Clinimetric properties of relevant criteria for assessing writing and drawing orientation after right hemisphere stroke.

BACKGROUND: Writing and drawing orientation is rarely assessed in clinical routine, although it might have a potential value in detecting impaired verticality perception after right hemispheric stroke (RHS). Assessment tools and criteria must be conceived and validated. We therefore explored the clinimetric properties of a set of quantitative writing and drawing orientation criteria, their ranges of normality, and their tilt prevalence in RHS individuals. NEW METHODS: We asked 69 individuals with subacute RHS and 64 matched healthy controls to write three lines and to copy the Gainotti Figure (house and trees). We determined six criteria referring to the orientation of writing and drawing main axes: for writing, the line and margin orientations, and for drawing, the tree, groundline, wall, and roofline orientations. Orientations were measured by using an electronic protractor from specific landmarks positioned by independent evaluators. RESULTS: The set of criteria fulfilling all clinimetric properties (feasibility, measurability, reliability) comprised the line orientation of the writing and the wall and roofline orientations of the drawing. Writing and drawing tilts were frequent after RHS (about 30% by criterion). COMPARISON WITH EXISTING METHODS: So far, graphomotor orientation was mostly tested qualitatively and could not be objectively appreciated in absence of validated tools and criteria, and without ranges of normality. Writing and drawing tilts may now be assessed both in routine clinical practice and research. CONCLUSIONS: Our study paves the way for investigating the clinical determinants of graphomotor tilts, including impaired verticality perception, to better understand their underlying mechanisms.

Human pluripotent stem cells-derived inner ear organoids recapitulate otic development in vitro.

Our molecular understanding of the early stages of human inner ear development has been limited by the difficulty in accessing fetal samples at early gestational stages. As an alternative, previous studies have shown that inner ear morphogenesis can be partially recapitulated using induced pluripotent stem cells (iPSCs) directed to differentiate into Inner Ear Organoids (IEOs). Once validated and benchmarked, these systems could represent unique tools to complement and refine our understanding of human otic differentiation and model developmental defects. Here, we provide the first direct comparisons of the early human embryonic otocyst and human iPSC-derived IEOs. We use multiplexed immunostaining, and single-cell RNA sequencing to characterize IEOs at three key developmental steps, providing a new and unique signature of in vitro derived otic -placode, -epithelium, -neuroblasts, and -sensory epithelia. In parallel, we evaluate the expression and localization of critical markers at these equivalent stages in human embryos. We show that the placode derived in vitro (days 8-12) has similar marker expression to the developing otic placode of Carnegie Stage (CS) 11 embryos and subsequently (days 20-40) this gives rise to otic epithelia and neuroblasts comparable to the CS13 embryonic stage. Differentiation of sensory epithelia, including supporting cells and hair cells starts in vitro at days 50-60 of culture. The maturity of these cells is equivalent to vestibular sensory epithelia at week 10 or cochlear tissue at week 12 of development, before functional onset. Together, our data indicate that the current state-of-the-art protocol enables the specification of bona fide otic tissue, supporting the further application of IEOs to inform inner ear biology and disease.

Final results of the IFCT-0803 study, a phase II study of cetuximab, pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced, unresectable, stage III, non-squamous, non-small-cell lung cancer.

PURPOSE: Roughly 20% of patients with non-small-cell lung cancer exhibit locally advanced, unresectable, stage III disease. Concurrent platinum-based chemoradiotherapy is the backbone treatment, which is followed by maintenance immunotherapy, yet with poor long-term prognosis. This phase II trial (IFCT-0803) sought to evaluate whether adding cetuximab to cisplatin and pemetrexed chemoradiotherapy would improve its efficacy in these patients. MATERIALS AND METHODS: Eligible patients received weekly cetuximab (loading dose 400mg/m2 day 1; subsequent weekly 250mg/m2 doses until two weeks postradiotherapy). Chemotherapy comprised cisplatin (75mg/m2) and pemetrexed (500mg/m2), both delivered on day 1 of a 21-day cycle of maximally four. Irradiation with maximally 66Gy started on day 22. Disease control rate at week 16 was the primary endpoint. RESULTS: One hundred and six patients were included (99 eligible patients). Compliance exceeded 95% for day 1 of chemotherapy cycles 1 to 4, with 76% patients receiving the 12 planned cetuximab doses. Maximal grade 3 toxicity occurred in 63% patients, and maximal grade 4 in 9.6%. The primary endpoint involving the first 95 eligible patients comprised two (2.1%) complete responses, 57 (60.0%) partial responses, and 27 (28.4%) stable diseases. This 90.5% disease control rate (95% confidence interval [95% CI]: 84.6%-96.4%) was achieved at week 16. After median 63.0-month follow-up, one-year and two-year survival rates were 75.8% and 59.5%. Median overall survival was 35.8months (95% CI: 23.5-NR), and median progression-free survival 14.4months (95% CI: 11.2-18.8), with one-year and two-year progression-free survival rates of 57.6% and 34.3%. CONCLUSION: These survival rates compare favourably with published data, thus justifying further development of cetuximab-based induction chemoradiotherapy.

[Lung cancer screening with low-dose thoracic CT-scan in the Somme area]. / Dépistage des cancers bronchopulmonaires par tomodensitométrie thoracique à faible dose dans la Somme.

RATIONALE: This feasibility trial proposes to set up in the department of the Somme an annual screening for lung cancer with low-dose thoracic CT. It responds to the first objective of the third cancer plan and follows the publication of the results of the National Lung Screening Trial in 2011. METHODS: The method of this study is to use the existing networks among and between healthcare professionals and the departmental cancer screening structure. The inclusion criteria will be those of the National Lung Screening Trial. Screening will be proposed by treating physicians and chest physicians. The CT-scan will be performed in radiological centers that adhere to the good practice charter for low radiation scanning. A copy of CT results will be sent to the departmental structure of cancer screening (ADEMA80) which will ensure traceability and will perform statistical analysis. The study received funding from the Agence régionale de santé de la Picardie and la ligue contre le cancer. EXPECTED RESULTS: The primary endpoints of this screening will be the number of cancers diagnosed and the survival of the patients. The follow-up of positive examinations, delays in management and the level of participation will also be assessed.

Statistics of color-matching experimental data.

By assuming that color matches are normally distributed in XYZ space, we present a rigorous statistical technique to obtain regions of equally noticeable chromaticity differences. The probability density function of color matches in (x, y, Y) space is calculated according to standard techniques in probability theory. The geometry of the chromaticity thresholds is computed for various confidence levels alpha. Because of the asymmetry of the probability density function in (x, y, Y) space, the chromaticity thresholds are not symmetrical around the color center. The asymmetries depend on the color center, and they increase when high confidence levels (alpha < 0.32) are considered. It is our opinion that the technique proposed here can provide a useful tool for checking and evaluating deviations from the elliptic geometry of the chromaticity thresholds. It is formally demonstrated that regions of equally noticeable chromaticity differences are not ellipses when the normality hypothesis is assumed in XYZ space.