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Unresolved Questions (unresolved + question)
Selected AbstractsAllegiance Effects in Assessment: Unresolved Questions, Potential Explanations, and Constructive RemediesCLINICAL PSYCHOLOGY: SCIENCE AND PRACTICE, Issue 4 2008Scott O. Lilienfeld The provocative results of Blair, Marcus, and Boccaccini (2008) suggest that the allegiance effect, previously suggested in psychotherapy outcome studies, may apply to studies of actuarial risk assessment. Despite this finding, the mechanisms of the effect, particularly in assessment research, are unknown and warrant further investigation. We discuss the file drawer effect, selective reporting, and "data massaging" as three potential explanations for allegiance effects in the assessment domain. Furthermore, we offer four suggestions for minimizing allegiance effects and their impact: routinely coding for allegiance in meta-analytic studies, operationalizing allegiance in multiple ways, encouraging collaborations among authors with differing allegiances, and creating study registries to track all dependent variables measured in studies. [source] Nonlinear determinism in river flow: prediction as a possible indicatorEARTH SURFACE PROCESSES AND LANDFORMS, Issue 7 2007Bellie SivakumarArticle first published online: 6 DEC 200 Abstract Whether or not river flow exhibits nonlinear determinism remains an unresolved question. While studies on the use of nonlinear deterministic methods for modeling and prediction of river flow series are on the rise and the outcomes are encouraging, suspicions and criticisms of such studies continue to exist as well. An important reason for this situation is that the correlation dimension method, used as a nonlinear determinism identification tool in most of those studies, may possess certain limitations when applied to real river flow series, which are always finite and often short and also contaminated with noise (e.g. measurement error). In view of this, the present study addresses the issue of nonlinear determinism in river flow series using prediction as a possible indicator. This is done by (1) reviewing studies that have employed nonlinear deterministic methods (coupling phase-space reconstruction and local approximation techniques) for river flow predictions and (2) identifying nonlinear determinism (or linear stochasticity) based on the level of prediction accuracy in general, and on the prediction accuracy against the phase-space reconstruction parameters in particular (termed as the ,inverse approach'). The results not only provide possible indications to the presence of nonlinear determinism in the river flow series studied, but also support, both qualitatively and quantitatively, the low correlation dimensions reported for such. Therefore, nonlinear deterministic methods are a viable complement to linear stochastic ones for studying river flow dynamics, if sufficient caution is exercised in their applications and in interpreting the outcomes. Copyright © 2006 John Wiley & Sons, Ltd. [source] Origin of the earliest correlated neuronal activity in the chick embryo revealed by optical imaging with voltage-sensitive dyesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2009Yoko Momose-Sato Abstract Spontaneous correlated neuronal activity during early development spreads like a wave by recruiting a large number of neurons, and is considered to play a fundamental role in neural development. One important and as yet unresolved question is where the activity originates, especially at the earliest stage of wave expression. In other words, which part of the brain differentiates first as a source of the correlated activity, and how does it change as development proceeds? We assessed this issue by examining the spatiotemporal patterns of the depolarization wave, the optically identified primordial correlated activity, using the optical imaging technique with voltage-sensitive dyes. We surveyed the region responsible for the induction of the evoked and spontaneous depolarization waves in chick embryos, and traced its developmental changes. The results showed that the wave initially originated in a restricted area near the obex and was generated by multiple regions at later stages. We suggest that the upper cervical cord/lower medulla near the obex is the kernel that differentiates first as the source of the correlated activity, and that regional and temporal differences in neuronal excitability might underlie the developmental profile of wave generation in early chick embryos. [source] From Agrarian Reform to Ethnodevelopment in the Highlands of EcuadorJOURNAL OF AGRARIAN CHANGE, Issue 4 2008VÍCTOR BRETÓN SOLO DE ZALDÍVAR Through an examination of interventions in the agrarian structures and rural society of the Ecuadorian Andes over the past 40 years, this article explores the gradual imposition of a particular line of action that separates rural development from the unresolved question of the concentration of land ownership and wealth among the very few. This imposition has been the consequence, it is argued, of the new development paradigms implemented in Andean peasant communities since the end of land reform in the 1970s. The new paradigms emphasize identity and organizational aspects of indigenous populations at the expense of anything connected with the class-based campesinista agenda, which was still operational in the indigenous movement in the early 1990s. The essay concludes with some thoughts on the remarkable parallels between the 1990s neoliberal and counter-reformist models of action, and the pre-reformist indigenist policies of the period that ended in the 1960s. [source] Long distance migration and marine habitation in the tropical Asian catfish, Pangasius krempfiJOURNAL OF FISH BIOLOGY, Issue 3 2007Z. Hogan A synthesis of catch data from southern Laos and life-history information indicate that adult Pangasius krempfi, an important Asian catfish, migrates up the Mekong River from the South China Sea in Vietnam past Cambodia, arriving in southern Laos each year in May. Strontium concentrations in the otoliths of river-caught P. krempfi are, on average, three to four times higher than the levels of strontium in the otoliths of related freshwater species, indicating marine and estuary habitation for fish caught in southern Laos. Pangasius krempfi muscle tissue samples from the same fish also exhibit stable isotope (,15N and ,13C) values characteristic of marine environments. The results of this investigation support the conclusion that P. krempfi is anadromous, spending a part of its life at sea and in the brackish water of the Mekong Delta before returning to spawn in fresh water. The fish travels at least 720 km to the Khone Falls in southern Laos, and possibly further. Spawning probably occurs in fresh water from June to August at which time young fish move down the Mekong River to the Mekong Delta. The data answer a previously unresolved question (the long-distance migratory behaviour of P. krempfi) and have important implications for the management and conservation of Mekong River fishes. [source] Cancer incidence among people with intellectual disabilityJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 4 2001K. Patja Abstract The aim of the present study was to address the unresolved question of the risk of neoplasms among people with intellectual disability (ID). A total of 2173 individuals with ID from a large, representative, nation-wide population study conducted in Finland in 1962 were followed-up for cancer incidence between 1967 and 1997. Standardized incidence ratios (SIRs) were defined as ratios of observed to expected numbers of cancer cases. Expected rates were based on national incidence rates. The observed number of cancers in the cohort (173) was close to what was expected [SIR = 0.9, 95% confidence interval (95% CI) = 0.8,1.0]. There was a significantly reduced risk of cancers of the prostate (SIR = 0.2, 95% CI = 0.0,0.5), urinary tract (SIR = 0.3, 95% CI = 0.1,0.7) and lung (SIR = 0.6, 95% CI = 0.4,1.0). The risk was increased in cancers of the gallbladder (SIR = 2.8, 95% CI = 1.1,5.8) and thyroid gland (SIR = 2.1, 95% CI = 1.0,4.8). The risks of lung and gallbladder cancer were lowest and highest, respectively, in those subjects with profound and severe ID, a group who also had significantly elevated SIRs for brain cancer (SIR = 3.46, 95% CI = 1.5,14.4) and testicular cancer (SIR = 9.9, 95% CI = 1.2,35.6). The incidence of cancer among people with ID was comparable with the general population, despite their low prevalence of smoking and apparently decreased diagnostic screening activity. Nevertheless, a few types of cancer carry a higher risk in the population with ID, possibly because of conditions typical among this group, such as gallstones or oesophageal reflux. [source] Remote visualisation of Labrador convection in large oceanic datasetsATMOSPHERIC SCIENCE LETTERS, Issue 4 2005L. J. West Abstract The oceans relinquish O(1PW) of heat into the atmosphere at high latitudes, the lion's share of which originates in localised ,hotspots' of violent convective mixing, but despite their small horizontal scale,O(10,100km),these features may penetrate deeply into the thermocline and are vital in maintaining the Atlantic Meridional Overturning Circulation (MOC). Accurate modelling of the MOC, therefore, requires a large-scale numerical model with very fine resolution. The global high-resolution ocean model, Ocean Circulation Climate Advanced Model (OCCAM) has been developed and run at the Southampton Oceanography Centre (SOC) for many years. It was configured to resolve the energetic scales of oceanic motions, and its output is stored at the Manchester Supercomputer Centre. Although this community resource represents a treasure trove of potential new insights into the nature of the world ocean, it remains relatively unexploited for a number of reasons, not the least of which is its sheer size. A system being developed at SOC under the auspices of the Grid for Ocean Diagnostics, Interactive Visualisation and Analysis (GODIVA) project makes the remote visualisation of very large volumes of data on modest hardware (e.g. a laptop with no special graphics capability) a present reality. The GODIVA system is enabling the unresolved question of oceanic convection and its relationship to large-scale flows to be investigated; a question that lies at the heart of many current climate change issues. In this article, one aspect of the GODIVA is presented, and used to locate and visualise regions of convective mixing in the OCCAM Labrador Sea. Copyright © 2006 Royal Meteorological Society [source] Adverse effects of tocolytic therapyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2005Steve Caritis The rationale for using tocolytics in preterm labour is to enable transfer of the mother to a tertiary centre and to prolong pregnancy sufficiently so that glucocorticoids can be administered to the mother. There is little question that these short term objectives can be achieved with contemporary tocolytics. Whether tocolytics can maintain pregnancy for sufficient periods to enable in utero maturation to occur remains an unresolved question. When a decision is made to use tocolytics, the clinician is faced with a multitude of choices with side effects, efficacy and ease of administration generally being the most important considerations. Placebo-controlled studies suggest that the ,-agonists, prostaglandin inhibitors and atosiban are effective in prolonging pregnancy for 24,48 hours. Of these three agents, atosiban has the best safety profile. There are no placebo-controlled studies with calcium channel blockers or nitric oxide donors. However, because of their ease of use and efficacy compared with the ,-agonists, calcium channel blockers are widely used. Calcium channel blockers appear to have a better safety profile than the ,-agonists, but there are still significant cardiovascular side effects associated with their use. Indomethacin, although proven to be efficacious, has a safety profile that limits its utility for other than short courses. Magnesium sulphate is the most commonly used tocolytic in the United States, despite a lack of evidence for its efficacy. Although magnesium sulphate appears to have a good safety profile, serious side effects have been reported with its use. The choice of tocolytics is commonly based on personal preference. Whichever tocolytic is chosen, the fundamental parturitional process is not reversed by contemporary treatment, rather a reduction in uterine response to a stimulant; thus, the expectations of tocolytic treatment need to be reconsidered. [source] Style of Knowing Regarding UncertaintiesCURRICULUM INQUIRY, Issue 1 2007DEBORAH HELSING This article addresses a key contrast in how teachers may regard the uncertainties of their work, considering how an orientation to uncertainty can be regarded as a decision-making style. Through the use of case studies, the author contrasts two teachers. One is oriented toward uncertainties in her work and describes her herself as being always "on the edge" of her capabilities, constantly seeking out perspectives that differ from and challenge her own and remaining vigilant to the need for improvising to respond to the circumstances of the moment. The other is oriented away from uncertainties and describes herself as prepared and deliberate; committed to achieving outcomes in line with her articulated goals and purposes; and purposeful about which unresolved questions she chooses to pursue. This contrast has implications not only for how these teachers make decisions and view their professional growth, but also for how some teachers may be understood, and misunderstood, by others. In a culture that often seeks to ignore pervasive moral ambiguities and focuses instead on questions for which there are easily identifiable answers (Cuban, 1992), an orientation toward uncertainty is more likely to be devalued or seen as an indication that one is not teaching well. Identifying these different approaches to decision-making styles enables us to appreciate the integrity and strength of each, as well as the limitations of each, suggesting new possibilities for research and for teachers' professional development. [source] Morphogenesis of the node and notochord: The cellular basis for the establishment and maintenance of left,right asymmetry in the mouseDEVELOPMENTAL DYNAMICS, Issue 12 2008Jeffrey D. Lee Abstract Establishment of left,right asymmetry in the mouse embryo depends on leftward laminar fluid flow in the node, which initiates a signaling cascade that is confined to the left side of the embryo. Leftward fluid flow depends on two cellular processes: motility of the cilia that generate the flow and morphogenesis of the node, the structure where the cilia reside. Here, we provide an overview of the current understanding and unresolved questions about the regulation of ciliary motility and node structure. Analysis of mouse mutants has shown that the motile cilia must have a specific structure and length, and that they must point posteriorly to generate the necessary leftward fluid flow. However, the precise structure of the motile cilia is not clear and the mechanisms that position cilia on node cells have not been defined. The mouse node is a teardrop-shaped pit at the distal tip of the early embryo, but the morphogenetic events that create the mature node from cells derived from the primitive streak are only beginning to be characterized. Recent live imaging experiments support earlier scanning electron microscopy (SEM) studies and show that node assembly is a multi-step process in which clusters of node precursors appear on the embryo surface as overlying endoderm cells are removed. We present additional SEM and confocal microscopy studies that help define the transition stages during node morphogenesis. After the initiation of left-sided signaling, the notochordal plate, which is contiguous with the node, generates a barrier at the embryonic midline that restricts the cascade of gene expression to the left side of the embryo. The field is now poised to dissect the genetic and cellular mechanisms that create and organize the specialized cells of the node and midline that are essential for left,right asymmetry. Developmental Dynamics 237:3464,3476, 2008. © 2008 Wiley-Liss, Inc. [source] THE INTERSECTIONS OF GENDER AND GENERATION IN ALBANIAN MIGRATION, REMITTANCES AND TRANSNATIONAL CAREGEOGRAFISKA ANNALER SERIES B: HUMAN GEOGRAPHY, Issue 1 2009Russell King ABSTRACT. The Albanian case represents the most dramatic instance of post-communist migration: about one million Albanians, a quarter of the country's total population, are now living abroad, most of them in Greece and Italy, with the UK becoming increasingly popular since the late 1990s. This paper draws on three research projects based on fieldwork in Italy, Greece, the UK and Albania. These projects have involved in-depth interviews with Albanian migrants in several cities, as well as with migrant-sending households in different parts of Albania. In this paper we draw out those findings which shed light on the intersections of gender and generations in three aspects of the migration process: the emigration itself, the sending and receiving of remittances, and the care of family members (mainly the migrants' elderly parents) who remain in Albania. Theoretically, we draw on the notion of ,gendered geographies of power' and on how spatial change and separation through migration reshapes gender and generational relations. We find that, at all stages of the migration, Albanian migrants are faced with conflicting and confusing models of gender, behavioural and generational norms, as well as unresolved questions about their legal status and the likely economic, social and political developments in Albania, which make their future life plans uncertain. Legal barriers often prevent migrants and their families from enjoying the kinds of transnational family lives they would like. [source] Local outbreaks of Operophtera brumata and Operophtera fagata cannot be explained by low vulnerability to pupal predationAGRICULTURAL AND FOREST ENTOMOLOGY, Issue 1 2010Annette Heisswolf 1One of the unresolved questions in studies on population dynamics of forest Lepidoptera is why some populations at times reach outbreak densities, whereas others never do. Resolving this question is especially challenging if populations of the same species in different areas or of closely-related species in the same area are considered. 2The present study focused on three closely-related geometrid moth species, autumnal Epirrita autumnata, winter Operophtera brumata and northern winter moths Operophtera fagata, in southern Finland. There, winter and northern winter moth populations can reach outbreak densities, whereas autumnal moth densities stay relatively low. 3We tested the hypothesis that a lower vulnerability to pupal predation may explain the observed differences in population dynamics. The results obtained do not support this hypothesis because pupal predation probabilities were not significantly different between the two genera within or without the Operophtera outbreak area or in years with or without a current Operophtera outbreak. 4Overall, pupal predation was even higher in winter and northern winter moths than in autumnal moths. Differences in larval predation and parasitism, as well as in the reproductive capacities of the species, might be other candidates. [source] Asthma prevention: Breast is best?JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 7 2004A Kemp Abstract: Whilst breastfeeding has been considered to exert a preventative effect on the development of allergic disease, several recent publications have challenged this view, particularly with respect to the long-term outcomes for asthma. There are many other beneficial effects of breastfeeding apart from the possibility of allergy prevention. The suggestion that breastfeeding may increase the development of allergic disease raises concerns about the appropriate steps to take for primary prevention of allergy. It is concluded that breastfeeding can still be recommended for the beneficial effects in reducing atopic disease in childhood in addition to the other demonstrated benefits, and that there are unresolved questions concerning the few studies that suggest the possibility of increased allergic disease in later life. [source] Induction chemotherapy in the management of head and neck cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010Matthew G. Fury MD Abstract The strategy of induction chemotherapy prior to planned definitive local therapy for head and neck squamous cell carcinoma has been studied for over 30 years, and appears to have a role in select clinical situations. Here we review landmark studies regarding induction chemotherapy, both in the pre-taxane era and in the current taxane era, and we address some of the unresolved questions regarding the role of induction chemotherapy in head and neck cancer. J. Surg. Oncol. 2010; 101:292,298. © 2010 Wiley-Liss, Inc. [source] Biodiversity effects on ecosystem functioning: emerging issues and their experimental test in aquatic environmentsOIKOS, Issue 3 2004Paul S. Giller Recent experiments, mainly in terrestrial environments, have provided evidence of the functional importance of biodiversity to ecosystem processes and properties. Compared to terrestrial systems, aquatic ecosystems are characterised by greater propagule and material exchange, often steeper physical and chemical gradients, more rapid biological processes and, in marine systems, higher metazoan phylogenetic diversity. These characteristics limit the potential to transfer conclusions derived from terrestrial experiments to aquatic ecosystems whilst at the same time provide opportunities for testing the general validity of hypotheses about effects of biodiversity on ecosystem functioning. Here, we focus on a number of unique features of aquatic experimental systems, propose an expansion to the scope of diversity facets to be considered when assessing the functional consequences of changes in biodiversity and outline a hierarchical classification scheme of ecosystem functions and their corresponding response variables. We then briefly highlight some recent controversial and newly emerging issues relating to biodiversity-ecosystem functioning relationships. Based on lessons learnt from previous experimental and theoretical work, we finally present four novel experimental designs to address largely unresolved questions about biodiversity-ecosystem functioning relationships. These include (1) investigating the effects of non-random species loss through the manipulation of the order and magnitude of such loss using dilution experiments; (2) combining factorial manipulation of diversity in interconnected habitat patches to test the additivity of ecosystem functioning between habitats; (3) disentangling the impact of local processes from the effect of ecosystem openness via factorial manipulation of the rate of recruitment and biodiversity within patches and within an available propagule pool; and (4) addressing how non-random species extinction following sequential exposure to different stressors may affect ecosystem functioning. Implementing these kinds of experimental designs in a variety of systems will, we believe, shift the focus of investigations from a species richness-centred approach to a broader consideration of the multifarious aspects of biodiversity that may well be critical to understanding effects of biodiversity changes on overall ecosystem functioning and to identifying some of the potential underlying mechanisms involved. [source] A stem-group caecilian (Lissamphibia: Gymnophiona) from the Lower Cretaceous of North AfricaPALAEONTOLOGY, Issue 2 2001Susan E. Evans Of living amphibian groups, the limbless burrowing caecilians are amongst the most highly specialised, but are the least known. Their fossil record is extremely poor, leaving unresolved questions as to their origins, relationships and early distribution. We describe here caecilian remains from a Lower Cretaceous (Berriasian) microfossil locality near Anoual, Morocco. This material represents the second oldest record for the group, after the Jurassic Eocaecilia of North America, and the earliest caecilian record for Gondwana. It forms the basis of a new genus, Rubricacaecilia, which appears slightly more derived than Eocaecilia, but lacks major features of crown-group taxa. We support the use of Apoda Oppel, 1811 for the crown-group alone, and Gymnophiona Rafinesque 1814 for the clade comprising stem-group taxa + Apoda. [source] Insights into the cell of origin in breast cancer and breast cancer stem cellsASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2 2010Geoffrey J LINDEMAN Abstract The precise cell types that give rise to tumors and mechanisms that underpin tumor heterogeneity are poorly understood. There is increasing evidence to suggest that diverse solid tumors are hierarchically organized and may be sustained by a distinct subpopulation of cancer stem cells (CSCs). The CSC hypothesis provides an attractive cellular mechanism that can account for the therapeutic refractoriness and dormant behavior exhibited by many tumor types. Breast cancer was the first solid malignancy from which CSCs were identified and isolated. Direct evidence for the CSC hypothesis has also recently emerged from mouse models of mammary tumorigenesis, although alternative models to explain heterogeneity also seem to apply. Our group has found that the luminal epithelial progenitor marker CD61/,3 integrin identified a CSC population in mammary tumors from MMTV- wnt-1 mice. However, no CSCs could be identified in the more homogeneous MMTV- neu/erbB2 model, suggesting an alternate (clonal evolution or stochastic) model of tumorigenesis. It seems likely that both paradigms of tumor propagation exist in human cancer. From a clinical perspective, the CSC concept has significant implications. Quiescent CSCs are thought to be more resistant to chemotherapy and targeted therapy. Enrichment of putative CSCs has been noted in studies of chemotherapy-treated patients, lending support to the CSC hypothesis and their potential role in chemoresistance. Although many unresolved questions on CSCs remain, ongoing efforts to identify and characterize CSCs continue to be an important area of investigation, with the potential to identify novel tumor targeting strategies. [source] Dronedarone: Current Evidence and Future QuestionsCARDIOVASCULAR THERAPEUTICS, Issue 1 2010Jeremy A. Schafer Atrial fibrillation (AF) is the most common sustained arrhythmia, affecting more than 2.2 million Americans. ACC/AHA/ESC guidelines for the management of patients with AF recommend amiodarone for maintaining sinus rhythm. Dronedarone is a derivative of amiodarone indicated for the treatment of AF. To provide an overview of dronedarone with a focus on the phase III trials and discuss unresolved questions of dronedarone. A literature search was conducted via the PubMed database using the keyword "dronedarone." Search was limited to human trials in english. The FDA website was searched for briefing documents and subcommittee meetings on dronedarone. Clinicaltrials.gov was searched with the keyword dronedarone for upcoming or unpublished clinical trials. Five phase III trials are available for dronedarone: ANDROMEDA, EURIDIS/ADONIS, ATHENA, ERATO, and DIONYSIS. EURIDIS/ADONIS and ATHENA demonstrated a reduction AF recurrence with dronedarone compared to placebo. The ANDROMEDA trial recruited patients with recent hospitalization for heart failure and was terminated due to an excess of deaths in the dronedarone group. The DIONYSIS trial was a comparative effectiveness trial that demonstrated less efficacy for dronedarone but improved tolerability compared to amiodarone. Dronedarone represents an option in the management of AF in select patients. Dronedarone is not appropriate in patients with recently decompensated heart failure or those treated with strong CYP3A4 inhibitors or medications prolonging the QT interval. Dronedarone appears to have improved tolerability at the expense of decreased efficacy when compared to amiodarone. Questions remain on the long-term safety, use in patients with heart failure, retreatment after dronedarone or amiodarone failure, and comparative efficacy with a rate control strategy. [source] Validation of MCADD newborn screeningCLINICAL GENETICS, Issue 2 2009EM Maier Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid ,-oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut-off policies, false-positive and negative rates. In a retrospective case-control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false-positives, and 34 patients. c.985A>G was more frequently identified in the study group and false-positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false-positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false-negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C8) and three secondary markers in the initial and follow-up sample. The new approach allowed a reduction of false-positives (by defining high cut-offs: 1.4 ,mol/l for C8; 7 for C8/C12) and false-negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42,88%) and to target NBS to MCADD-subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS-based NBS. [source] | |||||||||||||||||||