Addressing patient treatment preferences at trial recruitment.

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Development and validation of a RAD-Seq target-capture based genotyping assay for routine application in advanced black tiger shrimp (Penaeus monodon) breeding programs

Background: The development of genome-wide genotyping resources has provided terrestrial livestock and crop industries with the unique ability to accurately assess genomic relationships between individuals, uncover the genetic architecture of commercial traits, as well as identify superior individuals for selection based on their specific genetic profile. Utilising recent advancements in de-novo genome-wide genotyping technologies, it is now possible to provide aquaculture industries with these same important genotyping resources, even in the absence of existing genome assemblies. Here, we present the development of a genome-wide SNP assay for the Black Tiger shrimp (Penaeus monodon) through utilisation of a reduced-representation whole-genome genotyping approach (DArTseq). Results: Based on a single reduced-representation library, 31,262 polymorphic SNPs were identified across 650 individuals obtained from Australian wild stocks and commercial aquaculture populations. After filtering to remove SNPs with low read depth, low MAF, low call rate, deviation from HWE, and non-Mendelian inheritance, 7542 high-quality SNPs were retained. From these, 4236 high-quality genome-wide loci were selected for baits-probe development and 4194 SNPs were included within a finalized target-capture genotype-by-sequence assay (DArTcap). This assay was designed for routine and cost effective commercial application in large scale breeding programs, and demonstrates higher confidence in genotype calls through increased call rate (from 80.2 ± 14.7 to 93.0% ± 3.5%), increased read depth (from 20.4 ± 15.6 to 80.0 ± 88.7), as well as a 3-fold reduction in cost over traditional genotype-by-sequencing approaches. Conclusion: Importantly, this assay equips the P. monodon industry with the ability to simultaneously assign parentage of communally reared animals, undertake genomic relationship analysis, manage mate pairings between cryptic family lines, as well as undertake advance studies of genome and trait architecture. Critically this assay can be cost effectively applied as P. monodon breeding programs transition to undertaking genomic selection

Direct observations of electrochemically induced intergranular cracking in polycrystalline NMC811 particles

Establishing the nature of crack generation, formation, and propagation is paramount to understanding the degradation modes that govern decline in battery performance. Cracking has several possible origins; however, it can be classified in two general cases: mechanically induced, during manufacturing, or electrochemically induced, during operation. Accurate and repeatable tracking of operational cracking to sequentially image the same material as it undergoes cracking is highly challenging; observing these features requires the highest resolutions possible for 3D imaging techniques, necessitating very small sample geometry, while also achieving realistic electrochemical performance. Here, we present a technique in which particle cracking can be completely attributed to electrochemical stimulation via sequential ex situ imaging in a laboratory X-ray nano computed tomography (CT) instrument. This technique preserves the mechanical and electrochemical response of each particle without inducing damage in the particles except for the effects of high voltage. Significant cracking within the core of secondary particles was observed upon the electrochemical delithiation of NMC811, which propagated radially. As X-ray computed tomography allows for imaging of the particle cores, the particles were not required to be modified/milled, guaranteeing any synthesis induced strain in the particles was maintained during the whole technique, resulting in an observation that contrasts crystallographic data, suggesting a significant volume expansion of the secondary particles

Direct observations of electrochemically induced intergranular cracking in polycrystalline NMC811 particles

Establishing the nature of crack generation, formation, and propagation is paramount to understanding the degradation modes that govern decline in battery performance. Cracking has several possible origins; however, it can be classified in two general cases: mechanically induced, during manufacturing, or electrochemically induced, during operation. Accurate and repeatable tracking of operational cracking to sequentially image the same material as it undergoes cracking is highly challenging; observing these features requires the highest resolutions possible for 3D imaging techniques, necessitating very small sample geometry, while also achieving realistic electrochemical performance. Here, we present a technique in which particle cracking can be completely attributed to electrochemical stimulation via sequential ex situ imaging in a laboratory X-ray nano computed tomography (CT) instrument. This technique preserves the mechanical and electrochemical response of each particle without inducing damage in the particles except for the effects of high voltage. Significant cracking within the core of secondary particles was observed upon the electrochemical delithiation of NMC811, which propagated radially. As X-ray computed tomography allows for imaging of the particle cores, the particles were not required to be modified/milled, guaranteeing any synthesis induced strain in the particles was maintained during the whole technique, resulting in an observation that contrasts crystallographic data, suggesting a significant volume expansion of the secondary particles

Men's experiences of radiotherapy treatment for localized prostate cancer and its long-term treatment side effects: a longitudinal qualitative study.

PURPOSE: To investigate men's experiences of receiving external-beam radiotherapy (EBRT) with neoadjuvant Androgen Deprivation Therapy (ADT) for localized prostate cancer (LPCa) in the ProtecT trial. METHODS: A longitudinal qualitative interview study was embedded in the ProtecT RCT. Sixteen men with clinically LPCa who underwent EBRT in ProtecT were purposively sampled to include a range of socio-demographic and clinical characteristics. They participated in serial in-depth qualitative interviews for up to 8 years post-treatment, exploring experiences of treatment and its side effects over time. RESULTS: Men experienced bowel, sexual, and urinary side effects, mostly in the short term but some persisted and were bothersome. Most men downplayed the impacts, voicing expectations of age-related decline, and normalizing these changes. There was some reticence to seek help, with men prioritizing their relationships and overall health and well-being over returning to pretreatment levels of function. Some unmet needs with regard to information about treatment schedules and side effects were reported, particularly among men with continuing functional symptoms. CONCLUSIONS: These findings reinforce the importance of providing universal clear, concise, and timely information and supportive resources in the short term, and more targeted and detailed information and care in the longer term to maintain and improve treatment experiences for men undergoing EBRT

Near-source passive sampling for monitoring viral outbreaks within a university residential setting

\ua9 2024 Cambridge University Press. All rights reserved. Wastewater based epidemiology (WBE) has proven to be a powerful tool for the population-level monitoring of pathogens, particularly SARS-CoV-2. For accurate and timely assessment, several wastewater sampling regimes and methods of viral concentration have been investigated, mainly targeting SARS-CoV-2. However, the use of passive samplers in near-source environments for a range of viruses in wastewater is yet under-investigated. To address this, near-source passive samples were taken at four locations targeting student halls of residence. These were chosen as an exemplar due to their high population density and perceived risk of disease transmission. Viruses investigated were SARS-CoV-2 and its variants of concern (VOCs), influenza-A and B viruses and enteroviruses. Sampling was conducted either in the morning, where passive samplers were in place overnight (17 h) and during the day, where samplers remained in the sewer for 7 h. We demonstrated the usefulness of near-source passive sampling for the detection of VOCs using qPCR and Next Generation Sequencing. Furthermore, several outbreaks of influenza-A and sporadic outbreaks of enteroviruses (some associated with enterovirus D68 and coxsackieviruses) were identified amongst the resident student population, providing evidence of the usefulness of near-source, in-sewer sampling for monitoring the health of high population density communities

Multiscale dynamics of charging and plating in graphite electrodes coupling operando microscopy and phase-field modelling

The phase separation dynamics in graphitic anodes significantly affects lithium plating propensity, which is the major degradation mechanism that impairs the safety and fast charge capabilities of automotive lithium-ion batteries. In this study, we present comprehensive investigation employing operando high-resolution optical microscopy combined with non-equilibrium thermodynamics implemented in a multi-dimensional (1D+1D to 3D) phase-field modeling framework to reveal the rate-dependent spatial dynamics of phase separation and plating in graphite electrodes. Here we visualize and provide mechanistic understanding of the multistage phase separation, plating, inter/intra-particle lithium exchange and plated lithium back-intercalation phenomena. A strong dependence of intra-particle lithiation heterogeneity on the particle size, shape, orientation, surface condition and C-rate at the particle level is observed, which leads to early onset of plating spatially resolved by a 3D image-based phase-field model. Moreover, we highlight the distinct relaxation processes at different state-of-charges (SOCs), wherein thermodynamically unstable graphite particles undergo a drastic intra-particle lithium redistribution and inter-particle lithium exchange at intermediate SOCs, whereas the electrode equilibrates much slower at low and high SOCs. These physics-based insights into the distinct SOC-dependent relaxation efficiency provide new perspective towards developing advanced fast charge protocols to suppress plating and shorten the constant voltage regime

Direct activation of KCC2 arrests benzodiazepine refractory status epilepticus and limits the subsequent neuronal injury in mice

Hyperpolarizing GABAAR currents, the unitary events that underlie synaptic inhibition, are dependent upon efficient Cl− extrusion, a process that is facilitated by the neuronal specific K+/Cl− co-transporter KCC2. Its activity is also a determinant of the anticonvulsant efficacy of the canonical GABAAR-positive allosteric: benzodiazepines (BDZs). Compromised KCC2 activity is implicated in the pathophysiology of status epilepticus (SE), a medical emergency that rapidly becomes refractory to BDZ (BDZ-RSE). Here, we have identified small molecules that directly bind to and activate KCC2, which leads to reduced neuronal Cl− accumulation and excitability. KCC2 activation does not induce any overt effects on behavior but prevents the development of and terminates ongoing BDZ-RSE. In addition, KCC2 activation reduces neuronal cell death following BDZ-RSE. Collectively, these findings demonstrate that KCC2 activation is a promising strategy to terminate BDZ-resistant seizures and limit the associated neuronal injury

Bayesian paternity analysis and mating patterns in a parasitic nematode, Trichostrongylus tenuis

Mating behaviour is a fundamental aspect of the evolutionary ecology of sexually reproducing species, but one that has been under-researched in parasitic nematodes. We analysed mating behaviour in the parasitic nematode Trichostrongylus tenuis by performing a paternity analysis in a population from a single red grouse host. Paternity of the 150 larval offspring of 25 mothers (sampled from one of the two host caeca) was assigned among 294 candidate fathers (sampled from both caeca). Each candidate father's probability of paternity of each offspring was estimated from 10-locus microsatellite genotypes. Seventy-six (51%) offspring were assigned a father with a probability of >0.8, and the estimated number of unsampled males was 136 (95% credible interval (CI) 77-219). The probability of a male from one caecum fathering an offspring in the other caecum was estimated as 0.024 (95% CI 0.003-0.077), indicating that the junction of the caeca is a strong barrier to dispersal. Levels of promiscuity (defined as the probability of two of an adult's offspring sharing only one parent) were high for both sexes. Variance in male reproductive success was moderately high, possibly because of a combination of random mating and high variance in post-copulatory reproductive success. These results provide the first data on individual mating behaviour among parasitic nematodes