A review of key terminology and definitions used for birth defects globally.

Birth defects, also known as congenital disorders, are a significant health issue impacting at least five million births annually worldwide. For policymakers to mount a relevant healthcare response to care for those affected, the burden of disease of these conditions must be quantified. Estimates of the contribution of birth defects to under-5 child mortality and morbidity are generated by several groups globally. These estimates often differ, causing confusion for policymakers. While some differences may be attributed to the data sources and methods used, much is due to a lack of clarity in the terminology used for the group of disorders classed as "congenital". This study aimed to gain insight into the diversity of terms and definitions for birth defects, including those used routinely by relevant international/national organisations and in the peer-reviewed literature. This two-part study included (1) scoping review of peer-reviewed literature to identify terms and definitions in use for birth defects and (2) review of key websites and grey literature to identify terms and definitions used. The results of this study indicate a wide variety of terms being used, often interchangeably and undefined, in peer-reviewed publications, on institutional websites and related literature. This suggests a lack of clarity related to terminology and sets the scene for further discussion, recommending that the community of practice working on birth defects comes to a consensus on standard terminology and definitions for global uptake and implementation. Such standardisation will facilitate a common understanding of the burden of these disorders globally, regionally and within countries so that action can be taken to support affected children and their families.

Ubiquitous atmospheric production of organic acids mediated by cloud droplets.

Atmospheric acidity is increasingly determined by carbon dioxide and organic acids1-3. Among the latter, formic acid facilitates the nucleation of cloud droplets4 and contributes to the acidity of clouds and rainwater1,5. At present, chemistry-climate models greatly underestimate the atmospheric burden of formic acid, because key processes related to its sources and sinks remain poorly understood2,6-9. Here we present atmospheric chamber experiments that show that formaldehyde is efficiently converted to gaseous formic acid via a multiphase pathway that involves its hydrated form, methanediol. In warm cloud droplets, methanediol undergoes fast outgassing but slow dehydration. Using a chemistry-climate model, we estimate that the gas-phase oxidation of methanediol produces up to four times more formic acid than all other known chemical sources combined. Our findings reconcile model predictions and measurements of formic acid abundance. The additional formic acid burden increases atmospheric acidity by reducing the pH of clouds and rainwater by up to 0.3. The diol mechanism presented here probably applies to other aldehydes and may help to explain the high atmospheric levels of other organic acids that affect aerosol growth and cloud evolution.

Atmospheric implications of large C2-C5 alkane emissions from the U.S. oil and gas industry.

Emissions of C2-C5 alkanes from the U.S. oil and gas sector have changed rapidly over the last decade. We use a nested GEOS-Chem simulation driven by updated 2011NEI emissions with aircraft, surface and column observations to 1) examine spatial patterns in the emissions and observed atmospheric abundances of C2-C5 alkanes over the U.S., and 2) estimate the contribution of emissions from the U.S. oil and gas industry to these patterns. The oil and gas sector in the updated 2011NEI contributes over 80% of the total U.S. emissions of ethane (C2H6) and propane (C3H8), and emissions of these species are largest in the central U.S. Observed mixing ratios of C2-C5 alkanes show enhancements over the central U.S. below 2 km. A nested GEOS-Chem simulation underpredicts observed C3H8 mixing ratios in the boundary layer over several U.S. regions and the relative underprediction is not consistent, suggesting C3H8 emissions should receive more attention moving forward. Our decision to consider only C4-C5 alkane emissions as a single lumped species produces a geographic distribution similar to observations. Due to the increasing importance of oil and gas emissions in the U.S., we recommend continued support of existing long-term measurements of C2-C5 alkanes. We suggest additional monitoring of C2-C5 alkanes downwind of northeastern Colorado, Wyoming and western North Dakota to capture changes in these regions. The atmospheric chemistry modeling community should also evaluate whether chemical mechanisms that lump larger alkanes are sufficient to understand air quality issues in regions with large emissions of these species.

Choices of incidental findings of individuals undergoing genome wide sequencing, a single center's experience.

Genome wide sequencing is an emerging clinical tool that may provide information on genetic variants that are not directly related to the patient's primary disorder. These incidental findings (IFs) may include information about conditions that can be treated and may also indicate conditions for which treatments are not currently available. Data is currently limited regarding what IFs an individual would want to disclose. This study reports on 305 individual choices for return of IFs that were completed at the Medical College of Wisconsin's clinical sequencing laboratory. Individuals were given access to five categories of IFs to select from: no incidental findings, untreatable childhood disorders, treatable adulthood disorders, untreatable adulthood disorders, and carrier of a disorder. Retrospective chart review was conducted and individual choices were recorded and analyzed. The majority of individuals (76.1%) selected every IF to be reported, 14.4% wanted a subset of the options, and 9.5% did not want any IFs reported. This study contributes to the limited data that demonstrates what an individual would actually choose when undergoing genetic sequencing. Furthermore, this data supports the opinion that individuals want and utilize the ability to choose the findings reported.

Narrative Symposium: Patient and Research Participant experiences with Genetic Testing.

Twelve personal narratives address the challenges, benefits, and pitfalls of genetic testing. Three commentary articles explore these stories and suggest lessons that can be learned from them. The commentators come from backgrounds that include bioethics, public health, psychology, and philosophy.

Views of primary care providers regarding the return of genome sequencing incidental findings.

Sequencing of the entire exome or genome is increasingly used in clinical practice. Debate continues, however, regarding which incidental findings (IFs) should be returned and who should be involved in those decisions. Previous empirical research regarding stakeholder attitudes to the return of IFs has primarily involved genetics professionals; non-genetics health professionals have not been widely surveyed. Given this, a survey regarding return of IFs was administered at the Best Practices in Pediatrics Conference following an educational presentation on genetics terminology and genetic condition examples. A total of 258 participants completed the survey. Of particular note, respondents who were positively disposed to sequencing did not always report wanting to learn about IFs, even if actionable. This is noteworthy given recent American College of Medical Genetics and Genomics guidelines recommending particular actionable IF be returned 'without reference to patient preference'. This study's findings are important because they provide insight regarding the attitudes to the return of genome sequencing results for an important professional group, primary care providers. Ultimately, as likely gatekeepers to referrals for this technology, their opinions about the test will be key to its successful deployment.

Dysmorphology at a distance: results of a web-based diagnostic service.

In 2007, the DYSCERNE pilot project funded by the European Commission Public Health Executive Agency (EU DG Sanco) aimed at setting up a network of expertise for patients with rare dysmorphic disorders. As part of DYSCERNE, a Dysmorphology Diagnostic System (DDS) was set up to enable clinicians throughout the EU to submit cases electronically for diagnosis using a secure, web-based interface, hosted at specified access points (Submitting nodes), in 26 different European countries. We report the outcome of this service for 200 cases submitted consecutively between January 2010 and 2012. Each case was reviewed by an average of five expert reviewers. An average of three possible syndromic diagnoses was suggested per case. In 22.5% of the cases, a consensus clinical diagnosis was reached. Genetic testing was suggested in 70.5% of the cases, whereas other laboratory investigations and diagnostic imaging were recommended in 35.5 and 26% of the cases, respectively. Further specialized opinions were suggested in 23.5% of the cases. Overall, a total of 181 very rare or extremely rare genetic syndromes were considered in the differential diagnosis of the 200 cases. In two cases, the reviewers suggested that the findings represented a new syndrome, and in one of these syndromes the underlying genetic cause was subsequently identified. Other benefits of the submission process included the possibility of directing the case submitters to specific centres for diagnostic testing or participation in research and educational benefit derived for both case submitters and reviewers.

A prospective study assessing anxiety, depression and maternal-fetal attachment in women using PGD.

BACKGROUND: PGD has been described in previous cross-sectional and retrospective studies as a stressful experience. No prospective studies of the psychological impact of PGD are currently available. METHODS: Using a prospective study design, validated measures exploring anxiety and depression were used to assess women using PGD prior to treatment, following embryo transfer, following the pregnancy test result and at 24 weeks of pregnancy. Maternal-fetal attachment was also assessed during pregnancy. RESULTS: The prospective design revealed the cyclical pathway through PGD for many women, often comprising repeated cycles of ovarian stimulations and IVF and frozen embryo transfers. As predicted, there were significant fluctuations in women's anxiety scores, with increases observed following embryo transfer and pregnancy testing. Women's anxiety scores returned to baseline levels during pregnancy as assessed at 24 weeks gestation. Depression scores did not significantly fluctuate during PGD. Maternal-fetal attachment scores in this sample did not differ from the normative Australian data. CONCLUSIONS: For some women, the PGD pathway is convoluted and requires multiple IVF cycles and embryo transfers to achieve pregnancy. A subset of women experience significant emotional burden during PGD treatment, and it is these women who require closer attention and support. In this sample, emotional adjustment in pregnancy following PGD appears to be sound.

Women's experience of pre-implantation genetic diagnosis: a qualitative study.

OBJECTIVE: To provide an in-depth account of the experience of pre-implantation genetic diagnosis (PGD). METHOD: Exploratory qualitative interview study. Participants were recruited from one major in vitro fertilization (IVF) clinic in Sydney, Australia. Data were collected through 14 in-depth interviews with women at different stages of PGD, utilized a thematic approach and facilitated by NVivo software. RESULTS: Women reported using PGD as empowering and led them to feel in control of their reproductive futures. Health professionals who did not tell women about PGD were seen as a barrier to accessing treatment. The ability to select embryos free from the genetic condition (for which it was at risk) alleviated stress. Despite this, stress experienced with PGD was significant for women, and often related to past experiences of reproductive trauma and grief. The outcome of embryos was also the cause of stress for women. CONCLUSION: Women undergoing PGD have a diverse range of reproductive and genetic histories, psychosocial circumstances and world views that all interact and impact their experience of PGD. Successful support and care of these women should address all of these factors and tailor the support provided for women using this physically and emotionally complex form of reproductive technology.

Psychological adjustment, knowledge and unmet information needs in women undergoing PGD.

BACKGROUND: Women often enter preimplantation genetic diagnosis (PGD) treatment following traumatic reproductive and genetic histories, the detrimental psychological effects of which are known to be long lasting in some cases. In addition, attempting IVF with PGD requires an in-depth understanding of the aspects of the technology. The level of information that is required and retained by women entering treatment is important for clinicians to understand. To date, neither of these issues has been explored empirically. To address this, we assessed mood and information-seeking behavior in a sample of women entering PGD. METHODS: Fifty women entering PGD treatment completed self-administered questionnaires that assessed anxiety, depression, knowledge of technical aspects of PGD, expectancy of establishing a pregnancy and unmet information needs. RESULTS: Anxiety and depression rates were similar to normal population data. State anxiety was associated with degree of financial worry [beta = 0.36, t = 2.60, P = 0.01, 95% confidence interval (CI): 0.03-0.23], and living in an inner metropolitan area (beta = 0.30, P = 0.03, 95% CI: 0.32-10.81). Unmet information needs were positively associated with women's education (beta = 0.97, P = 0.01, 95% CI: 0.22-1.73). Lastly, expectancy of establishing a pregnancy was above that of what clinicians provide as realistic PGD pregnancy chances and, unexpectedly, was also associated with degree of financial worry (beta = 0.36, P = 0.01, 95% CI: 0.07-0.56). CONCLUSIONS: Women entering PGD are emotionally well adjusted although the financial costs associated with PGD are associated with increases in anxiety. The study is limited by its small sample size and the fact that partners were not assessed.

Psychological impact of preimplantation genetic diagnosis: a review of the literature.

Preimplantation genetic diagnosis (PGD) was first reported as successful in humans in the early 1990s and nearly two decades later the psychological impact of PGD has not yet been clearly defined. As PGD requires the use of IVF, this paper provides a brief summary of literature related to the various psychological aspects of IVF followed by a review of the literature related to the psychological and broader psychosocial impact of PGD. The current literature includes attitudinal studies of couples for whom PGD may be beneficial and results suggest that those with traumatic reproductive and genetic histories are more likely to find PGD an acceptable treatment option. A small number of studies have used samples of women and couples who have used PGD. Due to a general lack of homogeneity in scope, method and results, these studies have not provided a uniform understanding of the PGD experience. Promisingly, however, two studies on parents of children born after PGD that explored parental stress show no differences between PGD, IVF and natural conception couples. The paper concludes that the missing link in the literature is a prospective study of PGD using validated psychological scales. Suggestions for future research are provided.

The strengths and limitations of empirical bioethics.

The past two decades have been witness to an "empirical turn" in bioethics. Whereas once this field of study concerned itself purely with theoretical analysis of ethical issues emerging in the design and delivery of health care, increasingly bioethics has embraced a range of empirical research methods from the social sciences and humanities. The emergence of "empirical bioethics" has, however, been the subject of enormous debate, both in regard to its methods and its purpose. For the most part these criticisms fail to appreciate the assumptions that underpin empirical bioethics or misrepresent the claims that are made about its moral utility. This article provides a brief account of the assumptions, strengths and limitations of empirical bioethics.

Establishing the role of pre-implantation genetic diagnosis with human leucocyte antigen typing: what place do "saviour siblings" have in paediatric transplantation?

BACKGROUND: Not all children in need of a haematopoietic stem cell transplant have a suitable relative or unrelated donor available. Recently, in vitro fertilisation (IVF) with pre-implantation genetic diagnosis (PGD) for human leucocyte antigen (HLA) tissue typing has been used to selectively transfer an IVF embryo in order to produce a child who may provide umbilical cord blood for transplantation to an ill sibling. Such children are sometimes called "saviour siblings". OBJECTIVE: To examine the published clinical and epidemiological evidence relevant to the use of this technology, with the aim of clarifying those situations where IVF and PGD for HLA typing should be discussed with parents of an ill child. DESIGN: A critical analysis of published literature on comparative studies of umbilical cord blood versus other sources of stem cells for transplantation; comparative studies of matched unrelated donor versus matched related donor transplantation; and the likelihood of finding an unrelated stem cell donor. CONCLUSION: IVF and PGD for HLA typing is only applicable when transplantation is non-urgent and parents are of reproductive age. Discussions regarding this technology may be appropriate where no suitable related or unrelated donor is available for a child requiring a transplant, or where no suitable related donor is available and transplantation is only likely to be entertained with a matched sibling donor. Discussion may also be considered in the management of any child lacking a matched related donor who requires a non-urgent transplant or may require a transplant in the future.

Detection of stratospheric ozone intrusions by windprofiler radars.

Stratospheric ozone attenuates harmful ultraviolet radiation and protects the Earth's biosphere. Ozone is also of fundamental importance for the chemistry of the lowermost part of the atmosphere, the troposphere. At ground level, ozone is an important by-product of anthropogenic pollution, damaging forests and crops, and negatively affecting human health. Ozone is critical to the chemical and thermal balance of the troposphere because, via the formation of hydroxyl radicals, it controls the capacity of tropospheric air to oxidize and remove other pollutants. Moreover, ozone is an important greenhouse gas, particularly in the upper troposphere. Although photochemistry in the lower troposphere is the major source of tropospheric ozone, the stratosphere-troposphere transport of ozone is important to the overall climatology, budget and long-term trends of tropospheric ozone. Stratospheric intrusion events, however, are still poorly understood. Here we introduce the use of modern windprofiler radars to assist in such transport investigations. By hourly monitoring the radar-derived tropopause height in combination with a series of frequent ozonesonde balloon launches, we find numerous intrusions of ozone from the stratosphere into the troposphere in southeastern Canada. On some occasions, ozone is dispersed at altitudes of two to four kilometres, but on other occasions it reaches the ground, where it can dominate the ozone density variability. We observe rapid changes in radar tropopause height immediately preceding these intrusion events. Such changes therefore serve as a valuable diagnostic for the occurrence of ozone intrusion events. Our studies emphasize the impact that stratospheric ozone can have on tropospheric ozone, and show that windprofiler data can be used to infer the possibility of ozone intrusions, as well as better represent tropopause motions in association with stratosphere-troposphere transport.

Current concepts in screening for noncommunicable disease: World Health Organization Consultation Group Report on methodology of noncommunicable disease screening.

Screening people for serious diseases is receiving increasing attention as studies demonstrates the potential benefits of early detection and early intervention in preventing morbidity and mortality. Screening tests are available for some of the most important noncommunicable diseases, including cardiovascular disease, type 2 diabetes and several site-specific cancers. However, screening guidelines for cardiovascular disease, cancers and diabetes vary within and between countries because many national and international organizations are developing their own guidelines. There is a need to address the issue of screening for disease, with an emphasis on providing accurate and practical information relevant to all countries. This report arose from a Consultation Group meeting held at WHO headquarters in Geneva. It presents an examination of the principles of screening with an emphasis on noncommunicable disease prevention and control policy.

Accounting for differences in dieting status: steps in the refinement of a model.

OBJECTIVE: The overriding objective of this paper is to outline the steps involved in refining a structural model to explain differences in dieting status. METHODS: Cross-sectional data (representing the responses of 1,644 teenage girls) derive from the preliminary testing in a 3-year longitudinal study. A battery of measures assessed social influence, vulnerability (to conformity) disposition, protective (social coping) skills, and aspects of positive familial context as core components in a model proposed to account for the initiation of dieting. Path analyses were used to establish the predictive ability of those separate components and their interrelationships in accounting for differences in dieting status. RESULTS: Several components of the model were found to be important predictors of dieting status. The model incorporates significant direct, indirect (or mediated), and moderating relationships. Taking all variables into account, the strongest prediction of dieting status was from peer competitiveness, using a new scale developed specifically for this study. CONCLUSION: Systematic analyses are crucial for the refinement of models to be used in large-scale multivariate studies. In the short term, the model investigated in this study has been shown to be useful in accounting for cross-sectional differences in dieting status. The refined model will be most powerfully employed in large-scale time-extended studies of the initiation of dieting to lose weight.

An evaluation of a structural model for studies of the initiation of dieting among adolescent girls.

A model proposed to elucidate the sociopsychological processes involved in the initiation of dieting behavior among female adolescents was evaluated in the present study. The model incorporates social influence (as modeling, conformity, and compliance), autonomous functioning (as conformity disposition, individuation, self-reliance, and locus of control), skill-related functioning (as interpersonal negotiation skills and social self-efficacy), and parental style (in care and overprotection). It was investigated using path analytic procedures. One hundred forty-eight female high school students, aged between 13 and 16 years, completed a battery of questionnaires and were also interviewed individually. The results emphasized that adolescent dieting needs to be understood as a complex multicausal phenomenon. Adolescents' perceptions of direct pressure from their parents to diet was found to be a significant predictor of dieting, and perceived parental encouragement of autonomy, and self-confidence were associated with less dieting behavior. Moreover, whereas body mass index (BMI) and body dissatisfaction significantly predicted dieting, the three sociopsychological variables remained significant predictors of dieting when taking BMI into account, and perceived parent influence to diet remained a significant predictor when taking body dissatisfaction into account. The effect of autonomous functioning on dieting was mediated by body dissatisfaction. The findings suggest a reformulated model for use in large-scale longitudinal investigations.