Examination of optimizing information flow in networks

The central role of the Internet and the World-Wide-Web in global communications has refocused much attention on problems involving optimizing information flow through networks. The most basic formulation of the question is called the "max flow" optimization problem: given a set of channels with prescribed capacities that connect a set of nodes in a network, how should the materials or information be distributed among the various routes to maximize the total flow rate from the source to the destination. Theory in linear programming has been well developed to solve the classic max flow problem. Modern contexts have demanded the examination of more complicated variations of the max flow problem to take new factors or constraints into consideration; these changes lead to more difficult problems where linear programming is insufficient. In the workshop we examined models for information flow on networks that considered trade-offs between the overall network utility (or flow rate) and path diversity to ensure balanced usage of all parts of the network (and to ensure stability and robustness against local disruptions in parts of the network). While the linear programming solution of the basic max flow problem cannot handle the current problem, the approaches primal/dual formulation for describing the constrained optimization problem can be applied to the current generation of problems, called network utility maximization (NUM) problems. In particular, primal/dual formulations have been used extensively in studies of such networks. A key feature of the traffic-routing model we are considering is its formulation as an economic system, governed by principles of supply and demand. Considering channel capacities as a commodity of limited supply, we might suspect that a system that regulates traffic via a pricing scheme would assign prices to channels in a manner inversely proportional to their respective capacities. Once an appropriate network optimization problem has been formulated, it remains to solve the optimization problem; this will need to be done numerically, but the process can greatly benefit from simplifications and reductions that follow from analysis of the problem. Ideally the form of the numerical solution scheme can give insight on the design of a distributed algorithm for a Transmission Control Protocol (TCP) that can be directly implemented on the network. At the workshop we considered the optimization problems for two small prototype network topologies: the two-link network and the diamond network. These examples are small enough to be tractable during the workshop, but retain some of the key features relevant to larger networks (competing routes with different capacities from the source to the destination, and routes with overlapping channels, respectively). We have studied a gradient descent method for solving obtaining the optimal solution via the dual problem. The numerical method was implemented in MATLAB and further analysis of the dual problem and properties of the gradient method were carried out. Another thrust of the group's work was in direct simulations of information flow in these small networks via Monte Carlo simulations as a means of directly testing the efficiencies of various allocation strategies

Integrating the digital and the traditional to deliver therapy for depression:lessons from a pragmatic study

Traditional approaches to psychotherapy emphasise face-to-face contact between patients and therapists. In contrast, current computerised approaches tend to minimise this contact. This can limit the range of mental health difficulties for which computerised approaches are effective. Here, we explore an alternative approach that integrates face-to-face contact, electronic contact, online collaboration, and support for between-session activities. Our discussion is grounded in the design of a platform to deliver psychotherapy for depression. We report findings of an 11-month pragmatic study in which 17 patients received treatment for depression via the platform. Results show how design decisions had a significant impact on the dynamics of therapeutic sessions and the establishment of patient-therapist relationships. For example, the use of instant messaging for synchronous, in-session contact slowed communication, but also provided a valuable space for reflection and helped to maintain session focus. We discuss the impact of flexibility and the potential of integrated approaches to both enhance and reduce patient engagement

Dissection of QTL effects for root traits using a chromosome arm-specific mapping population in bread wheat

A high-resolution chromosome arm-specific mapping population was used in an attempt to locate/detect gene(s)/QTL for different root traits on the short arm of rye chromosome 1 (1RS) in bread wheat. This population consisted of induced homoeologous recombinants of 1RS with 1BS, each originating from a different crossover event and distinct from all other recombinants in the proportions of rye and wheat chromatin present. It provides a simple and powerful approach to detect even small QTL effects using fewer progeny. A promising empirical Bayes method was applied to estimate additive and epistatic effects for all possible marker pairs simultaneously in a single model. This method has an advantage for QTL analysis in minimizing the error variance and detecting interaction effects between loci with no main effect. A total of 15 QTL effects, 6 additive and 9 epistatic, were detected for different traits of root length and root weight in 1RS wheat. Epistatic interactions were further partitioned into inter-genomic (wheat and rye alleles) and intra-genomic (rye–rye or wheat–wheat alleles) interactions affecting various root traits. Four common regions were identified involving all the QTL for root traits. Two regions carried QTL for almost all the root traits and were responsible for all the epistatic interactions. Evidence for inter-genomic interactions is provided. Comparison of mean values supported the QTL detection

A global perspective on the trophic geography of sharks

Sharks are a diverse group of mobile predators that forage across varied spatial scales and have the potential to influence food web dynamics. The ecological consequences of recent declines in shark biomass may extend across broader geographic ranges if shark taxa display common behavioural traits. By tracking the original site of photosynthetic fixation of carbon atoms that were ultimately assimilated into muscle tissues of 5,394 sharks from 114 species, we identify globally consistent biogeographic traits in trophic interactions between sharks found in different habitats. We show that populations of shelf-dwelling sharks derive a substantial proportion of their carbon from regional pelagic sources, but contain individuals that forage within additional isotopically diverse local food webs, such as those supported by terrestrial plant sources, benthic production and macrophytes. In contrast, oceanic sharks seem to use carbon derived from between 30° and 50° of latitude. Global-scale compilations of stable isotope data combined with biogeochemical modelling generate hypotheses regarding animal behaviours that can be tested with other methodological approaches.This research was conducted as part of C.S.B.’s Ph.D dissertation, which was funded by the University of Southampton and NERC (NE/L50161X/1), and through a NERC Grant-in-Kind from the Life Sciences Mass Spectrometry Facility (LSMSF; EK267-03/16). We thank A. Bates, D. Sims, F. Neat, R. McGill and J. Newton for their analytical contributions and comments on the manuscripts.Peer reviewe

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article