Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues

In a randomized, double-blind, Phase III study, we compared pasireotide long-acting release (pasireotide LAR) with octreotide long-acting repeatable (octreotide LAR) in managing carcinoid symptoms refractory to first-generation somatostatin analogues. Adults with carcinoid tumors of the digestive tract were randomly assigned (1:1) to receive pasireotide LAR (60 mg) or octreotide LAR (40 mg) every 28 days. Primary outcome was symptom control based on frequency of bowel movements and flushing episodes. Objective tumor response was a secondary outcome. Progression-free survival (PFS) was calculated in a post hoc analysis. Adverse events were recorded. At the time of a planned interim analysis, the data monitoring committee recommended halting the study because of a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (n=43 pasireotide LAR, 20.9%; n=45 octreotide LAR, 26.7%; odds ratio, 0.73; 95% confidence interval [CI], 0.27–1.97; P=0.53). Tumor control rate at month 6 was 62.7% with pasireotide and 46.2% with octreotide (odds ratio, 1.96; 95% CI, 0.89–4.32; P=0.09). Median (95% CI) PFS was 11.8 months (11.0 – not reached) with pasireotide versus 6.8 months (5.6 – not reached) with octreotide (hazard ratio, 0.46; 95% CI, 0.20–0.98; P=0.045). The most frequent drug-related adverse events (pasireotide vs octreotide) included hyperglycemia (28.3% vs 5.3%), fatigue (11.3% vs 3.5%), and nausea (9.4% vs 0%). We conclude that, among patients with carcinoid symptoms refractory to available somatostatin analogues, similar proportions of patients receiving pasireotide LAR or octreotide LAR achieved symptom control at month 6. Pasireotide LAR showed a trend toward higher tumor control rate at month 6, although it was statistically not significant, and was associated with a longer PFS than octreotide LAR

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio

Language Learning Approaches: Unity in Diversity

This is a conceptual paper based on the existing literature related to three famous language learning theories; Audio-lingual Method, Communicative method and the hypotheses of Stephen D. Krashen. These three schools of thought are not usually seen as similar or it is not common to find much literature regarding these theories having any common traits. The individual criticism on each of these theories focuses on many of their individual aspects but not on similarities among these three. The researchers however, after studying these theories closely, have been able to extract some striking similarities in spite of all the commonly known differences. The aim of this paper is to invite more focus and more research on similarities shared by these apparently independent schools of thought and consequently exploit the maximum fruits of these powerful theories. The findings suggest that the multiple similarities among the three schools of thought under study can jointly be named as one very vividly common trait: stress on the communicative skills involving listening and speaking to be the key towards successful language learning

Efficient in vitro propagation of Amaranthus viridis L. using node explants

Hyperhydricity is a frequently problem in plants during in vitro culture and affected micropropagation of plants. To develop an efficient in vitro regenerated system without hyperdydricity, we demonstrated the effect of different disinfected agents (mercuric chlorite and hypochlorite), growth regulators, their concentrations and combinations, Agar, pH, ammonium nitrate (NH₄NO₃) and number of subcultures. Mercuric chlorite at 0.07% and exposing time (9–10 min) was appropriate for hygienic culture. The shoots induced by Benzyladnine (BA) alone or in combination with α-Naphthaleneacetic acid (NAA) exhibited maximum multiplication with symptoms of hyperhydricity than those induced by Kinetin alone or in combination with NAA. Hyperhydricity was also reduced by increasing the concentration of agar, pH and elimination of NH₄NO₃ from the macroelements of Murashig and Skoog (MS) medium. Repeated subcultures affected both multiplication and hyperhydricity. The multiplication of shoots increased from parental culture up to 5th subculture and thereafter declined in 6th subculture. Although shoot hyperhydricity were observed from 1st subculture (19%) and then increased up to 85% in 6th subculture. This increased in hyperhydricity could be due to the remaining influence of hormones. In shoots of 5th subculture the content of chlorophyll (dark green) were higher than shoots of 6th subculture

Haemostasis in ischaemic stroke and vascular dementia

Abnormalities of coagulation and fibrinolysis may play an important role in the pathogenesis of ischaemic stroke and vascular dementia. We aimed to determine whether haemostatic function is altered in acute recent-onset or chronic ischaemic cerebrovascular disease. We studied consecutive patients with ischaemic stroke (n = 74) and vascular dementia (n = 42) compared with healthy controls (n = 40) in a case-control study. The ischaemic stroke group was assessed twice, 3-10 days after the acute stroke and at 1-3 months. Fibrinogen, fibrin D- dimer (marker of fibrin turnover) and von Willebrand factor (vWF) (marker of endothelial disturbance) were elevated acutely (P lt 0.0001) and in the convalescent phase after ischaemic stroke (P lt 0.0001, P lt 0.0001, and P lt 0.01 respectively, compared with controls). Similar results were seen in the vascular dementia group. Stepwise multivariate regression analyses showed that cerebrovascular disease correlated independently with fibrinogen (P lt 0.001) and fibrin D-dimer levels (P lt 0.001), while vWF correlated independently with electrocardiograph evidence of ischaemic heart disease (P = 0.004). Changes between acute and convalescent phases in ischaemic stroke were slightly inconsistent. However, in the acute stage there were tendencies for fibrinogen, D-dimer and vWF to be increased, and factor VIII was significantly higher. Abnormalities of haemostasis, including increased fibrin turnover and endothelial disturbance, are found in both acute and chronic cerebral ischaemia. Many of these patients have co- existent ischaemic heart disease and this may contribute to some of these changes. Acute ischaemic stroke is associated with transient changes in haemostatic factors; however, most abnormalities persist into the convalescent phase, and are also demonstrable in subjects with vascular dementia

Water safety plans - Book 3: Risk assessment of contaminant intrusion into water distribution systems

This book has been written specifically for practitioners involved in the operation, maintenance and management of piped water distribution systems in urban areas of developing countries. These practitioners include engineers, planners, managers, and water professionals involved in the monitoring, control and rehabilitation of water distribution networks. The book explains in detail how to evaluate the risk of deterioration of the water distribution network of a water supply system. It begins with the conceptualization of risk evaluation and its three different components (hazard, vulnerability and risk). The book further elaborates on each of these three components, explains the methodologies used to estimate the components, and presents the background to the mathematical models. Finally, the book explains how these components are integrated to form a GIS-based decision support system for risk evaluation. The book is designed to help practitioners understand the concept of risk evaluation and supports the manual of the IRA-WDS software, a GIS-based decision support system for risk evaluation. The IRA-WDS software is developed for the evaluation of risk to piped water distribution systems in urban areas of developing countries. The user of this software needs to know about the consideration of different factors, data type and requirement, which may vary from one region to another. The user can understand the concept of evaluation from this book and decide upon the importance of the different factors involved and associated data collection. It should be noted that combining this book with Water Safety Plans Book 1 provides the decision-maker with a valuable tool to assess the overall risk of contaminant intrusion into a water supply system. It is also important to consider this book in relation to Water Safety Plans Book 2, as it is imperative that the institutions and authorities responsible for water management have the capacity to use and implement IRA-WDS, and also to recognize the importance of developing an integrated approach to water management. The WEDC Water Safety Plans series comprises: Book 1: Planning Water Safety Management for Urban Piped Water Supplies in Developing Countries; Book 2: Supporting Water Safety Management for Urban Piped Water Supplies in Developing Countries; Book 3: Risk Assessment of Contaminant Intrusion into Water Distribution Systems; Book 4: IRA-WDS Software and Manual for Risk Assessment of Contaminant Intrusion into Water Distribution Systems

Fighting geminiviruses by RNAi and vice versa

Geminiviruses have recently emerged not only as the cause of devastating diseases of important crop plants but also as a tool to study fundamental aspects of RNA interference (RNAi) and virus-induced gene silencing. RNA silencing is an evolutionary conserved mechanism protecting cell from pathogenic RNA and DNA, which is increasingly viewed as an adaptive immune system of plants against viruses. Here we summarize recent developments in the field of geminivirology presented by several leading groups at the Meeting "Gemini2004" (a total of 85 participants from all over the world) with the main focus on the anti-viral strategies that exploit RNAi and related silencing phenomena