The acyl chain specificity of biliary phosphatidylcholine is independent from its biosynthetic origin

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Solid-state 3He^3\mathrm{He} NMR of the superconducting rubidium endofulleride Rb3(3He@C60)\mathrm{Rb_3(^3He@C_{60})}

A new variant of the superconducting fulleride $\mathrm{Rb_{3}C_{60}}$ is presented, with $\mathrm{^{3}He}$ atoms encapsulated in the $\mathrm{C_{60}}$ cages. The $\mathrm{^{3}He}$ nuclei act as sensitive NMR probes embedded in the material. The superconducting and normal states are characterised by $\mathrm{^{3}He}$ NMR. Evidence is found for co-existing vortex liquid and vortex solid phases below the superconducting transition temperature. A strong dependence of the spin-lattice relaxation time constant on spectral frequency is observed in the superconducting state, as revealed by two-dimensional NMR utilising an inverse Laplace transform. Surprisingly, this phenomenon persists, in attenuated form, at temperatures well above the superconducting transition.Comment: 20 pages, 15 figure

Relationship between islet autoantibody status and the clinical characteristics of children and adults with incident type 1 diabetes in a UK cohort.

OBJECTIVES: To describe the characteristics of children and adults with incident type 1 diabetes in contemporary, multiethnic UK, focusing on differences between the islet autoantibody negative and positive. DESIGN: Observational cohort study. SETTING: 146 mainly secondary care centres across England and Wales. PARTICIPANTS: 3312 people aged ≥5 years were recruited within 6 months of a clinical diagnosis of type 1 diabetes via the National Institute for Health Research Clinical Research Network. 3021 were of white European ethnicity and 291 (9%) were non-white. There was a small male predominance (57%). Young people <17 years comprised 59%. MAIN OUTCOME MEASURES: Autoantibody status and characteristics at presentation. RESULTS: The majority presented with classical osmotic symptoms, weight loss and fatigue. Ketoacidosis was common (42%), especially in adults, and irrespective of ethnicity. 35% were overweight or obese. Of the 1778 participants who donated a blood sample, 85% were positive for one or more autoantibodies against glutamate decarboxylase, islet antigen-2 and zinc transporter 8. Presenting symptoms were similar in the autoantibody-positive and autoantibody-negative participants, as was the frequency of ketoacidosis (43%vs40%, P=0.3). Autoantibody positivity was less common with increasing age (P=0.0001), in males compared with females (82%vs90%, P<0.0001) and in people of non-white compared with white ethnicity (73%vs86%, P<0.0001). Body mass index was higher in autoantibody-negative adults than autoantibody-positive adults (median, IQR 25.5, 23.1-29.2vs23.9, 21.4-26.7 kg/m2; P=0.0001). Autoantibody-negative participants were more likely to have a parent with diabetes (28%vs16%, P<0.0001) and less likely to have another autoimmune disease (4%vs8%, P=0.01). CONCLUSIONS: Most people assigned a diagnosis of type 1 diabetes presented with classical clinical features and islet autoantibodies. Although indistinguishable at an individual level, autoantibody-negative participants as a group demonstrated features more typically associated with other diabetes subtypes. TRIAL REGISTRATION NUMBER: ISRCTN66496918; Pre-results

Promoting the achievement in schools of children and young people in care

As of March 2017, there were 72,670 children and young people in care in England. The number of looked after children has continued to increase steadily over the last eight years. Sixty per cent of these children are in care because of abuse or neglect and three-quarters are placed in foster care arrangements. Children and young people who are in or have experienced care remain one of the lowest performing groups in terms of educational outcomes. The average Attainment 8 score for children in care is 19.3 compared to 44.5 for non-looked after children and 19.3 for children in need. In 2017 there was an increase in the percentage of children in care achieving a pass in English and Mathematics from 17.4% to 17.5% and also in entering EBacc. Care leavers can experience poorer employment and health outcomes after leaving school compared to their peers. They are over-represented amongst the offender population and those who experience homelessness. However, research is emerging to show that children and young people in care can have very positive experiences of school if they are supported effectively to reach their full potential academically and socially. The purpose of this report is to share practice in local authorities (LA) from across England and Wales that is contributing to improved outcomes and school experiences for children and young people in care. The case studies were all undertaken as part of the Promoting the Achievement of Looked after Children (PALAC) programme between 2014 and 2017. This report presents an account of the programme, including the activities undertaken by the participants and the outcomes of the programme to date for pupils in care and staff in the participating virtual schools (VS) and local authorities

Adsorption at cell surface and cellular uptake of silica nanoparticles with different surface chemical functionalizations: impact on cytotoxicity

International audienceSilica nanoparticles are particularly interesting for medical applications because of the high inertness and chemical stability of silica material. However, at the nanoscale their innocuousness must be carefully verified before clinical use. The aim of this study was to investigate the in vitro biological toxicity of silica nanoparticles depending on their surface chemical functionalization. To that purpose, three kinds of 50 nm fluorescent silica-based nanoparticles were synthesized: 1) sterically stabilized silica nanoparticles coated with neutral polyethylene glycol (PEG) molecules, 2) positively charged silica nanoparticles coated with amine groups and 3) negatively charged silica nanoparticles coated with carboxylic acid groups. RAW 264.7 murine macrophages were incubated for 20 hours with each kind of nanoparticles. Their cellular uptake and adsorption at the cell membrane were assessed by a fluorimetric assay and cellular responses were evaluated in terms of cytotoxicity, pro-inflammatory factor production and oxidative stress. Results showed that the highly positive charged nanoparticle, were the most adsorbed at cell surface and triggered more cytotoxicity than other nanoparticles types. To conclude, this study clearly demonstrated that silica nanoparticles surface functionalization represents a key parameter in their cellular uptake and biological toxicity

Long-term medical utilization following ventilator-associated pneumonia in acute stroke and traumatic brain injury patients: a case-control study

<p>Abstract</p> <p>Background</p> <p>The economic burden of ventilator-associated pneumonia (VAP) during the index hospitalization has been confirmed in previous studies. However, the long-term economic impact is still unclear. The aim of this study is to examine the effect of VAP on medical utilization in the long term.</p> <p>Methods</p> <p>This is a retrospective case-control study. Study subjects were patients experiencing their first traumatic brain injury, acute hemorrhagic stroke, or acute ischemic stroke during 2004. All subjects underwent endotracheal intubation in the emergency room (ER) on the day of admission or the day before admission, were transferred to the intensive care unit (ICU) and were mechanically ventilated for 48 hours or more. A total of 943 patients who developed VAP were included as the case group, and each was matched with two control patients without VAP by age ( ± 2 years), gender, diagnosis, date of admission ( ± 1 month) and hospital size, resulting in a total of 2,802 patients in the study. Using robust regression and Poisson regression models we examined the effect of VAP on medical utilization including hospitalization expenses, outpatient expenses, total medical expenses, number of ER visits, number of readmissions, number of hospitalization days and number of ICU days, during the index hospitalization and during the following 2-year period.</p> <p>Results</p> <p>Patients in the VAP group had higher hospitalization expenses, longer length of stay in hospital and in ICU, and a greater number of readmissions than the control group patients.</p> <p>Conclusions</p> <p>VAP has a significant impact on medical expenses and utilization, both during the index hospitalization during which VAP developed and in the longer term.</p

Development and assessment of a new framework for disease surveillance, prediction, and risk adjustment: the diagnostic items classification system

IMPORTANCE: Current disease risk-adjustment formulas in the US rely on diagnostic classification frameworks that predate the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). OBJECTIVE: To develop an ICD-10-CM-based classification framework for predicting diverse health care payment, quality, and performance outcomes. DESIGN SETTING AND PARTICIPANTS: Physician teams mapped all ICD-10-CM diagnoses into 3 types of diagnostic items (DXIs): main effect DXIs that specify diseases; modifiers, such as laterality, timing, and acuity; and scaled variables, such as body mass index, gestational age, and birth weight. Every diagnosis was mapped to at least 1 DXI. Stepwise and weighted least-squares estimation predicted cost and utilization outcomes, and their performance was compared with models built on (1) the Agency for Healthcare Research and Quality Clinical Classifications Software Refined (CCSR) categories, and (2) the Health and Human Services Hierarchical Condition Categories (HHS-HCC) used in the Affordable Care Act Marketplace. Each model's performance was validated using R 2, mean absolute error, the Cumming prediction measure, and comparisons of actual to predicted outcomes by spending percentiles and by diagnostic frequency. The IBM MarketScan Commercial Claims and Encounters Database, 2016 to 2018, was used, which included privately insured, full- or partial-year eligible enrollees aged 0 to 64 years in plans with medical, drug, and mental health/substance use coverage. MAIN OUTCOMES AND MEASURES: Fourteen concurrent outcomes were predicted: overall and plan-paid health care spending (top-coded and not top-coded); enrollee out-of-pocket spending; hospital days and admissions; emergency department visits; and spending for 6 types of services. The primary outcome was annual health care spending top-coded at $250 000. RESULTS: A total of 65 901 460 person-years were split into 90$5821 [$17 653]) selected 76% of the main effect DXIs with no evidence of overfitting. Validated R 2 was 0.589 in the DXI model, 0.539 for CCSR, and 0.428 for HHS-HCC. Use of DXIs reduced underpayment for enrollees with rare (1-in-a-million) diagnoses by 83% relative to HHS-HCCs. CONCLUSIONS: In this diagnostic modeling study, the new DXI classification system showed improved predictions over existing diagnostic classification systems for all spending and utilization outcomes considered.Published versio

Surgical resectability of pancreatic adenocarcinoma: CTA

Imaging studies play an important role in the diagnosis and management of patients with pancreatic adenocarcinoma. Computed tomography (CT) is the most widely available and best validated modality for imaging these patients. Meticulous technique following a well-designed pancreas protocol is essential for maximizing the diagnostic efficacy of CT. After the diagnosis of pancreatic adenocarcinoma is made, the key to management is staging to determine resectability. In practice, staging often entails predicting the presence or absence of vascular invasion by tumor, for which several radiologic grading systems exist. With advances in surgical techniques, the definition of resectability is in evolution, and it is crucial that radiologists have an understanding of the implications of findings that are relevant to the determination of resectability

In situ measurement of bovine serum albumin interaction with gold nanospheres

Here we present in situ observations of adsorption of bovine serum albumin (BSA) on citratestabilized gold nanospheres. We implemented scattering correlation spectroscopy as a tool to quantify changes in the nanoparticle Brownian motion resulting from BSA adsorption onto the nanoparticle surface. Protein binding was observed as an increase in the nanoparticle hydrodynamic radius. Our results indicate the formation of a protein monolayer at similar albumin concentrations as those found in human blood. Additionally, by monitoring the frequency and intensity of individual scattering events caused by single gold nanoparticles passing the observation volume, we found that BSA did not induce colloidal aggregation, a relevant result from the toxicological viewpoint. Moreover, to elucidate the thermodynamics of the gold nanoparticle-BSA association, we measured an adsorption isotherm which was best described by an anti-cooperative binding model. The number of binding sites based on this model was consistent with a BSA monolayer in its native state. In contrast, experiments using poly-ethylene glycol capped gold nanoparticles revealed no evidence for adsorption of BSA

Comparison Study of Gold Nanohexapods, Nanorods, and Nanocages for Photothermal Cancer Treatment

Gold nanohexapods represent a novel class of optically tunable nanostructures consisting of an octahedral core and six arms grown on its vertices. By controlling the length of the arms, their localized surface plasmon resonance peaks could be tuned from the visible to the near-infrared region for deep penetration of light into soft tissues. Herein we compare the in vitro and in vivo capabilities of Au nanohexapods as photothermal transducers for theranostic applications by benchmarking against those of Au nanorods and nanocages. While all these Au nanostructures could absorb and convert near-infrared light into heat, Au nanohexapods exhibited the highest cellular uptake and the lowest cytotoxicity in vitro for both the as-prepared and PEGylated nanostructures. In vivo pharmacokinetic studies showed that the PEGylated Au nanohexapods had significant blood circulation and tumor accumulation in a mouse breast cancer model. Following photothermal treatment, substantial heat was produced in situ and the tumor metabolism was greatly reduced for all these Au nanostructures, as determined with ^(18)F-flourodeoxyglucose positron emission tomography/computed tomography (^(18)F-FDG PET/CT). Combined together, we can conclude that Au nanohexapods are promising candidates for cancer theranostics in terms of both photothermal destruction and contrast-enhanced diagnosis