High p_T Triggered Delta-eta,Delta-phi Correlations over a Broad Range in Delta-eta

The first measurement of pseudorapidity (Delta-eta) and azimuthal angle (Delta-phi) correlations between high transverse momentum charged hadrons (p_T > 2.5 GeV/c) and all associated particles is presented at both short- (small Delta-eta) and long-range (large Delta-eta) over a continuous pseudorapidity acceptance (-4<Delta-eta<2). In these proceedings, the various near- and away-side features of the correlation structure are discussed as a function of centrality in Au+Au collisions measured by PHOBOS at sqrt(s_NN)=200 GeV. In particular, this measurement allows a much more complete determination of the longitudinal extent of the ridge structure, first observed by the STAR collaboration over a limited eta range. In central collisions the ridge persists to at least Delta-eta=4, diminishing in magnitude as collisions become more peripheral until it disappears around Npart=80.Comment: 5 pages, 2 figures, presented at the 20th International Conference on Ultra-Relativistic Nucleus-Nucleus Collisions, "Quark Matter 2008", Jaipur, India, February 4-10, 2008. Full author list included and typo corrected in equation

Diagnostic accuracy of magnetic resonance imaging targeted biopsy techniques compared to transrectal ultrasound guided biopsy of the prostate: a systematic review and meta-analysis

Background: Multiparametric MRI localizes cancer in the prostate, allowing for MRI guided biopsy (MRI-GB) 43 alongside transrectal ultrasound-guided systematic biopsy (TRUS-GB). Three MRI-GB approaches exist; visual estimation (COG-TB); fusion software-assisted (FUS-TB) and MRI ‘in-bore’ biopsy (IB-TB). It is unknown whether any of these are superior. We conducted a systematic review and meta-analysis to address three questions. First, whether MRI-GB is superior to TRUS-GB at detecting clinically significant PCa (csPCa). Second, whether MRI-GB is superior to TRUS-GB at avoiding detection of insignificant PCa. Third, whether any MRI-GB strategy is superior at detecting csPCa. Methods: A systematic literature review from 2015 to 2019 was performed in accordance with the START recommendations. Studies reporting PCa detection rates, employing MRI-GB and TRUS-GB were included and evaluated using the QUADAS-2 checklist. 1553 studies were found, of which 43 were included in the meta-analysis. Results: For csPCa, MRI-GB was superior in detection to TRUS-GB (0.83 vs. 0.63 [p = 0.02]). MRI-GB was superior in detection to TRUS-GB at avoiding detection of insignificant PCa. No MRI-GB technique was superior at detecting csPCa (IB-TB 0.87; COG TB 0.81; FUS-TB 0.81, [p = 0.55]). There was significant heterogeneity observed between the included studies. Conclusions: In patients with suspected PCa on MRI, MRI-GB offers superior rates of csPCa detection and reduces detection of insignificant PCa compared to TRUS-GB. No individual MRI-GB technique was found to be better in csPCa detection. Prospective adequately powered randomized controlled trials are required

A Systematic Review of Patients’ Values, Preferences, and Expectations for the Treatment of Metastatic Prostate Cancer

Peer reviewedPublisher PD

Motor unit dysregulation following 15 days of unilateral lower limb immobilisation

Muscle mass and function decline rapidly in situations of disuse such as bed rest and limb immobilisation. The reduction in muscle function commonly exceeds that of muscle mass, which may be associated with the dysregulation of neural input to muscle. We have used intramuscular electromyography to sample individual motor unit and near fibre potentials from the vastus lateralis following 15 days of unilateral limb immobilisation. Following disuse, the disproportionate loss of muscle strength when compared to size coincided with suppressed motor unit firing rate. These motor unit adaptations were observed at multiple contraction levels and in the immobilised limb only. Our findings demonstrate neural dysregulation as a key component of functional loss following muscle disuse in humans. Disuse atrophy, caused by situations of unloading such as limb immobilisation, causes a rapid yet diverging reduction in skeletal muscle function when compared to muscle mass. While mechanistic insight into the loss of mass is well studied, deterioration of muscle function with a focus towards the neural input to muscle remains underexplored. This study aimed to determine the role of motor unit adaptation in disuse-induced neuromuscular deficits. Ten young, healthy male volunteers underwent 15 days of unilateral lower limb immobilisation with intramuscular electromyography (iEMG) bilaterally recorded from the vastus lateralis (VL) during knee extensor contractions normalised to maximal voluntary contraction (MVC), pre and post disuse. Muscle cross-sectional area was determined by ultrasound. Individual MUs were sampled and analysed for changes in motor unit (MU) discharge and MU potential (MUP) characteristics. VL CSA was reduced by approximately 15% which was exceeded by a two-fold decrease of 31% in muscle strength in the immobilised limb, with no change in either parameter in the non-immobilised limb. Parameters of MUP size were reduced by 11 to 24% with immobilisation, while neuromuscular junction (NMJ) transmission instability remained unchanged, and MU firing rate decreased by 8 to 11% at several contraction levels. All adaptations were observed in the immobilised limb only. These findings highlight impaired neural input following immobilisation reflected by suppressed MU firing rate which may underpin the disproportionate reductions of strength relative to muscle size. Abstract figure legend Ten healthy young males underwent 15 days of unilateral lower limb immobilisation with an irremovable leg brace. Muscle size, strength and neuromuscular characteristics were measured bilaterally. Muscle strength reduced to a greater extent than muscle size in the immobilised leg while remaining unaltered in the non-immobilised leg. Motor unit firing rate, measured bilaterally using intramuscular electromyography, was also reduced in the immobilised leg only. This occurred at contraction intensities both relative to follow-up muscle strength and muscle strength normalised to pre-immobilisation. These findings suggest that neural dysregulation contributes to the loss of muscle strength observed in situations of disuse atrophy in humans

Personal non-commercial use only

ABSTRACT. Objective. To implement a rheumatology department education retreat to systematically identify and address the key factors necessary to improve medical education in our division in preparation for developing a rheumatology academy. Methods. The Hospital for Special Surgery organized a retreat for the Rheumatology Department aimed at (1) providing formal didactics and (2) assessing participants&apos; self-reported skills and interest in education with the goal of directing this information toward formalizing improvement. In a mixed-methods study design, faculty and fellows in the Division of Rheumatology were surveyed online pre-and post-retreat regarding various aspects of the current education program, their teaching abilities, interest and time spent in teaching, divisional resources allocated, and how education is valued. Results. Enthusiasm for teaching was high before and rose further after the retreat. Confidence in abilities was higher than expected before but fell afterward. Many noted that the lack of specific feedback on teaching skills and useful metrics to assess performance prevented the achievement of educational excellence. Most responding felt lack of time, knowledge of how to teach well, and resources prevented them from making greater commitments to educational endeavors and participating fully and effectively in the department&apos;s teaching activities. Conclusion. While most rheumatology faculty members want to improve as teachers, they know neither where their educational strengths and weaknesses lie nor where or how to begin to change their teaching abilities. The key elements for an academy would thus be an educational environment that elevates the quality of teaching throughout the division and promotes teaching careers and education research, and raises the importance and quality of teaching to equivalence with clinical care and research. (J Rheumatol First Release April 15 2012

Exploring the utility of ultrasound to assess disuse atrophy in different muscles of the lower leg

Background Skeletal muscle is a highly plastic tissue crucial for many functions associated with whole-body health across the life course. Magnetic resonance imaging (MRI) is the current gold standard for measuring skeletal muscle size. However, MRI is expensive, and access to facilities is often limited. B-mode ultrasonography (U/S) has been proposed as a potential alternative to MRI for the assessment of muscle size. However, to date, no work has explored the utility of U/S to assess disuse muscle atrophy (DMA) across muscles with different atrophy susceptibility profiles, an omission which may limit the clinical application of previous work. Methods To address this significant knowledge gap, 10 young men (22 ± years, 24.1 ± 2.3 kg/m2) underwent 15-day unilateral leg immobilization using a knee-brace and air boot. Cross-sectional area (CSA) and muscle thickness (MT) of the tibialis anterior (TA) and medial gastrocnemius (MG) were assessed via U/S before and after immobilization, with CSA and muscle volume assessed via MRI. Results With both muscles combined, there were good correlations between each U/S and MRI measure, both before (e.g., CSAMRI vs. MTU/S and CSAU/S: r = 0.88 and 0.94, respectively, both P < 0.0001) and after (e.g., VOLMRI vs. MTU/S and CSAU/S: r = 0.90 and 0.96, respectively, both P < 0.0001) immobilization. The relationship between the methods was notably stronger for MG than TA at each time-point (e.g., CSAMRI vs. MTU/S: MG, r = 0.70, P = 0.0006; TA, r = 0.37, P = 0.10). There was no relationship between the degree of DMA determined by the two methods in either muscle (e.g., TA pre- vs. post-immobilization, VOLMRI: 136 ± 6 vs. 133 ± 5, P = 0.08; CSAU/S: 6.05 ± 0.3 vs. 5.92 ± 0.4, P = 0.70; relationship between methods: r = 0.12, P = 0.75). Conclusions Both MTU/S and CSAU/S provide comparable static measures of lower leg muscle size compared with MRI, albeit with weaker agreement in TA compared to MG. Although both MTU/S and CSAU/S can discern differences in DMA susceptibility between muscles, neither can reliably assess degree of DMA. Based on the growing recognition of heterogeneous atrophy profiles between muscles, and the topical importance of less commonly studied muscles (i.e., TA for falls prevention in older adults), future research should aim to optimize accessible methods to determine muscle losses across the body

Amenability of groups and GG-sets

This text surveys classical and recent results in the field of amenability of groups, from a combinatorial standpoint. It has served as the support of courses at the University of G\"ottingen and the \'Ecole Normale Sup\'erieure. The goals of the text are (1) to be as self-contained as possible, so as to serve as a good introduction for newcomers to the field; (2) to stress the use of combinatorial tools, in collaboration with functional analysis, probability etc., with discrete groups in focus; (3) to consider from the beginning the more general notion of amenable actions; (4) to describe recent classes of examples, and in particular groups acting on Cantor sets and topological full groups

Mitochondria Regulate Proliferation in Adult Cardiac Myocytes

Newborn mammalian cardiomyocytes quickly transition from a fetal to an adult phenotype that utilizes mitochondrial oxidative phosphorylation but loses mitotic capacity. We tested whether forced reversal of adult cardiomyocytes back to a fetal glycolytic phenotype would restore proliferative capacity. We deleted Uqcrfs1 (mitochondrial Rieske iron-sulfur protein, RISP) in hearts of adult mice. As RISP protein decreased, heart mitochondrial function declined, and glucose utilization increased. Simultaneously, the hearts underwent hyperplastic remodeling during which cardiomyocyte number doubled without cellular hypertrophy. Cellular energy supply was preserved, AMPK activation was absent, and mTOR activation was evident. In ischemic hearts with RISP deletion, new cardiomyocytes migrated into the infarcted region, suggesting the potential for therapeutic cardiac regeneration. RNA sequencing revealed upregulation of genes associated with cardiac development and proliferation. Metabolomic analysis revealed a decrease in α-ketoglutarate (required for TET-mediated demethylation) and an increase in S-adenosylmethionine (required for methyltransferase activity). Analysis revealed an increase in methylated CpGs near gene transcriptional start sites. Genes that were both differentially expressed and differentially methylated were linked to upregulated cardiac developmental pathways. We conclude that decreased mitochondrial function and increased glucose utilization can restore mitotic capacity in adult cardiomyocytes, resulting in the generation of new heart cells, potentially through the modification of substrates that regulate epigenetic modification of genes required for proliferation

Serum Penicillin G Levels Are Lower Than Expected in Adults within Two Weeks of Administration of 1.2 Million Units

When introduced in the 1950s, benzathine penicillin G (BPG) was shown to be effective in eradicating group A beta-hemolytic streptococcus (GAS) for at least 3 weeks after administration. Several studies since the 1990s suggest that at 3–4 weeks serum penicillin G levels are less than adequate (below MIC90 of 0.016 µg/ml). We studied these levels for 4 weeks after the recommended dose of BPG in military recruits, for whom it is used as prophylaxis against GAS. The 329 subjects (mean age 20 years) each received 1.2 million units BPG IM and gave sera 1 day post injection and twice more at staggered time points over 4 weeks. Serum penicillin G levels were measured by liquid chromatography/tandem mass spectometry. The half-life of serum penicillin G was 4.1 days. By day 11, mean levels were <0.02 µg/ml, and by day 15<0.01 µg/ml. Levels in more than 50% of the subjects were below 0.02 µg/ml on day 9, and <.01 µg/ml on day 16. There was no demonstrable effect of subject body-surface area nor of the four different lots of BPG used. These data indicate that in healthy young adults serum penicillin G levels become less than protective <2½ weeks after injection of 1.2 million units of BPG. The findings require serious consideration in future medical and public health recommendations for treatment and prophylaxis of GAS upper respiratory tract infections

Underpinning Sustainable Vector Control through Informed Insecticide Resistance Management

Background: There has been rapid scale-up of malaria vector control in the last ten years. Both of the primary control strategies, long-lasting pyrethroid treated nets and indoor residual spraying, rely on the use of a limited number of insecticides. Insecticide resistance, as measured by bioassay, has rapidly increased in prevalence and has come to the forefront as an issue that needs to be addressed to maintain the sustainability of malaria control and the drive to elimination. Zambia’s programme reported high levels of resistance to the insecticides it used in 2010, and, as a result, increased its investment in resistance monitoring to support informed resistance management decisions. Methodology/Principal Findings: A country-wide survey on insecticide resistance in Zambian malaria vectors was performed using WHO bioassays to detect resistant phenotypes. Molecular techniques were used to detect target-site mutations and microarray to detect metabolic resistance mechanisms. Anopheles gambiae s.s. was resistant to pyrethroids,DDT and carbamates, with potential organophosphate resistance in one population. The resistant phenotypes were conferred by both target-site and metabolic mechanisms. Anopheles funestus s.s. was largely resistant to pyrethroids and carbamates, with potential resistance to DDT in two locations. The resistant phenotypes were conferred by elevated levels of cytochrome p450s. Conclusions/Significance: Currently, the Zambia National Malaria Control Centre is using these results to inform their vector control strategy. The methods employed here can serve as a template to all malaria-endemic countries striving to create a sustainable insecticide resistance management pla