How indicative is a self-reported driving behaviour profile of police registered traffic law offences?

Science.gov (United States)

Martinussen, L M; Møller, M; Prato, C G; Haustein, S

2017-02-01

Although most motorised countries have experienced massive improvements in road safety over the last decades, human behaviour and differences in accident risk across sub-groups of drivers remains a key issue in the area of road safety. The identification of risk groups requires the identification of reliable predictors of safe or unsafe driving behaviour. Given this background, the aim of this study was to test whether driver sub-groups identified based on self-reported driving behaviour and skill differed in registered traffic law offences and accidents, and whether group membership was predictive of having traffic law offences. Sub-groups of drivers were identified based on the Driver Behaviour Questionnaire (DBQ) and the Driver Skill Inventory (DSI), while traffic offences and accidents were register-based (Statistics Denmark). The participants (N=3683) were aged 18-84 years and randomly selected from the Danish Driving License Register. Results show that the driver sub-groups differed significantly in registered traffic offences but not in registered accidents. In a logistic regression analysis, the sub-group "Violating unsafe drivers" was found predictive of having a traffic offence, even when socio-demographic variables and exposure were controlled for. The most important predictive factor, however, was having a criminal record for non-traffic offences, while gender, living without a partner, and being self-employed also had a significant effect. The study confirms the use of the DBQ and DSI as suitable instruments for predicting traffic offences while also confirming previous results on accumulation of problematic behaviours across life contexts. The finding that driver sub-groups did not differ in registered accidents supports the recent research activities in finding and modelling surrogate safety measures. Copyright © 2016 Elsevier Ltd. All rights reserved.

How indicative is a self-reported driving behaviour profile of police registered traffic law offences?

DEFF Research Database (Denmark)

Martinussen, Laila Marianne; Møller, Mette; Prato, Carlo Giacomo

2017-01-01

of reliable predictors of safe or unsafe driving behaviour. Given this background, the aim of this study was to test whether driver sub-groups identified based on self-reported driving behaviour and skill differed in registered traffic law offences and accidents, and whether group membership was predictive...... from the Danish Driving License Register. Results show that the driver sub-groups differed significantly in registered traffic offences but not in registered accidents. In a logistic regression analysis, the sub-group “Violating unsafe drivers” was found predictive of having a traffic offence, even...... when socio-demographic variables and exposure were controlled for. The most important predictive factor, however, was having a criminal record for non-traffic offences, while gender, living without a partner, and being self-employed also had a significant effect. The study confirms the use of the DBQ...

Impact of Regulation Change on Half-Court Offence in the Polish Basketball League

Directory of Open Access Journals (Sweden)

Gryko Karol

2016-06-01

Full Text Available Introduction. Each change in the rules of a sport affects the way it is performed. Therefore, changes in regulations require that new training models be developed. The aim of the study was to determine whether FIBA’s introduction of new regulations in the 2010/2011 season pertaining to the dimensions of certain parts of the playing area, which changed the conditions under which the game was played, impacted the offensive actions of the top three teams in the Polish Basketball League. Material and methods. The study analysed qualitative data describing the offences (n = 16,694 performed during 200 matches of the Polish Basketball League, that is the highest-level men’s professional basketball league in Poland, during two periods: the 2009/2010 season (110 matches; n = 9,343 offences, before the regulations were modified, and the 2010/2011 season (90 matches; n = 7,351 offences, after they were changed. The research involved the players of three teams who received the gold, silver, and bronze medals in the final standings of the Polish National Championship in the 2009/2010 season. Results. The study found a statistically significant (p < 0.001 decrease in the overall number of tactical offensive actions of 3.84% and a significant (p < 0.05 5% decrease in the mean number of points scored. A significant (p < 0.05 decrease in half-court offences, amounting to almost 2% was also observed. This offensive system was characterised by a minor shift toward individual offences with the back to the basket and pick-and-roll offences; these changes, however, did not cause an increase in the level of effectiveness. Conclusions. The direction of the changes observed have been determined, which consisted in a reduction in the overall number of offensive actions and a shift in the place where they were completed, from the three-point area in particular, to the two-point area.

Money Laundering – an Economic Offence

OpenAIRE

Camelia ŞERBAN MORĂREANU

2011-01-01

Preventing and combating money laundering, the product of the transnational organized crime, in general, is one of the most efficient means of stopping this activity, which is a threat for the national or international economic operations. The penal incrimination and sanction of money laundering is a useful instrument for the accountability of all categories of offenders, but also with the purpose of imposing more severe sanctions for those who commit offences generating dirty money, behind s...

THE CRIMINAL OFFENCE OF MONEY LAUNDERING – A SERIES OF THEORETICAL AND PRACTICAL CONSIDERATIONS

Directory of Open Access Journals (Sweden)

Constantin NEDELCU

2016-05-01

Full Text Available The paper at hand addresses the extremely complex and sensitive matter relating to one of the most controversial offences in the criminal laws of Romania – in particular, the criminal offence of money laundering. This paper bears both theoretical and practical interest, in that it points out specific instances of court case-law which were given different constructions by various judiciary authorities.

Predicting Crashes Using Traffic Offences. A Meta-Analysis that Examines Potential Bias between Self-Report and Archival Data

Science.gov (United States)

af Wåhlberg, Anders; Freeman, James; Watson, Barry; Watson, Angela

2016-01-01

Background Traffic offences have been considered an important predictor of crash involvement, and have often been used as a proxy safety variable for crashes. However the association between crashes and offences has never been meta-analysed and the population effect size never established. Research is yet to determine the extent to which this relationship may be spuriously inflated through systematic measurement error, with obvious implications for researchers endeavouring to accurately identify salient factors predictive of crashes. Methodology and Principal Findings Studies yielding a correlation between crashes and traffic offences were collated and a meta-analysis of 144 effects drawn from 99 road safety studies conducted. Potential impact of factors such as age, time period, crash and offence rates, crash severity and data type, sourced from either self-report surveys or archival records, were considered and discussed. After weighting for sample size, an average correlation of r = .18 was observed over the mean time period of 3.2 years. Evidence emerged suggesting the strength of this correlation is decreasing over time. Stronger correlations between crashes and offences were generally found in studies involving younger drivers. Consistent with common method variance effects, a within country analysis found stronger effect sizes in self-reported data even controlling for crash mean. Significance The effectiveness of traffic offences as a proxy for crashes may be limited. Inclusion of elements such as independently validated crash and offence histories or accurate measures of exposure to the road would facilitate a better understanding of the factors that influence crash involvement. PMID:27128093

Page | 131 RISING CASES OF RAPE OFFENCES IN NIGERIA: NEW ...

African Journals Online (AJOL)

Fr. Ikenga

Key words: Rape, Rising Cases, New Measures, Penetration, Criminal Justice System, Tripod. 1. Introduction ... International Law and Jurisprudence, Faculty of Law, Nnamdi Azikiwe University, Awka. .... 10 Sexual Offences Act 2003 of the UK.

Information technology-based approaches to reducing repeat drug exposure in patients with known drug allergies.

Science.gov (United States)

Cresswell, Kathrin M; Sheikh, Aziz

2008-05-01

There is increasing interest internationally in ways of reducing the high disease burden resulting from errors in medicine management. Repeat exposure to drugs to which patients have a known allergy has been a repeatedly identified error, often with disastrous consequences. Drug allergies are immunologically mediated reactions that are characterized by specificity and recurrence on reexposure. These repeat reactions should therefore be preventable. We argue that there is insufficient attention being paid to studying and implementing system-based approaches to reducing the risk of such accidental reexposure. Drawing on recent and ongoing research, we discuss a number of information technology-based interventions that can be used to reduce the risk of recurrent exposure. Proven to be effective in this respect are interventions that provide real-time clinical decision support; also promising are interventions aiming to enhance patient recognition, such as bar coding, radiofrequency identification, and biometric technologies.

Page | 226 TAX OFFENCES: CLOGS IN THE WHEEL OF ...

African Journals Online (AJOL)

Fr. Ikenga

The jurisprudence of this paper is on the examination of criminality in tax offences and the effects of ... Lecturer and Formerly, Coordinator, Department of Business Law, Faculty of Law, ..... for about 80 percent of government revenue in the past has also drastically decrees .... The FIRS made similar arrests earlier in the year.

Trends in alcohol-related harms and offences in a liberalized alcohol environment.

Science.gov (United States)

Huckle, Taisia; Pledger, Megan; Casswell, Sally

2006-02-01

To assess alcohol-related harms and offences in New Zealand from 1990 to 2003, a period of alcohol policy liberalization, that included the lowering of the purchase age from 20 to 18 years in 1999. Time trend analyses were carried out on routinely collected data for prosecutions for driving with excess alcohol; alcohol-involved vehicle crashes (all and fatal) and prosecutions for disorder offences. These were carried out separately for those aged 14-15, 16-17, 18-19, 20-24 and 25 years and over. Rates of: prosecutions for driving with excess alcohol (1990-2003); rates of alcohol- involved vehicle crashes (all and fatal) (1990-2003); and rates of prosecutions for disorder offences (1994-2003). Effects of alcohol policy liberalization: positive trends were found in the rates of prosecutions for disorder in the 16-17, 18-19, 20-24 and 25 + age groups; with 18-19-year-olds and 16-17-year-olds having the largest rates and largest positive trend in rates. For 16-17-year-olds, there was a positive trend in the rates of prosecutions for excess breath alcohol. Negative trends in rates were found for alcohol-related crashes (all and fatal) among all age groups. Negative trends for those over 16-17 years were found for prosecutions for driving with excess breath alcohol (this was prior to the lowering of the purchase age). Effects of lowering the minimum purchase age: the lowering of minimum purchase age coincided with an increase in the trend of alcohol-related crashes for 18-19-year-olds; the next largest increase was among the 20-24-year-olds (all other age groups also increased but at a much lower rate). A similar result was found for driving with excess alcohol for those aged 18-19 (and those aged 20-24 years). An increase in the rates of prosecutions for disorder offences occurred for the 14-15-year-old group following the lowering of the purchase age. The liberalization of alcohol throughout the 1990s may have influenced younger people more, as reflected in increases

Several criminal, phenomenological and etiological features of criminal offences of counterfeiting money in Kosovo

Directory of Open Access Journals (Sweden)

MSc. Milot Krasniqi

2012-12-01

Full Text Available The Republic of Kosovo is making efforts as a young state to strengthen rule of law and efficiently combat criminality in general, and specifically organized crime, as a condition for its journey towards European integration perspectives.  For a normal functioning of the economic system, the safety and protection of controlled circulation of money are of vital importance. In this direction, the state takes actions and measures to ensure that manufacturing and emissions of banknotes and bonds are undertaken by competent authorities, such as the Central Bank, and render impossible the counterfeiting of money. In Kosovo, money counterfeiting is not widely studied. Consequently, there are no recent research papers over the time when these offences have marked rather high records. This circumstance, and especially the fact that these offences are rather frequent in Kosovo, made me enter the research of this type of criminality.    Apart from principles and rules stipulated by special laws of the field of economy, protection of the economic system is also helped by the Criminal Code, which incriminates the act of counterfeit money as a criminal offence against the economic system, thereby ensuring general prevention of potential offenders, and repressive measures against confirmed offenders. Protection of economic and monetary systems is also provided upon by numerous international acts.  The paper is permeated by conclusions, analysis and independent recommendations, which I believe will contribute de lege ferrenda to criminal policies in preventing and combating this type of crime. In researching the criminal offences of counterfeiting money, I have used the method of historical materialism, dogmatic law method, statistical methods, surveys and interviews, and studies of individual cases.    From the research of this type of crime, I have concluded that these criminal offences are a serious type of crime, which may result in major individual

Workplace Offences in the Light of the New Criminal Code

OpenAIRE

Amalia-Mihaela Lazer-Gavrilă

2015-01-01

From the perspective of current regulations, workplace offences and also the concept of public service require shaping of a shared vision, creating effective structures, but also a rational adoption of a European vision. Also, the personality of a nation is appreciated by the degree of appreciation of its values.

Stressing Academia? Stress-as-Offence-to-Self at Danish Universities

Science.gov (United States)

Opstrup, Niels; Pihl-Thingvad, Signe

2016-01-01

Academic work has traditionally been seen as relatively stress free. However, a growing number of studies have reported increases in occupational stress experienced by university researchers. In order to explain stress among this group, we build on a new perspective in occupational stress research: the so-called stress-as-offence-to-self…

Workplace Offences in the Light of the New Criminal Code

Directory of Open Access Journals (Sweden)

Amalia-Mihaela Lazer-Gavrilă

2015-05-01

Full Text Available From the perspective of current regulations, workplace offences and also the concept of public service require shaping of a shared vision, creating effective structures, but also a rational adoption of a European vision. Also, the personality of a nation is appreciated by the degree of appreciation of its values.

Teoretical basis for the study of reparation by the state physical person, the victim of a criminal offence

Directory of Open Access Journals (Sweden)

Наталія Анатоліївна Хмельова

2016-06-01

Full Text Available Theoretical aspects of harm caused a criminal offence, that is, damage that is the basis for the adoption of measures to ensure reparation to the victim, in the science of civil procedural law received significant attention. However, despite the serious scientific elaboration of this problem and its issues, still have a lot of issues that are still insufficiently study, while they are essential for the theory of civil law. Analysis of recent research gives reason to believe that the affected problems has been the subject of research by scholars such as G. A. Atanesyan, S. P. Golubyatnikov, B. T. Bezlepkin, M. I. Goshovsky, O. I. Kuchinska, V. T. Nor, and others. However, the update of the regulatory material, in particular amendments to the Civil code of Ukraine, adoption of the new Criminal procedural code of Ukraine, can not affect scientific and practical interest in the conditions of modernity. Civil-legal nature of compensation of property harm involves understanding it as an object of tort obligations, which it is in civil law. In the legal literature there are two opposite positions of the scholars on this issue. Civil legislation proceeds from the principle of full compensation for losses. The concept of property damage caused by a criminal offence to the victim, covers: 1 caused by a criminal offence the face of a direct, imminent harm to his property and in monetary terms; 2 loss due to criminal offence, and income; 3 evaluated in monetary terms, the cost of treatment, prosthetics, restoration of health of the victim, and in case of his death, burial and payments for the maintenance of physical well-being and education of the disabled family members of the victim and their minor children; 4 the funds spent by state or municipal health protection institution on hospitalization of the person injured from the criminal offence. In summary clarification of the concept of property damage caused by a criminal offence, we distinguish three

Criminal Narrative Experience: Relating Emotions to Offence Narrative Roles During Crime Commission.

Science.gov (United States)

Ioannou, Maria; Canter, David; Youngs, Donna

2017-10-01

A neglected area of research within criminality has been that of the experience of the offence for the offender. The present study investigates the emotions and narrative roles that are experienced by an offender while committing a broad range of crimes and proposes a model of criminal narrative experience (CNE). Hypotheses were derived from the circumplex of emotions, Frye, narrative theory, and its link with investigative psychology. The analysis was based on 120 cases. Convicted for a variety of crimes, incarcerated criminals were interviewed and the data were subjected to smallest space analysis (SSA). Four themes of CNE were identified: Elated Hero, Calm Professional, Distressed Revenger, and Depressed Victim in line with the recent theoretical framework posited for narrative offence roles. The theoretical implications for understanding crime on the basis of the CNE as well as practical implications are discussed.

Do doctors attending sexual-offence victims have to notify sexual ...

African Journals Online (AJOL)

2017-12-03

Dec 3, 2017 ... the Sexual Offences Act);[1] and (iii) the ethical rules and guidelines ... and the duty on doctors to treat their patients with the skill and care ... duty on the doctor to counsel the patient to warn such partner and to ... persons may suffer injury as a result of interactions with their patients, and that this applies to.

'Trafficking' or 'personal use': do people who regularly inject drugs understand Australian drug trafficking laws?

Science.gov (United States)

Hughes, Caitlin E; Ritter, Alison; Cowdery, Nicholas; Sindicich, Natasha

2014-11-01

Legal thresholds for drug trafficking, over which possession of an illicit drug is deemed 'trafficking' as opposed to 'personal use', are employed in all Australian states and territories excepting Queensland. In this paper, we explore the extent to which people who regularly inject drugs understand such laws. Participants from the seven affected states/territories in the 2012 Illicit Drug Reporting System (n = 823) were asked about their legal knowledge of trafficking thresholds: whether, if arrested, quantity possessed would affect legal action taken; and the quantities of heroin, methamphetamine, cocaine and cannabis that would constitute an offence of supply. Data were compared against the actual laws to identify the accuracy of knowledge by drug type and state, and sociodemographics, use and purchasing patterns related to knowledge. Most Illicit Drug Reporting System participants (77%) correctly said that quantity possessed would affect charge received. However, only 55.8% nominated any specific quantity that would constitute an offence of supply, and of those 22.6% nominated a wrong quantity, namely a quantity that was larger than the actual quantity for supply (this varied by state and drug). People who regularly inject drugs have significant gaps in knowledge about Australian legal thresholds for drug trafficking, particularly regarding the actual threshold quantities. This suggests that there may be a need to improve education for this population. Necessity for accurate knowledge would also be lessened by better design of Australian drug trafficking laws. © 2014 Australasian Professional Society on Alcohol and other Drugs.

Environmental offences in 1995. An evaluation of statistics; Umweltdelikte 1995. Eine Auswertung der Statistiken

Energy Technology Data Exchange (ETDEWEB)

Goertz, M.; Werner, J.; Sanchez de la Cerda, J.; Schwertfeger, C.; Winkler, K.

1997-06-01

This publication deals with the execution of environmental criminal law. On the basis of police and judicial statistics it is pointed out how often an environmental criminal offence was at least suspected by the police or law courts, how they reacted to their suspicion, which individual environmental criminal offences were committed particularly frequently, and what segment of the population the typical perpetrator belonged to. (orig./SR) [Deutsch] Mit der vorliegenden Schrift soll ein Blick auf den Vollzug des Umweltstrafrechts geworfen werden. Auf der Basis der Polizei- und Gerichtsstatistiken wird dargelegt, wie oft bei diesen Stellen mindestens der Verdacht einer Umweltstraftat bestand, wie auf diesen Verdacht reagiert wurde, welche einzelnen Umweltstraftaten besonders haeufig registriert wurden und aus welchem Personenkreis der tpische Taeter stammt. (orig./SR)

Keeping a common bawdy house becomes a "serious offence" under Criminal Code.

Science.gov (United States)

2010-10-01

New federal regulations targeting organized crime will make keeping a common bawdy house a "serious offence" under the Criminal Code. Sex work advocates reacted by calling the measure a serious step back that will undermine the protection of sex workers' human rights, safety, dignity and health.

“They Know, But Do Not Tell”: Examining the Link Between Animal Cruelty and Other Criminal Offences in British Columbia

OpenAIRE

Hinz, Jessica Marie

2016-01-01

Animal cruelty is a significantly under researched topic in Criminology. An exploratory study was undertaken to determine whether there is a link between cruelty offences and other crimes in British Columbia (BC). Data were compiled using open source websites to identify convicted animal cruelty offenders and examine any further criminal convictions. Using the frameworks of the graduation hypothesis and generalized deviance theory, criminal offending patterns and timing of offences were analy...

Translations on Narcotics and Dangerous Drugs, Number 318

Science.gov (United States)

1977-09-08

cent of those ar- rested for drug offences had no religious back- ground. He therefore called on ’ the Malaysian Inter-Re- , ligions...illicit drugs, it would mean that 15 out of every 1,000 Malaysians have drug- tainted fingers (based on a population figure of 12 mil- lion).. An idea...a certain de- gree of misunderstanding concerning crime and ad-’ diets . Addicts have, been ac- cused of being violent as a result of their drug

Predicate Offences of Money Laundering and Anti Money Laundering Practices in Bangladesh Among South Asian Countries

Directory of Open Access Journals (Sweden)

Islam Mohammad Saiful

2017-12-01

Full Text Available The purpose of the study is to identify the main reasons of money laundering in Bangladesh among the twenty seven predicate offences of money laundering prescribed by Bangladesh Bank and position of Bangladesh among South Asian Countries regarding anti-money laundering practices. Besides, an anti-money laundering model has been developed to combat against money laundering as 14 percent bankers think that only existing know your customer form and transaction profile of banking sector are not enough to detect money laundering. To conduct the study, 91 bankers have been surveyed to take response through structured questionnaire regarding their opinion about the predicate offences of money laundering and sufficiency of existing KYC form of banking sector to detect money laundering. From the responses, factor analysis, test of hypothesis, correlation and regression analysis have been conducted using SPSS software. The study identifies that predicate offences of money laundering can be minimized mainly through scrutinizing the activities of local criminals with foreign network and strict anti-corruption measures through automation in National Board of Revenue, strict policy adoption of criminal detection and support from foreign experts. Besides, regression model shows that only six predicate offences of money laundering explains 87.2 percent of money laundering that should get more emphasize to combat against money laundering. From the comparative analysis, it has been found that Bangladesh in holding better position just after India among six South Asian Countries according to Basel AML Index score. This study provides a complete understanding of the position of Bangladesh in case of money laundering and anti-money laundering practices. The integration of four domains, i.e. AML model development, factor analysis, econometric analysis and comparative analysis of AML index will provide insights to managers and policy makers about the money laundering

The role of alcohol, drugs, suicide attempts and situational strains in homicide committed by offenders seen for psychiatric assessment. A controlled study.

Science.gov (United States)

Langevin, R; Paitich, D; Orchard, B; Handy, L; Russon, A

1982-09-01

The use of alcohol and drugs at the time of offence, suicide attempts and situational strains were compared in 109 killers and 38 nonviolent offenders seen for psychiatric assessment. More killers than nonviolent offenders used alcohol and drugs at the time of their offence but there was no difference in previous attempts at suicide nor in situational strains. Killers, however, did have more recent frustrations than the other group. Results suggest that the use of intoxicants in violence-prone individuals is the most important factor in homicide.

MEDIATION IN THE OFFENCES FROM THE SPECIAL LAWS

Directory of Open Access Journals (Sweden)

Gabriel-Cristian Constantinescu

2016-11-01

Full Text Available Changesin Romanian penal laws coming into force from 1st February 2014 brought an increasing number of offenses for which it is possible a penal mediation, including the offenses from the special laws (not included in the main Penal Code, for which the withdrawal of the advance complaint or the reconciliation of the parties removes the penal responsibility. These offences from the special laws are reviewed and detailed by the author with the mark of the removal mode of the penal responsibility, achieving a practical table for practitioners. Mediation procedure in the special laws crimes is similar into the general criminal mediation, but the application of the most favourable in time law may require special attention.

EUTHANASIA STIPULATED BY ROMANIAN CRIMINAL LAW, MITIGATING CIRCUMSTANCES VS. OFFENCE

Directory of Open Access Journals (Sweden)

MONICA POCORA

2012-05-01

Full Text Available This paper aims to be a scientific approach to the issue of euthanasia, bringing into the debate current and future controversies raised by euthanasia, as a result of the introduction into the Romanian penal law of the criminal offence of homicide by request of the victim. The study represents an approach to moral, religious, constitutional, civil, criminal procedure debates and last but not least to criminal debates regarding the legalization of the euthanasia, as the most difficult task lies with the criminal law.

The prison system in the Czech Republic: Analysis of the current state of illicit drug use and prevention and treatment measures

Czech Academy of Sciences Publication Activity Database

Miovský, Michal; Gajdošíková, H.

2005-01-01

Roč. 16, č. 4 (2005), s. 262-266 ISSN 0955-3959 Institutional research plan: CEZ:AV0Z70250504 Keywords : Criminal offences * drug crime * illicit drugs * drug user * prevetntion and treatment measures Subject RIV: AN - Psychology

Traffic Offences: Planned or Habitual? Using the Theory of Planned Behaviour and habit strength to explain frequency and magnitude of speeding and driving under the influence of alcohol.

Science.gov (United States)

Lheureux, Florent; Auzoult, Laurent; Charlois, Colette; Hardy-Massard, Sandrine; Minary, Jean-Pierre

2016-02-01

This study addresses the socio-cognitive determinants of traffic offences, in particular of speeding and drinking and driving. It has two aims: (1) to test the hypothesis of a direct effect of habits on offences (i.e., independent of intentions) by employing a specific measure of habits (i.e., the SRIH) and (2) to analyse the offences by taking account of three distinct parameters: Frequency, usual magnitude (i.e., the most frequent deviation from the law) and maximal magnitude (i.e., the greatest deviation occasionally adopted) in order to represent more accurately the variability of the offending behaviours. A total of 642 drivers replied to a questionnaire. The results corroborate the idea that intention and habit are distinct and direct determinants of offences. The use of the SRIH dismisses the criticisms made with regard to the measure of past behaviour. The distinction between the three behavioural parameters proves to be relevant, as their determinants are not exactly similar. Finally, attitude and subjective norm had direct effects on the maximal magnitude and/or on the frequency of the offence. The discussion concerns the contribution of this study to the analysis of offences as well as its limitations and addresses the theoretical plausibility of the direct effects of attitude and the subjective norm. © 2015 The British Psychological Society.

Individual and psychological predictors of the offence severity

Directory of Open Access Journals (Sweden)

Lysenko N.E.

2017-10-01

Full Text Available The article analyzes the relationship parameters of temperament with offence severity in mental health subjects. The results of a comparative study of males with violent, nonviolent civil disturbances and non-criminals were observed. The proposition of the study is to measure individual traits in two ways: as a quantitate factor, that includes assessment of gradual change from lower to higher crime severity, like State Anxiety and Behavior Inhibition, or as qualitative factor, that includes revealing of multilevel combinations of individual characteristics based on innate traits of nervous system. There are correlation of activation processes and physical aggression in group of subjects with violent crimes, and activation processes and characteristics of communication sphere in subjects with nonviolent crimes.

Can experiments on animals constitute a criminal offence of cruelty to animals?

Directory of Open Access Journals (Sweden)

Ristivojevic Branislav

2014-01-01

Full Text Available The criminal offence “killing and torturing animals” under Article 269 of the Criminal Code says that it can be committed only “contrary to regulations”. The regulations governing the treatment of experimental animals are the Animal Welfare Law from 2009 and the Law on the Ratification of the European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes amended by the Protocol of amendment to the European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes from 2010. The first one imposes numerous obligations and introduces numerous prohibitions in the treatment of experimental animals, which at first sight make the possibilities of committing this criminal offence greater. The other law does not contain most of the prohibitions and restrictions that are included in the Animal Welfare Law. Thanks to a legal rule which says that a later law regulating the same subject replaces the former one (lex posterior derogate legi priori and the aforementioned unconstitutionality of many provisions of the Animal Welfare Law, researchers and teachers in Serbia are not in particular danger of criminal prosecution. [Projekat Ministarstva nauke Republike Srbije, br. 179079: Biomedicine, Environmental Protection and the Law

Criminal Liability for Serious Traffic Offences : Essays on Causing Death, Injury and Danger in Traffic

NARCIS (Netherlands)

van Dijk, Alwin; Wolswijk, Hein

2015-01-01

The criminal law on serious traffic offences is a fascinating area. The traffic context presents legislators with numerous controversial issues. One such issue is when severe consequences are matched with low moral culpability. How should the law deal with a driver who kills someone because she

Women convicted of a sexual offence, including child pornography production: two case reports.

Science.gov (United States)

Prat, S; Bertsch, I; Chudzik, L; Réveillère, Ch

2014-03-01

All available studies addressing the clinical and legal aspects of child pornography have systematically concerned male abusers. The social lens through which women are viewed tends to play down their responsibility in the sexual abuse of children. Unlike men, women rarely abuse children outside the close or family circle. Furthermore, they have frequently been abused themselves in their childhood. To our knowledge, no cases of women charged with sex-related offences, including child pornography, have been described in the literature. The psychopathological characteristics of female sexual abusers and of the two women in our cases tend to suggest that the deliberate downloading of child pornography images by women is unusual, as their deviant behaviour is not related to paedophile sexual arousal It is hypothesized that the act enables women perpetrators to satisfy the sexual urges of their spouse. Sexual abuse by women exists, but the nature of the abuse appears to be specific to the gender of the perpetrator. We present two cases of women charged with sexual offences concerning minors, including the production of child pornography material. Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Repeat participation in annual cross-sectional surveys of drug users and its implications for analysis.

Science.gov (United States)

Agius, P A; Aitken, C K; Breen, C; Dietze, P M

2018-06-04

We sought to establish the extent of repeat participation in a large annual cross-sectional survey of people who inject drugs and assess its implications for analysis. We used "porn star names" (the name of each participant's first pet followed by the name of the first street in which they lived) to identify repeat participation in three Australian Illicit Drug Reporting System surveys. Over 2013-2015, 2468 porn star names (96.2%) appeared only once, 88 (3.4%) twice, and nine (0.4%) in all 3 years. We measured design effects, based on the between-cluster variability for selected estimates, of 1.01-1.07 for seven key variables. These values indicate that the complex sample is (e.g.) 7% less efficient in estimating prevalence of heroin use (ever) than a simple random sample, and 1% less efficient in estimating number of heroin overdoses (ever). Porn star names are a useful means of tracking research participants longitudinally while maintaining their anonymity. Repeat participation in the Australian Illicit Drug Reporting System is low (less than 5% per annum), meaning point-prevalence and effect estimation without correction for the lack of independence in observations is unlikely to seriously affect population inference.

Myths and legends: The reality of rape offences reported to a UK police force

Directory of Open Access Journals (Sweden)

Genevieve F. Waterhouse

2016-01-01

Full Text Available Rape myths affect many aspects of the investigative and criminal justice systems. One such myth, the ‘real rape’ myth, states that most rapes involve a stranger using a weapon attacking a woman violently at night in an isolated, outdoor area, and that women sustain serious injuries from these attacks. The present study examined how often actual offences reported to a central UK police force over a two year period matched the ‘real rape’ myth. Out of 400 cases of rape reported, not a single incident was found with all the characteristics of the ‘real rape’ myth. The few stranger rapes that occurred had a strong link to night-time economy activities, such as the victim and offender both having visited pubs, bars, and clubs. By contrast, the majority of reported rape offences (280 cases, 70.7% were committed by people known to the victim (e.g., domestic and acquaintance rapes, occurred inside a residence, with most victims sustaining no physical injuries from the attack. The benefits of these naturalistic findings from the field for educating people about the inaccuracy of rape myths are discussed.

Differences of Driving Experience and Gender on Traffic Offences Among Malaysian Motorists

Directory of Open Access Journals (Sweden)

Liew Sharifah

2017-01-01

Full Text Available This study attempt to examine the influence of driving experience and gender on different traffic offences. Questionnaire survey was conducted to measure the frequency of committing eleven types of traffic. Data collected were analysed using t-test and Chi-square. Results indicate that male drivers have high score in speeding, red light running, tailgating and using emergency lane. Significant differences emerged between driving experiences in speeding, red light running, dangerously cutting into traffic, using hand phone while driving/riding and driving/riding with noncompliance specification vehicle.

Why run the risk? Motivation for offences by patients with substance use and antisocial personality disorders which they rated as most risky to their own well-being.

Science.gov (United States)

Thylstrup, Birgitte; Hesse, Morten

2018-04-01

Understanding motives for offending is important for the development and delivery of effective interventions. To explore associations between variables with motivational implications and the offence committed in the past year rated by people with antisocial personality disorder and substance use disorder as putting them and their status at most risk. Participants were 127 outpatients from a sample recruited for a pragmatic randomised controlled trial of an intervention for adults attending substance abuse treatment clinics in 13 municipalities in Denmark. Motives for offending were assessed on one occasion, using the Offending Motivation Questionnaire, aggression was assessed using the Buss-Perry Aggression Questionnaire and substance-related problems, including mental state difficulties, were assessed using the Substance Use Risk Profile. Attributing offending to provocation, excitement or financial gain differed substantially by type of offence, whereas attribution of offending to compliance did not. Personality scale scores were associated with attributing offences to provocation, excitement or compliance but not with financial gain. Motives for offending among substance users with antisocial personality disorder must be understood both in light of the type of offence and personality traits. Offending behaviour prevention strategies that draw on these distinctions, run in parallel to treatment for substance use, could improve reduction in recidivism. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

The role of alcohol and drugs in homicides in England and Wales.

Science.gov (United States)

Shaw, Jenny; Hunt, Isabelle M; Flynn, Sandra; Amos, Tim; Meehan, Janet; Robinson, Jo; Bickley, Harriet; Parsons, Rebecca; McCann, Kerry; Burns, James; Kapur, Nav; Appleby, Louis

2006-08-01

The annual number of homicide convictions in England and Wales is increasing. Previous studies have highlighted the aetiological role of alcohol and drugs in homicide. To examine rates of alcohol and drug misuse and dependence in people convicted of homicide; the role of alcohol and drugs in the offence; the social and clinical characteristics of alcohol- and drug-related homicides; and the social and clinical characteristics of patients with dual diagnosis who commit homicide. A national clinical survey based on a 3-year (1996-9) consecutive sample of people convicted of homicide in England and Wales. Information on rates of alcohol and drug misuse/dependence, the role of alcohol and drugs in the offence and social and clinical characteristics of perpetrators were collected from psychiatric reports prepared for the court in homicide convictions. Detailed clinical information was gathered from questionnaires completed by mental health teams for those in contact with mental health services. Of the 1594 homicide perpetrators, more than one-third (42%) occurred in people with a history of alcohol misuse or dependence and 40% in people with a history of drug misuse or dependence. Alcohol or drug misuse played a contributory role in two-fifths of homicides. Alcohol played a major role in 52 (6%) and a minor role in 364 (39%) homicides. Drugs played a major role in six (1%) and a minor role in 138 (14%) homicides. Forty-two homicides (17%) were committed by patients with severe mental illness and substance misuse. Alcohol- and drug-related homicides were generally associated with male perpetrators who had a history of violence, personality disorders, mental health service contact and with stranger victims. Substance misuse contributes to the majority of homicides in England and Wales. A public health approach to homicide would highlight alcohol and drugs before severe mental illness.

Mental diseases and criminal offences committed by persons placed at the Forensic Department of the Penitentiary in Zenica, Federation of Bosnia and Herzegovina.

Science.gov (United States)

Bjelošević, Edin; Krehmić, Adisa; Hadžikapetanović, Halima; Čoralić, Sanel; Bjelošević, Sonja

2017-08-01

Aim To investigate an impact of various biological, psychological and social factors on perpetration of criminal offences by persons with mental disorders and to examine legal requirements for placement of persons with mental disorders, who committed criminal offences. Methods This retrospective, descriptive study based on the analysis of data collected from records of the Zenica Penitentiary, Forensic Department (age, qualifications, employment status, marital status, mental disorders, information related to earlier treatments, type of committed criminal offense, duration of the security measure of mandatory psychiatric treatment and custody) included 154 examinees. Results The study included 154 male examinees. An average age of the examinees was 34 years. An average duration spent at the Forensic Department was 3 years, murder was committed by 68 (44.15%) examinees, and 34 (22.07%) examinees committed attempted murder. Eighty-five (55. 19 %) examinees suffered from schizophrenia, 30 (19.48%) had delusional disorder, and 19 (12.33%) had mental retardation. Conclusion The highest number of committed crimes was in correlation with schizophrenia, (the highest number of examinees suffered from schizophrenia). It is necessary to work on the establishment of a forensic hospital in the territory of the Federation of Bosnia and Herzegovina in order to create good conditions for rehabilitation of patients with mental disorders who committed criminal offences. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Within-host selection of drug resistance in a mouse model of repeated interrupted treatment of Plasmodium yoelii infection

NARCIS (Netherlands)

Nuralitha, Suci; Siregar, Josephine E; Syafruddin, Din; Hoepelman, Andy I M; Marzuki, Sangkot

2017-01-01

BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone

Impact of repeated intravenous cocaine administration on incentive motivation depends on mode of drug delivery.

Science.gov (United States)

LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

2014-11-01

The incentive sensitization theory of addiction posits that repeated exposure to drugs of abuse, like cocaine, can lead to long-term adaptations in the neural circuits that support motivated behavior, providing an account of pathological drug-seeking behavior. Although pre-clinical findings provide strong support for this theory, much remains unknown about the conditions that support incentive sensitization. The current study examined whether the mode of cocaine administration is an important factor governing that drug's long-term impact on behavior. Separate groups of rats were allowed either to self-administer intravenous cocaine or were given an equivalent number and distribution of unsignaled cocaine or saline infusions. During the subsequent test of incentive motivation (Pavlovian-to-instrumental transfer), we found that rats with a history of cocaine self-administration showed strong cue-evoked food seeking, in contrast to rats given unsignaled cocaine or saline. This finding indicates that the manner in which cocaine is administered can determine its lasting behavioral effects, suggesting that subjective experiences during drug use play a critical role in the addiction process. Our findings may therefore have important implications for the study and treatment of compulsive drug seeking. © 2013 Society for the Study of Addiction.

Incorporation of punishable offences against the law on protection of the environment into the penal code

International Nuclear Information System (INIS)

Moehrenschlager, M.

1979-01-01

The government bill on the sixteenth act amending the penal legislation - act on the prevention of environmental offences - is presented, with comments being given on the most important stipulations. Paragraph 328 of the penal code deals with the unauthorized handling of nuclear fuels and represents an almost complete adoption of Paragraph 45 of the Atomic Energy law. The prohibition of the operation of nuclear facilities laid down in Paragraph 45, par. 1, No.4 of the Atomic Energy law, has been incorporated into the factural characteristics of illegal operation of facilities (Paragraph 327, par. 1,3 No. 1 of the penal code). The illegal handling of other radioactive substances has been dealt with in regard to some important cases: specifically for the case of illegal waste disposal (Paragraph 326, par. 1 No. 2, par. 2 of the penal code), and for the case of irregular transport leading to concrete danger or nuisance (Paragraph 330, par. 1 No. 4 of the penal code), as well as for the case of release of ionizing radiation having any such consequences (Paragraph 330, par. 1 No. 2, item c of the penal code). According to Paragraph 324 of the penal code, radioactive contamination of waters is a punishable offence. The rule of qualification of Paragraph 330 par. 1 of the penal code is to be applied to all these facts. (orig./HP) 891 HP/orig.- 892 MB [de

Repeated nicotine exposure enhances reward-related learning in the rat.

Science.gov (United States)

Olausson, Peter; Jentsch, J David; Taylor, Jane R

2003-07-01

Repeated exposure to addictive drugs causes neuroadaptive changes in cortico-limbic-striatal circuits that may underlie alterations in incentive-motivational processes and reward-related learning. Such drug-induced alterations may be relevant to drug addiction because enhanced incentive motivation and increased control over behavior by drug-associated stimuli may contribute to aspects of compulsive drug-seeking and drug-taking behaviors. This study investigated the consequences of repeated nicotine treatment on the acquisition and performance of Pavlovian discriminative approach behavior, a measure of reward-related learning, in male rats. Water-restricted rats were trained to associate a compound conditioned stimulus (tone+light) with the availability of water (the unconditioned stimulus) in 15 consecutive daily sessions. In separate experiments, rats were repeatedly treated with nicotine (0.35 mg/kg, s.c.) either (1) prior to the onset of training, (2) after each daily training session was completed (ie postsession injections), or (3) received nicotine both before the onset of training as well as after each daily training session. In this study, all nicotine treatment schedules increased Pavlovian discriminative approach behavior and, thus, prior repeated exposure to nicotine, repeated postsession nicotine injections, or both, facilitated reward-related learning.

Criminal offence domestic violence: Legal practice in Niš area

Directory of Open Access Journals (Sweden)

Vilić-Konstantinović Slobodanka

2003-01-01

Full Text Available In this paper authors analyze seven cases of domestic violence in Niš area during one year of implementation of the new criminal offence domestic violence. Using the method of indirect observation and interviews, authors give us an overview of police's, prosecutors and court's intervention in domestic violence cases. In spite of small number of registered and processed domestic violence cases, some negative phenomenons are observed. Those phenomenons unable efficient and accurate preventive and repressive actions toward abuser. Majority of these observed facts are noted and explained, with underlining the consequences and a way for overcoming them. In order to reach valid and scientifically based conclusion about implementation of laws regarding domestic violence, it is essential to undertake extensive research in Serbia, including a research of a practice of the police, prosecutors and courts. Results of such research would allow qualitative theoretical overview of law enforcement practice regarding domestic violence. Knowledge gained in this way would help us to establish programs for education of individuals who, in different roles, participate in preventive and repressive actions against domestic violence.

On roots and nature of the normative regulation of the criminal offence of theft in the tradition of Tsar Dusan legislation

Directory of Open Access Journals (Sweden)

Vujović Ognjen B.

2015-01-01

Full Text Available In this paper the comparison between several norms of the Crimi­nal Offence of Theft in the tradition of Tsar Dusan legislation and certain provisions of the Roman law was performed. On this occa­sion, the issue of robbery, theft of fruits and complicity to theft were treated in particular.

Criminal Sanctions Against Official Corruption and other Offences Against Official Duty Offenders in Kosovo for the Period 2008-2015

Directory of Open Access Journals (Sweden)

Flutura Tahiraj

2017-08-01

Full Text Available The need to fight corruption, with the focus on official corruption in Kosovo continues to be addressed by both national and international reports. The objective of this paper is to find out the number of the cases and analyse the sactions against official corruption and other offences against official duty delivered by Municipality Courts in Kosovo during the period 2008-2015 with the aim to assess the developments during a period of eight years since most of the other researches are focused on annual performance of the courts. All data presented in this article are taken from the Kosovo Statistical Office and include statistical information on the types and frequency of criminal sanctions to perpetrators of the official corruption and other offences against official duty. Case study is also applied to analyse some court judgments. The study shows there is a slight incresase of the number of convicted perpetrators over years, the number of corruption cases addressed by the courts remained very limited, followed by low sentences or even prescription of cases. The findings will add additional scientific insights to the existing knowledge about preventing and fighting official corruption and it can be useful for scholars, policy makers and practitioners in Kosovo.

Progressief boetestelsel en verkeersveiligheid : geschatte veiligheidseffecten van hogere boetes bij herhaalde snelheidsovertredingen. In opdracht van het Ministerie van Justitie, Wetenschappelijk Onderzoek- en Documentatiecentrum WODC.

NARCIS (Netherlands)

Hoekstra, A.T.G. Eenink, R.G. & Goldenbeld, C.

2017-01-01

Progressive penalty system and road safety; Estimated safety effects of progressive fines for repeated speeding offences. A traffic offence is typically more heavily penalized if it comes with a greater risk. As one exceeds the limit — for driving speed or blood alcohol content — to a greater

Was an increase in cocaine use among injecting drug users in New South Wales, Australia, accompanied by an increase in violent crime?

Directory of Open Access Journals (Sweden)

Conroy Elizabeth

2005-04-01

Full Text Available Abstract Background A sharp reduction in heroin supply in Australia in 2001 was followed by a large but transient increase in cocaine use among injecting drug users (IDU in Sydney. This paper assesses whether the increase in cocaine use among IDU was accompanied by increased rates of violent crime as occurred in the United States in the 1980s. Specifically, the paper aims to examine the impact of increased cocaine use among Sydney IDU upon police incidents of robbery with a weapon, assault and homicide. Methods Data on cocaine use among IDU was obtained from the Illicit Drug Reporting System (IDRS. Monthly NSW Police incident data on arrests for cocaine possession/use, robbery offences, homicides, and assaults, were obtained from the Bureau of Crime Statistics and Research. Time series analysis was conducted on the police data series where possible. Semi-structured interviews were conducted with representatives from law enforcement and health agencies about the impacts of cocaine use on crime and policing. Results There was a significant increase in cocaine use and cocaine possession offences in the months immediately following the reduction in heroin supply. There was also a significant increase in incidents of robbery where weapons were involved. There were no increases in offences involving firearms, homicides or reported assaults. Conclusion The increased use of cocaine among injecting drug users following the heroin shortage led to increases in violent crime. Other States and territories that also experienced a heroin shortage but did not show any increases in cocaine use did not report any increase in violent crimes. The violent crimes committed did not involve guns, most likely because of its stringent gun laws, in contrast to the experience of American cities that have experienced high rates of cocaine use and violent crime.

Sexual orientation and self-rated health: the role of social capital, offence, threat of violence, and violence.

Science.gov (United States)

Axelsson, Jakob; Modén, Birgit; Rosvall, Maria; Lindström, Martin

2013-07-01

To study the association between sexual orientation and self-rated health, including trust, offence, threat of violence, and violence. DESIGN/SETTING/PARTICIPANTS/MEASUREMENT: The 2008 Public Health Survey in Skåne is a cross-sectional postal questionnaire study. A total of 28,198 persons aged 18-80 years responded (55%). Logistic regressions analysed the association between sexual orientation and self-rated health. 27.4% of all men and 30.0% of all women rated their health as poor. Poor self-rated health was significantly more prevalent in higher age, among immigrants, people with lower education, low social support, low trust, experience of being offended, experience of threat of violence and violence, and bisexual and other orientation. Homosexual and bisexual men and women had higher age-adjusted odds ratios of having felt offended compared to heterosexual respondents. The odds ratios of low trust, threat of violence (men), and experience of violence (women) were significant for respondents with bisexual orientation but not for respondents with homosexual orientation. In the age-adjusted model, no significant association was observed between homosexual orientation and poor self-rated health among women. All other associations between sexual orientation and health were significant in the age-adjusted model but non-significant in the multiple models. Associations between sexual orientation and health disappear after multiple adjustments including trust and experience of offence, threat of violence, and violence. The study suggests that the group with bisexual orientation seems to be more exposed to low social capital (trust), threat of violence, and violence than the group with homosexual orientation.

Within-host selection of drug resistance in a mouse model of repeated interrupted treatment of Plasmodium yoelii infection

OpenAIRE

Nuralitha, Suci; Siregar, Josephine E; Syafruddin, Din; Hoepelman, Andy I M; Marzuki, Sangkot

2017-01-01

BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone and pyrimethamine in Plasmodium yoelii was examined in such a model. METHODS: Treatment of P. yoelii infected mice, with atovaquone or pyrimethamine, was started at parasitaemia level of 3-5%, inter...

An examination of outlaw motorcycle gangs and their involvement in the illicit drug market and the effectiveness of anti-association legislative responses.

Science.gov (United States)

Goldsworthy, Terry; McGillivray, Laura

2017-03-01

In 2013 the Queensland Government introduced criminal association and mandatory sentencing laws for members of outlaw motorcycle gangs (OMCGs). Forms of "criminal association" or "anti-bikie" laws have been introduced in several Australian jurisdictions, and recent High Court decisions upholding their constitutionality will ensure that they remain part of our justice landscape. Generally, the aims of these laws are to declare a specific organisation as "criminal" and impose various legal orders and offences that thwart the consorting of members and address organised crime, such as unexplained wealth regimes. There have been significant criticisms of these styles of association laws both here and internationally. The aim of this research is to show the extent of involvement of OMCGs in the drug trade and associated organised crime activity, and whether anti-association laws are an effective response to this type of organised criminal activity. This paper relied on six years of data outlining the criminal activity of OMCGs from the Queensland Police Service (QPS) obtained under the legislative framework of The Queensland Right to Information Act (RTI) 2009. Information obtained from the Queensland Commission into Organised Crime (2015) and Queensland Taskforce into organised crime legislation (2015) was also used. The data suggest that the role of OMCGs in the drug market has been overstated and is not as dominant as has been portrayed by government agencies and the popular media. Generally, OMCGs account for less than one percent of organised crime type activity. This is also true for drug type offences where OMCGs are responsible for less than one percent of offences. The findings show that the Queensland example has highlighted the ineffectiveness of the criminal association laws and the mandatory sentencing provisions in that they have had little impact on drug market activity and little success in the courts. The analysis presented here is twofold: an

[Clinical decision making with regard to the granting of escorted leave for forensic patients detained by court order in a Dutch psychiatric clinic. Role of gender, disorder and the type of offence in the procedure].

Science.gov (United States)

Ter Horst, P; Jessen, A; Bogaerts, S; Spreen, M

2015-01-01

An increase in the length of time until the first escorted leave is granted to a patient detained by court order (tbs) results in a longer period of treatment. Physicians involved in the treatment and clinic managers are striving to reduce, in a responsible manner, the length of the period of treatment preceding the patient's first escorted leave. Forensic Psychiatric Clinic (fpk) 'De Woenselse Poort' aims to find out to what extent gender, pathology and the type of offence committed by the detainee influence the length of time that elapses before the patient's first leave is granted. We conducted a retrospective study based on patients' records. Although men use physical aggression more often than women, we found that gender, pathology and the type of offence had no influence on the length of the treatment period that preceded the granting of the patient's first escorted leave. Partly on the basis of risk management scales, clinicians judge whether the patient has adopted a more positive or a more negative attitude to risk factors relating to his or her offence. If the risk factors have become more positive, one would expect the application for leave to be made earlier. Surprisingly, this was not the case. In order to speed up the decision-making process regarding the application for leave, a clinical method for evaluating risk related treatment needs to be developed in which offence related risk factors are identified and the patient's positive or negative attitude to these risks are measured and monitored. At each treatment evaluation practitioners should be required to produce arguments that determine whether or not the patient is to be granted permission to go on leave at a particular moment.

Pattern of psychiatric morbidity among theft offenders remanded or referred for psychiatric evaluation and factors associated with reoffence.

Science.gov (United States)

Chan, Lai Gwen; Bharat, Saluja; Dani, Dhaval Kirti

2013-06-01

In Singapore, theft and related crimes constitute more than 50% of all reported crime, and are the most common offences committed by accused persons remanded to the Institute of Mental Health (IMH), Singapore. There is a need for better understanding of the forensic psychiatric aspects of such offenders. This study aimed to determine the prevalence of psychiatric disorders among theft offenders remanded or referred for forensic assessment in 2010, compare the differences between first-time and repeat theft offenders, and identify the factors associated with reoffence. Forensic evaluations of inpatient and outpatient theft offenders that were conducted at IMH in the year 2010 were retrieved and reviewed. The sociodemographic and clinical data of first-time and repeat theft offenders were collected and compared using Student's t-test and chi-square test for continuous and categorical variables, respectively. Multivariate regression was used to identify the factors that were predictive of repeat offence. Overall, 10% of offenders had no mental illness. Substance use disorders, mood disorders and psychotic disorders were the most common diagnoses. Psychotic disorders were significantly less common in repeat offenders. Repeat offenders also tended to have a history of conduct problems in childhood. Noncompliance with psychiatric treatment was positively associated with repeat offence, while psychotic disorders were negatively associated. The pattern of psychiatric morbidity among theft offenders in Singapore has changed over the last ten years. Kleptomania remains rare. Significant differences between first-time and repeat offenders have implications on the treatment, follow-up and rehabilitation of theft offenders in Singapore.

Factors associated with dropout among patients in opioid maintenance treatment (OMT) and predictors of re-entry. A national registry-based study.

Science.gov (United States)

Bukten, Anne; Skurtveit, Svetlana; Waal, Helge; Clausen, Thomas

2014-10-01

Retention in treatment is often highlighted as one of the key indicators of success in opioid maintenance treatment (OMT). To identify factors associated with long-term retention in opioid maintenance treatment and to analyse predictors of subsequent treatment episodes. Treatment retention and re-entry were examined for a national cohort of patients admitted to OMT in Norway in the period 1997-2003. Multivariate Cox regression models were used to investigate factors associated with treatment dropout 18months after treatment entry. The 18month retention rate among patients admitted to OMT in Norway (n=2431) was 65.8% (n=1599). Dropout from OMT within 18months was associated with younger age (HR 0.97 [0.96-0.98]), high levels of general pre-treatment criminal offences (HR 1.66 [1.32-2.09]) and having drug-related offences during the 30days prior to dropout (HR 1.80 [1.36-2.38]). Of the patients who dropped out (n=832), 42.7% (n=355) were re-engaged in subsequent treatment episodes. Pre-treatment criminal offences were associated with increased odds for treatment re-entry, whereas being younger and having drug-related offences during the first OMT episode were associated with lower odds for re-engagement in OMT. Gender was not associated with treatment dropout and re-entry. High levels of pre-treatment criminal offences and drug offences during the 30days prior to dropout were associated with treatment dropout. Efforts to increase support services to these patients may contribute to higher rates of retention in OMT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Using 'payment by results' to fund the treatment of dependent drug users--proceed with care!

Science.gov (United States)

Maynard, Alan; Street, Andrew; Hunter, Rachael

2011-10-01

The UK government is changing its system of payment for drug treatment services in order to reward the achievement of better patient outcomes. This is a model that may be taken up internationally. This 'payment by results' funding system will reward providers for achieving good outcomes in terms of whether clients are drug free, employed and/or not convicted of a criminal offence. Providers will also receive a payment based on health and wellbeing outcome measurement. The definition and measurement of success in achieving these outcomes is complex and challenging, as is the need to bridge treatment costs during the period in which outcomes are pursued. This experiment requires careful evaluation if the delivery of drug treatment is not to be jeopardized or fragmented. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4- methylenedioxymethamphetamine ("Ecstasy").

Science.gov (United States)

Taylor, J R; Jentsch, J D

2001-07-15

Psychomotor stimulant drugs can produce long-lasting changes in neurochemistry and behavior after multiple doses. In particular, neuroadaptations within corticolimbic brain structures that mediate incentive learning and motivated behavior have been demonstrated after chronic exposure to cocaine, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). As stimulus-reward learning is likely relevant to addictive behavior (i.e., augmented conditioned reward and stimulus control of behavior), we have investigated whether prior repeated administration of psychomotor stimulant drugs (of abuse, including cocaine, d-amphetamine, or MDMA, would affect the acquisition of Pavlovian approach behavior. Water-deprived rats were tested for the acquisition of Pavlovian approach behavior after 5 days treatment with cocaine (15-20 mg/kg once or twice daily), d-amphetamine (2.5 mg/kg once or twice daily), or MDMA (2.5 mg/kg twice daily) followed by a 7-day, drug-free period. Prior repeated treatment with cocaine or d-amphetamine produced a significant enhancement of acquisition of Pavlovian approach behavior, indicating accelerated stimulus-reward learning, whereas MDMA administration produced increased inappropriate responding, indicating impulsivity. Abnormal drug-induced approach behavior was found to persist throughout the testing period. These studies demonstrate that psychomotor stimulant-induced sensitization can produce long-term alterations in stimulus-reward learning and impulse control that may contribute to the compulsive drug taking that typifies addiction.

Pharmacokinetics of repeated sodium salicylate administration to laying hens: evidence for time dependent increase in drug elimination from plasma and eggs.

Directory of Open Access Journals (Sweden)

Błażej Poźniak

Full Text Available Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus salicylate (SA may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1st, 7th and 14th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT, minimal plasma concentration (Cmin, C16h and elimination half-life (T1/2el of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (ClB increased. Layers administered with the higher dose showed a decrease only in the T1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment.

A comparison of Australian men with psychotic disorders remanded for criminal offences and a community group of psychotic men who have not offended.

Science.gov (United States)

White, Paul; Chant, David; Whiteford, Harvey

2006-03-01

People remanded into custody by the courts have a substantially higher rate of severe mental disorder than other prisoners and the general population. Knowledge of their prevalence, needs and characteristics and an analysis of pathways to care may be necessary to provide mental health care effectively and efficiently. Previous prison studies focusing on psychotic offenders have suffered from the use of instruments not validated in a forensic setting and lack of a relevant comparison group. The Diagnostic Interview for Psychosis (DP) is a composite semi-structured standardized interview schedule. It combines social and demographic descriptors with measures of functioning adapted from the World Health Organisation Disability Assessment Schedule (DAS). The remand centre surveyed had 466 cells and is the main remand and reception centre for males for the southern region of the state of Queensland, Australia. Of the 621 men screened, 65 answered yes to at least one question in the DP and were interviewed. Six hundred and twenty-one remandees were screened and of these 61 were interviewed as screened positive for psychotic disorder. Thirty-five per cent had been homeless for an average of 32 weeks during the previous year. Most had had little contact with families or close friends. Eighty-one per cent were receiving no treatment at the time of offence. Seventy-eight per cent were unemployed and in receipt of a pension. Eighty per cent were dependent on alcohol, cannabis or amphetamines. Statistical issues of power are detailed in the text. The simplistic 'prison, hospital or community treatment' debate is misleading. Instead, the development of flexible preventative, management and accommodation services for people with severe mental disorder who have committed offences is a priority.

‘Zero Tolerance’ Drug Driving Laws in Australia: A Gap Between Rationale and Form?

Directory of Open Access Journals (Sweden)

Julia Ann Quilter

2017-08-01

Full Text Available Legislation in all Australian states and territories creates offences and provides for police roadside testing in relation to ‘drug driving’. Ostensibly motivated by the same road safety objectives and impairment paradigm as drink driving laws, drug driving laws adopt a significantly different approach. Whereas random breath testing tests for all forms of alcohol and is designed to determine whether there is a sufficient concentration of alcohol in the driver’s body that s/he should be deemed to be impaired, random drug testing typically tests for the presence of any quantity of only the three most widely used illicit drugs—cannabis, methamphetamine and ecstasy—in the driver’s oral fluids, without reference to what is known about the different pharmacokinetic and pharmacodynamic qualities of different drugs. This article examines this idiosyncratic approach to the criminalisation of drug driving, highlighting its weak correlation with the important road safety objective of deterring substance-impaired driving, and the risks of both over- and under-criminalisation that it creates. It argues that public policy on the prohibition of certain drugs and the criminalisation of their use should be disentangled from public policy on impaired driving. It recommends that drug driving laws in all Australian jurisdictions should be brought back into line with drink driving laws, via legislation and testing practices that turn on substance-specific prescribed concentrations for all drugs (illicit and licit that have the potential to impair drivers.

Predictive typing of drug-induced neurological sufferings from studies of the distribution of labelled drugs

International Nuclear Information System (INIS)

Takasu, T.

1980-01-01

A drug given to an animal becomes widely distributed throughout the body, acting on the living mechanisms or structures, and is gradually excreted. Some drugs can remain in some parts of the body for a long period. For example, 14 C-chloramphenical was found to remain preferentially in the salivary gland, liver and bone marrow of mice 24 hours after its oral administration. If such a drug is given repeatedly, it could possibly accumulate gradually in these organs. Thus, when its accumulation in a particular part of the body exceeds a certain level, the living mechanism or structure may possibly be injured. The harmful effects of a drug in repeated administration are called its chronic toxicity. The author discusses whether it is possible to predict the toxicity of a drug by studying its distribution in relation to time, and, if possible, the points in time. This problem is studied especially in relation to the nervous system. (Auth.)

Phasic Mesolimbic Dopamine Signaling Encodes the Facilitation of Incentive Motivation Produced by Repeated Cocaine Exposure

OpenAIRE

Ostlund, SB; LeBlanc, KH; Kosheleff, AR; Wassum, KM; Maidment, NT

2014-01-01

Drug addiction is marked by pathological drug seeking and intense drug craving, particularly in response to drug-related stimuli. Repeated psychostimulant administration is known to induce long-term alterations in mesolimbic dopamine (DA) signaling that are hypothesized to mediate this heightened sensitivity to environmental stimuli. However, there is little direct evidence that drug-induced alteration in mesolimbic DA function underlies this hypersensitivity to motivational cues. In the curr...

Repeated mild closed head injury impairs short-term visuospatial memory and complex learning.

Science.gov (United States)

Hylin, Michael J; Orsi, Sara A; Rozas, Natalia S; Hill, Julia L; Zhao, Jing; Redell, John B; Moore, Anthony N; Dash, Pramod K

2013-05-01

Concussive force can cause neurocognitive and neurobehavioral dysfunction by inducing functional, electrophysiological, and/or ultrastructural changes within the brain. Although concussion-triggered symptoms typically subside within days to weeks in most people, in 15%-20% of the cases, symptomology can continue beyond this time point. Problems with memory, attention, processing speed, and cognitive flexibility (e.g., problem solving, conflict resolution) are some of the prominent post-concussive cognitive symptoms. Repeated concussions (with loss or altered consciousness), which are common to many contact sports, can exacerbate these symptoms. The pathophysiology of repeated concussions is not well understood, nor is an effective treatment available. In order to facilitate drug discovery to treat post-concussive symptoms (PCSs), there is a need to determine if animal models of repeated mild closed head injury (mCHI) can mimic the neurocognitive and histopathological consequences of repeated concussions. To this end, we employed a controlled cortical impact (CCI) device to deliver a mCHI directly to the skull of mice daily for 4 days, and examined the ensuing neurological and neurocognitive functions using beam balance, foot-fault, an abbreviated Morris water maze test, context discrimination, and active place avoidance tasks. Repeated mCHI exacerbated vestibulomotor, motor, short-term memory and conflict learning impairments as compared to a single mCHI. Learning and memory impairments were still observed in repeated mCHI mice when tested 3 months post-injury. Repeated mCHI also reduced cerebral perfusion, prolonged the inflammatory response, and in some animals, caused hippocampal neuronal loss. Our results show that repeated mCHI can reproduce some of the deficits seen after repeated concussions in humans and may be suitable for drug discovery studies and translational research.

Radiosensitivity of drug-resistant human tumour xenografts

International Nuclear Information System (INIS)

Mattern, J.; Bak, M. Jr.; Volm, M.; Hoever, K.H.

1989-01-01

The radiosensitivity of three drug-resistant sublines of a human epidermoid lung carcinoma growing as xenografts in nude mice was investigated. Drug resistance to vincristine, actinomycin D and cisplatin was developed in vivo by repeated drug treatment. It was found that all three drug-resistant tumour lines were not cross-resistant to irradiation. (orig.) [de

Protection provided by criminal law against hazards of nuclear energy and the harmful effects of ionizing radiation. Also a survey of the history of definition of offences against the atomic energy law and radiation protection law in the Federal Republic of Germany. Der strafrechtliche Schutz vor den Gefahren der Kernenergie und den schaedlichen Wirkungen ionisierender Strahlen. Zugleich eine Darstellung der historischen Entwicklung der Kernenergie- und Strahlendelikte in der Bundesrepublik Deutschland

Energy Technology Data Exchange (ETDEWEB)

Reinhardt, M

1989-01-01

The subjects, principles and purpose of the atomic energy law and the radiation protection law are set out, and criminal offences under atomic energy law are outlined explaining the legal terminology applied. The peaceful uses of nuclear energy and radioactive materials are briefly discussed, primarily looking at the hazards involved and the protective role of criminal law principles that have been developed in connection with the atomic energy law and its application in practice. The draft version of the 16th criminal law amendment act - Act to combat environmental delinquency - is discussed, which aims at adoption of all criminal offences under atomic energy law by the Criminal Code. The book furthermore presents considerations about basic features of delinquency under atomic energy and radiation protection law, revealing elements and facts of offences defined, and particular problems resulting thereof. The question arises, e.g., whether an incorporation of the provisions into the Special Annex to the Criminal Code, in sections 27 and 28, is a wise and suitable decision. The book finally discusses the development of definition of criminal offences by a de lege feranda approach, referring to (1) the Chernobyl reactor accident, (2) the Nuclear Safeguards agreements, and (3) the definition of maximum permissible radiation dose. (HP).

Strategies for a risky business: How drug dealers manage customers, suppliers and competitors in Italy, Slovenia and Germany.

Science.gov (United States)

Tzvetkova, Marina; Pardal, Mafalda; Disley, Emma; Rena, Alice; Talic, Sanela; Forberger, Sarah

2016-05-01

A growing body of literature aims to improve understanding of the operations of drug trafficking markets through conducting interviews with dealers and traffickers. Insight into how these individuals conduct business can provide evidence to inform the efforts by policy makers, law enforcement and practitioners to disrupt illicit markets. This paper aims to make a contribution to this evidence base by extending the number of European countries in which interviews have been conducted with incarcerated drug dealers and traffickers. It draws on interviews with 135 men convicted of offences related to the distribution or sale of heroin or cocaine and imprisoned in Italy, Slovenia and Germany. The research was conducted as part of the Reframing Addictions Project (ALICE-RAP) funded by the European Commission. The sample was diverse. It included a range of nationalities and some individuals who were members of organised crime groups. The majority of the interviewees were dealers who sold at the retail and street level, but there were some who were importers and wholesalers. Most dealers in each of the three countries reported having more than one regular supplier, and were able to respond to periods of over and under supply without losing customers. Supply arrangements varied in terms of frequency and quantities bought. Dealers engaged in repeated transactions and their relationships with customers were based on trust and reputation. Dealers aimed to sell to regular customers and to provide drugs of good quality. While dealers sought to maximise their profits by cutting drugs with cutting agents, the quality of drugs that they sold could affect their reputation and thus their profits and position in the market. Lastly, while there are some significant differences in the approach between those involved in organised crime groups and those who are not, and between street dealers and those operating at higher levels of the market, there were striking similarities in terms of

Drugs as elements of criminal offences against people's health in the legislation of the Republic of Serbia

Directory of Open Access Journals (Sweden)

Lazić Dragana

2017-01-01

Full Text Available The paper presents the results of criminal offenses related to drugs. The study included adults and the entire course of criminal proceedings, including reported, accused and convicted persons. Also, we put emphasis on gender, age, educational background and employment status of persons who have committed crime against human health. The survey was conducted on the territory of the Republic of Serbia and covers the year of 2015. The article presented the regulation of this issue in the legislation of the Republic of Serbia and disadvantages of the regulation. Finally, in conclusion, we presented the views and suggestions on possible ways of combating and solving the issue of this deviant behavior.

Comparison of drug abuse in Germany and China.

Science.gov (United States)

Michels, Ingo Ilja; Fang, Yu-Xia; Zhao, Dong; Zhao, Li-Yan; Lu, Lin

2007-10-01

Drug abuse has a long, but also different history in Germany and China. The Opium War largely influenced the history of China in 19th century; however, China was once recognized as a drug-free nation for 3 decades from the 1950s to the 1980s. Drug abuse has spread quickly since re-emerging as a national problem in China in the late 1980s. The number of registered drug abusers increased from 70 000 in 1990 to more than 1 million by the end of 2005. In past decades, illicit drug trafficking and production have swept most provinces in China, and drug abuse has caused many problems for both abusers and the community. One major drug-related problem is the spread of HIV, which has caused major social and economic damage in China. Germany, the largest developed European country, also faces the drug and addiction problem. Germany has about 150 000 heroin addicts, for whom HIV/AIDS has become a serious threat since the mid 1980s. To control the drug problem, the German Government adopted the pAction Plan on Drugs and Addictionq in 2003; the China Central Government approved a similar regulation in the antidrug campaign in 2005. Germany has experience in reducing drug-related harm. The methadone maintenance treatment (MMT) program has run for more than 20 years and the public has become more tolerant of addicts. In 2003, China began the MMT program for controlling the spread of HIV/AIDS. It is necessary for China to learn from developed countries to acquire success in its antidrug campaign. In this review, we will go over the differences and similarities in drug abuse between Germany and China. The differences are related to history, population and economics, drug policy context, drug laws, HIV/hepatitis C virus infection, the MMT program and so on. These 2 nations have drug abuse problems with different histories and currently use different approaches to handle illicit drug marketing and use. The legal penalties for illicit drug offences reflect the social differences of

The relationship of the temperament of the subject of crime with the characteristics of offences

Directory of Open Access Journals (Sweden)

Dyakov S.

2016-01-01

Full Text Available The features of communication psychological characteristics of temperament types of crimes. The analysis of scientific views on the role of temperament in the predisposition of the individual to the crime. With the help of empirical study confirmed the hypothesis that the subjects who had committed certain type of crime have specific personal psychological characteristics that reveal the determinants of their offences. The personality questionnaires EPI and MMPI used methods of analysis of personal files of prisoners; observation of their behaviour and discussions with them; drawing up of psychological portraits. Also developed and used an original questionnaire. The results showed that among criminals-murderers is dominated by people with a tendency to choleric expression of properties of temperament, expressed the need for self-affirmation, affective behavior, impulsivity, and disregard for social demands. The perpetrators of the theft inherent in the assertion of his personality not only in the eyes of the environment, but above all in its own. The perpetrators of rape there is usually no clear idea of traditionally male and female traits in behaviour, the relationship between a man and a woman are limited to sexual function. Criminals convicted of fraud and hooliganism, unable to establish contact with others not able to take the point of view of another, there is a disregard for moral and ethical standards.

Repeated attempted homicide by administration of drugs documented by hair analysis.

Science.gov (United States)

Baillif-Couniou, Valérie; Bartoli, Christophe; Sastre, Caroline; Chèze, Marjorie; Deveaux, Marc; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

2018-02-01

Attempted murder by repeated poisoning is quite rare. The authors describe the case of a 62-year-old man who was admitted to an intensive care unit (ICU) for neurological disturbances complicated by inhalation pneumopathy. He presented a loss of consciousness while his wife was visiting him at the ICU (H0). Forty-eight hours later (H48), police officers apprehended the patient's wife pouring a liquid into his fruit salad at the hospital. Toxicological analyses of a blood sample and the infusion equipment (H0), as well as the fruit salad and its container (H48), confirmed the attempted poisoning with cyamemazine (H0) and hydrochloric acid (H48). In order to evaluate the anteriority of poisonings, hair analysis was requested and the medical records of the 6 previous months were also examined. Two 6-cm brown hair strands were sampled and the victim's medical record was seized in order to determine the treatments he had been given during the previous six months. Segmental hair testing on two 6-cm brown hair was conducted by GC-MS, LC-DAD and LC-MS/MS (0-2/2-4/4-6 cm; pg/mg). Haloperidol (9200/1391/227), amitriptyline (7450/1850/3260), venlafaxine (332/560/260), that had never been part of the victim's treatment were detected, as well as some benzodiazepines (alprazolam, bromazepam, nordazepam); cyamemazine was also detected in all the segments (9960/1610/2367) though only a single dose administration was reported in the medical records. The toxicological analyses performed at H0 and H48 confirmed the homicide attempts in the ICU. In addition, comparison of the results in hair analysis with the medical records confirmed repeated poisoning attempts over the previous six months, and thus explain the origin of the disorders presented by the victim. This case serves to remind us that repeated attempted murder can be difficult to diagnose and that hair analysis can be an effective way to detect such attempts. Copyright © 2018. Published by Elsevier Ltd.

Punishability of transfrontier environmental offences. Also a contribution to the dogmatic aspects of hazards and on international law in the field of ecology. Strafbarkeit grenzueberschreitender Umweltbeeintraechtigungen. Zugleich ein Beitrag zur Gefaehrdungsdogmatik und zum Umweltvoelkerrecht

Energy Technology Data Exchange (ETDEWEB)

Martin, J.

1989-01-01

National environmental Acts include a great number of areas and this applies even more if there is an international component. It is not only the German international criminal law but also questions of general criminal law dogmatic and the relationship between environmental criminal law and administrative law that must be taken into account. In order to prevent inadmissible interferences with another country's sovereign rights it is necessary to harmonize the international environmental law and the international environmental criminal law. Aspects of the international civil law and the administrative law have to be considered as well. The book concludes that even abstract offences that carry the potential of endangerment also qualify as statutorily proscribed harm. The German environmental criminal law is therefore applicable even if the offence cause only a domestic danger. An action which is permissible under another country's administrative law is not punishable under some few regulations. In all other cases it is punishable unless the foreign country's Sovereign Act is recognised. This applies if the Federal Republic of Germany has to tolerate harm under international environmental law. Claims under international law to refrain from transformer pollution can often be much more extensive than commonly assumed. (orig.).

[The harm to health of the under-age individuals as an objective criterion for the differentiation of criminal responsibilities for committing non-violent sexual offence against them].

Science.gov (United States)

Bimbinov, A A

2016-01-01

The present publication is devoted to the search for the objective criterion for the differentiation of criminal responsibilities for committing non-violent sexual offence against the juveniles under the age of 16 years. It has been shown that the current version of articles 134 and 135 of the criminal code of the Russian Federation does not adequately reflect the true character and the social danger of such actions. The formal methods of the legal, logical, and concrete sociological analysis were employed to substantiate the necessity of differentiation of criminal liability for the non-violent sexual abuse depending on the degree of potential harm to the health of the under-age individuals.

[Detection of CRISPR and its relationship to drug resistance in Shigella].

Science.gov (United States)

Wang, Linlin; Wang, Yingfang; Duan, Guangcai; Xue, Zerun; Guo, Xiangjiao; Wang, Pengfei; Xi, Yuanlin; Yang, Haiyan

2015-04-04

To detect clustered regularly interspaced short palindromic repeats (CRISPR) in Shigella, and to analyze its relationship to drug resistance. Four pairs of primers were used for the detection of convincing CRISPR structures CRISPR-S2 and CRISPR-S4, questionable CRISPR structures CRISPR-S1 and CRISPR-S3 in 60 Shigella strains. All primers were designed using sequences in CRISPR database. CRISPR Finder was used to analyze CRISPR and susceptibilities of Shigella strains were tested by agar diffusion method. Furthermore, we analyzed the relationship between drug resistance and CRISPR-S4. The positive rate of convincing CRISPR structures was 95%. The four CRISPR loci formed 12 spectral patterns (A-L), all of which contained convincing CRISPR structures except type K. We found one new repeat and 12 new spacers. The multi-drug resistance rate was 53. 33% . We found no significant difference between CRISPR-S4 and drug resistant. However, the repeat sequence of CRISPR-S4 in multi- or TE-resistance strains was mainly R4.1 with AC deletions in the 3' end, and the spacer sequences of CRISPR-S4 in multi-drug resistance strains were mainly Sp5.1, Sp6.1 and Sp7. CRISPR was common in Shigella. Variations df repeat sequences and diversities of spacer sequences might be related to drug resistance in Shigella.

Some Problems of the Implementation of Administrative Responsibility for Violations of the Legislation on Contract System in the Procurement Sphere

Directory of Open Access Journals (Sweden)

Andrei E. Yuritsin

2017-12-01

Full Text Available The article considers the issues of application of Article 6.9 of the Code of Administrative Offences of the Russian Federation and the significance of the practice of implementation of this legal norm to counteraction to illegal drug use. The author estimates the possibility of dealing all cases of illegal use of narcotic drugs and psychotropic substances and their analogues by law enforcement practice as well as the sufficiency of administrative penalties provided for by the Article. Critical evaluation is given to the suitability of criminalization of systematic illegal drug use. The significance of Article 6.9 of the Code of Administrative Offences of RF is connected with the demonstration of the state policy vector regarding illegal drug use, the substantiation of possibility of applying certain measures of state coercion, as well as with the legal statement of the fact of unlawful act and the change of environment in which the offender realizes his/her rights and obligations.

Relationship between drug resistance and the clustered, regularly interspaced, short, palindromic repeat-associated protein genes cas1 and cas2 in Shigella from giant panda dung.

Science.gov (United States)

Ren, Lu; Deng, Lin-Hua; Zhang, Ri-Peng; Wang, Cheng-Dong; Li, De-Sheng; Xi, Li-Xin; Chen, Zhen-Rong; Yang, Rui; Huang, Jie; Zeng, Yang-Ru; Wu, Hong-Lin; Cao, San-Jie; Wu, Rui; Huang, Yong; Yan, Qi-Gui

2017-02-01

To detect drug resistance in Shigella obtained from the dung of the giant panda, explore the factors leading to drug resistance in Shigella, understand the characteristics of clustered, regularly interspaced, short, palindromic repeats (CRISPR), and assess the relationship between CRISPR and drug resistance. We collected fresh feces from 27 healthy giant pandas in the Giant Panda Conservation base (Wolong, China). We identified the strains of Shigella in the samples by using nucleotide sequence analysis. Further, the Kirby-Bauer paper method was used to determine drug sensitivity of the Shigella strains. CRISPR-associated protein genes cas1 and cas2 in Shigella were detected by polymerase chain reaction (PCR), and the PCR products were sequenced and compared. We isolated and identified 17 strains of Shigella from 27 samples, including 14 strains of Shigella flexneri, 2 strains of Shigella sonnei, and 1 strain of Shigella dysenteriae. Further, drug resistance to cefazolin, imipenem, and amoxicillin-clavulanic acid was identified as a serious problem, as multidrug-resistant strains were detected. Further, cas1 and cas2 showed different degrees of point mutations. The CRISPR system widely exists in Shigella and shares homology with that in Escherichia coli. The cas1 and cas 2 mutations contribute to the different levels of resistance. Point mutations at sites 3176455, 3176590, and 3176465 in cas1 (a); sites 3176989, 3176992, and 3176995 in cas1 (b); sites 3176156 and 3176236 in cas2 may affect the resistance of bacteria, cause emergence of multidrug resistance, and increase the types of drug resistance.

Assessing the concordance between illicit drug laws on the books and drug law enforcement: Comparison of three states on the continuum from "decriminalised" to "punitive".

Science.gov (United States)

Belackova, Vendula; Ritter, Alison; Shanahan, Marian; Hughes, Caitlin E

2017-03-01

Variations in drug laws, as well as variations in enforcement practice, exist across jurisdictions. This study explored the feasibility of categorising drug laws "on the books" in terms of their punitiveness, and the extent of their concordance with "laws in practice" in a cross-national comparison. "Law on the books", classified with respect to both cannabis and other drug offences in the Czech Republic, NSW (AU) and Florida (USA) were analysed in order to establish an ordinal relationship between the three states. Indicators to assess the "laws in practice" covered both police (arrests) and court (sentencing) activity between 2002 and 2013. Parametric and non-parametric tests of equality of means, tests of stationarity and correlation analysis were used to examine the concordance between the ordinal categorisation of "laws on the books" and "laws in practice", as well as trends over time. The Czech Republic had the most lenient drug laws; Florida had the most punitive and NSW was in-between. Examining the indicators of "laws in practice", we found that the population adjusted number of individuals sentenced to prison ranked across the three states was concordant with categorisation of "laws on the books", but the average sentence length and percentage of court cases sentenced to prison were not. Also, the de jure decriminalisation of drug possession in the Czech Republic yielded a far greater share of administrative offenses than the de facto decriminalisation of cannabis use / possession in NSW. Finally, the mean value of most "laws in practice" indicators changed significantly over time although the "laws on the books" didn't change. While some indicators of "laws in practice" were concordant with the ordinal categorisation of drug laws, several indicators of "laws in practice" appeared to operate independently from the drug laws as stated. This has significant implications for drug policy analysis and means that research should not assume they are

X-ray analysis of the effect of the 5-HT3 receptor antagonist granisetron on gastrointestinal motility in rats repeatedly treated with the antitumoral drug cisplatin.

Science.gov (United States)

Vera, Gema; López-Pérez, Ana Esther; Martínez-Villaluenga, María; Cabezos, Pablo Antonio; Abalo, Raquel

2014-08-01

Cancer chemotherapy is associated with the development of numerous adverse effects, including nausea, emesis and other alterations in gastrointestinal (GI) motility. The administration of 5-HT3 receptor antagonists has provided a clinical advance in the treatment of chemotherapy-induced vomiting but these drugs lose efficacy throughout chronic treatment. The effects of these drugs in experimental animals under chronic administration are not well known. Our aim was to study, using radiographic methods, the effect of the 5-HT3 receptor antagonist granisetron on GI dysmotility induced in the rat by repeated cisplatin administration. First, invasive methods were used to select a dose of granisetron capable of reducing increased stomach weight due to acute cisplatin administration (6 mg/kg, ip). Second, rats received two intraperitoneal (ip) injections once a week for 4 weeks: granisetron (1 mg/kg, ip) or saline and, thirty min later, saline or cisplatin (2 mg/kg, ip). Body weight gain was measured throughout treatment. Radiological techniques were used to determine the acute (after first dose) and chronic (after last dose) effects of cisplatin and/or granisetron on GI motility. Repeated cisplatin-induced weight loss which granisetron did not prevent. Gastric emptying was delayed after the first cisplatin administration. Granisetron completely prevented this effect. After weekly administration, cisplatin-induced gastric dysmotility was enhanced and granisetron was not capable of completely preventing this effect. Granisetron prevents gastric emptying alterations, but its efficacy decreases throughout antineoplastic treatment. This might be due to the enhanced effect of cisplatin.

Retrospective use of PBPK modelling to understand a clinical drug-drug interaction between dextromethorphan and GSK1034702.

Science.gov (United States)

Hobbs, Michael J; Bloomer, Jackie; Dear, Gordon

2017-08-01

1. In a clinical trial, a strong drug-drug interaction (DDI) was observed between dextromethorphan (DM, the object or victim drug) and GSK1034702 (the precipitant or perpetrator drug), following single and repeat doses. This study determined the inhibition parameters of GSK1034702 in vitro and applied PBPK modelling approaches to simulate the clinical observations and provide mechanistic hypotheses to understand the DDI. 2. In vitro assays were conducted to determine the inhibition parameters of human CYP2D6 by GSK1034702. PBPK models were populated with the in vitro parameters and DDI simulations conducted and compared to the observed data from a clinical study with DM and GSK1034702. 3. GSK1034702 was a potent direct and metabolism-dependent inhibitor of human CYP2D6, with inhibition parameters of: IC 50  =   1.6 μM, K inact  = 3.7 h -1 and K I  = 0.8 μM. Incorporating these data into PBPK models predicted a DDI after repeat, but not single, 5 mg doses of GSK1034702. 4. The DDI observed with repeat administration of GSK1034702 (5 mg) can be attributed to metabolism-dependent inhibition of CYP2D6. Further, in vitro data were generated and several potential mechanisms proposed to explain the interaction observed following a single dose of GSK1034702.

Injectable In-Situ Gelling Controlled Release Drug Delivery System

OpenAIRE

Kulwant Singh; S. L. HariKumar

2012-01-01

The administration of poorly bioavailable drug through parenteral route is regarded the most efficient for drug delivery. Parenteral delivery provides rapid onset even for the drug with narrow therapeutic window, but to maintain the systemic drug level repeated installation are required which cause the patient discomfort. This can be overcome by designing the drug into a system, which control the drug release even through parenteral delivery, which improve patient compliance as well as pharma...

Analysis of Dextromethorphan and Dextrorphan in Skeletal Remains Following Differential Microclimate Exposure: Comparison of Acute vs. Repeated Drug Exposure.

Science.gov (United States)

Morrison, Lucas M; Unger, Kirk A; Watterson, James H

2017-07-01

Analysis of dextromethorphan (DXM) and its metabolite dextrorphan (DXT) in skeletal remains of rats following acute (ACU, 75 mg/kg, IP, n = 10) or three repeated (REP, 25 mg/kg, IP, n = 10, 40-min interval) doses of DXM is described. Following dosing and euthanasia, rats decomposed outdoors to skeleton in two different microclimate environments (n = 5 ACU and n = 5 REP at each site): Site A (shaded forest microenvironment) and Site B (rocky substrate exposed to direct sunlight, 600 m from Site A). Two drug-free rats at each site served as negative controls. Skeletal elements (vertebrae, ribs, pelvic girdles, femora, tibiae, skulls and scapulae) were recovered, pulverized and underwent methanolic microwave assisted extraction (MAE). Extracts were analyzed by GC-MS following clean-up by solid-phase extraction (SPE). Drug levels, expressed as mass-normalized response ratios and the ratios of DXT and DXM levels (RRDXT/RRDXM) were compared between drug exposures, microclimate sites, and across skeletal elements. DXM levels differed significantly (P < 0.05) between corresponding bone elements across exposure groups (5/7-site A; 4/7-site B), but no significant differences in DXT levels were observed between corresponding elements. RRDXT/RRDXM differed significantly (P < 0.05) between corresponding bone elements across exposure groups (6/7-site A; 5/7-site B). No significant differences were observed in levels of DXM, DXT or RRDXT/RRDXM between corresponding elements from either group between sites. When data from all bone elements was pooled, levels of DXM and RRDXT/RRDXM differed significantly between exposure groups at each site, while those of DXT did not. For both exposure groups, comparison of pooled data between sites showed no significant differences in levels of DXM, DXT or RRDXT/RRDXM. Different decomposition microclimates did not impede the discrimination of DXM exposure patterns from the analyses of DXM, DXT and RRDXT/RRDXM in bone samples. © The Author 2017

A theory of drug tolerance and dependence I: a conceptual analysis.

Science.gov (United States)

Peper, Abraham

2004-08-21

A mathematical model of drug tolerance and its underlying theory is presented. The model extends a first approach, published previously. The model is essentially more complex than the generally used model of homeostasis, which is demonstrated to fail in describing tolerance development to repeated drug administrations. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary only in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behavior to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity to small changes in drug dose, the rebound phenomenon and the large reactions following withdrawal in dependence. The mathematical model verifies the proposed theory and provides a basis for the implementation of mathematical models of specific physiological processes. In addition, it establishes a relation between the drug dose at any moment, and the resulting drug effect and relates the magnitude of the reactions following withdrawal to the rate of tolerance and other parameters involved in the tolerance process. The present paper analyses the concept behind the model. The next paper discusses the mathematical model.

Aberrant approach-avoidance conflict resolution following repeated cocaine pre-exposure.

Science.gov (United States)

Nguyen, David; Schumacher, Anett; Erb, Suzanne; Ito, Rutsuko

2015-10-01

Addiction is characterized by persistence to seek drug reinforcement despite negative consequences. Drug-induced aberrations in approach and avoidance processing likely facilitate the sustenance of addiction pathology. Currently, the effects of repeated drug exposure on the resolution of conflicting approach and avoidance motivational signals have yet to be thoroughly investigated. The present study sought to investigate the effects of cocaine pre-exposure on conflict resolution using novel approach-avoidance paradigms. We used a novel mixed-valence conditioning paradigm to condition cocaine-pre-exposed rats to associate visuo-tactile cues with either the delivery of sucrose reward or shock punishment in the arms in which the cues were presented. Following training, exploration of an arm containing a superimposition of the cues was assessed as a measure of conflict resolution behavior. We also used a mixed-valence runway paradigm wherein cocaine-pre-exposed rats traversed an alleyway toward a goal compartment to receive a pairing of sucrose reward and shock punishment. Latency to enter the goal compartment across trials was taken as a measure of motivational conflict. Our results reveal that cocaine pre-exposure attenuated learning for the aversive cue association in our conditioning paradigm and enhanced preference for mixed-valence stimuli in both paradigms. Repeated cocaine pre-exposure allows appetitive approach motivations to gain greater influence over behavioral output in the context of motivational conflict, due to aberrant positive and negative incentive motivational processing.

The Rewarding and Locomotor-Sensitizing Effects of Repeated Cocaine Administration are Distinct and Separable in Mice

Science.gov (United States)

Riday, Thorfinn T.; Kosofsky, Barry E.; Malanga, C.J.

2011-01-01

Repeated psychostimulant exposure progressively increases their potency to stimulate motor activity in rodents. This behavioral or locomotor sensitization is considered a model for some aspects of drug addiction in humans, particularly drug craving during abstinence. However, the role of increased motor behavior in drug reward remains incompletely understood. Intracranial self-stimulation (ICSS) was measured concurrently with locomotor activity to determine if acute intermittent cocaine administration had distinguishable effects on motor behavior and perception of brain stimulation-reward (BSR) in the same mice. Sensitization is associated with changes in neuronal activity and glutamatergic neurotransmission in brain reward circuitry. Expression of AMPA receptor subunits (GluR1 and GluR2) and CRE binding protein (CREB) was measured in the ventral tegmental area (VTA), dorsolateral striatum (STR) and nucleus accumbens (NAc) before and after a sensitizing regimen of cocaine, with and without ICSS. Repeated cocaine administration sensitized mice to its locomotor stimulating effects but not its ability to potentiate BSR. ICSS increased GluR1 in the VTA but not NAc or STR, demonstrating selective changes in protein expression with electrical stimulation of discrete brain structures. Repeated cocaine reduced GluR1, GluR2 and CREB expression in the NAc, and reductions of GluR1 and GluR2 but not CREB were further enhanced by ICSS. These data suggest that the effects of repeated cocaine exposure on reward and motor processes are dissociable in mice, and that reduction of excitatory neurotransmission in the NAc may predict altered motor function independently from changes in reward perception. PMID:22197517

Social adversities in first-time and repeat prisoners.

Science.gov (United States)

Kjelsberg, Ellen; Friestad, Christine

2008-11-01

To explore possible systematic differences between prison inmates serving their first sentence and inmates having experienced previous incarcerations. It is hoped that a better knowledge of these issues will make us better equipped to meet the rehabilitation needs of our prisoners and decrease their risk of reoffending and reincarceration. In this cross-sectional study a randomly selected and nationally representative sample of 260 Norwegian prisoners, 100 serving their first sentence and 160 recidivists, was interviewed with special focus on childhood circumstances, education, work experience, and present social and economic situation. In addition their criminal records were collected from the National Crime Registry. In males multivariate analyses identified a number of variables independently and significantly associated with being a repeat offender. The odds for reincarceration increased significantly if the person fulfilled any one of the following criteria: having experienced the incarceration of a family member during childhood (OR = 3.6); having experienced childcare interventions during childhood (OR = 3.2); current drug abuse (OR = 2.6); current housing problems (OR = 2.3). In females only one strong correlation emerged: if the person had current drug problems the odds for being a recidivist increased substantially (OR = 10.9). While criminal reoffending and reincarceration seemed to be primarily associated with drug abuse in females, the childhood problems of male repeat offenders, compared with males serving their first sentence, indicate that these individuals' current multiple social and economic disadvantages were complex in origin and of long standing. Interventions aimed at preventing reoffending must take into account the gender differences demonstrated. ing at primary prevention, the negative effects associated with parental incarceration are crucial: how can one prevent the perpetuation of these problems from one generation to the next?

Screening for drugs of abuse (II): Cannabinoids, lysergic acid diethylamide, buprenorphine, methadone, barbiturates, benzodiazepines and other drugs.

Science.gov (United States)

Simpson, D; Braithwaite, R A; Jarvie, D R; Stewart, M J; Walker, S; Watson, I W; Widdop, B

1997-09-01

Requirements for the provision of an efficient and reliable service for drugs of abuse screening in urine have been summarized in Part I of this review. The requirements included rapid turn-around times, good communications between requesting clinicians and the laboratory, and participation in quality assessment schemes. In addition, the need for checking/confirmation of positive results obtained for preliminary screening methods was stressed. This aspect of the service has assumed even greater importance with widespread use of dip-stick technology and the increasing number of reasons for which drug screening is performed. Many of these additional uses of drug screening have possible serious legal implications, for example, screening school pupils, professional footballers, parents involved in child custody cases, persons applying for renewal of a driving licence after disqualification for a drug-related offence, doctors seeking re-registration after removal for drug abuse, and checking for compliance with terms of probation orders; as well as pre-employment screening and work-place testing. In many cases these requests will be received from a general practitioner or drug clinic with no indication of the reason for which testing has been requested. This also raises the serious problems of a chain of custody, provision of two samples, stability of samples, and secure and lengthy storage of samples in the laboratory-samples may be requested by legal authorities several months after the initial testing. The need for confirmation of positive results is now widely accepted but it may be equally important to confirm unexpected negative results. Failure to detect the presence of maintenance drugs may lead to the patient being discharged from a drug treatment clinic and, if attendance at the clinic is one of the terms of continued employment, to dismissal. It seems likely that increasing abuse of drugs and the efforts of regulatory authorities to control this, will lead to

Forensic drug intelligence: an important tool in law enforcement.

Science.gov (United States)

Esseiva, Pierrre; Ioset, Sylvain; Anglada, Frédéric; Gasté, Laëtitia; Ribaux, Olivier; Margot, Pierre; Gallusser, Alain; Biedermann, Alex; Specht, Yves; Ottinger, Edmond

2007-04-11

magistrates, forensic scientists, law enforcement investigators and crime analysts from different institutions with the aim of generating, using and validating relevant profiling case data as integral part of investigative and crime analysis processes. Original advances are highlighted through experiences from criminal investigations of offences related to the unlawful importation, exportation, supply and possession of illicit drugs.

Clinical characteristics associated with paedophilia and child sex offending - Differentiating sexual preference from offence status.

Science.gov (United States)

Gerwinn, Hannah; Weiß, Simone; Tenbergen, Gilian; Amelung, Till; Födisch, Carina; Pohl, Alexander; Massau, Claudia; Kneer, Jonas; Mohnke, Sebastian; Kärgel, Christian; Wittfoth, Matthias; Jung, Stefanie; Drumkova, Krassimira; Schiltz, Kolja; Walter, Martin; Beier, Klaus M; Walter, Henrik; Ponseti, Jorge; Schiffer, Boris; Kruger, Tillmann H C

2018-06-01

Contrary to public perception, child sex offending (CSO) and paedophilia are not the same. Only half of all cases of CSO are motivated by paedophilic preference, and a paedophilic preference does not necessarily lead to CSO. However, studies that investigated clinical factors accompanying and contributing to paedophilia so far mainly relied on paedophiles with a history of CSO. The aim of this study was to distinguish between factors associated with sexual preference (paedophile versus non-paedophile) and offender status (with versus without CSO). Accordingly, a 2 (sexual preference) × 2 (offender status) factorial design was used for a comprehensive clinical assessment of paedophiles with and without a history of CSO (n = 83, n = 79 respectively), child sex offenders without paedophilia (n = 32) and healthy controls (n = 148). Results indicated that psychiatric comorbidities, sexual dysfunctions and adverse childhood experiences were more common among paedophiles and child sex offenders than controls. Offenders and non-offenders differed in age, intelligence, educational level and experience of childhood sexual abuse, whereas paedophiles and non-paedophiles mainly differed in sexual characteristics (e.g., additional paraphilias, onset and current level of sexual activity). Regression analyses were more powerful in segregating offender status than sexual preference (mean classification accuracy: 76% versus 68%). In differentiating between offence- and preference-related factors this study improves clinical understanding of both phenomena and may be used to develop scientifically grounded CSO prevention and treatment programmes. It also highlights that some deviations are not traceable to just one of these two factors, thus raising the issue of the mechanism underlying both phenomena. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Expected impacts of the Cannabis Infringement Notice scheme in Western Australia on attitudes and drug use of school children.

Science.gov (United States)

Lenton, Simon; Farringdon, Fiona

2005-07-01

Western Australia (WA) became the fourth Australian jurisdiction to adopt a prohibition with civil penalties scheme for minor cannabis offences when its Cannabis Infringement Notice (CIN) scheme came into effect on 22 March 2004. This study, part of the pre--post evaluation of the legislative reforms, aimed to measure the impact of the changes on attitudes and drug use of school children. A self-completion survey was conducted of 2,638 students in years 9 and 12 from a selection of 11 government secondary schools in Perth. The students knew more about the risks and harms associated with cannabis than they did about prevalence of use and cannabis law. Half the year 12s and 28% of the year 9s had used the drug. Only 32% of students understood the term 'prohibition with civil penalties'. Once explained, 70% of those who had never used the drug said they would not try it if such a scheme were introduced, 5% said they would try it and 24% did not know. Significantly more (11%) said that they would try the drug if it were legalized. Although the CIN scheme applies only to adults there was a concern that such a change would indirectly affect cannabis use by children. This pre-change study suggests this is unlikely, but this will be monitored in the post-change phase of the research.

Factors influencing GPs’ choice between drugs in a therapeutic drug group. A qualitative study

DEFF Research Database (Denmark)

Buusman, Allan; Andersen, Morten; Merrild, Camilla Hoffmann

2007-01-01

(GPs) were selected with reference to variation in organizational structure, age, and gender. Main outcome measures. GPs' description of drug choice in relation to specific patient encounters involving a prescription. Results. All informants appeared to consider drug price important...... as it was a recurring theme during all interviews. External factors outside the GP's control such as governmental regulation on prescribing and the pharmaceutical industry influenced most GPs. Internal factors related to the actual consultation included characteristics of the GP and the patient, drug characteristics......, and repeat prescriptions. These factors interact in a non-linear and unpredictable way similar to complex adaptive systems. Conclusion. GPs balance both internal and external factors when choosing between analogues. Drug choice is a regulated process in the realm of complex prescribing behaviour with drug...

Behavioral sensitization after repeated formaldehyde exposure in rats.

Science.gov (United States)

Sorg, B A; Hochstatter, T

1999-01-01

Multiple chemical sensitivity (MCS) is a phenomenon whereby individuals report increased sensitivity to chemicals in the environment, and attribute their sensitivities to prior exposure to the same or often structurally unrelated chemicals. A leading hypothesis suggests that MCS is akin to behavioral sensitization observed in rodents after repeated exposure to drugs of abuse or environmental stressors. Sensitization occurring within limbic circuitry of the central nervous system (CNS) may explain the multisymptom complaints in individuals with MCS. The present studies represent the continuing development of an animal model for MCS, the basis of which is the CNS sensitization hypothesis. Three behaviors were assessed in rats repeatedly exposed to formaldehyde (Form) inhalation. In the first series of experiments, rats were given high-dose Form exposure (11 parts per million [ppm]; 1 h/day x 7 days) or low-dose Form exposure (1 ppm; either 1 h/day x 7 days or 1 h/day x 5 days/week x 4 weeks). Within a few days after discontinuing daily Form, cocaine-induced locomotor activity was elevated after high-dose Form or 20 days of low-dose Form inhalation. Approximately 1 month later, cocaine-induced locomotor activity remained significantly elevated in the 20-day Form-exposed rats. The second experiment assessed whether prior exposure to Form (20 days, as above) would alter the ability to condition to an odor (orange oil) paired with footshock. The results suggested a tendency to increase the conditioned fear response to the odor but not the context of the footshock box, and a decreased tendency to extinguish the conditioned fear response to odor. The third experiment examined whether CNS sensitization to daily cocaine or stress would alter subsequent avoidance responding to odor (Form). Daily cocaine significantly elevated approach responses to Form, while daily stress pretreatment produced a trend in the opposite direction, producing greater avoidance of Form. Preliminary

Differences between youth with a single suicide attempt and repeaters regarding their and their parents history of psychiatric illness

DEFF Research Database (Denmark)

Jakobsen, Ida Skytte; Christiansen, Erik; Juul Larsen, Kim

2011-01-01

, psychiatric diagnoses, and psychopharmacological medications prescribed to youth before and after the index attempt were risk factors for repeated suicide attempts. Parental diagnoses and drug prescriptions following a child's first suicide attempt moderated the risk of repeated attempts. Psychiatric illness......The objective of this study was to determine predictors of repeated suicide attempts in young people, focusing on psychiatric illness. A longitudinal population-based register study of all adolescents born in Denmark between 1984 and 2006 was conducted. Greater numbers of hospitalizations...... is a strong predictor of repeated suicide attempts in young people, and those with co-morbid diagnoses are at increased risk of repeated suicide attempts. Treatment of psychiatric illness in the parents after their child's first suicide attempt is a potential protective factor....

Perturbations in different forms of cost/benefit decision making induced by repeated amphetamine exposure.

Science.gov (United States)

Floresco, Stan B; Whelan, Jennifer M

2009-08-01

Psychostimulant abuse has been linked to impairments in cost-benefit decision making. We assessed the effects of repeated amphetamine (AMPH) treatment in rodents on two distinct forms of decision making. Separate groups of rats were trained for 26 days on either a probabilistic (risk) or effort-discounting task, each consisting of four discrete blocks of ten choice trials. One lever always delivered a smaller reward (one or two pellets), whereas another lever delivered a four-pellet reward. For risk-discounting, the probability of receiving the larger reward decreased across trial blocks (100-12.5%), whereas on the effort task, four pellets could be obtained after a ratio of presses that increased across blocks (2-20). After training, rats received 15 saline or AMPH injections (escalating from 1 to 5 mg/kg) and were then retested during acute and long-term withdrawal. Repeated AMPH administration increased risky choice 2-3 weeks after drug exposure, whereas these treatments did not alter effort-based decision making in a separate group of animals. However, prior AMPH exposure sensitized the effects of acute AMPH on both forms of decision making, whereby lower doses were effective at inducing "risky" and "lazy" patterns of choice. Repeated AMPH exposure leads to relatively long-lasting increases in risky choice, as well as sensitization to the effects of acute AMPH on different forms of cost/benefit decision making. These findings suggest that maladaptive decision-making processes exhibited by psychostimulant abusers may be caused in part by repeated drug exposure.

Repeating and non-repeating fast radio bursts from binary neutron star mergers

Science.gov (United States)

Yamasaki, Shotaro; Totani, Tomonori; Kiuchi, Kenta

2018-04-01

Most fast radio bursts (FRB) do not show evidence of repetition, and such non-repeating FRBs may be produced at the time of a merger of binary neutron stars (BNS), provided that the BNS merger rate is close to the high end of the currently possible range. However, the merger environment is polluted by dynamical ejecta, which may prohibit the radio signal from propagating. We examine this by using a general-relativistic simulation of a BNS merger, and show that the ejecta appears about 1 ms after the rotation speed of the merged star becomes the maximum. Therefore there is a time window in which an FRB signal can reach outside, and the short duration of non-repeating FRBs can be explained by screening after ejecta formation. A fraction of BNS mergers may leave a rapidly rotating and stable neutron star, and such objects may be the origin of repeating FRBs like FRB 121102. We show that a merger remnant would appear as a repeating FRB on a time scale of ˜1-10 yr, and expected properties are consistent with the observations of FRB 121102. We construct an FRB rate evolution model that includes these two populations of repeating and non-repeating FRBs from BNS mergers, and show that the detection rate of repeating FRBs relative to non-repeating ones rapidly increases with improving search sensitivity. This may explain why only the repeating FRB 121102 was discovered by the most sensitive FRB search with Arecibo. Several predictions are made, including the appearance of a repeating FRB 1-10 yr after a BNS merger that is localized by gravitational waves and subsequent electromagnetic radiation.

Repeated treatment with nitric oxide synthase inhibitor attenuates learned helplessness development in rats and increases hippocampal BDNF expression.

Science.gov (United States)

Stanquini, Laura Alves; Biojone, Caroline; Guimarães, Francisco Silveira; Joca, Sâmia Regiane

2017-11-20

Nitric oxide synthase (NOS) inhibitors induce antidepressant-like effects in animal models sensitive to acute drug treatment such as the forced swimming test. However, it is not yet clear if repeated treatment with these drugs is required to induce antidepressant-like effects in preclinical models. The aim of this study was to test the effect induced by acute or repeated (7 days) treatment with 7-nitroindazole (7-NI), a preferential inhibitor of neuronal NOS, in rats submitted to the learned helplessness (LH) model. In addition, we aimed at investigating if 7-NI treatment would increase brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus, similarly to the effect of prototype antidepressants. Animals were submitted to a pre-test (PT) session with inescapable footshocks or habituation (no shocks) to the experimental shuttle box. Six days later they were exposed to a test with escapable footshocks. Independent groups received acute (a single injection after PT or before test) or repeated (once a day for 7 days) treatment with vehicle or 7-NI (30 mg/kg). Repeated, but not acute, treatment with 7-NI attenuated LH development. The effect was similar to repeated imipramine treatment. Moreover, in an independent experimental group, only repeated treatment with 7-NI and imipramine increased BDNF protein levels in the hippocampus. The results suggest the nitrergic system could be a target for the treatment of depressive-like conditions. They also indicate that, similar to the positive control imipramine, the antidepressant-like effects of NOS inhibition could involve an increase in hippocampal BDNF levels.

Is law enforcement of drug-impaired driving cost-efficient? An explorative study of a methodology for cost-benefit analysis.

Science.gov (United States)

Veisten, Knut; Houwing, Sjoerd; Mathijssen, M P M René; Akhtar, Juned

2013-03-01

Road users driving under the influence of psychoactive substances may be at much higher relative risk (RR) in road traffic than the average driver. Legislation banning blood alcohol concentrations above certain threshold levels combined with roadside breath-testing of alcohol have been in lieu for decades in many countries, but new legislation and testing of drivers for drug use have recently been implemented in some countries. In this article we present a methodology for cost-benefit analysis (CBA) of increased law enforcement of roadside drug screening. This is an analysis of the profitability for society, where costs of control are weighed against the reduction in injuries expected from fewer drugged drivers on the roads. We specify assumptions regarding costs and the effect of the specificity of the drug screening device, and quantify a deterrence effect related to sensitivity of the device yielding the benefit estimates. Three European countries with different current enforcement levels were studied, yielding benefit-cost ratios in the approximate range of 0.5-5 for a tripling of current levels of enforcement, with costs of about 4000 EUR per convicted and in the range of 1.5 and 13 million EUR per prevented fatality. The applied methodology for CBA has involved a simplistic behavioural response to enforcement increase and control efficiency. Although this methodology should be developed further, it is clearly indicated that the cost-efficiency of increased law enforcement of drug driving offences is dependent on the baseline situation of drug-use in traffic and on the current level of enforcement, as well as the RR and prevalence of drugs in road traffic. Copyright © 2012 Elsevier B.V. All rights reserved.

Transnational social movement theory and the waning war on drugs: Case studies from UNGASS 2016.

Science.gov (United States)

Mostyn, Ben; Gibbon, Helen

2018-01-01

The United Nations Convention against Illicit Traffic in Narcotic Drugs 1988 ("1988 Convention") expresses a strong normative preference for criminalising drug possession. Historically, the United Nations offices responsible for overseeing the treaties have held that decriminalisation of drug possession is contrary to the treaties. Leading up to and during UNGASS 2016, however, rather than emphasise criminalisation, the high-ranking officials from the drug control offices emphasised the treaties' allowance of alternatives to punishment for drug possession offences. This paper applies transnational social movement theory to analyse the political opportunity structure for drug law reform at the UN. Data was collected from documents created by important United Nations agencies in the lead up to UNGASS 2016. By analysing the statements of prominent UN officials within a social movement theory framework, we can assess whether those responsible for administering global drug policy are offering concession to drug law reform social movement and whether a political opportunity structure is opening up for drug law reformers to pursue further reforms. from the United Nations documents demonstrated significant reference to local drug law reforms and the benefits of non-punitive treatment of drug users. However, given the strong normative preference and mandatory language ("shall") in the 1988 Convention, policy leaders at the UN can only offer very moderate concessions to drug law reformers - primarily the advocacy of alternatives to incarceration. Such policies still suffer many problems caused by using the criminal justice system to funnel people into treatment. Indeed, many other offices at the UN explicitly drew attention to the problem of pre-trial punishment in their contributions to UNGASS 2016. A schism is developing at the UN as other UN offices are pointing out that advocating for alternatives to punishment is inadequate due to the many problems of "pre

The business cycle and drug use in Australia: evidence from repeated cross-sections of individual level data.

Science.gov (United States)

Chalmers, Jenny; Ritter, Alison

2011-09-01

This paper examined the implications of the business cycle for cannabis and alcohol use. What little we know about cannabis use suggests that young Americans (teenagers and adults in their early 20s) seem more inclined to use illicit drugs and to use them more frequently with rises in the unemployment rate. In contrast, a more fulsome alcohol literature suggests that participation in drinking is unaffected by the business cycle. Heavy drinkers drink less during economic downturns and their reduced use counteracts the fact that light drinkers might drink a little more. Using individual level data from repeated cross-sections of Australia's National Drug Strategy Household Survey (NDSHS), spanning 1991-2007, this study examined the relationship between cannabis and alcohol use of Australians aged 14-49 years and the unemployment rate and real income per capita, two indicators of the business cycle. Australians in their late 20s, 30s and 40s drink less frequently during economic downturns. If unemployment rate rises are accompanied by falls in income per capita, younger Australians will also drink less frequently. Recent participation in cannabis use (within the last year) increases with falls in income per capita regardless of age, although the increase is less marked for young people (14-24 years). Whereas the participation rate of people aged 25-49 years also falls with rising unemployment rates, the participation of younger people increases. Cannabis users younger than 35 will use more frequently as the unemployment rate rises. In contrast, older Australians will use less frequently. Australia's recent economic slowdown has been characterised by rising unemployment rates without accompanying falls in income per capita. Based on our findings this slowdown should have encouraged young Australians aged 14-24 years to both drink and use cannabis more frequently. The slowdown would have had little impact on the frequency of drinking of older Australians. However it

Drugs of abuse specifically sensitize noradrenergic and serotonergic neurons via a non-dopaminergic mechanism.

Science.gov (United States)

Lanteri, Christophe; Salomon, Lucas; Torrens, Yvette; Glowinski, Jacques; Tassin, Jean-Pol

2008-06-01

A challenge in drug dependence is to delineate long-term neurochemical modifications induced by drugs of abuse. Repeated d-amphetamine was recently shown to disrupt a mutual regulatory link between noradrenergic and serotonergic neurons, thus inducing long-term increased responses to d-amphetamine and para-chloroamphetamine, respectively. We show here that such a sensitization of noradrenergic and serotonergic neurons also occurs following repeated treatment with cocaine, morphine, or alcohol, three compounds belonging to main groups of addictive substances. In all cases, this sensitization is prevented by alpha 1b-adrenergic and 5-HT2A receptors blockade, indicating the critical role of these receptors on long-term effects of drugs of abuse. However, repeated treatments with two non-addictive antidepressants, venlafaxine, and clorimipramine, which nevertheless inhibit noradrenergic and serotonergic reuptake, do not induce noradrenergic and serotonergic neurons sensitization. Similarly, this sensitization does not occur following repeated treatments with a specific inhibitor of dopamine (DA) reuptake, GBR12783. Moreover, we show that the effects of SCH23390, a D1 receptor antagonist known to inhibit development of d-amphetamine behavioral sensitization, are due to its 5-HT2C receptor agonist property. SCH23390 blocks amphetamine-induced release of norepinephrine and RS102221, a 5-HT2C antagonist, can reverse this inhibition as well as inhibition of noradrenergic sensitization and development of behavioral sensitization induced by repeated d-amphetamine. We propose that noradrenergic/serotonergic uncoupling is a common neurochemical consequence of repeated consumption of drugs of abuse, unrelated with DA release. Our data also suggest that compounds able to restore the link between noradrenergic and serotonergic modulatory systems could represent important therapeutic targets for investigation.

Drug delivery across length scales.

Science.gov (United States)

Delcassian, Derfogail; Patel, Asha K; Cortinas, Abel B; Langer, Robert

2018-02-20

Over the last century, there has been a dramatic change in the nature of therapeutic, biologically active molecules available to treat disease. Therapies have evolved from extracted natural products towards rationally designed biomolecules, including small molecules, engineered proteins and nucleic acids. The use of potent drugs which target specific organs, cells or biochemical pathways, necessitates new tools which can enable controlled delivery and dosing of these therapeutics to their biological targets. Here, we review the miniaturisation of drug delivery systems from the macro to nano-scale, focussing on controlled dosing and controlled targeting as two key parameters in drug delivery device design. We describe how the miniaturisation of these devices enables the move from repeated, systemic dosing, to on-demand, targeted delivery of therapeutic drugs and highlight areas of focus for the future.

Repeated cocaine exposure facilitates the expression of incentive motivation and induces habitual control in rats.

Directory of Open Access Journals (Sweden)

Kimberly H LeBlanc

Full Text Available There is growing evidence that mere exposure to drugs can induce long-term alterations in the neural systems that mediate reward processing, motivation, and behavioral control, potentially causing the pathological pursuit of drugs that characterizes the addicted state. The incentive sensitization theory proposes that drug exposure potentiates the influence of reward-paired cues on behavior. It has also been suggested that drug exposure biases action selection towards the automatic execution of habits and away from more deliberate goal-directed control. The current study investigated whether rats given repeated exposure to peripherally administered cocaine would show alterations in incentive motivation (assayed using the Pavlovian-to-instrumental transfer (PIT paradigm or habit formation (assayed using sensitivity to reward devaluation. After instrumental and Pavlovian training for food pellet rewards, rats were given 6 daily injections of cocaine (15 mg/kg, IP or saline, followed by a 10-d period of rest. Consistent with the incentive sensitization theory, cocaine-treated rats showed stronger cue-evoked lever pressing than saline-treated rats during the PIT test. The same rats were then trained on a new instrumental action with a new food pellet reward before undergoing a reward devaluation testing. Although saline-treated rats exhibited sensitivity to reward devaluation, indicative of goal-directed performance, cocaine-treated rats were insensitive to this treatment, suggesting a reliance on habitual processes. These findings, when taken together, indicate that repeated exposure to cocaine can cause broad alterations in behavioral control, spanning both motivational and action selection processes, and could therefore help explain aberrations of decision-making that underlie drug addiction.

Repeated cocaine exposure facilitates the expression of incentive motivation and induces habitual control in rats.

Science.gov (United States)

LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

2013-01-01

There is growing evidence that mere exposure to drugs can induce long-term alterations in the neural systems that mediate reward processing, motivation, and behavioral control, potentially causing the pathological pursuit of drugs that characterizes the addicted state. The incentive sensitization theory proposes that drug exposure potentiates the influence of reward-paired cues on behavior. It has also been suggested that drug exposure biases action selection towards the automatic execution of habits and away from more deliberate goal-directed control. The current study investigated whether rats given repeated exposure to peripherally administered cocaine would show alterations in incentive motivation (assayed using the Pavlovian-to-instrumental transfer (PIT) paradigm) or habit formation (assayed using sensitivity to reward devaluation). After instrumental and Pavlovian training for food pellet rewards, rats were given 6 daily injections of cocaine (15 mg/kg, IP) or saline, followed by a 10-d period of rest. Consistent with the incentive sensitization theory, cocaine-treated rats showed stronger cue-evoked lever pressing than saline-treated rats during the PIT test. The same rats were then trained on a new instrumental action with a new food pellet reward before undergoing a reward devaluation testing. Although saline-treated rats exhibited sensitivity to reward devaluation, indicative of goal-directed performance, cocaine-treated rats were insensitive to this treatment, suggesting a reliance on habitual processes. These findings, when taken together, indicate that repeated exposure to cocaine can cause broad alterations in behavioral control, spanning both motivational and action selection processes, and could therefore help explain aberrations of decision-making that underlie drug addiction.

A Unified Model for Repeating and Non-repeating Fast Radio Bursts

International Nuclear Information System (INIS)

Bagchi, Manjari

2017-01-01

The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

A Unified Model for Repeating and Non-repeating Fast Radio Bursts

Energy Technology Data Exchange (ETDEWEB)

Bagchi, Manjari, E-mail: manjari@imsc.res.in [The Institute of Mathematical Sciences (IMSc-HBNI), 4th Cross Road, CIT Campus, Taramani, Chennai 600113 (India)

2017-04-01

The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

Safety level of Levofloxacin following repeated oral adminstration in White Leg Horn layer birds

Directory of Open Access Journals (Sweden)

Jatin H. Patel

2009-08-01

Full Text Available Levofloxacin is a fluorinated quinolone which has broad-spectrum antibacterial activity at low plasma/tissue concentration. The present study was designed to investigate safety of levofloxacin (10 mg/kg after repeated oral administration at 12 hours interval for 14 days in layer birds (30-35 weeks old and weighing between 1.5-2.0 kg and to determine tissue concentration of the drug following oral administration (10 mg/kg for 5 days. Drug concentration in tissue was determined using High Performance Liquid Chromatography (HPLC. Repeated oral administration of levofloxacin in layer birds was found safe based on evaluation of haematological (Hb, PCV, TLC and DLC, blood biochemical (AST, ALT, AKP, ACP, LDH, BUN, Serum total protein, Serum albumin, Serum Creatinine, Blood glucose and Total bilirubin and histopathology of liver, kidney and joint cartilage. Levofloxacin could not be detected in body tissues (liver and skeletal muscle at 12 hours after the last administration. [Vet. World 2009; 2(4.000: 137-139

Repeatability of Cryogenic Multilayer Insulation

Science.gov (United States)

Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

2017-12-01

Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation (MLI) has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five Glenn Research Center (GRC) provided coupons with 25 layers was shown to be +/- 8.4% whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0%. A second group of 10 coupons has been fabricated by Yetispace and tested by Florida State University, the repeatability between coupons has been shown to be +/- 15-25%. Based on detailed statistical analysis, the data has been shown to be statistically significant.

Deployment Repeatability

Science.gov (United States)

2016-04-01

evaluating the deployment repeatability builds upon the testing or analysis of deployment kinematics (Chapter 6) and adds repetition. Introduction...material yield or failure during a test. For the purposes of this chapter, zero shift will refer to permanent changes in the structure, while reversible ...the content of other chapters in this book: Gravity Compensation (Chapter 4) and Deployment Kinematics and Dynamics (Chapter 6). Repeating the

Reconfigurable multiport EPON repeater

Science.gov (United States)

Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

2009-11-01

An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

A theory of drug tolerance and dependence II: the mathematical model.

Science.gov (United States)

Peper, Abraham

2004-08-21

The preceding paper presented a model of drug tolerance and dependence. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behaviour to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity to small changes in drug dose, the rebound phenomenon and the large reactions following withdrawal in dependence. The present paper discusses the mathematical model in terms of its design. The model is a nonlinear, learning feedback system, fully satisfying control theoretical principles. It accepts any form of the stimulus-the drug intake-and describes how the physiological processes involved affect the distribution of the drug through the body and the stability of the regulation loop. The mathematical model verifies the proposed theory and provides a basis for the implementation of mathematical models of specific physiological processes.

Mexico's "ley de narcomenudeo" drug policy reform and the international drug control regime.

Science.gov (United States)

Mackey, Tim K; Werb, Daniel; Beletsky, Leo; Rangel, Gudelia; Arredondo, Jaime; Strathdee, Steffanie A

2014-11-14

It has been over half a century since the landmark Single Convention on Narcotic Drugs was adopted, for the first time unifying international drug policy under a single treaty aimed at limiting use, manufacture, trade, possession, and trafficking of opiates, cannabis, and other narcotics. Since then, other international drug policy measures have been adopted, largely emphasizing enforcement-based approaches to reducing drug supply and use. Recently, in response to concerns that the historic focus on criminalization and enforcement has had limited effectiveness, international drug policies have begun to undergo a paradigm shift as countries seek to enact their own reforms to partially depenalize or deregulate personal drug use and possession. This includes Mexico, which in 2009 enacted national drug policy reform partially decriminalizing possession of small quantities of narcotics for personal consumption while also requiring drug treatment for repeat offenders. As countries move forward with their own reform models, critical assessment of their legal compatibility and effectiveness is necessary. In this commentary we conduct a critical assessment of the compatibility of Mexico's reform policy to the international drug policy regime and describe its role in the current evolving drug policy environment. We argue that Mexico's reform is consistent with flexibilities allowed under international drug treaty instruments and related commentaries. We also advocate that drug policy reforms and future governance efforts should be based on empirical evidence, emphasize harm reduction practices, and integrate evidence-based evaluation and implementation of drug reform measures.

The prevalence of low self-esteem in an intellectually disabled forensic population.

Science.gov (United States)

Johnson, P

2012-03-01

This was a quantitative study to measure the prevalence low self-esteem in an intellectually disabled forensic population. The dependent variables used were the adapted six-item Rosenberg Self-Esteem Scale and the adapted Evaluative Beliefs Scale. It had a repeated measures design with independent variables including consideration of differences between the low and medium secure parts of the service, the influences of types of offences and the effects of disrupted childhood attachments. Forty-four male clients, with mild to borderline intellectual disabilities, were recruited. Data were collected by one key researcher during individual research interviews using the two structured instruments to measure self-esteem. Further data were then obtained from routinely recorded clinical information held on the hospital computer system. Unexpectedly, the majority of clients scored as having moderate or high self-esteem on both self-esteem measures. There was a statistically significant positive correlation between the two scales. In all, 64% of the population studied had committed either sexual offences or fire setting offences. Contrary to expectation, those who had evidence of disrupted attachments had slightly higher self-esteem than those who had not experienced disrupted attachments. Self-esteem is a complex personal concept with many influencing factors. Cognitive behaviour therapy has a unique role in realising and overcoming negative core beliefs and feelings of low self-worth. The offence types concurred with previously noted patterns of offending within the intellectually disabled forensic population. © 2011 The Author. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

Corporate Criminal Liability for Corruption Offences and the Due Diligence Defence: A Comparison of the Dutch and English Legal Frameworks

Directory of Open Access Journals (Sweden)

Bram Meyer

2014-07-01

Full Text Available This article addresses the question of to what extent companies can be held criminally liable for – active – bribery offences perpetrated by their employees. It focuses on the questions of to what extent companies have a duty of care to prevent bribery by employees and to what extent can a breach of such a duty of care cause criminal liability to ensue.In this contribution, the authors set out to answer these questions by comparing the Dutch and the British legal systems. After assessing the international and national legal frameworks, they conclude that the Dutch anti-corruption provisions are, compared to the British, broadly formulated, including ambiguous terms and that – as a result of this – their scope is somewhat vague. Due diligence measures have a varying effect on determining the criminal liability of companies. In contrast, the due diligence question has a fixed, unequivocal place in the UK system of determining criminal liability, making the UK system seem more straightforward. But still, neither anti-corruption legislation nor case law provides clarity as to the scope of due diligence measures. To increase legal certainty, this article calls upon the Dutch Government to produce guidelines, similar to the British MoJ Guidance, that provide specific examples of the details of a compliance scheme.

Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

Directory of Open Access Journals (Sweden)

Luis Alfonso Moreno-Rocha

2016-11-01

Full Text Available Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P  0.05. The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites’ pharmacokinetics (P < 0.05 were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

Repeated restraint stress exposure during early withdrawal accelerates incubation of cue-induced cocaine craving.

Science.gov (United States)

Glynn, Ryan M; Rosenkranz, J Amiel; Wolf, Marina E; Caccamise, Aaron; Shroff, Freya; Smith, Alyssa B; Loweth, Jessica A

2018-01-01

A major challenge for treating cocaine addiction is the propensity for abstinent users to relapse. Two important triggers for relapse are cues associated with prior drug use and stressful life events. To study their interaction in promoting relapse during abstinence, we used the incubation model of craving and relapse in which cue-induced drug seeking progressively intensifies ('incubates') during withdrawal from extended-access cocaine self-administration. We tested rats for cue-induced cocaine seeking on withdrawal day (WD) 1. Rats were then subjected to repeated restraint stress or control conditions (seven sessions held between WD6 and WD14). All rats were tested again for cue-induced cocaine seeking on WD15, 1 day after the last stress or control session. Although controls showed a time-dependent increase in cue-induced cocaine seeking (incubation), rats exposed to repeated stress in early withdrawal exhibited a more robust increase in seeking behavior between WD1 and WD15. In separate stressed and control rats, equivalent cocaine seeking was observed on WD48. These results indicate that repeated stress in early withdrawal accelerates incubation of cocaine craving, although craving plateaus at the same level were observed in controls. However, 1 month after the WD48 test, rats subjected to repeated stress in early withdrawal showed enhanced cue-induced cocaine seeking following acute (24 hours) food deprivation stress. Together, these data indicate that chronic stress exposure enhances the initial rate of incubation of craving during early withdrawal, resulting in increased vulnerability to cue-induced relapse during this period, and may lead to a persistent increase in vulnerability to the relapse-promoting effects of stress. © 2016 Society for the Study of Addiction.

Expansion of protein domain repeats.

Directory of Open Access Journals (Sweden)

Asa K Björklund

2006-08-01

Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

The leucine-rich repeat structure.

Science.gov (United States)

Bella, J; Hindle, K L; McEwan, P A; Lovell, S C

2008-08-01

The leucine-rich repeat is a widespread structural motif of 20-30 amino acids with a characteristic repetitive sequence pattern rich in leucines. Leucine-rich repeat domains are built from tandems of two or more repeats and form curved solenoid structures that are particularly suitable for protein-protein interactions. Thousands of protein sequences containing leucine-rich repeats have been identified by automatic annotation methods. Three-dimensional structures of leucine-rich repeat domains determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. As the essential structural principles become well established, the leucine-rich repeat architecture is emerging as an attractive framework for structural prediction and protein engineering. This review presents an update of the current understanding of leucine-rich repeat structure at the primary, secondary, tertiary and quaternary levels and discusses specific examples from recently determined three-dimensional structures.

Rulings in Argentinean and Colombian courts decriminalize possession of small amounts of narcotics.

Science.gov (United States)

Cozac, David

2009-12-01

Two recent court decisions in South America have reflected a growing backlash in the region against the so-called, U.S.-led "war on drugs". In Argentina, the Supreme Court of Justice ruled unanimously on 25 August 2009 that the second paragraph of Article 14 of the country's drug control legislation, which punishes the possession of drugs for personal consumption, was unconstitutional. In Colombia, the Supreme Court of Justice ruled on 8 July 2009 that the possession of illegal drugs for personal use was not a criminal offence.

Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

Science.gov (United States)

Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

2014-02-01

The Gd5Ge2Si2 alloy and the off-stoichiometric Ni50Mn35In15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd5Ge2Si2 and Ni50Mn35In15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

International Nuclear Information System (INIS)

Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

2014-01-01

The Gd 5 Ge 2 Si 2 alloy and the off-stoichiometric Ni 50 Mn 35 In 15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd 5 Ge 2 Si 2 and Ni 50 Mn 35 In 15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis

Revisiting the TALE repeat.

Science.gov (United States)

Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

2014-04-01

Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

Natural Rewards, Neuroplasticity, and Non-Drug Addictions

Science.gov (United States)

Olsen, Christopher M.

2011-01-01

There is a high degree of overlap between brain regions involved in processing natural rewards and drugs of abuse. “Non-drug” or “behavioral” addictions have become increasingly documented in the clinic, and pathologies include compulsive activities such as shopping, eating, exercising, sexual behavior, and gambling. Like drug addiction, non-drug addictions manifest in symptoms including craving, impaired control over the behavior, tolerance, withdrawal, and high rates of relapse. These alterations in behavior suggest that plasticity may be occurring in brain regions associated with drug addiction. In this review, I summarize data demonstrating that exposure to non-drug rewards can alter neural plasticity in regions of the brain that are affected by drugs of abuse. Research suggests that there are several similarities between neuroplasticity induced by natural and drug rewards and that, depending on the reward, repeated exposure to natural rewards might induce neuroplasticity that either promotes or counteracts addictive behavior. PMID:21459101

All-photonic quantum repeaters

Science.gov (United States)

Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

2015-01-01

Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

盗窃毒品行为的刑法性质评析%Analysis on Nature of the Criminal Law of the Behavior of Stealing the Drugs

Institute of Scientific and Technical Information of China (English)

徐志军; 王伟民; 曹玉玉

2013-01-01

The drug is contraband, which doesn’t have nature of property, so it does not belong to the object of larceny. The serious plot is not plot of sentencing, which should be incriminating plot. If someone knew the drugs that he stole, and then he sold or illegally hold drugs, the judge should sentence drug offenses or crime of holding drugs to him. If someone did not know the drugs that he stole, which is the problem of object, it should be larceny. Then he sold or illegally hold drugs, according to the principle of absorbable offence, we should sentence drug offenses or crime of holding drugs to him.%毒品是违禁品，不具有财物的属性，不属于盗窃罪的对象。盗窃毒品“情节严重”，应当为定罪情节，而非量刑情节。明知是毒品而盗窃，又贩卖或者非法持有的，以贩卖毒品罪或者非法持有毒品罪定罪处罚。不明知是毒品而盗窃，属于对象认识错误的问题，以盗窃罪论。事后又贩卖或者非法持有的，按照吸收犯的处理原则，以贩卖毒品罪或者非法持有毒品罪定罪处罚。

Interaction of mianserin and some hypotensive drugs in Wistar rats.

Science.gov (United States)

Górska, Dorota; Andrzejczak, Dariusz

2004-01-01

Mianserin is thought to exert little effect on the cardiovascular system. In fact its safety in comparison with tricyclic drugs is high. Various experiments gave varying results as for the influence of the drug on arterial blood pressure in people and animals. Therefore, a study was undertaken in Wistar rats to evaluate interactions of mianserin administered intraperitoneally as a single dose, and for 21 days with 3 hypotensive drugs showing different mechanism of action (propranolol, enalapril, prazosine). The systolic, diastolic and mean blood pressure was measured with a LETICA apparatus. The results of the study revealed that administration of mianserin in normotensive rats leads to a short-term decrease in blood pressure and significantly enhanced the hypotensive effect of prazosine. Repeated doses of mianserin lead to a temporary increase in blood pressure after 2 weeks of administration. Single and repeated administration of mianserin did not change the hypotensive effect of propranolol and enalapril. Three-week therapy with mianserin significantly enhanced the hypotensive effect of prazosine.

MicroRNAs in CAG trinucleotide repeat expansion disorders: an integrated review of the literature.

Science.gov (United States)

Dumitrescu, Laura; Popescu, Bogdan O

2015-01-01

MicroRNAs are small RNAs involved in gene silencing. They play important roles in transcriptional regulation and are selectively and abundantly expressed in the central nervous system. A considerable amount of the human genome is comprised of tandem repeating nucleotide streams. Several diseases are caused by above-threshold expansion of certain trinucleotide repeats occurring in a protein-coding or non-coding region. Though monogenic, CAG trinucleotide repeat expansion disorders have a complex pathogenesis, various combinations of multiple coexisting pathways resulting in one common final consequence: selective neurodegeneration. Mutant protein and mutant transcript gain of toxic function are considered to be the core pathogenic mechanisms. The profile of microRNAs in CAG trinucleotide repeat disorders is scarcely described, however microRNA dysregulation has been identified in these diseases and microRNA-related intereference with gene expression is considered to be involved in their pathogenesis. Better understanding of microRNAs functions and means of manipulation promises to offer further insights into the pathogenic pathways of CAG repeat expansion disorders, to point out new potential targets for drug intervention and to provide some of the much needed etiopathogenic therapeutic agents. A number of disease-modifying microRNA silencing strategies are under development, but several implementation impediments still have to be resolved. CAG targeting seems feasible and efficient in animal models and is an appealing approach for clinical practice. Preliminary human trials are just beginning.

PAIN RELIEF MEDIATED BY IMPLANTABLE DRUG-DELIVERY DEVICES

NARCIS (Netherlands)

HOEKSTRA, A

Various totally implantable drug delivery systems from single access ports to micropumps are now available for administration of repeated boluses, and continuous or programmable infusions. In this respect, emphasis is given to a relatively cheap, totally implantable system for self-administering

Sample preparation composite and replicate strategy for assay of solid oral drug products.

Science.gov (United States)

Harrington, Brent; Nickerson, Beverly; Guo, Michele Xuemei; Barber, Marc; Giamalva, David; Lee, Carlos; Scrivens, Garry

2014-12-16

In pharmaceutical analysis, the results of drug product assay testing are used to make decisions regarding the quality, efficacy, and stability of the drug product. In order to make sound risk-based decisions concerning drug product potency, an understanding of the uncertainty of the reportable assay value is required. Utilizing the most restrictive criteria in current regulatory documentation, a maximum variability attributed to method repeatability is defined for a drug product potency assay. A sampling strategy that reduces the repeatability component of the assay variability below this predefined maximum is demonstrated. The sampling strategy consists of determining the number of dosage units (k) to be prepared in a composite sample of which there may be a number of equivalent replicate (r) sample preparations. The variability, as measured by the standard error (SE), of a potency assay consists of several sources such as sample preparation and dosage unit variability. A sampling scheme that increases the number of sample preparations (r) and/or number of dosage units (k) per sample preparation will reduce the assay variability and thus decrease the uncertainty around decisions made concerning the potency of the drug product. A maximum allowable repeatability component of the standard error (SE) for the potency assay is derived using material in current regulatory documents. A table of solutions for the number of dosage units per sample preparation (r) and number of replicate sample preparations (k) is presented for any ratio of sample preparation and dosage unit variability.

Improved recovery of repeat intoxicated drivers using fingernails and blood spots to monitor alcohol and other substance abuse.

Science.gov (United States)

Bean, Pamela; Brown, Guida; Hallinan, Patricia; Becerra, Sergio; Lewis, Doug

2017-01-02

This study reports the results of a pilot program in Kenosha County that used a combination of direct biomarkers extracted from blood spots and nails to monitor repeat intoxicated drivers for their use of alcohol and drugs with a detection window spanning from 3 weeks to several months. The objectives were to test whether the direct biomarkers phosphatidylethanol (PEth), ethylglucuronide (EtG), and 5 drug metabolites would (1) help assessors obtain a more objective evaluation of repeat offenders during the assessment interview, (2) allow for timely identification of relapses and improve classification of drivers into risk categories, and (3) predict recidivism by identifying offenders most likely to obtain a subsequent operating while intoxicated (OWI) offense within 4 years of enrollment in the program. All (N = 261) repeat offenders were tested using PEth obtained from blood spots and EtG obtained from fingernails; 159 participants were also tested for a 5 drugs of abuse nail panel. Drivers were tested immediately after the assessment interview (baseline) and at 3, 6, 9, and 12 months after baseline. Based on biomarker results and self-reports of abstinence, offenders were classified into different risk categories and required to follow specific testing timelines based on the program's decision tree. The baseline analysis shows that 60% of drivers tested positive for alcohol biomarkers (EtG, PEth, or both) at the assessment interview, with lower detection rates (0-11%) for the 5 drug metabolites. The comparison of biomarkers results to self-reports of abstinence identified 28% of all offenders as high risk and assigned them to more frequent testing and more intense monitoring. The longitudinal analysis shows that 56% (completers) of participants completed the program successfully and the remaining 44% (noncompliant) terminated prematurely. Two thirds (68%) of the completers were able to reduce or control their drinking and one third relapsed at least one time

Towards clinical use of a laser-induced microjet system aimed at reliable and safe drug delivery

Science.gov (United States)

Jang, Hun-jae; Yu, Hyeonju; Lee, Seonggeun; Hur, Eugene; Kim, Yoonkwan; Lee, Seol-Hoon; Kang, Naegyu; Yoh, Jack J.

2014-05-01

An Er:YAG laser with 2940-nm wavelength and 250-μs pulse duration is used to generate a microjet that is ejected at ˜50 m/s in air. The strength of the microjet depends on the bubble dynamics from the beam-water interaction within the driving chamber as well as the discharging of the drug solution underneath the elastic membrane that separates the drug from the driving liquid. The jet characteristics, such as velocity, volume, and level of atomization, are obtained by high-speed camera images taken at 42,000 fps. The enhancements in jet volume (dosage) and repeated jet generation, which are aimed at making the injector suitable for general clinical applications, are achieved. The generation of repeated microjets is achieved with the help of a stepping motor that provides a uniform pressure within the drug reservoir before an ejection occurs through a micro nozzle. Also, two types of human growth hormones are used for monitoring any potential thermal damage to the drug solution due to a repeated laser ablation when driving the microjet. We provide strong evidence to support that the drugs, as they are injected to porcine skins, are free of the damage associated with the present delivery method.

Analysis of illicit drugs seized in the Province of Florence from 2006 to 2016.

Science.gov (United States)

Bertol, Elisabetta; Bigagli, Laura; D'Errico, Stefano; Mari, Francesco; Palumbo, Diego; Pascali, Jennifer P; Vaiano, Fabio

2018-03-01

Comprehension of illicit drug market's features at local level is useful to plan and to correctly set-up specific informative and contrast activities. In this paper we report trends, purities and consumption estimations of illicit substances available on the Florentine territory from 2006 to 2016. These data were obtained by the analysis of 10,451 samples seized by the Law Enforcement Agencies in case of personal use offence. Analytical procedures consisted in targeted and untargeted analyses by gas chromatography-flame ionization detector, gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. The most detected substances were: cannabis (78.0%; resin: 51.7%; herb: 26.3%), cocaine (10.4%), opiates (6.6%; heroin: 6.5%; morphine: 0.1%), ketamine (1.4%), amphetamines (1.3%; 3,4-methylenedioxymethamphetamine - MDMA -: 0.7%; methamphetamine: 0.6%; amphetamine: market, while THC content in cannabis seizures was unexpectedly below the European mean values. Starting from 2015, a total of 5 new psychoactive substances (NPS) were detected in seized material, mainly composed of white powders (pentedrone, 3-methylmethcathinone, 4-fluoroamphetamine, methoxethamine and AB-FUBINACA). Most of the seizures (75.5%) were from young male adults (14-34 years old). These data contribute to highlight new trends in the illicit drug market in the Tuscany area, but also to verify the persistence of old habits of drug consumption, confirming the need for more effective counteraction and prevention plans, especially among young people, where the diffusion of the legal highs is worrisome, also in consideration of the young age and the unconsciousness of the possible health effects. Copyright © 2018 Elsevier B.V. All rights reserved.

78 FR 65594 - Vehicular Repeaters

Science.gov (United States)

2013-11-01

... coordinators estimate the effect on coordination fees? Does the supposed benefit that mobile repeater stations... allow the licensing and operation of vehicular repeater systems and other mobile repeaters by public... email: [email protected] or phone: 202-418- 0530 or TTY: 202-418-0432. For detailed instructions for...

Tevatron serial data repeater system

International Nuclear Information System (INIS)

Ducar, R.J.

1981-01-01

A ten megabit per second serial data repeater system has been developed for the 6.28km Tevatron accelerator. The repeaters are positioned at each of the thirty service buildings and accommodate control and abort system communications as well as distribution of the Tevatron time and energy clocks. The repeaters are transparent to the particular protocol of the transmissions. Serial data are encoded locally as unipolar two volt signals employing the self-clocking Manchester Bi-Phase code. The repeaters modulate the local signals to low-power bursts of 50 MHz rf carrier for the 260m transmission between service buildings. The repeaters also demodulate the transmission and restructure the data for local utilization. The employment of frequency discrimination techniques yields high immunity to the characteristic noise spectrum

Repeat Customer Success in Extension

Science.gov (United States)

Bess, Melissa M.; Traub, Sarah M.

2013-01-01

Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

Film repeats in radiology department

International Nuclear Information System (INIS)

Suwan, A. Z.; Al-Shakharah, A. I

1997-01-01

During a one year period, 4910 radiographs of 55780 films were repeated. The objective of our study was to analyse and to classify the causes in order to minimize the repeats, cut the expenses and to provide optimal radiographs for accurate diagnosis. Analysis of the different factors revealed that, 43.6% of film repeats in our service were due to faults in exposure factors, centering comprises 15.9% of the repeats, while too much collimation was responsible for 7.6% of these repeats. All of which can be decreased by awareness and programmed training of technicians. Film blurring caused by patient motion was also responsible for 4.9% for radiographs reexamination, which can be minimized by detailed explanation to the patient and providing the necessary privacy. Fogging of X-Ray films by improper storage or inadequate handling or processing faults were responsible for 14.5% in repeats in our study. Methods and criteria for proper storage and handling of films were discussed. Recommendation for using modern day-light and laser processor has been high lighted. Artefacts are noticeably high in our cases, due to spinal dresses and frequent usage of precious metals for c osmotic purposes in this part of the world. The repeated films comprise 8.8% of all films We conclude that, the main factor responsible for repeats of up to 81.6% of cases was the technologists, thus emphasizing the importance of adequate training of the technologists. (authors). 15 refs., 9 figs., 1 table

Drug affordability-potential tool for comparing illicit drug markets.

Science.gov (United States)

Groshkova, Teodora; Cunningham, Andrew; Royuela, Luis; Singleton, Nicola; Saggers, Tony; Sedefov, Roumen

2018-06-01

The importance of illicit drug price data and making appropriate adjustments for purity has been repeatedly highlighted for understanding illicit drug markets. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) has been collecting retail price data for a number of drug types alongside drug-specific purity information for over 15 years. While these data are useful for a number of monitoring and analytical purposes, they are not without their limitations and there are circumstances where additional adjustment needs to be considered. This paper reviews some conceptual issues and measurement challenges relevant to the interpretation of price data. It also highlights the issues with between-country comparisons of drug prices and introduces the concept of affordability of drugs, going beyond purity-adjustment to account for varying national economies. Based on a 2015 European data set of price and purity data across the heroin and cocaine retail markets, the paper demonstrates a new model for drug market comparative analysis; calculation of drug affordability is achieved by applying to purity-adjusted prices 2015 Price Level Indices (PLI, Eurostat). Available data allowed retail heroin and cocaine market comparison for 27 European countries. The lowest and highest unadjusted prices per gram were observed for heroin: in Estonia, Belgium, Greece and Bulgaria (lowest) and Finland, Ireland, Sweden and Latvia (highest); for cocaine: the Netherlands, Belgium and the United Kingdom (lowest) and Turkey, Finland, Estonia and Romania (highest). The affordability per gram of heroin and cocaine when taking into account adjustment for both purity and economy demonstrates different patterns. It is argued that purity-adjusted price alone provides an incomplete comparison of retail price across countries. The proposed new method takes account of the differing economic conditions within European countries, thus providing a more sophisticated tool for cross

Repeat migration and disappointment.

Science.gov (United States)

Grant, E K; Vanderkamp, J

1986-01-01

This article investigates the determinants of repeat migration among the 44 regions of Canada, using information from a large micro-database which spans the period 1968 to 1971. The explanation of repeat migration probabilities is a difficult task, and this attempt is only partly successful. May of the explanatory variables are not significant, and the overall explanatory power of the equations is not high. In the area of personal characteristics, the variables related to age, sex, and marital status are generally significant and with expected signs. The distance variable has a strongly positive effect on onward move probabilities. Variables related to prior migration experience have an important impact that differs between return and onward probabilities. In particular, the occurrence of prior moves has a striking effect on the probability of onward migration. The variable representing disappointment, or relative success of the initial move, plays a significant role in explaining repeat migration probabilities. The disappointment variable represents the ratio of actural versus expected wage income in the year after the initial move, and its effect on both repeat migration probabilities is always negative and almost always highly significant. The repeat probabilities diminish after a year's stay in the destination region, but disappointment in the most recent year still has a bearing on the delayed repeat probabilities. While the quantitative impact of the disappointment variable is not large, it is difficult to draw comparisons since similar estimates are not available elsewhere.

Quantum repeated games revisited

International Nuclear Information System (INIS)

Frąckiewicz, Piotr

2012-01-01

We present a scheme for playing quantum repeated 2 × 2 games based on Marinatto and Weber’s approach to quantum games. As a potential application, we study the twice repeated Prisoner’s Dilemma game. We show that results not available in the classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games proposed by Iqbal and Toor. We point out the drawbacks that make their results unacceptable. (paper)

Some Problems of the Implementation of Administrative Responsibility for Violations of the Legislation on Contract System in the Procurement Sphere

OpenAIRE

Andrei E. Yuritsin; Yurii B. Lavrov

2017-01-01

The article considers the issues of application of Article 6.9 of the Code of Administrative Offences of the Russian Federation and the significance of the practice of implementation of this legal norm to counteraction to illegal drug use. The author estimates the possibility of dealing all cases of illegal use of narcotic drugs and psychotropic substances and their analogues by law enforcement practice as well as the sufficiency of administrative penalties provided for by the Article. Critic...

Repeatability of visual acuity measurement.

Science.gov (United States)

Raasch, T W; Bailey, I L; Bullimore, M A

1998-05-01

This study investigates features of visual acuity chart design and acuity testing scoring methods which affect the validity and repeatability of visual acuity measurements. Visual acuity was measured using the Sloan and British Standard letter series, and Landolt rings. Identifiability of the different letters as a function of size was estimated, and expressed in the form of frequency-of-seeing curves. These functions were then used to simulate acuity measurements with a variety of chart designs and scoring criteria. Systematic relationships exist between chart design parameters and acuity score, and acuity score repeatability. In particular, an important feature of a chart, that largely determines the repeatability of visual acuity measurement, is the amount of size change attributed to each letter. The methods used to score visual acuity performance also affect repeatability. It is possible to evaluate acuity score validity and repeatability using the statistical principles discussed here.

Educator sexual misconduct: Exposing or causing learners to be ...

African Journals Online (AJOL)

The law recognises that non-contact sexual offences can cause harm and several offences were created to regulate non-contact sexual child abuse offences. Several of these offences deal with the exposure or causing exposure of children to child pornography or pornography. Sexual grooming of children and the ...

Effecting attitudinal change towards rational drug use.

Science.gov (United States)

Singh, T; Natu, M V

1995-01-01

Attitudes of 40 interns towards rational drug use (RDU) were assessed, using a standardized Likert type scale. The assessment was repeated after 4 months to evaluate the effect of usual working conditions of the hospital. After this period, the attitudes had slided towards negative side (p attitudes of test group returned towards positive side (p attitudes.

Fostering repeat donations in Ghana.

Science.gov (United States)

Owusu-Ofori, S; Asenso-Mensah, K; Boateng, P; Sarkodie, F; Allain, J-P

2010-01-01

Most African countries are challenged in recruiting and retaining voluntary blood donors by cost and other complexities and in establishing and implementing national blood policies. The availability of replacement donors who are a cheaper source of blood has not enhanced repeat voluntary donor initiatives. An overview of activities for recruiting and retaining voluntary blood donors was carried out. Donor records from mobile sessions were reviewed from 2002 to 2008. A total of 71,701 blood donations; 45,515 (63.5%) being voluntary donations with 11,680 (25%) repeat donations were collected during the study period. Donations from schools and colleges contributed a steady 60% of total voluntary whilst radio station blood drives increased contribution from 10 to 27%. Though Muslim population is less than 20%, blood collection was above the 30-donation cost-effectiveness threshold with a repeat donation trend reaching 60%. In contrast Christian worshippers provided donations. Repeat donation trends amongst school donors and radio blood drives were 20% and 70% respectively. Repeat donations rates have been variable amongst different blood donor groups in Kumasi, Ghana. The impact of community leaders in propagating altruism cannot be overemphasized. Programs aiming at motivating replacement donors to be repeat donors should be developed and assessed. Copyright 2009 The International Association for Biologicals. All rights reserved.

Enhanced appetitive conditioning following repeated pretreatment with d-amphetamine.

Science.gov (United States)

Harmer, C J; Phillips, G D

1998-07-01

The behavioural response to psychomotor stimulants is augmented with repeated exposure to these drugs. Enhanced stimulated dopamine overflow within the nucleus accumbens and amygdala has been found to accompany this behavioural sensitization. In the present experiment, rats received 2 mg/kg d-amphetamine or 1 ml/kg physiological saline once per day for 5 days. Five days later, a behavioural assay confirmed that prior repeated d-amphetamine treatment markedly enhanced the locomotor activating effects of a d-amphetamine (0.5 mg/kg, i.p.) challenge. Training on a Pavlovian conditioning task began six days subsequently. In Stage 1, a stimulus (light or tone, S-) was presented negatively correlated with a sucrose reward. In Stage 2, presentation of the alternative counterbalanced stimulus (light or tone, S+) was paired with the availability of a 10% sucrose solution. There were no differences between the two groups in their response to the the S- stimulus. However, sensitized animals showed a selective enhancement in the acquisition of conditioned responding to S+, relative to vehicle-injected controls. No differences in behaviour were recorded during the prestimulus periods, nor during presentations of sucrose. Levels of activity within the operant chamber extraneous to alcove approach were also similar in both groups of animals. The conditioned instrumental efficacy of S+, relative to S- was assessed in Stage 3, in which stimulus availability was made contingent on a novel lever-pressing response. Both groups showed a similar preference for the S+ over the S- stimulus. Hence, rats sensitized by prior repeated d-amphetamine showed enhanced appetitive Pavlovian conditioning, without subsequent effect on conditioned reward efficacy. These data are discussed in light of possible changes in mesoamygdaloid dopamine functioning.

Short tandem repeat (STR) DNA markers are hypervariable and informative in Cannabis sativa: implications for forensic investigations.

Science.gov (United States)

Gilmore, Simon; Peakall, Rod; Robertson, James

2003-01-09

Short tandem repeat (STR) markers are the DNA marker of choice in forensic analysis of human DNA. Here we extend the application of STR markers to Cannabis sativa and demonstrate their potential for forensic investigations. Ninety-three individual cannabis plants, representing drug and fibre accessions of widespread origin were profiled with five STR makers. A total of 79 alleles were detected across the five loci. All but four individuals from a single drug-type accession had a unique multilocus genotype. An analysis of molecular variance (AMOVA) revealed significant genetic variation among accessions, with an average of 25% genetic differentiation. By contrast, only 6% genetic difference was detected between drug and fibre crop accessions and it was not possible to unequivocally assign plants as either drug or fibre type. However, our results suggest that drug strains may typically possess lower genetic diversity than fibre strains, which may ultimately provide a means of genetic delineation. Our findings demonstrate the promise of cannabis STR markers to provide information on: (1) agronomic type, (2) the geographical origin of drug seizures, and (3) evidence of conspiracy in production of clonally propagated drug crops.

Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects.

Science.gov (United States)

Sun, Wei-Lun; Quizon, Pamela M; Zhu, Jun

2016-01-01

Addiction to psychostimulants has been considered as a chronic psychiatric disorder characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that result in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction. Copyright © 2016. Published by Elsevier Inc.

Perspectivas de género en las condenas por tráfico de drogas

OpenAIRE

Luz M. Puente Aba

2012-01-01

This article pretends to examine sentences for drug trafficking from a gender perspective. An in-depth analysis of sentences and prison statistics from this point of view reveals that women are most affected by this repressive policy. The most remarkable fact is that while the number of convicted women in general is low, a large percentage of female offenders’ sentences are related to drug offences, thus representing a higher percentage in this group than in the male group. Yet if we an...

Repeated DNA sequences in fungi

Energy Technology Data Exchange (ETDEWEB)

Dutta, S K

1974-11-01

Several fungal species, representatives of all broad groups like basidiomycetes, ascomycetes and phycomycetes, were examined for the nature of repeated DNA sequences by DNA:DNA reassociation studies using hydroxyapatite chromatography. All of the fungal species tested contained 10 to 20 percent repeated DNA sequences. There are approximately 100 to 110 copies of repeated DNA sequences of approximately 4 x 10/sup 7/ daltons piece size of each. Repeated DNA sequence homoduplexes showed on average 5/sup 0/C difference of T/sub e/50 (temperature at which 50 percent duplexes dissociate) values from the corresponding homoduplexes of unfractionated whole DNA. It is suggested that a part of repetitive sequences in fungi constitutes mitochondrial DNA and a part of it constitutes nuclear DNA. (auth)

Topological characteristics of helical repeat proteins

NARCIS (Netherlands)

Groves, M R; Barford, D

The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem

Vertical Integration Heats Up in Drug Industry: Will Medication Price Hikes Cool Down as a Result?

Science.gov (United States)

Barlas, Stephen

2018-01-01

Is industry consolidation a response to President Donald Trump's repeated denunciation of high drug prices and congressional hearings on the issue? The author considers whether any of this corporate collaboration will get at some of the significant, underlying problems in the drug-pricing space.

A flow-cytometric NK-cytotoxicity assay adapted for use in rat repeated dose toxicity studies

International Nuclear Information System (INIS)

Marcusson-Staahl, Maritha; Cederbrant, Karin

2003-01-01

A recent regulatory document for immunotoxicity testing of new pharmaceutical drugs includes cytotoxic natural killer (NK)-cell function as a required parameter in repeated dose toxicity studies. The classical 51 Cr-release assay is the conventional test for cytotoxicity testing but several drawbacks with this assay has increased the demand for new reliable test systems. Here, we describe the optimisation of a flow-cytometric cytotoxicity assay especially adapted for regulatory rat studies in drug development. The test principle is based on target cell labelling with 5-(6)-carboxy-fluorescein succinimidyl ester (CFSE) and subsequent DNA-labelling with propidium iodide (PI) for identification of target cells with compromised cell membranes. The results are expressed as percentage of dead targets on a cell-to-cell basis. The final format of the assay includes 0.5 ml peripheral blood, 1.25x10 5 effector cells per sample, and collection of 500 target events by flow-cytometry. When NKR-P1+ cells were removed from the effector cell population by magnetic depletion the relative proportion decreased from 6 to 0.08%. The corresponding cytotoxic activity decreased from 68 to 8%. Also, the cytotoxic activity showed a significant and positive correlation with the proportion of NK-cells present in the effector cell suspension. Thus, the cytotoxicity measured is almost exclusively exerted by NK-cells. The current flow-cytometric test benefits from using peripheral blood as a source for effector cells since it will not conflict with the use of spleen for histopathological investigations in repeated dose toxicity studies. Additionally, since only a minimal number of effector cells are required per sample repeated testing of the same animal is enabled

Unique Behavioral and Neurochemical Effects Induced by Repeated Adolescent Consumption of Caffeine-Mixed Alcohol in C57BL/6 Mice.

Directory of Open Access Journals (Sweden)

Meridith T Robins

Full Text Available The number of highly caffeinated products has increased dramatically in the past few years. Among these products, highly caffeinated energy drinks are the most heavily advertised and purchased, which has resulted in increased incidences of co-consumption of energy drinks with alcohol. Despite the growing number of adolescents and young adults reporting caffeine-mixed alcohol use, knowledge of the potential consequences associated with co-consumption has been limited to survey-based results and in-laboratory human behavioral testing. Here, we investigate the effect of repeated adolescent (post-natal days P35-61 exposure to caffeine-mixed alcohol in C57BL/6 mice on common drug-related behaviors such as locomotor sensitivity, drug reward and cross-sensitivity, and natural reward. To determine changes in neurological activity resulting from adolescent exposure, we monitored changes in expression of the transcription factor ΔFosB in the dopaminergic reward pathway as a sign of long-term increases in neuronal activity. Repeated adolescent exposure to caffeine-mixed alcohol exposure induced significant locomotor sensitization, desensitized cocaine conditioned place preference, decreased cocaine locomotor cross-sensitivity, and increased natural reward consumption. We also observed increased accumulation of ΔFosB in the nucleus accumbens following repeated adolescent caffeine-mixed alcohol exposure compared to alcohol or caffeine alone. Using our exposure model, we found that repeated exposure to caffeine-mixed alcohol during adolescence causes unique behavioral and neurochemical effects not observed in mice exposed to caffeine or alcohol alone. Based on similar findings for different substances of abuse, it is possible that repeated exposure to caffeine-mixed alcohol during adolescence could potentially alter or escalate future substance abuse as means to compensate for these behavioral and neurochemical alterations.

13,915 reasons for equity in sexual offences legislation: A national school-based survey in South Africa

Directory of Open Access Journals (Sweden)

Ho-Foster Ari

2008-07-01

Full Text Available Abstract Objective Prior to 2007, forced sex with male children in South Africa did not count as rape but as "indecent assault", a much less serious offence. This study sought to document prevalence of male sexual violence among school-going youth. Design A facilitated self-administered questionnaire in nine of the 11 official languages in a stratified (province/metro/urban/rural last stage random national sample. Setting Teams visited 5162 classes in 1191 schools, in October and November 2002. Participants A total of 269,705 learners aged 10–19 years in grades 6–11. Of these, 126,696 were male. Main outcome measures Schoolchildren answered questions about exposure in the last year to insults, beating, unwanted touching and forced sex. They indicated the sex of the perpetrator, and whether this was a family member, a fellow schoolchild, a teacher or another adult. Respondents also gave the age when they first suffered forced sex and when they first had consensual sex. Results Some 9% (weighted value based on 13915/127097 of male respondents aged 11–19 years reported forced sex in the last year. Of those aged 18 years at the time of the survey, 44% (weighted value of 5385/11450 said they had been forced to have sex in their lives and 50% reported consensual sex. Perpetrators were most frequently an adult not from their own family, followed closely in frequency by other schoolchildren. Some 32% said the perpetrator was male, 41% said she was female and 27% said they had been forced to have sex by both male and female perpetrators. Male abuse of schoolboys was more common in rural areas while female perpetration was more an urban phenomenon. Conclusion This study uncovers endemic sexual abuse of male children that was suspected but hitherto only poorly documented. Legal recognition of the criminality of rape of male children is a first step. The next steps include serious investment in supporting male victims of abuse, and in prevention of

UK 2009-2010 repeat station report

Directory of Open Access Journals (Sweden)

Thomas J.G. Shanahan

2013-03-01

Full Text Available The British Geological Survey is responsible for conducting the UK geomagnetic repeat station programme. Measurements made at the UK repeat station sites are used in conjunction with the three UK magnetic observatories: Hartland, Eskdalemuir and Lerwick, to produce a regional model of the local field each year. The UK network of repeat stations comprises 41 stations which are occupied at approximately 3-4 year intervals. Practices for conducting repeat station measurements continue to evolve as advances are made in survey instrumentation and as the usage of the data continues to change. Here, a summary of the 2009 and 2010 UK repeat station surveys is presented, highlighting the measurement process and techniques, density of network, reduction process and recent results.

Reject/repeat analysis and the effect prior film viewing has on a department's reject/repeat rate

International Nuclear Information System (INIS)

Clark, P.A.; Hogg, P.

2003-01-01

Purpose: Achieving cost-effectiveness within the NHS is an old initiative but one that has again been highlighted by recent government policies (The New NHS-Modern and Dependable, Stationary Office, London, 1997). It has been reiterated that it is the responsibility of individual Trusts to devise means to provide such a service. Reject/repeat analyses have long been the primary tool used to assess the cost-effectiveness of radiography departments (Quality Assurance in Diagnostic Radiology, WHO, Geneva, 1982). This research paper examines an in-house initiative (viewing patients' previous films) commonly employed in other Health Trusts in order to reduce departmental repeat/reject rates. Method: Three hundred orthopaedic patients with hip, knee and ankle prostheses were included in a reject/repeat analysis. The aim was to investigate whether or not viewing patient's previous relevant radiographs would be advantageous to the practicing radiographer. This was done through an audit cycle consisting of two audit periods each lasting for 3 months. The primary audit period recorded the baseline repeat/reject rate, with the secondary audit period recording the repeat/reject rate under an experimental condition of viewing the relevant radiographs. Results: The baseline audit revealed repeat rates of 33% in orthopaedic patients with hip, knee and ankle prostheses. The availability of prior film viewing to the radiographer reduced this repeat rate to 10.6%. Conclusion: Prior film viewing dramatically reduced the department's repeat/reject rate by 22.4%. This provides scope for significant patient dose reductions as well as reducing departmental film expenses. This is an underestimated initiative and should be used appropriately in routine clinical practice

Temporal asthma patterns using repeated questionnaires over 13 years in a large French cohort of women.

Directory of Open Access Journals (Sweden)

Margaux Sanchez

Full Text Available Variable expression is one aspect of the heterogeneity of asthma. We aimed to define a variable pattern, which is relevant in general health epidemiological cohorts. Our objectives were to assess whether: 1 asthma patterns defined using simple asthma questions through repeated measurements could reflect disease variability 2 these patterns may further be classified according to asthma severity/control. Among 70,428 French women, we used seven questionnaires (1992-2005 and a comprehensive reimbursement database (2004-2009 to define three reliable asthma patterns based on repeated positive answers to the ever asthma attack question: "never asthma" (n = 64,061; "inconsistent" ("yes" followed by "no", n = 3,514; "consistent" (fully consistent positive answers, n = 2,853. The "Inconsistent" pattern was related to both long-term (childhood-onset asthma with remission in adulthood and short-term (reported asthma attack in the last 12 months, associated with asthma medication asthma variability, showing that repeated questions are relevant markers of the variable expression of asthma. Furthermore, in this pattern, the number of positive responses (1992-2005 predicted asthma drug consumption in subsequent years, a marker of disease severity. The "Inconsistent" pattern is a phenotype that may capture the variable expression of asthma. Repeated answers, even to a simple question, are too often neglected.

Repeating Marx

DEFF Research Database (Denmark)

Fuchs, Christian; Monticelli, Lara

2018-01-01

This introduction sets out the context of the special issue “Karl Marx @ 200: Debating Capitalism & Perspectives for the Future of Radical Theory”, which was published on the occasion of Marx’s bicentenary on 5 May 2018. First, we give a brief overview of contemporary capitalism’s development...... and its crises. Second, we argue that it is important to repeat Marx today. Third, we reflect on lessons learned from 200 years of struggles for alternatives to capitalism. Fourth, we give an overview of the contributions in this special issue. Taken together, the contributions in this special issue show...... that Marx’s theory and politics remain key inspirations for understanding exploitation and domination in 21st-century society and for struggles that aim to overcome these phenomena and establishing a just and fair society. We need to repeat Marx today....

Repeated administration of amitriptyline reduces oxaliplatin-induced mechanical allodynia in rats.

Science.gov (United States)

Sada, Hikaru; Egashira, Nobuaki; Ushio, Soichiro; Kawashiri, Takehiro; Shirahama, Masafumi; Oishi, Ryozo

2012-01-01

Oxaliplatin is a key drug in the treatment of colorectal cancer, but it causes acute and chronic neuropathies in patients. Amitriptyline has widely been used in patients with painful neuropathy. In this study, we investigated the effect of amitriptyline on the oxaliplatin-induced neuropathy in rats. Repeated administration of amitriptyline (5 and 10 mg/kg, p.o., once a day) reduced the oxaliplatin-induced mechanical allodynia but not cold hyperalgesia and reversed the oxaliplatin-induced increase in the expression of NR2B protein and mRNA in rat spinal cord. These results suggest that amitriptyline is useful for the treatment of oxaliplatin-induced neuropathy clinically.

Analysis of repeated measures data

CERN Document Server

Islam, M Ataharul

2017-01-01

This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

Microdialysis as a tool for drug quantification in the bronchioles of anaesthetized pigs

DEFF Research Database (Denmark)

Rottbøll, Lisa Amanda Holm; Friis, Christian

2014-01-01

through a tracheostomy into the distal bronchioles using an insertion tube. Intravenously administered inulin served as a marker of extracellular fluid contamination of PELF. Concentrations of free drug in MD fractions were compared to total and non-protein-bound drug concentrations in plasma. Rising...... equipment, the danofloxacin concentrations in PELF were consistent within the different administration groups. The described MD method for drug quantification in PELF is easily accessible and provides repeatable results. However, trace amount of inulin was detected in the MD fractions, suggesting a local...

Generic and crime type specific correlates of youth crime: a Finnish population-based study.

Science.gov (United States)

Elonheimo, Henrik; Sourander, Andre; Niemelä, Solja; Helenius, Hans

2011-09-01

The aim of this study was to examine the psychosocial correlates of various crime types among adolescent males born in Finland in 1981. Data on crime registered in the Finnish National Police Register between 1998 and 2001 were received for 2,866 boys, of whom 81% (n = 2,330) filled in a questionnaire at obligatory military call-up at age 18 in 1999. Crime was divided into five types: drug, violent, property, traffic, and drunk driving offences. Of the 2,866 boys, 23% had been registered for offending; 4% for drug, 7% for violent, 11% for property, 11% for traffic, and 5% for drunk driving offences during the 4-year period in late adolescence. All the crime types correlated with each other and shared many of the psychosocial problems. Small community size, parents' divorce, aggressiveness, daily smoking, and weekly drunkenness were generic correlates of crime, being independently related to various crime types. The results support general rather than specific accounts of youth crime. In particular, measures moderating the adverse effects of divorce, alleviating parental adversities and supporting parenthood, and tackling substance abuse seem relevant in social and criminal policy because they address psychosocial problems characterizing youth crime in general.

simple sequence repeats (EST-SSR)

African Journals Online (AJOL)

Yomi

2012-01-19

Jan 19, 2012 ... 212 primer pairs selected, based on repeat patterns of n≥8 for di-, tri-, tetra- and penta-nucleotide repeat ... Cluster analysis revealed a high genetic similarity among the sugarcane (Saccharum spp.) breeding lines which could reduce the genetic gain in ..... The multiple allele characteristic of SSR com-.

Nifty Nines and Repeating Decimals

Science.gov (United States)

Brown, Scott A.

2016-01-01

The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

Repeated Prescribed Burning in Aspen

Science.gov (United States)

Donald A. Perala

1974-01-01

Infrequent burning weather, low flammability of the aspen-hardwood association, and prolific sprouting and seeding of shrubs and hardwoods made repeated dormant season burning a poor tool to convert good site aspen to conifers. Repeat fall burns for wildlife habitat maintenance is workable if species composition changes are not important.

Receptionist input to quality and safety in repeat prescribing in UK general practice: ethnographic case study.

Science.gov (United States)

Swinglehurst, Deborah; Greenhalgh, Trisha; Russell, Jill; Myall, Michelle

2011-11-03

To describe, explore, and compare organisational routines for repeat prescribing in general practice to identify contributors and barriers to safety and quality. Ethnographic case study. Four urban UK general practices with diverse organisational characteristics using electronic patient records that supported semi-automation of repeat prescribing. 395 hours of ethnographic observation of staff (25 doctors, 16 nurses, 4 healthcare assistants, 6 managers, and 56 reception or administrative staff), and 28 documents and other artefacts relating to repeat prescribing locally and nationally. Potential threats to patient safety and characteristics of good practice. Observation of how doctors, receptionists, and other administrative staff contributed to, and collaborated on, the repeat prescribing routine. Analysis included mapping prescribing routines, building a rich description of organisational practices, and drawing these together through narrative synthesis. This was informed by a sociological model of how organisational routines shape and are shaped by information and communications technologies. Results Repeat prescribing was a complex, technology-supported social practice requiring collaboration between clinical and administrative staff, with important implications for patient safety. More than half of requests for repeat prescriptions were classed as "exceptions" by receptionists (most commonly because the drug, dose, or timing differed from what was on the electronic repeat list). They managed these exceptions by making situated judgments that enabled them (sometimes but not always) to bridge the gap between the idealised assumptions about tasks, roles, and interactions that were built into the electronic patient record and formal protocols, and the actual repeat prescribing routine as it played out in practice. This work was creative and demanded both explicit and tacit knowledge. Clinicians were often unaware of this input and it did not feature in policy

Behavioral Characteristics and Neurobiological Substrates Shared by Pavlovian Sign-Tracking and Drug Abuse

OpenAIRE

Tomie, Arthur; Grimes, Kathryn L.; Pohorecky, Larissa A.

2007-01-01

Drug abuse researchers have noted striking similarities between behaviors elicited by Pavlovian sign-tracking procedures and prominent symptoms of drug abuse. In Pavlovian sign-tracking procedures, repeated paired presentations of a small object (conditioned stimulus, CS) with a reward (unconditioned stimulus, US) elicits a conditioned response (CR) that typically consists of approaching the CS, contacting the CS, and expressing consummatory responses at the CS. Sign-tracking CR performance i...

Radiopharmaceuticals drug interactions: a critical review

International Nuclear Information System (INIS)

Santos-Oliveira, Ralph; Smith, Sheila W.; Carneiro-Leao, Ana Maria A.

2008-01-01

Radiopharmaceuticals play a critical role in modern medicine primarily for diagnostic purposes, but also for monitoring disease progression and response to treatment. As the use of image has been increased, so has the use of prescription medications. These trends increase the risk of interactions between medications and radiopharmaceuticals. These interactions which have an impact on image by competing with the radiopharmaceutical for binding sites for example can lead to false negative results. Drugs that accelerate the metabolism of the radiopharmaceutical can have a positive impact (i.e. speeding its clearance) or, if repeating image is needed, a negative impact. In some cases, for example in cardiac image among patients taking doxirubacin, these interactions may have a therapeutic benefit. The incidence of drug-radiopharmaceuticals adverse reactions is unknown, since they may not be reported or even recognized. Here, we compiled the medical literature, using the criteria of a systematic review established by the Cochrane Collaboration, on pharmaceutical-drug interactions to provide a summary of documented interactions by organ system and radiopharmaceuticals. The purpose is to provide a reference on drug interactions that could inform the nuclear medicine staff in their daily routine. Efforts to increase adverse event reporting, and ideally consolidate reports worldwide, can provide a critically needed resource for prevention of drug-radiopharmaceuticals interactions. (author)

Effectiveness of HIV prevention social marketing with injecting drug users.

Science.gov (United States)

Gibson, David R; Zhang, Guili; Cassady, Diana; Pappas, Les; Mitchell, Joyce; Kegeles, Susan M

2010-10-01

Social marketing involves applying marketing principles to promote social goods. In the context of health behavior, it has been used successfully to reduce alcohol-related car crashes, smoking among youths, and malaria transmission, among other goals. Features of social marketing, such as audience segmentation and repeated exposure to prevention messages, distinguish it from traditional health promotion programs. A recent review found 8 of 10 rigorously evaluated social marketing interventions responsible for changes in HIV-related behavior or behavioral intentions. We studied 479 injection drug users to evaluate a community-based social marketing campaign to reduce injection risk behavior among drug users in Sacramento, California. Injecting drugs is associated with HIV infection in more than 130 countries worldwide.

Repeat HIV Testing at Voluntary Testing and Counseling Centers in Croatia: Successful HIV Prevention or Failure to Modify Risk Behaviors?

Science.gov (United States)

Matković Puljić, Vlatka; Kosanović Ličina, Mirjana Lana; Kavić, Marija; Nemeth Blažić, Tatjana

2014-01-01

HIV testing plays a critical role in preventing the spread of the virus and identifying infected individuals in need of care. Voluntary counseling and testing centers (VCTs) not only conduct testing but they also provide counseling. Since a proportion of people who test negative for HIV on their previous visit will return for retesting, the frequency of retesting and the characteristics of those who retest may provide insights into the efficacy of testing and counseling strategies. In this cross-sectional, retrospective study of 1,482 VCT clients in Croatia in 2010, 44.3% had been tested for HIV before. The rate of repeat HIV testing is lower in Croatia than in other countries. Men who have sex with men (MSM) clients, those with three or more sexual partners in the last 12 months, consistent condom users with steady partners, and intravenous drug users were more likely to be repeat testers. This finding suggests that clients presenting for repeat HIV testing are those who self-identify as being at a higher risk of infection. Our data showed that testing positive for HIV was not associated with repeat testing. However, the effects of repeat testing on HIV epidemiology needs to be explored. PMID:24705595

The Pentapeptide Repeat Proteins

OpenAIRE

Vetting, Matthew W.; Hegde, Subray S.; Fajardo, J. Eduardo; Fiser, Andras; Roderick, Steven L.; Takiff, Howard E.; Blanchard, John S.

2006-01-01

The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S,T,A,V][D,N][L,F]-[S,T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Myc...

The journey from traffic offender to severe road trauma victim: destiny or preventive opportunity?

Science.gov (United States)

Ho, Kwok M; Rao, Sudhakar; Burrell, Maxine; Weeramanthri, Tarun S

2015-01-01

Road trauma is a leading cause of death and injury in young people. Traffic offences are common, but their importance as a risk indicator for subsequent road trauma is unknown. This cohort study assessed whether severe road trauma could be predicted by a history of prior traffic offences. Clinical data of all adult road trauma patients admitted to the Western Australia (WA) State Trauma Centre between 1998 and 2013 were linked to traffic offences records at the WA Department of Transport. The primary outcomes were alcohol exposure prior to road trauma, severe trauma (defined by Injury Severity Score >15), and intensive care admission (ICU) or death, analyzed by logistic regression. Traffic offences directly leading to the road trauma admissions were excluded. Of the 10,330 patients included (median age 34 years-old, 78% male), 1955 (18.9%) had alcohol-exposure before road trauma, 2415 (23.4%) had severe trauma, 1360 (13.2%) required ICU admission, and 267 (2.6%) died. Prior traffic offences were recorded in 6269 (60.7%) patients. The number of prior traffic offences was significantly associated with alcohol-related road trauma (odds ratio [OR] per offence 1.03, 95% confidence interval [CI] 1.02-1.05), severe trauma (OR 1.13, 95%CI 1.14-1.15), and ICU admission or death (OR 1.10, 95%CI 1.08-1.11). Drink-drinking, seat-belt, and use of handheld electronic device offences were specific offences strongly associated with road trauma leading to ICU admission or death--all in a 'dose-related' fashion. For those who recovered from road trauma after an ICU admission, there was a significant reduction in subsequent traffic offences (mean difference 1.8, 95%CI 1.5 to 2.0) and demerit points (mean difference 7.0, 95%CI 6.5 to 7.6) compared to before the trauma event. Previous traffic offences were a significant risk factor for alcohol-related road trauma and severe road trauma leading to ICU admission or death.

The journey from traffic offender to severe road trauma victim: destiny or preventive opportunity?

Directory of Open Access Journals (Sweden)

Kwok M Ho

Full Text Available Road trauma is a leading cause of death and injury in young people. Traffic offences are common, but their importance as a risk indicator for subsequent road trauma is unknown. This cohort study assessed whether severe road trauma could be predicted by a history of prior traffic offences.Clinical data of all adult road trauma patients admitted to the Western Australia (WA State Trauma Centre between 1998 and 2013 were linked to traffic offences records at the WA Department of Transport. The primary outcomes were alcohol exposure prior to road trauma, severe trauma (defined by Injury Severity Score >15, and intensive care admission (ICU or death, analyzed by logistic regression. Traffic offences directly leading to the road trauma admissions were excluded. Of the 10,330 patients included (median age 34 years-old, 78% male, 1955 (18.9% had alcohol-exposure before road trauma, 2415 (23.4% had severe trauma, 1360 (13.2% required ICU admission, and 267 (2.6% died. Prior traffic offences were recorded in 6269 (60.7% patients. The number of prior traffic offences was significantly associated with alcohol-related road trauma (odds ratio [OR] per offence 1.03, 95% confidence interval [CI] 1.02-1.05, severe trauma (OR 1.13, 95%CI 1.14-1.15, and ICU admission or death (OR 1.10, 95%CI 1.08-1.11. Drink-drinking, seat-belt, and use of handheld electronic device offences were specific offences strongly associated with road trauma leading to ICU admission or death--all in a 'dose-related' fashion. For those who recovered from road trauma after an ICU admission, there was a significant reduction in subsequent traffic offences (mean difference 1.8, 95%CI 1.5 to 2.0 and demerit points (mean difference 7.0, 95%CI 6.5 to 7.6 compared to before the trauma event.Previous traffic offences were a significant risk factor for alcohol-related road trauma and severe road trauma leading to ICU admission or death.

Educator Sexual Misconduct: Exposing or Causing Learners to Be Exposed to Child Pornography or Pornography

Directory of Open Access Journals (Sweden)

Susan Coetzee

2016-02-01

Full Text Available he law recognises that non-contact sexual offences can cause harm and several offences were created to regulate non-contact sexual child abuse offences. Several of these offences deal with the exposure or causing exposure of children to child pornography or pornography. Sexual grooming of children and the “Exposure or display of or causing exposure or display of child pornography or pornography to children” are criminalised in sections 18(2 and 19 of the Criminal Law (Sexual Offences and Related Matters Amendment Act 32 of 2007. And offences in relation to exposing children to disturbing, harmful and age-inappropriate materials are criminalised in sections 24A(2 and (4 of the Films and Publications Act 65 of 1996. In this article the author considered the content of the offences of “Exposure or display of or causing exposure or display of child pornography or pornography to children” in relation to the other offences dealing with exposure of children to child pornography or pornography. Benchmarked against these criminal offences the author then conceptualised exposing learners, or causing the exposure of learners to child pornography or pornography as forms of educator misconduct. The seriousness that should be attached to these forms of misconduct was considered in light of the various criminal offences. The review of the criminal offences and the forms of educator misconduct brought the ineffectiveness of current forms of serious educator misconduct to the fore. There is no form of serious misconduct that covers the transgression of educators who expose learners to child pornography or pornography that can be classified as “XX”. In conclusion a suggestion is made with regard to how a new form of serious misconduct could be worded so as to cover this gap, eg An educator must be dismissed if he or she is found guilty of – (g exposing a learner to or causing exposure of a learner to material classified as “Refused” or �

Making an Arsonist: A Psychological Approach to Understanding Expressive Arson

OpenAIRE

Mojtahedi, Dara; Prince, Rebecca J.; Ryan, Saskia

2017-01-01

The offence of arson comes under the category of property crime, although the serious consequences of the offence often have a huge impact on both people and public costs, with serious injury and death potential outcomes. As with many crimes, there are various motivations that may behind a person committing arson. These can be understood under whether the offence was instrumental and therefore carrying out the crime for personal gain, or expressive, carrying out the offence due to difficulty ...

Using Nonexperts for Annotating Pharmacokinetic Drug-Drug Interaction Mentions in Product Labeling: A Feasibility Study.

Science.gov (United States)

Hochheiser, Harry; Ning, Yifan; Hernandez, Andres; Horn, John R; Jacobson, Rebecca; Boyce, Richard D

2016-04-11

Because vital details of potential pharmacokinetic drug-drug interactions are often described in free-text structured product labels, manual curation is a necessary but expensive step in the development of electronic drug-drug interaction information resources. The use of nonexperts to annotate potential drug-drug interaction (PDDI) mentions in drug product label annotation may be a means of lessening the burden of manual curation. Our goal was to explore the practicality of using nonexpert participants to annotate drug-drug interaction descriptions from structured product labels. By presenting annotation tasks to both pharmacy experts and relatively naïve participants, we hoped to demonstrate the feasibility of using nonexpert annotators for drug-drug information annotation. We were also interested in exploring whether and to what extent natural language processing (NLP) preannotation helped improve task completion time, accuracy, and subjective satisfaction. Two experts and 4 nonexperts were asked to annotate 208 structured product label sections under 4 conditions completed sequentially: (1) no NLP assistance, (2) preannotation of drug mentions, (3) preannotation of drug mentions and PDDIs, and (4) a repeat of the no-annotation condition. Results were evaluated within the 2 groups and relative to an existing gold standard. Participants were asked to provide reports on the time required to complete tasks and their perceptions of task difficulty. One of the experts and 3 of the nonexperts completed all tasks. Annotation results from the nonexpert group were relatively strong in every scenario and better than the performance of the NLP pipeline. The expert and 2 of the nonexperts were able to complete most tasks in less than 3 hours. Usability perceptions were generally positive (3.67 for expert, mean of 3.33 for nonexperts). The results suggest that nonexpert annotation might be a feasible option for comprehensive labeling of annotated PDDIs across a broader

Influence of some anti-inflammatory drugs on the activity of aryl hydrocarbon hydroxylase and the cytochrome P450 content

Energy Technology Data Exchange (ETDEWEB)

Mostafa, M.H.; Sheweita, S.A.; Abdel-Moneam, N.M. (Alexandria Univ. (Egypt))

1990-06-01

The metabolism of benzo({alpha})pyrene is mediated by the mixed function oxidase system including the cytochrome P450-dependent aryl hydrocarbon hydroxylase. The data of the present study revealed the ability of various commonly used anti-inflammatory drugs to alter the activity of this enzyme system, where all the tested drugs, namely phenyl butazone, ketoprofen, piroxicam, and acetaminophen, caused an increase in both the activity of aryl hydrocarbon hydroxylase and the cytochrome P450 content whether administered as a single dose or as a repeated dose for 6 consecutive days. The percentage of change for all drugs except phenyl butazone was proportional to the duration of drug administration. On the other hand, pyrazole which is chemically related to phenyl butazone, had no significant effect when administered as a single dose but caused a decrease in both studied parameters when administered as a repeated dose for 6 consecutive days. The mechanisms by which these commonly used drugs modify the aryl hydrocarbon hydroxylase activity and the cytochrome p450 content are discussed in the text.

In situ detection of tandem DNA repeat length

Energy Technology Data Exchange (ETDEWEB)

Yaar, R.; Szafranski, P.; Cantor, C.R.; Smith, C.L. [Boston Univ., MA (United States)

1996-11-01

A simple method for scoring short tandem DNA repeats is presented. An oligonucleotide target, containing tandem repeats embedded in a unique sequence, was hybridized to a set of complementary probes, containing tandem repeats of known lengths. Single-stranded loop structures formed on duplexes containing a mismatched (different) number of tandem repeats. No loop structure formed on duplexes containing a matched (identical) number of tandem repeats. The matched and mismatched loop structures were enzymatically distinguished and differentially labeled by treatment with S1 nuclease and the Klenow fragment of DNA polymerase. 7 refs., 4 figs.

Automated genotyping of dinucleotide repeat markers

Energy Technology Data Exchange (ETDEWEB)

Perlin, M.W.; Hoffman, E.P. [Carnegie Mellon Univ., Pittsburgh, PA (United States)]|[Univ. of Pittsburgh, PA (United States)

1994-09-01

The dinucleotide repeats (i.e., microsatellites) such as CA-repeats are a highly polymorphic, highly abundant class of PCR-amplifiable markers that have greatly streamlined genetic mapping experimentation. It is expected that over 30,000 such markers (including tri- and tetranucleotide repeats) will be characterized for routine use in the next few years. Since only size determination, and not sequencing, is required to determine alleles, in principle, dinucleotide repeat genotyping is easily performed on electrophoretic gels, and can be automated using DNA sequencers. Unfortunately, PCR stuttering with these markers generates not one band for each allele, but a pattern of bands. Since closely spaced alleles must be disambiguated by human scoring, this poses a key obstacle to full automation. We have developed methods that overcome this obstacle. Our model is that the observed data is generated by arithmetic superposition (i.e., convolution) of multiple allele patterns. By quantitatively measuring the size of each component band, and exploiting the unique stutter pattern associated with each marker, closely spaced alleles can be deconvolved; this unambiguously reconstructs the {open_quotes}true{close_quotes} allele bands, with stutter artifact removed. We used this approach in a system for automated diagnosis of (X-linked) Duchenne muscular dystrophy; four multiplexed CA-repeats within the dystrophin gene were assayed on a DNA sequencer. Our method accurately detected small variations in gel migration that shifted the allele size estimate. In 167 nonmutated alleles, 89% (149/167) showed no size variation, 9% (15/167) showed 1 bp variation, and 2% (3/167) showed 2 bp variation. We are currently developing a library of dinucleotide repeat patterns; together with our deconvolution methods, this library will enable fully automated genotyping of dinucleotide repeats from sizing data.

Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys.

Science.gov (United States)

Banks, Matthew L

2016-08-01

Preclinical drug vs. food choice is an emerging group of drug self-administration procedures that have shown predictive validity to clinical drug addiction. Emerging data suggest that serotonin (5-HT)2A receptors modulate mesolimbic dopamine function, such that 5-HT2A antagonists blunt the abuse-related neurochemical effects of monoamine transporter substrates, such as amphetamine or methamphetamine. Whether subchronic 5-HT2A antagonist treatment attenuates methamphetamine reinforcement in any preclinical drug self-administration procedure is unknown. The study aim was therefore to determine 7-day treatment effects with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in monkeys. Behavior was maintained under a concurrent schedule of food delivery (1g pellets, fixed-ratio 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=3). Methamphetamine choice dose-effect functions were determined daily before and during 7-day repeated pimavanserin (1.0-10mg/kg/day, intramuscular) treatment periods. Under control conditions, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Repeated pimavanserin administration failed to attenuate methamphetamine choice and produce a reciprocal increase in food choice in any monkey up to doses (3.2-10mg/kg) that suppressed rates of operant responding primarily during components where behavior was maintained by food pellets. Repeated 5-HT2A receptor inverse agonist/antagonist treatment did not attenuate methamphetamine reinforcement under a concurrent schedule of intravenous methamphetamine and food presentation in nonhuman primates. Overall, these results do not support the therapeutic potential of 5-HT2A inverse agonists/antagonists as candidate medications for methamphetamine addiction. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights

Joornaalii Seeraa Oromiyaa [Jiil.5, Lak.1, 2008] Oromia Law Journal ...

African Journals Online (AJOL)

court structure presupposes that the federal courts adjudicate federal ... power. This article explores how the state courts are adjudicating federal ...... the internal security of the state, offences against foreign states, offences ... services operating within more than one region or at the international level, offences against.

Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment

NARCIS (Netherlands)

Chaudhari, U.; Nemade, H.; Wagh, V.; Ellis, J.K.; Srinivasan, S.; Louisse, J.

2016-01-01

The currently available techniques for the safety evaluation of candidate drugs are usually cost-intensive and time-consuming and are often insufficient to predict human relevant cardiotoxicity. The purpose of this study was to develop an in vitro repeated exposure toxicity methodology allowing the

Beyond recidivism: changes in health and social service involvement following exposure to drug treatment court.

Science.gov (United States)

Rezansoff, Stefanie N; Moniruzzaman, Akm; Clark, Elenore; Somers, Julian M

2015-10-31

The majority of Drug Treatment Court (DTC) research has examined the impact of DTCs on criminal recidivism. Comparatively little research has addressed the association between DTC participation and engagement with community-based health and social services. The present study investigated changes in participant involvement with outpatient healthcare and income assistance within a DTC cohort. We hypothesized that involvement with community-based (outpatient) health and social services would increase post-DTC participation, and that service levels would be higher among program graduates and offenders with histories of co-occurring mental and substance use disorders. Participants were 631 offenders at the DTC in Vancouver, Canada (DTCV). Administrative data representing hospital, outpatient medical care, and income assistance were examined one-year pre/post program to assess differences over time. Generalized estimating equations were used to investigate the association between changes in service use and program involvement. We also examined the relationship between level of service use and offender characteristics. Members of the cohort were disproportionately Aboriginal (33 %), had been sentenced 2.7 times in the 2 years preceding their index offence, and 50 % had been diagnosed with a non substance-related mental disorder in the five years preceding the index offence. The mean number of outpatient services post DTCV was 51, and the mean amount of social assistance paid was $5,897. Outpatient service use increased following exposure to DTCV (Adjusted Rate Ratio (ARR) = 1.45) and was significantly higher among women (ARR = 1.47), program graduation (ARR = 1.23), and those previously diagnosed with concurrent substance use and mental disorders (ARR = 4.92). Overall, hospital admissions did not increase post-program, although rates were significantly higher among women (ARR = 1.76) and those with concurrent disorders (ARR = 2.71). Income

Evaluation of the health effects of occupational exposure of analytic laboratory workers processing illicit drug investigation files.

Science.gov (United States)

Bentur, Y; Bentur, L; Rotenberg, M; Tepperberg, M; Leiba, R; Wolf, E Udi

2013-05-01

The Analytic Laboratory of Israel Police processes illicit drug files. In recent years, workers of this laboratory have complained of health problems. Limited information exists on the effect of occupational exposure to illicit drugs; biomonitoring was never done. To assess health effects and systemic absorption of illicit drugs in workers of the Analytic Laboratory occupationally exposed to illicit drugs. A prospective cohort study using health and occupational questionnaires, clinical assessments, and monitoring of urinary excretion of illicit drugs was conducted. The study included three blocks of one week each. At each week workers were assessed at the beginning (baseline), and the assessments were repeated at the end of the three working days. Urine specimens were analyzed for illicit drugs in an independent laboratory. Demographic, clinical, occupational, and laboratory data were subjected to descriptive analysis, and paired Student's t-test, chi-square analysis, and repeated measures model. Twenty-seven workers (age, 39.2 ± 8.3 years; 77.8% females) were included, yielding 122 paired samples. The following parameters were reduced at the end of shift compared with baseline: diastolic blood pressure (71.2 ± 11.2 and 77.2 ± 13.6 mmHg, respectively, p health complaints included headache, fatigue, and dry eyes. No illicit drug was detected in the urine specimens. It is suggested that the health concerns of the laboratory workers were not related to the absorption of illicit drugs; environmental conditions (e.g. inadequate ventilation and respirable dust) can contribute to these concerns.

Prescription of the High Risk Narcotics and Trading or Illicit Purchasing of High Risk Narcotics

Directory of Open Access Journals (Sweden)

Nicoleta-Elena Buzatu

2012-05-01

Full Text Available The present essay will analyze the offence of prescribing high risk narcotics and trading or illicit purchasing of high risk narcotics, as it was regulated - together with other offences - by Law no 143 of July 26, 2000 on preventing and fighting against the traffic and illicit consumption of narcotics. The same law defines the meaning of such a phrase “substances which are under national control” by mentioning the fact that they are the narcotics and their precursors listed in Annexes I-IV of the law. The analysis of the offence of prescribing the high risk narcotics and trading or illicit purchasing of high risk narcotics is following the already known structure mentioned in the doctrine and which consists of: object and subjects of the offence, its constituent content: the objective side with its material element, the immediate consequence and causality connections; the subjective side of the offence, as well as forms and modalities of these offences, and the applicable sanctions, of course.

Handling stolen goods in Iranian and English criminal law

Directory of Open Access Journals (Sweden)

Sayyed Mohammad Hoseini

2014-07-01

Full Text Available Handling stolen goods has been recognized as an independent offence in both Iranian and English law. Committing this offence, tacitly support those actions that are called theft. However, penal policy of Iran’s legislator does not provide effective fighting against the handlers of stolen goods. In others words, comparing the two Iranian and English legal system, make this issue clear that criminalization of stolen goods has some restrictions about physical element as well as the amount of relevant punishment that we can have more effective fighting against supporting factors of larceny with eliminating them and hereto, in the course of exercising appropriate reaction to the handlers, reducing the offence of theft. The article seeks to recommend some solutions for a better penal policy, such as increasing punishment of the offence and extending the scope of its physical behaviour, through comparative analysis of the offence of stolen goods; meanwhile different elements of the offence have been studied.

Effects of repeated treatment with MDMA on working memory and behavioural flexibility in mice.

Science.gov (United States)

Viñals, Xavier; Maldonado, Rafael; Robledo, Patricia

2013-03-01

Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) produces dopaminergic neurotoxicity in mice. However, it is still not clear whether this exposure induces deficits in cognitive processing related to specific subsets of executive functioning. We evaluated the effects of neurotoxic and non-neurotoxic doses of MDMA (0, 3 and 30 mg/kg, twice daily for 4 days) on working memory and attentional set-shifting in mice, and changes in extracellular levels of dopamine (DA) in the striatum. Treatment with MDMA (30 mg/kg) disrupted performance of acquired operant alternation, and this impairment was still apparent 5 days after the last drug administration. Decreased alternation was not related to anhedonia because no differences were observed between groups in the saccharin preference test under similar experimental conditions. Correct responding on delayed alternation was increased 1 day after repeated treatment with MDMA (30 mg/kg), probably because of general behavioural quiescence. Notably, the high dose regimen of MDMA impaired attentional set-shifting related to an increase in total perseveration errors. Finally, basal extracellular levels of DA in the striatum were not modified in mice repeatedly treated with MDMA with respect to controls. However, an acute challenge with MDMA (10 mg/kg) failed to increase DA outflow in mice receiving the highest MDMA dose (30 mg/kg), corroborating a decrease in the functionality of DA transporters. Seven days after this treatment, the effects of MDMA on DA outflow were recovered. These results suggest that repeated neurotoxic doses of MDMA produce lasting impairments in recall of alternation behaviour and reduce cognitive flexibility in mice. © 2012 The Authors, Addiction Biology © 2012 Society for the Study of Addiction.

Digital repeat analysis; setup and operation.

Science.gov (United States)

Nol, J; Isouard, G; Mirecki, J

2006-06-01

Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

NK-cell activity in immunotoxicity drug evaluation

International Nuclear Information System (INIS)

Cederbrant, Karin; Marcusson-Staaahl, Maritha; Condevaux, Fabienne; Descotes, Jacques

2003-01-01

NK-cell activity as a tool for detection of immunotoxic effects of new human drugs has gained further attention when the recent European note for guidance CPMP/SWP/1042/99 was adopted. The inclusion of NK-cell activity plus distribution of lymphocyte subsets were suggested as an alternative to the primary antibody response to a T-cell dependent antigen. Either of the two test alternatives should be included as a routine parameter in at least one repeated dose-toxicity study, rats or mice being the species of choice. The standard procedure for measuring NK-cell activity is the 51 Cr-release assay. However, a new flow-cytometric assay, adapted for rat peripheral blood, does not require dedicated groups of animals, offers the possibility of repeated testing, and shows at least as sensitive as the conventional 51 Cr-release assay

Very long Detection Times after High and repeated intake of Heroin and Methadone, measured in Oral Fluid

Directory of Open Access Journals (Sweden)

Vindenes V.

2014-12-01

Full Text Available When detection times for psychoactive drugs in oral fluid are reported, they are most often based on therapeutic doses administered in clinical studies. Repeated ingestions of high doses, as seen after drug abuse, are however likely to cause positive samples for extended time periods. Findings of drugs of abuse in oral fluid might lead to negative sanctions, and the knowledge of detection times of these drugs are important to ensure correct interpretation. The aim of this study was to investigate the detection times of opioids in oral fluid. 25 patients with a history of heavy drug abuse admitted to a detoxification ward were included. Oral fluid and urine were collected daily and, if the patient gave consent, a blood sample was drawn during the first five days after admission. Morphine, codeine and/or 6-monoacetyl morphine (6-MAM were found in oral fluid and/or urine from 20 patients. The maximum detection times in oral fluid for codeine, morphine and 6-MAM were 1, 3 and 8 days, respectively. Positive oral fluid samples were interspersed with negative samples, mainly for concentrations around cut off. Elimination curves for methadone in oral fluid were found for two subjects, and the detection times were 5 and 8 days. Oral fluid is likely to become a good method for detection of drug abuse in the future

Transmission assessment surveys (TAS) to define endpoints for lymphatic filariasis mass drug administration

DEFF Research Database (Denmark)

Chu, Brian K.; Deming, Michael; Biritwum, Nana-Kwadwo

2013-01-01

Lymphatic filariasis (LF) is targeted for global elimination through treatment of entire at-risk populations with repeated annual mass drug administration (MDA). Essential for program success is defining and confirming the appropriate endpoint for MDA when transmission is presumed to have reached...

Prevention of fraud, corruption and bribery committed through legal entities for the purpose of financial and economic gain

NARCIS (Netherlands)

A. Hartmann (Arndt); J.W. van der Hulst (Jaap)

2012-01-01

textabstractIn Dutch law there is no overall criminal offence on corruption. In Dutch criminal law corruption is divided in specific criminal offences which all have their own specific definition. Most corruption can be qualified as a criminal offence but it is sometimes difficult to qualify them as

Drug development in Parkinson's disease: from emerging molecules to innovative drug delivery systems.

Science.gov (United States)

Garbayo, E; Ansorena, E; Blanco-Prieto, M J

2013-11-01

Current treatments for Parkinson's disease (PD) are aimed at addressing motor symptoms but there is no therapy focused on modifying the course of the disease. Successful treatment strategies have been so far limited and brain drug delivery remains a major challenge that restricts its treatment. This review provides an overview of the most promising emerging agents in the field of PD drug discovery, discussing improvements that have been made in brain drug delivery for PD. It will be shown that new approaches able to extend the length of the treatment, to release the drug in a continuous manner or to cross the blood-brain barrier and target a specific region are still needed. Overall, the results reviewed here show that there is an urgent need to develop both symptomatic and disease-modifying treatments, giving priority to neuroprotective treatments. Promising perspectives are being provided in this field by rasagiline and by neurotrophic factors like glial cell line-derived neurotrophic factor. The identification of disease-relevant genes has also encouraged the search for disease-modifying therapies that function by identifying molecularly targeted drugs. The advent of new molecular and cellular targets like α-synuclein, leucine-rich repeat serine/threonine protein kinase 2 or parkin, among others, will require innovative delivery therapies. In this regard, drug delivery systems (DDS) have shown great potential for improving the efficacy of conventional and new PD therapy and reducing its side effects. The new DDS discussed here, which include microparticles, nanoparticles and hydrogels among others, will probably open up possibilities that extend beyond symptomatic relief. However, further work needs to be done before DDS become a therapeutic option for PD patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Genus-specific protein binding to the large clusters of DNA repeats (short regularly spaced repeats) present in Sulfolobus genomes

DEFF Research Database (Denmark)

Peng, Xu; Brügger, Kim; Shen, Biao

2003-01-01

terminally modified and corresponds to SSO454, an open reading frame of previously unassigned function. It binds specifically to DNA fragments carrying double and single repeat sequences, binding on one side of the repeat structure, and producing an opening of the opposite side of the DNA structure. It also...... recognizes both main families of repeat sequences in S. solfataricus. The recombinant protein, expressed in Escherichia coli, showed the same binding properties to the SRSR repeat as the native one. The SSO454 protein exhibits a tripartite internal repeat structure which yields a good sequence match...... with a helix-turn-helix DNA-binding motif. Although this putative motif is shared by other archaeal proteins, orthologs of SSO454 were only detected in species within the Sulfolobus genus and in the closely related Acidianus genus. We infer that the genus-specific protein induces an opening of the structure...

MYCOTIC FEMORAL PSEUDOANEURYSMS FROM INTRAVENOUS DRUG ABUSE

Directory of Open Access Journals (Sweden)

Vojko Flis

2004-04-01

Full Text Available Background. Parenteral drug abuse is the most common cause of infected femoral artery pseudoaneurysms (IFAP. This complication of intravenous drug abuse is not only limb threatening but can also be life threatening. The management of the IFAP is difficult and controversial. Generally speaking, ligation and excision of the pseudoaneurysm without revascularization is accepted procedure in majority of the patients. However it is not regarded as an appropriate procedure for cases where the high probability of amputation is expected from acute interruption of the femoral artery flow.Patients, methods and results. We present three cases of young (average 20 years, range 18–24 patients with IFAP, in which a primary reconstruction was performed due to absence of doppler signal over pedal arteries after ligation of common femoral artery. In two of them complications in form of haemorrhage and repeated infection developed in late postoperative period. The first one, had an excision and ligation while the second one had a reconstruction made by means of a silver impregnated dacron prosthesis. None of the patients required an amputation.Conclusions. Overall prognosis and prognosis of the reconstruction in parenteral drug abuse patients is uncertain because there is a high incidence of postoperative drug injection despite aggressive drug rehabilitation.

Coexistence of 3G repeaters with LTE base stations.

Science.gov (United States)

Yeo, Woon-Young; Lee, Sang-Min; Hwang, Gyung-Ho; Kim, Jae-Hoon

2013-01-01

Repeaters have been an attractive solution for mobile operators to upgrade their wireless networks at low cost and to extend network coverage effectively. Since the first LTE commercial deployment in 2009, many mobile operators have launched LTE networks by upgrading their 3G and legacy networks. Because all 3G frequency bands are shared with the frequency bands for LTE deployment and 3G mobile operators have an enormous number of repeaters, reusing 3G repeaters in LTE networks is definitely a practical and cost-efficient solution. However, 3G repeaters usually do not support spatial multiplexing with multiple antennas, and thus it is difficult to reuse them directly in LTE networks. In order to support spatial multiplexing of LTE, the role of 3G repeaters should be replaced with small LTE base stations or MIMO-capable repeaters. In this paper, a repeater network is proposed to reuse 3G repeaters in LTE deployment while still supporting multilayer transmission of LTE. Interestingly, the proposed network has a higher cluster throughput than an LTE network with MIMO-capable repeaters.

Repeatability & Workability Evaluation of SIGMOD 2009

KAUST Repository

Manegold, Stefan

2010-12-15

SIGMOD 2008 was the first database conference that offered to test submitters\\' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

Repeatability & Workability Evaluation of SIGMOD 2009

KAUST Repository

Manegold, Stefan; Manolescu, Ioana; Afanasiev, Loredana; Feng, Jieling; Gou, G.; Hadjieleftheriou, Marios; Harizopoulos, Stavros; Kalnis, Panos; Karanasos, Konstantinos; Laurent, Dominique; Lupu, M.; Onose, N.; Ré , C.; Sans, Virginie; Senellart, Pierre; Wu, T.; Shasha, Dennis E.

2010-01-01

SIGMOD 2008 was the first database conference that offered to test submitters' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

FRB 121102: A Starquake-induced Repeater?

Science.gov (United States)

Wang, Weiyang; Luo, Rui; Yue, Han; Chen, Xuelei; Lee, Kejia; Xu, Renxin

2018-01-01

Since its initial discovery, the fast radio burst (FRB) FRB 121102 has been found to be repeating with millisecond-duration pulses. Very recently, 14 new bursts were detected by the Green Bank Telescope during its continuous monitoring observations. In this paper, we show that the burst energy distribution has a power-law form which is very similar to the Gutenberg–Richter law of earthquakes. In addition, the distribution of burst waiting time can be described as a Poissonian or Gaussian distribution, which is consistent with earthquakes, while the aftershock sequence exhibits some local correlations. These findings suggest that the repeating FRB pulses may originate from the starquakes of a pulsar. Noting that the soft gamma-ray repeaters (SGRs) also exhibit such distributions, the FRB could be powered by some starquake mechanisms associated with the SGRs, including the crustal activity of a magnetar or solidification-induced stress of a newborn strangeon star. These conjectures could be tested with more repeating samples.

Effects of dopaminergic drug treatments on in vivo radioligand binding to brain vesicular monoamine transporters

Energy Technology Data Exchange (ETDEWEB)

Kilbourn, Michael R; Frey, Kirk A; Vander Borght, Thierry; Sherman, Phillip S

1996-05-01

The effects of various dopaminergic drug treatments on the in vivo regional brain distribution of high-affinity radioligands ([{sup 11}C]dihydrotetrabenazine and [{sup 11}C]methoxytetrabenazine) for the rat brain vesicular monoamine transporter (VMAT2) were determined. Acute treatments with reserpine (2 mg/kg i.p.), tetrabenazine (10 mg/kg i.v.) or related benzoisoquinolines significantly reduced radiotracer binding in vivo. In contrast, radiotracer distributions remained unchanged after treatments with other dopaminergic drugs, whether given by single injection (haloperidol, 1 mg/kg i.p., pargyline 80 mg/kg), repeatedly (pargyline, 80 mg/kg s.c., 14 days), or by continuous infusion (deprenyl, 10 mg/kg/day, 5 days; L-DOPA methyl ester 100 mg/kg/day, 5 days). Repeated injections of tetrabenazine (5 mg/kg i.p., twice daily, 3 days) did not alter in vivo radioligand binding measured after allowing drug washout from the brain. These studies support the proposal that in vivo PET imaging of VMAT2 radioligands in patients with extrapyramidal movement disorders will not be affected by concurrent use of L-DOPA or deprenyl.

Repeatability, Reproducibility and Standardisation of a Laser Doppler Imaging Technique for the Evaluation of Normal Mouse Hindlimb Perfusion

Directory of Open Access Journals (Sweden)

Arturo Brunetti

2012-12-01

Full Text Available Background. Preclinical perfusion studies are useful for the improvement of diagnosis and therapy in dermatologic, cardiovascular and rheumatic human diseases. The Laser Doppler Perfusion Imaging (LDPI technique has been used to evaluate superficial alterations of the skin microcirculation in surgically induced murine hindlimb ischemia. We assessed the reproducibility and the accuracy of LDPI acquisitions and identified several critical factors that could affect LDPI measurements in mice. Methods. Twenty mice were analysed. Statistical standardisation and a repeatability and reproducibility analysis were performed on mouse perfusion signals with respect to differences in body temperature, the presence or absence of hair, the type of anaesthesia used for LDPI measurements and the position of the mouse body. Results. We found excellent correlations among measurements made by the same operator (i.e., repeatability under the same experimental conditions and by two different operators (i.e., reproducibility. A Bland-Altman analysis showed the absence of bias in repeatability (p = 0.29 or reproducibility (p = 0.89. The limits of agreement for repeatability were –0.357 and –0.033, and for reproducibility, they were –0.270 and 0.238. Significant differences in perfusion values were observed in different experimental groups. Conclusions. Different experimental conditions must be considered as a starting point for the evaluation of new drugs and strategic therapies.

Multilayer encapsulated mesoporous silica nanospheres as an oral sustained drug delivery system for the poorly water-soluble drug felodipine

Energy Technology Data Exchange (ETDEWEB)

Hu, Liang [Department of Pharmaceutics, Shenyang Pharmaceutical University, P.O. Box 32, Liaoning Province, Shenyang 110016 (China); Sun, Hongrui [English Teaching Department, School of Basic Courses, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang 110016 (China); Zhao, Qinfu; Han, Ning; Bai, Ling; Wang, Ying; Jiang, Tongying [Department of Pharmaceutics, Shenyang Pharmaceutical University, P.O. Box 32, Liaoning Province, Shenyang 110016 (China); Wang, Siling, E-mail: silingwang@syphu.edu.cn [Department of Pharmaceutics, Shenyang Pharmaceutical University, P.O. Box 32, Liaoning Province, Shenyang 110016 (China)

2015-02-01

We used a combination of mesoporous silica nanospheres (MSN) and layer-by-layer (LBL) self-assembly technology to establish a new oral sustained drug delivery system for the poorly water-soluble drug felodipine. Firstly, the model drug was loaded into MSN, and then the loaded MSN were repeatedly encapsulated by chitosan (CHI) and acacia (ACA) via LBL self-assembly method. The structural features of the samples were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The encapsulating process was monitored by zeta-potential and surface tension measurements. The physical state of the drug in the samples was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The influence of the multilayer with different number of layers on the drug release rate was studied using thermal gravimetric analysis (TGA) and surface tension measurement. The swelling effect and the structure changes of the multilayer were investigated to explore the relationship between the drug release behavior and the state of the multilayer under different pH conditions. The stability and mucosa adhesive ability of the prepared nanoparticles were also explored. After multilayer coating, the drug release rate was effectively controlled. The differences in drug release behavior under different pH conditions could be attributed to the different states of the multilayer. And the nanoparticles possessed good stability and strong mucosa adhesive ability. We believe that this combination offers a simple strategy for regulating the release rate of poorly water-soluble drugs and extends the pharmaceutical applications of inorganic materials and polymers. - Highlights: • A combination of inorganic and organic materials was applied. • Mesoporous silica nanospheres (MSN) were used as drug carriers. • Chitosan and acacia were encapsulated through layer-by-layer self-assembly. • The release rate of the poorly

Multilayer encapsulated mesoporous silica nanospheres as an oral sustained drug delivery system for the poorly water-soluble drug felodipine

International Nuclear Information System (INIS)

Hu, Liang; Sun, Hongrui; Zhao, Qinfu; Han, Ning; Bai, Ling; Wang, Ying; Jiang, Tongying; Wang, Siling

2015-01-01

We used a combination of mesoporous silica nanospheres (MSN) and layer-by-layer (LBL) self-assembly technology to establish a new oral sustained drug delivery system for the poorly water-soluble drug felodipine. Firstly, the model drug was loaded into MSN, and then the loaded MSN were repeatedly encapsulated by chitosan (CHI) and acacia (ACA) via LBL self-assembly method. The structural features of the samples were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and nitrogen adsorption. The encapsulating process was monitored by zeta-potential and surface tension measurements. The physical state of the drug in the samples was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). The influence of the multilayer with different number of layers on the drug release rate was studied using thermal gravimetric analysis (TGA) and surface tension measurement. The swelling effect and the structure changes of the multilayer were investigated to explore the relationship between the drug release behavior and the state of the multilayer under different pH conditions. The stability and mucosa adhesive ability of the prepared nanoparticles were also explored. After multilayer coating, the drug release rate was effectively controlled. The differences in drug release behavior under different pH conditions could be attributed to the different states of the multilayer. And the nanoparticles possessed good stability and strong mucosa adhesive ability. We believe that this combination offers a simple strategy for regulating the release rate of poorly water-soluble drugs and extends the pharmaceutical applications of inorganic materials and polymers. - Highlights: • A combination of inorganic and organic materials was applied. • Mesoporous silica nanospheres (MSN) were used as drug carriers. • Chitosan and acacia were encapsulated through layer-by-layer self-assembly. • The release rate of the poorly

Patterns of drug dependence in a Queensland (Australia) sample of Indigenous and non-Indigenous people who inject drugs.

Science.gov (United States)

Smirnov, Andrew; Kemp, Robert; Ward, James; Henderson, Suzanna; Williams, Sidney; Dev, Abhilash; Najman, Jake M

2016-09-01

Despite over-representation of Indigenous Australians in sentinel studies of injecting drug use, little is known about relevant patterns of drug use and dependence. This study compares drug dependence and possible contributing factors in Indigenous and non-Indigenous Australians who inject drugs. Respondent-driven sampling was used in major cities and 'peer recruitment' in regional towns of Queensland to obtain a community sample of Indigenous (n = 282) and non-Indigenous (n = 267) injectors. Data are cross sectional. Multinomial models were developed for each group to examine types of dependence on injected drugs (no dependence, methamphetamine-dependent only, opioid-dependent only, dependent on methamphetamine and opioids). Around one-fifth of Indigenous and non-Indigenous injectors were dependent on both methamphetamine and opioids in the previous 12 months. Psychological distress was associated with dual dependence on these drugs for Indigenous [adjusted relative risk (ARR) 4.86, 95% confidence interval (CI) 2.08-11.34] and non-Indigenous (ARR 4.14, 95% CI 1.59-10.78) participants. Unemployment (ARR 8.98, 95% CI 2.25-35.82) and repeated (> once) incarceration as an adult (ARR 3.78, 95% CI 1.43-9.97) were associated with dual dependence for Indigenous participants only. Indigenous participants had high rates of alcohol dependence, except for those dependent on opioids only. The drug dependence patterns of Indigenous and non-Indigenous people who inject drugs were similar, including the proportions dependent on both methamphetamine and opioids. However, for Indigenous injectors, there was a stronger association between drug dependence and contextual factors such as unemployment and incarceration. Expansion of treatment options and community-level programs may be required. [Smirnov A, Kemp R, Ward J, Henderson S, Williams S, Dev A, Najman J M. Patterns of drug dependence in a Queensland (Australia) sample of Indigenous and non-Indigenous people who

Factors influencing drug uptake during mass drug administration for control of lymphatic filariasis in rural and urban Tanzania.

Directory of Open Access Journals (Sweden)

William J Kisoka

Full Text Available BACKGROUND: In most countries of Sub-Saharan Africa, control of lymphatic filariasis (LF is based on annual mass drug administration (MDA with a combination of ivermectin and albendazole. Treatment coverages are however often suboptimal for programmes to reach the goal of transmission interruption within reasonable time. The present study aimed to identify predictors and barriers to individual drug uptake during MDA implementation by the National LF Elimination Programme in Tanzania. METHODS: A questionnaire based cross sectional household survey was carried out in two rural and two urban districts in Lindi and Morogoro regions shortly after the 2011 MDA. 3279 adults (≥15 years were interviewed about personal characteristics, socio-economic status, MDA drug uptake among themselves and their children, reasons for taking/not taking drugs, and participation in previous MDA activities for LF control. FINDINGS: The overall drug uptake rate was 55.1% (range of 44.5-75.6% between districts. There was no overall major difference between children (54.8% and adults (55.2% or between females (54.9% and males (55.8%, but the role of these and other predictors varied to some extent between study sites. Major overall predictors of drug uptake among the interviewed adults were increasing age and history of previous drug uptake. Being absent from home during drug distribution was the main reason for not taking the drugs (50.2% followed by clinical contraindications to treatment (10.8%, missing household visits of drug distributors (10.6%, and households not being informed about the distribution (9.0%. CONCLUSION: Drug uptake relied more on easily modifiable provider-related factors than on individual perceptions and practices in the target population. Limited investments in appropriate timing, dissemination of accurate timing information to recipients and motivation of drug distributors to visit all households (repeatedly when residents are absent are likely

Novel expressed sequence tag- simple sequence repeats (EST ...

African Journals Online (AJOL)

Using different bioinformatic criteria, the SUCEST database was used to mine for simple sequence repeat (SSR) markers. Among 42,189 clusters, 1,425 expressed sequence tag- simple sequence repeats (EST-SSRs) were identified in silico. Trinucleotide repeats were the most abundant SSRs detected. Of 212 primer pairs ...

Audit of the Forensic Psychiatry Liaison Service to Glasgow Sheriff Court 1994 to 1998.

Science.gov (United States)

White, T; Ramsay, L; Morrison, R

2002-01-01

This study seeks to describe the demographic, offence, and diagnostic details of subjects referred by the Procurator Fiscal at Glasgow Sheriff Court to the Forensic Psychiatry Liaison between 1994 and 1997. The initial outcome of the assessment and an assessment of medical time involved is presented. This study is a retrospective review of audit forms completed between 1993 and 1994 and once more in 1997. The referral criteria, age structure and offence pattern was broadly similar to that reported in court diversion schemes in England. A primary diagnosis of alcohol and/or drug dependence was seen in one third of referrals during both years of the audit. A marked increase (250%) in referrals between 1994 and 1997 resulted in a marked reduction of those admitted to hospital, and an increase in the percentage who had 'no psychiatric diagnosis'. The need for ongoing liaison between the Procurators Fiscal and the Forensic Psychiatrists involved would appear important in modifying referral criteria.

Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period

DEFF Research Database (Denmark)

Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose

2018-01-01

analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology......Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug......-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid...

High repeatability from 3D experimental platform for quantitative analysis of cellular branch pattern formations.

Science.gov (United States)

Hagiwara, Masaya; Nobata, Rina; Kawahara, Tomohiro

2018-04-24

Three-dimensional (3D) cell and tissue cultures more closely mimic biological environments than two-dimensional (2D) cultures and are therefore highly desirable in culture experiments. However, 3D cultures often fail to yield repeatable experimental results because of variation in the initial culture conditions, such as cell density and distribution in the extracellular matrix, and therefore reducing such variation is a paramount concern. Here, we present a 3D culture platform that demonstrates highly repeatable experimental results, obtained by controlling the initial cell cluster shape in the gel cube culture device. A micro-mould with the desired shape was fabricated by photolithography or machining, creating a 3D pocket in the extracellular matrix contained in the device. Highly concentrated human bronchial epithelial cells were then injected in the pocket so that the cell cluster shape matched the fabricated mould shape. Subsequently, the cubic device supplied multi-directional scanning, enabling high-resolution capture of the whole tissue structure with only a low-magnification lens. The proposed device significantly improved the repeatability of the developed branch pattern, and multi-directional scanning enabled quantitative analysis of the developed branch pattern formations. A mathematical simulation was also conducted to reveal the mechanisms of branch pattern formation. The proposed platform offers the potential to accelerate any research field that conducts 3D culture experiments, including tissue regeneration and drug development.

Role of memory errors in quantum repeaters

International Nuclear Information System (INIS)

Hartmann, L.; Kraus, B.; Briegel, H.-J.; Duer, W.

2007-01-01

We investigate the influence of memory errors in the quantum repeater scheme for long-range quantum communication. We show that the communication distance is limited in standard operation mode due to memory errors resulting from unavoidable waiting times for classical signals. We show how to overcome these limitations by (i) improving local memory and (ii) introducing two operational modes of the quantum repeater. In both operational modes, the repeater is run blindly, i.e., without waiting for classical signals to arrive. In the first scheme, entanglement purification protocols based on one-way classical communication are used allowing to communicate over arbitrary distances. However, the error thresholds for noise in local control operations are very stringent. The second scheme makes use of entanglement purification protocols with two-way classical communication and inherits the favorable error thresholds of the repeater run in standard mode. One can increase the possible communication distance by an order of magnitude with reasonable overhead in physical resources. We outline the architecture of a quantum repeater that can possibly ensure intercontinental quantum communication

Ocular surface sensitivity repeatability with Cochet-Bonnet esthesiometer.

Science.gov (United States)

Chao, Cecilia; Stapleton, Fiona; Badarudin, Ezailina; Golebiowski, Blanka

2015-02-01

To determine the repeatability of ocular surface threshold measurements using the Cochet-Bonnet esthesiometer on the same day and 3 months apart. Two separate studies were conducted to determine the repeatability of ocular surface threshold measurements made on the same day (n = 20 subjects) and 3 months apart (n = 29 subjects). The Cochet-Bonnet esthesiometer was used to measure corneal and inferior conjunctival thresholds using the ascending method of limits. The pressure exerted by the Cochet-Bonnet esthesiometer was determined using an analytical balance, for both the 0.08- and 0.12-mm-diameter filaments. This calibration was then used to convert filament length measurements to pressure. Repeatability was determined using a Bland and Altman analysis. The pressure exerted at each filament length differed between the two filament diameters. The measured pressure also differed from values provided by the manufacturer. Repeatability of threshold measurements at the central cornea was shown to be good, with better repeatability for same-day measurements (coefficient of repeatability [CoR] = ±0.23 g/mm²) than for those 3 months apart (CoR = ±0.52 g/mm²). Threshold measurements at the inferior conjunctiva, in contrast, were poorly repeatable (CoR = ±12.78 g/mm²). Cochet-Bonnet esthesiometry is repeatable when performed on the central cornea on the same day and 3 months apart, but this instrument is not recommended for conjunctival threshold measurements.

Safety of Repeated Yttrium-90 Radioembolization

International Nuclear Information System (INIS)

Lam, Marnix G. E. H.; Louie, John D.; Iagaru, Andrei H.; Goris, Michael L.; Sze, Daniel Y.

2013-01-01

Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver’s cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51–71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction

Safety of Repeated Yttrium-90 Radioembolization

Energy Technology Data Exchange (ETDEWEB)

Lam, Marnix G. E. H.; Louie, John D. [Stanford University School of Medicine, Division of Interventional Radiology (United States); Iagaru, Andrei H.; Goris, Michael L. [Stanford University School of Medicine, Division of Nuclear Medicine (United States); Sze, Daniel Y., E-mail: dansze@stanford.edu [Stanford University School of Medicine, Division of Interventional Radiology (United States)

2013-10-15

Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

Genotypic diversity of multidrug-, quinolone- and extensively drug-resistant Mycobacterium tuberculosis isolates in Thailand.

Science.gov (United States)

Disratthakit, Areeya; Meada, Shinji; Prammananan, Therdsak; Thaipisuttikul, Iyarit; Doi, Norio; Chaiprasert, Angkana

2015-06-01

Drug-resistant tuberculosis (TB), which includes multidrug-resistant (MDR-TB), quinolone-resistant (QR-TB) and extensively drug-resistant tuberculosis (XDR-TB), is a serious threat to TB control. We aimed to characterize the genotypic diversity of drug-resistant TB clinical isolates collected in Thailand to establish whether the emergence of drug-resistant TB is attributable to transmitted resistance or acquired resistance. We constructed the first molecular phylogeny of MDR-TB (n=95), QR-TB (n=69) and XDR-TB (n=28) in Thailand based on spoligotyping and proposed 24-locus multilocus variable-number of tandem repeat analysis (MLVA). Clustering analysis was performed using the unweighted pair group method with arithmetic mean. Spoligotyping identified the Beijing strain (SIT1) as the most predominant genotype (n=139; 72.4%). The discriminatory power of 0.9235 Hunter-Gaston Discriminatory Index (HGDI) with the 15-locus variable-number tandem repeats of mycobacterial interspersed repetitive units typing was improved to a 0.9574 HGDI with proposed 24-locus MLVA, thereby resulting in the subdivision of a large cluster of Beijing strains (SIT1) into 17 subclusters. We identified the spread of drug-resistant TB clones caused by three different MLVA types in the Beijing strain (SIT1) and a specific clone of XDR-TB caused by a rare genotype, the Manu-ancestor strain (SIT523). Overall, 49.5% of all isolates were clustered. These findings suggest that a remarkable transmission of drug-resistant TB occurred in Thailand. The remaining 50% of drug-resistant TB isolates were unique genotypes, which may have arisen from the individual acquisition of drug resistance. Our results suggest that transmitted and acquired resistance have played an equal role in the emergence of drug-resistant TB. Further characterization of whole genome sequences of clonal strains could help to elucidate the mycobacterial genetic factors relevant for drug resistance, transmissibility and virulence

A new method to assess Pavlovian conditioning of psychostimulant drug effects.

Science.gov (United States)

Damianopoulos, E N; Carey, R J

1994-07-01

Experimental studies of psychoactive drugs by pavlovian drug-conditioning methods, which originally began with investigations of drug-induced responses mediated by the autonomic nervous system, have now been expanded to include drug-induced response effects expressed as modulations of spontaneous motoric behaviors. In the latter application, however, equivalent behavioral response outcomes in post-treatment tests for conditioning can occur following a psychostimulant drug treatment either through drug interference effects on habituation processes, drug-induced stress effects and/or by pavlovian conditioning of the drug-induced motoric activation effect. Current methodologies for the study of pavlovian conditioned drug effects and/or drug sensitization cannot distinguish among these possibilities. This methodological inadequacy was addressed by a modification of the conventional paired-unpaired treatment protocol. In the new protocol, the animal is sequentially placed into two test compartments with the drug treatment administered in conjunction with placement into the second test compartment. This design permits a differentiation of a pavlovian conditioned drug responses from non-conditioned drug effects through continuous measurement of the non-drug behavioral baseline in both the drug and non-drug control treatment groups combined with multiple response measurements and post-treatment tests for conditioning at variable post-conditioning intervals. The present study details the use of the new modified pavlovian protocol with repeated cocaine (10 mg/kg) treatment. A cocaine conditioned response at 1, 7, and 21 days post-conditioning was identified and distinguished from habituation and stress effects.

Properties of Protein Drug Target Classes

Science.gov (United States)

Bull, Simon C.; Doig, Andrew J.

2015-01-01

Accurate identification of drug targets is a crucial part of any drug development program. We mined the human proteome to discover properties of proteins that may be important in determining their suitability for pharmaceutical modulation. Data was gathered concerning each protein’s sequence, post-translational modifications, secondary structure, germline variants, expression profile and drug target status. The data was then analysed to determine features for which the target and non-target proteins had significantly different values. This analysis was repeated for subsets of the proteome consisting of all G-protein coupled receptors, ion channels, kinases and proteases, as well as proteins that are implicated in cancer. Machine learning was used to quantify the proteins in each dataset in terms of their potential to serve as a drug target. This was accomplished by first inducing a random forest that could distinguish between its targets and non-targets, and then using the random forest to quantify the drug target likeness of the non-targets. The properties that can best differentiate targets from non-targets were primarily those that are directly related to a protein’s sequence (e.g. secondary structure). Germline variants, expression levels and interactions between proteins had minimal discriminative power. Overall, the best indicators of drug target likeness were found to be the proteins’ hydrophobicities, in vivo half-lives, propensity for being membrane bound and the fraction of non-polar amino acids in their sequences. In terms of predicting potential targets, datasets of proteases, ion channels and cancer proteins were able to induce random forests that were highly capable of distinguishing between targets and non-targets. The non-target proteins predicted to be targets by these random forests comprise the set of the most suitable potential future drug targets, and should therefore be prioritised when building a drug development programme. PMID

PLGA based drug delivery systems: Promising carriers for wound healing activity.

Science.gov (United States)

Chereddy, Kiran Kumar; Vandermeulen, Gaëlle; Préat, Véronique

2016-03-01

Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Current treatment options are limited and require repeated administrations which led to the development of new therapeutics to satisfy the unmet clinical needs. Many potent wound healing agents were discovered but most of them are fragile and/or sensitive to in vivo conditions. Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer approved by food and drug administration and European medicines agency as an excipient for parenteral administrations. It is a well-established drug delivery system in various medical applications. The aim of the current review is to elaborate the applications of PLGA based drug delivery systems carrying different wound healing agents and also present PLGA itself as a wound healing promoter. PLGA carriers encapsulating drugs such as antibiotics, anti-inflammatory drugs, proteins/peptides, and nucleic acids targeting various phases/signaling cycles of wound healing, are discussed with examples. The combined therapeutic effects of PLGA and a loaded drug on wound healing are also mentioned. © 2016 by the Wound Healing Society.

Dental Fear in Children with Repeated Tooth Injuries.

Science.gov (United States)

Negovetić Vranić, Dubravka; Ivančić Jokić, Nataša; Bakarčić, Danko; Carek, Andreja; Rotim, Željko; Verzak, Željko

2016-06-01

Tooth injuries are serious clinical conditions. Some children experience dental trauma only once, while others are more prone to repeated tooth injuries. Repeated dental trauma occurs in 19.4% to 30% of patients. Pain and dental trauma are the most common reasons for fear and anxiety. The main objective of this study was to investigate how dental trauma, as well as repeated dental trauma affects the occurrence and development of dental fear in children. The study was conducted on a random sample of 147 subjects (88 boys and 59 girls) aged 5-8 and 9-12 years. Subjects in both age groups were divided into subroups without dental trauma, with one dental trauma and with repeated dental trauma. The validated Children’s Fear Survey Schedule – Dental Subscale was used on fear assessment. Results showed that only 12.2% of children without trauma, 33.3% with one trauma and 51.7% with repeated trauma were not afraid of injection. Older children had a significantly lower fear of injections, touch of an unknown person, choking, going to the hospital and people in white uniforms. Dentist was not the cause of fear in 65.5% of patients with repeated trauma. With each repeated injury of teeth, the degree of their fear of dental treatment was lower.

Erroneous Memories Arising from Repeated Attempts to Remember

Science.gov (United States)

Henkel, Linda A.

2004-01-01

The impact of repeated and prolonged attempts at remembering on false memory rates was assessed in three experiments. Participants saw and imagined pictures and then made repeated recall attempts before taking a source memory test. Although the number of items recalled increased with repeated tests, the net gains were associated with more source…

Repeated intravenous doxapram induces phrenic motor facilitation.

Science.gov (United States)

Sandhu, M S; Lee, K Z; Gonzalez-Rothi, E J; Fuller, D D

2013-12-01

Doxapram is a respiratory stimulant used to treat hypoventilation. Here we investigated whether doxapram could also trigger respiratory neuroplasticity. Specifically, we hypothesized that intermittent delivery of doxapram at low doses would lead to long-lasting increases (i.e., facilitation) of phrenic motor output in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was delivered intravenously in a single bolus (2 or 6mg/kg) or as a series of 3 injections (2mg/kg) at 5min intervals. Control groups received pH-matched saline injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked an immediate increase in phrenic output in all groups, but a persistent increase in burst amplitude only occurred after repeated dosing with 2mg/kg. At 60min following the last injection, phrenic burst amplitude was 168±24% of baseline (%BL) in the group receiving 3 injections (Pphrenic response to doxapram (2mg/kg) was reduced by 68% suggesting that at low doses the drug was acting primarily via the carotid chemoreceptors. We conclude that intermittent application of doxapram can trigger phrenic neuroplasticity, and this approach might be of use in the context of respiratory rehabilitation following neurologic injury. © 2013.

Identification, variation and transcription of pneumococcal repeat sequences

Science.gov (United States)

2011-01-01

Background Small interspersed repeats are commonly found in many bacterial chromosomes. Two families of repeats (BOX and RUP) have previously been identified in the genome of Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen of humans. However, little is known about the role they play in pneumococcal genetics. Results Analysis of the genome of S. pneumoniae ATCC 700669 revealed the presence of a third repeat family, which we have named SPRITE. All three repeats are present at a reduced density in the genome of the closely related species S. mitis. However, they are almost entirely absent from all other streptococci, although a set of elements related to the pneumococcal BOX repeat was identified in the zoonotic pathogen S. suis. In conjunction with information regarding their distribution within the pneumococcal chromosome, this suggests that it is unlikely that these repeats are specialised sequences performing a particular role for the host, but rather that they constitute parasitic elements. However, comparing insertion sites between pneumococcal sequences indicates that they appear to transpose at a much lower rate than IS elements. Some large BOX elements in S. pneumoniae were found to encode open reading frames on both strands of the genome, whilst another was found to form a composite RNA structure with two T box riboswitches. In multiple cases, such BOX elements were demonstrated as being expressed using directional RNA-seq and RT-PCR. Conclusions BOX, RUP and SPRITE repeats appear to have proliferated extensively throughout the pneumococcal chromosome during the species' past, but novel insertions are currently occurring at a relatively slow rate. Through their extensive secondary structures, they seem likely to affect the expression of genes with which they are co-transcribed. Software for annotation of these repeats is freely available from ftp://ftp.sanger.ac.uk/pub/pathogens/strep_repeats/. PMID:21333003

Nonparametric additive regression for repeatedly measured data

KAUST Repository

Carroll, R. J.; Maity, A.; Mammen, E.; Yu, K.

2009-01-01

We develop an easily computed smooth backfitting algorithm for additive model fitting in repeated measures problems. Our methodology easily copes with various settings, such as when some covariates are the same over repeated response measurements

Quantum key distribution with two-segment quantum repeaters

Energy Technology Data Exchange (ETDEWEB)

Kampermann, Hermann; Abruzzo, Silvestre; Bruss, Dagmar [Theoretische Physik III, Heinrich-Heine-Universitaet Duesseldorf (Germany)

2014-07-01

Quantum repeaters represent one possible way to achieve long-distance quantum key distribution. One way of improving the repeater rate and decreasing the memory coherence time is the usage of multiplexing. Motivated by the experimental fact that long-range connections are practically demanding, we extend the analysis of the quantum repeater multiplexing protocol to the case of short-range connections. We derive formulas for the repeater rate and we show that short-range connections lead to most of the benefits of a full-range multiplexing protocol. A less demanding QKD-protocol without quantum memories was recently introduced by Lo et al. We generalize this measurement-device-independent quantum key Distribution protocol to the scenario where the repeater Station contains also heralded quantum memories. We assume either single-photon sources or weak coherent pulse sources plus decay states. We show that it is possible to significantly outperform the original proposal, even in presence of decoherence of the quantum memory. We give formulas in terms of device imperfections i.e., the quantum bit error rate and the repeater rate.

Repeated vertebral augmentation for new vertebral compression fractures of postvertebral augmentation patients: a nationwide cohort study

Directory of Open Access Journals (Sweden)

Liang CL

2015-03-01

anti-inflammatory drugs (NSAIDs (AOR=6.14; 95% CI: 5.08–7.41 were more likely to undergo repeat vertebral augmentation.Conclusion: We conclude that the incidence of repeat vertebral augmentation is rather high. An understanding of risk factors predicting repeat vertebral augmentation provides valuable basis to improve health care for geriatric populations. Keywords: vertebroplasty, kyphoplasty, comorbidity, bisphosphonate, old ageTwo Letters to the Editor have been recieved and published İlhan et alWilson et al 

What is the future of peer review? Why is there fraud in science? Is plagiarism out of control? Why do scientists do bad things? Is it all a case of: "all that is necessary for the triumph of evil is that good men do nothing"?

Science.gov (United States)

Triggle, Chris R; Triggle, David J

2007-01-01

Peer review is an essential component of the process that is universally applied prior to the acceptance of a manuscript, grant or other scholarly work. Most of us willingly accept the responsibilities that come with being a reviewer but how comfortable are we with the process? Peer review is open to abuse but how should it be policed and can it be improved? A bad peer review process can inadvertently ruin an individual's career, but are there penalties for policing a reviewer who deliberately sabotages a manuscript or grant? Science has received an increasingly tainted name because of recent high profile cases of alleged scientific misconduct. Once considered the results of work stress or a temporary mental health problem, scientific misconduct is increasingly being reported and proved to be a repeat offence. How should scientific misconduct be handled--is it a criminal offence and subject to national or international law? Similarly plagiarism is an ever-increasing concern whether at the level of the student or a university president. Are the existing laws tough enough? These issues, with appropriate examples, are dealt with in this review.

What is the future of peer review? Why is there fraud in science? Is plagiarism out of control? Why do scientists do bad things? Is it all a case of:“All that is necessary for the triumph of evil is that good men do nothing?”

Science.gov (United States)

Triggle, Chris R; Triggle, David J

2007-01-01

Peer review is an essential component of the process that is universally applied prior to the acceptance of a manuscript, grant or other scholarly work. Most of us willingly accept the responsibilities that come with being a reviewer but how comfortable are we with the process? Peer review is open to abuse but how should it be policed and can it be improved? A bad peer review process can inadvertently ruin an individual’s career, but are there penalties for policing a reviewer who deliberately sabotages a manuscript or grant? Science has received an increasingly tainted name because of recent high profile cases of alleged scientific misconduct. Once considered the results of work stress or a temporary mental health problem, scientific misconduct is increasingly being reported and proved to be a repeat offence. How should scientific misconduct be handled—is it a criminal offence and subject to national or international law? Similarly plagiarism is an ever-increasing concern whether at the level of the student or a university president. Are the existing laws tough enough? These issues, with appropriate examples, are dealt with in this review. PMID:17583174

The Legal Regulation of Cybersecurity

OpenAIRE

Darius Štitilis

2013-01-01

Cybercrime has become a global phenomenon, which is causing more harm to individual citizens, organizations, society and the state. Most countries in the world compare cybercrime with offences such as terrorism and drug trafficking due to its risks and profitability. Cybersecurity is the central category to fight cybercrime in cyberspace. Therefore, the strategic legal regulation of cybersecurity is one of the most relevant problems in EU, including Lithuania. So far cybersecurity legal regul...

Deployment Repeatability

Science.gov (United States)

2016-08-31

large cohort of trials to spot unusual cases. However, deployment repeatability is inherently a nonlinear phenomenon, which makes modeling difficult...and GEMS tip position were both tracked during ground testing by a laser target tracking system. Earlier SAILMAST testing in 2005 [8] used...recalls the strategy used by SRTM, where a constellation of lights was installed at the tip of the boom and a modified star tracker was used to track tip

R-loops: targets for nuclease cleavage and repeat instability.

Science.gov (United States)

Freudenreich, Catherine H

2018-01-11

R-loops form when transcribed RNA remains bound to its DNA template to form a stable RNA:DNA hybrid. Stable R-loops form when the RNA is purine-rich, and are further stabilized by DNA secondary structures on the non-template strand. Interestingly, many expandable and disease-causing repeat sequences form stable R-loops, and R-loops can contribute to repeat instability. Repeat expansions are responsible for multiple neurodegenerative diseases, including Huntington's disease, myotonic dystrophy, and several types of ataxias. Recently, it was found that R-loops at an expanded CAG/CTG repeat tract cause DNA breaks as well as repeat instability (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Two factors were identified as causing R-loop-dependent breaks at CAG/CTG tracts: deamination of cytosines and the MutLγ (Mlh1-Mlh3) endonuclease, defining two new mechanisms for how R-loops can generate DNA breaks (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Following R-loop-dependent nicking, base excision repair resulted in repeat instability. These results have implications for human repeat expansion diseases and provide a paradigm for how RNA:DNA hybrids can cause genome instability at structure-forming DNA sequences. This perspective summarizes mechanisms of R-loop-induced fragility at G-rich repeats and new links between DNA breaks and repeat instability.

Repeat profile analysis in an x-ray department

International Nuclear Information System (INIS)

Bassey, C.E.; Ojo, O.O.; Akpabio, I.

1991-01-01

The repeat profile of an x-ray department in a developing country was analysed monthly between July 1989 and June 1990. Results showed an average repeat rate of 3.7% for the period of study. The main causes of film repetition were: equipment fault, 33.9%; radiographer's fault, 27.4%; film fault, 19.3%; processing fault, 10.8% and patient's fault, 8.6%. The average repeat rate in the first 6 months of study reduced by 50% in the last 6 months. This was due to the effectiveness of implementation of corrective actions. The overall repeat rate was found to correlate well with both the equipment fault and radiographer's fault with correlation coefficients, r, of 0.94 and 0.91, respectively. It is expected that a further reduction in the repeat rate will be obtained after the introduction of quality assurance programmes. (author)

Systemic provocation in doxycycline induced fixed drug eruption: a case report

Directory of Open Access Journals (Sweden)

Anik Murwaningsih Rosmarini Estri Sih Hananti Niken Indrastuti

2014-04-01

Full Text Available Fixed drug eruption (FDE is recurrent lesions that upon repeated uptake of causative drug, always appears at the same skin and mucosal site. Determination of causal relationship in drug allergy is very important. In this case report, cases of doxycycline-induced FDE was reported. The subject of the research was a 29-year-old male, referred by dermatologist, with history of reccurent FDE. Physical examination revealed an oval well demarcated patch hyperpigmentation. Patch test was perfomed on previous involved and uninvolved site. The result of the patch test was irrelevant. Retesting patch test gave similar result. Systemic provocation test or drug provocation test (DPT  with doxcycline were done with suspected drug under ambulatory survelance and gave positive result. In this case, the DPT succeeded to identify doxycycline as the causal agent of FDE. The work-up of a suspected drug hypersensitivity includes a detailed clinical history, physical examination, skin tests, and provocation tests. The DPT is recommended to confirm drug’s hypersensitivity reactions. Systemic provocation test is considered as the gold standard for diagnosing FDE. Keywords:   fixed drug eruption - doxycycline - causal relationship - patch test - systemic provocation test

Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse.

Science.gov (United States)

Tomie, Arthur; Grimes, Kathryn L; Pohorecky, Larissa A

2008-06-01

Drug abuse researchers have noted striking similarities between behaviors elicited by Pavlovian sign-tracking procedures and prominent symptoms of drug abuse. In Pavlovian sign-tracking procedures, repeated paired presentations of a small object (conditioned stimulus, CS) with a reward (unconditioned stimulus, US) elicits a conditioned response (CR) that typically consists of approaching the CS, contacting the CS, and expressing consummatory responses at the CS. Sign-tracking CR performance is poorly controlled and exhibits spontaneous recovery and long-term retention, effects that resemble relapse. Sign-tracking resembles psychomotor activation, a syndrome of behavioral responses evoked by addictive drugs, and the effects of sign-tracking on corticosterone levels and activation of dopamine pathways resemble the neurobiological effects of abused drugs. Finally, the neurobiological profile of individuals susceptible to sign-tracking resembles the pathophysiological profile of vulnerability to drug abuse, and vulnerability to sign-tracking predicts vulnerability to impulsive responding and alcohol self-administration. Implications of sign-tracking for models of drug addiction are considered.

Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs.

Science.gov (United States)

Sudhakar, Yajaman; Kuotsu, Ketousetuo; Bandyopadhyay, A K

2006-08-10

Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of these drugs as potential therapeutic agents is their extensive presystemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Parenteral route of administration is the only established route that overcomes all these drawbacks associated with these orally less/inefficient drugs. But, these formulations are costly, have least patient compliance, require repeated administration, in addition to the other hazardous effects associated with this route. Over the last few decades' pharmaceutical scientists throughout the world are trying to explore transdermal and transmucosal routes as an alternative to injections. Among the various transmucosal sites available, mucosa of the buccal cavity was found to be the most convenient and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery as retentive dosage forms, because it has expanse of smooth muscle which is relatively immobile, abundant vascularization, rapid recovery time after exposure to stress and the near absence of langerhans cells. Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Further, these dosage forms are self-administrable, cheap and have superior patient compliance. Developing a dosage form with the optimum pharmacokinetics is a promising area for continued research as it is enormously important and intellectually challenging. With the right dosage form design, local environment of the mucosa can be controlled and manipulated in order to

A proposal for a drug information database and text templates for generating package inserts

Directory of Open Access Journals (Sweden)

Okuya R

2013-07-01

Full Text Available Ryo Okuya,1 Masaomi Kimura,2 Michiko Ohkura,2 Fumito Tsuchiya3 1Graduate School of Engineering and Science, 2Faculty of Engineering, Shibaura Institute of Technology, Tokyo, 3School of Pharmacy, International University of Health and Welfare, Tokyo, Japan Abstract: To prevent prescription errors caused by information systems, a database to store complete and accurate drug information in a user-friendly format is needed. In previous studies, the primary method for obtaining data stored in a database is to extract drug information from package inserts by employing pattern matching or more sophisticated methods such as text mining. However, it is difficult to obtain a complete database because there is no strict rule concerning expressions used to describe drug information in package inserts. The authors' strategy was to first build a database and then automatically generate package inserts by embedding data in the database using templates. To create this database, the support of pharmaceutical companies to input accurate data is required. It is expected that this system will work, because these companies can earn merit for newly developed drugs to decrease the effort to create package inserts from scratch. This study designed the table schemata for the database and text templates to generate the package inserts. To handle the variety of drug-specific information in the package inserts, this information in drug composition descriptions was replaced with labels and the replacement descriptions utilizing cluster analysis were analyzed. To improve the method by which frequently repeated ingredient information and/or supplementary information are stored, the method was modified by introducing repeat tags in the templates to indicate repetition and improving the insertion of data into the database. The validity of this method was confirmed by inputting the drug information described in existing package inserts and checking that the method could

Effects of Repeated Morphine on Intracranial Self-Stimulation in Male Rats In the Absence or Presence of a Noxious Pain Stimulus

Science.gov (United States)

Miller, Laurence L.; Altarifi, Ahmad A.; Negus, S. Stevens

2015-01-01

Research on opioid analgesics such as morphine suggests that expression of abuse-related effects increases with repeated exposure. Repeated exposure to opioids often occurs clinically in the context of pain management, and a major concern for clinicians is the risk of iatrogenic addiction and dependence in patients receiving opioids for treatment of pain. This study compared abuse-related morphine effects in male rats in an intracranial self-stimulation (ICSS) procedure after repeated treatment either with morphine alone or with morphine in combination with a repeated noxious stimulus (intraperitoneal administration of dilute acid). The study also permitted comparison of morphine potency and effectiveness to block acid-induced depression of ICSS (antinociception) and to produce enhanced facilitation of ICSS (abuse-related effect). There were three main findings. First, initial morphine exposure to drug naïve rats did not produce abuse-related ICSS facilitation. Second, repeated daily treatment with 3.2 mg/kg/day morphine for six days increased expression of ICSS facilitation. This occurred whether morphine was administered in the absence or presence of the noxious stimulus. Finally, a lower dose of 1.0 mg/kg/day morphine was sufficient to produce antinociception during repeated acid treatment, but this lower dose did not reliably increase abuse-related morphine effects. Taken together, these results suggest that prior morphine exposure can increase abuse liability of subsequent morphine treatments even when that morphine exposure occurs in the context of a pain state. However, it may be possible to relieve pain with relatively low morphine doses that do not produce increases in abuse-related morphine effects. PMID:26375515

Within-host selection of drug resistance in a mouse model of repeated incomplete malaria treatment : Comparison between atovaquone and pyrimethamine

NARCIS (Netherlands)

Nuralitha, Suci; Siregar, Josephine E.; Syafruddin, Din; Roelands, Jessica; Verhoef, Jan; Hoepelman, Andy I M; Marzuki, Sangkot

2016-01-01

The evolutionary selection of malaria parasites within individual hosts is an important factor in the emergence of drug resistance but is still not well understood. We have examined the selection process for drug resistance in the mouse malaria agent Plasmodium berghei and compared the dynamics of

Drug-sensitive reward in crayfish: an invertebrate model system for the study of SEEKING, reward, addiction, and withdrawal.

Science.gov (United States)

Huber, Robert; Panksepp, Jules B; Nathaniel, Thomas; Alcaro, Antonio; Panksepp, Jaak

2011-10-01

In mammals, rewarding properties of drugs depend on their capacity to activate appetitive motivational states. With the underlying mechanisms strongly conserved in evolution, invertebrates have recently emerged as a powerful new model in addiction research. In crayfish natural reward has proven surprisingly sensitive to human drugs of abuse, opening an unlikely avenue of research into the basic biological mechanisms of drug addiction. In a series of studies we first examined the presence of natural reward systems in crayfish, then characterized its sensitivity to a wide range of human drugs of abuse. A conditioned place preference (CPP) paradigm was used to demonstrate that crayfish seek out those environments that had previously been paired with the psychostimulants cocaine and amphetamine, and the opioid morphine. The administration of amphetamine exerted its effects at a number of sites, including the stimulation of circuits for active exploratory behaviors (i.e., SEEKING). A further study examined morphine-induced reward, extinction and reinstatement in crayfish. Repeated intra-circulatory infusions of morphine served as a reward when paired with distinct visual or tactile cues. Morphine-induced CPP was extinguished after repeated saline injections. Following this extinction phase, morphine-experienced crayfish were once again challenged with the drug. The priming injections of morphine reinstated CPP at all tested doses, suggesting that morphine-induced CPP is unrelenting. In an exploration of drug-associated behavioral sensitization in crayfish we concurrently mapped measures of locomotion and rewarding properties of morphine. Single and repeated intra-circulatory infusions of morphine resulted in persistent locomotory sensitization, even 5 days following the infusion. Moreover, a single dose of morphine was sufficient to induce long-term behavioral sensitization. CPP for morphine and context-dependent cues could not be disrupted over a drug free period of 5

Repeated chemical immobilization of a captive greater one-horned rhinoceros (Rhinoceros unicornis), using combinations of etorphine, detomidine, and ketamine.

Science.gov (United States)

Atkinson, Mark W; Hull, Bruce; Gandolf, A Rae; Blumer, Evan S

2002-06-01

An adult, 23 yr-old, male greater one-horned rhinoceros (Rhinoceros unicornis) was repeatedly immobilized with combinations of etorphine, detomidine, and ketamine to provide medical and surgical care to chronic, bilateral, soft tissue lesions on the hind feet and to collect semen by electroejaculation. The rhinoceros was successfully immobilized on 24 occasions over a 55 mo period at approximately 8-10 wk intervals, 17 times with a combination of etorphine and detomidine (M99-D, i.m.) by projectile dart and seven times with a combination of etorphine, ketamine, and detomidine (M99-K-D, i.m.) by pole syringe. The combination of etorphine, detomidine, and ketamine repeatedly and safely induced prolonged anesthesia, and a suitable drug combination includes 3.5-3.8 mg etorphine, 14 mg detomidine, and 400 mg ketamine (M99-K-D) administered i.m. into the neck.

Pharmacokinetics of Anti-Epileptic Drugs and their Clinical Significance

Directory of Open Access Journals (Sweden)

Svein I. Johannessen

1990-01-01

Full Text Available The serum concentration achieved and maintained following the administration of a fixed drug dosage is a direct consequence of the interactions of a wide variety of interrelated processes, including drug absorption, distribution, metabolism, and excretion, and the physiological status of the patient. These interrelationships are reviewed with specific reference to the major anti-epileptic drugs, phenobarbitone, phenytoin, sodium valproate, and carbamazepine, as well as a new first-line antiepileptic, oxcarbazepine. Both older drugs, such as phenobarbitone and phenytoin, and newer drugs, such as carbamazepine (CBZ and sodium valproate, have been studied extensively over the past years giving valuable information for drug treatment. An important feature of oxcarbazepine (OXC , which was developed through minimal changes in the structure of CBZ in order to improve on the tolerability of CBZ without sacrificing efficacy, is that its metabolites do not include the 11-epoxide which has been implicated in the side-effects of CBZ. In man, OXC is metabolized to a monohydroxy derivative which has independent anti-epileptic properties. OXC seems to lack several disadavantageous pharmacokinetic properties common to other major anti-epileptic drugs. OXC does not influence its own metabolism after repeated administration, in contrast to the auto-induction displayed by CBZ. The metabolism of OXC is not influenced by anti-epileptic co-medication and does not influence the kinetics of other anti-epileptic drugs – or if it does, then to a lesser extent than CBZ.

Development of analog watch with minute repeater

Science.gov (United States)

Okigami, Tomio; Aoyama, Shigeru; Osa, Takashi; Igarashi, Kiyotaka; Ikegami, Tomomi

A complementary metal oxide semiconductor with large scale integration was developed for an electronic minute repeater. It is equipped with the synthetic struck sound circuit to generate natural struck sound necessary for the minute repeater. This circuit consists of an envelope curve drawing circuit, frequency mixer, polyphonic mixer, and booster circuit made by using analog circuit technology. This large scale integration is a single chip microcomputer with motor drivers and input ports in addition to the synthetic struck sound circuit, and it is possible to make an electronic system of minute repeater at a very low cost in comparison with the conventional type.

RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

Directory of Open Access Journals (Sweden)

Aisling Frizzell

2014-03-01

Full Text Available Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG repeat expansions and fragility, likely by unwinding problematic hairpins.

Isolation of human simple repeat loci by hybridization selection.

Science.gov (United States)

Armour, J A; Neumann, R; Gobert, S; Jeffreys, A J

1994-04-01

We have isolated short tandem repeat arrays from the human genome, using a rapid method involving filter hybridization to enrich for tri- or tetranucleotide tandem repeats. About 30% of clones from the enriched library cross-hybridize with probes containing trimeric or tetrameric tandem arrays, facilitating the rapid isolation of large numbers of clones. In an initial analysis of 54 clones, 46 different tandem arrays were identified. Analysis of these tandem repeat loci by PCR showed that 24 were polymorphic in length; substantially higher levels of polymorphism were displayed by the tetrameric repeat loci isolated than by the trimeric repeats. Primary mapping of these loci by linkage analysis showed that they derive from 17 chromosomes, including the X chromosome. We anticipate the use of this strategy for the efficient isolation of tandem repeats from other sources of genomic DNA, including DNA from flow-sorted chromosomes, and from other species.

Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

Science.gov (United States)

Subramaniam, B; Claudius, J S

1990-03-08

for optimum scheduling of subsequent bolus injections in a multiple bolus dosing regimen. There are no reported applications of the FFT method to solve repeated input functions in either the chemical engineering or pharmaceutical science literature. Thus, the application of FFT method to solve multiple bolus injections is a unique one. Use of this FFT based analysis as a predictor tool can limit the number of costly experiments which are being done now to achieve this purpose. Even though the model in its present form is simplified, the analysis thereof has nevertheless led to a better understanding of the various factors that must be taken into account for rational design of drug therapy.

Crowdsourcing Sexual Objectification

Directory of Open Access Journals (Sweden)

Carissima Mathen

2014-08-01

Full Text Available This paper analyzes the criminal offence of the non-consensual distribution of intimate images (what some call “revenge porn”. Focussing on the debate currently underway in Canada, it notes that such an offence would fill a grey area in that country’s criminal law. Arguing, more broadly, that the criminal law has an important expressive function, the paper posits that the offence targets the same general type of wrongdoing—sexual objectification—that undergirds sexual assault. While not all objectification merits criminal sanction, the paper explains why the non-consensual distribution of intimate images does and why a specific offence is legitimate.

The impact of repeated rounds of mass drug administration with diethylcarbamazine plus albendazole on bancroftian filariasis in Papua New Guinea.

Directory of Open Access Journals (Sweden)

Gary J Weil

Full Text Available This study employed various monitoring methods to assess the impact of repeated rounds of mass drug administration (MDA on bancroftian filariasis in Papua New Guinea, which has the largest filariasis problem in the Pacific region.Residents of rural villages near Madang were studied prior to and one year after each of three rounds of MDA with diethylcarbamazine plus albendazole administered per World Health Organization (WHO guidelines. The mean MDA compliance rate was 72.9%. Three rounds of MDA decreased microfilaremia rates (Mf, 1 ml night blood by filter from 18.6% pre-MDA to 1.3% after the third MDA (a 94% decrease. Mf clearance rates in infected persons were 71%, 90.7%, and 98.1% after 1, 2, and 3 rounds of MDA. Rates of filarial antigenemia assessed by card test (a marker for adult worm infection decreased from 47.5% to 17.1% (a 64% decrease after 3 rounds of MDA. The filarial antibody rate (IgG(4 antibodies to Bm14, an indicator of filarial infection status and/or exposure to mosquito-borne infective larvae decreased from 59.3% to 25.1% (a 54.6% decrease. Mf, antigen, and antibody rates decreased more rapidly in children <11 years of age (by 100%, 84.2%, and 76.8%, respectively relative to older individuals, perhaps reflecting their lighter infections and shorter durations of exposure/infection prior to MDA. Incidence rates for microfilaremia, filarial antigenemia, and antifilarial antibodies also decreased significantly after MDA. Filarial DNA rates in Anopheles punctulatus mosquitoes that had recently taken a blood meal decreased from 15.1% to 1.0% (a 92.3% decrease.MDA had dramatic effects on all filariasis parameters in the study area and also reduced incidence rates. Follow-up studies will be needed to determine whether residual infection rates in residents of these villages are sufficient to support sustained transmission by the An. punctulatus vector. Lymphatic filariasis elimination should be feasible in Papua New Guinea if MDA can

Repeated rat-forced swim test: reducing the number of animals to evaluate gradual effects of antidepressants.

Science.gov (United States)

Mezadri, T J; Batista, G M; Portes, A C; Marino-Neto, J; Lino-de-Oliveira, C

2011-02-15

The forced swim test (FST) is a pre-clinical test to short and long term treatment with antidepressant drugs (ADT), which requires between-subject designs. Herein a modified protocol of the FST using within-subject design (repeated rat-FST) was evaluated. Male Wistar rats were submitted to 15 min of swimming (Day 1: pretest) followed by three subsequent 5 min-swimming tests one week apart (Day 2: test, Day 7: retest 1, Day 14: retest 2). To determine the temporal and factorial characteristics of the variables scored in the repeated rat-FST, the protocol was carried out in untreated animals (E1). To validate the method, daily injections of Fluoxetine (FLX, 2.5mg/kg, i.p.) or saline were given over a 2-week period (E2). Tests and retests have been videotaped for further register of the latency, frequency and duration of behaviors. Over retesting the latency to immobility decreased whereas duration of immobility tended to increase. Factorial analysis revealed that the test, the retest 1 as well as the retest 2 have variables suitable to detection of antidepressant-like effects of ADT. Compared to saline, FLX chronically administrated reduced duration of immobility whereas increased duration of swimming in retest 2. The data suggest that repeated rat-FST detected the gradual increase in the efficacy of low doses of FLX over time. Therefore, repeated rat-FST seemed suitable to detect short and long term effects of selective serotonin reuptake inhibitors, or other ADT, thus reducing the number of animals used in the screenings of this type of compounds. © 2010 Elsevier B.V. All rights reserved.

Drug repurposing based on drug-drug interaction.

Science.gov (United States)

Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

2015-02-01

Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

Psychostimulant Drugs and Neuroplasticity

Directory of Open Access Journals (Sweden)

Emilio Fernandez-Espejo

2011-06-01

Full Text Available Drugs of abuse induce plastic changes in the brain that seem to underlie addictive phenomena. These plastic changes can be structural (morphological or synaptic (biochemical, and most of them take place in the mesolimbic and mesostriatal circuits. Several addiction-related changes in brain circuits (hypofrontality, sensitization, tolerance as well as the outcome of treatment have been visualized in addicts to psychostimulants using neuroimaging techniques. Repeated exposure to psychostimulants induces morphological changes such as increase in the number of dendritic spines, changes in the morphology of dendritic spines, and altered cellular coupling through new gap junctions. Repeated exposure to psychostimulants also induces various synaptic adaptations, many of them related to sensitization and neuroplastic processes, that include up- or down-regulation of D1, D2 and D3 dopamine receptors, changes in subunits of G proteins, increased adenylyl cyclase activity, cyclic AMP and protein kinase A in the nucleus accumbens, increased tyrosine hydroxylase enzyme activity, increased calmodulin and activated CaMKII in the ventral tegmental area, and increased deltaFosB, c-Fos and AP-1 binding proteins. Most of these changes are transient, suggesting that more lasting plastic brain adaptations should take place. In this context, protein synthesis inhibitors block the development of sensitization to cocaine, indicating that rearrangement of neural networks must develop for the long-lasting plasticity required for addiction to occur. Self-administration studies indicate the importance of glutamate neurotransmission in neuroplastic changes underlying transition from use to abuse. Finally, plastic changes in the addicted brain are enhanced and aggravated by neuroinflammation and neurotrophic disbalance after repeated psychostimulants.

On balanced minimal repeated measurements designs

Directory of Open Access Journals (Sweden)

Shakeel Ahmad Mir

2014-10-01

Full Text Available Repeated Measurements designs are concerned with scientific experiments in which each experimental unit is assigned more than once to a treatment either different or identical. This class of designs has the property that the unbiased estimators for elementary contrasts among direct and residual effects are obtainable. Afsarinejad (1983 provided a method of constructing balanced Minimal Repeated Measurements designs p < t , when t is an odd or prime power, one or more than one treatment may occur more than once in some sequences and  designs so constructed no longer remain uniform in periods. In this paper an attempt has been made to provide a new method to overcome this drawback. Specifically, two cases have been considered                RM[t,n=t(t-t/(p-1,p], λ2=1 for balanced minimal repeated measurements designs and  RM[t,n=2t(t-t/(p-1,p], λ2=2 for balanced  repeated measurements designs. In addition , a method has been provided for constructing              extra-balanced minimal designs for special case RM[t,n=t2/(p-1,p], λ2=1.

ATXN2 trinucleotide repeat length correlates with risk of ALS.

Science.gov (United States)

Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H; van den Berg, Leonard H; Shaw, Christopher E; Powell, John F; Al-Chalabi, Ammar

2017-03-01

We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10 -18 ), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R 2  = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

The effect of repeated testing vs repeated practice on skills learning in undergraduate dental education.

Science.gov (United States)

Sennhenn-Kirchner, S; Goerlich, Y; Kirchner, B; Notbohm, M; Schiekirka, S; Simmenroth, A; Raupach, T

2018-02-01

Recent studies in undergraduate medical education have demonstrated the advantage of repeated testing over repeated practice with regard to knowledge and skills retention. The aim of this study was to investigate whether this "testing effect" also applies to skills retention in undergraduate dental education. In this prospective, randomised controlled trial, fourth-year dental students at Göttingen University Medical Centre participated in a training session on surgical suturing in winter term 2014/2015. Following this, they were either assigned to two sessions of additional skills training (group A) or two sessions of skills assessment with feedback (group B). These sessions were spaced over a period of 4 weeks. Skills retention was assessed in a summative objective structured clinical examination (OSCE) at the end of term, that is 6 months after the initial teaching session. A total of 32 students completed the study. With regard to suturing, OSCE performance was significantly better in group B than group A (81.9±13.1% vs 63.0±15.4%; P=0.001; Cohen's d=1.33). There was no significant OSCE performance difference in the two groups with regard to other learning objectives that were addressed in the end-of-term examination. Thus, the group difference was specific to suturing skills. This is the first study to demonstrate that in dental education, repeated testing produces more favourable skills retention than repeated practice. Test-enhanced learning might be a viable concept for skills retention in undergraduate dentistry education. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

OpenAIRE

Aisling Frizzell; Jennifer H.G. Nguyen; Mark I.R. Petalcorin; Katherine D. Turner; Simon J. Boulton; Catherine H. Freudenreich; Robert S. Lahue

2014-01-01

SUMMARY Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG·CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vi...

Repeated Time-to-event Analysis of Consecutive Analgesic Events in Postoperative Pain

DEFF Research Database (Denmark)

Juul, Rasmus Vestergaard; Rasmussen, Sten; Kreilgaard, Mads

2015-01-01

BACKGROUND: Reduction in consumption of opioid rescue medication is often used as an endpoint when investigating analgesic efficacy of drugs by adjunct treatment, but appropriate methods are needed to analyze analgesic consumption in time. Repeated time-to-event (RTTE) modeling is proposed as a way...... to describe analgesic consumption by analyzing the timing of consecutive analgesic events. METHODS: Retrospective data were obtained from 63 patients receiving standard analgesic treatment including morphine on request after surgery following hip fracture. Times of analgesic events up to 96 h after surgery...... were extracted from hospital medical records. Parametric RTTE analysis was performed with exponential, Weibull, or Gompertz distribution of analgesic events using NONMEM®, version 7.2 (ICON Development Solutions, USA). The potential influences of night versus day, sex, and age were investigated...

Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2

DEFF Research Database (Denmark)

Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten

2013-01-01

The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective ...... of paternal germ-line repeat sequence instability of the expanded SCA2 locus.European Journal of Human Genetics advance online publication, 10 October 2012; doi:10.1038/ejhg.2012.231....

Vaccines against drugs of abuse: a viable treatment option?

Science.gov (United States)

Kantak, Kathleen M

2003-01-01

Drug addiction is a chronically relapsing brain disorder. There is an urgent need for new treatment options for this disease because the relapse rate among drug abusers seeking treatment is quite high. During the past decade, many groups have explored the feasibility of using vaccines directed against drugs of abuse as a means of eliminating illicit drug use as well as drug overdose and neurotoxicity. Vaccines work by inducing drug-specific antibodies in the bloodstream that bind to the drug of abuse and prevent its entry into the brain. The majority of work in this area has been conducted with vaccines and antibodies directed against cocaine and nicotine. On the basis of preclinical work, vaccines for cocaine and nicotine are now in clinical trials because they can offer long-term protection with minimal treatment compliance. In addition, vaccines and antibodies for phencyclidine, methamphetamine and heroin abuse are currently under development. An underlying theme in this research is the need for high concentrations of circulating drug-specific antibodies to reduce drug-seeking and drug-taking behaviour when the drug is repeatedly available, especially in high doses. Although vaccines against drugs of abuse may become a viable treatment option, there are several drawbacks that need to be considered. These include: a lack of protection against a structurally dissimilar drug that produces the same effects as the drug of choice;a lack of an effect on drug craving that predisposes an addict to relapse; and tremendous individual variability in antibody formation. Forced or coerced vaccination is not likely to work from a scientific perspective, and also carries serious legal and ethical concerns. All things considered, vaccination against a drug of abuse is likely to work best with individuals who are highly motivated to quit using drugs altogether and as part of a comprehensive treatment programme. As such, the medical treatment of drug abuse will not be radically

Repeated Microneedle Stimulation Induces Enhanced Hair Growth in a Murine Model.

Science.gov (United States)

Kim, Yoon Seob; Jeong, Kwan Ho; Kim, Jung Eun; Woo, Young Jun; Kim, Beom Joon; Kang, Hoon

2016-10-01

Microneedle is a method that creates transdermal microchannels across the stratum corneum barrier layer of skin. No previous study showed a therapeutic effect of microneedle itself on hair growth by wounding. The aim of this study is to investigate the effect of repeated microwound formed by microneedle on hair growth and hair growth-related genes in a murine model. A disk microneedle roller was applied to each group of mice five times a week for three weeks. First, to identify the optimal length and cycle, microneedles of lengths of 0.15 mm, 0.25 mm, 0.5 mm, and 1 mm and cycles of 3, 6, 10, and 13 cycles were applied. Second, the effect of hair growth and hair-growth-related genes such as Wnt3a, β-catenin, vascular endothelial growth factor (VEGF), and Wnt10b was observed using optimized microneedle. Outcomes were observed using visual inspection, real-time polymerase chain reaction, and immunohistochemistry. We found that the optimal length and cycle of microneedle treatment on hair growth was 0.25 mm/10 cycles and 0.5 mm/10 cycles. Repeated microneedle stimulation promoted hair growth, and it also induced the enhanced expression of Wnt3a, β-catenin, VEGF, and Wnt10b. Our study provides evidence that microneedle stimulation can induce hair growth via activation of the Wnt/β-catenin pathway and VEGF. Combined with the drug delivery effect, we believe that microneedle stimulation could lead to new approaches for alopecia.

Performance Comparisons of Improved Regular Repeat Accumulate (RA and Irregular Repeat Accumulate (IRA Turbo Decoding

Directory of Open Access Journals (Sweden)

Ahmed Abdulkadhim Hamad

2017-08-01

Full Text Available In this paper, different techniques are used to improve the turbo decoding of regular repeat accumulate (RA and irregular repeat accumulate (IRA codes. The adaptive scaling of a-posteriori information produced by Soft-output Viterbi decoder (SOVA is proposed. The encoded pilots are another scheme that applied for short length RA codes. This work also suggests a simple and a fast method to generate a random interleaver having a free 4 cycle Tanner graph. Progressive edge growth algorithm (PEG is also studied and simulated to create the Tanner graphs which have a great girth.

Electromagnetically powered electrolytic pump and thermo-responsive valve for drug delivery

KAUST Repository

Yi, Ying; Zaher, Amir; Yassine, Omar; Buttner, Ulrich; Kosel, Jü rgen; Foulds, Ian G.

2015-01-01

A novel drug delivery device is presented, implementing an electrolytic pump and a thermo-responsive valve. The device is remotely operated by an AC electromagnetic field (40.5∼58.5 mT, 450 kHz) that provides the power for the pump and the valve. It is suitable for long-term therapy applications, which use a solid drug in reservoir (SDR) approach and avoids unwanted drug diffusion. When the electromagnetic field is on, the electrolytic pump drives the drug towards the valve. The valve is made of a magnetic composite consisting of a smart hydrogel: Poly (N-Isopropylacrylamide) (PNIPAm) and iron powder. The heat generated in the iron powder via magnetic losses causes the PNIPAm to shrink, allowing the drug to flow past it. When the electromagnetic field is off, the PNIPAm swells, sealing the outlet. In the meantime, the bubbles generated by electrolysis recombine into water, causing a pressure reduction in the pumping chamber. This draws fresh fluid from outside the pump into the drug reservoir before the valve is fully sealed. The recombination can be accelerated by a platinum (Pt) coated catalytic reformer, allowing more fluid to flow back to the drug reservoir and dissolve the drug. By repeatedly turning on and off the magnetic field, the drug solution can be delivered cyclically. © 2015 IEEE.

Electromagnetically powered electrolytic pump and thermo-responsive valve for drug delivery

KAUST Repository

Yi, Ying

2015-04-01

A novel drug delivery device is presented, implementing an electrolytic pump and a thermo-responsive valve. The device is remotely operated by an AC electromagnetic field (40.5∼58.5 mT, 450 kHz) that provides the power for the pump and the valve. It is suitable for long-term therapy applications, which use a solid drug in reservoir (SDR) approach and avoids unwanted drug diffusion. When the electromagnetic field is on, the electrolytic pump drives the drug towards the valve. The valve is made of a magnetic composite consisting of a smart hydrogel: Poly (N-Isopropylacrylamide) (PNIPAm) and iron powder. The heat generated in the iron powder via magnetic losses causes the PNIPAm to shrink, allowing the drug to flow past it. When the electromagnetic field is off, the PNIPAm swells, sealing the outlet. In the meantime, the bubbles generated by electrolysis recombine into water, causing a pressure reduction in the pumping chamber. This draws fresh fluid from outside the pump into the drug reservoir before the valve is fully sealed. The recombination can be accelerated by a platinum (Pt) coated catalytic reformer, allowing more fluid to flow back to the drug reservoir and dissolve the drug. By repeatedly turning on and off the magnetic field, the drug solution can be delivered cyclically. © 2015 IEEE.

Drug Resistance and Pseudoresistance: An Unintended Consequence of Enteric Coating Aspirin

Science.gov (United States)

Grosser, Tilo; Fries, Susanne; Lawson, John A.; Kapoor, Shiv C.; Grant, Gregory R.; FitzGerald, Garret A.

2013-01-01

Background Low dose aspirin reduces the secondary incidence of myocardial infarction and stroke. Drug resistance to aspirin might result in treatment failure. Despite this concern, no clear definition of “aspirin resistance” has emerged and estimates of its incidence have varied remarkably. We aimed to determine the commonality of a mechanistically consistent, stable and specific phenotype of true pharmacological resistance to aspirin – such as might be explained by genetic causes. Methods and Results Healthy volunteers (n=400) were screened for their response to a single oral dose of 325 mg immediate release or enteric coated aspirin. Response parameters reflected the activity of aspirin's molecular target, cyclooxygenase-1. Individuals who appeared “aspirin resistant” on one occasion underwent repeat testing and if still “resistant” were exposed to low dose enteric coated aspirin (81 mg) and clopidogrel (75 mg) for one week each. Variable absorption caused a high frequency of apparent resistance to a single dose of 325 mg enteric coated aspirin (up to 49%) but not to immediate release aspirin (0%). All individuals responded to aspirin upon repeated exposure, extension of the post dosing interval or addition of aspirin to their platelets ex vivo. Conclusions Pharmacological resistance to aspirin is rare; this study failed to identify a single case of true drug resistance. Pseudoresistance, reflecting delayed and reduced drug absorption, complicates enteric coated but not immediate release aspirin administration. Clinical Trial Registration Information clinicaltrials.gov. Identifier: NCT00948987. PMID:23212718

Analysis of CR1 Repeats in the Zebra Finch Genome

Directory of Open Access Journals (Sweden)

George E. Liu

2013-06-01

Full Text Available Most bird species have smaller genomes and fewer repeats than mammals. Chicken Repeat 1 (CR1 repeat is one of the most abundant families of repeats, ranging from ~133,000 to ~187,000 copies accounting for ~50 to ~80% of the interspersed repeats in the zebra finch and chicken genomes, respectively. CR1 repeats are believed to have arisen from the retrotransposition of a small number of master elements, which gave rise to multiple CR1 subfamilies in the chicken. In this study, we performed a global assessment of the divergence distributions, phylogenies, and consensus sequences of CR1 repeats in the zebra finch genome. We identified and validated 34 CR1 subfamilies and further analyzed the correlation between these subfamilies. We also discovered 4 novel lineage-specific CR1 subfamilies in the zebra finch when compared to the chicken genome. We built various evolutionary trees of these subfamilies and concluded that CR1 repeats may play an important role in reshaping the structure of bird genomes.

Measurement of repeat effects in Chicago’s criminal social network

Directory of Open Access Journals (Sweden)

Paul Kump

2016-07-01

Full Text Available The “near-repeat” effect is a well-known criminological phenomenon in which the occurrence of a crime incident gives rise to a temporary elevation of crime risk within close physical proximity to an initial incident. Adopting a social network perspective, we instead define a near repeat in terms of geodesic distance within a criminal social network, rather than spatial distance. Specifically, we report a statistical analysis of repeat effects in arrest data for Chicago during the years 2003–2012. We divide the arrest data into two sets (violent crimes and other crimes and, for each set, we compare the distributions of time intervals between repeat incidents to theoretical distributions in which repeat incidents occur only by chance. We first consider the case of the same arrestee participating in repeat incidents (“exact repeats” and then extend the analysis to evaluate repeat risks of those arrestees near one another in the social network. We observe repeat effects that diminish as a function of geodesic distance and time interval, and we estimate typical time scales for repeat crimes in Chicago.

Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

Directory of Open Access Journals (Sweden)

Shanshan Huang

2015-10-01

Full Text Available In polyglutamine (polyQ diseases, large polyQ repeats cause juvenile cases with different symptoms than those of adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knockin mouse models of spinal cerebellar ataxia-17 (SCA17, we found that a large polyQ (105 glutamines in the TATA-box-binding protein (TBP preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases.

Large Polyglutamine Repeats Cause Muscle Degeneration in SCA17 Mice

Science.gov (United States)

Huang, Shanshan; Yang, Su; Guo, Jifeng; Yan, Sen; Gaertig, Marta A.; Li, Shihua; Li, Xiao-Jiang

2015-01-01

SUMMARY In polyglutamine (polyQ) diseases, large polyQ repeats cause juvenile cases with different symptoms than adult-onset patients, who carry smaller expanded polyQ repeats. The mechanisms behind the differential pathology mediated by different polyQ repeat lengths remain unknown. By studying knock-in mouse models of spinal cerebellar ataxia-17 (SCA17), we found that a large polyQ (105 glutamines) in the TATA box-binding protein (TBP) preferentially causes muscle degeneration and reduces the expression of muscle-specific genes. Direct expression of TBP with different polyQ repeats in mouse muscle revealed that muscle degeneration is mediated only by the large polyQ repeats. Different polyQ repeats differentially alter TBP’s interaction with neuronal and muscle-specific transcription factors. As a result, the large polyQ repeat decreases the association of MyoD with TBP and DNA promoters. Our findings suggest that specific alterations in protein interactions by large polyQ repeats may account for the unique pathology in juvenile polyQ diseases. PMID:26387956

Plasticity of the Leishmania genome leading to gene copy number variations and drug resistance [version 1; referees: 5 approved

Directory of Open Access Journals (Sweden)

Marie-Claude N. Laffitte

2016-09-01

Full Text Available Leishmania has a plastic genome, and drug pressure can select for gene copy number variation (CNV. CNVs can apply either to whole chromosomes, leading to aneuploidy, or to specific genomic regions. For the latter, the amplification of chromosomal regions occurs at the level of homologous direct or inverted repeated sequences leading to extrachromosomal circular or linear amplified DNAs. This ability of Leishmania to respond to drug pressure by CNVs has led to the development of genomic screens such as Cos-Seq, which has the potential of expediting the discovery of drug targets for novel promising drug candidates.

Modelling Formation of a Drug Reservoir in the Stratum Corneum and Its Impact on Drug Monitoring Using Reverse Iontophoresis

Directory of Open Access Journals (Sweden)

Yvonne Paulley

2010-01-01

Full Text Available Reverse iontophoresis is a relatively new technique for non-invasive drug monitoring in the body. It involves a small electrical current being passed through the skin to facilitate the movement of small charged ions and polar molecules on the skin's surface where the amount of drug can then be measured and hence an accurate estimate of the blood concentration can be made. In vivo studies for several molecules show that initially large amounts of drug are extracted from the body, which are unrelated to the magnitude of the blood concentration; over time the fluxes of extraction decrease to a level proportional to the steady state blood concentration. This suggests that, at first, the drug is being extracted from some source other than the blood; one such candidate for this source is the dead cells which form the stratum corneum. In this paper, we construct two related mathematical models; the first describes the formation of the drug reservoir in the stratum corneum as a consequence of repeated drug intake and natural death of skin cells in the body. The output from this model provides initial conditions for the model of reverse iontophoresis in which charged ions from both the blood and the stratum corneum reservoir compete for the electric current. Model parameters are estimated from data collected for lithium monitoring. Our models will improve interpretation of reverse iontophoretic data by discriminating the subdermal from the skin contribution to the fluxes of extraction. They also suggest that analysis of the skin reservoir might be a valuable tool to investigate patients' exposure to chemicals including therapeutic drugs.

Complaints against health-care professionals providing police custodial and forensic medical/health-care services and sexual offence examiner services in England, Wales and Northern Ireland.

Science.gov (United States)

Kennedy, Kieran M; Green, Peter G; Payne-James, J Jason

2017-01-01

Complaints management is an integral component of good clinical governance and an essential contributor to patient safety. Little is known about complaints against health-care professionals (HCPs) in police custodial settings and sexual assault referral centres. This study explored the frequency with which complaints are made against such HCPs working in England, Wales and Northern Ireland. It explored the nature of those complaints and the procedures by which they are investigated. Relevant information was requested from all police services in England, Wales and Northern Ireland; professional regulatory bodies; and the Independent Police Complaints Commission under the Freedom of Information Act (FOIA). Eighty-nine per cent of police services responded to the FOIA request. However, only a minority of these provided detailed information. Many police services cited the provision of health-care services by external providers as the reason for not holding information upon complaints. There was no evidence of any upward trend in the numbers of complaints over the study period. Delayed response to a request for attendance, incivility, medication issues and issues regarding the quality of reports and evidence were amongst the most common types of complaints described. A small number of responders provided copies of the disciplinary procedures used to manage complaints against HCPs. Significant heterogeneity exists in respect of complaints handling procedures across custodial and forensic medical/health-care services and sexual offence examiner services. An opportunity to identify learning for improvement is being missed as a result of the absence of standardised complaints handling procedures.

A Phase I randomized clinical trial testing the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy volunteers.

Science.gov (United States)

Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

2017-11-15

Preclinical work suggests that the metabotropic glutamate receptor subtype 5 (mGlu5) may represent a novel target to treat neuropsychiatric disorders, including alcohol use disorder and obesity. The goal of this first-in-man study was to evaluate the safety, tolerability and pharmacokinetics (PK) of GET 73 (PubChem SID: 329974174), a novel mGluR5 negative allosteric modulator. This was a double-blind, placebo-controlled, ascending dose, Phase I study conducted in healthy male volunteers in two experiments. GET 73 was administered as single ascending doses (N=48; Experiment 1; 10, 30, 100, 300, 450, 600-mg) or multiple ascending doses (N=32; Experiment 2; 100, 300, 450, 450-mg twice a day). Primary endpoints were the incidence of adverse events (AEs) among drug conditions and drug tolerability. The secondary endpoints were the PK parameters of GET 73 and its metabolite MET 2. Single GET 73 doses of up to 600-mg and repeated ascending doses of up to 450-mg twice/day were safe and well-tolerated. There were no serious or severe AEs. All AEs were mild or moderate in severity. Total GET 73 exposure increased with each increased GET 73 dose. A dose-related increase in mean maximum plasma drug concentration was observed after repeated dosing. Maximum plasma drug concentrations occurred between 0.5 and 2.05h after administration in all groups for both single and repeated doses. This first-in-human study indicates that GET 73, as single or multiple ascending doses, is safe and well-tolerated when administered to healthy male volunteers. Copyright © 2017 Elsevier B.V. All rights reserved.

Epitopes of MUC1 Tandem Repeats in Cancer as Revealed by Antibody Crystallography: Toward Glycopeptide Signature-Guided Therapy

Directory of Open Access Journals (Sweden)

Dapeng Zhou

2018-05-01

Full Text Available Abnormally O-glycosylated MUC1 tandem repeat glycopeptide epitopes expressed by multiple types of cancer have long been attractive targets for therapy in the race against genetic mutations of tumor cells. Glycopeptide signature-guided therapy might be a more promising avenue than mutation signature-guided therapy. Three O-glycosylated peptide motifs, PDTR, GSTA, and GVTS, exist in a tandem repeat HGVTSAPDTRPAPGSTAPPA, containing five O-glycosylation sites. The exact peptide and sugar residues involved in antibody binding are poorly defined. Co-crystal structures of glycopeptides and respective monoclonal antibodies are very few. Here we review 3 groups of monoclonal antibodies: antibodies which only bind to peptide portion, antibodies which only bind to sugar portion, and antibodies which bind to both peptide and sugar portions. The antigenicity of peptide and sugar portions of glyco-MUC1 tandem repeat were analyzed according to available biochemical and structural data, especially the GSTA and GVTS motifs independent from the most studied PDTR. Tn is focused as a peptide-modifying residue in vaccine design, to induce glycopeptide-binding antibodies with cross reactivity to Tn-related tumor glycans, but not glycans of healthy cells. The unique requirement for the designs of antibody in antibody-drug conjugate, bi-specific antibodies, and chimeric antigen receptors are also discussed.

The complete chloroplast genome sequence of Taxus chinensis var. mairei (Taxaceae): loss of an inverted repeat region and comparative analysis with related species.

Science.gov (United States)

Zhang, Yanzhen; Ma, Ji; Yang, Bingxian; Li, Ruyi; Zhu, Wei; Sun, Lianli; Tian, Jingkui; Zhang, Lin

2014-05-01

Taxus chinensis var. mairei (Taxaceae) is a domestic variety of yew species in local China. This plant is one of the sources for paclitaxel, which is a promising antineoplastic chemotherapy drugs during the last decade. We have sequenced the complete nucleotide sequence of the chloroplast (cp) genome of T. chinensis var. mairei. The T. chinensis var. mairei cp genome is 129,513 bp in length, with 113 single copy genes and two duplicated genes (trnI-CAU, trnQ-UUG). Among the 113 single copy genes, 9 are intron-containing. Compared to other land plant cp genomes, the T. chinensis var. mairei cp genome has lost one of the large inverted repeats (IRs) found in angiosperms, fern, liverwort, and gymnosperm such as Cycas revoluta and Ginkgo biloba L. Compared to related species, the gene order of T. chinensis var. mairei has a large inversion of ~110kb including 91 genes (from rps18 to accD) with gene contents unarranged. Repeat analysis identified 48 direct and 2 inverted repeats 30 bp long or longer with a sequence identity greater than 90%. Repeated short segments were found in genes rps18, rps19 and clpP. Analysis also revealed 22 simple sequence repeat (SSR) loci and almost all are composed of A or T. Copyright © 2014 Elsevier B.V. All rights reserved.

A repeating fast radio burst.

Science.gov (United States)

Spitler, L G; Scholz, P; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

2016-03-10

Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

RTEL1 inhibits trinucleotide repeat expansions and fragility.

Science.gov (United States)

Frizzell, Aisling; Nguyen, Jennifer H G; Petalcorin, Mark I R; Turner, Katherine D; Boulton, Simon J; Freudenreich, Catherine H; Lahue, Robert S

2014-03-13

Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG) repeat expansions and fragility, likely by unwinding problematic hairpins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Legal Drugs Are Good Drugs And Illegal Drugs Are Bad Drugs

Directory of Open Access Journals (Sweden)

Dina Indrati

2011-07-01

Full Text Available ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing setting and dual diagnosis.Key words: Legal, good drugs, illegal, bad drugs.

Contraceptive Use among Women Seeking Repeat Abortion in ...

African Journals Online (AJOL)

AJRH Managing Editor

Compared with women seeking their first abortion, significantly more repeat abortion clients had ever used contraceptives ... findings, the level of repeat abortions in Europe, .... and contraceptive history, and post-abortion ..... working women.

Environmental stress induces trinucleotide repeat mutagenesis in human cells.

Science.gov (United States)

Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A; Yotnda, Patricia; Wilson, John H

2015-03-24

The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)-the cause of multiple human diseases-have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential.

Oxidative stress adaptation with acute, chronic, and repeated stress.

Science.gov (United States)

Pickering, Andrew M; Vojtovich, Lesya; Tower, John; A Davies, Kelvin J

2013-02-01

Oxidative stress adaptation, or hormesis, is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells and the fruit fly Drosophila melanogaster are capable of adapting to chronic or repeated stress by upregulating protective systems, such as their proteasomal proteolytic capacity to remove oxidized proteins. Repeated stress adaptation resulted in significant extension of adaptive responses. Repeated stresses must occur at sufficiently long intervals, however (12-h or more for MEF cells and 7 days or more for flies), for adaptation to be successful, and the levels of both repeated and chronic stress must be lower than is optimal for adaptation to acute stress. Regrettably, regimens of adaptation to both repeated and chronic stress that were successful for short-term survival in Drosophila nevertheless also caused significant reductions in life span for the flies. Thus, although both repeated and chronic stress can be tolerated, they may result in a shorter life. Copyright © 2012 Elsevier Inc. All rights reserved.

Stress, habits, and drug addiction: a psychoneuroendocrinological perspective.

Science.gov (United States)

Schwabe, Lars; Dickinson, Anthony; Wolf, Oliver T

2011-02-01

It is well known that stress is a significant risk factor for the development of drug addiction and addiction relapse. Remarkably, the cognitive processes involved in the effects of stress on addictive behavior remain poorly understood. Here it is proposed that stress-induced changes in the neural circuits controlling instrumental action provide a potential mechanism by which stress affects the development of addiction and relapse vulnerability. Instrumental action can be controlled by two anatomically distinct systems: a goal-directed system that involves learning of action-outcome associations, and a habit system that learns stimulus-response associations. The transition from initial voluntary drug use to subsequent involuntary, compulsive drug use represents a switch from goal-directed to habitual control of action. Recent evidence indicates that this switch from goal-directed to habit action can be prompted by stress and stress hormones. We argue (i) that acute stressors reinstate habitual responding to drug-related cues and thus trigger relapse to addictive behavior, and (ii) that prolonged or repeated stress may accelerate the transition from voluntary to involuntary drug use and thus promote the development of addiction. The suggested mechanism encompasses cognitive processes that may contribute to the effects of stress on addictive behavior and could have important implications for the treatment of addiction and the prevention of relapse. (c) 2011 APA, all rights reserved

Kebijakan Penal Mengenai Kriminalisasi Di Bidang Keuangan

OpenAIRE

Luthan, Salman

2009-01-01

Research of penal policy on criminalization in financial affairs discusses two main problems: regulating policy on criminal offences, and regulating policy on criminal sanction for financial offences. The regulating policy on criminal offences shows an increase of various conducts that have been criminalized by legislator as a consequence of social change, economic and trade globalization, as well as technological development. Justification of criminalization base on liberal individualiatic t...

Legal Drugs Are Good Drugs and Illegal Drugs Are Bad Drugs

OpenAIRE

Indrati, Dina; Prasetyo, Herry

2011-01-01

ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing s...

Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

International Nuclear Information System (INIS)

Aubuchon, Adam C.; Chan, Michael D.; Lovato, James F.; Balamucki, Christopher J.; Ellis, Thomas L.; Tatter, Stephen B.; McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G.

2011-01-01

Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80–90). The mean retreatment dose was 84.4 Gy (range, 60–90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

Energy Technology Data Exchange (ETDEWEB)

Aubuchon, Adam C., E-mail: acaubuchon@gmail.com [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Lovato, James F. [Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Balamucki, Christopher J. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

2011-11-15

Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

Repeat Assessed Values Model for Housing Price Index

Directory of Open Access Journals (Sweden)

Carini Manuela

2017-12-01

Full Text Available This study proposes an innovative methodology, named Repeat Appraised Price Model (RAV, useful for determining the price index numbers for real estate markets and the corresponding index numbers of hedonic prices of main real estate characteristics in the case of a lack of data. The methodological approach proposed in this paper aims to appraise the time series of price index numbers. It integrates the principles of the method of repeat sales with the peculiarities of the Hedonic Price Method, overcoming the problem of an almost total absence of repeat sales for the same property in a given time range; on the other hand, the technique aims to overcome the limitation of the repeat sales technique concerning the inability to take into account the characteristics of individual properties.

Repeatability and reproducibility of decisions by latent fingerprint examiners.

Directory of Open Access Journals (Sweden)

Bradford T Ulery

Full Text Available The interpretation of forensic fingerprint evidence relies on the expertise of latent print examiners. We tested latent print examiners on the extent to which they reached consistent decisions. This study assessed intra-examiner repeatability by retesting 72 examiners on comparisons of latent and exemplar fingerprints, after an interval of approximately seven months; each examiner was reassigned 25 image pairs for comparison, out of total pool of 744 image pairs. We compare these repeatability results with reproducibility (inter-examiner results derived from our previous study. Examiners repeated 89.1% of their individualization decisions, and 90.1% of their exclusion decisions; most of the changed decisions resulted in inconclusive decisions. Repeatability of comparison decisions (individualization, exclusion, inconclusive was 90.0% for mated pairs, and 85.9% for nonmated pairs. Repeatability and reproducibility were notably lower for comparisons assessed by the examiners as "difficult" than for "easy" or "moderate" comparisons, indicating that examiners' assessments of difficulty may be useful for quality assurance. No false positive errors were repeated (n = 4; 30% of false negative errors were repeated. One percent of latent value decisions were completely reversed (no value even for exclusion vs. of value for individualization. Most of the inter- and intra-examiner variability concerned whether the examiners considered the information available to be sufficient to reach a conclusion; this variability was concentrated on specific image pairs such that repeatability and reproducibility were very high on some comparisons and very low on others. Much of the variability appears to be due to making categorical decisions in borderline cases.

Reproducibility and Reliability of Repeated Quantitative Fluorescence Angiography

DEFF Research Database (Denmark)

Nerup, Nikolaj; Knudsen, Kristine Bach Korsholm; Ambrus, Rikard

2017-01-01

INTRODUCTION: When using fluorescence angiography (FA) in perioperative perfusion assessment, repeated measures with re-injections of fluorescent dye (ICG) may be required. However, repeated injections may cause saturation of dye in the tissue, exceeding the limit of fluorescence intensity...... that the camera can detect. As the emission of fluorescence is dependent of the excitatory light intensity, reduction of this may solve the problem. The aim of the present study was to investigate the reproducibility and reliability of repeated quantitative FA during a reduction of excitatory light....

Microbial receptor assay for rapid detection and identification of seven families of antimicrobial drugs in milk: collaborative study

International Nuclear Information System (INIS)

Charm, S.E.; Chi, R.

1988-01-01

A microbial competitive receptor assay for detecting residues of antibiotic families in milk was studied collaboratively by 13 laboratories. In this method, microbial cells added to a milk sample provide specific binding sites for which 14 C or 3 H labeled drug competes with drug resides in the sample. The 14 C or 3 H binding to the specific binding sites is measured in a scintillation counter and compared with a zero standard milk. If the sample is statistically different from the zero standard, it is positive. The assay takes about 15 min. The binding reaction occurs between the receptor site and the drug functional group, so all members of a drug family are detected. In this case, beta-lactams, tetracyclines, macrolides, aminoglycosides, novobiocin, chloramphenicol, and sulfonamides, including p-amino-benzoic acid (PABA) and its other analogs, are detectable. The incidence of false negative determinations among samples is about 1%; the incidence of false positives is about 3%. For negative cases, the relative standard deviations for repeatability ranged from 0 to 5% and for reproducibility from 0 to 6%. For positive cases, relative standard deviations ranged from 0 to 13% for repeatability and from 0 to 14% for reproducibility. The method has been adopted official first action

Original article Latent classes of criminal intent associated with criminal behaviour

Directory of Open Access Journals (Sweden)

Daniel Boduszek

2014-07-01

Full Text Available Background This study aimed to examine the number of latent classes of criminal intent that exist among prisoners and to look at the associations with recidivism, number of police arrests, type of offending (robbery, violent offences, murder, and multiple offences, and age. Participants and procedure Latent class analysis was used to identify homogeneous subgroups of prisoners based on their responses to the 10 questions reflecting criminal intent. Participants were 309 male recidivistic prisoners incarcerated in a maximum security prison. Multinomial logistic regression was used to interpret the nature of the latent classes, or groups, by estimating the association between recidivism and latent classes of criminal intent while controlling for offence type (robbery, violent offences, murder, and multiple offences, number of arrests, and age. Results The best fitting latent class model was a three-class solution: ‘High criminal intent’ (49.3%, ‘Intermediate criminal intent’ (41.3%, and ‘Low criminal intent’ (9.4%. The latent classes were differentially related to the external variables (recidivism, violent offences, and age. Conclusions Criminal intent is best explained by three homogeneous classes that appear to represent an underlying continuum. Future work is needed to identify whether these distinct classes of criminal intent may predict engagement in various types of criminal behaviour.

Clinical oversight and the avoidance of repeat induced abortion.

Science.gov (United States)

Jacovetty, Erica L; Clare, Camille A; Squire, Mary-Beatrice; Kubal, Keshar P; Liou, Sherry; Inchiosa, Mario A

2018-06-03

To evaluate the impact of patient counseling, demographics, and contraceptive methods on repeat induced abortion in women attending family planning clinics. A retrospective chart review of repeat induced abortions was performed. The analysis included patients with an initial induced abortion obtained between January 1, 2001, and March 31, 2014, at New York City Health + Hospitals/Metropolitan. The duration of involvement in the family planning program, the use of contraceptive interventions, and 18 patient factors were analyzed for their correlation with the incidence of repeat induced abortions per year of follow-up. A decreased rate of repeat induced abortions was associated with a longer duration of clinical oversight (r 2 =0.449, Pabortions. By determining the patient characteristics that most influence repeat induced abortion rates, providers can best choose the most efficacious method of contraception available. © 2018 International Federation of Gynecology and Obstetrics.

A comparison of the intrasubject variation in drug exposure between generic and brand-name drugs: a retrospective analysis of replicate design trials.

Science.gov (United States)

Yu, Yang; Teerenstra, Steven; Neef, Cees; Burger, David; Maliepaard, Marc

2016-04-01

The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due to differences between formulations or to intrasubject pharmacokinetic variability of the active substance. The study was designed as a retrospective reanalysis of existing studies. Nine replicate design bioequivalence studies representing six drug classes - i.e. for alendronate, atorvastatin, cyclosporin, ebastine, exemestane, mycophenolate mofetil, and ropinirole - were retrieved from the Dutch Medicines Regulatory Authority. In most studies, the intrasubject variability in total and peak drug exposure was comparable for the brand-name [in the range 0.01-0.24 for area under the concentration-time curve (AUCt ) and 0.02-0.29 for peak plasma concentration (Cmax ) on a log scale] and generic (0.01-0.23 for AUCt and 0.08-0.33 for Cmax ) drugs, and was comparable with the intrasubject variability upon switching between those drugs (0.01-0.23 for AUCt and 0.06-0.33 for Cmax ). The variance related to subject-by-formulation interaction could be considered negligible (-0.069 to 0.047 for AUCt and -0.091 to 0.02 for Cmax ). In the investigated studies, the variation in total and peak exposure seen when a patient is switched from a brand-name to a generic drug is comparable with that seen following repeated administration of the brand-name drug in the patient. Only the intrasubject variability seems to play a crucial and decisive role in the variation in drug exposure seen; no additional formulation-dependent variation in exposure is observed upon switching. Thus, our data support that, for the medicines that were included in the present investigation, from a clinical pharmacological perspective, the benefit-risk balance of a generic drug is comparable with that of the brand-name drug. © 2015 The British Pharmacological Society.

Methods for analysing cardiovascular studies with repeated measures

NARCIS (Netherlands)

Cleophas, T. J.; Zwinderman, A. H.; van Ouwerkerk, B. M.

2009-01-01

Background. Repeated measurements in a single subject are generally more similar than unrepeated measurements in different subjects. Unrepeated analyses of repeated data cause underestimation of the treatment effects. Objective. To review methods adequate for the analysis of cardiovascular studies

TALEN-Induced Double-Strand Break Repair of CTG Trinucleotide Repeats

Directory of Open Access Journals (Sweden)

Valentine Mosbach

2018-02-01

Full Text Available Trinucleotide repeat expansions involving CTG/CAG triplets are responsible for several neurodegenerative disorders, including myotonic dystrophy and Huntington’s disease. Because expansions trigger the disease, contracting repeat length could be a possible approach to gene therapy for these disorders. Here, we show that a TALEN-induced double-strand break was very efficient at contracting expanded CTG repeats in yeast. We show that RAD51, POL32, and DNL4 are dispensable for double-strand break repair within CTG repeats, the only required genes being RAD50, SAE2, and RAD52. Resection was totally abolished in the absence of RAD50 on both sides of the break, whereas it was reduced in a sae2Δ mutant on the side of the break containing the longest repeat tract, suggesting that secondary structures at double-strand break ends must be removed by the Mre11-Rad50 complex and Sae2. Following the TALEN double-strand break, single-strand annealing occurred between both sides of the repeat tract, leading to repeat contraction.

In silico reversal of repeat-induced point mutation (RIP identifies the origins of repeat families and uncovers obscured duplicated genes

Directory of Open Access Journals (Sweden)

Hane James K

2010-11-01

Full Text Available Abstract Background Repeat-induced point mutation (RIP is a fungal genome defence mechanism guarding against transposon invasion. RIP mutates the sequence of repeated DNA and over time renders the affected regions unrecognisable by similarity search tools such as BLAST. Results DeRIP is a new software tool developed to predict the original sequence of a RIP-mutated region prior to the occurrence of RIP. In this study, we apply deRIP to the genome of the wheat pathogen Stagonospora nodorum SN15 and predict the origin of several previously uncharacterised classes of repetitive DNA. Conclusions Five new classes of transposon repeats and four classes of endogenous gene repeats were identified after deRIP. The deRIP process is a new tool for fungal genomics that facilitates the identification and understanding of the role and origin of fungal repetitive DNA. DeRIP is open-source and is available as part of the RIPCAL suite at http://www.sourceforge.net/projects/ripcal.

Changes in contractile properties of muscles receiving repeat injections of botulinum toxin (Botox).

Science.gov (United States)

Fortuna, Rafael; Vaz, Marco Aurélio; Youssef, Aliaa Rehan; Longino, David; Herzog, Walter

2011-01-04

Botulinum toxin type A (BTX-A) is a frequently used therapeutic tool to denervate muscles in the treatment of neuromuscular disorders. Although considered safe by the US Food and Drug Administration, BTX-A can produce adverse effects in target and non-target muscles. With an increased use of BTX-A for neuromuscular disorders, the effects of repeat injections of BTX-A on strength, muscle mass and structure need to be known. Therefore, the purpose of this study was to investigate the changes in strength, muscle mass and contractile material in New Zealand White (NZW) rabbits. Twenty NZW rabbits were divided into 4 groups: control and 1, 3 and 6 months of unilateral, repeat injections of BTX-A into the quadriceps femoris. Outcome measures included knee extensor torque, muscle mass and the percentage of contractile material in the quadriceps muscles of the target and non-injected contralateral hindlimbs. Strength in the injected muscles was reduced by 88%, 89% and 95% in the 1, 3 and 6 months BTX-A injected hindlimbs compared to controls. Muscle mass was reduced by 50%, 42% and 31% for the vastus lateralis (VL), rectus femoris (RF) and vastus medialis (VM), respectively, at 1 month, by 68%, 51% and 50% at 3 months and by 76%, 44% and 13% at 6 months. The percentage of contractile material was reduced for the 3 and 6 months animals to 80-64%, respectively, and was replaced primarily by fat. Similar, but less pronounced results were also observed for the quadriceps muscles of the contralateral hindlimbs, suggesting that repeat BTX-A injections cause muscle atrophy and loss of contractile tissue in target muscles and also in non-target muscles that are far removed from the injection site. Copyright © 2010 Elsevier Ltd. All rights reserved.

[Pharmacotherapy of hyperthyreosis--adverse drug reactions].

Science.gov (United States)

Perger, Ludwig; Bürgi, Ulrich; Fattinger, Karin

2011-06-01

The antithyroid drugs mainly include thioimidazole (carbimazole, methimazole=thiamazole) and propylthiouracil. After absorption, carbimazole is rapidly metabolized to methimazole and thus switching between these two drugs should not be considered in case of side effects. Furthermore, in case of side effects, sometimes even cross reactions between thioimidazoles and propylthiouracil occur. Common and typical adverse reactions of antithyroid drugs include dose dependent hypothyroidism and thus thyroid function should be repeatedly checked while the patient is on antithyroid drugs. Furthermore, pruritus and rash may develop. In this case, one might try to switch from thioimidazoles to propylthiouracil or vice versa. Antithyroid drugs may cause mild dose dependent neutropenia or severe allergy-mediated agranulocytosis, which typically occurs during the first three months of treatment, has an incidence of 3 per 10,000 patients and cross reactivity between thioimidazoles to propylthiouracil may occur. Rarely, antithyroid drugs can cause aplastic anemia. Mainly propylthiouracil, but sometimes also methimazole may lead to an asymptomatic transient increase in liver enzymes or to severe, even lethal liver injury of cholestatic or hepatocellular pattern. Since propylthiouracil associated liver injury was observed increasingly among children and adolescent, it has been suggested to prefer thioimidazoles for these patients. Because of these potential serious adverse effects, physicians should advise patients to immediately seek medical help if they get a fever or sore throat or malaise, abdominal complaints or jaundice, respectively. Furthermore, arthralgias may develop in 1-5% of patients under both antithyroid drugs. Since arthralgias may be the first symptom of more serious immunologic side effects, it is recommended to stop the antithyroid drug in this case. Drug induced polyarthritis mainly develops during the first month of therapy, whereas ANCA-positive vasculitis is

[Pre-trial psychiatric reports on Antillean suspected offenders in the Netherlands and on the Dutch Antilles].

Science.gov (United States)

Vinkers, D J; Heytel, F G M; Matroos, G M; Hermans, K M; Hoek, H W

2010-01-01

The registered criminality among Antilleans living in the Netherlands is much higher than among Antilleans living on the Dutch Antilles (113 offences and 11 offences respectively, per year per 1000 persons, pDutch Antilles (n=199) between 2000 and 2006. A careful study was made of pre-trial psychiatric reports on Antillean suspected offenders (referred to as suspects) in the Netherlands and of comparable reports on Antillean suspects on the Dutch Antilles. There was no significant difference in the prevalence of mental disorders among Antillean suspects in the Netherlands (22.3%) and on the Dutch Antilles (20.3%). Abuse of drugs and cannabis was more prevalent on the Dutch Antilles where treatment for addiction is less frequently available than in the Netherlands. Mental retardation was ascertained more often among Antilleans in the Netherlands (22.4%) than among Antilleans on the Dutch Antilles (15.1%). Antillean suspects on the Dutch Antilles were more often found to be fully responsible for their actions than were Antillean suspects in the Netherlands (65.3% versus 19.1%, pDutch Antilles.

simple sequence repeat (SSR)

African Journals Online (AJOL)

In the present study, 78 mapped simple sequence repeat (SSR) markers representing 11 linkage groups of adzuki bean were evaluated for transferability to mungbean and related Vigna spp. 41 markers amplified characteristic bands in at least one Vigna species. The transferability percentage across the genotypes ranged ...

Simple sequence repeat marker development and genetic mapping ...

Indian Academy of Sciences (India)

polymorphic SSR (simple sequence repeats) markers from libraries enriched for GA, CAA and AAT repeats, as well as 6 ... ers for quinoa was the development of a genetic linkage map ...... Weber J. L. 1990 Informativeness of human (dC-dA)n.

Repeatability study of replicate crash tests: A signal analysis approach.

Science.gov (United States)

Seppi, Jeremy; Toczyski, Jacek; Crandall, Jeff R; Kerrigan, Jason

2017-10-03

To provide an objective basis on which to evaluate the repeatability of vehicle crash test methods, a recently developed signal analysis method was used to evaluate correlation of sensor time history data between replicate vehicle crash tests. The goal of this study was to evaluate the repeatability of rollover crash tests performed with the Dynamic Rollover Test System (DRoTS) relative to other vehicle crash test methods. Test data from DRoTS tests, deceleration rollover sled (DRS) tests, frontal crash tests, frontal offset crash tests, small overlap crash tests, small overlap impact (SOI) crash tests, and oblique crash tests were obtained from the literature and publicly available databases (the NHTSA vehicle database and the Insurance Institute for Highway Safety TechData) to examine crash test repeatability. Signal analysis of the DRoTS tests showed that force and deformation time histories had good to excellent repeatability, whereas vehicle kinematics showed only fair repeatability due to the vehicle mounting method for one pair of tests and slightly dissimilar mass properties (2.2%) in a second pair of tests. Relative to the DRS, the DRoTS tests showed very similar or higher levels of repeatability in nearly all vehicle kinematic data signals with the exception of global X' (road direction of travel) velocity and displacement due to the functionality of the DRoTS fixture. Based on the average overall scoring metric of the dominant acceleration, DRoTS was found to be as repeatable as all other crash tests analyzed. Vertical force measures showed good repeatability and were on par with frontal crash barrier forces. Dynamic deformation measures showed good to excellent repeatability as opposed to poor repeatability seen in SOI and oblique deformation measures. Using the signal analysis method as outlined in this article, the DRoTS was shown to have the same or better repeatability of crash test methods used in government regulatory and consumer evaluation test

Repeating pneumatic pellet injector in JAERI

Energy Technology Data Exchange (ETDEWEB)

Kasai, Satoshi; Hasegawa, Kouichi; Suzuki, Sadaaki; Miura, Yukitoshi (Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment); Oda, Yasushi; Onozuka, Masanori; Tsujimura, Seiichi.

1992-09-01

A repeating pneumatic pellet injector has been developed and constructed at Japan Atomic Energy Research Institute. This injector can provide repetitive pellet injection to fuel tokamak plasmas for an extended period of time, aiming at the improvement of plasma performance. The pellets with nearly identical speed and mass can be repeatedly injected with a repetition rate of 2-3.3 Hz and a speed of up to 1.7 km/s by controlling the temperature of the cryogenic system, the piston speed and the pressure of the propellant gas. (author).

Repeating pneumatic pellet injector in JAERI

International Nuclear Information System (INIS)

Kasai, Satoshi; Hasegawa, Kouichi; Suzuki, Sadaaki; Miura, Yukitoshi; Oda, Yasushi; Onozuka, Masanori; Tsujimura, Seiichi.

1992-09-01

A repeating pneumatic pellet injector has been developed and constructed at Japan Atomic Energy Research Institute. This injector can provide repetitive pellet injection to fuel tokamak plasmas for an extended period of time, aiming at the improvement of plasma performance. The pellets with nearly identical speed and mass can be repeatedly injected with a repetition rate of 2-3.3 Hz and a speed of up to 1.7 km/s by controlling the temperature of the cryogenic system, the piston speed and the pressure of the propellant gas. (author)

ACCA phosphopeptide recognition by the BRCT repeats of BRCA1.

Science.gov (United States)

Ray, Hind; Moreau, Karen; Dizin, Eva; Callebaut, Isabelle; Venezia, Nicole Dalla

2006-06-16

The tumour suppressor gene BRCA1 encodes a 220 kDa protein that participates in multiple cellular processes. The BRCA1 protein contains a tandem of two BRCT repeats at its carboxy-terminal region. The majority of disease-associated BRCA1 mutations affect this region and provide to the BRCT repeats a central role in the BRCA1 tumour suppressor function. The BRCT repeats have been shown to mediate phospho-dependant protein-protein interactions. They recognize phosphorylated peptides using a recognition groove that spans both BRCT repeats. We previously identified an interaction between the tandem of BRCA1 BRCT repeats and ACCA, which was disrupted by germ line BRCA1 mutations that affect the BRCT repeats. We recently showed that BRCA1 modulates ACCA activity through its phospho-dependent binding to ACCA. To delineate the region of ACCA that is crucial for the regulation of its activity by BRCA1, we searched for potential phosphorylation sites in the ACCA sequence that might be recognized by the BRCA1 BRCT repeats. Using sequence analysis and structure modelling, we proposed the Ser1263 residue as the most favourable candidate among six residues, for recognition by the BRCA1 BRCT repeats. Using experimental approaches, such as GST pull-down assay with Bosc cells, we clearly showed that phosphorylation of only Ser1263 was essential for the interaction of ACCA with the BRCT repeats. We finally demonstrated by immunoprecipitation of ACCA in cells, that the whole BRCA1 protein interacts with ACCA when phosphorylated on Ser1263.

Criminal law aspects of assisted human reproduction in Serbia

Directory of Open Access Journals (Sweden)

Samardžić Stefan

2013-01-01

Full Text Available Numerous shortcomings of the Law on Infertility Treatment by Biomedically Assisted Fertilization culminate in provisions defining criminal offences. A question is raised regarding the possibility and results of the application of such criminal provisions due to the legislative technique used in the process of their creation, language, qualified forms of the offences, span of criminal sanctions, as well as having in mind the overlapping of such criminal offences with some of the misdemeanors punishable by the same Law. A possibility to provide for a criminal law protection in this highly sensitive area is put into question due to a very courageous action of the legislator reflected in the attempt to introduce criminal offences, punishable by long prison sentences.

A high-speed drug interaction search system for ease of use in the clinical environment.

Science.gov (United States)

Takada, Masahiro; Inada, Hiroshi; Nakazawa, Kazuo; Tani, Shoko; Iwata, Michiaki; Sugimoto, Yoshihisa; Nagata, Satoru

2012-12-01

With the advancement of pharmaceutical development, drug interactions have become increasingly complex. As a result, a computer-based drug interaction search system is required to organize the whole of drug interaction data. To overcome problems faced with the existing systems, we developed a drug interaction search system using a hash table, which offers higher processing speeds and easier maintenance operations compared with relational databases (RDB). In order to compare the performance of our system and MySQL RDB in terms of search speed, drug interaction searches were repeated for all 45 possible combinations of two out of a group of 10 drugs for two cases: 5,604 and 56,040 drug interaction data. As the principal result, our system was able to process the search approximately 19 times faster than the system using the MySQL RDB. Our system also has several other merits such as that drug interaction data can be created in comma-separated value (CSV) format, thereby facilitating data maintenance. Although our system uses the well-known method of a hash table, it is expected to resolve problems common to existing systems and to be an effective system that enables the safe management of drugs.

Electromyographic analysis of repeated bouts of eccentric exercise.

Science.gov (United States)

McHugh, M P; Connolly, D A; Eston, R G; Gartman, E J; Gleim, G W

2001-03-01

The repeated bout effect refers to the protective effect provided by a single bout of eccentric exercise against muscle damage from a similar subsequent bout. The aim of this study was to determine if the repeated bout was associated with an increase in motor unit activation relative to force production, an increased recruitment of slow-twitch motor units or increased motor unit synchronization. Surface electromyographic (EMG) signals were recorded from the hamstring muscles during two bouts of submaximal isokinetic (2.6 rad x s(-1)) eccentric (11 men, 9 women) or concentric (6 men, 4 women) contractions separated by 2 weeks. The EMG per unit torque and median frequency were analysed. The initial bout of eccentric exercise resulted in strength loss, pain and muscle tenderness, while the repeated eccentric bout resulted in a slight increase in strength, no pain and no muscle tenderness (bout x time effects, P exercise. The EMG per unit torque and median frequency were not different between the initial and repeated bouts of eccentric exercise. The EMG per unit torque and median frequency increased during both bouts of eccentric exercise (P < 0.01) but did not change during either concentric bout. In conclusion, there was no evidence that the repeated bout effect was due to a neural adaptation.

Laws and regulations

International Nuclear Information System (INIS)

Abd Nasir Ibrahim; Azali Muhammad; Ab Razak Hamzah; Abd Aziz Mohamed; Mohammad Pauzi Ismail

2004-01-01

This chapter discusses the following subjects - Licensing: classification of licenses, licensing procedure, issuance of license. safety requirements: inspection: penalty under the Act: obstruction of inspection, search or investigation an offence, offence

40 CFR 1065.305 - Verifications for accuracy, repeatability, and noise.

Science.gov (United States)

2010-07-01

..., repeatability, and noise. 1065.305 Section 1065.305 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Verifications for accuracy, repeatability, and noise. (a) This section describes how to determine the accuracy, repeatability, and noise of an instrument. Table 1 of § 1065.205 specifies recommended values for individual...

The dopamine motive system: implications for drug and food addiction.

Science.gov (United States)

Volkow, Nora D; Wise, Roy A; Baler, Ruben

2017-11-16

Behaviours such as eating, copulating, defending oneself or taking addictive drugs begin with a motivation to initiate the behaviour. Both this motivational drive and the behaviours that follow are influenced by past and present experience with the reinforcing stimuli (such as drugs or energy-rich foods) that increase the likelihood and/or strength of the behavioural response (such as drug taking or overeating). At a cellular and circuit level, motivational drive is dependent on the concentration of extrasynaptic dopamine present in specific brain areas such as the striatum. Cues that predict a reinforcing stimulus also modulate extrasynaptic dopamine concentrations, energizing motivation. Repeated administration of the reinforcer (drugs, energy-rich foods) generates conditioned associations between the reinforcer and the predicting cues, which is accompanied by downregulated dopaminergic response to other incentives and downregulated capacity for top-down self-regulation, facilitating the emergence of impulsive and compulsive responses to food or drug cues. Thus, dopamine contributes to addiction and obesity through its differentiated roles in reinforcement, motivation and self-regulation, referred to here as the 'dopamine motive system', which, if compromised, can result in increased, habitual and inflexible responding. Thus, interventions to rebalance the dopamine motive system might have therapeutic potential for obesity and addiction.

Two tandemly repeated telomere-associated sequences in Nicotiana plumbaginifolia.

Science.gov (United States)

Chen, C M; Wang, C T; Wang, C J; Ho, C H; Kao, Y Y; Chen, C C

1997-12-01

Two tandemly repeated telomere-associated sequences, NP3R and NP4R, have been isolated from Nicotiana plumbaginifolia. The length of a repeating unit for NP3R and NP4R is 165 and 180 nucleotides respectively. The abundance of NP3R, NP4R and telomeric repeats is, respectively, 8.4 x 10(4), 6 x 10(3) and 1.5 x 10(6) copies per haploid genome of N. plumbaginifolia. Fluorescence in situ hybridization revealed that NP3R is located at the ends and/or in interstitial regions of all 10 chromosomes and NP4R on the terminal regions of three chromosomes in the haploid genome of N. plumbaginifolia. Sequence homology search revealed that not only are NP3R and NP4R homologous to HRS60 and GRS, respectively, two tandem repeats isolated from N. tabacum, but that NP3R and NP4R are also related to each other, suggesting that they originated from a common ancestral sequence. The role of these repeated sequences in chromosome healing is discussed based on the observation that two to three copies of a telomere-similar sequence were present in each repeating unit of NP3R and NP4R.

DNA fingerprinting of Mycobacterium leprae strains using variable number tandem repeat (VNTR) - fragment length analysis (FLA).

Science.gov (United States)

Jensen, Ronald W; Rivest, Jason; Li, Wei; Vissa, Varalakshmi

2011-07-15

The study of the transmission of leprosy is particularly difficult since the causative agent, Mycobacterium leprae, cannot be cultured in the laboratory. The only sources of the bacteria are leprosy patients, and experimentally infected armadillos and nude mice. Thus, many of the methods used in modern epidemiology are not available for the study of leprosy. Despite an extensive global drug treatment program for leprosy implemented by the WHO, leprosy remains endemic in many countries with approximately 250,000 new cases each year. The entire M. leprae genome has been mapped and many loci have been identified that have repeated segments of 2 or more base pairs (called micro- and minisatellites). Clinical strains of M. leprae may vary in the number of tandem repeated segments (short tandem repeats, STR) at many of these loci. Variable number tandem repeat (VNTR) analysis has been used to distinguish different strains of the leprosy bacilli. Some of the loci appear to be more stable than others, showing less variation in repeat numbers, while others seem to change more rapidly, sometimes in the same patient. While the variability of certain VNTRs has brought up questions regarding their suitability for strain typing, the emerging data suggest that analyzing multiple loci, which are diverse in their stability, can be used as a valuable epidemiological tool. Multiple locus VNTR analysis (MLVA) has been used to study leprosy evolution and transmission in several countries including China, Malawi, the Philippines, and Brazil. MLVA involves multiple steps. First, bacterial DNA is extracted along with host tissue DNA from clinical biopsies or slit skin smears (SSS). The desired loci are then amplified from the extracted DNA via polymerase chain reaction (PCR). Fluorescently-labeled primers for 4-5 different loci are used per reaction, with 18 loci being amplified in a total of four reactions. The PCR products may be subjected to agarose gel electrophoresis to verify the

47 CFR 80.469 - Maritime mobile repeater stations in Alaska.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Maritime mobile repeater stations in Alaska. 80... RADIO SERVICES STATIONS IN THE MARITIME SERVICES Public Coast Stations Use of Telephony § 80.469 Maritime mobile repeater stations in Alaska. (a) Maritime mobile repeater stations are authorized to extend...

RNA FISH for detecting expanded repeats in human diseases.

Science.gov (United States)

Urbanek, Martyna O; Krzyzosiak, Wlodzimierz J

2016-04-01

RNA fluorescence in situ hybridization (FISH) is a widely used technique for detecting transcripts in fixed cells and tissues. Many variants of RNA FISH have been proposed to increase signal strength, resolution and target specificity. The current variants of this technique facilitate the detection of the subcellular localization of transcripts at a single molecule level. Among the applications of RNA FISH are studies on nuclear RNA foci in diseases resulting from the expansion of tri-, tetra-, penta- and hexanucleotide repeats present in different single genes. The partial or complete retention of mutant transcripts forming RNA aggregates within the nucleoplasm has been shown in multiple cellular disease models and in the tissues of patients affected with these atypical mutations. Relevant diseases include, among others, myotonic dystrophy type 1 (DM1) with CUG repeats, Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3) with CAG repeats, fragile X-associated tremor/ataxia syndrome (FXTAS) with CGG repeats, myotonic dystrophy type 2 (DM2) with CCUG repeats, amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) with GGGGCC repeats and spinocerebellar ataxia type 32 (SCA32) with GGCCUG. In this article, we summarize the results obtained with FISH to examine RNA nuclear inclusions. We provide a detailed protocol for detecting RNAs containing expanded CAG and CUG repeats in different cellular models, including fibroblasts, lymphoblasts, induced pluripotent stem cells and murine and human neuronal progenitors. We also present the results of the first single-molecule FISH application in a cellular model of polyglutamine disease. Copyright © 2015 Elsevier Inc. All rights reserved.

StaRProtein, A Web Server for Prediction of the Stability of Repeat Proteins

Science.gov (United States)

Xu, Yongtao; Zhou, Xu; Huang, Meilan

2015-01-01

Repeat proteins have become increasingly important due to their capability to bind to almost any proteins and the potential as alternative therapy to monoclonal antibodies. In the past decade repeat proteins have been designed to mediate specific protein-protein interactions. The tetratricopeptide and ankyrin repeat proteins are two classes of helical repeat proteins that form different binding pockets to accommodate various partners. It is important to understand the factors that define folding and stability of repeat proteins in order to prioritize the most stable designed repeat proteins to further explore their potential binding affinities. Here we developed distance-dependant statistical potentials using two classes of alpha-helical repeat proteins, tetratricopeptide and ankyrin repeat proteins respectively, and evaluated their efficiency in predicting the stability of repeat proteins. We demonstrated that the repeat-specific statistical potentials based on these two classes of repeat proteins showed paramount accuracy compared with non-specific statistical potentials in: 1) discriminate correct vs. incorrect models 2) rank the stability of designed repeat proteins. In particular, the statistical scores correlate closely with the equilibrium unfolding free energies of repeat proteins and therefore would serve as a novel tool in quickly prioritizing the designed repeat proteins with high stability. StaRProtein web server was developed for predicting the stability of repeat proteins. PMID:25807112

Psychosocial characteristics of drunk drivers assessed by the Addiction Severity Index, prediction of relapse.

Science.gov (United States)

Hubicka, Beata; Laurell, Hans; Bergman, Hans

2010-02-01

To investigate psychosocial characteristics and problems of a representative sample of Swedish drunk drivers with special consideration of the gender of the driver; analyze criminal records of the drivers before and after enrollment in the study; identify psychosocial predictors of relapse to drunk driving. Psychosocial characteristics were assessed by the Addiction Severity Index (ASI). Alcohol problems were additionally assessed by the Alcohol Use Disorders Identification Test (AUDIT). Criminal records were collected for the five year period before the enrollment, and for the subsequent two years, from Sweden's official crime statistics. About half of the investigated drivers had other psychosocial problems besides the drink driving offence. Female drivers had more alcohol, drug, psychiatric and relational problems, including with parents when growing up, than male drivers, but less previous and subsequent criminality. Heavily drunk drivers (blood alcohol concentration > or = 0.1%) had more problems with alcohol, legal status and employment and support than the other drunk drivers. Problems with legal status, family and social relations and alcohol use increased the risk of relapse in drunk driving, while medical problems seemed to be a protective factor. Different ASI risk factors were identified for relapse in either traffic offences or other crimes. As well as the drunk driving offence, drunk drivers often have other psychosocial problems, female drivers in particular. Already the blood alcohol concentration per se gives some indication of the psychosocial problem profile of a drunk driver and the ASI profile has some prognostic value for relapse in drunk driving.

Differential Regulation of Strand-Specific Transcripts from Arabidopsis Centromeric Satellite Repeats.

Directory of Open Access Journals (Sweden)

2005-12-01

Full Text Available Centromeres interact with the spindle apparatus to enable chromosome disjunction and typically contain thousands of tandemly arranged satellite repeats interspersed with retrotransposons. While their role has been obscure, centromeric repeats are epigenetically modified and centromere specification has a strong epigenetic component. In the yeast Schizosaccharomyces pombe, long heterochromatic repeats are transcribed and contribute to centromere function via RNA interference (RNAi. In the higher plant Arabidopsis thaliana, as in mammalian cells, centromeric satellite repeats are short (180 base pairs, are found in thousands of tandem copies, and are methylated. We have found transcripts from both strands of canonical, bulk Arabidopsis repeats. At least one subfamily of 180-base pair repeats is transcribed from only one strand and regulated by RNAi and histone modification. A second subfamily of repeats is also silenced, but silencing is lost on both strands in mutants in the CpG DNA methyltransferase MET1, the histone deacetylase HDA6/SIL1, or the chromatin remodeling ATPase DDM1. This regulation is due to transcription from Athila2 retrotransposons, which integrate in both orientations relative to the repeats, and differs between strains of Arabidopsis. Silencing lost in met1 or hda6 is reestablished in backcrosses to wild-type, but silencing lost in RNAi mutants and ddm1 is not. Twenty-four-nucleotide small interfering RNAs from centromeric repeats are retained in met1 and hda6, but not in ddm1, and may have a role in this epigenetic inheritance. Histone H3 lysine-9 dimethylation is associated with both classes of repeats. We propose roles for transcribed repeats in the epigenetic inheritance and evolution of centromeres.

Cumulative Vulnerability: A Case Study on intrafamilial violence, Drug Addiction and Adolescent Pregnancy.

Science.gov (United States)

Miura, Paula Orchiucci; Passarini, Gislaine Martins Ricardo; Ferreira, Loraine Seixas; Paixão, Rui Alexandre Paquete; Tardivo, Leila Salomão de La Plata Cury; Barrientos, Dora Mariela Salcedo

2014-12-01

A pregnant adolescent's vulnerability increases when she is a victim of intrafamilial violence and drug addiction, which cause physical and biopsychosocial damage to the mother and her baby. Objective Present and analyze the case of an adolescent who is addicted to drugs, pregnant and the victim of lifelong intrafamilial violence. Method A case study based on a semi-structured interview conducted in the Obstetrics Emergency Unit at the Teaching Hospital of the University of São Paulo. The data were interpreted and analyzed using Content Analysis. Results intrafamilial violence experienced at the beginning of the adolescent's early relationships seriously affected her emotional maturity, triggering the development of psychopathologies and leaving her more susceptible to the use and abuse of alcohol and other drugs. The adolescent is repeating her history with her daughter, reproducing the cycle of violence. Conclusion Adolescent pregnancy combined with intrafamilial violence and drug addiction and multiplies the adolescent's psychosocial vulnerability increased the adolescent's vulnerability.

Cumulative Vulnerability: A Case Study on intrafamilial violence, Drug Addiction and Adolescent Pregnancy

Directory of Open Access Journals (Sweden)

Paula Orchiucci Miura

2014-12-01

Full Text Available A pregnant adolescent’s vulnerability increases when she is a victim of intrafamilial violence and drug addiction, which cause physical and biopsychosocial damage to the mother and her baby. Objective Present and analyze the case of an adolescent who is addicted to drugs, pregnant and the victim of lifelong intrafamilial violence. Method A case study based on a semi-structured interview conducted in the Obstetrics Emergency Unit at the Teaching Hospital of the University of São Paulo. The data were interpreted and analyzed using Content Analysis. Results intrafamilial violence experienced at the beginning of the adolescent’s early relationships seriously affected her emotional maturity, triggering the development of psychopathologies and leaving her more susceptible to the use and abuse of alcohol and other drugs. The adolescent is repeating her history with her daughter, reproducing the cycle of violence. Conclusion Adolescent pregnancy combined with intrafamilial violence and drug addiction and multiplies the adolescent’s psychosocial vulnerability increased the adolescent’s vulnerability.

[Paracetamol (acetaminophen) use in neonatology: a (re)appreciation of an old drug].

Science.gov (United States)

Langhendries, J-P

2015-10-01

In neonates, paracetamol is mainly used for its analgesic action. This drug is actually preferred by neonatologists because of its broad therapeutic index. Recently, it has been demonstrated that paracetamol is also an anti-cyclooxygenase (COX) medication through its inhibitory action on the peroxidase arm of central and peripheral COX (Boutaud et al., 2002; Toussaint et al., 2010; Graham et al., 2013; Hinz et al., 2008; Hinz and Brune, 2011). As such, this drug interferes with the synthesis of prostaglandins. This inhibition of peroxidase is, however, limited to a low concentration of arachidonic acid (AA) (around 2μM, in vitro) when the plasmatic concentration of paracetamol is experimentally 10μM, actually within the same range as compared to the therapeutic concentrations in vivo. This may partly explain its low anti-inflammatory effect as compared to ibuprofen and indomethacin, which exert their inhibition on COX whatever the AA concentrations are. This new well-demonstrated action of paracetamol on peripheral COX-2 of intact cells could explain recent observations making this drug a potential alternative in treating patent ductus arteriosus. However, the higher dosages that have been claimed by some authors in this indication still remain to be validated. This inhibition that paracetamol shows on the physiological synthesis of prostaglandins E2 (PGE2) could also explain some long-term immune deviations because the physiological concentration of PGE2 is a well-known actor in the genesis of immune homeostasis in the submucosal area. Indeed, recent epidemiology studies have pointed out immune deviations in children repeatedly exposed to paracetamol earlier in life. Consequently, this is actually the new discovery of an old drug. From these new data on paracetamol, a more focused pharmacovigilance on the long-term effects of paracetamol repeatedly given in the early stage should be urgently initiated. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Assessment of deoxyhypusine hydroxylase as a putative, novel drug target.

Science.gov (United States)

Kerscher, B; Nzukou, E; Kaiser, A

2010-02-01

Antimalarial drug resistance has nowadays reached each drug class on the market for longer than 10 years. The focus on validated, classical targets has severe drawbacks. If resistance is arising or already present in the field, a target-based High-Throughput-Screening (HTS) with the respective target involves the risk of identifying compounds to which field populations are also resistant. Thus, it appears that a rewarding albeit demanding challenge for target-based drug discovery is to identify novel drug targets. In the search for new targets for antimalarials, we have investigated the biosynthesis of hypusine, present in eukaryotic initiation factor 5A (eIF5A). Deoxyhypusine hydroxylase (DOHH), which has recently been cloned and expressed from P. falciparum, completes the modification of eIF5A through hydroxylation. Here, we assess the present druggable data on Plasmodium DOHH and its human counterpart. Plasmodium DOHH arose from a cyanobacterial phycobilin lyase by loss of function. It has a low FASTA score of 27 to its human counterpart. The HEAT-like repeats present in the parasite DOHH differ in number and amino acid identity from its human ortholog and might be of considerable interest for inhibitor design.

Telomerase Repeated Amplification Protocol (TRAP).

Science.gov (United States)

Mender, Ilgen; Shay, Jerry W

2015-11-20

Telomeres are found at the end of eukaryotic linear chromosomes, and proteins that bind to telomeres protect DNA from being recognized as double-strand breaks thus preventing end-to-end fusions (Griffith et al. , 1999). However, due to the end replication problem and other factors such as oxidative damage, the limited life span of cultured cells (Hayflick limit) results in progressive shortening of these protective structures (Hayflick and Moorhead, 1961; Olovnikov, 1973). The ribonucleoprotein enzyme complex telomerase-consisting of a protein catalytic component hTERT and a functional RNA component hTR or hTERC - counteracts telomere shortening by adding telomeric repeats to the end of chromosomes in ~90% of primary human tumors and in some transiently proliferating stem-like cells (Shay and Wright, 1996; Shay and Wright, 2001). This results in continuous proliferation of cells which is a hallmark of cancer. Therefore, telomere biology has a central role in aging, cancer progression/metastasis as well as targeted cancer therapies. There are commonly used methods in telomere biology such as Telomere Restriction Fragment (TRF) (Mender and Shay, 2015b), Telomere Repeat Amplification Protocol (TRAP) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this detailed protocol we describe Telomere Repeat Amplification Protocol (TRAP). The TRAP assay is a popular method to determine telomerase activity in mammalian cells and tissue samples (Kim et al. , 1994). The TRAP assay includes three steps: extension, amplification, and detection of telomerase products. In the extension step, telomeric repeats are added to the telomerase substrate (which is actually a non telomeric oligonucleotide, TS) by telomerase. In the amplification step, the extension products are amplified by the polymerase chain reaction (PCR) using specific primers (TS upstream primer and ACX downstream primer) and in the detection step, the presence or absence of telomerase is

Recent Trends in Alcohol and Other Drug Use Among Police Detainees in New Zealand, 2010-2015.

Science.gov (United States)

Wilkins, Chris; Prasad, Jitesh; Parker, Karl; Rychert, Marta; Barnes, Helen Moewaka

New Zealand has unusual patterns of recreational substance use by international standards including low levels of cocaine and heroin use, and high methamphetamine use. This paper examines recent trends in alcohol and other drug use among police detainees in New Zealand over the past six years. The paper utilises data from the New Zealand Arrestee Drug Use Monitoring (NZ-ADUM) study. NZ-ADUM interviewed approximately 800 police detainees each year at four central city police watch houses (i.e. Whangarei, Auckland, Wellington, Christchurch) from 2010 to 2015. The proportion of police detainees who had used methamphetamine in the previous year increased from 28% in 2012 to 36% in 2015. Drinking prior to arrest declined from 41% in 2013 to 28% in 2015. The use of cannabis in the past year declined slightly from 76% in 2011 to 69% in 2015. The proportion using ecstasy in the previous year steadily declined from 28% in 2011 to 19% in 2015. Only small minorities had recently used cocaine or an opioid. Use of methamphetamine and ecstasy increased in Christchurch. Growing methamphetamine use is consistent with record seizures of methamphetamine over the past 2-3 years. Increasing drug use in Christchurch may reflect factors related to the devastating earthquakes in 2011 and the subsequent city rebuild, including an influx of construction workers, more organised trafficking groups and earthquake-related stress. The decline in cannabis use may be related to the emergence of 'legal' synthetic cannabinoids. The decline in ecstasy use may be the result of recent domestic enforcement operations and the overall global shortage of MDMA. The decline in alcohol drinking may be due to the introduction of pre-charge formal warnings for minor alcohol and disorder offences, and new restrictions on alcohol premise opening hours. Acknowledgements: The New Zealand Drug Use Monitoring (NZ-ADUM) research study is funded by the New Zealand Police and is conducted by SHORE and Whariki Research

Structure of thrombospondin type 3 repeats in bacterial outer membrane protein A reveals its intra-repeat disulfide bond-dependent calcium-binding capability

Energy Technology Data Exchange (ETDEWEB)

Dai, Shuyan; Sun, Cancan; Tan, Kemin; Ye, Sheng; Zhang, Rongguang

2017-09-01

Eukaryotic thrombospondin type 3 repeat (TT3R) is an efficient calcium ion (Ca2+) binding motif only found in mammalian thrombospondin family. TT3R has also been found in prokaryotic cellulase Cel5G, which was thought to forfeit the Ca2+-binding capability due to the formation of intra-repeat disulfide bonds, instead of the inter-repeat ones possessed by eukaryotic TT3Rs. In this study, we have identified an enormous number of prokaryotic TT3R-containing proteins belonging to several different protein families, including outer membrane protein A (OmpA), an important structural protein connecting the outer membrane and the periplasmic peptidoglycan layer in gram-negative bacteria. Here, we report the crystal structure of the periplasmic region of OmpA from Capnocytophaga gingivalis, which contains a linker region comprising five consecutive TT3Rs. The structure of OmpA-TT3R exhibits a well-ordered architecture organized around two tightly-coordinated Ca2+ and confirms the presence of abnormal intra-repeat disulfide bonds. Further mutagenesis studies showed that the Ca2+-binding capability of OmpA-TT3R is indeed dependent on the proper formation of intra-repeat disulfide bonds, which help to fix a conserved glycine residue at its proper position for Ca2+ coordination. Additionally, despite lacking inter repeat disulfide bonds, the interfaces between adjacent OmpA-TT3Rs are enhanced by both hydrophobic and conserved aromatic-proline interactions.

Discrepancy variation of dinucleotide microsatellite repeats in eukaryotic genomes

Directory of Open Access Journals (Sweden)

HUAN GAO

2009-01-01

Full Text Available To address whether there are differences of variation among repeat motif types and among taxonomic groups, we present here an analysis of variation and correlation of dinucleotide microsatellite repeats in eukaryotic genomes. Ten taxonomic groups were compared, those being primates, mammalia (excluding primates and rodentia, rodentia, birds, fish, amphibians and reptiles, insects, molluscs, plants and fungi, respectively. The data used in the analysis is from the literature published in the Journal of Molecular Ecology Notes. Analysis of variation reveals that there are no significant differences between AC and AG repeat motif types. Moreover, the number of alleles correlates positively with the copy number in both AG and AC repeats. Similar conclusions can be obtained from each taxonomic group. These results strongly suggest that the increase of SSR variation is almost linear with the increase of the copy number of each repeat motif. As well, the results suggest that the variability of SSR in the genomes of low-ranking species seem to be more than that of high-ranking species, excluding primates and fungi.

Murder by YouTube - anti-Islamic speech and homicide liability.

OpenAIRE

Bohlander, Michael

2014-01-01

Usually, hate-speech and its criminalisation are looked at from the angle of a separate hate-speech offence, and often in the context of human rights law, especially freedom of speech and religion. In the Islamic world, such issues are treated under blasphemy laws and the availability of severe sanctions for that offence, not infrequently the death penalty, may make a separate recourse to homicide offences unnecessary. Yet, recent events in the Islamic world suggest that it would not be unima...

REPEATABILITY OF FRUIT QUALITY TRAITS OF CACTUS PEAR

Directory of Open Access Journals (Sweden)

VALTÂNIA XAVIER NUNES

2017-12-01

Full Text Available ABSTRACT Repeatability analysis has been used to study traits in several crops, assisting in the definition of the minimum number needed to evaluate genotypes more efficiently and with less time and resource consumption. So far, however, no repeatability studies on cactus pear have been found in the literature. The objective of this study was to determine the coefficient of repeatability for cactus pear fruits traits and the minimum number of evaluations (fruit that can provide acceptable accuracy for the prediction of the true value. The experiment was conducted at the Federal Institute of Bahia/Campus Guanambi, with 150 fruits collected from three municipalities in the state of Bahia. The coefficients of repeatability were estimated by the methods of analysis of variance, principal components based on the covariance (PCCV and correlation (PCC matrices, and structural analysis based on the correlation matrix (SA. The analysis of variance showed that, except for fruit diameter, the effect of the production site (municipality was significant for all traits evaluated. The PCCV method was proven the most suitable for studying the repeatability of quality traits of cactus pear fruits. Seven fruits were required to determine, with 90% confidence, the traits length, diameter, fruit firmness, skin thickness, number of seeds, fruit mass, bark mass, pulp mass, pH, titratable acidity, soluble solids, SS/AT ratio, and pulp yield.

Improvement of Repeated-Sprint Ability and Horizontal-Jumping Performance in Elite Young Basketball Players With Low-Volume Repeated-Maximal-Power Training.

Science.gov (United States)

Gonzalo-Skok, Oliver; Tous-Fajardo, Julio; Arjol-Serrano, José Luis; Suarez-Arrones, Luis; Casajús, José Antonio; Mendez-Villanueva, Alberto

2016-05-01

To examine the effects of a low-volume repeated-power-ability (RPA) training program on repeated-sprint and change-of- direction (COD) ability and functional jumping performance. Twenty-two male elite young basketball players (age 16.2 ± 1.2 y, height 190.0 ± 10.0 cm, body mass 82.9 ± 10.1 kg) were randomly assigned either to an RPA-training group (n = 11) or a control group (n = 11). RPA training consisted of leg-press exercise, twice a week for 6 wk, of 1 or 2 blocks of 5 sets × 5 repetitions with 20 s of passive recovery between sets and 3 min between blocks with the load that maximized power output. Before and after training, performance was assessed by a repeated-sprint-ability (RSA) test, a repeated-COD-ability test, a hop for distance, and a drop jump followed by tests of a double unilateral hop with the right and left legs. Within-group and between-groups differences showed substantial improvements in slowest (RSAs) and mean time (RSAm) on RSA; best, slowest and mean time on repeated-COD ability; and unilateral right and left hop in the RPA group in comparison with control. While best time on RSA showed no improvement in any group, there was a large relationship (r = .68, 90% CI .43;.84) between the relative decrement in RSAm and RSAs, suggesting better sprint maintenance with RPA training. The relative improvements in best and mean repeated-COD ability were very largely correlated (r = .89, 90% CI .77;.94). Six weeks of lowvolume (4-14 min/wk) RPA training improved several physical-fitness tests in basketball players.

The absolute number of repeat operations for complex intra ...

African Journals Online (AJOL)

abdominal sepsis, questions about futility of treatment frequently arise. This study focuses specifically on patients who required two or more repeat laparotomies and describes the spectrum of disease necessitating multiple repeat laparotomies ...

Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation

Directory of Open Access Journals (Sweden)

Najeeba Riyaz

2012-01-01

Full Text Available A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6. Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.

Assembly of Repeat Content Using Next Generation Sequencing Data

Energy Technology Data Exchange (ETDEWEB)

labutti, Kurt; Kuo, Alan; Grigoriev, Igor; Copeland, Alex

2014-03-17

Repetitive organisms pose a challenge for short read assembly, and typically only unique regions and repeat regions shorter than the read length, can be accurately assembled. Recently, we have been investigating the use of Pacific Biosciences reads for de novo fungal assembly. We will present an assessment of the quality and degree of repeat reconstruction possible in a fungal genome using long read technology. We will also compare differences in assembly of repeat content using short read and long read technology.

Treat the whole patient and be aware of drug interactions.

Science.gov (United States)

Breivik, Harald

2015-03-01

The case of an elderly male with bilateral shoulder pain is presented. The pain had been successfully treated years earlier with surgery, but a repeat rotator cuff procedure when the pain recurred was not effective. The patient's physician asked about impact of systemic analgesics on the elderly patient and interactions with his blood pressure medications. Cardiovascular and renal risks of NSAOIDs are discussed as are potential toxicities of tramadol and too rapid withdrawal from it. Drug interactions of medications used are described.

A study on the repeatability of ultrasonic testing data

International Nuclear Information System (INIS)

Yoshimura, Seiichi; Fukumoto, Hiroshi

1980-01-01

Reliability improvement of ultrasonic testing data is strongly desired in ultrasonic testing working of nuclear power plants. This paper deals with the problems of the testing by the manual and the remote control apparatus, and with the factors which influence the repeatability of ultrasonic testing data. Following results are found in it. (1) In the testing by the manual, working time and posture influence the repeatability of testing data. (2) Glycerin in suitable for the couplant in the respect of the repeatability of testing data. In the case of using machine oil, the pressure to the probe necessitates to be over 0.2 kg/cm 2 . (3) In the testing by the remote control apparatus, working time, working environment and defect position does not influence the repeatability of testing data. (author)

The Effects of Repeated Experience on Children's Suggestibility.

Science.gov (United States)

Powell, Martine B.; Roberts, Kim P.; Ceci, Stephen J.; Hembrooke, Helene

1999-01-01

Examined effect of suggestive questions on 3- to 5-year-olds' and 6- to 8-year-olds' recall of the final occurrence of repeated event. Found that relative to reports of children experiencing single occurrence, reports about fixed items of repeated events were less contaminated by false suggestions. Children's age and delay of interview were…

Non-radioactive detection of trinucleotide repeat size variability.

Science.gov (United States)

Tomé, Stéphanie; Nicole, Annie; Gomes-Pereira, Mario; Gourdon, Genevieve

2014-03-06

Many human diseases are associated with the abnormal expansion of unstable trinucleotide repeat sequences. The mechanisms of trinucleotide repeat size mutation have not been fully dissected, and their understanding must be grounded on the detailed analysis of repeat size distributions in human tissues and animal models. Small-pool PCR (SP-PCR) is a robust, highly sensitive and efficient PCR-based approach to assess the levels of repeat size variation, providing both quantitative and qualitative data. The method relies on the amplification of a very low number of DNA molecules, through sucessive dilution of a stock genomic DNA solution. Radioactive Southern blot hybridization is sensitive enough to detect SP-PCR products derived from single template molecules, separated by agarose gel electrophoresis and transferred onto DNA membranes. We describe a variation of the detection method that uses digoxigenin-labelled locked nucleic acid probes. This protocol keeps the sensitivity of the original method, while eliminating the health risks associated with the manipulation of radiolabelled probes, and the burden associated with their regulation, manipulation and waste disposal.

Novel anti-HIV peptides containing multiple copies of artificially designed heptad repeat motifs

International Nuclear Information System (INIS)

Shi Weiguo; Qi Zhi; Pan Chungen; Xue Na; Debnath, Asim K.; Qie Jiankun; Jiang Shibo; Liu Keliang

2008-01-01

The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively). We hypothesize that novel anti-HIV peptides may be designed by using artificial sequences containing multiple copies of HR motifs plus zero, one or two functional domains. Surprisingly, we found that the peptides containing only the non-natural HR sequences could significantly inhibit HIV-1 infection, while addition of PBD and/or LBD to the peptides resulted in significant improvement of anti-HIV-1 activity. These results suggest that these artificial HR sequences, which may serve as structural domains, could be used as templates for the design of novel antiviral peptides against HIV and other viruses with class I fusion proteins

Repeated Causal Decision Making

Science.gov (United States)

Hagmayer, York; Meder, Bjorn

2013-01-01

Many of our decisions refer to actions that have a causal impact on the external environment. Such actions may not only allow for the mere learning of expected values or utilities but also for acquiring knowledge about the causal structure of our world. We used a repeated decision-making paradigm to examine what kind of knowledge people acquire in…

Single and repeated dose pharmacokinetics of dexketoprofen trometamol in patients with impaired liver function.

Science.gov (United States)

Valles, J; Artigas, R; Bertolotti, M; Crea, A; Muller, F; Paredes, I; Capriati, A

2006-06-01

Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain relief. This study compared the pharmacokinetics of dexketoprofen in patients with impaired liver function and normal subjects following single and repeated oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label and parallel study. They received 25 mg dexketoprofen (equivalent to 37 mg of its tromethamine salt) as a single (day 1) and a 3-day repeated dose (1 dose every 8 hours for a total of 10 doses). Dexketoprofen concentrations were determined in plasma and urine by reverse-phase high performance liquid chromatography (HPLC). Model-independent pharmacokinetic parameters were obtained. All subjects completed the study. No serious adverse events were recorded. Following the single dose, mean (+/- SEM) Cmax were 3027.7 +/- 429.3 ng/ml (healthy subjects), 2856.3 +/- 340.3 ng/ml (Child-Pugh A) and 1937.2 +/- 328.0 ng/ml (Child-Pugh B). Median tmax were 0.49 h (0.33-0.68) h, 0.50 h (0.33-0.67) h and 0.67 h (0.33-1.50) h. AUC0-x averaged 3778.0 +/- 439.0 ng.h/ml, 4890.4 +/- 539.1 ng.h/ml and 3985.0 +/- 712.0 ng.h/ml. Mean CL/F were 101.1 +/- 11.3 ml/h/kg, 73.3 +/- 9.9 ml/h/kg and 88.8 +/- 15.5 ml/h/kg and V/F averaged 0.192 +/- 0.018 l/kg, 0.162 +/- 0.006 l/kg and 0.214 +/- 0.044 l/kg. Following the repeated administration, similar results were obtained showing no drug accumulation. As related to the administered dose, median excretions of unchanged and conjugated dexketoprofen in urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced urinary excretion of conjugated dexketoprofen in hepatic patients, more evident in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared with healthy

[Sexual offences--selected cases].

Science.gov (United States)

Łabecka, Marzena; Jarzabek-Bielecka, Grazyna; Lorkiewicz-Muszyńska, Dorota

2013-04-01

Expert testimony on violence victims also includes victims of sexual assault. The role of an expert is to classify the injuries by their severity as defined in art. 157 156 or 217 of the Criminal Code pertaining to crimes against health and life. Also, the role of an expert opinion is to determine whether the injuries identified during the exam occurred at the time and under the circumstances stated in medical history. The examination of sexual assault victims is conducted by two experts: a gynecologist and a forensic physician. Most examinations are performed at different times and various medical centers. The conclusions are presented in an official report. Regardless of victim age, all sexual crimes are investigated ex officio by the Police Department and the Prosecutor's Office. Further legal classification of criminal offenses is the task of an appropriate legal body and the offenses are codified in accordance with the provisions of chapter XXV of the Criminal Code, articles 197 - 205. In controversial cases, i.e. when two different expert opinions appear on the same case, or if, according to the law enforcement, a medical opinion is insufficient for some reason, an appropriate expert or team of experts is appointed to resolve the problem. To present selected cases of sexual violence victims treated at the Department of Gynecology and assessed at the Department of Forensic Medicine with reference to the challenges regarding qualification of the sustained injuries and clinical diagnoses. Research material included selected forensic opinions developed for law enforcement offices that involved victims of sexual violence. The expert opinions were prepared either on the basis of submitted evidence, or both, submitted evidence and examination of the victim at the Department of Forensic Medicine. Moreover the article presents a case of a patient examined and treated at the Department of Gynecology in Poznan. Based on the selected cases, the authors conclude that a medico-legal expert cannot uncritically accept previous diagnoses. Moreover every expert is given the right and obligation to verify them. The need for complete, rapid and almost simultaneous colaboration between physicians in charge of the case, forensic doctors, police officers and prosecutors was demonstrated. Lack of cooperation may give rise to different opinions, leading to unnecessary elongation of the medico-legal procedures. It was observed that time plays a crucial role if qualification of an injury is required. The obligation of medical staff to inform the law enforcement about all cases of child abuse was also emphasized.

Waiting time - an offence?

DEFF Research Database (Denmark)

Ludvigsen, Mette Spliid

2004-01-01

The purpose of the original study: Patient-culture - a qualitative study among hospitalised patients, which is inspired by the work of Album and Isaksen, is to discover, and describe patients' experiences of informal relations and interpret the meaning of having fellow-patients during hospitalisa......The purpose of the original study: Patient-culture - a qualitative study among hospitalised patients, which is inspired by the work of Album and Isaksen, is to discover, and describe patients' experiences of informal relations and interpret the meaning of having fellow-patients during...... fieldwork is set up consisting of participant observation and interviews.   Based on the qualitative analysis completed to date on a data set consisting of field notes from participant observations and informal interviews I explore patients' social interactions in their day-to-day lives on two adult...

Intra-examiner repeatability and agreement in accommodative response measurements.

Science.gov (United States)

Antona, B; Sanchez, I; Barrio, A; Barra, F; Gonzalez, E

2009-11-01

Clinical measurement of the accommodative response (AR) identifies the focusing plane of a subject with respect to the accommodative target. To establish whether a significant change in AR has occurred, it is important to determine the repeatability of this measurement. This study had two aims: First, to determine the intraexaminer repeatability of AR measurements using four clinical methods: Nott retinoscopy, monocular estimate method (MEM) retinoscopy, binocular crossed cylinder test (BCC) and near autorefractometry. Second, to study the level of agreement between AR measurements obtained with the different methods. The AR of the right eye at one accommodative demand of 2.50 D (40 cm) was measured on two separate occasions in 61 visually normal subjects of mean age 19.7 years (range 18-32 years). The intraexaminer repeatability of the tests, and agreement between them, were estimated by the Bland-Altman method. We determined mean differences (MD) and the 95% limits of agreement [coefficient of repeatability (COR) and coefficient of agreement (COA)]. Nott retinoscopy and BCC offered the best repeatability, showing the lowest MD and narrowest 95% interval of agreement (Nott: -0.10 +/- 0.66 D, BCC: -0.05 +/- 0.75 D). The 95% limits of agreement for the four techniques were similar (COA = +/- 0.92 to +/-1.00 D) yet clinically significant, according to the expected values of the AR. The two dynamic retinoscopy techniques (Nott and MEM) had a better agreement (COA = +/-0.64 D) although this COA must be interpreted in the context of the low MEM repeatability (COR = +/-0.98 D). The best method of assessing AR was Nott retinoscopy. The BCC technique was also repeatable, and both are recommended as suitable methods for clinical use. Despite better agreement between MEM and Nott, agreement among the remaining methods was poor such that their interchangeable use in clinical practice is not recommended.

Retracted publications in the drug literature.

Science.gov (United States)

Samp, Jennifer C; Schumock, Glen T; Pickard, A Simon

2012-07-01

Recent studies have suggested an increase in the number of retracted scientific publications. It is unclear how broadly the issue of misleading and fraudulent publications pertains to retractions of drug therapy studies. Therefore, we sought to determine the trends and factors associated with retracted publications in drug therapy literature. A PubMed search was conducted to identify retracted drug therapy articles published from 2000-2011. Articles were grouped according to reason for retraction, which was classified as scientific misconduct or error. Scientific misconduct was further divided into data fabrication, data falsification, questions of data veracity, unethical author conduct, and plagiarism. Error was defined as duplicate publication, scientific mistake, journal error, or unstated reasons. Additional data were extracted from the retracted articles, including type of article, funding source, author information, therapeutic area, and retraction issue. A total of 742 retractions were identified from 2000-2011 in the general biomedical literature, and 102 drug studies met our inclusion criteria. Of these, 73 articles (72%) were retracted for a reason classified as scientific misconduct, whereas 29 articles (28%) were retracted for error. Among the 73 articles classified as scientific misconduct, those classified as unethical author conduct (32 articles [44%]) and data fabrication (24 articles [33%]) constituted the majority. The median time from publication of the original article to retraction was 31 months (range 1-130). Fifty percent of retracted articles did not state a funding source, whereas pharmaceutical manufacturer funding accounted for only 13 articles (13%) analyzed. Many retractions were due to repeat offenses by a small number of authors, with nearly 40% of the retracted studies associated with two individuals. We found that a greater proportion of drug therapy articles were retracted for reasons of misconduct and fraud compared with other

Fixed drug eruption: topical provocation and subsequent phenomena

Energy Technology Data Exchange (ETDEWEB)

Mahboob, A; Haroon, T S [Shaikh Zayed FPGMI, Lahore (Pakistan). Dept. of Dermatology; Haroon, T S [King Edward Medical Univ., Lahore (Pakistan). Dept. of Dematology; Iqbal, Z; Iqbal, F [Shaikh Zayed FPGMI, Lahore (Pakistan). Dept. of Medicine

2006-12-15

To determine the usefulness of topical provocation in detecting the incriminated drug causing fixed eruption. Three hundred and five, clinically diagnosed cases of Fixed Drug Eruption (FDE) of either gender and of any age were subjected to topical provocation with different drugs by using concentration of 1% (n=203), 2% (n=210) and 5% (n=235) in white soft paraffin. Drug ointment of one strength was applied one at a time on normal skin of flexor surface of right or left forearm. The effects of tests on involved and uninvolved skin were observed for 48 hours. The changes in lesions like erythema, hyperpigmentation, itching, burning or appearance of new lesion were considered a positive response. In case of no change, the patients (n=5) were subjected to oral provocation test, by giving half to full therapeutic dose of the suspected drug depending upon the severity of the initial attack. A patient who exhibited see-sawing phenomenon with 5% metamizole TPT was given oral challenge with same drug. Control topical tests were repeated in equal number of normal persons with various drug ointments and in patients of FDE with white soft paraffin on normal and affected skin. One hundred and thirty-seven patients were males and one hundred and sixty-eight patients were females. Maximum number of patients belonged to third decade. With 1% drug preparations 12 out of 316, with 2% drug preparations 28 out of 422 and with 5% drug preparations, 312 out of 523 TPTs were positive. The comparison revealed a highly significant association (Chi-square 448.1 and p<0.000) among various strengths of preparations and positive response. Sulphamethoxazole was found to be the most commonly incriminated cause of FDE applied in 5% concentration yielded sensitivity rate of 91% compared to 4% with lower concentrations. Positive patch test was also observed with oxytetracycline. Five patients who were given oral provocation with different drugs were found to be positive to tinidazole, dapsone

Fixed drug eruption: topical provocation and subsequent phenomena

International Nuclear Information System (INIS)

Mahboob, A.; Haroon, T.S.; Haroon, T.S.; Iqbal, Z.; Iqbal, F.

2006-01-01

To determine the usefulness of topical provocation in detecting the incriminated drug causing fixed eruption. Three hundred and five, clinically diagnosed cases of Fixed Drug Eruption (FDE) of either gender and of any age were subjected to topical provocation with different drugs by using concentration of 1% (n=203), 2% (n=210) and 5% (n=235) in white soft paraffin. Drug ointment of one strength was applied one at a time on normal skin of flexor surface of right or left forearm. The effects of tests on involved and uninvolved skin were observed for 48 hours. The changes in lesions like erythema, hyperpigmentation, itching, burning or appearance of new lesion were considered a positive response. In case of no change, the patients (n=5) were subjected to oral provocation test, by giving half to full therapeutic dose of the suspected drug depending upon the severity of the initial attack. A patient who exhibited see-sawing phenomenon with 5% metamizole TPT was given oral challenge with same drug. Control topical tests were repeated in equal number of normal persons with various drug ointments and in patients of FDE with white soft paraffin on normal and affected skin. One hundred and thirty-seven patients were males and one hundred and sixty-eight patients were females. Maximum number of patients belonged to third decade. With 1% drug preparations 12 out of 316, with 2% drug preparations 28 out of 422 and with 5% drug preparations, 312 out of 523 TPTs were positive. The comparison revealed a highly significant association (Chi-square 448.1 and p<0.000) among various strengths of preparations and positive response. Sulphamethoxazole was found to be the most commonly incriminated cause of FDE applied in 5% concentration yielded sensitivity rate of 91% compared to 4% with lower concentrations. Positive patch test was also observed with oxytetracycline. Five patients who were given oral provocation with different drugs were found to be positive to tinidazole, dapsone

Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease.

Science.gov (United States)

Gunay, Mine Silindir; Ozer, A Yekta; Chalon, Sylvie

2016-01-01

Although a variety of therapeutic approaches are available for the treatment of Parkinson's disease, challenges limit effective therapy. Among these challenges are delivery of drugs through the blood brain barier to the target brain tissue and the side effects observed during long term administration of antiparkinsonian drugs. The use of drug delivery systems such as liposomes, niosomes, micelles, nanoparticles, nanocapsules, gold nanoparticles, microspheres, microcapsules, nanobubbles, microbubbles and dendrimers is being investigated for diagnosis and therapy. This review focuses on formulation, development and advantages of nanosized drug delivery systems which can penetrate the central nervous system for the therapy and/or diagnosis of PD, and highlights future nanotechnological approaches. It is esential to deliver a sufficient amount of either therapeutic or radiocontrast agents to the brain in order to provide the best possible efficacy or imaging without undesired degradation of the agent. Current treatments focus on motor symptoms, but these treatments generally do not deal with modifying the course of Parkinson's disease. Beyond pharmacological therapy, the identification of abnormal proteins such as α -synuclein, parkin or leucine-rich repeat serine/threonine protein kinase 2 could represent promising alternative targets for molecular imaging and therapy of Parkinson's disease. Nanotechnology and nanosized drug delivery systems are being investigated intensely and could have potential effect for Parkinson's disease. The improvement of drug delivery systems could dramatically enhance the effectiveness of Parkinson's Disease therapy and reduce its side effects.

Individual, family and offence characteristics of high risk childhood offenders: comparing non-offending, one-time offending and re-offending Dutch-Moroccan migrant children in the Netherlands

Directory of Open Access Journals (Sweden)

Stevens Gonneke WJM

2011-10-01

Full Text Available Abstract Background Childhood offenders are at an increased risk for developing mental health, social and educational problems later in life. An early onset of offending is a strong predictor for future persistent offending. Childhood offenders from ethnic minority groups are a vulnerable at-risk group. However, up until now, no studies have focused on them. Aims To investigate which risk factors are associated with (re-offending of childhood offenders from an ethnic minority. Method Dutch-Moroccan boys, who were registered by the police in the year 2006-2007, and their parents as well as a control group (n = 40 were interviewed regarding their individual and family characteristics. Two years later a follow-up analysis of police data was conducted to identify one-time offenders (n = 65 and re-offenders (n = 35. Results All groups, including the controls, showed substantial problems. Single parenthood (OR 6.0 and financial problems (OR 3.9 distinguished one-time offenders from controls. Reading problems (OR 3.8, having an older brother (OR 5.5 and a parent having Dutch friends (OR 4.3 distinguished re-offenders from one-time offenders. First offence characteristics were not predictive for re-offending. The control group reported high levels of emotional problems (33.3%. Parents reported not needing help for their children but half of the re-offender's families were known to the Child Welfare Agency, mostly in a juridical framework. Conclusion The Moroccan subgroup of childhood offenders has substantial problems that might hamper healthy development. Interventions should focus on reaching these families tailored to their needs and expectations using a multi-system approach.

Repeatability of cervical joint flexion and extension within and between days

DEFF Research Database (Denmark)

Wang, Xu; Lindstroem, René; Plocharski, Maciej

2018-01-01

OBJECTIVE: The purpose of this study was to investigate within- and between-day repeatability of free and unrestricted healthy cervical flexion and extension motion when assessing dynamic cervical spine motion. METHODS: Fluoroscopy videos of 2 repeated cervical flexion and 2 repeated extension...

Analysis of genetic polymorphism of nine short tandem repeat loci in ...

African Journals Online (AJOL)

Yomi

2012-03-15

Mar 15, 2012 ... Key words: short tandem repeat, repeat motif, genetic polymorphism, Han population, forensic genetics. INTRODUCTION. Short tandem repeat (STR) is widely .... Data analysis. The exact test of Hardy-Weinberg equilibrium was conducted with. Arlequin version 3.5 software (Computational and Molecular.

Repeated checking causes memory distrust

NARCIS (Netherlands)

van den Hout, M.; Kindt, M.

2003-01-01

This paper attempts to explain why in obsessive-compulsive disorder (OCD) checkers distrust in memory persists despite extensive checking. It is argued that: (1) repeated checking increases familiarity with the issues checked; (2) increased familiarity promotes conceptual processing which inhibits

Disclosure of Professional Secrecy – A Criminal Law Analysis and Dilemmas (Dileme kaznivega dejanja neupravičene izdaje poklicne skrivnosti

Directory of Open Access Journals (Sweden)

Miha Šepec

2017-12-01

Full Text Available Disclosure of professional secrecy is incriminated in Article 142 of the Slovenian Penal Code (KZ-1. The offence protects the privacy of individuals in order to protect them from abuse when personal information and secrets are communicated to persons of certain professions (doctors, lawyers, priests, etc.. The issue is analyzed briefly; however, the context raises extremely complex dogmatic issues, particularly in the direction when unlawfulness of the crime shall be excluded, whether it is reasonable that such a complex offence is not prosecuted ex officio or upon request by the injured person, and the nature of relationship between the offence of disclosure of professional secrecy according to Article 142 and offences under Articles 280 (Failure to Inform Authorities of Preparations for Crime and 281 (Failure to Provide Information of Crime or Perpetrator of the Slovenian Penal Code. The aim of this paper is to highlight some legal dogmatic issues that have not yet been discussed in legal practice. On the other hand, the authors would also like to urge the legislature to amend the current criminal offence of disclosure of professional secrecy.

[Scope of the cause of justification of the legitimate exercise of a right in the area of genetic criminality].

Science.gov (United States)

Romeo Malanda, Sergio

2009-01-01

The Spanish penal Code of 1995 creates various crimes in relation to biotechnology, namely, the offence of genetic manipulation, the offence of cloning and the offence of fertilization of human eggs for purpose others than procreation. These new offences seek to protect new legal interests. But besides these interests, we must not forget that there also exist certain rights of the person that rely on reproductive and genetic technologies to be fully effective. That is why it is inevitable to bring to the discussion other interests of a different nature that may be in conflict with these new legal interests. This is the case in relation to the right to procreate and the right to scientific research. According to Article 20.7 of the Spanish penal Code, a person may justifiably engage in conduct that satisfies the elements of an offence if he has a right to do so. In this work the author analyses if certain conduct that could harm some legal interests, and therefore would be criminally punishable could be justified on the basis of the abovementioned rights to procreate and to undertake scientific research.

A family of DNA repeats in Aspergillus nidulans has assimilated degenerated retrotransposons

DEFF Research Database (Denmark)

Nielsen, M.L.; Hermansen, T.D.; Aleksenko, Alexei Y.

2001-01-01

In the course of a chromosomal walk towards the centromere of chromosome IV of Aspergillus nidulans, several cross- hybridizing genomic cosmid clones were isolated. Restriction mapping of two such clones revealed that their restriction patterns were similar in a region of at least 15 kb, indicati......) phenomenon, first described in Neurospora crassa, may have operated in A. nidulans. The data indicate that this family of repeats has assimilated mobile elements that subsequently degenerated but then underwent further duplications as a part of the host repeats....... the presence of a large repeat. The nature of the repeat was further investigated by sequencing and Southern analysis. The study revealed a family of long dispersed repeats with a high degree of sequence similarity. The number and location of the repeats vary between wild isolates. Two copies of the repeat...

The influence of age and repeated LPS administration on body temperature and the relation with interleukin-6 and IgM antibodies in broiler chickens

OpenAIRE

De Boever , Sandra; Beyaert , Rudi; Vandemaele , Fréderic; Baert , Kris; Duchateau , Luc; Goddeeris , Bruno; De Backer , Patrick; Croubels , Siska

2008-01-01

Abstract Our objective was to create a standardized and reproducible inflammation model in chickens in order to study the pharmacodynamics of several anti-pyretic and anti-inflammatory drugs. We studied the influence of age and repeated lipopolysaccharide (LPS) administration on body temperature and the correlation of this with concentrations of interleukin 6 (IL-6) and IgM antibodies against LPS in plasma of chickens. Three and five week old broilers were injected intravenously...

Influence of mianserin on the activity of some hypotensive drugs in spontaneously hypertensive rats.

Science.gov (United States)

Górska, Dorota; Andrzejczak, Dariusz

2003-01-01

Mianserin might be an alternative drug in patients with depression accompanied by hypertension because of its effectiveness and lack of side effects in the circulatory system. However, a few studies reported in literature show influence of the drug on blood pressure. We investigate interactions between mianserin and commonly used hypotensive drugs (propranolol, enalapril and prazosin) in spontaneously hypertensive rats (SHR). The experiments were performed in two experimental designs: a single administration of both mianserin and a hypotensive drug, and repeated administration of mianserin with a single administration of a hypotensive drug. Arterial blood pressure was measured by bloodless method with manometer made by LETICA. A single administration of mianserin caused a statistically significant decrease in systolic, diastolic and mean blood pressure in the 60th minute of observation and intensified hypotensive effect of prazosin. However, long-term administration of mianserin in SHR rats had no significant influence on arterial blood pressure. Chronic and single administration of mianserin with propranolol or enalapril did not influence the circulatory system. A long-term administration of mianserin intensified the hypotensive effect of prazosin. This interaction might suggest possibility of dangerous complications in the treatment of humans with this drug combination.

Repeated radiation injuries by fission products

International Nuclear Information System (INIS)

Vasilenko, I.Ya.

1986-01-01

Attention is given to repeated radiation injuries during internal irradiation of theoretical and practical interest, particularly in case of the intake into organism of young products of nuclear fission (PNF). The results of experiments with dogs with repeated radioactive iodine injury the isotopes of which (131-135sub(I)) constitute a considerable part of PNF activity are discussed. The blood reaction and protein metabolism state have been studied. Observations for dogs have been continued for about 4 years. The doses for thyroid, gastrointestinal tract and liver subjected to the most intensive irradiation consituted in the first series of experiments after the first intake about 3;0.3;0.05 Gy, after the second - 5;0.5;0.08 Gy and in the second series of experiments - 3;0.3;0.05 Gy and 0.6;0.06;0.01 Gy, respectively. Hematologic factors,thyroid function, changes in exchange and immunologic reactivity have been studied. The dogs have been under observation for 5 years. It is shown in case of repeated intake of Isup(131) PNF into animals organism in quantity which does not cause during the acute period a clinically outlined sickness, substantial differences in the organism reaction as compared with the first intake of radionuclides have not been found. The presence of residual radiation injuries did not cause charging action during the acute period during PNF and repeated intake which in the author's opinion testifies to perfection of compensator mechanisms in case of intake of such quantities of radioactive products. At the remote periods blastomogenic action manifested which is estimated as a result of general biological action of radionuclides administered to the organism. The necessity in subsequent investigations for obtaining the data on organism reactivity, clinic and pathogenesis with the aim of prophylaxis and treatment of such injuries is indicated

The paraventricular nucleus of the thalamus is recruited by both natural rewards and drugs of abuse: recent evidence of a pivotal role for orexin/hypocretin signaling in this thalamic nucleus in drug-seeking behavior

Directory of Open Access Journals (Sweden)

Alessandra eMatzeu

2014-04-01

Full Text Available A major challenge for the successful treatment of drug addiction is the long-lasting susceptibility to relapse and multiple processes that have been implicated in the compulsion to resume drug intake during abstinence. Recently, the orexin/hypocretin (Orx/Hcrt system has been shown to play a role in drug-seeking behavior. The Orx/Hcrt system regulates a wide range of physiological processes, including feeding, energy metabolism, and arousal. It has also been shown to be recruited by drugs of abuse. Orx/Hcrt neurons are predominantly located in the lateral hypothalamus that projects to the paraventricular nucleus of the thalamus (PVT, a region that has been identified as a way-station that processes information and then modulates the mesolimbic reward and extrahypothalamic stress systems. Although not thought to be part of the drug addiction circuitry, recent evidence indicates that the PVT is involved in the modulation of reward function in general and drug-directed behavior in particular. Evidence indicates a role for Orx/Hcrt transmission in the PVT in the modulation of reward function in general and drug-directed behavior in particular. One hypothesis is that following repeated drug exposure, the Orx/Hcrt system acquires a preferential role in mediating the effects of drugs vs. natural rewards. The present review discusses recent findings that suggest maladaptive recruitment of the PVT by drugs of abuse, specifically Orx/Hcrt-PVT neurotransmission.

Design and analysis of communication protocols for quantum repeater networks

International Nuclear Information System (INIS)

Jones, Cody; Kim, Danny; Rakher, Matthew T; Ladd, Thaddeus D; Kwiat, Paul G

2016-01-01

We analyze how the performance of a quantum-repeater network depends on the protocol employed to distribute entanglement, and we find that the choice of repeater-to-repeater link protocol has a profound impact on entanglement-distribution rate as a function of hardware parameters. We develop numerical simulations of quantum networks using different protocols, where the repeater hardware is modeled in terms of key performance parameters, such as photon generation rate and collection efficiency. These parameters are motivated by recent experimental demonstrations in quantum dots, trapped ions, and nitrogen-vacancy centers in diamond. We find that a quantum-dot repeater with the newest protocol (‘MidpointSource’) delivers the highest entanglement-distribution rate for typical cases where there is low probability of establishing entanglement per transmission, and in some cases the rate is orders of magnitude higher than other schemes. Our simulation tools can be used to evaluate communication protocols as part of designing a large-scale quantum network. (paper)

Repeated morphine treatment influences operant and spatial learning differentially

Institute of Scientific and Technical Information of China (English)

Mei-Na WANG; Zhi-Fang DONG; Jun CAO; Lin XU

2006-01-01

Objective To investigate whether repeated morphine exposure or prolonged withdrawal could influence operant and spatial learning differentially. Methods Animals were chronically treated with morphine or subjected to morphine withdrawal. Then, they were subjected to two kinds of learning: operant conditioning and spatial learning.Results The acquisition of both simple appetitive and cued operant learning was impaired after repeated morphine treatment. Withdrawal for 5 weeks alleviated the impairments. Single morphine exposure disrupted the retrieval of operant memory but had no effect on rats after 5-week withdrawal. Contrarily, neither chronic morphine exposure nor 5-week withdrawal influenced spatial learning task of the Morris water maze. Nevertheless, the retrieval of spatial memory was impaired by repeated morphine exposure but not by 5-week withdrawal. Conclusion These observations suggest that repeated morphine exposure can influence different types of learning at different aspects, implicating that the formation of opiate addiction may usurp memory mechanisms differentially.

Vital signs: Repeat births among teens - United States, 2007-2010.

Science.gov (United States)

2013-04-05

Teen childbearing has potential negative health, economic, and social consequences for mother and child. Repeat teen childbearing further constrains the mother's education and employment possibilities. Rates of preterm and low birth weight are higher in teens with a repeat birth, compared with first births. To assess patterns of repeat childbearing and postpartum contraceptive use among teens, CDC analyzed natality data from the National Vital Statistics System (NVSS) and the Pregnancy Risk Assessment Monitoring System (PRAMS) from 2007-2010. Based on 2010 NVSS data from all 50 states and the District of Columbia, of more than 367,000 births to teens aged 15-19 years, 18.3% were repeat births. The percentage of teen births that represented repeat births decreased by 6.2% between 2007 and 2010. Disparities in repeat teen births exist by race/ethnicity, with the highest percentages found among American Indian/Alaska Natives (21.6%), Hispanics (20.9%), and non-Hispanic blacks (20.4%) and lowest among non-Hispanic whites (14.8%). Wide geographic disparities in the percentage of teen births that were repeat births also exist, ranging from 22% in Texas to 10% in New Hampshire. PRAMS data from 16 reporting areas (15 states and New York City) indicate that 91.2% of teen mothers used a contraceptive method 2-6 months after giving birth, but only 22.4% of teen mothers used the most effective methods. Teens with a previous live birth were significantly more likely to use the most effective methods postpartum compared with those with no prior live birth (29.6% versus 20.9%, respectively). Non-Hispanic white and Hispanic teens were significantly more likely to use the most effective methods than non-Hispanic black teens (24.6% and 27.9% versus 14.3%, respectively). The percentage of teens reporting postpartum use of the most effective methods varied greatly geographically across the PRAMS reporting areas, ranging from 50.3% in Colorado to 7.2% in New York State. Although the

t2prhd: a tool to study the patterns of repeat evolution

Directory of Open Access Journals (Sweden)

Pénzes Zsolt

2008-01-01

Full Text Available Abstract Background The models developed to characterize the evolution of multigene families (such as the birth-and-death and the concerted models have also been applied on the level of sequence repeats inside a gene/protein. Phylogenetic reconstruction is the method of choice to study the evolution of gene families and also sequence repeats in the light of these models. The characterization of the gene family evolution in view of the evolutionary models is done by the evaluation of the clustering of the sequences with the originating loci in mind. As the locus represents positional information, it is straightforward that in the case of the repeats the exact position in the sequence should be used, as the simple numbering according to repeat order can be misleading. Results We have developed a novel rapid visual approach to study repeat evolution, that takes into account the exact repeat position in a sequence. The "pairwise repeat homology diagram" visualizes sequence repeats detected by a profile HMM in a pair of sequences and highlights their homology relations inferred by a phylogenetic tree. The method is implemented in a Perl script (t2prhd available for downloading at http://t2prhd.sourceforge.net and is also accessible as an online tool at http://t2prhd.brc.hu. The power of the method is demonstrated on the EGF-like and fibronectin-III-like (Fn-III domain repeats of three selected mammalian Tenascin sequences. Conclusion Although pairwise repeat homology diagrams do not carry all the information provided by the phylogenetic tree, they allow a rapid and intuitive assessment of repeat evolution. We believe, that t2prhd is a helpful tool with which to study the pattern of repeat evolution. This method can be particularly useful in cases of large datasets (such as large gene families, as the command line interface makes it possible to automate the generation of pairwise repeat homology diagrams with the aid of scripts.

Validity of self-reported criminal justice system involvement in substance abusing women at five-year follow-up

Directory of Open Access Journals (Sweden)

Hesse Morten

2008-01-01

Full Text Available Abstract Background Few studies have compared self-reported criminal behaviour with high-quality databases of criminal offences and judicial sanctions. Self-reported problems from drug abusers are generally believed to be valid. We assessed the validity of self-reported theft, drug offences and prison sentences from a five-year follow-up of female substance abusers who were originally treated in a compulsory care unit in Lund, run by the Swedish Board of Institutional Care. Methods Data from a total of 106 of a consecutive sample of 132 women inter-viewed in a five-year follow-up. All were thoroughly assessed for somatic complaints, psychiatric and psychological problems, background factors with standardized instruments. Data over the five years were linked to official records of judicial sanctions, retrieved from The National Council for Crime Prevention, Stockholm, Sweden. Register data have a full cover for the whole cohort. The current data base contain full data back to 1975 up to 2004. Results Agreement was assessed for each year, as well as for the total period. Statistical control was performed for other types of crimes and prison. Although statistically significant, agreement was modest, and in contrast to previous studies, patients under-reported violence charges. Conclusion The findings suggest that self-reports of criminal behaviour from women can be used with some caution, and that the validity of self-report may vary between types of criminal justice system involvement.

Learning With Repeated-Game Strategies

Directory of Open Access Journals (Sweden)

Christos A. Ioannou

2014-07-01

Full Text Available We use the self-tuning Experience Weighted Attraction model with repeated-game strategies as a computer testbed to examine the relative frequency, speed of convergence and progression of a set of repeated-game strategies in four symmetric 2x2 games: Prisoner's Dilemma, Battle of the Sexes, Stag-Hunt, and Chicken. In the Prisoner's Dilemma game, we fi□nd that the strategy with the most occurrences is the Grim-Trigger. In the Battle of the Sexes game, a cooperative pair that alternates between the two pure-strategy Nash equilibria emerges as the one with the most occurrences. In the Stag-Hunt and Chicken games, the Win-Stay, Lose-Shift and Grim-Trigger strategies are the ones with the most occurrences. Overall, the pairs that converged quickly ended up at the cooperative outcomes, whereas the ones that were extremely slow to reach convergence ended up at non-cooperative outcomes.

Gene conversion homogenizes the CMT1A paralogous repeats

Directory of Open Access Journals (Sweden)

Hurles Matthew E

2001-12-01

Full Text Available Abstract Background Non-allelic homologous recombination between paralogous repeats is increasingly being recognized as a major mechanism causing both pathogenic microdeletions and duplications, and structural polymorphism in the human genome. It has recently been shown empirically that gene conversion can homogenize such repeats, resulting in longer stretches of absolute identity that may increase the rate of non-allelic homologous recombination. Results Here, a statistical test to detect gene conversion between pairs of non-coding sequences is presented. It is shown that the 24 kb Charcot-Marie-Tooth type 1A paralogous repeats (CMT1A-REPs exhibit the imprint of gene conversion processes whilst control orthologous sequences do not. In addition, Monte Carlo simulations of the evolutionary divergence of the CMT1A-REPs, incorporating two alternative models for gene conversion, generate repeats that are statistically indistinguishable from the observed repeats. Bounds are placed on the rate of these conversion processes, with central values of 1.3 × 10-4 and 5.1 × 10-5 per generation for the alternative models. Conclusions This evidence presented here suggests that gene conversion may have played an important role in the evolution of the CMT1A-REP paralogous repeats. The rates of these processes are such that it is probable that homogenized CMT1A-REPs are polymorphic within modern populations. Gene conversion processes are similarly likely to play an important role in the evolution of other segmental duplications and may influence the rate of non-allelic homologous recombination between them.

The impact of repeat-testing of common chemistry analytes at critical concentrations.

Science.gov (United States)

Onyenekwu, Chinelo P; Hudson, Careen L; Zemlin, Annalise E; Erasmus, Rajiv T

2014-12-01

Early notification of critical values by the clinical laboratory to the treating physician is a requirement for accreditation and is essential for effective patient management. Many laboratories automatically repeat a critical value before reporting it to prevent possible misdiagnosis. Given today's advanced instrumentation and quality assurance practices, we questioned the validity of this approach. We performed an audit of repeat-testing in our laboratory to assess for significant differences between initial and repeated test results, estimate the delay caused by repeat-testing and to quantify the cost of repeating these assays. A retrospective audit of repeat-tests for sodium, potassium, calcium and magnesium in the first quarter of 2013 at Tygerberg Academic Laboratory was conducted. Data on the initial and repeat-test values and the time that they were performed was extracted from our laboratory information system. The Clinical Laboratory Improvement Amendment criteria for allowable error were employed to assess for significant difference between results. A total of 2308 repeated tests were studied. There was no significant difference in 2291 (99.3%) of the samples. The average delay ranged from 35 min for magnesium to 42 min for sodium and calcium. At least 2.9% of laboratory running costs for the analytes was spent on repeating them. The practice of repeating a critical test result appears unnecessary as it yields similar results, delays notification to the treating clinician and increases laboratory running costs.

Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period.

Science.gov (United States)

Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose; Linnet, Kristian

2018-04-01

Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology. A literature review on concentrations in the published DFC-related hair cases and on concentrations in hair of these substances after single and multiple doses is included. These cases demonstrate the value of segmental hair analysis in DFCs and facilitate future interpretations of results. Copyright © 2018 Elsevier B.V. All rights reserved.

Flanking Variation Influences Rates of Stutter in Simple Repeats

Directory of Open Access Journals (Sweden)

August E. Woerner

2017-11-01

Full Text Available It has been posited that the longest uninterrupted stretch (LUS of tandem repeats, as defined by the number of exactly matching repeating motif units, is a better predictor of rates of stutter than the parental allele length (PAL. While there are cases where this hypothesis is likely correct, such as the 9.3 allele in the TH01 locus, there can be situations where it may not apply as well. For example, the PAL may capture flanking indel variations while remaining insensitive to polymorphisms in the repeat, and these haplotypic changes may impact the stutter rate. To address this, rates of stutter were contrasted against the LUS as well as the PAL on different flanking haplotypic backgrounds. This study shows that rates of stutter can vary substantially depending on the flanking haplotype, and while there are cases where the LUS is a better predictor of stutter than the PAL, examples to the contrary are apparent in commonly assayed forensic markers. Further, flanking variation that is 7 bp from the repeat region can impact rates of stutter. These findings suggest that non-proximal effects, such as DNA secondary structure, may be impacting the rates of stutter in common forensic short tandem repeat markers.

A COMPARISON OF PAIRS FIGURE SKATERS IN REPEATED JUMPS

Directory of Open Access Journals (Sweden)

William A. Sands

2012-03-01

Full Text Available Trends in pairs figure skating have shown that increasingly difficult jumps have become an essential aspect of high-level performance, especially in the latter part of a competitive program. We compared a repeated jump power index in a 60 s repeated jump test to determine the relationship of repeated jump test to competitive rank and to measure 2D hip, knee, and ankle angles and angular velocities at 0, 20, 40, and 60 s. Eighteen National Team Pairs Figure Skaters performed a 60 s repeated jump test on a large switch-mat with timing of flight and ground durations and digital video recording. Each 60-s period was divided into 6, 10-s intervals, with power indexes (W/kg calculated for each 10-s interval. Power index by 10-s interval repeated measures ANOVAs (RMANOVA showed that males exceeded females at all intervals, and the highest power index interval was during 10 to 20 s for both sexes. RMANOVAs of angles and angular velocities showed main effects for time only. Power index and jumping techniques among figure skaters showed rapid and steady declines over the test duration. Power index can predict approximately 50% of competitive rank variance, and sex differences in jumping technique were rare

Characteristics of intergenerational contractions of the CTG repeat in myotonic dystropy

Energy Technology Data Exchange (ETDEWEB)

Ashizawa, T.; Anvret, M.; Grandell, U.; Baiget, M.; Cobo, A.M.; Barcelo, J.M.; Korneluk, R.G.; Dallapiccola, B.; Novelli, G.; Fenwick, R.G. Jr. (and others)

1994-03-01

In myotonic dystropy (DM), the size of a CTG repeat in the DM kinase gene generally increases in successive generations with clinical evidence of anticipation. However, there have also been cases with an intergenerational contraction of the repeat. The authors have examined 1,489 DM parent-offspring pairs, of which 95 (6.4%) showed such contractions in peripheral blood leukocytes (PBL). In 56 of th 95 pairs, clinical data allowed an analysis of their anticipation status. It is surprising that anticipation occurred in 27 (48%) of these 56 pairs, while none clearly showed a later onset of DM in the asymptomatic offspring. The contraction occurred in 76 (10%) of 753 paternal transmission and in 19 (3%) of 736 maternal transmissions. Anticipation was observed more frequently in maternal (85%) than in paternal (37%) transmissions (P<.001). The parental repeat size correlated with the size of intergenerational contraction (r[sup 2] = .50, P [much lt].001), and the slope of linear regression was steeper in paternal ([minus].62) than in maternal ([minus].30) transmissions (P [much lt].001). Sixteen DM parents had multiple DM offspring with the CTG repeat contractions. This frequency was higher than the frequency expected from the probability of the repeat contractions (6.4%) and the size of DM sib population (1.54 DM offspring per DM parent, in 968 DM parents). The authors conclude that (1) intergenerational contraction of the CTG repeat in leukocyte DNA frequently accompanies apparent anticipation, especially when DM is maternally transmitted, and (2) the paternal origin of the repeat and the presence of the repeat contraction in a sibling increase the probability of the CTG repeat contraction. 43 refs., 1 fig., 4 tabs.

[The original nootropic and neuroprotective drug noopept potentiates the anticonvulsant activity of valproate in mice].

Science.gov (United States)

Kravchenko, E V; Ponteleeva, I V; Trofimov, S S; Lapa, V I; Ostrovskaia, R U; Voronina, T A

2009-01-01

The influence of the original dipeptide drug noopept, known to possess nootrope, neuroprotector, and anxiolytic properties, on the anticonvulsant activity of the antiepileptic drug valproate has been studied on the model of corazole-induced convulsions in mice. Neither a single administration of noopept (0.5 mg/kg, i.p.) nor its repeated introduction in 10 or 35 days enhanced the convulsant effect of corazole, which is evidence that noopept alone does not possess anticonvulsant properties. Prolonged (five weeks) preliminary administration of noopept enhanced the anticonvulsant activity of valproate. This result justifies the joint chronic administration of noopept in combination with valproate in order to potentiate the anticonvulsant effect of the latter drug. In addition, the administration of noopept favorably influences the cognitive functions and suppresses the development of neurodegenerative processes.

Huntingtin gene repeat size variations affect risk of lifetime depression.

Science.gov (United States)

Gardiner, Sarah L; van Belzen, Martine J; Boogaard, Merel W; van Roon-Mom, Willeke M C; Rozing, Maarten P; van Hemert, Albert M; Smit, Johannes H; Beekman, Aartjan T F; van Grootheest, Gerard; Schoevers, Robert A; Oude Voshaar, Richard C; Roos, Raymund A C; Comijs, Hannie C; Penninx, Brenda W J H; van der Mast, Roos C; Aziz, N Ahmad

2017-12-11

Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

Towards accurate de novo assembly for genomes with repeats

NARCIS (Netherlands)

Bucur, Doina

2017-01-01

De novo genome assemblers designed for short k-mer length or using short raw reads are unlikely to recover complex features of the underlying genome, such as repeats hundreds of bases long. We implement a stochastic machine-learning method which obtains accurate assemblies with repeats and

Repeat cesarean delivery: what indications are recorded in the medical chart?

Science.gov (United States)

Lydon-Rochelle, Mona T; Gardella, Carolyn; Cárdenas, Vicky; Easterling, Thomas R

2006-03-01

National surveillance estimates reported a troubling 63 percent decline in the rate of vaginal birth after cesarean delivery (VBAC) from 1996 (28.3%) to 2003 (10.6%), with subsequent rising rates of repeat cesarean delivery. The study objective was to examine patterns of documented indications for repeat cesarean delivery in women with and without labor. We conducted a population-based validation study of 19 nonfederal short-stay hospitals in Washington state. Of the 4,541 women who had live births in 2000, 11 percent (n = 493) had repeat cesarean without labor and 3 percent (n = 138) had repeat cesarean with labor. Incidence of medical conditions and pregnancy complications, patterns of documented indications for repeat cesarean delivery, and perioperative complications in relation to repeat cesarean delivery with and without labor were calculated. Of the 493 women who underwent a repeat cesarean delivery without labor, "elective"(36%) and "maternal request"(18%) were the most common indications. Indications for maternal medical conditions (3.0%) were uncommon. Among the 138 women with repeat cesarean delivery with labor, 60.1 percent had failure to progress, 24.6 percent a non-reassuring fetal heart rate, 8.0 percent cephalopelvic disproportion, and 7.2 percent maternal request during labor. Fetal indications were less common (5.8%). Breech, failed vacuum, abruptio placentae, maternal complications, and failed forceps were all indicated less than 5.0 percent. Women's perioperative complications did not vary significantly between women without and with labor. Regardless of a woman's labor status, nearly 10 percent of women with repeat cesarean delivery had no documented indication as to why a cesarean delivery was performed. "Elective" and "maternal request" were common indications among women undergoing repeat cesarean delivery without labor, and nearly 10 percent of women had undocumented indications for repeat cesarean delivery in their medical record

Dietary supplementation with cysteine prevents adverse metabolic outcomes of repeated cures with paracetamol in old rats.

Science.gov (United States)

Mast, Carole; Pourpe, Charlène; Voyard, Guillaume; Rémond, Didier; Migné, Carole; Centeno, Delphine; Dardevet, Dominique; Savary-Auzeloux, Isabelle; Papet, Isabelle

2017-12-01

Cysteine (Cys), a conditionally indispensable amino acid, is required for the detoxification of paracetamol (acetaminophen, N-acetyl-para-aminophenol, 4-hydroxy-acetanilide, APAP), a drug of widespread use in older persons. We recently reported that repeated APAP cures could worsen sarcopenia in old rats, likely to be due to the impairment of Cys/GSH homoeostasis. The aim of the study was to evaluate whether a dietary Cys supplementation during APAP cures could improve Cys/GSH homoeostasis and thus preserve skeletal muscle. Male 21·5-month-old Wistar rats received three 2-week-long cures of APAP (1 % of diet) alone or with extra Cys (0·5 % of diet), intercalated with washout periods of 2 weeks (APAP and APAP-Cys groups, respectively). They were compared with untreated control rats (CT group). CT and APAP-Cys groups were pair-fed to the APAP group. Dietary Cys supplementation was efficient to prevent increase in liver mass (P<0·0001), decrease in liver GSH (P<0·0001), increase in blood GSH concentration (P<0·0001), and to some extent, decrease in plasma free Cys concentration (P<0·05), all induced by repeated APAP cures. The addition of Cys to APAP cures decreased plasma alanine transaminase (P<0·05), the fractional synthesis rate of liver proteins (P<0·01), and increased masses of extensor digitorum longus (P<0·01), and soleus (P<0·05), compared with the APAP group. Cys supplementation prevented alteration in Cys/GSH homoeostasis and increased some muscle masses in old rats under repeated cures with a non-toxic dose of APAP.

Drug-related disorders and the criminal and clinical background of the prison population of São Paulo State, Brazil.

Directory of Open Access Journals (Sweden)

Maíra Mendes dos Santos

Full Text Available OBJECTIVE: To analyze the association between drug (DAD and alcohol (AAD abuse and dependency and criminal and clinical background by gender of prisoners in São Paulo, Brazil. METHOD: Cross-sectional study, random sample stratified by administrative district, from which prisons and prisoners were selected via random, multistage sampling. Psychiatric diagnoses were made with the CIDI 2.1. Lifetime prevalence and 95% CI were calculated and adjusted via analysis of complex samples. Multinomial logistic regression analysis was carried out with four categories of dependent variables: presence AAD; presence DAD; presence of another mental disorder; no mental disorders. For female alcohol and drug abuse and dependency (ADAD were combined into a single category. RESULTS: The sample was composed by 1809 interviewed prisoners (1192 men and 617 women. Prevalence of DAD and AAD was 25.2% and 15.6%, respectively, among female prisoners, and 26.5% and 18.5% among males. Male prisoners with DAD were more likely to have a criminal record as an adolescent (OR 2.17, to be a repeat offender (OR 2.85, and to have committed a property crime (OR 2.18. Prisoners with AAD were repeat offenders (OR 2.18. Among female prisoners, ADAD was associated with repeat offenses (OR 3.39, a criminal record as an adolescent (OR 9.24, a clinical or infectious condition (OR 5.09, another health problem (OR 3.04, and violent crime (OR 2.5. CONCLUSION: The study confirmed an association between drug-use disorders and the criminal and clinical background in the study population. Prisoners with such disorders were more likely to be repeat offenders and to have a criminal record as adolescents. Among female prisoners disorders were also associated with violent crime and health problems, while among males they were associated with property crime. These patterns in clinical and criminal backgrounds illustrate the need for social rehabilitation programs and specific medical treatment for

Selection pressure on human STR loci and its relevance in repeat expansion disease

KAUST Repository

Shimada, Makoto K.; Sanbonmatsu, Ryoko; Yamaguchi-Kabata, Yumi; Yamasaki, Chisato; Suzuki, Yoshiyuki; Chakraborty, Ranajit; Gojobori, Takashi; Imanishi, Tadashi

2016-01-01

Short Tandem Repeats (STRs) comprise repeats of one to several base pairs. Because of the high mutability due to strand slippage during DNA synthesis, rapid evolutionary change in the number of repeating units directly shapes the range of repeat

Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence.

Science.gov (United States)

Ersche, Karen D; Bullmore, Edward T; Craig, Kevin J; Shabbir, Shaila S; Abbott, Sanja; Müller, Ulrich; Ooi, Cinly; Suckling, John; Barnes, Anna; Sahakian, Barbara J; Merlo-Pich, Emilio V; Robbins, Trevor W

2010-06-01

There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges. To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D(2)/D(3) receptor antagonist and agonist challenges. Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging. Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England. Stimulant-dependent individuals (n = 18) and healthy volunteers (n = 18). Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions. Attentional bias for stimulant-related words was measured during functional magnetic resonance imaging by a drug-word Stroop paradigm; trait impulsivity and compulsivity of dependence were assessed at baseline by questionnaire. Drug users demonstrated significant attentional bias for drug-related words, which was correlated with greater activation of the left prefrontal and right cerebellar cortex. Attentional bias was greater in people with highly compulsive patterns of stimulant abuse; the effects of dopaminergic challenges on attentional interference and related frontocerebellar activation were different between high- and low-compulsivity subgroups. Greater attentional bias for and greater prefrontal activation by stimulant-related words constitute a candidate neurocognitive marker for dependence. Individual differences in compulsivity of stimulant dependence had significant effects on attentional bias, its brain functional representation, and its short-term modulation

Surveillance of drug use among young people attending a music festival in Australia, 2005-2008.

Science.gov (United States)

Lim, Megan S C; Hellard, Margaret E; Hocking, Jane S; Spelman, Tim D; Aitken, Campbell K

2010-03-01

In order to monitor trends in illicit drug use among youth, surveillance of drug use behaviours among a variety of populations in different settings is required. We monitored drug use among music festival attendees. Cross-sectional studies of young people's reported drug use were performed at a music festival in Melbourne from 2005 to 2008. Self-administered questionnaires collected information on drug use, demographics and other risk behaviour. From 2005 to 2008, over 5000 questionnaires were completed by people aged 16-29; 2273 men and 3011 women. Overall, use of any illicit drug in the past month was reported by 44%. After adjusting for demographic and behavioural characteristics, the prevalence of recent illicit drug use decreased significantly from 46% in 2005 to 43% in 2008 (OR 0.92, 95% CI 0.87-0.97). After adjusting for age and sex the downwards trend was repeated for amphetamines and cannabis, but a significant increase in prevalence was observed in hallucinogen, ecstasy and inhalant use. Drug use was more common among men, older participants and those engaging in high-risk sexual behaviour. Illicit drug use was much more common in this sample than in the National Drug Strategy Household survey, but the direction of trends in drug use were similar; drug use prevalences were much lower than in the Ecstasy and Related Drugs Reporting System, the Illicit Drug Reporting System or National Needle and Syringe Program Survey. Music festival attendees are a potentially useful group for monitoring trends in illicit drug use.

Characteristics of persons with repeat syphilis - Idaho, 2011-2015.

Science.gov (United States)

Kassem, Ahmed M; Bartschi, Jared; Carter, Kris K

2018-03-14

During 2011-2015 in Idaho, 14 (7%) of 193 persons with early syphilis had repeat syphilis. Persons with repeat infections were more likely to have had secondary or early latent syphilis (P = 0.037) and be infected with HIV (P < 0.001) compared with those having one infection.

Relationship between quantum repeating devices and quantum seals

International Nuclear Information System (INIS)

He Guangping

2009-01-01

It is revealed that quantum repeating devices and quantum seals have a very close relationship, thus the theory in one field can be applied to the other. Consequently, it is shown that the fidelity bounds and optimality of quantum repeating devices for decoding quantum information can be violated when they are used for decoding classical information from quantum states and the security bounds for protocols sealing quantum data exist.

High throughput miniature drug-screening platform using bioprinting technology

International Nuclear Information System (INIS)

Rodríguez-Dévora, Jorge I; Reyna, Daniel; Xu Tao; Zhang Bimeng; Shi Zhidong

2012-01-01

In the pharmaceutical industry, new drugs are tested to find appropriate compounds for therapeutic purposes for contemporary diseases. Unfortunately, novel compounds emerge at expensive prices and current target evaluation processes have limited throughput, thus leading to an increase of cost and time for drug development. This work shows the development of the novel inkjet-based deposition method for assembling a miniature drug-screening platform, which can realistically and inexpensively evaluate biochemical reactions in a picoliter-scale volume at a high speed rate. As proof of concept, applying a modified Hewlett Packard model 5360 compact disc printer, green fluorescent protein expressing Escherichia coli cells along with alginate gel solution have been arrayed on a coverslip chip under a repeatable volume of 180% ± 26% picoliters per droplet; subsequently, different antibiotic droplets were patterned on the spots of cells to evaluate the inhibition of bacteria for antibiotic screening. The proposed platform was compared to the current screening process, validating its effectiveness. The viability and basic function of the printed cells were evaluated, resulting in cell viability above 98% and insignificant or no DNA damage to human kidney cells transfected. Based on the reduction of investment and compound volume used by this platform, this technique has the potential to improve the actual drug discovery process at its target evaluation stage. (paper)

A study on radiographic repeat rate data of several hospitals in Jeddah

International Nuclear Information System (INIS)

Al-Malki, M.A.; Abulfaraj, W.H.; Bhuiyan, S.I.; Kinsara, A.A.

2003-01-01

Radiographic repeat rate data in diagnostic radiology in King Fahad Hospital (KFH), King Abdulaziz Hospital (KAH), and Maternity and Children Hospital (MCH) in Jeddah, Saudi Arabia, have been studied. The study provided valuable information to suggest preventive measures to reduce repeats. The variables included in the study are exposure techniques, examination types, total number of films used, number of films repeated, the film sizes, gender, the age groups of the patients, and reason for repetition. The total number of examinations in all three hospitals is 6001 using 8887 films on 5412 patients. The average repeat rate was 7.93%, where the individual hospital repeat rates were 9.57% in the MCH, 7.84% in KAH and 7.44% in KFH. The repeat rate for children and infants was found to be undesirable. The quality assurance (QA) programme can effectively reduce the unnecessary exposure and can identify the cause of the exposure. The overexposure, underexposure and position fault were the foremost contributors for repeats and constitute 32.91%, 28.94% and 22.98% of the total respectively. The QA study identified that human error and equipment malfunction are the major contributors to these causes of repeats. The highest repetition rate was for pelvis, 13.64%, followed by skull, 11.59%, and abdomen, 10.41%. It is estimated that the total area of wasted film in all three hospitals is 74.3 m 2 . As per the average repeat rate, the cost of repeat films in the entire kingdom per year has been projected to be about US$1.82 million (SR 6.83 million) in the government hospitals only. Based on the findings of this study a set of recommendations have been prescribed for the radiology department to reduce the repeat rate and to improve the safety culture. (author)

A study on radiographic repeat rate data of several hospitals in Jeddah

Energy Technology Data Exchange (ETDEWEB)

Al-Malki, M.A.; Abulfaraj, W.H.; Bhuiyan, S.I.; Kinsara, A.A

2003-07-01

Radiographic repeat rate data in diagnostic radiology in King Fahad Hospital (KFH), King Abdulaziz Hospital (KAH), and Maternity and Children Hospital (MCH) in Jeddah, Saudi Arabia, have been studied. The study provided valuable information to suggest preventive measures to reduce repeats. The variables included in the study are exposure techniques, examination types, total number of films used, number of films repeated, the film sizes, gender, the age groups of the patients, and reason for repetition. The total number of examinations in all three hospitals is 6001 using 8887 films on 5412 patients. The average repeat rate was 7.93%, where the individual hospital repeat rates were 9.57% in the MCH, 7.84% in KAH and 7.44% in KFH. The repeat rate for children and infants was found to be undesirable. The quality assurance (QA) programme can effectively reduce the unnecessary exposure and can identify the cause of the exposure. The overexposure, underexposure and position fault were the foremost contributors for repeats and constitute 32.91%, 28.94% and 22.98% of the total respectively. The QA study identified that human error and equipment malfunction are the major contributors to these causes of repeats. The highest repetition rate was for pelvis, 13.64%, followed by skull, 11.59%, and abdomen, 10.41%. It is estimated that the total area of wasted film in all three hospitals is 74.3 m{sup 2}. As per the average repeat rate, the cost of repeat films in the entire kingdom per year has been projected to be about US$1.82 million (SR 6.83 million) in the government hospitals only. Based on the findings of this study a set of recommendations have been prescribed for the radiology department to reduce the repeat rate and to improve the safety culture. (author)

Reinforcement principles for addiction medicine; from recreational drug use to psychiatric disorder.

Science.gov (United States)

Edwards, Scott

2016-01-01

The transition from recreational drug use to addiction can be conceptualized as a pathological timeline whereby the psychological mechanisms responsible for disordered drug use evolve from positive reinforcement to favor elements of negative reinforcement. Abused substances (ranging from alcohol to psychostimulants) are initially ingested at regular occasions according to their positive reinforcing properties. Importantly, repeated exposure to rewarding substances sets off a chain of secondary reinforcing events, whereby cues and contexts associated with drug use may themselves become reinforcing and thereby contribute to the continued use and possible abuse of the substance(s) of choice. Indeed, the powerful reinforcing efficacy of certain drugs may eclipse that of competing social rewards (such as career and family) and lead to an aberrant narrowing of behavioral repertoire. In certain vulnerable individuals, escalation of drug use over time is thought to drive specific molecular neuroadaptations that foster the development of addiction. Research has identified neurobiological elements of altered reinforcement following excessive drug use that comprise within-circuit and between-circuit neuroadaptations, both of which contribute to addiction. Central to this process is the eventual potentiation of negative reinforcement mechanisms that may represent the final definitive criterion locking vulnerable individuals into a persistent state of addiction. Targeting the neural substrates of reinforcement likely represents our best chances for therapeutic intervention for this devastating disease. © 2016 Elsevier B.V. All rights reserved.

Group sex offending by juveniles: coercive sex as a group activity

NARCIS (Netherlands)

Bijleveld, C.C.J.H.; Weerman, F.; Looije, D.; Hendriks, J.

2007-01-01

We study sex offences carried out by groups of juveniles, focusing on offender characteristics and the interaction patterns within offender groups and between offenders and victims. Using reconstructions of offences from court files as well as information retrieved from personality screenings, we

Mechanism of Repeat-Associated MicroRNAs in Fragile X Syndrome

Directory of Open Access Journals (Sweden)

Karen Kelley

2012-01-01

Full Text Available The majority of the human genome is comprised of non-coding DNA, which frequently contains redundant microsatellite-like trinucleotide repeats. Many of these trinucleotide repeats are involved in triplet repeat expansion diseases (TREDs such as fragile X syndrome (FXS. After transcription, the trinucleotide repeats can fold into RNA hairpins and are further processed by Dicer endoribonuclases to form microRNA (miRNA-like molecules that are capable of triggering targeted gene-silencing effects in the TREDs. However, the function of these repeat-associated miRNAs (ramRNAs is unclear. To solve this question, we identified the first native ramRNA in FXS and successfully developed a transgenic zebrafish model for studying its function. Our studies showed that ramRNA-induced DNA methylation of the FMR1 5′-UTR CGG trinucleotide repeat expansion is responsible for both pathological and neurocognitive characteristics linked to the transcriptional FMR1 gene inactivation and the deficiency of its protein product FMRP. FMRP deficiency often causes synapse deformity in the neurons essential for cognition and memory activities, while FMR1 inactivation augments metabotropic glutamate receptor (mGluR-activated long-term depression (LTD, leading to abnormal neuronal responses in FXS. Using this novel animal model, we may further dissect the etiological mechanisms of TREDs, with the hope of providing insights into new means for therapeutic intervention.

Kinematic repeatability of a multi-segment foot model for dance.

Science.gov (United States)

Carter, Sarah L; Sato, Nahoko; Hopper, Luke S

2018-03-01

The purpose of this study was to determine the intra and inter-assessor repeatability of a modified Rizzoli Foot Model for analysing the foot kinematics of ballet dancers. Six university-level ballet dancers performed the movements; parallel stance, turnout plié, turnout stance, turnout rise and flex-point-flex. The three-dimensional (3D) position of individual reflective markers and marker triads was used to model the movement of the dancers' tibia, entire foot, hindfoot, midfoot, forefoot and hallux. Intra and inter-assessor reliability demonstrated excellent (ICC ≥ 0.75) repeatability for the first metatarsophalangeal joint in the sagittal plane. Intra-assessor reliability demonstrated excellent (ICC ≥ 0.75) repeatability during flex-point-flex across all inter-segmental angles except for the tibia-hindfoot and hindfoot-midfoot frontal planes. Inter-assessor repeatability ranged from poor to excellent (0.5 > ICC ≥ 0.75) for the 3D segment rotations. The most repeatable measure was the tibia-foot dorsiflexion/plantar flexion articulation whereas the least repeatable measure was the hindfoot-midfoot adduction/abduction articulation. The variation found in the inter-assessor results is likely due to inconsistencies in marker placement. This 3D dance specific multi-segment foot model provides insight into which kinematic measures can be reliably used to ascertain in vivo technical errors and/or biomechanical abnormalities in a dancer's foot motion.

Automated detection of repeated structures in building facades

Directory of Open Access Journals (Sweden)

M. Previtali

2013-10-01

Full Text Available Automatic identification of high-level repeated structures in 3D point clouds of building façades is crucial for applications like digitalization and building modelling. Indeed, in many architectural styles building façades are governed by arrangements of objects into repeated patterns. In particular, façades are generally designed as the repetition of some few basic objects organized into interlaced and\\or concatenated grid structures. Starting from this key observation, this paper presents an algorithm for Repeated Structure Detection (RSD in 3D point clouds of building façades. The presented methodology consists of three main phases. First, in the point cloud segmentation stage (i the building façade is decomposed into planar patches which are classified by means of some weak prior knowledge of urban buildings formulated in a classification tree. Secondly (ii, in the element clustering phase detected patches are grouped together by means of a similarity function and pairwise transformations between patches are computed. Eventually (iii, in the structure regularity estimation step the parameters of repeated grid patterns are calculated by using a Least- Squares optimization. Workability of the presented approach is tested using some real data from urban scenes.

Various anti-motion sickness drugs and core body temperature changes.

Science.gov (United States)

Cheung, Bob; Nakashima, Ann M; Hofer, Kevin D

2011-04-01

Blood flow changes and inactivity associated with motion sickness appear to exacerbate the rate of core temperature decrease during subsequent body cooling. We investigated the effects of various classes of anti-motion sickness drugs on core temperature changes. There were 12 healthy male and female subjects (20-35 yr old) who were given selected classes of anti-motion sickness drugs prior to vestibular Coriolis cross coupling induced by graded yaw rotation and periodic pitch-forward head movements in the sagittal plane. All subjects were then immersed in water at 18 degrees C for a maximum of 90 min or until their core temperature reached 35 degrees C. Double-blind randomized trials were administered, including a placebo, a non-immersion control with no drug, and six anti-motion sickness drugs: meclizine, dimenhydrinate, chlorpheniramine, promethazine + dexamphetamine, promethazine + caffeine, and scopolamine + dexamphetamine. A 7-d washout period was observed between trials. Core temperature and the severity of sickness were monitored throughout each trial. A repeated measures design was performed on the severity of sickness and core temperature changes prior to motion provocation, immediately after the motion sickness end point, and throughout the period of cold-water immersion. The most effective anti-motion sickness drugs, promethazine + dexamphetamine (with a sickness score/duration of 0.65 +/- 0.17) and scopolamine + dexamphetamine (with a sickness score/duration of 0.79 +/- 0.17), significantly attenuated the decrease in core temperature. The effect of this attenuation was lower in less effective drugs. Our results suggest that the two most effective anti-motion sickness drugs are also the most effective in attenuating the rate of core temperature decrease.

Kidnapping: a criminal profile of persons convicted 1979-2001.

Science.gov (United States)

Soothill, Keith; Francis, Brian; Ackerley, Elizabeth

2007-01-01

Kidnapping has been a neglected crime in criminological research. In fact, there has been a dramatic increase in the yearly numbers of police recorded kidnapping offences in England and Wales in the last 25 years, but this has not been matched by a similar increase in convictions. This study focuses on the official criminal histories of the 7042 males and 545 females who were convicted at least once for kidnapping between 1979 and 2001. Of these, 3.9% of the males and 2.6% of the females had convictions for kidnapping on more than one occasion. We examined two subgroups to ensure long observation periods for prior and subsequent convictions. Of those convicted of kidnapping in 2001, around one-half (51.1%) of the males and around one-third (36.6%) of the females had previous convictions. The previous convictions consist of a wide range of offences, with the most common being theft and violent offences. A 20-year follow-up of those convicted in 1979-81 showed that three in five males and one in three females are subsequently convicted on at least one more occasion for a standard-list offence. An examination of convictions for other offences brought to court at the same time as the kidnap offence enabled a typology of kidnaps to be proposed. Those kidnaps with co-convictions of an acquisitive nature declined over the period, whereas other types, including sexual and violent, showed rises. Changing shifts in the nature of kidnaps have important policy implications.

Long-term results of repeated anti-vascular endothelial growth factor therapy in eyes with retinal pigment epithelial tears.

Science.gov (United States)

Moreira, Carlos A; Arana, Luis A; Zago, Rommel J

2013-02-01

To evaluate the long-term results of retinal pigment epithelium tears in eyes treated with repeated anti-vascular endothelial growth factor (VEGF) therapy. Five patients with retinal pigment epithelial tears (without foveal center involvement) after anti-VEGF injection were studied retrospectively. Mean follow-up time was 52 months, with measurements of visual acuity and evaluation of macular findings by angiography and optical coherence tomography during this period. All eyes had a persistent submacular neovascular membrane 30 days after the tear. An anti-VEGF drug was reinjected until the membranes stopped leaking. The mean initial visual acuity immediately after the tear was 20/160, and the mean final visual acuity was 20/60. The number of anti-VEGF reinjections varied from two to eight during the follow-up period. Long-term optical coherence tomography analysis showed reduced fluid and remodeling of the torn retinal pigment epithelium. Long-term visual results with repeated anti-VEGF therapy are not as devastating as suggested previously. Visual acuity and metamorphopsia improve with time as long as the neovascular membrane is inactive. Optical coherence tomography changes in the macular area reflect the visual acuity improvement.

Highly sensitive detection of individual HEAT and ARM repeats with HHpred and COACH.

Science.gov (United States)

Kippert, Fred; Gerloff, Dietlind L

2009-09-24

HEAT and ARM repeats occur in a large number of eukaryotic proteins. As these repeats are often highly diverged, the prediction of HEAT or ARM domains can be challenging. Except for the most clear-cut cases, identification at the individual repeat level is indispensable, in particular for determining domain boundaries. However, methods using single sequence queries do not have the sensitivity required to deal with more divergent repeats and, when applied to proteins with known structures, in some cases failed to detect a single repeat. Testing algorithms which use multiple sequence alignments as queries, we found two of them, HHpred and COACH, to detect HEAT and ARM repeats with greatly enhanced sensitivity. Calibration against experimentally determined structures suggests the use of three score classes with increasing confidence in the prediction, and prediction thresholds for each method. When we applied a new protocol using both HHpred and COACH to these structures, it detected 82% of HEAT repeats and 90% of ARM repeats, with the minimum for a given protein of 57% for HEAT repeats and 60% for ARM repeats. Application to bona fide HEAT and ARM proteins or domains indicated that similar numbers can be expected for the full complement of HEAT/ARM proteins. A systematic screen of the Protein Data Bank for false positive hits revealed their number to be low, in particular for ARM repeats. Double false positive hits for a given protein were rare for HEAT and not at all observed for ARM repeats. In combination with fold prediction and consistency checking (multiple sequence alignments, secondary structure prediction, and position analysis), repeat prediction with the new HHpred/COACH protocol dramatically improves prediction in the twilight zone of fold prediction methods, as well as the delineation of HEAT/ARM domain boundaries. A protocol is presented for the identification of individual HEAT or ARM repeats which is straightforward to implement. It provides high

Assessing the quality of pharmacist answers to telephone drug information questions.

Science.gov (United States)

Woodward, C T; Stevenson, J G; Poremba, A

1990-04-01

A quality assurance (QA) program is described in which frontline pharmacists were asked test drug information questions via anonymous telephone calls. The program was instituted at a university hospital that began providing decentralized pharmaceutical services in 1985. Questions were developed on the basis of a pilot study conducted to determine the types and complexity of drug information questions received by frontline pharmacists at the hospital. Data on departmental clinical productivity were used to determine the number of questions that would be posed during each shift in the various service areas. The questions were posed during a 10-day period; the pharmacists were aware of the program, but the callers did not identify their affiliation with it. In response to 105 questions asked, 86 were judged to have been answered correctly, 13 answers were deemed incomplete, and 6 were judged incorrect. Pharmacists were more likely to respond incorrectly to complex questions and questions posed during the night shift. As a result of the audit, staff members with advanced clinical knowledge were asked to help less experienced pharmacists, the position of assistant director for drug information and staff development was created, and educational programs were instituted. The QA audit has been repeated twice. Posing test drug information questions via anonymous telephone calls is effective in assessing the quality of drug information provided by pharmacists in patient-care areas.

Perfectionism and negative affect after repeated failure: Anxiety, depression, and anger

OpenAIRE

Stoeber, Joachim; Schneider, Natalia; Hussain, Rimi; Matthews, Kelly

2014-01-01

Perfectionists have shown increased negative affect after failure compared to nonperfectionists. However, little is known about how perfectionists react to repeated failure. This study investigated the effects of two forms of perfectionism--self-oriented perfectionism and socially prescribed perfectionism--on 100 university students’ reactions to repeated failure (versus repeated success) examining three negative emotions: anxiety, depression, and anger. Results showed that socially prescribe...

Coordination in continuously repeated games

NARCIS (Netherlands)

Weeren, A.J.T.M.; Schumacher, J.M.; Engwerda, J.C.

1995-01-01

In this paper we propose a model to describe the effectiveness of coordination in a continuously repeated two-player game. We study how the choice of a decision rule by a coordinator affects the strategic behavior of the players, resulting in more or less cooperation. Our model requires the analysis

Repeat-aware modeling and correction of short read errors.

Science.gov (United States)

Yang, Xiao; Aluru, Srinivas; Dorman, Karin S

2011-02-15

High-throughput short read sequencing is revolutionizing genomics and systems biology research by enabling cost-effective deep coverage sequencing of genomes and transcriptomes. Error detection and correction are crucial to many short read sequencing applications including de novo genome sequencing, genome resequencing, and digital gene expression analysis. Short read error detection is typically carried out by counting the observed frequencies of kmers in reads and validating those with frequencies exceeding a threshold. In case of genomes with high repeat content, an erroneous kmer may be frequently observed if it has few nucleotide differences with valid kmers with multiple occurrences in the genome. Error detection and correction were mostly applied to genomes with low repeat content and this remains a challenging problem for genomes with high repeat content. We develop a statistical model and a computational method for error detection and correction in the presence of genomic repeats. We propose a method to infer genomic frequencies of kmers from their observed frequencies by analyzing the misread relationships among observed kmers. We also propose a method to estimate the threshold useful for validating kmers whose estimated genomic frequency exceeds the threshold. We demonstrate that superior error detection is achieved using these methods. Furthermore, we break away from the common assumption of uniformly distributed errors within a read, and provide a framework to model position-dependent error occurrence frequencies common to many short read platforms. Lastly, we achieve better error correction in genomes with high repeat content. The software is implemented in C++ and is freely available under GNU GPL3 license and Boost Software V1.0 license at "http://aluru-sun.ece.iastate.edu/doku.php?id = redeem". We introduce a statistical framework to model sequencing errors in next-generation reads, which led to promising results in detecting and correcting errors

Low-Normal FMR1 CGG Repeat Length: Phenotypic Associations

Directory of Open Access Journals (Sweden)

Marsha eMailick

2014-09-01

Full Text Available This population-based study investigates genotype-phenotype correlations of low-normal CGG repeats in the fragile X mental retardation 1 (FMR1 gene. FMR1 plays an important role in brain development and function, and encodes FMRP (fragile X mental retardation protein, an RNA-binding protein that regulates protein synthesis impacting activity-dependent synaptic development and plasticity. Most past research has focused on CGG premutation expansions (41 to 200 CGG repeats and on fragile X syndrome (200+ CGG repeats, with considerably less attention on the other end of the spectrum of CGG repeats. Using existing data, older adults with 23 or fewer CGG repeats (2 SDs below the mean were compared with age-peers who have normal numbers of CGGs (24-40 with respect to cognition, mental health, cancer, and having children with disabilities. Men (n = 341 with an allele in the low-normal range and women (n = 46 with two low-normal alleles had significantly more difficulty with their memory and ability to solve day to day problems. Women with both FMR1 alleles in the low-normal category had significantly elevated odds of feeling that they need to drink more to get the same effect as in the past. These women also had two and one-half times the odds of having had breast cancer and four times the odds of uterine cancer. Men and women with low-normal CGGs had higher odds of having a child with a disability, either a developmental disability or a mental health condition. These findings are in line with the hypothesis that there is a need for tight neuronal homeostatic control mechanisms for optimal cognitive and behavioral functioning, and more generally that low numbers as well as high numbers of CGG repeats may be problematic for health.

Does Dry Eye Affect Repeatability of Corneal Topography Measurements?

Directory of Open Access Journals (Sweden)

Aysun Şanal Doğan

2018-04-01

Full Text Available Objectives: The purpose of this study was to assess the repeatability of corneal topography measurements in dry eye patients and healthy controls. Materials and Methods: Participants underwent consecutive corneal topography measurements (Sirius; Costruzione Strumenti Oftalmici, Florence, Italy. Two images with acquisition quality higher than 90% were accepted. The following parameters were evaluated: minimum and central corneal thickness, aqueous depth, apex curvature, anterior chamber volume, horizontal anterior chamber diameter, iridocorneal angle, cornea volume, and average simulated keratometry. Repeatability was assessed by calculating intra-class correlation coefficient. Results: Thirty-three patients with dry eye syndrome and 40 healthy controls were enrolled to the study. The groups were similar in terms of age (39 [18-65] vs. 30.5 [18-65] years, p=0.198 and gender (M/F: 4/29 vs. 8/32, p=0.366. Intra-class correlation coefficients among all topography parameters within both groups showed excellent repeatability (>0.90. Conclusion: The anterior segment measurements provided by the Sirius corneal topography system were highly repeatable for dry eye patients and are sufficiently reliable for clinical practice and research.

Does Dry Eye Affect Repeatability of Corneal Topography Measurements?

Science.gov (United States)

Doğan, Aysun Şanal; Gürdal, Canan; Köylü, Mehmet Talay

2018-04-01

The purpose of this study was to assess the repeatability of corneal topography measurements in dry eye patients and healthy controls. Participants underwent consecutive corneal topography measurements (Sirius; Costruzione Strumenti Oftalmici, Florence, Italy). Two images with acquisition quality higher than 90% were accepted. The following parameters were evaluated: minimum and central corneal thickness, aqueous depth, apex curvature, anterior chamber volume, horizontal anterior chamber diameter, iridocorneal angle, cornea volume, and average simulated keratometry. Repeatability was assessed by calculating intra-class correlation coefficient. Thirty-three patients with dry eye syndrome and 40 healthy controls were enrolled to the study. The groups were similar in terms of age (39 [18-65] vs. 30.5 [18-65] years, p=0.198) and gender (M/F: 4/29 vs. 8/32, p=0.366). Intra-class correlation coefficients among all topography parameters within both groups showed excellent repeatability (>0.90). The anterior segment measurements provided by the Sirius corneal topography system were highly repeatable for dry eye patients and are sufficiently reliable for clinical practice and research.

Device-independent secret-key-rate analysis for quantum repeaters

Science.gov (United States)

Holz, Timo; Kampermann, Hermann; Bruß, Dagmar

2018-01-01

The device-independent approach to quantum key distribution (QKD) aims to establish a secret key between two or more parties with untrusted devices, potentially under full control of a quantum adversary. The performance of a QKD protocol can be quantified by the secret key rate, which can be lower bounded via the violation of an appropriate Bell inequality in a setup with untrusted devices. We study secret key rates in the device-independent scenario for different quantum repeater setups and compare them to their device-dependent analogon. The quantum repeater setups under consideration are the original protocol by Briegel et al. [Phys. Rev. Lett. 81, 5932 (1998), 10.1103/PhysRevLett.81.5932] and the hybrid quantum repeater protocol by van Loock et al. [Phys. Rev. Lett. 96, 240501 (2006), 10.1103/PhysRevLett.96.240501]. For a given repeater scheme and a given QKD protocol, the secret key rate depends on a variety of parameters, such as the gate quality or the detector efficiency. We systematically analyze the impact of these parameters and suggest optimized strategies.

Repfinder: Finding approximately repeated scene elements for image editing

KAUST Repository

Cheng, Ming-Ming

2010-07-26

Repeated elements are ubiquitous and abundant in both manmade and natural scenes. Editing such images while preserving the repetitions and their relations is nontrivial due to overlap, missing parts, deformation across instances, illumination variation, etc. Manually enforcing such relations is laborious and error-prone. We propose a novel framework where user scribbles are used to guide detection and extraction of such repeated elements. Our detection process, which is based on a novel boundary band method, robustly extracts the repetitions along with their deformations. The algorithm only considers the shape of the elements, and ignores similarity based on color, texture, etc. We then use topological sorting to establish a partial depth ordering of overlapping repeated instances. Missing parts on occluded instances are completed using information from other instances. The extracted repeated instances can then be seamlessly edited and manipulated for a variety of high level tasks that are otherwise difficult to perform. We demonstrate the versatility of our framework on a large set of inputs of varying complexity, showing applications to image rearrangement, edit transfer, deformation propagation, and instance replacement. © 2010 ACM.

30 CFR 250.522 - When do I have to repeat casing diagnostic testing?

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false When do I have to repeat casing diagnostic... Operations Casing Pressure Management § 250.522 When do I have to repeat casing diagnostic testing? Casing diagnostic testing must be repeated according to the following table: When * * * you must repeat diagnostic...

Online child pornography offenders are different: a meta-analysis of the characteristics of online and offline sex offenders against children.

Science.gov (United States)

Babchishin, Kelly M; Hanson, R Karl; VanZuylen, Heather

2015-01-01

The current meta-analysis compared the characteristics of online child pornography-only offenders, typical (offline) sex offenders against children, and offenders with both child pornography and contact sex offences against children (mixed). Based on 30 unique samples (comparison ns ranging from 98 to 2,702), the meta-analysis found key differences between groups. Offenders who committed contact sex offences were more likely to have access to children than those with only child pornography offences. In contrast, offenders who used the internet to commit sexual offences had greater access to the internet than those with contact sex offenders. Differences between the groups, however, were not limited to differential opportunities. Sex offenders against children and mixed offenders were found to score higher on indicators of antisociality than online child pornography offenders (CPOs). CPOs were also more likely to have psychological barriers to sexual offending than sex offenders against children and mixed offenders (e.g., greater victim empathy). Mixed offenders were found to be the most pedophilic, even more than CPOs. The findings suggest that offenders who restricted their offending behavior to online child pornography offences were different from mixed offenders and offline sex offenders against children, and that mixed offenders were a particularly high risk group.

INCRIMINATING THE CONFLICT OF INTERESTS IN ROMANIA: RECENT LEGAL DEVELOPMENTS

Directory of Open Access Journals (Sweden)

Mihai MAREȘ

2018-05-01

Full Text Available The present paper aims at outlining the evolution of the Romanian criminal law provisions incriminating the conflict of interests, starting from its insertion, as of 2006, into the Criminal Code of 1968, until the up-to-date version of the offence as per the Criminal Code in force, renamed as use of the position for favouring persons, as amended by Law no. 193/2017. In this context, the approaches of the legal text in the well-established case-law of the judicial bodies as well as of the Constitutional Court and legal literature are highly relevant in order to explain the rationale behind the shaping of the legal content of the offence. The diachronic delineation shall be supplemented by elements of comparative law. Where appropriate, reference shall also be made to the administrative type of liability that may be incurred in a conflict of interest case and the relationship thereof with the proceedings in criminal matters or to distinctions between the analysed offence and other offences falling into the category of malfeasance in office or corruption offences. The conclusions of this examination emphasise the need for predictability and proper understanding of the criminological layer in tackling the conflict of interest phenomenon.

Repeated-dose effects of mequitazine, cetirizine and dexchlorpheniramine on driving and psychomotor performance.

Science.gov (United States)

Theunissen, Eef L; Vermeeren, Annemiek; Ramaekers, Johannes G

2006-01-01

Previous studies have demonstrated that the antihistamines mequitazine, cetirizine and dexchlorpheniramine produce mild sedation after single doses. It is unknown, however, whether acute sedation persists after repeated dosing. Therefore, this study assessed the effects of repeated dosing of these antihistamines on driving and psychomotor performance. Sixteen healthy volunteers were treated with mequitazine 10 mg q.a.m., cetirizine 10 mg q.a.m., dexchlorpheniramine Repetab 6 mg b.i.d. and placebo for four separate 8-day periods. Drug effects were assessed on days 1 and 8 using on-the-road driving tests (highway driving and car following), psychomotor tests (tracking and divided attention) and subjective questionnaires. Dexchlorpheniramine and mequitazine significantly impaired driving performance on the highway driving test on the first day; dexchlorpheniramine increased Standard Deviation of Lateral Position by 2 cm [95% confidence interval (CI) 0.5, 3.8] and mequitazine by 2.5 cm (CI 1.0, 4.3). These effects on driving performance disappeared after 8 days of treatment. No effect of treatment was found on car following, tracking and divided attention. Although subjective ratings confirmed that subjects knew their driving had been impaired in the mequitazine and dexchlorpheniramine condition after completion of the highway driving test on day 1, they did not expect their driving to be affected before the start of the test. Cetirizine did not impair performance on any of the tests. Single doses of mequitazine 10 mg and dexchlorpheniramine Repetab 6 mg cause mild driving impairment. However, when taken over several days, the impairing effect wears off, possibly as a result of tolerance.

Repeated swim stress alters brain benzodiazepine receptors measured in vivo

International Nuclear Information System (INIS)

Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

1989-01-01

The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of [ 3 H]Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in [14C]iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress [an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures], although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results

Repeated swim stress alters brain benzodiazepine receptors measured in vivo

Energy Technology Data Exchange (ETDEWEB)

Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

1989-06-01

The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats

Science.gov (United States)

Amodeo, Leslie R.; Greenfield, Venuz Y.; Humphrey, Danielle E.; Varela, Veronica; Pipkin, Joseph A.; Eaton, Shannon E.; Johnson, Jelesa D.; Plant, Christopher P.; Harmony, Zachary R.; Wang, Li; Crawford, Cynthia A.

2015-01-01

Rationale The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. Objective The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. Methods In Experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In Experiment 2, rats were injected with paroxetine (2.5, 5 or 10 mg/kg), fluoxetine (5, 10 or 20 mg/kg), or vehicle during the same time frame as Experiment 1 and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. Results Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. Discussion These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors. PMID:26141193

The Legal Importance of Blood Alcohol Limits for Driving in German Law with a Comparative Study of Emirati and Egyptian Legislation

Directory of Open Access Journals (Sweden)

Abdulsallam A. Bakdash

2017-06-01

Full Text Available Driving under the influence of alcohol or drugs (DUI is a crime or offence according to the laws of most countries. DUI increases the risk of traffic accidents as well as the severity and outcome of injuries that result from them. Some countries have a sophisticated control system to monitor DUI of alcohol in all traffic accidents. There is variation between different countries regarding the concept of driving under the influence of alcohol as well as the legal limits of Blood Alcohol Concentration (BAC and the requirements to test the victims of accidents. This paper reviews the limit values for BAC in German traffic law (Administrative Offences Act, which stipulates a BAC value of 0.50 mg/g and a breath alcohol value of 0.25 mg/L as a marginal value for the application of punitive measures. German criminal law defines the minimum BAC values of relative unfitness to drive and absolute unfitness to drive as 0.3 mg/g and 1.10 mg/g, respectively (1.60 mg/g for cyclists.The minimum BAC values representing significant impairment and absolute impairment in criminal cases are 2.00 mg/g and 3.00 mg/g, respectively. Different penalties and legal consequences result according to the BAC level of an offender. In contrast, only eight out of twenty-two Arab countries recognise BAC limit values only in traffic laws. In Jordan, the BAC limit is 0.75 mg/g (0.08 g/dL.in the UAE, the BAC limit is 0.094 mg/g (0.01 g/dL, while Egyptian law does not recognise BAC values in the application of sanctions: the mere presence of alcohol in blood, regardless of its concentration and effect, is a sufficient and adequate condition for punishment. Accordingly, this study encourages lawmakers in Arab countries to define the limit values for BAC when investigating any crime in general and traffic offences in particular, in close cooperation with forensic doctors and toxicologists. It urges them to consider different BAC and their effects in relation to traffic offences. It

Crystal structures of the human G3BP1 NTF2-like domain visualize FxFG Nup Repeat Specificity

DEFF Research Database (Denmark)

Vognsen, Tina Reinholdt; Möller, Ingvar Rúnar; Kristensen, Ole

2013-01-01

Ras GTPase Activating Protein SH3 Domain Binding Protein (G3BP) is a potential anti-cancer drug target implicated in several cellular functions. We have used protein crystallography to solve crystal structures of the human G3BP1 NTF2-like domain both alone and in complex with an FxFG Nup repeat...... peptide. Despite high structural similarity, the FxFG binding site is located between two alpha helices in the G3BP1 NTF2-like domain and not at the dimer interface as observed for nuclear transport factor 2. ITC studies showed specificity towards the FxFG motif but not FG and GLFG motifs. The unliganded...

Preventing Repeat Teen Births PSA (:60)

Centers for Disease Control (CDC) Podcasts

This 60 second public service announcement is based on the April 2013 CDC Vital Signs report, which discusses repeat teen births and ways teens, parents and guardians, health care providers, and communities can help prevent them.

Intentie tot exploratie, sociale binding en delinquent gedrag van Nederlandse jongeren

NARCIS (Netherlands)

Luijpers, E.T.H.

2000-01-01

The scientific literature indicates that the majority of adolescents have committed one or two offences in the past. However, most of the offences committed involve petty crime. The main questions that this study addresses are: why is there an increase from early to middle adolescence in the

Strafbare belediging

NARCIS (Netherlands)

Janssens, Alfred Ludovicus Joannes Maria

1998-01-01

The Dutch law of criminal defamation consists of a number of offences protecting a legal interest considered of great importance: a person’s honour and reputation. The nucleus of the present book consists of a description and analysis of those offences. Particular attention is devoted to the

Discrepancies in reporting the CAG repeat lengths for Huntington's disease

DEFF Research Database (Denmark)

Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty

2011-01-01

Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...

Trinucleotide repeat microsatellite markers for Black Poplar (Populus nigra L.)

NARCIS (Netherlands)

Smulders, M.J.M.; Schoot, van der J.; Arens, P.; Vosman, B.

2001-01-01

Using an enrichment procedure, we have cloned microsatellite repeats from black poplar (Populus nigra L.) and developed primers for microsatellite marker analysis. Ten primer pairs, mostly for trinucleotide repeats, produced polymorphic fragments in P. nigra. Some of them also showed amplification

A laser syringe aimed at delivering drug into the outer layer of human skin

Science.gov (United States)

Yoh, Jack J.; Jang, Hun-jae; Park, Mi-ae; Han, Tae-hee; Hah, Jung-moo

2012-07-01

A desire to eliminate hypodermic needle in transdermal drug delivery may now be realized. Imaging of the skin after injection of fluorescent probe and biotin via the bio-ballistic technique revealed the epidermal and dermal layers which were stained well below 60 μm underneath the abdominal skin of the guinea-pig. An extensive network of cells are shown in the deeper layer of the stained dermis as the distributed fluorescein isothiocyanate (FITC) dose is administered by repeated injection via the laser-based microjet. Here, we show our method of laser-based microjet drug delivery is capable of breaching guinea-pig's skin tissue and then delivering controlled dose of drug to the targeted region between 10 to 400 μm underneath the outermost layer of the skin. While minimizing pain and tissue damage by reducing the injection volume to ˜100 nl per pulse and the microjet diameter of half the conventional syringe needle in 100 μm, the optimally controlled delivery of liquid drug by the irradiated laser pulse is shown possible.

Effects of dibutyl phthalate on lipid metabolism and drug metabolising enzyme system in rats

International Nuclear Information System (INIS)

Arakaki, Mitsuo; Ariyoshi, Toshihiko.

1976-01-01

Effects of dibutyl phthalate (DBP) on the liver constituents and the drug metabolizing enzyme system were investigated in rats. 1. In the experiments at a single oral dose of DBP (630 or 1260 mg/kg), the glycogen content was decreased only at the high dose, but no effects were observed on the contents of glycogen, triglyceride, microsomal protein and cytochromes, and on the activities of drug metabolizing enzymes. 2. In the repeated oral dose of DBP (630 or 1260 mg/kg/day) for 5 days, the ratio of liver weight to body weight was increased in both female and male rats, whereas the increases of cytochrome P-450 content and aniline hydroxylase activity were noted only in male rats. However, the contents of liver triglyceride, phospholipids, and cholesterol were unchanged. On the other hand, serum cholesterol content which showed the tendency to be decreased at the low dose was significantly decreased at the high dose. 3. In the incorporation of 1- 14 C-acetate into liver and serum lipids after repeated oral dose of DBP (630 mg/kg/day) for 5 days in male rats, the incorporation into triglyceride showed tendency to be increased, whereas the incorporation into cholesterol and cholesterol ester remained unchanged in vivo and in vitro. (auth.)

Adolescent violence against parents. Is it a consequence of gender inequality?

Directory of Open Access Journals (Sweden)

Oscar Diaz

2009-01-01

Full Text Available The aim of the present study was to explore the psychosocial profile of juveniles reported for violent behaviours against their parents, as well as the extent to which the phenomenon of violence against parents (VAP can be explained by the hypothesis of the bi-directionality of intra-family violence. For this purpose we selected a sample of 103 juveniles classified in three groups –(a VAP offences, (b VAP offences and other types of offence, and (c other offences. In total we analyzed 413 files from the office of the Public Prosecutor for Juveniles in Bilbao (Basque Country, northern Spain. We extracted personal, family context and judicial variables for the juveniles. The results suggest the existence of a specific profile of juveniles reported for VAP, and also show that through the hypothesis of the bi-directionality of intra-family violence it is possible to explain one-third of the cases analyzed.

Fumigation of Folia belladonnae with 14C-labelled ethylene oxide to reduce the germ number - activity distributions in the drug and preparations made from it

International Nuclear Information System (INIS)

Strohmeier, H.

1988-01-01

The study described here provided evidence to prove that considerable quantities of ethylene oxide, ethylene chlorhydrin and ethylene glycol are retained, when a drug is fumigated with ethylene oxide under standard fumigation conditions in order to reduce the germ number. Ethylene oxide bound by adsorption may be eliminated from the drug by repeated aeration. If an aqueous-ethanolic percolate is prepared from a drug showing very high levels of ethylene chlorhydrin and then carefully distilled at 40 C using only little pressure, a dry extract can be obtained that contains no such residue. (orig.) [de

Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner.

Science.gov (United States)

Tai, S; Hyatt, W S; Gu, C; Franks, L N; Vasiljevik, T; Brents, L K; Prather, P L; Fantegrossi, W E

2015-12-01

These studies probed the relationship between intrinsic efficacy and tolerance/cross-tolerance between ∆(9)-THC and synthetic cannabinoid drugs of abuse (SCBs) by examining in vivo effects and cellular changes concomitant with their repeated administration in mice. Dose-effect relationships for hypothermic effects were determined in order to confirm that SCBs JWH-018 and JWH-073 are higher efficacy agonists than ∆(9)-THC in mice. Separate groups of mice were treated with saline, sub-maximal hypothermic doses of JWH-018 or JWH-073 (3.0mg/kg or 10.0mg/kg, respectively) or a maximally hypothermic dose of 30.0mg/kg ∆(9)-THC once per day for 5 consecutive days while core temperature and locomotor activity were monitored via biotelemetry. Repeated administration of all drugs resulted in tolerance to hypothermic effects, but not locomotor effects, and this tolerance was still evident 14 days after the last drug administration. Further studies treated mice with 30.0mg/kg ∆(9)-THC once per day for 4 days, then tested with SCBs on day 5. Mice with a ∆(9)-THC history were cross-tolerant to both SCBs, and this cross-tolerance also persisted 14 days after testing. Select brain regions from chronically treated mice were examined for changes in CB1 receptor expression and function. Expression and function of hypothalamic CB1Rs were reduced in mice receiving chronic drugs, but cortical CB1R expression and function were not altered. Collectively, these data demonstrate that repeated ∆(9)-THC, JWH-018 and JWH-073 can induce long-lasting tolerance to some in vivo effects, which is likely mediated by region-specific downregulation and desensitization of CB1Rs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chromosome-specific DNA Repeat Probes

Energy Technology Data Exchange (ETDEWEB)

Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.

2006-03-16

In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

Roles of "Wanting" and "Liking" in Motivating Behavior: Gambling, Food, and Drug Addictions.

Science.gov (United States)

Robinson, M J F; Fischer, A M; Ahuja, A; Lesser, E N; Maniates, H

2016-01-01

The motivation to seek out and consume rewards has evolutionarily been driven by the urge to fulfill physiological needs. However in a modern society dominated more by plenty than scarcity, we tend to think of motivation as fueled by the search for pleasure. Here, we argue that two separate but interconnected subcortical and unconscious processes direct motivation: "wanting" and "liking." These two psychological and neuronal processes and their related brain structures typically work together, but can become dissociated, particularly in cases of addiction. In drug addiction, for example, repeated consumption of addictive drugs sensitizes the mesolimbic dopamine system, the primary component of the "wanting" system, resulting in excessive "wanting" for drugs and their cues. This sensitizing process is long-lasting and occurs independently of the "liking" system, which typically remains unchanged or may develop a blunted pleasure response to the drug. The result is excessive drug-taking despite minimal pleasure and intense cue-triggered craving that may promote relapse long after detoxification. Here, we describe the roles of "liking" and "wanting" in general motivation and review recent evidence for a dissociation of "liking" and "wanting" in drug addiction, known as the incentive sensitization theory (Robinson and Berridge 1993). We also make the case that sensitization of the "wanting" system and the resulting dissociation of "liking" and "wanting" occurs in both gambling disorder and food addiction.

Viral delivery of C9orf72 hexanucleotide repeat expansions in mice leads to repeat-length-dependent neuropathology and behavioural deficits

Directory of Open Access Journals (Sweden)

Saul Herranz-Martin

2017-07-01

Full Text Available Intronic GGGGCC repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Two major pathologies stemming from the hexanucleotide RNA expansions (HREs have been identified in postmortem tissue: intracellular RNA foci and repeat-associated non-ATG dependent (RAN dipeptides, although it is unclear how these and other hallmarks of disease contribute to the pathophysiology of neuronal injury. Here, we describe two novel lines of mice that overexpress either 10 pure or 102 interrupted GGGGCC repeats mediated by adeno-associated virus (AAV and recapitulate the relevant human pathology and disease-related behavioural phenotypes. Similar levels of intracellular RNA foci developed in both lines of mice, but only mice expressing 102 repeats generated C9orf72 RAN pathology, neuromuscular junction (NMJ abnormalities, dispersal of the hippocampal CA1, enhanced apoptosis, and deficits in gait and cognition. Neither line of mice, however, showed extensive TAR DNA-binding protein 43 (TDP-43 pathology or neurodegeneration. Our data suggest that RNA foci pathology is not a good predictor of C9orf72 RAN dipeptide formation, and that RAN dipeptides and NMJ dysfunction are drivers of C9orf72 disease pathogenesis. These AAV-mediated models of C9orf72-associated ALS/FTD will be useful tools for studying disease pathophysiology and developing new therapeutic approaches.

Repeat Stereotactic Radiosurgery for Acoustic Neuromas

International Nuclear Information System (INIS)

Kano, Hideyuki; Kondziolka, Douglas; Niranjan, Ajay M.Ch.; Flannery, Thomas J.; Flickinger, John C.; Lunsford, L. Dade

2010-01-01

Purpose: To evaluate the outcome of repeat stereotactic radiosurgery (SRS) for acoustic neuromas, we assessed tumor control, clinical outcomes, and the risk of adverse radiation effects in patients whose tumors progressed after initial management. Methods and Materials: During a 21-year experience at our center, 1,352 patients underwent SRS as management for their acoustic neuromas. We retrospectively identified 6 patients who underwent SRS twice for the same tumor. The median patient age was 47 years (range, 35-71 years). All patients had imaging evidence of tumor progression despite initial SRS. One patient also had incomplete surgical resection after initial SRS. All patients were deaf at the time of the second SRS. The median radiosurgery target volume at the time of the initial SRS was 0.5 cc and was 2.1 cc at the time of the second SRS. The median margin dose at the time of the initial SRS was 13 Gy and was 11 Gy at the time of the second SRS. The median interval between initial SRS and repeat SRS was 63 months (range, 25-169 months). Results: At a median follow-up of 29 months after the second SRS (range, 13-71 months), tumor control or regression was achieved in all 6 patients. No patient developed symptomatic adverse radiation effects or new neurological symptoms after the second SRS. Conclusions: With this limited experience, we found that repeat SRS for a persistently enlarging acoustic neuroma can be performed safely and effectively.

Resveratrol ameliorates depressive-like behavior in repeated corticosterone-induced depression in mice.

Science.gov (United States)

Ali, Syed Hamid; Madhana, Rajaram Mohanrao; K V, Athira; Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Pitta, Sathish; Mahareddy, Jalandhar Reddy; Lahkar, Mangala

2015-09-01

A mouse model of depression has been recently developed by exogenous corticosterone (CORT) administration, which has shown to mimic HPA-axis induced depression-like state in animals. The present study aimed to examine the antidepressant-like effect and the possible mechanisms of resveratrol, a naturally occurring polyphenol of phytoalexin family, on depressive-like behavior induced by repeated corticosterone injections in mice. Mice were injected subcutaneously (s.c.) with 40mg/kg corticosterone (CORT) chronically for 21days. Resveratrol and fluoxetine were administered 30min prior to the CORT injection. After 21-days treatment with respective drugs, behavioral and biochemical parameters were estimated. Since brain derived neurotrophic factor (BDNF) has been implicated in antidepressant activity of many drugs, we also evaluated the effect of resveratrol on BDNF in the hippocampus. Three weeks of CORT injections in mice resulted in depressive-like behavior, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test and tail suspension test. Further, there was a significant increase in serum corticosterone level and a significant decrease in hippocampus BDNF level in CORT-treated mice. Treatment of mice with resveratrol significantly ameliorated all the behavioral and biochemical changes induced by corticosterone. These results suggest that resveratrol produces an antidepressant-like effect in CORT-induced depression in mice, which is possibly mediated by rectifying the stress-based hypothalamic-pituitary-adrenal (HPA) axis dysfunction paradigm and upregulation of hippocampal BDNF levels. Copyright © 2015 Elsevier Inc. All rights reserved.

Repeat: a framework to assess empirical reproducibility in biomedical research

Directory of Open Access Journals (Sweden)

Leslie D. McIntosh

2017-09-01

Full Text Available Abstract Background The reproducibility of research is essential to rigorous science, yet significant concerns of the reliability and verifiability of biomedical research have been recently highlighted. Ongoing efforts across several domains of science and policy are working to clarify the fundamental characteristics of reproducibility and to enhance the transparency and accessibility of research. Methods The aim of the proceeding work is to develop an assessment tool operationalizing key concepts of research transparency in the biomedical domain, specifically for secondary biomedical data research using electronic health record data. The tool (RepeAT was developed through a multi-phase process that involved coding and extracting recommendations and practices for improving reproducibility from publications and reports across the biomedical and statistical sciences, field testing the instrument, and refining variables. Results RepeAT includes 119 unique variables grouped into five categories (research design and aim, database and data collection methods, data mining and data cleaning, data analysis, data sharing and documentation. Preliminary results in manually processing 40 scientific manuscripts indicate components of the proposed framework with strong inter-rater reliability, as well as directions for further research and refinement of RepeAT. Conclusions The use of RepeAT may allow the biomedical community to have a better understanding of the current practices of research transparency and accessibility among principal investigators. Common adoption of RepeAT may improve reporting of research practices and the availability of research outputs. Additionally, use of RepeAT will facilitate comparisons of research transparency and accessibility across domains and institutions.

Drug dealers' rational choices on which customers to rip-off.

Science.gov (United States)

Jacques, Scott; Allen, Andrea; Wright, Richard

2014-03-01

Drug dealers are infamous for overcharging customers and handing over less than owed. One reason rip-offs frequently occur is blackmarket participants have limited access to formal means of dispute resolution and, as such, are attractive prey. Yet drug dealers do not cheat every customer. Though this is implicitly understood in the literature, sparse theoretical attention has been given to which customers are ripped-off and why. To address that lacuna, this paper uses the rationality perspective to analyze qualitative data obtained in interviews with 25 unincarcerated drug sellers operating in disadvantaged neighborhoods of St. Louis, Missouri. We find that dealers typically rip-off six types of customers: persons who are strangers, first-time or irregular customers; do not have sufficient money on hand to make a purchase; are uninformed about going market rates; are deemed unlikely to retaliate; are offensive; or are addicted to drugs. Dealers target these groups due to perceiving them as unlikely to be repeat business; not worth the hassle of doing business with; unlikely to realize they are being ripped-off; in the wrong and thus deserving of payback; and, unwilling to retaliate or take their money elsewhere. Our findings are discussed in relation to their practical implications, including the importance of giving blackmarket participants greater access to law, and how customers may prevent being ripped-off. Copyright © 2013 Elsevier B.V. All rights reserved.

Medico-legal and legal-penal aspects of expert opinions and adjudication in cases of intoxications with intoxicating agents and ethanol-like intoxicants

Directory of Open Access Journals (Sweden)

Monika Ćwiklińska

2015-08-01

Full Text Available Introduction: The available legal regulations in Poland do not define the concentration thresholds enabling to differentiate between the states of “after-use” versus “under the influence” of a drug, as it is in the case of alcohol. The aim of the study was to analyse jurisdiction in cases regarding the evaluation of the effects of intoxicating agents and ethanol-like intoxicants and to identify ambiguities and gaps in the applicable regulations leading to problems in preparing expert opinions. Material and methods: The material included the opinions of experts in the field of toxicology and forensic medicine made by the Department of Forensic Medicine in Lublin in the years 2009–2011 and records obtained in the process of inquiry from the regional prosecutor’s offices and courts in 52 cases. Results : Amongst 52 cases in which the ordered toxicology examinations demonstrated the presence of intoxicating agents in drivers’ blood (tetrahydrocannabinols in 39 and amphetamine in 21 cases in 2 cases petty offence proceedings were instituted (Art. 87 of the Petty Offence Code although high concentrations of xenobiotics indicated the state of being “under the influence” of a narcotic drug (Art. 178a of the Penal Code. Three cases were discontinued despite expert opinions that the drivers were at least in the after-narcotic use state. In only 3 cases were witnesses asked to provide testimony about the circumstances of the driver’s conduct. Conclusions : The analysis has demonstrated that judicial bodies expect forensic expertise based exclusively on toxicological examination results; when expert findings are inconclusive, they only administer litigations opportunistically applying the principle of the presumption of innocence understood literally. Considering the above, threshold values of “use” and “influence” of the most commonly detected drugs should be urgently determined.

The relationship of social support concept and repeat mammography among Iranian women.

Science.gov (United States)

Farhadifar, Fariba; Taymoori, Parvaneh; Bahrami, Mitra; Zarea, Shamsy

2015-10-24

Breast cancer ranks as the first most common cancer among the Iranian women. The regular repeat of mammography with 1-2 year intervals leads to the increased efficiency of early detection of breast cancer. The present study examined the predictors of repeat mammography. It was hypothesized that higher social support is connected with mammography repeat. A cross-sectional study was carried out among 400 women 50 years and older in Sanandaj, Iran. Data was collected by the questionnaire including information on socio demographical variables and measuring social support level. Data was analyzed by SPSS16 software. Multiple logistic regression was used to determine the predictive power of demographic variables and dimensions of social support for repeat mammography. Women aged 50-55 years had three times odds of repeat mammography compared to women aged 56-60 years) OR, 3.02). Married women had greater odds of repeat mammography compared to single women (P women with higher social support was 0.93 times greater than the women with lower social support (OR, 0.93; 95 % CI, 0.91-0.95; P women are less likely repeat mammography than other Asian women. Identifying the associations between perceived social support and repeat mammography may offer detailed information to allow for future study and guide the development of interventions not only for Iranian women but also for similar cultural that received pay too little attention to date in the breast cancer literature.

Amiodarone biokinetics, the formation of its major oxidative metabolite and neurotoxicity after acute and repeated exposure of brain cell cultures.

Science.gov (United States)

Pomponio, Giuliana; Zurich, Marie-Gabrielle; Schultz, Luise; Weiss, Dieter G; Romanelli, Luca; Gramowski-Voss, Alexandra; Di Consiglio, Emma; Testai, Emanuela

2015-12-25

The difficulty in mimicking nervous system complexity and cell-cell interactions as well as the lack of kinetics information has limited the use of in vitro neurotoxicity data. Here, we assessed the biokinetic profile as well as the neurotoxicity of Amiodarone after acute and repeated exposure in two advanced rodent brain cell culture models, consisting of both neurons and glial cells organized in 2 or 3 dimensions to mimic the brain histiotypic structure and function. A strategy was applied to evidence the abiotic processes possibly affecting Amiodarone in vitro bioavailability, showing its ability to adsorb to the plastic devices. At clinically relevant Amiodarone concentrations, known to induce neurotoxicity in some patients during therapeutic treatment, a complete uptake was observed in both models in 24 h, after single exposure. After repeated treatments, bioaccumulation was observed, especially in the 3D cell model, together with a greater alteration of neurotoxicity markers. After 14 days, Amiodarone major oxidative metabolite (mono-N-desethylamiodarone) was detected at limited levels, indicating the presence of active drug metabolism enzymes (i.e. cytochrome P450) in both models. The assessment of biokinetics provides useful information on the relevance of in vitro toxicity data and should be considered in the design of an Integrated Testing Strategy aimed to identify specific neurotoxic alerts, and to improve the neurotoxicity assay predictivity for human acute and repeated exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Constructs for the expression of repeating triple-helical protein domains

International Nuclear Information System (INIS)

Peng, Yong Y; Werkmeister, Jerome A; Vaughan, Paul R; Ramshaw, John A M

2009-01-01

The development of novel scaffolds will be an important aspect in future success of tissue engineering. Scaffolds will preferably contain information that directs the cellular content of constructs so that the new tissue that is formed is closely aligned in structure, composition and function to the target natural tissue. One way of approaching this will be the development of novel protein-based constructs that contain one or more repeats of functional elements derived from various proteins. In the present case, we describe a strategy to make synthetic, recombinant triple-helical constructs that contain repeat segments of biologically relevant domains. Copies of a DNA fragment prepared by PCR from human type III collagen have been inserted in a co-linear contiguous fashion into the yeast expression vector YEpFlag-1, using sequential addition between selected restriction sites. Constructs containing 1, 2 and 3 repeats were designed to maintain the (Gly-X-Y) repeat, which is essential for the formation of an extended triple helix. All constructs gave expressed protein, with the best being the 3-repeat construct which was readily secreted. This material had the expected composition and N-terminal sequence. Incubation of the product at low temperature led to triple-helix formation, shown by reaction with a conformation dependent monoclonal antibody.

Incremental Dynamic Analysis of Koyna Dam under Repeated Ground Motions

Science.gov (United States)

Zainab Nik Azizan, Nik; Majid, Taksiah A.; Nazri, Fadzli Mohamed; Maity, Damodar; Abdullah, Junaidah

2018-03-01

This paper discovers the incremental dynamic analysis (IDA) of concrete gravity dam under single and repeated earthquake loadings to identify the limit state of the dam. Seven ground motions with horizontal and vertical direction as seismic input considered in the nonlinear dynamic analysis based on the real repeated earthquake in the worldwide. All the ground motions convert to respond spectrum and scaled according to the developed elastic respond spectrum in order to match the characteristic of the ground motion to the soil type. The scaled was depends on the fundamental period, T1 of the dam. The Koyna dam has been selected as a case study for the purpose of the analysis by assuming that no sliding and rigid foundation, has been estimated. IDA curves for Koyna dam developed for single and repeated ground motions and the performance level of the dam identifies. The IDA curve of repeated ground motion shown stiffer rather than single ground motion. The ultimate state displacement for a single event is 45.59mm and decreased to 39.33mm under repeated events which are decreased about 14%. This showed that the performance level of the dam based on seismic loadings depend on ground motion pattern.

Constructs for the expression of repeating triple-helical protein domains

Energy Technology Data Exchange (ETDEWEB)

Peng, Yong Y; Werkmeister, Jerome A; Vaughan, Paul R; Ramshaw, John A M, E-mail: jerome.werkmeister@csiro.a [CSIRO Molecular and Health Technologies, Bag 10, Clayton South, VIC 3169 (Australia)

2009-02-15

The development of novel scaffolds will be an important aspect in future success of tissue engineering. Scaffolds will preferably contain information that directs the cellular content of constructs so that the new tissue that is formed is closely aligned in structure, composition and function to the target natural tissue. One way of approaching this will be the development of novel protein-based constructs that contain one or more repeats of functional elements derived from various proteins. In the present case, we describe a strategy to make synthetic, recombinant triple-helical constructs that contain repeat segments of biologically relevant domains. Copies of a DNA fragment prepared by PCR from human type III collagen have been inserted in a co-linear contiguous fashion into the yeast expression vector YEpFlag-1, using sequential addition between selected restriction sites. Constructs containing 1, 2 and 3 repeats were designed to maintain the (Gly-X-Y) repeat, which is essential for the formation of an extended triple helix. All constructs gave expressed protein, with the best being the 3-repeat construct which was readily secreted. This material had the expected composition and N-terminal sequence. Incubation of the product at low temperature led to triple-helix formation, shown by reaction with a conformation dependent monoclonal antibody.

[Analysis of variance of repeated data measured by water maze with SPSS].

Science.gov (United States)

Qiu, Hong; Jin, Guo-qin; Jin, Ru-feng; Zhao, Wei-kang

2007-01-01

To introduce the method of analyzing repeated data measured by water maze with SPSS 11.0, and offer a reference statistical method to clinical and basic medicine researchers who take the design of repeated measures. Using repeated measures and multivariate analysis of variance (ANOVA) process of the general linear model in SPSS and giving comparison among different groups and different measure time pairwise. Firstly, Mauchly's test of sphericity should be used to judge whether there were relations among the repeatedly measured data. If any (PSPSS statistical package is available to fulfil this process.

Drugs@FDA: FDA Approved Drug Products

Science.gov (United States)

... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

Smuggling of migrants in Kosovo

Directory of Open Access Journals (Sweden)

MSc. Albulena Hajdari

2012-06-01

Full Text Available Smuggling of migrants, as a serious type of criminality, takes an important place in legal science and criminal legislation. This is due to the fact that actions creating the image of these criminal offences also cause numerous individual, family and societal consequences. Smuggling migrants, with all its consequences, attracts the attention not only of the state authorities, but also the wider public, and numerous researchers and scholars. Nevertheless, despite this fact, this phenomenon has not been studied thoroughly. There is a dire lack of such research in recent years, specifically because of the presence of such crimes in a relatively higher number. This circumstance, specifically the fact that in Kosovo, smuggling migrants is a frequent occurrence, made me engage in studying this type of criminality. The aim of this paper is to research on criminal offences of migrant smuggling in Kosovo, and especially their causes. The causes of these criminal offences may be of numerous natures, but the main causes may be sought in social and economic circumstances, and other conditions related to the unstable political setting, weaknesses in operations of justice authorities, lack of implementation of criminal legislation, etc. In researching the criminal offences of smuggling migrants, I have used the method of historical materialism, legal-dogmatic method, statistical method, complaint method and interviews, and the method of studying individual cases. In the case of addressing criminal offences of smuggling migrants, I have concluded that these offences represent a serious type of crime, thereby resulting in dire individual, family and societal consequences. They are found in all modern societies, including Kosovo.

Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

KAUST Repository

Viterbo, David; Michoud, Gregoire; Mosbach, Valentine; Dujon, Bernard; Richard, Guy-Franck

2016-01-01

Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded.

Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

KAUST Repository

Viterbo, David

2016-03-16

Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded.

Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment.

Science.gov (United States)

Chaudhari, Umesh; Nemade, Harshal; Wagh, Vilas; Gaspar, John Antonydas; Ellis, James K; Srinivasan, Sureshkumar Perumal; Spitkovski, Dimitry; Nguemo, Filomain; Louisse, Jochem; Bremer, Susanne; Hescheler, Jürgen; Keun, Hector C; Hengstler, Jan G; Sachinidis, Agapios

2016-11-01

The currently available techniques for the safety evaluation of candidate drugs are usually cost-intensive and time-consuming and are often insufficient to predict human relevant cardiotoxicity. The purpose of this study was to develop an in vitro repeated exposure toxicity methodology allowing the identification of predictive genomics biomarkers of functional relevance for drug-induced cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). The hiPSC-CMs were incubated with 156 nM doxorubicin, which is a well-characterized cardiotoxicant, for 2 or 6 days followed by washout of the test compound and further incubation in compound-free culture medium until day 14 after the onset of exposure. An xCELLigence Real-Time Cell Analyser was used to monitor doxorubicin-induced cytotoxicity while also monitoring functional alterations of cardiomyocytes by counting of the beating frequency of cardiomyocytes. Unlike single exposure, repeated doxorubicin exposure resulted in long-term arrhythmic beating in hiPSC-CMs accompanied by significant cytotoxicity. Global gene expression changes were studied using microarrays and bioinformatics tools. Analysis of the transcriptomic data revealed early expression signatures of genes involved in formation of sarcomeric structures, regulation of ion homeostasis and induction of apoptosis. Eighty-four significantly deregulated genes related to cardiac functions, stress and apoptosis were validated using real-time PCR. The expression of the 84 genes was further studied by real-time PCR in hiPSC-CMs incubated with daunorubicin and mitoxantrone, further anthracycline family members that are also known to induce cardiotoxicity. A panel of 35 genes was deregulated by all three anthracycline family members and can therefore be expected to predict the cardiotoxicity of compounds acting by similar mechanisms as doxorubicin, daunorubicin or mitoxantrone. The identified gene panel can be applied in the safety

Thyroid nodules with nondiagnostic results on repeat fine-needle aspiration biopsy: which nodules should be considered for repeat biopsy or surgery rather than follow-up?

Energy Technology Data Exchange (ETDEWEB)

Eun, Na Lae; Chang, Hang Seok; Gweon, Hye Mi; Kim, Jeong Ah; Youk, Ji Hyun; Son, Eun Jun [Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Yoo, Mi Ri [Dept. of Radiology, Dongjak Kyunghee Hospital, Seoul (Korea, Republic of); Park, Ah Young [Dept. of Radiology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan (Korea, Republic of); Moon, Hee Jung [Dept. of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2016-07-15

The goal of this study was to assess the clinicopathologic and ultrasonographic features of thyroid nodules with nondiagnostic results on repeat ultrasonography (US)-guided fineneedle aspiration biopsy (FNAB) according to size and the number of suspicious findings and to determine the proper management of nodules with consecutive nondiagnostic results. This retrospective study included 297 nodules with nondiagnostic results on repeat FNAB that were evaluated by US over the course of at least 12 months of follow-up, a follow-up biopsy, or an operation. We compared clinical and US variables between benign and malignant nodules in thyroid nodules with repeat nondiagnostic results. The comparison of benign and malignant nodules with repeat nondiagnostic results revealed that age, marked hypoechogenicity, irregular or microlobulated margins, microcalcifications, and nonparallel shape were significantly associated with malignancy. Multivariate logistic regression analysis in malignant nodules revealed that microcalcifications and irregular or microlobulated margins were independently associated with malignancy. Among them, only irregular or microlobulated margins were independently significant as a predictor of malignancy in repeatedly nondiagnostic nodules measuring >10 mm. Using receiver operating characteristic analysis, the best cutoff value for the “number of suspicious findings” between benign and malignant nodules was three in nodules of all sizes, three in nodules measuring ≤10 mm, and two in nodules measuring >10 mm. Irregular or microlobulated margins may be the most frequent US features in repeatedly nondiagnostic nodules >10 mm. The presence of “two or more suspicious findings” can be used as the cutoff for distinguishing benign and malignant nodules.

The role of exosomes and miRNAs in drug-resistance of cancer cells.

Science.gov (United States)

Bach, Duc-Hiep; Hong, Ji-Young; Park, Hyen Joo; Lee, Sang Kook

2017-07-15

Chemotherapy, one of the principal approaches for cancer patients, plays a crucial role in controlling tumor progression. Clinically, tumors reveal a satisfactory response following the first exposure to the chemotherapeutic drugs in treatment. However, most tumors sooner or later become resistant to even chemically unrelated anticancer agents after repeated treatment. The reduced drug accumulation in tumor cells is considered one of the significant mechanisms by decreasing drug permeability and/or increasing active efflux (pumping out) of the drugs across the cell membrane. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated, including drug efflux, which is mediated by extracellular vesicles (EVs). Exosomes, a subset of EVs with a size range of 40-150 nm and a lipid bilayer membrane, can be released by all cell types. They mediate specific cell-to-cell interactions and activate signaling pathways in cells they either fuse with or interact with, including cancer cells. Exosomal RNAs are heterogeneous in size but enriched in small RNAs, such as miRNAs. In the primary tumor microenvironment, cancer-secreted exosomes and miRNAs can be internalized by other cell types. MiRNAs loaded in these exosomes might be transferred to recipient niche cells to exert genome-wide regulation of gene expression. How exosomal miRNAs contribute to the development of drug resistance in the context of the tumor microenvironment has not been fully described. In this review, we will highlight recent studies regarding EV-mediated microRNA delivery in formatting drug resistance. We also suggest the use of EVs as an advancing method in antiresistance treatment. © 2017 UICC.

Huntingtin gene repeat size variations affect risk of lifetime depression

DEFF Research Database (Denmark)

Gardiner, Sarah L.; van Belzen, Martine J.; Boogaard, Merel W.

2017-01-01

Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect...

Development of Repeated Sprint Ability in Talented Youth Basketball Players

NARCIS (Netherlands)

te Wierike, Sanne C. M.; de Jong, Mark C.; Tromp, Eveline J. Y.; Vuijk, Pieter J.; Lemmink, Koen A. P. M.; Malina, Robert M.; Elferink-Gemser, Marije T.; Visscher, Chris

te Wierike, SCM, de Jong, MC, Tromp, EJY, Vuijk, PJ, Lemmink, KAPM, Malina, RM, Elferink-Gemser, MT, and Visscher, C. Development of repeated sprint ability in talented youth basketball players. J Strength Cond Res 28(4): 928-934, 2014-Factors affecting repeated sprint ability (RSA) were evaluated

poolHiTS: A Shifted Transversal Design based pooling strategy for high-throughput drug screening

Directory of Open Access Journals (Sweden)

Woolf Peter J

2008-05-01

Full Text Available Abstract Background A key goal of drug discovery is to increase the throughput of small molecule screens without sacrificing screening accuracy. High-throughput screening (HTS in drug discovery involves testing a large number of compounds in a biological assay to identify active compounds. Normally, molecules from a large compound library are tested individually to identify the activity of each molecule. Usually a small number of compounds are found to be active, however the presence of false positive and negative testing errors suggests that this one-drug one-assay screening strategy can be significantly improved. Pooling designs are testing schemes that test mixtures of compounds in each assay, thereby generating a screen of the whole compound library in fewer tests. By repeatedly testing compounds in different combinations, pooling designs also allow for error-correction. These pooled designs, for specific experiment parameters, can be simply and efficiently created using the Shifted Transversal Design (STD pooling algorithm. However, drug screening contains a number of key constraints that require specific modifications if this pooling approach is to be useful for practical screen designs. Results In this paper, we introduce a pooling strategy called poolHiTS (Pooled High-Throughput Screening which is based on the STD algorithm. In poolHiTS, we implement a limit on the number of compounds that can be mixed in a single assay. In addition, we show that the STD-based pooling strategy is limited in the error-correction that it can achieve. Due to the mixing constraint, we show that it is more efficient to split a large library into smaller blocks of compounds, which are then tested using an optimized strategy repeated for each block. We package the optimal block selection algorithm into poolHiTS. The MATLAB codes for the poolHiTS algorithm and the corresponding decoding strategy are also provided. Conclusion We have produced a practical version

Profiling Nonrecipients of Mass Drug Administration for Schistosomiasis and Hookworm Infections : A Comprehensive Analysis of Praziquantel and Albendazole Coverage in Community-Directed Treatment in Uganda

NARCIS (Netherlands)

Chami, Goylette F.; Kontoleon, Andreas A.; Bulte, Erwin; Fenwick, Alan; Kabatereine, Narcis B.; Tukahebwa, Edridah M.; Dunne, David W.

2016-01-01

Background. Repeated mass drug administration (MDA) with preventive chemotherapies is the mainstay of morbidity control for schistosomiasis and soil-transmitted helminths, yet the World Health Organization recently reported that less than one-third of individuals who required preventive

Natively Unfolded FG Repeats Stabilize the Structure of the Nuclear Pore Complex.

Science.gov (United States)

Onischenko, Evgeny; Tang, Jeffrey H; Andersen, Kasper R; Knockenhauer, Kevin E; Vallotton, Pascal; Derrer, Carina P; Kralt, Annemarie; Mugler, Christopher F; Chan, Leon Y; Schwartz, Thomas U; Weis, Karsten

2017-11-02

Nuclear pore complexes (NPCs) are ∼100 MDa transport channels assembled from multiple copies of ∼30 nucleoporins (Nups). One-third of these Nups contain phenylalanine-glycine (FG)-rich repeats, forming a diffusion barrier, which is selectively permeable for nuclear transport receptors that interact with these repeats. Here, we identify an additional function of FG repeats in the structure and biogenesis of the yeast NPC. We demonstrate that GLFG-containing FG repeats directly bind to multiple scaffold Nups in vitro and act as NPC-targeting determinants in vivo. Furthermore, we show that the GLFG repeats of Nup116 function in a redundant manner with Nup188, a nonessential scaffold Nup, to stabilize critical interactions within the NPC scaffold needed for late steps of NPC assembly. Our results reveal a previously unanticipated structural role for natively unfolded GLFG repeats as Velcro to link NPC subcomplexes and thus add a new layer of connections to current models of the NPC architecture. Copyright © 2017 Elsevier Inc. All rights reserved.

Instability of (CTGn•(CAGn trinucleotide repeats and DNA synthesis

Directory of Open Access Journals (Sweden)

Liu Guoqi

2012-02-01

Full Text Available Abstract Expansion of (CTGn•(CAGn trinucleotide repeat (TNR microsatellite sequences is the cause of more than a dozen human neurodegenerative diseases. (CTGn and (CAGn repeats form imperfectly base paired hairpins that tend to expand in vivo in a length-dependent manner. Yeast, mouse and human models confirm that (CTGn•(CAGn instability increases with repeat number, and implicate both DNA replication and DNA damage response mechanisms in (CTGn•(CAGn TNR expansion and contraction. Mutation and knockdown models that abrogate the expression of individual genes might also mask more subtle, cumulative effects of multiple additional pathways on (CTGn•(CAGn instability in whole animals. The identification of second site genetic modifiers may help to explain the variability of (CTGn•(CAGn TNR instability patterns between tissues and individuals, and offer opportunities for prognosis and treatment.

How can the criminal law support the provision of quality in healthcare?

Science.gov (United States)

Yeung, Karen; Horder, Jeremy

2014-06-01

The egregious failings in patient safety at Mid Staffordshire NHS Foundation Trust between 2005 and 2009 identified by Sir Robert Francis QC in his public inquiry prompted him to recommend the introduction of a new criminal offence into English law in circumstances where a patient dies or is seriously harmed by a breach of fundamental standards. The authors evaluate whether, from the perspective of fairness and justice, a new criminal offence in this context is necessary and desirable. The authors considered the basic principles and functions of the criminal law and compared them with the principles and functions of the civil law. They then identify two primary tasks for the criminal law to perform in healthcare settings: (a) to establish primary duties to patients consisting of appropriately graded offences targeted at conduct that harms patients or unjustifiably poses risks to patients, and (b) to establish secondary duties to patients, consisting of offences aimed at punishing and deterring instances in which healthcare management and workers undermine the goals of regulation by lying or giving misleading information to regulatory officials or by obstructing their work. The authors focus on the first of these functions, identifying the scope of existing regulatory schemes that may give rise to criminal liability in English law when applied to healthcare contexts to identify whether a new criminal offence is needed. A gap in the existing regime of criminal liability is identified, and it is this gap which a new criminal offence seeks to fill. The authors suggest how such an offence should be structured, drawing primarily upon foundational principles of criminal liability. It is suggested that a new general offence of wilfully neglecting or ill-treating a patient that can be committed by any healthcare organisation or worker (appropriately defined) is warranted. The criminal law has an important role to play in the healthcare context. Its central function is not

Nonparametric additive regression for repeatedly measured data

KAUST Repository

Carroll, R. J.

2009-05-20

We develop an easily computed smooth backfitting algorithm for additive model fitting in repeated measures problems. Our methodology easily copes with various settings, such as when some covariates are the same over repeated response measurements. We allow for a working covariance matrix for the regression errors, showing that our method is most efficient when the correct covariance matrix is used. The component functions achieve the known asymptotic variance lower bound for the scalar argument case. Smooth backfitting also leads directly to design-independent biases in the local linear case. Simulations show our estimator has smaller variance than the usual kernel estimator. This is also illustrated by an example from nutritional epidemiology. © 2009 Biometrika Trust.

Poor methodological detail precludes experimental repeatability and hampers synthesis in ecology.

Science.gov (United States)

Haddaway, Neal R; Verhoeven, Jos T A

2015-10-01

Despite the scientific method's central tenets of reproducibility (the ability to obtain similar results when repeated) and repeatability (the ability to replicate an experiment based on methods described), published ecological research continues to fail to provide sufficient methodological detail to allow either repeatability of verification. Recent systematic reviews highlight the problem, with one example demonstrating that an average of 13% of studies per year (±8.0 [SD]) failed to report sample sizes. The problem affects the ability to verify the accuracy of any analysis, to repeat methods used, and to assimilate the study findings into powerful and useful meta-analyses. The problem is common in a variety of ecological topics examined to date, and despite previous calls for improved reporting and metadata archiving, which could indirectly alleviate the problem, there is no indication of an improvement in reporting standards over time. Here, we call on authors, editors, and peer reviewers to consider repeatability as a top priority when evaluating research manuscripts, bearing in mind that legacy and integration into the evidence base can drastically improve the impact of individual research reports.

Attenuation of stress induced memory deficits by nonsteroidal anti-inflammatory drugs (NSAIDs) in rats: Role of antioxidant enzymes.

Science.gov (United States)

Emad, Shaista; Qadeer, Sara; Sadaf, Sana; Batool, Zehra; Haider, Saida; Perveen, Tahira

2017-04-01

Repeated stress paradigms have been shown to cause devastating alterations on memory functions. Stress is linked with inflammation. Psychological and certain physical stressors could lead to neuroinflammation. Inflammatory process may occur by release of mediators and stimulate the production of prostaglandins through cyclooxygenase (COX). Treatment with COX inhibitors, which restrain prostaglandin production, has enhanced memory in a number of neuroinflammatory states showing a potential function for raised prostaglandins in these memory shortfalls. In the present study, potential therapeutic effects of indomethacin and diclofenac sodium on memory in both unrestraint and restraint rats were observed. Two components, long term memory and short term memory were examined by Morris water maze (MWM) and elevated plus maze (EPM) respectively. The present study also demonstrated the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on lipid peroxidation (LPO) and activities of antioxidant enzymes along with the activity of acetylcholinesterase (AChE). Results of MWM and EPM showed significant effects of drugs in both unrestraint and restraint rats as escape latency and transfer latency, in respective behavioral models were decreased as compared to that of control. This study also showed NSAIDs administration decreased LPO and increased antioxidant enzymes activity and decreased AChE activity in rats exposed to repeated stress. In conclusion this study suggests a therapeutic potential of indomethacin and diclofenac against repeated stress-induced memory deficits. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Repeat photography as a tool for detecting and monitoring historical ...

African Journals Online (AJOL)

Repeat photography was used to illustrate long-term changes occurring in coastal habitats in the Western Cape, South Africa. Hi storic images were sourced from books and theses, the public and subject specialists, and repeat photographs were then taken from the same perspectives. Visible changes could be categorised ...