Divyalakshmi Bhaskaran, Joshua Savage, Amit Patel
et al.
Abstract Background Glioblastoma (GBM) is the most common adult malignant brain tumour, with an incidence of 5 per 100,000 per year in England. Patients with tumours showing O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation represent around 40% of newly diagnosed GBM. Relapse/tumour recurrence is inevitable. There is no agreed standard treatment for patients with GBM, therefore, it is aimed at delaying further tumour progression and maintaining health-related quality of life (HRQoL). Limited clinical trial data exist using cannabinoids in combination with temozolomide (TMZ) in this setting, but early phase data demonstrate prolonged overall survival compared to TMZ alone, with few additional side effects. Jazz Pharmaceuticals (previously GW Pharma Ltd.) have developed nabiximols (trade name Sativex®), an oromucosal spray containing a blend of cannabis plant extracts, that we aim to assess for preliminary efficacy in patients with recurrent GBM. Methods ARISTOCRAT is a phase II, multi-centre, double-blind, placebo-controlled, randomised trial to assess cannabinoids in patients with recurrent MGMT methylated GBM who are suitable for treatment with TMZ. Patients who have relapsed ≥ 3 months after completion of initial first-line treatment will be randomised 2:1 to receive either nabiximols or placebo in combination with TMZ. The primary outcome is overall survival time defined as the time in whole days from the date of randomisation to the date of death from any cause. Secondary outcomes include overall survival at 12 months, progression-free survival time, HRQoL (using patient reported outcomes from QLQ-C30, QLQ-BN20 and EQ-5D-5L questionnaires), and adverse events. Discussion Patients with recurrent MGMT promoter methylated GBM represent a relatively good prognosis sub-group of patients with GBM. However, their median survival remains poor and, therefore, more effective treatments are needed. The phase II design of this trial was chosen, rather than phase III, due to the lack of data currently available on cannabinoid efficacy in this setting. A randomised, double-blind, placebo-controlled trial will ensure an unbiased robust evaluation of the treatment and will allow potential expansion of recruitment into a phase III trial should the emerging phase II results warrant this development. Trial registration ISRCTN: 11460478. ClinicalTrials.Gov: NCT05629702.
Abstract Purpose Self-management can have clinical and quality-of-life benefits. However, people with lower-grade gliomas (LGG) may face chronic tumour- and/or treatment-related symptoms and impairments (e.g. cognitive deficits, seizures), which could influence their ability to self-manage. Our study aimed to identify and understand the barriers and facilitators to self-management in people with LGG. Methods We conducted semi-structured interviews with 28 people with LGG across the United Kingdom, who had completed primary treatment. Sixteen participants were male, mean age was 50.4 years, and mean time since diagnosis was 8.7 years. Interviews were audio-recorded and transcribed. Following inductive open coding, we deductively mapped codes to Schulman-Green et al.’s framework of factors influencing self-management, developed in chronic illness. Results Data suggested extensive support for all five framework categories (‘Personal/lifestyle characteristics’, ‘Health status’, ‘Resources’, ‘Environmental characteristics’, ‘Healthcare system’), encompassing all 18 factors influencing self-management. How people with LGG experience many of these factors appears somewhat distinct from other cancers; participants described multiple, often co-occurring, challenges, primarily with knowledge and acceptance of their incurable condition, the impact of seizures and cognitive deficits, transport difficulties, and access to (in)formal support. Several factors were on a continuum, for example, sufficient knowledge was a facilitator, whereas lack thereof, was a barrier to self-management. Conclusions People with LGG described distinctive experiences with wide-ranging factors influencing their ability to self-manage. Implications for cancer survivors These findings will improve awareness of the potential challenges faced by people with LGG around self-management and inform development of self-management interventions for this population.
Given a function $f \in \omega^\omega$, a set $A \in [\omega]^\omega$ is free for $f$ if $f[A] \cap A$ is finite. For a class of functions $\Gamma \subseteq \omega^{\omega}$, we define $\mathfrak{ros}_\Gamma$ as the smallest size of a family $\mathcal{A}\subseteq [\omega]^\omega$ such that for every $f\in\Gamma$ there is a set $A \in \mathcal{A}$ which is free for $f$, and $\Delta_\Gamma$ as the smallest size of a family $\mathcal{F}\subseteq\Gamma$ such that for every $A\in[\omega]^\omega$ there is $f\in\mathcal{F}$ such that $A$ is not free for $f$. We compare several versions of these cardinal invariants with some of the classical cardinal characteristics of the continuum. Using these notions, we partially answer some questions from arXiv:1911.01336 [math.LO] and arXiv:2004.01979 [math.GN].
Abstract Purpose Lower-grade gliomas (LGG) are mostly diagnosed in working-aged adults and rarely cured. LGG patients may face chronic impairments (e.g. fatigue, cognitive deficits). Self-management can improve clinical and psychosocial outcomes, yet how LGG patients self-manage the consequences of their tumour and its treatment is not fully understood. This study, therefore, aimed to identify and understand how LGG patients engage in the self-management of their condition. Methods A diverse group of 28 LGG patients (age range 22–69 years; male n = 16, female n = 12; mean time since diagnosis = 8.7 years) who had completed primary treatment, were recruited from across the United Kingdom. Semi-structured interviews were conducted. Informed by a self-management strategy framework developed in cancer, directed content analysis identified and categorised self-management types and strategies used by patients. Results Overall, 20 self-management strategy types, comprising 123 self-management strategies were reported; each participant detailed extensive engagement in self-management. The most used strategy types were ‘using support’ (n = 28), ‘creating a healthy environment’ (n = 28), ‘meaning making’ (n = 27), and ‘self-monitoring’ (n = 27). The most used strategies were ‘accepting the tumour and its consequences’ (n = 26), ‘receiving support from friends (n = 24) and family’ (n = 24), and ‘reinterpreting negative consequences’ (n = 24). Conclusions This study provides a comprehensive understanding of the strategies used by LGG patients to self-manage their health and wellbeing, with a diverse, and substantial number of self-management strategies reported. Implications for Cancer Survivors The findings will inform the development of a supported self-management intervention for LGG patients, which will be novel for this patient group.
Yasmin Boyle, Terrance G. Johns, Emily V. Fletcher
Malignant central nervous system (CNS) cancers are among the most difficult to treat, with low rates of survival and a high likelihood of recurrence. This is primarily due to their location within the CNS, hindering adequate drug delivery and tumour access via surgery. Furthermore, CNS cancer cells are highly plastic, an adaptive property that enables them to bypass targeted treatment strategies and develop drug resistance. Potassium ion channels have long been implicated in the progression of many cancers due to their integral role in several hallmarks of the disease. Here, we will explore this relationship further, with a focus on malignant CNS cancers, including high-grade glioma (HGG). HGG is the most lethal form of primary brain tumour in adults, with the majority of patient mortality attributed to drug-resistant secondary tumours. Hence, targeting proteins that are integral to cellular plasticity could reduce tumour recurrence, improving survival. This review summarises the role of potassium ion channels in malignant CNS cancers, specifically how they contribute to proliferation, invasion, metastasis, angiogenesis, and plasticity. We will also explore how specific modulation of these proteins may provide a novel way to overcome drug resistance and improve patient outcomes.
\"{O}zavsar and Cevikel(Fixed point of multiplicative contraction mappings on multiplicative metric space.arXiv:1205.5131v1 [math.GN] 23 may 2012)initiated the concept of the multiplicative metric space in such a way that the usual triangular inequality is replaced by "multiplicative triangle inequality $d(x,y)\leq d(x,z).d(z,y)$ for all $x,y,z\in X$". In this manuscript, we discussed some unique fixed point theorems in the context of multiplicative metric spaces. The established results carry some well known results from the literature to multiplicative metric space. We note that some fixed point theorems can be deduced in multiplicative metric space by using the established results. Appropriate examples are also given.
This paper is the first part of a series which provides a systematic treatment of the space-filling curves of self-similar sets. In the present paper, we introduce a notion of linear graph-directed IFS (linear GIFS in short). We show that to construct a space-filling curve of a self-similar set, it amounts to exploring its linear GIFS structures. Compared to the previous methods, such as the L-system or recurrent set method, the linear GIFS approach is simpler, more rigorous and leads to further studies on this topic. We also propose a new algorithm for the beautiful visualization of space-filling curves. In a series of papers Dai et al (2015 arXiv:1511.05411 [math.GN]), Rao and Zhang (2015) and Rao and Zhang (2015), we investigate for a given self-similar set how to get ‘substitution rules’ for constructing space-filling curves, which was obscure in the literature. We solve the problem for self-similar sets of finite type, which covers most of the known results on constructions of space-filling curves.
We present a notion of precompactness, and study some of its properties, in
the context of apartness spaces whose apartness structure is not necessarily
induced by any uniform one. The presentation lies entirely with a Bishop-style
constructive framework, and is a contribution to the ongoing development of the
constructive theories of apartness and uniformity.
Abstract Machura, Shelah and Tsaban showed in [M. Machura, S. Shelah, B. Tsaban, Squares of Menger-bounded groups, Trans. Amer. Math. Soc., in press, http://arxiv.org/pdf/math.GN/0611353 , 2007] that under the condition, that a relative d ′ ( P ) of the dominating number is at least d , there are subgroups of the Baer–Specker group whose kth power is Menger-bounded and whose ( k + 1 ) st power is not. We show that the sufficient condition implies r ⩾ d and indeed can be replaced by r ⩾ d . This result includes an affirmative answer to a question by Tsaban on a possibly weaker still sufficient condition. We show that it is consistent relative to ZFC that g ⩽ r d and there are subgroups of the Baer–Specker group whose kth power is Menger-bounded and whose ( k + 1 ) st power is not.
This is the second issue of the SPM Bulletin (SPM stands for "Selection Principles in Mathematics"). The first issue is math.GN/0301011 and contains some background and details.