Isatuximab in combination with lenalidomide and dexamethasone in patients with high-risk smoldering multiple myeloma: Updated safety run-in results from the randomized phase 3 ithaca study

Background: Results from a randomized, Phase 3 study by the Spanish Myeloma Group (PETHEMA/GEM) previously showed that treatment with lenalidomide plus dexamethasone (Rd) may delay progression to active disease in patients (pts) with high-risk smoldering multiple myeloma (SMM), compared with observation. To further improve outcomes, addition of the anti-CD38 antibody isatuximab (Isa) to lenalidomide and dexamethasone (Isa-Rd) for the treatment of pts with high-risk SMM is being evaluated in the ongoing, randomized, multi-center, Phase 3 ITHACA study (NCT04270409). Initial findings from the safety run-in analysis of this trial have shown a manageable safety profile and encouraging, preliminary anti-myeloma activity. We now report updated safety and efficacy results from the safety run-in part of ITHACA at a median follow-up of 19.4 months. Methods: Pts were included in the study if they had been diagnosed within 5 years with SMM (per the International Myeloma Working Group [IMWG] criteria) and had high-risk SMM according to the Mayo '20-2-20' and/or updated PETHEMA model criteria. Pts who had received prior anti-myeloma treatment were not eligible. Enrolled pts received Isa 10 mg/kg IV on day (D) 1, 8, 15, and 22 in cycle (C) 1, D1 and D15 C2-12, D1 C13-36; plus R D1-21 (25 mg C1-9; 10 mg C10-24) and d weekly (40 mg, 20 mg for ≥75 yr-old pts C1-9; 20 mg C10-24). Cycle duration was 28 days. Safety evaluations included treatment-emergent AEs (TEAEs)/serious AEs and laboratory parameters, graded by NCI-CTCAE v5.0. Response was determined by IMWG criteria (2016). Mandatory imaging by MRI and/or low-dose whole-body CT/PET-CT, and assessments of minimal residual disease (MRD, by next-generation sequencing in pts with very good partial response [VGPR] or better), were performed at protocol-defined time points. The primary study objective for the safety run-in was to confirm the recommended dose of Isa in combination with Rd. Overall response rate (ORR) and MRD negativity rate at 10-5 sensitivity were included as secondary endpoints.Sanof

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Gender and sociocultural factors in animal source foods (ASFs) access and consumption in lower-income households in urban informal settings of Nairobi, Kenya

Background Gender shapes household decision-making and access for nutritious diets, including animal source foods (ASFs) that impact on child health and nutrition status. However, research shows that the poorest households in the urban informal settlements of Nairobi have low ASFs consumption. This study was conducted to explore further from a qualitative perspective the gender, sociocultural factors affecting household ASF consumption this study. Methods To explore further on the topic of study, an exploratory qualitative study was carried out to establish the factors that influence access, allocation and consumption of animal source foods (ASFs) by households in urban informal settings of Nairobi. Nineteen focus group discussions with men and women were conducted to enable in-depth exploration of ASFs consumption. Results Gender influences decision-making of household ASFs dietary intake. Gendered power dynamics prevail with men as breadwinners and household heads often determining the food access and consumption of ASFs. Women are increasingly accessing short-term waged-based incomes in urban informal settings and now play a role in food and nutrition security for their households. This enforces the idea that women’s decision-making autonomy is an important aspect of women empowerment, as it relates to women’s dietary diversity and subsequently, better household nutritional status. As evidenced in this study, if a woman has bargaining power based on accessing incomes to support their household food needs, she will not jeopardize food security. The mobile digital money platform was key in enabling access to resources to access food. Use of trust to access food on credit and purchasing smaller packaged quantities of food were also enablers to access of food/ASFs

Are Self-Reported Fertility Preferences Biased? Evidence from Indirect Elicitation Methods

Desired fertility measures are routinely collected and used by researchers and policy makers, but their self-reported nature raises the possibility of reporting bias. In this paper we test for the presence of such bias by comparing responses to direct survey questions with indirect questions offering a varying, randomized, degree of confidentiality to respondents in a socioeconomically diverse sample of Nigerian women (N = 6,256). We find that women report higher fertility preferences when asked indirectly, but only when their responses afford them complete confidentiality, not when their responses are simply blind to the enumerator. Our results suggest that there may be fewer unintended pregnancies than currently thought, and that the effectiveness of family planning policy targeting may be weakened by the bias we uncover. We conclude with suggestions for future work on how to mitigate reporting bias

Identification of amyloid beta in small extracellular vesicles via Raman spectroscopy.

One of the hallmarks of Alzheimer's disease (AD) pathogenesis is believed to be the production and deposition of amyloid-beta (Aβ) peptide into extracellular plaques. Existing research indicates that extracellular vesicles (EVs) can carry Aβ associated with AD. However, characterization of the EVs-associated Aβ and its conformational variants has yet to be realized. Raman spectroscopy is a label-free and non-destructive method that is able to assess the biochemical composition of EVs. This study reports for the first time the Raman spectroscopic fingerprint of the Aβ present in the molecular cargo of small extracellular vesicles (sEVs). Raman spectra were measured from sEVs isolated from Alzheimer's disease cell culture model, where secretion of Aβ is regulated by tetracycline promoter, and from midbrain organoids. The averaged spectra of each sEV group showed considerable variation as a reflection of the biochemical content of sEVs. Spectral analysis identified more intense Raman peaks at 1650 cm-1 and 2930 cm-1 attributable to the Aβ peptide incorporated in sEVs produced by the Alzheimer's cell culture model. Subsequent analysis of the spectra by principal component analysis differentiated the sEVs of the Alzheimer's disease cell culture model from the control groups of sEVs. Moreover, the results indicate that Aβ associated with secreted sEVs has a α-helical secondary structure and the size of a monomer or small oligomer. Furthermore, by analyzing the lipid content of sEVs we identified altered fatty acid chain lengths in sEVs that carry Aβ that may affect the fluidity of the EV membrane. Overall, our findings provide evidence supporting the use of Raman spectroscopy for the identification and characterization of sEVs associated with potential biomarkers of neurological disorders such as toxic proteins