A Note on Edwards' Hypothesis for Zero-Temperature Ising Dynamics

We give a simple criterion for checking the so called Edwards' hypothesis in certain zero-temperature, ferromagnetic spin-flip dynamics and use it to invalidate the hypothesis in various examples in dimension one and higher.Comment: 11 pages, 4 figure

Design of a Versatile, Teleoperable, Towable Lifting Machine with Robotic Capabilities for Use in Nasa's Lunar Base Operations

The lifting machine will assist in lifting cargo off of landers sent to the Moon and in the construction of a lunar base. Three possible designs were considered for the overall configuration of the lifting machine: the variable angle crane, the tower crane, and the gantry crane. Alternate designs were developed for the major components of the lifting machine. A teleoperable, variable angle crane was chosen as its final design. The design consists of a telescoping boom mounted to a chassis that is supported by two conical wheels for towing and four outriggers for stability. Attached to the end of the boom is a seven degree of freedom robot arm for light, dexterous, lifting operations. A cable and hook suspends from the end of the boom for heavy, gross, lifting operations. Approximate structural sizes were determined for the lifter and its components. However, further analysis is needed to determine the optimum design dimensions. The design team also constructed a model of the design which demonstrates its features and operating principals

IL-1 regulates the IL-23 response to wheat gliadin, the etiologic agent of Celiac Disease

Celiac disease (CD) is an autoimmune disease prevalent in ~1% of the general population. CD is unique because both the major genetic (Human Leukocyte Antigen-DQ2/DQ8 alleles) and etiologic factors (dietary glutens) for susceptibility are known. While these alleles are responsible for the inappropriate T cell response that characterizes CD, they are not sufficient since most HLA-DQ2+/DQ8+ individuals exposed to glutens never develop disease. The reasons for this have not been explained; however our novel findings strongly advocate a role for interleukin-23 (IL-23) in the immunopathogenesis of CD. We demonstrate that wheat gliadin stimulates monocytes to produce significantly higher amounts of inflammatory cytokines IL-1b, IL-23, and tumor necrosis factor-a (TNFa) in CD patients compared to HLA-DQ2+ healthy individuals. Furthermore, we determine that IL-1 signalling is obligatory for production of IL-23, since IL-1b triggers IL-23 secretion in a dose-dependent manner and IL-1 receptor antagonist (IL-1ra) blocks IL-23 responses to gliadin. Our results suggest that gliadin activation of monocytes and the subsequent robust secretion of IL-1b and IL-23 initiate the immune response cascade that is manifest as CD, and reveal for the first time that the IL-1 system regulates production of IL-23. The discovery of IL-23 has highlighted the critical role of the innate immune response in autoimmunity and other inflammatory conditions. We anticipate that our novel findings will lead to the discovery of therapeutic targets for this disease and other inflammatory diseases mediated by IL-23

Population dynamics in HIV-1 transmitted antiretroviral drug resistance

A dissertation submitted to Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Master of Science in Medicine, Johannesburg, June 2018It is well known that antiretroviral (ARV) drug resistant variants of HIV-1 can be sexually transmitted. Several studies have shown that in resource-rich geographical locations as many as 15-20% of individuals are newly infected with HIV-1 containing at least one drug resistant mutation. In contract, resource limited geographical locations, such as Sub-Saharan Africa, have shown prevalences in the range of 5 to 10%. Since the ART rollout in these resource-limited locations are generally not well monitored with virological genotyping, the transmission of drug resistant HIV-1 is likely to increase, with significant clinical and public health consequences. HIV-1 transmission is characterised by the transmission of a single founder virus, or narrow spectrum of founder viruses, that develop into the viral quasispecie. It is unlikely that drug resistant virus will coexist with wild type (wt) virus, in the case of non-drug resistance transmission. However, initiating in ARV treatment, drug non-adherence may select of ARV drug resistance mutations and may subsequent lead to treatment failure. Drug resistant virus may be transmitted to a new host, as drug resistant mutations do not appear to hamper transmission efficiency of the mutated virus. Several studies have shown that transmitted drug resistance mutations (TDRMs) persist either as the dominant species or as minority variants, or revert to wild type over time, in the absence of drug pressure. It is generally acknowledged that many drug resistance mutations decrease the replicative capacity of HIV-1, and thus reversion confers a potential survival advantage. Because of the emergence of wild type variants from TDRM quasispecies requires evolution and back-mutation, the rate at which individual TDRMs become undetectable may vary substantially. Contradictory findings of persistence versus reversion of TDRMs have been reported, and may be attributed to the fact that minority variants are difficult to detect by conventional population based Sanger sequencing, and patient numbers studied are small. Consequently, individuals infected with HIV-1 harbouring TDRM have a higher chance of failing their first-line therapy. Understanding the population dynamics of transmitted drug resistant HIV-1 in the absence of drug pressure is essential for clinical management and public health strategies. The individuals identified with TDRMs from the IAVI-Early Infections Cohort (Protocol C) provides a unique research opportunity to address the aforementioned issue. This study describes III the evolutionary mechanisms of ARV drug resistant HIV-1 after transmission to a new host to provide insight into persistence and/or rates of reversion to wild type. TDRMs initially identified by Price et al. (2011) in the IAVI-Early Infections Cohort (Protocol C) using population-based Sanger sequencing (the current diagnostic gold standard), were confirmed in this study by newer ultra-deep next generation sequencing (NGS) technology on the Illumina Miseq platform. Longitudinal samples were made available for individuals in which transmitted drug resistance were identified, and we also sequenced using NGS on the Illumina Miseq platform. Additional minority variants (present at <20% of the sequenced viral population) were identified by NGS. This study found a large percentage of TDRMs to persist for a significant amount of time after transmission to a new, drug naïve host, in the longitudinal samples. The level of persistence, or rate of reversion of TDRMs, appear to be subject to the type of resistance (NRTI, NNRTI or PI), level of resistance the mutation confers, as well as the combination of mutations that are cotransmitted. Findings of this study highlight the importance of drug resistance screening prior to ART initiation, as well as the importance of the drug resistance screening assay sensitivity. As rates of transmitted drug resistance are increasing in developing countries of which the IAVI-Early Infections Cohort (Protocol C) are composed of, understanding the population dynamics of transmitted drug resistant HIV-1 in the absence of drug pressure is essential for clinical management, public health strategies and informing future vaccine design.XL201

Vicarious Antitrust Liability in the Health Care Field

In order to understand the interface between vicarious antitrust liability and the decline of the independent contractor defense in the health care field, it is necessary to understand the complex relationship between the hospital and the physician, as well as the recent changes that have taken place in that relationship. Therefore, this article will briefly trace the changes that have occurred in the traditional rules of the hospital\u27s relationship with its physicians. Then, the current relationship between hospital and staff physician will be examined in light of legal requirements, accreditation standards and practical considerations. After a brief introduction to the health care marketplace as a context for antitrust law, the new theories of liability will be applied to the health care field, in order to give examples of claims likely to be asserted by plaintiffs and defenses that can be raised by health care institutions

A novel blood based triage test for colorectal cancer in primary care: a pilot study

Background: The majority of colorectal cancers (CRCs) are detected after symptomatic presentation to primary care. Given the shared symptoms of CRC and benign disorders, it is challenging to manage the risk of missed diagnosis. Colonoscopy resources cannot keep pace with increasing demand. There is a pressing need for access to simple triage tools in primary care to help prioritise patients for referral. Aim: To evaluate the performance of a novel spectroscopy-based CRC blood test in primary care. Design & setting: Mixed-methods pilot study of test performance and GP focus group discussions in South Wales. Method: Patients on the urgent suspected cancer (USC) pathway were recruited for the Raman spectroscopy (RS) test coupled to machine learning classification (‘Raman-CRC’) to identify CRC within the referred population. Qualitative focus group work evaluated the acceptability of the test in primary care by thematic analysis of focus group theorising. Results: A total of 532 patients aged ≥50 years referred on the USC pathway were recruited from 27 GP practices. Twenty-nine patients (5.0%) were diagnosed with CRC. Raman-CRC identified CRC with sensitivity 95.7%, specificity 69.3% with area under curve (AUC) of 0.80 compared with colonoscopy as the reference test (248 patients). Stage I and II cancers were detected with 78.6% sensitivity. Focus group themes underlined the convenience of a blood test for the patient and the test’s value as a risk assessment tool in primary care. Conclusion: The findings support this novel, non-invasive, blood-based method to prioritise those patients most likely to have CRC. Raman-CRC may accelerate access to diagnosis with potential to improve cancer outcomes

A Longitudinal Study of Human Exposure to Potential Nuclear Power Plant Risk

This study constructs a potential risk index (PRI) for the 65 U.S.-based commercial nuclear power plant (NPP) sites in relation to their surrounding populations. Four risk levels are defined: low risk, moderate risk, high risk, and very high risk. Discrepancies that exist in the sociodemographic characteristics of the host communities’ populations are examined as sorted by risk-level category. It is found that a greater percentage of minority groups are exposed to the highest levels of risk. In addition, percent “Hispanic” and percent “Other,” a grouping that includes multiracial, mixed, interracial, as well as Hispanic and Latino groups (for example, Mexican, Puerto Rican, Cuban, or Spanish) are categories that show the greatest percent change in both the period 1990–2000 and 2000–2010

Intestinal microbiota and their metabolic contribution to type 2 diabetes and obesity

Obesity and type 2 diabetes mellitus (T2DM) are common, chronic metabolic disorders with associated significant long-term health problems at global epidemic levels. It is recognised that gut microbiota play a central role in maintaining host homeostasis and through technological advances in both animal and human models it is becoming clear that gut microbiota are heavily involved in key pathophysiological roles in the aetiology and progression of both conditions. This review will focus on current knowledge regarding microbiota interactions with short chain fatty acids, the host inflammatory response, signaling pathways, integrity of the intestinal barrier, the interaction of the gut-brain axis and the subsequent impact on the metabolic health of the host