Germline mosaicism complicates molecular diagnosis of Lesch–Nyhan syndrome

A healthy female with a brother suffering from Lesch–Nyhan syndrome was assigned a carrier status on the basis of haplotype analysis employing flanking and intragenic polymorphic markers of the HPRT gene. Her mother has been confirmed as a definite carrier by cell growth selection studies in cultured fibroblasts. In our proposita's first pregnancy, a male fetus was identified carrying the risk allele. Afterwards, the underlying novel mutation A161E (GCA→GAA at position c482) could be identified in the affected brother and in the heterozygous mother but not in the DNA of the pregnant sister and fetus. The fetus was also confirmed to be normal by uptake of 14C-hypoxanthine in cultured amniotic cells. To test the discrepancy, the investigation was extended by recruiting additional family members. The data obtained showed that the mother had passed her risk haplotype to the affected son as well as to her mutation-carrying and non–mutation-carrying daughters. This provides the first evidence of concomitant somatic and germline mosaicism in Lesch–Nyhan syndrome. The study has a bearing on genetic counselling and cautions against the reliability of only using indirect genetic diagnosis even with intragenic markers. Copyright © 2004 John Wiley & Sons, Ltd.     

Are all experiments created equal? A framework for analysis of the learning potential of policy experiments in environmental governance

Environmental changes are increasing the need to understand complex cross-scale feedbacks in social–ecological systems. However, consistent conceptualisation of learning associated with environmental governance is lacking, and research mainly centres on individual variables. This paper identifies a typology of such learning, and theorises about configurations of variables. Focusing on experimentation as an intervention geared towards learning, it proposes a definition of policy experiment. A theoretical framework is presented, summarising a typology of experiments based on learning-related variables embedded in design choices, and reflected in institutional rule aggregations. The framework facilitates systematic analysis of real-world cases and testing of hypotheses on the effects of different types of experiment on learning. A case study demonstrates application of the framework. Results suggest future research paths that include attention to additional relevant variables. The findings have relevance for scholars interested in experimentation and learning, and environmental policy-makers considering experimentation to assess policy innovations.     

Investigation of suitable precursors for manganese oxide catalysts in ethyl acetate oxidation

The control of ethyl acetate emissions from fermentation and extraction processes in the pharmaceutical industry is of great importance to the environment. We have developed three Mn₂O₃ catalysts by using different Mn precursors (MnCl₂, Mn(CH₃COO)₂, MnSO₄), named as Mn₂O₃-Cl, -Ac, -SO₄. The tested catalytic activity results showed a sequence with Mn precursors as: Mn₂O₃-Cl > Mn₂O₃-Ac > Mn₂O₃-SO₄. The Mn₂O₃-Cl catalyst reached a complete ethyl acetate conversion at 212℃ (75℃ lower than that of Mn₂O₃-SO₄), and this high activity 100% could be maintained high at 212℃ for at least 100 hr. The characterization data about the physical properties of catalysts did not show an obvious correlation between the structure and morphology of Mn₂O₃ catalysts and catalytic performance, neither was the surface area the determining factor for catalytic activity in the ethyl acetate oxidation. Here we firstly found there is a close linear relationship between the catalytic activity and the amount of lattice oxygen species in the ethyl acetate oxidation, indicating that lattice oxygen species were essential for excellent catalytic activity. Through H₂ temperature-programmed reduction (H₂-TPR) results, we found that the lowest initial reduction temperature over the Mn₂O₃-Cl had stronger oxygen mobility, thus more oxygen species participated in the oxidation reaction, resulting in the highest catalytic performance. With convenient preparation, high efficiency, and stability, Mn₂O₃ prepared with MnCl₂ will be a promising catalyst for removing ethyl acetate in practical application.     

Uncertainties in the assessment of “significant effect” on the Dutch Natura 2000 Wadden Sea site – The mussel seed fishery and powerboat race controversies

Natura 2000, the nature network based on the European Bird and Habitat Directives, is explicitly grounded on ecological science. To acquire a permit under the Dutch Nature Conservation Act, an appropriate assessment of significant effects must be conducted based on the best available scientific knowledge. In this way the scientific and policy world are directly linked. This article focuses on ‘significant effect’ as a boundary object to analyse how science–policy interactions shape the meaning and assessment of significant effect and how these interpretations influence the decision-making process. To this end, two conflicts over significant effect are investigated: the conflict over the 2006-spring permit for the mussel seed fishery, and the 2011 permit for the planned World Championship powerboat races. In both cases nature organisations started a court process against the government-granted permits in protest to the “no significant effect” claim, stating that there was insufficient certainty for this conclusion. These conflicts are approached as controversies between discourse coalitions with different interpretations of the ecological knowledge. We show how significant effect became a focal point in the controversies, limiting the debate to ecological arguments and science-based expertise, but also creating options for parties to advance their protest by articulating uncertainties. Only uncertainty of incomplete knowledge was explicitly addressed, excluding ambiguity of values and unpredictability of the actual ecosystem. We suggest that acknowledging the value aspect in disputes on significant effect would leave more space for effective solutions of the problems under debate.     

How the DPSIR framework can be used for structuring problems and facilitating empirical research in coastal systems

As pressures on coastal zones mount, there is a growing need for frameworks that can be used to conceptualize complex sustainability challenges and help organize research that increases understand about interacting ecological and societal processes, predicts change, and supports the management, persistence, and resilience of coastal systems. The Driver–Pressure–State–Impact–Response (DPSIR) framework is one such approach that has been adopted in some coastal zones around the world. Although the application of the DPSIR framework has considerable potential to bridge the gap between scientific disciplines and link science to coastal policy and management, current applications of DPSIR in coastal environments have been limited and new innovations in the application of the DPSIR model are needed. We conducted a structured review of literature on the DPSIR framework as applied to the function, process and components of complex coastal systems. Our specific focus was on how the DPSIR framework has been used as a tool to organize sophisticated empirical scientific research, support transdisciplinary knowledge at a level appropriate for building understanding about coastal systems, and how adopting a DPSIR approach can help stakeholders to articulate and structure challenges in coastal systems and use the framework to support policy and management outcomes. The review revealed that DPSIR models of coastal systems have been largely used to support and develop conceptual understanding of coastal social–ecological systems and to identify drivers and pressures in the coastal realm. A limited number of studies have used DPSIR as a starting point for semi-quantitative or quantitative analyses, although our review highlights the continued need for, and potential of, transformative quantitative analyses and transdisciplinary applications of the DPSIR framework. The DPSIR models we reviewed were predominantly single sector, encompassing ecological or biophysical factors or focusing primarily on socio-cultural dimensions rather than full integration of both types of information. Only in eight of 24 shortlisted articles did researchers actively engage decision-makers or citizens in their research: given the potential opportunity for using DPSIR as a tool to successfully engage policy-makers and stakeholders, it appears that the DPSIR framework has been under-utilized in this regard.     

Bicycle helmet effectiveness is not overstated

Objective: The objective of this study was to discuss the challenges in estimating bicycle helmet effectiveness from case–control studies of injured cyclists and to estimate helmet effectiveness from cases and available exposure data.

Methods: Data were extracted from studies of cyclists in Seattle; Victoria and New South Wales, Australia; and The Netherlands. Estimates of helmet use were used as exposure to compute relative risks for Seattle and Victorian data. Cycling distance data are routinely collected in The Netherlands; however, these data cannot be disaggregated by helmet use, which makes it unsuitable for estimating helmet effectiveness. Alternative controls were identified from larger cohorts for the Seattle and New South Wales cases.

Results: Estimates of helmet effectiveness were similar from odds ratios (ORs) using hospital controls or from relative risks (RRs) using helmet use estimates (Seattle: OR = 0.339, RR = 0.444; Victoria: OR = 0.500, RR = 0.353). Additionally, the odds ratios using hospital controls were similar when controls were taken from a larger cohort for head injury of any severity (Seattle: OR = 0.250, alt OR = 0.257; NSW: OR = 0.446, alt OR = 0.411) and for serious head injury (Seattle: OR = 0.135, alt OR = 0.139; NSW: OR = 0.335, alt OR = 0.308). Although relevant exposure data were unavailable for The Netherlands, the odds ratio for helmet effectiveness of those using racing, mountain, or hybrid bikes was similar to other estimates (OR = 0.371).

Conclusions: Despite potential weaknesses with case–control study designs, the best available evidence suggests that helmet use is an effective measure of reducing cycling head injury.     

Road accident fatality risks for “vulnerable” versus “protected” road users in northern Ghana

Background: Road traffic injuries (RTIs) are a serious epidemic that claims more than a million lives across the globe each year. The burden of RTIs is particularly pronounced in Africa and other low- and middle-income countries. The unfavorable disparity of the burden of road trauma in the world is largely attributable to unsafe vehicles, lack of appropriate road infrastructure, and the predominance of vulnerable road users (VRUs) in developing countries. However, little research exists in northern Ghana to highlight the scale and risk of death among road users.

Objective: The objective of this research was to establish the relative risk of death among road users in northern Ghana.

Methods: Crash data from police reports between 2007 and 2011 were analyzed for the Upper Regions of Ghana. Conditional probabilities and multivariable logistic regression techniques were used to report proportions and adjusted odds ratios (AORs), respectively.

Results: Generally, crashes in northern Ghana were extremely severe; that is, 35% of all injury related collisions were fatal. The proportion of fatal casualties ranged between 21% among victims of sideswipe collisions and 41% among pedestrians and victims of rear-end collisions. Though males were 6 times more likely to die than females overall, females were more likely to die as pedestrians (90% of all female casualty deaths) and males were more likely to die as riders/drivers (78% of all male casualty deaths). Pedestrians were 3 times more likely to die (odds ratio [OR] = 3.1; 95% confidence interval [CI], 2.4 to 4.1) compared with drivers/riders. Compared with drivers, the odds of death among cyclists was about 4 times higher (AOR = 3.6; 95% CI, 2.3 to 5.6) and about 2 times higher among motorcyclists (AOR = 1.6; 95% CI, 1.2 to 2.2). Compared with casualties aged between 30 and 59 years, children under 10 years and those aged 60 years and above were independently 2 times more likely to die in traffic collisions.

Conclusion: Provision of requisite road infrastructure is vital for the safety of VRUs in northern Ghana. Cycle paths and lanes (for cyclists) as well as sidewalks (for pedestrians) in particular will separate VRUs from motorists and improve their safety. Enforcement of traffic laws particularly regarding helmet use, speeding, and alcohol use will be beneficial. Introduction of the demerit points system in the enforcement of traffic regulations may have significant deterrent effects on road users who have the penchant for violating traffic regulations. Road safety education is also required to create responsible road users.     

Tetrasomy 12p—unusual presentation in CVS

CVS direct preparations usually achieve limited resolution and are better at detecting numerical rather than structural abnormalities. A CVS direct preparation analyzed using G-banding revealed a 47,XY,+G karyotype in 5 of 11 cells and was reported as mosaic for trisomy 21. Subsequent analysis of the CVS culture found only normal male cells. Amniocentesis revealed both normal male cells and cells with an extra F-group chromosome. Fluorescence in situ hybridization (FISH) identified this chromosome to be an isochromosome from the short arm of chromosome 12 [i(12)(p10)]. The amniocyte karyotype was reported as 47,XY,+i(12)(p10)[12]/46,XY[8].ish i(12)(p10)(wcp12+), which is associated with Pallister–Killian syndrome. Reexamination of the CVS direct preparation by FISH with a chromosome 12 centromere probe confirmed the karyotype of this tissue to be 47,XY,+mar[5]/46,XY[6].nuc ish 12cen(D12Z3 × 3)/12cen(D12Z3 × 2). Thus, multiple studies, including amniocentesis and fluorescence in situ hybridization, may be required to fully and accurately evaluate abnormalities detected by CVS. This case also indicates that mosaicism for supernumerary isochromosomes may have a complex origin. Copyright © 2003 John Wiley & Sons, Ltd.