Digital image analysis using video microscopy of human-derived prostate cancer vs normal prostate organoids to assess migratory behavior on extracellular matrix proteins

The advent of perpetuating living organoids derived from patient tissue is a promising avenue for cancer research but is limited by difficulties with precise characterization. In this brief communication, we demonstrate via time-lapse imaging distinct phenotypes of prostate organoids derived from patient material– without confirmation of cellular identity. We show that organoids derived from histologically normal tissue more readily spread on a physiologic extracellular matrix (ECM) than on pathologic ECM (p<0.0001), while tumor-derived organoids spread equally on either substrate (p=0.2406). This study is an important proof-of-concept to defer precise characterization of organoids and still glean information into disease pathology

Constraints on the Clustering, Biasing and Redshift Distribution of Radio Sources

We discuss how different theoretical predictions for the variance $\sigma^2$ of the distribution of radio sources can be matched to measurements from the FIRST survey at different flux limits. The predictions are given by the integration of models for the angular correlation function $w(\theta)$ for three different functional forms of the redshift distribution $N(z)$, different spatial correlation functions and by different evolutions of the bias $b(z)$ with redshift. We also consider the two cases of open and flat Universes. Although the predicted $w(\theta)$ show substantial differences due to differences in the $N(z)$'s, these differences are not significant compared to the uncertainties in the current observations. It turns out that the best fit is provided by models with constant biasing at all times, although the difference between models with epoch-independent bias and models with bias that evolves linearly with redshift is not very large. All models with strong evolution of bias with epoch are ruled out. As a further step we directly calculated $w_{obs}(\theta)$ at 3mJy from the catalogue and matched it with our models for the angular correlation function in the hypothesis that the clustering signal comes from two different populations, namely AGN-powered sources and starbursting galaxies. The results are consistent with a scenario for hierarchical clustering where the fainter starbursting galaxies trace the mass at all epochs, while brighter AGN's are strongly biased, with $b(z)$ evolving linearly with redshift, as suggested by some theories of galaxy formation and evolution.Comment: 14 pages, 12 figures, version to appear on MNRA

New Constraint on Open Cold-Dark-Matter Models

We calculate the large-angle cross-correlation between the cosmic-microwave-background (CMB) temperature and the x-ray-background (XRB) intensity expected in an open Universe with cold dark matter (CDM) and a nearly scale-invariant spectrum of adiabatic density perturbations. Results are presented as a function of the nonrelativistic-matter density $\Omega_0$ (in units of the critical density) and the x-ray bias $b_x$ (evaluated at a redshift $z\simeq1$ in evolving-bias models) for both an open Universe and a flat cosmological-constant Universe. Recent experimental upper limits to the amplitude of this cross-correlation provide a new constraint to the $\Omega_0$-$b_x$ parameter space that open-CDM models (and the open-inflation models that produce them) must satisfy.Comment: 4 pages, LaTeX. Revised version contains additional figure that clarifies new constraint. (To appear in PRL.

A giant radio halo in a low-mass SZ-selected galaxy cluster: ACT-CL J0256.5+0006

We present the detection of a giant radio halo (GRH) in the Sunyaev-Zel'dovich (SZ)-selected merging galaxy cluster ACT-CL J0256.5+0006 (z = 0.363), observed with the Giant Metrewave Radio Telescope at 325 and 610 MHz. We find this cluster to host a faint (S610= 5.6 ± 1.4 mJy) radio halo with an angular extent of 2.6 arcmin, corresponding to 0.8 Mpc at the cluster redshift, qualifying it as a GRH. J0256 is one of the lowest mass systems, M500, SZ= (5.0 ± 1.2) × 1014M?, found to host a GRH. We measure the GRH at lower significance at 325 MHz (S325= 10.3 ± 5.3 mJy), obtaining a spectral index measurement of a325610= 1.0-0.9+0.7. This result is consistent with the mean spectral index of the population of typical radio haloes, a = 1.2 ± 0.2. Adopting the latter value, we determine a 1.4 GHz radio power of P1.4 GHz= (1.0 ± 0.3) × 1024W Hz-1, placing this cluster within the scatter of known scaling relations. Various lines of evidence, including the intracluster medium morphology, suggest that ACT-CL J0256.5+0006 is composed of two subclusters. We determine a merger mass ratio of 7:4, and a line-of-sight velocity difference of v? = 1880 ± 210 km s-1. We construct a simple merger model to infer relevant time-scales in the merger. From its location on the P1.4 GHz-LXscaling relation, we infer that we observe ACT-CL J0256.5+0006 just before first core crossing

A 'Performative' Social Movement: The Emergence of Collective Contentions within Collaborative Governance

The enmeshment of urban movements in networks of collaborative governance has been characterised as a process of co-option in which previously disruptive contentions are absorbed by regimes and reproduced in ways that do not threaten the stability of power relations. Applying a theoretical framework drawn from feminist philosopher Judith Butler this paper directs attention to the development of collective oppositional identities that remain embedded in conventional political processes. In a case study of the English tenants' movement, it investigates the potential of regulatory discourses that draw on market theories of performative voice to offer the collectivising narratives and belief in change that can generate the emotional identification of a social movement. The paper originates the concept of the ‘performative social movement’ to denote the contentious claims that continue to emerge from urban movements that otherwise appear quiescent

Phenotype plasticity and altered sensitivity to chemotherapeutic agents in aggressive prostate cancer cells

In 2023, approximately 288,300 new diagnoses of prostate cancer will occur, with 34,700 disease-related deaths. Death from prostate cancer is associated with metastasis, enabled by progression of tumor phenotypes and successful extracapsular extension to reach Batson’s venous plexus, a specific route to the spine and brain. Using a mouse-human tumor xenograft model, we isolated an aggressive muscle invasive cell population of prostate cancer, called DU145J7 with a distinct biophysical phenotype, elevated histone H3K27, and increased matrix metalloproteinase 14 expression as compared to the non-aggressive parent cell population called DU145WT. Our goal was to determine the sensitivities to known chemotherapeutic agents of the aggressive cells as compared to the parent population. High-throughput screening was performed with 5,578 compounds, comprising of approved and investigational drugs for oncology. Eleven compounds were selected for additional testing, which revealed that vorinostat, 5-azacitidine, and fimepinostat (epigenetic inhibitors) showed 2.6-to-7.5-fold increases in lethality for the aggressive prostate cancer cell population as compared to the parent, as judged by the concentration of drug to inhibit 50% cell growth (IC50). On the other hand, the DU145J7 cells were 2.2-to-4.0-fold resistant to mitoxantrone, daunorubicin, and gimatecan (topoisomerase inhibitors) as compared to DU145WT. No differences in sensitivities between cell populations were found for docetaxel or pirarubicin. The increased sensitivity of DU145J7 prostate cancer cells to chromatin modifying agents suggests a therapeutic vulnerability occurs after tumor cells invade into and through muscle. Future work will determine which epigenetic modifiers and what combinations will be most effective to eradicate early aggressive tumor populations

Effectiveness of Oral Nutritional Supplementation for Older Women after a Fracture: Rationale, Design and Study of the Feasibility of a Randomized Controlled Study

<p>Abstract</p> <p>Background</p> <p>Malnutrition is a problem for many older people recovering from a hip and other major fractures. Oral supplementation with high calorie high protein nutrients is a simple intervention that may help older people with fractures to improve their recovery in terms of rehabilitation time, length of hospital stay and mortality. This paper reports a pilot study to test the feasibility of a trial initiated in a hospital setting with an oral supplement to older people with recent fractures.</p> <p>Method</p> <p>A randomized controlled trial with 44 undernourished participants admitted to a hospital following a fracture. The intervention group (n = 23) received a high calorie high protein supplement for forty days in addition to their diet of choice. The control group (n = 21) received high protein milk during their hospital stay in addition to their diet of choice and their usual diet when discharged from hospital.</p> <p>Results</p> <p>All participants were women and their mean age was 85.3 (± 6.1) years. Twenty nine (65%) participants had a hip fracture. At baseline no differences were measured between the two groups regarding their nutritional status, their cognitive ability or their abilities in activities of daily living. There were no significant differences between the intervention and control group with reference to nutritional or functional parameters at 40 day and 4 month follow-ups. Median length of stay in hospital was 18.0 days, with 12 participants being readmitted for a median of 7.0 days.</p> <p>Conclusion</p> <p>It is feasible to perform a randomised trial in a hospital and community setting to test the effect of an oral high energy high protein supplement for older people. Due to the limited number of participants and incomplete adherence with use of the supplements no conclusion can be drawn about the efficacy or effectiveness of this intervention.</p

Modeling early recovery of physical function following hip and knee arthroplasty

BACKGROUND: Information on early recovery after arthroplasty is needed to help benchmark progress and make appropriate decisions concerning patient rehabilitation needs. The purpose of this study was to model early recovery of physical function in patients undergoing total hip (THA) and knee (TKA) arthroplasty, using physical performance and self-report measures. METHODS: A sample of convenience of 152 subjects completed testing, of which 69 (mean age: 66.77 ± 8.23 years) underwent THA and 83 (mean age: 60.25 ± 11.19 years) TKA. Postoperatively, patients were treated using standardized care pathways and rehabilitation protocols. Using a repeated measures design, patients were assessed at multiple time points over the first four postoperative months. Outcome measures included the Lower Extremity Function Scale (LEFS), the physical function subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC PF), the 6 minute walk test (6 MWT), timed up and go test (TUG) and a timed stair test (ST). Average recovery curves for each of the measures were characterized using hierarchical linear modeling. Predictors of recovery were sequentially modeled after validation of the basic developmental models. RESULTS: Slopes of recovery were greater in the first 6 to 9 weeks with a second-degree polynomial growth term (weeks squared) providing a reasonable fit for the data over the study interval. Different patterns of recovery were observed between the self-report measures of physical function and the performance measures. In contrast to the models for the WOMAC PF and the LEFS, site of arthroplasty was a significant predictor (p = 0.001) in all of the physical performance measure models with the patients post TKA initially demonstrating higher function. Site of arthroplasty (p = 0.025) also predicted the rate of change for patients post THA and between 9 to 11 weeks after surgery, the THA group surpassed the function of the patients post TKA. CONCLUSION: Knowledge about the predicted growth curves will assist clinicians in referencing patient progress, and determining the critical time points for measuring change. The study has contributed further evidence to highlight the benefit of using physical performance measures to learn about the patients' actual level of disability