Physics of Ultra-Peripheral Nuclear Collisions

Moving highly-charged ions carry strong electromagnetic fields that act as a field of photons. In collisions at large impact parameters, hadronic interactions are not possible, and the ions interact through photon-ion and photon-photon collisions known as {\it ultra-peripheral collisions} (UPC). Hadron colliders like the Relativistic Heavy Ion Collider (RHIC), the Tevatron and the Large Hadron Collider (LHC) produce photonuclear and two-photon interactions at luminosities and energies beyond that accessible elsewhere; the LHC will reach a $\gamma p$ energy ten times that of the Hadron-Electron Ring Accelerator (HERA). Reactions as diverse as the production of anti-hydrogen, photoproduction of the $\rho^0$, transmutation of lead into bismuth and excitation of collective nuclear resonances have already been studied. At the LHC, UPCs can study many types of `new physics.'Comment: 47 pages, to appear in Annual Review of Nuclear and Particle Scienc

Advance Care Planning for Adults With CKD: A Systematic Integrative Review

Author version made avilable in accordance with the publisher's policy. © 2014, the National Kindney Foundation, inc. 
Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/Background Recent clinical practice guidelines have highlighted the importance of advance care planning (ACP) for improving end-of-life care for people with chronic kidney disease (CKD). Study Design We conducted a systematic integrative review of the literature to inform future ACP practice and research in CKD, searching electronic databases in April 2013. Synthesis used narrative methods. Setting & Population We focused on adults with a primary diagnosis of CKD in any setting. Selection Criteria for Studies We included studies of any design, quantitative or qualitative.. Interventions ACP was defined as any formal means taken to ensure health professionals and family members are aware of patients’ wishes for care in the event they become too unwell to speak for themselves. Outcomes Measures of all kinds were considered to be of interest. Results Fifty-five articles met criteria reporting on 51 discrete samples. All patient samples included people with Stage 5 CKD; two also included patients with Stage 4. Seven interventions were tested; all were narrowly focused and none was evaluated by comparing wishes for end-of-life care with care received. One intervention demonstrated effects on patient/family outcomes in the form of improved wellbeing and anxiety following sessions with a peer mentor. Insights from qualitative studies that have not been emphasised in interventions include the importance of instilling patient confidence that their advance directives will be enacted and discussing decisions about (dis)continuing dialysis separately from ‘aggressive’ life-sustaining treatments (e.g. ventilation). Limitations Whilst quantitative and qualitative findings were integrated according to best practice, methods for this are in their infancy. Conclusions Research on ACP in patients with CKD is limited, especially regarding intervention studies. Interventions in CKD should attend to barriers and facilitators at the levels of patient, caregiver, health professional and system. Intervention studies should measure impact on compliance with patient wishes for end-of-life care. Index words Chronic kidney disease, Renal failure, Advance care planning, Advance directives, Decision-makin

Advance care planning in chronic kidney disease: A survey of current practice in Australia

© 2016 Asian Pacific Society of Nephrology Aim: Advance care planning (ACP) in nephrology is widely advocated but not always implemented. The aims of this study were to describe current ACP practice and identify barriers/facilitators and perceived need for health professional education and chronic kidney disease (CKD)-specific approaches. Methods: An anonymous cross-sectional survey was administered online. Nephrology health professionals in Australia and New Zealand were recruited via professional societies, email lists and nephrology conferences. Multiple regression explored the influence of respondents' attributes on extent of involvement in ACP and willingness to engage in future. Results: A total of 375 respondents included nephrologists (23%), nurses (65%), social workers (4%) and others (8%) with 54% indicated that ACP at their workplace was performed ad hoc and 61% poorly. Perceived barriers included patient/family discomfort (84%), difficulty engaging families (83%), lack of clinician expertise (83%) and time (82%), health professional discomfort (72%), cultural/language barriers (65%), lack of private space (61%) and lack of formal policy/procedures (60%). Respondents overwhelmingly endorsed the need for more dialysis-specific ACP programs (96%) and education (95%). Whilst 85% thought ACP would be optimally performed by specially trained staff, comments emphasized that all clinicians should have a working proficiency. Respondents who were more willing to engage in future ACP tended to be non-physicians (odds ratio (OR) 4.96, 95% confidence intervals (CI) 1.74–14.07) and reported a greater need for CKD-specific ACP materials (OR 10.88, 95% CI 2.38–49.79). Conclusion: Advance care planning in nephrology needs support through education and CKD-specific resources. Endorsement by nephrologists is important. A multidisciplinary approach with a gradient of ACP expertise is also recommended

TRNT1 deficiency: clinical, biochemical and molecular genetic features

BACKGROUND: TRNT1 (CCA-adding transfer RNA nucleotidyl transferase) enzyme deficiency is a new metabolic disease caused by defective post-transcriptional modification of mitochondrial and cytosolic transfer RNAs (tRNAs). RESULTS: We investigated four patients from two families with infantile-onset cyclical, aseptic febrile episodes with vomiting and diarrhoea, global electrolyte imbalance during these episodes, sideroblastic anaemia, B lymphocyte immunodeficiency, retinitis pigmentosa, hepatosplenomegaly, exocrine pancreatic insufficiency and renal tubulopathy. Other clinical features found in children include sensorineural deafness, cerebellar atrophy, brittle hair, partial villous atrophy and nephrocalcinosis. Whole exome sequencing and bioinformatic filtering were utilised to identify recessive compound heterozygous TRNT1 mutations (missense mutation c.668T>C, p.Ile223Thr and a novel splice mutation c.342+5G>T) segregating with disease in the first family. The second family was found to have a homozygous TRNT1 mutation (c.569G>T), p.Arg190Ile, (previously published). We found normal mitochondrial translation products using passage matched controls and functional perturbation of 3' CCA addition to mitochondrial tRNAs (tRNA(Cys), tRNA(LeuUUR) and tRNA(His)) in fibroblasts from two patients, demonstrating a pathomechanism affecting the CCA addition to mt-tRNAs. Acute management of these patients included transfusion for anaemia, fluid and electrolyte replacement and immunoglobulin therapy. We also describe three-year follow-up findings after treatment by bone marrow transplantation in one patient, with resolution of fever and reversal of the abnormal metabolic profile. CONCLUSIONS: Our report highlights that TRNT1 mutations cause a spectrum of disease ranging from a childhood-onset complex disease with manifestations in most organs to an adult-onset isolated retinitis pigmentosa presentation. Systematic review of all TRNT1 cases and mutations reported to date revealed a distinctive phenotypic spectrum and metabolic and other investigative findings, which will facilitate rapid clinical recognition of future cases

Do female association preferences predict the likelihood of reproduction?

Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (<i>Xiphophorus helleri</i>) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

Pediatric Cushing disease: disparities in disease severity and outcomes in the Hispanic and African-American populations.

BackgroundLittle is known about the contribution of racial and socioeconomic disparities to severity and outcomes in children with Cushing disease (CD).MethodsA total of 129 children with CD, 45 Hispanic/Latino or African-American (HI/AA) and 84 non-Hispanic White (non-HW), were included in this study. A 10-point index for rating severity (CD severity) incorporated the degree of hypercortisolemia, glucose tolerance, hypertension, anthropomorphic measurements, disease duration, and tumor characteristics. Race, ethnicity, age, gender, local obesity prevalence, estimated median income, and access to care were assessed in regression analyses of CD severity.ResultsThe mean CD severity in the HI/AA group was worse than that in the non-HW group (4.9±2.0 vs. 4.1±1.9, P=0.023); driving factors included higher cortisol levels and larger tumor size. Multiple regression models confirmed that race (P=0.027) and older age (P=0.014) were the most important predictors of worse CD severity. When followed up a median of 2.3 years after surgery, the relative risk for persistent CD combined with recurrence was 2.8 times higher in the HI/AA group compared with that in the non-HW group (95% confidence interval: 1.2-6.5).ConclusionOur data show that the driving forces for the discrepancy in severity of CD are older age and race/ethnicity. Importantly, the risk for persistent and recurrent CD was higher in minority children

Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation

Understanding the function of histone modifications across inducible genes in mammalian cells requires quantitative, comparative analysis of their fate during gene activation and identification of enzymes responsible. We produced high-resolution comparative maps of the distribution and dynamics of H3K4me3, H3K36me3, H3K79me2 and H3K9ac across c-fos and c-jun upon gene induction in murine fibroblasts. In unstimulated cells, continuous turnover of H3K9 acetylation occurs on all K4-trimethylated histone H3 tails; distribution of both modifications coincides across promoter and 5′ part of the coding region. In contrast, K36- and K79-methylated H3 tails, which are not dynamically acetylated, are restricted to the coding regions of these genes. Upon stimulation, transcription-dependent increases in H3K4 and H3K36 trimethylation are seen across coding regions, peaking at 5′ and 3′ ends, respectively. Addressing molecular mechanisms involved, we find that Huntingtin-interacting protein HYPB/Setd2 is responsible for virtually all global and transcription-dependent H3K36 trimethylation, but not H3K36-mono- or dimethylation, in these cells. These studies reveal four distinct layers of histone modification across inducible mammalian genes and show that HYPB/Setd2 is responsible for H3K36 trimethylation throughout the mouse nucleus

Clinical Implication of Targeting of Cancer Stem Cells

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers. Copyright (c) 2012 S. Karger AG, Base

Current State of the Science: Health Effects and Indoor Environmental Quality

Our understanding of the relationship between human health and the indoor environment continues to evolve. Previous research on health and indoor environments has tended to concentrate on discrete pollutant sources and exposures and on specific disease processes. Recently, efforts have been made to characterize more fully the complex interactions between the health of occupants and the interior spaces they inhabit. In this article we review recent advances in source characterization, exposure assessment, health effects associated with indoor exposures, and intervention research related to indoor environments. Advances in source characterization include a better understanding of how chemicals are transported and processed within spaces and the role that other factors such as lighting and building design may play in determining health. Efforts are under way to improve our ability to measure exposures, but this remains a challenge, particularly for biological agents. Researchers are also examining the effects of multiple exposures as well as the effects of exposures on vulnerable populations such as children and the elderly. In addition, a number of investigators are also studying the effects of modifying building design, materials, and operations on occupant health. Identification of research priorities should include input from building designers, operators, and the public health community