Longitudinal study of informed consent in innovative therapy research: experience and provisional recommendations from a multicenter trial of intracerebral grafting.

BACKGROUND: There is an urgent need to assess and improve the consent process in clinical trials of innovative therapies for neurodegenerative disorders. METHODS: We performed a longitudinal study of the consent of Huntington's disease patients during the Multicenter Fetal Cell Intracerebral Grafting Trial in Huntington's Disease (MIG-HD) in France and Belgium. Patients and their proxies completed a consent questionnaire at inclusion, before signing the consent form and after one year of follow-up, before randomization and transplantation. The questionnaire explored understanding of the protocol, satisfaction with the information delivered, reasons for participating in the trial and expectations regarding the transplant. Forty-six Huntington's disease patients and 27 proxies completed the questionnaire at inclusion, and 27 Huntington's disease patients and 16 proxies one year later. RESULTS: The comprehension score was high and similar for Huntington's disease patients and proxies at inclusion (72.6% vs 77.8%; P > 0.1) but only decreased in HD patients after one year. The information satisfaction score was high (73.5% vs 66.5%; P > 0.1) and correlated with understanding in both patients and proxies. The motivation and expectation profiles were similar in patients and proxies and remained unchanged after one year. CONCLUSIONS: Cognitively impaired patients with Huntington's disease were capable of consenting to participation in this trial. This consent procedure has presumably strengthened their understanding and should be proposed before signing the consent form in future gene or cell therapy trials for neurodegenerative disorders. Because of the potential cognitive decline, proxies should be designated as provisional surrogate decision-makers, even in competent patients

In, Against and Beyond Precarity: Work in Insecure Times

In this Foreword to the special issue ‘In, Against and Beyond Precarity’ the guest editors take stock of the existing literature on precarity, highlighting the strengths and limitations of using this concept as an analytical tool for examining the world of work. Concluding that the overstretched nature of concept has diluted its political effectiveness, the editors suggest instead a focus on precarization as a process, drawing from perspectives that focus on the objective conditions, as well as subjective and heterogeneous experiences and perceptions of insecure employment. Framed in this way, they present a summary of the contributions to the special issue spanning a range of countries and organizational contexts, identifying key drivers, patterns and forms of precarization. These are conceptualized as implicit, explicit, productive and citizenship precarization. These forms and patterns indicate the need to address precariousness in the realm of social reproduction and post-wage politics, while holding these in tension with conflicts at the point of production. Finally, the guest editors argue for a dramatic re-think of current forms of state and non-state social protections as responses to the precarization of work and employment across countries in both the Global ‘North’ and ‘South’

Revisiting the university front

dc.subject: Postdemocracy / Public function of the university / Governance / Knowledge society / research university / Managerialism / Academic audit / Quality contro

The meta-crisis of secular capitalism

The current global economic crisis concerns the way in which contemporary capitalism has turned to financialisation as a double cure for both a falling rate of profit and a deficiency of demand. Although this turning is by no means unprecedented, policies of financialisation have depressed demand (in part as a result of the long-term stagnation of average wages) while at the same time not proving adequate to restore profits and growth. This paper argues that the current crisis is less the ‘normal’ one that has to do with a constitutive need to balance growth of abstract wealth with demand for concrete commodities. Rather, it marks a meta-crisis of capitalism that is to do with the difficulties of sustaining abstract growth as such. This meta-crisis is the tendency at once to abstract from the real economy of productive activities and to reduce everything to its bare materiality. By contrast with a market economy that binds material value to symbolic meaning, a capitalist economy tends to separate matter from symbol and reduce materiality to calculable numbers representing ‘wealth’. Such a conception of wealth rests on the aggregation of abstract numbers that cuts out all the relational goods and the ‘commons’ on which shared prosperity depends

Dunno if you've any plans for the future: medical student indirect questioning in simulated oncology interviews

<p>Abstract</p> <p>Background</p> <p>This exploratory study investigated the motives of medical students (N = 63) for using indirect questions of the type <it>I don't know if </it>[you have already heard about chemotherapies], <it>I don't know how </it>[you are], or <it>I don't know what </it>[you do for a living] in simulated patient interviews during a communication skills course.</p> <p>Methods</p> <p><it>I don't know </it>questions (IDK-Qs) were observed during the initial evaluation of students' communication skills; they were systematically identified through video screening and subjected to a qualitative content and discourse analysis considering their context, their content, their intent and their effect on the simulated patients. To evaluate the specificity of medical students' IDK-Qs, the data were compared with a data set of oncologists (N = 31) conducting simulated patient interviews in the context of a Communication Skills Training (CST).</p> <p>Results</p> <p>During the interviews, 41.3% of the students asked 1-6 IDK-Qs. The IDK-Qs were attributed to three content categories: medical/treatment questions (N = 24); lifestyle/psychosocial questions (N = 18); and "inviting questions" questions (N = 11). Most of the IDK-Qs had an exploratory function (46/53), with simulated patients providing detailed responses or asking for more information (36/53). IDK-Qs were rare in the oncologist sample compared to the student sample (5 vs. 53 occurrences).</p> <p>Conclusions</p> <p>IDK-Qs showed a question design difference between medical students and oncologists in simulated patient interviews. Among other reasons for this difference, the possible function of IDK-Qs as a protective linguistic strategy and marker for psychological discomfort is discussed.</p

How to Capitalize on the Retest Effect in Future Trials on Huntington&#039;s Disease

The retest effect-improvement of performance on second exposure to a task-may impede the detection of cognitive decline in clinical trials for neurodegenerative diseases. We assessed the impact of the retest effect in Huntington\u27s disease trials, and investigated its possible neutralization. We enrolled 54 patients in the Multicentric Intracerebral Grafting in Huntington\u27s Disease (MIG-HD) trial and 39 in the placebo arm of the Riluzole trial in Huntington\u27s Disease (RIL-HD). All were assessed with the Unified Huntington\u27s Disease Rating Scale (UHDRS) plus additional cognitive tasks at baseline (A1), shortly after baseline (A2) and one year later (A3). We used paired t-tests to analyze the retest effect between A1 and A2. For each task of the MIG-HD study, we used a stepwise algorithm to design models predictive of patient performance at A3, which we applied to the RIL-HD trial for external validation. We observed a retest effect in most cognitive tasks. A decline in performance at one year was detected in 3 of the 15 cognitive tasks with A1 as the baseline, and 9 of the 15 cognitive tasks with A2 as the baseline. We also included the retest effect in performance modeling and showed that it facilitated performance prediction one year later for 14 of the 15 cognitive tasks. The retest effect may mask cognitive decline in patients with neurodegenerative diseases. The dual baseline can improve clinical trial design, and better prediction should homogenize patient groups, resulting in smaller numbers of participants being required

Recurrent, low-frequency coding variants contributing to colorectal cancer in the Swedish population

<div><p>Genome-wide association studies (GWAS) have identified dozens of common genetic variants associated with risk of colorectal cancer (CRC). However, the majority of CRC heritability remains unclear. In order to discover low-frequency, high-risk CRC susceptibility variants in Swedish population, we genotyped 1 515 CRC patients enriched for familial cases, and 12 108 controls. Case/control association analysis suggested eight novel variants associated with CRC risk (OR 2.0–17.6, p-value < 2.0E-07), comprised of seven coding variants in genes <i>RAB11FIP5</i>, <i>POTEA</i>, <i>COL27A1</i>, <i>MUC5B</i>, <i>PSMA8</i>, <i>MYH7B</i>, and <i>PABPC1L</i> as well as one variant downstream of <i>NEU1</i> gene. We also confirmed 27 out of 30 risk variants previously reported from GWAS in CRC with a mixed European population background. This study identified rare, coding sequence variants associated with CRC risk through analysis in a relatively homogeneous population. The segregation data suggest a complex mode of inheritance in seemingly dominant pedigrees.</p></div

Russia’s Legal Transitions: Marxist Theory, Neoclassical Economics and the Rule of Law

We review the role of economic theory in shaping the process of legal change in Russia during the two transitions it experienced during the course of the twentieth century: the transition to a socialist economy organised along the lines of state ownership of the means of production in the 1920s, and the transition to a market economy which occurred after the fall of the Soviet Union in the 1990s. Despite differences in methodology and in policy implications, Marxist theory, dominant in the 1920s, and neoclassical economics, dominant in the 1990s, offered a similarly reductive account of law as subservient to wider economic forces. In both cases, the subordinate place accorded to law undermined the transition process. Although path dependence and history are frequently invoked to explain the limited development of the rule of law in Russia during the 1990s, policy choices driven by a deterministic conception of law and economics also played a role.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s40803-015-0012-