RCAAP Repository

As pessoas são consideradas os motores de funcionamento e sucesso de uma organização. O investimento no seu desenvolvimento consiste numa prioridade para as organizações que procuram alcançar uma vantagem competitiva no mercado. Deste modo, a presente investigação incide sobre o estudo da relação entre as condições oferecidas pela organização com o objectivo de desenvolver as competências dos seus colaboradores, mais especificamente através da implementação de um novo modelo de avaliação de desempenho, e o reconhecimento deste apoio por parte dos colaboradores. Para tal, procedeu-se à construção do Questionário sobre Percepção de Apoio ao Desenvolvimento de Competências, que foi aplicado a uma amostra de 30 colaboradores de uma Empresa de Distribuição. Os resultados obtidos tendem a indicar uma percepção positiva por parte destes quanto ao apoio disponibilizado pela organização relativamente ao desenvolvimento de competências. No final são apresentados os contributos deste estudo a nível empírico e teórico, assim como as suas limitações, e sugestões para futuras linhas de investigação.

With climate change, drought is expected to increase, and its negative impacts will be particularly important in developing countries, usually with rainfall-dependent agriculture. The Cabo Verde archipelago is characterized by limited resources, remoteness, vulnerability to natural disasters, and a fragile environment. In this study, we provide the first report of the current status and trends of agriculture in Cabo Verde. We present data on the current performance of agricultural production areas in these islands and discuss them in terms of their most important natural constraint, water. Also, we assess the impact of institutional strategies on crop production and evaluate recent mechanisms that have been engaged towards agrarian development in this archipelago. Our results show that, among the ten Cabo Verde Islands, Santiago has the largest area used for agriculture (52.5%), followed by Santo Antão (16%) and Fogo (15.8%), and that rainfed farming dominates in all of them. The staple crops, such as maize and beans, are produced through rainfed subsistence farming, whereas irrigated crops (i.e., sugarcane, tomatoes) are mostly grown for commercial purposes. The prolonged drought periods, exposure, erosion and soil degradation, which led to increasing desertification over the last decades, have been identified as the main constraints to agrarian development across the ten islands of the archipelago. The strategies of Cabo Verde government to mitigate water scarcity through small-scale irrigation based mainly on small dams and drip irrigation technology have a marked effect on agricultural production in the predominantly arid and semi-arid areas of this archipelago.

Serendipita indica (former Piriformospora indica) is a non-obligate endophytic fungus and generally a plant growth and defence promoter with high potential to be used in agriculture. However, S. indica may switch from biotrophy to saprotrophy losing its plant growth promoting traits. Our aim was to understand if the free-living stage growth conditions (namely C availability) regulate S. indica’s phenotype, and its potential as plant-growth-promoting-microbe (PGPM). We grew S. indica in its free-living stage under increasing C availabilities (2–20 g L–1 of glucose or sucrose). We first characterised the effect of C availability during free-living stage growth on fungal phenotype: colonies growth and physiology (plasma membrane proton pumps, stable isotopic signatures, and potential extracellular decomposing enzymes). The effect of the C availability during the free-living stage of the PGPM was evaluated on wheat. We observed that C availability during the free-living stage regulated S. indica’s growth, ultrastructure and physiology, resulting in two distinct colony phenotypes: compact and explorer. The compact phenotype developed at low C, used peptone as the major C and N source, and displayed higher decomposing potential for C providing substrates; while the explorer phenotype developed at high C, used glucose and sucrose as major C sources and casein and yeast extract as major N sources, and displayed higher decomposing potential for N and P providing substrates. The C availability, or the C/N ratio, during the free-living stage left a legacy to the symbiosis stage, regulating S. indica’s potential to promote plant growth: wheat growth promotion by the explorer phenotype was ± 40% higher than that by the compact phenotype. Our study highlights the importance of considering microbial ecology in designing PGPM/biofertilizers. Further studies are needed to test the phenotypes under more extreme conditions, and to understand if the in vitro acquired characteristics persist under field conditions.

A new species of the miniaturised microhylid frog genus Stumpffia, from north-western Madagascar, is described. Stumpffia froschaueri sp. nov. differs from all other described Stumpffia species in colouration and morphology and is genetically divergent (≥ 7% uncorrected p-distance to all other nominal species of the genus) in a fragment of the mitochondrial 16S rRNA gene and in a segment of the nuclear Rag-1 gene. The new species is reliably known only from a few specimens collected in the Sahamalaza (and surroundings) region. Its known distribution is limited to three forest patches severely threatened by fire, drought and high levels of forest clearance, thus suggesting a classification of “Critically Endangered” according to IUCN Red List criteria.

Atmospheric nitrogen deposition and other sources of environmental eutrophication have increased substantially over the past century worldwide, notwithstanding the recent declining trends in Europe. Despite the recognized susceptibility of plants to eutrophication, few studies evaluated how impacts propagate to consumers, such as pollinators. Here we aim to test if soil eutrophication contributes to the temporal dynamics of pollinators and their larval resources. We used a temporally and spatially explicit historical dataset with information on species occurrences to test if soil eutrophication, and more specifically nitrogen deposition, contributes to the patterns of change of plant and pollinator richness in the Netherlands over an 80 yr period. We focus on bees and butterflies, two groups for which we have good knowledge of larval resources that allowed us to define groups of species with different nitrogen related diet preferences. For each group we estimated richness changes between different 20-yr periods at local, regional and national scale, using analytical methods developed for analyzing richness changes based on collection data. Our findings suggest that the impacts of soil eutrophication on plant communities propagate to higher trophic levels, but with a time-lag. Pollinators with nitrogen-related diet preferences were particularly affected, in turn potentially impairing the performance of pollinator-dependent plants. Pollinator declines continued even after their focal plants started to recover. In addition, our results suggest that current levels of nitrogen deposition still have a negative impact on most groups here analyzed, constraining richness recoveries and accentuating declines. Our results indicate that the global increase in nitrogen availability plays an important role in the ongoing pollinator decline. Consequently, species tolerances to soil nitrogen levels should be considered across all trophic levels in management plans that aim to halt biodiversity loss and enhance ecosystems services worldwide.

The genus Colletotrichum has witnessed tremendous variations over the years in the number of species recognized, ranging from 11 to several hundreds. Host-specific fungal species, once the rule, are now the exception, with polyphagous behavior regarded as normal in this genus. The species Colletotrichum kahawae was created to accommodate the pathogens that have the unique ability to infect green developing coffee berries causing the devastating Coffee Berry Disease in Africa, but its close phylogenetic relationship to a polyphagous group of fungi in the C. gloeosporioides species complex led some researchers to regard these pathogens as members of a wider species. In this work we combine pathological, morphological, cytogenomic, biochemical, and molecular data of a comprehensive set of phylogenetically-related isolates to show that the Coffee Berry Disease pathogen forms a separate species, C. kahawae, and also to assign the closely related fungi, previously in C. kahawae subsp. cigarro, to a new species, C. cigarro comb. et stat. nov. This taxonomic clarification provides an opportunity to link phylogeny and functional biology, and additionally enables a much-needed tool for plant pathology and agronomy, associating exclusively C. kahawae to the Coffee Berry Disease pathogen.

This chapter explores the structural similarities and differences between these three countries: on the one hand, in their respective health sectors’ capacities and reorganization; and on the other hand, in the different degrees of state capacity to respond to the pressing needs of their populations. In the last great epidemic, the 1918 flu, there was a transparent north-south gradient in the extent to which European countries were hit by the pandemic, with Portugal, Spain, and Italy among those that were hit the hardest (Ansart et al., 2009). How was it this time? To what extent does the impact of COVID-19 reflect resilient societal and institutional vulnerabilities in these countries? And to what extent have national specificities interacted with those shared vulnerabilities, leading to different outcomes?

Ineffective governance is known to weaken support for governments and leaders. However, it is less clear whether these effects spill over to the regime and erode support for the democratic system. This article returns to this classic question, now using time-series, cross-sectional data to test whether the effectiveness of governments in sustaining economic growth, providing quality healthcare, and tackling violent crime affects popular attitudes to democracy. We find that satisfaction with democracy is driven by fluctuations in economic performance and violent crime (but not healthcare quality). Diffuse support for democracy, in contrast, remains relatively impervious to changes in government effectiveness. Violent crime is the only indicator of effectiveness which has an impact on democratic support, and does so indirectly, via its influence on democratic satisfaction. These findings confirm that democratic support—which, unlike democratic satisfaction, is thought to help sustain democracy—is mostly immune to crises of performance.

Children and young people have been deeply affected by the COVID-19 pandemic. Lockdowns and new ways of living have necessitated massive adjustments. Despite heroic efforts from teachers, there has been a huge impact on education, and children lost the psychosocial benefits of being in school. News coverage is incessant, and polarised narratives and opinions are amplified in social media echo-chambers. In this report, co-authored with an adolescent from our clinic, we discuss the psychological impact of the COVID-19 pandemic on children and young people with respiratory problems.

Objective: With this study, we aimed to assess the importance of including psychiatric disorders in a comprehensive prediction model for epilepsy surgery. Methods: Ambispective observational study with a sample of adults who underwent resective surgery. Participants were evaluated, before and one year after surgery, to collect data regarding their neurological and psychiatric history. The one-year post-surgical outcome was classified according to the Engel Outcome Scale. Previously identified predictors of post-surgical Engel Class were included in a logistic regression model. Then, the accuracy of alternative predictive models, including or excluding, past and current psychiatric diagnoses, were tried. Results: One hundred and forty-six people participated in this study. The inclusion of psychiatric diagnosis resulted in a model with a higher AUC curve, however, the Delong method showed no significant statistical differences between the models. Significance: Despite the fact that presurgical psychiatric diagnoses have shown to contribute to the prediction of epilepsy surgery outcome they do not contribute to a significant improvement of predictive models.

Neuroinflammation in patients with Alzheimer's disease (AD) and related mouse models has been recognized for decades, but the contribution of the recently described meningeal immune population to AD pathogenesis remains to be addressed. Here, using the 3xTg-AD model, we report an accumulation of interleukin-17 (IL-17)-producing cells, mostly γδ T cells, in the brain and the meninges of female, but not male, mice, concomitant with the onset of cognitive decline. Critically, IL-17 neutralization into the ventricles is sufficient to prevent short-term memory and synaptic plasticity deficits at early stages of disease. These effects precede blood-brain barrier disruption and amyloid-beta or tau pathology, implying an early involvement of IL-17 in AD pathology. When IL-17 is neutralized at later stages of disease, the onset of short-memory deficits and amyloidosis-related splenomegaly is delayed. Altogether, our data support the idea that cognition relies on a finely regulated balance of "inflammatory" cytokines derived from the meningeal immune system.

Restrições físicas e eléctricas limitam o aumento da velocidade do relógio dos processadores, pelo que não se espera que o poder computacional por unidade de processamento aumente muito num futuro próximo. Em vez disso, os fabricantes estão a aumentar o número de unidades de processamento (cores) por processador para continuarem a criar produtos com aumentos de performance. A indústria fez grandes investimentos em projectos como o RAMP e BEE2 que permitem a emulação de arquitecturas multi-core, mostrando interesse em suportar as fundações para a investigação de software que se destina a essas arquitecturas. Para tirar vantagem de arquitecturas multi-core, tem de se dominar tanto a programação concorrente como a paralela. Com a grande disponibilidade de sistemas paralelos que vai desde sistemas embebidos até a super computadores, acreditamos que os programadores têm de fazer uma mudança de paradigma passando da programação sequencial para a programação paralela e produzir software adaptado, de raiz, a plataformas multi-core. O multithreading é uma escolha bem conhecida e usada pela indústria para desenvolver sistemas explicitamente paralelos. Os locks são um mecanismo utilizado para sincronizar programas multithreaded de uma forma altamente eficiente. Porém, é comum surgirem problemas relacionados com concorrência como deter um lock tempo demais, não compreender quando se usam locks leitores/escritores ou escolher um mecanismo de sincronização desadequado. Estes problemas podem ser mitigados com recurso a abstracções de concorrência. Os tipos e as regras de tipos são formas simples e eficazes de garantir segurança. Os tipos não são só usados por sistemas de tipos para garantir que programas não têm erros de execução, mas servem também como especificações (verificáveis de uma forma automática). A informação dada pelos tipos é expressiva o suficiente para representar propriedades operacionais importantes, como segurança de memória. Os compiladores que preservam tipos perduram a informação dada pelos tipos por todos os passos de compilação, permitindo uma compilação mais segura e que preserva a semântica (representada pelos tipos). Propomos um compilador que endereça os problemas que levantámos até agora:-uma linguagem fonte com abstracções para concorrência e para o paralelismo;-um compilador que se destine a uma arquitectura multi-core;-uma tradução que preserve a informação dada pelos tipos. Em relação à linguagem fonte, os cálculos de processos evidenciam-se como um bom modelo de programação para a computação concorrente. O cálculo π em particular, tem uma semântica bem compreendida, consiste num conjunto pequeno de operadores em que a comunicação é o passo fundamental de computação. Os cálculos de processos oferecem esquemas de compilação natural que expõe o paralelismo ao nível dos threads. Por estas razões, escolhemos o cálculo π simplesmente tipificado como linguagem fonte. Vasconcelos e Martins propõem o MIL como uma linguagem assembly tipificada para arquitecturas multithreaded, um modelo que assenta numa máquina abstracta multi-core com memória principal partilhada. Esta linguagem fortemente tipificada oferece as seguintes propriedades de segurança: de memória, de controlo de fluxo e de liberdade de race conditions. O MIL contradiz a ideia que considera a associação entre a memória e locks uma convenção, ao torná-la explícita na linguagem. O sistema de tipos faz cumprir uma política de utilização de lock que inclui: proibir apanhar um lock em posse (fechado), proibir libertar um lock que não está em posse e faz com que os threads não se esqueçam de libertar todos os locks no final da sua execução. Propomos uma tradução que preserva os tipos do cálculo π para o MIL. O cálculo π é uma álgebra de processos para descrever mobilidade: uma rede de processos interligados computa comunicando ligações (ou referências a outros processos). No cálculo π, a comunicação reconfigura dinamicamente a rede, fazendo com que os processos passem a estar visíveis a diferentes nós quando o sistema evolui. Ao traduzirmos o cálculo π em MIL, partimos de uma linguagem onde os processos comunicam através de passagem de mensagens e chegamos a uma linguagem onde threads comunicam por memória partilhada. O processo de compilação não é directo nem trivial: certas abstracções, como canais, não têm uma representação complementar no MIL. Para ajudar a tradução, desenvolvemos, na linguagem de destino, uma biblioteca de tampões não limitados e polimórficos que são usados como canais. Estes tampões não limitados são monitores de Hoare, daí introduzirem uma forma de sincronização aos threads que estejam a aceder o tampão, e que encapsulam a manipulação directa de locks. A disciplina de locks do MIL permite representar explicitamente a noção da transferência ininterrupta da região crítica dos monitores — vai do thread que assinala a condição, e que termina, para o thread que está à espera nessa mesma condição, e que é activado. Os tampões não limitados são uma boa forma de representar canais, o que por sua vez simplifica a tradução, já que enviar uma mensagem corresponde a colocar um elemento no tampão, e que receber uma mensagem equivale a retirar um elemento do tampão. Impomos uma ordem FIFO no tampão, para assegurarmos que as mensagens enviadas têm a oportunidade de serem alguma vez recebidas. A função de tradução que definimos é uma especificação formal do compilador. A tradução do cálculo π para MIL comporta a tradução de tipos, de valores e de processos. Os compiladores que preservam os tipos dão garantias em termos de segurança (os programas gerados não vão correr mal) e também em termos de correcção parcial (as propriedades semânticas dadas pelos tipos perduram no programa gerado). O nosso resultado principal é, portanto, uma tradução que preserva os tipos: o compilador gera programas MIL correctos ao nível dos tipos para processos π fechados e bem tipificados. Outra preocupação da nossa função de tradução é que o programa gerado tente manter o nível de concorrência do programa fonte, o que inclui a criação dinâmica de threads e a sincronização entre threads. As contribuições deste trabalho são:-um algoritmo de compilação que preserva os tipos, mostrando a flexibilidade do MIL num ambiente tipificado e race-free.-Exemplos de programação e estruturas de dados feitos em MIL. Mostramos a implementação de tampões polimórficos não limitados sob a forma de monitores, de variáveis de condição genéricas (primitivas dos monitores) e de filas polimórficas. Também descrevemos como codificar monitores na linguagem MIL.-Ferramentas. Criámos um protótipo para o compilador de π para MIL, o que consiste em: o analisador sintáctico, o analisador semântico (estático) e o gerador de código. Refinámos o protótipo do MIL: adicionámos suporte para tipos universais e existenciais, locks de leitores/escritores, locks lineares e tuplos locais. Criámos uma applet Java que mostra de uma forma rápida e intuitiva o nosso trabalho sem ser necessário qualquer instalação (desde que o navegador web suporte applets de Java): podemos gerar código MIL a partir de código π, alterar o código MIL gerado e executá-lo. Os nossos protótipos estão disponíveis on-line, em http://gloss.di.fc.ul.pt/mil/: a applet Java, o código fonte e exemplos π e MIL.

The value of physical activity (PA) counselling and its impact on PA behaviour and weight management have been in question. The main aim of this study was to analyse 6 and 12-month effects of a PA consultation (PAC—a structured form of PA counselling) with and without the inclusion of structured exercise, on body mass index (BMI) z-score, body composition and PA levels of adolescents with excess weight (BMI ≥p85), as part of a clinical multicomponent weight management program. Participants were allocated at baseline into a control (CG—standard care, including paediatric and nutrition consultations) and two experimental groups (EGI and EGII). Both EG's were exposed to standard care plus PAC for 12 months. During the first 6 months, EGII additionally participated in two weekly exercise sessions. From 165 participants recruited, 102 completed the intervention (CG n = 28, EGI n = 36 and EGII n = 38). According to generalized estimating equations, at 6 months both EG's improved (p < 0.05) their BMI z-score, waist-height ratio (WHtR), body fat mass, skeletal muscle mass, sedentary time and moderate-vigorous PA (MVPA) compared to CG. Further improvements were observed in BMI z-score between 6 and 12 months in EG's compared to CG. At 6 months, EGII showed a higher (p < 0.05) increase in MVPA compared to EGI, and EGI a higher decrease in WHtR. No other differences were found between EG's. This study suggests that PAC is a timeeffective approach to improve BMI z-score, body composition and PA levels in adolescents with excess weight, even without the inclusion of structured exercise

Parkinson's disease (PD) is mainly driven by dopaminergic neuronal degeneration in the substantia nigra pars compacta accompanied by chronic neuroinflammation. Despite being mainly sporadic, approximately 10% of all cases are defined as heritable forms of PD, with mutations in the leucine-rich repeat kinase (LRRK2) gene being the most frequent known cause of familial PD. MicroRNAs (miRNAs or miRs), including miR-335, are frequently deregulated in neurodegenerative diseases, such as PD. Here, we aimed to dissect the protective role of miR-335 during inflammation and/or neurodegenerative events in experimental models of PD. Our results showed that miR-335 is significantly downregulated in different PD-mimicking conditions, including BV2 microglia cells stimulated with lipopolysaccharide (LPS) and/or overexpressing wild-type LRRK2. Importantly, these results were confirmed in serum of mice injected with 1-methyl-1-4-phenyl-1,2,3,6-tetrahydripyridine hydrochloride (MPTP), and further validated in patients with idiopathic PD (iPD) and those harboring mutations in LRRK2 (LRRK2-PD), thus corroborating potential clinical relevance. Mechanistically, miR-335 directly targeted LRRK2 mRNA. In the BV2 and N9 microglia cell lines, miR-335 strongly counteracted LPS-induced proinflammatory gene expression, and downregulated receptor interacting protein 1 (RIP1) and RIP3, two important players of necroptotic and inflammatory signaling pathways. Further, miR-335 inhibited LPS-mediated ERK1/2 activation. LRRK2-Wt-induced proinflammatory gene expression was also significantly reduced by miR-335 overexpression. Finally, in SH-SY5Y neuroblastoma cells, miR-335 decreased the expression of pro-inflammatory genes triggered by α-synuclein. In conclusion, we revealed novel roles for miR-335 in both microglia and neuronal cells that strongly halt the effects of classical inflammatory stimuli or LRRK2-Wt overexpression, thus attenuating chronic neuroinflammation.

Esta Newsletter (NL) resulta de uma parceria entre o Instituto de Saúde Baseada na Evidência e a Cochrane Portugal, e tem como objectivo disponibilizar informação sobre áreas interessantes para a prática clínica, com base na melhor evidência científica. São incluídos estudos relevantes, criticamente avaliados pela sua validade, importância dos resultados e aplicabilidade prática, resumidos numa óptica de suporte à decisão. É dada prioridade a estudos de causalidade incluindo-se ainda, quando justificado, estudos qualitativos e metodológicos, assim como revisões científicas. O conteúdo da NL é da exclusiva responsabilidade do(s) seu(s) autor(es).

A perda, diminuição ou ausência de autonomia é um dos fatores principais de psicopatologia, com impacto no bem-estar geral e na capacidade de prossecução dos objetivos de cada um. Esta investigação pretendeu contribuir para a promoção da decisividade -a capacidade de tomar decisões de qualidade -em adultos emergentes, tendo sido construído o Programa de Desenvolvimento da Tomada de Decisão (TD+), dirigido a estudantes do ensino superior, influenciado pela Teoria do Conflito, a Competência de Tomada de Decisão Adulta, modelos de duplo processamento e o modelo da Qualidade da Decisão. Para além da construção do programa, foi validado o Questionário de Melbourne de Tomada de Decisão (QMTD) para avaliação do TD+ e foram realizados grupos focais com adultos emergentes para recolha de perceções sobre a decisividade para utilização na construção do programa. O TD+ foi aplicado e avaliado numa amostra de estudantes universitários (N = 49), através de um desenho quasi-experimental de pré-teste/pós-teste com grupo de controlo (n = 16) e grupo experimental (n = 33), incluindo um follow-up no grupo experimental (n = 11). O QMTD manteve a sua estrutura original e mostrou ser invariante em termos de género e idade. Nos grupos focais os participantes indicaram considerar útil uma formação para a promoção da decisividade, apontando ainda a gestão emocional, a gestão das influências sociais, criatividade e maior consciência da decisão como aspetos a promover. O TD+ aumentou o uso do padrão vigilante de decisão, a autoestima na tomada de decisão, a frequência de emoções positivas, enquanto diminuiu as emoções negativas. O programa promoveu maior satisfação com a vida e tendência a maior sucesso académico. Com esta investigação passamos a ter disponível em português um questionário de avaliação da tomada de decisão e um programa dirigido ao desenvolvimento da decisividade que melhora a competência de tomada de decisão. Simultaneamente, são disponibilizados dados descritivos que contribuem para uma melhor compreensão da decisão em adultos emergentes

Introduction: Influenza vaccination may be beneficial in coronary disease patients; however the infection and vaccination are associated with acute inflammation, a trigger of cardiovascular events. We aimed to review the risk of myocardial infarction (MI) associated with Influenza infection and the safety of vaccination in self-controlled case series (SCCS).Methods: We performed a systematic review with meta-analysis of SCCS studies to evaluate the risk of MI associated with Influenza infection/vaccination. Database search was performed in August/2018. The data were reported using the incident rate ratio (IRR) and 95% confidence interval (95%CI).Results: three studies for Influenza infection and two studies for Influenza vaccination were eligible. The risk of MI following an Influenza infection was significantly increased in the first 3 days (IRR 5.79; 95%CI: 3.59-9.38) and between 4-7 days (IRR 4.52; 95%CI: 2.80-7.32). In the first 4 weeks following the Influenza vaccination, there was a significant decrease of MI risk (IRR 0.84, 95%CI: 0.78-0.91).Conclusions: Short-term MI risk in Influenza infection is significantly increased, with a low-to-moderate confidence in the pooled evidence. The Influenza vaccine was safe regarding the short-term risk for MI, and the risk reduction is possibly related to a healthy period bias.

Tight regulation of IL-7Rα expression is essential for normal T-cell development. IL-7Rα gain-of-function mutations are known drivers of T-cell acute lymphoblastic leukemia (T-ALL). Although a subset of patients with T-ALL display high IL7R messenger RNA levels and cases with IL7R gains have been reported, the impact of IL-7Rα overexpression, rather than mutational activation, during leukemogenesis remains unclear. In this study, overexpressed IL-7Rα in tetracycline-inducible Il7r transgenic and Rosa26 IL7R knockin mice drove potential thymocyte self-renewal, and thymus hyperplasia related to increased proliferation of T-cell precursors, which subsequently infiltrated lymph nodes, spleen, and bone marrow, ultimately leading to fatal leukemia. The tumors mimicked key features of human T-ALL, including heterogeneity in immunophenotype and genetic subtype between cases, frequent hyperactivation of the PI3K/Akt pathway paralleled by downregulation of p27Kip1 and upregulation of Bcl-2, and gene expression signatures evidencing activation of JAK/STAT, PI3K/Akt/mTOR and Notch signaling. Notably, we also found that established tumors may no longer require high levels of IL-7R expression upon secondary transplantation and progressed in the absence of IL-7, but remain sensitive to inhibitors of IL-7R-mediated signaling ruxolitinib (Jak1), AZD1208 (Pim), dactolisib (PI3K/mTOR), palbociclib (Cdk4/6), and venetoclax (Bcl-2). The relevance of these findings for human disease are highlighted by the fact that samples from patients with T-ALL with high wild-type IL7R expression display a transcriptional signature resembling that of IL-7-stimulated pro-T cells and, critically, of IL7R-mutant cases of T-ALL. Overall, our study demonstrates that high expression of IL-7Rα can promote T-cell tumorigenesis, even in the absence of IL-7Rα mutational activation.

Bone is constantly being renewed: in the adult skeleton, bone resorption and formation are in a tightly coupled balance, allowing for a constant bone density to be maintained. Yet this micro-environment provides the necessary conditions for the growth and proliferation of tumor cells, and thus bone is a common site for the development of metastases, mainly from primary breast and prostate cancer. Mathematical and computational models with differential equations can replicate this bone remodeling process. These models have been extended to include the effects of disruptive tumor pathologies in the bone dynamics, as metastases contribute to the decoupling between bone resorption and formation and to the self-perpetuating tumor growth cycle. Such models may also contemplate the counteraction effects of currently used therapies, and, in the case of treatments with drugs, their pharmocokinetics and pharmacodynamics. We present a thorough overview of biochemical models for bone remodeling, in the presence of a tumour together with anti-cancer and anti-resorptive therapy, formulated as systems of first-order differential equations, or simplified using variable order derivatives. The latter models, of which some are new to this paper, result in equations with fewer parameters, and allow accounting for anomalous diffusion processes. In this way, more compact and parsimonious models, that promptly highlight tumorous bone interactions, are achieved, providing an effective framework to counteract the loss of bone integrity on the affected areas.

We are said to be living in a time of multiple failures and crises (climate, biodiversity, health, inequality – to name a few now in the headlines) all playing out within a fast changing world. Behind the grand narratives of planetary boundaries and Anthropocene, is a world of increasing injustice and inequitable relationships – between humans and between humans and more-than human life. If our dominant systems fail to change, the unravelling of an existential crisis seems increasingly certain. Taking this, and much else, into account, a series of global policy agendas are combining to make a strong case for transformative change, through the rethinking of the so-called ‘human-nature relationship’.5 Indeed, we might say that the ‘Covid crisis’ has made the case for this irresistible, as well as opening up hitherto sealed doors of possibility to alternative pasts, presents and futures.