Explore the vast range of titles available.

COSINE is a dark matter search experiment based on an array of low background NaI(Tl) crystals located at the Yangyang underground laboratory. The assembly of COSINE-100 was completed in the summer of 2016 and the detector is currently collecting physics quality data aimed at reproducing the DAMA/LIBRA experiment that reported an annual modulation signal. Stable operation has been achieved and will continue for at least 2 years. Here, we describe the design of COSINE-100, including the shielding arrangement, the configuration of the NaI(Tl) crystal detection elements, the veto systems, and the associated operational systems, and we show the current performance of the experiment.

The COSINE-100 dark matter search experiment is an array of NaI(Tl) crystal detectors located in the Yangyang Underground Laboratory (Y2L). To understand measured backgrounds in the NaI(Tl) crystals we have performed Monte Carlo simulations using the Geant4 toolkit and developed background models for each crystal that consider contributions from both internal and external sources, including cosmogenic nuclides. The background models are based on comparisons of measurement data with Monte Carlo simulations that are guided by a campaign of material assays and are used to evaluate backgrounds and identify their sources. The average background level for the six crystals (70 kg total mass) that are studied is 3.5 counts/day/keV/kg in the (2–6) keV energy interval. The dominant contributors in this energy region are found to be 210Pb and 3H.

Background Patients with incurable head and neck cancer (HNC) face complex care pathways, significant symptom burdens and psychosocial challenges. The complexity of symptoms, disease trajectory and the centralised, but often inequitable, services frequently lead to the patients’ and caregivers’ needs for support and care not being fully met. To address this gap, this study adopts a co-design approach, where patients, caregivers, and professionals collaborate to develop solutions that address service issues, aligning with the needs and priorities of both patients and caregivers. Methods This qualitative exploration of co-design processes involved patients, caregivers, and healthcare professionals (HCPs) participating in one online and two in-person multi-stakeholder co-design workshops in Sheffield, UK. Patient vignettes were developed to illustrate typical care journeys and ‘stress points’ in service interactions. These vignettes were shared with 13 participants, including patients with lived experience of head and neck cancer, family caregivers, specialist nurses, and allied HCPs, to identify areas for improvement and co-develop potential solutions using prioritisation activities, group concept mapping, and facilitated group discussions. Results During the first in-person workshop, co-design participants (co-designers) identified and prioritised critical stress points in the care pathway, including a lack of support in caregivers’ preparedness and challenges navigating healthcare systems (specifically contacting the clinical team). Using these findings, the co-designers proposed various solutions, including introducing a single point of contact (care navigator) or a printed version of a personalised ‘roadmap’ of services, instituting a multidisciplinary discharge planning process to aid transitions to home care and implementing a dedicated 24-hour helpline staffed by knowledgeable personnel (HNC specialist staff) to provide patients with information. Conclusion The co-design workshops have developed practical, user-informed intervention solutions to address the specific navigation challenges faced by people with incurable HNC. While the interventions developed are relevant in many ways to the broader HNC care pathway, they are particularly relevant to the complex needs of this group and are now guiding the next phase of interventions for improving patient-centred services.

The recent advancement of high-intensity lasers has made all-optical Compton scattering become a promising way to produce ultrashort brilliant γ-rays in an ultra-compact system. However, so far achieved Compton γ-ray sources are limited by low conversion efficiency and spectral intensity. Here we present a highly efficient gamma photon emitter obtained by irradiating a high-intensity laser pulse on a miniature plasma device consisting of a plasma lens and a plasma mirror. This concept exploits strong spatiotemporal laser-shaping process and high-charge electron acceleration process in the plasma lens, as well as an efficient nonlinear Compton scattering process enabled by the plasma mirror. Our full three-dimensional particle-in-cell simulations demonstrate that in this novel scheme, brilliant γ-rays with very high conversion efficiency (higher than 10−2) and spectral intensity (∼109 photons 0.1 % BW ) can be achieved by employing currently available petawatt-class lasers with intensity of 1021 W cm−2. Such efficient and intense γ-ray sources would find applications in wide-ranging areas.

The aim of the current study was to identify which subgroups of children with Attention Deficit Hyperactivity Disorder (ADHD) benefitted the most from playing a Serious Game (SG) intervention shown in a randomized trial to improve behavioral outcomes. Pre-intervention characteristics [i.e., gender, age, intellectual level of functioning, medication use, computer experience, ADHD subtype, severity of inattention problems, severity of hyperactivity/impulsivity problems, comorbid Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) symptoms] were explored as potential moderators in a Virtual Twins (VT) analysis to identify subgroups for whom the SG intervention was most effective. Primary outcome measures were parent-reported time management, planning/organizing and cooperation skills. Two subgroups were identified. Girls (n = 26) were identified as the subgroup that was most likely to show greater improvements in planning/organizing skills as compared to the estimated treatment effect of the total group of participants. Furthermore, among the boys, those (n = 47) with lower baseline levels of hyperactivity and higher levels of CD symptoms showed more improvements in their planning/organizing skills when they played the SG intervention as compared to the estimated treatment effect of the total group of participants. Using a VT analysis two subgroups of children with ADHD, girls, and boys with both higher levels of CD and lower levels of hyperactivity, were identified. These subgroups mostly benefit from playing the SG intervention developed to improve ADHD related behavioral problems. Our results imply that these subgroups have a higher chance of treatment success.

Self monitoring, personal goal-setting and coaching, education and social support are strategies to help patients with chronic conditions in their daily care. Various tools have been developed, e.g., mobile digital coaching systems connected with wearable sensors, serious games and patient web portals to personal health records, that aim to support patients with chronic conditions and their caregivers in realizing the ideal of self-management. We describe a platform that integrates these tools to support young patients in diabetes self-management through educational game playing, monitoring and motivational feedback. We describe the design of the platform referring to principles from healthcare, persuasive system design and serious game design. The virtual coach is a game guide that can also provide personalized feedback about the user’s daily care related activities which have value for making progress in the game world. User evaluations with patients under pediatric supervision revealed that the use of mobile technology in combination with web-based elements is feasible but some assumptions made about how users would connect to the platform were not satisfied in reality, resulting in less than optimal user experiences. We discuss challenges with suggestions for further development of integrated pervasive coaching and gamification platforms in medical practice.

The need for accessible and motivating treatment approaches within mental health has led to the development of an Internet-based serious game intervention (called \"Plan-It Commander\") as an adjunct to treatment as usual for children with attention-deficit/hyperactivity disorder (ADHD). The aim was to determine the effects of Plan-It Commander on daily life skills of children with ADHD in a multisite randomized controlled crossover open-label trial. Participants (N=170) in this 20-week trial had a diagnosis of ADHD and ranged in age from 8 to 12 years (male: 80.6%, 137/170; female: 19.4%, 33/170). They were randomized to a serious game intervention group (group 1; n=88) or a treatment-as-usual crossover group (group 2; n=82). Participants randomized to group 1 received a serious game intervention in addition to treatment as usual for the first 10 weeks and then received treatment as usual for the next 10 weeks. Participants randomized to group 2 received treatment as usual for the first 10 weeks and crossed over to the serious game intervention in addition to treatment as usual for the subsequent 10 weeks. Primary (parent report) and secondary (parent, teacher, and child self-report) outcome measures were administered at baseline, 10 weeks, and 10-week follow-up. After 10 weeks, participants in group 1 compared to group 2 achieved significantly greater improvements on the primary outcome of time management skills (parent-reported; P=.004) and on secondary outcomes of the social skill of responsibility (parent-reported; P=.04), and working memory (parent-reported; P=.02). Parents and teachers reported that total social skills improved over time within groups, whereas effects on total social skills and teacher-reported planning/organizing skills were nonsignificant between groups. Within group 1, positive effects were maintained or further improved in the last 10 weeks of the study. Participants in group 2, who played the serious game during the second period of the study (weeks 10 to 20), improved on comparable domains of daily life functioning over time. Plan-It Commander offers an effective therapeutic approach as an adjunct intervention to traditional therapeutic ADHD approaches that improve functional outcomes in daily life. International Standard Randomized Controlled Trial Number (ISRCTN): 62056259; http://www.controlled-trials.com/ISRCTN62056259 (Archived by WebCite at http://www.webcitation.org/6eNsiTDJV).

Duck hepatitis was first reported in 1985 in Korea. The complete nucleotide sequence of two past Korean isolates, DHV-HS and DHV-HSS, isolated in 1994 and 1995, and four recent Korean isolates, AP-03337, AP-04009, AP-04114 and AP-04203 isolated in 2003 and 2004, were determined. Phylogenetic analysis using the 3D protein sequence confirmed that the previously characterized duck hepatitis virus type 1 strains and the six Korean isolates described here constitute a monophyletic group and form two clades/genotypes in which all except the four recent Korean isolates form one group (A) and the recent Korean isolates of 2003 and 2004 constitute a second group (B). Phylogenetic analysis of the VP1 protein supported the division into two different groups. Antisera raised against viruses of group A showed significant neutralizing cross-reaction against a member of the same genotype but not to a strain of group B and vice versa. These results demonstrated that the two genotypes also could be regarded as two different serotypes.

Hyaloperonospora arabidopsidis (Hpa) is an obligately biotrophic downy mildew that is routinely cultured on Arabidopsis thaliana hosts that harbour complex microbiomes. We hypothesized that the culturing procedure proliferates Hpa-associated microbiota (HAM) in addition to the pathogen and exploited this model system to investigate which microorganisms consistently associate with Hpa. Using amplicon sequencing, we found nine bacterial sequence variants that are shared between at least three out of four Hpa cultures in the Netherlands and Germany and comprise 34% of the phyllosphere community of the infected plants. Whole-genome sequencing showed that representative HAM bacterial isolates from these distinct Hpa cultures are isogenic and that an additional seven published Hpa metagenomes contain numerous sequences of the HAM. Although we showed that HAM benefit from Hpa infection, HAM negatively affect Hpa spore formation. Moreover, we show that pathogen-infected plants can selectively recruit HAM to both their roots and shoots and form a soil-borne infection-associated microbiome that helps resist the pathogen. Understanding the mechanisms by which infection-associated microbiomes are formed might enable breeding of crop varieties that select for protective microbiomes. Near-identical downy-mildew-associated microbiomes are recruited by infected Arabidopsis plants in different laboratories and reduce the impact of subsequent infection.

Emicizumab is a new treatment option for people with hemophilia A. Emicizumab was approved with a body‐weight‐based dosage regimen, without laboratory monitoring requirements. Guidelines, however, recommend measuring emicizumab concentrations when the presence of antidrug antibodies is suspected. Furthermore, drug monitoring can be useful in clinical decision making, in adherence checking, and for research purposes. Therefore, we developed a liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method for quantifying emicizumab. We performed a validation study on this LC‐MS/MS method quantifying emicizumab in the plasma of people with hemophilia A. Sample preparation for LC‐MS/MS analysis included ammonium sulfate protein precipitation and trypsin digestion. A signature peptide of emicizumab and a matching stable isotope‐labeled internal standard were used to quantify emicizumab by LC‐MS/MS analysis. Validation was performed in accordance with the “Guideline on Bioanalytical Method Validation” of the European Medicines Agency (EMA). The LC‐MS/MS method was cross validated against a modified and calibrated (r2 Diagnostics) one‐stage clotting assay (OSA). The LC‐MS/MS method demonstrated linearity over a wide range of emicizumab concentrations, far exceeding the concentrations observed in people with hemophilia A. Precision and accuracy were excellent, and all other validation parameters were also within the acceptance EMA criteria. Cross validation showed that the LC‐MS/MS method and the OSA‐based method can be used interchangeably for drug monitoring of emicizumab without the application of a correction factor. [Display omitted] [Display omitted]