Number-space associations in synaesthesia are not influenced by finger-counting habits

In many cultures, one of the earliest representations of number to be learned is a finger-counting system. Although most children stop using their fingers to count as they grow more confident with number, traces of this system can still be seen in adulthood. For example, an individual's finger-counting habits appear to affect the ways in which numbers are implicitly associated with certain areas of space, as inferred from the spatial–numerical association of response codes (SNARC) effect. In this study, we questioned the finger-counting habits of 98 participants who make explicit, idiosyncratic associations between number and space, known as number-space synaesthesia. Unexpectedly, neither handedness nor finger-counting direction (left-to-right or right-to-left) was associated with the relative positions of 1 and 10 in an individual's number-space synaesthesia. This lack of association between finger-counting styles and number-space synaesthesia layout may result from habitual use of synaesthetic space rather than fingers when learning to count; we offer some testable hypotheses that could assess whether this is the case

Apport diagnostique du dosage des chaînes légères libres sériques d'immunoglobulines pour l'exploration des gammapathies monoconales

RésuméLes gammapathies monoclonales sont d\u27occurrence non négligeable (3,2 %) chez les sujets de plus de 50 ans. Pour environ la moitié d\u27entre elles, elles correspondent, lors de leur découverte, à une gammapathie monoclonale de signification indéterminée (ou MGUS en anglais pour monoclonal gammopathy of undetermined significance). Un peu plus du tiers sont des hémopathies lymphoïdes B avérées (myélome multiple, maladie de Waldenström, amylose) qui représentent le stade ultime de progression des MGUS avec une incidence annuelle de 1 %. L\u27exploration biologique immunologique validée à ce jour repose sur une analyse conjointe du sérum et des urines par immunoélectrophorèse/immunofixation qui vise à typer l\u27immunoglobuline monoclonale. Depuis 2001, un nouveau dosage est proposé pour la prise en charge diagnostique de ces patients : la détermination néphélémétrique ou turbidimétrique des chaînes légères libres (CLL) d\u27immunoglobulines kappa et lambda à l\u27aide d\u27anti-sérums spécifiques avec détermination du rapport κ/λ dont le déséquilibre peut être indicateur d\u27un excès de production monoclonale. Cela reste cependant un dosage quantitatif qui ne peut faire la preuve d\u27une anomalie qualitative (monoclonalité). L\u27apport pour le diagnostic et pour le suivi de ce dosage doit tenir compte des propriétés de la réaction antigène/anticorps en milieu liquide (phénomène de zone), du métabolisme rénal des chaînes légères avec ses conséquences en cas d\u27insuffisance rénale et des interférences possibles avec les chaînes légères liées des immunoglobulines intactes. L\u27apport diagnostique du dosage des CLL est patent dans les situations cliniques où l\u27absence de marqueur monoclonal peut être un handicap : myélome à chaîne légère, myélome apparemment non sécrétant, amylose et maladie de dépôt des chaînes d\u27immunoglobulines. Dans les autres situations (myélome à immunoglobuline intacte, MGUS), l\u27apport du dosage des CLL comme marqueur diagnostique ou comme indicateur de pronostic ou de suivi thérapeutique n\u27est pas encore prouvé. Son évaluation nécessitera des études prospectives particulièrement rigoureuses

Les immunothérapies spécifiques dans le traitement des cancers

The offer of anti-cancer drugs has recently been disrupted by the introduction of checkpoint inhibitors on the market. Currently, one anti-CTLA-4, two anti-PD-1 and two anti-PD-L1 are authorized in the European Union, in seven different types of cancer. The clinical development of these therapies is still in full swing: in July 2017, more than 1 500 clinical trials were evaluating anti-PD-1, anti-PD-L1 and anti-CTLA-4 drugs in about twenty different locations and this number continues to increase. In the short term in France, other immunotherapies, the CAR-T cells, will complete this therapeutic arsenal. These immunotherapies appear as a real revolution in the treatment of some cancers. Nevertheless, many issues are associated with these therapies, particularly regarding the identification of good responders, the proper use of these drugs including the management of therapeutic strategies and safety profile, as well as the organization of care. In addition, the expenses associated with ipilimumab, nivolumab and pembrolizumab are substantial and almost tripled in one year, going from 120 million euros in 2015 to more than 340 million euros in 2016. This raises the question of the ability of the current healthcare system to maintain equitable access to innovation and best treatments for all patients. For all these reasons, the French National Cancer Institute decided to dedicate its thematic annual report on these innovative immunotherapies, targeting in particular checkpoint inhibitors and CAR-T cells, in order to produce an inventory of current data and an analysis regarding the different issues associated with these therapies

Prognosis of vasculitis associated myelodysplasia

Systemic and immune manifestations have been reported in patients with MDS. The correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients remains controversial. Most of the authors agree that the median survival in myelodysplastic syndrome is not related to the presence of systemic and immune manifestations, but only with the existence of a systemic vasculitis

Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data

Gender Asymmetry in Okun's Law in the Four PIGS Countries

AbstractCentred on the four PIGS countries (Portugal, Italy, Greece and Spain) and using the quarterly data from Q2/1998 until Q4/2014, the paper investigates whether there exists gender asymmetries in Okun's law and whether male unemployment reacts identically to economic fluctuations as female unemployment does. Whilst the trend components of output, male and female unemployment are estimated with the aid of the HP filter, Okun's relationships are modelled in the SVAR framework assuming that cyclical fluctuations of the economy and the labour market with both male and female labour force are endogenous. It is established that gender is indeed a factor that makes the respective segments of the labour market respond slightly differently to changes in real output

Clonal interference of signaling mutations worsens prognosis in core-binding factor acute myeloid leukemia

Mutations in receptor tyrosine kinase/RAS signaling pathway genes are frequent in core-binding factor (CBF) acute myeloid leukemias (AMLs), but their prognostic relevance is debated. A subset of CBF AML patients harbors several signaling gene mutations. Genotyping of colonies and of relapse samples indicates that these arise in independent clones, thus defining a process of clonal interference (or parallel evolution). Clonal interference is pervasive in cancers, but the mechanisms underlying this process remain unclear, and its prognostic impact remains unknown. We analyzed a cohort of 445 adult and pediatric patients with CBF AML treated with intensive chemotherapy and with deep sequencing of 6 signaling genes (, , , , , ). A total of 152 (34%), 167 (38%), and 126 (28%) patients harbored no, a single, and multiple signaling clones (clonal interference), respectively. Clonal interference of signaling mutations was associated with older age ( = .004) and inv(16) subtype ( = .025) but not with white blood cell count or mutations in chromatin or cohesin genes. The median allele frequency of signaling mutations was 31% in patients with a single clone or clonal interference ( = .14). The repertoire of , , and / variants differed between groups. Clonal interference did not affect complete remission rate or minimal residual disease after 1-2 courses, but it did convey inferior event-free survival ( < 10), whereas the presence of a single signaling clone did not ( = .44). This inferior outcome was independent of clinical parameters and of the presence of specific signaling clones. Our results suggest that specific clonal architectures can herald distinct prognoses in AML

Prognostic impact of progression to induction chemotherapy and prior paclitaxel therapy in patients with germ cell tumors receiving salvage high-dose chemotherapy in the last 10 years: A study of the European Society for Blood and Marrow Transplantation Solid Tumors Working Party

Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P<0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel