Definitive chemoradiation in patients with inoperable oesophageal carcinoma

We performed a retrospective study of 90 consecutive cases with inoperable carcinoma of the oesophagus treated with definitive chemoradiation at a single cancer centre between 1995 and 2002. For the last 4 years, 73 patients have received therapy according to an agreed protocol. This outpatient-based regimen involves four cycles of chemotherapy, cycles 3 and 4 given concurrently with 50 Gy external beam radiotherapy (XRT) delivered in 25 fractions over 5 weeks. Cisplatin 60 mg m-2 day-1 is given every 3 weeks together with continuous infusional 5-fluorouracil 300 mg m-2 day-1, reduced to 225 mg m-2 day-1 during the XRT. In all, 45 (50%) patients suffered one or more WHO grade 3/4 toxicity, grade 3 in 93% cases. Patients received more than 90% of the planned chemoradiation schedule. The median overall survival was 26 (15, >96) months, 51% (41, 64) and 26% (13, 52) surviving 2 and 5 years, respectively. Advanced stage, particularly T4 disease, was associated with a worse prognosis. Patients considered not suitable for surgery for reasons other than their disease, mainly co-morbidity, had a significantly better outcome, median survival 40 (26, >96) months, 2- and 5-year survivals 67% (54, 84) and 32% (13, 79), respectively (P<0.001). This schedule is a feasible, tolerable and effective treatment for patients with oesophageal cancer considered unsuitable for surgery

Ectopic T Cell Receptor-α Locus Control Region Activity in B Cells Is Suppressed by Direct Linkage to Two Flanking Genes at Once

The molecular mechanisms regulating the activity of the TCRα gene are required for the production of the circulating T cell repertoire. Elements of the mouse TCRα locus control region (LCR) play a role in these processes. We previously reported that TCRα LCR DNA supports a gene expression pattern that mimics proper thymus-stage, TCRα gene-like developmental regulation. It also produces transcription of linked reporter genes in peripheral T cells. However, TCRα LCR-driven transgenes display ectopic transcription in B cells in multiple reporter gene systems. The reasons for this important deviation from the normal TCRα gene regulation pattern are unclear. In its natural locus, two genes flank the TCRα LCR, TCRα (upstream) and Dad1 (downstream). We investigated the significance of this gene arrangement to TCRα LCR activity by examining transgenic mice bearing a construct where the LCR was flanked by two separate reporter genes. Surprisingly, the presence of a second, distinct, reporter gene downstream of the LCR virtually eliminated the ectopic B cell expression of the upstream reporter observed in earlier studies. Downstream reporter gene activity was unaffected by the presence of a second gene upstream of the LCR. Our findings indicate that a gene arrangement in which the TCRα LCR is flanked by two distinct transcription units helps to restrict its activity, selectively, on its 5′-flanking gene, the natural TCRα gene position with respect to the LCR. Consistent with these findings, a TCRα/Dad1 locus bacterial artificial chromosome dual-reporter construct did not display the ectopic upstream (TCRα) reporter expression in B cells previously reported for single TCRα transgenes

Dispersion and release of embelin from electrospun biodegradable, polymeric, membranes

In this work, microfiber meshes containing embelin, a poorly water-soluble bioactive agent, were prepared by solubilizing embelin in a biodegradable and biocompatible polymer matrix of poly(ε-caprolactone) (PCL). Plain or drug-loaded, highly porous, fibrous membranes with a high area-to-volume ratio were obtained by electrospinning. Non-woven microfibrous meshes were formed by uniform bead-free fibers with a mean diameter of 1.2 μm. Non-porous films were obtained by solution casting, and were used for comparison. The drug-loading content of the prepared systems was appropriate for topical applications. The thermal properties revealed that the crystallinity of embelin significantly decreased, the drug having almost completely dissolved in the PCL fibers. The in situ bioavailability of embelin, an antimycotic agent, is an important aspect to consider in topical drug applications. The drug-loaded systems presented different contact areas with the biological environment. When comparing the ability to expose embelin with the biological environment of the prepared systems, drug-loaded fibrous scaffolds showed a higher bioavailability of the bioactive agent because of an increase by 86% in the area-to-volume ratio, providing an effective area per unit mass that was 5.8-fold higher than that of the film. For the meshes, 90% embelin release was observed after 12h of exposure to phosphate-buffered saline, whereas for the films a comparable level of release occurred only after 72h.Fil: Cortez Tornello, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Feresin, Gabriela Egly. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Tapia, Alejandro. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaFil: Veiga, Itiara G.. Universidade Estadual de Campinas; BrasilFil: Moraes, Ângela M.. Universidade Estadual de Campinas; BrasilFil: Abraham, Gustavo Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; ArgentinaFil: Cuadrado, Teresita Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mar del Plata. Instituto de Investigación En Ciencia y Tecnología de Materiales (i); Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería; Argentin

Cryptic Diversity of African Tigerfish (Genus Hydrocynus) Reveals Palaeogeographic Signatures of Linked Neogene Geotectonic Events

The geobiotic history of landscapes can exhibit controls by tectonics over biotic evolution. This causal relationship positions ecologically specialized species as biotic indicators to decipher details of landscape evolution. Phylogeographic statistics that reconstruct spatio-temporal details of evolutionary histories of aquatic species, including fishes, can reveal key events of drainage evolution, notably where geochronological resolution is insufficient. Where geochronological resolution is insufficient, phylogeographic statistics that reconstruct spatio-temporal details of evolutionary histories of aquatic species, notably fishes, can reveal key events of drainage evolution. This study evaluates paleo-environmental causes of mitochondrial DNA (mtDNA) based phylogeographic records of tigerfishes, genus Hydrocynus, in order to reconstruct their evolutionary history in relation to landscape evolution across Africa. Strong geographical structuring in a cytochrome b (cyt-b) gene phylogeny confirms the established morphological diversity of Hydrocynus and reveals the existence of five previously unknown lineages, with Hydrocynus tanzaniae sister to a clade comprising three previously unknown lineages (Groups B, C and D) and H. vittatus. The dated phylogeny constrains the principal cladogenic events that have structured Hydrocynus diversity from the late Miocene to the Plio-Pleistocene (ca. 0–16 Ma). Phylogeographic tests reveal that the diversity and distribution of Hydrocynus reflects a complex history of vicariance and dispersals, whereby range expansions in particular species testify to changes to drainage basins. Principal divergence events in Hydrocynus have interfaced closely with evolving drainage systems across tropical Africa. Tigerfish evolution is attributed to dominant control by pulses of geotectonism across the African plate. Phylogenetic relationships and divergence estimates among the ten mtDNA lineages illustrates where and when local tectonic events modified Africa's Neogene drainage. Haplotypes shared amongst extant Hydrocynus populations across northern Africa testify to recent dispersals that were facilitated by late Neogene connections across the Nilo-Sahelian drainage. These events in tigerfish evolution concur broadly with available geological evidence and reveal prominent control by the African Rift System, evident in the formative events archived in phylogeographic records of tigerfish

The state of HRM in the Middle East:Challenges and future research agenda

Based on a robust structured literature analysis, this paper highlights the key developments in the field of human resource management (HRM) in the Middle East. Utilizing the institutional perspective, the analysis contributes to the literature on HRM in the Middle East by focusing on four key themes. First, it highlights the topical need to analyze the context-specific nature of HRM in the region. Second, via the adoption of a systematic review, it highlights state of development in HRM in the research analysis set-up. Third, the analysis also helps to reveal the challenges facing the HRM function in the Middle East. Fourth, it presents an agenda for future research in the form of research directions. While doing the above, it revisits the notions of “universalistic” and “best practice” HRM (convergence) versus “best-fit” or context distinctive (divergence) and also alternate models/diffusion of HRM (crossvergence) in the Middle Eastern context. The analysis, based on the framework of cross-national HRM comparisons, helps to make both theoretical and practical implications

Global variation in diabetes diagnosis and prevalence based on fasting glucose and hemoglobin A1c

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) are both used to diagnose diabetes, but these measurements can identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening, had elevated FPG, HbA1c or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardized proportion of diabetes that was previously undiagnosed and detected in survey screening ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the age-standardized proportion who had elevated levels of both FPG and HbA1c was 29–39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c was more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global shortfall in diabetes diagnosis and surveillance

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background: Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories.Methods: We used data from 1990 to 2019 on people aged 30-79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age.Findings: The number of people aged 30-79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306-359) million women and 317 (292-344) million men in 1990 to 626 (584-668) million women and 652 (604-698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55-62) of women and 49% (46-52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43-51) of women and 38% (35-41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20-27) for women and 18% (16-21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran.Interpretation: Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings.Copyright (C) 2021 World Health Organization; licensee Elsevier.</p