COLOR III: a multicentre randomised clinical trial comparing transanal TME versus laparoscopic TME for mid and low rectal cancer

Total mesorectal excision (TME) is an essential component of surgical management of rectal cancer. Both open and laparoscopic TME have been proven to be oncologically safe. However, it remains a challenge to achieve complete TME with clear circumferential resections margin (CRM) with the conventional transabdominal approach, particularly in mid and low rectal tumours. Transanal TME (TaTME) was developed to improve oncological and functional outcomes of patients with mid and low rectal cancer.An international, multicentre, superiority, randomised trial was designed to compare TaTME and conventional laparoscopic TME as the surgical treatment of mid and low rectal carcinomas. The primary endpoint is involved CRM. Secondary endpoints include completeness of mesorectum, residual mesorectum, morbidity and mortality, local recurrence, disease-free and overall survival, percentage of sphincter-saving procedures, functional outcome and quality of life. A Quality Assurance Protocol including centralised MRI review, histopathology re-evaluation, standardisation of surgical techniques, and monitoring and assessment of surgical quality will be conducted.The difference in involvement of CRM between the two treatment strategies is thought to be in favour of the TaTME. TaTME is therefore expected to be superior to laparoscopic TME in terms of oncological outcomes in case of mid and low rectal carcinomas

New approximations for the cone of copositive matrices and its dual

We provide convergent hierarchies for the cone C of copositive matrices and its dual, the cone of completely positive matrices. In both cases the corresponding hierarchy consists of nested spectrahedra and provide outer (resp. inner) approximations for C (resp. for its dual), thus complementing previous inner (resp. outer) approximations for C (for the dual). In particular, both inner and outer approximations have a very simple interpretation. Finally, extension to K-copositivity and K-complete positivity for a closed convex cone K, is straightforward.Comment: 8

Error bounds for monomial convexification in polynomial optimization

Convex hulls of monomials have been widely studied in the literature, and monomial convexifications are implemented in global optimization software for relaxing polynomials. However, there has been no study of the error in the global optimum from such approaches. We give bounds on the worst-case error for convexifying a monomial over subsets of $[0,1]^n$. This implies additive error bounds for relaxing a polynomial optimization problem by convexifying each monomial separately. Our main error bounds depend primarily on the degree of the monomial, making them easy to compute. Since monomial convexification studies depend on the bounds on the associated variables, in the second part, we conduct an error analysis for a multilinear monomial over two different types of box constraints. As part of this analysis, we also derive the convex hull of a multilinear monomial over $[-1,1]^n$.Comment: 33 pages, 2 figures, to appear in journa

An exact duality theory for semidefinite programming based on sums of squares

Farkas' lemma is a fundamental result from linear programming providing linear certificates for infeasibility of systems of linear inequalities. In semidefinite programming, such linear certificates only exist for strongly infeasible linear matrix inequalities. We provide nonlinear algebraic certificates for all infeasible linear matrix inequalities in the spirit of real algebraic geometry: A linear matrix inequality is infeasible if and only if -1 lies in the quadratic module associated to it. We also present a new exact duality theory for semidefinite programming, motivated by the real radical and sums of squares certificates from real algebraic geometry.Comment: arXiv admin note: substantial text overlap with arXiv:1108.593

Immobile indices and CQ-free optimality criteria for linear copositive programming problems

We consider problems of linear copositive programming where feasible sets consist of vectors for which the quadratic forms induced by the corresponding linear matrix combinations are nonnegative over the nonnegative orthant. Given a linear copositive problem, we define immobile indices of its constraints and a normalized immobile index set. We prove that the normalized immobile index set is either empty or can be represented as a union of a finite number of convex closed bounded polyhedra. We show that the study of the structure of this set and the connected properties of the feasible set permits to obtain new optimality criteria for copositive problems. These criteria do not require the fulfillment of any additional conditions (constraint qualifications or other). An illustrative example shows that the optimality conditions formulated in the paper permit to detect the optimality of feasible solutions for which the known sufficient optimality conditions are not able to do this. We apply the approach based on the notion of immobile indices to obtain new formulations of regularized primal and dual problems which are explicit and guarantee strong duality.publishe

Small-Bodied Humans from Palau, Micronesia

UNLABELLED: Newly discovered fossil assemblages of small bodied Homo sapiens from Palau, Micronesia possess characters thought to be taxonomically primitive for the genus Homo. BACKGROUND: Recent surface collection and test excavation in limestone caves in the rock islands of Palau, Micronesia, has produced a sizeable sample of human skeletal remains dating roughly between 940-2890 cal ybp. PRINCIPLE FINDINGS: Preliminary analysis indicates that this material is important for two reasons. First, individuals from the older time horizons are small in body size even relative to "pygmoid" populations from Southeast Asia and Indonesia, and thus may represent a marked case of human insular dwarfism. Second, while possessing a number of derived features that align them with Homo sapiens, the human remains from Palau also exhibit several skeletal traits that are considered to be primitive for the genus Homo. SIGNIFICANCE: These features may be previously unrecognized developmental correlates of small body size and, if so, they may have important implications for interpreting the taxonomic affinities of fossil specimens of Homo

Depression and anxiety, an Indicated Prevention (DIP) protocol in homes for the elderly: feasibility and (cost) effectiveness of a stepped care programme

BACKGROUND: Depressive and anxiety disorders are a very common, serious and underdetected problem in homes for the elderly. Elderly persons in residential homes are at high risk for developing major depressive and anxiety disorders, and, therefore, deserve attention with regard to prevention. METHODS/DESIGN: This protocol describes a randomised trial on the feasibility and (cost) effectiveness of a stepped-care programme for prevention of depressive and anxiety disorders in homes for the elderly. The main outcome measure is the incidence of depressive and anxiety disorder in one year with a two years follow up. Secondary outcomes are symptoms of depression and anxiety, quality of life, direct health care costs and satisfaction with treatment. DISCUSSION: The number of studies examining the effects of preventive interventions on the incidence of mental disorders in the elderly population is very small. However, indicated prevention by means of a stepped-care programme seems to be an important option for decreasing the burden of illness for residents and their caregivers. This study contributes to the body of knowledge in this field. Positive effects may contribute to further use and development of tailored, (cost-) effective and easy to use interventions in a preventive stepped-care programme. TRIAL REGISTRATION: The Dutch Cochrane Centre, ISRCTN2754073

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches