Ibrutinib has shown activity in non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL). This double-blind phase III study evaluated ibrutinib and rituximab plus cyclophosphamide, ...doxorubicin, vincristine, and prednisone (R-CHOP) in untreated non-germinal center B-cell DLBCL.
Patients were randomly assigned at a one-to-one ratio to ibrutinib (560 mg per day orally) plus R-CHOP or placebo plus R-CHOP. The primary end point was event-free survival (EFS) in the intent-to-treat (ITT) population and the activated B-cell (ABC) DLBCL subgroup. Secondary end points included progression-free survival (PFS), overall survival (OS), and safety.
A total of 838 patients were randomly assigned to ibrutinib plus R-CHOP (n = 419) or placebo plus R-CHOP (n = 419). Median age was 62.0 years; 75.9% of evaluable patients had ABC subtype disease, and baseline characteristics were balanced. Ibrutinib plus R-CHOP did not improve EFS in the ITT (hazard ratio HR, 0.934) or ABC (HR, 0.949) population. A preplanned analysis showed a significant interaction between treatment and age. In patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS (HR, 0.579), PFS (HR, 0.556), and OS (HR, 0.330) and slightly increased serious adverse events (35.7%
28.6%), but the proportion of patients receiving at least six cycles of R-CHOP was similar between treatment arms (92.9%
93.0%). In patients age 60 years or older, ibrutinib plus R-CHOP worsened EFS, PFS, and OS, increased serious adverse events (63.4%
38.2%), and decreased the proportion of patients receiving at least six cycles of R-CHOP (73.7%
88.8%).
The study did not meet its primary end point in the ITT or ABC population. However, in patients age younger than 60 years, ibrutinib plus R-CHOP improved EFS, PFS, and OS with manageable safety. In patients age 60 years or older, ibrutinib plus R-CHOP was associated with increased toxicity, leading to compromised R-CHOP administration and worse outcomes. Further investigation is warranted.
To provide evidence-based recommendations on the treatment of multiple myeloma to practicing physicians and others.
ASCO and Cancer Care Ontario convened an Expert Panel of medical oncology, surgery, ...radiation oncology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and some phase II studies published from 2005 through 2018. Outcomes of interest included survival, progression-free survival, response rate, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.
The literature search identified 124 relevant studies to inform the evidence base for this guideline.
Evidence-based recommendations were developed for patients with multiple myeloma who are transplantation eligible and those who are ineligible and for patients with relapsed or refractory disease.
We construct a consistent Kaluza-Klein reduction of D = 11 supergravity on , where or H2, or a quotient thereof, at the level of the bosonic fields. The result is a gauged N = 4, D = 5 ...supergravity theory coupled to three vector multiplets, with the gauging lying in an subgroup of the global symmetry group of the ungauged theory. For , the D = 5 theory has a maximally supersymmetric AdS5 vacuum which uplifts to the known solution of D = 11 supergravity corresponding to M5-branes wrapping a Riemann surface with genus greater than one and dual to an N = 2 SCFT in d = 4. For , we find two AdS5 solutions, one of which is new, and both of which are unstable. There is an additional subtruncation to an N = 2 gauged supergravity coupled to two vector multiplets, with very special real manifold , and a single hypermultiplet, with quaternionic Kähler manifold and gauging associated with an subgroup.
The two main functions of bioinformatics are the organization and analysis of biological data using computational resources. Geneious Basic has been designed to be an easy-to-use and flexible desktop ...software application framework for the organization and analysis of biological data, with a focus on molecular sequences and related data types. It integrates numerous industry-standard discovery analysis tools, with interactive visualizations to generate publication-ready images. One key contribution to researchers in the life sciences is the Geneious public application programming interface (API) that affords the ability to leverage the existing framework of the Geneious Basic software platform for virtually unlimited extension and customization. The result is an increase in the speed and quality of development of computation tools for the life sciences, due to the functionality and graphical user interface available to the developer through the public API. Geneious Basic represents an ideal platform for the bioinformatics community to leverage existing components and to integrate their own specific requirements for the discovery, analysis and visualization of biological data.
Binaries and public API freely available for download at http://www.geneious.com/basic, implemented in Java and supported on Linux, Apple OSX and MS Windows. The software is also available from the Bio-Linux package repository at http://nebc.nerc.ac.uk/news/geneiousonbl.
A
bstract
We construct consistent Kaluza-Klein truncations of type IIA supergravity on (i) Σ
2
×
S
3
and (ii) Σ
3
×
S
3
, where Σ
2
=
S
2
/
Γ, ℝ
2
/
Γ, or ℍ
2
/
Γ, and Σ
3
=
S
3
/
Γ, ℝ
3
/
Γ, or ℍ
3
.../
Γ, with Γ a discrete group of symmetries, corresponding to NS5-branes wrapped on Σ
2
and Σ
3
. The resulting theories are a
D
= 5,
N
= 4 gauged supergravity coupled to three vector multiplets with scalar manifold SO(1
,
1) × SO(5
,
3)
/
(SO(5) × SO(3)) and gauge group SO(2) × (SO(2)
⋉
Σ
2
ℝ
4
) which depends on the curvature of Σ
2
, and a
D
= 4,
N
= 2 gauged supergravity coupled to one vector multiplet and two hypermultiplets with scalar manifold SU(1
,
1)
/
U(1) ×
G
2(2)
/
SO(4) and gauge group ℝ
+
× ℝ
+
for truncations (i) and (ii) respectively. Instead of carrying out the truncations at the 10-dimensional level, we show that they can be obtained directly by performing Inönü-Wigner contractions on the 5 and 4-dimensional gauged supergravity theories that come from consistent truncations of 11-dimensional supergravity associated with M5-branes wrapping Σ
2
and Σ
3
. This suggests the existence of a broader class of lower-dimensional gauged supergravity theories related by group contractions that have a 10 or 11-dimensional origin.
This paper reports the findings of a qualitative study on a group of mainland Chinese students' multilingual experiences during their cross-border studies in a Hong Kong university from a language ...ideological perspective. Drawing on in-depth interviews as the primary dataset, the study investigated the language ideologies held by the participants about Cantonese, Putonghua and English. Findings indicated that while the participants espoused a distinct set of language ideologies about Cantonese, Putonghua and English underlying their multilingual experiences in the university, the ideology of language as identity and the ideology of language as commodity emerged as the two major language ideologies. It was also revealed that the ideological tensions arising from the co-existence of the multiple and competing language ideologies resulted in the participants' ambivalences in their use of, and/or investment in, particular languages. Findings also point to the role of the participants' language ideologies in maintaining the social hierarchy of languages within the local language ecology and reproducing the group boundaries between local and mainland Chinese students.
The treatment outcome for diffuse large B-cell lymphoma has not been improved in nearly 20 years. However, the replacement of vincristine in R-CHOP with polatuzumab vedotin, an anti-CD79b antibody ...linked to emtansine, led to a progression-free survival benefit over R-CHOP at 2 years (76.7% vs. 70.2%), with a similar safety profile.
A
bstract
We construct infinite new classes of AdS
4
× S
1
× S
5
solutions of type IIB string theory which have non-trivial SL(2
,
ℤ) monodromy along the
S
1
direction. The solutions are ...supersymmetric and holographically dual, generically, to
N
= 1 SCFTs in
d
= 3. The solutions are first constructed as AdS
4
×
ℝ solutions in
D
= 5 SO(6) gauged supergravity and then uplifted to
D
= 10. Unlike the known AdS
4
×
ℝ S-fold solutions, there is no continuous symmetry associated with the ℝ direction. The solutions all arise as limiting cases of Janus solutions of
d
= 4,
N
= 4 SYM theory which are supported both by a different value of the coupling constant on either side of the interface, as well as by fermion and boson mass deformations. As special cases, the construction recovers three known S-fold constructions, preserving
N
= 1
,
2 and 4 supersymmetry, as well as a recently constructed
N
= 1 AdS
4
× S
1
× S
5
solution (not S-folded). We also present some novel “one-sided Janus” solutions that are non-singular.
This paper reports findings of a qualitative study that explored international students' identity negotiation during their cross-border studies against the backdrop of the internationalisation of ...higher education in Asia. Through a comparative narrative-based case study of two Burmese international students' experiences during their studies in a Hong Kong university, the paper reveals both similarities and differences in their negotiation of (i) identities as 'non-local'/'international' students in the university context and (ii) national identities in relation to the local community and the imagined global/international community. In particular, the findings illustrate the divergent ways in which the two international students negotiate the meanings they attach to the 'non-local' student label, respond to local students' (mis)recognition of their national identities, and perceive the (in)compatibility between their national and global identities. Overall, the findings point to the diversity and heterogeneity in international students' experiences which appear to be variably shaped by differential dispositions and capacities in exercising strategic agency for identity (re)construction. The case study also calls for the need to problematise the reification and over-simplification of the so-called 'international student experience' and argues for the importance of paying attention to the complexity of international students' identity negotiation in the context of international education.
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