Thoughts on opportunities from high-energy nuclear collisions

This document summarizes thoughts on opportunities from high-energy nuclear collisions.Comment: 10 pages, pd

Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation

International audienceBackground: In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold‑storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold‑preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation. Methods: The preservation solution Celsior saturated with pure argon (Argon‑Celsior) or xenon (Xenon‑Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air‑Celsior). The left kidney was removed, and Air‑Celsior (n = 8 pigs), Argon‑Celsior (n = 8) or Xenon‑Celsior (n = 6) was used at 4 °C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air‑Celsior was used. Hetero‑ topic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days. Results: The use of Argon‑Celsior vs. Air‑Celsior: (1) improved function recovery as monitored via creatinine clear‑ ance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2–3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day‑21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the " reduced ascorbic acid/thiobarbituric acid reactive substances " ratio and Hsp27 expression; (6) limited the inflamma‑ tory response as shown by expression of TNF‑alpha, IL1‑beta and IL6 as observed after the natural death/euthanasia. Conversely, Xenon‑Celsior was detrimental, no animal surviving by day‑8 in a context where functional recovery, renal tissue properties and the antioxidant and inflammation responses were significantly altered. Thus, the positive effects of argon were not attributable to the noble gases as a group. Conclusions: The saturation of Celsior with argon improved early functional recovery, graft quality and survival. Manipulating the gas composition of a preservation medium constitutes therefore a promising approach to improve preservation

AIS Politics: The Contested Use of Vessel Tracking at the EU’s Maritime Frontier

Automatic identification system (AIS) is a vessel tracking system, which since 2004 has become a global tool for the detection and analysis of seagoing traffic. In this article, we look at how this technology, initially designed as a collision avoidance system, has recently become involved in debates concerning migration across the Mediterranean Sea. In particular, after having briefly discussed its emergence and characteristics, we examine how through different practices of (re)appropriation AIS, and the data it generate, have been seized upon, both to contest and to sustain the exclusionary nature of borders, and the mass dying of migrants at sea to which it leads. We do so by referring to forms of data activism we have contributed to in the frame of our Forensic Oceanography project as well as to situations in which AIS has been mobilized by xenophobic groups to demand even stronger exclusionary measures. At the same time, we point to the multiplicity of actors who participate in the politics of migration through AIS in unexpected ways. We conclude by highlighting the irreducible ambivalence of practices of appropriation and call for persistent attention to one’s own positioning within the global datascape constituted by AIS and other data

The effectiveness, acceptability and cost-effectiveness of psychosocial interventions for maltreated children and adolescents: an evidence synthesis.

BACKGROUND: Child maltreatment is a substantial social problem that affects large numbers of children and young people in the UK, resulting in a range of significant short- and long-term psychosocial problems. OBJECTIVES: To synthesise evidence of the effectiveness, cost-effectiveness and acceptability of interventions addressing the adverse consequences of child maltreatment. STUDY DESIGN: For effectiveness, we included any controlled study. Other study designs were considered for economic decision modelling. For acceptability, we included any study that asked participants for their views. PARTICIPANTS: Children and young people up to 24 years 11 months, who had experienced maltreatment before the age of 17 years 11 months. INTERVENTIONS: Any psychosocial intervention provided in any setting aiming to address the consequences of maltreatment. MAIN OUTCOME MEASURES: Psychological distress [particularly post-traumatic stress disorder (PTSD), depression and anxiety, and self-harm], behaviour, social functioning, quality of life and acceptability. METHODS: Young Persons and Professional Advisory Groups guided the project, which was conducted in accordance with Cochrane Collaboration and NHS Centre for Reviews and Dissemination guidance. Departures from the published protocol were recorded and explained. Meta-analyses and cost-effectiveness analyses of available data were undertaken where possible. RESULTS: We identified 198 effectiveness studies (including 62 randomised trials); six economic evaluations (five using trial data and one decision-analytic model); and 73 studies investigating treatment acceptability. Pooled data on cognitive-behavioural therapy (CBT) for sexual abuse suggested post-treatment reductions in PTSD [standardised mean difference (SMD) -0.44 (95% CI -4.43 to -1.53)], depression [mean difference -2.83 (95% CI -4.53 to -1.13)] and anxiety [SMD -0.23 (95% CI -0.03 to -0.42)]. No differences were observed for post-treatment sexualised behaviour, externalising behaviour, behaviour management skills of parents, or parental support to the child. Findings from attachment-focused interventions suggested improvements in secure attachment [odds ratio 0.14 (95% CI 0.03 to 0.70)] and reductions in disorganised behaviour [SMD 0.23 (95% CI 0.13 to 0.42)], but no differences in avoidant attachment or externalising behaviour. Few studies addressed the role of caregivers, or the impact of the therapist-child relationship. Economic evaluations suffered methodological limitations and provided conflicting results. As a result, decision-analytic modelling was not possible, but cost-effectiveness analysis using effectiveness data from meta-analyses was undertaken for the most promising intervention: CBT for sexual abuse. Analyses of the cost-effectiveness of CBT were limited by the lack of cost data beyond the cost of CBT itself. CONCLUSIONS: It is not possible to draw firm conclusions about which interventions are effective for children with different maltreatment profiles, which are of no benefit or are harmful, and which factors encourage people to seek therapy, accept the offer of therapy and actively engage with therapy. Little is known about the cost-effectiveness of alternative interventions. LIMITATIONS: Studies were largely conducted outside the UK. The heterogeneity of outcomes and measures seriously impacted on the ability to conduct meta-analyses. FUTURE WORK: Studies are needed that assess the effectiveness of interventions within a UK context, which address the wider effects of maltreatment, as well as specific clinical outcomes. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013003889. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Evaluating triple oxygen isotope estimates of gross primary production at the Hawaii Ocean Time-series and Bermuda Atlantic Time-series Study sites

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 117 (2012): C05012, doi:10.1029/2010JC006856.The triple oxygen isotopic composition of dissolved oxygen (17Δ) is a promising tracer of gross oxygen productivity (P) in the ocean. Recent studies have inferred a high and variable ratio of P to 14C net primary productivity (12–24 h incubations) (e.g., P:NPP(14C) of 5–10) using the 17Δ tracer method, which implies a very low efficiency of phytoplankton growth rates relative to gross photosynthetic rates. We added oxygen isotopes to a one-dimensional mixed layer model to assess the role of physical dynamics in potentially biasing estimates of P using the 17Δ tracer method at the Bermuda Atlantic Time-series Study (BATS) and Hawaii Ocean Time-series (HOT). Model results were compared to multiyear observations at each site. Entrainment of high 17Δ thermocline water into the mixed layer was the largest source of error in estimating P from mixed layer 17Δ. At both BATS and HOT, entrainment bias was significant throughout the year and resulted in an annually averaged overestimate of mixed layer P of 60 to 80%. When the entrainment bias is corrected for, P calculated from observed 17Δ and 14C productivity incubations results in a gross:net productivity ratio of 2.6 (+0.9 −0.8) at BATS. At HOT a gross:net ratio decreasing linearly from 3.0 (+1.0 −0.8) at the surface to 1.4 (+0.6 −0.6) at depth best reproduced observations. In the seasonal thermocline at BATS, however, a significantly higher gross:net ratio or large lateral fluxes of 17Δ must be invoked to explain 17Δ field observations.We acknowledge support from Center for Microbial Oceanography Research and Education (CMORE) (NSF EF-0424599) and NOAA Global Carbon Program (NA 100AR4310093). BL thanks the USA-Israel Binational Science Foundation for supporting his project at BATS.2012-11-0

Comparison of the Gene Expression Profiles from Normal and Fgfrl1 Deficient Mouse Kidneys Reveals Downstream Targets of Fgfrl1 Signaling

Fgfrl1 (fibroblast growth factor receptor-like 1) is a transmembrane receptor that is essential for the development of the metanephric kidney. It is expressed in all nascent nephrogenic structures and in the ureteric bud. Fgfrl1 null mice fail to develop the metanephric kidneys. Mutant kidney rudiments show a dramatic reduction of ureteric branching and a lack of mesenchymal-to-epithelial transition. Here, we compared the expression profiles of wildtype and Fgfrl1 mutant kidneys to identify genes that act downstream of Fgfrl1 signaling during the early steps of nephron formation. We detected 56 differentially expressed transcripts with 2-fold or greater reduction, among them many genes involved in Fgf, Wnt, Bmp, Notch, and Six/Eya/Dach signaling. We validated the microarray data by qPCR and whole-mount in situ hybridization and showed the expression pattern of candidate genes in normal kidneys. Some of these genes might play an important role during early nephron formation. Our study should help to define the minimal set of genes that is required to form a functional nephron

Isoform-specific targeting of PKA to multivesicular bodies

PKA RIα subunit is localized to MVBs by the A-kinase–anchoring protein AKAP11 when disassociated from the PKA catalytic subunit

Heimler Syndrome is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6

Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities and occasional or late onset retinal pigmentation. We ascertained eight families with HS, and - using a whole exome sequencing approach - identified biallelic mutations in PEX1 or PEX6 in six of them. Loss of function mutations in both genes are known causes of a spectrum of autosomal recessive peroxisome biogenesis disorders (PBDs), including Zellweger syndrome. PBDs are characterized by leukodystrophy, hypotonia, SNHL, retinopathy, and skeletal, craniofacial, and liver abnormalities. We demonstrate that each HS family has at least one hypomorphic allele that results in extremely mild peroxisomal dysfunction. Although individuals with HS share some subtle clinical features found in PBDs, the overlap is minimal and the diagnosis was not suggested by routine blood and skin fibroblast analyses used to detect PBDs. In conclusion, our findings define Heimler syndrome as a mild PBD, expanding the pleiotropy of mutations in PEX1 and PEX6