DEPRESSION AND EMOTIONAL DISTRESS IN YOUNG, LOW-INCOME AFRICAN-AMERICAN MEN AND FATHERS

Depression is a debilitating mental illness that in its most serious form, major depression, has affected between 3.6% to 12.7% of men in the United States (Cochran & Rabinowitz, 2000; Jonas, Brody, Roper, & Narrow, 2003; Kessler, McGonagle, Zhao, & Nelson, 1994). It has consistently been found to be twice as prevalent in women as in men, and yet the suicide rate of men is four to five times that of women (Singh, Kochanek, & MacDorman, 1996; World Health Organization, 2005). Despite this, little is known about the experience and expression of the full range of depression in men, and specifically, young, low-income men of color who are fathers. When young fathers suffer from depression, there are enormous consequences for young families, both financial and emotional (Ansseau et al., 2008; Mirowsky & Ross, 2002; Montgomery, Cook, Bartley, & Wadsworth, 1999; Patten et al., 2006; Rehman, Gollan, & Mortimer, 2008; Soares, Macassa, Grossi, & Viitasara, 2008). It is possible that the risk for depression increases when fatherhood includes the challenges of nonresidential parenting and financial stress (Cochran & Rabinowitz, 2002; Roy, 2004). This has implications for their co-parenting relationships, and shapes their identities and roles as parents and providers (Bouma, Ormel, Verhulst, & Oldehinkel, 2008; Kim, Capaldi, & Stoolmiller, 2003). However, fatherhood also brings many opportunities for young men; it is a chance for them to be generative for the first time in their lives and to experience the joys that accompany the challenges of parenthood (Palkovitz, Copes, & Woolfolk, 2001). I conducted research guided by a combination of symbolic interaction theory and the cognitive theory of depression to answer the following questions: how does depression emerge in toxic environments, how do young men experience and express the full range of depression in those environments over time, and, what was the reciprocal relationship between depression and fatherhood? I conducted in-depth interviews with 40 at risk, low-income young African-American men and fathers. Growing up in high crime neighborhoods meant that many had strained and fractured relationships with law enforcement, teachers, peers, and families. Young men engaged in identity work while trying to avoid problems at school and with law enforcement. They also reported substantial substance abuse, usually starting recreationally, but moving to daily self-medication for stress and anger. Depression was expressed at multiple points, through depressive language, extensive anger histories, fatigue, protracted cycles of avoidance, and episodes of major depression. Young men who were also young fathers found that fatherhood brought added responsibilities, which added to stress, but also found great joy and motivation in their children

Training and HIV-Treatment Scale-Up: Establishing an Implementation Research Agenda

McCarthy and colleagues discuss the various approaches to training the health workforce for an expanding HIV treatment program in a resource-limited setting

Rift Valley fever virus infection induces activation of the NLRP3 inflammasome

AbstractInflammasome activation is gaining recognition as an important mechanism for protection during viral infection. Here, we investigate whether Rift Valley fever virus, a negative-strand RNA virus, can induce inflammasome responses and IL-1β processing in immune cells. We have determined that RVFV induces NLRP3 inflammasome activation in murine dendritic cells, and that this process is dependent upon ASC and caspase-1. Furthermore, absence of the cellular RNA helicase adaptor protein MAVS/IPS-1 significantly reduces extracellular IL-1β during infection. Finally, direct imaging using confocal microscopy shows that the MAVS protein co-localizes with NLRP3 in the cytoplasm of RVFV infected cells

RNA helicase signaling is critical for type I interferon production and protection against rift valley fever virus during mucosal challenge

Rift Valley fever virus (RVFV) is an emerging RNA virus with devastating economic and social consequences. Clinically, RVFV induces a gamut of symptoms ranging from febrile illness to retinitis, hepatic necrosis, hemorrhagic fever, and death. It is known that type I interferon (IFN) responses can be protective against severe pathology; however, it is unknown which innate immune receptor pathways are crucial for mounting this response. Using both in vitro assays and in vivo mucosal mouse challenge, we demonstrate here that RNA helicases are critical for IFN production by immune cells and that signaling through the helicase adaptor molecule MAVS (mitochondrial antiviral signaling) is protective against mortality and more subtle pathology during RVFV infection. In addition, we demonstrate that Toll-like-receptor-mediated signaling is not involved in IFN production, further emphasizing the importance of the RNA cellular helicases in type I IFN responses to RVFV

GPI spectra of HR 8799 c, d, and e from 1.5 to 2.4μ\mum with KLIP Forward Modeling

We explore KLIP forward modeling spectral extraction on Gemini Planet Imager coronagraphic data of HR 8799, using PyKLIP and show algorithm stability with varying KLIP parameters. We report new and re-reduced spectrophotometry of HR 8799 c, d, and e in H & K bands. We discuss a strategy for choosing optimal KLIP PSF subtraction parameters by injecting simulated sources and recovering them over a range of parameters. The K1/K2 spectra for HR 8799 c and d are similar to previously published results from the same dataset. We also present a K band spectrum of HR 8799 e for the first time and show that our H-band spectra agree well with previously published spectra from the VLT/SPHERE instrument. We show that HR 8799 c and d show significant differences in their H & K spectra, but do not find any conclusive differences between d and e or c and e, likely due to large error bars in the recovered spectrum of e. Compared to M, L, and T-type field brown dwarfs, all three planets are most consistent with mid and late L spectral types. All objects are consistent with low gravity but a lack of standard spectra for low gravity limit the ability to fit the best spectral type. We discuss how dedicated modeling efforts can better fit HR 8799 planets' near-IR flux and discuss how differences between the properties of these planets can be further explored.Comment: Accepted to AJ, 25 pages, 16 Figure

An Open Label, Adaptive, Phase 1 Trial of High-Dose Oral Nitazoxanide in Healthy Volunteers: An Antiviral Candidate for SARS-CoV-2.

Funder: UnitaidRepurposing approved drugs may rapidly establish effective interventions during a public health crisis. This has yielded immunomodulatory treatments for severe coronavirus disease 2019 (COVID-19), but repurposed antivirals have not been successful to date because of redundancy of the target in vivo or suboptimal exposures at studied doses. Nitazoxanide is a US Food and Drug Administration (FDA) approved antiparasitic medicine, that physiologically-based pharmacokinetic (PBPK) modeling has indicated may provide antiviral concentrations across the dosing interval, when repurposed at higher than approved doses. Within the AGILE trial platform (NCT04746183) an open label, adaptive, phase I trial in healthy adult participants was undertaken with high-dose nitazoxanide. Participants received 1,500 mg nitazoxanide orally twice-daily with food for 7 days. Primary outcomes were safety, tolerability, optimum dose, and schedule. Intensive pharmacokinetic (PK) sampling was undertaken day 1 and 5 with minimum concentration (Cmin ) sampling on days 3 and 7. Fourteen healthy participants were enrolled between February 18 and May 11, 2021. All 14 doses were completed by 10 of 14 participants. Nitazoxanide was safe and with no significant adverse events. Moderate gastrointestinal disturbance (loose stools or diarrhea) occurred in 8 participants (57.1%), with urine and sclera discoloration in 12 (85.7%) and 9 (64.3%) participants, respectively, without clinically significant bilirubin elevation. This was self-limiting and resolved upon drug discontinuation. PBPK predictions were confirmed on day 1 but with underprediction at day 5. Median Cmin was above the in vitro target concentration on the first dose and maintained throughout. Nitazoxanide administered at 1,500 mg b.i.d. with food was safe with acceptable tolerability a phase Ib/IIa study is now being initiated in patients with COVID-19

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

GPI Spectra of HR 8799 c, d, and e from 1.5 To 2.4 μm with KLIP Forward Modeling

We explore KLIP forward modeling spectral extraction on Gemini Planet Imager coronagraphic data of HR 8799, using PyKLIP, and show algorithm stability with varying KLIP parameters. We report new and re-reduced spectrophotometry of HR 8799 c, d, and e in the H and K bands. We discuss a strategy for choosing optimal KLIP PSF subtraction parameters by injecting simulated sources and recovering them over a range of parameters. The K1/K2 spectra for HR 8799 c and d are similar to previously published results from the same data set. We also present a K-band spectrum of HR 8799 e for the first time and show that our H-band spectra agree well with previously published spectra from the VLT/SPHERE instrument. We show that HR 8799 c and d show significant differences in their H and K spectra, but do not find any conclusive differences between d and e, nor between c and e, likely due to large error bars in the recovered spectrum of e. Compared to M-, L-, and T-type field brown dwarfs, all three planets are most consistent with mid- and late-L spectral types. All objects are consistent with low gravity, but a lack of standard spectra for low gravity limit the ability to fit the best spectral type. We discuss how dedicated modeling efforts can better fit HR 8799 planets\u27 near-IR flux, as well as how differences between the properties of these planets can be further explored

Direct Imaging of the HD 35841 Debris Disk: a Polarized Dust Ring from Gemini Planet Imager and an Outer Halo From \u3ci\u3eHST/\u3c/i\u3eSTIS

We present new high resolution imaging of a light-scattering dust ring and halo around the young star HD 35841. Using spectroscopic and polarimetric data from the Gemini Planet Imager in H-band (1.6 μm), we detect the highly inclined (i = 85°) ring of debris down to a projected separation of ∼12 au (∼0.″12) for the first time. Optical imaging from HST/STIS shows a smooth dust halo extending outward from the ring to \u3e140 au (\u3e1.″4). We measure the ring\u27s scattering phase function and polarization fraction over scattering angles of 22°-125°, showing a preference for forward scattering and a polarization fraction that peaks at ∼30% near the ansae. Modeling of the scattered-light disk indicates that the ring spans radii of ∼60-220 au, has a vertical thickness similar to that of other resolved dust rings, and contains grains as small as 1.5 μm in diameter. These models also suggest the grains have a low porosity, are more likely to consist of carbon than astrosilicates, and contain significant water ice. The halo has a surface brightness profile consistent with that expected from grains pushed by radiation pressure from the main ring onto highly eccentric but still bound orbits. We also briefly investigate arrangements of a possible inner disk component implied by our spectral energy distribution models, and speculate about the limitations of Mie theory for doing detailed analyses of debris disk dust populations