Integrating data mining within a strategic knowledge management framework: A platform for sustainable competitive advantage within the Australian Minerals and Metals Mining sector

<p>N = 4–10 mice.</p

Calcein accumulation in guinea pig primary brain endothelial cells (n = 6) presented as % of control with increasing doses of sertraline (SERT) and 10⁻⁴ of verapamil (VPL).

<p>Calcein accumulation was assessed at (A) 15 min, (B) 60 min, (C), 120 min and (D) 240 min. * indicates p<0.05 and ** indicates p<0.01 compared to control cells.</p

Accumulation of [3H] digoxin in FVB mice (n = 4–9) co-administered sertraline (10 mg/kg; closed bars) or saline (control; open bars).

<p>Mice were euthanized at various time points (1 m, 5 min, 15 min, 1 h, 4 h, 12 h, 24 h) and DPM measured in the testes, heart and plasma. All data is expressed as mean±SEM. (A) testes∶plasma DPM ratio, (B) heart∶plasma DPM ratio. * indicates p<0.05 vs. control. ** indicates p<0.01 vs. control.</p

Novel multipurpose pod-intravaginal ring for the prevention of HIV, HSV, and unintended pregnancy: Pharmacokinetic evaluation in a macaque model

<div><p>Globally, women bear an uneven burden for sexual HIV acquisition. Results from two clinical trials evaluating intravaginal rings (IVRs) delivering the antiretroviral agent dapivirine have shown that protection from HIV infection can be achieved with this modality, but high adherence is essential. Multipurpose prevention technologies (MPTs) can potentially increase product adherence by offering protection against multiple vaginally transmitted infections and unintended pregnancy. Here we describe a coitally independent, long-acting pod-IVR MPT that could potentially prevent HIV and HSV infection as well as unintended pregnancy. The pharmacokinetics of MPT pod-IVRs delivering tenofovir alafenamide hemifumarate (TAF₂) to prevent HIV, acyclovir (ACV) to prevent HSV, and etonogestrel (ENG) in combination with ethinyl estradiol (EE), FDA-approved hormonal contraceptives, were evaluated in pigtailed macaques (<i>N</i> = 6) over 35 days. Pod IVRs were exchanged at 14 days with the only modification being lower ENG release rates in the second IVR. Plasma progesterone was monitored weekly to determine the effect of ENG/EE on menstrual cycle. The mean <i>in vivo</i> release rates (mg d^-1) for the two formulations over 30 days ranged as follows: TAF₂ 0.35–0.40; ACV 0.56–0.70; EE 0.03–0.08; ENG (high releasing) 0.63; and ENG (low releasing) 0.05. Mean peak progesterone levels were 4.4 ± 1.8 ng mL^-1 prior to IVR insertion and 0.075 ± 0.064 ng mL^-1 for 5 weeks after insertion, suggesting that systemic EE/ENG levels were sufficient to suppress menstruation. The TAF₂ and ACV release rates and resulting vaginal tissue drug concentrations (medians: TFV, 2.4 ng mg^-1; ACV, 0.2 ng mg^-1) may be sufficient to protect against HIV and HSV infection, respectively. This proof of principle study demonstrates that MPT-pod IVRs could serve as a potent biomedical prevention tool to protect women’s sexual and reproductive health and may increase adherence to HIV PrEP even among younger high-risk populations.</p></div

CLA does not restore CCI-induced decreases in circulating sex hormone concentrations.

<p>Plasma concentrations (mean ± SEM) of P₄, T, 11-DOC and corticosterone (ng/mL) at PID’s -10, 1, 11, 19 and 29 for Sham + saline (n = 5), Sham + CLA (n = 5), CCI + saline (n = 8) and CCI + CLA (n = 5) groups. Data were analyzed using 2-way repeated measures ANOVA; post-hoc analyses were performed using the Tukey multiple comparison test (p < 0.05, letters indicate differences between post-injury days and treatments for T, 11-DOC and corticosterone; for P₄, results did not reach significance for main effect of post-injury day or treatment, p = 0.068).</p

CLA does not reduce gross lesion size following a CCI.

<p>Top: Representative figures for each group, illustrating lesion size 1-month post-CCI. Bottom: Lesion size depicted as a percentage of surface area damaged (y-axis) for rats in each surgery/treatment group (x-axis). Gross lesion size data (mean ± SEM) at PID 29 were analyzed from 29 rats as follows: Sham + saline (n = 5), Sham + CLA (n = 7), CCI + saline (n = 8) and CCI + CLA (n = 9). Data were analyzed using ANOVA; post-hoc analyses were performed using the Tukey multiple comparison test (p < 0.01; letter indicates differences between groups).</p

CLA does not improve vestibulomotor function following CCI.

<p>Rats were placed on a rotating rod accelerating at a constant rate (1 rotation per second per second) and allowed to run for up to 300 s at PID’s -3, 2, 6, 9, 13 and 23. Time elapsed (seconds) before fall was recorded. Rotarod latency data (mean ± SEM) on PID’s 6–10 and 21–22 were analyzed from 29 rats as follows: Sham + saline (n = 5), Sham + CLA (n = 7), CCI + saline (n = 8) and CCI + CLA (n = 9). Data were analyzed using 2-way repeated measures ANOVA; post-hoc analyses were performed using the Tukey multiple comparison test; letters indicate differences between groups and times compared to baseline and sham groups, <i>p</i> < 0.05.</p

Chronic CLA administration compromises medium-long term learning and memory in both uninjured and CCI-injured rats as assessed by latency to locate the Morris water maze (MWM) platform.

<p>First Run: Latency in seconds to reach the hidden platform at PID’s 6–10 (Acquisition Phase; platform in SE quadrant) and at PID 20–22 (Re-acquisition Phase; platform changed to NE quadrant, ‘Novel Platform Placement’). MWM Run 1 latency data (mean ± SEM) on PID’s 6–10 and 21–22 were analyzed from 29 rats as follows: Sham + saline (n = 5), Sham + CLA (n = 7), CCI + saline (n = 8) and CCI + CLA (n = 9). Data were analyzed using 2-way repeated measures ANOVA; post-hoc analyses were performed using the Tukey multiple comparison test (p < 0.05; a, b, c and d = differences between time and group, e = differences within groups between the acquisition (PID 10) and re-acquisition phases (PID 20)).</p

Chronic CLA administration compromises short-medium term learning and memory in both uninjured and CCI-injured rats as assessed by latency to locate the Morris water maze (MWM) following novel platform placement.

<p>Second Run: Five minutes after Run 1 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169494#pone.0169494.g004" target="_blank">Fig 4</a>), latency in seconds to reach the hidden platform at PID 6–10 (Acquisition Phase; platform in SE quadrant) and at PID’s 20–22 (Re-acquisition Phase; platform changed to NE quadrant, ‘Novel Platform Placement’) was tested. MWM Run 2 latency data (mean ± SEM) on PID’s 6–10 and 21–22 were analyzed from 29 rats as follows: Sham + saline (n = 5), Sham + CLA (n = 7), CCI + saline (n = 8) and CCI + CLA (n = 9). Data were analyzed using 2-way repeated measures ANOVA; post-hoc analyses were performed using the Tukey multiple comparison test (p < 0.05; a, b, c and d = differences between time and group, e = differences within groups between the acquisition (PID 10) and re-acquisition phases (PID 20)).</p

Summary of drug and drug metabolite concentrations at all sampled anatomic sites (six animals).

<p>Summary of drug and drug metabolite concentrations at all sampled anatomic sites (six animals).</p