Will Turkey remember the Syrian citizenship debate?

It was on 2 July 2016 that President Recep Tayyip Erdoğan announced that Syrian ‘guests under temporary protection’ (i.e. refugees) in Turkey would be granted Turkish citizenship. He deferred to the Interior Ministry for further comment, though members of the government themselves seemed to have been taken by surprise. The proposal sparked immediate debate in the political arena and on social media, with not only opposition parties speaking against it but even grassroots supporters of the Justice and Development Party (Adalet ve Kalkınma Partisi, AKP). Over one week after the statement, Deputy Prime Minister Numan Kurtulmuş said that the Interior Ministry had ‘not yet completed the work on the issue of giving citizenship to Syrians.’ It became clear at this point that not all Syrian refugees would have been eligible to acquire Turkish citizenship but only ‘qualified and educated Syrians with a clean record’. The estimated number was around 300,000. Then, on 11 July, Erdoğan detailed his proposition, saying, ‘there is no need to hesitate’ and that Turkey was big enough to welcome Syrians as citizens

Detection of activating estrogen receptor gene (ESR1) mutations in single circulating tumor cells

Purpose: Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 (ESR1) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hotspot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch and DEPArray technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were subjected to whole genome amplification by MALBAC and Sanger sequencing. Results: Among 3 selected patients, 2 had an ESR1 mutation (Y537). One showed two different ESR1 variants in a single CTC and another showed loss of heterozygosity. All mutations were detected in matched cell-free DNA (cfDNA). Furthermore, one had 2 serial blood samples analyzed and showed changes in both cfDNA and CTCs with emergence of mutations in ESR1 (Y537S and T570I), which has not been reported previously. Conclusions: CTCs are easily accessible biomarkers to monitor and better personalize management of patients with previously demonstrated ER-MBC who are progressing on endocrine therapy. We showed that single CTC analysis can yield important information on clonal heterogeneity and can be a source of discovery of novel and potential driver mutations. Finally, we also validate a workflow for liquid biopsy that will facilitate early detection of ESR1 mutations, the emergence of endocrine resistance and the choice of further target therapy. ©2017 AACR

Work as a Calling in the Humanitarian Sector - Exploring Cross-Cultural Differences

openQuesto studio interculturale (238 intervistati/e provenienti da 44 Paesi) esplora il concetto di lavoro come chiamata affrontando la questione della generalizzabilità attraverso i confini occupazionali e culturali, con focus su un particolare ambito lavorativo: il settore umanitario. La ricerca ha fornito prove a sostegno dell'idea che la chiamata professionale è più forte in situazioni in cui vi sia un chiaro bisogno sociale da soddisfare, che rafforza il senso di necessità esterna (outer requiredness) della chiamata, ed anche il bisogno di specifiche competenze personali, che a sua volta promuove il senso di necessità interiore (inner requiredness). Il settore umanitario presenta entrambe queste caratteristiche e i dati raccolti hanno confermato che gli operatori e le operatrici umanitari/e vivono fortemente il lavoro come chiamata. Inoltre, tutte le dimensioni della chiamata utilizzate in questo studio (passione, identità, scopo, sacrificio, pervasività, pro-sociliatà e chiamata trascendente - misurate dall'UMCS_28, oltre al dovere morale) sono rilevanti in tutte le culture. I risultati ottenuti nello studio hanno anche confermato che il costrutto di chiamata varia qualitativamente tra i vari settori: nel campo umanitario, la dimensione della pro-socialità si è confermata più forte all’interno del costrutto rispetto alle altre dimensioni. Dal punto di vista interculturale, la chiamata è risultata negativamente correlata alla weirdness (acronimo indicante i Paesi occidentali, con alti livelli di istruzione, industrializzati, ricchi, democratici - Western, Educated, Industralised, Rich, Democratic - WEIRD) del Paese/cultura degli intervistati. Ciò deriva principalmente dal fatto che gli operatori e le operatrici umanitari/e dei Paesi WEIRD presentano valori elevati per le dimensioni della chiamata legate al senso di necessità interiore (come la passione, l'identità, lo scopo), ma hanno valori relativamente più bassi per le dimensioni più legate al senso di necessità esterna, come il dovere morale e la chiamata trascendente. I partecipanti provenienti da Paesi meno WEIRD (che, nel presente studio, corrispondono a culture più collettivistiche e a società con una maggiore tolleranza per l'ineguale distribuzione del potere) presentano invece valori elevati per entrambe le dimensioni della richiesta interna ed esterna, risultando complessivamente in una chiamata più forte.This cross-cultural study (238 respondents from 44 countries) explores the concept of Work as a Calling addressing the question of generalisability across occupational and cultural boundaries, with a focus on a specific work domain: the humanitarian sector. The research provided evidence to support the idea that callings are stronger in situations in which there is both a clear societal need to be filled, which reinforces the sense of outer requiredness of the calling, and a need for distinct skills, which in turns foster the sense of inner requiredness. The humanitarian sector presents both these characteristics and the data collected confirmed that humanitarian workers strongly live work as a calling. Furthermore, all dimensions of calling utilised in this study (passion,identity, purpose, sacrifice, pervasiveness, moral duty and transcendent summons - as measured by the UMCS_28, plus moral duty) are relevant across cultures. The results obtained in the study also confirmed that the construct of calling varies qualitatively across sectors: in the humanitarian field, the dimension of pro-sociality was confirmed to bear more relevance in defining the construct in comparison to the other dimensions. Quite importantly from the cross-cultural perspective, calling resulted to be negatively correlated to the weirdness (acronymous indicating Western, Educated, Industralised, Rich, Democratic - WEIRD countries) of the country/culture of the respondents. This mainly resulted from the fact that humanitarian workers in WEIRD countries present high values for the inner-requiredness dimensions of calling (such as passion, identity, purpose), but they have comparatively lower values for dimensions more related to the outer-requiredness pole of the spectrum, such as moral duty and transcendent summons. Participants coming from less-WEIRD countries (which, in the present study, correspond to more collectivistic cultures and societies with higher tolerance for unequal distribution of power) present instead high values for both the inner- and the outer-requiredness dimensions, resulting overall in stronger calling

Guidance Statement On BRCA1/2 Tumor Testing in Ovarian Cancer Patients

International audienceThe approval, in 2015, of the first poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi; olaparib, Lynparza) for platinum-sensitive relapsed high-grade ovarian cancer with either germline or somatic BRCA1/2 deleterious mutations is changing the way that BRCA1/2 testing services are offered to patients with ovarian cancer. Ovarian cancer patients are now being referred for BRCA1/2 genetic testing for treatment decisions, in addition to familial risk estimation, and irrespective of a family history of breast or ovarian cancer. Furthermore, testing of tumor samples to identify the estimated 3%-9% of patients with somatic BRCA1/2 mutations who, in addition to germline carriers, could benefit from PARPi therapy is also now being considered. This new testing paradigm poses some challenges, in particular the technical and analytical difficulties of analyzing chemically challenged DNA derived from formalin-fixed, paraffin-embedded specimens. The current manuscript reviews some of these challenges and technical recommendations to consider when undertaking BRCA1/2 testing in tumor tissue samples to detect both germline and somatic BRCA1/2 mutations. Also provided are considerations for incorporating genetic analysis of ovarian tumor samples into the patient pathway and ethical requirements

The value proposition of integrative diagnostics for (early) detection of cancer. On behalf of the EFLM interdisciplinary Task and Finish Group “CNAPS/CTC for early detection of cancer”

Disruptive imaging and laboratory technologies can improve clinical decision processes and outcomes in oncology. However, certain obstacles must be overcome before these technologies can be fully implemented as part of the standard for care. An integrative diagnostic approach represents a unique opportunity to unleash the full diagnostic potential and paves the way towards personalized cancer diagnostics. To meet this demand, an interdisciplinary Task Force of the EFLM was initiated as a consequence of an EFLM/ESR during the CELME 2019 meeting in order to evaluate the clinical value of CNAPS/CTC (circulating nucleic acids in plasma and serum/circulating tumor cells) in early detection of cancer. Here, an overview of current disruptive techniques, their clinical implications and potential value of an integrative diagnostic approach is provided. Furthermore, requirements such as the establishment of diagnostic tumor boards, development of adequate software solutions and a change of mindset towards a new generation of diagnosticians providing actionable health information are presented. This development has the potential to elevate the position and clinical recognition of diagnosticians

Alternative academic approaches for testing homologous recombination deficiency in ovarian cancer in the MITO16A/MaNGO-OV2 trial

Molecular testing; Ovarian cancerProves moleculars; Càncer d'ovarisPruebas moleculares; Cáncer de ovariosBackground The detection of homologous recombination deficiency (HRD) can identify patients who are more responsive to platinum and poly ADP ribose polymerase inhibitors (PARPi). MyChoice CDx (Myriad) is the most used HRD test in ovarian cancer (OC). However, some limitations of commercial tests exist, because of the high rate of inconclusive results, costs, and the impossibility of evaluating functional resistance mechanisms. Patients and methods Two academic genomic tests and a functional assay, the RAD51 foci, were evaluated to detect HRD. One hundred patients with high-grade OC enrolled in the MITO16A/MaNGO-OV2 trial and treated with first-line therapy with carboplatin, paclitaxel, and bevacizumab were analyzed. Results The failure rate of the two genomic assays was 2%. The sensitivity in detecting HRD when compared with Myriad was 98.1% and 90.6%, respectively. The agreement rate with Myriad was 0.92 and 0.87, with a Cohen’s κ coefficient corresponding to 0.84 and 0.74, respectively. For the RAD51 foci assay, the failure rate was 30%. When the test was successful, discordant results for deficient and proficient tumors were observed, and additional HRD patients were identified compared to Myriad; sensitivity was 82.9%, agreement rate was 0.65, and Cohen’s κ coefficient was 0.18. The HRD detected by genomic assays and residual tumor at primary surgery and stage was correlated with progression-free survival at multivariate analysis. Conclusions Results suggest the feasibility of academic tests for assessing HRD status that show robust concordance with Myriad and correlation with clinical outcome. The contribution of the functional information related to the RAD51 foci test to the genomic data needs further investigation.This work was supported by funding from the AIRC [grant numbers IG 2016 – ID. 18921 and IG 2021 – ID. 25932 projects – P.I. SP and CO-2018-12367051 (Ministero della Salute) P.I SP]; Ricerca Corrente grant M2/7 from Ministero della Salute to DC, Ricerca Corrente from Ministero della Salute to SP. SM is supported by the Italian Association for Cancer Research [grant number IG-2017 n: IG19997]. MITO16A/MaNGO-OV2 trial was partially supported by Roche. AL is a recipient of a grant from the Asociación Española contra el Cáncer (AECC) [grant number INVES20095LLOP]. VS is a recipient of a grant from the Instituto de Salud Carlos III [grant number CPII19/00033] and a European grant for personalized medicine [grant number ERAPERMED 2019-215]. BP is a recipient of a grant from GOIRC. BP was supported by ESMO with a Clinical Translational Fellowship aid supported by Roche. Any views, opinions, findings, conclusions, or recommendations expressed in this material are those solely of the authors and do not necessarily reflect those of ESMO or Roche. NC has received funding from AstraZeneca (to the institution). FP has received funding from Roche, AstraZeneca, Pfizer, Merck Sharp & Dome, Bayer, Incyte, Taiho Oncology, Janssen Cilag, Exelixis, Aileron, and Daiichi Sankyo (grants to the institution for clinical trial activities)