Genomic information and a person's right not to know: A closer look at variations in hypothetical informational preferences in a German sample

In clinical practice and in research, there is an ongoing debate on how to return incidental and secondary findings of genetic tests to patients and research participants. Previous investigations have found that most of the people most of the time are in favor of full disclosure of results. Yet, the option to reject disclosure, based on the so-called right not to know, can be valuable especially for some vulnerable subgroups of recipients. In the present study we investigated variations in informational preferences in the context of genetic testing in a large and diverse German sample. This survey examined health care professionals, patients, participants of genetic counseling sessions and members of the general population (N = 518). Survey participants were assessed regarding their openness to learning about findings under various hypothetical scenarios, as well as their attitudes about the doctor-patient-relationship in a disclosure situation and about informational transfer to third parties. While the majority of participants wanted to learn about their findings, the extent of support of disclosure varied with features of the hypothetical diagnostic scenarios (e.g., controllability of disease;abstract vs. concrete scenario description) and demographic characteristics of the subjects. For example, subjects with higher levels of education were more selective with regards to the kind of information they want to receive than those with lower levels of education. We discuss implications of these findings for the debate about the right not to know and for the clinical practice of informed consent procedures

Intracerebral Human Regulatory T Cells: Analysis of CD4+CD25+FOXP3+ T Cells in Brain Lesions and Cerebrospinal Fluid of Multiple Sclerosis Patients

Impaired suppressive capacity of CD4+CD25+FOXP3+ regulatory T cells (Treg) from peripheral blood of patients with multiple sclerosis (MS) has been reported by multiple laboratories. It is, however, currently unresolved whether Treg dysfunction in MS patients is limited to reduced control of peripheral T cell activation since most studies analyzed peripheral blood samples only. Here, we assessed early active MS lesions in brain biopsies obtained from 16 patients with MS by FOXP3 immunohistochemistry. In addition, we used six-color flow cytometry to determine numbers of Treg by analysis of FOXP3/CD127 expression in peripheral blood and cerebrospinal fluid (CSF) of 17 treatment-naïve MS patients as well as quantities of apoptosis sensitive CD45ROhiCD95hi cells in circulating and CSF Treg subsets. Absolute numbers of FOXP3+ and CD4+ cells were rather low in MS brain lesions and Treg were not detectable in 30% of MS biopsies despite the presence of CD4+ cell infiltrates. In contrast, Treg were detectable in all CSF samples and Treg with a CD45ROhiCD95hi phenotype previously shown to be highly apoptosis sensitive were found to be enriched in the CSF compared to peripheral blood of MS patients. We suggest a hypothetical model of intracerebral elimination of Treg by CD95L-mediated apoptosis within the MS lesion

Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: Impact of alcohol deterrents on outcome

Objective: (1) To perform a 9-year study of abstinence, lapse, and relapse in 180 chronic alcoholic patients, participants of the Outpatient Longterm Intensive Therapy for Alcoholics (OLITA); (2) To investigate the role of supervised alcohol deterrents (AD) in relapse prevention and as an adjunct for maintenance of long-term abstinence. Method: This prospective open treatment study evaluates the long-term course of drinking outcomes and AD use of 180 chronic alcoholics consecutively admitted from 1993 to 2002. Subsamples are compared for (1) sham-AD versus verum-AD (disulfiram/calcium carbimide), (2) coped lapses versus finally detrimental lapses versus malignant relapses, and (3) AD use for 13 to 20 versus > 20 months. Results: In this 9-year study, the cumulative probability of not having relapsed was 0.52, and that of not having consumed any alcohol was 0.26. Despite long-term use, disulfiram/calcium carbimide was well tolerated. Patients on sham-AD (due to contraindications to verum-AD) showed higher cumulative abstinence probability than patients on verum (S = 0.86 vs. S = 0.49, p = 0.03). Detrimental lapses and malignant relapses occurred earlier than successfully coped lapses (p < 0.001); patients with detrimental lapse and with malignant relapse had rewer days of AD intake and less subsequent days without AD than patients with coped lapse (p < 0.001). The cumulative abstinence probability was S = 0.75 for patients with long-term intake compared with S = 0.50 for patients who stopped AD between months 13 and 20 (p < 0.001). Conclusions: An abstinence rate of > 50% in this 9-year study strongly supports the concept of comprehensive, long-term outpatient treatment of alcoholics. Supervised, guided intake of AD, also over extended periods, can be used as a predominantly psychologically acting ingredient of successful alcoholism therapy

Correcting dynamic distortions in 7T echo planar imaging using a jittered echo time sequence

Purpose: To develop a distortion correction method for echo planar imaging (EPI) that is able to measure dynamic changes in B. Theory and Methods: The approach we propose is based on single-echo EPI with a jittering of the echo time between two values for alternate time points. Field maps are calculated between phase images from adjacent volumes and are used to remove distortion from corresponding magnitude images. The performance of our approach was optimized using an analytical model and by comparison with field maps from dual-echo EPI. The method was tested in functional MRI experiments at 7T with motor tasks and compared with the conventional static approach. Results: Unwarping using our method was accurate even for head rotations up to 8.2°, where the static approach introduced errors up to 8.2 mm. Jittering the echo time between 19 and 25 ms had no measurable effect on blood oxygenation level–dependent (BOLD) sensitivity. Our approach reduced the distortions in activated regions t

Specifi c Attentional Dysfunction in Adults Following Early Start of Cannabis Use

Abstract. Rationale and objective: The present study tested the hypothesis that chronic interference by cannabis with endogenous cannabinoid systems during peripubertal development causes specifi c and persistent brain alterations in humans. As an index of cannabinoid action, visual scanning, along with other attentional functions, was chosen. Visual scanning undergoes a major maturation process around age 12–15 years and, in addition, the visual system is known to react specifi cally and sensitively to cannabinoids. Methods: From 250 individuals consuming cannabis regularly, 99 healthy pure cannabis users were selected. They were free of any other past or present drug abuse, or history of neuropsychiatrie disease. After an interview, physical examination, analysis of routine laboratory parameters, plasma/urine analyses for drugs, and MMPI testing, users and respective controls were subjected to a computer-assisted attention test battery comprising visual scanning, alertness, divided attention, fl exibility, and working memory. Results: Of the potential predictors of test performance within the user group, including present age, age of onset of cannabis use, degree of acute intoxication (THC + THCOH plasma levels), and cumulative toxicity (estimated total life dose), an early age of onset turned out to be the only predictor, predicting impaired reaction times exclusively in visual scanning. Early-onset users (onset before age 16; n = 48) showed a signifi cant impairment in reaction times in this function, whereas late-onset users (onse