Asymmetric Arbitage and Normal Backwardation

This paper provides a theoretical explanation for the existence of backwardation on the futures markets, based on Routhakker's work dealing with asymmetry of arbitrage on such markets. The central assumption of the paper is that cash and futures prices tend to be more highly correlated at low than at high cash prices. This assumption reflects the asymmetry in arbitrage opportunities in futures markets; in particular, at the maturity date of a futures contract, the futures price cannot exceed the cash price of any grade-location combination deliverable under the futures contract. The main result of the paper is a proposition that asserts that with identical long and short hedgers, with the same wheat commitments on both sides of the market, and with utility functions exhibiting constant or decreasing absolute risk aversion, if the probability density function over cash and futures prices is sufficiently concentrated at low cash prices, then the resulting market equilibrium will exhibit backwardation, that is, the current future price is a downward biased estimator of the future futures price as well as being a downward biased estimator of the future cash price

Post-traumatic osteoarthritis in mice following mechanical injury to the synovial joint

We investigated the spectrum of lesions characteristic of post-traumatic osteoarthritis (PTOA) across the knee joint in response to mechanical injury. We hypothesized that alteration in knee joint stability in mice reproduces molecular and structural features of PTOA that would suggest potential therapeutic targets in humans. The right knees of eight-week old male mice from two recombinant inbred lines (LGXSM-6 and LGXSM-33) were subjected to axial tibial compression. Three separate loading magnitudes were applied: 6N, 9N, and 12N. Left knees served as non-loaded controls. Mice were sacrificed at 5, 9, 14, 28, and 56 days post-loading and whole knee joint changes were assessed by histology, immunostaining, micro-CT, and magnetic resonance imaging. We observed that tibial compression disrupted joint stability by rupturing the anterior cruciate ligament (except for 6N) and instigated a cascade of temporal and topographical features of PTOA. These features included cartilage extracellular matrix loss without proteoglycan replacement, chondrocyte apoptosis at day 5, synovitis present at day 14, osteophytes, ectopic calcification, and meniscus pathology. These findings provide a plausible model and a whole-joint approach for how joint injury in humans leads to PTOA. Chondrocyte apoptosis, synovitis, and ectopic calcification appear to be targets for potential therapeutic intervention

Asymmetric Arbitage and Normal Backwardation

This paper provides a theoretical explanation for the existence of backwardation on the futures markets, based on Routhakker's work dealing with asymmetry of arbitrage on such markets. The central assumption of the paper is that cash and futures prices tend to be more highly correlated at low than at high cash prices. This assumption reflects the asymmetry in arbitrage opportunities in futures markets; in particular, at the maturity date of a futures contract, the futures price cannot exceed the cash price of any grade-location combination deliverable under the futures contract. The main result of the paper is a proposition that asserts that with identical long and short hedgers, with the same wheat commitments on both sides of the market, and with utility functions exhibiting constant or decreasing absolute risk aversion, if the probability density function over cash and futures prices is sufficiently concentrated at low cash prices, then the resulting market equilibrium will exhibit backwardation, that is, the current future price is a downward biased estimator of the future futures price as well as being a downward biased estimator of the future cash price

An online repository for pre-clinical imaging protocols (PIPs)

Providing method descriptions that are more detailed than currently available in typical peer reviewed journals has been identified as an actionable area for improvement. In the biochemical and cell biology space, this need has been met through the creation of new journals focused on detailed protocols and materials sourcing. However, this format is not well suited for capturing instrument validation, detailed imaging protocols, and extensive statistical analysis. Furthermore, the need for additional information must be counterbalanced by the additional time burden placed upon researchers who may be already overtasked. To address these competing issues, this white paper describes protocol templates for positron emission tomography (PET), X-ray computed tomography (CT), and magnetic resonance imaging (MRI) that can be leveraged by the broad community of quantitative imaging experts to write and self-publish protocols in protocols.io. Similar to the Structured Transparent Accessible Reproducible (STAR) or Journal of Visualized Experiments (JoVE) articles, authors are encouraged to publish peer reviewed papers and then to submit more detailed experimental protocols using this template to the online resource. Such protocols should be easy to use, readily accessible, readily searchable, considered open access, enable community feedback, editable, and citable by the author

Reducing conflict and containment rates on acute psychiatric wards:The Safewards cluster randomised controlled trial

BACKGROUND: Acute psychiatric wards manage patients whose actions may threaten safety (conflict). Staff act to avert or minimise harm (containment). The Safe wards model enabled the identification of ten interventions to reduce the frequency of both. OBJECTIVE: To test the efficacy of these interventions. DESIGN: A pragmatic cluster randomised controlled trial with psychiatric hospitals and wards as the units of randomisation. The main outcomes were rates of conflict and containment. PARTICIPANTS: Staff and patients in 31 randomly chosen wards at 15 randomly chosen hospitals. RESULTS: For shifts with conflict or containment incidents, the experimental condition reduced the rate of conflict events by 15% (95% CI 5.6-23.7%) relative to the control intervention. The rate of containment events for the experimental intervention was reduced by 26.4% (95% CI 9.9-34.3%). CONCLUSIONS: Simple interventions aiming to improve staff relationships with patients can reduce the frequency of conflict and containment. TRIAL REGISTRATION: IRSCTN38001825. Crown Copyright.</p

Co-clinical imaging metadata information (CIMI) for cancer research to promote open science, standardization, and reproducibility in preclinical imaging

Preclinical imaging is a critical component in translational research with significant complexities in workflow and site differences in deployment. Importantly, the National Cancer Institute\u27s (NCI) precision medicine initiative emphasizes the use of translational co-clinical oncology models to address the biological and molecular bases of cancer prevention and treatment. The use of oncology models, such as patient-derived tumor xenografts (PDX) and genetically engineered mouse models (GEMMs), has ushered in an era of co-clinical trials by which preclinical studies can inform clinical trials and protocols, thus bridging the translational divide in cancer research. Similarly, preclinical imaging fills a translational gap as an enabling technology for translational imaging research. Unlike clinical imaging, where equipment manufacturers strive to meet standards in practice at clinical sites, standards are neither fully developed nor implemented in preclinical imaging. This fundamentally limits the collection and reporting of metadata to qualify preclinical imaging studies, thereby hindering open science and impacting the reproducibility of co-clinical imaging research. To begin to address these issues, the NCI co-clinical imaging research program (CIRP) conducted a survey to identify metadata requirements for reproducible quantitative co-clinical imaging. The enclosed consensus-based report summarizes co-clinical imaging metadata information (CIMI) to support quantitative co-clinical imaging research with broad implications for capturing co-clinical data, enabling interoperability and data sharing, as well as potentially leading to updates to the preclinical Digital Imaging and Communications in Medicine (DICOM) standard

Optimal co-clinical radiomics: Sensitivity of radiomic features to tumour volume, image noise and resolution in co-clinical T1-weighted and T2-weighted magnetic resonance imaging

BACKGROUND: Radiomics analyses has been proposed to interrogate the biology of tumour as well as to predict/assess response to therapy in vivo. The objective of this work was to assess the sensitivity of radiomics features to noise, resolution, and tumour volume in the context of a co-clinical trial. METHODS: Triple negative breast cancer (TNBC) patients were recruited into an ongoing co-clinical imaging trial. Sub-typed matched TNBC patient-derived tumour xenografts (PDX) were generated to investigate optimal co-clinical MR radiomic features. The MR imaging protocol included T1-weighed and T2-weighted imaging. To test the sensitivity of radiomics to resolution, PDX were imaged at three different resolutions. Multiple sets of images with varying signal-to-noise ratio (SNR) were generated, and an image independent patch-based method was implemented to measure the noise levels. Forty-eight radiomic features were extracted from manually segmented 2D and 3D segmented tumours and normal tissues of T1- and T2- weighted co-clinical MR images. FINDINGS: Sixteen radiomics features were identified as volume dependent and corrected for volume-dependency following normalization. Features from grey-level run-length matrix (GLRLM), grey-level size zone matrix (GLSZM) were identified as most sensitive to noise. Radiomic features Kurtosis and Run-length variance (RLV) from GLSZM were most sensitive to changes in resolution in both T1w and T2w MRI. In general, 3D radiomic features were more robust compared to 2D (single slice) measures, although the former exhibited higher variability between subjects. INTERPRETATION: Tumour volume, noise characteristics, and image resolution significantly impact radiomic analysis in co-clinical studies

Modeling the R2* relaxivity of blood at 1.5 Tesla

BOLD (Blood Oxygenation Level Dependent) imaging is used in fMRI to show differences in activation of the brain based on the relative changes of the T2* (= 1/R2*) signal of the blood. However, quantification of blood oxygenation level based on the T2* signal has been hindered by the lack of a predictive model which accurately correlates the T2* signal to the oxygenation level of blood. The T2* signal decay in BOLD imaging is generated due to blood containing paramagnetic deoxyhemoglobin (in comparison to diamagnetic oxyhemoglobin). This generates local field inhomogeneities, which cause protons to experience different phase shifts, leading to dephasing and the MR signal decay. The blood T2* signal has been shown to decay with a complex behavior1, termed Non-Lorenztian, and thus is not adequately described by the traditional model of simplemono-exponential decay. Theoretical calculations show that diffusion narrowing substantially affects signal loss in our data. Over the past decade, several theoretical models have been proposed to describe this Non-Lorenztian behavior in the blood T2* signal in BOLD fMRI imaging. The goal of this project was to investigate different models which have been proposed over the years and determine a semi-phenomenological model for the T2* behaviorusing actual MR blood data

Rapamycin perfluorocarbon nanoparticle mitigates cisplatin-induced acute kidney injury

For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10-20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and were retained in injured kidneys. Histologic evaluation and blood urea nitrogen (BUN) confirmed that renal structure and function were preserved 48 h after cisplatin injury. Similarly, weight loss was slowed down. Using western blotting and immunofluorescence staining, mechanistic studies revealed that rapamycin PFC NP significantly enhanced autophagy in the kidney, reduced the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as decreased the expression of the apoptotic protein Bax, all of which contributed to the suppression of apoptosis that was confirmed with TUNEL staining. In summary, the delivery of an approved agent such as rapamycin in a PFC NP format enhances local delivery and offers a novel mechanism-based prophylactic therapy for cisplatin-induced acute kidney injury