Characterisation of the sensitivity of Zymoseptoria tritici to demethylation inhibitors in Europe

The fungal pathogen Zymoseptoria tritici (formerly Septoria tritici) causes Septoria tritici blotch (STB), one of the most yield reducing diseases of wheat worldwide. In addition to cultural control measures and the cultivation of wheat varieties with a level of disease resistance, STB control relies heavily on the application of foliar fungicides with different modes of action. The demethylation inhibitors (DMIs) have been one of the most widely applied fungicides for many decades and belong to one of the most important fungicide modes of action in STB management. DMIs inhibit the sterol 14α-demethylase, an essential enzyme in the ergosterol biosynthesis pathway, encoded by the CYP51 gene of fungi. Widespread and intensive use of the DMIs over time has led to a continuous negative shift in the sensitivity of Z. tritici towards DMIs that have been used for a long time. This shift in sensitivity is mainly driven by the accumulation of mutations in the CYP51 gene resulting in the selection of various CYP51 haplotypes. More recently, CYP51 overexpression and an increased efflux activity, based on the overexpression of the MFS1 transporter, have been shown to be additional mechanisms affecting DMI sensitivity of Z. tritici. Inserts in the CYP51 promotor (CYP51p) and MFS1 promotor (MFS1p) were observed to be responsible for CYP51 and MFS1 overexpression. The prevalence and contribution of different DMI resistance mechanisms to a reduced DMI sensitivity of Z. tritici were investigated in isolates from across Europe in 2016 and 2017. The CYP51 gene of all isolates was sequenced and the CYP51p and MFS1p was investigated for inserts in order to determine the character of the CYP51 haplotypes as well as to identify CYP51 overexpression or if an increased efflux activity was occurring in these isolates. Overall, it was shown that the occurrence of CYP51 haplotypes was still the most frequent and important mechanism conferring a reduction in sensitivity to DMIs by Z. tritici in Europe. Nevertheless, an increase in the frequency of isolates exerting CYP51 overexpression and those exhibiting increased efflux activity was observed compared to earlier studies. Glasshouse data demonstrated that DMIs can still contribute to disease control, and in some cases give full control, of STB even if isolates expressed CYP51 overexpression and/or an increased efflux in addition to also carrying moderately or highly adapted CYP51 haplotypes. However, in order to prevent the further increase and spread of further adapted CYP51 haplotypes plus additional resistance mechanisms in the Z. tritici population across Europe, anti-resistance-management strategies should be a high priority in the use of DMIs. In addition, especially integrated disease management strategies, such as the appropriate choice of cultivars, should be applied in order to keep STB disease pressure low and consequently reduce the number of fungicide applications. Moreover, resistance-management strategies may exploit the limited cross-resistance between different DMIs, for example, by the use of mixtures or alternation of different DMI fungicides. However, control strategies should also incorporate the use of fungicides with different MOAs. The aim of all these strategies is to reduce selection of adapted Z. tritici isolates and consequently to prolong the efficacy of DMIs in STB management.Der pilzliche Schaderreger Zymoseptoria tritici verursacht die Septoria-Blattdürre (STB) an Weizen, eine der wichtigsten Krankheiten hinsichtlich der Ertragsreduktion im Weizenanbau. Neben ackerbaulichen Maßnahmen und dem Anbau von Weizensorten mit geringerer Krankheitsanfälligkeit, beruht die Kontrolle dieses Pathogens überwiegend auf der Anwendung von blattaktiven Fungiziden mit unterschiedlichen Wirkmechanismen. In den letzten Jahrzenten stellten hierbei die Demethylierungsinhibitoren (DMIs) eine der meist genutzten Fungizidklassen dar. Bis heute kommt den DMIs noch immer eine große Bedeutung in der Bekämpfung von Z. tritici zu. DMIs inhibieren die Sterol 14α-Demethylase, ein wichtiges Enzym im Sterolbiosyntheseweg von Pilzen, welches durch das CYP51 Gen kodiert wird. Die langanhaltende und intensive Nutzung führte zu einer kontinuierlichen Sensitivitätsreduktion von STB gegenüber DMIs, die über einen langen Zeitraum genutzt wurden. Diese Sensitivitätsverschiebung beruht hauptsächlich auf der Akkumulation von Mutationen im CYP51 Gen. Hieraus wurden in der Vergangenheit zahlreiche CYP51 Haplotypen selektiert. Zusätzlich wurde in den letzten Jahren berichtet, dass eine CYP51 Überexpression und gesteigerte Effluxaktivität, die auf der Überexpression des MFS1 Membrantransporters beruht, die DMI-Sensitivität von STB beeinflussen. Die Überexpression wird hierbei durch Insertionen in der Promotorregion des CYP51 (CYP51P) und MFS1 (MFS1P) Gens hervorgerufen. In der vorliegenden Arbeit wurde das Vorkommen unterschiedlicher DMI-Resistenzmechanismen in Z. tritici in den Jahren 2016 und 2017 über Europa untersucht. Der Effekt unterschiedlicher Mechanismen auf die DMI Anpassung von STB wurde analysiert. Um die CYP51 Haplotypen zu bestimmen, wurde das CYP51 Gen von allen Isolaten sequenziert. Zusätzlich wurde die CYP51P sowie MFS1P Region auf Insertionen untersucht, um eine CYP51 Überexpression sowie gesteigerte Effluxaktivität zu identifizieren. Insgesamt konnte gezeigt werden, dass das Auftreten von verschiedenen CYP51 Haplotypen noch immer den häufigsten und wichtigsten DMI-Resistenzmechanismus in Z. tritici in Europa darstellt. Im Vergleich zu früheren Studien wurde jedoch ein Anstieg in der Häufigkeit von Isolaten mit CYP51 Überexpression oder mit gesteigerter Effluxaktivität beobachtet. Sensitivitätsstudien im Gewächshaus zeigten, dass DMIs noch immer zu einer STB Kontrolle beitragen oder die Krankheit in manchen Fällen komplett kontrollieren können, auch wenn Isolate moderat oder stark angepasste CYP51 Haplotypen und/oder CYP51 Überexpression, sowie eine gesteigerte Effluxaktivität zeigten. Um eine weitere Verbreitung von immer stärker angepassten CYP51 Haplotypen und zusätzlichen DMI-Resistenzmechanismen in Europa zu verhindern, sollten Antiresistenz-Strategien in der Anwendung von DMIs eine große Bedeutung zukommen. Vor allem sollten ebenfalls die Prinzipien des integrierten Pflanzenschutzes, wie z.B. eine geeignete Sortenwahl beachtet werden, um den STB-Krankheitsdruck und somit die Anzahl der Fungizidapplikationen zu verringern. Des Weiteren könnten Resistenzmanagement-Strategien auf der begrenzten Kreuzresistenz zwischen verschiedener DMIs beruhen, zum Beispiel durch die Anwendung von Mischungen oder der Alternierung verschiedener DMI Fungizide. Zudem sollten Fungizide mit anderen Wirkmechanismen in die Bekämpfungsstrategie einbezogen werden. Das Ziel all dieser Maßnahmen ist es die Selektion angepasster Z. tritici Isolate zu vermindern und somit die Effizienz der DMIs in der STB-Bekämpfung zu verlängern

The use of behavioural sciences in targeted health messages to improve the participation in cervical and breast screening programmes

The aim of this thesis was to examine the effects of behaviourally informed interventions deployed in text message reminders and invitation letters on the participation in cervical and breast cancer screening. Cancer screening saves lives through detecting cancer or precancerous changes early, when medical intervention is more likely to reduce morbidity and mortality. A key factor in the success of any screening programme is public participation. Although some individuals may object to cancer screening, evidence suggests that public support for cancer screening provision in the UK is above 90%. Yet despite this, participation rates across all three cancer screening programmes (breast, cervical and colorectal) remain lower than expected given reported intentions. This thesis explores the role of decision making – both reflective and automatic in the context of cancer screening behaviour and highlights the potential for the application of behavioural economic theory and behavioural science to inform intervention design aimed at increasing cancer screening uptake. Through the application of frameworks informed by behaviour change theory, three randomised controlled trials were designed to test the impact of behavioural interventions on participation rates in regional cervical and breast cancer screening programmes within the London area. The intervention design of each trial focused on the message content within either text message reminders or invitation letters. The first randomised controlled trial (RCT) tested different behaviourally-informed invitation letters in cervical screening and found that a shortened letter that contained a loss framed message has a small but significant positive impact on cervical screening rates. The second RCT tested different text message reminder content against a no-text message control and found that text message reminders can improve participation in cervical cancer screening. However, the content of such text message reminders further affects screening participation behaviour. The final RCT tested the effect different behaviour message content in text message reminders for timed appointments in the breast screening programme. No significant difference in breast screening participation was noticed as a result of the message content within text message reminders. However, due to logistical barriers encountered during the trial, which included a reconfiguration of regional screening services, this study had to be closed early, prior to the sample size being reached and was therefore underpowered. This research highlights the importance of the message content within health communications in cancer screening to improve participation rates. Exploratory subgroup analyses within these trials, indicates that different subgroups of women with common characteristics such as age, level of deprivation or previous exposure to cancer screening affected which message content was most effective and improving cancer screening participation.Open Acces

Ernst Fischer: Thirty Years of Service at the Medical College of Virginia

Dedication essay by Ernst Huf to Dr. Ernst Fischer, who recently retired after thirty years of service to the Medical College of Virginia

TensorPack : a Maple-based software package for the manipulation of algebraic expressions of tensors in general relativity

In this paper we: (1) introduce TensorPack, a software package for the algebraic manipulation of tensors in covariant index format in Maple; (2) briefly demonstrate the use of the package with an orthonormal tensor proof of the shearfree conjecture for dust. TensorPack is based on the Riemann and Canon tensor software packages and uses their functions to express tensors in an indexed covariant format. TensorPack uses a string representation as input and provides functions for output in index form. It extends the functionality to basic algebra of tensors, substitution, covariant differentiation, contraction, raising/lowering indices, symmetry functions and other accessory functions. The output can be merged with text in the Maple environment to create a full working document with embedded dynamic functionality. The package offers potential for manipulation of indexed algebraic tensor expressions in a flexible software environment

FORMAÇÃO DE PROFESSORES EM SERVIÇO NA MODALIDADE DE EDUCAÇÃO À DISTÂNCIA: UMA EXPERIÊNCIA SIGNIFICATIVA NO SUL DO BRASIL.

Este artigo busca apresentar e analisar experiências de formação de professores em serviço graduados pelo Curso de Pedagogia a Distância ofertada pela Universidade Federal do Paraná. O presente estudo centrou-se especificamente no ponto de vista dos egressos dos Centros Associados de Maringá e de Taquara. Todos os estudantes do referido curso já atuavam na área educacional da educação básica, e por vários motivos não cursaram o ensino superior. Com o objetivo de aproximar-se das concepções e experiências construídas por este grupo de alunos a respeito desta modalidade de ensino para sua prática pedagógica, foi necessário coletar dados por meio de pareceres emitidos por estes protagonistas. Seus depoimentos foram analisados na perspectiva metodológica da pesquisa qualitativa do tipo etnográfica. O curso, na concepção dos alunos, teve um papel social decisivo no atendimento aos “excluídos” da educação regular presencial, como se sentiam, a qual não conseguiria atendê-los por não poderem prescindir da atividade laboral para sua sobrevivência. Foi notório na pesquisa que os alunos do Curso de Pedagogia além de mudarem as suas concepções sobre a modalidade de EaD, evidenciaram mudanças nas práticas pedagógicas

Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study

The medical management of aggressive and violent behaviour is a critical situation for which there is little evidence. In order to prepare for a randomised trial, due to start in the psychiatric emergency rooms of Rio de Janeiro in 2001, a survey of current practice was necessary. A seven day survey of pharmacological management of aggressive people with psychosis in the emergency rooms of all four public psychiatric hospitals in Rio de Janeiro, Brazil. In one hospital data were not available. Of the 764 people with psychosis attending these ERs, 74 were given IM medication for rapid tranquillisation (9.7%, 2.1/week/100,000). A haloperidol-promethazine mix (with or without other drugs) was used for the majority of patients (83%). The haloperidol-promethazine mix, given intramuscularly for rapid tranquilization, is prevalent in Rio, where it is considered both safe and efficient. However, scientific evaluation of all pharmacological approaches to rapid tranquilization of psychotic people is inadequate or incomplete and a randomized trial of IM haloperidol-promethazine is overdue

Quanto tempo o tempo tem

TCC (graduação) - Universidade Federal de Santa Catarina. Centro de Comunicação e Expressão. Jornalismo."A inserção da tecnologia, a velocidade da comunicação e a rapidez de circulação de informações alteram o ritmo do cotidiano do ser humano. Isso altera também a percepção da passagem do tempo: as 24 horas de um dia não são mais suficientes para todas as atividades e demandas que precisam ser cumpridas. Este Trabalho de Conclusão de Curso é um ensaio jornalístico, dividido em três partes, que pretende debater e analisar como se dá essa percepção do tempo em relação à velocidade do cotidiano. O primeiro texto, intitulado “Tempo”, busca traçar um panorama de como a sociedade chegou a este ritmo frenético; o segundo, “Pressa”, discute o que é viver nessas circunstâncias; e o terceiro, “Calma”, aborda as maneiras de desacelerar, desde a prática da meditação até os movimentos slow