Jaws from the deep: biological and ecological insights on the kitefin shark Dalatias licha from the Mediterranean Sea

Due to their late maturation, extreme longevity, low fecundity and slow growth rates, deep-sea Chondrichthyes are extremely vulnerable to human impacts. Moreover, assessing the impact of deep-sea fisheries is difficult, as many species (including sharks) are part of the bycatch and are often discarded at sea, and/or landed under generic commercial-species codes. The lack of this information on fishery data sets and the limited availability of species-specific life history data make challenging the management of deep-sea Chondrichthyes. The kitefin shark Dalatias licha is a cosmopolitan elasmobranch, mainly found on continental and insular shelf-breaks and slopes in warm-temperate and tropical waters. This species is a common by-catch of the deep-sea trawling, considered as “Endangered” by the IUCN Red List for all European waters, Mediterranean Sea included. Here we present the results of a study based on a total of 78 specimens of kitefin shark collected over 3 years in the Ligurian Sea (NW Mediterranean) as by-catch from deep-water fisheries. Total length ranged from 380 to 1164 mm, and individual weight ranged from 198 to 8000 g. Immature and mature individuals showed a sex ratio dominated by males. Adult males were observed throughout the year, while mature females were observed only in spring-summer. These data lead to hypothesise a spatial segregation between genders. The kitefin shark diet was dominated by bony fish (mainly Macrouridae) and other small sharks (e.g., Galeus melastomus and Etmopterus spinax), but their gut included plastic items and parasites. Data reported here underline the rarity, complex ecology and the threat for this shark species and support the urgency of promoting initiatives for their monitoring and conservation

Game-Play Breakdowns and Breakthroughs: Exploring the Relationship Between Action, Understanding, and Involvement

Game developers have to ensure their games are appealing to, and playable by, a range of people. However, although there has been interest in the game-play experience, we know little about how learning relates to player involvement. This is despite challenge being an integral part of game-play, providing players with potential opportunities to learn. This article reports on a multiple case-study approach that explored how learning and involvement come together in practice. Participants consisted of a mix of gamers and casual players. Data included interviews, multiple observations of game-play, postplay cued interviews, and diary entries. A set of theoretical claims representing suggested relationships between involvement and learning were developed on the basis of previous literature; these were then assessed through a critical examination of the data set. The resulting theory is presented as 14 refined claims that relate to micro and macro involvement; breakdowns and breakthroughs in action, understanding, and involvement; progress; and agency, meaning and compelling game-play. The claims emphasize how players experience learning via breakthroughs in understanding, where involvement is increased when the player feels responsible for progress. Supporting the relationship between learning and involvement is important for ensuring the success of commercial and educational games

Challenging notions of gendered game play: teenagers playing `The Sims`

This paper challenges notions of gendered game playing practice implicit in much research into young women\u27s involvement with the computer gaming culture. It draws on a study of Australian teenagers playing The Sims Deluxe as part of an English curriculum unit and insights from feminist media studies to explore relationships between gender and game playing practices. Departing from a reliance on predetermined notions of &ldquo;gender&rdquo;, &ldquo;domestic space&rdquo;, and &ldquo;successful game play&rdquo;, it conceptualizes The Sims as a game in which the boundaries between gender and domestic space are disturbed. It argues that observing students\u27 constructions of gender and domestic space through the act of game play itself provides a more productive insight into the gendered dimensions of game play for educators wishing to work computer games such as The Sims into curriculum development.<br /

ELN2017 risk stratification improves outcome prediction when applied to the prospective GIMEMA AML1310 protocol

The 2017 version of the European LeukemiaNet (ELN) recommendations, by integrating cytogenetics and mutational status of specific genes, divides patients with acute myeloid leukemia into 3 prognostically distinct risk categories: favorable (ELN2017-FR), intermediate (ELN2017-IR), and adverse (ELN2017-AR). We performed a post hoc analysis of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell’Adulto) AML1310 trial to investigate the applicability of the ELN2017 risk stratification to our study population. In this trial, after induction and consolidation, patients in complete remission were to receive an autologous stem cell transplant (auto-SCT) if categorized as favorable risk or an allogeneic stem cell transplant (allo-SCT) if adverse risk. Intermediate-risk patients were to receive auto-SCT or allo-SCT based on the postconsolidation levels of measurable residual disease as measured by using flow cytometry. Risk categorization was originally conducted according to the 2009 National Comprehensive Cancer Network recommendations. Among 500 patients, 445 (89%) were reclassified according to the ELN2017 criteria: ELN2017-FR, 186 (41.8%) of 455; ELN2017-IR, 179 (40.2%) of 445; and ELN2017-AR, 80 (18%) of 455. In 55 patients (11%), ELN2017 was not applicable. Two-year overall survival (OS) was 68.8%, 51.3%, 45.8%, and 42.8% for the ELN2017-FR, ELN2017-IR, ELN2017-not classifiable, and ELN2017-AR groups, respectively (P, .001). When comparing the 2 different transplant strategies in each ELN2017 risk category, a significant benefit of auto-SCT over allo-SCT was observed among ELN2017-FR patients (2-year OS of 83.3% vs 66.7%; P 5 .0421). The 2 transplant procedures performed almost equally in the ELN2017-IR group (2-year OS of 73.9% vs 70.8%; P 5 .5552). This post hoc analysis of the GIMEMA AML1310 trial confirms that the ELN2017 classification is able to accurately discriminate patients with different outcomes and who may benefit from different transplant strategies. This trial was registered as EudraCT number 2010-023809-36 and at www.clinicaltrials.gov as #NCT01452646

Direct CD32 T-cell cytotoxicity: implications for breast cancer prognosis and treatment

The FcγRII (CD32) ligands are IgFc fragments and pentraxins. The existence of additional ligands is unknown. We engineered T cells with human chimeric receptors resulting from the fusion between CD32 extracellular portion and transmembrane CD8α linked toCD28/ζ chain intracellular moiety (CD32-CR). Transduced T cells recognized three breast cancer (BC) and one colon cancer cell line among 15 tested in the absence of targeting antibodies. Sensitive BC cell conjugation with CD32-CR T cells induced CD32 polarization and down-regulation, CD107a release, mutual elimination, and proinflammatory cytokine production unaffected by human IgGs but enhanced by cetuximab. CD32-CR T cells protected immunodeficient mice from subcutaneous growth of MDA-MB-468 BC cells. RNAseq analysis identified a 42 gene fingerprint predicting BC cell sensitivity and favorable outcomes in advanced BC. ICAM1 was a major regulator of CD32-CR T cell–mediated cytotoxicity. CD32-CR T cells may help identify cell surface CD32 ligand(s) and novel prognostically relevant transcriptomic signatures and develop innovative BC treatments

The brief international cognitive assessment for multiple sclerosis (BICAMS): Normative values with gender, age and education corrections in the Italian population

Background: BICAMS (Brief International Cognitive Assessment for Multiple Sclerosis) has been recently developed as brief, practical and universal assessment tool for cognitive impairment in MS subjects. It includes the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-2 (CVLT2) and the Brief Visuospatial Memory Test-Revised (BVMT-R) . In this study we aimed at gathering regression based normative data for the BICAMS battery in the Italian population.Methods: Healthy subjects were consecutively recruited among patient friends and relatives. Corrections for demographics were calculated using multivariable linear regression models. Test-retest reliability was assessed using the Pearson correlation coefficient.Results: The BICAMS battery was administered to 273 healthy subjects (180 women, mean age 38.9 ± 13.0&nbsp;years, mean education 14.9 ± 3.0&nbsp;years). Test-retest reliability was good for all the tests.Conclusions: The study provided normative data of the BICAMS for the Italian population confirming good test-retest reliability which can facilitate the use of the battery in clinical practice, also for longitudinal patient assessments

Association of ultra-rare coding variants with genetic generalized epilepsy: A case\u2013control whole exome sequencing study

Objective: We aimed to identify genes associated with genetic generalized epilepsy (GGE) by combining large cohorts enriched with individuals with a positive family history. Secondarily, we set out to compare the association of genes independently with familial and sporadic GGE. Methods: We performed a case\u2013control whole exome sequencing study in unrelated individuals of European descent diagnosed with GGE (previously recruited and sequenced through multiple international collaborations) and ancestry-matched controls. The association of ultra-rare variants (URVs; in 18&nbsp;834 protein-coding genes) with epilepsy was examined in 1928 individuals with GGE (vs. 8578 controls), then separately in 945 individuals with familial GGE (vs. 8626 controls), and finally in 1005 individuals with sporadic GGE (vs. 8621 controls). We additionally examined the association of URVs with familial and sporadic GGE in two gene sets important for inhibitory signaling (19&nbsp;genes encoding \u3b3-aminobutyric acid type A [GABAA] receptors, 113&nbsp;genes representing the GABAergic pathway). Results: GABRG2 was associated with GGE (p&nbsp;=&nbsp;1.8&nbsp; 7&nbsp;10 125), approaching study-wide significance in familial GGE (p&nbsp;=&nbsp;3.0&nbsp; 7&nbsp;10 126), whereas no gene approached a significant association with sporadic GGE. Deleterious URVs in the most intolerant subgenic regions in genes encoding GABAA receptors were associated with familial GGE (odds ratio [OR]&nbsp;=&nbsp;3.9, 95% confidence interval [CI]&nbsp;=&nbsp;1.9\u20137.8, false discovery rate [FDR]-adjusted p&nbsp;=.0024), whereas their association with sporadic GGE had marginally lower odds (OR&nbsp;=&nbsp;3.1, 95% CI&nbsp;=&nbsp;1.3\u20136.7, FDR-adjusted p&nbsp;=.022). URVs in GABAergic pathway genes were associated with familial GGE (OR&nbsp;=&nbsp;1.8, 95% CI&nbsp;=&nbsp;1.3\u20132.5, FDR-adjusted p&nbsp;=.0024) but not with sporadic GGE (OR&nbsp;=&nbsp;1.3, 95% CI&nbsp;=.9\u20131.9, FDR-adjusted p&nbsp;=.19). Significance: URVs in GABRG2 are likely an important risk factor for familial GGE. The association of gene sets of GABAergic signaling with familial GGE is more prominent than with sporadic GGE

Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data

The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox–Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients with IS or LGS. The contribution of autosomal recessive genetic variation, however, is less well understood. We implemented a rare variant transmission disequilibrium test (TDT) to search for autosomal recessive epileptic encephalopathy genes in a cohort of 320 outbred patient–parent trios that were generally prescreened for rare metabolic disorders. In the current sample, our rare variant transmission disequilibrium test did not identify individual genes with significantly distorted transmission over expectation after correcting for the multiple tests. While the rare variant transmission disequilibrium test did not find evidence of a role for individual autosomal recessive genes, our current sample is insufficiently powered to assess the overall role of autosomal recessive genotypes in an outbred epileptic encephalopathy population

Author Correction: The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The following authors were omitted from the original version of this Data Descriptor: Markus Reichstein and Nicolas Vuichard. Both contributed to the code development and N. Vuichard contributed to the processing of the ERA-Interim data downscaling. Furthermore, the contribution of the co-author Frank Tiedemann was re-evaluated relative to the colleague Corinna Rebmann, both working at the same sites, and based on this re-evaluation a substitution in the co-author list is implemented (with Rebmann replacing Tiedemann). Finally, two affiliations were listed incorrectly and are corrected here (entries 190 and 193). The author list and affiliations have been amended to address these omissions in both the HTML and PDF versions