1,354,386 research outputs found
Pre-positioning of emergency supplies: does putting a price on human life help to save lives?
No full textUtilising novel therapies in the treatment of gastrointestinal cancers
No full textBackground:
Gastrointestinal (GI) malignancies are common and frequently lethal diseases. For most, treatment options revolve around chemotherapy where efficacy beyond second line is negligible, and toxicity is high. Novel and better tolerated treatments which improve survival are thus urgently required.
Hypothesis:
Recently elucidated oncogenic pathways in oesophagogastric and colorectal cancer can be therapeutically exploited for patient benefit.
Results:
1. Based on pre-clinical models of c-MYC/HER2 amplified OG cancer which demonstrated a profound synthetic lethal interaction with BTK inhibition, 8 patients with c-MYC/HER2 amplified oesophagogastric cancer were treated with the BTK-inhibitor ibrutinib in the iMYC trial. No responses were observed; however, one patient with a dual c-MYC and HER2 co-amplified tumour achieved disease control for 32 weeks with a marked metabolic response in the primary tumour. Grade >3 GI haemorrhage occurred in 3 patients and was fatal in 2 cases which was considered a new safety finding for ibrutinib in this population.
2. Dermatinostat (HDAC inhibitor) can favourably reprogramme the TME for collaboration with ICIs. The combination of domatinostat and avelumab was found to be safe and tolerable in patients with OGA and CRC in the phase IIa EMERGE study. 5 patients with CRC experienced disease control at 6 months and 1 patient with OGA had a PR. Domatinostat 200mg BD combined with avelumab 10mg/kg was determined as the R2PD.
3. DKK1 modulates Wnt/beta-catenin signalling and promotes a T cell excluded or 'immune desert' TME. The DKK1 neutralising antibody, DKN-01, in combination with atezolizumab was found to be safe and tolerable in 11 patients treated in the phase IIa WAKING study. One patient with DKK1-high tumour achieved a PR. DKN-01 600mg with atezolizumab 840mg was the R2PD for ongoing expansion phase.
Conclusion:
Some signals of efficacy have been seen in these early trials of novel therapies in GI cancer patients. Consideration into how to deal with intratumoural heterogeneity and incorporate novel trial design into future efforts to evaluate new therapies will be required
Contemporary Tailored Oncology Treatment of Biliary Tract Cancers.
No full textBiliary tract cancers (BTCs) are poor prognosis malignancies with limited treatment options. Capecitabine has recently emerged as an effective agent in the adjuvant setting; however, treatment of advanced disease is still limited to first-line cisplatin and gemcitabine chemotherapy. Recent global efforts in genomic profiling and molecular subtyping of BTCs have uncovered a wealth of genomic aberrations which may carry prognostic significance and/or predict response to treatment, and several targeted agents have shown promising results in clinical trials. As such, the uptake of comprehensive genomic profiling for patients with BTCs and the expansion of basket trials to include these patients are growing. This review describes the currently approved systemic therapies for BTCs and provides insight into the emerging targeted and immunotherapeutic agents, as well as conventional chemotherapeutic regimes, currently being investigated in clinical trials
The lives of the Othoman kings and emperors: [electronic resource] : faithfully gathered outof the best histories, both antient and moderne and digested into one continuat historie /
No full textDetached from Knolles' "The generall historie of the Turkes."Fragments: E4:1[138a] has engraved head-piece, initial "W", and tail-piece from preliminiaries; E4:1[139b] has a head-piece used variously throughout the work; E4:1[140] has sub t.p. "The lives of the Othoman kings and emperors..., 1609"; E4:1[141] is portrait from p. 130; E4:1[142] is initial letter "T" found at p. [5] of prelims. and p. 499; E4:1[143a] has port. at p. 245; E4:1[145b-c] are ports. found at p. 335 and 245 respectively; E4:1[146a] has port. found at p. 230; E4:1[147b] has port found at p. 202; E4:1[148a-b] has ports. found at p. 188 and 239 respectively."The liues of the Othoman kings and emperors" has separate title page dated 1609; pagination and register are continuous.Reproduction of original in the British Library.STC (2nd ed.)Early English books tract supplement interim guideElectronic reproduction
Alparslan Turkes in the Process Towards Discharge on November 13, 1960 and a Dispute Within the National Unity Committee
No full textThe National Unity Committee formed by the soldiers after the coup on May 27 had a very heterogeneous identity. In addition to the composition of the committee with various ranks and age groups, the disagreements among the members led to division around roughly two groups. The head of one of these groups was Alparslan Turkes, who became the Undersecretary of the Prime Ministry after the coup, while the other was Cemal Madanoglu. Alparslan Turkes gained the sympathies of the officers, especially who were relatively young in the Committee, besides his identity as a Colonel, and this group wished to make the National Unity Committee implement the reforms that Ataturk could not have completed. Thus, while this group was classified as "radicals", Turkes was described as the "Mighty Colonel of Coup", inspired from Nasser, the nationalist-socialist leader of his time. On the other hand, Madanoglu's group acted with the thought of "transfer of the administration to the civilians by making the elections as soon as possible". Due to this difference of this basic mentality between the two views, together with other problems, the Committee carried out an auto-discharge on November 13, 1960 and 14 members, including Turkes, were appointed as civil servants abroad
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
- …
