The role of intestinal microbiota in colorectal and breast cancer treatment:a pathway to personalised medicine?

Colorectal and breast cancer are common cancers worldwide. Classical chemotherapeutics remain the systemic backbone of cancer treatments here. However, chemotherapeutics have side effects and tumour response can be optimized. Pre-clinical studies have indicated that intestinal microbiota (bacteria) might be involved in the development of cancer and influence cancer treatment efficacy and side effects. However, limited clinical studies are available. This doctoral study examined the role of intestinal microbiota in colorectal and breast cancer and cancer treatment specifically. It was concluded that in patients with metastatic colorectal cancer the intestinal microbiota did not change during chemotherapy treatment with capecitabine. In addition, baseline intestinal microbiota composition could not predict tumour response in metastatic colorectal cancer patients. In postmenopausal hormone positive breast cancer patients the intestinal microbiota changed during the course of chemotherapy treatment with adriamycin, cyclophosphamide, and docetaxel. Postmenopausal women with or without breast cancer could not be differentiated based on the intestinal microbiota composition

Petri net modeling of cyber-physical attacks on smart grid

This paper investigates the use of Petri nets for modeling coordinated cyber-physical attacks on the smart grid. Petri nets offer more flexibility and expressiveness than traditional attack trees to represent the actions of simultaneous attackers. However, Petri net models for attacks on very large critical infrastructures such as the smart grid require a great amount of manual effort and detailed expertise in cyber-physical threats. To overcome these obstacles, we propose a novel hierarchical method to construct large Petri nets from a number of smaller Petri nets that can be created separately by different domain experts. The construction method is facilitated by a model description language that enables identical places in different Petri nets to be matched. The new modeling approach is described for an example attack on smart meters, and its efficacy is demonstrated by a proof-of-concept Python program

Perceived effectiveness of clinical pathway software: A before-after study in the Netherlands

Background: Clinical pathways (CPs) increase in popularity and are known to lead to several benefits in the hospital environment. Clinical pathways can be either paper-based or software-based. It is

The significance of text in the teaching of reading in the early years

The goal of this study was (1) to investigate the development of decoding (efficiency), reading comprehension, vocabulary and spelling during the elementary school years and (2) to determine the differences between poor, average and good performers with regard to the development of these skills. Twice each year two standardized tests for each skill were administered. For two successive periods, one of the tests for each skill was the same. To describe the development in terms of a latent variable evolving across grades, the structured-means version of the structural equation model was used. The growth was expressed in terms of effect size. With respect to the first question, clear seasonal effects were found for reading comprehension, vocabulary and spelling, while the seasonal effect for decoding efficiency was restricted to the early grades. Progress tended to be greater from fall to spring than from spring to fall. For decoding efficiency, and to a lesser degree for vocabulary and spelling, growth showed a declining trend across grades. For reading comprehension, the progress in grade 2 was lower than the progress in grade 3, but progress was declining across higher grades. With respect to the second question, it appeared that initially low performers on reading comprehension, vocabulary and spelling tended to show a greater progress, especially in periods where the largest amount of instruction was given. Although it was found that the low, medium and high ability groups remain in the same order, as far as their means are concerned, these findings do not confirm the existence of a Matthew effect for reading comprehension, vocabulary and spelling. For decoding efficiency no clear differential effect could be found: the gap between the poor and good performers did not widen over time for this skill

Prediction of word recognition in the first half of grade 1

Item does not contain fulltextEarly detection of reading problems is important to prevent an enduring lag in reading skills. We studied the relationship between speed of word recognition (after six months of grade 1 education) and four kindergarten pre-literacy skills: letter knowledge, phonological awareness and naming speed for both digits and letters. Our sample consisted of 178 pupils divided over seven classes. In agreement with the literature, we found that all four kindergarten tests were related to speed of word recognition in grade 1. We also performed a multiple regression analysis with a set of background variables and the four kindergarten tests. The model explained 53% of the variance in speed of word recognition. However, only letter knowledge and naming speed for digits had a significant direct effect. Our conclusion is, nevertheless, that all four kindergarten tests should be used to identify children at risk for reading problems.10 p

Perceived effectiveness of clinical pathway software: A before-after study in the Netherlands

Background: Clinical pathways (CPs) increase in popularity and are known to lead to several benefits in the hospital environment. Clinical pathways can be either paper-based or software-based. It is known that paper-based CPs can result in more paperwork instead of simplifying daily routines of healthcare workers. Insufficient research has been done o

Spatial Reference in Momu

Spatial reference - how we communicate notions such as location, motion and direction - is an important area of current research. Recent studies involving detailed analysis of geographically and typologically diverse languages have uncovered extensive and unexpected variation in the means languages utilise to encode spatial relations. This thesis aims to contribute to the growing body of knowledge about the cross-linguistic representation of the spatial domain. It is an analysis of fieldwork data which was collected for a preliminary investigation into the spatial reference system of Momu (also known as Fas), a Kwomtari language spoken in the West Sepik region of Papua New Guinea. The analysis focuses on descriptions of static location, motion and the use of frames of reference. In Momu, all basic locative, directional and motion verbs are deictically anchored, such that there are few expressions of spatial reference that do not obligatorily require deictic specification. This thesis demonstrates the particular attention Momu pays to the specification of deixis across all major sub-areas of the spatial domain.Australian Research Council [William Foley, Chief Investigator

Стилі керівництва як моделі вербальної поведінки у корпоративному дискурсі

Статья посвящена анализу лингвистических особенностей директивного и демократического стилей руководства как распространенных моделей вербального поведения в корпоративном дискурсе. Внимание уделяется также гендерному фактору, который учитывается при авторитарном коммуникативном поведении.Стаття присвячена аналізові лінгвістичних особливостей директивного та демократичного стилів керівництва як поширених моделей вербальної поведінки у корпоративному дискурсі. Увага приділяється також гендерному фактору, який враховується в авторитарній комунікативній поведінці.The article is dedicated to the analysis of linguistic peculiarities of the directive and democratic management styles as models of the verbal behaviour in the corporate discourse. Attention is also paid to the gender factor, which is considered in the authoritarian communicative behaviour

Pharmacokinetics and safety/tolerability of isoniazid, rifampicin and pyrazinamide in children and adolescents treated for tuberculous meningitis

OBJECTIVE: To assess the pharmacokinetics and safety/tolerability of isoniazid, rifampicin and pyrazinamide in children and adolescents with tuberculous meningitis (TBM). DESIGN: Prospective observational pharmacokinetic study with an exploratory pharmacokinetic/pharmacodynamic analysis. SETTING: Hasan Sadikin Hospital, Bandung, Indonesia. PATIENTS: Individuals aged 0–18 years clinically diagnosed with TBM and receiving first-line anti-tuberculosis drug dosages according to revised WHO-recommended treatment guidelines. INTERVENTIONS: Plasma and cerebrospinal fluid (CSF) concentrations of isoniazid, rifampicin and pyrazinamide were assessed on days 2 and 10 of treatment. MAIN OUTCOME MEASURES: Plasma exposures during the daily dosing interval (AUC(0–24)), peak plasma concentrations (C (max)) and CSF concentrations. RESULTS: Among 20 eligible patients, geometric mean AUC(0–24) of isoniazid, rifampicin and pyrazinamide was 18.5, 66.9 and 315.5 hour∙mg/L on day 2; and 14.5, 71.8 and 328.4 hour∙mg/L on day 10, respectively. Large interindividual variabilities were observed in AUC(0–24) and C (max) of all drugs. All patients had suboptimal rifampicin AUC(0–24) for TBM treatment indication and very low rifampicin CSF concentrations. Four patients developed grade 2–3 drug-induced liver injury (DILI) within the first 4 weeks of treatment, in whom anti-tuberculosis drugs were temporarily stopped, and no DILI recurred after reintroduction of rifampicin and isoniazid. AUC(0–24) of isoniazid, rifampicin and pyrazinamide along with C (max) of isoniazid and pyrazinamide on day 10 were higher in patients who developed DILI than those without DILI (p<0.05). CONCLUSION: Higher rifampicin doses are strongly warranted in treatment of children and adolescents with TBM. The association between higher plasma concentrations of isoniazid, rifampicin and pyrazinamide and the development of DILI needs confirmatory studies