Malaria in South Africa the past, the present and selected implications for the future

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Inhibition of mTORC1 inhibits lytic replication of Epstein-Barr virus in a cell-type specific manner

BACKGROUND: Epstein-Barr virus is a human herpesvirus that infects a majority of the human population. Primary infection of Epstein-Barr virus (EBV) causes the syndrome infectious mononucleosis. This virus is also associated with several cancers, including Burkitt’s lymphoma, post-transplant lymphoproliferative disorder and nasopharyngeal carcinoma. As all herpesvirus family members, EBV initially replicates lytically to produce abundant virus particles, then enters a latent state to remain within the host indefinitely. METHODS: Through a genetic screen in Drosophila, we determined that reduction of Drosophila Tor activity altered EBV immediate-early protein function. To further investigate this finding, we inhibited mTOR in EBV-positive cells and investigated subsequent changes to lytic replication via Western blotting, flow cytometry, and quantitative PCR. The student T-test was used to evaluate significance. RESULTS: mTOR, the human homolog of Drosophila Tor, is an important protein at the center of a major signaling pathway that controls many aspects of cell biology. As the EBV immediate-early genes are responsible for EBV lytic replication, we examined the effect of inhibition of mTORC1 on EBV lytic replication in human EBV-positive cell lines. We determined that treatment of cells with rapamycin, which is an inhibitor of mTORC1 activity, led to a reduction in the ability of B cell lines to undergo lytic replication. In contrast, EBV-positive epithelial cell lines underwent higher levels of lytic replication when treated with rapamycin. CONCLUSIONS: Overall, the responses of EBV-positive cell lines vary when treated with mTOR inhibitors, and this may be important when considering such inhibitors as anti-cancer therapeutic agents

Phase Ib study of the combination of pexidartinib (PLX3397), a CSF-1R inhibitor, and paclitaxel in patients with advanced solid tumors.

Purpose:To evaluate the safety, recommended phase II dose (RP2D) and efficacy of pexidartinib, a colony stimulating factor receptor 1 (CSF-1R) inhibitor, in combination with weekly paclitaxel in patients with advanced solid tumors. Patients and Methods:In part 1 of this phase Ib study, 24 patients with advanced solid tumors received escalating doses of pexidartinib with weekly paclitaxel (80 mg/m2). Pexidartinib was administered at 600 mg/day in cohort 1. For subsequent cohorts, the dose was increased by ⩽50% using a standard 3+3 design. In part 2, 30 patients with metastatic solid tumors were enrolled to examine safety, tolerability and efficacy of the RP2D. Pharmacokinetics and biomarkers were also assessed. Results:A total of 51 patients reported ≥1 adverse event(s) (AEs) that were at least possibly related to either study drug. Grade 3-4 AEs, including anemia (26%), neutropenia (22%), lymphopenia (19%), fatigue (15%), and hypertension (11%), were recorded in 38 patients (70%). In part 1, no maximum tolerated dose was achieved and 1600 mg/day was determined to be the RP2D. Of 38 patients evaluable for efficacy, 1 (3%) had complete response, 5 (13%) partial response, 13 (34%) stable disease, and 17 (45%) progressive disease. No drug-drug interactions were found. Plasma CSF-1 levels increased 1.6- to 53-fold, and CD14dim/CD16+ monocyte levels decreased by 57-100%. Conclusions:The combination of pexidartinib and paclitaxel was generally well tolerated. RP2D for pexidartinib was 1600 mg/day. Pexidartinib blocked CSF-1R signaling, indicating potential for mitigating macrophage tumor infiltration

Learning ultrasound plane pose regression: assessing generalized pose coordinates in the fetal brain

In obstetric ultrasound (US) scanning, the learner's ability to mentally build a three-dimensional (3D) map of the fetus from a two-dimensional (2D) US image represents a significant challenge in skill acquisition. We aim to build a US plane localization system for 3D visualization, training, and guidance without integrating additional sensors. This work builds on top of our previous work, which predicts the six-dimensional (6D) pose of arbitrarily-oriented US planes slicing the fetal brain with respect to a normalized reference frame using a convolutional neural network (CNN) regression network. Here, we analyze in detail the assumptions of the normalized fetal brain reference frame and quantify its accuracy with respect to the acquisition of transventricular (TV) standard plane (SP) for fetal biometry. We investigate the impact of registration quality in the training and testing data and its subsequent effect on trained models. Finally, we introduce data augmentations and larger training sets that improve the results of our previous work, achieving median errors of 3.53 mm and 6.42 degrees for translation and rotation, respectively.Comment: 12 pages, 9 figures, 2 tables. This work has been submitted to the IEEE for possible publication (IEEE TMRB). Copyright may be transferred without notice, after which this version may no longer be accessibl

Probing the Inner Disk Emission of the Herbig Ae Stars HD 163296 and HD 190073

The physical processes occurring within the inner few astronomical units of proto-planetary disks surrounding Herbig Ae stars are crucial to setting the environment in which the outer planet-forming disk evolves and put critical constraints on the processes of accretion and planet migration. We present the most complete published sample of high angular resolution H- and K-band observations of the stars HD 163296 and HD 190073, including 30 previously unpublished nights of observations of the former and 45 nights of the latter with the CHARA long-baseline interferometer, in addition to archival VLTI data. We confirm previous observations suggesting significant near-infrared emission originates within the putative dust evaporation front of HD 163296 and show this is the case for HD 190073 as well. The H- and K-band sizes are the same within $(3 \pm 3)\%$ for HD 163296 and within $(6 \pm 10)\%$ for HD 190073. The radial surface brightness profiles for both disks are remarkably Gaussian-like with little or no sign of the sharp edge expected for a dust evaporation front. Coupled with spectral energy distribution analysis, our direct measurements of the stellar flux component at H and K bands suggest that HD 190073 is much younger (<400 kyr) and more massive (~5.6 M$_\odot$) than previously thought, mainly as a consequence of the new Gaia distance (891 pc).Comment: 19 pages, 6 figure

A time-domain control signal detection technique for OFDM

Transmission of system-critical control information plays a key role in efficient management of limited wireless network resources and successful reception of payload data information. This paper uses an orthogonal frequency division multiplexing (OFDM) architecture to investigate the detection performance of a time-domain approach used to detect deterministic control signalling information. It considers a type of control information chosen from a finite set of information, which is known at both transmitting and receiving wireless terminals. Unlike the maximum likelihood (ML) estimation method, which is often used, the time-domain detection technique requires no channel estimation and no pilots as it uses a form of time-domain correlation as the means of detection. Results show that when compared with the ML method, the time-domain approach improves detection performance even in the presence of synchronisation error caused by carrier frequency offset

Lessons Learned in the Early Stages of a Community-Academic Partnership to Address Health Disparities in a Rural Community

In rural Georgia, African American men are burdened by chronic health diseases such as cancer, diabetes, and cardiovascular disease. Community-academic partnerships that leverage community-based participatory research (CBPR) principles can facilitate the adaptation and translation of multilevel programs to address chronic disease prevention and management in rural areas. The objective of this study was to explore key components of the CBPR process that bolstered the early stages of a partnership established between rural-residing community leaders and academic partners in Georgia. Qualitative methodology was used to collect and assess data regarding the initial engagement between the community and academic partners. Findings indicate that five components supported initial engagement: utilizing the public service and outreach arm of the university to connect with rural communities; creating synergy around identified community health needs; encouraging community members to provide input into the research design to ensure the research goals reflect community values; enhancing the capacity of community partners; and following the lead of the community. Findings provide insights into how to begin engaging rural communities in the southeast in order to strengthen the adaptation and translation of initiatives to improve cancer, diabetes and cardiovascular disease outcomes

Benefits and resource implications of family meetings for hospitalized palliative care patients: research protocol.

BACKGROUND:Palliative care focuses on supporting patients diagnosed with advanced, incurable disease; it is 'family centered', with the patient and their family (the unit of care) being core to all its endeavours. However, approximately 30-50% of carers experience psychological distress which is typically under recognised and consequently not addressed. Family meetings (FM) are recommended as a means whereby health professionals, together with family carers and patients discuss psychosocial issues and plan care; however there is minimal empirical research to determine the net effect of these meetings and the resources required to implement them systematically. The aims of this study were to evaluate: (1) if family carers of hospitalised patients with advanced disease (referred to a specialist palliative care in-patient setting or palliative care consultancy service) who receive a FM report significantly lower psychological distress (primary outcome), fewer unmet needs, increased quality of life and feel more prepared for the caregiving role; (2) if patients who receive the FM experience appropriate quality of end-of-life care, as demonstrated by fewer hospital admissions, fewer emergency department presentations, fewer intensive care unit hours, less chemotherapy treatment (in last 30 days of life), and higher likelihood of death in the place of their choice and access to supportive care services; (3) the optimal time point to deliver FM and; (4) to determine the cost-benefit and resource implications of implementing FM meetings into routine practice.METHODS:Cluster type trial design with two way randomization for aims 1-3 and health economic modeling and qualitative interviews with health for professionals for aim 4.DISCUSSION:The research will determine whether FMs have positive practical and psychological impacts on the family, impacts on health service usage, and financial benefits to the health care sector. This study will also provide clear guidance on appropriate timing in the disease/care trajectory to provide a family meeting.<br/