Improving the assessment and outcome of free tissue transfer breast reconstruction

Introduction: Free tissue transfer using an abdominal tissue flap is a commonly used method of breast reconstruction. However, there are well recognised complications including venous congestion, fat necrosis and flap loss associated with the perfusion of these flaps. Post-operative aesthetic outcome assessment of such breast reconstructions have also proven to be difficult with current methods displaying poor inter-rater reliability and patient correlation. The aim of this research was to investigate potential improvements to the post-operative outcome of free abdominal tissue transfer breast reconstruction by assessing the effects of vascular augmentation interventions on flap perfusion and to assess the use of real-time digital video as a post-operative assessment tool. Methods: An in-vivo pilot study carried out on 12 patients undergoing DIEP flap breast reconstruction assessed the effect on Zone IV perfusion, using LDI and ICG angiography, of vascular augmentation of the flap using the contralateral SIEA and SIEV. A further animal experimental study was carried out on 12 Sprague Dawley rats to assess the effects on main pedicle arterial blood flow and on Zone I and Zone IV perfusion of vascular augmentation of the abdominal flap using the contralateral vascular system. A separate post-operative assessment study was undertaken on 35 breast reconstruction patients who evaluated their own reconstructions via patient questionnaire and underwent photograph and real-time digital video capture of their reconstructions with subsequent panel assessment. Results: Our results showed that combined vascular augmentation of DIEP flaps, using both the SIEA and SIEV together, led to an increase in Zone IV perfusion. Vascular augmentation of the rat abdominal flaps also led to a significant increase in Zone I/IV perfusion, but the augmentation procedure resulted in a decreased main pedicle arterial blood flow. Our post-operative assessment study revealed that real-time digital video footage led to greater inter-rater agreement with regards to cosmesis and shape than photography and also correlated more with patient self-assessment. Conclusion: Vascular augmentation of abdominal free tissue flaps using the contralateral vascular system results in an increase to Zone IV perfusion, however this may lead to decreased main pedicle arterial blood flow. Real-time digital video is a valid post-operative aesthetic assessment method of breast reconstruction outcome and is superior to static photography when coupled with panel assessment.

The accuracy of protein structure alignment servers

Background: Protein structural alignment is one of the most fundamental and crucial areas of research in the domain of computational structural biology. Comparison of a protein structure with known structures helps to classify it as a new or belonging to a known group of proteins. This, in turn, is useful to determine the function of protein, its evolutionary relationship with other protein molecules and grasping principles underlying protein architecture and folding. Results: A large number of protein structure alignment methods are available. Each protein structure alignment tool has its own strengths andweaknesses that need to be highlighted.We compared and presented results of six most popular and publically available servers for protein structure comparison. These web-based servers were compared with the respect to functionality (features provided by these servers) and accuracy (how well the structural comparison is performed). The CATH was used as a reference. The results showed that overall CE was top performer. DALI and PhyreStorm showed similar results whereas PDBeFold showed the lowest performance. In case of few secondary structural elements, CE, DALI and PhyreStorm gave 100% success rate. Conclusion: Overall none of the structural alignment servers showed 100% success rate. Studies of overall performance, effect of mainly alpha and effect of mainly beta showed consistent performance. CE, DALI, FatCat and PhyreStorm showed more than 90% success rate.

Using an end-of-life care pathway in acute stroke: a mixed methods study of decision-making and care experiences

Background: The evidence base on end-of-life care in acute stroke is limited, particularly with regard to recognising dying and related decision-making. There is also limited evidence to support the use of end-of-life care pathways (standardised care plans) for patients who are dying after stroke. Aim: This study aimed to explore the clinical decision-making involved in placing patients on an end-of-life care pathway, evaluate predictors of care pathway use, and investigate the role of families in decision-making. The study also aimed to examine experiences of end-of-life care pathway use for stroke patients, their relatives and the multi-disciplinary health care team. Methods: A mixed methods design was adopted. Data were collected in four Scottish acute stroke units. Case-notes were identified prospectively from 100 consecutive stroke deaths and reviewed. Multivariate analysis was performed on case-note data. Semi-structured interviews were conducted with 17 relatives of stroke decedents and 23 healthcare professionals, using a modified grounded theory approach to collect and analyse data. The VOICES survey tool was also administered to the bereaved relatives and data were analysed using descriptive statistics and thematic analysis of free-text responses. Results: Relatives often played an important role in influencing aspects of end-of-life care, including decisions to use an end-of-life care pathway. Some relatives experienced enduring distress with their perceived responsibility for care decisions. Relatives felt unprepared for and were distressed by prolonged dying processes, which were often associated with severe dysphagia. Pro-active information-giving by staff was reported as supportive by relatives. Healthcare professionals generally avoided discussing place of care with families. Decisions to use an end-of-life care pathway were not predicted by patients’ demographic characteristics; decisions were generally made in consultation with families and the extended health care team, and were made within regular working hours. Conclusion: Distressing stroke-related issues were more prominent in participants’ accounts than concerns with the end-of-life care pathway used. Relatives sometimes perceived themselves as responsible for important clinical decisions. Witnessing prolonged dying processes was difficult for healthcare professionals and families, particularly in relation to the management of persistent major swallowing difficulties.

Bayesian alignment of continuous molecular shapes using random fields

Statistical methodology is proposed for comparing molecular shapes. In order to account for the continuous nature of molecules, classical shape analysis methods are combined with techniques used for predicting random fields in spatial statistics. Applying a modification of Procrustes analysis, Bayesian inference is carried out using Markov chain Monte Carlo methods for the pairwise alignment of the resulting molecular fields. Superimposing entire fields rather than the configuration matrices of nuclear positions thereby solves the problem that there is usually no clear one--to--one correspondence between the atoms of the two molecules under consideration. Using a similar concept, we also propose an adaptation of the generalised Procrustes analysis algorithm for the simultaneous alignment of multiple molecular fields. The methodology is applied to a dataset of 31 steroid molecules.

Effects of acute exercise on salivary free insulin-like growth factor 1 and interleukin 10 in sportsmen.

Background: Saliva analysis is rapidly developing as a tool for the assessment of biomarkers of sports training. It remains poorly understood whether a short bout of sport training can alter some salivary immune biomarkers. Aim: To investigate the effect of acute exercise using football training session on salivary flow rate, salivary free Insulin-like Growth Factor-1 (IGF-1) and Interleukin 10 (IL-10). Methods: Saliva samples were collected before and immediately after a football session. Salivary flow rates, salivary levels of free IGF-1 and IL-10 (using ELISA) were determined. Data was analyzed and compared using Related Samples Wilcoxon Signed Rank test (non-parametric test). Relationships between salivary flow rate and levels of free IGF-1 and IL-10 were determined using Spearman correlation test. Results: There were 22 male footballers with a mean age of 20.46 years. Salivary flow rate reduced significantly (p = 0.01) after the training session while salivary levels of free IGF-1 and IL-10 did not show any significant change. Also, there were no correlations between salivary flow rates and salivary levels of free IGF-1 and IL-10 before and after exercise. Conclusion: These findings suggest that acute exercise caused significant reduction in salivary flow rate but no change in the levels of salivary free IGF-1 and IL-10.

Optimization models and methods for real-time transportation planning in forestry

Lors du transport du bois de la forêt vers les usines, de nombreux événements imprévus peuvent se produire, événements qui perturbent les trajets prévus (par exemple, en raison des conditions météo, des feux de forêt, de la présence de nouveaux chargements, etc.). Lorsque de tels événements ne sont connus que durant un trajet, le camion qui accomplit ce trajet doit être détourné vers un chemin alternatif. En l’absence d’informations sur un tel chemin, le chauffeur du camion est susceptible de choisir un chemin alternatif inutilement long ou pire, qui est lui-même "fermé" suite à un événement imprévu. Il est donc essentiel de fournir aux chauffeurs des informations en temps réel, en particulier des suggestions de chemins alternatifs lorsqu’une route prévue s’avère impraticable. Les possibilités de recours en cas d’imprévus dépendent des caractéristiques de la chaîne logistique étudiée comme la présence de camions auto-chargeurs et la politique de gestion du transport. Nous présentons trois articles traitant de contextes d’application différents ainsi que des modèles et des méthodes de résolution adaptés à chacun des contextes. Dans le premier article, les chauffeurs de camion disposent de l’ensemble du plan hebdomadaire de la semaine en cours. Dans ce contexte, tous les efforts doivent être faits pour minimiser les changements apportés au plan initial. Bien que la flotte de camions soit homogène, il y a un ordre de priorité des chauffeurs. Les plus prioritaires obtiennent les volumes de travail les plus importants. Minimiser les changements dans leurs plans est également une priorité. Étant donné que les conséquences des événements imprévus sur le plan de transport sont essentiellement des annulations et/ou des retards de certains voyages, l’approche proposée traite d’abord l’annulation et le retard d’un seul voyage, puis elle est généralisée pour traiter des événements plus complexes. Dans cette ap- proche, nous essayons de re-planifier les voyages impactés durant la même semaine de telle sorte qu’une chargeuse soit libre au moment de l’arrivée du camion à la fois au site forestier et à l’usine. De cette façon, les voyages des autres camions ne seront pas mo- difiés. Cette approche fournit aux répartiteurs des plans alternatifs en quelques secondes. De meilleures solutions pourraient être obtenues si le répartiteur était autorisé à apporter plus de modifications au plan initial. Dans le second article, nous considérons un contexte où un seul voyage à la fois est communiqué aux chauffeurs. Le répartiteur attend jusqu’à ce que le chauffeur termine son voyage avant de lui révéler le prochain voyage. Ce contexte est plus souple et offre plus de possibilités de recours en cas d’imprévus. En plus, le problème hebdomadaire peut être divisé en des problèmes quotidiens, puisque la demande est quotidienne et les usines sont ouvertes pendant des périodes limitées durant la journée. Nous utilisons un modèle de programmation mathématique basé sur un réseau espace-temps pour réagir aux perturbations. Bien que ces dernières puissent avoir des effets différents sur le plan de transport initial, une caractéristique clé du modèle proposé est qu’il reste valable pour traiter tous les imprévus, quelle que soit leur nature. En effet, l’impact de ces événements est capturé dans le réseau espace-temps et dans les paramètres d’entrée plutôt que dans le modèle lui-même. Le modèle est résolu pour la journée en cours chaque fois qu’un événement imprévu est révélé. Dans le dernier article, la flotte de camions est hétérogène, comprenant des camions avec des chargeuses à bord. La configuration des routes de ces camions est différente de celle des camions réguliers, car ils ne doivent pas être synchronisés avec les chargeuses. Nous utilisons un modèle mathématique où les colonnes peuvent être facilement et naturellement interprétées comme des itinéraires de camions. Nous résolvons ce modèle en utilisant la génération de colonnes. Dans un premier temps, nous relaxons l’intégralité des variables de décision et nous considérons seulement un sous-ensemble des itinéraires réalisables. Les itinéraires avec un potentiel d’amélioration de la solution courante sont ajoutés au modèle de manière itérative. Un réseau espace-temps est utilisé à la fois pour représenter les impacts des événements imprévus et pour générer ces itinéraires. La solution obtenue est généralement fractionnaire et un algorithme de branch-and-price est utilisé pour trouver des solutions entières. Plusieurs scénarios de perturbation ont été développés pour tester l’approche proposée sur des études de cas provenant de l’industrie forestière canadienne et les résultats numériques sont présentés pour les trois contextes.

Changes in Diadenosine Polyphosphates during Alignment-Fit and Orthokeratology Rigid Gas Permeable

Purpose.: To evaluate the levels of dinucleotides diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) in tears of patients wearing rigid gas permeable (RGP) contact lenses on a daily wear basis and of patients wearing reverse-geometry RGP lenses overnight for orthokeratology treatment. Methods.: Twenty-two young volunteers (10 females, 12 males; 23.47 ± 4.49 years) were fitted with an alignment-fit RGP lens (paflufocon B) for a month, and after a 15-day washout period they were fitted with reverse-geometry RGP lenses for corneal reshaping (paflufocon D) for another month. During each period, tears were collected at baseline day 1, 7, 15, and 28. Ap4A and Ap5A were measured by high-pressure liquid chromatography (HPLC). Additionally, corneal staining, break-up time (BUT), Schirmer test, and dryness symptoms were evaluated. Results.: Ap4A concentrations increased significantly from baseline during the whole period of daily wear of RGP lenses (P < 0.001); concentration was also significantly higher than in the orthokeratology group, which remained at baseline levels during the study period except at day 1 (P < 0.001) and day 28 (P = 0.041). While BUT and Schirmer remained unchanged in both groups, discomfort and dryness were significantly increased during alignment-fit RGP daily wear but not during the orthokeratology period. Conclusions.: Daily wear of RGP lenses increased the levels of Ap4A due to mechanical stimulation by blinking of the corneal epithelium, and this is associated with discomfort. Also, orthokeratology did not produce symptoms or signs of ocular dryness, which could be a potential advantage over soft contact lenses in terms of contact lens-induced dryness.

ArrayMining: a modular web-application for microarray analysis combining ensemble and consensus methods with cross-study normalization

Background: Statistical analysis of DNA microarray data provides a valuable diagnostic tool for the investigation of genetic components of diseases. To take advantage of the multitude of available data sets and analysis methods, it is desirable to combine both different algorithms and data from different studies. Applying ensemble learning, consensus clustering and cross-study normalization methods for this purpose in an almost fully automated process and linking different analysis modules together under a single interface would simplify many microarray analysis tasks. Results: We present ArrayMining.net, a web-application for microarray analysis that provides easy access to a wide choice of feature selection, clustering, prediction, gene set analysis and cross-study normalization methods. In contrast to other microarray-related web-tools, multiple algorithms and data sets for an analysis task can be combined using ensemble feature selection, ensemble prediction, consensus clustering and cross-platform data integration. By interlinking different analysis tools in a modular fashion, new exploratory routes become available, e.g. ensemble sample classification using features obtained from a gene set analysis and data from multiple studies. The analysis is further simplified by automatic parameter selection mechanisms and linkage to web tools and databases for functional annotation and literature mining. Conclusion: ArrayMining.net is a free web-application for microarray analysis combining a broad choice of algorithms based on ensemble and consensus methods, using automatic parameter selection and integration with annotation databases.

Transcultural adaptation and validation of the Celiac Dietary Adherence Test: a simple questionnaire to measure adherence to a gluten-free diet

Background and aims: A gluten-free diet is to date the only treatment available to celiac disease sufferers. However, systematic reviews indicate that, depending on the method of evaluation used, only 42% to 91% of patients adhere to the diet strictly. Transculturally adapted tools that evaluate adherence beyond simple self-informed questions or invasive analyses are, therefore, of importance. The aim is to obtain a Spanish transcultural adaption and validation of Leffler's Celiac Dietary Adherence Test. Methods: A two-stage observational transversal study: translation and back translation by four qualified translators followed by a validation stage in which the questionnaire was administered to 306 celiac disease patients aged between 12 and 72 years and resident in Aragon. Factorial structure, criteria validity and internal consistency were evaluated. Results: The Spanish version maintained the 7 items in a 3-factor structure. Feasibility was very high in all the questions answered and the floor and ceiling effects were very low (4.3% and 1%, respectively). The Spearman correlation with the self-efficacy and life quality scales and the self-informed question were statistically significant (p < 0.01). According to the questionnaire criteria, adherence was 72.3%. Conclusion: The Spanish version of the Celiac Dietary Adherence Test shows appropriate psychometric properties and is, therefore, suitable for studying adherence to a gluten-free diet in clinical and research environments.

Erosive potential of sugar-free hard candies dissolved in water and artificial saliva

Aim: To compare the acidity of sugar-free hard candies dissolved in water and artificial saliva. Methods: Sugar-free Flopi Florestal hard candies (grape, strawberry, cherry, orange, ginger, lemon balm, fennel) were selected and grouped in 2 groups: G-1 (candies dissolved in distilled water) and G-2 (candies dissolved in artificial saliva). Candies were triturated with a porcelain pestle, yielding two samples of 20 g. Samples were dissolved in 120 mL distilled water (G-1) and 120 mL artificial saliva (20 mM NaHCO3, 3 mM NaH2PO4.H2O and 1 mM CaCl2.2H2O) (G-2), obtaining three samples of 30 mL for each of the flavors and groups. pH was measured using potentiometer and combined glass electrode. Titratable acidity was evaluated by adding 100 μL 1M NaOH aliquots until reaching pH 5.5. For statistical analysis, analysis of variance (ANOVA) was used. Means were compared by the Tukey test at 5% significance level (p<0.05) Results: All flavors of G-1 showed pH values below 5.5. Comparison of groups in the same flavor showed a significant increase in pH in flavors of G-2. Comparison of the titratable acidity between G-1 and G-2, showed that fruit flavors were significantly different from each other, with reduced acidity in G-2. Conclusions: All evaluated candies are acid, and dilution in artificial saliva raised their pH and lowered their titratable acidity, reducing their erosive potential.

Systematic Improvement of Density Functionals through Parameter-Free Hybridization Schemes

It is suggested here that the ultimate accuracy of DFT methods arises from the type of hybridization scheme followed. This idea can be cast into a mathematical formulation utilizing an integrand connecting the noninteracting and the interacting particle system. We consider two previously developed models for it, dubbed as HYB0 and QIDH, and assess a large number of exchange-correlation functionals against the AE6, G2/148, and S22 reference data sets. An interesting consequence of these hybridization schemes is that the error bars, including the standard deviation, are found to markedly decrease with respect to the density-based (nonhybrid) case. This improvement is substantially better than variations due to the underlying density functional used. We thus finally hypothesize about the universal character of the HYB0 and QIDH models.

Understanding Co-translational Protein Targeting and Lithium Dendrite Formation through Free Energy Simulations and Coarse-Grained Models

We describe the application of alchemical free energy methods and coarse-grained models to study two key problems: (i) co-translational protein targeting and insertion to direct membrane proteins to the endoplasmic reticulum for proper localization and folding, (ii) lithium dendrite formation during recharging of lithium metal batteries. We show that conformational changes in the signal recognition particle, a central component of the protein targeting machinery, confer additional specificity during the the recognition of signal sequences. We then develop a three-dimensional coarse-grained model to study the long-timescale dynamics of membrane protein integration at the translocon and a framework for the calculation of binding free energies between the ribosome and translocon. Finally, we develop a coarse-grained model to capture the dynamics of lithium deposition and dissolution at the electrode interface with time-dependent voltages to show that pulse plating and reverse pulse plating methods can mitigate dendrite growth.

Design and application of experimental methods for steel sheet shearing

Shearing is the process where sheet metal is mechanically cut between two tools. Various shearing technologies are commonly used in the sheet metal industry, for example, in cut to length lines, slitting lines, end cropping etc. Shearing has speed and cost advantages over competing cutting methods like laser and plasma cutting, but involves large forces on the equipment and large strains in the sheet material. The constant development of sheet metals toward higher strength and formability leads to increased forces on the shearing equipment and tools. Shearing of new sheet materials imply new suitable shearing parameters. Investigations of the shearing parameters through live tests in the production are expensive and separate experiments are time consuming and requires specialized equipment. Studies involving a large number of parameters and coupled effects are therefore preferably performed by finite element based simulations. Accurate experimental data is still a prerequisite to validate such simulations. There is, however, a shortage of accurate experimental data to validate such simulations. In industrial shearing processes, measured forces are always larger than the actual forces acting on the sheet, due to friction losses. Shearing also generates a force that attempts to separate the two tools with changed shearing conditions through increased clearance between the tools as result. Tool clearance is also the most common shearing parameter to adjust, depending on material grade and sheet thickness, to moderate the required force and to control the final sheared edge geometry. In this work, an experimental procedure that provides a stable tool clearance together with accurate measurements of tool forces and tool displacements, was designed, built and evaluated. Important shearing parameters and demands on the experimental set-up were identified in a sensitivity analysis performed with finite element simulations under the assumption of plane strain. With respect to large tool clearance stability and accurate force measurements, a symmetric experiment with two simultaneous shears and internal balancing of forces attempting to separate the tools was constructed. Steel sheets of different strength levels were sheared using the above mentioned experimental set-up, with various tool clearances, sheet clamping and rake angles. Results showed that tool penetration before fracture decreased with increased material strength. When one side of the sheet was left unclamped and free to move, the required shearing force decreased but instead the force attempting to separate the two tools increased. Further, the maximum shearing force decreased and the rollover increased with increased tool clearance. Digital image correlation was applied to measure strains on the sheet surface. The obtained strain fields, together with a material model, were used to compute the stress state in the sheet. A comparison, up to crack initiation, of these experimental results with corresponding results from finite element simulations in three dimensions and at a plane strain approximation showed that effective strains on the surface are representative also for the bulk material. A simple model was successfully applied to calculate the tool forces in shearing with angled tools from forces measured with parallel tools. These results suggest that, with respect to tool forces, a plane strain approximation is valid also at angled tools, at least for small rake angles. In general terms, this study provide a stable symmetric experimental set-up with internal balancing of lateral forces, for accurate measurements of tool forces, tool displacements, and sheet deformations, to study the effects of important shearing parameters. The results give further insight to the strain and stress conditions at crack initiation during shearing, and can also be used to validate models of the shearing process.

Quantification of free auxins in semi-hardwood plant cuttings and microshoots by dispersive liquid–liquid microextraction/microwave derivatization and GC/MS analysis

Several studies have suggested that differences in the natural rooting ability of plant cuttings could be attributed to differences in endogenous auxin levels. Hence, during rooting experiments, it is important to be able to routinely monitor the evolution of endogenous levels of plant hormones. This work reports the development of a new method for the quantification of free auxins in auxin-treated Olea europaea (L.) explants, using dispersive liquid–liquid microextraction (DLLME) and microwave assisted derivatization (MAD) followed by gas chromatography/mass spectrometry (GC/MS) analysis. Linear ranges of 0.5–500 ng mL 1 and 1–500 mg mL 1 were used for the quantification of indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA), respectively. Determined by serial dilutions, the limits of detection (LOD) and quantification (LOQ) were 0.05 ng mL 1 and 0.25 ng mL 1, respectively for both compounds. When using the calibration curve for determination, the LOQ corresponded to 0.5 ng mL 1 (IAA) and 0.5 mg mL 1 (IBA). The proposed method proved to be substantially faster than other alternatives, and allowed free auxin quantification in real samples of semi-hardwood cuttings and microshoots of two olive cultivars. The concentrations found in the analyzed samples are in the range of 0.131–0.342 mg g 1 (IAA) and 20–264 mg g 1 (IBA).

Evaluation of frozen ground conditions along a coastal topographic gradient at Byers Peninsula (Livingston Island, Antarctica) by geophysical and geoecological methods

Geophysical surveying and geoelectricalmethods are effective to study permafrost distribution and conditions in polar environments. Geoelectrical methods are particularly suited to study the spatial distribution of permafrost because of its high electrical resistivity in comparison with that of soil or rock above 0 °C. In the South Shetland Islands permafrost is considered to be discontinuous up to elevations of 20–40ma.s.l., changing to continuous at higher altitudes. There are no specific data about the distribution of permafrost in Byers Peninsula, in Livingston Island, which is the largest ice-free area in the South Shetland Islands. With the purpose of better understanding the occurrence of permanent frozen conditions in this area, a geophysical survey using an electrical resistivity tomography (ERT)methodologywas conducted during the January 2015 field season, combined with geomorphological and ecological studies. Three overlapping electrical resistivity tomographies of 78meach were done along the same profile which ran from the coast to the highest raised beaches. The three electrical resistivity tomographies are combined in an electrical resistivitymodel which represents the distribution of the electrical resistivity of the ground to depths of about 13malong 158m. Several patches of high electrical resistivity were found, and interpreted as patches of sporadic permafrost. The lower limits of sporadic to discontinuous permafrost in the area are confirmed by the presence of permafrost-related landforms nearby. There is a close correspondence between moss patches and permafrost patches along the geoelectrical transect.