The syntheses and reactivity of 6- and 8-azaindolizines.

Synthetic routes leading to indolitine and its mono-aza derivatives, and the reactivity of these systems have been briefly reviewed. A number of simple alkyl, aryl, methoxy and chloro substituted 6- and 8- azaindolizines have been synthesised via the Chichibabin reaction between suitably-substituted 2- or 4- methylpyrimidines and alpha-bromo ketones. The structures of the products obtained have been confirmed spectroscopically, principally by 'H NMR spectroscopy, and by formylation procedures. The reaction between 2,4,6-trimethylpyrimidine and phenacyl bromide has been showm to yield a 6-azaindolizine structure rather than an 8-azaindolizine structure as previously reported. The reaction between 2-methylpyrimidine and ethyl bromopyruvate gave 2-carbethoxy-8-azaindolizine, which gave the parent 8-azaindolizine system on hydrolysis and decarboxylation. Formylation of 6-azaindolizines bearing a C-5 methyl group gave - along with their formyl derivatives - 5-azacycl[3,2,2]azine structures, which were also synthesised by 1,3-dipolar addition reactions betvieen dimethyl acetylenedicarboxylate and 6- or 8- azaindolizines. An examination of the 'H NMR spectra of 6- and 8- azaindolizines in trifluoroacetic acid showed both systems to have a preference for protonation at their non-bridgehead nitrogen atoms, although partial carbon protonation at C-3 was observed in a number of alkyl derivatives. The protonation of 6- and 8- azaindolizinones and 5-azacycl[3,2,2]azines was also investigated. Formylation of 6- and 8- azaindolizines occurred preferentially at C-3 and then at C-1. A number of other electrophilic substitution reactions on 2,7-dimethyl-8-azaindolizine also occurred at C-3. Nucleophilic replacement of chlorine by methoxide from a 5-chloro-6-azaindolizine and a 7-chloro-8-azaindolizine occurred readily. Ammonolysis and hydrolysis were, however, only successful in the case of the former compound. These experimentally-determined sites of reactivity in 6- and 8- azaindolizines are in accord with those predicted from reported pi-electron density calculations. Formylation of 5-amino-7-methyl-2-phenyl-6-azaindolizine gave a 4,5-diazacycl[3,2,2]azine structure, and refluxing a solution of 7-methyl-2-phenyl-6-azaindolizin-5(6H)-one in phosphoryl chloride gave a peri-condensed di(6-azaindolizino)pyrazine

Prelabor cesarean delivery for twin pregnancies close to term is associated with reduced mortality

Objectives: To examine short and longer term outcomes for twins born at or near term, comparing prelabor cesarean delivery (CD) to birth after trial of labor. Methods: A retrospective cohort of twin pregnancies delivered ≥ 36 weeks gestation from 2000 to 2009. Pregnancies with an antenatal death, lethal anomaly, birthweight discordance ≥25% or birthweight 4000 grams were excluded. Outcomes included severe hypoxia, stillbirth and neonatal death, and hospital admissions or death during the first 5 years of life. Results: 45.3% of 7099 twin pregnancies were delivered by prelabor CD. Compared to delivery after labor, prelabor CD was associated with significantly reduced risks of adverse infant outcomes including severe birth hypoxia (0.08% vs. 0.75%, RR 0.10, 95% CI 0.04-0.26), neonatal death (0.00% vs. 0.15%, RR 0.05, 95% CI 0.00-0.82), and death up to 5 years of age (0.16% vs. 0.40%, RR 0.41, 95% CI 0.20-0.85). Whereas total mortality for first twins was similar after labor (0.15%) compared to prelabor CD (0.16%), total mortality was four times more common in second twins born after labor (0.64%) compared to second twins born after prelabor CD (0.16%). Conclusions: Twin pregnancies at and beyond 36 weeks who are delivered after labor have increased risks for birth outcomes associated with hypoxia. These risks do not result in increased mortality in the first twin, but second twins have significantly increased mortality up to 5 years of age. However, the absolute mortality rate for relatively uncomplicated twin pregnancies born at or near term is low.The New South Wales (NSW) Ministry of Health provided access to the population health data and the NSW Centre for Health Record Linkage linked the data sets. This work was supported by an Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence Grant (1001066). CLR is supported by a NHMRC Senior Research Fellowship (#APP1021025)

Multivariate analysis of Scotch whisky by total reflection X-ray fluorescence and chemometric methods: a potential tool in the identification of counterfeits.

Most methods used in the identification of counterfeit whisky have focused on the profiling of volatile organic congeners determined by gas chromatography. We tested the use of total reflection x-ray fluorescence (TXRF) for trace element analysis of whisky and application of the data as a potential tool in the identification of counterfeit samples. Twenty five whiskies that were produced in different regions of Scotland or were blends, 5 counterfeit whiskies, 1 unmatured grain whisky, and 1 matured grain whisky were analysed for 11 elements (P, S, Cl, K, Ca, Mn, Fe, Cu, Zn, Br and Rb). The effect of cold plasma ashing with oxygen on whisky residues evaporated on the TXRF reflector on the instrument performance was investigated. Cold plasma ashing with oxygen reduced beam scatter and improved the limits of detection but was ultimately deemed unnecessary. The element concentration data for whisky obtained by TXRF (after log transformation) was compared with the values obtained by inductively coupled plasma spectroscopy and showed correlation values (R2) - 0.942 for K, Mn and Cu: - 0.800 for Ca, Fe and Rb; and - 0.535 for P, S and Zn. The range of concentration values for individual elements was variable and principal components analysis of the elemental concentrations partially differentiated the whiskies by region but showed clear separation of the counterfeit samples from the other samples. Using the principal component scores of the elemental concentration data, linear discriminant analysis also distinguished the counterfeits from the other samples

Risk factors for human brucellosis in northern Tanzania

Little is known about the epidemiology of human brucellosis in sub-Saharan Africa. This hampers prevention and control efforts at the individual and population levels. To evaluate risk factors for brucellosis in northern Tanzania, we conducted a study of patients presenting with fever to two hospitals in Moshi, Tanzania. Serum taken at enrollment and at 4–6 week follow-up was tested by Brucella microagglutination test. Among participants with a clinically compatible illness, confirmed brucellosis cases were defined as having a ≥ 4-fold rise in agglutination titer between paired sera or a blood culture positive for Brucella spp., and probable brucellosis cases were defined as having a single reciprocal titer ≥ 160. Controls had reciprocal titers < 20 in paired sera. We collected demographic and clinical information and administered a risk factor questionnaire. Of 562 participants in the analysis, 50 (8.9%) had confirmed or probable brucellosis. Multivariable analysis showed that risk factors for brucellosis included assisting goat or sheep births (Odds ratio [OR] 5.9, 95% confidence interval [CI] 1.4, 24.6) and having contact with cattle (OR 1.2, 95% CI 1.0, 1.4). Consuming boiled or pasteurized dairy products was protective against brucellosis (OR 0.12, 95% CI 0.02, 0.93). No participants received a clinical diagnosis of brucellosis from their healthcare providers. The under-recognition of brucellosis by healthcare workers could be addressed with clinician education and better access to brucellosis diagnostic tests. Interventions focused on protecting livestock keepers, especially those who assist goat or sheep births, are needed

Risk factors for human acute leptospirosis in northern Tanzania

Introduction: Leptospirosis is a major cause of febrile illness in Africa but little is known about risk factors for human infection. We conducted a cross-sectional study to investigate risk factors for acute leptospirosis and Leptospira seropositivity among patients with fever attending referral hospitals in northern Tanzania. Methods: We enrolled patients with fever from two referral hospitals in Moshi, Tanzania, 2012–2014, and performed Leptospira microscopic agglutination testing on acute and convalescent serum. Cases of acute leptospirosis were participants with a four-fold rise in antibody titers, or a single reciprocal titer ≥800. Seropositive participants required a single titer ≥100, and controls had titers <100 in both acute and convalescent samples. We administered a questionnaire to assess risk behaviors over the preceding 30 days. We created cumulative scales of exposure to livestock urine, rodents, and surface water, and calculated odds ratios (OR) for individual behaviors and for cumulative exposure variables. Results: We identified 24 acute cases, 252 seropositive participants, and 592 controls. Rice farming (OR 14.6), cleaning cattle waste (OR 4.3), feeding cattle (OR 3.9), farm work (OR 3.3), and an increasing cattle urine exposure score (OR 1.2 per point) were associated with acute leptospirosis. Conclusions: In our population, exposure to cattle and rice farming were risk factors for acute leptospirosis. Although further data is needed, these results suggest that cattle may be an important source of human leptospirosis. Further investigation is needed to explore the potential for control of livestock Leptospira infection to reduce human disease

A holistic approach to understanding the desorption of phosphorus in soils

The mobility and resupply of inorganic phosphorus (P) from the solid phase were studied in 32 soils from the UK. The combined use of diffusive gradients in thin films (DGT), diffusive equilibration in thin films (DET) and the “DGT-induced fluxes in sediments” model (DIFS) were adapted to explore the basic principles of solid-to-solution P desorption kinetics in previously unattainable detail. On average across soil types, the response time (Tc) was 3.6 h, the desorption rate constant (k–1) was 0.0046 h–1, and the desorption rate was 4.71 nmol l–1 s–1. While the relative DGT-induced inorganic P flux responses in the first hour is mainly a function of soil water retention and % Corg, at longer times it is a function of the P resupply from the soil solid phase. Desorption rates and resupply from solid phase were fundamentally influenced by P status as reflected by their high correlation with P concentration in FeO strips, Olsen, NaOH–EDTA and water extracts. Soil pH and particle size distribution showed no significant correlation with the evaluated mobility and resupply parameters. The DGT and DET techniques, along with the DIFS model, were considered accurate and practical tools for studying parameters related to soil P desorption kinetics

Designing programs for eliminating canine rabies from islands: Bali, Indonesia as a case study

<p>Background: Canine rabies is one of the most important and feared zoonotic diseases in the world. In some regions rabies elimination is being successfully coordinated, whereas in others rabies is endemic and continues to spread to uninfected areas. As epidemics emerge, both accepted and contentious control methods are used, as questions remain over the most effective strategy to eliminate rabies. The Indonesian island of Bali was rabies-free until 2008 when an epidemic in domestic dogs began, resulting in the deaths of over 100 people. Here we analyze data from the epidemic and compare the effectiveness of control methods at eliminating rabies.</p> <p>Methodology/Principal Findings: Using data from Bali, we estimated the basic reproductive number, R0, of rabies in dogs, to be ~1·2, almost identical to that obtained in ten–fold less dense dog populations and suggesting rabies will not be effectively controlled by reducing dog density. We then developed a model to compare options for mass dog vaccination. Comprehensive high coverage was the single most important factor for achieving elimination, with omission of even small areas (<0.5% of the dog population) jeopardizing success. Parameterizing the model with data from the 2010 and 2011 vaccination campaigns, we show that a comprehensive high coverage campaign in 2012 would likely result in elimination, saving ~550 human lives and ~$15 million in prophylaxis costs over the next ten years.</p> <p>Conclusions/Significance: The elimination of rabies from Bali will not be achieved through achievable reductions in dog density. To ensure elimination, concerted high coverage, repeated, mass dog vaccination campaigns are necessary and the cooperation of all regions of the island is critical. Momentum is building towards development of a strategy for the global elimination of canine rabies, and this study offers valuable new insights about the dynamics and control of this disease, with immediate practical relevance.</p&gt