Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

Autographed portrait of Martin Buber Portraits; Men

Handwritten dedication: Robert Weltsch in herzlicher Gesinnung MB

The conservation status of the world’s reptiles

Effective and targeted conservation action requires detailed information about species, their distribution, systematics and ecology as well as the distribution of threat processes which affect them. Knowledge of reptilian diversity remains surprisingly disparate, and innovative means of gaining rapid insight into the status of reptiles are needed in order to highlight urgent conservation cases and inform environmental policy with appropriate biodiversity information in a timely manner. We present the first ever global analysis of extinction risk in reptiles, based on a random representative sample of 1500 species (16% of all currently known species). To our knowledge, our results provide the first analysis of the global conservation status and distribution patterns of reptiles and the threats affecting them, highlighting conservation priorities and knowledge gaps which need to be addressed urgently to ensure the continued survival of the world’s reptiles. Nearly one in five reptilian species are threatened with extinction, with another one in five species classed as Data Deficient. The proportion of threatened reptile species is highest in freshwater environments, tropical regions and on oceanic islands, while data deficiency was highest in tropical areas, such as Central Africa and Southeast Asia, and among fossorial reptiles. Our results emphasise the need for research attention to be focussed on tropical areas which are experiencing the most dramatic rates of habitat loss, on fossorial reptiles for which there is a chronic lack of data, and on certain taxa such as snakes for which extinction risk may currently be underestimated due to lack of population information. Conservation actions specifically need to mitigate the effects of human-induced habitat loss and harvesting, which are the predominant threats to reptiles.

Control of Variable Watermilfoil in Bashan Lake, CT with 2,4-D: Monitoring of Lake and Well Water.

Variable watermilfoil (Myriophyllum heterophyllum Michx.) has recently become a problem in Bashan Lake, East Haddam, CT, USA. By 1998, approximately 4 ha of the 110 ha lake was covered with variable watermilfoil. In 1999, the milfoil was spot treated with Aquacide®, an 18% active ingredient of the sodium salt of 2,4-D [(2,4-dichlorophenoxy) acetic acid], applied at a rate of 114 kg/ha. Aquacide® was used because labeling regarding domestic water intakes and irrigation limitations prevented the use of Navigate® or AquaKleen®, a 19% active ingredient of the butoxyethyl ester of 2,4-D. Variable watermilfoil was partially controlled in shallow protected coves but little control occurred in deeper more exposed locations. 2,4-D levels in the treatment sites were lower than desired and offsite dilution was rapid. In 2000, the United States Environmental Protection Agency (USEPA) issued a special local need (SLN) registration to allow the use of Navigate ® or AquaKleen® in lakes with potable and irrigation water intakes. Navigate® was applied at a rate of 227 kg/ha to the same areas as treated in 1999. An additional 2 ha of variable watermilfoil was treated with Navigate® in 2001, and 0.4 ha was treated in mid-September. Dilution of the 2,4-D ester formulation to untreated areas was slower than with the salt formulation. Concentrations of 2,4-D exceeded 1000 μg/ L in several lake water samples in 2000 but not 2001. Nearly all of the treated variable watermilfoil was controlled in both years. The mid-September treatment appeared as effective as the spring and early summer treatments. Testing of homeowner wells in all 3 years found no detectable levels of 2,4-D.(PDF contains 8 pages.)

Flores de l. anneo seneca : traduzidas de latin en romance castellano por Iuan Martin Cordeiro Valenciano, Y dirigidas al Muy Magnifico Senor Martin Lopez

Compõe-se de trechos selecionados da obra de Sêneca e traz uma pequena biografia do filósofo, além de partes das cento e vinte quatro "epístolas" dirigidas a seu amigo Lucílio. Constituem, na realidade, ensaios morais sobre vários aspectos da vida. Foi editado pelo célebre impressor francês Critóvão Plantin (ou Plantino), radicado na Bélgica, que notabilizou-se pela preciosidade de seu trabalho tipográfico, o que lhe valeu o título de "Grande Impressor", atribuído por Filipe II, rei da Espanha (Filipe I de Portugal).

TRANSFER OF ANALYTICAL METHODS FOR THE CHARACTERISATION OF NATURAL PRODUCTS TO R&D PROCESSES OF IDOKI

IDOKI SCF Technologies S.L. is a technology-based company, set up on September 2006 in Derio (Biscay) with the main scope of developing extraction and purification processes based on the use of supercritical fluid extraction technology (SFE) in food processing, extraction of natural products and the production of personal care products. IDOKI¿s researchers have been working on many different R&D projects so far, most of them using this technology. However, the optimization of a SFE method for the different matrices cannot be performed unless we have an analytical method for the characterisation of the extracts obtained in each experiment. The analytical methods are also essential for the quality control of the raw materials that are going to be used and also for the final product. This PhD thesis was born to tackle this problem and therefore, it is based on the development of different analytical methods for the characterisation of the extracts and products. The projects that we could include in this thesis were the following: the extraction propolis, the recovery of agroindustrial residues (soy and wine) and the dealcoholisation of wine.On the one hand, for the extraction of propolis, several UV-Vis spectroscopic methods were used in order to measure the antioxidant capacity and the total polyphenol and flavonoid content of the extracts. A SFC method was also developed in order to measure more specific phenolic compounds. On the other hand, for the recovery of agroindustrial residues UV-Vis spectroscopy was used to determine the total polyphenol content and two SFC methods were developed to analyse different phenolic compounds. Extraction methods such as MAE, FUSE and rotary agitation were also evaluated for the characterisation of the raw materials.Finally, for the dealcoholisation of wine, the development of a SBSE-TD-GC-MS and DHS-TD-GC-MS methods for the analysis of aromas and a NIR spectroscopic method for the determination of ethanol content with the help of chemometrics was necessary. Most of these methods are typically used in IDOKI¿s lab as routine analyses apart from others not included in this PhD thesis.

Estudio de una serie musteriense de La Quina (Charente, Francia): el ejemplo de la trinchera C (excavaciones DR. L. y G. Henri-Martin)

[ES] El análisis de una serie industrial correspondiente a los cinco niveles arqueológicos de la trinchera C de La Quina (Charente, Francia), proveniente de las excavaciones del Dr. L. Henri-Martin y de G. Henri-Martin, pone de manifiesto, junto a la caracterización del conjunto estratigráfico por la presencia de raederas, el progresivo incremento de los denticulados en el devenir temporal. Este hecho asociado a otros particulares fenómenos secundarios (en el alargamiento de las formas, en la tipología de las raederas, en la elaboración del retoque, ... ) traducen una complicación diacrónica creciente en la dinámica de este complejo musteroide, presagiando, quizás, su relativa afinidad con el proceso leptolitizante de las series industriales evolucionadas del Paleolítico medio.

Anglo-Norman Dictionary: revised edition, A-C : D-E

Rothwell, W., S. Gregory and David Trotter, Anglo-Norman Dictionary: revised edition, A-C; D-E (MHRA, 2005) RAE2008

The Whitby life of Gregory the Great: exegesis and hagiography

The eight-century Whitby Vita Gregorii is one of the earliest examples of Anglo-Saxon hagiography, and is the earliest surviving life of Gregory the Great (590-604). The work has proved itself an anomaly in subject matter, style and approach, not least because of the writer’s apparently arbitrary insertion of an account of the retrieval of the relics of the Anglo-Saxon King Edwin (d.633). There has, however, been relatively little research on the document to date, the most recent concentrating on elements in the Gregorian material in the work. The present thesis adapts a methodology which identifies patristic exegetical themes and techniques in the Vita. That is not only in material originating from the pen of Gregory himself, which is freely quoted and cited by the writer, but also in the narrative episodes concerning the Pope. It also identifies related exegetical themes underlying the narrative of the Anglo-Saxon material in the document, and this suggests that the work is of much greater coherence then has previously been thought. In the course of the thesis some of the Vita Gregorii’s major patristic themes are compared with Bede and other insular writers in the presentation of topics that have been of considerable interest to insular historians in recent years. That is themes including: the conversion and salvation of the English people; the ideal pastor; monastic influence on formation of Episcopal spiritual authority; relations between king and bishop. The thesis also includes a re-evaluation of the possible historical context and purpose of the work, and demonstrates the value of a proper understanding of the Vita’s spiritual nature in order to achieve this. Finally the research is supported by a new structural analysis of the entire Vita Gregorii as an artefact formed within literary traditions.

Hyperacetylation in prostate cancer induces cell cycle aberrations, chromatin reorganization and altered gene expression profiles.

Histone acetylation is a fundamental mechanism in the regulation of local chromatin conformation and gene expression. Research has focused on the impact of altered epigenetic environments on the expression of specific genes and their pathways. However, changes in histone acetylation also have a global impact on the cell. In this study we used digital texture analysis to assess global chromatin patterns following treatment with trichostatin A (TSA) and have observed significant alterations in the condensation and distribution of higher-order chromatin, which were associated with altered gene expression profiles in both immortalised normal PNT1A prostate cell line and androgen-dependent prostate cancer cell line LNCaP. Furthermore, the extent of TSA-induced disruption was both cell cycle and cell line dependent. This was illustrated by the identification of sub-populations of prostate cancer cells expressing high levels of H3K9 acetylation in the G2/M phase of the cell cycle that were absent in normal cell populations. In addition, the analysis of enriched populations of G1 cells showed a global decondensation of chromatin exclusively in normal cells.

A rare haplotype of the vitamin D receptor gene is protective against diabetic nephropathy

Background. Vitamin D and its analogues are reported to have renoprotective effects in chronic kidney disease including diabetic nephropathy (DN). Vitamin D3 is converted to 1,25(OH) D3 by CYP2R1 and CYP27B1. The biological action of 1,25(OH) D3 is mediated via its receptor. VDR, CYP27B1 or CYP2R1 gene variants could modify the biological activity of vitamin D3. We have conducted the first case- control association study to determine the relationship between polymorphisms in VDR, CYP27B1 and CYP2R1 genes, and the risk of DN in individuals with type 1 diabetes.

Verwirklichende Raume - Poetik und Raumkonzeption bei Paul Celan und Martin Buber

This article with the conception of space in Paul Celan's poetics, comparing it to Martin Buber's and developing a notion of 'realisation', important to both Celan and Buber. Partant du concept du fantastique en tant qu'espace dans laquelle les phénomènes sont véritablement perçus au lieu de simplement se dérouler, l'article montre comment la rupture avec la réalité accoutumée peut mener à une sensation intense de l'être. Chez Martin Buber se trouve la description d'un telle espace, où l'unité est créée à partir de la polarité de tout ce qui est. Le poème peut représenter un exemple d'un tel espace « réalisant ». La conception de l'espace chez Buber est démontrée en dialogue avec le poème STEHEN de Paul Celan, afin de montrer comment le monde réifié est « réalisé » par la poésie. Ainsi sont mis en valeur le rapport mutuel et le lien indispensable entre réalités sociales et la réalité du non-espace.