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1.  Rating the Quality of Trials in Systematic Reviews of Physical Therapy Interventions 
Physical therapists seeking to use evidence to guide their practice may have limited time to read research reports. One way to reduce the time required to identify and read about the research that is relevant to a particular clinical question is to read a systematic review that summarizes multiple studies. This paper explains the process that is used to conduct systematic reviews, which includes the establishment of a protocol, comprehensive searching, appraisal of the quality of the included studies, data extraction and metaanalysis, and consideration of the clinical and research implications of the findings. We also consider how the reader of a systematic review can determine whether the review is likely to provide an unbiased (believable) estimate of the treatment effect. A systematic review of randomized trials of a cardiopulmonary physical therapy intervention is used as an example. The issue of appraisal of quality is then discussed further, with a demonstration of how one validated tool for quality appraisal–the PEDro scale–can be used to evaluate a randomized trial in cardiopulmonary physical therapy.
PMCID: PMC2941354  PMID: 20957075
systematic review; physical therapy
2.  A qualitative study into the difficulties experienced by healthcare decision makers when reading a Cochrane diagnostic test accuracy review 
Systematic Reviews  2013;2:32.
Cochrane reviews are one of the best known and most trusted sources of evidence-based information in health care. While steps have been taken to make Cochrane intervention reviews accessible to a diverse readership, little is known about the accessibility of the newcomer to the Cochrane library: diagnostic test accuracy reviews (DTARs). The current qualitative study explored how healthcare decision makers, who varied in their knowledge and experience with test accuracy research and systematic reviews, read and made sense of DTARs.
A purposive sample of clinicians, researchers and policy makers (n = 21) took part in a series of think-aloud interviews, using as interview material the first three DTARs published in the Cochrane library. Thematic qualitative analysis of the transcripts was carried out to identify patterns in participants’ ‘reading’ and interpretation of the reviews and the difficulties they encountered.
Participants unfamiliar with the design and methodology of DTARs found the reviews largely inaccessible and experienced a range of difficulties stemming mainly from the mismatch between background knowledge and level of explanation provided in the text. Experience with systematic reviews of interventions did not guarantee better understanding and, in some cases, led to confusion and misinterpretation. These difficulties were further exacerbated by poor layout and presentation, which affected even those with relatively good knowledge of DTARs and had a negative impact not only on their understanding of the reviews but also on their motivation to engage with the text. Comparison between the readings of the three reviews showed that more accessible presentation, such as presenting the results as natural frequencies, significantly increased participants’ understanding.
The study demonstrates that authors and editors should pay more attention to the presentation as well as the content of Cochrane DTARs, especially if the reports are aimed at readers with various levels of background knowledge and experience. It also raises the question as to the anticipated target audience of the reports and suggests that different groups of healthcare decision-makers may require different modes of presentation.
PMCID: PMC3663697  PMID: 23680077
Cochrane reviews; Diagnostic accuracy; Sensitivity and specificity; Qualitative research; Think -aloud interview
3.  Reading, writing and systematic review 
Journal of advanced nursing  2008;64(1):104-110.
This paper offers a discussion of the reading and writing practices that define systematic review.
Although increasingly popular, systematic review has engendered a critique of the claims made for it as a more objective method for summing up research findings than other kinds of reviews.
An alternative understanding of systematic review is as a highly subjective, albeit disciplined, engagement between resisting readers and resistant texts. Reviewers of research exemplify the resisting reader when they exclude reports on grounds of relevance, quality, or methodological difference. Research reports exemplify resistant texts as they do not simply yield their findings, but rather must be made docile to review. These acts of resistance make systematic review possible, but challenge claims of its greater capacity to control bias.
An understanding of the reading and writing practices that define systematic review still holds truth and objectivity as regulative ideals, but is aware of the reading and writing practices that both enable and challenge those ideals.
PMCID: PMC2569151  PMID: 18721156
bias; qualitative research; quantitative research; research methods; resisting reader; systematic review; textual practices
4.  Reviewing evidence on complex social interventions: appraising implementation in systematic reviews of the health effects of organisational-level workplace interventions 
The reporting of intervention implementation in studies included in systematic reviews of organisational-level workplace interventions was appraised. Implementation is taken to include such factors as intervention setting, resources, planning, collaborations, delivery and macro-level socioeconomic contexts. Understanding how implementation affects intervention outcomes may help prevent erroneous conclusions and misleading assumptions about generalisability, but implementation must be adequately reported if it is to be taken into account.
Data on implementation were obtained from four systematic reviews of complex interventions in workplace settings. Implementation was appraised using a specially developed checklist and by means of an unstructured reading of the text.
103 studies were identified and appraised, evaluating four types of organisational-level workplace intervention (employee participation, changing job tasks, shift changes and compressed working weeks). Many studies referred to implementation, but reporting was generally poor and anecdotal in form. This poor quality of reporting did not vary greatly by type or date of publication. A minority of studies described how implementation may have influenced outcomes. These descriptions were more usefully explored through an unstructured reading of the text, rather than by means of the checklist.
Evaluations of complex interventions should include more detailed reporting of implementation and consider how to measure quality of implementation. The checklist helped us explore the poor reporting of implementation in a more systematic fashion. In terms of interpreting study findings and their transferability, however, the more qualitative appraisals appeared to offer greater potential for exploring how implementation may influence the findings of specific evaluations. Implementation appraisal techniques for systematic reviews of complex interventions require further development and testing.
PMCID: PMC2596297  PMID: 18718981
5.  Annual Research Review: The nature and classification of reading disorders – a commentary on proposals for DSM-5 
This article reviews our understanding of reading disorders in children and relates it to current proposals for their classification in DSM-5. There are two different, commonly occurring, forms of reading disorder in children which arise from different underlying language difficulties. Dyslexia (as defined in DSM-5), or decoding difficulty, refers to children who have difficulty in mastering the relationships between the spelling patterns of words and their pronunciations. These children typically read aloud inaccurately and slowly, and experience additional problems with spelling. Dyslexia appears to arise principally from a weakness in phonological (speech sound) skills, and there is good evidence that it can be ameliorated by systematic phonic teaching combined with phonological awareness training. The other major form of reading difficulty is reading comprehension impairment. These children read aloud accurately and fluently, but have difficulty understanding what they have read. Reading comprehension impairment appears to arise from weaknesses in a range of oral language skills including poor vocabulary knowledge, weak grammatical skills and difficulties in oral language comprehension. We suggest that the omission of reading comprehension impairment from DSM-5 is a serious one that should be remedied. Both dyslexia and reading comprehension impairment are dimensional in nature, and show strong continuities with other disorders of language. We argue that recognizing the continuities between reading and language disorders has important implications for assessment and treatment, and we note that the high rates of comorbidity between reading disorders and other seemingly disparate disorders (including ADHD and motor disorders) raises important challenges for understanding these disorders.
PMCID: PMC3492851  PMID: 22141434
Reading disorders; language disorders; dyslexia; reading comprehension impairment; intervention
6.  Visual Skills and Cross-Modal Plasticity in Deaf Readers 
Most research on reading skill acquisition in deaf individuals has been conducted from the perspective of a hearing child learning to read. This approach may limit our understanding of how a deaf child approaches the task of learning to read and successfully acquires reading skills. An alternative approach is to consider how the cognitive skills that a deaf child brings to the reading task may influence the route by which he or she achieves reading fluency. A review of the literature on visual spatial attention suggests that deaf individuals are more distracted by visual information in the parafovea and periphery. We discuss how this may have an influence upon the perceptual processing of written text in deaf students.
PMCID: PMC2896825  PMID: 19076390
deaf; reading; visual attention; distractibility; cross-modal plasticity
7.  Is single reading with computer-aided detection (CAD) as good as double reading in mammography screening? A systematic review 
BMC Medical Imaging  2012;12:22.
In accordance with European guidelines, mammography screening comprises independent readings by two breast radiologists (double reading). CAD (computer-aided detection) has been suggested to complement or replace one of the two readers (single reading + CAD).
The aim of this systematic review is to address the following question: Is the reading of mammographic x-ray images by a single breast radiologist together with CAD at least as accurate as double reading?
The electronic literature search included the databases Pub Med, EMBASE and The Cochrane Library. Two independent reviewers assessed abstracts and full-text articles.
1049 abstracts were identified, of which 996 were excluded with reference to inclusion and exclusion criteria; 53 full-text articles were assessed for eligibility. Finally, four articles were included in the qualitative analysis, and one in a GRADE synthesis.
The scientific evidence is insufficient to determine whether the accuracy of single reading + CAD is at least equivalent to that obtained in standard practice, i.e. double reading where two breast radiologists independently read the mammographic images.
PMCID: PMC3464719  PMID: 22827803
CAD; Mammography; Screening; Breast; Cancer; Single reading; Double reading
8.  Room for improvement? A survey of the methods used in systematic reviews of adverse effects 
Although the methods for conducting systematic reviews of efficacy are well established, there is much less guidance on how systematic reviews of adverse effects should be performed.
In order to determine where methodological research is most needed to improve systematic reviews of adverse effects of health care interventions, we conducted a descriptive analysis of systematic reviews published between 1994 and 2005. We searched the Database of Abstracts of Reviews of Effects (DARE) and The Cochrane Database of Systematic Reviews (CDSR) to identify systematic reviews in which the primary outcome was an adverse effect or effects. We then extracted data on many of the elements of the systematic review process including: types of interventions studied, adverse effects of interest, resources searched, search strategies, data sources included in reviews, quality assessment of primary data, nature of the data analysis, and source of funding.
256 reviews were included in our analysis, of which the majority evaluated drug interventions and pre-specified the adverse effect or effects of interest. A median of 3 resources were searched for each review and very few reviews (13/256) provided sufficient information to reproduce their search strategies. Although more than three quarters (185/243) of the reviews sought to include data from sources other than randomised controlled trials, fewer than half (106/256) assessed the quality of the studies that were included. Data were pooled quantitatively in most of the reviews (165/256) but heterogeneity was not always considered. Less than half (123/256) of the reviews reported on the source of funding.
There is an obvious need to improve the methodology and reporting of systematic reviews of adverse effects. The methodology around identification and quality assessment of primary data is the main concern.
PMCID: PMC1402311  PMID: 16441876
9.  Case Series Investigations in Cognitive Neuropsychology 
Cognitive neuropsychology  2011;27(6):477-494.
Case series methodology involves the systematic assessment of a sample of related patients, with the goal of understanding how and why they differ from one another. This method has become increasingly important in cognitive neuropsychology, which has long been identified with single-subject research. We review case series studies dealing with impaired semantic memory, reading, and language production, and draw attention to the affinity of this methodology for testing theories that are expressed as computational models and for addressing questions about neuroanatomy. It is concluded that case series methods usefully complement single-subject techniques.
PMCID: PMC3162112  PMID: 21714756
case series; single-subject; cognitive neuropsychology; computational models; lexical access; semantic dementia; aphasia; semantic memory
10.  Clarifying the abstracts of systematic literature reviews* 
Background: There is a small body of research on improving the clarity of abstracts in general that is relevant to improving the clarity of abstracts of systematic reviews.
Objectives: To summarize this earlier research and indicate its implications for writing the abstracts of systematic reviews.
Method: Literature review with commentary on three main features affecting the clarity of abstracts: their language, structure, and typographical presentation.
Conclusions: The abstracts of systematic reviews should be easier to read than the abstracts of medical research articles, as they are targeted at a wider audience. The aims, methods, results, and conclusions of systematic reviews need to be presented in a consistent way to help search and retrieval. The typographic detailing of the abstracts (type-sizes, spacing, and weights) should be planned to help, rather than confuse, the reader.
PMCID: PMC35254  PMID: 11055300
11.  Refining the Experimental Analysis of Academic Skills Deficits: Part I. An Investigation of Variables That Affect Generalized Oral Reading Performance 
Experimental analyses for improving reading fluency deficits have rarely targeted generalized increases in academic responding. As a consequence, the variables that may help students to generalize newly learned forms of academic responding like reading are not well understood. Furthermore, experimental analyses of reading fluency interventions have not systematically examined difficulty level as a variable that may affect instructional outcomes. The experiment reported in this paper expands (a) the measurement of the dependent variables to include generalized increases across tasks (reading passages) and (b) the combination of independent variables used to produce measurable generalized increases. The results demonstrate the importance of combining reward and instructional variables (including difficulty level) to produce generalized increases and how those variables can be meaningfully investigated prior to making treatment recommendations.
PMCID: PMC1309711  PMID: 16463529
academic performance; experimental analysis; generalization; reading fluency
12.  Errors in Multi-Digit Arithmetic and Behavioral Inattention in Children With Math Difficulties 
Journal of learning disabilities  2009;42(4):356-371.
Errors in written multi-digit computation were investigated in children with math difficulties. Third-and fourth-grade children (n = 291) with coexisting math and reading difficulties, math difficulties, reading difficulties, or no learning difficulties were compared. A second analysis compared those with severe math learning difficulties, low average achievement in math, and no learning difficulties. Math fact errors were related to the severity of the math difficulties, not to reading status. Contrary to predictions, children with poorer reading, regardless of math achievement, committed more visually based errors. Operation switch errors were not systematically related to group membership. Teacher ratings of behavioral inattention were related to accuracy, math fact errors, and procedural bugs. The findings are discussed with respect to hypotheses about the cognitive origins of arithmetic errors and in relation to current discussions about how to conceptualize math disabilities.
PMCID: PMC2788949  PMID: 19380494
mathematical disabilities; multi-digit arithmetic; attention
13.  Assessment of methodological quality of primary studies by systematic reviews: results of the metaquality cross sectional study 
BMJ : British Medical Journal  2005;330(7499):1053.
Objectives To describe how the methodological quality of primary studies is assessed in systematic reviews and whether the quality assessment is taken into account in the interpretation of results.
Data sources Cochrane systematic reviews and systematic reviews in paper based journals.
Study selection 965 systematic reviews (809 Cochrane reviews and 156 paper based reviews) published between 1995 and 2002.
Data synthesis The methodological quality of primary studies was assessed in 854 of the 965 systematic reviews (88.5%). This occurred more often in Cochrane reviews than in paper based reviews (93.9% v 60.3%, P < 0.0001). Overall, only 496 (51.4%) used the quality assessment in the analysis and interpretation of the results or in their discussion, with no significant differences between Cochrane reviews and paper based reviews (52% v 49%, P = 0.58). The tools and methods used for quality assessment varied widely.
Conclusions Cochrane reviews fared better than systematic reviews published in paper based journals in terms of assessment of methodological quality of primary studies, although they both largely failed to take it into account in the interpretation of results. Methods for assessment of methodological quality by systematic reviews are still in their infancy and there is substantial room for improvement.
PMCID: PMC557223  PMID: 15817526
14.  Behavioral Genetic Approach to the Study of Dyslexia 
Dyslexia is a prominent focus of practitioners, educators, and researchers due to the myriad consequences of failing to read proficiently. The aim of the current study was to provide a brief overview of how twin studies can offer insight on the etiology of many human behaviors and disorders including dyslexia, discuss common misconceptions regarding findings from behavioral genetic studies, briefly review the evidence on the relationship between genes, environment, and dyslexia, and finally present some findings from a large-scale twin study on reading and dyslexia.
Participants were twins from a large ethnically and socioeconomically diverse twin sample in an ongoing longitudinal study of reading and dyslexia. Heritabilities of reading ability and dyslexia were calculated for 1,024 first grade twins on a standardized reading measure. Children were identified as dyslexic if they scored at the fifteenth percentile or below on a reading measure.
Relatively high heritabilities were observed for both reading ability and dyslexia indicating substantial genetic influences. Further, results indicated some overlap of genetic factors influencing reading ability and dyslexia.
Behavioral genetic studies offer a means of understanding the etiology of dyslexia. The current study extended research to a more diverse sample than extant studies and found lower heritability estimates of reading ability and dyslexia, but a similar pattern of results indicating genetic overlap. Twin studies provide perspective for discoveries of specific genes involved in dyslexia by quantifying the amount of variance waiting to be accounted for by genes while simultaneously providing an impetus to continue working on efforts for environmental intervention.
PMCID: PMC2952936  PMID: 20814252
dyslexia; heritability; twins; genetic
15.  Models of the Reading Process 
Reading is a complex skill involving the orchestration of a number of components. Researchers often talk about a “model of reading” when talking about only one aspect of the reading process (for example, models of word identification are often referred to as “models of reading”). Here, we review prominent models that are designed to account for (1) word identification, (2) syntactic parsing, (3) discourse representations, and (4) how certain aspects of language processing (e.g., word identification), in conjunction with other constraints (e g., limited visual acuity, saccadic error, etc.), guide readers’ eyes. Unfortunately, it is the case that these various models addressing specific aspects of the reading process seldom make contact with models dealing with other aspects of reading. Thus, for example, the models of word identification seldom make contact with models of eye movement control, and vice versa. While this may be unfortunate in some ways, it is quite understandable in other ways because reading itself is a very complex process. We discuss prototypical models of aspects of the reading process in the order mentioned above. We do not review all possible models, but rather focus on those we view as being representative and most highly recognized.
PMCID: PMC3001687  PMID: 21170142
16.  Form–meaning links in the development of visual word recognition 
Learning to read takes time and it requires explicit instruction. Three decades of research has taught us a good deal about how children learn about the links between orthography and phonology during word reading development. However, we have learned less about the links that children build between orthographic form and meaning. This is surprising given that the goal of reading development must be for children to develop an orthographic system that allows meanings to be accessed quickly, reliably and efficiently from orthography. This review considers whether meaning-related information is used when children read words aloud, and asks what we know about how and when children make connections between form and meaning during the course of reading development.
PMCID: PMC2846312  PMID: 19933139
word reading; children's reading; orthography; word learning
17.  The rough guide to systematic reviews and meta-analyses  
The hierarchy of evidence based medicine postulates that systematic reviews of homogenous randomized trials represent one of the uppermost levels of clinical evidence. Indeed, the current overwhelming role of systematic reviews, meta-analyses and meta-regression analyses in evidence based heath care calls for a thorough knowledge of the pros and cons of these study designs, even for the busy clinician. Despite this sore need, few succinct but thorough resources are available to guide users or would-be authors of systematic reviews. This article provides a rough guide to reading and, summarily, designing and conducting systematic reviews and meta-analyses
PMCID: PMC3484632  PMID: 23439862
meta-analysis; meta-regression; systematic review
18.  Building blocks for meta-synthesis: data integration tables for summarising, mapping, and synthesising evidence on interventions for communicating with health consumers 
Systematic reviews have developed into a powerful method for summarising and synthesising evidence. The rise in systematic reviews creates a methodological opportunity and associated challenges and this is seen in the development of overviews, or reviews of systematic reviews. One of these challenges is how to summarise evidence from systematic reviews of complex interventions for inclusion in an overview. Interventions for communicating with and involving consumers in their care are frequently complex. In this article we outline a method for preparing data integration tables to enable review-level synthesis of the evidence on interventions for communication and participation in health.
Methods and Results
Systematic reviews published by the Cochrane Consumers and Communication Review Group were utilised as the basis from which to develop linked steps for data extraction, evidence assessment and synthesis. The resulting output is called a data integration table. Four steps were undertaken in designing the data integration tables: first, relevant information for a comprehensive picture of the characteristics of the review was identified from each review, extracted and summarised. Second, results for the outcomes of the review were assessed and translated to standardised evidence statements. Third, outcomes and evidence statements were mapped into an outcome taxonomy that we developed, using language specific to the field of interventions for communication and participation. Fourth, the implications of the review were assessed after the mapping step clarified the level of evidence available for each intervention.
The data integration tables represent building blocks for constructing overviews of review-level evidence and for the conduct of meta-synthesis. Individually, each table aims to improve the consistency of reporting on the features and effects of interventions for communication and participation; provides a broad assessment of the strength of evidence derived from different methods of analysis; indicates a degree of certainty with results; and reports outcomes and gaps in the evidence in a consistent and coherent way. In addition, individual tables can serve as a valuable tool for accurate dissemination of large amounts of complex information on communication and participation to professionals as well as to members of the public.
PMCID: PMC2678150  PMID: 19261177
19.  Functional Neuroimaging Insights Into the Development of Skilled Reading 
Typically developing children require years of overt training and practice to learn to read with skill. The relatively recent advent of functional neuroimaging methods amenable to the study of children has provided insight into the neurobiological underpinnings of skilled reading development. In this brief review, we discuss how neuroimaging during reading-related tasks has revealed that, when adult and child skilled readers perform identical reading-related tasks with comparable levels of performance, these groups show similar, but nonidentical patterns of regional brain activity. Children activate some neural regions that adults do not activate (or activate less), and vice versa. The activity patterns in these regions transition to mature levels with increased proficiency and maturity. The dynamic nature of the reading brain as the child matures is thought to be a demonstration of both the inherent flexibility and the increasing efficiency of brain processing over development.
PMCID: PMC2741313  PMID: 19750204
development; reading; phonology; children; fMRI
20.  Brain Mechanisms and Reading Remediation: More Questions Than Answers 
Scientifica  2014;2014:802741.
Dyslexia is generally diagnosed in childhood and is characterised by poor literacy skills with associated phonological and perceptual problems. Compensated dyslexic readers are adult readers who have a documented history of childhood dyslexia but as adults can read and comprehend written text well. Uncompensated dyslexic readers are adults who similarly have a documented history of reading impairment but remain functionally reading-impaired all their lives. There is little understanding of the neurophysiological basis for how or why some children become compensated, while others do not, and there is little knowledge about neurophysiological changes that occur with remedial programs for reading disability. This paper will review research looking at reading remediation, particularly in the context of the underlying neurophysiology.
PMCID: PMC3913493  PMID: 24527259
21.  The Hip and Knee Book: developing an active management booklet for hip and knee osteoarthritis 
The pain and disability of hip and knee osteoarthritis can be improved by exercise, but the best method of encouraging this is not known.
To develop an evidence-based booklet for patients with hip or knee osteoarthritis, offering information and advice on maintaining activity.
Design of study
Systematic review of reviews and guidelines, then focus groups.
Four general practices in North East Wales.
Evidence-based messages were developed from a systematic review, synthesised into patient-centred messages, and then incorporated into a narrative. A draft booklet was examined by three focus groups to improve the phrasing of its messages and discuss its usefulness. The final draft was examined in a fourth focus group.
Six evidence-based guidelines and 54 systematic reviews were identified. The focus groups found the draft booklet to be informative and easy to read. They reported a lack of clarity about the cause of osteoarthritis and were surprised that the pain could improve. The value of exercise and weight loss beliefs was accepted and reinforced, but there was a perceived contradiction about heavy physical work being causative, while moderate exercise was beneficial. There was a fear of dependency on analgesia and misinterpretation of the message on hyaluranon injections. The information on joint replacement empowered patients to discuss referral with their GP. The text was revised to accommodate these issues.
The booklet was readable, credible, and useful to end-users. A randomised controlled trial is planned, to test whether the booklet influences beliefs about osteoarthritis and exercise.
PMCID: PMC2814291  PMID: 20132695
focus groups; osteoarthritis, hip; osteoarthritis, knee; patient education handout; primary health care; systematic review
Enumeration of parasites by microscopic examination of blood smears is the only method available for quantifying parasitemia in infected blood. However, the sources and scale of error inherent in this technique have not been systematically investigated. Here we use data collected in outpatient clinics in Peru and Thailand to elucidate important sources of variation in parasite density measurements. We show that discrepancies between readings from two independent microscopists and multiple readings from a single microscopist are inversely related to the density of the infection. We present an example of how differences in reader technique, specifically the number of white blood cells counted, can contribute to the differences between readings. We discuss the implications of this analysis for field studies and clinical trials.
PMCID: PMC2500224  PMID: 16172488
23.  Get the Story Straight: Contextual Repetition Promotes Word Learning from Storybooks 
Although shared storybook reading is a common activity believed to improve the language skills of preschool children, how children learn new vocabulary from such experiences has been largely neglected in the literature. The current study systematically explores the effects of repeatedly reading the same storybooks on both young children's fast and slow mapping abilities. Specially created storybooks were read to 3-year-old children three times during the course of 1 week. Each of the nine storybooks contained two novel name–object pairs. At each session, children either heard three different stories with the same two novel name–object pairs or the same story three times. Importantly, all children heard each novel name the same number of times. Both immediate recall and retention were tested with a four-alternative forced-choice task with pictures of the novel objects. Children who heard the same stories repeatedly were very accurate on both the immediate recall and retention tasks. In contrast, children who heard different stories were only accurate on immediate recall during the last two sessions and failed to learn any of the new words. Overall, then, we found a dramatic increase in children's ability to both recall and retain novel name–object associations encountered during shared storybook reading when they heard the same stories multiple times in succession. Results are discussed in terms of contextual cueing effects observed in other cognitive domains.
PMCID: PMC3111254  PMID: 21713179
shared book reading; fast mapping; word learning; contextual learning; language acquisition
24.  How deep is deep enough for RNA-Seq profiling of bacterial transcriptomes? 
BMC Genomics  2012;13:734.
High-throughput sequencing of cDNA libraries (RNA-Seq) has proven to be a highly effective approach for studying bacterial transcriptomes. A central challenge in designing RNA-Seq-based experiments is estimating a priori the number of reads per sample needed to detect and quantify thousands of individual transcripts with a large dynamic range of abundance.
We have conducted a systematic examination of how changes in the number of RNA-Seq reads per sample influences both profiling of a single bacterial transcriptome and the comparison of gene expression among samples. Our findings suggest that the number of reads typically produced in a single lane of the Illumina HiSeq sequencer far exceeds the number needed to saturate the annotated transcriptomes of diverse bacteria growing in monoculture. Moreover, as sequencing depth increases, so too does the detection of cDNAs that likely correspond to spurious transcripts or genomic DNA contamination. Finally, even when dozens of barcoded individual cDNA libraries are sequenced in a single lane, the vast majority of transcripts in each sample can be detected and numerous genes differentially expressed between samples can be identified.
Our analysis provides a guide for the many researchers seeking to determine the appropriate sequencing depth for RNA-Seq-based studies of diverse bacterial species.
PMCID: PMC3543199  PMID: 23270466
25.  Systematic review of the fetal effects of prenatal binge‐drinking 
The effects of binge‐drinking during pregnancy on the fetus and child have been an increasing concern for clinicians and policy‐makers. This study reviews the available evidence from human observational studies.
Systematic review of observational studies.
Pregnant women or women who are trying to become pregnant.
A computerised search strategy was run in Medline, Embase, Cinahl and PsychInfo for the years 1970–2005. Titles and abstracts were read by two researchers for eligibility. Eligible papers were then obtained and read in full by two researchers to decide on inclusion. The papers were assessed for quality using the Newcastle–Ottawa Quality Assessment Scales and data were extracted.
Main outcome measures
Adverse outcomes considered in this study included miscarriage; stillbirth; intrauterine growth restriction; prematurity; birth‐weight; small for gestational age at birth; and birth defects, including fetal alcohol syndrome and neurodevelopmental effects.
The search resulted in 3630 titles and abstracts, which were narrowed down to 14 relevant papers. There were no consistently significant effects of alcohol on any of the outcomes considered. There was a possible effect on neurodevelopment. Many of the reported studies had methodological weaknesses despite being assessed as having reasonable quality.
This systematic review found no convincing evidence of adverse effects of prenatal binge‐drinking, except possibly on neurodevelopmental outcomes.
PMCID: PMC2465662  PMID: 18000129
fetus; pregnancy; binge‐drinking

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