Unmarried Couples and Income Taxes in France,

French tax laws do not allow unmarried couples to declare their income jointly. Thus they lose out, when compared to married couples, on the married couples' tax relief, a system which can decrease a couple's tax liability. The married couples' tax relief has the fullest effect when the structure of the spouses' contribution to the total is significantly asymmetric. It pinpoints the provisions that reduce the effectiveness of the married couple's tax allowance: the graduated relief and the minimum payment threshold. Marriage can then result in financial loss. Myriade, a microsimulation model, shows that non-marital union offers the most possibilities for people in the lowest income brackets. Simulating the marriage of unmarried couples shows a small advantage to marriage: this is mostly explained by the asymmetry in resources and a lower standard of living, both lower in unmarried couples.: Cohabitees, Married Couples, Income Tax System

Drinking Patterns and Their Predictive Factors in CONTROL: a 12-Month Prospective Study in a Sample of Alcohol-Dependent Patients Initiating Treatment

Aims: To describe the drinking patterns and their baseline predictive factors during a 12-month period after an initial evaluation for alcohol treatment. Methods CONTROL is a single-center, prospective, observational study evaluating consecutive alcohol-dependent patients. Using a curve clustering methodology based on a polynomial regression mixture model, we identified three clusters of patients with dominant alcohol use patterns described as mostly abstainers, mostly moderate drinkers and mostly heavy drinkers. Multinomial logistic regression analysis was used to identify baseline factors (socio-demographic, alcohol dependence consequences and related factors) predictive of belonging to each drinking cluster. ResultsThe sample included 143 alcohol-dependent adults (63.6% males), mean age 44.6 ± 11.8 years. The clustering method identified 47 (32.9%) mostly abstainers, 56 (39.2%) mostly moderate drinkers and 40 (28.0%) mostly heavy drinkers. Multivariate analyses indicated that mild or severe depression at baseline predicted belonging to the mostly moderate drinkers cluster during follow-up (relative risk ratio (RRR) 2.42, CI [1.02-5.73, P = 0.045] P = 0.045), while living alone (RRR 2.78, CI [1.03-7.50], P = 0.044) and reporting more alcohol-related consequences (RRR 1.03, CI [1.01-1.05], P = 0.004) predicted belonging to the mostly heavy drinkers cluster during follow-up. Conclusion In this sample, the drinking patterns of alcohol-dependent patients were predicted by baseline factors, i.e. depression, living alone or alcohol-related consequences and findings that may inform clinicians about the likely drinking patterns of their alcohol-dependent patient over the year following the initial evaluation for alcohol treatmen

Head-to-tail cyclization of side chain-protected linear peptides to recapitulate genetically-encoded cyclized peptides

Genetically‐encoded cyclic peptide libraries allow rapid in vivo screens for inhibitors of any target protein of interest. In particular, the Split Intein Circular Ligation of Protein and Peptides (SICLOPPS) system exploits spontaneous protein splicing of inteins to produce intracellular cyclic peptides. A previous SICLOPPS screen against Aurora B kinase, which plays a critical role during chromosome segregation, identified several candidate inhibitors that we sought to recapitulate by chemical synthesis. We describe the syntheses of cyclic peptide hits and analogs via solution‐phase macrocyclization of side chain‐protected linear peptides obtained from standard solid‐phase peptide synthesis. Cyclic peptide targets, including cyclo‐[CTWAR], were designed to match both the variable portions and conserved cysteine residue of their genetically‐encoded counterparts. Synthetic products were characterized by tandem high‐resolution mass spectrometry to analyze a combination of exact mass, isotopic pattern, and collisional dissociation‐induced fragmentation pattern. The latter analyses facilitated the distinction between targets and oligomeric side products, and served to confirm peptidic sequences in a manner that can be readily extended to analyses of complex biological samples. This alternative chemical synthesis approach for cyclic peptides allows cost‐effective validation and facile chemical elaboration of hit candidates from SICLOPPS screens

Système rénine-angiotensine et cancers urologiques / Renin-angiotensin system and urological cancers.

International audienceIntroduction: A controversy animates the literature on the potential role of the rennin-angiotensin system (RAS) in tumorogenesis. The objective of this review was to determine the involvement of this pathway in cancer, and more specifically in urological cancers. Material and Method: We made a systematic review of articles referenced in Pubmed, using the following keywords alone or combined: cancer, renin, angiotensin, VEGF, AT1R, antagonists of angiotensin-2 receptors, inhibitors of angiotensinogen converting. Results: Many types of cancers overexpress AT1-R in their tumoral tissues (breast, stomach, bladder, astrocytoma, glioblastoma, ovary, uterus, pancreas, kidney, prostate, adrenal gland). Ang-II can induce VEGF-A expression and promote neoangiogenesis, but also can trigger different molecular pathways involved in cell proliferation or inhibit apoptosis. Several xenograft murin models demonstrated anti-tumoral efficacy of RAS blockers, alone or using combined therapies, targeting angiogenesis and slowing down tumor growth. Retrospective studies in patients have also revealed a better progression-free survival and a better response to therapies in those treated with RAS blockers. Conclusion: Many data seem to demonstrate the involvement of the RAS in carcinogenesis, as well as anti-tumoral effect of RAS blockers in addition to anti-cancer treatments. Clinical data are now expected to confirm these experimental findings

Creating opportunities through science symposia

For most marine scientists, unless we work in the field of fisheries development or at the interface of science and policy, it is rare to feel that we are making an impact on the lives of people in the wider community. Most research scientists at universities and government laboratories also have limited opportunity to engage with schools and the general public outside of once-a-year open days. But beyond the science and networking, conferences, especially international conferences, can provide a myriad of opportunities for us to redress both these issues in a way that enriches all. Here, we describe the programme of development-related activities that supported the 6th International Jellyfish Blooms Symposium, and their impact, and we urge it be used as a template for other scientific meetings in the future. Jellyfish are far more than merely an interesting find on the beach. On the one hand, when abundant, jellyfish can cause economic harm to the tourism, aquaculture, fisheries and energy sectors1, but on the other hand, they provide food for other animals, e.g. turtles, shelter for juvenile fish and a potential resource to exploit2. In recognition of their role in marine ecosystems, the international jellyfish community updates and renews itself at a conference every 3 years or so. The first meeting was held in the USA in January 2000 and after conferences in Australia, Argentina, Japan and Spain, Africa’s turn came in 2019, after Monty Graham (University of Southern Mississippi) convinced one of us (M.J.G.) to host the conference at the University of the Western Cape

Development of an analytical workflow for bronchoalveolar lavage fluids analysis using GCxGC-TOFMS

editorial reviewe

Thermo-responsive Diels-Alder stabilized hydrogels for ocular drug delivery of a corticosteroid and an anti-VEGF fab fragment

In the present study, a novel in situ forming thermosensitive hydrogel system was investigated as a versatile drug delivery system for ocular therapy. For this purpose, two thermosensitive ABA triblock copolymers bearing either furan or maleimide moieties were synthesized, named respectively poly(NIPAM-co-HEA/Furan)-PEG 6K-P(NIPAM-co-HEA/Furan) (PNF) and poly(NIPAM-co-HEA/Maleimide)-PEG 6K-P(NIPAM-co-HEA/-Maleimide) (PNM). Hydrogels were obtained upon mixing aqueous PNF and PNM solutions followed by incubation at 37 °C. The hydrogel undergoes an immediate (<1 min) sol-gel transition at 37 °C. In situ hydrogel formation at 37 °C was also observed after intravitreal injection of the formulation into an ex vivo rabbit eye. The hydrogel network formation was due to physical self-assembly of the PNIPAM blocks and a catalyst-free furan-maleimide Diels-Alder (DA) chemical crosslinking in the hydrophobic domains of the polymer network. Rheological studies demonstrated sol-gel transition at 23 °C, and DA crosslinks were formed in time within 60 min by increasing the temperature from 4 to 37 °C. When incubated at 37 °C, these hydrogels were stable for at least one year in phosphate buffer of pH 7.4. However, the gels degraded at basic pH 10 and 11 after 13 and 3 days, respectively, due to hydrolysis of ester bonds in the crosslinks of the hydrogel network. The hydrogel was loaded with an anti-VEGF antibody fragment (FAB; 48.4 kDa) or with corticosteroid dexamethasone (dex) by dissolving (FAB) or dispersing (DEX) in the hydrogel precursor solution. The FAB fragment in unmodified form was quantitatively released over 13 days after an initial burst release of 46, 45 and 28 % of the loading for the 5, 10 and 20 wt% hydrogel, respectively, due to gel dehydration during formation. The low molecular weight drug dexamethasone was almost quantitively released in 35 days. The slower release of dexamethasone compared to the FAB fragement can likely be explained by the solubilization of this hydrophobic drug in the hydrophobic domains of the gel. The thermosensitive gels showed good cytocompatibility when brought in contact with macrophage-like mural cells (RAW 264.7) and human retinal pigment epithelium-derived (ARPE-19) cells. This study demonstrates that PNF-PNM thermogel may be a suitable formulation for sustained release of bioactive agents into the eye for treating posterior segment eye diseases

The Maunakea Spectroscopic Explorer Book 2018

(Abridged) This is the Maunakea Spectroscopic Explorer 2018 book. It is intended as a concise reference guide to all aspects of the scientific and technical design of MSE, for the international astronomy and engineering communities, and related agencies. The current version is a status report of MSE's science goals and their practical implementation, following the System Conceptual Design Review, held in January 2018. MSE is a planned 10-m class, wide-field, optical and near-infrared facility, designed to enable transformative science, while filling a critical missing gap in the emerging international network of large-scale astronomical facilities. MSE is completely dedicated to multi-object spectroscopy of samples of between thousands and millions of astrophysical objects. It will lead the world in this arena, due to its unique design capabilities: it will boast a large (11.25 m) aperture and wide (1.52 sq. degree) field of view; it will have the capabilities to observe at a wide range of spectral resolutions, from R2500 to R40,000, with massive multiplexing (4332 spectra per exposure, with all spectral resolutions available at all times), and an on-target observing efficiency of more than 80%. MSE will unveil the composition and dynamics of the faint Universe and is designed to excel at precision studies of faint astrophysical phenomena. It will also provide critical follow-up for multi-wavelength imaging surveys, such as those of the Large Synoptic Survey Telescope, Gaia, Euclid, the Wide Field Infrared Survey Telescope, the Square Kilometre Array, and the Next Generation Very Large Array.Comment: 5 chapters, 160 pages, 107 figure

La TD-GC×GC-HRTOFMS pour investiguer la fibrose pulmonaire chez des patients

Comprehensive two-dimensional gas chromatography has a great potential for exhaled breath analysis. The increased peak capacity and sensitivity, provided by the combination of two capillary columns of different stationary phases by means of a modulator, enable the chromatographic separation and detection of thousands of compounds from a complex matrix. For this reason, we carried out an exploratory study on SSc. Basically, breath samples were collected in 5L Tedlar® bags. Volatiles contained in the sampling bag were then transferred onto Tenax®GR/Carbopack™B thermal desorption tubes and finally released and separated into a Pegasus GC-HRT 4D through a mid-polar Rxi-624SilMS as first column (dimension) and a polar Stabilwax as second dimension. The exhaled breath of 32 patients and 30 healthy subjects was therefore analyzed. The high resolving power of this approach and the use of statistical models enabled the identification of 16 compounds discriminating SSC patients from healthy ones. However, further investigations had to be held to reach a better disease classification. In fact, the biomarkers highlighted here could be related to the scarring of the lungs making these non-specific to SSCs. The second phase of the study aims to go deeper in patient stratification. Three groups were investigated: 50 SSC patients, 50 SSC-fibrosis patients and 50 ILD ones. The samples were collected at Maastricht medical center and CHU of Liège. All samples were then analyzed in the OBiACHem lab. Currently, a classification model is under construction to stratify patients based on their fibrosis status

BREATHOMICS APPROACH TO INVESTIGATE SYSTEMIC SCLEROSIS USING THERMAL DESORPTION AND COMPREHENSIVE TWO-DIMENSIONAL GAS CHROMATOGRAPHY HIGH-RESOLUTION TIME-OF-FLIGHT MASS SPECTROMETRY

Systemic sclerosis (SSc) is a chronic and heterogenous auto-immune disease of unknown origin characterized by fibrosis, inflammation, vascular damages, and involvement of internal organs. Organ involvement appears at the early stage of the disease[1,2]. Interstitial lung disease (ILD) is one of the most common types of pulmonary involvement, responsible for the disease severity, and leading to high morbidity and mortality. One of the challenges in SSc remains the early diagnosis of patients with a high risk of disease progression driving mortality[3]. There is an unmet need for biological markers enabling SSc early diagnosis, prognosis, disease progression monitoring, and improving patients’ classification for more targeted therapies. Ideally, new diagnostic methods for SSc should be simple, fast, accurate, and cost-effective. Comprehensive two-dimensional gas chromatography (GC×GC) has a great potential for exhaled breath analysis. The increased peak capacity and sensitivity of GC×GC, provided by the combination of two capillary columns of different stationary phases by means of a modulator, enable the chromatographic separation and detection of thousands of compounds from a complex matrix[4]. For this reason, we carried out an exploratory study on SSc[5]. Basically, breath samples were collected in 5L Tedlar® bags. Volatiles contained in the sampling bag were then transferred onto Tenax®GR/Carbopack™B thermal desorption tubes (Markes International Ltd., Llantrisant, UK) and finally released and separated into a Pegasus GC-HRT 4D (LECO Corporation, St Joseph, MI, USA) through a mid-polar Rxi-624SilMS (30 m × 0.25 mm × 1.4 μm) as first column (dimension) and a polar Stabilwax (2 m × 0.25 mm ×0.5μm) as second dimension. The exhaled breath of 32 patients and 30 healthy subjects was therefore analyzed. The high resolving power of this approach and the use of statistical models enabled the identification of 16 compounds discriminating SSC patients from healthy ones[5]. However, further investigations had to be held to reach a better disease classification. In fact, the biomarkers highlighted here could be related to the scarring (fibrosis) of the lungs making these non-specific to SSCs. The second phase of the study aims to go deeper in patient stratification. Three groups were investigated: 50 SSC patients, 50 SSC-fibrosis patients and 50 ILD ones. The samples were collected at Maastricht medical center and CHU of Liège. All samples were then analyzed in the OBiACHem lab. Currently, a classification model is under construction to stratify patients based on their fibrosis status. [1] E. Zanatta, V. Codullo, J. Avouac, Y.A.-J. bone spine, undefined 2020, Elsevier (2019). [2] O. Bonhomme, B. André, F. Gester, … D. de S.-, undefined 2019, Academic.Oup.Com (n.d.). [3] J. Guiot, M. Henket, B. Andre, M. Herzog, N. Hardat, M.S. Njock, C. Moermans, M. Malaise, R. Louis, Clin. Epigenetics 12 (2020). [4] D. Zanella, J. Focant, F.A. Franchina, Anal. Sci. Adv. 2 (2021) 213–224. [5] D. Zanella, J. Guiot, P.-H. Stefanuto, L. Giltay, M. Henket, F. Guissard, B. André, M. Malaise, J. Potjewijd, F. Schleich, R. Louis, J.-F. Focant, Anal. Bioanal. Chem. 2021 41314 413 (2021) 3813–3822