Transgenic, high-protein sorghums display promise in poultry diets in an initial comparison.

This study aimed to compare the inclusion of transgenic sorghums against commercially available sorghums on growth performance in broiler chickens. Isonitrogenous and isoenergetic diets were offered to a total 288 male Ross 308 broiler chickens from 14 to 35 d posthatch. Three dietary treatments were diets based on transgenic sorghums with a mean protein content of 154.7 g/kg and 5 treatments were based on commercially available sorghum hybrids with a mean protein content of 90.6 g/kg. Soybean meal inclusions in the commercial sorghum diets averaged 215 g/kg, which was reduced to 171 g/kg in the transgenic sorghum diets because of the higher protein contents. Overall growth performance was highly satisfactory, and commercial sorghums supported 2.55% (2,330 vs. 2,272 g/bird; P = 0.010) more weight gains and 2.74% (2,929 vs. 2,851 g/bird; P = 0.012) higher feed intakes; however, the transgenic sorghums supported a fractionally better FCR (1.255 vs 1.257; P = 0.826). There were no statistical differences in apparent jejunal and ileal starch and protein (N) digestibility coefficients between treatments. The transgenic sorghum diets generated slightly, but significantly, higher AME:GE ratios and AMEn, but the commercial sorghum diets generated 6.33% (235 vs. 221 g/kg; P < 0.001) greater breast meat yields. Apparent ileal digestibility coefficients of 16 amino acids averaged 0.839 and 0.832 for transgenic and commercial sorghum-based diets, respectively, without any significant differences in individual amino acids. This outcome suggests amino acid digestibilities of the transgenic sorghums may be inherently higher than commercial hybrid sorghums as the 25.7% higher average soybean meal inclusions would have advantaged amino acid digestibilities in commercial sorghum diets. The possibility that the digestibilities of amino acids in the kafirin component of transgenic sorghums was enhanced by modifications to the structure of kafirin protein bodies is discussed. In conclusion, transgenic sorghums with higher protein concentrations led to 20.5% reduction of soybean meal inclusions in broiler diets, and this change did not compromise feed conversion efficiency compared to standard commercial hybrid sorghums.

Divergent dynamics: disasters and conflicts as 'drivers' of internal displacement?

Disasters and conflicts are both widely recognised as 'drivers' of internal displacement. Yet, despite a growing body of research and policy, there has been little consideration to date of how the different features of each 'context' shape the micro-level dynamics of internal displacement. Where and why are these dynamics similar across the two contexts and how do they differ? This paper draws on general concepts from the disaster field to develop a comparative analytical model of internal displacement dynamics in the disaster and conflict contexts. Based on inferences from the patchy extant data across the two contexts, it identifies and explains points of convergence and divergence between internal displacement dynamics in both the disaster and conflict contexts. This 'contextual' model of the micro-level dynamics of internal displacement has implications for academic debates, as well as for policy and practice, in the disaster, conflict, peace, climate change, and forced migration/displacement fields.

Rationale, Procedures, and Response Rates for a Pilot Study to Sample Cancer Survivors for NCI's Health Information National Trends Survey: HINTS-SEER 2021.

The National Cancer Institute's (NCI) Health Information National Trends Survey (HINTS) is a nationally representative survey of U.S. adults in which 12-17% of respondents report a cancer history. To increase representation from adult cancer survivors, in 2021, NCI sampled survivors from three Surveillance, Epidemiology, and End Results (SEER) program cancer registries: Iowa, New Mexico, and the Greater Bay Area. Sampling frames were stratified by time since diagnosis and race/ethnicity, with nonmalignant tumors and non-melanoma skin cancers excluded. Participants completed a self-administered postal questionnaire. The overall response rate for HINTS-SEER (N = 1,234) was 12.6%; a non-response bias analysis indicated few demographic differences between respondents and the pool of sampled patients in each registry. Most of the sample was 10+ years since diagnosis (n = 722; 60.2%); 392 respondents were 5 to < 10 years since diagnosis (29.6%); and 120 were < 5 years since diagnosis (10.2%). Common cancers included male reproductive (n = 304; 24.6%), female breast (n = 284; 23.0%), melanoma (n = 119; 9.6%), and gastrointestinal (n = 106; 8.6%). Tumors were mostly localized (67.8%; n = 833), with 22.4% (n = 282) regional, 6.2% (n = 72) distant, and 3.7% (n = 47) unknown. HINTS-SEER data are available by request and may be used for secondary analyses to examine a range of social, behavioral, and healthcare outcomes among cancer survivors.

Targeting KRAS-Mutated NSCLC: Novel TKIs and Beyond.

KRAS-mutated non-small cell lung cancer (NSCLC) is the most common genetically altered subtype of NSCLC, yet targeted therapies remain limited. Multiple studies have investigated combinations of MEK inhibitors with chemotherapy without success. Here we discuss these studies and novel approaches to targeting KRAS-mutated NSCLC. See related article by Gadgeel et al., p. 3641.

Analysis of health overseas development aid for internally displaced persons in low- and middle-income countries.

Background: There are an estimated 55 million internally displaced persons (IDPs) globally. IDPs commonly have worse health outcomes than host populations and other forcibly displaced populations such as refugees. Official development assistance (ODA) is a major source of the global financial response for health in low- and middle-income countries (LMICs), including for populations affected by armed conflict and forced displacement. Analysis of ODA supports efforts to improve donor accountability, transparency and the equitable use of ODA. The aim of this study is to examine international donor support and responsiveness to IDP health needs through analysis of ODA disbursements to LMICs between 2010 and 2019. Methods: ODA disbursement data to LMICs from 2010 to 2019 were extracted from the Creditor Reporting System (CRS) database and analysed with Stata software using a combination of: (i) text searching for IDP and refugee related terms; and (ii) relevant health and humanitarian CRS purpose codes. Descriptive analysis was used to examine patterns of ODA disbursement, and nonlinear least squared regression analysis was used to examine responsiveness of ODA disbursement to recipient country IDP population size and health system capacity and health characteristics. Findings: The study highlighted declining per IDP capita health ODA from USD 5.34 in 2010 to USD 3.72 in 2019 (with annual average decline of -38% from the 2010 baseline). In contrast, health ODA for refugees in LMICs increased from USD 18.55 in 2010 to USD 23.31 in 2019 (with an annual average increase of +14%). Certain health topics for IDPs received very low ODA, with only 0.44% of IDP health ODA disbursed for non-communicable diseases (including mental health). There was also weak evidence of IDP health ODA being related to recipient country IDP population size, and health system capacity and health characteristics. The paper highlights the need for increased investment by donors in IDP health ODA and to ensure that it is responsive to their health needs.

Three-dimensional compaction of soft granular packings.

This paper analyzes the compaction behavior of assemblies composed of soft (elastic) spherical particles beyond the jammed state, using three-dimensional non-smooth contact dynamic simulations. The assemblies of particles are characterized using the evolution of the packing fraction, the coordination number, and the von Misses stress distribution within the particles as the confining stress increases. The packing fraction increases and tends toward a maximum value close to 1, and the mean coordination number increases as a square root of the packing fraction. As the confining stress increases, a transition is observed from a granular-like material with exponential tails of the shear stress distributions to a continuous-like material characterized by Gaussian-like distributions of the shear stresses. We develop an equation that describes the evolution of the packing fraction as a function of the applied pressure. This equation, based on the micromechanical expression of the granular stress tensor, the limit of the Hertz contact law for small deformation, and the power-law relation between the packing fraction and the coordination of the particles, provides good predictions from the jamming point up to very high densities without the need for tuning any parameters.

Understanding the health needs of internally displaced persons: A scoping review.

We seek to strengthen understanding of the health needs of internally displaced persons (IDPs) in contexts of conflict or violence. Based upon a scoping review, our paper identified limited evidence on IDP health, but nevertheless indicates that IDPs tend to experience worse health outcomes than other conflict-affected populations across a range of health issues; and this is due to the particularly vulnerable situation of IDPs relative to these other populations, including reduced access to health services. Further research is required to better understand these needs and the interventions that can most effectively address these needs.

Implications of excreta uric acid concentrations in broilers offered reduced-crude protein diets and dietary glycine requirements for uric acid synthesis.

In a previous experiment, male Ross 308 broiler chickens were offered dietary treatments with 3 levels of crude protein (222, 193, 165 g/kg) and 3 feed grains (ground maize, ground wheat, whole wheat) from 7 to 35 d post-hatch. Maize-based diets supported superior growth performance in comparison to wheat-based diets. Uric acid concentrations in excreta were retrospectively determined and related to total nitrogen (N) excreta concentrations. Uric acid concentrations ranged from 28.5 to 69.4 mg/g and proportions of uric acid-N to total excreta-N ranged from 27.4% to 42.6% in broiler chickens offered the 3 × 3 factorial array of dietary treatments. Proportions of uric acid-N to total N in excreta in birds offered the 165 g/kg CP, maize-based diet were significantly lower by 10.6 percentage units (27.4% versus 38.0%; P = 0.00057) than their wheat-based counterparts. Total excreta analysed had been collected from 35 to 37 d post-hatch when feed intakes and excreta outputs were monitored. There were linear relationships between proportions of uric acid-N to total N in excreta in birds offered the three 165 g/kg CP diets with weight gain (r = -0.587; P = 0.010), feed intake (r = -0.526; P = 0.025) and feed conversion ratios (r = 0.635; P = 0.005). The possibility that increasing uric acid-N proportions in excreta is indicative of excessive ammonia accumulations compromising growth performance is discussed. The mean proportion of dietary glycine involved in uric acid excretion was 49.2% across all dietary treatments but ranged from 25.0% to 80.9%. Thus, the appropriate amount of dietary glycine is variable and largely dependent on the volume of uric acid synthesised and excreted.

Micromechanical description of the compaction of soft pentagon assemblies.

We analyze the isotropic compaction of assemblies composed of soft pentagons interacting through classical Coulomb friction via numerical simulations. The effect of the initial particle shape is discussed by comparing packings of pentagons with packings of soft circular particles. We characterize the evolution of the packing fraction, the elastic modulus, and the microstructure (particle rearrangement, connectivity, contact force, and particle stress distributions) as a function of the applied stresses. Both systems behave similarly: the packing fraction increases and tends asymptotically to a maximum value ϕ_{max}, where the bulk modulus diverges. At the microscopic scale we show that particle rearrangements occur even beyond the jammed state, the mean coordination increases as a square root of the packing fraction, and the force and stress distributions become more homogeneous as the packing fraction increases. Soft pentagons experience larger particle rearrangements than circular particles, and such behavior decreases proportionally to the friction. Interestingly, the friction between particles also contributes to a better homogenization of the contact force network in both systems. From the expression of the granular stress tensor we develop a model that describes the compaction behavior as a function of the applied pressure, the Young modulus, and the initial shape of the particles. This model, settled on the joint evolution of the particle connectivity and the contact stress, provides outstanding predictions from the jamming point up to very high densities.

Compaction of mixtures of rigid and highly deformable particles: A micromechanical model.

We analyze the isotropic compaction of mixtures composed of rigid and deformable incompressible particles by the nonsmooth contact dynamics approach. The deformable bodies are simulated using a hyperelastic neo-Hookean constitutive law by means of classical finite elements. We characterize the evolution of the packing fraction, the elastic modulus, and the connectivity as a function of the applied stresses when varying the interparticle coefficient of friction. We show first that the packing fraction increases and tends asymptotically to a maximum value ϕ_{max}, which depends on both the mixture ratio and the interparticle friction. The bulk modulus is also shown to increase with the packing fraction and to diverge as it approaches ϕ_{max}. From the micromechanical expression of the granular stress tensor, we develop a model to describe the compaction behavior as a function of the applied pressure, the Young modulus of the deformable particles, and the mixture ratio. A bulk equation is also derived from the compaction equation. This model lays on the characterization of a single deformable particle under compression together with a power-law relation between connectivity and packing fraction. This compaction model, set by well-defined physical quantities, results in outstanding predictions from the jamming point up to very high densities and allows us to give a direct prediction of ϕ_{max} as a function of both the mixture ratio and the friction coefficient.

Microstructural analysis of sheared polydisperse polyhedral grains.

This article presents an analysis of the shear strength of numerical samples composed of polyhedra presenting a grain size dispersion. Previous numerical studies using, for instance, disks, polygons, and spheres, have consistently shown that microstructural properties linked to the fabric and force transmission allow granular media to exhibit a constant shear resistance although packing fraction can dramatically change as a broader grain-size distribution is considered. To have a complete picture of such behavior, we developed a set of numerical experiments in the frame of the discrete element method to test the shear strength of polydisperse samples composed of polyhedral grains. Although the contact networks and force transmission are quite more complex for such generalized grain shape, we can verify that the shear strength independence still holds up for 3D regular polyhedra. We make a particular focus upon the role of different contact types in the assemblies and their relative contributions to the granular connectivity and sample strength. The invariance of shear strength at the macroscopic scale results deeply linked to fine compensations at the microstructural level involving geometrical and force anisotropies of the assembly.

Compaction Model for Highly Deformable Particle Assemblies.

The compaction behavior of deformable grain assemblies beyond jamming remains bewildering, and existing models that seek to find the relationship between the confining pressure P and solid fraction ϕ end up settling for empirical strategies or fitting parameters. Using a coupled discrete-finite element method, we analyze assemblies of highly deformable frictional grains under compression. We show that the solid fraction evolves nonlinearly from the jamming point and asymptotically tends to unity. Based on the micromechanical definition of the granular stress tensor, we develop a theoretical model, free from ad hoc parameters, correctly mapping the evolution of ϕ with P. Our approach unveils the fundamental features of the compaction process arising from the joint evolution of grain connectivity and the behavior of single representative grains. This theoretical framework also allows us to deduce a bulk modulus equation showing an excellent agreement with our numerical data.

Proteomic investigations into resistance in colorectal cancer.

Introduction: Despite advances in screening and treatment options, colorectal cancer (CRC) remains one of the most prevalent and lethal cancer subtypes. Resistance to cytotoxic or targeted therapy has remained a constant challenge to the treatment and long-term management of patients, attracting intense worldwide investigation since the 1950s. Through extensive investigations into the proteomic mechanisms and functions that convey resistance to therapy/s, researchers have become able to implicate alterations in several signaling pathways that provide and sustain resistance to treatment.Areas covered: In this review, we summarize how protein alterations are associated with resistance to therapy, with particular emphasis on CRC. An overview of the mechanisms of therapeutic resistance is described, highlighting recent studies which endeavor to elucidate the proteomic changes that are associated with the acquisition and promulgation of therapeutic resistance.Expert opinion: While cancers such as CRC have been intensively studied for decades, unresponsiveness and the resistance to therapy remain critical obstacles in the treatment of patients. Due to the inherent biological and clinical heterogeneity of individual CRCs, proteomic methods stand to become powerful tools to provide biological insights that may guide therapeutic strategies with the ultimate goal of refining emergent immunotherapeutic treatments.

Asking Survey Questions About Criminal Justice Involvement.

Criminal justice involvement is a multifaceted construct encompassing various forms of contact with the criminal justice system. It is a sensitive topic to ask about in surveys and also a sensitive topic for respondents to answer. This article provides guidance for writing survey questions on criminal justice involvement, starting with a review of potential causes for reporting error and nonresponse error associated with survey questions on criminal justice involvement. Questions about criminal justice involvement are subject to errors that are common to any survey (eg, misunderstanding questions, recall bias, telescoping). Reponses to these questions are also subject to underreporting because of social desirability concerns. We also address strategies to reduce error for questions pertaining to criminal justice involvement (eg, self-administered data collection, wording of forgiving questions, indirect methods). We then discuss common design decisions associated with writing survey questions on criminal justice involvement (eg, type and frequency of criminal justice involvement, reference period,) and provide examples of questions from current surveys.

Impaired Expression of Rearranged Immunoglobulin Genes and Premature p53 Activation Block B Cell Development in BMI1 Null Mice.

B cell development is a highly regulated process that requires stepwise rearrangement of immunoglobulin genes to generate a functional B cell receptor (BCR). The polycomb group protein BMI1 is required for B cell development, but its function in developing B cells remains poorly defined. We demonstrate that BMI1 functions in a cell-autonomous manner at two stages during early B cell development. First, loss of BMI1 results in a differentiation block at the pro-B cell to pre-B cell transition due to the inability of BMI1-deficient cells to transcribe newly rearranged Igh genes. Accordingly, introduction of a pre-rearranged Igh allele partially restored B cell development in Bmi1-/- mice. In addition, BMI1 is required to prevent premature p53 signaling, and as a consequence, Bmi1-/- large pre-B cells fail to properly proliferate. Altogether, our results clarify the role of BMI1 in early B cell development and uncover an unexpected function of BMI1 during VDJ recombination.

The HDAC-Associated Sin3B Protein Represses DREAM Complex Targets and Cooperates with APC/C to Promote Quiescence.

The mammalian DREAM complex is responsible for the transcriptional repression of hundreds of cell-cycle-related genes in quiescence. How the DREAM complex recruits chromatin-modifying entities to aid in its repression remains unknown. Using unbiased proteomics analysis, we have uncovered a robust association between the chromatin-associated Sin3B protein and the DREAM complex. We have determined that genetic inactivation of Sin3B results in the de-repression of DREAM target genes during quiescence but is insufficient to allow quiescent cells to resume proliferation. However, inactivation of APC/CCDH1 was sufficient for Sin3B-/- cells, but not parental cells, to re-enter the cell cycle. These studies identify Sin3B as a transcriptional corepressor associated with the DREAM complex in quiescence and reveals a functional cooperation between E2F target repression and APC/CCDH1 in the negative regulation of cell-cycle progression.

Tissue and plasma proteomics for early stage cancer detection.

The pursuit of novel and effective biomarkers is essential in the struggle against cancer, which is a leading cause of mortality worldwide. Biomarkers can be used as specific diagnostic tools, prognostic predictors, markers of the development of therapeutic resistance or even as therapeutic targets themselves. Through the application of sensitive and specific proteomic techniques, oncoproteomics investigates the proteins associated with cancer processes, to better understand their biological function/s and their associated pathways during tumorigenesis. Such studies seek to identify both potential biomarkers and drug targets in order to improve patient survival and quality of life whilst reducing the global health budget. Tissue and plasma are the most commonly utilised biological samples for such studies as they are readily available, non-invasive and generally acceptable. Here, we outline the relative advantages and disadvantages of the most frequently used techniques for cancer diagnosis, prognosis, treatment and surveillance, concentrating on the latest advances and application of tissue and plasma proteomics for novel cancer biomarker discovery and disease surveillance.

The potential of targeting Sin3B and its associated complexes for cancer therapy.

INTRODUCTION: Sin3B serves as a scaffold for chromatin-modifying complexes that repress gene transcription to regulate distinct biological processes. Sin3B-containing complexes are critical for cell cycle withdrawal, and abrogation of Sin3B-dependent cell cycle exit impacts tumor progression. Areas covered: In this review, we discuss the biochemical characteristics of Sin3B-containing complexes and explore how these complexes regulate gene transcription. We focus on how Sin3B-containing complexes, through the association of the Rb family of proteins, repress the expression of E2F target genes during quiescence, differentiation, and senescence. Finally, we speculate on the potential benefits of the inhibition of Sin3B-containing complexes for the treatment of cancer. Expert opinion: Further identification and characterization of specific Sin3B-containing complexes provide a unique opportunity to prevent the pro-tumorigenic effects of the senescence-associated secretory phenotype, and to abrogate cancer stem cell quiescence and the associated resistance to therapy.

Chromatin-Associated Protein SIN3B Prevents Prostate Cancer Progression by Inducing Senescence.

Distinguishing between indolent and aggressive prostate adenocarcinoma remains a priority to accurately identify patients who need therapeutic intervention. SIN3B has been implicated in the initiation of senescence in vitro Here we show that in a mouse model of prostate cancer, SIN3B provides a barrier to malignant progression. SIN3B was required for PTEN-induced cellular senescence and prevented progression to invasive prostate adenocarcinoma. Furthermore, SIN3B was downregulated in human prostate adenocarcinoma correlating with upregulation of its target genes. Our results suggest a tumor suppressor function for SIN3B that limits prostate adenocarcinoma progression, with potential implications for the use of SIN3B and its target genes as candidate diagnostic markers to distinguish indolent from aggressive disease. Cancer Res; 77(19); 5339-48. ©2017 AACR.