The estimated 50 million nomadic pastoralists in Africa are among the most "hard-to-reach" populations for health-service delivery. While data are limited, some studies have identified these communities as potential disease reservoirs relevant to neglected tropical disease programs, particularly those slated for elimination and eradication. Although previous literature has emphasized the role of these populations' mobility, the full range of factors influencing health service utilization has not been examined systematically. We systematically reviewed empirical literature on health services uptake among African nomadic pastoralists from seven online journal databases. Papers meeting inclusion criteria were reviewed using STROBE-and PRISMA-derived guidelines. Study characteristics were summarized quantitatively, and 10 key themes were identified through inductive qualitative coding. One-hundred two papers published between 1974-2019 presenting data from 16 African countries met our inclusion criteria. Among the indicators of study-reporting quality, limitations (37%) and data analysis were most frequently omitted (18%). We identified supply-and demandside influences on health services uptake that related to geographic access (79%); service quality (90%); disease-specific knowledge and awareness of health services (59%); patient costs (35%); contextual tailoring of interventions (75%); social structure and gender (50%); subjects' beliefs, behaviors, and attitudes (43%); political will (14%); social, political, and armed conflict (30%); and community agency (10%). A range of context-specific factors beyond distance to facilities or population mobility affects health service uptake. Approaches tailored to the nomadic pastoralist lifeway, e.g., that integrated human and veterinary health service delivery (a.k.a., "One Health") and initiatives that engaged communities in program design to address social structures were especially promising. Better causal PLOS NEGLECTED TROPICAL DISEASES

Populations affected by humanitarian emergencies may require unique strategies to ensure access to life-saving vaccines and attain sufficiently high population immunity to interrupt virus circulation. Vaccination strategies among displaced populations should not be an afterthought and must be part of the vaccine-preventable disease eradication and elimination initiatives from the start.

Estrogen receptor-α (ER) targeted therapies are routinely used to treat breast cancer. However, patient responses are limited by resistance to endocrine therapy. Breast cancer cells resistant to the pure steroidal ER antagonist fulvestrant (fulv) demonstrate increased activation of epidermal growth factor receptor (EGFR) family members and downstream ERK signaling. In this study we investigated the effects of fulv on EGFR signaling and ligand regulation in several breast cancer cell lines. EGFR/HER2/HER3 phosphorylation and ERK1,2 activation was seen after 24–48 hours after fulvestrant treatment in ER-positive breast cancer cell lines. 4-hydroxy-tamoxifen (4HT) and estradiol (E2) did not cause EGFR activation. Fulvestrant did not affect EGFR expression. Cycloheximide abolished the ability of fulv to activate EGFR suggesting autocrine production of EGFR ligands might be responsible for fulvestrant induced EGFR signaling. qRT-PCR results showed fulv differentially regulated EGFR ligands; HB-EGF mRNA was increased while amphiregulin (AREG) and epiregulin (EPR) mRNAs were decreased. Fulvestrant induced EGFR activation and upregulation of EGFR ligands was ER dependent since fulv treatment in C4-12, an ER negative cell line derivative of MCF-7 cells, did not result in EGFR activation or change in ligand mRNA levels. ER down regulation by siRNA induced similar EGFR activation and regulation of EGFR ligands as fulvestrant. Neutralizing HB-EGF antibody blocked fulv induced EGFR activation. Combination of fulv and EGFR family tyrosine kinase inhibitors (erlotinib and lapatinib) significantly decreased EGFR signaling and cell survival. In conclusion, fulvestrant activated EGFR family members accompanied by ER dependent upregulation of HB-EGF within 48 hours. EGF receptor or ligand inhibition might enhance or prolong the therapeutic effects of targeting ER by fulvestrant in breast cancer.