Multimodal Treatment Eliminates Cancer Stem Cells and Leads to Long-Term Survival in Primary Human Pancreatic Cancer Tissue Xenografts.

Copyright: 2013 Hermann et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PURPOSE: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. EXPERIMENTAL DESIGN: Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. RESULTS: The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. CONCLUSIONS: This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma

Decoherence-Free Rotational Degrees of Freedom for Quantum Applications

We employ spherical $t$-designs for the systematic construction of solids whose rotational degrees of freedom can be made robust to decoherence due to external fluctuating fields while simultaneously retaining their sensitivity to signals of interest. Specifically, the ratio of signal phase accumulation rate from a nearby source to the decoherence rate caused by fluctuating fields from more distant sources can be incremented to any desired level by using increasingly complex shapes. This allows for the generation of long-lived macroscopic quantum superpositions of rotational degrees of freedom and the robust generation of entanglement between two or more such solids with applications in robust quantum sensing and precision metrology as well as quantum registers

Double-degenerate Fermi mixtures of 6^6Li and 53^{53}Cr atoms

We report on the realization of a novel degenerate mixture of ultracold fermionic lithium and chromium atoms. Based on an all-optical approach, with an overall duty-cycle of about 13 seconds, we produce large and degenerate samples of more than 2$\times 10^5$ $^6$Li atoms and $10^5$ $^{53}$Cr atoms, with both species exhibiting normalized temperatures of about $T/T_{F}$=0.25. Additionally, through the exploitation of a crossed bichromatic optical dipole trap, we can controllably vary the density and degree of degeneracy of the two components almost independently, and widely tune the lithium-to-chromium density ratio. Our $^{6}$Li-$^{53}$Cr Fermi mixture opens the way to the investigation of a variety of exotic few- and many-body regimes of quantum matter, and it appears as an optimally-suited system to realize ultracold paramagnetic polar molecules, characterized by both electric and magnetic dipole moments. Ultimately, our strategy also provides an efficient pathway to produce dipolar Fermi gases, or spin-mixtures, of ultracold $^{53}$Cr atoms.Comment: 14 pages, 5 figure

Effectiveness and cost-effectiveness of a patient-initiated botulinum toxin treatment model for blepharospasm and hemifacial spasm: a study protocol for a randomised controlled trial

Background Blepharospasm and hemifacial spasm are debilitating conditions that significantly impact on patient quality of life. Cyclical treatment with botulinum toxin injections offers temporary relief, but the duration of treatment efficacy is variable. The standard model of patient care defines routine fixed-time based scheduled treatment cycles which may lead to unnecessarily frequent treatment for some patients and experience of distressing symptoms in others, if symptoms return before the scheduled follow-up period. Methods/Design A randomised controlled trial will compare a patient-initiated model of care, where patients determine botulinum toxin treatment timing, to the standard model of care in which care is scheduled by the clinical team. A sample of 266 patients with blepharospasm or hemifacial spasm will be recruited from Moorfields Eye Hospital (MEH), London. The trial will be accompanied by a mixed methods evaluation of acceptability of the new service. Patients who meet eligibility criteria will be assessed at baseline and those in the intervention group will be provided instructions on how to book their own treatment appointments. Patients in both groups will be followed up 3 and 9 months into the trial and all patients will be returned to usual care after 9 months to meet safety protocols. Primary outcome measures include disease severity (questionnaire), functional disability (questionnaire) and patient satisfaction with care (questionnaire). Secondary outcomes include disease-specific quality of life (questionnaire), mood (questionnaire), illness and treatment perceptions (questionnaire and semi-structured interviews), economic impact (questionnaire) and acceptability (questionnaire and semi-structured interviews). Discussion This trial will assess the effectiveness and cost-effectiveness of a patient-led care model for botulinum toxin therapy. If the new model is shown to be effective in reducing distress and disability in these populations and is found to be acceptable to patients, whilst being cost-effective, this will have significant implications for service organisation across the NHS. Trial registration UK Clinical Research Network (UKCRN) Portfolio 18660. Clinicaltrials.gov ID NCT102577224 (registered 29th October 2015

What is the relationship between validated frailty scores and mortality for adults with COVID-19 in acute hospital care? A systematic review

Background & aim: The aim of this systematic review was to quantify the association between frailty and COVID-19 in relation to mortality in hospitalised patients. / Methods: Medline, Embase, Web of Science and the grey literature were searched for papers from inception to 10th September 2020; the search was re-run in Medline up until the 9th December 2020. Screening, data extraction and quality grading were undertaken by two reviewers. Results were summarised using descriptive statistics, including a meta-analysis of overall mortality; the relationships between frailty and COVID-19 mortality were summarised narratively. / Results: 2,286 papers were screened resulting in 26 being included in the review. Most studies were from Europe, half from the UK, and one from Brazil; the median sample size was 242.5, median age 73.1 and 43.5% were female. 22/26 used the Clinical Frailty Scale; reported mortality ranged from 14 to 65%. Most, but not all studies showed an association between increasing frailty and a greater risk of dying. Two studies indicated a sub-additive relationship between frailty, COVID-19 and death, and two studies showed no association. / Conclusions: Whilst the majority of studies have shown a positive association between COVID-19 related death and increasing frailty, some studies suggested a more nuanced understanding of frailty and outcomes in COVID-19 is needed. Clinicians should exert caution in placing too much emphasis on the influence of frailty alone when discussing likely prognosis in older people with COVID-19 illness

Momentum-resolved and correlation spectroscopy using quantum probes

We address some key conditions under which many-body lattice models, intended mainly as simulated condensed-matter systems, can be investigated via immersed, fully controllable quantum objects, namely quantum probes. First, we present a protocol that, for a certain class of many-body systems, allows for full momentum-resolved spectroscopy using one single probe. Furthermore, we demonstrate how one can extract the two-point correlations using two entangled probes. We apply our theoretical proposal to two well-known exactly solvable lattice models, a one-dimensional (1D) Kitaev chain and 2D superfluid Bose-Hubbard model, and show its accuracy as well as its robustness against external noise