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In phase 1 trials, the HIV-1 integrase strand transfer inhibitor cabotegravir (GSK1265744) was well tolerated, both alone, and in combination with the non-nucleoside reverse transcriptase inhibitor rilpivirine. We assessed cabotegravir plus rilpivirine, as a two-drug oral antiretroviral regimen, for the maintenance of viral suppression in antiretroviral-naive HIV-1-infected individuals. In the phase 2b Long-Acting antireTroviral Treatment Enabling (LATTE) trial, a multicentre study done in Canada and the USA, antiretroviral-naive HIV-1-infected adults (aged ≥18 years) were randomly allocated in a 1:1:1:1 ratio to oral cabotegravir 10 mg once a day, 30 mg once a day, 60 mg once a day, or oral efavirenz 600 mg once a day with dual nucleoside reverse transcriptase inhibitors (NRTIs) for 24 weeks of induction. Patients who were virologically suppressed by week 24 received a two-drug maintenance regimen consisting of their randomly allocated cabotegravir dose plus oral rilpivirine 25 mg or continued efavirenz plus NRTIs for an additional 72 weeks. Patients and investigators were masked to doses of cabotegravir received for 96 weeks, but not to the assignment of cabotegravir or efavirenz. The primary endpoint was the proportion of patients with fewer than 50 copies per mL of HIV-1 RNA (US Food and Drug Administration snapshot algorithm) at week 48. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, NCT01641809. Of 243 patients randomly allocated and treated, 156 (86%) of 181 patients in the cabotegravir groups (52 [87%] of 60, 51 [85%] of 60, and 53 [87%] of 61 patients in the 10 mg, 30 mg, and 60 mg groups, respectively) and 46 (74%) of 62 in the efavirenz group had fewer than 50 copies per mL of HIV-1 RNA after induction therapy. After patients in the cabotegravir groups were changed over from dual NRTIs to rilpivirine at week 24, 149 (82%; 95% CI 77–88) patients in the cabotegravir groups (48 [80%; 70–90], 48 [80%; 70–90], and 53 [87%; 78–95] patients in the 10 mg, 30 mg, and 60 mg groups, respectively) versus 44 (71%; 60–82) in the efavirenz group were virologically suppressed at week 48, and 137 (76%; 69–82) receiving cabotegravir (41 [68%; 57–80], 45 [75%; 64–86], and 51 [84%; 74–93] patients in the 10 mg, 30 mg, and 60 mg groups, respectively) versus 39 (63%; 51–75) in the efavirenz group were virologically suppressed at week 96. Treatment-related adverse events were reported by 93 (51%) cabotegravir-treated patients (28 [47%], 32 [53%], and 33 [54%] patients in the 10 mg, 30 mg, and 60 mg groups, respectively) and 42 (68%) efavirenz-treated patients. Six (3%) patients in the cabotegravir groups (one [2%], one [2%], and four [7%] patients in the 10 mg, 30 mg, and 60 mg groups, respectively) withdrew because of treatment-emergent adverse events compared with nine (15%) in the efavirenz group. Cabotegravir plus dual NRTI therapy had potent antiviral activity during the induction phase. As a two-drug maintenance therapy, cabotegravir plus rilpivirine provided antiviral activity similar to efavirenz plus dual NRTIs until the end of week 96. Combined efficacy and safety results lend support to our selection of oral cabotegravir 30 mg once a day for further assessment. LATTE precedes studies of the assessment of longacting injectable formulations of both drugs as a two-drug regimen for the treatment of HIV-1 infection. ViiV Healthcare and Janssen Research and Development.

Simplified treatment regimens for HIV management may increase adherence. In this open-label, randomized, controlled trial, longer-acting (monthly) injectable cabotegravir plus rilpivirine was compared with standard oral treatment. At 48 weeks, similar viral suppression was seen with the two regimens.

Cabotegravir and rilpivirine are antiretroviral drugs in development as long-acting injectable formulations. The LATTE-2 study evaluated long-acting cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through 96 weeks. In this randomised, phase 2b, open-label study, treatment-naive adults infected with HIV-1 initially received oral cabotegravir 30 mg plus abacavir–lamivudine 600–300 mg once daily. The objective of this study was to select an intramuscular dosing regimen based on a comparison of the antiviral activity, tolerability, and safety of the two intramuscular dosing regimens relative to oral cabotegravir plus abacavir–lamivudine. After a 20-week induction period on oral cabotegravir plus abacavir–lamivudine, patients with viral suppression (plasma HIV-1 RNA <50 copies per mL) were randomly assigned (2:2:1) to intramuscular long-acting cabotegravir plus rilpivirine at 4-week intervals (long-acting cabotegravir 400 mg plus rilpivirine 600 mg; two 2 mL injections) or 8-week intervals (long-acting cabotegravir 600 mg plus rilpivirine 900 mg; two 3 mL injections) or continued oral cabotegravir plus abacavir–lamivudine. Randomisation was computer-generated with stratification by HIV-1 RNA (<50 copies per mL, yes or no) during the first 12 weeks of the induction period. The primary endpoints were the proportion of patients with viral suppression at week 32 (as defined by the US Food and Drug Administration snapshot algorithm), protocol-defined virological failures, and safety events through 96 weeks. All randomly assigned patients who received at least one dose of study drug during the maintenance period were included in the primary efficacy and safety analyses. The primary analysis used a Bayesian approach to evaluate the hypothesis that the proportion with viral suppression for each long-acting regimen is not worse than the oral regimen proportion by more than 10% (denoted comparable) according to a prespecified decision rule (ie, posterior probability for comparability >90%). Difference in proportions and associated 95% CIs were supportive to the primary analysis. The trial is registered at ClinicalTrials.gov, number NCT02120352. Among 309 enrolled patients, 286 were randomly assigned to the maintenance period (115 to each of the 4-week and 8-week groups and 56 to the oral treatment group). This study is currently ongoing. At 32 weeks following randomisation, both long-acting regimens met primary criteria for comparability in viral suppression relative to the oral comparator group. Viral suppression was maintained at 32 weeks in 51 (91%) of 56 patients in the oral treatment group, 108 (94%) of 115 patients in the 4-week group (difference 2·8% [95% CI −5·8 to 11·5] vs oral treatment), and 109 (95%) of 115 patients in the 8-week group (difference 3·7% [−4·8 to 12·2] vs oral treatment). At week 96, viral suppression was maintained in 47 (84%) of 56 patients receiving oral treatment, 100 (87%) of 115 patients in the 4-week group, and 108 (94%) of 115 patients in the 8-week group. Three patients (1%) experienced protocol-defined virological failure (two in the 8-week group; one in the oral treatment group). Injection-site reactions were mild (3648 [84%] of 4360 injections) or moderate (673 [15%] of 4360 injections) in intensity and rarely resulted in discontinuation (two [<1%] of 230 patients); injection-site pain was reported most frequently. Serious adverse events during maintenance were reported in 22 (10%) of 230 patients in the intramuscular groups (4-week and 8-week groups) and seven (13%) of 56 patients in the oral treatment group; none were drug related. The two-drug combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4 weeks or every 8 weeks was as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression through 96 weeks and was well accepted and tolerated. ViiV Healthcare and Janssen R&D.

PurposeThe purpose of this study was to examine the influence of socio-cognitive mindfulness on resilience, stress and thriving among middle managers in higher education at two separate periods during the COVID-19 pandemic. In Study 1, the authors examined how socio-cognitive mindfulness predicted perceived stress and whether the relationship between mindfulness and perceived stress was mediated by resilience. In Study 2, the authors replicated the first study and further hypothesized that the link between mindfulness and thriving was also mediated by resilience.Design/methodology/approachThe authors conducted cross-sectional correlational studies to test the hypotheses using data from 163 middle managers in higher education early in the pandemic in Study 1 and 204 middle managers a year later in Study 2.FindingsStudy 1 findings showed socio-cognitive mindfulness predicted perceived stress, and that resilience fully mediated this relationship. In Study 2, socio-cognitive mindfulness did not predict perceived stress, but it did predict thriving, and that relationship was fully mediated by resilience.Originality/valueThis research is the first to address how socio-cognitive mindfulness directly impacts perceived stress and thriving and its impact through building resilience. To date, few studies have focused on stress in higher education middle managers or addressed the importance of building socio-cognitive mindfulness and resilience to thrive amid ongoing challenges. Implications of the pandemic's influence on the results are also addressed.

PurposeThe purpose of this paper is to understand the experience of three formerly abrasive leaders who improved their conduct and management strategies following a workplace intervention.Design/methodology/approachNarrative inquiry, a personal and collaborative research method, revealed the experience of three leaders in their shift from destructive behaviors. Concepts from adult development, specifically Kegan's constructive-development theory (CDT) and Mezirow's transformative learning theory (TL), provided a lens to better understand the leaders' personal development.FindingsThis study culminated with three co-composed narrative accounts and an analysis of narrative threads. The focus of this paper is the interpretive narrative thread analysis. The developmental experience of these three leaders included disruption, awakening and equipping.Research limitations/implicationsThis study included three leaders. The experience of these leaders may not be representative of other formerly abrasive leaders.Practical implicationsThis initial exploratory study contributes to CDT and TL by suggesting leader interpersonal development is an intensely emotional experience that transcends the mechanics of developmental stages. In practice, this study indicates abrasive leaders may improve their conduct and management strategies with organizational support, including supervisor intervention and specialized professionals.Originality/valueThis paper offers insight for scholars and human resource (HR) professionals on the emotionally intense experiential journey of leaders who improved their interpersonal conduct. This study introduces concepts from CDT and TL into the study of workplace psychological aggression (WPA), and it expands the limited knowledge of how HR can support positive perpetrator change.

Co-temporal Doppler images from Solar and Heliospheric Observatory (SOHO)/ Michelson Doppler Imager (MDI) and Solar Dynamics Observatory (SDO)/ Helioseismic Magnetic Imager (HMI) have been analyzed to extract quantitative information about global properties of the spatial and temporal characteristics of solar supergranulation. Preliminary comparisons show that supergranules appear to be smaller and have stronger horizontal velocity flows within HMI data than was measured with MDI. There appears to be no difference in their evolutionary timescales. Supergranule sizes and velocities were analyzed over a ten-day time period at a 15-minute cadence. While the averages of the time-series retain the aforementioned differences, fluctuations of these parameters first observed in MDI data were seen in both MDI and HMI time-series, exhibiting a strong cross-correlation. This verifies that these fluctuations are not instrumental, but are solar in origin. The observed discrepancies between the averaged values from the two sets of data are a consequence of instrument resolution. The lower spatial resolution of MDI results in larger observed structures with lower velocities than is seen in HMI. While these results offer a further constraint on the physical nature of supergranules, they also provide a level of calibration between the two instruments.

Sixty days of Doppler images from the Solar and Heliospheric Observatory (SOHO) / Michelson Doppler Imager (MDI) investigation during the 1996 and 2008 solar minima have been analyzed to show that certain supergranule characteristics (size, size range, and horizontal velocity) exhibit fluctuations of three to five days. Cross-correlating parameters showed a good, positive correlation between supergranulation size and size range, and a moderate, negative correlation between size range and velocity. The size and velocity do exhibit a moderate, negative correlation, but with a small time lag (less than 12 hours). Supergranule sizes during five days of co-temporal data from MDI and the Solar Dynamics Observatory (SDO) / Helioseismic Magnetic Imager (HMI) exhibit similar fluctuations with a high level of correlation between them. This verifies the solar origin of the fluctuations, which cannot be caused by instrumental artifacts according to these observations. Similar fluctuations are also observed in data simulations that model the evolution of the MDI Doppler pattern over a 60-day period. Correlations between the supergranule size and size range time-series derived from the simulated data are similar to those seen in MDI data. A simple toy-model using cumulative, uncorrelated exponential growth and decay patterns at random emergence times produces a time-series similar to the data simulations. The qualitative similarities between the simulated and the observed time-series suggest that the fluctuations arise from stochastic processes occurring within the solar convection zone. This behavior, propagating to surface manifestations of supergranulation, may assist our understanding of magnetic-field-line advection, evolution, and interaction.

The corn distilling industry is a major processor of grain, but the high fiber co-product (DDGS), has limited application in feed. Simple mechanical stillage separation downstream of fermentation produces a high protein (52.4 % DM), highly digestible, low crude fiber (4.4% DM) product containing approximately 25% DM spent brewer’s yeast (high density distillers’ protein: HDDP). Currently, approximately 300 ktons of HDDP are produced annually in the USA, and the volume will double in 2020. The effect of graded inclusion levels of HDDP on growth, feed efficiency, nutrient utilization, blood chemistry and gut histology of 525 post-smolt Atlantic salmon (initial body weight 304 ± 10.7g), randomly allocated to three tanks per treatment, was tested in a salt-water recirculating aquaculture system. One control diet with no HDDP was formulated to meet the nutrient requirements of Atlantic salmon. Four test diets were formulated to contain graded levels of HDDP at 5, 10, 15 and 20% respectively. HDDP partially replaced soy protein concentrate and corn protein concentrate in the diets. Salmon were hand-fed to satiety, 3 times daily during the 84-day trial. Throughout the trial the performance of fish on all treatments exceeded commercial growth rates with thermal growth coefficients (TGC) in excess of 0.160 and feed conversion efficiency of ≤ 1.0. Overall HDDP was a nutritious feed ingredient and had no significant impact on performance. Overall TGC was highest (0.200 over the 84-day trial period) in fish fed the diet containing 10% HDDP. Both villi length and villi width in the distal intestine of salmon fed diets containing HDDP tended to be higher than in the controls. Overall, HDDP derived from the dry grind ethanol process was a safe and nutritious novel feed ingredient for Atlantic salmon, and the potential beneficial effect on gut morphology merits investigation.