Orphan drug incentives in the pharmacogenomic context: policy responses in the US and Canada

Advances in pharmacogenomic research and increasing industry interest in personalized medicine have important implications for the way that orphan drug policies are interpreted and applied. Concerns have been raised about the potential impact of pharmacogenomics and new genomic technologies on our understanding of how disease categories are delineated, and subsequently, how the concept of rare disease should be defined for the purposes of orphan drug policies. This article considers whether orphan drug legislation can be drafted in a way that will maximize benefits and minimize concerns relating to the impact of pharmacogenomics on orphan drug research and development. After reviewing the issues that may arise at the intersection of orphan drug policies and pharmacogenomics, this article will discuss the potential impact of pharmacogenomics at two critical points: orphan designation and approval of the drug product. At each of these points, the relevant aspects of current US orphan drug legislation are examined, focusing on the extent to which recent amendments may address concerns that have been raised previously. This analysis will then provide the foundation for a critical review and recommendations regarding the proposed new Canadian orphan drug framework.     

Variability in Citizens’ Reactions to Different Types of Negative Campaigns

Do negative advertisements lower voters’ evaluations of the targeted candidate? We theorize that there is much to be gained by examining the variance in the content and tone of negative campaign messages and the variance in voters’ sensitivity to negative political rhetoric. We employ data from the 2006 Cooperative Congressional Election Study to investigate the impact of negative campaigning in U.S. Senate campaigns. We sampled 1,045 respondents in 21 of the 28 U.S. Senate races featuring a majority party incumbent and challenger. In addition to the survey data, we collected contextual data regarding the political advertisements aired during the campaigns and the news coverage of these campaigns in state newspapers. The evidence suggests that the impact of negative information is multifaceted, and under some circumstances, substantial. We find that uncivil and relevant negative messages are the most powerful, especially for people with less tolerance for negative political rhetoric.     

The Influence of Religiosity and Spirituality on Adolescent Mothers and Their Teenage Children

This project assessed the influence of religiosity and spirituality on the socioemotional and behavioral adjustment of 110 adolescent mothers and their teenage offspring at age 14. Maternal religiosity, measured prenatally and when children were 3, 5, and 8 years of age, was defined as involvement in church as well as contact with and dependence on church officials and members. Levels of spirituality, defined as religious practices and beliefs, were assessed for both mothers and their children at 14 years postpartum. Hierarchical regression analyses suggested that maternal religiosity was a strong predictor of maternal and child adjustment; children’s own spirituality served as a predictor of their socioemotional adjustment as well. Furthermore, child spirituality mediated the relationship between maternal religiosity and children’s externalizing behavior. Implications for designing intervention programs with high risk families are discussed.     

From Victim to Offender: The Effects of Male Initiated Violence on Women Arrested for Using Intimate Partner Violence

A number of theorists posit that most women who are arrested for using violence against their intimate partners are in-fact victims of IPV themselves and should be treated as such. However, in this population of women IPV arrestees empirical investigation has yet to explore how physical and emotional victimization experiences are associated with arrest related factors, propensity to be abusive or attitude toward using relationship violence. The current study explores these factors finding no difference in arrest factors between women who (a) deny abuse, (b) report rare/occasional abuse and (c) report frequent/very frequent abuse. However, mixed results were found with regard to participants’ responses on scales measuring propensity to be abusive and attitudes about using violence in marriage. Theoretical and practical related issues are addressed.     

Newborn screening in the genomics era

Newborn screening (NBS) exists in every state for the purpose of testing newborns for genetic medical conditions that can be severe, may be treatable, and are often not clinically evident at birth. While almost all of the diseases screened for in newborns have underlying genetic causes, NBS in its current form is performed not by testing for genetic mutations, but by testing for biochemical markers that indicate a disorder. The potential use of whole-genome newborn screening (WG-NBS) as an alternative to the current biochemical testing utilized for NBS would dramatically expand the quantity and types of information parents could learn from screening and is likely to have many implications, both positive and negative. As whole-genome sequencing (WGS) becomes more economical, it probably will be used for the purposes of NBS. However, such an expansion of NBS would contradict many of the principles that have historically guided public health screening programs and, if implemented without sufficient preparation, could result in insufficient infrastructure to accommodate the health care and data management needs that would arise. This article will first look at the past and present of NBS, then the rise of whole genome sequencing, before considering the challenges of WG-NBS, and will end with some thoughts on the path forward.     

Labor Rights for All? The Role of Undocumented Immigrant Status for Worker Claims Making

Drawing on forty-one interviews with both documented and undocumented Latino restaurant workers in San Jose, California, and Houston, Texas, this article examines how documentation status shapes the legal consciousness of immigrant workers. I identify three common narratives that undocumented workers provide to justify not making claims on workplace protection. First, I highlight that an ever-present fear of deportation inhibits any formal confrontation. Second, I demonstrate how undocumented status leaves undocumented immigrants with a particularly pragmatic and short-term understanding of their working life in the United States, rendering their working conditions temporary and endurable to them. Third, I expand Gordon and Lenhardt's (2008 ) discussion of the centrality of work to the American conception of citizenship. I reiterate that this particular sense of belonging is situated vis-à-vis other low-wage workers. These findings provide sociolegal scholars important theoretical contributions for crafting a research agenda on the role of undocumented status and legal mobilization.     

Domestic violence: a complex health care issue for dentistry today

As a natural outgrowth of the dental professional's role in recognizing and reporting child abuse the topic has been broadened in recent years to domestic violence, that is child, spouse/intimate partner, disabled and elder abuse. Forty years ago in the US there were 662 cases of child abuse reported to authorities. Today that reported number is in excess of 3 million per year [D. Wiese, D. Daro, Current trends in reporting and fatalities; the results of the 1994 annual 50 state survey, National Committee to Prevent Child Abuse, Working Paper 808, 1995]. The "dirty secret" of spousal/intimate partner violence is believed to affect 3-4 million individuals per year in the US. Studies have also found that between 50 and 70% of these perpetrators also abuse their children or those of their intimate partner [J. Kessman, Domestic violence, identifying the deadly silence, Texas Dent. J. (2000) 43]. Just as child abuse is most often manifested in the head or neck regions, likewise the evidence of physical violence to intimate partners and the elderly can be seen in the head or neck regions. The insidious part of partner and elder abuse is that often the largest component of these behaviors is psychological, emotional and indirect neglect, which leave no physical evidence [M. Bowers, Forensic Dental Evidence: An Investigator's Handbook, Elesevier, San Diego, CA, 2004, p. 119].     

The application of an automated allele concordance analysis system (CompareCalls) to ensure the accuracy of single-source STR DNA profiles

A powerful method for validating a scientific result is to confirm specific results utilizing independent methodologies and processing pathways. Thus, we have designed, developed and validated an automated allele concordance analysis system (CompareCalls, patent pending) that performs comparisons between two independent DNA analysis platforms to ensure the highest accuracy for allele calls. Application of this system in a quality assurance role has shown the potential to eliminate greater than 90% of the STR analysis required of a DNA data analyst. While this system is broadly applicable for use with any two independent STR analysis programs, either prior to or following human data review, we are presenting its application to data generated with the ABI Prism Genotyper software system versus data generated with the SurelockID system. With the automated allele concordance analysis system, the GeneScan DNA fragment data generated from an ABI 377 gel image are analyzed in two independent pathways. In one analysis pathway, the GeneScan data are imported into Genotyper software where STR labels are assigned to the fragment data based upon the criteria of the Kazam 20% macro. The "Kazam" macro provided with the Genotyper program works by labeling all peaks in a category (or locus) and then filtering (or removing) the labels from peaks, such as those in stutter positions, that meet predefined criteria. In the second pathway, the GeneScan data are imported into the SurelockID analysis platform where STR labels and error messages are assigned to the fragment data based upon hard-coded allele calling criteria and quality parameters. The resulting STR allele calls for each analysis platform are then compared, utilizing the automated allele concordance analysis system. Any differences in the STR allele calls between the two systems are flagged in a discordance report for further review by a qualified DNA data analyst. The automated allele concordance analysis system guides the DNA data analyst to the discordant data generated by either analysis platform. Additionally, the analyst is also directed to data that are of less than pristine quality which may have an increased potential for errors in interpretation by either analysis platform or by a human DNA data analyst. Implementation of an automated allele concordance analysis system will yield high-quality data for CODIS and free the human DNA data analyst to perform other critical duties within the laboratory.     

Characteristics of individuals petitioned for civil commitment

This article explores the demographic and criminal characteristics of a group of sex offenders currently residing in a facility for civilly committed sex offenders. Legal and clinical records were used and data coded. This sample is compared to published data on a group of civilly committed sex offenders in another state. Results indicated that there were numerous similarities and some differences between the two groups. Further research needs to be conducted on civilly committed sex offenders in other states to better understand this population.