Circulating cell-free DNA: Translating prostate cancer genomics into clinical care.

Only in the past decade tremendous advances have been made in understanding prostate cancer genomics and consequently in applying new treatment strategies. As options regarding treatments are increasing so are the challenges in selecting the right treatment option for each patient and not the least, understanding the optimal time-point and sequence of applying available treatments. Critically, without reliable methods that enable sequential monitoring of evolving genotypes in individual patients, we will never reach effective personalised driven treatment approaches. This review focuses on the clinical implications of prostate cancer genomics and the potential of cfDNA in facilitating treatment management

Galactic Cepheids with Spitzer: I. Leavitt Law and Colors

Classical Cepheid variable stars have been important indicators of extragalactic distance and Galactic evolution for over a century. The Spitzer Space Telescope has opened the possibility of extending the study of Cepheids into the mid- and far-infrared, where interstellar extinction is reduced. We have obtained photometry from images of a sample of Galactic Cepheids with the IRAC and MIPS instruments on Spitzer. Here we present the first mid-infrared period-luminosity relations for Classical Cepheids in the Galaxy, and the first ever Cepheid period-luminosity relations at 24 and 70 um. We compare these relations with theoretical predictions, and with period-luminosity relations obtained in recent studies of the Large Magellanic Cloud. We find a significant period-color relation for the [3.6]-[8.0] IRAC color. Other mid-infrared colors for both Cepheids and non-variable supergiants are strongly affected by variable molecular spectral features, in particular deep CO absorption bands. We do not find strong evidence for mid-infrared excess caused by warm (~500 K) circumstellar dust. We discuss the possibility that recent detections with near-infrared interferometers of circumstellar shells around delta Cep, l Car, Polaris, Y Oph and RS Pup may be a signature of shocked gas emission in a dust-poor wind associated to pulsation-driven mass loss.Comment: Accepted by The Astrophysical Journal on Nov 11, 200

Superconductivity in a Molecular Metal Cluster Compound

Compelling evidence for band-type conductivity and even bulk superconductivity below $T\_{\text{c}}\approx 8$ K has been found in $^{69,71}$Ga-NMR experiments in crystalline ordered, giant Ga$\_{84}$ cluster-compounds. This material appears to represent the first realization of a theoretical model proposed by Friedel in 1992 for superconductivity in ordered arrays of weakly coupled, identical metal nanoparticles.Comment: 5 pages, 4 figure

Cepheid Mass-loss and the Pulsation -- Evolutionary Mass Discrepancy

I investigate the discrepancy between the evolution and pulsation masses for Cepheid variables. A number of recent works have proposed that non-canonical mass-loss can account for the mass discrepancy. This mass-loss would be such that a 5Mo star loses approximately 20% of its mass by arriving at the Cepheid instability strip; a 14Mo star, none. Such findings would pose a serious challenge to our understanding of mass-loss. I revisit these results in light of the Padova stellar evolutionary models and find evolutionary masses are ($17\pm5$)% greater than pulsation masses for Cepheids between 5<M/Mo<14. I find that mild internal mixing in the main-sequence progenitor of the Cepheid are able to account for this mass discrepancy.Comment: 15 pages, 3 figures, ApJ accepte

Muon Spin Relaxation Studies of Superconductivity in a Crystalline Array of Weakly Coupled Metal Nanoparticles

We report Muon Spin Relaxation studies in weak transverse fields of the superconductivity in the metal cluster compound, Ga$\_{84}$[N(SiMe$\_{3}$)$\_{2}$]$\_{20}$-Li$\_{6}$Br$\_{2}$(thf)$\_{20}\cdot$2toluene. The temperature and field dependence of the muon spin relaxation rate and Knight shift clearly evidence type II bulk superconductivity below $T\_{\text{c}}\approx7.8$ K, with $B\_{\text{c1}}\approx 0.06$ T, $B\_{\text{c2}}\approx 0.26$ T, $\kappa\sim 2$ and weak flux pinning. The data are well described by the s-wave BCS model with weak electron-phonon coupling in the clean limit. A qualitative explanation for the conduction mechanism in this novel type of narrow band superconductor is presented.Comment: 4 figures, 5 page

Reactome - a knowledgebase of human biological pathways

Pathway curation is a powerful tool for systematically associating gene products with functions. Reactome (www.reactome.org) is a manually curated human pathway knowledgebase describing a wide range of biological processes in a computationally accessible manner. The core unit of the Reactome data model is the Reaction, whose instances form a network of biological interactions through entities that are consumed, produced, or act as catalysts. Entities are distinguished by their molecular identities and cellular locations. Set objects allow grouping of related entities. Curation is based on communication between expert authors and staff curators, facilitated by freely available data entry tools. Manually curated data are subjected to quality control and peer review by a second expert. Reactome data are released quarterly. At release time, electronic orthology inference performed on human data produces reaction predictions in 22 species ranging from mouse to bacteria. Cross-references to a large number of publicly available databases are attached, providing multiple entry points into the database. The Reactome Mart allows query submission and data retrieval from Reactome and across other databases. The SkyPainter tool provides visualization and statistical analysis of user supplied data, e.g. from microarray experiments. Reactome data are freely available in a number of data formats (e.g. BioPax, SBML)

Validation of the log e–log σ normal compression law using particle strength data

This note is a study of experimental data on particle strength and normal compression, to establish whether the recently proposed normal compression law by McDowell and de Bono (2013) is supported and confirmed. A number of different sands are examined and found to support the hypothesis. In addition, some new simulations on sand mixtures are used to explain experimental results for quartz-feldspar mixtures. It would appear that the proposed compression law is also supported by the data for the sand mixtures

An Infrared Nebula Associated with Delta Cephei: Evidence of Mass Loss?

We present the discovery of an infrared nebula around the Cepheid prototype delta Cephei and its hot companion HD 213307. Large scale (~2.1x10^4 AU) nebulosity is detected at 5.8, 8.0, 24 and 70 um. Surrounding the two stars, the 5.8 and 8.0 um emission is largely attributable to Polycyclic Aromatic Hydrocarbon (PAH) emission swept from the ISM by a wind originating from delta Cephei and/or its companion. Stochastically heated small dust grains are the most likely source of the 24 and 70 um extended emission. The 70 um emission, in particular, resembles a bow shock aligned in the direction of the proper motion of delta Cephei. This discovery supports the hypothesis that delta Cephei may be currently losing mass, at a rate in the range ~ 5x10^-9 to 6x10^-8 Mo/yr.Comment: Published on The Astrophysical Journa

Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

Hormonal treatment; Prostate cancer; Side effectsTratamiento hormonal; Cáncer de próstata; Efectos secundariosTractament hormonal; Càncer de pròstata; Efectes secundarisBackground Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. Objective To present consensus voting results for select questions from APCCC 2022. Design, setting, and participants Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3. Outcome measurements and statistical analysis Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. Results and limitations The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. Conclusions These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials

Deficits in episodic future thinking following acute alcohol consumption

Rationale Acute alcohol consumption adversely affects many cognitive abilities, including episodic memory and executive functioning. However, no study to date has tested whether these acute effects of alcohol also extend to episodic future thinking (EFT). This is a surprising omission given that EFT refers to the ability to imagine oneself experiencing the future, a highly adaptive ability that has been implicated in many important functional behaviours. EFT is also thought to impose demands on episodic memory and executive control. Objectives The current study was designed to provide the first test of whether a moderate dose of alcohol influences EFT and whether any observed EFT difficulties are secondary to broader problems in episodic memory and executive functioning. Sex differences in EFT following acute alcohol consumption were also examined. Methods One hundred and twenty-four healthy adult social drinkers were recruited and randomly assigned to either the alcohol (n = 61) or placebo (n = 63) condition. Participants were administered a dose of 0.6 g/kg alcohol or a matched placebo drink. Results Relative to the placebo condition, EFT was impaired by acute alcohol consumption. This impairment was underpinned by broader difficulties with episodic memory, but not executive functioning. There were no sex differences in EFT performance following acute alcohol use. Conclusion These data provide novel insights into the effects of acute alcohol consumption on EFT and the broader cognitive mechanisms that contribute to these difficulties. The results are discussed in relation to their implications for understanding many of the maladaptive behaviours commonly associated with acute alcohol use