Resistance Mechanisms to Novel Therapies in Myeloma

The number of novel therapies for the treatment of multiple myeloma (MM) is rapidly increasing with proteasome inhibitors, immunomodulatory agents and monoclonal antibodies being the most well-known therapeutic classes whilst histone deacetylase inhibitors, selective inhibitors of nuclear export and CAR-T cells amongst others also being actively investigated. However, in parallel with the development and application of these novel myeloma therapies is the emergence of novel mechanisms of resistance, many of which remain elusive, particularly for more recently developed agents. Whilst resistance mechanisms have been best studied for proteasome inhibitors, particularly Bortezomib, class effects do not universally apply to all proteasome inhibitors, and within-class differences in efficacy, toxicity and resistance mechanisms have been observed. Immunomodulatory agents share the common cellular target cereblon and thus resistance patterns relate to cereblon expression and its pathway components. However, the cell surface antigens to which monoclonal antibodies are directed means these agents frequently exhibit unique within-class differences in clinical efficacy and resistance patterns. Despite the progressive biological elucidation of resistance mechanisms to these novel therapies, attempts to specifically exploit these processes lag considerably behind and until such approaches become available, resistance to these therapies will remain a concern

Seasonal distribution and drivers of surface fine particulate matter and organic aerosol over the Indo-Gangetic Plain

The Indo-Gangetic Plain (IGP) is home to 9 % of the global population and is responsible for a large fraction of agricultural crop production in Pakistan, India, and Bangladesh. Levels of fine particulate matter (mean diameter &lt;2.5 µm, PM2.5) across the IGP often exceed human health recommendations, making cities across the IGP among the most polluted in the world. Seasonal changes in the physical environment over the IGP are dominated by the large-scale south Asian monsoon system that dictates the timing of agricultural planting and harvesting. We use the WRF-Chem model to study the seasonal anthropogenic, pyrogenic, and biogenic influences on fine particulate matter and its constituent organic aerosol (OA) over the IGP that straddles Pakistan, India, and Bangladesh during 2017–2018. We find that surface air quality during pre-monsoon (March–May) and monsoon (June–September) seasons is better than during post-monsoon (October–December) and winter (January–February) seasons, but all seasonal mean values of PM2.5 still exceed the recommended levels, so that air pollution is a year-round problem. Anthropogenic emissions influence the magnitude and distribution of PM2.5 and OA throughout the year, especially over urban sites, while pyrogenic emissions result in localised contributions over the central and upper parts of IGP in all non-monsoonal seasons, with the highest impact during post-monsoon seasons that correspond to the post-harvest season in the agricultural calendar. Biogenic emissions play an important role in the magnitude and distribution of PM2.5 and OA during the monsoon season, and they show a substantial contribution to secondary OA (SOA), particularly over the lower IGP. We find that the OA contribution to PM2.5 is significant in all four seasons (17 %–30 %), with primary OA generally representing the larger fractional contribution. We find that the volatility distribution of SOA is driven mainly by the mean total OA loading and the washout of aerosols and gas-phase aerosol precursors that result in SOA being less volatile during the pre-monsoon and monsoon season than during the post-monsoon and winter seasons.</p

Depressive Symptoms and Length of U.S. Residency Are Associated with Obesity among Low-Income Latina Mothers: A Cross-Sectional Analysis

Latinos are the largest minority population group in the United States (U.S.), and low-income Latina women are at elevated risk of depression and obesity. Thus, the prevention of these two problems is a pressing public health concern in this population. Both depressive symptoms and obesity are modifiable factors that can be addressed by culturally relevant interventions. However, the association between depressive symptoms and obesity in Latina immigrant women is not well understood. Therefore, this cross-sectional study examined the association between depressive symptoms and obesity among Latina women of childbearing age (15–44). Participants (n = 147) were low-income, predominantly immigrant Latina mothers enrolled in the Latina Mothers′ Child Feeding Practices and Style Study. Women were eligible to participate if they self-identified as Latina; were enrolled in or eligible for the Special Supplemental Nutrition Program for Women, Infants and Children program; had a child between ages two and five years; and were living in the U.S. for at least one year, and residing in Rhode Island. Enrolled participants completed a survey in their language of preference (English or Spanish) administered by bilingual interviewers. About one-third (34%) of participants were classified as having obesity (BMI ≥ 30 kg/m2), 28.3% had elevated depressive symptoms (CES-D ≥ 16), and 70.1% were immigrants. Women with elevated depressive symptoms had increased odds of having obesity (odds ratio (OR) = 2.80, 95% confidence interval (CI): 1.24–6.33). Additionally, among immigrants, length of U.S. residency was associated with increased odds of obesity (OR = 1.05, 95% CI: 1.02–1.09). Findings underscore the need for screening and culturally relevant interventions designed to address both depressive symptoms and obesity among low-income Latina women of childbearing age. Furthermore, findings highlight the importance of taking into account the length of residency in the U.S. when designing interventions targeting Latina immigrants

Brazilian Immigrant Mothers’ Beliefs and Practices Related to Infant Feeding: A Qualitative Study

Background: Exclusive breastfeeding for the first 6 months of life and timely introduction of appropriate solid foods are important determinants of weight status in infancy and later life stages. Disparities in obesity rates among young children suggest that maternal feeding practices during the first 2 years of life may contribute to these disparities. Brazilians are a growing immigrant group in the United States, yet little research has focused on parental beliefs and behaviors affecting the health of Brazilian immigrant children in the United States. Research aim: This study aimed to explore beliefs and infant-feeding practices of Brazilian immigrant mothers in the United States. Methods: Focus group discussions were conducted with Brazilian immigrant mothers. Transcripts were analyzed using thematic analysis and themes categorized using the socioecological model. Results: Twenty-nine immigrant Brazilian mothers participated in the study. Analyses revealed that all participants breastfed their infants. The majority initiated breastfeeding soon after childbirth. However, most mothers did not exclusively breastfeed. They used formula and human milk concomitantly. Family and culture influenced mothers’ infant-feeding beliefs and practices in early introduction of solid foods. Conclusion: As the number of children in the United States growing up in families of immigrant parents increases, understanding influences on Brazilian immigrant mothers’ infant-feeding practices will be important to the development of effective interventions to promote healthy infant feeding and weight status among Brazilian children. Interventions designed for Brazilian immigrant families should incorporate an understanding of social context, family, and cultural factors to develop health promotion messages tailored to the needs of this ethnic group

Global warming potentials and radiative efficiencies of halocarbons and related compounds: a comprehensive review

In the mid-1970s it was recognized that, as well as being substances that deplete stratospheric ozone, chlorofluorocarbons (CFCs) were strong greenhouse gases that could have substantial impacts on radiative forcing of climate change. Around a decade later, this group of radiatively active compounds was expanded to include a large number of replacements for ozone-depleting substances such as chlorocarbons, hydrochlorocarbons, hydrochlorofluorocarbons (HCFCs), hydrofluorocarbons (HFCs), perfluorocarbons (PFCs), bromofluorocarbons, and bromochlorofluorocarbons. This paper systematically reviews the published literature concerning the radiative efficiencies (REs) of CFCs, bromofluorocarbons and bromochlorofluorocarbons (halons), HCFCs, HFCs, PFCs, SF6, NF3, and related halogen containing compounds. In addition we provide a comprehensive and self-consistent set of new calculations of REs and global warming potentials (GWPs) for these compounds, mostly employing atmospheric lifetimes taken from the available literature. We also present Global Temperature change Potentials (GTPs) for selected gases. Infrared absorption spectra used in the RE calculations were taken from databases and individual studies, and from experimental and ab initio computational studies. Evaluations of REs and GWPs are presented for more than 200 compounds. Our calculations yield REs significantly (> 5%) different from those in the Intergovernmental Panel on Climate Change Fourth Assessment Report (AR4) for 49 compounds. We present new RE values for more than 100 gases which were not included in AR4. A widely-used simple method to calculate REs and GWPs from absorption spectra and atmospheric lifetimes is assessed and updated. This is the most comprehensive review of the radiative efficiencies and global warming potentials of halogenated compounds performed to date

Strengthening impact assessment: a call for integration and focus

We suggest that the impact assessment community has lost its way based on our observation that impact assessment is under attack because of a perceived lack of efficiency. Specifically, we contend that the proliferation of different impact assessment types creates separate silos of expertise and feeds arguments for not only a lack of efficiency but also a lack of effectiveness of the process through excessive specialisation and a lack of interdisciplinary practice. We propose that the solution is a return to the basics of impact assessment with a call for increased integration around the goal of sustainable development and focus through better scoping. We rehearse and rebut counter arguments covering silo-based expertise, advocacy, democracy, sustainability understanding and communication. We call on the impact assessment community to rise to the challenge of increasing integration and focus, and to engage in the debate about the means of strengthening impact assessment

A Systematic Review of Strong Gravitational Lens Modeling Software

Despite expanding research activity in gravitational lens modeling, there is no particular software which is considered a standard. Much of the gravitational lens modeling software is written by individual investigators for their own use. Some gravitational lens modeling software is freely available for download but is widely variable with regard to ease of use and quality of documentation. This review of 13 software packages was undertaken to provide a single source of information. Gravitational lens models are classified as parametric models or non-parametric models, and can be further divided into research and educational software. Software used in research includes the GRAVLENS package (with both gravlens and lensmodel), Lenstool, LensPerfect, glafic, PixeLens, SimpLens, Lensview, and GRALE. In this review, GravLensHD, G-Lens, Gravitational Lensing, lens and MOWGLI are categorized as educational programs that are useful for demonstrating various aspects of lensing. Each of the 13 software packages is reviewed with regard to software features (installation, documentation, files provided, etc.) and lensing features (type of model, input data, output data, etc.) as well as a brief review of studies where they have been used. Recent studies have demonstrated the utility of strong gravitational lensing data for mass mapping, and suggest increased use of these techniques in the future. Coupled with the advent of greatly improved imaging, new approaches to modeling of strong gravitational lens systems are needed. This is the first systematic review of strong gravitational lens modeling software, providing investigators with a starting point for future software development to further advance gravitational lens modeling research

Evaluated kinetic and photochemical data for atmospheric chemistry: Volume V – heterogeneous reactions on solid substrates

This article, the fifth in the ACP journal series, presents data evaluated by the IUPAC Subcommittee on Gas Kinetic Data Evaluation for Atmospheric Chemistry. It covers the heterogeneous processes on surfaces of solid particles present in the atmosphere, for which uptake coefficients and adsorption parameters have been presented on the IUPAC website in 2010. The article consists of an introduction and guide to the evaluation, giving a unifying framework for parameterisation of atmospheric heterogeneous processes. We provide summary sheets containing the recommended uptake parameters for the evaluated processes. Four substantial appendices contain detailed data sheets for each process considered for ice, mineral dust, sulfuric acid hydrate and nitric acid hydrate surfaces, which provide information upon which the recommendations are made