Histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome: phenotypes linked by truncating variants in NDUFB11

Variants in NDUFB11, which encodes a structural component of complex I of the mitochondrial respiratory chain (MRC), were recently independently reported to cause histiocytoid cardiomyopathy (histiocytoid CM) and microphthalmia with linear skin defects syndrome (MLS syndrome). Here we report an additional case of histiocytoid CM, which carries a de novo nonsense variant in NDUFB11 (ENST00000276062.8: c.262C > T; p.[Arg88*]) identified using whole-exome sequencing (WES) of a family trio. An identical variant has been previously reported in association with MLS syndrome. The case we describe here lacked the diagnostic features of MLS syndrome, but a detailed clinical comparison of the two cases revealed significant phenotypic overlap. Heterozygous variants in HCCS (which encodes an important mitochondrially targeted protein) and COX7B, which, like NDUFB11, encodes a protein of the MRC, have also previously been identified in MLS syndrome including a case with features of both MLS syndrome and histiocytoid CM. However, a systematic review of WES data from previously published histiocytoid CM cases, alongside four additional cases presented here for the first time, did not identify any variants in these genes. We conclude that NDUFB11 variants play a role in the pathogenesis of both histiocytoid CM and MLS and that these disorders are allelic (genetically related)

Synthesized grain size distribution in the interstellar medium

We examine a synthetic way of constructing the grain size distribution in the interstellar medium (ISM). First we formulate a synthetic grain size distribution composed of three grain size distributions processed with the following mechanisms that govern the grain size distribution in the Milky Way: (i) grain growth by accretion and coagulation in dense clouds, (ii) supernova shock destruction by sputtering in diffuse ISM, and (iii) shattering driven by turbulence in diffuse ISM. Then, we examine if the observational grain size distribution in the Milky Way (called MRN) is successfully synthesized or not. We find that the three components actually synthesize the MRN grain size distribution in the sense that the deficiency of small grains by (i) and (ii) is compensated by the production of small grains by (iii). The fraction of each {contribution} to the total grain processing of (i), (ii), and (iii) (i.e., the relative importance of the three {contributions} to all grain processing mechanisms) is 30-50%, 20-40%, and 10-40%, respectively. We also show that the Milky Way extinction curve is reproduced with the synthetic grain size distributions.Comment: 10 pages, 6 figures, accepted for publication in Earth, Planets, and Spac

The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs

The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised

Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: Study protocol for a multicentre randomized controlled trial

Background: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.Methods/Design: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.Discussion: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.Trial Registration: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007. © 2011 Longo et al; licensee BioMed Central Ltd

Heart failure guidelines and prescribing in primary care across Europe

BACKGROUND: Major international differences in heart failure treatment have been repeatedly described, but the reasons for these differences remain unclear. National guideline recommendations might be a relevant factor. This study, therefore, explored variation of heart failure guideline recommendations in Europe. METHODS: Treatment recommendations of 14 national guidelines published after 1994 were analyzed in relation to the heart failure treatment guideline of the European Society of Cardiology. To test potential relations between recommendations and prescribing, national prescribing patterns as obtained by a European study in primary care (IMPROVEMENT-HF) were related to selected recommendations in those countries. RESULTS: Besides the 14 national guidelines used by primary care physicians in the countries contacted, the European guideline was used in four countries, and separate guidelines for specialists and primary care were available in another four countries. Two countries indicated that no guideline was used up to 2000. Comprehensiveness of the guidelines varied with respect to length, literature included and evidence ratings. Relevant differences in treatment recommendations were seen only in drug classes where evidence had changed recently (β-blockers and spironolactone). The relation between recommendation and prescribing for selected recommendations was inconsistent among countries. CONCLUSION: Differences in guideline recommendations are not sufficient to explain variation of prescribing among countries, thus other factors must be considered

Reforming sanitary-epidemiological service in Central and Eastern Europe and the former Soviet Union: an exploratory study

<p>Abstract</p> <p>Background</p> <p>Public health services in the Soviet Union and its satellite states in Central and Eastern Europe were delivered through centrally planned and managed networks of sanitary-epidemiological (san-epid) facilities. Many countries sought to reform this service following the political transition in the 1990s. In this paper we describe the major themes within these reforms.</p> <p>Methods</p> <p>A review of literature was conducted. A conceptual framework was developed to guide the review, which focused on the two traditional core public health functions of the san-epid system: communicable disease surveillance, prevention and control and environmental health. The review included twenty-two former communist countries in the former Soviet Union (fSU) and in Central and Eastern Europe (CEE).</p> <p>Results</p> <p>The countries studied fall into two broad groups. Reforms were more extensive in the CEE countries than in the fSU. The CEE countries have moved away from the former centrally managed san-epid system, adopting a variety of models of decentralization. The reformed systems remain mainly funded centrally level, but in some countries there are contributions by local government. In almost all countries, epidemiological surveillance and environmental monitoring remained together under a single organizational umbrella but in a few responsibilities for environmental health have been divided among different ministries.</p> <p>Conclusions</p> <p>Progress in reform of public health services has varied considerably. There is considerable scope to learn from the differing experiences but also a need for rigorous evaluation of how public health functions are provided.</p

Magnetic support of the optical emission line filaments in NGC 1275

The giant elliptical galaxy NGC 1275, at the centre of the Perseus cluster, is surrounded by a well-known giant nebulosity of emission-line filaments, which are plausibly about >10^8 yr old. The filaments are dragged out from the centre of the galaxy by the radio bubbles rising buoyantly in the hot intracluster gas before later falling back. They act as dramatic markers of the feedback process by which energy is transferred from the central massive black hole to the surrounding gas. The mechanism by which the filaments are stabilized against tidal shear and dissipation into the surrounding 4x10^7 K gas has been unclear. Here we report new observations that resolve thread-like structures in the filaments. Some threads extend over 6 kpc, yet are only 70 pc wide. We conclude that magnetic fields in the threads, in pressure balance with the surrounding gas, stabilize the filaments, so allowing a large mass of cold gas to accumulate and delay star formation.Comment: Published in Nature, includes supplementary information, high resolution images available at http://www-xray.ast.cam.ac.uk/papers/ngc1275

A review of reporting of participant recruitment and retention in RCTs in six major journals

<p>Abstract</p> <p>Background</p> <p>Poor recruitment and retention of participants in randomised controlled trials (RCTs) is problematic but common. Clear and detailed reporting of participant flow is essential to assess the generalisability and comparability of RCTs. Despite improved reporting since the implementation of the CONSORT statement, important problems remain. This paper aims: (i) to update and extend previous reviews evaluating reporting of participant recruitment and retention in RCTs; (ii) to quantify the level of participation throughout RCTs.</p> <p>Methods</p> <p>We reviewed all reports of RCTs of health care interventions and/or processes with individual randomisation, published July–December 2004 in six major journals. Short, secondary or interim reports, and Phase I/II trials were excluded. Data recorded were: general RCT details; inclusion of flow diagram; participant flow throughout trial; reasons for non-participation/withdrawal; target sample sizes.</p> <p>Results</p> <p>133 reports were reviewed. Overall, 79% included a flow diagram, but over a third were incomplete. The majority reported the flow of participants at each stage of the trial after randomisation. However, 40% failed to report the numbers assessed for eligibility. Percentages of participants retained at each stage were high: for example, 90% of eligible individuals were randomised, and 93% of those randomised were outcome assessed. On average, trials met their sample size targets. However, there were some substantial shortfalls: for example 21% of trials reporting a sample size calculation failed to achieve adequate numbers at randomisation, and 48% at outcome assessment. Reporting of losses to follow up was variable and difficult to interpret.</p> <p>Conclusion</p> <p>The majority of RCTs reported the flow of participants well after randomisation, although only two-thirds included a complete flow chart and there was great variability over the definition of "lost to follow up". Reporting of participant eligibility was poor, making assessments of recruitment practice and external validity difficult. Reporting of participant flow throughout RCTs could be improved by small changes to the CONSORT chart.</p

Formation of Supermassive Black Holes

Evidence shows that massive black holes reside in most local galaxies. Studies have also established a number of relations between the MBH mass and properties of the host galaxy such as bulge mass and velocity dispersion. These results suggest that central MBHs, while much less massive than the host (~ 0.1%), are linked to the evolution of galactic structure. In hierarchical cosmologies, a single big galaxy today can be traced back to the stage when it was split up in hundreds of smaller components. Did MBH seeds form with the same efficiency in small proto-galaxies, or did their formation had to await the buildup of substantial galaxies with deeper potential wells? I briefly review here some of the physical processes that are conducive to the evolution of the massive black hole population. I will discuss black hole formation processes for `seed' black holes that are likely to place at early cosmic epochs, and possible observational tests of these scenarios.Comment: To appear in The Astronomy and Astrophysics Review. The final publication is available at http://www.springerlink.co

Radio emission from Supernova Remnants

The explosion of a supernova releases almost instantaneously about 10^51 ergs of mechanic energy, changing irreversibly the physical and chemical properties of large regions in the galaxies. The stellar ejecta, the nebula resulting from the powerful shock waves, and sometimes a compact stellar remnant, constitute a supernova remnant (SNR). They can radiate their energy across the whole electromagnetic spectrum, but the great majority are radio sources. Almost 70 years after the first detection of radio emission coming from a SNR, great progress has been achieved in the comprehension of their physical characteristics and evolution. We review the present knowledge of different aspects of radio remnants, focusing on sources of the Milky Way and the Magellanic Clouds, where the SNRs can be spatially resolved. We present a brief overview of theoretical background, analyze morphology and polarization properties, and review and critical discuss different methods applied to determine the radio spectrum and distances. The consequences of the interaction between the SNR shocks and the surrounding medium are examined, including the question of whether SNRs can trigger the formation of new stars. Cases of multispectral comparison are presented. A section is devoted to reviewing recent results of radio SNRs in the Magellanic Clouds, with particular emphasis on the radio properties of SN 1987A, an ideal laboratory to investigate dynamical evolution of an SNR in near real time. The review concludes with a summary of issues on radio SNRs that deserve further study, and analyzing the prospects for future research with the latest generation radio telescopes.Comment: Revised version. 48 pages, 15 figure