Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] >= 50 copies/mL) and VL = 50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52-96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF

Effect of sensitization on the stress corrosion cracking of AA5083

Stress corrosion cracking of AA5083 was evaluated using both slow strain rate testing, there was a strong effect of sensitization with aging time. Increasing aging time leads to a sharp decrease in strain to failure, as well as ultimate tensile strength (UTS). In the fully sensitized condition (175°C/240h) there was a significant effect of chloride concentration, with increasing chloride concentration leading to a sharp decrease in strain to failure and UTS. However, in the as received condition there was no significant effect of chloride concentration on the slow strain rate behavior. The difference in behavior is likely associated with continuous precipitation of β phase along the boundaries. Rising displacement tests were performed as a function of sensitization time and the Kth measured decreased sharply with aging time reaching ~4MPaÖm at 240h. The effect of chloride concentration and applied potential in the sensitized condition (175C/240h) was evaluated and the Kth decreased with increasing chloride concentration. At applied potentials below the breakdown potential of β there was an increase in the Kth but the values of Kth were not as those observed in the as received condition. The observations made suggest that the stress corrosion cracking of AA5083 was sensitive to the applied potential and chloride concentration which in turn control the crack tip conditions. The observed data were analyzed in terms of a crack tip strain rate model to quantify the behavior of AA5083

SCC characterization of AL-Li-Cu-x Alloys

In the past several decades many Al-Li-X alloys have been studied to understand the fracture properties due to its superior specific strength and modulus over the currently dominated 2024 & 7075 type aircraft structural alloys. It is also observed that their stress corrosion resistance is also good in the peak aged condition depending on the (Li/Cu) ratio. To understand its behavior with respect to its heat treatment, a systematic collection of data is required from the published literature. We have collected such systematic data for three alloys from the early 1980’s on Al-3Li, Al-2Li-3Cu and Al-1.5Li-4.5Cu, all with 0.12Zr to keep the grain structure predominantly un-recrystalized. Such alloys were tested in the S-T direction in 3.5%NaCl solution to obtain the plateau velocities (da/dt) and threshold KIscc. It is observed that in all the alloys, (da/dt) decreased with aging heat treatment time, the decrease increased with (Li/Cu) ratio. This decrease is interpreted in terms of the degree of anodic dissolution of the grain boundary precipitates. The results are compared with theSCCbehavior of 7050 and 2024 alloys. Additional data where reversion aging treatment was given shows that grain boundary precipitates play an important role in theSCCbehavior. The overall trend in theSCCbehavior is discussed in light of the current understanding of the aluminum alloy behavior in terms of anodic dissolution and the role of hydrogen

Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study

BACKGROUND: Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved renal and bone safety compared with TDF-containing regimens. We report the 48 week safety and efficacy of a once-daily single tablet regimen of elvitegravir 150 mg (E), cobicistat 150 mg (C), emtricitabine 200 mg (F), and TAF 10 mg (E/C/F/TAF) in HIV-1-infected patients with mild to moderate renal impairment. METHODS: We enrolled virologically suppressed HIV-1-infected subjects with estimated creatinine clearance (CrCl) 30-69 mL/min in a single-arm, open-label study to switch regimens to E/C/F/TAF. The primary endpoint was the change from baseline in glomerular filtration rate estimated using various formulae. This study is registered with ClinicalTrials.gov, number NCT01818596. FINDINGS: We enrolled and treated 242 patients with mean age 58 years, 18% Black, 39% hypertension, 14% diabetes. Through week 48, no significant change in estimated CrCl was observed. Two patients (0.8%) discontinued study drug for decreased creatinine clearance, neither had evidence of renal tubulopathy and both had uncontrolled hypertension. Subjects had significant improvements in proteinuria, albuminuria, and tubular proteinuria (P < 0.001 for all). Hip and spine bone mineral density significantly increased from baseline to week 48 (mean percent change +1.47 and +2.29, respectively, P < 0.05). Ninety-two percent (222 patients) maintained HIV-1 RNA <50 copies per milliliter at week 48. INTERPRETATION: Switch to E/C/F/TAF was associated with minimal change in GFR. Proteinuria, albuminuria and bone mineral density significantly improved. These data support the efficacy and safety of once daily E/C/F/TAF in HIV+ patients with mild or moderate renal impairment without dose adjustment

Some hematological and biochemical parameters in smokeless tobacco (Jharda) chewers

The effect of Jharda powder (smokeless tobacco) on some hematological and biochemical parameters in consumers was investigated. Hematological parameters including hemoglobin content and white blood cell and leukocyte counts were higher in jharda powder consumers, while monocytes and basophiles counts were lower. Higher biochemical parameters like serum cholesterol, glucose and protein were observed in blood samples of Jharda consumers

The Anointed Son, The Hired Gun, and the Chai Wala: Enemies and Insults in Politicians’ Tweets in the Run-Up to the 2019 Indian General Elections

This study seeks to assess the prevalence, style, and impact of antagonistic messaging on Twitter in the two years preceding the 2019 Indian General Elections. Focusing on the leadership of the two key parties – the ruling BJP, with Prime Minister Narendra Modi and party president Amit Shah, and the opposition INC’s president Rahul Gandhi, we attempt to understand how the politicians sought to portray each other on Twitter, and how their followers reacted to these characterizations, through the lens of Murray Edelman’s work on the ‘Political Enemy’. By thematically coding tweets and quantitatively analyzing their retweets, we find that negative tweets by and large are significantly more popular for all three politicians, and that the opposition leader allocated a significantly larger proportion of his tweets to attacks. We conclude that while leaders in power and those in opposition may take different stances with messaging, Twitter as a social networking site can perpetuate the online reward for attacking behavior

How mothers talk to their children about failure, mistakes and setbacks is related to their children's fear of failure.

BACKGROUND: Many people fear failure and making mistakes. This fear can be transmitted from parents to children, suggesting that parental communication regarding failures and setbacks may play a critical role in shaping a child's perception of mistakes. AIMS: In this study, we investigated how everyday parent-child conversations about setbacks influence children's fear of making mistakes. SAMPLE: Drawing on the large pre-birth Growing Up in New Zealand cohort, we focused on a sub-sample of 231 mother-child dyads who engaged in a recorded conversations about a "recent disappointment or setback" when the children were 8 years old. METHOD: Conversations between mothers and children about the recent disappointments were coded to identify whether parents recognised or acknowledge their child's emotional response, if action plans were discussed, and the types of resources that the child could draw on. The children also completed a questionnaire about their global self-worth and their fear of making mistakes. RESULTS AND CONCLUSIONS: The discussion of clear action plans, in the absence of a discussion about collaborative resources, was found to be associated with an increased fear of making mistakes among children. Conversely, when mothers clearly acknowledged their child's emotions and discussed ways to work collaboratively with their child on future problems, there was a notable decrease in the child's fear of mistakes. However, it is noteworthy that many mothers in our study either minimally acknowledged or dismissed their child's emotions(40%), rarely discussed action plans (55%), or collaborative resources (79%)when discussing the recent setback