The NHS England Jewish BRCA Testing Programme: overview after first year of implementation (2023-2024).

Background: The NHS Jewish BRCA Testing Programme is offering germline and genetic testing to people with ≥1 Jewish grandparent. Who have an increased likelihood of having an Ashkenazi Jewish (AJ) founder germline pathogenic variant (gPV) compared with the general population.Testing is offered via a self-referral, home-based saliva sampling pathway, supported by a genetic counsellor telephone helpline.

f-Block hydride complexes - synthesis, structure and reactivity.

Complexes formed between the heaviest and lightest elements in the periodic table yield the f-block hydrides, a unique class of compounds with wide-ranging utility and interest, from catalysis to light-responsive materials and nuclear waste storage. Recent developments in syntheses and analytics, such as exploiting low-oxidation state metal ions and improvements in X-ray diffraction tools, have transformed our ability to understand, access and manipulate these important species. This perspective brings together insights from binary metal hydrides, with molecular solution phase studies on heteroleptic complexes and gas phase investigations.

Investigating and Quantifying Molecular Complexity Using Assembly Theory and Spectroscopy.

Current approaches to evaluate molecular complexity use algorithmic complexity, rooted in computer science, and thus are not experimentally measurable. Directly evaluating molecular complexity could be used to study directed vs undirected processes in the creation of molecules, with potential applications in drug discovery, the origin of life, and artificial life. Assembly theory has been developed to quantify the complexity of a molecule by finding the shortest path to construct the molecule from building blocks, revealing its molecular assembly index (MA).

Aqueous solutions of super reduced polyoxotungstates as electron storage systems.

Due to the increasing energy density demands of battery technology, it is vital to develop electrolytes with high electron storage capacity. Polyoxometalate (POM) clusters can act as electron sponges, storing and releasing multiple electrons and have potential as electron storage electrolytes for flow batteries. Despite this rational design of clusters for high storage ability can not yet be achieved as little is known about the features influencing storage ability.

Modulations of right hemisphere connectivity in young children relates to the perception of spoken words.

The early school years shape a young brain's capability to comprehend and contextualize words within milliseconds of exposure. Parsing word sounds (phonological interpretation) and word recognition (enabling semantic interpretation) are integral to this process. Yet little is known about the causal mechanisms of cortical activity during these early developmental stages.

Automated Library Generation and Serendipity Quantification Enables Diverse Discovery in Coordination Chemistry.

Library generation experiments are a key part of the discovery of new materials, methods, and models in chemistry, but the question of how to generate high quality libraries to enable discovery is nontrivial. Herein, we use coordination chemistry to demonstrate the automation of many of the workflows used for library generation in automated hardware including the Chemputer. First, we explore the target-oriented synthesis of three influential coordination complexes, to validate key synthetic operations in our system; second, the generation of focused libraries in chemical and process space; and third, the development of a new workflow for prospecting library formation.

Water-soluble Self-assembled {Pd } Polyoxopalladate Nano-wheel as a Supramolecular Host.

Polyoxopalladates (POPs) are a class of self-assembling palladium-oxide clusters that span a variety of sizes, shapes and compositions. The largest of this family, {Pd } , is constructed from 14 building units of {Pd } and lined on the inner and outer torus by 28 acetate ligands. Due to its high water solubility, large hydrophobic cavity and distinct H NMR fingerprint {Pd } is an ideal molecule for exploring supramolecular behaviour with small organic molecules in aqueous media.

Engineering Highly Reduced Molybdenum Polyoxometalates via the Incorporation of d and f Block Metal Ions.

The assembly of nanoscale polyoxometalate (POM) clusters has been dominated by the highly reduced icosahedral {Mo } "browns" and the toroidal {Mo } "blues" which are 45 % and 18 % reduced, respectively. We hypothesised that there is space for a greater diversity of structures in this immediate reduction zone. Here we show it is possible to make highly reduced mix-valence POMs by presenting new classes of polyoxomolybdates: [Mo Mo H O ] {Mo } and [Mo Mo H O ] {Mo }, 81 % and 57 % reduced, respectively.

Facile and Reproducible Electrochemical Synthesis of the Giant Polyoxomolybdates.

Giant polyoxomolybdates are traditionally synthesized by chemical reduction of molybdate in aqueous solutions, generating complex nanostructures such as the highly symmetrical spherical {Mo} and {Mo}, ring-shaped {Mo} and {Mo}, and the gigantic protein sized {Mo}, which combines both positive and negative curvature. These complex polyoxometalates are known to be highly sensitive to reaction conditions and are often difficult to reproduce, especially {Mo}, which is often produced in yields far below 1%, meaning further investigation has always been limited. While the electrochemical properties of these materials have been studied, their electrochemical synthesis has not been explored.

Chemputation and the Standardization of Chemical Informatics.

The explosion in the use of machine learning for automated chemical reaction optimization is gathering pace. However, the lack of a standard architecture that connects the concept of chemical transformations universally to software and hardware provides a barrier to using the results of these optimizations and could cause the loss of relevant data and prevent reactions from being reproducible or unexpected findings verifiable or explainable. In this Perspective, we describe how the development of the field of digital chemistry or chemputation, that is the universal code-enabled control of chemical reactions using a standard language and ontology, will remove these barriers allowing users to focus on the chemistry and plug in algorithms according to the problem space to be explored or unit function to be optimized.

Exploring the Geometric Space of Metal-Organic Polyhedrons (MOPs) of Metal-Oxo Clusters.

Metal organic polyhedra (MOPs) such as coordination cages and clusters are increasingly utilized across many fields, but their geometrically selective assembly during synthesis is nontrivial. When ligand coordination along these polyhedral edges is arranged in an unsymmetrical mode or the bridging ligand itself is nonsymmetric, a vast combinatorial space of potential isomers exists complicating formation and isolation. Here we describe two generalizable combinatorial methodologies to explore the geometrical space and enumerate the configurational isomers of MOPs with discrimination of the chiral and achiral structures.

Enantioselective Recognition of Racemic Amino Alcohols in Aqueous Solution by Chiral Metal-Oxide Keplerate {Mo } Cluster Capsules.

Determining the relative configuration or enantiomeric excess of a substance may be achieved using NMR spectroscopy by employing chiral shift reagents (CSRs). Such reagents interact noncovalently with the chiral solute, resulting in each chiral form experiencing different magnetic anisotropy; this is then reflected in their NMR spectra. The Keplerate polyoxometalate (POM) is a molybdenum-based, water-soluble, discrete inorganic structure with a pore-accessible inner cavity, decorated by differentiable ligands.

Peptide sequence mediated self-assembly of molybdenum blue nanowheel superstructures.

The precise control over the formation of complex nanostructures, polyoxometalates (POMs), at the sub-nanoscale is challenging but critical if non-covalent architectures are to be designed. Combining biologically-evolved systems with inorganic nanostructures could lead to sequence-mediated assembly. Herein, we exploit oligopeptides as multidentate structure-directing ligands metal-coordination and hydrogen bonded interactions to modulate the self-assembly of POM superstructures.

Elucidating the paramagnetic interactions of an inorganic-organic hybrid radical-functionalized Mn-Anderson cluster.

A family of six polyoxometalate-based magnetic compounds were synthesized by anchoring N-oxide type TEMPO radicals onto an Anderson type polyoxometalate cluster. The complexes were structurally characterised by single crystal X-ray diffraction and the intramolecular paramagnetic interactions between TEMPO radicals and Mn ions of the resulting hybrids were investigated in detail by electron paramagnetic resonance and the Evans NMR method.

Cu(OTf) -Mediated Cross-Coupling of Nitriles and N-Heterocycles with Arylboronic Acids to Generate Nitrilium and Pyridinium Products*.

Metal-catalyzed C-N cross-coupling generally forms C-N bonds by reductive elimination from metal complexes bearing covalent C- and N-ligands. We have identified a Cu-mediated C-N cross-coupling that uses a dative N-ligand in the bond-forming event, which, in contrast to conventional methods, generates reactive cationic products. Mechanistic studies suggest the process operates via transmetalation of an aryl organoboron to a Cu complex bearing neutral N-ligands, such as nitriles or N-heterocycles.

Reactivity, Formation, and Solubility of Polyoxometalates Probed by Calorimetry.

Room temperature calorimetry methods were developed to describe the energy landscapes of six polyoxometalates (POMs), Li-U, Li-U, K-U, Li/K-U, Mo, and Mo, in terms of three components: enthalpy of dissolution (Δ), enthalpy of formation of aqueous POMs (Δ), and enthalpy of formation of POM crystals (Δ). Δ is controlled by a combination of cation solvation enthalpy and the favorability of cation interactions with binding sites on the POM. In the case of the four uranyl peroxide POMs studied, clusters with hydroxide bridges have lower Δ and are more stable than those containing only peroxide bridges.

A Modular Programmable Inorganic Cluster Discovery Robot for the Discovery and Synthesis of Polyoxometalates.

The exploration of complex multicomponent chemical reactions leading to new clusters, where discovery requires both molecular self-assembly and crystallization, is a major challenge. This is because the systematic approach required for an experimental search is limited when the number of parameters in a chemical space becomes too large, restricting both exploration and reproducibility. Herein, we present a synthetic strategy to systematically search a very large set of potential reactions, using an inexpensive, high-throughput platform that is modular in terms of both hardware and software and is capable of running multiple reactions with in-line analysis, for the automation of inorganic and materials chemistry.

Synthesis, Assembly, and Sizing of Neutral, Lanthanide Substituted Molybdenum Blue Wheels {MoLn}.

Polyoxometalate molybdenum blue (MB) complexes typically exist as discrete multianionic clusters and are composed of repeating Mo building units. MB wheels such as {Mo} and {Mo} are made from pentagon-centered {Mo} building blocks joined by equal number of {Mo} units as loin, and {Mo} dimer units as skirt along the ring edge, with the ring sizes of the MB wheels modulated by the {Mo} units. Herein we report a new class of contracted lanthanide-doped MB structures that have replaced all the {Mo} units with lanthanide ions on the inner rim, giving the general formula {MoLn}.

An Autonomous Chemical Robot Discovers the Rules of Inorganic Coordination Chemistry without Prior Knowledge.

We present a chemical discovery robot for the efficient and reliable discovery of supramolecular architectures through the exploration of a huge reaction space exceeding ten billion combinations. The system was designed to search for areas of reactivity found through autonomous selection of the reagent types, amounts, and reaction conditions aiming for combinations that are reactive. The process consists of two parts where reagents are mixed together, choosing from one type of aldehyde, one amine and one azide (from a possible family of two amines, two aldehydes and four azides) with different volumes, ratios, reaction times, and temperatures, whereby the reagents are passed through a copper coil reactor.

Embedding alkenes within an icosahedral inorganic fullerene {(NH)[MoO(L)(HO)]} for trapping volatile organics.

Eight alkene-functionalized molybdenum-based spherical Keplerate-type (inorganic fullerene) structures have been obtained both direct and multistep synthetic approaches. Driven by the opportunity to design unique host-guest interactions within hydrophobic, π-electron rich confined environments, we have synthesised {(NH)[MoO(L)(HO)]}, where L = () acrylic acid, () crotonic acid, () methacrylic acid, () tiglic acid, () 3-butenoic acid, () 4-pentenoic acid, () 5-hexenoic acid, and () sorbic acid. The compounds, which are obtained in good yield (10-40%), contain 30 carboxylate-coordinated alkene ligands which create a central cavity with hydrophobic character.

Donkey Nutrition and Malnutrition.

The domestic donkey is a unique equid species with specific nutritional requirements. This article examines the importance of feeding strategies that mimic the donkey's natural environment using poor nutritional quality fibers and access to browsing materials. The relationship between nutrition and health is examined and practical approaches to the healthy and sick donkey are discussed.

Reading Development in Children With Cochlear Implants Who Communicate via Spoken Language: A Psycholinguistic Investigation.

Purpose This study sought to comprehensively examine the reading skills and subskills of children with cochlear implants (CIs) and gain insight into the processes underlying their early reading development. Method Fourteen 6- to 9-year-old children with CIs were assessed on a range of reading and spoken language measures. Their performances were compared to a control group of 31 children with normal hearing (NH) of the same chronological and mental age.

Semantic processing in children with cochlear implants: Evidence from event-related potentials.

: Existing research has shown that children with significant hearing loss who use cochlear implants (CIs) perform worse than their hearing peers on behavioral measures of spoken language. The present study sought to examine how children with CIs process lexical-semantic incongruence, as indexed by electrophysiological evidence of the N400 effect. : Twelve children with CIs, aged between 6 and 9 years, participated in a spoken word-picture matching task while event-related potentials (ERPs) were recorded.

Spelling in Children With Cochlear Implants: Evidence of Underlying Processing Differences.

This study compared the spelling skills and sub-skills of young children with cochlear implants (CIs) who use spoken language only (n = 14) with those of a same-aged typically hearing (TH) control group (n = 30). Spelling accuracy was assessed using irregular and nonsense word stimuli. Error and regression analyses were conducted to provide insight into the phonological and orthographic spelling strategies used by each group.

Uranyl to Uranium(IV) Conversion through Manipulation of Axial and Equatorial Ligands.

The controlled manipulation of the axial oxo and equatorial halide ligands in the uranyl dipyrrin complex, UOCl(L), allows the uranyl reduction potential to be shifted by 1.53 V into the range accessible to naturally occurring reductants that are present during uranium remediation and storage processes. Abstraction of the equatorial halide ligand to form the uranyl cation causes a 780 mV positive shift in the U/U reduction potential.