Reflecting the debate between state-centered and human-security approaches to security strategy, Africa-US Relations explores the interactions between the US and African countries in a wide spectrum ...of key arenas. The authors range from such traditional security issues as peacekeeping and terrorism to concerns with HIV/AIDS, environmental degradation, aid policies, and international trade. Their contributions place in sharp relief the differences in inner logic and preferred consequences among alternative strategic perspectives--as well as the implications of those differences for policy choices.
In the course of investigating the malignant catarrhal fever (MCF) subgroup of rhadinoviruses, seven novel rhadinoviruses were identified in a variety of ruminants, including domestic sheep, bighorn ...sheep, bison, black-tailed deer, mule deer, fallow deer, elk and addax. Based on the DNA polymerase gene sequences, these newly recognized viruses clustered into a second distinct subgroup in ruminants with three members identified previously in cattle, goats and oryx. Phylogenetic analysis revealed that the currently known ruminant rhadinoviruses appear to comprise three distinct genetic lineages: (i) the MCF subgroup, defined by sequence identity and the presence of the 15A antigenic epitope; (ii) a second distinct subgroup, devoid of the 15A epitope, which contains the previously reported bovine lymphotropic herpesvirus and related viruses; and (iii) a third distinct subgroup represented by Bovine herpesvirus 4. Comparison of phylogenetic trees between the rhadinoviruses and their corresponding hosts further supports the gammaherpesvirus and host co-evolution theory.
Background Infants with critical congenital heart disease ( CCHD ) are more likely to be small for gestational age (GA). It is unclear how this affects mortality. The authors investigated the effect ...of birth weight Z score on 1-year mortality separately in preterm (GA <37 weeks), early-term (GA 37-38 weeks), and full-term (GA 39-42 weeks) infants with CCHD . Methods and Results Live-born infants with CCHD and GA 22 to 42 weeks born in California 2007-2012 were included in the analysis. The primary predictor was Z score for birth weight and the primary outcome was 1-year mortality. Multivariable logistic regression was used. Results are presented as adjusted odds ratios and 95% confidence intervals ( CIs ). The authors identified 6903 infants with CCHD . For preterm and full-term infants, only a Z score for birth weight <-2 was associated with increased mortality compared with the reference group ( Z score 0-0.5, adjusted odds ratio, 2.15 95% CI , 1.1-4.21 and adjusted odds ratio, 3.93 95% CI , 2.32-6.68, respectively). In contrast, in early-term infants, the adjusted odds ratios for Z scores <-2, -2 to -1, and -1 to -0.5 were 3.42 (95% CI , 1.93-6.04), 1.78 (95% CI , 1.12-2.83), and 2.03 (95% CI , 1.27-3.23), respectively, versus the reference group. Conclusions GA seems to modify the effect of birth weight Z score on mortality in infants with CCHD . In preterm and full-term infants, only the most severe small-for-GA infants ( Z score <-2) were at increased risk for mortality, while, in early-term infants, the risk extended to mild to moderate small-for-GA infants ( Z score <-0.5). This information helps to identify high-risk infants and is useful for surgical planning.
An experimental group (N = 19) was trained to receive Morse code with signals that were weighted with respect to frequency of presentation in rough proportion to their order of difficulty for ...beginners. A control group (N = 19), matched on a code aptitude test performance, was trained with each signal presented an equal number of times. On the test runs, no significant differences were observed in the progress of the two groups.
Ralph J. Bunche (1904-1971), winner of the Nobel Peace Prize in 1950, was a key U.S. diplomat in the planning and creation of the United Nations in 1945. In 1947 he was invited to join the permanent ...UN Secretariat as director of the new Trusteeship Department. In this position, Bunche played a key role in setting up the trusteeship system that provided important impetus for postwar decolonization ending European control of Africa as well as an international framework for the oversight of the decolonization process after the Second World War.Trustee for the Human Communityis the first volume to examine the totality of Bunche's unrivalled role in the struggle for African independence both as a key intellectual and an international diplomat and to illuminate it from the broader African American perspective.These commissioned essays examine the full range of Ralph Bunche's involvement in Africa. The scholars explore sensitive political issues, such as Bunche's role in the Congo and his views on the struggle in South Africa.Trustee for the Human Communitystands as a monument to the profoundly important role of one of the greatest Americans in one of the greatest political movements in the history of the twentieth century.Contributors: David Anthony, Ralph A. Austen, Abena P. A. Busia, Neta C. Crawford, Robert R. Edgar, Charles P. Henry, Robert A. Hill, Edmond J. Keller, Martin Kilson, Georges Nzongola-Ntalaja, Jon Olver, Pearl T. Robinson, Elliott P. Skinner, Crawford Young
BACKGROUND:Rilpivirine pharmacokinetics are defined by its absorption, distribution, metabolism, and excretion. Pregnancy can affect these factors by changes in cardiac output, protein binding, ...volume of distribution, and cytochrome P450 (CYP) 3A4 activity. Rilpivirine is metabolized by CYP3A4. The impact of pregnancy on rilpivirine pharmacokinetics is largely unknown.
METHODS:IMPAACT P1026s is a multicenter, non-blinded, prospective study evaluating antiretroviral pharmacokinetics in HIV-infected pregnant women that included a cohort receiving rilpivirine 25mg once daily as part of their combination antiretrovirals for clinical care. Thirty-two women were enrolled in this study. Intensive PK sampling was performed at steady state during the second trimester, third trimester and postpartum. Maternal and umbilical cord blood samples were obtained at delivery. Plasma rilpivirine concentration was measured using liquid chromatography-mass spectrometry; lower limit of quantitation was 10 ng/mL.
RESULTS:Median (range) AUC0-24 were 1969 (867–4987, n=15), 1669 (556–4312, n=28) and 2387 (188–6736, n=28) ng*hr/mL in the second trimester, third trimester and postpartum, respectively (p<0.05 for either trimester vs postpartum). Median (range) C24 were 63 (37–225, n=17), 56 (<10–181, n=30), and 81 (<10–299, n=28) ng/mL (p<0.05 for either trimester vs postpartum). High variability in pharmacokinetic parameters was observed between subjects. Median (range) cord blood/maternal concentration ratio was 0.55 (0.4–0.8, n=9). Delivery HIV-1 RNA was ≤ 50 copies/mL in 70% and ≤ 400 copies/mL in 90% of women. Cmin were significantly lower at 14 visits with detectable HIV-1 RNA compared to 62 visits with undetectable HIV-1 RNA, 30 (<10 – 93) versus 63 (15 – 199) ng/mL (p=0.0004). Cmin was below the protein-binding adjusted EC90 concentration (12.2 ng/mL) at 4 visits in 3 of 31 women (10%).
CONCLUSIONS:Rilpivirine exposure is lower during pregnancy compared to postpartum, and highly variable. Ninety percent of women had minimum concentrations above the protein-binding adjusted EC90 for rilpivirine.
Abstract The impact of novel drugs for treating multiple myeloma (MM) on the utilization and outcomes of autologous hematopoietic progenitor cell transplantation (AHPCT) is unknown. We reviewed ...characteristics and outcomes of 20,278 patients who underwent AHPCT within 12 months of diagnosis of MM in the United States and Canada and registered at the Center for International Blood and Marrow Transplant Research (CIBMTR) in 3 time cohorts reflecting the increasing availability of novel drugs: 1995 to 1999 (n = 2226), 2000 to 2004 (n = 6408), and 2005 to 2010 (n = 11,644). In the United States, the number of AHPCTs performed increased at a greater rate than new MM cases. Patients in recent cohorts were older, less likely to have stage 3 MM, and more likely to have received previous thalidomide, lenalidomide, or bortezomib. On multivariate analysis, AHPCT in the 2000 to 2004 cohort (HR = 0.77) or in the 2005 to 2010 cohort (HR = 0.68) were associated with lower risk of death. Survival at 60 months post-AHPCT improved from 47% in 1995 to 1999 to 55% in 2000 to 2004 and to 57% in 2005 to 2010, owing less to improvement in progression-free survival (50% versus 55% versus 57% at 24 months) than to postrelapse/progression survival (58% versus 65% versus 72% at 24 months). AHPCT and new biological agents are complementary, nonredundant therapies and should be combined in the management of MM in suitable patients.
Application of PF-03671148 to rat wounds leads to a dose dependent inhibition of multiple fibrotic genes in vivo.
A series of 2-(1H-pyrazol-1-yl)pyridines are described as inhibitors of ALK5 (TGFβ ...receptor I kinase). Modeling compounds in the ALK5 kinase domain enabled some optimization of potency via substitutions on the pyrazole core. One of these compounds PF-03671148 gave a dose dependent reduction in TGFβ induced fibrotic gene expression in human fibroblasts. A similar reduction in fibrotic gene expression was observed when PF-03671148 was applied topically in a rat wound repair model. Thus these compounds have potential utility for the prevention of dermal scarring.
The safety and pharmacokinetics of nelfinavir coadministered with zidovudine and lamivudine were studied in 26 infants during the first 6 weeks of life. Cohort 1 infants (n = 7) received 10 mg/kg 3 ...times a day, and cohort 2 infants (n = 19) received 40 mg/kg twice a day. Two cohort 1 infants at week 1 and none at week 6 exceeded the target 24-hour area under the curve (AUC) of 30 μg·h/mL, equal to the 10th percentile of the AUC for adults receiving standard nelfinavir dosing. In cohort 2, the median 24-hour AUC was 38 μg·h/mL at both time points, with considerable variability among the infants. Three of 11 cohort 2 infants at week 1 and 4 of 11 at week 6 did not meet the AUC target. Median nelfinavir oral clearance was 2.1 L/h/kg at weeks 1 and 6. The median ratio of the plasma concentrations of the nelfinavir metabolite M8 to unchanged nelfinavir increased from 0.16 (range0-0.38) during week 1 to 0.56 (range0.4-1.47) during week 6 (P < 0.01). There were no significant differences in any of the other pharmacokinetic parameters when week 1 and week 6 results were compared. Few adverse events were attributed to nelfinavir. These data suggest that nelfinavir is well tolerated in infants at these doses, but exposure was frequently less than that seen in adults taking standard nelfinavir dosing. Further investigations of larger doses, such as 75 mg/kg twice a day, should be undertaken.
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