C-Reactive Protein (CRP) levels in neonatal meningitis in England: an analysis of national variations in CRP cut-offs for lumbar puncture.

BACKGROUND: Recent National Institute for Health and Care Excellence (NICE) CG149 guidelines suggest considering performing a lumbar puncture (LP) to investigate for meningitis in early-onset sepsis in a neonate when a C-reactive protein (CRP) level >10mg/L, but the evidence for this recommendation is poorly defined. METHODS: Data on trust-wide LP protocols, neonatal meningitis incidence, lumbar punctures, and CRP levels seen in cases of neonatal meningitis were asked of all 137 trusts in England that recorded a birth in 2017. Our local Kingston Hospital data on every LP performed was obtained to estimate the specificity of CRP rises. RESULTS: 73/123 (59.3%) of trusts follow the NICE CG149 recommendation of considering an LP if the CRP >10mg/L. The national incidence of neonatal meningitis was 0.467/1,000 births, and an LP was performed in 1.37% of all babies, which was significantly higher in trusts considering the CRP > 10mg/L cut-off. A CRP > 10mg/L cut-off sensitivity was 88.9% based on the highest CRP level 4 days around the LP from national data of 199 cases; specificity was 78.8% based on our single-unit analysis. CONCLUSIONS: Proposing a universal CRP > 10mg/L cut-off for a lumbar puncture has been counter-productive in England. Following it generates significantly more LPs, to the point that 40.7% of trusts have chosen not to follow it. It also has poor sensitivity missing over 11% of meningitis. We therefore do not recommend a universal cut-off, rather considering the whole clinical picture (including prematurity) when considering whether to do an LP

Subcellular elements responsive to the biomechanical activity of triple-negative breast cancer-derived small extracellular vesicles

Abstract Triple-negative breast cancer (TNBC) stands out for its aggressive, fast spread, and highly metastatic behavior and for being unresponsive to the classical hormonal therapy. It is considered a disease with a poor prognosis and limited treatment options. Among the mechanisms that contribute to TNBC spreading, attention has been recently paid to small extracellular vesicles (sEVs), nano-sized vesicles that by transferring bioactive molecules to recipient cells play a crucial role in the intercellular communication among cancer, healthy cells, and tumor microenvironment. In particular, TNBC-derived sEVs have been shown to alter proliferation, metastasis, drug resistance, and biomechanical properties of target cells. To shed light on the molecular mechanisms involved in sEVs mediation of cell biomechanics, we investigated the effects of sEVs on the main subcellular players, i.e., cell membrane, cytoskeleton, and nuclear chromatin organization. Our results unveiled that TNBC-derived sEVs are able to promote the formation and elongation of cellular protrusions, soften the cell body, and induce chromatin decondensation in recipient cells. In particular, our data suggest that chromatin decondensation is the main cause of the global cell softening. The present study added new details and unveiled a novel mechanism of activity of the TNBC-derived sEVs, providing information for the efficient translation of sEVs to cancer theranostics

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Detectable clonal mosaicism and its relationship to aging and cancer

In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases

Analisi ed utilizzo del modello di traffico SUMO: un'applicazione alla città di Piombino.

La mia tesi è incentrata sullo studio del modello di traffico Sumo, con conseguente applicazione alla città portuale di Piombino. Su questa ho effettuato una modellizzazione della rete di trasporto, seguita dalla stima della domanda di trasporto con assegnazione di quest'ultima alla rete mediante una micro-simulazione. Tale lavoro ha preso l'avvio dal Progetto Europeo List Port ("Limitazione Inquinamento Sonoro da Traffico nei Porti Commerciali") che mira ad apportare un miglioramento del clima acustico delle città portuali attraverso l'utilizzo di sistemi integrati ITS di gestione del traffico. Il progetto prevedeva la realizzazione dei modelli di traffico di 4 città portuali ma, per la mancanza dei dati sulla domanda di trasporto relativa ai vari scenari, è stata completata l'analisi di traffico solo per la città di Piombino. L'area di studio da me condotta si è concentrata quindi sull'analisi del corridoio principale di accesso al porto. In seguito alla rilevazione di una criticità relativa alla congestione del traffico in prossimità del porto, è stata studiata la possibilità di inserire alcune "aree polmone" in zone non urbanizzate in corrispondenza dell'area portuale

An insight into the first stages of the Ferrar magmatism: ultramafic cumulates from Harrow Peaks, northern Victoria Land, Antarctica

A group of ultramafic xenoliths hosted in Cenozoic hypabyssal rocks from Harrow Peaks (northern Victoria Land, Antarctica) show textural and geochemical features far removed from anything previously observed in mantle xenoliths of this region and elsewhere in Antarctica. They consist of spinel-bearing lherzolites and harzburgites, characterised by a predominant equigranular texture with orthopyroxene modal contents remarkably higher in lherzolites (18–26 volume%) with respect to the harzburgite (13 vol%), one orthopyroxenite, and three composite xenoliths. The latter are formed by an olivine-dominant assemblage (olivine > 70%) crosscut by large monomineralic (amphibole or clinopyroxene) or bimineralic (amphibole + clinopyroxene) veins. No significant correlation was observed between the lithology and the Fo content (90.21–82.81) of olivine, suggesting that these rocks could be derived from a cumulus process. The presence of the orthopyroxenite suggests that the inferred melt/s from which they stemmed was close (or even above) to silica saturation. Based on major and trace-element mineral/melt and mineral/mineral equilibrium modelling, these rocks were formed by progressive extraction of olivine from a high magnesium (Mg = 72)—high temperature (~ 1300 °C) melt following a very short fractionation line. Thermobarometric results indicate the stationing of Harrow Peaks cumulates in the P field of 1.3 ± 0.2 (dunites)—0.5 ± 0.2 (orthopyroxenite) GPa. These values well match the crust/mantle boundary (Moho) of the region. The combined geochemical and petrological data suggest that Harrow Peaks melts could be related to the initial stage of the Jurassic Ferrar magmatism, whose deep cumulates were subsequently affected by the Cenozoic alkaline metasomatism, widely detected in the northern Victoria Land lithosphere and responsible for the formation of the late amphibole/amphibole + clinopyroxene veins

Coltivare risorse. Stress lavoro correlato e burnout in un campione di docenti

Lo  stress  lavoro  correlato  ed  il  burnout  sono  processi  sempre  più  dilaganti  nei  contesti   lavorativi  e  tali  fenomeni  si  registrano  maggiormente  nelle  cosiddette  “helping  professions”,   quelle  professioni  che  prevedono  un  continuo  contatto  con  l’utenza  e  che  hanno  come   principali  obiettivi  la  cura,  l’aiuto  e  l’assistenza.  Avere  come  finalità  il  benessere  lavorativo,   inteso  non  come  assenza  di  disagio  ma  come  completo  stato  di  salute,  significa  lavorare  sia  in   termini  di  prevenzione,  diritto  dei  singoli  lavoratori  e  interesse  della  collettività,  sia  in  termini   di  strategie  di  intervento  basate  sul  supporto  psicologico.  Lo  scopo  della  ricerca  è  stato,   pertanto,  quello  di  indagare  l’eventuale  presenza  di  stress  lavoro  correlato  e  burnout  in  un   campione  di  120  docenti  (74  uomini  e  46  donne)  di  tre  Istituti  di  secondo  grado  genovesi,   tramite  la  somministrazione  dei  seguenti  strumenti:  Maugeri  Stress  Index  (2011)  e  Maslach   Burnout  Inventory.  Il  primo  questionario  è  stato  somministrato  con  la  finalità  di  valutare  il   rischio  di  stress  lavorativo  e  delle  componenti  che  lo  possono  determinare;  è  stato,  inoltre,   attuato  un  confronto  tra  il  campione  di  studio  con  un  campione  costituto  da  727  soggetti,  di   cui  69  lamentavano  stress  e  vessazioni  lavorative.  Il  Maslach  Burnout  Inventory  è  stato,   invece,  utilizzato  per  misurare  il  livello  di  burnout  nei  diversi  Istituti  scolastici  con  specifico   riferimento  al  genere  dei  partecipanti.     44     Poster         Infine  sono  state  verificate  le  correlazioni  esistenti  tra  le  dimensioni  dei  due  strument

The evaluation of «Quality» in psychology: A turbulent commentary on a much-needed manuscript

With this contribution we intend to offer some elements for reflection related to Tommasi’s article «La valutazione della psicologia: considerazioni su un decennio turbolento». In particular, we focused on the somewhat fuzzy definition of «quality» by taking up some elements already highlighted in the target article and adding some considerations relating to the consequences of an a posteriori definition. We wanted to highlight, in particular, the critical implications both in relation to the careers of individuals and in terms of the ability to generate truly quality products, capable of influencing the directions and implications of the research itself. We have also reported some findings relating to the hybrid nature (bibliometric and otherwise) of some macro-sectors. We conclude our contribution by highlighting that the objective of the evaluation should be to create virtuous circles between the passions of those at the early stages of the academic career and the requirements and opportunities inherent the academic system