Synaesthesia: a distinct entity that is an emergent feature of adaptive neurocognitive differences

In this article, I argue that synaesthesia is not on a continuum with neurotypical cognition. Synaesthesia is special: its phenomenology is different; it has distinct causal mechanisms; and is likely to be associated with a distinct neurocognitive profile. However, not all synaesthetes are the same, and there are quantifiable differences between them. In particular, the number of types of synaesthesia that a person possesses is a hitherto underappreciated variable that predicts cognitive differences along a number of dimensions (mental imagery, sensory sensitivity, attention to detail). Together with enhanced memory, this may constitute a common core of abilities that may go some way to explaining why synaesthesia might have evolved. I argue that the direct benefits of synaesthesia are generally limited (i.e. the synaesthetic associations do not convey novel information about the world) but, nevertheless, synaesthesia may develop due to other adaptive functions (e.g. perceptual ability, memory) that necessitate changes to design features of the brain. The article concludes by suggesting that synaesthesia forces us to reconsider what we mean by a ‘normal’ mind/brain. There may be multiple ‘normal’ neurodevelopmental trajectories that can sculpt very different ways of experiencing the world, of which synaesthesia is but one. This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’

Has the 'Fast-Track' referral system affected the route of presentation and/or clinical outcomes in patients with colorectal cancer?

Background: The aim of this study is to determine whether the 'Fast-Track' referral system has changed the route by which patients present with colorectal cancer (CRC) and whether the route of presentation has any effect on clinical outcome. Methods: A retrospective cohort study of patients diagnosed with CRC under the care of two consultant colorectal surgeons between April 2006 and December 2012. The route by which patients presented was categorised as Fast-Track (FT), non-Fast-Track (non-FT) or acute. Outcome variables were operative intent, disease stage and 2- and 5-year survival. Results: A total of 558 patients were identified. One hundred ninety-seven patients (35.3%) were referred as FT, 108 (19.4%) presented acutely and 253 patients (45.3%) presented via other routes (non-FT). Over the study period, the route of presentation did not change significantly (P=0.135). There was no significant difference between FT and non-FT groups in terms of the proportion of patients undergoing potentially curative surgery (70.6 vs 74.3%, P=0.092) or with node-negative disease (48.2 vs 52.2%, P=0.796) nor was there any difference in 2-year or 5-year survival (74.1 vs 73.9%, P=0.837 and 52.3 vs 53.8%, P=0.889, respectively). Patients who presented acutely were less likely to undergo curative resection, had more advanced disease and had worse 2- and 5-year survival. Conclusions: The Fast-Track referral system has not affected the route by which patients present with CRC nor has it had any effect on clinical outcomes. Alternative strategies are required if the desired improvement in outcomes is to be achieved

Response of stone wool-insulated building barriers under severe heating exposures

This article presents the experimental results of stone wool-layered sandwich constructions, with either steel or gypsum claddings, tested under four different heating exposures: 7kW/m(2) incident radiant heat flux exposure, 60kW/m(2) incident radiant heat flux exposure, parametric time-temperature curve exposure and ISO 834 standard time-temperature exposure. The test apparatus used were a movable radiant panel system, a mid-scale furnace (1.5m(3)) and a large-scale furnace (15m(3)). The results show that reduced-scale tests are capable of reproducing the heat transferred through the construction at large scale provided there is limited mechanical degradation. The results indicate that the availability of oxygen is fundamental to the fire behaviour of the sandwich composites tested. Reactions occurring in stone wool micro-scale testing, such as oxidative combustion of the binder or crystallisation of the fibres, have a limited effect on the temperature increase when wool is protected from air entrainment

miRNA signature associated with outcome of gastric cancer patients following chemotherapy

<p>Abstract</p> <p>Background</p> <p>Identification of patients who likely will or will not benefit from cytotoxic chemotherapy through the use of biomarkers could greatly improve clinical management by better defining appropriate treatment options for patients. microRNAs may be potentially useful biomarkers that help guide individualized therapy for cancer because microRNA expression is dysregulated in cancer. In order to identify miRNA signatures for gastric cancer and for predicting clinical resistance to cisplatin/fluorouracil (CF) chemotherapy, a comprehensive miRNA microarray analysis was performed using endoscopic biopsy samples.</p> <p>Methods</p> <p>Biopsy samples were collected prior to chemotherapy from 90 gastric cancer patients treated with CF and from 34 healthy volunteers. At the time of disease progression, post-treatment samples were additionally collected from 8 clinical responders. miRNA expression was determined using a custom-designed Agilent microarray. In order to identify a miRNA signature for chemotherapy resistance, we correlated miRNA expression levels with the time to progression (TTP) of disease after CF therapy.</p> <p>Results</p> <p>A miRNA signature distinguishing gastric cancer from normal stomach epithelium was identified. 30 miRNAs were significantly inversely correlated with TTP whereas 28 miRNAs were significantly positively correlated with TTP of 82 cancer patients (<it>P</it><0.05). Prominent among the upregulated miRNAs associated with chemosensitivity were miRNAs known to regulate apoptosis, including let-7g, miR-342, miR-16, miR-181, miR-1, and miR-34. When this 58-miRNA predictor was applied to a separate set of pre- and post-treatment tumor samples from the 8 clinical responders, all of the 8 pre-treatment samples were correctly predicted as low-risk, whereas samples from the post-treatment tumors that developed chemoresistance were predicted to be in the high-risk category by the 58 miRNA signature, suggesting that selection for the expression of these miRNAs occurred as chemoresistance arose.</p> <p>Conclusions</p> <p>We have identified 1) a miRNA expression signature that distinguishes gastric cancer from normal stomach epithelium from healthy volunteers, and 2) a chemoreresistance miRNA expression signature that is correlated with TTP after CF therapy. The chemoresistance miRNA expression signature includes several miRNAs previously shown to regulate apoptosis <it>in vitro</it>, and warrants further validation.</p

Deep-Inelastic Inclusive ep Scattering at Low x and a Determination of alpha_s

A precise measurement of the inclusive deep-inelastic e^+p scattering cross section is reported in the kinematic range 1.5<= Q^2 <=150 GeV^2 and 3*10^(-5)<= x <=0.2. The data were recorded with the H1 detector at HERA in 1996 and 1997, and correspond to an integrated luminosity of 20 pb^(-1). The double differential cross section, from which the proton structure function F_2(x,Q^2) and the longitudinal structure function F_L(x,Q^2) are extracted, is measured with typically 1% statistical and 3% systematic uncertainties. The measured partial derivative (dF_2(x,Q^2)/dln Q^2)_x is observed to rise continuously towards small x for fixed Q^2. The cross section data are combined with published H1 measurements at high Q^2 for a next-to-leading order DGLAP QCD analysis.The H1 data determine the gluon momentum distribution in the range 3*10^(-4)<= x <=0.1 to within an experimental accuracy of about 3% for Q^2 =20 GeV^2. A fit of the H1 measurements and the mu p data of the BCDMS collaboration allows the strong coupling constant alpha_s and the gluon distribution to be simultaneously determined. A value of alpha _s(M_Z^2)=0.1150+-0.0017 (exp) +0.0009-0.0005 (model) is obtained in NLO, with an additional theoretical uncertainty of about +-0.005, mainly due to the uncertainty of the renormalisation scale.Comment: 68 pages, 24 figures and 18 table

Lattice Boltzmann simulations of soft matter systems

This article concerns numerical simulations of the dynamics of particles immersed in a continuum solvent. As prototypical systems, we consider colloidal dispersions of spherical particles and solutions of uncharged polymers. After a brief explanation of the concept of hydrodynamic interactions, we give a general overview over the various simulation methods that have been developed to cope with the resulting computational problems. We then focus on the approach we have developed, which couples a system of particles to a lattice Boltzmann model representing the solvent degrees of freedom. The standard D3Q19 lattice Boltzmann model is derived and explained in depth, followed by a detailed discussion of complementary methods for the coupling of solvent and solute. Colloidal dispersions are best described in terms of extended particles with appropriate boundary conditions at the surfaces, while particles with internal degrees of freedom are easier to simulate as an arrangement of mass points with frictional coupling to the solvent. In both cases, particular care has been taken to simulate thermal fluctuations in a consistent way. The usefulness of this methodology is illustrated by studies from our own research, where the dynamics of colloidal and polymeric systems has been investigated in both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures, 76 page

Results of a randomized, double blind, placebo controlled, crossover trial of melatonin for treatment of Nocturia in adults with multiple sclerosis (MeNiMS)

© 2018 The Author(s). Background: Nocturia is a common urinary symptom of multiple sclerosis (MS) which can affect quality of life (QoL) adversely. Melatonin is a hormone known to regulate circadian rhythm and reduce smooth muscle activity such as in the bladder. There is limited evidence supporting use of melatonin to alleviate urinary frequency at night in the treatment of nocturia. The aim of this study was to evaluate the effect of melatonin on the mean number of nocturia episodes per night in patients with MS. Methods: A randomized, double blind, placebo controlled crossover trial was conducted. 34 patients with nocturia secondary to multiple sclerosis underwent a 4-day pre-treatment monitoring phase. The patients were randomized to receive either 2 mg per night (taken at bedtime) of capsulated sustained-release melatonin (Circadin®) or 1 placebo capsule for 6 weeks followed by a crossover to the other regimen for an additional 6 weeks after a 1-month washout period. Results: From the 26 patients who completed the study, there was no significant difference observed in the signs or symptoms of nocturia when taking 2 mg melatonin compared to placebo. The primary outcome measure, mean number of nocturia episodes on bladder diaries, was 1.8/night at baseline, and 1.4/night on melatonin, compared with 1.6 for placebo (Medians 1.70, 1.50, and 1.30 respectively, p = 0.85). There was also no significant difference seen in LUTS, QoL and sleep quality when taking melatonin. No significant safety concerns arose. Conclusions: This small study suggests that a low dose of melatonin taken at bedtime may be ineffective therapy for nocturia in MS. Trial registration: (EudraCT reference) 2012-00418321 registered: 25/01/13. ISRCTN Registry: ISRCTN38687869

Thermal Stabilization of an Endoglucanase by Cyclization

An intein-driven protein splicing approach allowed for the covalent linkage between the N- and C-termini of a polypeptide chain to create circular variants of the endo-β-1,3-1,4-glucanase, LicA, from Bacillus licheniformis. Two circular variants, LicA-C1 and LicA-C2, which have connecting loops of 20 and 14 amino acids, respectively, showed catalytic activities that are approximately two and three times higher, respectively, compared to that of the linear LicA (LicA-L1). The thermal stability of the circular variants was significantly increased compared to the linear form. Whereas the linear glucanase lost half of its activity after 3 min at 65 °C, the two circular variants have 6-fold (LicA-C1) and 16-fold (LicA-C2) increased half-life time of inactivation. In agreement with this, fluorescence spectroscopy and differential scanning calorimetry studies revealed that circular enzymes undergo structural changes at higher temperatures compared to that of the linear form. The effect of calcium on the conformational stability and function of the circular LicAs was also investigated, and we observed that the presence of calcium ions results in increased thermal stability. The impact of the length of the designed loops on thermal stability of the circular proteins is discussed, and it is suggested that cyclization may be an efficient strategy for the increased stability of proteins

Dominant Negative Mutants of Bacillus thuringiensis Cry1Ab Toxin Function as Anti-Toxins: Demonstration of the Role of Oligomerization in Toxicity

BACKGROUND:Bacillus thuringiensis Cry toxins, that are used worldwide in insect control, kill insects by a mechanism that depends on their ability to form oligomeric pores that insert into the insect-midgut cells. These toxins are being used worldwide in transgenic plants or spray to control insect pests in agriculture. However, a major concern has been the possible effects of these insecticidal proteins on non-target organisms mainly in ecosystems adjacent to agricultural fields. METHODOLOGY/PRINCIPAL FINDINGS:We isolated and characterized 11 non-toxic mutants of Cry1Ab toxin affected in different steps of the mechanism of action namely binding to receptors, oligomerization and pore-formation. These mutant toxins were analyzed for their capacity to block wild type toxin activity, presenting a dominant negative phenotype. The dominant negative phenotype was analyzed at two levels, in vivo by toxicity bioassays against susceptible Manduca sexta larvae and in vitro by pore formation activity in black lipid bilayers. We demonstrate that some mutations located in helix alpha-4 completely block the wild type toxin activity at sub-stoichiometric level confirming a dominant negative phenotype, thereby functioning as potent antitoxins. CONCLUSIONS/SIGNIFICANCE:This is the first reported case of a Cry toxin dominant inhibitor. These data demonstrate that oligomerization is a fundamental step in Cry toxin action and represent a potential mechanism to protect special ecosystems from the possible effect of Cry toxins on non-target organisms