Reactions of nitrogen nucleophiles with enantiopure cyclohexenyl electrophiles:a stereo- and regio- selective study

The reactions of enantiopure cyclohexene epoxides and trans-1,2-bromoacetates, derived from the corresponding substituted benzene cis-dihydrodiol metabolites, with nitrogen nucleophiles, were examined and possible mechanisms proposed. An initial objective was the synthesis of new 1,2-aminoalcohol enantiomers as potential chiral ligands and synthetic scaffolds for library generation. These apparently simple substitution reactions proved to be more complex than initially anticipated and were found to involve a combination of different reaction mechanisms. Allylic trans-1,2-azidohydrins were prepared by Lewis acid-catalysed ring-opening of cyclic vinyl epoxides with sodium azide via an S(N)2 mechanism. On heating, these trans-1,2-azidohydrins isomerized to the corresponding trans-1,4-azidohydrins via a suprafacial allyl azide [3,3]-sigmatropic rearrangement mechanism. Conversion of a 1,2-azidohydrin to a 1,2-azidoacetate moved the equilibrium position in favour of the 1,4-substitution product. Allylic trans-1,2-bromoacetates reacted with sodium azide at room temperature to give C-2 and C-4 substituted products. A clean inversion of configuration at C-2 was found, as expected, from a concerted S(N)2-pathway. However, substitution at C-4 was not stereoselective and resulted in mixtures of 1,4-cis and 1,4-trans products. This observation can be rationalized in terms of competitive S(N)2 and S(N)2 reactions allied to a [3,3]-sigmatropic rearrangement. cis-1,2-Azidohydrins and cis-1,2-azidoacetates were much more prone to rearrange than the corresponding trans-isomers. Reaction of the softer tosamide nucleophile with trans-1,2-bromoacetates resulted, predominantly, in C-4 substitution via a syn-S(N)2 mechanism. One application of the reaction of secondary amines with allylic cyclohexene epoxides, to give trans-1,2-aminoalcohols, is in the synthesis of the anticholinergic drug vesamicol, via an S(N)2 mechanism. Copyright (c) 2013 John Wiley & Sons, Ltd.

The paternal genome and the health of the assisted reproductive technology child

As a number of children born by assisted reproductive technology (ART) are increasing each year across the developed world, the health of such offspring is a matter of public concern. Does the integrity of the paternal genome impact on offspring health? In societal terms, as birth rates fall, and the Western population become unsustainable, do the benefits outweigh the costs of creating and providing for this ART conceived sub population? There are little data to date to answer these questions. The long‑term health of such children has largely been ignored, and success measured only by early (pre-birth) outcomes such as embryo quality or pregnancy. However, there are powerful paradigms such as ageing and smoking that give vital clues as to the potential impact of unhealthy spermatozoa on disease risk, mental and physical health, fertility and mortality of these offspring.

Towards core outcome set (COS) development: a follow-up descriptive survey of outcomes in Cochrane reviews

BACKGROUND: A core outcome set (COS) can address problems of outcome heterogeneity and outcome reporting bias in trials and systematic reviews, including Cochrane reviews, helping to reduce waste. One of the aims of the international Core Outcome Measures in Effectiveness Trials (COMET) Initiative is to link the development and use of COS with the outcomes specified and reported in Cochrane reviews, including the outcomes listed in the summary of findings (SoF) tables. As part of this work, an earlier exploratory survey of the outcomes of newly published 2007 and 2011 Cochrane reviews was performed. This survey examined the use of COS, the variety of specified outcomes, and outcome reporting in Cochrane reviews by Cochrane Review Group (CRG). To examine changes over time and to explore outcomes that were repeatedly specified over time in Cochrane reviews by CRG, we conducted a follow-up survey of outcomes in 2013 Cochrane reviews.

METHODS: A descriptive survey of outcomes in Cochrane reviews that were first published in 2013. Outcomes specified in the methods sections and reported in the results section of the Cochrane reviews were examined by CRG. We also explored the uptake of SoF tables, the number of outcomes included in these, and the quality of the evidence for the outcomes.

RESULTS: Across the 50 CRGs, 375 Cochrane reviews that included at least one study specified a total of 3142 outcomes. Of these outcomes, 32 % (1008) were not reported in the results section of these reviews. For 23 % (233) of these non-reported outcomes, we did not find any reason in the text of the review for this non-report. Fifty-seven percent (216/375) of reviews included a SoF table.

CONCLUSIONS: The proportion of specified outcomes that were reported in Cochrane reviews had increased in 2013 (68 %) compared to 2007 (61 %) and 2011 (65 %). Importantly, 2013 Cochrane reviews that did not report specified outcomes were twice as likely to provide an explanation for why the outcome was not reported. There has been an increased uptake of SoF tables in Cochrane reviews. Outcomes that were repeatedly specified in Cochrane reviews by CRG in 2007, 2011, and 2013 may assist COS development.

Highly CO2 sensitive extruded fluorescent plastic indicator film based on HPTS

Highly-sensitive optical fluorescent extruded plastic films are reported for the detection of gaseous and dissolved CO2. The pH-sensitive fluorescent dye used is 8-Hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS, PTS-) coated on the surface of hydrophilic fumed silica and the base is tetrabutylammonium hydroxide (TBAH). The above components are used to create an HPTS pigment (i.e. HPTS/SiO2/TBAH) with a high CO2 sensitivity (%CO2(S=1/2) = 0.16%) and fast 50% response (t50↓) = 2 s and recovery (t50↑) = 5 s times. Highly CO2-sensitive plastic films are then fabricated, via the extrusion of the HPTS pigment powder in low-density polyethylene (LDPE). As with the HPTS-pigment, the luminescence intensity (at 515 nm) and absorbance (at 475 nm) of the HPTS plastic film decreases as the %CO2 in the ambient gas phase increases. The HPTS plastic film exhibits a high CO2 sensitivity, %CO2(S=1/2), of 0.29%, but a response time ˂2 min and recovery time ˂40 min, which is slower than that of the HPTS pigment. The HPTS plastic film is very stable under ambient conditions, (with a shelf life ˃ six month when stored in the dark but under otherwise ambient conditions). Moreover, the HPTS-film is stable in water, salt solution and even in acid (pH=2), and in each of these media it can be used to detect dissolved CO2.

Presbyopia and near-vision impairment in rural northern China.

PURPOSE: Presbyopia limits activities of daily living, but population-based data from rural China are scarce. METHODS: A population-based, cross-sectional study was conducted in 2009 among all persons aged 40+ years in a rural area near Shenyang, China. Distance and near VA were measured using logMAR E charts. Individuals with pinhole-corrected distance vision ≥20/63 underwent detailed eye examination and near refraction. RESULTS: A total of 1008 (91.5%) respondents were examined (mean age, 58.4 ± 10.7 years for men, 56.8 ± 9.89 years for women). Women and older subjects were more likely to participate. The prevalence of functional presbyopia (near vision <20/50 [N8] improved by ≥1 line with correction) was 67.3% (95% confidence interval [CI], 64.30%-70.09%), increasing from 27.6% at 40 to 49 years of age to 81.8% at 60 to 69 years. Multivariate analysis showed that older age (P < 0.001), but not gender or education, was significantly associated with a higher risk of presbyopia. Self-reported presbyopic spectacle correction coverage was 51.5%. In multivariate logistic regression models, worse presenting near vision (P = 0.013) and higher required spherical equivalent power (P < 0.001) were associated with having correction, while age, gender, education, and distance vision were unassociated. Major barriers reported by persons without near correction included poor quality of available glasses (33.1%) and lack of awareness of the condition and its treatment (28.8%). CONCLUSIONS: Presbyopia is highly prevalent in rural China, and nearly half of affected persons have no access to correction. Interventions should focus on education and improvement in the quality of refractive services.

Quality of life and near vision impairment due to functional presbyopia among rural Chinese adults.

PURPOSE: To evaluate the impact of near-vision impairment on visual functioning and quality of life in a rural adult population in Shenyang, northern China. METHODS: A population-based, cross-sectional study was conducted among persons aged 40+ years, during which functional presbyopia (correctable presenting near vision < 20/50 [N8] at 40 cm) was assessed. Near-vision-related quality of life and spectacle usage questionnaires were administered by trained interviewers to determine the degree of self-rated difficulty with near tasks. RESULTS: A total of 1008 respondents (91.5% of 1102 eligible persons) were examined, and 776 (78%) of completed the questionnaires (mean age, 57.0 ± 10.2 years; 63.3% women). Near-vision spectacle wearers obtained their spectacles primarily from markets (74.5%) and optical shops (21.7%), and only 1.14% from eye clinics. Among 538 (69.3%) persons with functional presbyopia, self-rated overall (distance and near) vision was worse (P < 0.001) and difficulty with activities of daily living greater (P < 0.001) than among nonpresbyopes. Odds of reporting any difficulty with daily tasks remained higher (OR = 2.32; P < 0.001) for presbyopes after adjustment for age, sex, education and distance vision. Compared to persons without presbyopia, presbyopic persons were more likely to report diminished accomplishment due to vision (P = 0.01, adjusted for age, sex, education, and distance vision.) CONCLUSIONS: Difficulties with activities of daily living and resulting social impediments are common due to presbyopia in this setting. Most spectacle wearers with presbyopia in rural China obtain near correction from sources that do not provide comprehensive vision care.

Micro/nanoreservoirs for controlled release of active species in smart functional coatings

This work reports one possible way to develop new functional coatings used to increase the life time of metallic structures. The functionalities selected and attributed to model coatings in the frame of this work were corrosion protection, self-sensing and prevention of fouling (antifouling). The way used to confer those functionalities to coatings was based on the encapsulation of active compounds (corrosion inhibitors, pH indicators and biocides) in micro and nanocontainers followed by their incorporation into the coating matrices. To confer active corrosion protection, one corrosion inhibitor (2-mercaptobenzothiazole, MBT) was encapsulated in two different containers, firstly in silica nanocapsules (SiNC) and in polyurea microcapsules (PU-MC). The incorporation of both containers in different models coatings shows a significant improvement in the corrosion protection of aluminum alloy 2024 (AA2024). Following the same approach, SiNC and PU-MC were also used for the encapsulation of phenolphthalein (one well known pH indicator) to introduce sensing properties in polymeric coatings. SiNC and PU-MC containing phenolphthalein acted as corrosion sensor, showing a pink coloration due to the beginning of cathodic reaction, resulting in a pH increase identified by those capsules. Their sensing performance was proved in suspension and when integrated in coatings for aluminium alloy 2024 and magnesium alloy AZ31. In a similar way, the biocide activity (antifouling) was assigned to two polymeric matrices using SiNC for encapsulation of one biocide (Dichloro-2-octyl-2H-isothiazol-3-one, DCOIT) and also SiNC-MBT was tested as biocide. The antifouling activity of those two encapsulated compounds was assessed through inhibition and consequent decrease in the bioluminescence of modified E. coli. That effect was verified in suspension and when incorporated in coatings for AISI 1008 carbon steel. The developed micro and nanocontainers presented the desired performance, allowing the introduction of new functionalities to model coatings, showing potential to be used as functional additives in the next generation of multifunctional coatings.

Características del ambiente marino frente a la costa peruana

El ambiente marino frente al Perú es modificado considerablemente por eventos transcendentes de características opuestas: El Niño y La Niña, los mismos que se presentan alternadamente, con diferente intensidad y duración. La temperatura presenta sus máximos y mínimos valores en verano e invierno, respectivamente;ambos E:xtremos dela salinidad se registran en el verano; los nutrientes presentan sus mínimos valores en verano y máximos en el invierno, intensificándose el afloramiento. Frente a la costa peruana se presentan masas de aguas superficiales y subsuperficiales procedentes de la región subtropical, tropical, ecuatorial y de la región subantártica. La Corriente Peruana, se subdivide en Corriente Costera Peruana y Corriente Oceánica Peruana. En la capa subsuperficial se presentan la Corriente Peruana Subsuperficial y la Extensión Sur de la Corriente de Cromwell. El afloramiento, mecanismo esencial de la alta producción marina, se produce sobre todo en las zonas de los 4-5°S,7-8°S, 11-12°S y 14-15°S. Durante las últimas tres décadas tres eventos El Niño y dos Niñas de gran intensidad han afectado severamente el ecosistema marino peruano.

L'Écho de Paris

1886/12/16 (Numéro 1008).

Inventaire des lettres d'anoblissement, de légitimation et de naturalité, enregistrées à la chambre des comptes de 1349 à 1655.

Contient : a Acte, en latin, du roi CHARLES VIII. Le roi y anoblit Éloi Gigaud et sa postérité. Éloi Gigaud est dit demeurer « in parrochia de Mehers, prope Castriam, in provincia Bituriae ». Plessis lez Tours, mai 1489 ; b Note concernant la famille Nicolay, de 1440 à 1588, où l'on examine à quelle date la qualité de noble à été donnée à Jean Nicolay, père du premier Nicolay qui fut « premier president aux comptes à Paris ». On a joint à cette note la copie de trois actes, en latin, des années 1452, 1469, 1522. Jean Nicolay figure dans les deux premiers, et son fils, le premier président, dans le troisième ; c Acte par lequel le roi LOUIS XIV déclare légitimés ses enfants naturels Louis-Auguste, duc du Maine, Louis-César, comte du Vexin, Louise-Françoise de Nantes. St-Germain-en-Laye, décembre 1673 ; d Le « lieu de Mouchy le Vieil », donné à « Jean, bastard de Tyen, bailly de Senlis, au mois de juin 1422 » ; e « Me Jean Bruslard,... ordonné avocat... du roy en la prevosté de Chastillon sur Marne, par lettres du roy du 28 fevrier 1423 » ; f La famille de Jeanne d'Arc. 1429 et 1473 ; g Un mandement du roi Louis XI « au seigneur de La Roche-Guyon », pour « laisser passer 60 tonneaux de vin », envoyés par ledit roi au roi d'Angleterre, Henri VI. Paris, 16 nov. 1470