Durable response to palbociclib and letrozole in ovarian cancer with CDKN2A loss.

Alterations of the Retinoblastoma (Rb) pathway are frequent in ovarian cancer, typically resulting from CDKN2A down-regulation, CCNE1 amplification, CCND1/2 amplification, and RB1 loss. However, bi-allelic CDKN2A mutation or homozygous deletion is a very rare event, concerning less than 5% of patients.Initial trials with palbociclib in serous ovarian cancer have shown very modest benefit in unselected patient populations, thus underlining the need for a biomarker predicting response. We report the case of a heavily pre-treated patient with a serous ovarian tumor harboring a homozygous deletion of the CDKN2A gene that derived significant, prolonged clinical benefit from palbociclib, a CDK4/6 oral inhibitor, with letrozole. Treatment with palbociclib and letrozole started on February 2018, with an ongoing response after 12 months.In conclusion, homozygous CDKN2A deletion is rare and could be used to predict response to CDK4/6 inhibitors in association with other genomic features. We encourage further trials in this direction

Patient-reported experiences of cancer care related to the COVID-19 pandemic in Switzerland.

This study aims to describe the experience of Swiss oncological patients during the COVID-19 pandemic. A national multi-center study including five hospitals covering the three main language regions of Switzerland was conducted between March and July 2021. Patients with melanoma, breast, lung, or colon cancer receiving active systemic anti-cancer treatment at the time of the COVID-19 pandemic were included. We conducted semi-structured telephone or onsite interviews alongside the administration of distress and resilience-validated questionnaires. Thematic analysis was performed for the qualitative data and descriptive statistics for the quantitative data. Sixty-two cancer patients with a mean age of 61 (SD=14) (58% female) were interviewed. Based on the interviews, we identified that the experience of having cancer during the COVID-19 pandemic was related to five dimensions: psychological, social, support, healthcare, and vaccination. Three themes transverse the five dimensions: (a) needs, (b) positive changes, and (c) phases of the pandemic. In general, patients did not experience delays or disruptions in their cancer treatment nor felt additionally burdened by the pandemic. Lockdown and isolation were reported as mixed experiences (positive and negative), and access to vaccination reassured patients against the risk of infection and instilled hope to return to normalcy. Additionally, we found low distress levels (M=2.9; SD=2.5) and high resilience scores (M=7; SD=1.3) in these patients. Swiss patients with cancer did not express major needs or disruptions in their care during this period of the COVID-19 pandemic. Results identify the mixed experiences of patients and highlight the high resilience levels

Comparative Law Research on the Personal Data Protection Law in Various Countries

In the JST Moonshot R&D Project (Goal 9), "Legal Principles of Decentralized Management" (proposed by Tatsuhiko Yamamoto, professor at Keio University), we discuss the benefits and challenges that arise from social implementation of personal AI from a legal perspective. It is analyzed from Personal AI is AI that manages personal data on behalf of the individual based on the individual's privacy preferences. This can be seen as a tool to back up the right to information self-determination (the right to control one's own information). This research is a comparative study of personal information protection legislation in the EU, Germany, France, Switzerland, the United States, Canada, South Korea, Taiwan, Thailand, and China. We asked report authors from each country to investigate how mechanisms for individual involvement (right to request deletion, right to access, consent, right to data portability) are stipulated in personal information protection laws. We examined the significance and challenges of the right to information self-determination, paying particular attention to the relationship between the Constitution and the Personal Information Protection Act

Lung function from school age to adulthood in primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) presents with symptoms early in life and the disease course may be progressive, but longitudinal data on lung function are scarce. This multinational cohort study describes lung function trajectories in children, adolescents and young adults with PCD. We analysed data from 486 patients with repeated lung function measurements obtained between the age of 6 and 24 years from the International PCD Cohort and calculated z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio using the Global Lung Function Initiative 2012 references. We described baseline lung function and change of lung function over time and described their associations with possible determinants in mixed-effects linear regression models. Overall, FEV1, FVC and FEV1/FVC z-scores declined over time (average crude annual FEV1 decline was -0.07 z-scores), but not at the same rate for all patients. FEV1 z-scores improved over time in 21% of patients, remained stable in 40% and declined in 39%. Low body mass index was associated with poor baseline lung function and with further decline. Results differed by country and ultrastructural defect, but we found no evidence of differences by sex, calendar year of diagnosis, age at diagnosis, diagnostic certainty or laterality defect. Our study shows that on average lung function in PCD declines throughout the entire period of lung growth, from childhood to young adult age, even among patients treated in specialised centres. It is essential to develop strategies to reverse this tendency and improve prognosi

HCN emission from translucent gas and UV-illuminated cloud edges revealed by wide-field IRAM 30m maps of Orion B GMC: Revisiting its role as tracer of the dense gas reservoir for star formation

We present 5 deg^2 (~250 pc^2) HCN, HNC, HCO+, and CO J=1-0 maps of the Orion B GMC, complemented with existing wide-field [CI] 492 GHz maps, as well as new pointed observations of rotationally excited HCN, HNC, H13CN, and HN13C lines. We detect anomalous HCN J=1-0 hyperfine structure line emission almost everywhere in the cloud. About 70% of the total HCN J=1-0 luminosity arises from gas at A_V < 8 mag. The HCN/CO J=1-0 line intensity ratio shows a bimodal behavior with an inflection point at A_V < 3 mag typical of translucent gas and UV-illuminated cloud edges. We find that most of the HCN J=1-0 emission arises from extended gas with n(H2) < 10^4 cm^-3, even lower density gas if the ionization fraction is > 10^-5 and electron excitation dominates. This result explains the low-A_V branch of the HCN/CO J=1-0 intensity ratio distribution. Indeed, the highest HCN/CO ratios (~0.1) at A_V < 3 mag correspond to regions of high [CI] 492 GHz/CO J=1-0 intensity ratios (>1) characteristic of low-density PDRs. Enhanced FUV radiation favors the formation and excitation of HCN on large scales, not only in dense star-forming clumps. The low surface brightness HCN and HCO+ J=1-0 emission scale with I_FIR (a proxy of the stellar FUV radiation field) in a similar way. Together with CO J=1-0, these lines respond to increasing I_FIR up to G0~20. On the other hand, the bright HCN J=1-0 emission from dense gas in star-forming clumps weakly responds to I_FIR once the FUV radiation field becomes too intense (G0>1500). The different power law scalings (produced by different chemistries, densities, and line excitation regimes) in a single but spatially resolved GMC resemble the variety of Kennicutt-Schmidt law indexes found in galaxy averages. As a corollary for extragalactic studies, we conclude that high HCN/CO J=1-0 line intensity ratios do not always imply the presence of dense gas.Comment: accepted for publication in A&A. 24 pages, 18 figures, plus Appendix. Abridged Abstract. English language not edite

Infection control, genetic assessment of drug resistance and drug susceptibility testing in the current management of multidrug/extensively-resistant tuberculosis (M/XDR-TB) in Europe: A tuberculosis network European Trialsgroup (TBNET) study

Aim Europe has the highest documented caseload and greatest increase in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) of all World Health Organization (WHO) regions. This survey examines how recommendations for M/XDR-TB management are being implemented. Methods TBNET is a pan-European clinical research collaboration for tuberculosis. An email survey of TBNET members collected data in relation to infection control, access to molecular tests and basic microbiology with drug sensitivity testing. Results 68/105 responses gave valid information and were from countries within the WHO European Region. Inpatient beds matched demand, but single rooms with negative pressure were only available in low incidence countries; ultraviolet decontamination was used in 5 sites, all with &gt;10 patients with M/XDR-TB per year. Molecular tests for mutations associated with rifampicin resistance were widely available (88%), even in lower income and especially in high incidence countries. Molecular tests for other first line and second line drugs were less accessible (76 and 52% respectively). A third of physicians considered that drug susceptibility results were delayed by &gt; 2 months. Conclusion Infection control for inpatients with M/XDR-TB remains a problem in high incidence countries. Rifampicin resistance is readily detected, but tests to plan regimens tailored to the drug susceptibilities of the strain of Mycobacterium tuberculosis are significantly delayed, allowing for further drug resistance to develop

HCN emission from translucent gas and UV-illuminated cloud edges revealed by wide-field IRAM 30m maps of Orion B GMC: Revisiting its role as tracer of the dense gas reservoir for star formation

35 pags., 28 figs., 14 tabs.We present 5 deg^2 (~250 pc^2) HCN, HNC, HCO+, and CO J=1-0 maps of the Orion B GMC, complemented with existing wide-field [CI] 492 GHz maps, as well as new pointed observations of rotationally excited HCN, HNC, H13CN, and HN13C lines. We detect anomalous HCN J=1-0 hyperfine structure line emission almost everywhere in the cloud. About 70% of the total HCN J=1-0 luminosity arises from gas at A_V < 8 mag. The HCN/CO J=1-0 line intensity ratio shows a bimodal behavior with an inflection point at A_V < 3 mag typical of translucent gas and UV-illuminated cloud edges. We find that most of the HCN J=1-0 emission arises from extended gas with n(H2) ~< 10^4 cm^-3, even lower density gas if the ionization fraction is > 10^-5 and electron excitation dominates. This result explains the low-A_V branch of the HCN/CO J=1-0 intensity ratio distribution. Indeed, the highest HCN/CO ratios (~0.1) at A_V < 3 mag correspond to regions of high [CI] 492 GHz/CO J=1-0 intensity ratios (>1) characteristic of low-density PDRs. Enhanced FUV radiation favors the formation and excitation of HCN on large scales, not only in dense star-forming clumps. The low surface brightness HCN and HCO+ J=1-0 emission scale with I_FIR (a proxy of the stellar FUV radiation field) in a similar way. Together with CO J=1-0, these lines respond to increasing I_FIR up to G0~20. On the other hand, the bright HCN J=1-0 emission from dense gas in star-forming clumps weakly responds to I_FIR once the FUV radiation field becomes too intense (G0>1500). The different power law scalings (produced by different chemistries, densities, and line excitation regimes) in a single but spatially resolved GMC resemble the variety of Kennicutt-Schmidt law indexes found in galaxy averages. As a corollary for extragalactic studies, we conclude that high HCN/CO J=1-0 line intensity ratios do not always imply the presence of dense gas.M.G.S.M. and J.R.G. thank the Spanish MICINN for funding support under grant PID2019-106110GB-I00. This work was supported by the French Agence Nationale de la Recherche through the DAOISM grant ANR-21-CE31–0010, and by the Programme National “Physique et Chimie du Milieu Interstellaire” (PCMI) of CNRS/INSU with INC/INP, co-funded by CEA and CNES. Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration (80NM0018D0004).Peer reviewe