Value sensitive design and the artificial placenta.

Artificial placenta technologies (also termed 'artificial wombs') for use in place of conventional neonatal intensive care are increasingly closer to first-in-human use. There is growing ethical interest in partial ectogestation (the use of an artificial placenta to continue gestation of an underdeveloped human entity extra uterum), however, there has been little reflection on the ethical issues in the design of the technology. While some have noted the importance of such reflection, and others have noted that a 'value sensitive design' approach should be preferred, they have not elaborated on what this means. In this article, we consider what a value sensitive design approach to artificial placenta design might encompass. We believe that applying this framework to the topic at hand raises theoretical and substantive ethical questions that merit further elucidation. Highlighting that there is a careful need to separate preferences from values and that our intervention should be considered only a starting point, we explore some of the values that could be used to make ethical design choices about the artificial placenta: efficacy, compassion and accessibility.

Functional recovery of secondary tropical forests.

One-third of all Neotropical forests are secondary forests that regrow naturally after agricultural use through secondary succession. We need to understand better how and why succession varies across environmental gradients and broad geographic scales. Here, we analyze functional recovery using community data on seven plant characteristics (traits) of 1,016 forest plots from 30 chronosequence sites across the Neotropics. By analyzing communities in terms of their traits, we enhance understanding of the mechanisms of succession, assess ecosystem recovery, and use these insights to propose successful forest restoration strategies. Wet and dry forests diverged markedly for several traits that increase growth rate in wet forests but come at the expense of reduced drought tolerance, delay, or avoidance, which is important in seasonally dry forests. Dry and wet forests showed different successional pathways for several traits. In dry forests, species turnover is driven by drought tolerance traits that are important early in succession and in wet forests by shade tolerance traits that are important later in succession. In both forests, deciduous and compound-leaved trees decreased with forest age, probably because microclimatic conditions became less hot and dry. Our results suggest that climatic water availability drives functional recovery by influencing the start and trajectory of succession, resulting in a convergence of community trait values with forest age when vegetation cover builds up. Within plots, the range in functional trait values increased with age. Based on the observed successional trait changes, we indicate the consequences for carbon and nutrient cycling and propose an ecologically sound strategy to improve forest restoration success.

Biomass resilience of Neotropical secondary forests.

Land-use change occurs nowhere more rapidly than in the tropics, where the imbalance between deforestation and forest regrowth has large consequences for the global carbon cycle. However, considerable uncertainty remains about the rate of biomass recovery in secondary forests, and how these rates are influenced by climate, landscape, and prior land use. Here we analyse aboveground biomass recovery during secondary succession in 45 forest sites and about 1,500 forest plots covering the major environmental gradients in the Neotropics. The studied secondary forests are highly productive and resilient. Aboveground biomass recovery after 20 years was on average 122 megagrams per hectare (Mg ha(-1)), corresponding to a net carbon uptake of 3.05 Mg C ha(-1) yr(-1), 11 times the uptake rate of old-growth forests. Aboveground biomass stocks took a median time of 66 years to recover to 90% of old-growth values. Aboveground biomass recovery after 20 years varied 11.3-fold (from 20 to 225 Mg ha(-1)) across sites, and this recovery increased with water availability (higher local rainfall and lower climatic water deficit). We present a biomass recovery map of Latin America, which illustrates geographical and climatic variation in carbon sequestration potential during forest regrowth. The map will support policies to minimize forest loss in areas where biomass resilience is naturally low (such as seasonally dry forest regions) and promote forest regeneration and restoration in humid tropical lowland areas with high biomass resilience.

Serum cytokine patterns in immunoglobulin m monoclonal gammopathy-associated polyneuropathy.

INTRODUCTION: Polyneuropathy with immunoglobulin M monoclonal gammopathy (IgM-PNP) is associated with the presence of IgM antibodies against nerve constituents such as myelin associated glycoprotein (MAG) and gangliosides. METHODS: To test whether B-cell-stimulating cytokines are increased in IgM-PNP, we measured serum concentrations of 11 cytokines in 81 patients with IgM-PNP and 113 controls. RESULTS: Median interleukin (IL)-6 concentrations were higher in patients with IgM-PNP, and median IL-10 concentrations were higher in the subgroup with anti-MAG IgM antibodies. These serum concentrations were not increased in 110 patients with multifocal motor neuropathy. DISCUSSION: Median IL-6 and IL-10 serum concentrations differ between patients with anti-MAG neuropathy and other patients with IgM-PNP compared with healthy and neuropathy controls. These differences may indicate differences in immune-mediated disease mechanisms. Muscle Nerve 59:694-698, 2019.

Mannose-binding lectin and l-ficolin polymorphisms in patients with community-acquired pneumonia caused by intracellular pathogens.

Community-acquired pneumonia (CAP) is the leading infectious disease requiring hospitalization in the western world. Genetic variability affecting the host response to infection may play a role in susceptibility and outcome in patients with CAP. Mannose-binding lectin (MBL) and l-ficolin (l-FCN) are two important activators of the complement system and they can enhance phagocytosis by opsonization. In a prospective cohort of 505 Dutch patients with CAP and 227 control participants we studied whether polymorphisms in the MBL (MBL2) and FCN (FCN2) genes influenced susceptibility and outcome. No difference in frequency of these genotypes was found between patients with CAP in general and controls. However, the +6424G>T single nucleotide polymorphism (SNP) in FCN2 was more common in patients with a Coxiella burnetii pneumonia (P = 0·014). Moreover, the haplotypes coding for the highest MBL serum levels (YA/YA and YA/XA) predisposed to atypical pneumonia (C. burnetii, Legionella or Chlamydia species or Mycoplasma pneumoniae) compared with controls (P = 0·016). Furthermore, patients with these haplotypes were more often bacteraemic (P = 0·019). It can therefore be concluded that MBL2 and FCN2 polymorphisms are not major risk factors for CAP in general, but that the +6424G>T SNP in the FCN2 gene predisposes to C. burnetii pneumonia. In addition, patients with genotypes corresponding with high serum MBL levels are at risk for atypical pneumonia, possibly caused by enhanced phagocytosis, thereby promoting cell entry of these intracellular bacteria.

Strong floristic distinctiveness across Neotropical successional forests.

Forests that regrow naturally on abandoned fields are important for restoring biodiversity and ecosystem services, but can they also preserve the distinct regional tree floras? Using the floristic composition of 1215 early successional forests (≤20 years) in 75 human-modified landscapes across the Neotropic realm, we identified 14 distinct floristic groups, with a between-group dissimilarity of 0.97. Floristic groups were associated with location, bioregions, soil pH, temperature seasonality, and water availability. Hence, there is large continental-scale variation in the species composition of early successional forests, which is mainly associated with biogeographic and environmental factors but not with human disturbance indicators. This floristic distinctiveness is partially driven by regionally restricted species belonging to widespread genera. Early secondary forests contribute therefore to restoring and conserving the distinctiveness of bioregions across the Neotropical realm, and forest restoration initiatives should use local species to assure that these distinct floras are maintained.

Molecular analysis of ciprofloxacin resistance and clonal relatedness of clinical Escherichia coli isolates from haematology patients receiving ciprofloxacin prophylaxis.

OBJECTIVES: Widespread use of fluoroquinolones has led to increased levels of resistance in clinical isolates of Escherichia coli. We investigated the evolution of ciprofloxacin susceptibility and molecular epidemiology of clinical E. coli isolates in haematology patients receiving ciprofloxacin prophylaxis on the population and individual patient level. METHODS: From August 2006 through December 2007 we collected all E. coli isolates (n = 404) from surveillance and infection-site cultures from 169 haematology patients receiving ciprofloxacin prophylaxis. Analysis of the gyrase A (gyrA) gene was performed by denaturing gradient gel electrophoresis (DGGE) in 364 isolates and clonal relatedness was determined by the single-enzyme amplified fragment length polymorphism (seAFLP) technique in 162 isolates. One hundred of these isolates were also subjected to qnrA analysis. RESULTS: The average number of samples per patient was 2.4 (maximum 20) and 122 (30%) of 404 E. coli isolates were resistant to ciprofloxacin. In 124 patients only ciprofloxacin-susceptible strains were detected. DGGE revealed 11 different gyrA sequence patterns and, based on AFLP analysis, there was evidence of selection of ciprofloxacin-resistant strains under antibiotic pressure, as well as the occurrence of genetically indistinguishable ciprofloxacin-resistant and -susceptible E. coli isolates within one patient. Clonal dissemination of ciprofloxacin-resistant E. coli was observed, but did not predominate. CONCLUSIONS: The genetic evolution of clinical E. coli isolates in haematology patients receiving ciprofloxacin prophylaxis is characterized by selection of ciprofloxacin-resistant strains. However, we did find evidence for de novo resistance mutation in ciprofloxacin-susceptible E. coli in individual patients under selective pressure.

Mannose-binding lectin (MBL2) and ficolin-2 (FCN2) polymorphisms in patients on peritoneal dialysis with staphylococcal peritonitis.

BACKGROUND: Mannose-binding lectin (MBL) and ficolin-2 (FCN) are activators of the lectin pathway of complement and act as primary defences against infection. Single-nucleotide polymorphisms (SNPs) in the MBL2 and FCN2 genes influence the functionality of the proteins. Both proteins are capable of binding staphylococci, which are pathogens that frequently cause peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD). We studied the role of polymorphisms in the MBL2 and FCN2 genes as a risk factor for developing CAPD peritonitis caused by staphylococci. METHODS: We analysed SNPs in the MBL2 and FCN2 genes in 40 CAPD patients with staphylococcal peritonitis and in 65 CAPD patients without any history of peritonitis. Additionally, we analysed the prevalence of exit site infections and nasal Staphylococcus aureus carriage in both groups. RESULTS: The + 6359C > T SNP leading to the Thr236Met amino acid alteration in the FCN2 gene, associated with decreased substrate binding, was significantly more prevalent in CAPD patients with a history of staphylococcal peritonitis compared with patients on CAPD without a history of peritonitis (P = 0.037). No difference was found in MBL2 genotypes between the two groups. In CAPD patients with a history of staphylococcal peritonitis, exit site infection with S. aureus was also more prevalent (P < 0.01), while S. aureus carriage was not (P = 0.073). CONCLUSIONS: In addition to known risk factors such as exit site infection, the + 6359C > T SNP in the FCN2 gene might be a risk factor for staphylococcal peritonitis in CAPD patients due to decreased binding of FCN to staphylococci.

Sensitivity and specificity of the 3-item memory test in the assessment of post traumatic amnesia.

PRIMARY OBJECTIVE: To investigate how the type of stimulus (pictures or words) and the method of reproduction (free recall or recognition after a short or a long delay) affect the sensitivity and specificity of a 3-item memory test in the assessment of post traumatic amnesia (PTA). METHODS: Daily testing was performed in 64 consecutively admitted traumatic brain injured patients, 22 orthopedically injured patients and 26 healthy controls until criteria for resolution of PTA were reached. Subjects were randomly assigned to a test with visual or verbal stimuli. Short delay reproduction was tested after an interval of 3-5 minutes, long delay reproduction was tested after 24 hours. Sensitivity and specificity were calculated over the first 4 test days. RESULTS: The 3-word test showed higher sensitivity than the 3-picture test, while specificity of the two tests was equally high. Free recall was a more effortful task than recognition for both patients and controls. In patients, a longer delay between registration and recall resulted in a significant decrease in the number of items reproduced. CONCLUSIONS: Presence of PTA is best assessed with a memory test that incorporates the free recall of words after a long delay.

Multilaboratory Comparison of Pneumococcal Multiplex Immunoassays Used in Immunosurveillance of Streptococcus pneumoniae across Europe.

Surveillance studies are required to estimate the impact of pneumococcal vaccination in both children and the elderly across Europe. The World Health Organization (WHO) recommends use of enzyme immunoassays (EIAs) as standard methods for immune surveillance of pneumococcal antibodies. However, as levels of antibodies to multiple serotypes are monitored in thousands of samples, a need for a less laborious and more flexible method has evolved. Fluorescent-bead-based multiplex immunoassays (MIAs) are suitable for this purpose. An increasing number of public health and diagnostic laboratories use MIAs, although the method is not standardized and no international quality assessment scheme exists. The EU Pneumo Multiplex Assay Consortium was initiated in 2013 to advance harmonization of MIAs and to create an international quality assessment scheme. In a multilaboratory comparison organized by the consortium, agreement among nine laboratories that used their own optimized MIA was assessed on a panel of 15 reference sera for 13 pneumococcal serotypes with the new WHO standard 007sp. Agreement was assessed in terms of assay accuracy, reproducibility, repeatability, precision, and bias. The results indicate that the evaluated MIAs are robust and reproducible for measurement of vaccine-induced antibody responses. However, some serotype-specific variability in the results was observed in comparisons of polysaccharides from different sources and of different conjugation methods, especially for serotype 4. On the basis of the results, the consortium has contributed to the harmonization of MIA protocols to improve reliability of immune surveillance of Streptococcus pneumoniaeIMPORTANCE Serology of Streptococcus pneumoniae is challenging due to existence of multiple clinically relevant serotypes and the introduction of multivalent vaccines in national immunization programs. Multiplex immunoassays (MIAs) are applied as high-throughput cost-effective methods for serosurveillance, and yet laboratories use their own protocols. The aims of this study were to assess the agreement of results generated by MIAs in different laboratories within the EU Pneumo Multiplex Assay Consortium, to analyze factors contributing to differences in outcome, and to create a harmonized protocol. The study demonstrated good agreement of results of MIAs performed by laboratories using controlled assays for determination of levels of vaccine-induced pneumococcal antibodies. The EU Pneumo Multiplex Assay Consortium is open to everyone working in public health services, and it aims to facilitate efforts by participants to run and maintain a cost-effective, reproducible, high-quality MIA platform.

Biodiversity recovery of Neotropical secondary forests.

Old-growth tropical forests harbor an immense diversity of tree species but are rapidly being cleared, while secondary forests that regrow on abandoned agricultural lands increase in extent. We assess how tree species richness and composition recover during secondary succession across gradients in environmental conditions and anthropogenic disturbance in an unprecedented multisite analysis for the Neotropics. Secondary forests recover remarkably fast in species richness but slowly in species composition. Secondary forests take a median time of five decades to recover the species richness of old-growth forest (80% recovery after 20 years) based on rarefaction analysis. Full recovery of species composition takes centuries (only 34% recovery after 20 years). A dual strategy that maintains both old-growth forests and species-rich secondary forests is therefore crucial for biodiversity conservation in human-modified tropical landscapes.

Wet and dry tropical forests show opposite successional pathways in wood density but converge over time.

Tropical forests are converted at an alarming rate for agricultural use and pastureland, but also regrow naturally through secondary succession. For successful forest restoration, it is essential to understand the mechanisms of secondary succession. These mechanisms may vary across forest types, but analyses across broad spatial scales are lacking. Here, we analyse forest recovery using 1,403 plots that differ in age since agricultural abandonment from 50 sites across the Neotropics. We analyse changes in community composition using species-specific stem wood density (WD), which is a key trait for plant growth, survival and forest carbon storage. In wet forest, succession proceeds from low towards high community WD (acquisitive towards conservative trait values), in line with standard successional theory. However, in dry forest, succession proceeds from high towards low community WD (conservative towards acquisitive trait values), probably because high WD reflects drought tolerance in harsh early successional environments. Dry season intensity drives WD recovery by influencing the start and trajectory of succession, resulting in convergence of the community WD over time as vegetation cover builds up. These ecological insights can be used to improve species selection for reforestation. Reforestation species selected to establish a first protective canopy layer should, among other criteria, ideally have a similar WD to the early successional communities that dominate under the prevailing macroclimatic conditions.

The safety and efficacy of nicotine replacement therapy in the intensive care unit: a randomised controlled pilot study.

BACKGROUND: Studies evaluating nicotine replacement therapy (NRT) to prevent nicotine withdrawal symptoms in ICU patients have yielded conflicting results. We performed a randomised controlled double-blind pilot study to assess the safety and efficacy of NRT in critically ill patients. Mechanically ventilated patients admitted to two medical-surgical intensive care units and smoking more than 10 cigarettes per day before ICU admission were enrolled in this study. Participants were randomised to transdermal NRT (14 or 21 mg per day) or placebo until ICU discharge or day 30. Smoking status was confirmed by the biomarkers serum cotinine and urinary NNAL. The primary endpoint was 30-day mortality. Among secondary endpoints and post hoc endpoints, 90-day mortality, safety, time spent without delirium, sedation and coma, and patient destination at day 30 were addressed. RESULTS: We enrolled 47 patients. No differences were found between NRT and control group patients concerning 30-day mortality (9.5 vs. 7.7%, p = 0.84) and 90-day mortality (14.3 vs. 19.2%, p = 0.67). The number of serious adverse events was comparable between groups (NRT: 4, control: 11, p = 0.13). At day 20, average time alive without delirium, sedation and coma was 16.6 days among NRT patients versus 12.6 days among control patients (p = 0.03). At day 30, more NRT group patients were discharged from the ICU or hospital compared with controls (p = 0.03). CONCLUSIONS: NRT did not affect mortality or the number of (serious) adverse events compared with placebo. Time alive without delirium, sedation and coma at day 20 in NRT patients was longer than in control patients. An adequately powered randomised controlled trial to further study safety and efficacy of NRT in ICU patients seems feasible and is warranted. Trial registration ClinicalTrials.gov, number NCT01362959, registered 1 June 2011.

Legume abundance along successional and rainfall gradients in Neotropical forests.

The nutrient demands of regrowing tropical forests are partly satisfied by nitrogen-fixing legume trees, but our understanding of the abundance of those species is biased towards wet tropical regions. Here we show how the abundance of Leguminosae is affected by both recovery from disturbance and large-scale rainfall gradients through a synthesis of forest inventory plots from a network of 42 Neotropical forest chronosequences. During the first three decades of natural forest regeneration, legume basal area is twice as high in dry compared with wet secondary forests. The tremendous ecological success of legumes in recently disturbed, water-limited forests is likely to be related to both their reduced leaflet size and ability to fix N2, which together enhance legume drought tolerance and water-use efficiency. Earth system models should incorporate these large-scale successional and climatic patterns of legume dominance to provide more accurate estimates of the maximum potential for natural nitrogen fixation across tropical forests.

Coding and non-coding polymorphisms in the lectin pathway activator L-ficolin gene in 188 Dutch blood bank donors.

Human L-ficolin (FCN) is a serum lectin characterized by a collagen-like and a fibrinogen-like domain that can activate the lectin pathway of complement. Structural and functional similarities to mannose-binding lectin (MBL) suggest a role for L-ficolin in innate immunity. Structural polymorphisms in the MBL2 gene lead to functional deficiency of MBL. Polymorphisms in the FCN2 gene have not been studied previously. We developed 10 denaturing gradient gel electrophoresis (DGGE) assays to screen a total of 188 Dutch Caucasians for polymorphisms in FCN2. Total gene screening in this large cohort revealed 10 single nucleotide polymorphisms (SNPs). Interestingly, two conserved coding SNPs were found in exon 8, leading to amino acid substitutions within the fibrinogen-like domain. Fibrinogen-like domains are highly conserved among several proteins in many species. As this domain is responsible for binding of L-ficolin, these newly found coding polymorphisms could alter the affinity of the protein for its substrates and possibly alter the ability of L-ficolin to recognize invading microorganisms.

Classical and lectin complement pathway activity in polyneuropathy associated with IgM monoclonal gammopathy.

Polyneuropathy associated with IgM monoclonal gammopathy (IgM-PNP) is a slowly progressive, sensorimotor neuropathy. It is assumed that complement activation contributes to IgM-PNP pathogenesis. We investigated whether innate differences in complement activity of the classical and mannose binding lectin (MBL) pathways are associated with IgM-PNP or its severity. We measured complement activity using ELISA and determined MBL serumc oncentrations and MBL gene polymorphisms in 83 patients and 83 healthy controls. We did not observe differences between IgM-PNP patients and healthy controls nor associations with different disease severities. Differences in innate complement activity are not likely to explain susceptibility to or severity of IgM-PNP.

Carbon sequestration potential of second-growth forest regeneration in the Latin American tropics.

Regrowth of tropical secondary forests following complete or nearly complete removal of forest vegetation actively stores carbon in aboveground biomass, partially counterbalancing carbon emissions from deforestation, forest degradation, burning of fossil fuels, and other anthropogenic sources. We estimate the age and spatial extent of lowland second-growth forests in the Latin American tropics and model their potential aboveground carbon accumulation over four decades. Our model shows that, in 2008, second-growth forests (1 to 60 years old) covered 2.4 million km(2) of land (28.1% of the total study area). Over 40 years, these lands can potentially accumulate a total aboveground carbon stock of 8.48 Pg C (petagrams of carbon) in aboveground biomass via low-cost natural regeneration or assisted regeneration, corresponding to a total CO2 sequestration of 31.09 Pg CO2. This total is equivalent to carbon emissions from fossil fuel use and industrial processes in all of Latin America and the Caribbean from 1993 to 2014. Ten countries account for 95% of this carbon storage potential, led by Brazil, Colombia, Mexico, and Venezuela. We model future land-use scenarios to guide national carbon mitigation policies. Permitting natural regeneration on 40% of lowland pastures potentially stores an additional 2.0 Pg C over 40 years. Our study provides information and maps to guide national-level forest-based carbon mitigation plans on the basis of estimated rates of natural regeneration and pasture abandonment. Coupled with avoided deforestation and sustainable forest management, natural regeneration of second-growth forests provides a low-cost mechanism that yields a high carbon sequestration potential with multiple benefits for biodiversity and ecosystem services.

A multi-criteria index for ecological evaluation of tropical agriculture in southeastern Mexico.

The aim of this study was to generate an easy to use index to evaluate the ecological state of agricultural land from a sustainability perspective. We selected environmental indicators, such as the use of organic soil amendments (green manure) versus chemical fertilizers, plant biodiversity (including crop associations), variables which characterize soil conservation of conventional agricultural systems, pesticide use, method and frequency of tillage. We monitored the ecological state of 52 agricultural plots to test the performance of the index. The variables were hierarchically aggregated with simple mathematical algorithms, if-then rules, and rule-based fuzzy models, yielding the final multi-criteria index with values from 0 (worst) to 1 (best conditions). We validated the model through independent evaluation by experts, and we obtained a linear regression with an r2 = 0.61 (p = 2.4e-06, d.f. = 49) between index output and the experts' evaluation.

[A patient in a methoxetamine-induced dissociative psychosis]. / Dissociatieve psychose door methoxetamine.

BACKGROUND: The international drug market has dramatically changed with the emergence of various new psychoactive substances that are mostly being sold on the internet. One of those new psychoactive substances is methoxetamine (MXE), a structural analogue of ketamine. CASE DESCRIPTION: A 30-year-old man with no history of illness was presented to the accident and emergency department. He had lost his balance and could not move. He was in a dissociative psychosis, felt he had no control over his body and was extremely frightened. Most of this symptoms disappeared within two hours of arrival. The next day there were no indications of a psychosis, and only headache and nausea remained. The state of dissociative psychosis was caused by MXE, which was sold to him as an ecstasy tablet. CONCLUSION: Whether mixed with alcohol and other drugs or not, MXE can cause serious feelings of dissociation resulting in extreme anxiety and psychosis. This might cause severely lowered consciousness in these patients. Currently, use of MXE in the Netherlands is limited, but ketamine or MXE intoxication should be considered in patients with these symptoms.