Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005

Surfactant protein-D and pulmonary host defense

Surfactant protein-D (SP-D) participates in the innate response to inhaled microorganisms and organic antigens, and contributes to immune and inflammatory regulation within the lung. SP-D is synthesized and secreted by alveolar and bronchiolar epithelial cells, but is also expressed by epithelial cells lining various exocrine ducts and the mucosa of the gastrointestinal and genitourinary tracts. SP-D, a collagenous calcium-dependent lectin (or collectin), binds to surface glycoconjugates expressed by a wide variety of microorganisms, and to oligosaccharides associated with the surface of various complex organic antigens. SP-D also specifically interacts with glycoconjugates and other molecules expressed on the surface of macrophages, neutrophils, and lymphocytes. In addition, SP-D binds to specific surfactant-associated lipids and can influence the organization of lipid mixtures containing phosphatidylinositol in vitro. Consistent with these diverse in vitro activities is the observation that SP-D-deficient transgenic mice show abnormal accumulations of surfactant lipids, and respond abnormally to challenge with respiratory viruses and bacterial lipopolysaccharides. The phenotype of macrophages isolated from the lungs of SP-D-deficient mice is altered, and there is circumstantial evidence that abnormal oxidant metabolism and/or increased metalloproteinase expression contributes to the development of emphysema. The expression of SP-D is increased in response to many forms of lung injury, and deficient accumulation of appropriately oligomerized SP-D might contribute to the pathogenesis of a variety of human lung diseases

A critical review on operation and performance of source water control strategies for cyanobacterial blooms: Part I-chemical control methods.

Cyanobacterial blooms produce nuisance metabolites (e.g., cyanotoxins and T&O compounds) thereby posing water quality management issues for aquatic sources used for potable water production, aquaculture, and recreation. A variety of in-lake/reservoir control measures are implemented to reduce the abundance of nuisance cyanobacteria biomass or decrease the amount of available phosphorous (P). This paper critically reviews the chemical control strategies implemented for in-lake/reservoir management of cyanobacterial blooms, i.e., algaecides and nutrient sequestering coagulants/flocculants, by highlighting (i) their mode of action, (ii) cases of successful and unsuccessful treatment, (iii) and factors influencing performance (e.g., water quality, process control techniques, source water characteristics, etc.). Algaecides generally result in immediate improvements in water quality and offer selective cyanobacterial control when peroxide-based alagecides are used. However, they have a range of limitations: causing cell lysis and release of cyanotoxins, posing negative impacts on aquatic plants and animals, leaving behind environmentally relevant treatment residuals (e.g., Cu in water and sediments), and offering only short-term bloom control characterized by cyanobacterial rebound. Coagulants/flocculants (alum, iron, calcium, and lanthanum bentonite) offer long-term internal nutrient control when external nutrient loading is controlled. Treatment performance is often influenced by background water quality conditions, and source water characteristics (e.g., surface area, depth, mixing regimes, and residence time). The reviewed case studies highlight that external nutrient load reduction is the most fundamental aspect of cyanobacterial control. None of the reviewed control strategies provide a comprehensive solution to cyanobacterial blooms

A critical review on operation and performance of source water control strategies for cyanobacterial blooms: Part II-mechanical and biological control methods.

This review summarizes current knowledge on mechanical (artificial mixing, hypolimnetic aeration, dredging, and sonication) and biological (biomanipulation, macrophytes, and straws) methods for the management of cyanobacterial blooms in drinking water sources. Emphasis has been given to (i) the mechanism of cyanobacterial control, (ii) successful and unsuccessful case studies, and (iii) factors influencing successful implementation. Most mechanical and biological control strategies offer long-term control. However, their application can be cost-prohibitive and treatment efficacy is influenced by source water geometry and continual nutrient inputs from external sources. When artificial mixing and hypolimnetic oxygenation units are optimized based on source water characteristics, observed water quality benefits included increased dissolved oxygen contents, reduced internal loading of nutrients, and lower concentrations of reduced ions . Treatment efficacy during oxygenation and aeration was derailed by excessive sedimentation of organic matter and sediment characteristics such as low Fe/P ratios. Dredging is beneficial for contaminated sediment removal, but it is too costly to be a practical bloom control strategy for most systems. Sonication control methods have contradictory findings requiring further research to evaluate the efficacy and applicability for field-scale control of cyanobacteria. Biological control methods such as biomanipulation offer long-term treatment benefits; however, investigations on the mechanisms of field-scale cyanobacterial control are still limited, particularly with the use of macrophytes and straws. Each control method has site-specific strengths, limitations, and ecological impacts. Reduction of external nutrient inputs should still be a significant focus of restoration efforts as treatment benefits from mechanical and biological control were commonly offset by continued nutrient inputs

Delayed Release of Intracellular Microcystin Following Partial Oxidation of Cultured and Naturally Occurring Cyanobacteria.

Oxidation processes can provide an effective barrier to eliminate cyanotoxins by damaging cyanobacteria cell membranes, releasing intracellular cyanotoxins, and subsequently oxidizing these toxins (now in extracellular form) based on published reaction kinetics. In this work, cyanobacteria cells from two natural blooms (from the United States and Canada) and a laboratory-cultured Microcystis aeruginosa strain were treated with chlorine, monochloramine, chlorine dioxide, ozone, and potassium permanganate. The release of microcystin was measured immediately after oxidation (t ≤ 20 min), and following oxidant residual quenching (stagnation times = 96 or 168 h). Oxidant exposures (CT) were determined resulting in complete release of intracellular microcystin following chlorine (21 mg-min/L), chloramine (72 mg-min/L), chlorine dioxide (58 mg-min/L), ozone (4.1 mg-min/L), and permanganate (391 mg-min/L). Required oxidant exposures using indigenous cells were greater than lab-cultured Microcystis. Following partial oxidation of cells (oxidant exposures ≤ CT values cited above), additional intracellular microcystin and dissolved organic carbon (DOC) were released while the samples remained stagnant in the absence of an oxidant (>96 h after quenching). The delayed release of microcystin from partially oxidized cells has implications for drinking water treatment as these cells may be retained on a filter surface or in solids and continue to slowly release cyanotoxins and other metabolites into the finished water

Impact of hydrogen peroxide and copper sulfate on the delayed release of microcystin

Algicides, like hydrogen peroxide and copper sulfate, are commonly applied to recreational waters and drinking water sources to mitigate cyanobacterial blooms. In this work, the effects of hydrogen peroxide and copper sulfate were evaluated in two natural bloom samples (collected from Canadian and American waterbodies) and one lab-cultured Microcystis aeruginosa suspended in Colorado River water. Five algicide to dissolved organic carbon (DOC) dose ratios were evaluated during an initial exposure period of 24 h. One dose ratio (0.4 H2O2:DOC or 0.25 CuSO4:DOC) was then evaluated during stagnation after quenching (hydrogen peroxide) or extended exposure (copper sulfate) for up to 96 or 168 h. During the initial hydrogen peroxide exposure, the CA bloom had no release of intracellular microcystins (MCs) and the USA bloom only released MC at 4 H2O2:DOC. The reverse occurred with copper sulfate, where the CA bloom released MCs at 0.6 CuSO4:DOC but the USA bloom had no detectable extracellular MCs. Extracellular MC was released from the lab-cultured Microcystis at the lowest hydrogen peroxide and copper sulfate doses. In the hydrogen peroxide stagnation experiment, intracellular MC decreased in the USA bloom after 168 h despite the low dose applied. Similarly, the extended copper sulfate exposure led to intracellular MC decreases in both bloom samples after 168 h, despite showing no impact during the initial 24 h monitoring period. The lab-cultured Microcystis was again less resistant to both algicides, with releases observed after less than 2 h of stagnation or exposure. The damage to cells as measured by pigments during these experiments did not match the MC data, indicating that blooms with depressed pigment levels can still be a risk to nearby drinking water sources or recreational activities. These results provide insight on the timeline (up to one week) required for monitoring the potential release of MCs after algicide application

Utility practices and perspectives on monitoring and source control of cyanobacterial blooms

Abstract Thirty‐five utilities across the United States (54%), Australia (26%), and Canada (20%) were surveyed to identify their experiences with early warning monitoring and source control of cyanobacteria. All utilities experience pelagic blooms, but only 20% monitor for benthic cyanobacteria. Most utilities (86%) have early warning monitoring programs. However, monitoring frequencies and long analytical turnaround times negatively impacted the effective use of monitoring data for rapid bloom detection and prompt implementation of reactive measures to control blooms/bloom‐related issues. Thus, a tiered monitoring approach is recommended: Tier 1–event detection, Tier 2–cyanobacteria confirmation, and Tier 3–metabolite confirmation. Most utilities (68%) implement source control strategies for cyanobacteria, with algaecides and aeration being the most frequently used (36%). Utilities relied on manufacturer recommendations to design source control strategies, although site‐specific optimization is needed based on water quality/bloom conditions. Control strategies were restricted by source geometry, limited optimization, metabolite generation, and environmental impacts. Successful source control of cyanobacteria was further negatively impacted by external nutrient loading. Therefore, source control strategies should be implemented jointly with external nutrient control initiatives

Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening

This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non-laboratory aspects such as information and counseling), education of professionals, systematic evaluation of all aspects of prenatal screening, development of better evaluation tools in the light of the aim of the practice, accountability to all stakeholders including children born from screened pregnancies and persons living with the conditions targeted in prenatal screening and promotion of equity of access