U.S. Energy Scenarios for the 21st Century

Discusses three divergent paths for U.S. energy supply and use from 2000 through 2035, and the effect of climate policy on the three scenarios

Personality structure in east and west Africa: Lexical studies of personality in Maa and Supyire-Senufo.

The field of psychology relies heavily on evidence from North America and Northern Europe. Universally-applicable models require input from around the globe. Indigenous lexical studies of personality, which define the most salient person-descriptive concepts and their structure in a population, provide this. Such results are reported from two non-industrialized communities, representing two of the three main language families of Africa, in groups with differing cultural characteristics. Maasai participants, traditionally herders in rural Kenya and Tanzania, have a highly-structured, traditional culture. Supyire-Senufo participants are traditional horticulturalists in Mali. The 203 most common person-descriptive terms in Maasai were administered to 166 participants, who described 320 persons (166 highly-regarded, 154 less so). The optimal emic solution included 5 factors: virtue/moral-character, debilitation/vulnerability, boldness/surgency, hubris/pride, timidity. In the Maasai context, descriptions of well-regarded individuals were exceptionally uniform, suggesting the role of personality language in norm socialization in tight, traditional cultures. In Supyire, 115 participants used 208 person-descriptive terms to describe 227 targets (half highly-regarded). The optimal emic solution included 10 factors: social self-regulation, well-being, vitality/resilience, broadmindedness, diligence versus laziness, madness, stubbornness versus attractiveness, acceptance versus discontent, hurry/worry, peacefulness. The best convergence between the languages was at the three-factor level, where factors relate to moral character, low agreeableness coupled with high extraversion, and emotional stability. Beginning with the four-factor level, content related to local cultural characteristics became apparent. In both languages, two-factor solutions matched the Big Two, but three-, five-, and six-factor solutions failed to overlap with etic Pan-Cultural Three, Big Five, or Big Six models

C3d adjuvant effects are mediated through the activation of C3d-specific autoreactive T cells

Complement fragment C3d covalently attached to antigens enhances immune responses, particularly for antigens lacking T cell epitopes. Enhancement has been attributed to receptor cross-linking between complement receptor CR2 (CD21) and polysaccharide antigen to surface IgM on naïve B cells. Paradoxically, C3d has still been shown to increase immune responses in CD21 KO mice, suggesting that an auxiliary activation pathway exists. In prior studies, we demonstrated the CD21-independent C3d adjuvant effect might be due to T cell recognition of C3d T helper epitopes processed and presented by MHC class II on the B cell surface. C3d peptide sequences containing concentrated clusters of putative human C3 T cell epitopes were identified using the epitope-mapping algorithm, EpiMatrix. These peptide sequences were synthesized and shown in vitro to bind multiple HLA-DR alleles with high affinity, and induce IFNγ responses in healthy donor PBMCs. In the present studies, we establish further correlations between HLA binding and HLA-specific lymphocyte reactions with select epitope clusters. Additionally, we show that the T cell phenotype of C3d-specific reactive T cells is CD4+CD45RO+ memory T cells. Finally, mutation of a single T cell epitope residing within the P28 peptide segment of C3d resulted in significantly diminished adjuvant activity in BALB/c mice. Collectively, these studies support the hypothesis that the paradoxical enhancement of immune responses by C3d in the absence of CD21 is due to internalization and processing of C3d into peptides that activate autoreactive CD4+ T helper cells in the context of HLA class II

Assessment of body composition in spinal cord injury: A scoping review.

The objective of this scoping review was to map the evidence on measurement properties of body composition tools to assess whole-body and regional fat and fat-free mass in adults with SCI, and to identify research gaps in order to set future research priorities. Electronic databases of PubMed, EMBASE and the Cochrane library were searched up to April 2020. Included studies employed assessments related to whole-body or regional fat and/or fat-free mass and provided data to quantify measurement properties that involved adults with SCI. All searches and data extractions were conducted by two independent reviewers. The scoping review was designed and conducted together with an expert panel (n = 8) that represented research, clinical, nutritional and lived SCI experience. The panel collaboratively determined the scope and design of the review and interpreted its findings. Additionally, the expert panel reached out to their professional networks to gain further stakeholder feedback via interactive practitioner surveys and workshops with people with SCI. The research gaps identified by the review, together with discussions among the expert panel including consideration of the survey and workshop feedback, informed the formulation of future research priorities. A total of 42 eligible articles were identified (1,011 males and 143 females). The only tool supported by studies showing both acceptable test-retest reliability and convergent validity was whole-body dual-energy x-ray absorptiometry (DXA). The survey/workshop participants considered the measurement burden of DXA acceptable as long as it was reliable, valid and would do no harm (e.g. radiation, skin damage). Practitioners considered cost and accessibility of DXA major barriers in applied settings. The survey/workshop participants expressed a preference towards simple tools if they could be confident in their reliability and validity. This review suggests that future research should prioritize reliability and validity studies on: (1) DXA as a surrogate 'gold standard' tool to assess whole-body composition, regional fat and fat-free mass; and (2) skinfold thickness and waist circumference as practical low-cost tools to assess regional fat mass in persons with SCI, and (3) females to explore potential sex differences of body composition assessment tools. Registration review protocol: CRD42018090187 (PROSPERO)

The effects of collagen peptides on exercise-induced gastro-intestinal stress: a randomized, controlled trial

Purpose: We examined the effects of collagen peptides (CP) supplementation on exercise induced-gastro-intestinal (GI) stress. Methods: In a randomized, crossover design, 20 volunteers (16 males: V ̇O2max, 53.4±5.9 ml·kg-1) completed 3 trials: a non-exercise rest trial, with no supplement (REST) and then an exercise trial with CP (10 g·day-1) or placebo control (CON) supplements, which were consumed for 7 days prior to, and 45 min before, a 70 min run at 70-90% of V ̇O2max. Outcome measures included urinary lactulose and rhamnose (L/R), intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), anti-LPS antibody, monocyte chemoattractant protein-1 (MCP-1), interleukin (IL) 6 and 8, cortisol, alkaline phosphatase (ALP) (measured pre, 10 min post and 2 h post) and subjective GI symptoms. Results: There were no differences in heart rate, perceived exertion, thermal comfort, or core temperature during exercise in the CP and CON trials (all P>0.05). I-FABP was higher in CP (2538±1221pg/ml) and CON (2541±766pg/ml) vs. REST 2 h post (1893±1941pg/ml) (both P0.05), and no differences in L/R or GI symptoms between CON and CP (all P>0.05). Conclusion: Collagen peptides did not modify exercise-induced changes in inflammation, GI integrity or subjective GI symptoms but LPS was higher in CON 2 h post-exercise and thus future studies may be warranted

ROR1 and ROR2 expression in pancreatic cancer

Background: The Wnt receptors ROR1 and ROR2 are generating increased interest as cancer therapeutic targets but remain understudied in pancreatic ductal adenocarcinoma (PDAC). Compared to canonical Wnt/ β-catenin signalling, the role of noncanonical Wnt signalling in PDAC remains largely unknown. Only one study has investigated the prognostic significance of the noncanonical Wnt signalling receptor, ROR2 in PDAC. No studies have investigated the prognostic role of ROR1 in PDAC. Methods: Here, we performed analysis of ROR1 and ROR2 mRNA expression in three publicly available datasets ICGC-PACA-AU (n = 81), TCGA-PAAD (n = 150) and CPTAC-PDAC (n = 137). ROR1 and ROR2 protein expression from the CPTAC-PDAC discovery cohort were also analysed. Immunohistochemistry (IHC) using the validated anti ROR1 monoclonal antibody (4A5) was performed on the Australian Pancreatic Cancer Genome Initiative (APGI) cohort of PDAC samples (n = 152). Association between ROR1 cytoplasmic staining intensity and clinicopathological parameters including stage, grade and overall survival (OS) was investigated. Results: High ROR1 mRNA expression levels correlated with a favourable OS outcome in all of the ICGC-PACA-AU, TCGA-PAAD and CPTAC-PDAC cohorts. ROR1 protein expression was not associated with stage, grade or OS in the APGI cohort. Conclusion: ROR1 and ROR2 have potential as prognostic markers when measured at the mRNA level in PDAC. Our IHC cohort did not support ROR1 protein expression in predicting OS, and highlighted the discrepancy of prognostic biomarkers when measured by MS, IHC and RNAseq

Baseline population health conditions ahead of a health system strengthening program in rural Madagascar

Background: A model health district was initiated through a program of health system strengthening (HSS) in Ifanadiana District of southeastern Madagascar in 2014. We report population health indicators prior to initiation of the program. Methods: A representative household survey based on the Demographic Health Survey was conducted using a two-stage cluster sampling design in two strata – the initial program catchment area and the future catchment area. Chi-squared and t-tests were used to compare data by stratum, using appropriate sampling weights. Madagascar data for comparison were taken from a 2013 national study. Results: 1522 households were surveyed, representing 8310 individuals including 1635 women ages 15–49, 1685 men ages 15–59 and 1251 children under age 5. Maternal mortality rates in the district are 1044/100,000. 81% of women’s last childbirth deliveries were in the home; only 20% of deliveries were attended by a doctor or nurse/midwife (not different by stratum). 9.3% of women had their first birth by age 15, and 29.5% by age 18. Under-5 mortality rate is high: 145/1000 live births vs. 62/1000 nationally. 34.6% of children received all recommended vaccines by age 12 months (compared to 51.5% in Madagascar overall). In the 2 weeks prior to interview, approximately 28% of children under age 5 had acute respiratory infections of whom 34.7% were taken for care, and 14% of children had diarrhea of whom 56.6% were taken for care. Under-5 mortality, illness, care-seeking and vaccination rates were not significantly different between strata. Conclusions: Indicators of population health and health care-seeking reveal low use of the formal health system, which could benefit from HSS. Data from this survey and from a longitudinal follow-up study will be used to target needed interventions, to assess change in the district and the impact of HSS on individual households and the population of the district

Deletion of the Ubiquitin Ligase CHIP Leads to the Accumulation, But Not the Aggregation, of Both Endogenous Phospho- and Caspase-3-Cleaved Tau Species

Accumulation of the microtubule-associated protein tau into neurofibrillary lesions is a pathological consequence of several neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Hereditary mutations in th

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies