Molecular signaling in zebrafish development and the vertebrate phylotypic period

During development vertebrate embryos pass through a stage where their morphology is most conserved between species, the phylotypic period (approximately the pharyngula). To explain the resistance to evolutionary changes of this period, one hypothesis suggests that it is characterized by a high level of interactions. Based on this hypothesis, we examined protein-protein interactions, signal transduction cascades and miRNAs over the course of zebrafish development, and the conservation of expression of these genes in mouse development. We also investigated the characteristics of genes highly expressed before or during the presumed phylotypic period. We show that while there is a high diversity of interactions during the phylotypic period (protein-DNA, RNA-RNA, cell-cell, and between tissues), which is well conserved with mouse, there is no clear difference with later, more morphologically divergent, stages. We propose that the phylotypic period may rather be the expression at the morphological level of strong conservation of molecular processes earlier in development.

Simulations in Evolution. III. Randomness as a Generator of Opportunities.

In Neo-Darwinism, variation and natural selection are the two evolutionary mechanisms which propel biological evolution. Our previous reports presented a histogram model to simulate the evolution of populations of individuals classified into bins according to an unspecified, quantifiable phenotypic character, and whose number in each bin changed generation after generation under the influence of fitness, while the total population was maintained constant. The histogram model also allowed Shannon entropy (SE) to be monitored continuously as the information content of the total population decreased or increased. Here, a simple Perl (Practical Extraction and Reporting Language) application was developed to carry out these computations, with the critical feature of an added random factor in the percent of individuals whose offspring moved to a vicinal bin. The results of the simulations demonstrate that the random factor mimicking variation increased considerably the range of values covered by Shannon entropy, especially when the percentage of changed offspring was high. This increase in information content is interpreted as facilitated adaptability of the population.

A model of cellular dosimetry for macroscopic tumors in radiopharmaceutical therapy.

PURPOSE: In the radiopharmaceutical therapy approach to the fight against cancer, in particular when it comes to translating laboratory results to the clinical setting, modeling has served as an invaluable tool for guidance and for understanding the processes operating at the cellular level and how these relate to macroscopic observables. Tumor control probability (TCP) is the dosimetric end point quantity of choice which relates to experimental and clinical data: it requires knowledge of individual cellular absorbed doses since it depends on the assessment of the treatment's ability to kill each and every cell. Macroscopic tumors, seen in both clinical and experimental studies, contain too many cells to be modeled individually in Monte Carlo simulation; yet, in particular for low ratios of decays to cells, a cell-based model that does not smooth away statistical considerations associated with low activity is a necessity. The authors present here an adaptation of the simple sphere-based model from which cellular level dosimetry for macroscopic tumors and their end point quantities, such as TCP, may be extrapolated more reliably. METHODS: Ten homogenous spheres representing tumors of different sizes were constructed in GEANT4. The radionuclide 131I was randomly allowed to decay for each model size and for seven different ratios of number of decays to number of cells, N(r): 1000, 500, 200, 100, 50, 20, and 10 decays per cell. The deposited energy was collected in radial bins and divided by the bin mass to obtain the average bin absorbed dose. To simulate a cellular model, the number of cells present in each bin was calculated and an absorbed dose attributed to each cell equal to the bin average absorbed dose with a randomly determined adjustment based on a Gaussian probability distribution with a width equal to the statistical uncertainty consistent with the ratio of decays to cells, i.e., equal to Nr-1/2. From dose volume histograms the surviving fraction of cells, equivalent uniform dose (EUD), and TCP for the different scenarios were calculated. Comparably sized spherical models containing individual spherical cells (15 microm diameter) in hexagonal lattices were constructed, and Monte Carlo simulations were executed for all the same previous scenarios. The dosimetric quantities were calculated and compared to the adjusted simple sphere model results. The model was then applied to the Bortezomib-induced enzyme-targeted radiotherapy (BETR) strategy of targeting Epstein-Barr virus (EBV)-expressing cancers. RESULTS: The TCP values were comparable to within 2% between the adjusted simple sphere and full cellular models. Additionally, models were generated for a nonuniform distribution of activity, and results were compared between the adjusted spherical and cellular models with similar comparability. The TCP values from the experimental macroscopic tumor results were consistent with the experimental observations for BETR-treated 1 g EBV-expressing lymphoma tumors in mice. CONCLUSIONS: The adjusted spherical model presented here provides more accurate TCP values than simple spheres, on par with full cellular Monte Carlo simulations while maintaining the simplicity of the simple sphere model. This model provides a basis for complementing and understanding laboratory and clinical results pertaining to radiopharmaceutical therapy.

Iowa Sex Offender Treatment and Supervision Task Force Report to the Iowa General Assembly, January 15, 2007

Over the last several years, lawmakers have been responding to several highly publicized child abduction, assault and murder cases. While such cases remain rare in Iowa, the public debates they have generated are having far-reaching effects. Policy makers are responsible for controlling the nature of such effects. Challenges they face stem from the need to avoid primarily politically-motivated responses and the desire to make informed decisions that recognize both the strengths and the limitations of the criminal justice system as a vehicle for promoting safe and healthy families and communities. Consensus was reached by the Task Force at its first meeting that one of its standing goals is to provide nonpartisan guidance to help avoid or fix problematic sex offense policies and practices. Setting this goal was a response to the concern over what can result from elected officials’ efforts to respond to the types of sex offender-related concerns that can easily become emotionally laden and politically charged due to the universally held abhorrence of sex crimes against children. The meetings of the Task Force and the various work groups it has formed have included some spirited and perhaps emotionally charged discussions, despite the above-stated ground rule. However, as is described in the report, the Task Force’s first set of recommendations and plans for further study were approved through consensus. It is hoped that in upcoming legislative deliberations, it will be remembered that the non-legislative members of the Task Force all agreed on the recommendations contained in this report. The topics discussed in this first report from the Task Force are limited to the study issues specifically named in H.F. 619, the Task Force’s enabling legislation. However, other topics of concern were discussed by the Task Force because of their immediacy or because of their possible relationships with one or more of the Task Force’s mandated study issues. For example, it has been reported by some probation/parole officers and others that the 2000 feet rule has had a negative influence on treatment participation and supervision compliance. While such concerns were noted, the Task Force did not take it upon itself to investigate them at this time and thus broaden the agenda it was given by the General Assembly last session. As a result, the recently reinstated 2000 feet rule, the new cohabitation/child endangerment law and other issues of interest to Task Force members but not within the scope of their charge are not discussed in the body of this report. An issue of perhaps the greatest interest to most Task Force members that was not a part of their charge was a belief in the benefit of viewing Iowa’s efforts to protect children from sex crimes with as comprehensive a platform as possible. It has been suggested that much more can be done to prevent child-victim sex crimes than would be accomplished by only concentrating on what to do with offenders after a crime has occurred. To prevent child victimization, H.F. 619 policy provisions rely largely on incapacitation and future deterrent effects of increased penalties, more restrictive supervision practices and greater public awareness of the risk presented by a segment of Iowa’s known sex offenders. For some offenders, these policies will no doubt prevent future sex crimes against children, and the Task Force has begun long-term studies to look for the desired results and for ways to improve such results through better supervision tools and more effective offender treatment. Unfortunately, much of the effects from the new policies may primarily influence persons who have already committed sex offenses against minors and who have already been caught doing so. Task Force members discussed the need for a range of preventive efforts and a need to think about sex crimes against children from other than just a “reaction- to-the-offender” perspective. While this topic is not addressed in the report that follows, it was suggested that some of the Task Force’s discussions could be briefly shared through these opening comments. Along with incapacitation and deterrence, comprehensive approaches to the prevention of child-victim sex crimes would also involve making sure parents have the tools they need to detect signs of adults with sex behavior problems, to help teach their children about warning signs and to find the support they need for healthy parenting. School, faithbased and other community organizations might benefit from stronger supports and better tools they can use to more effectively promote positive youth development and the learning of respect for others, respect for boundaries and healthy relationships. All of us who have children, or who live in communities where there are children, need to understand the limitations of our justice system and the importance of our own ability to play a role in preventing sexual abuse and protecting children from sex offenders, which are often the child’s own family members. Over 1,000 incidences of child sexual abuse are confirmed or founded each year in Iowa, and most such acts take place in the child’s home or the residence of the caretaker of the child. Efforts to prevent child sexual abuse and to provide for early interventions with children and families at risk could be strategically examined and strengthened. The Sex Offender Treatment and Supervision Task Force was established to provide assistance to the General Assembly. It will respond to legislative direction for adjusting its future plans as laid out in this report. Its plans could be adjusted to broaden or narrow its scope or to assign different priority levels of effort to its current areas of study. Also, further Task Force considerations of the recommendations it has already submitted could be called for. In the meantime, it is hoped that the information and recommendations submitted through this report prove helpful.

Iowa Sex Offender Treatment and Supervision Task Force Report to the Iowa General Assembly, January 15, 2008

Over the last several years, lawmakers have been responding to several highly publicized child abduction, assault and murder cases. While such cases remain rare in Iowa, the public debates they have generated are having far-reaching effects. Policy makers are responsible for controlling the nature of such effects. Challenges they face stem from the need to avoid primarily politically-motivated responses and the desire to make informed decisions that recognize both the strengths and the limitations of the criminal justice system as a vehicle for promoting safe and healthy families and communities. Consensus was reached by the Task Force at its first meeting that one of its standing goals is to provide nonpartisan guidance to help avoid or fix problematic sex offense policies and practices. Setting this goal was a response to the concern over what can result from elected officials’ efforts to respond to the types of sex offender-related concerns that can easily become emotionally laden and politically charged due to the universally held abhorrence of sex crimes against children. The meetings of the Task Force and the various work groups it has formed have included some spirited and perhaps emotionally charged discussions, despite the above-stated ground rule. However, as is described in the report, the Task Force’s first set of recommendations and plans for further study were approved through consensus. It is hoped that in upcoming legislative deliberations, it will be remembered that the non-legislative members of the Task Force all agreed on the recommendations contained in this report. The topics discussed in this first report from the Task Force are limited to the study issues specifically named in H.F. 619, the Task Force’s enabling legislation. However, other topics of concern were discussed by the Task Force because of their immediacy or because of their possible relationships with one or more of the Task Force’s mandated study issues. For example, it has been reported by some probation/parole officers and others that the 2000 feet rule has had a negative influence on treatment participation and supervision compliance. While such concerns were noted, the Task Force did not take it upon itself to investigate them at this time and thus broaden the agenda it was given by the General Assembly last session. As a result, the recently reinstated 2000 feet rule, the new cohabitation/child endangerment law and other issues of interest to Task Force members but not within the scope of their charge are not discussed in the body of this report. An issue of perhaps the greatest interest to most Task Force members that was not a part of their charge was a belief in the benefit of viewing Iowa’s efforts to protect children from sex crimes with as comprehensive a platform as possible. It has been suggested that much more can be done to prevent child-victim sex crimes than would be accomplished by only concentrating on what to do with offenders after a crime has occurred. To prevent child victimization, H.F. 619 policy provisions rely largely on incapacitation and future deterrent effects of increased penalties, more restrictive supervision practices and greater public awareness of the risk presented by a segment of Iowa’s known sex offenders. For some offenders, these policies will no doubt prevent future sex crimes against children, and the Task Force has begun long-term studies to look for the desired results and for ways to improve such results through better supervision tools and more effective offender treatment. Unfortunately, much of the effects from the new policies may primarily influence persons who have already committed sex offenses against minors and who have already been caught doing so. Task Force members discussed the need for a range of preventive efforts and a need to think about sex crimes against children from other than just a “reaction- to-the-offender” perspective. While this topic is not addressed in the report that follows, it was suggested that some of the Task Force’s discussions could be briefly shared through these opening comments. Along with incapacitation and deterrence, comprehensive approaches to the prevention of child-victim sex crimes would also involve making sure parents have the tools they need to detect signs of adults with sex behavior problems, to help teach their children about warning signs and to find the support they need for healthy parenting. School, faithbased and other community organizations might benefit from stronger supports and better tools they can use to more effectively promote positive youth development and the learning of respect for others, respect for boundaries and healthy relationships. All of us who have children, or who live in communities where there are children, need to understand the limitations of our justice system and the importance of our own ability to play a role in preventing sexual abuse and protecting children from sex offenders, which are often the child’s own family members. Over 1,000 incidences of child sexual abuse are confirmed or founded each year in Iowa, and most such acts take place in the child’s home or the residence of the caretaker of the child. Efforts to prevent child sexual abuse and to provide for early interventions with children and families at risk could be strategically examined and strengthened. The Sex Offender Treatment and Supervision Task Force was established to provide assistance to the General Assembly. It will respond to legislative direction for adjusting its future plans as laid out in this report. Its plans could be adjusted to broaden or narrow its scope or to assign different priority levels of effort to its current areas of study. Also, further Task Force considerations of the recommendations it has already submitted could be called for. In the meantime, it is hoped that the information and recommendations submitted through this report prove helpful.

Iowa Sex Offender Research Council Report to the Iowa General Assembly January 22, 2009

Over the last several years, lawmakers have been responding to several highly publicized child abduction, assault and murder cases. While such cases remain rare in Iowa, the public debates they have generated are having far-reaching effects. Policy makers are responsible for controlling the nature of such effects. Challenges they face stem from the need to avoid primarily politically-motivated responses and the desire to make informed decisions that recognize both the strengths and the limitations of the criminal justice system as a vehicle for promoting safe and healthy families and communities. Consensus was reached by the Task Force at its first meeting that one of its standing goals is to provide nonpartisan guidance to help avoid or fix problematic sex offense policies and practices. Setting this goal was a response to the concern over what can result from elected officials’ efforts to respond to the types of sex offender-related concerns that can easily become emotionally laden and politically charged due to the universally held abhorrence of sex crimes against children. The meetings of the Task Force and the various work groups it has formed have included some spirited and perhaps emotionally charged discussions, despite the above-stated ground rule. However, as is described in the report, the Task Force’s first set of recommendations and plans for further study were approved through consensus. It is hoped that in upcoming legislative deliberations, it will be remembered that the non-legislative members of the Task Force all agreed on the recommendations contained in this report. The topics discussed in this first report from the Task Force are limited to the study issues specifically named in H.F. 619, the Task Force’s enabling legislation. However, other topics of concern were discussed by the Task Force because of their immediacy or because of their possible relationships with one or more of the Task Force’s mandated study issues. For example, it has been reported by some probation/parole officers and others that the 2000 feet rule has had a negative influence on treatment participation and supervision compliance. While such concerns were noted, the Task Force did not take it upon itself to investigate them at this time and thus broaden the agenda it was given by the General Assembly last session. As a result, the recently reinstated 2000 feet rule, the new cohabitation/child endangerment law and other issues of interest to Task Force members but not within the scope of their charge are not discussed in the body of this report. An issue of perhaps the greatest interest to most Task Force members that was not a part of their charge was a belief in the benefit of viewing Iowa’s efforts to protect children from sex crimes with as comprehensive a platform as possible. It has been suggested that much more can be done to prevent child-victim sex crimes than would be accomplished by only concentrating on what to do with offenders after a crime has occurred. To prevent child victimization, H.F. 619 policy provisions rely largely on incapacitation and future deterrent effects of increased penalties, more restrictive supervision practices and greater public awareness of the risk presented by a segment of Iowa’s known sex offenders. For some offenders, these policies will no doubt prevent future sex crimes against children, and the Task Force has begun long-term studies to look for the desired results and for ways to improve such results through better supervision tools and more effective offender treatment. Unfortunately, much of the effects from the new policies may primarily influence persons who have already committed sex offenses against minors and who have already been caught doing so. Task Force members discussed the need for a range of preventive efforts and a need to think about sex crimes against children from other than just a “reaction- to-the-offender” perspective. While this topic is not addressed in the report that follows, it was suggested that some of the Task Force’s discussions could be briefly shared through these opening comments. Along with incapacitation and deterrence, comprehensive approaches to the prevention of child-victim sex crimes would also involve making sure parents have the tools they need to detect signs of adults with sex behavior problems, to help teach their children about warning signs and to find the support they need for healthy parenting. School, faithbased and other community organizations might benefit from stronger supports and better tools they can use to more effectively promote positive youth development and the learning of respect for others, respect for boundaries and healthy relationships. All of us who have children, or who live in communities where there are children, need to understand the limitations of our justice system and the importance of our own ability to play a role in preventing sexual abuse and protecting children from sex offenders, which are often the child’s own family members. Over 1,000 incidences of child sexual abuse are confirmed or founded each year in Iowa, and most such acts take place in the child’s home or the residence of the caretaker of the child. Efforts to prevent child sexual abuse and to provide for early interventions with children and families at risk could be strategically examined and strengthened. The Sex Offender Treatment and Supervision Task Force was established to provide assistance to the General Assembly. It will respond to legislative direction for adjusting its future plans as laid out in this report. Its plans could be adjusted to broaden or narrow its scope or to assign different priority levels of effort to its current areas of study. Also, further Task Force considerations of the recommendations it has already submitted could be called for. In the meantime, it is hoped that the information and recommendations submitted through this report prove helpful.

Iowa Sex Offender Research Council Report to the Iowa General Assembly, January 15, 2010

Over the last several years, lawmakers have been responding to several highly publicized child abduction, assault and murder cases. While such cases remain rare in Iowa, the public debates they have generated are having far-reaching effects. Policy makers are responsible for controlling the nature of such effects. Challenges they face stem from the need to avoid primarily politically-motivated responses and the desire to make informed decisions that recognize both the strengths and the limitations of the criminal justice system as a vehicle for promoting safe and healthy families and communities. Consensus was reached by the Task Force at its first meeting that one of its standing goals is to provide nonpartisan guidance to help avoid or fix problematic sex offense policies and practices. Setting this goal was a response to the concern over what can result from elected officials’ efforts to respond to the types of sex offender-related concerns that can easily become emotionally laden and politically charged due to the universally held abhorrence of sex crimes against children. The meetings of the Task Force and the various work groups it has formed have included some spirited and perhaps emotionally charged discussions, despite the above-stated ground rule. However, as is described in the report, the Task Force’s first set of recommendations and plans for further study were approved through consensus. It is hoped that in upcoming legislative deliberations, it will be remembered that the non-legislative members of the Task Force all agreed on the recommendations contained in this report. The topics discussed in this first report from the Task Force are limited to the study issues specifically named in H.F. 619, the Task Force’s enabling legislation. However, other topics of concern were discussed by the Task Force because of their immediacy or because of their possible relationships with one or more of the Task Force’s mandated study issues. For example, it has been reported by some probation/parole officers and others that the 2000 feet rule has had a negative influence on treatment participation and supervision compliance. While such concerns were noted, the Task Force did not take it upon itself to investigate them at this time and thus broaden the agenda it was given by the General Assembly last session. As a result, the recently reinstated 2000 feet rule, the new cohabitation/child endangerment law and other issues of interest to Task Force members but not within the scope of their charge are not discussed in the body of this report. An issue of perhaps the greatest interest to most Task Force members that was not a part of their charge was a belief in the benefit of viewing Iowa’s efforts to protect children from sex crimes with as comprehensive a platform as possible. It has been suggested that much more can be done to prevent child-victim sex crimes than would be accomplished by only concentrating on what to do with offenders after a crime has occurred. To prevent child victimization, H.F. 619 policy provisions rely largely on incapacitation and future deterrent effects of increased penalties, more restrictive supervision practices and greater public awareness of the risk presented by a segment of Iowa’s known sex offenders. For some offenders, these policies will no doubt prevent future sex crimes against children, and the Task Force has begun long-term studies to look for the desired results and for ways to improve such results through better supervision tools and more effective offender treatment. Unfortunately, much of the effects from the new policies may primarily influence persons who have already committed sex offenses against minors and who have already been caught doing so. Task Force members discussed the need for a range of preventive efforts and a need to think about sex crimes against children from other than just a “reaction- to-the-offender” perspective. While this topic is not addressed in the report that follows, it was suggested that some of the Task Force’s discussions could be briefly shared through these opening comments. Along with incapacitation and deterrence, comprehensive approaches to the prevention of child-victim sex crimes would also involve making sure parents have the tools they need to detect signs of adults with sex behavior problems, to help teach their children about warning signs and to find the support they need for healthy parenting. School, faithbased and other community organizations might benefit from stronger supports and better tools they can use to more effectively promote positive youth development and the learning of respect for others, respect for boundaries and healthy relationships. All of us who have children, or who live in communities where there are children, need to understand the limitations of our justice system and the importance of our own ability to play a role in preventing sexual abuse and protecting children from sex offenders, which are often the child’s own family members. Over 1,000 incidences of child sexual abuse are confirmed or founded each year in Iowa, and most such acts take place in the child’s home or the residence of the caretaker of the child. Efforts to prevent child sexual abuse and to provide for early interventions with children and families at risk could be strategically examined and strengthened. The Sex Offender Treatment and Supervision Task Force was established to provide assistance to the General Assembly. It will respond to legislative direction for adjusting its future plans as laid out in this report. Its plans could be adjusted to broaden or narrow its scope or to assign different priority levels of effort to its current areas of study. Also, further Task Force considerations of the recommendations it has already submitted could be called for. In the meantime, it is hoped that the information and recommendations submitted through this report prove helpful.

Iowa Sex Offender Research Council Report to the Iowa General Assembly, January 15, 2011

Over the last several years, lawmakers have been responding to several highly publicized child abduction, assault and murder cases. While such cases remain rare in Iowa, the public debates they have generated are having far-reaching effects. Policy makers are responsible for controlling the nature of such effects. Challenges they face stem from the need to avoid primarily politically-motivated responses and the desire to make informed decisions that recognize both the strengths and the limitations of the criminal justice system as a vehicle for promoting safe and healthy families and communities. Consensus was reached by the Task Force at its first meeting that one of its standing goals is to provide nonpartisan guidance to help avoid or fix problematic sex offense policies and practices. Setting this goal was a response to the concern over what can result from elected officials’ efforts to respond to the types of sex offender-related concerns that can easily become emotionally laden and politically charged due to the universally held abhorrence of sex crimes against children. The meetings of the Task Force and the various work groups it has formed have included some spirited and perhaps emotionally charged discussions, despite the above-stated ground rule. However, as is described in the report, the Task Force’s first set of recommendations and plans for further study were approved through consensus. It is hoped that in upcoming legislative deliberations, it will be remembered that the non-legislative members of the Task Force all agreed on the recommendations contained in this report. The topics discussed in this first report from the Task Force are limited to the study issues specifically named in H.F. 619, the Task Force’s enabling legislation. However, other topics of concern were discussed by the Task Force because of their immediacy or because of their possible relationships with one or more of the Task Force’s mandated study issues. For example, it has been reported by some probation/parole officers and others that the 2000 feet rule has had a negative influence on treatment participation and supervision compliance. While such concerns were noted, the Task Force did not take it upon itself to investigate them at this time and thus broaden the agenda it was given by the General Assembly last session. As a result, the recently reinstated 2000 feet rule, the new cohabitation/child endangerment law and other issues of interest to Task Force members but not within the scope of their charge are not discussed in the body of this report. An issue of perhaps the greatest interest to most Task Force members that was not a part of their charge was a belief in the benefit of viewing Iowa’s efforts to protect children from sex crimes with as comprehensive a platform as possible. It has been suggested that much more can be done to prevent child-victim sex crimes than would be accomplished by only concentrating on what to do with offenders after a crime has occurred. To prevent child victimization, H.F. 619 policy provisions rely largely on incapacitation and future deterrent effects of increased penalties, more restrictive supervision practices and greater public awareness of the risk presented by a segment of Iowa’s known sex offenders. For some offenders, these policies will no doubt prevent future sex crimes against children, and the Task Force has begun long-term studies to look for the desired results and for ways to improve such results through better supervision tools and more effective offender treatment. Unfortunately, much of the effects from the new policies may primarily influence persons who have already committed sex offenses against minors and who have already been caught doing so. Task Force members discussed the need for a range of preventive efforts and a need to think about sex crimes against children from other than just a “reaction- to-the-offender” perspective. While this topic is not addressed in the report that follows, it was suggested that some of the Task Force’s discussions could be briefly shared through these opening comments. Along with incapacitation and deterrence, comprehensive approaches to the prevention of child-victim sex crimes would also involve making sure parents have the tools they need to detect signs of adults with sex behavior problems, to help teach their children about warning signs and to find the support they need for healthy parenting. School, faithbased and other community organizations might benefit from stronger supports and better tools they can use to more effectively promote positive youth development and the learning of respect for others, respect for boundaries and healthy relationships. All of us who have children, or who live in communities where there are children, need to understand the limitations of our justice system and the importance of our own ability to play a role in preventing sexual abuse and protecting children from sex offenders, which are often the child’s own family members. Over 1,000 incidences of child sexual abuse are confirmed or founded each year in Iowa, and most such acts take place in the child’s home or the residence of the caretaker of the child. Efforts to prevent child sexual abuse and to provide for early interventions with children and families at risk could be strategically examined and strengthened. The Sex Offender Treatment and Supervision Task Force was established to provide assistance to the General Assembly. It will respond to legislative direction for adjusting its future plans as laid out in this report. Its plans could be adjusted to broaden or narrow its scope or to assign different priority levels of effort to its current areas of study. Also, further Task Force considerations of the recommendations it has already submitted could be called for. In the meantime, it is hoped that the information and recommendations submitted through this report prove helpful.

Impact of relative size and language on the attitudes between nations and linguistic groups : The case of Switzerland

This study explores the impact of relative size on the intra- and intergroup attitudes of groups who either share a language or have a different language. For that purpose, we examined international attitudes, comparing a small nation, Switzerland, and two larger nations, Germany and France. We found support for the assumption that large neighbouring nations pose a threat to the smaller nation's identity, especially when they are linguistically similar. Consequently, in line with Tajfel's Social Identity Theory (1978), the smaller nation's inhabitants evaluate those of the larger nation less positively, liking them less and perceiving them to be more arrogant than vice versa. By investigating the special case of the French-speaking and the German-speaking Swiss as linguistic groups within their own nation we were able to demonstrate that these groups seek support with the larger-linguistically-similar nation to defend themselves against the more direct in-country threat to their identity. They acknowledge the similarity with the larger nation, yet keep defending their social identity by expressing a dislike for this perceived similarity.

Valoriser le géopatrimoine par la médiation indirecte et la visualisation des objets géomorphologiques

Résumé: Valoriser le géopatrimoine par la médiation indirecte et la visualisation des objets géomorphologiques Le géopatrimoine regroupe des objets géologiques lato sensu auxquels certaines valeurs sont attribuées, en fonction de leur intérêt pour la science, de leur rareté, de leurs particularités culturelles ou écologiques, etc. Valoriser le géopatrimoine signifie avant tout faire partager cette approche aux non-spécialistes, en expliquant ce qui fait la valeur de ces objets. Cette valorisation peut s'effectuer, entre autres, sous la forme d'une activité touristique et contribuer ainsi au développement régional. Faire comprendre l'origine, la singularité et la valeur des formes du relief implique le recours à une communication éducative, désignée par le terme de médiation. Les implications de la dimension éducative du processus, comme la prise en compte des connaissances et attentes du public, la création d'un environnement favorable à l'apprentissage ou l'attractivité du contenu, sont souvent négligées. Du point de vue conceptuel, un modèle de la médiation indirecte (c'est-à-dire au moyen de supports médiatiques) a été proposé et appliqué au développement empirique de produits de médiation et à leur évaluation. Ce modèle ne garantit pas la réussite de la communication éducative, mais contribue à créer un cadre favorable au processus. De plus, plusieurs lignes directrices pour le choix du type de média et sa mise en forme ont été définies sur la base d'une compilation de résultats de la psychologie cognitive sur l'usage des médias pour l'apprentissage. Des méthodes qualitatives et quantitatives variées ont été mobilisées : enquêtes par questionnaire ex situ et in situ, auprès des visiteurs de géomorphosites de montagne, réalisation de médias interactifs testés ensuite auprès de divers publics (parcours enregistré, pré- et post-questionnaires) et entretiens collectifs. Les résultats obtenus éclairent divers aspects de la problématique. L'étude du public a montré, par exemple, que le géotourisme possède un réel public parmi les visiteurs des sites de montagnes : trois-quarts d'entre eux expriment de l'intérêt pour des explications sur la géologie et l'évolution du paysage. Cette thèse a exploré ces aspects liés au processus d'apprentissage en se focalisant sur les médias visuels, surtout interactifs. La plupart des médias visuels couramment utilisés en géomorphologie ont été considérés. Le développement de versions interactives de ces médias sous forme d'applications web a fourni un aperçu concret des possibilités des nouvelles technologies. Les utilisateurs apprécient en particulier a richesse du contenu, le haut degré d'interactivité et la variété de ces applications. De tels médias incitent à visiter le site naturel et semblent aussi répondre aux intérêts de publics variés. Abstract: Geoheritage promotion through non-personal interpretation and visualisation of geomorphological features Geoheritage concerns all geological features lato sensu to which some values are attributed, according to their scientific interest, their rarity, their cultural or ecological dimensions, etc. Geoheritage promotion implies sharing this point of view with non-specialists, explaining what gives value to those objects. Geotourism is one of the many ways to achieve geoheritage promotion, while contributing also to regional development. In order to make non-specialists understand the origin, the specificity and the value of landforms, educational communication is needed, that is called interpretation (French: médiation). This education dimension has several, and often neglected, implications, like taking into account public's knowledge and expectations, creating a favourable learning environment, attractive design, etc. From the conceptual point of view, a model for non-personal interpretation has been proposed and applied for the empirical development and for the assessment of interpretive products. This model does not guarantee success of educational communication, but help creating a favourable environment for this process. Moreover, some guidelines were defined from a compilation of several results of cognitive psychology on media use for learning. They guide the choice of the kind of media and its design. Several qualitative and quantitative methods were applied: survey questionnaires ex situ and in situ by mountain geomorphosites visitors, interactive medias developed and then tested by different kinds of users (with usertracking, pre- and post-survey questionnaires), group interviews. The results answered different aspects of the research questions. Visitor surveys revealed for example that geotourism could attract many visitors of mountain areas: three quarters of them say they are interested in getting explanations about geology and landscape (in particular its dynamic dimensions). This thesis examined those aspects with a focus on visual medias, both statics and interactive. Most of currently used medias in geomorphology were considered. Interactive versions of those medias were developed in web applications; they gave a concrete overview on the opportunities that new technologies offer. The content richness, the high interaction level and the diversity of the applications are the most liked aspects by the users. Such medias drive to visit the natural site and seem to correspond to the interests of various kinds of publics. Zusammenfassung: Aufwertung des erdwissenschaftlichen Erbes durch mediale Vermittlung und Visualisierung von geomorphologischen Objekten Das erdwissenschaftliche Erbe besteht aus geologischen Gegebenheiten lato sensu, denen entsprechend ihrer Bedeutung für die Wissenschaft, ihrer Seltenheit, ihrer kulturellen oder ökologischen Besonderheiten usw. bestimmte Werte zugeordnet werden. Das erdwissenschaftliche Erbe aufzuwerten bedeutet in erster Linie, diesen Ansatz Nichtspezialisten näher zu bringen, indem ihnen erklärt wird, was den Wert dieser Gegebenheiten ausmacht. Dies kann etwa im Rahmen eines touristischen Angebots geschehen und so die regionale Entwicklung unterstützen. Um Entstehung, Besonderheit und Wert von Geländeformen verständlich zu machen, wird eine pädagogische Kommunikationsform verwendet, die als mediale Vermittlung (franz. médiation) bezeichnet wird. Die Bedeutung der pädagogischen Dimension des Vermittlungsprozesses wie etwa der Einbezug des Wissens und der Erwartungen des Publikums, die Gestaltung eines positiven Lernklimas oder die Attraktivität des Inhalts wird oft vernachlässigt. Auf konzeptueller Ebene wurde ein Modell der indirekten Interpretation erarbeitet (d. h. anhand von Medien), das bei der empirischen Entwicklung der Interpretationsprodukte und ihrer Evaluation Anwendung fand. Dieses Modell garantiert zwar nicht den Erfolg der pädagogischen Kommunikation. Es trägt aber dazu bei, einen für den Prozess günstigen Kontext zu schaffen. Des Weiteren wurden mehrere Richtlinien für die Wahl des Medientyps und dessen Ausgestaltung anhand einer Zusammenstellung von Resultaten der kognitiven Psychologie über den Gebrauch von Medien in Lernprozessen definiert. Es wurden verschiedene qualitative und quantitative Methoden eingesetzt: Befragung mittels Fragebogen der Besucher von geomorphologischen Geotopen im Gebirge - ex situ und in situ -, Erarbeitung von interaktiven Medien, die anschliessend anhand verschiedener Zielgruppen gestestet wurden (Aufnahme des Besuchparcours, Vor- und Nachfragebögen) sowie kollektive Interviews. Die Ergebnisse geben Aufschluss zu verschiedenen Aspekten der Fragestellung. Die Befragung des Publikums hat zum Beispiel deutlich gemacht, dass der Geotourismus unter den Besuchern von Berggebieten tatsächlich auf eine Nachfrage stösst: drei Viertel von ihnen zeigen ein Interesse für Erläuterungen zur Geologie und der Landschaftsentwicklung. Die vorliegende Doktorarbeit hat die genannten Aspekte der Lernprozesse untersucht, wobei der Fokus auf visuellen, insbesondere interaktiven Medien lag. Die meisten gängigen visuellen Medien der Geomorphologie wurden berücksichtigt. Die Entwicklung von interaktiven Versionen dieser Medien in Form von Web-Anwendungen hat die Möglichkeiten der neuen Technologien veranschaulicht. Die Benutzer schätzten insbesondere die Vielfalt des Inhalts, die hohe Interaktivität und die Diversität dieser Anwendungen. Solche Medien laden dazu ein, ein Naturgebiet zu besuchen und scheinen den Interessen der verschiedenen Publikumsgruppen entgegenzukommen.

Vancomycin exposure from active calcium sulfate bone filler

Objective: Bone cements and substitutes are commonly used in surgery to deliver antibiotics locally. The objective of this study was to assess the systemic absorption and disposition of vancomycin in patients treated with active calcium sulfate bone filler and to predict systemic concentrations under various conditions. Method: 277 blood samples were taken from 42 patients receiving vancomycin in bone cement during surgery. Blood samples were collected from 3h to 10 days after implantation. Vancomycin was measured by immunoenzymatic assay. Population pharmacokinetic (PK) analysis was performed using NONMEM to assess average estimates and variability of PK parameters. Based on the final model, simulations with various doses and renal function levels were performed. Results: The patients were 64 ± 20 years old, their body weight was 81 ± 22 kg and Cockcroft-Gault creatinine clearance (CLcr) 98 ± 55 mL/min. Vancomycin doses ranged from 200 mg to 6000 mg and implantation sites were hip (n=16), tibia (10) or others (16). Concentration profiles remained low and consistent with absorption rate-limited first-order release, while showing prominent variability. Mean clearance (CL) was 3.87 L/h (CV 35%), absorption rate constant (ka) 0.004 h-1 (66%) and volume of distribution (V) 9.5 L. Simulations with up to 8000 mg vancomycin implant showed systemic concentrations exceeding 20 mg/L for 3.5 days in 43% of the patients with CLcr 15 mL/min, whereas 7% of the patients with normal renal function had a concentration above 20 mg/L for 1.1 days. Subtherapeutic concentrations (0.4-4 mg/L) were predicted during a median of 22 days in patients with normal renal function and 4000 mg vancomycin implant, with limited influence of dose or renal function. Conclusion: Vancomycin-laden calcium sulfate implant does not raise toxicity concern. Selection of resistant bacteria, such as Enterococcus and Staphylococcus species, might however be a concern, as simulations show persistent subtherapeutic systemic concentrations during 3 to 4 weeks in these patients.

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Alveolar haemorrhage (AH) is a rare and potentially life-threatening condition characterised by diffuse blood leakage from the pulmonary microcirculation into the alveolar spaces due to microvascular damage. It is not a single disease but a clinical syndrome that may have numerous causes. Autoimmune disorders account for fewer than half of cases, whereas the majority are due to nonimmune causes such as left heart disease, infections, drug toxicities, coagulopathies and malignancies. The clinical picture includes haemoptysis, diffuse alveolar opacities at imaging and anaemia. Bronchoalveolar lavage is the gold standard method for diagnosing AH. The lavage fluid appears macroscopically haemorrhagic and/or contains numerous haemosiderin-laden macrophages. The diagnostic work-up includes search for autoimmune disorders, review of drugs and exposures, assessment of coagulation and left heart function, and search for infectious agents. Renal biopsy is often indicated if AH is associated with renal involvement, whereas lung biopsy is only rarely useful. Therapy aims at correction of reversible factors and immunosuppressive therapy in autoimmune causes, with plasmapheresis in selected situations.

Substituição do farelo de soja por uréia ou amiréia na dieta de bovinos de corte confinados

O objetivo deste trabalho foi avaliar a substituição do farelo de soja por uréia ou amiréia no desempenho de bovinos de corte em crescimento. Foram utilizados oitenta e um machos não castrados das raças Nelore (27), Canchim (27) e Holandesa (27), com peso médio inicial de 250 kg e idade média de 15 meses. O delineamento experimental foi o de blocos ao acaso com três tratamentos, constituídos de três animais por baia e nove baias por tratamento. Os blocos foram arranjados segundo o peso inicial e raça. Os tratamentos foram: 1) farelo de soja (FS); 2) uréia e 3) amiréia (A-150S) em dietas isoprotéicas (13,0%) utilizando o bagaço de cana in natura (BIN) como única fonte de volumoso (20% da MS). O consumo de matéria seca (MS) foi 6,56, 7,18 e 6,97 kg/dia; o ganho de peso vivo foi 0,889, 1,114 e 1,088 kg/dia e a conversão alimentar de 7,3, 6,5 e 6,7 kg MS/kg de ganho nos tratamentos farelo de soja, uréia e amiréia, respectivamente. O tratamento FS apresentou menor consumo e ganho de peso e também pior conversão alimentar (P<0,01). Os tratamentos uréia e A-150S não diferiram (P>0,05) entre si.