New reference tables and user-friendly Internet application for predicted heart weights.

BACKGROUND: Knowledge of normal heart weight ranges is important information for pathologists. Comparing the measured heart weight to reference values is one of the key elements used to determine if the heart is pathological, as heart weight increases in many cardiac pathologies. The current reference tables are old and in need of an update. AIMS: The purposes of this study are to establish new reference tables for normal heart weights in the local population and to determine the best predictive factor for normal heart weight. We also aim to provide technical support to calculate the predictive normal heart weight. METHODS: The reference values are based on retrospective analysis of adult Caucasian autopsy cases without any obvious pathology that were collected at the University Centre of Legal Medicine in Lausanne from 2007 to 2011. We selected 288 cases. The mean age was 39.2 years. There were 118 men and 170 women. Regression analyses were performed to assess the relationship of heart weight to body weight, body height, body mass index (BMI) and body surface area (BSA). RESULTS: The heart weight increased along with an increase in all the parameters studied. The mean heart weight was greater in men than in women at a similar body weight. BSA was determined to be the best predictor for normal heart weight. New reference tables for predicted heart weights are presented as a web application that enable the comparison of heart weights observed at autopsy with the reference values. CONCLUSIONS: The reference tables for heart weight and other organs should be systematically updated and adapted for the local population. Web access and smartphone applications for the predicted heart weight represent important investigational tools.

Ubiquitin Ligases of the N-End Rule Pathway: Assessment of Mutations in UBR1 That Cause the Johanson-Blizzard Syndrome.

Background: Johanson-Blizzard syndrome (JBS; OMIM 243800) is an autosomal recessive disorder that includes congenital exocrine pancreatic insufficiency, facial dysmorphism with the characteristic nasal wing hypoplasia, multiple malformations, and frequent mental retardation. Our previous work has shown that JBS is caused by mutations in human UBR1, which encodes one of the E3 ubiquitin ligases of the N-end rule pathway. The N-end rule relates the regulation of the in vivo half-life of a protein to the identity of its N-terminal residue. One class of degradation signals (degrons) recognized by UBR1 are destabilizing N-terminal residues of protein substrates.Methodology/Principal Findings: Most JBS-causing alterations of UBR1 are nonsense, frameshift or splice-site mutations that abolish UBR1 activity. We report here missense mutations of human UBR1 in patients with milder variants of JBS. These single-residue changes, including a previously reported missense mutation, involve positions in the RING-H2 and UBR domains of UBR1 that are conserved among eukaryotes. Taking advantage of this conservation, we constructed alleles of the yeast Saccharomyces cerevisiae UBR1 that were counterparts of missense JBS-UBR1 alleles. Among these yeast Ubr1 mutants, one of them (H160R) was inactive in yeast-based activity assays, the other one (Q1224E) had a detectable but weak activity, and the third one (V146L) exhibited a decreased but significant activity, in agreement with manifestations of JBS in the corresponding JBS patients.Conclusions/Significance: These results, made possible by modeling defects of a human ubiquitin ligase in its yeast counterpart, verified and confirmed the relevance of specific missense UBR1 alleles to JBS, and suggested that a residual activity of a missense allele is causally associated with milder variants of JBS.

Política i empresa, companyes de viatge La qüestió catalana Reportatge digital sobre l’empresariat català i l’encaix Catalunya- Espanya. Valoracions entorn el debat sobiranista

El debat sobiranista català està a l‟ordre del dia i actualment no passa desapercebut en cap mitjà de comunicació ni tampoc en el món polític, econòmic i empresarial. El fet d‟estar tan viva una temàtica així de delicada està ocasionant controvèrsies dins l‟empresariat català o que té la seva empresa ubicada a Catalunya perquè tot plegat provoca moltes incerteses, que són el pitjor enemic dels empresaris i dels negocis. Tanmateix, però, les informacions publicades o emeses venen marcades per les opinions polítiques i periodístiques, que es troben censurades en certa mesura perquè segueixen una determinada línia política i/o editorial. Per això s‟ha elaborat un reportatge digital focalitzat en l‟empresariat català i l‟encaix Catalunya-Espanya que pretén aportar noves valoracions entorn a aquest debat donant veu a empresaris i professionals, entre altres. La part teòrica de la memòria defineix els conceptes bàsics que són de forçat coneixement per realitzar una part pràctica que ha de ser entesa per qualsevol persona i que s‟ha de tractar amb la major objectivitat possible. Per això, el web http://laquestiocatalana.cat aporta un llenguatge planer i les eines bàsiques per donar a conèixer una matèria molt criticada per alguns sectors. A través d‟entrevistes a personatges rellevants, el web introdueix nous punts de vista sobre una qüestió marcada, a simple vista, per la preocupació d‟un possible boicot per part d‟Espanya. Però aquesta no sembla ser la principal inquietud dels entesos, i és que hi ha altres aspectes encara més alarmants que poden influir en l‟empresariat i que no són tractats per cap mitjà de comunicació convencional.

Minimal information about T cell assays: the process of reaching the community of T cell immunologists in cancer and beyond.

Many assays to evaluate the nature, breadth, and quality of antigen-specific T cell responses are currently applied in human medicine. In most cases, assay-related protocols are developed on an individual laboratory basis, resulting in a large number of different protocols being applied worldwide. Together with the inherent complexity of cellular assays, this leads to unnecessary limitations in the ability to compare results generated across institutions. Over the past few years a number of critical assay parameters have been identified which influence test performance irrespective of protocol, material, and reagents used. Describing these critical factors as an integral part of any published report will both facilitate the comparison of data generated across institutions and lead to improvements in the assays themselves. To this end, the Minimal Information About T Cell Assays (MIATA) project was initiated. The objective of MIATA is to achieve a broad consensus on which T cell assay parameters should be reported in scientific publications and to propose a mechanism for reporting these in a systematic manner. To add maximum value for the scientific community, a step-wise, open, and field-spanning approach has been taken to achieve technical precision, user-friendliness, adequate incorporation of concerns, and high acceptance among peers. Here, we describe the past, present, and future perspectives of the MIATA project. We suggest that the approach taken can be generically applied to projects in which a broad consensus has to be reached among scientists working in fragmented fields, such as immunology. An additional objective of this undertaking is to engage the broader scientific community to comment on MIATA and to become an active participant in the project.

Needs, expectations, and concerns of medical students regarding end-of-life issues before the introduction of a mandatory undergraduate palliative care curriculum.

BACKGROUND: In the past, implementation of effective palliative care curricula has emerged as a priority in medical education. In order to gain insight into medical students' needs and expectations, we conducted a survey before mandatory palliative care education was introduced in our faculty. METHODS: Seven hundred nine students answered a questionnaire mainly consisting of numeric rating scales (0-10). RESULTS: Participants attributed a high importance to palliative care for their future professional life (mean, 7.51 ± 2.2). For most students, symptom control was crucial (7.72 ± 2.2). However, even higher importance was assigned to ethical and legal issues (8.16 ± 1.9). "Self-reflection regarding their own role as a physician caring for the terminally ill along with psychological support" was also regarded as highly important (7.25 ± 2.4). Most students were moderately concerned at the prospect of being confronted with suffering and death (5.13 ± 2.4). This emotional distress was rated significantly higher by female students (5.4 ± 2.4 versus 4.6 ± 2.4; p < 0.001). Seventeen percent of all students rated their distress as being 7 of 10 or higher, which indicates a considerable psychological strain in terms of dealing with end-of-life issues in the future. Professional or personal experience with terminally ill persons lowered these anxieties significantly (4.99 ± 2.34 versus 5.47 ± 2.5, p < 0.05). CONCLUSIONS: Medical students stated a remarkably high interest in learning palliative care competencies. Responding to their specific concerns and needs-especially with regard to the acquisition of emotional coping skills-may be key for the development of successful palliative care curricula.

Remote collaborative multi-user informal learning experiences: design and evaluation

This paper presents a customizable system used to develop a collaborative multi-user problem solving game. It addresses the increasing demand for appealing informal learning experiences in museum-like settings. The system facilitates remote collaboration by allowing groups of learners tocommunicate through a videoconferencing system and by allowing them to simultaneously interact through a shared multi-touch interactive surface. A user study with 20 user groups indicates that the game facilitates collaboration between local and remote groups of learners. The videoconference and multitouch surface acted as communication channels, attracted students’ interest, facilitated engagement, and promoted inter- and intra-group collaboration—favoring intra-group collaboration. Our findings suggest that augmentingvideoconferencing systems with a shared multitouch space offers newpossibilities and scenarios for remote collaborative environments and collaborative learning.

A regulatory role for the cohesin loader NIPBL in nonhomologous end joining during immunoglobulin class switch recombination.

DNA double strand breaks (DSBs) are mainly repaired via homologous recombination (HR) or nonhomologous end joining (NHEJ). These breaks pose severe threats to genome integrity but can also be necessary intermediates of normal cellular processes such as immunoglobulin class switch recombination (CSR). During CSR, DSBs are produced in the G1 phase of the cell cycle and are repaired by the classical NHEJ machinery. By studying B lymphocytes derived from patients with Cornelia de Lange Syndrome, we observed a strong correlation between heterozygous loss-of-function mutations in the gene encoding the cohesin loading protein NIPBL and a shift toward the use of an alternative, microhomology-based end joining during CSR. Furthermore, the early recruitment of 53BP1 to DSBs was reduced in the NIPBL-deficient patient cells. Association of NIPBL deficiency and impaired NHEJ was also observed in a plasmid-based end-joining assay and a yeast model system. Our results suggest that NIPBL plays an important and evolutionarily conserved role in NHEJ, in addition to its canonical function in sister chromatid cohesion and its recently suggested function in HR.

Laboratory Investigation of Concrete Beam-End Treatments, RB08-013, 2015

The ends of prestressed concrete beams under expansion joints are often exposed to moisture and chlorides. Left unprotected, the moisture and chlorides come in contact with the ends of the prestressing strands and/or the mild reinforcing, resulting in corrosion. Once deterioration begins, it progresses unless some process is employed to address it. Deterioration can lead to loss of bearing area and therefore a reduction in bridge capacity. Previous research has looked into the use of concrete coatings (silanes, epoxies, fiber-reinforced polymers, etc.) for protecting prestressed concrete beam ends but found that little to no laboratory research has been done related to the performance of these coatings in this specific type of application. The Iowa Department of Transportation (DOT) currently specifies coating the ends of exposed prestressed concrete beams with Sikagard 62 (a high-build, protective, solvent-free, epoxy coating) at the precast plant prior to installation on the bridge. However, no physical testing of Sikagard 62 in this application has been completed. In addition, the Iowa DOT continues to see deterioration in the prestressed concrete beam ends, even those treated with Sikagard 62. The goals of this project were to evaluate the performance of the Iowa DOT-specified beam-end coating as well as other concrete coating alternatives based on the American Association of State Highway and Transportation Officials (AASHTO) T259-80 chloride ion penetration test and to test their performance on in-service bridges throughout the duration of the project. In addition, alternative beam-end forming details were developed and evaluated for their potential to mitigate and/or eliminate the deterioration caused by corrosion of the prestressing strands on prestressed concrete beam ends used in bridges with expansion joints. The alternative beam-end details consisted of individual strand blockouts, an individual blockout for a cluster of strands, dual blockouts for two clusters of strands, and drilling out the strands after they are flush cut. The goal of all of the forming alternatives was to offset the ends of the prestressing strands from the end face of the beam and then cover them with a grout/concrete layer, thereby limiting or eliminating their exposure to moisture and chlorides.

Iowa Bridge Backwater Software User Manual, Version 2.0, TR-564, 2010

This manual describes how to use the Iowa Bridge Backwater software. It also documents the methods and equations used for the calculations. The main body describes how to use the software and the appendices cover technical aspects. The Bridge Backwater software performs 5 main tasks: Design Discharge Estimation; Stream Rating Curves; Floodway Encroachment; Bridge Backwater; and Bridge Scour. The intent of this program is to provide a simplified method for analysis of bridge backwater for rural structures located in areas with low flood damage potential. The software is written in Microsoft Visual Basic 6.0. It will run under Windows 95 or newer versions (i.e. Windows 98, NT, 2000, XP and later).

Origin of cadmium enrichments in carbonate rocks deposited in the Alpine Tethys area during the Middle-Late Jurassic

ABSTRACTThe pollution of air, soil and water by heavy metals through anthropogenic activities is an object of numerous environmental studies since long times. A number of natural processes, such as volcanic activity, hydrothermal fluid circulation and weathering of metal-rich deposits may lead to an additional and potentially important input and accumulation of heavy metals in the environment. In the Swiss and French Jura Mountains, anomalous high cadmium (Cd) concentrations (up to 16 ppm) in certain soils are related to the presence of underlying Cd-enriched (up to 21 ppm) carbonate rocks of Middle to Late Jurassic age. The aim of this study is to understand the processes controlling Cd incorporation into carbonate rocks of Middle and Late Jurassic age and to reconstruct the sedimentary and environmental conditions, which have led to Cd enrichments in these sedimentary rocks.Cd concentrations in studied hemipelagic sections in France vary between 0.1 and 0.5 ppm (mean 0.15 ppm). Trace-element behavior and high Mn concentrations suggest that sediment accumulation occurred in a well-oxygenated environment. Increases in Cd contents in the bulk-rock carbonate sediments may be related to increases in surface-water productivity under oxic conditions and important remineralization of organic matter within the water column. In platform settings preserved in the Swiss Jura Mountains, no correlation is observed between Cd contents and evolution of environmental conditions. Cd concentrations in these platform sections are often below the detection limit, with isolated peaks of up to 21 ppm. These important Cd enrichments are associated with peaks in Zn concentrations and are present in carbonate rocks independently of facies and age. The high Cd contents in these shallow-water carbonate rocks are partly related to the presence of disseminated, Cd-rich (up to 1.8%), sphalerite (ZnS) mineralization. The basement rocks are considered to be the source of metals for sulfide mineralization in the overlying Jurassic strata, as the sphalerite Pb isotope pattern is comparable to that of granite rocks from the nearby southern Black Forest crystalline massif. The Rb-Sr ages of sphalerite samples indicate that a main phase of sphalerite formation occurred near the boundary between the late Middle and early Late Jurassic, at around 162 Ma, as a result of enhanced tectonic and hydrothermal activity in Europe, related to the opening of the Central Atlantic and to the tectonic/thermal subsidence during spreading of the Alpine Tethys. I therefore propose to use unusually high Cd concentrations in carbonates as a tracer of tectonic activity in the Jura Mountains area, especially in the case when important enrichments in Zn co-occur. Paleoproductivity reconstructions based on records of authigenic Cd may be compromised not only by post-depositional redistribution, but also by incorporation of additional Cd from hydrothermal solutions circulating in the rock.The circulation of metal-rich hydrothermal fluids through the sediment sequence, in addition to specific environmental conditions during sedimentation, contributes to the incorporation of Cd into the carbonate rocks. However, only hydrothermal activity has led to the unusually high concentrations of Cd in carbonate rocks of Bajocian-Oxfordian age, through the formation of sphalerite mineralization.

Rapid marine recovery after the end-Permian mass-extinction event in the absence of marine anoxia

A new Early Triassic marine fauna is described from the Central Oman Mountains. The fauna is Griesbachian in age, on the basis of abundant conodonts and ammonoids, and was deposited in an oxygenated seamount setting off the Arabian platform margin. It is the first Griesbachian assemblage from a well-oxygenated marine setting and thus provides a test for the hypothesis that widespread anoxia prevented rapid recovery. The earliest Griesbachian (parvus zone) contains a low-diversity benthic fauna dominated by the bivalves Promyalina and Claraia. A similar level of recovery characterizes the immediate postextinction interval worldwide. However, the middle upper Griesbachian sedimentary rocks (isarcica and catinata zones) contain an incredibly diverse benthic fauna of bivalves, gastropods, articulate brachiopods, a new undescribed crinoid, echinoids, and ostracods. This fauna is more diverse and ecologically complex than the typical middle to late Griesbachian faunas described from oxygen-restricted settings worldwide. The level of postextinction recovery observed in the Oman fauna is not recorded elsewhere until the Spathian. These data support the hypothesis that the apparent delay in recovery after the end-Permian extinction event was due to widespread and prolonged benthic oxygen restriction: in the absence of anoxia, marine recovery is much faster.

Evaluation of reed canary grass for different end-uses and in breeding

Selostus: Ruokohelven soveltuvuus non-food-, rehun- ja siementuotantoon