Development of Halofluorochromic Polymer Nanoassemblies for the Potential Detection of Liver Metastatic Colorectal Cancer Tumors Using Experimental and Computational Approaches

Purpose—To develop polymer nanoassemblies (PNAs) modified with halofluorochromic dyes to allow for the detection of liver metastatic colorectal cancer (CRC) to improve therapeutic outcomes. Methods—We combine experimental and computational approaches to evaluate macroscopic and microscopic PNA distributions in patient-derived xenograft primary and orthotropic liver metastatic CRC tumors. Halofluorochromic and non-halofluorochromic PNAs (hfPNAs and n-hfPNAs) were prepared from poly(ethylene glycol), fluorescent dyes (Nile blue, Alexa546, and IR820), and hydrophobic groups (palmitate), all of which were covalently tethered to a cationic polymer scaffold [poly(ethylene imine) or poly(lysine)] forming particles with an average diameter \u3c 30 nm. Results—Dye-conjugated PNAs showed no aggregation under opsonizing conditions for 24 h and displayed low tissue diffusion and cellular uptake. Both hfPNAs and n-hfPNAs accumulated in primary and liver metastatic CRC tumors within 12 h post intravenous injection. In comparison to n-hfPNAs, hfPNAs fluoresced strongly only in the acidic tumor microenvironment (pH \u3c 7.0) and distinguished small metastatic CRC tumors from healthy liver stroma. Computational simulations revealed that PNAs would steadily accumulate mainly in acidic (hypoxic) interstitium of metastatic tumors, independently of the vascularization degree of the tissue surrounding the lesions. Conclusion—The combined experimental and computational data confirms that hfPNAs detecting acidic tumor tissue can be used to identify small liver metastatic CRC tumors with improved accuracy

Insomnia symptoms and repressive coping in a sample of older Black and White women

BACKGROUND: This study examined whether ethnic differences in insomnia symptoms are mediated by differences in repressive coping styles. METHODS: A total of 1274 women (average age = 59.36 ± 6.53 years) participated in the study; 28% were White and 72% were Black. Older women in Brooklyn, NY were recruited using a stratified, cluster-sampling technique. Trained staff conducted face-to-face interviews lasting 1.5 hours acquiring sociodemographic data, health characteristics, and risk factors. A sleep questionnaire was administered and individual repressive coping styles were assessed. Fisher's exact test and Spearman and Pearson analyses were used to analyze the data. RESULTS: The rate of insomnia symptoms was greater among White women [74% vs. 46%; χ(2 )= 87.67, p < 0.0001]. Black women scored higher on the repressive coping scale than did White women [Black = 37.52 ± 6.99, White = 29.78 ± 7.38, F(1,1272 )= 304.75, p < 0.0001]. We observed stronger correlations between repressive coping and insomnia symptoms for Black [r(s )= -0.43, p < 0.0001] than for White women [r(s )= -0.18, p < 0.0001]. Controlling for variation in repressive coping, the magnitude of the correlation between ethnicity and insomnia symptoms was substantially reduced. Multivariate adjustment for differences in sociodemographics, health risk factors, physical health, and health beliefs and attitudes had little effect on the relationships. CONCLUSION: Relationships between ethnicity and insomnia symptoms are jointly dependent on the degree of repressive coping, suggesting that Black women may be reporting fewer insomnia symptoms because of a greater ability to route negative emotions from consciousness. It may be that Blacks cope with sleep problems within a positive self-regulatory framework, which allows them to deal more effectively with sleep-interfering psychological processes to stressful life events and to curtail dysfunctional sleep-interpreting processes

THE COMMUNITY LEVERAGED UNIFIED ENSEMBLE (CLUE) IN THE 2016 NOAA/HAZARDOUS WEATHER TESTBED SPRING FORECASTING EXPERIMENT

One primary goal of annual Spring Forecasting Experiments (SFEs), which are coorganized by NOAA’s National Severe Storms Laboratory and Storm Prediction Center and conducted in the National Oceanic and Atmospheric Administration’s (NOAA) Hazardous Weather Testbed, is documenting performance characteristics of experimental, convection-allowing modeling systems (CAMs). Since 2007, the number of CAMs (including CAM ensembles) examined in the SFEs has increased dramatically, peaking at six different CAM ensembles in 2015. Meanwhile, major advances have been made in creating, importing, processing, verifying, and developing tools for analyzing and visualizing these large and complex datasets. However, progress toward identifying optimal CAM ensemble configurations has been inhibited because the different CAM systems have been independently designed, making it difficult to attribute differences in performance characteristics. Thus, for the 2016 SFE, a much more coordinated effort among many collaborators was made by agreeing on a set of model specifications (e.g., model version, grid spacing, domain size, and physics) so that the simulations contributed by each collaborator could be combined to form one large, carefully designed ensemble known as the Community Leveraged Unified Ensemble (CLUE). The 2016 CLUE was composed of 65 members contributed by five research institutions and represents an unprecedented effort to enable an evidence-driven decision process to help guide NOAA’s operational modeling efforts. Eight unique experiments were designed within the CLUE framework to examine issues directly relevant to the design of NOAA’s future operational CAM-based ensembles. This article will highlight the CLUE design and present results from one of the experiments examining the impact of single versus multicore CAM ensemble configurations

THE COMMUNITY LEVERAGED UNIFIED ENSEMBLE (CLUE) IN THE 2016 NOAA/HAZARDOUS WEATHER TESTBED SPRING FORECASTING EXPERIMENT

One primary goal of annual Spring Forecasting Experiments (SFEs), which are coorganized by NOAA’s National Severe Storms Laboratory and Storm Prediction Center and conducted in the National Oceanic and Atmospheric Administration’s (NOAA) Hazardous Weather Testbed, is documenting performance characteristics of experimental, convection-allowing modeling systems (CAMs). Since 2007, the number of CAMs (including CAM ensembles) examined in the SFEs has increased dramatically, peaking at six different CAM ensembles in 2015. Meanwhile, major advances have been made in creating, importing, processing, verifying, and developing tools for analyzing and visualizing these large and complex datasets. However, progress toward identifying optimal CAM ensemble configurations has been inhibited because the different CAM systems have been independently designed, making it difficult to attribute differences in performance characteristics. Thus, for the 2016 SFE, a much more coordinated effort among many collaborators was made by agreeing on a set of model specifications (e.g., model version, grid spacing, domain size, and physics) so that the simulations contributed by each collaborator could be combined to form one large, carefully designed ensemble known as the Community Leveraged Unified Ensemble (CLUE). The 2016 CLUE was composed of 65 members contributed by five research institutions and represents an unprecedented effort to enable an evidence-driven decision process to help guide NOAA’s operational modeling efforts. Eight unique experiments were designed within the CLUE framework to examine issues directly relevant to the design of NOAA’s future operational CAM-based ensembles. This article will highlight the CLUE design and present results from one of the experiments examining the impact of single versus multicore CAM ensemble configurations

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

OpenSAFELY: a platform for analysing electronic health records designed for reproducible research

Electronic health records (EHRs) and other administrative health data are increasingly used in research to generate evidence on the effectiveness, safety, and utilisation of medical products and services, and to inform public health guidance and policy. Reproducibility is a fundamental step for research credibility and promotes trust in evidence generated from EHRs. At present, ensuring research using EHRs is reproducible can be challenging for researchers. Research software platforms can provide technical solutions to enhance the reproducibility of research conducted using EHRs. In response to the COVID-19 pandemic, we developed the secure, transparent, analytic open-source software platform OpenSAFELY designed with reproducible research in mind. OpenSAFELY mitigates common barriers to reproducible research by: standardising key workflows around data preparation; removing barriers to code-sharing in secure analysis environments; enforcing public sharing of programming code and codelists; ensuring the same computational environment is used everywhere; integrating new and existing tools that encourage and enable the use of reproducible working practices; and providing an audit trail for all code that is run against the real data to increase transparency. This paper describes OpenSAFELY’s reproducibility-by-design approach in detail

Acute childhood diarrhoea in northern Ghana: epidemiological, clinical and microbiological characteristics

<p>Abstract</p> <p>Background</p> <p>Acute diarrhoea is a major cause of childhood morbidity and mortality in sub-Saharan Africa. Its microbiological causes and clinico-epidemiological aspects were examined during the dry season 2005/6 in Tamale, urban northern Ghana.</p> <p>Methods</p> <p>Stool specimens of 243 children with acute diarrhoea and of 124 control children were collected. Patients were clinically examined, and malaria and anaemia were assessed. Rota-, astro-, noro- and adenoviruses were identified by (RT-) PCR assays. Intestinal parasites were diagnosed by microscopy, stool antigen assays and PCR, and bacteria by culturing methods.</p> <p>Results</p> <p>Watery stools, fever, weakness, and sunken eyes were the most common symptoms in patients (mean age, 10 months). Malaria occurred in 15% and anaemia in 91%; underweight (22%) and wasting (19%) were frequent. Intestinal micro-organisms were isolated from 77% of patients and 53% of controls (<it>P </it>< 0.0001). The most common pathogens in patients were rotavirus (55%), adenovirus (28%) and norovirus (10%); intestinal parasites (5%) and bacteria (5%) were rare. Rotavirus was the only pathogen found significantly more frequently in patients than in controls (odds ratio 7.7; 95%CI, 4.2–14.2), and was associated with young age, fever and watery stools. Patients without an identified cause of diarrhoea more frequently had symptomatic malaria (25%) than those with diagnosed intestinal pathogens (12%, <it>P </it>= 0.02).</p> <p>Conclusion</p> <p>Rotavirus-infection is the predominant cause of acute childhood diarrhoea in urban northern Ghana. The abundance of putative enteropathogens among controls may indicate prolonged excretion or limited pathogenicity. In this population with a high burden of diarrhoeal and other diseases, sanitation, health education, and rotavirus-vaccination can be expected to have substantial impact on childhood morbidity.</p

Concept design of low frequency telescope for CMB B-mode polarization satellite LiteBIRD

LiteBIRD has been selected as JAXA’s strategic large mission in the 2020s, to observe the cosmic microwave background (CMB) B-mode polarization over the full sky at large angular scales. The challenges of LiteBIRD are the wide field-of-view (FoV) and broadband capabilities of millimeter-wave polarization measurements, which are derived from the system requirements. The possible paths of stray light increase with a wider FoV and the far sidelobe knowledge of -56 dB is a challenging optical requirement. A crossed-Dragone configuration was chosen for the low frequency telescope (LFT : 34–161 GHz), one of LiteBIRD’s onboard telescopes. It has a wide field-of-view (18° x 9°) with an aperture of 400 mm in diameter, corresponding to an angular resolution of about 30 arcminutes around 100 GHz. The focal ratio f/3.0 and the crossing angle of the optical axes of 90◦ are chosen after an extensive study of the stray light. The primary and secondary reflectors have rectangular shapes with serrations to reduce the diffraction pattern from the edges of the mirrors. The reflectors and structure are made of aluminum to proportionally contract from warm down to the operating temperature at 5 K. A 1/4 scaled model of the LFT has been developed to validate the wide field-of-view design and to demonstrate the reduced far sidelobes. A polarization modulation unit (PMU), realized with a half-wave plate (HWP) is placed in front of the aperture stop, the entrance pupil of this system. A large focal plane with approximately 1000 AlMn TES detectors and frequency multiplexing SQUID amplifiers is cooled to 100 mK. The lens and sinuous antennas have broadband capability. Performance specifications of the LFT and an outline of the proposed verification plan are presented

LiteBIRD satellite: JAXA's new strategic L-class mission for all-sky surveys of cosmic microwave background polarization

LiteBIRD, the Lite (Light) satellite for the study of B-mode polarization and Inflation from cosmic background Radiation Detection, is a space mission for primordial cosmology and fundamental physics. JAXA selected LiteBIRD in May 2019 as a strategic large-class (L-class) mission, with its expected launch in the late 2020s using JAXA's H3 rocket. LiteBIRD plans to map the cosmic microwave background (CMB) polarization over the full sky with unprecedented precision. Its main scientific objective is to carry out a definitive search for the signal from cosmic inflation, either making a discovery or ruling out well-motivated inflationary models. The measurements of LiteBIRD will also provide us with an insight into the quantum nature of gravity and other new physics beyond the standard models of particle physics and cosmology. To this end, LiteBIRD will perform full-sky surveys for three years at the Sun-Earth Lagrangian point L2 for 15 frequency bands between 34 and 448 GHz with three telescopes, to achieve a total sensitivity of 2.16 μK-arcmin with a typical angular resolution of 0.5° at 100 GHz. We provide an overview of the LiteBIRD project, including scientific objectives, mission requirements, top-level system requirements, operation concept, and expected scientific outcomes

Overview of the medium and high frequency telescopes of the LiteBIRD space mission

LiteBIRD is a JAXA-led Strategic Large-Class mission designed to search for the existence of the primordial gravitational waves produced during the inflationary phase of the Universe, through the measurements of their imprint onto the polarization of the cosmic microwave background (CMB). These measurements, requiring unprecedented sensitivity, will be performed over the full sky, at large angular scales, and over 15 frequency bands from 34 GHz to 448 GHz. The LiteBIRD instruments consist of three telescopes, namely the Low-, Medium-and High-Frequency Telescope (respectively LFT, MFT and HFT). We present in this paper an overview of the design of the Medium-Frequency Telescope (89{224 GHz) and the High-Frequency Telescope (166{448 GHz), the so-called MHFT, under European responsibility, which are two cryogenic refractive telescopes cooled down to 5 K. They include a continuous rotating half-wave plate as the first optical element, two high-density polyethylene (HDPE) lenses and more than three thousand transition-edge sensor (TES) detectors cooled to 100 mK. We provide an overview of the concept design and the remaining specific challenges that we have to face in order to achieve the scientific goals of LiteBIRD