A review of the methodological features of systematic reviews in maternal medicine

Background In maternal medicine, research evidence is scattered making it difficult to access information for clinical decision making. Systematic reviews of good methodological quality are essential to provide valid inferences and to produce usable evidence summaries to guide management. This review assesses the methodological features of existing systematic reviews in maternal medicine, comparing Cochrane and non-Cochrane reviews in maternal medicine. Methods Medline, Embase, Database of Reviews of Effectiveness (DARE) and Cochrane Database of Systematic Reviews (CDSR) were searched for relevant reviews published between 2001 and 2006. We selected those reviews in which a minimum of two databases were searched and the primary outcome was related to the maternal condition. The selected reviews were assessed for information on framing of question, literature search and methods of review. Results Out of 2846 citations, 68 reviews were selected. Among these, 39 (57%) were Cochrane reviews. Most of the reviews (50/68, 74%) evaluated therapeutic interventions. Overall, 54/68 (79%) addressed a focussed question. Although 64/68 (94%) reviews had a detailed search description, only 17/68 (25%) searched without language restriction. 32/68 (47%) attempted to include unpublished data and 11/68 (16%) assessed for the risk of missing studies quantitatively. The reviews had deficiencies in the assessment of validity of studies and exploration for heterogeneity. When compared to Cochrane reviews, other reviews were significantly inferior in specifying questions (OR 20.3, 95% CI 1.1–381.3, p = 0.04), framing focussed questions (OR 30.9, 95% CI 3.7- 256.2, p = 0.001), use of unpublished data (OR 5.6, 95% CI 1.9–16.4, p = 0.002), assessment for heterogeneity (OR 38.1, 95%CI 2.1, 688.2, p = 0.01) and use of meta-analyses (OR 3.7, 95% CI 1.3–10.8, p = 0.02). Conclusion This study identifies areas which have a strong influence on maternal morbidity and mortality but lack good quality systematic reviews. Overall quality of the existing systematic reviews was variable. Cochrane reviews were of better quality as compared to other reviews. There is a need for good quality systematic reviews to inform practice in maternal medicine

Atomic transition frequencies, isotope shifts, and sensitivity to variation of the fine structure constant for studies of quasar absorption spectra

Theories unifying gravity with other interactions suggest spatial and temporal variation of fundamental "constants" in the Universe. A change in the fine structure constant, alpha, could be detected via shifts in the frequencies of atomic transitions in quasar absorption systems. Recent studies using 140 absorption systems from the Keck telescope and 153 from the Very Large Telescope, suggest that alpha varies spatially. That is, in one direction on the sky alpha seems to have been smaller at the time of absorption, while in the opposite direction it seems to have been larger. To continue this study we need accurate laboratory measurements of atomic transition frequencies. The aim of this paper is to provide a compilation of transitions of importance to the search for alpha variation. They are E1 transitions to the ground state in several different atoms and ions, with wavelengths ranging from around 900 - 6000 A, and require an accuracy of better than 10^{-4} A. We discuss isotope shift measurements that are needed in order to resolve systematic effects in the study. The coefficients of sensitivity to alpha-variation (q) are also presented.Comment: Includes updated version of the "alpha line" lis

Political airs : from monitoring to attuned sensing air pollution

In Madrid, as in many European cities, air pollution is known about and made accountable through techno-scientific monitoring processes based on data, and the toxicity of the air is defined through epidemiological studies and made political through policy. In 2009, Madrid’s City Council changed the location of its air quality monitoring stations without notice, reducing the average pollution of the city and therefore provoking a public scandal. This scandal challenged the monitoring process, as the data that used to be the evidence of pollution could not be relied on anymore. To identify the characteristics of some of the diverse forms of public’s participation that emerged, I route theories of environmental sensing from STS and feminist theory through the notion of attuned sensing. Reading environmental sensing through the processual and orientational processes of attunement expands the ways in which toxicity can be sensed outside of quantitative data. This mode of sensing recognizes how the different spontaneous attunements to and with air pollution and the scandal acknowledged Madrid’s chemical infrastructure, rendering visible qualitative conditions of toxicity. This mode of sensing politicized the toxicity of the air not through management or policy making, nor only through established forms environmental activism, but through contagion and accumulation of the different forms of public participation. All together, they made air pollution a matter of public concern. They also redistributed the actors, practices and objects that make the toxicity not only knowable, but also accountable, and most importantly, they opened up spaces for citizen intervention

Bench-to-bedside review : targeting antioxidants to mitochondria in sepsis

Peer reviewedPublisher PD

A global disorder of imprinting in the human female germ line

Imprinted genes are expressed differently depending on whether they are carried by a chromosome of maternal or paternal origin. Correct imprinting is established by germline-specific modifications; failure of this process underlies several inherited human syndromes. All these imprinting control defects are cis-acting, disrupting establishment or maintenance of allele-specific epigenetic modifications across one contiguous segment of the genome. In contrast, we report here an inherited global imprinting defect. This recessive maternal-effect mutation disrupts the specification of imprints at multiple, non-contiguous loci, with the result that genes normally carrying a maternal methylation imprint assume a paternal epigenetic pattern on the maternal allele. The resulting conception is phenotypically indistinguishable from an androgenetic complete hydatidiform mole, in which abnormal extra-embryonic tissue proliferates while development of the embryo is absent or nearly so. This disorder offers a genetic route to the identification of trans-acting oocyte factors that mediate maternal imprint establishment

Coalescent-based genome analyses resolve the early branches of the euarchontoglires

Despite numerous large-scale phylogenomic studies, certain parts of the mammalian tree are extraordinarily difficult to resolve. We used the coding regions from 19 completely sequenced genomes to study the relationships within the super-clade Euarchontoglires (Primates, Rodentia, Lagomorpha, Dermoptera and Scandentia) because the placement of Scandentia within this clade is controversial. The difficulty in resolving this issue is due to the short time spans between the early divergences of Euarchontoglires, which may cause incongruent gene trees. The conflict in the data can be depicted by network analyses and the contentious relationships are best reconstructed by coalescent-based analyses. This method is expected to be superior to analyses of concatenated data in reconstructing a species tree from numerous gene trees. The total concatenated dataset used to study the relationships in this group comprises 5,875 protein-coding genes (9,799,170 nucleotides) from all orders except Dermoptera (flying lemurs). Reconstruction of the species tree from 1,006 gene trees using coalescent models placed Scandentia as sister group to the primates, which is in agreement with maximum likelihood analyses of concatenated nucleotide sequence data. Additionally, both analytical approaches favoured the Tarsier to be sister taxon to Anthropoidea, thus belonging to the Haplorrhine clade. When divergence times are short such as in radiations over periods of a few million years, even genome scale analyses struggle to resolve phylogenetic relationships. On these short branches processes such as incomplete lineage sorting and possibly hybridization occur and make it preferable to base phylogenomic analyses on coalescent methods

Genetically Engineered Phages: a Review of Advances over the Last Decade

Summary: Soon after their discovery in the early 20th century, bacteriophages were recognized to have great potential as antimicrobial agents, a potential that has yet to be fully realized. The nascent field of phage therapy was adversely affected by inadequately controlled trials and the discovery of antibiotics. Although the study of phages as anti-infective agents slowed, phages played an important role in the development of molecular biology. In recent years, the increase in multidrug-resistant bacteria has renewed interest in the use of phages as antimicrobial agents. With the wide array of possibilities offered by genetic engineering, these bacterial viruses are being modified to precisely control and detect bacteria and to serve as new sources of antibacterials. In applications that go beyond their antimicrobial activity, phages are also being developed as vehicles for drug delivery and vaccines, as well as for the assembly of new materials. This review highlights advances in techniques used to engineer phages for all of these purposes and discusses existing challenges and opportunities for future work.D.P.P. acknowledges financial support from the Portuguese Foundation for Science and Technology (FCT) through grant SFRH/BD/76440/2011. This work was funded by The Center for Microbiome Informatics and Therapeutics and NSF Expeditions in Computing Program award #1522074 as part of the Living Computing Project. This work was further supported by grants from the Defense Threat Reduction Agency (grants HDTRA1-14-1-0007 and HDTRA1-15-1-0050), the National Institutes of Health (grants 1DP2OD008435,1P50GM098792,1R01EB017755, and 1R21AI12166901), and the U.S. Army Research Laboratory and U.S. Army Research Office, through the Institute for Soldier Nanotechnologies, under contract number W911NF-13-D-0001.S.S.is an FCT investigator (IF/01413/2013). D.P.P., S.S., and J.A. also acknowledge financial support from FCT under the scope of the strategic funding of the UID/ BIO/04469/2013 unit and COMPETE 2020 (grant POCI-01-0145FEDER-006684). T.K.L. is a founder of Sample6 Inc. and Eligo Biosciences, two companies developing phage-based technologies

Marginalization of end-use technologies in energy innovation for climate protection

Mitigating climate change requires directed innovation efforts to develop and deploy energy technologies. Innovation activities are directed towards the outcome of climate protection by public institutions, policies and resources that in turn shape market behaviour. We analyse diverse indicators of activity throughout the innovation system to assess these efforts. We find efficient end-use technologies contribute large potential emission reductions and provide higher social returns on investment than energy-supply technologies. Yet public institutions, policies and financial resources pervasively privilege energy-supply technologies. Directed innovation efforts are strikingly misaligned with the needs of an emissions-constrained world. Significantly greater effort is needed to develop the full potential of efficient end-use technologies

Identifying chemokines as therapeutic targets in renal disease: Lessons from antagonist studies and knockout mice

Chemokines, in concert with cytokines and adhesion molecules, play multiple roles in local and systemic immune responses. In the kidney, the temporal and spatial expression of chemokines correlates with local renal damage and accumulation of chemokine receptor-bearing leukocytes. Chemokines play important roles in leukocyte trafficking and blocking chemokines can effectively reduce renal leukocyte recruitment and subsequent renal damage. However, recent data indicate that blocking chemokine or chemokine receptor activity in renal disease may also exacerbate renal inflammation under certain conditions. An increasing amount of data indicates additional roles of chemokines in the regulation of innate and adaptive immune responses, which may adversively affect the outcome of interventional studies. This review summarizes available in vivo studies on the blockade of chemokines and chemokine receptors in kidney diseases, with a special focus on the therapeutic potential of anti-chemokine strategies, including potential side effects, in renal disease. Copyright (C) 2004 S. Karger AG, Basel

Worldwide comparison of survival from childhood leukaemia for 1995-2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries.

Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (<1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year age-standardised net survival for all lymphoid leukaemias combined ranged from 10·6% (95% CI 3·1-18·2) in the Chinese registries to 86·8% (81·6-92·0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52·4% (95% CI 42·8-61·9) in Cali, Colombia, to 91·6% (89·5-93·6) in the German registries, and for AML ranged from 33·3% (18·9-47·7) in Bulgaria to 78·2% (72·0-84·3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood cancer survival. Canadian Partnership Against Cancer, Cancer Focus Northern Ireland, Cancer Institute New South Wales, Cancer Research UK, US Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, and the University of Kentucky