Stem-like cells with luminal progenitor phenotype survive castration in human prostate cancer

Castration is the standard therapy for advanced prostate cancer (PC). Although this treatment is initially effective, tumors invariably relapse as incurable, castration-resistant PC (CRPC). Adaptation of androgen-dependent PC cells to an androgen-depleted environment or selection of pre-existing,CRPC cells have been proposed as mechanisms of CRPC development. Stem cell (SC)-like PC cells have been implicated not only as tumor initiating/maintaining in PC but also as tumor-reinitiating cells in CRPC. Recently, castration-resistant cells expressing the NK3 homeobox 1 (Nkx3-1) (CARNs), the other luminal markers cytokeratin 18 (CK18) and androgen receptor (AR), and possessing SC properties, have been found in castrated mouse prostate and proposed as the cell-of-origin of CRPC. However, the human counterpart of CARNs has not been identified yet. Here, we demonstrate that in the human PC xenograft BM18, preexisting SC-like and neuroendocrine (NE) PC cells are selected by castration and survive as totally quiescent. SClike BM18 cells, displaying the SC markers aldehyde dehydrogenase 1A1 or NANOG, coexpress the luminal markers NKX3-1, CK18, and a low level of AR (ARlow) but not basal or NE markers. These CR luminal SC-like cells, but not NE cells, reinitiate BM18 tumor growth after androgen replacement. The ARlow seems to mediate directly both castration survival and tumor reinitiation. This study identifies for the first time in human PC SC-/CARN-like cells that may represent the cell-of-origin of tumor reinitiation as CRPC. This finding will be fundamental for refining the hierarchy among human PC cancer cells and may have important clinical implications.

Inspection of pole-like structures using a vision-controlled VTOL UAV and shared autonomy

We present an approach for the inspection of vertical pole-like infrastructure using a vertical take-off and landing (VTOL) unmanned aerial vehicle and shared autonomy. Inspecting vertical structures, such as light and power distribution poles, is a time consuming, dangerous and expensive task with high operator workload. To address these issues, we propose a VTOL platform that can operate at close-quarters, whilst maintaining a safe stand-off distance and rejecting environmental disturbances. We adopt an Image based Visual Servoing (IBVS) technique using only two line features to stabilise the vehicle with respect to a pole. Visual, inertial and sonar data are used, making the approach suitable for indoor or GPS-denied environments. Results from simulation and outdoor flight experiments demonstrate the system is able to successfully inspect and circumnavigate a pole.

Data as an asset : what the upstream oil & gas industry can learn about ‘big data’ from companies like Facebook

The upstream oil & gas industry has been contending with massive data sets and monolithic files for many years, but “Big Data”—that is, the ability to apply more sophisticated types of analytical tools to information in a way that extracts new insights or creates new forms of value—is a relatively new concept that has the potential to significantly re-shape the industry. Despite the impressive amount of value that is being realized by Big Data technologies in other parts of the marketplace, however, much of the data collected within the oil & gas sector tends to be discarded, ignored, or analyzed in a very cursory way. This paper examines existing data management practices in the upstream oil & gas industry, and compares them to practices and philosophies that have emerged in organizations that are leading the Big Data revolution. The comparison shows that, in companies that are leading the Big Data revolution, data is regarded as a valuable asset. The presented evidence also shows, however, that this is usually not true within the oil & gas industry insofar as data is frequently regarded there as descriptive information about a physical asset rather than something that is valuable in and of itself. The paper then discusses how upstream oil & gas companies could potentially extract more value from data, and concludes with a series of specific technical and management-related recommendations to this end.

Method of symptom assessment influences cognitive, affective and somatic post-concussion-like symptom base rates

Primary objective: To investigate whether assessment method influences the type of post-concussion-like symptoms. Methods and procedures: Participants were 73 Australian undergraduate students (Mage = 24.14, SD = 8.84; 75.3% female) with no history of mild traumatic brain injury (mTBI). Participants reported symptoms experienced over the previous 2 weeks in response to an open-ended question (free report), mock interview and standardized checklist (British Columbia Post-concussion Symptom Inventory; BC-PSI). Main outcomes and results: In the free report and checklist conditions, cognitive symptoms were reported significantly less frequently than affective (free report: p < 0.001; checklist: p < 0.001) or somatic symptoms (free report: p < 0.001; checklist: p = 0.004). However, in the mock structured interview condition, cognitive and somatic symptoms were reported significantly less frequently than affective symptoms (both p < 0.001). No participants reported at least one symptom from all three domains when assessed by free report, whereas most participants did so when symptoms were assessed by a mock structured interview (75%) or checklist (90%). Conclusions: Previous studies have shown that the method used to assess symptoms affects the number reported. This study shows that the assessment method also affects the type of reported symptoms.

Spectrophotometric analysis of phenols, which involves a hemin-graphene hybrid nanoparticles with peroxidase-like activity

Phenols are well known noxious compounds, which are often found in various water sources. A novel analytical method has been researched and developed based on the properties of hemin–graphene hybrid nanosheets (H–GNs). These nanosheets were synthesized using a wet-chemical method, and they have peroxidase-like activity. Also, in the presence of H2O2, the nanosheets are efficient catalysts for the oxidation of the substrate, 4-aminoantipine (4-AP), and the phenols. The products of such an oxidation reaction are the colored quinone-imines (benzodiazepines). Importantly, these products enabled the differentiation of the three common phenols – pyrocatechol, resorcin and hydroquinone, with the use of a novel, spectroscopic method, which was developed for the simultaneous determination of the above three analytes. This spectroscopic method produced linear calibrations for the pyrocatechol (0.4–4.0 mg L−1), resorcin (0.2–2.0 mg L−1) and hydroquinone (0.8–8.0 mg L−1) analytes. In addition, kinetic and spectral data, obtained from the formation of the colored benzodiazepines, were used to establish multi-variate calibrations for the prediction of the three phenol analytes found in various kinds of water; partial least squares (PLS), principal component regression (PCR) and artificial neural network (ANN) models were used and the PLS model performed best.

Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

IMU aided 3D visual odometry for car-like vehicles

We present a method for calculating odome- try in three-dimensions for car-like ground ve- hicles with an Ackerman-like steering model. In our approach we use the information from a single camera to derive the odometry in the plane and fuse it with roll and pitch informa- tion derived from an on-board IMU to extend to three-dimensions, thus providing odometric altitude as well as traditional x and y transla- tion. We have mounted the odometry module on a standard Toyota Prado SUV and present results from a car-park environment as well as from an off-road track.

Coverage algorithms for an under-actuated car-like vehicle in an uncertain environment

A coverage algorithm is an algorithm that deploys a strategy as to how to cover all points in terms of a given area using some set of sensors. In the past decades a lot of research has gone into development of coverage algorithms. Initially, the focus was coverage of structured and semi-structured indoor areas, but with time and development of better sensors and introduction of GPS, the focus has turned to outdoor coverage. Due to the unstructured nature of an outdoor environment, covering an outdoor area with all its obstacles and simultaneously performing reliable localization is a difficult task. In this paper, two path planning algorithms suitable for solving outdoor coverage tasks are introduced. The algorithms take into account the kinematic constraints of an under-actuated car-like vehicle, minimize trajectory curvatures, and dynamically avoid detected obstacles in the vicinity, all in real-time. We demonstrate the performance of the coverage algorithm in the field by achieving 95% coverage using an autonomous tractor mower without the aid of any absolute localization system or constraints on the physical boundaries of the area.

If you're going to be a leader, at least act like it! Prejudice towards women who are tentative in leader roles

Role congruity theory predicts prejudice towards women who meet the agentic requirements of the leader role. In line with recent findings indicating greater acceptance of agentic behaviour from women, we find evidence for a more subtle form of prejudice towards women who fail to display agency in leader roles. Using a classic methodology, the agency of male and female leaders was manipulated using assertive or tentative speech, presented through written (Study 1, N = 167) or verbal (Study 2, N = 66) communications. Consistent with predictions, assertive women were as likeable and influential as assertive men, while being tentative in leadership reduced the likeability and influence of women, but not of men. Although approval of agentic behaviour from women in leadership reflects progress, evidence that women are quickly singled out for disapproval if they fail to show agency is important for understanding how they continue to be at a distinct disadvantage to men in leader roles.

“They are like family”: The emotional cost experienced by nurses when caring for haemodialysis patients

Background Haemodialysis (HD) nursing is characterised by frequent, intense interactions with patients over long periods of time resulting in a unique nurse-patient relationship. Due to the life-limiting nature of end-stage renal failure, nurses are likely to have repeated exposures to the death of patients with whom they have formed relationships. Repeated exposure to patient death translates into frequent grief experiences. There is scant literature on the psychological impact of patient death for nurses working in the HD setting. Aims To explore HD nurses experiences of patient death and coping mechanisms used. Methods A sequential mixed method study investigating job satisfaction, stress and burnout found that HD nurses had high levels of stress and burnout. These results were explored in more detail during 8 semi-structured interviews with HD nurses. Interviews were audio-recorded, transcribed verbatim and subjected to thematic analysis. Results Three themes were identified that highlight the stress experienced by nurses when a haemodialysis patient dies. The first theme, “quazi-family” describes the close relationship which forms between nurses and patients. The “complicated grief” theme outlines the impact of death on HD nurses, and the final theme, “remembrance” explains some of the coping mechanisms used in the grieving process. Conclusion Nurses develop individual coping mechanisms to accommodate the grief and loss experienced when a “close” patient dies. The grieving process caused by the death of patient’s needs to be recognised by nurses and nurse managers as causing psychological stress and strain.

Measuring, understanding and reducing psychotic-like experiences (PLEs) in young people

Using large community samples, an existing screening instrument for unusual beliefs and perceptual experiences was refined, and a current version of the lifetime measure was developed and tested. Importantly, high scores on the instruments were associated with psychological distress and suicide risk. Acceptability testing of a web treatment was also undertaken. Routine use of the screening instrument and web program in health services may improve identification and support of young people at risk of distress and serious psychological disorder.

Analysis of killer immunoglobulin-like receptor genes in ankylosing spondylitis

Objectives: To assess the possible association of killer immunoglobulin-like receptor (KIR) genes, specifically KIR3DL1, KIR3DS1 and KIR3DL2, with ankylosing spondylitis (AS). Methods: 14 KIR genes were genotyped in 200 UK patients with AS and 405 healthy controls using multiplex polymerase chain reaction. Sequence-specific oligonucleotide probes were used to subtype 368 cases with AS and 366 controls for 12 KIR3DL2 alleles. Differences in KIR genotypes and KIR3DL2 allele frequencies were assessed using the χp2p test. Results: KIR3DL1 and KIR3DS1 gene frequencies were very similar in cases with AS and controls (odds ratio = 1.5, 95% confidence interval 0.8 to 3.0, and odds ratio = 1.02, 95% confidence interval 0.2 to 5.3, respectively). KIR3DL2 allele frequencies were not significantly different between cases with AS and controls. Conclusions: Neither the KIR gene content of particular KIR haplotypes nor KIR3DL2 polymorphisms contribute to AS.

Thinking like Disney: Supporting the Disney method using ambient feedback based on group performance

The Disney method is a collaborative creativity technique that uses three roles - dreamer, realist and critic - to facilitate the consideration of different perspectives on a topic. Especially for novices it is important to obtain guidance in applying this method. One way is providing groups with a trained moderator. However, feedback about the group’s behavior might interrupt the flow of the idea finding process. We built and evaluated a system that provides ambient feedback to a group about the distribution of their statements among the three roles. Our preliminary field study indicates that groups supported by the system contribute more and roles are used in a more balanced way while the visualization does not disrupt the group work.

Are we waiting too long for the cardiovascular outcome trials with the glucagon-like peptide-1 receptor agonists?

Several new medicines are in development for the treatment of type 2 diabetes, and cardiovascular outcome trials are the gold standard for these medicines. This editorial demonstrates that despite being available for over 10 years, there are no cardiovascular outcome studies for any of the glucagon-like peptide-1 (GLP-1) receptor agonists, which demonstrate cardiovascular safety or benefit in subjects with high cardiovascular risk. The author argues that the FDA should be ensuring that clinical outcome studies for subjects with type 2 diabetes and high cardiovascular risk be undertaken in a timelier manner.