The activity of French Research Ethics Committees and characteristics of biomedical research protocols involving humans: a retrospective cohort study

BACKGROUND: Clinical trials throughout the world must be evaluated by research ethics committees. No one has yet attempted to clearly quantify at the national level the activity of ethics committees and describe the characteristics of the protocols submitted. The objectives of this study were to describe 1) the workload and the activity of Research Ethics Committees in France, and 2) the characteristics of protocols approved on a nation-wide basis. METHODS: Retrospective cohort of 976 protocols approved by a representative sample of 25/48 of French Research Ethics Committees in 1994. Protocols characteristics (design, study size, investigator), number of revisions requested by the ethics committee before approval, time to approval and number of amendments after approval were collected for each protocol by trained research assistant using the committee's files and archives. RESULTS: Thirty-one percent of protocols were approved with no modifications requested in 16 days (95% CI: 14–17). The number of revisions requested by the committee, and amendments submitted by the investigator was on average respectively 39 (95% CI: 25–53) and 37 (95% CI: 27–46), per committee and per year. When revisions were requested, the main reasons were related to information to the patient (28%) and consent modalities (18%). Drugs were the object of research in 68% of the protocols examined. The majority of the research was national (80%) with a predominance of single-centre studies. Workload per protocol has been estimated at twelve and half hours on average for administrative support and at eleven and half hours for expertise. CONCLUSION: The estimated workload justifies specific and independent administrative and financial support for Research Ethics Committees

A Study of Wall-Crossing: Flavored Kinks in D=2 QED

We study spectrum of D=2 N=(2,2) QED with N+1 massive charged chiral multiplets, with care given to precise supermultiplet countings. In the infrared the theory flows to CP^N model with twisted masses, where we construct generic flavored kink solitons for the large mass regime, and study their quantum degeneracies. These kinks are qualitatively different and far more numerous than those of small mass regime, with features reminiscent of multi-pronged (p,q) string web, complete with the wall-crossing behavior. It has been also conjectured that spectrum of this theory is equivalent to the hypermultiplet spectrum of a certain D=4 Seiberg-Witten theory. We find that the correspondence actually extends beyond hypermultiplets in D=4, and that many of the relevant indices match. However, a D=2 BPS state is typically mapped to several different kind of dyons whose individual supermultiplets are rather complicated; the match of index comes about only after summing over indices of these different dyons. We note general wall-crossing behavior of flavored BPS kink states, and compare it to those of D=4 dyons.Comment: 47 pages, 5 figures; typos fixed; references adde

Fractional quantum Hall effect in a quantum point contact at filling fraction 5/2

Recent theories suggest that the excitations of certain quantum Hall states may have exotic braiding statistics which could be used to build topological quantum gates. This has prompted an experimental push to study such states using confined geometries where the statistics can be tested. We study the transport properties of quantum point contacts (QPCs) fabricated on a GaAs/AlGaAs two dimensional electron gas that exhibits well-developed fractional quantum Hall effect, including at bulk filling fraction 5/2. We find that a plateau at effective QPC filling factor 5/2 is identifiable in point contacts with lithographic widths of 1.2 microns and 0.8 microns, but not 0.5 microns. We study the temperature and dc-current-bias dependence of the 5/2 plateau in the QPC, as well as neighboring fractional and integer plateaus in the QPC while keeping the bulk at filling factor 3. Transport near QPC filling factor 5/2 is consistent with a picture of chiral Luttinger liquid edge-states with inter-edge tunneling, suggesting that an incompressible state at 5/2 forms in this confined geometry

The body in the library: adventures in realism

This essay looks at two aspects of the virtual ‘material world’ of realist fiction: objects encountered by the protagonist and the latter’s body. Taking from Sartre two angles on the realist pact by which readers agree to lend their bodies, feelings, and experiences to the otherwise ‘languishing signs’ of the text, it goes on to examine two sets of first-person fictions published between 1902 and 1956 — first, four modernist texts in which banal objects defy and then gratify the protagonist, who ends up ready and almost able to write; and, second, three novels in which the body of the protagonist is indeterminate in its sex, gender, or sexuality. In each of these cases, how do we as readers make texts work for us as ‘an adventure of the body’

Impact of funding on biomedical research: a retrospective cohort study

BACKGROUND: Public funding is aimed at facilitating the initiation, completion and publication of research study protocols. However, no evaluation is made to investigate the impact of grant success on the conduct of biomedical research. It is therefore of great interest to compare the fate of funded protocols versus not funded: Are they initiated? Are they completed? Did the results confirm the hypothesis? Were they published? The objective was to investigate the fate of protocols submitted for funding, whether they were funded or not. METHODS: Retrospective cohort study of protocols submitted for funding to the Greater Lyon regional scientific committee in 1997. Initial characteristics of protocols (design, study size, investigator status) were abstracted from archives, and follow-up characteristics (initiation, completion and publication) from a mailed questionnaire to the principal investigators. RESULTS: Among the 142 submitted protocols, follow-up information was available for 114 (80%). As a whole, 38% of studies were funded by the Greater Lyon research committee. The rate of initiation varied from 62% for studies with no acknowledged funding to 100% for studies with both committee and other simultaneous funding. When initiated, the rate of completion was 62% for studies with at least one funding and 40% for studies without acknowledged funding. When completed, publication was reached for 77% of studies with either committee or external funding, for 58% of studies without acknowledged funding and for 37% of studies with both committee and external funding. CONCLUSION: Some protocols submitted for funding were initiated and completed without any funding declared. To our understanding this mean that not all protocols submitted really needed funding and also that health care facilities are unaware that they implicitly financially support and pay for biomedical research

Three-dimensional cephalometric evaluation of maxillary growth following in utero repair of cleft lip and alveolar-like defects in the mid-gestational sheep model

Objective: To evaluate maxillary growth following in utero repair of surgically created cleft lip and alveolar (CLA)-like defects by means of three-dimensional (3D) computer tomographic (CT) cephalometric analysis in the mid-gestational sheep model. Methods: In 12 sheep fetuses a unilateral CLA-like defect was created in utero (untreated control group: 4 fetuses). Four different bone grafts were used for the alveolar defect closure. After euthanasia, CT scans of the skulls of the fetuses, 3D re-constructions, and a 3D-CT cephalometric analysis were performed. Results: The comparisons between the operated and nonoperated skull sides as well as of the maxillary asymmetry among the experimental groups revealed no statistically significant differences of the 12 variables used. Conclusions: None of the surgical approaches used for the in utero correction of CLA-like defects seem to affect significantly postsurgical maxillary growth; however, when bone graft healing takes place, a tendency for almost normal maxillary growth can be observed. Copyright (c) 2006 S. Karger AG, Basel

Novel Branches of (0,2) Theories

We show that recently proposed linear sigma models with torsion can be obtained from unconventional branches of conventional gauge theories. This observation puts models with log interactions on firm footing. If non-anomalous multiplets are integrated out, the resulting low-energy theory involves log interactions of neutral fields. For these cases, we find a sigma model geometry which is both non-toric and includes brane sources. These are heterotic sigma models with branes. Surprisingly, there are massive models with compact complex non-Kahler target spaces, which include brane/anti-brane sources. The simplest conformal models describe wrapped heterotic NS5-branes. We present examples of both types.Comment: 36 pages, LaTeX, 2 figures; typo in Appendix fixed; references added and additional minor change

Local modulation of the Wnt/β‐catenin and bone morphogenic protein (BMP) pathways recapitulates rib defects analogous to cerebro‐costo‐mandibular syndrome

Ribs are seldom affected by developmental disorders, however, multiple defects in rib structure are observed in the spliceosomal disease cerebro‐costo‐mandibular syndrome (CCMS). These defects include rib gaps, found in the posterior part of the costal shaft in multiple ribs, as well as missing ribs, shortened ribs and abnormal costotransverse articulations, which result in inadequate ventilation at birth and high perinatal mortality. The genetic mechanism of CCMS is a loss‐of‐function mutation in SNRPB, a component of the major spliceosome, and knockdown of this gene in vitro affects the activity of the Wnt/β‐catenin and bone morphogenic protein (BMP) pathways. The aim of the present study was to investigate whether altering these pathways in vivo can recapitulate rib gaps and other rib abnormalities in the model animal. Chick embryos were implanted with beads soaked in Wnt/β‐catenin and BMP pathway modulators during somitogenesis, and incubated until the ribs were formed. Some embryos were harvested in the preceding days for analysis of the chondrogenic marker Sox9, to determine whether pathway modulation affected somite patterning or chondrogenesis. Wnt/β‐catenin inhibition manifested characteristic rib phenotypes seen in CCMS, including rib gaps (P < 0.05) and missing ribs (P < 0.05). BMP pathway activation did not cause rib gaps but yielded missing rib (P < 0.01) and shortened rib phenotypes (P < 0.05). A strong association with vertebral phenotypes was also noted with BMP4 (P < 0.001), including scoliosis (P < 0.05), a feature associated with CCMS. Reduced expression of Sox9 was detected with Wnt/β‐catenin inhibition, indicating that inhibition of chondrogenesis precipitated the rib defects in the presence of Wnt/β‐catenin inhibitors. BMP pathway activators also reduced Sox9 expression, indicating an interruption of somite patterning in the manifestation of rib defects with BMP4. The present study demonstrates that local inhibition of the Wnt/β‐catenin and activation of the BMP pathway can recapitulate rib defects, such as those observed in CCMS. The balance of Wnt/β‐catenin and BMP in the somite is vital for correct rib morphogenesis, and alteration of the activity of these two pathways in CCMS may perturb this balance during somite patterning, leading to the observed rib defects

BPS States, Refined Indices, and Quiver Invariants

For D=4 BPS state construction, counting, and wall-crossing thereof, quiver quantum mechanics offers two alternative approaches, the Coulomb phase and the Higgs phase, which sometimes produce inequivalent counting. The authors have proposed, in arXiv:1205.6511, two conjectures on the precise relationship between the two, with some supporting evidences. Higgs phase ground states are naturally divided into the Intrinsic Higgs sector, which is insensitive to wall-crossings and thus an invariant of quiver, plus a pulled-back ambient cohomology, conjectured to be an one-to-one image of Coulomb phase ground states. In this note, we show that these conjectures hold for all cyclic quivers with Abelian nodes, and further explore angular momentum and R-charge content of individual states. Along the way, we clarify how the protected spin character of BPS states should be computed in the Higgs phase, and further determine the entire Hodge structure of the Higgs phase cohomology. This shows that, while the Coulomb phase states are classified by angular momentum, the Intrinsic Higgs states are classified by R-symmetry.Comment: 51 pages, 5 figure