The role of the Guayana Development Corporation in Venezuelan industrialization : diversification or vertical integration

Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of Urban Studies and Planning, 1987.Bibliography: leaves 81-83.by Antonio J. Azpurua C.M.C.P

Erratum to: Circulating tumor DNA as a biomarker for monitoring early treatment responses of patients with advanced lung adenocarcinoma receiving immune checkpoint inhibitors.

The following error appeared in Section 3.5 in Ref. [1]. Instead of ‘Progressive disease-L1 expression data were available for 87 patients’, the text should read ‘PD-L1 expression data were available for 87 patients’. We apologize for this error.</p

Circulating tumor DNA as a biomarker for monitoring early treatment responses of patients with advanced lung adenocarcinoma receiving immune checkpoint inhibitors

Immunotherapy for metastasized non-small-cell lung cancer (NSCLC) can show long-lasting clinical responses. Selection of patients based on programmed death-ligand 1 (PD-L1) expression shows limited predictive value for durable clinical benefit (DCB). We investigated whether early treatment effects as measured by a change in circulating tumor DNA (ctDNA) level is a proxy of early tumor response to immunotherapy according to response evaluation criteria in solid tumors v1.1 criteria, progression-free survival (PFS), DCB, and overall survival (OS). To this aim, blood tubes were collected from advanced-stage lung adenocarcinoma patients (n = 100) receiving immune checkpoint inhibitors (ICI) at baseline (t(0)) and prior to first treatment evaluation (4-6 weeks; t(1)). Nontargetable (driver) mutations detected in the pretreatment tumor biopsy were used to quantify tumor-specific ctDNA levels using droplet digital PCR. We found that changes in ctDNA levels were strongly associated with tumor response. A > 30% decrease in ctDNA at t(1) correlated with a longer PFS and OS. In total, 80% of patients with a DCB of >= 26 weeks displayed a > 30% decrease in ctDNA levels. For patients with a PD-L1 tumor proportion score of >= 1%, decreasing ctDNA levels were associated with a higher frequency a DCB (80%) and a prolonged median PFS (85 weeks) and OS (101 weeks) compared with patients with no decrease in ctDNA (34%; 11 and 39 weeks, respectively). This study shows that monitoring of ctDNA dynamics is an easy-to-use and promising tool for assessing PFS, DCB, and OS for ICI-treated NSCLC patients

Opportunities for organoids as new models of aging.

The biology of aging is challenging to study, particularly in humans. As a result, model organisms are used to approximate the physiological context of aging in humans. However, the best model organisms remain expensive and time-consuming to use. More importantly, they may not reflect directly on the process of aging in people. Human cell culture provides an alternative, but many functional signs of aging occur at the level of tissues rather than cells and are therefore not readily apparent in traditional cell culture models. Organoids have the potential to effectively balance between the strengths and weaknesses of traditional models of aging. They have sufficient complexity to capture relevant signs of aging at the molecular, cellular, and tissue levels, while presenting an experimentally tractable alternative to animal studies. Organoid systems have been developed to model many human tissues and diseases. Here we provide a perspective on the potential for organoids to serve as models for aging and describe how current organoid techniques could be applied to aging research

COVID-19 y Embarazo: Perspectivas para Venezuela

In this article we make a review evaluating the current sanitary conditions in Venezuela, in relation to the situation of COVID-19. This particular situation and factors associated with the complex humanitarian crisis that this Latin American country is experiencing could have an additional negative impact on access and quality of care for pregnant women in the midst of the COVID-19 pandemic. Urgent international cooperation and humanitarian aid interventions are needed in this population segment in order to provide better care and assistance, particularly to those infected with COVID-19 and their newborns.En el presente artículo hacemos una revisión evaluando las condiciones sanitarias actuales en Venezuela, en relación a la situación del COVID-19. Esta situación particular y factores asociados a la crisis humanitaria compleja que experimenta este país latinoamericano, pudieran tener un impacto negativo adicional en el acceso y la calidad de la atención de las embarazadas en medio de la pandemia de COVID-19. Se necesitan intervenciones urgentes de cooperación y ayuda humanitaria internacional en este segmento poblacional con la finalidad de brindar mejores cuidados y asistencia en particular a las infectadas con COVID-19 y sus recién nacidos

COVID-19 y Embarazo: Perspectivas para Venezuela

In this article we make a review evaluating the current sanitary conditions in Venezuela, in relation to the situation of COVID-19. This particular situation and factors associated with the complex humanitarian crisis that this Latin American country is experiencing could have an additional negative impact on access and quality of care for pregnant women in the midst of the COVID-19 pandemic. Urgent international cooperation and humanitarian aid interventions are needed in this population segment in order to provide better care and assistance, particularly to those infected with COVID-19 and their newborns.En el presente artículo hacemos una revisión evaluando las condiciones sanitarias actuales en Venezuela, en relación a la situación del COVID-19. Esta situación particular y factores asociados a la crisis humanitaria compleja que experimenta este país latinoamericano, pudieran tener un impacto negativo adicional en el acceso y la calidad de la atención de las embarazadas en medio de la pandemia de COVID-19. Se necesitan intervenciones urgentes de cooperación y ayuda humanitaria internacional en este segmento poblacional con la finalidad de brindar mejores cuidados y asistencia en particular a las infectadas con COVID-19 y sus recién nacidos

The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process

The naked truth:a comprehensive clarification and classification of current 'myths' in naked mole-rat biology

The naked mole-rat (Heterocephalus glaber) has fascinated zoologists for at least half a century. It has also generated considerable biomedical interest not only because of its extraordinary longevity, but also because of unusual protective features (e.g. its tolerance of variable oxygen availability), which may be pertinent to several human disease states, including ischemia/reperfusion injury and neurodegeneration. A recent article entitled 'Surprisingly long survival of premature conclusions about naked mole-rat biology' described 28 'myths' which, those authors claimed, are a 'perpetuation of beautiful, but falsified, hypotheses' and impede our understanding of this enigmatic mammal. Here, we re-examine each of these 'myths' based on evidence published in the scientific literature. Following Braude et al., we argue that these 'myths' fall into four main categories: (i) 'myths' that would be better described as oversimplifications, some of which persist solely in the popular press; (ii) 'myths' that are based on incomplete understanding, where more evidence is clearly needed; (iii) 'myths' where the accumulation of evidence over the years has led to a revision in interpretation, but where there is no significant disagreement among scientists currently working in the field; (iv) 'myths' where there is a genuine difference in opinion among active researchers, based on alternative interpretations of the available evidence. The term 'myth' is particularly inappropriate when applied to competing, evidence-based hypotheses, which form part of the normal evolution of scientific knowledge. Here, we provide a comprehensive critical review of naked mole-rat biology and attempt to clarify some of these misconceptions