A walk in the PARC: developing and implementing 21st century chemical risk assessment in Europe.

Current approaches for the assessment of environmental and human health risks due to exposure to chemical substances have served their purpose reasonably well. Nevertheless, the systems in place for different uses of chemicals are faced with various challenges, ranging from a growing number of chemicals to changes in the types of chemicals and materials produced. This has triggered global awareness of the need for a paradigm shift, which in turn has led to the publication of new concepts for chemical risk assessment and explorations of how to translate these concepts into pragmatic approaches. As a result, next-generation risk assessment (NGRA) is generally seen as the way forward. However, incorporating new scientific insights and innovative approaches into hazard and exposure assessments in such a way that regulatory needs are adequately met has appeared to be challenging. The European Partnership for the Assessment of Risks from Chemicals (PARC) has been designed to address various challenges associated with innovating chemical risk assessment. Its overall goal is to consolidate and strengthen the European research and innovation capacity for chemical risk assessment to protect human health and the environment. With around 200 participating organisations from all over Europe, including three European agencies, and a total budget of over 400 million euro, PARC is one of the largest projects of its kind. It has a duration of seven years and is coordinated by ANSES, the French Agency for Food, Environmental and Occupational Health & Safety.

Development and preliminary validation of the patient-reported Chronic Itch Burden Scale assessing health-related quality of life in chronic pruritus.

BACKGROUND: Chronic pruritus (CP) significantly affects patients' health-related quality of life (HRQoL). Very few self-reported HRQoL questionnaires exploring CP have been developed according to international guidelines, thus limiting their use in preauthorization trials. OBJECTIVES: To develop a self-reported HRQoL questionnaire in patients with CP owing to psoriasis, atopic dermatitis, seborrhoeic dermatitis of the scalp or idiopathic dermatitis, and to explore the preliminary psychometric properties of the questionnaire. METHODS: The study was performed in France. A conceptual framework was developed based on a structured literature review and expert insight, and was improved using three focus groups involving 19 participants. A 50-item questionnaire was created and tested with 21 participants using cognitive debriefings; 11 items were removed. A cross-sectional study including 251 participants was performed to explore the preliminary psychometric properties of the 39-item questionnaire. Dimensionality was explored using principal component analysis. Cronbach's alpha and correlation coefficients (interitem, item-total score and item-dimension score) were measured. The number of items was reduced through expert consensus. RESULTS: In the 39-item version, three main dimensions were identified (Cronbach's alpha = 0·94) and all correlation coefficients were > 0·34. Upon review, 13 items were deleted owing to poor quality and six items were deleted by the team, generating a 20-item version. The questionnaire's factorial structure was best reflected with a two-dimension solution, i.e. (i) social and emotional repercussions and (ii) relation to others, fear of judgement. CONCLUSIONS: The Chronic Itch Burden Scale patient-reported questionnaire explores broad aspects of HRQoL that are relevant for patients with various skin diseases. Its good cross-sectional validity makes it useful for trials and practitioners.

Tolerance and efficacy of a new celastrol-containing balm as adjunct care in psoriasis.

BACKGROUND: In patients with psoriasis, the non-lesional skin also presents abnormalities, requiring emollient application on the whole body. OBJECTIVES: To evaluate the tolerance of a new emollient balm containing celastrol, an active ingredient with anti-Th17 immunomodulatory properties used alone or in association with topical or systemic drug treatments or phototherapy, and its efficacy when used alone. METHODS: Adults with body plaque psoriasis applied the product over the whole body once a day for 4 weeks (balm used alone in 41 patients and with ongoing treatment in 50 patients). At D1, D8 ('balm alone' study) or D15 ('balm in association' study) and D29, the dermatologist rated physical and functional signs and assessed pruritus and body global lesion score (evaluating erythema, induration/thickness, scaling and dryness) in the 'balm alone' study. RESULTS: No reaction related to the product was reported, and the tolerance was deemed excellent. In the 'balm alone' study, mean pruritus intensity score significantly decreased at D8 (-39%, P < 0.001) and D29 (-60%, P < 0.001) compared with D1, together with the body global lesion score (-24% at D8 and -26% at D29, P < 0.001). In parallel, quality of life improved, as evidenced by a patient-reported outcome questionnaire. Cosmetic acceptability was good. CONCLUSION: This new emollient balm was very well tolerated by patients with body plaque psoriasis either alone or in association with drug treatment or phototherapy, which is important to ensure long-term compliance. Daily application during one month improved pruritus, physical signs and quality of life.

Beyond just the operating room: characterizing the complete caseload of a tertiary acute care surgery service.

BACKGROUND: Most studies evaluating acute care surgery (ACS) models of care for patients with emergency general surgery (EGS) conditions have focused on patients who undergo surgery while admitted under the care of the ACS service. The purpose of this study was to prospectively examine the case mix of admissions and consultations to an ACS service at a tertiary centre to identify the frequency and distribution of both operatively and nonoperatively managed EGS conditions. METHODS: In this prospective cohort study, we evaluated consecutive patients assessed by the ACS team between July 1 and Aug. 31, 2015, at a large Canadian tertiary care centre. This included all consultations and outside hospital transfers. Diagnoses, demographic characteristics, comorbidities, intervention(s), complications, readmission and in-hospital death were captured. RESULTS: The ACS team was involved in the care of 359 patients, 176 (49.0%) of whom were admitted under the direct care of the ACS team. Nonoperative care was indicated in 82 patients (46.6%) admitted to the ACS service and 151 (82.5%) of those admitted to a non-ACS service (p < 0.001). Bowel obstruction (37 patients [21.0%]) was the most common reason for admission, followed by wound/abscess (24 [13.6%), biliary disease (24 [13.6%]) and appendiceal disease (23 [13.1%]). Rates of 30-day return to the emergency department and readmission were 17.0% and 9.1%, respectively, and the in-hospital mortality rate was 1.7%. CONCLUSION: Acute care surgery teams care for a wide breadth of disease, a considerable amount of which is managed nonoperatively.

CONTEXTE: La plupart des études qui ont évalué les modèles de soins chirurgicaux aigus (SCA) chez des patients souffrant de problèmes de santé nécessitant un traitement de chirurgie générale (TCG) d'urgence ont porté sur des patients ayant subi une intervention lors de leur admission dans un service de SCA. Le but de cette étude était d'analyser de manière prospective la clientèle admise ou vue en consultation dans le service de SCA d'un centre de soins tertiaires pour connaître la fréquence et la distribution des problèmes de santé nécessitant un TCG d'urgence effectivement traités chirurgicalement ou autrement. MÉTHODES: Dans cette étude de cohorte prospective, nous avons évalué des patients consécutifs vus par l'équipe de SCA entre le 1er juillet et le 31 août 2015 dans un grand centre canadien de soins tertiaires. Cela incluait toutes les consultations et les transferts en provenance d'autres hôpitaux. Nous avons noté les diagnostics, les caractéristiques démographiques, les comorbidités, les interventions, les complications, réadmissions et les décès en cours d'hospitalisation. RÉSULTATS: L'équipe de SCA a assuré les soins de 359 patients, dont 176 (49,0 %) avaient été admis directement au service de SCA. Des soins non chirurgicaux étaient indiqués chez 82 patients (46,6 %) admis au service de SCA et chez 151 (82,5 %) patients admis dans d'autres services (p < 0,001). L'obstruction intestinale (37 patients [21,0 %]) a été la raison la plus fréquente des admissions, suivie de blessure ou d'abcès (24 patients [13,6 %), maladie biliaire (24 patients [13,6 %]) et maladie appendiculaire (23 patients [13,1 %]). Les taux de retour aux urgences et de réadmission dans les 30 jours ont été de 17,0 % et de 9,1 %, respectivement, et le taux de mortalité en cours d'hospitalisation a été de 1,7 %. CONCLUSION: Les équipes de soins chirurgicaux aigus prennent en charge un vaste éventail de pathologies, dont une part importante est gérée de manière non chirurgicale.

Medical school outreach and mentorship for rural secondary school students: a pilot of the Southwestern Ontario Medical Mentorship Program.

INTRODUCTION: Rural communities in Canada face challenges with physician recruitment. Physicians from rural backgrounds are more likely to practise in rural areas; however, rural students are underrepresented in medical schools. To address this, the Southwestern Ontario Medical Mentorship Program (SWOMMP) was created to expose rural secondary school students to medical careers. METHODS: This pilot project involved a school-based interactive session run by rural medical students on paths to medicine, medical specialties and skills workshops of roughly 2.5 hours targeted to grades 10-12 university-level students in rural southwestern Ontario. Two sessions were held, 1 in a town with a population of 20 000 and the other in a town with a population of 5000. A survey was administered before and after the session to assess changes in interest in medical careers and in perceived barriers. RESULTS: Forty-five students participated in the sessions. After the sessions, 32 students (71%) were considering a career in health care, compared to 26 (58%) before the sessions. Almost all students (43 [96%]) found the session helpful or extremely helpful, and all reported they would recommend it to other classes. Finances, grades and length of schooling were the most commonly perceived barriers to pursuing a career in medicine; fewer students had concerns about finances and length of schooling after the sessions. Twenty-nine students (64%) enrolled in longitudinal mentorship with a medical student. CONCLUSION: This pilot project showed that a rural secondary school outreach program run by medical students can increase high school students' interest in medical careers. The project will continue and aims to expand and improve using the pilot study's data.

INTRODUCTION: Les régions rurales au Canada ont de la difficulté à recruter des médecins et les médecins qui viennent eux-mêmes de milieux ruraux sont plus susceptibles d'exercer en région rurale. Cependant, les étudiants de régions rurales sont sous-représentés au sein des écoles de médecine. Pour aborder ce problème, le programme SWOMMP (Southwestern Ontario Medical Mentorship Program) a été créé afin de présenter des carrières en médecine aux élèves du secondaire de régions rurales. METHODS: Le projet pilote comprenait une séance interactive en milieu scolaire d'une durée d'environ 2.5 heures tenue par des étudiants en médecine de milieux ruraux. Les séances portaient sur le cheminement de carrière d'un médecin généraliste ou d'un médecin spécialiste et des ateliers sur les compétences ciblant les élèves de 10e, 11e et 12e année de régions rurales du sud-ouest de l'Ontario qui envisagent poursuivre des études universitaires. Deux séances ont été organisées, l'une dans une ville de 20 000 habitants et l'autre dans une localité de 5000 habitants. Un sondage a été mené avant et après la séance pour déterminer les changements d'intérêt pour une carrière de médecin et des obstacles perçus. RESULTS: Quarante-cinq élèves ont participé aux séances. À la suite de celles-ci, 32 élèves (71 %) envisageaient une carrière en soins de santé, comparativement à 26 (58 %) avant les séances. Presque tous les élèves (43 [96 %]) étaient d'avis que la séance leur avait été utile ou extrêmement utile et tous les élèves ont signalé qu'ils la recommanderaient aux élèves d'autres classes. Les ressources financières, les résultats scolaires et la durée des études étaient les obstacles perçus les plus courants à la poursuite d'une carrière de médecin. Moins d'élèves se préoccupaient des ressources financières et de la durée des études à la fin des séances. Vingt-neuf élèves (64 %) se sont inscrits à un mentorat longitudinal auprès d'un étudiant en médecine. CONCLUSION: Le projet pilote a permis de démontrer qu'un programme d'approche des écoles secondaires rurales, dirigé par des étudiants en médecine, peut accroître l'intérêt des élèves du secondaire pour une carrière en médecine. Le projet se poursuivra dans un but d'expansion et d'amélioration à l'aide des données de l'étude pilote.

Efficacy of a Rhealba® Oat Extract-based emollient on chronic pruritus in elderly French outpatients.

BACKGROUND: Chronic pruritus, defined as itch persisting more than 6 weeks, is a debilitating problem that affects one in four elderly adults. Emollients are recommended for the management of pruritus, but evidence of efficacy is scarce. OBJECTIVE: Assess the efficacy of a Rhealba® Oat Extract-based emollient in the management of chronic pruritus in elderly outpatients. METHODS: This was a randomized, mono-centric, open-label, cross-over study in adults ≥60 years of age with xerosis associated with chronic pruritus. Subjects were randomized 1:1 to start with a 2-week non-treatment phase or a 2-week treatment phase in which they applied the emollient once or twice daily. The primary outcome was subject-assessed pruritus using an established visual analogue scale. Subjects also assessed pruritus using the 5-D itch scale. Investigators assessed xerosis using the Overall Dry Skin Score and measured hydration index by Corneometer® , desquamation by D-Squame and transepidermal water loss by Aquaflux® . RESULTS: Thirty subjects were included. Pruritus intensity on the visual analogue scale improved significantly more during the treatment phase than during the non-treatment phase (P < 0.0001). This was also observed immediately after the first product application (P < 0.0001). According to the 5-D itch scale, pruritus decreased during the treatment phase but remained stable during the non-treatment phase (P = 0.0042). At the end of the treatment phase, more than half of the subjects reported an improvement in pruritus, and 30% reported complete disappearance, whereas pruritus remained stable during the non-treatment phase (P < 0.0001). Xerosis improved significantly more during the treatment phase than during the non-treatment phase as measured by D-Squame, clinical assessment and hydration index (P < 0.0001). Transepidermal water loss did not significantly change. CONCLUSION: Daily use of a Rhealba Oat Extract-based emollient can provide relief to elderly adults who suffer from xerosis associated with chronic pruritus.

Distorted octahedral environments in tricarbonylrhenium(I) complexes of 5-[2-(2,4,6-trimethylphenyl)diazen-1-yl]quinolin-8-olate and 5,7-bis[2-(2-methylphenyl)diazen-1-yl]quinolin-8-olate.

The Re(I) centres of two Re(I)-tricarbonyl complexes, viz. tricarbonyl(pyridine-κN){5-[2-(2,4,6-trimethylphenyl)diazen-1-yl]quinolin-8-olato-κ(2)N(1),O}rhenium(I), [Re(C23H21N4O)(CO)3], (I), and {5,7-bis[2-(2-methylphenyl)diazen-1-yl]quinolin-8-olato-κ(2)N(1),O}tricarbonyl(pyridine-κN)rhenium(I), [Re(C28H23N6O)(CO)3], (II), are facially surrounded by three carbonyl ligands, a pyridine ligand and either a 5-[2-(2,4,6-trimethylphenyl)diazen-1-yl]quinolin-8-olate [in (I)] or a 5,7-bis[2-(2-methylphenyl)diazen-1-yl]quinolin-8-olate [in (II)] ligand, in a slightly distorted octahedral environment. The crystal structure of (I) is stabilized by two intermolecular C-H···O interactions and that of (II) is stabilized by three intermolecular C-H···O hydrogen-bonding interactions.

N,N'-(4,5-Dimethyl-1,2-phenyl-ene)bis-(pyridine-2-carboxamide).

In the title compound, C(20)H(18)N(4)O(2), the dihedral angles between the central benzene ring and the pyridine rings are 57.55 (6) and 22.05 (8)°. The mol-ecular conformation is stabilized by intra-molecular N-H⋯N inter-actions and in the crystal structure an inter-molecular asymmetric cyclic hydrogen-bonding association involving both amide N-H donors and a common amide O-atom acceptor gives a chain extending along the c axis.

[Bis(pyridin-2-ylmeth-yl)amine-κ(3)N,N',N'']tricarbonyl-rhenium(I) bromide hemihydrate.

The title compound, fac-[Re(C(12)H(12)N(3))(CO)(3)]Br·0.5H(2)O, crystallizes with a cationic rhenium(I) unit, a bromide ion and half a water mol-ecule, situated on a twofold rotation axis, in the asymmetric unit. The Re(I) atom is facially surrounded by three carbonyl ligands and a tridentate bis-(pyridin-2-ylmeth-yl)amine ligand in a distorted octahedral environment. N-H⋯Br, O-H⋯Br, C-H⋯O and C-H⋯Br hydrogen bonds are present in the crystal structure and π-π stacking is also observed [centroid-centroid distances = 3.669 (1) Šand 4.054 (1) Å], giving rise to a three-dimentional network. The mol-ecules pack in a head-to-head fashion along the ac plane.

5-(3,4-Dimeth-oxy-benzyl-idene)-1,3-dimethyl-1,3-diazinane-2,4,6-trione.

In the title compound, C(15)H(16)N(2)O(5), the dihedral angle between 1,3-diazinane and benzene rings is only 4.27 (1)°. The essentially planar mol-ecular structure is characterized by a short intra-molecular C-H⋯O separation and by an exceptionally large bond angle of 138.25 (14)° at the bridging methine C atom. The meth-oxy groups deviate somewhat from the plane of the benzene ring, with C-C-O-C torsion angles of -15.6 (1) and 9.17 (6)°. In the crystal, mol-ecules form centrosymmetric dimers via donor-acceptor π-π inter-actions, with a centroid-centroid distance of 3.401 (1) Å.

cyclo-Tetra-µ-oxido-tetra-kis-[(acetyl-acetonato-κO,O')bis-(ethano-lato-κO)niobium(V)].

The asymmetric unit of the title tetra-nuclear niobium(V) compound, [Nb(4)(C(2)H(5)O)(8)(C(5)H(7)O(2))(4)O(4)], contains two Nb(V) atoms, two bridging O atoms, two acetyl-acetonate and four ethano-late ligands. Each Nb(V) atom is six-coordinated by the bridging O atoms, two ethano-late and one chelating acetyl-acetonate ligands. The Nb-O distances vary between 1.817 (2) and 2.201 (2) Šand the O-Nb-O angles vary between 78.88 (8) and 102.78 (9)°, illustrating the significant distortion from ideal ocahedral geometry. The rest of the tetra-nuclear unit is generated through an inversion centre. The C atoms of two of the ethano-late mol-ecules are disordered over two sites [occupancy ratio 0.601 (12):0.399 (12)].

Acetonitrile-trichloridobis(cyclo-hexyl-diphenyl-phosphane)rhodium(III) acetonitrile disolvate.

In the title compound, [RhCl(3)(CH(3)CN)(C(18)H(21)P)(2)]·2CH(3)CN, the complex mol-ecule lies on a twofold rotation axis that passes through the Rh(III) atom, one Cl atom, and the C and N atoms of the coordinated acetonitrile mol-ecule. The Rh(III) atom is coordinated by two P atoms in trans positions, three Cl atoms and an acetonitrile mol-ecule in a distorted octa-hedral geometry. Intra-molecular C-H⋯Cl inter-actions are observed. The uncoordinated acetonitrile mol-ecule is disordered over two sites with occupancies of 0.588 (4) and 0.412 (4).

1,1,1,5,5,5-Hexafluoro-2,4-dimeth-oxy-pentane-2,4-diol.

The title compound, C(7)H(10)F(6)O(4), was isolated as an unexpected product from a reaction of tantalum(V) methoxide with hexa-fluoro-acetyl-acetone in a methanol solution. The asymmetric unit consists of one half-mol-ecule with the middle C atom lying on a twofold axis. The crystal structure is stabilized by O-H⋯O and an array of C-H⋯F hydrogen-bonding inter-actions. These inter-actions link the mol-ecules into a stable supra-molecular three-dimensional network. The mol-ecules pack in a ribbon-like form in the ac plane as a result of these inter-actions.

Dimethyl 2,6-dimethyl-4-phenyl-pyridine-3,5-dicarboxyl-ate.

In the title compound, C(17)H(17)NO(4), the dihedral angle between the benzene and pyridine rings is 75.51 (4)°. The benzene and pyridine rings are both approximately planar (r.m.s. deviations of 0.0040 and 0.0083 Å, respectively), indicating that the pyridine N atom is not protonated. The crystal structure is stabilized by weak inter-molecular C-H⋯O and C-H⋯N inter-actions.

(2-Methyl-4-oxo-4H-pyran-3-olato-κO,O)bis-(triphenyl-phosphane-κP)copper(I)-triphenyl-phosphane-methanol (1/1/1).

In the title compound, [Cu(C(6)H(5)O(3))(C(18)H(15)P)(2)]·C(18)H(15)P·CH(3)OH, the pyran-4-one ring is appromimately planar (r.m.s deviation = 0.0138 Å), with the Cu(I) atom 0.451 (5) Šout of the plane. The Cu(I) atom has a distorted tetra-hedral coordination. The O-Cu-O angle is 80.07 (8)° and the P-Cu-P angle is 123.49 (3)°. The crystal packing is stablized by intra-molecular C-H⋯O inter-actions and inter-molecular C-H⋯O and O-H⋯O inter-actions.

Racemic tricarbon-yl[7-meth-oxy-2-(η-phen-yl)chromane]-chromium(0).

In the title compound, [Cr(C(16)H(16)O(2))(CO)(3)], the Cr(0) atom of the Cr(CO)(3) unit is coordinated to the phenyl ring of the flavan ligand in an η(6) mode, with a normal arene-to-metal distance. The Cr(CO)(3) unit exhibits a three-legged piano-stool conformation, while the dihydro-pyran ring displays a distorted envelope configuration. The phenyl ring is twisted away from the fused ring system by 25.5 (2)°. The meth-oxy group is almost coplanar with the phenyl ring [C(Me)-O-C(ar)-C(ar) torsion angle = 8.46 (2)°]. The crystal packing is stabilized by inter-molecular C-H⋯O inter-actions.

4,5-Bis(2,4-di-tert-butyl-phen-oxy)phthalonitrile.

In the title compound, C(36)H(44)N(2)O(2), the dihedral angles between the phthalonitrile ring and the two di-tert-butyl-benzene rings are 68.134 (8) and 70.637 (11)°. The two nitrile groups are almost coplanar with the phthalonitrile ring except for one of the N atoms which deviates from the plane by 0.125 (4) Å. One of the tert-butyl groups is disordered over two orientations, with refined occupancies of 0.814 (6) and 0.186 (6). Intra-molecular C-H⋯O inter-actions stabilize the molecular structure. The crystal packing is stabilized by inter-molecular C-H⋯N inter-actions.

Correlation analysis of noise and ultrafine particle counts in a street canyon.

Ultrafine particles (UFP, diameter<100 nm) are very likely to negatively affect human health, as underlined by some epidemiological studies. Unfortunately, further investigation and monitoring are hindered by the high cost involved in measuring these UFP. Therefore we investigated the possibility to correlate UFP counts with data coming from low-cost sensors, most notably noise sensors. Analyses are based on an experiment where UFP counts, noise levels, traffic counts, nitrogen oxide (NO, NO(2) and their combination NO(x)) concentrations, and meteorological data were collected simultaneously in a street canyon with a traffic intensity of 3200 vehicles/day, over a 3-week period during summer. Previous reports that NO(x) concentrations could be used as a proxy to UFP monitoring were verified in our setup. Traffic intensity or noise level data were found to correlate with UFP to a lesser degree than NO(x) did. This can be explained by the important influence of meteorological conditions (mainly wind and humidity), influencing UFP dynamics. Although correlations remain moderate, sound levels are more correlated to UFP in the 20-30 nm range. The particles in this size range have indeed rather short atmospheric residence times, and are thus more closely short-term traffic-related. Finally, the UFP estimates were significantly improved by grouping data with similar relative humidity and wind conditions. By doing this, we were able to devise noise indicators that correlate moderately with total particle counts, reaching a Spearman correlation of R=0.62. Prediction with noise indicators is even comparable to the more-expensive-to-measure NO(x) for the smallest UFP, showing the potential of using microphones to estimate UFP counts.

2',3,4,4'-Tetra-meth-oxy-chalcone.

IN THE TITLE COMPOUND [SYSTEMATIC NAME: 1-(2,4-dimethoxyphenyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one], C(19)H(20)O(5), the dihedral angle between the benzene rings is 26.88 (5)°. One of the meth-oxy groups is twisted slightly away from the plane [C-O-C-C torsion angle = -12.8 (3)°] while the others are almost co-planer [C-O-C-C torsion angles = -3.2 (3), 2.6 (3) and -3.6 (3)°]. The crystal packing is stabilized by inter-molecular C-H⋯O inter-actions. A weak intra-molecular C-H⋯O inter-action occurs.