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.

Regulation of Energy Metabolism by the Extracytoplasmic Function (ECF) σ Factors of Arcobacter butzleri

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Quando menos é mais: a criança e seu aniversário

Esta tese teve por objetivo compreender a relação da criança com seu próprio aniversário, considerando o aniversário como ―experiência‖ e comemoração. Em um primeiro momento, aborda o tema do aniversário ao longo da história, como este se apresenta em diferentes campos da cultura, analisando de que forma elementos como convite, bolo, tema e brindes tornam-se constituintes dessa efeméride. Tal análise adota como referência os estudos de Régine Sirota, Jean-Claude Schmitt, Christian Heslon, Françoise Lebrun e Alain Montandon. Em um segundo momento, transpondo a perspectiva da ―alteridade‖ tal como proposta por Mikhail Bakhtin e Marília Amorim para o campo da pesquisa com crianças, apresenta sentidos compartilhados com crianças sobre a experiência de seu aniversário. O trabalho de campo adotou como principais estratégias metodológicas entrevistas individuais e em grupo com crianças de idade entre 4 e 10 anos, e observação de diferentes festas de aniversário, cujos relatos são trazidos para o texto como ―imagens dialéticas‖, seguindo a orientação de Walter Benjamin. O aniversário, compreendido na perspectiva da criança primeiro como ―festa‖ e depois como ―condição para crescer‖, é analisado neste trabalho com base nas vozes das crianças, sua relação com o tempo e com o tema do aniversário. É trazido como contínuo de mudanças, manifestado pelo pertencimento a determinada idade cronológica que toma como referencia parâmetros de comportamento socialmente estabelecidos. A interlocução com as crianças e o estudo teórico mais aprofundado apontaram para a complexidade da temática, que se apresenta socialmente situada entre a noção de espetáculo, fenômeno abordado por Guy Debord, e a ideia de simplicidade, isto é, os pequenos gestos que desenham silenciosamente a experiência e buscam formas sutis para comunicá-la, como postula Benjamin. Assentado na premissa de que ―menos pode ser mais‖, este estudo abre mão de estabelecer uma fácil e determinista relação de oposição entre espetáculo e simplicidade. Em vez disso, aceitando o desafio de Walter Benjamin e Win Wenders, aposta na riqueza das contradições que se colocam entre estes como um desvio metodológico que convide a uma reflexão crítica, aguçando o olhar para diferentes comemorações de aniversários e buscando nelas estilhaços de histórias.

Análise da variabilidade gênica de antígenos de T. cruzi com aplicação para o diagnóstico sorológico da doença de Chagas

A doença de Chagas é uma zoonose causada pelo protozoário flagelado Trypanosoma cruzi. Estima-se que 8 milhões de pessoas estão infectadas com o T. cruzi em todo o mundo, principalmente na América Latina. Testes tradicionais de diagnóstico estão sendo gradualmente substituídos por métodos inovadores. A utilização de antígenos recombinantes foi proposta nos anos 90, e várias combinações foram testadas com soros de pacientes com diferentes formas clínicas de diferentes regiões da América Latina. Apesar do ganho em especificidade, estes testes apresentaram menor sensibilidade, frustrando expectativas. Este estudo objetivou analisar a variabilidade genética dos genes KMP11 e 1F8 que codificam antígenos comumente utilizados em diagnóstico experimental. Cepas de T. cruzi pertencentes a diferentes sub-grupos taxonômicos e de diferentes regiões foram analisadas para avaliar o impacto da variação antigênica em testes de diagnóstico. Maximizando a sensibilidade, evitar reatividade cruzada com epítopos de outros agentes patogênicos deve permitir a concepção de melhores testes rápidos. Num primeiro passo, DNA genômico foi extraído das seguintes cepas: Dm28c, Colombiana, Y, 3663, 4167, LL014 e CL Brener e foi realizada a amplificação dos genes 1F8 e KMP11 que codificam antígenos a partir destas cepas. Em seguida foram realizadas a clonagem, sequenciamento, expressão e detecção dos antígenos recombinantes. Na etapa final, análises de estruturas secundárias e terciárias, a última apenas para o antígeno 1F8, visualizaram as diferenças nas sequências de aminoácidos obtidas a partir de sequenciamento de DNA. Os resultados apresentados neste estudo mostram que o antígeno KMP11 de T. cruzi possui uma similaridade na sequência de aminoácidos muito elevada com o T. rangeli, mostrando a necessidade de um mapeamento antigênico desta proteína em todos os tripanosomatídeos que apresentaram alta similaridade com o antígeno de T. cruzi, como o T. rangeli, para verificar a presença de epítopos específicos de T. cruzi. O antígeno 1F8 pode ser uma ferramenta útil no diagnóstico da doença de Chagas e que será necessário aprofundar os conhecimentos sobre os determinantes antigênicos para futuramente elaborar poli-epítopos sintéticos adaptados de um maior número possível de antígenos, obtendo a maior especificidade e sensibilidade nos testes de diagnóstico sorológico e de teste rápido da doença de Chagas. Este estudo representa um passo crucial para a otimização de antígenos recombinantes para o diagnóstico da doença de Chagas.

An asymmetric MOSFET-C band-pass filter with on-chip charge pump auto-tuning

An asymmetric MOSFET-C band-pass filter(BPF)with on chip charge pump auto-tuning is presented.It is implemented in UMC (United Manufacturing Corporation)0.18μm CMOS process technology. The filter system with auto-tuning uses a master-slave technique for continuous tuning in which the charge pump OUtputs 2.663 V, much higher than the power supply voltage, to improve the linearity of the filter. The main filter with third order low-pass and second order high-pass properties is an asymmetric band-pass filter with bandwidth of 2.730-5.340 MHz. The in-band third order harmonic input intercept point(HP3) is 16.621 dBm,wim 50 Ω as the source impedance. The input referred noise iS about 47.455μVrms. The main filter dissipates 3.528 mW while the auto-tuning system dissipates 2.412 mW from a 1.8 V power supply. The filter with the auto-tuning system occupies 0.592 mm~2 and it can be utilized in GPS (global positioning system)and Bluetooth systems.

Salted fish products from the Coptic monastery at Bawit, Egypt: evidence from the bones and texts

Fish bone assemblages are described that were recently discovered in the storage area of two rooms, dated to the 7th century AD, from the monastery of Bawit, Egypt. The species composition, the reconstructed sizes of the fish and the find contexts show that this material represents pickled fish (salsamenta). This product was made in one case of medium-sized Clarias catfish, whereas another assemblage, found inside an amphora, consisted of small-sized fish, mainly cyprinids and alestiids. The latter product was stored in a Late Roman Amphora 5/6 of Palestinian origin, traditionally considered as a container for wine. The amphora was clearly re-used since the fish found in it are Nilotic species which excludes that the salsamenta came from outside Egypt. A few additional finds of fish inside amphorae were available, but due to the low number of bones it was unclear if salted fish products were stored in them. Textual information provided by ostraca and papyri from the same site shows that the monks exerted fishing activities themselves and also suggests that the production of pickled fish took place locally. One of the two Nilotic fish taxa (Labeo) that is specifically mentioned by written evidence is the most common ingredient found in the amphora with abundant fish remains. The paper ends with a brief summary of other faunal evidence for salted fish products from monastic and other historic sites in Egypt.

LPS-binding protein and IL-6 Mark paradoxical tuberculosis immune reconstitution inflammatory syndrome in HIV patients

Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB co-infected patients initiating antiretroviral therapy (ART). The role of the innate immune system in TB-IRIS is becoming increasingly apparent, however the potential involvement in TB-IRIS of a leaky gut and proteins that interfere with TLR stimulation by binding PAMPs has not been investigated before. Here we aimed to investigate the innate nature of the cytokine response in TB-IRIS and to identify novel potential biomarkers. Methods: From a large prospective cohort of HIV-TB co-infected patients receiving TB treatment, we compared 40 patients who developed TB-IRIS during the first month of ART with 40 patients matched for age, sex and baseline CD4 count who did not. We analyzed plasma levels of lipopolysaccharide (LPS)-binding protein (LBP), LPS, sCD14, endotoxin-core antibody, intestinal fatty acid-binding protein (I-FABP) and 18 pro-and anti-inflammatory cytokines before and during ART. Results: We observed lower baseline levels of IL-6 (p = 0.041), GCSF (p = 0.036) and LBP (p = 0.016) in TB-IRIS patients. At IRIS event, we detected higher levels of LBP, IL-1RA, IL-4, IL-6, IL-7, IL-8, G-CSF (p ≤ 0.032) and lower I-FABP levels (p = 0.013) compared to HIV-TB co-infected controls. Only IL-6 showed an independent effect in multivariate models containing significant cytokines from pre-ART (p = 0.039) and during TB-IRIS (p = 0.034). Conclusion: We report pre-ART IL-6 and LBP levels as well as IL-6, LBP and I-FABP levels during IRIS-event as potential biomarkers in TB-IRIS. Our results show no evidence of the possible contribution of a leaky gut to TB-IRIS and indicate that IL-6 holds a distinct role in the disturbed innate cytokine profile before and during TB-IRIS. Future clinical studies should investigate the importance and clinical relevance of these markers for the diagnosis and treatment of TB-IRIS. Copyright: © 2013 Goovaerts et al.

Antigen-specific interferon-gamma responses and innate cytokine balance in TB-IRIS.

Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of IFNγ responses to recall and TB-antigens and explored in vitro innate cytokine production in TB-IRIS patients.

The second round of Critical Assessment of Automated Structure Determination of Proteins by NMR: CASD-NMR-2013

The second round of the community-wide initiative Critical Assessment of automated Structure Determination of Proteins by NMR (CASD-NMR-2013) comprised ten blind target datasets, consisting of unprocessed spectral data, assigned chemical shift lists and unassigned NOESY peak and RDC lists, that were made available in both curated (i.e. manually refined) or un-curated (i.e. automatically generated) form. Ten structure calculation programs, using fully automated protocols only, generated a total of 164 three-dimensional structures (entries) for the ten targets, sometimes using both curated and un-curated lists to generate multiple entries for a single target. The accuracy of the entries could be established by comparing them to the corresponding manually solved structure of each target, which was not available at the time the data were provided. Across the entire data set, 71 % of all entries submitted achieved an accuracy relative to the reference NMR structure better than 1.5 Å. Methods based on NOESY peak lists achieved even better results with up to 100 % of the entries within the 1.5 Å threshold for some programs. However, some methods did not converge for some targets using un-curated NOESY peak lists. Over 90 % of the entries achieved an accuracy better than the more relaxed threshold of 2.5 Å that was used in the previous CASD-NMR-2010 round. Comparisons between entries generated with un-curated versus curated peaks show only marginal improvements for the latter in those cases where both calculations converged.

Organisational whistleblowing policies: making employees responsible or liable?

This paper explores the possible impact of the recent legal developments on organizational whistleblowing on the autonomy and responsibility of whistleblowers. In the past thirty years numerous pieces of legislation have been passed to offer protection to whistleblowers from retaliation for disclosing organisational wrongdoing. An area that remains uncertain in relation to whistleblowing and its related policies in organisations, is whether these policies actually increase the individualisation of work, allowing employees to behave in accordance with their conscience and in line with societal expectations or whether they are another management tool to control employees and protect organisations from them. The assumptions of whistleblower protection with regard to moral autonomy are examined in order to clarify the purpose of whistleblower protection at work. The two extreme positions in the discourse of whistleblowing are that whistleblowing legislation and policies either aim to enable individual responsibility and moral autonomy at work, or they aim to protect organisations by allowing them to control employees and make them liable for ethics at work.

Structured reflection breaks embedded in an online course – effects on learning experience, time on task and performance

The purpose of this article is to gain an insight into the effects of practicing short, frequent,and structured reflection breaks interspersed with the learning material in a computer-based course. To that end, the study sets up a standardized control trial with two groups of secondary school pupils. The study shows that while performance is not affected by these embedded “reflection rituals,” they significantly impact time on task and perceived learning. The study also suggests that the exposure to such built-in opportunities for reflection modifies the engagement with the content and fosters the claimed readiness for application of a similar reflective approach to learning in other occasions.

Performance assessment in serious games: Compensating for the effects of randomness

This paper is about performance assessment in serious games. We conceive serious gaming as a process of player-lead decision taking. Starting from combinatorics and item-response theory we provide an analytical model that makes explicit to what extent observed player performances (decisions) are blurred by chance processes (guessing behaviors). We found large effects both theoretically and practically. In two existing serious games random guess scores were found to explain up to 41% of total scores. Monte Carlo simulation of random game play confirmed the substantial impact of randomness on performance. For valid performance assessments, be it in-game or post-game, the effects of randomness should be included to produce re-calibrated scores that can reasonably be interpreted as the players´ achievements.

Towards Real-time Speech Emotion Recognition for Affective E-Learning

The original article is available as an open access file on the Springer website in the following link: http://link.springer.com/article/10.1007/s10639-015-9388-2

Evaluation of Serious Games: A Holistic Approach

Digital games constitute a major emerging technology that is expected to enter mainstream educational use within a few years. The highly engaging and motivating character of such games bears great potential to support immersive, meaningful, and situated learning experiences. To seize this potential, meaningful quality and impact measurements are indispensible. Although there is a growing body of evidence on the efficacy of games for learning, evaluation is often poorly designed, incomplete, biased, if not entirely absent. Well-designed evaluations demonstrating the educational effect as well as the return on investment of serious games may foster broader adoption by educational institutions and training providers, and support the development of the serious game industry. The European project RAGE introduces a comprehensive and multi-perspective framework for serious game evaluation, which is presented in this paper.