Eribulin demonstrated activity with manageable tolerability (including infrequent grade 3 and no grade 4 neuropathy) in heavily pretreated patients with MBC when dosed as a short IV infusion on days 1 and 8 of a 21-day cycle.
Background
The 2-drug regimen dolutegravir (DTG) + lamivudine (3TC) is indicated for treatment-naive adults with human immunodeficiency virus type 1 (HIV-1). We present efficacy and safety of switching to DTG/3TC in virologically suppressed individuals.
Methods
TANGO is an open-label, multicenter, phase 3 study that randomized adults (1:1, stratified by baseline third agent class) with HIV-1 RNA <50 copies/mL to switch to once-daily fixed-dose DTG/3TC or remain on a tenofovir alafenamide (TAF)–based regimen. The primary end point was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48 (US Food and Drug Administration Snapshot algorithm) in the intention-to-treat–exposed population (4% noninferiority margin).
Results
743 adults were enrolled; 741 received ≥1 dose of study drug (DTG/3TC, N = 369; TAF-based regimen, N = 372). At week 48, proportion of participants with HIV-1 RNA ≥50 copies/mL receiving DTG/3TC was 0.3% (1/369) vs 0.5% (2/372) with a TAF-based regimen (adjusted treatment difference [95% confidence interval], −0.3 [−1.2 to .7]), meeting noninferiority criteria. No participants receiving DTG/3TC and 1 receiving a TAF-based regimen met confirmed virologic withdrawal criteria, with no emergent resistance at failure. Drug-related grade ≥2 adverse events and withdrawals due to adverse events occurred in 17 (4.6%) and 13 (3.5%) participants with DTG/3TC and 3 (0.8%) and 2 (0.5%) with a TAF-based regimen, respectively.
Conclusions
DTG/3TC was noninferior in maintaining virologic suppression vs a TAF-based regimen at week 48, with no virologic failure or emergent resistance reported with DTG/3TC, supporting it as a simplification strategy for virologically suppressed people with HIV-1.
Clinical Trials Registration
NCT03446573.
This study examined the efficacy of UV light for reducing Escherichia coli O157:H7 in unpasteurized cider. Cider containing a mixture of acid-resistant E. coli O157:H7 (6.3 log CFU/ml) was treated using a thin-film UV disinfection unit at 254 nm. Dosages ranged from 9,402 to 61,005 microW-s/cm2. Treatment significantly reduced E. coli O157:H7 (P < or = 0.0001). Mean reduction for all treated samples was 3.81 log CFU/ml. Reduction was also affected by the level of background microflora in cider. Results indicate that UV light is effective for reducing this pathogen in cider. However, with the dosages used in this experiment, additional reduction measures are necessary to achieve the required 5-log reduction.
In patients with both SRF and PVD at baseline, similar BCVA outcomes were observed regardless of treatment frequency. These patients may require less frequent treatments compared with patients without SRF, without PVD, or without either who may require more frequent injections for maintenance of vision. This finding may have implications in clinical practice by helping to tailor an individualized re-treatment interval in nAMD patients.
We describe the evolution of the Entities, Relations and Events (ERE) annotation task, created to support research and technology development within the DARPA DEFT program. We begin by describing the specification for Light ERE annotation, including the motivation for the task within the context of DEFT. We discuss the transition from Light ERE to a more complex Rich ERE specification, enabling more comprehensive treatment of phenomena of interest to DEFT.
J. 2003. Do individual branches of immune defence correlate? A comparative case study of scavenging and non-scavenging birds. -Oikos 102: 340-350.Costs of immunity are widely believed to play an important role in life history evolution, but most studies of ecological immunology have considered only single aspects of immune function. It is unclear whether we should expect correlated responses in other aspects of immune function not measured, because individual branches of immune defence may differ in their running costs and thus may compete unequally for limiting resources, resulting in negatively correlated evolution. In theory such selection pressure may be most intense where species are hosts to more virulent parasites, thus facing a higher potential cost of parasitism. These issues are relatively unstudied, but could influence the efficacy of attempting to estimate the scale and cost of host investment in immune defence. Here, in a comparative study of birds we found that species that scavenge at carcasses, that were hypothesised to be hosts to virulent parasites, had larger spleens for their body size and higher blood total leukocyte concentrations (general measures of immune function) than nonscavengers. These results support the hypothesis that scavengers are subject to strong parasite-mediated selection on immune defences. However, measures of specific branches of immune function revealed that scavengers had a relatively lower proportion of lymphocytes than phagocytic types of leukocytes, suggesting robust front line immune defences that could potentially reduce the need for mounting relatively energetically costly lymphocyte-dependent immune responses. Following experimental inoculation, scavengers produced significantly larger humoral immune responses, but not cell-mediated immune responses, than non-scavengers. However, the sizes of cell-mediated and humoral immune responses were not correlated across species. These results suggest that single measures of immune defence may not characterise the overall immune strategy, or reveal the likely costs involved. ). -A. P. Møller, Laboratoire d'Ecologie E6oluti6e Parasitaire, CNRS FRE 2365, Uni6. Pierre et Marie Curie, Bât. A, 7 ème étage, 7 quai St. Bernard, Case 237, FR-75252 Paris Cedex 5, France.
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