Utilizing genetic variation to predict and extend long-term kidney transplant function

Abstract: Renal transplantation has transformed the life of patients with end-stage renal disease and other chronic kidney disorders by returning endogenous kidney function and enabling patients to cease dialysis. Several clinical indicators of graft outcome and long-term function have been established. Although rising creatinine levels and graft biopsy can be used to determine graft loss, identifying early predictors of graft function will not only improve our ability to predict long-term graft outcome but importantly provide a window of opportunity to therapeutically intervene to preserve graft function before graft failure has occurred. Since understanding the importance of matching genetic variation at the HLA region between donors and recipients and translating this into clinical practise to improve transplant outcome, much focus has been placed on trying to identify additional genetic predictors of transplant outcome/function. This review will focus on how candidate gene studies have identified variants within immunosuppression, immune response, fibrotic pathways, and specific ethnic groups, which correlate with graft outcome. We will also discuss the challenges faced by candidate gene studies, such as differences in donor and recipient selection criteria and use of small data sets, which have led to many genes failing to be consistently associated with transplant outcome. This review will also look at how recent advances in our understanding of and ability to screen the genome are starting to provide new insights into the mechanisms behind long-term graft loss and with it the opportunity to target these pathways therapeutically to ultimately increase graft lifespan and the associated benefits to patients

Self-contained breathing apparatus

A self-contained breathing apparatus with automatic redundant fluid pressure controls and a facemask mounted low pressure whistle alarm is described. The first stage of the system includes pair of pressure regulators connected in parallel with different outlet pressures, both of which reduce the pressure of the stored supply gas to pressures compatible with the second stage breathing demand regulator. A primary regulator in the first stage delivers a low output pressure to the demand regulator. In the event of a failure closed condition of the primary regulator an automatic transfer valve switches on the backup regulator. A warning that the supply pressure has been depleted is also provided by a supply pressure actuated transfer valve which transfers the output of the first stage pressure regulators from the primary to the backup regulator. The alarm is activated in either the failure closed condition or if the supply pressure is reduced to a dangerously low level

On the ergoregion instability in rotating gravastars

The ergoregion instability is known to affect very compact objects that rotate very rapidly and do not possess a horizon. We present here a detailed analysis on the relevance of the ergoregion instability for the viability of gravastars. Expanding on some recent results, we show that not all rotating gravastars are unstable. Rather, stable models can be constructed also with J/M^2 ~ 1, where J and M are the angular momentum and mass of the gravastar, respectively. The genesis of gravastars is still highly speculative and fundamentally unclear if not dubious. Yet, their existence cannot be ruled out by invoking the ergoregion instability. For the same reason, not all ultra-compact astrophysical objects rotating with J/M^2 <~ 1 are to be considered necessarily black holes.Comment: 10 pages, 7 figure

Parental perceptions of bladder dysfunction in children with symptomatic joint hypermobility

Children with symptomatic joint hypermobility (SJH) report chronic pain, fatigue, and joint instability as their main symptoms. Symptoms can extend beyond musculoskeletal and include lower urinary tract dysfunction (LUTD). There are no studies exploring parent-perceived quality of life (QoL) in children with LUTD, or strategies used to manage symptoms in this population. Our online cross-sectional survey assessed parents of 6–18-year-olds via two UK charitable organizations. It included the Pediatric Incontinence Questionnaire (PinQ), the Dysfunctional Voiding Symptom Score, and questions exploring treatments and efficacy. Sixty-seven parental questionnaires were analyzed. The majority of children were white females (95%, n = 64). Urgency (97%, n = 65) and enuresis (41.7%, n = 28) were the most frequently reported symptoms. The PinQ questionnaire showed that children were emotionally distressed by LUTD. Twenty-nine parents (43%, n = 29) reported pharmacotherapy as the most effective treatment. Few had accessed other treatments such as physiotherapy (16%, n = 18). Most parents reported that overall treatment did not meet their expectations. This study highlights that parents perceive LUTD as having a great impact on their child's QoL. There is need for education among clinicians about LUTD and hypermobility-related disorders, and for development and evaluation of treatments

Parametric coupling between macroscopic quantum resonators

Time-dependent linear coupling between macroscopic quantum resonator modes generates both a parametric amplification also known as a {}"squeezing operation" and a beam splitter operation, analogous to quantum optical systems. These operations, when applied properly, can robustly generate entanglement and squeezing for the quantum resonator modes. Here, we present such coupling schemes between a nanomechanical resonator and a superconducting electrical resonator using applied microwave voltages as well as between two superconducting lumped-element electrical resonators using a r.f. SQUID-mediated tunable coupler. By calculating the logarithmic negativity of the partially transposed density matrix, we quantitatively study the entanglement generated at finite temperatures. We also show that characterization of the nanomechanical resonator state after the quantum operations can be achieved by detecting the electrical resonator only. Thus, one of the electrical resonator modes can act as a probe to measure the entanglement of the coupled systems and the degree of squeezing for the other resonator mode.Comment: 15 pages, 4 figures, submitte

Pain-Related Fear: A Critical Review of the Related Measures

Objectives: In regards to pain-related fear, this study aimed to: (1) identify existing measures and review their measurement properties, and (2) identify the optimum measure for specific constructs of fear-avoidance, pain-related fear, fear of movement, and kinesiophobia. Design: Systematic literature search for instruments designed to measure fear of pain in patients with persistent musculoskeletal pain. Psychometric properties were evaluated by adjusted Wind criteria. Results: Five questionnaires (Fear-Avoidance Beliefs Questionnaire (FABQ), Fear-Avoidance of Pain Scale (FAPS), Fear of Pain Questionnaire (FPQ), Pain and Anxiety Symptoms Scale (PASS), and the Tampa Scale for Kinesiophobia (TSK)) were included in the review. The main findings were that for most questionnaires, there was no underlying conceptual model to support the questionnaire's construct. Psychometric properties were evaluated by diverse methods, which complicated comparisons of different versions of the same questionnaires. Construct validity and responsiveness was generally not supported and/or untested. Conclusion: The weak construct validity implies that no measure can currently identify who is fearful. The lack of evidence for responsiveness restricts the current use of the instruments to identify clinically relevant change from treatment. Finally, more theoretically driven research is needed to support the construct and thus the measurement of pain-related fear