The solar I-V cross-spectrum: A powerful diagnostic for Helioseismology

We discuss results and limitations of a new model for the components of the solar intensity (I) an d velocity (V ) photospheric fluctuations. The model is able to take into account the complex behavior of a low-frequency p-mode, as observed inall the four I and V spectra. We also demonstrate that the solar I-V cross-spectrum provides a sensitive diagnostic for the interaction between the oscillatory and non-oscillatory components of the solar velocity and intensity signals

Repeating the Errors of Our Parents? Family-of-Origin Spouse Violence and Observed Conflict Management in Engaged Couples

Based on a developmental social learning analysis, it was hypothesized that observing parental violence predisposes partners to difficulties in managing couple conflict. Seventy-one engaged couples were assessed on their observation of parental violence in their family of origin. All couples were videotaped discussing two areas of current relationship conflict, and their cognitions during the interactions were assessed using a video-mediated recall procedure. Couples in which the male partner reported observing parental violence (male-exposed couples) showed more negative affect and communication during conflict discussions than couples in which neither partner reported observing parental violence (unexposed couples). Couples in which only the female partner reported observing parental violence (female- exposed couples) did not differ from unexposed couples in their affect or behavior. Female-exposed couples reported more negative cognitions than unexposed couples, but male-exposed couples did not differ from unexposed couples in their reported cognitions

A Coherence-Based Approach for Tracking Waves in the Solar Corona

We consider the problem of automatically (and robustly) isolating and extracting information about waves and oscillations observed in EUV image sequences of the solar corona with a view to near real-time application to data from the Atmospheric Imaging Array (AIA) on the Solar Dynamics Observatory (SDO). We find that a simple coherence / travel-time based approach detects and provides a wealth of information on transverse and longitudinal wave phenomena in the test sequences provided by the Transition Region and Coronal Explorer (TRACE). The results of the search are "pruned" (based on diagnostic errors) to minimize false-detections such that the remainder provides robust measurements of waves in the solar corona, with the calculated propagation speed allowing automated distinction between various wave modes. In this paper we discuss the technique, present results on the TRACE test sequences, and describe how our method can be used to automatically process the enormous flow of data (~1Tb/day) that will be provided by SDO/AIA after launch in late 2008.Comment: 34 pages, 16 figures - in press Solar Physic

Concomitant use of contraceptives and potentially teratogenic medicinal products--results from a study using pharmacy dispensing data in the Netherlands

Item does not contain fulltextThe objective of this study was to analyze to what extent potentially teratogenic medicinal products are dispensed concomitantly with contraceptives. Data on dispensed medicinal products in this population-based study were obtained from the Dutch Foundation for Pharmaceutical Statistics. For over 178 potentially teratogenic medicinal products, concomitant use of contraceptives was assessed. The proportion of potentially teratogenic medicinal products dispensed concomitantly with a contraceptive varied significantly from 40.9% (95% CI 40.7-41.2) in 2005 to 43.4% in 2009 (95% CI 44.2-43.7). Significant differences existed as well between age categories with the lowest proportions of concomitant use of contraceptives for any potentially teratogenic drug in women aged 36 through 45 years (35.0%, 95% CI 34.9-35.1) in comparison to those aged 26 through 35 years (47.1%, 95% CI 46.9-47.3) and 15 through 25 years (53.6%, 95% CI 53.4-53.8). Although our data retrieval did not cover the use of nonpharmacological forms of contraception such as condoms and sterilization and as situations may occur during which the use of drugs with (low) teratogenic potential is a balanced decision, our results raise doubts about the safe use of medicinal products with teratogenic potential

Effect of safety issues with HIV drugs on the approval process of other drugs in the same class: an analysis of European public assessment reports

Background: Knowledge on the safety of new medicines is limited at the time of market entry. Nearly half of all drugs used to treat HIV registered in the EU required >/=1 Direct Healthcare Professional Communication (DHPC) in the past 10 years for safety issues identified post-approval. Objective: The aim was to evaluate the extent to which regulators and industry have addressed the risk of safety issues for HIV drugs based on prior experience with other drugs in the same class and whether doing so impacts development time of these drugs. Methods: HIV drugs receiving >/=1 DHPC in the Netherlands between January 1999 and December 2008 were identified. Each drug with a DHPC ('index' drug) was paired with subsequently approved HIV drug(s) in the same class (Anatomical Therapeutic Chemical [ATC] 4th level) ['follow-on' drugs]. Characteristics of safety issues were extracted from the DHPCs of the 'index' drugs. European Public Assessment Reports (EPARs) were reviewed regarding whether the safety issues had been considered during development and approval. Consideration of previously identified safety issues in 'follow-on' drug applications was assessed regarding attention paid to adverse drug reaction (ADR) symptoms in pre-marketing studies, Summary of Product Characteristics (SmPC) and postmarketing commitments, and whether size of the safety population was in accordance with Regulatory guidelines. 'Index' drugs were also paired with drugs in the same class already on the market ('older' drugs). For 'older' drugs, we identified whether the safety issue led to appropriate changes in the current SmPC (January 2011) compared with the SmPC at the time of marketing authorization. Clinical development time was assessed using time from first patent application to market authorization as proxy, and comparison was made between 'index' and 'follow-on' drugs. Results: For 9 (43%) of the 21 centrally authorized HIV drugs, 11 serious safety issues that required a DHPC were identified. Two drugs were excluded from our analysis (DHPCs related to contamination/medication error). Six 'index' drugs were paired, each with one to six 'follow-on' drugs. Three concerned drug-drug interactions (DDIs); the other three were intracranial haemorrhage, neuromuscular weakness and severe skin/hepatic reactions. All but one 'follow-on' drug had information in the EPAR on that specific ADR (i.e. attention was paid to the ADR). The DDIs were addressed in pre-marketing studies and/or the SmPC. Two of the other ADRs were addressed by postmarketing surveillance commitments; intracranial haemorrhage was not addressed. Three safety issues for two 'index' drugs could not be paired with a 'follow-on' drug as no drug in the same class was approved after the corresponding DHPCs were issued. Five of the nine safety issues were added to at least one of the current SmPCs for the 'older' drugs already on the market at the time of DHPC issue. Two safety issues were already in the SmPC of the 'older' drugs at time of market approval and two were not introduced into the SmPC of 'older' drugs. Population size to assess short-term safety complied with the guidelines for four 'index', seven 'follow-on' and three 'older' drugs; population size to assess long-term safety complied for one, three and two drugs, respectively. For five drugs, EPARs did not provide adequate information on population size. No statistically significant difference in development time between 'index' and 'follow-on' drugs was found. Conclusion: Generally, safety issues were taken into account in the approval process of other drugs in the class. The approaches were different and determined by the nature of the ADR. Taking safety issues into account in the approval process did not seem to impact on the time taken to perform the pre-approval clinical programme

Healthcare professionals' self-reported experiences and preferences related to direct healthcare professional communications: a survey conducted in the Netherlands

Background: In Europe, Direct Healthcare Professional Communications (DHPCs) are important tools to inform healthcare professionals of serious, new drug safety issues. However, this tool has not always been successful in effectively communicating the desired actions to healthcare professionals. Objective: The aim of this study was to explore healthcare providers' experiences and their preferences for improvement of risk communication, comparing views of general practitioners (GPs), internists, community pharmacists and hospital pharmacists. Methods: A questionnaire was developed and pilot tested to assess experiences and preferences of Dutch healthcare professionals with DHPCs. The questionnaire and two reminders were sent to a random sample of 3488 GPs, internists and community and hospital pharmacists in the Netherlands. Descriptive statistics were used to describe demographic characteristics of the respondents. Chi squares, ANOVAs and the Wilcoxon signed rank test were used, when appropriate, to compare healthcare professional groups. Results: The overall response rate was 34% (N = 1141, ranging from 24% for internists to 46% for community pharmacists). Healthcare providers trusted safety information more when provided by the Dutch Medicines Evaluation Board (MEB) than by the pharmaceutical industry. This was more the case for GPs than for the other healthcare professionals. Respondents preferred safety information to be issued by the MEB, the Dutch Pharmacovigilance Center or their own professional associations. The preferred alternative channels of drug safety information were e-mail, medical journals and electronic prescribing systems. Conclusions: Safety information of drugs does not always reach healthcare professionals through DHPCs. To improve current risk communication of drug safety issues, alternative and/or additional methods of risk communication should be developed using electronic methods and medical journals. Moreover, (additional) risk communication coming from an independent source such as the MEB should be considered. Special effort is needed to reach GPs

Compliance with pregnancy prevention programmes of isotretinoin in Europe: a systematic review

P>Most of the publications on isotretinoin, pregnancy and compliance with the pregnancy prevention programme (PPP) originate from North America. Information specific for the European situation is very limited. The aim of this study was to identify publications describing the use of isotretinoin in humans and the compliance with the PPP in Europe, a systematic search in Medline and Embase was conducted using the terms 'isotretinoin, pregnancy (and Europe)'. Furthermore, a manual search in publications was performed. A total of 17 publications were identified. Publications consisted of case reports of exposed pregnancies, surveys among dermatologists or pharmacists and database studies evaluating compliance with the PPP. The studies and surveys dealt with groups of patients exposed to isotretinoin before or during pregnancy and/or compliance with the isotretinoin PPP. Where the information was provided, in 6-26% of cases isotretinoin was prescribed in full accordance with the PPP. Pregnancy incidence was seen in 0 center dot 2-1 center dot 0 per 1000 women of childbearing age using isotretinoin. Between 65% and 87% of these pregnancies were terminated. This review of studies in Europe performed to date shows failures in the implementation of the PPP. Therefore, the isotretinoin PPP must be scrutinized to identify whether new measures should be taken or whether the failures in the implementation need to be corrected. New measures should take into account the definition of the ultimate goal of a PPP and the acceptable burden. In the meantime, stakeholders could make a start with adjustments in the implementation of the PPP by taking responsibility and enhancing the performance by explicit instructions, monitoring the performance and adjusting, if necessary