A New Method for the High-Precision Assessment of Tumor Changes in Response to Treatment

Imaging demonstrates that preclinical and human tumors are heterogeneous, i.e. a single tumor can exhibit multiple regions that behave differently during both normal development and also in response to treatment. The large variations observed in control group tumors can obscure detection of significant therapeutic effects due to the ambiguity in attributing causes of change. This can hinder development of effective therapies due to limitations in experimental design, rather than due to therapeutic failure. An improved method to model biological variation and heterogeneity in imaging signals is described. Specifically, Linear Poisson modelling (LPM) evaluates changes in apparent diffusion co-efficient (ADC) before and 72 hours after radiotherapy, in two xenograft models of colorectal cancer. The statistical significance of measured changes are compared to those attainable using a conventional t-test analysis on basic ADC distribution parameters. When LPMs were applied to treated tumors, the LPMs detected highly significant changes. The analyses were significant for all tumors, equating to a gain in power of 4 fold (i.e. equivelent to having a sample size 16 times larger), compared with the conventional approach. In contrast, highly significant changes are only detected at a cohort level using t-tests, restricting their potential use within personalised medicine and increasing the number of animals required during testing. Furthermore, LPM enabled the relative volumes of responding and non-responding tissue to be estimated for each xenograft model. Leave-one-out analysis of the treated xenografts provided quality control and identified potential outliers, raising confidence in LPM data at clinically relevant sample sizes

Contrainte suffixales et Ia disponibilite morphologique

Depuis les annees 1970 Ia question de productivite n'a cesse d'attirer J"attention des linguistes qui s·interessent a !"etude des precedes morphologiques. Toutefois, Ia plupart des tra\ aux dans ce domaine portent sur Ia mesure stati stique qui cherche a etabl ir Ia producti,·ite quantitati,·e des procedes en question. L'aspect qualitatif semble relati,·ement marginalise. Le point de vue adopte ici est que Ia di sponibilite des suffixes constructionnels peut etre etudiee d'un point de vue multidimensionnel. En nous appuyant. d'une part. sur ]"approche lexematique de Ia morphologie constructionnelle ct. d ·autre part. sur le principe de contraime de Ia Theorie de r Optimalite, no us proposons quatre criteres avec un systeme de contraintes pour r examen de Ia disponibilite des suffixes apprehendee d'un point de vue qual itatif en fran~ais et probablement applicable en d · autres langues com parables. otre proposition est ensuite appliquee a cinq suffixes du franyais- -ant. -eur -ier. -iste et -oi

Two Cooperating Manipulators with Fractional Controllers

This paper analyzes the dynamic performance of two cooperative robot manipulators. It is studied the implementation of fractional-order algorithms in the position/force control of two cooperating robotic manipulators holding an object. The simulations reveal that fractional algorithms lead to performances superior to classical integer-order controllers

A PROPOS DU STATUT AGENTIF DES SUFFIXES –ANT, -IER, -ISTE ET –OIR DU FRANCAIS

En français, certains suffixes sont considérés comme susceptibles de construire des noms d’agent. Cependant, il n’y a pas de consensus parmi les morphologues de la langue française lorsqu’il s’agit de la liste des suffixes que l’on peut utiliser pour former les noms d’agent. Dans ce travail, nous étudions le statut agentif de quatre suffixes français : -ant, -ier, -iste, et –oir. Nous prenons comme cadre théorique la morphologie constructionnelle. Nous considérons ainsi le lexème comme l’unité minimale pour la construction morphologique. Pour servir de base de matériel, nous nous reposons sur l’inventaire des noms d’agent fait à partir du Trésor de la langue française informatisé. Notre étude montre que les quatre suffixes ont été chacun utilisés pour former des noms d’agent et donc méritent le statut de suffixes agentifs en français

CONTRAINTES SUFFIXALES ET LA DISPONIBILITÉ MORPHOLOGIQUE

Depuis les années 1970 la question de productivité n’a cessé d’attirer l’attention des linguistes qui s’intéressent à l’étude des procédés morphologiques. Toutefois, la plupart des travaux dans ce domaine portent sur la mesure statistique qui cherche à établir la productivité quantitative des procédés en question. L’aspect qualitatif semble relativement marginalisé. Le point de vue adopté ici est que la disponibilité des suffixes constructionnels peut être étudiée d’un point de vue multidimensionnel. En nous appuyant, d’une part, sur l’approche lexématique de la morphologie constructionnelle et, d’autre part, sur le principe de contrainte de la Théorie de l’Optimalité, nous proposons quatre critères avec un système de contraintes pour l’examen de la disponibilité des suffixes appréhendée d'un point de vue qualitatif en français et probablement applicable en d’autres langues comparables. Notre proposition est ensuite appliquée à cinq suffixes du français - -ant, -eur –ier, -iste et –oir

Gene drive: Progress and prospects

This is the author accepted manuscript. The final version is available from the Royal Society via the DOI in this recordData accessibility: This article does not contain any additional data.Gene drive is a naturally occurring phenomenon in which selfish genetic elements manipulate gametogenesis and reproduction to increase their own transmission to the next generation. Currently, there is great excitement about the potential of harnessing such systems to control major pest and vector populations. If synthetic gene drive systems can be constructed and applied to key species, they may be able to rapidly spread either modifying or eliminating the targeted populations. This approach has been lauded as a revolutionary and efficient mechanism to control insect-borne diseases and crop pests. Driving endosymbionts have already been deployed to combat the transmission of dengue and Zika virus in mosquitoes. However, there are a variety of barriers to successfully implementing gene drive techniques in wild populations. There is a risk that targeted organisms will rapidly evolve an ability to suppress the synthetic drive system, rendering it ineffective. There are also potential risks of synthetic gene drivers invading nontarget species or populations. This Special Feature covers the current state of affairs regarding both natural and synthetic gene drive systems with the aim to identify knowledge gaps. By understanding how natural drive systems spread through populations, we may be able to better predict the outcomes of synthetic drive release

Selfish genetic elements and male fertility

This is the author accepted manuscript. The final version is available from the Royal Society via the DOI in this recordSelfish Genetic Elements (SGEs) are diverse and near ubiquitous in Eukaryotes and can be potent drivers of evolution. Here we discuss SGEs that specifically act on sperm to gain a transmission advantage to the next generation. The diverse SGEs that affect sperm often impose costs on carrier males, including damaging ejaculates, skewing offspring sex-ratios and in particular reducing sperm competitive success of SGE carrying males. How males and females tolerate and mitigate against these costs is a dynamic and expanding area of research. The intense intra-genomic conflict that these selfish elements generate could also have implications for male fertility and spermatogenesis more widely

Sinteza i antihipoksično djelovanje alifatskih i arilalifatskih amida kofein-8-tioglikolne kiseline

The synthesis of some aliphatic and arylaliphatic amides of caffeine-8-thioglycolic acid was studied. The structures of synthesized compounds were proved by microanalyses, IR- and 1H NMR data. Values of acute p.o. and i.p. toxicity in mice show lower toxicity compared to caffeine. Declines in spontaneous locomotor activity support the idea of depressive CNS activity of the compounds. Two compounds exhibited brain antihypoxic activity (5a and 5b against haemic and circulatory hypoxia, respectively).U radu je opisana sinteza alifatskih i arilalifatskih amida kofein-8-tioglikolne kiseline i njihova karakterizacija elementarnom analizom, IR- i 1H NMR spektroskopijom. Testiranja na miševima pokazuju da su sintetizirani spojevi primijenjeni p.o. i i.p. manje toksični od kofeina. Smanjenje lokomotoričke aktivnosti podupire ideju o njihovom depresivnom djelovanju na SŽS. Spojevi 5a i 5b djeluju antihipoksički u uvjetima krvne i cirkulacijske hipoksije u mozgu

Barriers to early presentation of self-discovered breast cancer in Singapore and Malaysia: a qualitative multicentre study

Objective: To explore and compare barriers to early presentation of self-discovered breast cancer in Singapore and Malaysia. Design: A qualitative interview study with thematic analysis of transcripts. Participants: 67 patients with self-discovered breast symptoms were included in the analysis. Of these, 36% were of Malay ethnicity, 39% were Chinese and 25% Indian, with an average age of 58 years (range 24–82 years). The number of women diagnosed at early stages of cancer almost equalled those at advanced stages. Approximately three-quarters presented with a painless lump, one-quarter experienced a painful lump and 10% had atypical symptoms. Setting: University hospital setting in Singapore and Malaysia. Results: Patients revealed barriers to early presentation not previously reported: the poor quality of online website information about breast symptoms, financial issues and the negative influence of relatives in both countries, while perceived poor quality of care and services in state-run hospitals and misdiagnosis by healthcare professionals were reported in Malaysia. The pattern of presentation by ethnicity remained unchanged where more Malay delayed help-seeking and had more advanced cancer compared to Chinese and Indian patients. Conclusions: There are few differences in the pattern of presentation and in the reported barriers to seek medical care after symptom discovery between Singapore and Malaysia despite their differing economic status. Strategies to reduce delayed presentation are: a need to improve knowledge of disease, symptoms and causes, quality of care and services, and quality of online information; and addressing fear of diagnosis, treatment and hospitalisation, with more effort focused on the Malay ethnic group. Training is needed to avoid missed diagnoses and other factors contributing to delay among health professionals