General practitioners' role in cancer care: a French-Norwegian study

<p>Abstract</p> <p>Background</p> <p>In cancer care, a GP's work is rarely defined clearly. Our aim was to assess GPs' work with cancer patients in France and in Norway, where the roles of the GP and the organization of the system are rather different.</p> <p>Findings</p> <p>A questionnaire with 40 closed-ended questions about GP involvement in diagnosis, treatment, follow-up and terminal care was constructed and mailed to samples of GPs. The patients had seen the doctor at least once over the past year. In France 1679 and in Norway 386 individual patient questionnaires were completed. GPs have a major role in the diagnosis of cancer, and this role varies according to cancer type. The GPs participated actively in different phases of follow-up after cancer treatment. Low response rates do not allow direct comparison between countries, but higher PSA screening rates in France seem to increase the percentage of patients diagnosed after screening rather than after a clinical suspicion. Interaction between GPs and specialists during cancer treatment and follow-up was important in both countries.</p> <p>Conclusion</p> <p>Both in France and in Norway GPs participate actively in cancer care. Early clinical diagnosis is a challenge. More research is needed about how GPs can improve their early diagnostic work. Organisational issues may influence cancer responsibilities for the GP, and national health systems should be challenged to look at possible new roles for GPs in cancer care. Medical training, both pre- and post-graduate, should prepare doctors for collaboration between primary and secondary care, particularly important in cancer care.</p

Verification of the Enhanced Integrated Climatic Module Soil Subgrade Input Parameters in the MEPDG

At the beginning of 2009, INDOT adopted the Mechanistic-Empirical Pavement Design Guide (MEPDG) method to study the tong-term pavement performance. The implementation of this new design approach led to difficulties for the pavement to pass the INDOT performance criteria; in particular pavement roughness (IRI) when A-6 or A-7-6 soils were considered as subgrade. This study focuses on investigating the influence of the soil input parameters in the Enhanced Integrated Climatic Model (EICM) on the prediction of the soil resilient modulus (MR) in the MEPDG. A total of four sites located around the state of Indiana are used to propose/validate the observations and conclusions made in the research. The study shows that (1) for the climatic conditions existing in Indiana, the location of the water table does not affect the value that the MEPDG uses for the subgrade MR; (2) the gravimetric water content is the most influential parameter on the EICM since it is directly related to the optimum degree of saturation of the subgrade; and (3) For A-7-6 soils, the overall deformation of the pavement structure is controlled by the subgrade (~80% of total deformation). In order to properly model the pavement structure, the MR input into the MEPDG for the subgrade should represent the optimum condition. This value will then be reduced within the EICM to reflect actual site conditions; and the MR input into the MEPDG for the treated layer should be a constant (i.e. not affected by EICM) and with PI and P200 values that are representative of the soil after treatment, given that the fines content and plasticity of a chemically-treated soil tend to decrease with treatment

Why People Participate in the Sharing Economy: An Empirical Investigation of Uber

Purpose - This study aimed at examining the effects of inhibiting, motivating, and technological factors on users’ intention to participate in the sharing economy. Design/methodology/approach - A self-reported online survey was conducted among Uber users in Hong Kong. A total of 295 valid responses were collected. The research model was empirically tested using the structural equation modeling (SEM) technique. Findings - The results suggested that perceived risks, perceived benefits, trust in the platform, and perceived platform qualities were significant predictors of users’ intention to participate in Uber. Research implications - This study bridged the research gaps in the sharing economy literature by examining the effects of perceived risks, perceived benefits, and trust in the platform on users’ intention to participate in the sharing economy. Moreover, this study enriched the extended valence framework by incorporating perceived platform qualities into the research model, responding to the calls for the inclusion of technological variables in information systems research. Practical implications - The findings provided practitioners with insights into enhancing users’ intention to participate in the sharing economy. Originality/value - This study presented one of the first attempts to systematically examine the effects of inhibiting, motivating and technological factors on users’ intention to participate in the sharing economy

An Empirical Investigation into the Antecedents and Consequences of Customer Engagement in Omnichannel Retailing

Engaging customers across channels has become one of the biggest challenges for retailers adopting an omnichannel strategy. In this study, we examine how channel integration quality influences customer engagement in the context of omnichannel retailing. Drawing on the conceptual model of customer engagement, we proposed a research model to explain the effects of breadth of channel choice, transparency of channel-service configuration, content consistency, and process consistency on customer engagement, as well as the positive outcomes associated with the engagement. The research model will be tested with a sample of 500 omnichannel customers using a structural equation modeling approach. This study is expected to contribute to the research on, and practice of, the omnichannel customer engagement by validating the antecedents and consequences of such engagement as well as providing practitioners with insights into devising a successful omnichannel retailing strategy

Synergistic effects between analogs of DNA and RNA improve the potency of siRNA-mediated gene silencing

We report that combining a DNA analog (2′F-ANA) with rigid RNA analogs [2′F-RNA and/or locked nucleic acid (LNA)] in siRNA duplexes can produce gene silencing agents with enhanced potency. The favored conformations of these two analogs are different, and combining them in a 1–1 pattern led to reduced affinity, whereas alternating short continuous regions of individual modifications increased affinity relative to an RNA:RNA duplex. Thus, the binding affinity at key regions of the siRNA duplex could be tuned by changing the pattern of incorporation of DNA-like and RNA-like nucleotides. These heavily or fully modified duplexes are active against a range of mRNA targets. Effective patterns of modification were chosen based on screens using two sequences targeting firefly luciferase. We then applied the most effective duplex designs to the knockdown of the eIF4E binding proteins 4E-BP1 and 4E-BP2. We identified modified duplexes with potency comparable to native siRNA. Modified duplexes showed dramatically enhanced stability to serum nucleases, and were characterized by circular dichroism and thermal denaturation studies. Chemical modification significantly reduced the immunostimulatory properties of these siRNAs in human peripheral blood mononuclear cells

WISE/NEOWISE observations of Active Bodies in the Main Belt

We report results based on mid-infrared photometry of 5 active main belt objects (AMBOs) detected by the Wide-field Infrared Survey Explorer (WISE) spacecraft. Four of these bodies, P/2010 R2 (La Sagra), 133P/Elst-Pizarro, (596) Scheila, and 176P/LINEAR, showed no signs of activity at the time of the observations, allowing the WISE detections to place firm constraints on their diameters and albedos. Geometric albedos were in the range of a few percent, and on the order of other measured comet nuclei. P/2010 A2 was observed on April 2-3, 2010, three months after its peak activity. Photometry of the coma at 12 and 22 {\mu}m combined with ground-based visible-wavelength measurements provides constraints on the dust particle mass distribution (PMD), dlogn/dlogm, yielding power-law slope values of {\alpha} = -0.5 +/- 0.1. This PMD is considerably more shallow than that found for other comets, in particular inbound particle fluence during the Stardust encounter of comet 81P/Wild 2. It is similar to the PMD seen for 9P/Tempel 1 in the immediate aftermath of the Deep Impact experiment. Upper limits for CO2 & CO production are also provided for each AMBO and compared with revised production numbers for WISE observations of 103P/Hartley 2.Comment: 32 Pages, including 5 Figure

Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR/4E-BP1 signaling

SummaryProtein synthesis is critical for circadian clock function, but little is known of how translational regulation controls the master pacemaker in mammals, the suprachiasmatic nucleus (SCN). Here we demonstrate that the pivotal translational repressor, the eukaryotic translational initiation factor 4E binding protein 1 (4E-BP1), is rhythmically regulated via the mechanistic target of rapamycin (mTOR) signaling in the SCN and preferentially represses vasoactive intestinal peptide (Vip) mRNA translation. Knockout (KO) of Eif4ebp1 (gene encoding 4E-BP1) leads to upregulation of VIP and higher amplitude of molecular rhythms in the SCN. Consequently, the 4E-BP1 null mice exhibit accelerated re-entrainment to a shifted light/dark cycle and are more resistant to the rhythm-disruptive effects of constant light. Conversely, in Mtor+/− mice VIP expression is decreased and susceptibility to the effects of constant light is increased. These results reveal a key role for mTOR/4E-BP1-mediated translational control in regulating entrainment and synchrony of the master clock

The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

The intracellular parasite Toxoplasma gondii promotes infection by targeting multiple host cell processes; however, whether it modulates mRNA translation is currently unknown. Here, we show that infection of primary murine macrophages with type I or II T. gondii strains causes a profound perturbation of the host cell translatome. Notably, translation of transcripts encoding proteins involved in metabolic activity and components of the translation machinery was activated upon infection. In contrast, the translational efficiency of mRNAs related to immune cell activation and cytoskeleton/cytoplasm organization was largely suppressed. Mechanistically, T. gondii bolstered mechanistic target of rapamycin (mTOR) signaling to selectively activate the translation of mTOR-sensitive mRNAs, including those with a 5'-terminal oligopyrimidine (5' TOP) motif and those encoding mitochondrion-related proteins. Consistent with parasite modulation of host mTOR-sensitive translation to promote infection, inhibition of mTOR activity suppressed T. gondii replication. Thus, selective reprogramming of host mRNA translation represents an important subversion strategy during T. gondii infection

S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3

Cytosolic DNA-mediated activation of the transcription factor IRF3 is a key event in host antiviral responses. Here we found that infection with DNA viruses induced interaction of the metabolic checkpoint kinase mTOR downstream effector and kinase S6K1 and the signaling adaptor STING in a manner dependent on the DNA sensor cGAS. We further demonstrated that the kinase domain, but not the kinase function, of S6K1 was required for the S6K1-STING interaction and that the TBK1 critically promoted this process. The formation of a tripartite S6K1-STING-TBK1 complex was necessary for the activation of IRF3, and disruption of this signaling axis impaired the early-phase expression of IRF3 target genes and the induction of T cell responses and mucosal antiviral immunity. Thus, our results have uncovered a fundamental regulatory mechanism for the activation of IRF3 in the cytosolic DNA pathway