Broad direct-acting antiviral (DAA) access may reduce hepatitis C virus (HCV) incidence through a “treatment as prevention” (TasP) effect. We assessed changes in primary HCV incidence following DAA ...access among people living with HIV (PLHIV).
We used pooled individual-level data from six cohorts from the International Collaboration on Hepatitis C Elimination in HIV Cohorts (InCHEHC). Follow-up started from the first recorded negative HCV antibody test date and ended at last negative antibody test or estimated infection date. Follow-up was restricted to 2010–2019. We used segmented Poisson regression to model trends across pre-, limited- (i.e., restrictions on access) and broad-DAA access periods.
Overall, 45,942 participants had at least one HCV antibody negative result and follow-up between 2010 and 2019. We observed 2042 incident HCV infections over 248,189 person-years (PY). Pooled incidence decreased from 0.91 per 100 PY in 2015 to 0.41 per 100 PY in 2019. Compared to the average pre-DAA period incidence (0.90 per 100 PY), average incidence was similar during the limited-DAA access period (Incidence rate ratio IRR = 0.98; 95%CI = 0.87, 1.11), and 52% lower during the broad-DAA access period (IRR = 0.48; 95%CI = 0.42, 0.52). The average annual decline in HCV incidence was 2% in the pre-DAA period; an additional 9% annual decline in incidence was observed during the limited-DAA access period (IRR = 0.91; 95%CI = 0.82, 1.00) and a further 20% decline in the broad-DAA access period (IRR = 0.80, 95%CI = 0.73, 0.89).
Our findings suggest that broad DAA access has a TasP effect on primary HCV incidence among PLHIV. Based on the initial years of DAA availability, the countries in the InCHEHC collaboration are on track to meet the World Health Organization's 80% HCV incidence reduction target for PLHIV by 2030.
This study was funded by the Australian Government National Health and Medical Research Council (Grant number GNT1132902).
Abstract
This study evaluated the progeny of sows fed a control or probiotic diet with Bacillus subtilis C-3102 (Calsporin®, Calpis Co. Ltd., Tokyo, Japan) at 500,000 and 1,000,000 CFU/g diet in ...gestation and lactation, respectively. A total of 358 weaned pigs (DNA 241 × 600) were used in a 42-d trial with 4–5 pigs/pen and 18–19 pens/treatment. Pens were allotted to treatments in a completely randomized design based on BW at weaning. Treatments were a 2×2 factorial with main effects of sow diet (control vs. probiotic) and nursery diet (control vs. probiotic). In the nursery probiotic diet, a product based on probiotic Bacillus subtilis C-3102 at 500,000 CFU/g diet and prebiotics β-glucans and mannan oligosaccharides was included at 0.05% (BacPack ABF™, Quality Technology International, Inc., Elgin, IL). Diets were corn-soybean meal-based. Growth performance and fecal consistency on a 1-to-5 scale were evaluated weekly. Fecal samples were collected for microbial analysis by culture method and bacterial quantification of Bacillus subtilis C-3102, total Bacillus sp., Lactobacillus sp., Clostridium perfringens, Salmonella spp., Enterococcus sp., Enterobacteriaceae, total aerobes, and total anaerobes. Data were analyzed using a linear mixed model (PROC GLIMMIX, SAS®) with pen as experimental unit. There was no evidence for effect of sow diet, nursery diet, or interactions (P > 0.10) on overall nursery growth performance and fecal consistency. However, growth performance from d 21 to 42 and final BW were greater (P < 0.05) in progeny of control-fed sows compared to probiotic-fed sows. Microbial analysis revealed an increase (P < 0.01) in Bacillus subtilis C-3102 and, consequently, total Bacillus sp. in fecal microflora of probiotic-fed pigs. In conclusion, probiotic inclusion to sow diets lowered growth performance of the progeny in late nursery. The probiotic diet provided to sows or nursery pigs did not influence fecal consistency, but altered the fecal microbial population in nursery pigs by increasing total Bacillus sp.
Abstract
This study evaluated the effects of supplementation of sow diets with Bacillus subtilis C-3102 (Calsporin®, Calpis Co. Ltd., Tokyo, Japan) during gestation and lactation. A total of 29 sows ...(DNA 241) with confirmed pregnancy on d 30 of gestation were assigned to dietary treatments in a randomized complete block design based on BW and parity. Treatments were: control diet or probiotic diet with Calsporin® at 500,000 and 1,000,000 CFU/g of diet in gestation and lactation, respectively. Data were collected on d 30 and 112 of gestation and d 2 and 19 of lactation. Fecal consistency was assessed on a 1-to-5 scale for each litter. Fecal samples were collected from sows and piglets for microbial analysis by culture method and bacterial quantification of Bacillus subtilis C-3102, total Bacillus sp., Lactobacillus sp., Clostridium perfringens, Salmonella spp., Enterococcus sp., Enterobacteriaceae, total aerobes, and total anaerobes. Data were analyzed using a linear mixed model (PROC GLIMMIX, SAS®) with sow as experimental unit. Probiotic-fed sows had a marginally significant (P < 0.10) increase in lactation ADFI, but it did not result (P > 0.10) in improvement in sow or piglet weight at weaning. Probiotic-fed sows had a marginally significant (P < 0.10) larger litter size after cross-fostering, but it did not result (P > 0.10) in larger litter size at weaning. Fecal consistency of piglets was not influenced (P > 0.10) by sow diet. Microbial analysis revealed an increase (P < 0.01) in Bacillus subtilis C-3102 and, consequently, total Bacillus sp. in fecal microflora of probiotic-fed sows and piglets born and nursed by probiotic-fed sows. In conclusion, this study demonstrates that providing Calsporin® to sows during gestation and lactation improved lactation ADFI and cross-fostering litter size, although further larger-scale studies are required for elucidation. The probiotic diet did not influence fecal consistency, but altered the fecal microbial population in sows and nursing piglets by increasing total Bacillus sp.
This study evaluated the progeny of sows fed a control or probiotic diet with Bacillus subtilis C-3102 (Calsporin®, Calpis Co. Ltd., Tokyo, Japan) at 500,000 and 1,000,000 CFU/g diet in gestation and ...lactation, respectively. A total of 358 weaned pigs (DNA 241 x 600) were used in a 42-d trial with 4-5 pigs/pen and 18-19 pens/ treatment. Pens were allotted to treatments in a completely randomized design based on BW at weaning. Treatments were a 2x2 factorial with main effects of sow diet (control vs. probiotic) and nursery diet (control vs. probiotic). In the nursery probiotic diet, a product based on probiotic Bacillus subtilis C-3102 at 500,000 CFU/g diet and prebiotics ß-glucans and mannan oligosaccharides was included at 0.05% (BacPack ABF™, Quality Technology International, Inc., Elgin, IL). Diets were corn-soybean meal-based. Growth performance and fecal consistency on a 1-to-5 scale were evaluated weekly. Fecal samples were collected for microbial analysis by culture method and bacterial quantification of Bacillus subtilis C-3102, total Bacillus sp., Lactobacillus sp., Clostridium perfringens, Salmonella spp., Enterococcus sp., Enterobacteriaceae, total aerobes, and total anaerobes. Data were analyzed using a linear mixed model (PROC GLIMMIX, SAS®) with pen as experimental unit. There was no evidence for effect of sow diet, nursery diet, or interactions (P > 0.10) on overall nursery growth performance and fecal consistency. However, growth performance from d 21 to 42 and final BW were greater (P < 0.05) in progeny of control-fed sows compared to probiotic-fed sows. Microbial analysis revealed an increase (P < 0.01) in Bacillus subtilis C-3102 and, consequently, total Bacillus sp. in fecal microflora of probiotic-fed pigs. In conclusion, probiotic inclusion to sow diets lowered growth performance of the progeny in late nursery. The probiotic diet provided to sows or nursery pigs did not influence fecal consistency, but altered the fecal microbial population in nursery pigs by increasing total Bacillus sp.
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Given animals of similar body mass, birds have been shown to have much higher plasma glucose concentrations than that of mammals. However, birds appear not to show the pathological ...symptoms associated with high plasma glucose levels as seen in mammals. As the glomerular filtration rates (on a mass specific basis) of birds and mammals are not significantly different and with higher plasma glucose levels, birds must have a larger filtered load of glucose. Despite this there is little or no detectable glucose in the ureteral urine of birds. This suggests that the mechanisms for glucose reabsorption by the bird kidney must be significantly up‐regulated. In mammals glucose reabsorption is achieved through the sodium‐glucose co‐transport proteins (SGLTs) located in the apical cell membrane of the proximal renal tubule. The putative SGLTs within the avian kidney have not been isolated or characterized. Antibodies against mammal (rabbit) SGLT2 were used to isolate SGLTs from renal tissue harvested from Mourning doves. We have been able to demonstrate the presence of an immuno‐reactive protein in the kidneys of doves albeit not at the same intensity as that the rat kidney used as control. Using primers developed from known sequences of bovine SGLT2 DNA, RT‐PCR was used to further identify avian SGLTs.
Polar growth requires the precise tuning of Rho GTPase signalling at distinct plasma membrane domains. The activity of Rho of plant (ROP) GTPases is regulated by the opposing action of guanine ...nucleotide-exchange factors (GEFs) and GTPase-activating proteins (GAPs). Whereas plant-specific ROPGEFs have been shown to be embedded in higher-level regulatory mechanisms involving membrane-bound receptor-like kinases, the regulation of GAPs has remained enigmatic. Here, we show that three Arabidopsis ARMADILLO REPEAT ONLY (ARO) proteins are essential for the stabilization of growth sites in root hair cells and trichomes. AROs interact with ROP1 enhancer GAPs (RENGAPs) and bind to the plasma membrane via a conserved polybasic region at the ARO amino terminus. The ectopic spreading of ROP2 in aro2/3/4 mutant root hair cells and the preferential interaction of AROs with active ROPs and anionic phospholipids suggests that AROs recruit RENGAPs into complexes with ROPs to confine ROP signalling to distinct membrane regions.
We report that Kepler Object of Interest 256 (KOI-256) is a mutually eclipsing post-common envelope binary (ePCEB), consisting of a cool white dwarf (Mlow * = 0.592 + or - 0.089 M sub(middot in ...circle), Rlow * = 0.01345 + or - 0.00091 R sub(middot in circle), T sub(eff) = 7100 + or - 700 K) and an active M3 dwarf (Mlow * = 0.51 + or - 0.16 M sub(middot in circle), Rlow * = 0.540 + or - 0.014 R sub(middot in circle), T sub(eff) = 3450 + or - 50 K) with an orbital period of 1.37865 + or - 0.00001 days. KOI-256 is listed as hosting a transiting planet-candidate by Borucki et al. and Batalha et ah; here we report that the planet-candidate transit signal is in fact the occultation of a white dwarf as it passes behind the M dwarf. We combine publicly-available long- and short-cadence Kepler light curves with ground-based measurements to robustly determine the system parameters. The occultation events are readily apparent in the Kepler light curve, as is spin-orbit synchronization of the M dwarf, and we detect the transit of the white dwarf in front of the M dwarf halfway between the occultation events. The size of the white dwarf with respect to the Einstein ring during transit (R sub(Ein) = 0.00473 + or - 0.00055 R sub(middot in circle)) causes the transit depth to be shallower than expected from pure geometry due to gravitational lensing. KOI-256 is an old, long-period ePCEB and serves as a benchmark object for studying the evolution of binary star systems as well as white dwarfs themselves, thanks largely to the availability of near-continuous, ultra-precise Kepler photometry.
Abstract Purpose This randomised phase II trial aimed to compare efficacy of the irreversible ErbB family blocker, afatinib, with cetuximab in patients with KRAS wild-type metastatic colorectal ...adenocarcinoma (mCRC) with progression following oxaliplatin- and irinotecan-based regimens. Efficacy in patients with KRAS mutations was also evaluated. Patients and methods Patients with KRAS wild-type tumours were randomised 2:1 to afatinib (40 mg/day, increasing to 50 mg/day if minimal toxicity) or cetuximab weekly (400 mg/m2 loading dose, then 250 mg/m2 /week) according to number of previous chemotherapy lines. All patients with KRAS-mutated tumours received afatinib. Primary end-points were objective response (OR) for the wild-type group and disease control for the KRAS-mutated group. Secondary end-points were progression-free survival (PFS) and overall survival (OS). Results Patients with KRAS wild-type tumours ( n = 50) received afatinib ( n = 36) or cetuximab ( n = 14). Unconfirmed and confirmed ORs were 3% and 0% for afatinib versus 20% and 13% for cetuximab (odds ratio: 0.122 P = 0.0735 and <0.001, respectively). Median PFS was 46.0 and 144.5 days for afatinib and cetuximab, respectively. Median OS was 355 days with afatinib but not reached for cetuximab. In the KRAS - mutated group ( n = 41), five (12%) patients achieved confirmed disease control (stable disease; P = 0.6394 comparison versus 10%); no ORs were reported. Median PFS and OS were 41.0 and 173 days, respectively. Most frequent treatment-related adverse events were diarrhoea and rash across groups. Conclusions The efficacy of afatinib was inferior to cetuximab in patients with KRAS wild-type mCRC. In patients with KRAS-mutated tumours, disease control was modest with afatinib. Afatinib had a manageable safety profile.
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