Experimental study of extended timescale dynamics of a plasma wakefield driven by a self-modulated proton bunch

Plasma wakefield dynamics over timescales up to 800 ps, approximately 100 plasma periods, are studied experimentally at the Advanced Wakefield Experiment (AWAKE). The development of the longitudinal wakefield amplitude driven by a self-modulated proton bunch is measured using the external injection of witness electrons that sample the fields. In simulation, resonant excitation of the wakefield causes plasma electron trajectory crossing, resulting in the development of a potential outside the plasma boundary as electrons are transversely ejected. Trends consistent with the presence of this potential are experimentally measured and their dependence on wakefield amplitude are studied via seed laser timing scans and electron injection delay scan

Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Individualising biologic disease-modifying anti-rheumatic drugs (bDMARDs) to maximise outcomes and deliver safe and cost-effective care is a key goal in the management of rheumatoid arthritis (RA). Investigation to identify predictive tools of bDMARD response is a highly active and prolific area of research. In addition to clinical phenotyping, cellular and molecular characterisation of synovial tissue and blood in patients with RA, using different technologies, can facilitate predictive testing. This narrative review will summarise the literature for the available bDMARD classes and focus on where progress has been made. We will also look ahead and consider the increasing use of ‘omics’ technologies, the potential they hold as well as the challenges, and what is needed in the future to fully realise our ambition of personalised bDMARD treatment

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

A importância da equipe interdisciplinar no diagnóstico de dislexia do desenvolvimento: relato de caso The importance of interdisciplinary staff in the diagnosis of developmental dyslexia: case report

Descrevemos o trabalho de uma equipe interdisciplinar da FCM/UNICAMP na avaliação de um menino de 9 anos e 3 meses aluno de escola pública de Campinas, com dislexia do desenvolvimento. O procedimento constou de 4 fases: 1) anamnese com a mãe; 2) avaliação neuropsicológica; 3) avaliação específica de leitura e escrita; 4) exames complementares. Os resultados das várias avaliações revelaram que o menino apresenta inteligência normal, ausência de déficit auditivo ou visual mas dificuldades em provas específicas de leitura, em memória de curto prazo (especialmente em sequências auditivas) e em consciência fonológica, além de lentidão, falta de concentração, sinais neurológicos menores e hipoperfusão da porção mesial do lobo temporal. Esses dados sugeriram que a criança apresenta dislexia do desenvolvimento do tipo misto, necessitando de intervenção psicopedagógica.<br>We describe the work of the interdisciplinary staff of FCM/UNICAMP for the diagnosis of developmental dyslexia, evaluating a 9 years old boy from the second year of a first grade public school. The procedure consisted of four stages: 1) Interview with the mother (anamnesis); 2) neuropsychological evaluation; 3) specific evaluation for reading and writing skills; 4) complementary exams. The results revealed that the child presented normal intelligence, normal auditory and visual function but difficulties in reading specific test, in auditory short-term memory (specially in auditory sequences), and in phonological conscience, as well as slowness, lack of concentration, slight neurological signs and hypoperfusion of the mesial portion of the temporal lobe. These data suggest that the child has developmental dyslexia of mixed type, requiring psychopedagogic follow-up

Elinsiirron saaneen nuoren siirtyminen lasten ja nuorten hoitotyöstä aikuisten terveyspalveluiden käyttäjäksi

Opinnäytetyömme tarkoituksena on kuvata saumaton, hoitoon sitoutumista tukeva hoitopolku nuoren elinsiirtopotilaan siirtyessä lasten ja nuorten hoitotyöstä aikuisten terveyspalvelujen käyttäjäksi. Työmme on osa lasten ja nuorten hoitotyön osaamisen tulevaisuuden hanketta. Hankkeen tarkoituksena on uusien toimintakäytäntöjen luominen, verkostomaisen työskentelyn vahvistaminen, sekä saumattomien hoitopolkujen kehittäminen. Hankkeessa yhteistyökumppaneina ovat HYKS Naisten- ja lastentautien tulosyksikkö, Metropolia ammattikorkeakoulun Hoitotyön koulutusohjelma ja Tampereen yliopiston Hoitotieteen laitos. Työssämme keskitymme potilaan siirtymävaiheen solmukohtiin, kuvaamme nykyisen hoitopolun ja pyrimme löytämään näkökulmia sekä toimintamalleja, jotka antaisivat nuorelle, hänen perheelleen sekä hoitoyksikölle valmiuksia siirtymisprosessin vaiheisiin. Työssämme keskitymme nuorten kehittymishaasteisiin ja pyrimme kartoittamaan nuorten hoitomyönteisyyttä ja vastaanottavaisuutta edistäviä keinoja ja välineitä. Opinnäytetyömme aihe on uusi hoitotieteellisen tutkimuksen kohde ja löytämämme materiaali on luonteeltaan täsmällistä, tuoretta ja vastaa hyvin työmme edistymisen vaateisiin. Käytimme työssämme kvantitatiivista tutkimusmenetelmää. Tutkimustyön tarve sekä prosessin kehittäminen potilaan tarpeita vastaavaksi tällä hoitotyön saralla on erittäin tärkeää. Kansainvälisesti siirtymisessä koetaan haastavimmaksi prosessin alkamisen äkillisyys, riittämätön tiedonkulku lasten ja aikuisten puolen välillä ja tätä kautta hoidon jatkuvuuden kankeus. Toisin sanoen siirtymiseen valmistavien toimintojen aikaistaminen, kirjallinen informaatio ja sujuvampi yhteistyö palveluiden tarjoajien välillä, ovat suurimmat kehittymishaasteet

Transition between instability and seeded self-modulation of a relativistic particle bunch in plasma

We use a relativistic ionization front to provide various initial transverse wakefield amplitudes for the self-modulation of a long proton bunch in plasma. We show experimentally that, with sufficient initial amplitude [&#x2265;(4.1&#xB1;0.4)&#x2009;&#x2009;MV/m], the phase of the modulation along the bunch is reproducible from event to event, with 3%-7% (of 2&#x3C0;) rms variations all along the bunch. The phase is not reproducible for lower initial amplitudes. We observe the transition between these two regimes. Phase reproducibility is essential for deterministic external injection of particles to be accelerated