Management of radioactive material safety programs at medical facilities. Final report

A Task Force, comprising eight US Nuclear Regulatory Commission and two Agreement State program staff members, developed the guidance contained in this report. This report describes a systematic approach for effectively managing radiation safety programs at medical facilities. This is accomplished by defining and emphasizing the roles of an institution`s executive management, radiation safety committee, and radiation safety officer. Various aspects of program management are discussed and guidance is offered on selecting the radiation safety officer, determining adequate resources for the program, using such contractual services as consultants and service companies, conducting audits, and establishing the roles of authorized users and supervised individuals; NRC`s reporting and notification requirements are discussed, and a general description is given of how NRC`s licensing, inspection and enforcement programs work

All hormone-producing cell types of the pituitary intermediate and anterior lobes derive from prop1-expressing progenitors

Mutations in PROP1, the most common known cause of combined pituitary hormone deficiency in humans, can result in the progressive loss of all hormones of the pituitary anterior lobe. In mice, Prop1 mutations result in the failure to initiate transcription of Pou1f1 (also known as Pit1) and lack somatotropins, lactotropins, and thyrotropins. The basis for this species difference is unknown. We hypothesized that Prop1 is expressed in a progenitor cell that can develop into all anterior lobe cell types, and not just the somatotropes, thyrotropes, and lactotropes, which are collectively known as the PIT1 lineage. To test this idea, we produced a transgenic Prop1-cre mouse line and conducted lineage-tracing experiments of Prop1-expressing cells. The results reveal that all hormone-secreting cell types of both the anterior and intermediate lobes are descended from Prop1-expressing progenitors. The Prop1-cre mice also provide a valuable genetic reagent with a unique spatial and temporal expression for generating tissue-specific gene rearrangements early in pituitary gland development. We also determined that the minimal essential sequences for reliable Prop1 expression lie within 10 kilobases of the mouse gene and demonstrated that human PROP1 can substitute functionally for mouse Prop1. These studies enhance our understanding of the pathophysiology of disease in patients with PROP1 mutations.Fil: Davis, Shannon W.. University of South Carolina; Estados UnidosFil: Keisler, Jessica L.. University of South Carolina; Estados UnidosFil: Pérez Millán, María Inés. University of Michigan; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Schade, Vanessa. University of Michigan; Estados UnidosFil: Camper, Sally A.. University of Michigan; Estados Unido

Transgenic mice expressing LHX3 transcription factor isoforms in the pituitary: Effects on the gonadotrope axis and sex-specific reproductive disease

The LHX3 transcription factor plays critical roles in pituitary and nervous system development. Mutations in the human LHX3 gene cause severe hormone deficiency diseases. The gene produces two mRNAs which can be translated to three protein isoforms. The LHX3a protein contains a central region with LIM domains and a homeodomain, and a carboxyl terminus with the major transactivation domain. LHX3b is identical to LHX3a except that it has a different amino terminus. M2-LHX3 lacks the amino terminus and LIM domains of LHX3a/b. In vitro experiments have demonstrated these three proteins have different biochemical and gene regulatory properties. Here, to investigate the effects of overexpression of LHX3 in vivo, the alpha glycoprotein subunit ( ΑGSU ) promoter was used to produce LHX3a, LHX3b, and M2-LHX3 in the pituitary glands of transgenic mice. Alpha GSU-beta galactosidase animals were generated as controls. Male ΑGSU-LHX3a and ΑGSU-LHX3b mice are infertile and die at a young age as a result of complications associated with obstructive uropathy including uremia. These animals have a reduced number of pituitary gonadotrope cells, low circulating gonadotropins, and possible sex hormone imbalance. Female ΑGSU-LHX3a and ΑGSU-LHX3b transgenic mice are viable but have reduced fertility. By contrast, ΑGSU-M2-LHX3 mice and control mice expressing beta galactosidase are reproductively unaffected. These overexpression studies provide insights into the properties of LHX3 during pituitary development and highlight the importance of this factor in reproductive physiology. J. Cell. Physiol. 212: 105–117, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56051/1/21010_ftp.pd

Vascular Smooth Muscle Cell Stiffness and Adhesion to Collagen I Modified by Vasoactive Agonists

In vascular smooth muscle cells (VSMCs) integrin-mediated adhesion to extracellular matrix (ECM) proteins play important roles in sustaining vascular tone and resistance. The main goal of this study was to determine whether VSMCs adhesion to type I collagen (COL-I) was altered in parallel with the changes in the VSMCs contractile state induced by vasoconstrictors and vasodilators. VSMCs were isolated from rat cremaster skeletal muscle arterioles and maintained in primary culture without passage. Cell adhesion and cell E-modulus were assessed using atomic force microscopy (AFM) by repetitive nano-indentation of the AFM probe on the cell surface at 0.1 Hz sampling frequency and 3200 nm Z-piezo travelling distance (approach and retraction). AFM probes were tipped with a 5 μm diameter microbead functionalized with COL-I (1mg\ml). Results showed that the vasoconstrictor angiotensin II (ANG-II; 10−6 ) significantly increased (p<0.05) VSMC E-modulus and adhesion probability to COL-I by approximately 35% and 33%, respectively. In contrast, the vasodilator adenosine (ADO; 10−4 ) significantly decreased (p<0.05) VSMC E-modulus and adhesion probability by approximately −33% and −17%, respectively. Similarly, the NO donor (PANOate, 10−6 M), a potent vasodilator, also significantly decreased (p<0.05) the VSMC E-modulus and COL-I adhesion probability by −38% and −35%, respectively. These observations support the hypothesis that integrin-mediated VSMC adhesion to the ECM protein COL-I is dynamically regulated in parallel with VSMC contractile activation. These data suggest that the signal transduction pathways modulating VSMC contractile activation and relaxation, in addition to ECM adhesion, interact during regulation of contractile state

The epidemiology of Varicella Zoster Virus infection in Italy

<p>Abstract</p> <p>Background</p> <p>The epidemiological importance of varicella and zoster and the availability of an efficacious and safe vaccine have led to an important international debate regarding the suitability of mass vaccination. The objective of the study was to describe the epidemiology of varicella and zoster in Italy and to determine whether there have been changes with respect to observations provided by an analogous study conducted 8 years ago, in order to define the most appropriate vaccination strategy.</p> <p>Methods</p> <p>A number of data sources were evaluated, a cross-sectional population-based seroprevalence study was conducted on samples collected in 2004, and the results were compared with data obtained in 1996.</p> <p>Results</p> <p>The data from active and passive surveillance systems confirm that varicella is a widespread infectious disease which mainly affects children. VZV seroprevalence did not substantially differ from that found in the previous study. The sero-epidemiological profile in Italy is different from that in other European countries. In particular, the percentage of susceptible adolescents is at least nearly twice as high as in other European countries and in the age group 20–39 yrs, approximately 9% of individuals are susceptible to VZV.</p> <p>Conclusion</p> <p>The results of this study can contribute to evaluating the options for varicella vaccination. It is possible that in a few years, in all Italian Regions, there will exist the conditions necessary for implementing a mass vaccination campaign and that the large-scale availability of MMRV tetravalent vaccines will facilitate mass vaccination.</p

The epidemiology of mumps in Italy

In Italy, although vaccination has been recommended for a number of years, vaccination coverage for mumps is still sub-optimal. The objective of the present study was to evaluate the seroprevalence of mumps antibodies in the Italian population, stratified by age, gender and geographical area. The proportion of individuals positive for mumps antibodies remained stable in the age classes 0-11 months and 1 year (25.4% and 30.8%, respectively) and showed a continuous increase after the second year of life. The percentage of susceptible individuals was higher than 20% in persons 2-14 years of age and exceeded 10% in persons 15-39 years of age. No statistically significant differences were observed by gender or geographical area. Comparison between these results and the data obtained from a 1996 survey showed a statistically significant increase in seroprevalence in the age class 2-4 years. No changes were observed in the other age-groups. The results of this study confirm that the efforts made in recent years to improve vaccination coverage within the second year of life should be strengthened. \ua9 2008 Elsevier Ltd. All rights reserved

Assessment of cognitive self-statements during marital problem solving: A comparison of two methods

Twenty maritally distressed couples (DC) and 20 nondistressed couples (NDC) were recruited and asked to undertake 10 minutes of problem-solving discussions, which were videotaped. Each individual partner’s cognitive self-statements during the interaction were assessed using two methods: video-assisted recall (VR) and thought listing (TL). Reported cognitions from each method were content- analysed and classified into five categories: partner- referent positive, partner- referent negative, self-referent positive, self- referent negative, and other. Proportions of reported cognitions falling into each category were analysed in two separate two-way MANOVAs (marital distress/ nondistress x sex) for the VR and TL measures. Results of each MANOVA indicated a highly significant effect of marital distress on cognitions, and a significant effect of sex on the VR but not the TL measure. Discriminant analyses showed that the VR and TL methods both discriminated between DC and NDC groups. Post hoc univariate ANOVAs indicated that DC had significantly higher proportions of negative partner- referent cognitions, and lower proportions of positive partner- referent cognitions, than NDC while problem solving. The relative merits of each cognitive assessment method, and their potential use in increasing marital therapy effectiveness, are discussed

Clocking Auger electrons

Intense X-ray free-electron lasers (XFELs) can rapidly excite matter, leaving it in inherently unstable states that decay on femtosecond timescales. The relaxation occurs primarily via Auger emission, so excited-state observations are constrained by Auger decay. In situ measurement of this process is therefore crucial, yet it has thus far remained elusive in XFELs owing to inherent timing and phase jitter, which can be orders of magnitude larger than the timescale of Auger decay. Here we develop an approach termed ‘self-referenced attosecond streaking’ that provides subfemtosecond resolution in spite of jitter, enabling time-domain measurement of the delay between photoemission and Auger emission in atomic neon excited by intense, femtosecond pulses from an XFEL. Using a fully quantum-mechanical description that treats the ionization, core-hole formation and Auger emission as a single process, the observed delay yields an Auger decay lifetime of 2.2_−0.3^+0.2 fs for the KLL decay channel

Clocking Auger Electrons

Intense X-ray free-electron lasers (XFELs) can rapidly excite matter, leaving it in inherently unstable states that decay on femtosecond timescales. As the relaxation occurs primarily via Auger emission, excited state observations are constrained by Auger decay. In situ measurement of this process is therefore crucial, yet it has thus far remained elusive at XFELs due to inherent timing and phase jitter, which can be orders of magnitude larger than the timescale of Auger decay. Here, we develop a new approach termed self-referenced attosecond streaking, based upon simultaneous measurements of streaked photo- and Auger electrons. Our technique enables sub-femtosecond resolution in spite of jitter. We exploit this method to make the first XFEL time-domain measurement of the Auger decay lifetime in atomic neon, and, by using a fully quantum-mechanical description, retrieve a lifetime of $2.2^{ + 0.2}_{ - 0.3}$ fs for the KLL decay channel. Importantly, our technique can be generalised to permit the extension of attosecond time-resolved experiments to all current and future FEL facilities.Comment: Main text: 20 pages, 3 figures. Supplementary information: 17 pages, 6 figure

Activated Met Signalling in the Developing Mouse Heart Leads to Cardiac Disease

BACKGROUND: The Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine involved in many physiological processes, including skeletal muscle, placenta and liver development. Little is known about its role and that of Met tyrosine kinase receptor in cardiac development. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we generated two transgenic mice with cardiac-specific, tetracycline-suppressible expression of either Hepatocyte Growth Factor (HGF) or the constitutively activated Tpr-Met kinase to explore: i) the effect of stimulation of the endogenous Met receptor by autocrine production of HGF and ii) the consequence of sustained activation of Met signalling in the heart. We first showed that Met is present in the neonatal cardiomyocytes and is responsive to exogenous HGF. Exogenous HGF starting from prenatal stage enhanced cardiac proliferation and reduced sarcomeric proteins and Connexin43 (Cx43) in newborn mice. As adults, these transgenics developed systolic contractile dysfunction. Conversely, prenatal Tpr-Met expression was lethal after birth. Inducing Tpr-Met expression during postnatal life caused early-onset heart failure, characterized by decreased Cx43, upregulation of fetal genes and hypertrophy. CONCLUSIONS/SIGNIFICANCE: Taken together, our data show that excessive activation of the HGF/Met system in development may result in cardiac damage and suggest that Met signalling may be implicated in the pathogenesis of cardiac disease