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"Bouchard, Denis"
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The nature and origin of language
This book looks at how the human brain got the capacity for language and how language then evolved. Its four parts are concerned with different views on the emergence of language, with what language is, how it evolved in the human brain, and finally how this process led to the properties of language. Part I considers the main approaches to the subject and how far language evolved culturally or genetically. Part II argues that language is a system of signs and considers how these elements first came together in the brain. Part III examines the evidence for brain mechanisms to allow the formation of signs. Part IV shows how the book's explanation of language origins and evolution is not only consistent with the complex properties of languages but provides the basis for a theory of syntax that offers insights into the learnability of language and to the nature of constructions that have defied decades of linguistic analysis, including including subject-verb inversion in questions, existential constructions, and long-distance dependencies. Denis Bouchard's outstandingly original account will interest linguists of all persuasions as well as cognitive scientists and others interested in the evolution of language.
Book
Surgical Ablation of Atrial Fibrillation during Mitral-Valve Surgery
In this trial, patients with atrial fibrillation undergoing mitral-valve surgery were assigned to surgical ablation of AF or no ablation. At 6 and 12 months, more patients in the ablation group were free from AF, but more patients in that group required permanent pacemakers.
Atrial fibrillation, which is associated with reduced survival and increased risk of stroke, is present in 30 to 50% of patients presenting for mitral-valve surgery.
1
,
2
The development of open surgical procedures for the ablation of atrial fibrillation has led to their widespread application during cardiac operations, but their effectiveness and safety have not been rigorously established. It is hypothesized that long-term outcomes can be improved by successful ablation in patients with preexisting persistent or long-standing persistent atrial fibrillation who are undergoing mitral-valve surgery.
The Cox maze III operation (sometimes called the “cut-and-sew” maze operation) is a complex surgical procedure . . .
Journal Article
Active clearance vs conventional management of chest tubes after cardiac surgery: a randomized controlled study
Background
Chest tubes are routinely used after cardiac surgery to evacuate shed mediastinal blood. Incomplete chest drainage due to chest tube clogging can lead to retained blood after cardiac surgery. This can include cardiac tamponade, hemothorax, bloody effusions and postoperative atrial fibrillation (POAF). Prior published non randomized studies have demonstrated that active tube clearance (ATC) of chest tubes can reduce retained blood complications prompting the ERAS Cardiac Society guidelines to recommend this modality.
Objective
A randomized prospective trial to evaluate whether an ATC protocol aimed at improving chest tube patency without breaking the sterile field could efficiently reduce complications related to retained blood after cardiac surgery.
Methods
This was a pragmatic, single-blinded, parallel randomized control trial held from November 2015 to June 2017 including a 30-day post index surgery follow-up. The setting was two academic centers affiliated with the
Université de Montréal
School of Medicine; the Montreal Heart Institute and the
Hôpital du Sacré-Coeur de Montréal
. Adult patients admitted for non-emergent coronary bypass grafting and/or valvular heart surgery through median sternotomy, in sinus rhythm for a minimum of 30 days prior to the surgical intervention were eligible for inclusion.
In the active tube clearance group (ATC), a 28F PleuraFlow device was positioned within the mediastinum. In the standard drainage group, a conventional chest tube (Teleflex Inc.) was used. Other chest tubes were left at the discretion of the operating surgeon.
Results
A total of 520 adult patients undergoing cardiac surgery were randomized to receive either ATC (
n
= 257) or standard drainage (
n
= 263). ATC was associated with a 72% reduction in re-exploration for bleeding (5.7% vs 1.6%,
p
= .01) and an 89% reduction in complete chest tube occlusion (2% vs 19%,
p
= .01). There was an 18% reduction in POAF between the ATC and control group that was not statistically significant (31% vs 38%,
p
= .08).
Conclusions and relevance
In this RCT, the implementation of active clearance of chest tubes reduced re-exploration and chest tube clogging in patients after cardiac surgery further supporting recommendations to consider this modality postoperatively.
Trial registration
Clinical Trials
NCT02808897
. Retrospectively registered 22 June 2016.
Journal Article
The role of surgery for secondary mitral regurgitation and heart failure in the era of transcatheter mitral valve therapies
The approach to the management of mitral valve (MV) disease and heart failure (HF) has dramatically changed over the last decades. It is well recognized that severe mitral regurgitation secondary to ischemic or non-ischemic cardiomyopathy is associated with an excess risk of mortality. Understanding the impact of the surgical treatment modality on mortality outcomes has been difficult due to the broad spectrum of secondary mitral regurgitation (SMR) phenotypes and lack of randomized surgical clinical trials. Over the last 30 years, surgeons have failed to provide compelling evidence to convince the medical community of the need to treat SMR in patients with severe HF. Therefore, the surgical treatment of SMR has never gained uniform acceptance as a significant option among patients suffering from SMR. Recent evidence from randomized trials in a non-surgical eligible patients treated with transcatheter therapies, has provided a new perspective on SMR treatment. Recently published European and American guidelines confirm the key role of percutaneous treatment of SMR and in parallel, these guidelines reinforce the role of mitral valve surgery in patients who require surgical revascularization. Complex mitral valve repair combining subvalvular apparatus repair along with annuloplasty seems to be a promising approach in selected patients in selected centers. Meanwhile, mitral valve replacement has become the preferred surgical strategy in most patients with advanced heart failure and severe LV remodeling or high risk of recurrent mitral regurgitation. In this comprehensive review, we aimed to discuss the role of mitral surgery for SMR in patients with heart failure in the contemporary era and to provide a practical approach for its surgical management.
Journal Article
Retrospective cohort analysis of 926 tricuspid valve surgeries: Clinical and hemodynamic outcomes with propensity score analysis
The objectives were to describe morbidity and mortality after tricuspid valve (TV) surgery, to compare outcomes after repair versus replacement, and to assess risk factors for mortality and tricuspid regurgitation (TR) recurrence.
A retrospective cohort study including 926 consecutive cases of TV surgery (792 repairs and 134 replacements) performed at the Montreal Heart Institute was conducted. Median follow-up was 4.3 years (4,657 patient-years). Median age was 62 years (interquartile range 53-69 years), and 72% of patients were women.
Operative mortality was 14% (128 patients: 1977-1998 20%, 1999-2008 7%, P < .001). Independent risk factors for operative mortality in the 1999 to 2008 period were hypertension (odds ratio [OR] 6.03, P = .02), daily furosemide dose (by 10 mg) (OR 1.06, P = .05), weight (by 10 kg) (OR 0.36, P < .01), and cardiopulmonary bypass time (by 10 minutes) (OR 1.29, P < .001). Ten-year survival was 49% ± 2% and 38 ± 5% in the repair and replacement groups, respectively (P = .012). At discharge, severity of TR was ≥3/4 in 13% and 2% of patients in the repair and replacement groups, respectively (P = .01). Propensity score analysis showed that tricuspid repair was associated with higher rates of TR ≥3/4 at follow-up compared with replacement (hazard ratio 2.15, P = .02). Forty-eight reoperations (7% of patients at risk) were performed during follow-up (repair group, 6%; replacement group, 15%; P = .01). At last follow-up, New York Heart Association functional class was improved compared with baseline in both groups (P < .001).
Tricuspid valve surgery is associated with substantial early and late mortalities but with significant functional improvement. Replacement is more effective in early and late corrections of regurgitation, but it does not translate into better survival outcomes.
Journal Article
La linguistique en toute simplicité / Linguistics, simply
La valeur explicative d'une théorie scientifique repose non seulement sur la quantité des éléments primitifs adoptés (principe de simplicité), mais aussi sur la qualité de ces éléments. En linguistique, les propriétés des substances perceptuelles et conceptuelles des signes offrent une base explicative solide parce qu'elles sont logiquement antérieures à l'objet qui est à l’étude. Ceci est particulièrement important parce que le langage est un phénomène neurologique, voire biologique. Moins les éléments d'une théorie linguistique sont spécifiques au domaine langagier, plus ils sont susceptibles d'avoir la granularité nécessaire pour être biologiquement plausibles (Poeppel et Embick 2005). Cette perspective est celle qui guide mes travaux depuis des décennies. Je l'illustre par l'analyse de plusieurs constructions maintenant classiques dans les études en syntaxe, pour donner une vision globale des conséquences de cette approche. Cette approche méthodologique renouvelle la notion d'adéquation explicative et répond à des questions laissées en suspens dans l'argumentation linguistique des six dernières décennies. The explanatory value of a scientific theory rests not only upon the quantity of primitive elements adopted (principle of simplicity), but also upon the quality of these elements. In linguistics, the properties of the perceptual and conceptual substances of the signs provide a solid explanatory basis because they are logically prior to the object under study. This is particularly important because language is a neurological, biological phenomenon. The less language-specific the elements of a linguistic theory are, the more likely they are to have the granularity required to be biologically plausible (Poeppel and Embick 2005). This perspective has been guiding my research for decades. I illustrate it by an analysis of several constructions now classic in syntactic studies, to give a global view of its consequences. This methodological approach renews the notion of explanatory adequacy and answers questions that have been left pending in linguistic argumentation for the past six decades.
Journal Article
Nur77 as a Survival Factor in Tumor Necrosis Factor Signaling
The immediate-early gene Nur77, which encodes an orphan nuclear receptor, is rapidly induced by various stress stimuli, including tumor necrosis factor (TNF). Nur77 has been implicated in mediating apoptosis, particularly in T cells and tumor cells. We report here that Nur77 can play a role in antagonizing apoptosis in TNF signaling. Nur77 expression is strongly induced by TNF. Interestingly, unlike most antiapoptotic molecules, this induced expression of Nur77 is largely independent of NF-κ B. Ectopic expression of Nur77 can protect wild-type, TRAF2-/-, and RelA-/-cells from apoptosis induced by TNF, whereas expression of a dominant-negative form of Nur77 (DN-Nur77) accelerates TNF-mediated cell death in the mutant cells. In mouse embryonic fibroblasts, Nur77 remains in the nucleus in response to TNF and is not translocated to the mitochondria, where it was reported to mediate apoptosis. Our results suggest that Nur77 is a survival effector protein in the context of TNF-mediated signaling.
Journal Article
Chk2 Regulates Irradiation-Induced, p53-Mediated Apoptosis in Drosophila
The tumor suppressor function of p53 has been attributed to its ability to regulate apoptosis and the cell cycle. In mammals, DNA damage, aberrant growth signals, chemotherapeutic agents, and UV irradiation activate p53, a process that is regulated by several posttranslational modifications. In Drosophila melanogaster, however, the regulation modes of p53 are still unknown. Overexpression of D. melanogaster p53 (Dmp53) in the eye induced apoptosis, resulting in a small eye phenotype. This phenotype was markedly enhanced by coexpression with D. melanogaster Chk2 (DmChk2) and was almost fully rescued by coexpression with a dominant-negative (DN), kinase-dead form of DmChk2. DN DmChk2 also inhibited Dmp53-mediated apoptosis in response to DNA damage, whereas overexpression of Grapes (Grp), the Drosophila Chk1-homolog, and its DN mutant had no effect on Dmp53-induced phenotypes. DmChk2 also activated the Dmp53 transactivation activity in cultured cells. Mutagenesis of Dmp53 amino terminal Ser residues revealed that Ser-4 is critical for its responsiveness toward DmChk2. DmChk2 activates the apoptotic activity of Dmp53 and Ser-4 is required for this effect. Contrary to results in mammals, Grapes, the Drosophila Chk1-homolog, is not involved in regulating Dmp53. Chk2 may be the ancestral regulator of p53 function.
Journal Article
Quercetin Reduces Vascular Senescence and Inflammation in Symptomatic Male but Not Female Coronary Artery Disease Patients
Recent studies suggest that vascular senescence and its associated inflammation fuel the inflammaging to favor atherogenesis; whether these pathways can be therapeutically targeted in coronary artery disease (CAD) patients remains unknown. In a randomized, double‐blind trial, 97 patients (78 men) undergoing coronary artery bypass graft surgery were treated with either quercetin (500 mg twice daily, 47 patients) or placebo (50 patients) for two days pre‐surgery through hospital discharge. Primary outcomes were reduced inflammation and improved endothelial function ex vivo. Exploratory analyses included plasma proteomics and single‐nuclei RNA sequencing of internal thoracic artery (ITA) samples. Quercetin treatment showed a trend toward reduced C‐reactive protein at discharge (p = 0.073) and differentially modulated circulating inflammatory protein expression between men and women, with a pro‐inflammatory effect of quercetin in females. Endothelial acetylcholine‐induced relaxation improved significantly with quercetin (p = 0.049), with effects in men (p = 0.043) but not in women (p = 0.852). ITA transcriptomics revealed the overexpression of senescence and inflammaging pathways in male vascular cells, which quercetin reversed. In female cells, quercetin had minimal endothelial benefit and increased inflammaging in fibroblasts. In male cells, a candidate target of quercetin involves interactions between the receptor PLAUR and its ligands PLAU and SERPINE1. Post‐operative atrial fibrillation incidence was significantly lower with quercetin, representing 4% of the patients compared to 18% in the placebo group (p = 0.033). In conclusion, short‐term quercetin treatment effectively targeted vascular senescence in male CAD patients, improving inflammatory and functional outcomes. However, these benefits were not observed in female patients. Trial Registration: https://clinicaltrials.gov, NCT04907253 In male patients undergoing CABG surgery, pretreatment with quercetin suppressed inflammaging and its associated inflammation, leading to improved endothelium‐dependent relaxation (measured ex vivo) and reducing new onset of post‐operative atrial fibrillation. These benefits were not observed in female patients, who exhibited minimal evidence of inflammaging.
Journal Article