System for HIV-1 Treatment to the Brain

While HIV-1 treatment has been revolutionized by combination antiretroviral therapy in the past two decades, HIV-1 remains persistent in organs that don’t allow easy penetration of anti-HIV drugs (e.g., brain) and cause persistent HIV-1 infections and inflammation. Researchers have turned towards nanotechnology-based drug carriers to combat this challenge, such as nanodiscoidal bicelles (ND) and liposomes. Bicelles entrap the drug in their interior hydrophobic core until metabolized by the body, and the payload can be released at the desired location in a controlled, long-lasting dosage. This study investigated the toxicity and extended-release of an anti-HIV drug-loaded within ND and liposomes for HIV-1 treatment to the brain. Results from both in-vitro and in-vivo characterization studies demonstrated that further optimization of the ND formulation needs to be adjusted towards liposomal structures for future studies

Refugee and Migrant Women's Views of Antenatal Ultrasound on the Thai Burmese Border: A Mixed Methods Study

Antenatal ultrasound suits developing countries by virtue of its versatility, relatively low cost and safety, but little is known about women's or local provider's perspectives of this upcoming technology in such settings. This study was undertaken to better understand how routine obstetric ultrasound is experienced in a displaced Burmese population and identify barriers to its acceptance by local patients and providers.Qualitative (30 observations, 19 interviews, seven focus group discussions) and quantitative methods (questionnaire survey with 644 pregnant women) were used to provide a comprehensive understanding along four major themes: safety, emotions, information and communication, and unintended consequences of antenatal ultrasound in refugee and migrant clinics on the Thai Burmese border. One of the main concerns expressed by women was the danger of childbirth which they mainly attributed to fetal malposition. Both providers and patients recognized ultrasound as a technology improving the safety of pregnancy and delivery. A minority of patients experienced transitory shyness or anxiety before the ultrasound, but reported that these feelings could be ameliorated with improved patient information and staff communication. Unintended consequences of overuse and gender selective abortions in this population were not common.The results of this study are being used to improve local practice and allow development of explanatory materials for this population with low literacy. We strongly encourage facilities introducing new technology in resource poor settings to assess acceptability through similar inquiry

A Global Ocean Oxygen Database and Atlas for Assessing and Predicting Deoxygenation and Ocean Health in the Open and Coastal Ocean

In this paper, we outline the need for a coordinated international effort toward the building of an open-access Global Ocean Oxygen Database and ATlas (GO2DAT) complying with the FAIR principles (Findable, Accessible, Interoperable, and Reusable). GO2DAT will combine data from the coastal and open ocean, as measured by the chemical Winkler titration method or by sensors (e.g., optodes, electrodes) from Eulerian and Lagrangian platforms (e.g., ships, moorings, profiling floats, gliders, ships of opportunities, marine mammals, cabled observatories). GO2DAT will further adopt a community-agreed, fully documented metadata format and a consistent quality control (QC) procedure and quality flagging (QF) system. GO2DAT will serve to support the development of advanced data analysis and biogeochemical models for improving our mapping, understanding and forecasting capabilities for ocean O2 changes and deoxygenation trends. It will offer the opportunity to develop quality-controlled data synthesis products with unprecedented spatial (vertical and horizontal) and temporal (sub-seasonal to multi-decadal) resolution. These products will support model assessment, improvement and evaluation as well as the development of climate and ocean health indicators. They will further support the decision-making processes associated with the emerging blue economy, the conservation of marine resources and their associated ecosystem services and the development of management tools required by a diverse community of users (e.g., environmental agencies, aquaculture, and fishing sectors). A better knowledge base of the spatial and temporal variations of marine O2 will improve our understanding of the ocean O2 budget, and allow better quantification of the Earth’s carbon and heat budgets. With the ever-increasing need to protect and sustainably manage ocean services, GO2DAT will allow scientists to fully harness the increasing volumes of O2 data already delivered by the expanding global ocean observing system and enable smooth incorporation of much higher quantities of data from autonomous platforms in the open ocean and coastal areas into comprehensive data products in the years to come. This paper aims at engaging the community (e.g., scientists, data managers, policy makers, service users) toward the development of GO2DAT within the framework of the UN Global Ocean Oxygen Decade (GOOD) program recently endorsed by IOC-UNESCO. A roadmap toward GO2DAT is proposed highlighting the efforts needed (e.g., in terms of human resources)

International Consortium on Mammographic Density:methodology and population diversity captured across 22 countries

Mammographic density (MD) is a quantitative trait, measurable in all women, and is among the strongest markers of breast cancer risk. The population-based epidemiology of MD has revealed genetic, lifestyle and societal/environmental determinants, but studies have largely been conducted in women with similar westernized lifestyles living in countries with high breast cancer incidence rates. To benefit from the heterogeneity in risk factors and their combinations worldwide, we created an International Consortium on Mammographic Density (ICMD) to pool individual-level epidemiological and MD data from general population studies worldwide. ICMD aims to characterize determinants of MD more precisely, and to evaluate whether they are consistent across populations worldwide. We included 11755 women, from 27 studies in 22 countries, on whom individual-level risk factor data were pooled and original mammographic images were re-read for ICMD to obtain standardized comparable MD data. In the present article, we present (i) the rationale for this consortium; (ii) characteristics of the studies and women included; and (iii) study methodology to obtain comparable MD data from original re-read films. We also highlight the risk factor heterogeneity captured by such an effort and, thus, the unique insight the pooled study promises to offer through wider exposure ranges, different confounding structures and enhanced power for sub-group analyses

Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening