Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling

The aim of this work is to review current knowledge relating the established cancer hallmark, sustained cell proliferation to the existence of chemicals present as low dose mixtures in the environment. Normal cell proliferation is under tight control, i.e. cells respond to a signal to proliferate, and although most cells continue to proliferate into adult life, the multiplication ceases once the stimulatory signal disappears or if the cells are exposed to growth inhibitory signals. Under such circumstances, normal cells remain quiescent until they are stimulated to resume further proliferation. In contrast, tumour cells are unable to halt proliferation, either when subjected to growth inhibitory signals or in the absence of growth stimulatory signals. Environmental chemicals with carcinogenic potential may cause sustained cell proliferation by interfering with some cell proliferation control mechanisms committing cells to an indefinite proliferative span.

Reading aloud in high schools: students and teachers across the curriculum

Reading aloud is apparently an indispensible part of teaching. Nevertheless, little is known about reading aloud across the curriculum by students and teachers in high schools. Nor do we understand teachers’ attitudes towards issues such as error correction, rehearsal time, and selecting students to read. A survey of 360 teachers in England shows that, although they have little training in reading aloud, they are extremely confident. Reading aloud by students and teachers is strongly related, and serves to further understanding rather than administrative purposes or pupils’ enjoyment. Unexpectedly, Modern Language teachers express views that set them apart from other subjects.

The grass-free lawn: floral performance and management implications

Grass lawns are a ubiquitous feature of urban green-space throughout much of the temperate world. Species poor and intensively managed, lawns are ecologically impoverished, however environmentally aware lawn owners are reluctant to implement alternatives due to aesthetic concerns. Developing an alternative lawn format which is both biodiversity friendly and aesthetically pleasing is an imperative for urban greening. We suggest that such an alternative can be provided by replacing the grass lawn by a forb-based mix. To advance this, we tested the floral performance of three groups of clonal perennial forbs (native, non-native and mixed), each maintained using standard lawn management mowing regimes. Our findings show that both the frequency of mowing and the height at which mowing is applied influence floral performance and lawn aesthetics. Species origin was found to influence floral productivity, floral visibility and floral variety within grass-free lawns, with native species providing the greatest floral performance. The behaviour and management of grass lawns was not found to be a suitable analogue for the management of grass-free lawns and grass-free lawns are sufficiently different from grass lawns to require an entirely original management approach. We suggest that the grass-free lawn can provide an aesthetically and environmentally relevant replacement for the ubiquitous and ecologically-poor grass lawn.

The practice of reading aloud in the high school: a preliminary investigation

The paper considers students’ views of why reading aloud takes place and what are its effects.The results of two small focus-group discussions are presented, in which high school students were given the opportunity to express their responses to the practice of reading aloud in the classroom. Their responses are considered in the context of theoretical perspectives: pedagogical, reader-response and social/vocational. Analysis of responses reveals acknowledgement that reading aloud is not only a useful skill but also that it is a site of anxiety and even conflict.

Global Gene Expression Analysis during Germination in the Chytridiomycete Blastocladiella emersonii

Blastocladiella emersonii is an aquatic fungus of the Chytridiomycete class. During germination, the zoospore, a motile nongrowing cell, goes through a cascade of morphological changes that culminates with its differentiation into the germling cell, capable of coenocytic vegetative growth. Transcriptome analyses of B. emersonii cells were carried out during germination induced under various environmental conditions. Microarray data analyzing 3,563 distinct B. emersonii genes revealed that 26% of them are differentially expressed during germination in nutrient medium at at least one of the time points investigated. Over 500 genes are upregulated during the time course of germination under those conditions, most being related to cell growth, including genes involved in protein biosynthesis, DNA transcription, energetic metabolism, carbohydrate and oligopeptide transport, and cell cycle control. On the other hand, several transcripts stored in the zoospores are downregulated during germination in nutrient medium, such as genes involved in signal transduction, amino acid transport, and chromosome organization. In addition, germination induced in the presence of nutrients was compared with that triggered either by adenine or potassium ions in inorganic salt solution. Several genes involved in cell growth, induced during germination in nutrient medium, do not show increased expression when B. emersonii zoospores germinate in inorganic solution, suggesting that nutrients exert a positive effect on gene transcription. The transcriptome data also revealed that most genes involved in cell signaling show the same expression pattern irrespective of the initial germination stimulus.

Individualisering i moderna språk : En kvalitativ studie om hur sex lärare i moderna språk förhåller sig till individualisering i undervisningen

Syftet med studien är att undersöka hur sex lärare i moderna språk förhåller sig till individualisering i undervisningen. Metoden som använts är kvalitativa forskningsintervjuer med språklärare verksamma inom såväl grundskolan som gymnasiet. Undersökningens resultat åskådliggör en mångfald av tolkningar kring individualiseringsuppdraget hos lärare i moderna språk. Utifrån informanternas svar identifieras tre skilda individualiseringsmodeller. I den första modellen framstår individualiseringen framförallt som en metod baserad på nivåindelning och användande av särskilt material. Individualisering beskrivs i den andra modellen som ett förhållningssätt, att beakta elevernas olikhet, och utformas under en rad olika inslag, från planering till utvärdering. I den tredje modellen nås individualisering i helklassundervisning genom varierande arbetsformer samt lärarens kontakt med eleverna under lektionen. Att läraren snarare ansluter sig till en av dessa tre modeller tycks hänga samman med vilka behov och risker denne förknippar med individualisering.

Detectando não-linearidades nos retornos dos fundos multimercados

Estudos recentes apontam que diversas estratégias implementadas em hedge funds geram retornos com características não lineares. Seguindo as sugestões encontradas no paper de Agarwal e Naik (2004), este trabalho mostra que uma série de hedge funds dentro da indústria de fundos de investimentos no Brasil apresenta retornos que se assemelham ao de uma estratégia em opções de compra e venda no índice de mercado Bovespa. Partindo de um modelo de fatores, introduzimos um índice referenciado no retorno sobre opções de modo que tal fator possa explicar melhor que os tradicionais fatores de risco a característica não linear dos retornos dos fundos de investimento.

Islamic law and international law: the terms of a relationship

The relationship between Islamic Law and other legal systems (basically western type domestic legal orders and international law) is often thought of in terms of compatibility or incompatibility. Concerning certain subject matters of choice, the compatibility of Islamic (legal) principles with the values embedded in legal systems that are regarded as characteristic of the Modern Age is tested by sets of questions: is democracy possible in Islam? Does Islam recognize human rights and are those rights equivalent to a more universal conception? Does Islam recognize or condone more extreme acts of violence and does it justify violence differently? Etc. Such questions and many more presuppose the existence of an ensemble of rules or principles which, as any other set of rules and principles, purport to regulate social behavior. This ensemble is generically referred to as Islamic Law. However, one set of questions is usually left unanswered: is Islamic Law a legal system? If it is a legal system, what are its specific characteristics? How does it work? Where does it apply? It is this paper`s argument that the relationship between Islamic Law and domestic and international law can only be understood if looked upon as a relationship between distinct legal systems or legal orders.

Crisis communication: organization's reactions to unexpected events

A reputação é considerada o ativo mais importante das empresas. Ela permite o estabelecimento de relações comerciais e garante um bom funcionamento da organização. Quando um evento inesperado surge, a reputação pode ser ameaçada. Os gerentes, líderes da organização, têm então que demonstrar reatividade e capacidade em responder as necessidades dos stakeholders, e capacidade de detectar e consertar as falhas dentro da organização através de um processo de aprendizagem, para evitar conseqüências negativas que poderiam danificar a reputação e impactar o desenvolvimento operacional da empresa. Através da comunicação de crise, observamos que depois da queda do avião AF 447, a companhia Air France adotou diferentes posturas adaptadas ao pedido dos stakeholders e ao grau de ameaça sofrido. Logo depois do acidente, a empresa decidiu adotar a estratégia do reconhecimento, assumindo uma responsabilidade simbólica e comunicando prioritariamente para as famílias das vitimas e para a mídia. Nas seguintes semanas ela utilizou a estratégia do silêncio que consiste em não comunicar diretamente a mídia. Finalmente, ela usou a estratégia do “bode expiatório” quando ela foi sujeita a ataques diretos. As reações da empresa somadas ao avanço das investigações judiciais revelaram falhas organizacionais “históricas” dentro da própria empresa, como por exemplo, a falta de comunicação entre pilotos e gerentes ou uma falha de sensibilidade técnica e operacional da parte dos gerentes. Apesar de problemas interno e externo, a Air France demonstrou que uma comunicação de crise bem gerenciada limita os impactos financeiros e de reputação. As conseqüências negativas sofridas pela companhia Air France foram limitadas.

Jus Cogens: ainda esse desconhecido

Existência de um jus cogens, categoria de normas imperativas do direito internacional, é cada vez mais aceita, apesar de ser ainda cercada de incertezas. Tendo recebido uma definição e um regime jurídico na convenção de viena sobre direito dos tratados, seu conceito, seu conteúdo e seus efeitos permanecem incertos. Seu estudo e sua compreensão impõem a análise de sua relação com a idéia de uma hierarquia de normas no direito internacional e dos elementos de proximidade e diferenciação com outras categorias polêmicas da teoria internacionalista: o direito internacional geral, as obrigações erga omnes, os crimes internacionais. As dúvidas que decorrem desse exercício devem orientar a reflexão sobre o conceito e sua contribuição para o direito internacional.