De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits:report of 25 new individuals and review of the literature

TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands

Transforming Epidemiology for 21st Century Medicine and Public Health

In 2012, the National Cancer Institute (NCI) engaged the scientific community to provide a vision for cancer epidemiology in the 21st century. Eight overarching thematic recommendations, with proposed corresponding actions for consideration by funding agencies, professional societies, and the research community emerged from the collective intellectual discourse. The themes are (i) extending the reach of epidemiology beyond discovery and etiologic research to include multilevel analysis, intervention evaluation, implementation, and outcomes research; (ii) transforming the practice of epidemiology by moving towards more access and sharing of protocols, data, metadata, and specimens to foster collaboration, to ensure reproducibility and replication, and accelerate translation; (iii) expanding cohort studies to collect exposure, clinical and other information across the life course and examining multiple health-related endpoints; (iv) developing and validating reliable methods and technologies to quantify exposures and outcomes on a massive scale, and to assess concomitantly the role of multiple factors in complex diseases; (v) integrating “big data” science into the practice of epidemiology; (vi) expanding knowledge integration to drive research, policy and practice; (vii) transforming training of 21st century epidemiologists to address interdisciplinary and translational research; and (viii) optimizing the use of resources and infrastructure for epidemiologic studies. These recommendations can transform cancer epidemiology and the field of epidemiology in general, by enhancing transparency, interdisciplinary collaboration, and strategic applications of new technologies. They should lay a strong scientific foundation for accelerated translation of scientific discoveries into individual and population health benefits

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Pepper spray injury severity: ten-year case experience of a poison control system.

BackgroundPepper spray is a common lacrimator used by law enforcement and the public to subdue individuals and for self-defense. The risk factors for severe injury due to pepper spray exposure are not well documented and there is a lack of guidelines to identify patients that require transport and medical evaluation in an emergency department.ObjectiveThe aim of this study was to determine the prevalence of and circumstances associated with symptoms suggestive of tissue injury beyond transient irritation in persons exposed to pepper spray.MethodsWe reviewed all human exposures to pepper spray reported to a poison control system between 2002 and 2011. Cases were differentiated into 2 outcome groups: minor or self-limiting symptoms versus those with more severe symptoms suggestive of tissue injury that warranted a medical evaluation. A comparison of the variables between the outcome groups was performed using odds ratios (ORs), 95% confidence intervals (CIs), and associated P values.ResultsA total of 4,544 cases were identified and 3,671 met the inclusion criteria. Of these, 249 cases (6.8%) were found to have more severe symptoms that warranted a medical evaluation. There were no reported deaths. The cases with more severe symptoms most commonly involved the ocular (53.8%), respiratory (31.7%), and dermal (17.7%) organ systems. Factors with largest independent associations with more severe outcomes were use for law enforcement training (OR, 7.39; 95% CI, 2.98-18.28), direct intentional exposure for purposeful use to incapacitate (OR, 3.02; 95% CI, 1.80-5.06), and for law enforcement on individual target suspects or crowd control (OR, 2.45; 95% CI, 1.42-4.23).ConclusionsThere was a low 1 in 15 potential risk for more severe adverse health effects in persons exposed to pepper spray that warranted a medical evaluation. The risk was highest when used for training of law enforcement personnel and involved severe ocular symptoms. This suggests that routine use of pepper spray for training of law enforcement or military personnel be reconsidered. Protective goggles may be an option when direct spraying into the face of trainees. Transport for medical evaluation should be considered for exposed persons that manifest persistent ocular or respiratory symptoms

Cancer screening: the journey from epidemiology to policy.

PurposeCancer screening procedures have brought great benefit to the public's health. However, the science of cancer screening and the evidence arising from research in this field as it is applied to policy is complex and has been difficult to communicate, especially on the national stage. We explore how epidemiologists have contributed to this evidence base and to its translation into policy.MethodsOur essay focuses on breast and lung cancer screening to identify commonalities of experience by epidemiologists across two different cancer sites and describe how epidemiologists interact with evolving scientific and policy environments.ResultsWe describe the roles and challenges that epidemiologists encounter according to the maturity of the data, stakeholders, and the related political context. We also explore the unique position of cancer screening as influenced by the legislative landscape where, due to recent healthcare reform, cancer screening research plays directly into national policy.ConclusionsIn the complex landscape for cancer screening policy, epidemiologists can increase their impact by learning from past experiences, being well prepared and communicating effectively

Cancer screening: the journey from epidemiology to policy.

PurposeCancer screening procedures have brought great benefit to the public's health. However, the science of cancer screening and the evidence arising from research in this field as it is applied to policy is complex and has been difficult to communicate, especially on the national stage. We explore how epidemiologists have contributed to this evidence base and to its translation into policy.MethodsOur essay focuses on breast and lung cancer screening to identify commonalities of experience by epidemiologists across two different cancer sites and describe how epidemiologists interact with evolving scientific and policy environments.ResultsWe describe the roles and challenges that epidemiologists encounter according to the maturity of the data, stakeholders, and the related political context. We also explore the unique position of cancer screening as influenced by the legislative landscape where, due to recent healthcare reform, cancer screening research plays directly into national policy.ConclusionsIn the complex landscape for cancer screening policy, epidemiologists can increase their impact by learning from past experiences, being well prepared and communicating effectively

Provider perceptions and expectations of breast cancer posttreatment care: a University of California Athena Breast Health Network project.

PurposeThe Athena Breast Health Network collaboration is a University of California system-wide project initiated with the intent to drive innovation in breast cancer prevention, screening, and treatment. This qualitative research examines provider perceptions and expectations of posttreatment breast cancer care across five network sites with the goal of better understanding provider behavior during the posttreatment phase of the cancer care trajectory.MethodsInvestigators at each site conducted semi-structured interviews with oncology specialists and primary care providers (PCPs). Interviews used case study examples and open- and closed-ended questions on the delivery of posttreatment breast cancer care. Informant responses were manually recorded by the interviewer, compiled in a database, then coded and analyzed using NVivo 9 software.ResultsThere were 39 key informants across the sites: 14 medical oncologists, 7 radiation oncologists, 11 surgeons, 3 oncology nurses, and 4 PCPs. Care coordination was a major unprompted theme identified in the interviews. There was a perceived need for greater care coordination across institutions in order to improve delivery of posttreatment health care services and a need for greater care coordination within oncology, particularly to help avoid duplication of follow-up care and services. Participants expect frequent follow-up visits and to use biomarker tests and advanced imaging services as part of routine surveillance care. Implementing survivorship care programs was perceived as a way to improve care delivery.ConclusionsThese results identify a need for increased focus on care coordination during the posttreatment phase of breast cancer care within the University of California system and the potential for system and provider-level interventions that could help increase coordination of posttreatment care.Implications for cancer survivorsBreast cancer survivors do not always receive evidence-based care. This research helps to better understand what motivates provider behavior during the posttreatment phase and lays a foundation for targeted interventions to increase adherence to evidence-based recommendations

Quality of Posttreatment Care Among Breast Cancer Survivors in the University of California Athena Breast Health Network (Athena).

IntroductionMultiple oncology providers are involved in the initial breast cancer treatment. To better understand the patterns and quality of posttreatment breast cancer care, we surveyed patients who had been treated at each of the 5 University of California (UC) cancer centers.Patients and methodsWe identified breast cancer patients diagnosed in 2008-2009 from hospital tumor registries; invitations for the mailed survey on posttreatment care were sent between September 2011 and November 2012. The survey requested information on the number and type of provider visits, discussion of key topics, use of treatment summaries, and survivorship care plans (SCP).ResultsA total of 329 patients completed the survey. The mean age of respondents was 60.5 years, and they were 3.2 years since diagnosis (range, 1.6-4.8 years). A total of 82% had continued posttreatment care at a UC facility, and they reported high numbers of clinical follow-up visits, with an average of > 2 providers (range, 1-5). Surgery-only patients reported an average of 4 to 5 office visits a year; patients who received surgery, radiation, and chemotherapy reported 5 to 6 office visits a year. Overall, 45% of women reported receiving a treatment summary; receipt of a SCP was reported by 59%, occurring significantly more often among those in follow-up at a UC (P = .004).ConclusionPatients reported visits to multiple providers during their follow-up care, in excess of what is recommended by current guidelines. This was in spite of many women reporting that they had received a SCP