Agreement between the Chinese Academy of Agricultural Sciences and the International Maize and Wheat Improvement Center

Agreement between CAAS and CIMMYT signed in Beijing, China on September 25, 1997. Agreement establishes cooperation for the promotion and acceleration in research and training for the scientific improvement of wheat and maize for China and other countries set forth in nine articles

Mass spectrometric methods for evaluation of voriconazole avian pharmacokinetics and the inhibition of its cytochrome P450-induced metabolism

Invasive fungal aspergillosis is a leading cause of morbidity and mortality in many species including avian species such as common ravens (Corvus corax). Methods were developed for mass spectral determination of voriconazole in raven plasma as a means of determining pharmacokinetics of this antifungal agent. Without further development, GC/MS/MS (gas chromatography-tandem quadrupole mass spectrometry) proved to be inferior to LC/MS/MS (liquid chromatography-tandem quadrupole mass spectrometry) for measurement of voriconazole levels in treated raven plasma owing to numerous heat-induced breakdown products despite protection of voriconazole functional groups with trimethylsilyl moieties. LC/MS/MS measurement revealed in multi-dosing experiments that the ravens were capable of rapid or ultrarapid metabolism of voriconazole. This accounted for the animals’ inability to raise the drug into the therapeutic range regardless of dosing regimen unless cytochrome P450 (CYP) inhibitors were included. Strategic selection of CYP inhibitors showed that of four selected compounds including cimetidine, enrofloxacin and omeprazole, only ciprofloxacin (Cipro) was able to maintain voriconazole levels in the therapeutic range until the end of the dosing period. The optimal method of administration involved maintenance doses of voriconazole at 6 mg/kg and ciprofloxacin at 20 mg/kg. Higher doses of voriconazole such as 18 mg/kg were also tenable without apparent induction of toxicity. Although most species employ CYP2C19 to metabolize voriconazole, it was necessary to speculate that voriconazole might be subject to metabolism by CYP1A2 in the ravens to explain the utility of ciprofloxacin, a previously unknown enzymatic route. Finally, despite its widespread catalog of CYP inhibitions including CYP1A2 and CYP2C19, cimetidine may be inadequate at enhancing voriconazole levels owing to its known effects on raising gastric pH, a result that may limit voriconazole solubility.</p

miRNA Correlations with IL-6 and D-dimer.

<p>MiR-16 normalised miRNA values were plotted against levels of established SNAE biomarkers (Il-6, D-dimer and hs-CRP). Both miRNA and biomarker levels were log transformed and correlated using the nonparametric Spearman’s Correlation co-efficient. Data was considered significant with a p value < 0.05. MiRs -200a, -122 and -21 all showed correlation with Il-6. MiR-21 additionally showed correlation with D-dimer. None of the miRNAs showed any correlation with hs-CRP.</p

Baseline Characteristics for Cases and Controls.

<p>¹ Details were available for the SMART study only; control n = 117, case n = 59</p><p>Baseline Characteristics for Cases and Controls.</p

miRNA Correlations with baseline CD4+ T cell number.

<p>MiR-16 normalised miRNA values were plotted against CD4+ T cells measured at baseline. Both miRNA and CD4+ T cell count were log transformed and correlated using the nonparametric Spearman’s Correlation co-efficient. Data was considered significant with a p value < 0.05. Only MiRs -31, -150 and -223 showed significant correlation with CD4+ T cell number.</p

Causes of Death for the SMART and ESPRIT cohorts.

<p>Causes of Death for the SMART and ESPRIT cohorts.</p

Associations of all-cause mortality with miRNA levels.

<p>Associations of all-cause mortality with miRNA levels.</p

Patient characteristics, overall and stratified by timing of cART (early <i>versus</i> deferred); entries are n (%) unless otherwise stated.

<p>*Included the following events: oesophageal candidiasis (n = 59); toxoplasmosis (n = 29); cytomegalovirus (n = 23); cryptococcal meningitis (n = 15); cryptosporidiosis (n = 7); progressive multifocal leukoencephalopathy (n = 5), herpes simplex infections (n = 8).</p

Patient characteristics, overall and stratified by type of AIDS-defining event^*; entries are n (%) unless otherwise stated.

<p>*As patients may have experienced more than one of the specific AIDS-defining events, each event is treated as a separate binary covariate.</p><p>**Included the following events: oesophageal candidiasis (n = 75); toxoplasmosis (n = 50); cytomegalovirus (n = 36); cryptococcal meningitis (n = 19); cryptosporidiosis (n = 8); progressive multifocal leukoencephalopathy (n = 18), herpes simplex infections (n = 10).</p><p>***Based on patients with sufficient follow-up to be categorized into one of the two groups (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026009#s2" target="_blank">Methods</a>).</p>§<p>A small number of patients developed AIDS-defining conditions or died that did not fall into one of the five specific categories (e.g. wasting syndrome) – these patients are included in the total column but will not be in the subcolumns.</p

Factors associated with clinical progression (a new AIDS event or death) (N = 584).

<p>*As patients may have experienced more than one of the specific AIDS-defining events, each event is treated as a separate binary covariate; therefore, patients with the event of interest are compared to those without that event (but who will have at least one of the other AIDS events).</p