well as housing conditions. Therefore, further studies on the risk factors in relation to management and housing conditions are required.

The fossil record of treeshrews, hedgehogs, and other micromammals from the Lower Siwaliks of India is sparse. Here, we report on a new genus and species of fossil treeshrew, specimens of the hedgehog Galerix, and other micromammals from the middle Miocene (Lower Siwalik) deposits surrounding Ramnagar (Udhampur District, Jammu and Kashmir), at a fossil locality known as Dehari. The treeshrew from Dehari (Sivatupaia ramnagarensis n. gen. n. sp.) currently represents the oldest record of fossil tupaiids in the Siwaliks, extending their time range by ca. 2.5–4.0 Myr in the region. Dietary analyses suggest that the new tupaiid was likely adapted for a less mechanically challenging or more frugivorous diet compared to other extant and fossil tupaiids. The occurrence of Galerix has only been recently documented from the Indian Siwaliks and the Dehari specimens help establish the likely presence of a relatively large Siwalik Galerix species in the Ramnagar region. In addition to the new treeshrew and hedgehogs, new specimens of the rodents Kanisamys indicus, Sayimys sivalensis, and Murinae indet. from Dehari help confirm that age estimates for the Ramnagar region are equivalent to the Chinji Formation in Pakistan, most likely corresponding to the middle to upper part of the Chinji Formation.

UUID: http://zoobank.org/56fb160c-2df8-4cd3-be91-af4dc02d0979

Yarkoni's analysis clearly articulates a number of concerns limiting the generalizability and explanatory power of psychological findings, many of which are compounded in infancy research. ManyBabies addresses these concerns via a radically collaborative, large-scale and open approach to research that is grounded in theory-building, committed to diversification, and focused on understanding sources of variation.

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.

Meeting the complex demands of conservation requires a multi-skilled workforce operating in a sector that is respected and supported. Although professionalization of conservation is widely seen as desirable, there is no consistent understanding of what that entails. Here, we review whether and how eight elements of professionalization observed in other sectors are applicable to conservation: (1) a defined and respected occupation; (2) official recognition; (3) knowledge, learning, competences and standards; (4) paid employment; (5) codes of conduct and ethics; (6) individual commitment; (7) organizational capacity; and (8) professional associations. Despite significant achievements in many of these areas, overall progress is patchy, and conventional concepts of professionalization are not always a good fit for conservation. Reasons for this include the multidisciplinary nature of conservation work, the disproportionate influence of elite groups on the development and direction of the profession, and under-representation of field practitioners and of Indigenous peoples and local communities with professional-equivalent skills. We propose a more inclusive approach to professionalization that reflects the full range of practitioners in the sector and the need for increased recognition in countries and regions of high biodiversity. We offer a new definition that characterizes conservation professionals as practitioners who act as essential links between conservation action and conservation knowledge and policy, and provide seven recommendations for building a more effective, inclusive and representative profession.