An epidemiological evaluation of pediatric long bone fractures - a retrospective cohort study of 2716 patients from two Swiss tertiary pediatric hospitals.

BACKGROUND: Children and adolescents are at high risk of sustaining fractures during growth. Therefore, epidemiological assessment is crucial for fracture prevention. The AO Comprehensive Injury Automatic Classifier (AO COIAC) was used to evaluate epidemiological data of pediatric long bone fractures in a large cohort. METHODS: Data from children and adolescents with long bone fractures sustained between 2009 and 2011, treated at either of two tertiary pediatric surgery hospitals in Switzerland, were retrospectively collected. Fractures were classified according to the AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF). RESULTS: For a total of 2716 patients (60% boys), 2807 accidents with 2840 long bone fractures (59% radius/ulna; 21% humerus; 15% tibia/fibula; 5% femur) were documented. Children's mean age (SD) was 8.2 (4.0) years (6% infants; 26% preschool children; 40% school children; 28% adolescents). Adolescent boys sustained more fractures than girls (p < 0.001). The leading cause of fractures was falls (27%), followed by accidents occurring during leisure activities (25%), at home (14%), on playgrounds (11%), and traffic (11%) and school accidents (8%). There was boy predominance for all accident types except for playground and at home accidents. The distribution of accident types differed according to age classes (p < 0.001). Twenty-six percent of patients were classed as overweight or obese - higher than data published by the WHO for the corresponding ages - with a higher proportion of overweight and obese boys than in the Swiss population (p < 0.0001). CONCLUSION: Overall, differences in the fracture distribution were sex and age related. Overweight and obese patients seemed to be at increased risk of sustaining fractures. Our data give valuable input into future development of prevention strategies. The AO PCCF proved to be useful in epidemiological reporting and analysis of pediatric long bone fractures

Integrated Akt/PKB Signaling in Immunomodulation and Its Potential Role in Cancer Immunotherapy

T cell development and maturation involve a variety of defined and coordinated developmental stages under the control of a variety of signaling networks. They function as the major mediator in cell-based immunity that defends against pathogen infections and executes immune surveillance against tumor cells. Protein kinase B (PKB, also called Akt) is central to multiple signaling pathways and transduces extracellular signals to dictate cellular responses towards proliferation, migration, anti-apoptosis, and maintenance of metabolic homeostasis. Although the prosurvival function of PKB was thought to be responsible for most of the functions regulated by PKB, emerging evidence has started to dissect its role in immunomodulation. More importantly, hyperactivation of PKB in cancer stroma frequently occurs in patients treated clinically with targeted cancer therapies, where it acts as a key mediator involved in the trapping of host immune cells in the vicinity of tumors, which supports cancer cell invasion and the escape of cancer cells from host immune surveillance. Encouragingly, recent studies have shown that inhibition of PKB improves the recognition of cancer cells by the host immune system, indicating a potential clinical strategy to rekindle the suppressed host immune response through the specific targeting of PKB. In this review, we explore how PKB signaling contributes to T cell development and cellular immune responses and discuss the mechanistic roles that PKB plays in the creation of immunosuppressive conditions and the escaping of immune recognition in the microenvironment of cance

Developing research priorities for palliative care of people with intellectual disabilities in Europe: a consultation process using nominal group technique

BACKGROUND: Empirical knowledge around palliative care provision and needs of people with intellectual disabilities is extremely limited, as is the availability of research resources, including expertise and funding. This paper describes a consultation process that sought to develop an agenda for research priorities for palliative care of people with intellectual disabilities in Europe. METHODS: A two-day workshop was convened, attended by 16 academics and clinicians in the field of palliative care and intellectual disability from six European countries. The first day consisted of round-table presentations and discussions about the current state of the art, research challenges and knowledge gaps. The second day was focused on developing consensus research priorities with 12 of the workshop participants using nominal group technique, a structured method which involved generating a list of research priorities and ranking them in order of importance. RESULTS: A total of 40 research priorities were proposed and collapsed into eleven research themes. The four most important research themes were: investigating issues around end of life decision making; mapping the scale and scope of the issue; investigating the quality of palliative care for people with intellectual disabilities, including the challenges in achieving best practice; and developing outcome measures and instruments for palliative care of people with intellectual disabilities. CONCLUSIONS: The proposal of four major priority areas and a range of minor themes for future research in intellectual disability, death, dying and palliative care will help researchers to focus limited resources and research expertise on areas where it is most needed and support the building of collaborations. The next steps are to cross-validate these research priorities with people with intellectual disabilities, carers, clinicians, researchers and other stakeholders across Europe; to validate them with local and national policy makers to determine how they could best be incorporated in policy and programmes; and to translate them into actual research studies by setting up European collaborations for specific studies that require such collaboration, develop research proposals and attract research funding

Protons in near earth orbit

The proton spectrum in the kinetic energy range 0.1 to 200 GeV was measured by the Alpha Magnetic Spectrometer (AMS) during space shuttle flight STS-91 at an altitude of 380 km. Above the geomagnetic cutoff the observed spectrum is parameterized by a power law. Below the geomagnetic cutoff a substantial second spectrum was observed concentrated at equatorial latitudes with a flux ~ 70 m^-2 sec^-1 sr^-1. Most of these second spectrum protons follow a complicated trajectory and originate from a restricted geographic region.Comment: 19 pages, Latex, 7 .eps figure

A Study of Cosmic Ray Secondaries Induced by the Mir Space Station Using AMS-01

The Alpha Magnetic Spectrometer (AMS-02) is a high energy particle physics experiment that will study cosmic rays in the $\sim 100 \mathrm{MeV}$ to $1 \mathrm{TeV}$ range and will be installed on the International Space Station (ISS) for at least 3 years. A first version of AMS-02, AMS-01, flew aboard the space shuttle \emph{Discovery} from June 2 to June 12, 1998, and collected $10^8$ cosmic ray triggers. Part of the \emph{Mir} space station was within the AMS-01 field of view during the four day \emph{Mir} docking phase of this flight. We have reconstructed an image of this part of the \emph{Mir} space station using secondary $\pi^-$ and $\mu^-$ emissions from primary cosmic rays interacting with \emph{Mir}. This is the first time this reconstruction was performed in AMS-01, and it is important for understanding potential backgrounds during the 3 year AMS-02 mission.Comment: To be submitted to NIM B Added material requested by referee. Minor stylistic and grammer change

The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors

International audienceWe recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps

Isotopic Composition of Light Nuclei in Cosmic Rays: Results from AMS-01

The variety of isotopes in cosmic rays allows us to study different aspects of the processes that cosmic rays undergo between the time they are produced and the time of their arrival in the heliosphere. In this paper we present measurements of the isotopic ratios 2H/4He, 3He/4He, 6Li/7Li, 7Be/(9Be+10Be) and 10B/11B in the range 0.2-1.4 GeV of kinetic energy per nucleon. The measurements are based on the data collected by the Alpha Magnetic Spectrometer, AMS-01, during the STS-91 flight in 1998 June.Comment: To appear in ApJ. 12 pages, 11 figures, 6 table

Modular assembly of proteins on nanoparticles

Generally, the high diversity of protein properties necessitates the development of unique nanoparticle bio-conjugation methods, optimized for each different protein. Here we describe a universal bio-conjugation approach which makes use of a new recombinant fusion protein combining two distinct domains. The N-terminal part is Glutathione S-Transferase (GST) from Schistosoma japonicum, for which we identify and characterize the remarkable ability to bind gold nanoparticles (GNPs) by forming gold–sulfur bonds (Au–S). The C-terminal part of this multi-domain construct is the SpyCatcher from Streptococcus pyogenes, which provides the ability to capture recombinant proteins encoding a SpyTag. Here we show that SpyCatcher can be immobilized covalently on GNPs through GST without the loss of its full functionality. We then show that GST-SpyCatcher activated particles are able to covalently bind a SpyTag modified protein by simple mixing, through the spontaneous formation of an unusual isopeptide bond