Evaluation of manufacturing processes for the production of atrazine

This report describes the results of investigations carried out with the view to find an alternative for MIBK as solvent for the production of atrazine as currently practised by Dow AgroSciences in South Africa. The main motivating factors for the said investigation was: · to increase the yield of atrazine produced, · to reduce the amount of organics, consisting essentially of reaction solvent containing dissolved product, in the aqueous process effluent, and · to improve the properties of the solid (crystalline) product to enable easier product formulation. Synthetic reactions carried out in the absence of organic solvent, i.e. in essentially a 10% NaCl solution containing a surfactant, proved rather disappointing. Low yields of atrazine were obtained together with relatively large amounts of by-products such as propazine and simazine, irrespective of the nature of the surfactant. The reason for the low yield of atrazine and high yields of by-products were established in competing substitution reactions. In these reactions, IPA was reacted with an equimolar mixture of cyanuric chloride and mono-i (first reaction intermediate) in both aqueous medium and in toluene as reaction solvent. The results of these experiments indicated that in aqueous medium IPA reacts faster with mono-i than cyanuric chloride to give propazine as by-product. In toluene, however, the preferred reaction is with cyanuric chloride to give more mono-i as product. Toluene was investigated as an alternative organic solvent to MIBK in view of its desirable properties such as low solubility in water and ease of recovery and recycling. The synthesis of atrazine was optimised in terms of addition sequence and rates of amine reagents and base (HCl acceptor), both by means of benchscale reactions and reaction calorimetry. Reaction energy profiles indicated that both the reaction of secondary amine/NaOH and primary amine/NaOH were virtually instantaneous. This implies that the reaction can be performed under feed control conditions. Of particular importance in ensuring high yields of high purity product was accurate temperature control (since both reaction steps are highly exothermic) and mixing. The latter was important in view of the rapid reaction of amine/NaOH with cyanuric chloride, as well as the possible reaction of mono-i, the first reaction intermediate, with IPA in cases of local excesses of reagent. Under optimum conditions, a yield of atrazine > 97% could be achieved where the resultant product was well within stipulated product specifications. In view of the results obtained, the following recommendations regarding the synthesis of atrazine in toluene as reaction solvent can be made: · Use a reagent addition sequence that staggers the addition of amine and NaOH in such a manner that amine is added first for a short while, followed by the simultaneous addition of amine and NaOH, and ending with NaOH. Use two reaction vessels in series, one for the IPA addition reaction and one for the MEA addition reaction. In this manner the reaction can be run on a continuous basis since no lag time between amine additions is required. Also, smaller reactors may be used whilst maintaining high production rates. Smaller reactors will improve both temperature control and mixing of reagents

Rabies in primates: are aggressive pet lemurs a risk to humans?

Non-human primates harbor zoonotic pathogens including the rabies virus (Rabies lyssavirus). Though the chances of rabies transmission from primates is low, guidelines currently recommend a post-exposure prophylaxis for unvaccinated persons. In Madagascar, lemurs have been described as carriers of the rabies virus, but a discussion about the risk of rabies transmission to humans from lemurs, particularly in the context of in-country ownership of lemurs, has not been studied. We use qualitative and quantitative data collected from household surveys (n = 271 interviewees who had seen a pet lemur across 1 2 urban towns), web-based surveys (n = 229), and the literature (publications using data collected by the Institute Pasteur of Madagascar over the last century) to examine the context in which the rabies virus could be transmitted from lemurs to humans. Though only a few wild and pet lemurs in Madagascar have tested positive for rabies, post-exposure treatment is sometimes also sought out following aggressive incidents with lemurs. Many interviewees (22 ± 6%, mean ± 95% confidence interval CI) across 1 2 towns indicated that pet lemurs they had seen, had a history of aggression. Some lemur owners appear to be aware that their pets could transmit the rabies virus and seek veterinary care to prevent this. The public health burden of rabies is relatively low in Madagascar and despite some anecdotes in the literature, it appears that lemurs are rarely the source of rabies when humans become infected. However, this case study highlights the lack of data and publications regarding the public health implications of human-lemur contact in Madagascar. RÉSUMÉLes primates non-humains hébergent des pathogènes zoonotiques incluant le virus de la rage (Rabies lyssavirus). Bien que les risques de transmission de la rage par les primates soient faibles, les lignes directrices recommandent actuellement une prophylaxie post-exposition pour les personnes non vaccinées. À Madagascar, les lémuriens ont été décrits comme porteurs du virus de la rage, mais une discussion sur le risque de transmission de la rage à l'Homme par les lémuriens, en particulier dans le contexte de la propriété locale des lémuriens, n'a pas été étudiée. Nous utilisons des données qualitatives et quantitatives collectées à partir d'enquêtes auprès des foyers (n = 271 interviewés ayant vu un lémurien dans 1 2 villes), des enquêtes en ligne (n = 229) et de la littérature (publications utilisant des données collectées par l' Institut Pasteur de Madagascar au cours du siècle dernier) pour examiner le contexte dans lequel le virus de la rage pourrait être transmis par les lémuriens aux humains. Bien que seuls quelques lémuriens sauvages et animaux de compagnie à Madagascar aient été testés positifs à la rage, un traitement post-exposition est parfois également recherché suite à des agressions par des lémuriens. De nombreuses personnes interrogées (22 ± 6%, moyenne ± Intervalle de confiance IC à 95%) dans 1 2 villes ont indiqué que les animaux de compagnie qu' ils avaient vus avaient des antécédents d'agression. Quelques propriétaires de lémuriens semblent être conscients que leurs animaux de compagnie peuvent transmettre le virus de la rage et demander des soins vétérinaires pour éviter cela. La rage constitue une charge relativement faible pour la santé publique à Madagascar et malgré quelques anecdotes dans la littérature, il semble que les lémuriens soient rarement la source de la rage lorsque les humains sont infectés. Cependant, cette étude de cas souligne le manque de données et de publications concernant les implications / conséquences du contact entre humains et lémuriens sur la santé publique à Madagascar

Constraints on the Progenitor System of the Type Ia Supernova 2014J from Pre-Explosion Hubble Space Telescope Imaging

We constrain the properties of the progenitor system of the highly reddened Type Ia supernova (SN) 2014J in Messier 82 (M82; d ~ 3.5 Mpc). We determine the SN location using Keck-II K-band adaptive optics images, and we find no evidence for flux from a progenitor system in pre-explosion near-ultraviolet through near-infrared Hubble Space Telescope (HST) images. Our upper limits exclude systems having a bright red giant companion, including symbiotic novae with luminosities comparable to that of RS Ophiuchi. While the flux constraints are also inconsistent with predictions for comparatively cool He-donor systems (T < ~35,000 K), we cannot preclude a system similar to V445 Puppis. The progenitor constraints are robust across a wide range of R_V and A_V values, but significantly greater values than those inferred from the SN light curve and spectrum would yield proportionally brighter luminosity limits. The comparatively faint flux expected from a binary progenitor system consisting of white dwarf stars would not have been detected in the pre-explosion HST imaging. Infrared HST exposures yield more stringent constraints on the luminosities of very cool (T < 3000 K) companion stars than was possible in the case of SN Ia 2011fe.Comment: Accepted by ApJ 14 May 2014 with only minor revision

Wound Botulism in Injection Drug Users: Time to Antitoxin Correlates with Intensive Care Unit Length of Stay

Objectives: We sought to identify factors associated with need for mechanical ventilation (MV), length of intensive care unit (ICU) stay, length of hospital stay, and poor outcome in injection drug users (IDUs) with wound botulism (WB).Methods: This is a retrospective review of WB patients admitted between 1991-2005. IDUs were included if they had symptoms of WB and diagnostic confirmation. Primary outcome variables were the need for MV, length of ICU stay, length of hospital stay, hospital-related complications, and death.Results: Twenty-nine patients met inclusion criteria. Twenty-two (76%) admitted to heroin use only and seven (24%) admitted to heroin and methamphetamine use. Chief complaints on initial presentation included visual changes, 13 (45%); weakness, nine (31%); and difficulty swallowing, seven (24%). Skin wounds were documented in 22 (76%). Twenty-one (72%) patients underwent mechanical ventilation (MV). Antitoxin (AT) was administered to 26 (90%) patients but only two received antitoxin in the emergency department (ED). The time from ED presentation to AT administration was associated with increased length of ICU stay (Regression coefficient = 2.5; 95% CI 0.45, 4.5). The time from ED presentation to wound drainage was also associated with increased length of ICU stay (Regression coefficient = 13.7; 95% CI = 2.3, 25.2). There was no relationship between time to antibiotic administration and length of ICU stay.Conclusion: MV and prolonged ICU stays are common in patients identified with WB. Early AT administration and wound drainage are recommended as these measures may decrease ICU length of stay.[West J Emerg Med. 2009;10(4):251-256.

Trade of parrots in urban areas of Madagascar

The live capture of parrots is causing increasing concern across Africa. In Madagascar, home to three species of parrot (Coracopsis nigra, C. vasa, Agapornis canus), no study has examined how these species are being extracted from the wild and traded. In this study, we examined the procurement, length of ownership, and the end of ownership of pet parrots. Data were collected via household surveys (n = 440 interviews in 9 towns), market visits (nd = 1 7 markets in 6 towns), and opportunistic data collection methods in urban, Malagasy towns. Most Coracopsis spp. are purchased (59%) or captured directly by the owner from the wild (22%), although we were unable to determine how A. canus was procured. Survey respondents reported purchasing Coracopsis spp. for the price of USD 5.36 ± 3.20. The average Coracopsis spp. was kept in captivity for 3.1 7 ± 2.51 years. No survey respondents provided information on the purchase price or length of ownership for A. canus. Ownership ended primarily when Coracopsis spp. escaped/flew away (36%) or died of unknown causes (21%). A. canus also flew away, although this was only reported in one instance. In-country demand appears to be met by a trade network of both informal and formal actors. It is unclear whether current protections for Madagascar’s parrots, as far as the domestic market is concerned, are sufficient to ensure sustainable extraction of live individuals

A Phase II Trial of Prexasertib (LY2606368) in Patients With Extensive-Stage Small-Cell Lung Cancer

Checkpoint kinase 1 inhibitor; Pharmacokinetics; Small cell lung cancerInhibidor de quinasa de punto de control 1; Farmacocinética; Cáncer de pulmón de células pequeñasInhibidor de la quinasa del punt de control 1; Farmacocinètica; Càncer de pulmó de cèl·lules petitesBackground This study assessed the checkpoint kinase 1 inhibitor prexasertib in patients with extensive-stage small-cell lung cancer (ED-SCLC). Patients and Methods This was a parallel-cohort phase II study of 105 mg/m2 prexasertib once every 14 days for patients who progressed after no more than two prior therapies and had platinum-sensitive (Cohort 1) or platinum-resistant/platinum-refractory (Cohort 2) disease. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetics. Exploratory endpoints included biomarker identification and assessment of an alternative regimen (Cohort 3: 40 mg/m2 days 1-3, 14-day cycle). Results In Cohort 1 (n = 58), ORR was 5.2%; DCR, 31%; median PFS, 1.41 months (95% confidence interval [CI], 1.31-1.64); and median OS, 5.42 months (95% CI, 3.75-8.51). In Cohort 2 (n = 60), ORR was 0%; DCR, 20%; median PFS, 1.36 months (95% CI, 1.25-1.45); and median OS, 3.15 months (95% CI, 2.27-5.52). The most frequent all-grade, related, treatment-emergent adverse events were decreased neutrophil count (Cohort 1, 69.6%; Cohort 2, 73.3%), decreased platelet count (Cohort 1, 51.8%; Cohort 2, 50.0%), decreased white blood cell count (Cohort 1, 28.6%; Cohort 2, 40.0%), and anemia (Cohort 1, 39.3%; Cohort 2, 28.3%). Eleven patients (19.6%) in Cohort 1 and one patient (1.7%) in Cohort 2 experienced grade ≥3 febrile neutropenia. Prexasertib pharmacokinetics were consistent with prior studies. Cohort 3 outcomes were similar to those of Cohorts 1 and 2. No actionable biomarkers were identified. Conclusion Prexasertib did not demonstrate activity to warrant future development as monotherapy in ED-SCLC.This research was funded by Eli Lilly and Company

Evolution of a Sexually Dimorphic Trait in a Broadly Distributed Topminnow (Fundulus Olivaceus)

Understanding the interaction between sexual and natural selection within variable environments is crucial to our understanding of evolutionary processes. The handicap principle predicts females will prefer males with exaggerated traits provided those traits are indicators of male quality to ensure direct or indirect female benefits. Spatial variability in ecological factors is expected to alter the balance between sexual and natural selection that defines the evolution of such traits. Male and female blackspotted topminnows (Fundulidae: Fundulus olivaceus) display prominent black dorsolateral spots that are variable in number across its broad range. We investigated variability in spot phenotypes at 117 sites across 13 river systems and asked if the trait was sexually dimorphic and positively correlated with measures of fitness (condition and gonadosomatic index [GSI]). Laboratory and mesocosm experiments assessed female mate choice and predation pressure on spot phenotypes. Environmental and community data collected at sampling locations were used to assess predictive models of spot density at the individual, site, and river system level. Greater number of spots was positively correlated with measures of fitness in males. Males with more spots were preferred by females and suffered greater mortality due to predation. Water clarity (turbidity) was the best predictor of spot density on the drainage scale, indicating that sexual and natural selection for the trait may be mediated by local light environments

Evolution of a Sexually Dimorphic Trait In a Broadly Distributed Topminnow (\u3ci\u3eFundulus olivaceus\u3c/i\u3e)

Understanding the interaction between sexual and natural selection within variable environments is crucial to our understanding of evolutionary processes. The handicap principle predicts females will prefer males with exaggerated traits provided those traits are indicators of male quality to ensure direct or indirect female benefits. Spatial variability in ecological factors is expected to alter the balance between sexual and natural selection that defines the evolution of such traits. Male and female blackspotted topminnows (Fundulidae: Fundulus olivaceus) display prominent black dorsolateral spots that are variable in number across its broad range. We investigated variability in spot phenotypes at 117 sites across 13 river systems and asked if the trait was sexually dimorphic and positively correlated with measures of fitness (condition and gonadosomatic index [GSI]). Laboratory and mesocosm experiments assessed femalemate choice and predation pressure on spot phenotypes. Environmental and community data collected at sampling locations were used to assess predictive models of spot density at the individual, site, and river system level. Greater number of spots was positively correlated with measures of fitness in males. Males with more spots were preferred by females and suffered greater mortality due to predation. Water clarity (turbidity) was the best predictor of spot density on the drainage scale, indicating that sexual and natural selection for the trait may be mediated by local light environments