Quality‐of‐life outcomes in patients with advanced melanoma: A review of the literature

For patients with metastatic melanoma, the emergence of immune checkpoint inhibitors and targeted BRAF and MEK inhibitors has markedly enhanced clinical outcomes compared with chemotherapy. However, these novel agents are also associated with unique sets of adverse events, and increased overall survival can lead to prolonged exposure to some novel agents. Therefore, clinical evaluation of these therapies has now included the analysis of health‐related quality of life (HRQoL) in addition to more traditional efficacy and safety outcomes as a measure of patient perception of benefit. The current review focuses on HRQoL outcomes in clinical trials of immune checkpoint inhibitors and targeted therapies in patients with advanced and metastatic melanoma to inform healthcare providers about patient perception of HRQoL as a new perspective in treatment decision making.     

Field estimates of fitness costs of the pace‐of‐life in an endangered damselfly

Theory predicts that within‐population differences in the pace‐of‐life can lead to cohort splitting and produce marked intraspecific variation in body size. Although many studies showed that body size is positively correlated with fitness, many argue that selection for the larger body is counterbalanced by opposing physiological and ecological selective mechanisms that favour smaller body. When a population split into cohorts with different paces of life (slow or fast cohort), one would expect to detect the fitness–size relationship among and within cohorts, that is, (a) slower‐developing cohort has larger body size and higher fitness than faster‐developing cohort, and (b) larger individuals within each cohort show higher fitness than smaller individuals. Here, we test these hypotheses in capture–mark–recapture field surveys that assess body size, lifespan, survival and lifetime mating success in two consecutive generations of a partially bivoltine aquatic insect, Coenagrion mercuriale, where the spring cohort is slower‐developing than the autumn cohort. As expected, body size was larger in the slow‐developing cohort, which is consistent with the temperature‐size rule and also with the duration of development. Body size seasonal variation was greater in slow‐developing cohort most likely because of the higher variation in age at maturity. Concordant with theory, survival probability, lifespan and lifetime mating success were higher in the slow‐developing cohort. Moreover, individual body size was positively correlated with survival and mating success in both cohorts. Our study confirms the fitness costs of fast pace‐of‐life and the benefits of larger body size to adult fitness.     

Development of microsatellite markers for the crown‐of‐thorns starfish Acanthaster planci

We isolated nine polymorphic microsatellites from the crown‐of‐thorns starfish, Acanthaster planci. These loci provide one class of highly variable genetic marker as the number of alleles ranged from three to 12 and the observed and expected heterozygosities ranged from 0.130 to 0.783 and from 0.163 to 0.862, respectively. We consider that these loci are potentially useful for detailing the genetic structure and gene flow among A. planci populations.     

Using expert knowledge to incorporate uncertainty in cause‐of‐death assignments for modeling of cause‐specific mortality

Implicit and explicit use of expert knowledge to inform ecological analyses is becoming increasingly common because it often represents the sole source of information in many circumstances. Thus, there is a need to develop statistical methods that explicitly incorporate expert knowledge, and can successfully leverage this information while properly accounting for associated uncertainty during analysis. Studies of cause‐specific mortality provide an example of implicit use of expert knowledge when causes‐of‐death are uncertain and assigned based on the observer's knowledge of the most likely cause. To explicitly incorporate this use of expert knowledge and the associated uncertainty, we developed a statistical model for estimating cause‐specific mortality using a data augmentation approach within a Bayesian hierarchical framework. Specifically, for each mortality event, we elicited the observer's belief of cause‐of‐death by having them specify the probability that the death was due to each potential cause. These probabilities were then used as prior predictive values within our framework. This hierarchical framework permitted a simple and rigorous estimation method that was easily modified to include covariate effects and regularizing terms. Although applied to survival analysis, this method can be extended to any event‐time analysis with multiple event types, for which there is uncertainty regarding the true outcome. We conducted simulations to determine how our framework compared to traditional approaches that use expert knowledge implicitly and assume that cause‐of‐death is specified accurately. Simulation results supported the inclusion of observer uncertainty in cause‐of‐death assignment in modeling of cause‐specific mortality to improve model performance and inference. Finally, we applied the statistical model we developed and a traditional method to cause‐specific survival data for white‐tailed deer, and compared results. We demonstrate that model selection results changed between the two approaches, and incorporating observer knowledge in cause‐of‐death increased the variability associated with parameter estimates when compared to the traditional approach. These differences between the two approaches can impact reported results, and therefore, it is critical to explicitly incorporate expert knowledge in statistical methods to ensure rigorous inference.     

Building the Coleoptera tree‐of‐life for >8000 species: composition of public DNA data and fit with Linnaean classification

The species representation of public databases is growing rapidly and permits increasingly detailed phylogenetic inferences. We present a supermatrix based on all gene sequences of Coleoptera available in Genbank for two nuclear (18S and 28S rRNA) and two mitochondrial (rrnL and cox1) genes. After filtering for unique species names and the addition of ?2000 unpublished sequences for cox1 and 18S rRNA, the resulting data matrix included 8441 species‐level terminals and 6600 aligned nucleotide positions. The concatenated matrix represents the equivalent of 2.17% of the 390 000 described species of Coleoptera and includes 152 beetle families. The remaining 29 families constitute small lineages with ?250 known species in total. Taxonomic coverage remains low for several major lineages, including Buprestidae (0.16% of described species), Staphylinidae (1.03%), Tenebrionidae (0.90%) and Cerambycidae (0.58%). The current taxon sampling was strongly biased towards the Northern Hemisphere. Phylogenetic trees obtained from the supermatrix were in very good agreement with the Linnaean classification, in particular at the family level, but lower for the subfamily and lowest for the genus level. The topology supports the basal split of Derodontidae and Scirtoidea from the remaining Polyphaga, and the broad paraphyly of Cucujoidea. The data extraction pipeline and detailed tree provide a framework for placement of any new sequences, including environmental samples, into a DNA‐based classification system of Coleoptera.     

Pace‐of‐life: Relationships among locomotor activity,life history,and circadian rhythm in the assassin bug,Amphibolus venator

The pace‐of‐life syndrome (POLS) hypothesis means that animal behavior is correlated with life history strategies. Studies have reported that the free‐running period of the circadian rhythm (length of the period) is correlated with life history strategies in some animals. Although the length of the circadian rhythm may be associated with the POLS hypothesis, few studies have investigated the relationships among animal behavior, life history traits, and circadian rhythm. We tested the POLS hypothesis in the assassin bug, Amphibolus venator, which shows individual variation in locomotor activity. We found higher repeatability of differences in locomotor activity between individuals. Moreover, we found a trade‐off between locomotor activity and developmental period such that active individuals developed faster. However, locomotor activity was not correlated with the length of the circadian rhythm in A. venator. Therefore, this study suggests that the length of the circadian rhythm in A. venator does not support the POLS hypothesis.     

Life‐history evolution under fluctuating density‐dependent selection and the adaptive alignment of pace‐of‐life syndromes

We present a novel perspective on life‐history evolution that combines recent theoretical advances in fluctuating density‐dependent selection with the notion of pace‐of‐life syndromes (POLSs) in behavioural ecology. These ideas posit phenotypic co‐variation in life‐history, physiological, morphological and behavioural traits as a continuum from the highly fecund, short‐lived, bold, aggressive and highly dispersive ‘fast’ types at one end of the POLS to the less fecund, long‐lived, cautious, shy, plastic and socially responsive ‘slow’ types at the other. We propose that such variation in life histories and the associated individual differences in behaviour can be explained through their eco‐evolutionary dynamics with population density – a single and ubiquitous selective factor that is present in all biological systems. Contrasting regimes of environmental stochasticity are expected to affect population density in time and space and create differing patterns of fluctuating density‐dependent selection, which generates variation in fast versus slow life histories within and among populations. We therefore predict that a major axis of phenotypic co‐variation in life‐history, physiological, morphological and behavioural traits (i.e. the POLS) should align with these stochastic fluctuations in the multivariate fitness landscape created by variation in density‐dependent selection. Phenotypic plasticity and/or genetic (co‐)variation oriented along this major POLS axis are thus expected to facilitate rapid and adaptively integrated changes in various aspects of life histories within and among populations and/or species. The fluctuating density‐dependent selection POLS framework presented here therefore provides a series of clear testable predictions, the investigation of which should further our fundamental understanding of life‐history evolution and thus our ability to predict natural population dynamics.     

Genome‐wide association analyses of child genotype effects and parent‐of‐origin effects in specific language impairment

Specific language impairment (SLI) is a neurodevelopmental disorder that affects linguistic abilities when development is otherwise normal. We report the results of a genome‐wide association study of SLI which included parent‐of‐origin effects and child genotype effects and used 278 families of language‐impaired children. The child genotype effects analysis did not identify significant associations. We found genome‐wide significant paternal parent‐of‐origin effects on chromosome 14q12 (P = 3.74 × 10^?8) and suggestive maternal parent‐of‐origin effects on chromosome 5p13 (P = 1.16 × 10^?7). A subsequent targeted association of six single‐nucleotide‐polymorphisms (SNPs) on chromosome 5 in 313 language‐impaired individuals and their mothers from the ALSPAC cohort replicated the maternal effects, albeit in the opposite direction (P = 0.001); as fathers' genotypes were not available in the ALSPAC study, the replication analysis did not include paternal parent‐of‐origin effects. The paternally‐associated SNP on chromosome 14 yields a non‐synonymous coding change within the NOP9 gene. This gene encodes an RNA‐binding protein that has been reported to be significantly dysregulated in individuals with schizophrenia. The region of maternal association on chromosome 5 falls between the PTGER4 and DAB2 genes, in a region previously implicated in autism and ADHD. The top SNP in this association locus is a potential expression QTL of ARHGEF19 (also called WGEF) on chromosome 1. Members of this protein family have been implicated in intellectual disability. In summary, this study implicates parent‐of‐origin effects in language impairment, and adds an interesting new dimension to the emerging picture of shared genetic etiology across various neurodevelopmental disorders .     

End‐of‐life product management as a resilience driver for developing countries: A policy experiment for used tires in Ecuador

Over the last decades, a number of new environmental policies have been designed to improve waste management. Among them, extended producer responsibility (EPR) has introduced a mechanism to shift the environmental and financial burden of end‐of‐life products from public management to producers. Recently, EPR has been adopted by a growing number of developing countries, but this policy often struggles in being effectively implemented in such contexts, missing the opportunity of using waste management as a sustainability driver. By discussing the EPR for end‐of‐life tires (ELTs) in Ecuador, this paper proposes a different approach in designing and implementing EPR schemes in developing countries: it recommends consideration of social sustainability, rather than merely copying foreign management frameworks. To address this point, two case studies on socially directed ELT applications were designed and carried out. The case studies aimed at improving resilience of vulnerable populations to natural disasters by increasing the resistance of housing and settlements against catastrophic events using civil engineering applications. The analysis of the case studies’ outcomes brings to light possible policy adjustments, in which social sustainability goals are taken into account within the national EPR scheme. The Ecuadorian case also highlights the benefit of employing an adaptive governance approach when dealing with challenging urban management topics, such as informality (a widespread phenomenon in developing countries) and resilience.     

Optimizing α for better statistical decisions: A case study involving the pace‐of‐life syndrome hypothesis

Setting optimal significance levels that minimize Type I and Type II errors allows for more transparent and well‐considered statistical decision making compared to the traditional α = 0.05 significance level. We use the optimal α approach to re‐assess conclusions reached by three recently published tests of the pace‐of‐life syndrome hypothesis, which attempts to unify occurrences of different physiological, behavioral, and life history characteristics under one theory, over different scales of biological organization. While some of the conclusions reached using optimal α were consistent to those previously reported using the traditional α = 0.05 threshold, opposing conclusions were also frequently reached. The optimal α approach reduced probabilities of Type I and Type II errors, and ensured statistical significance was associated with biological relevance. Biologists should seriously consider their choice of α when conducting null hypothesis significance tests, as there are serious disadvantages with consistent reliance on the traditional but arbitrary α = 0.05 significance level.     

Validation of the FEEL-KJ: An Instrument to Measure Emotion Regulation Strategies in Children and Adolescents

Although the field of emotion regulation in children and adolescents is growing, there is need for age-adjusted measures that assess a large variety of strategies. An interesting instrument in this respect is the FEEL-KJ because it measures 7 adaptive and 5 maladaptive emotion regulation strategies in response to three different emotions. However, the FEEL-KJ has not yet been validated extensively. Therefore, the current study aims to test the internal structure and validity of the FEEL-KJ in a large sample of Dutch-speaking Belgian children and adolescents (N = 1102, 8–18 years old). The investigation of the internal structure confirms earlier reports of a two-factor structure with Adaptive and Maladaptive Emotion Regulation as overarching categories. However, it also suggests that the two-factor model is more complex than what was previously assumed. The evaluation of the FEEL-KJ validity furthermore provides evidence for its construct and external validity. In sum, the current study confirms that the FEEL-KJ is a valuable and reliable measure of emotion regulation strategies in children and adolescents.     

Body Composition of African American and White Children: A 2‐Year Follow‐Up of the BAROC Study

Objective: To evaluate the 2‐year changes in body composition of white and African American boys and girls. Research Methods and Procedures: A total of 114 boys and girls ages 12 to 14 years with equal sex and ethnic distribution between African American and white races participated in measurements of body composition using DXA, underwater weighing (densitometry), skinfold thickness, corporal diameters, circumferences, isotope dilution (H₂¹⁸O), and bioelectric impedance. Results: Sixty‐eight of the 114 children advanced from Tanner Stages 1 and 2 to Tanner Stages 3 to 5 over a 2‐year period. More than 50% of the children were in the top 15th percentile according to normative data for body mass index but not for triceps skinfold. All measures except for percentage of fat, density, and four of the six skinfolds increased significantly during the 2 years, with no differences between races, genders, or fat group. The boys who advanced in Tanner Stage reduced their percentage of fat and a number of skinfolds and increased their lean body mass, but the girls did not. The percentage of water was significantly higher in the fatter children and declined significantly over 2 years. Most children remained in the same quartile of body fat, lean body mass, and bone mineral content over 2 years. Discussion: The data are consistent with the hypothesis that over 2 years, growth is the major determinant of changing body composition, with body‐fat group and sexual maturation being additional variables.     

Validation of an ultrasensitive and specific immunofluorometric assay for mouse follicle-stimulating hormone

Sensitive and specific measurement of FSH is critical to research in reproductive biology, and the increasing availability of transgenic mouse models has created a need for a robust, sensitive, and specific mouse (m) FSH assay. The present study evaluated a time-resolved immunofluorometric assay (IFMA) for mFSH using monoclonal antibody to human (h) FSHbeta as a capture antibody and a biotinylated polyclonal antibody to rat alpha subunit as a detection probe, with signaling amplified by europium-labeled streptavidin. The mFSH IFMA lowered the detection limit 34-fold (5 vs. 170 pg/sample) compared with standard mFSH RIA. The mFSH IFMA demonstrated parallelism of response to dilutions of castrated mouse serum and rat FSH but no cross-reactivity with hFSH and mLH or hLH, whereas the RIA demonstrated nonparallel cross-reactivity with hFSH. The IFMA has a wide analytical range, with a good precision profile for within- and between-assay reproducibility. Because the IFMA is a sandwich-type assay with strict dimer-specificity by design, the lower readings and recovery obtained were compared with the RIA when both assays used a pituitary-purified mFSH assay standard that contained isolated or fragmented subunits as well as intact dimeric FSH. When used with mouse serum sample, the mFSH IFMA demonstrated the expected increases following orchidectomy as well as markedly enhanced sensitivity to very low levels of endogenous mFSH in gonadotropin-deficient mice. Furthermore, the IFMA measured mFSH with fidelity in both intact and orchidectomized male mice without any interference from transgenic hFSH. The greatly enhanced sensitivity, specificity, and technical convenience of this mFSH IFMA will allow wider application of FSH measurements to very small blood samples in immature and mature mice as well as transgenic models.     

Development of taxon‐specific markers for high‐throughput screening of microbial‐feeding nematodes

In an effort to assess the taxonomic identity of large‐scale samplings of nematodes from the Konza Tallgrass Prairie, we sequenced a portion of the 18S rRNA gene and its associated internally transcribed spacer (ITS1) from 74 nematodes encompassing four taxonomic families. From these sequences, we have developed a series of molecular probes to distinguish 16 distinct microbivorous nematode taxa. Using a combination of low power microscopy and taxon‐specific real‐time probes, the 74 nematodes were correctly assigned to their respective taxonomic groups. This optimized method provides a high‐throughput assay to determine nematode identities across larger data sets.     

End‐of‐life decision‐making and advance care directives in Italy. A report and moral appraisal of recent legal provisions

The present article reviews the state of public debate and legal provisions concerning end‐of‐life decision‐making in Italy and offers an evaluation of the moral and legal issues involved. The article further examines the content of a recent law concerning informed consent and advance treatment directives, the main court pronouncements that formed the basis for the law, and developments in the public debate and important jurisprudential acts subsequent to its approval. The moral and legal grounds for a positive evaluation of this law, which attests that the patient may withhold or withdraw from life‐prolonging treatment, will be offered with reference to liberal approaches and particularly to the frameworks of care and virtue ethics; but reasons will also be offered in order to consider not only the latter but also broader range of end‐of‐life treatment decisions as morally apt options. In this light, we argue in favour of a further development of the Italian legislation to encompass forms of assisted suicide and active euthanasia.     

Combining near‐ and far‐field exposure for an organ‐specific and whole‐body RF‐EMF proxy for epidemiological research: A reference case

A framework for the combination of near‐field (NF) and far‐field (FF) radio frequency electromagnetic exposure sources to the average organ and whole‐body specific absorption rates (SARs) is presented. As a reference case, values based on numerically derived SARs for whole‐body and individual organs and tissues are combined with realistic exposure data, which have been collected using personal exposure meters during the Swiss Qualifex study. The framework presented can be applied to any study region where exposure data is collected by appropriate measurement equipment. Based on results derived from the data for the region of Basel, Switzerland, the relative importance of NF and FF sources to the personal exposure is examined for three different study groups. The results show that a 24‐h whole‐body averaged exposure of a typical mobile phone user is dominated by the use of his or her own mobile phone when a Global System for Mobile Communications (GSM) 900 or GSM 1800 phone is used. If only Universal Mobile Telecommunications System (UMTS) phones are used, the user would experience a lower exposure level on average caused by the lower average output power of UMTS phones. Data presented clearly indicate the necessity of collecting band‐selective exposure data in epidemiological studies related to electromagnetic fields. Bioelectromagnetics 34:366–374, 2013. © 2012 Wiley Periodicals, Inc.     

Graphene‐Based Electron Transport Layers in Perovskite Solar Cells: A Step‐Up for an Efficient Carrier Collection

The electron transport layer (ETL) plays a fundamental role in perovskite solar cells. Recently, graphene‐based ETLs have been proved to be good candidate for scalable fabrication processes and to achieve higher carrier injection with respect to most commonly used ETLs. Here, the effects of different graphene‐based ETLs in sensitized methylammonium lead iodide (MAPI) solar cells are experimentally studied. By means of time‐integrated and picosecond time‐resolved photoluminescence techniques, the carrier recombination dynamics in MAPI films embedded in different ETLs is investigated. Using graphene doped mesoporous TiO₂ (G+mTiO₂) with the addition of a lithium‐neutralized graphene oxide (GO‐Li) interlayer as ETL, it is found find that the carrier collection efficiency is increased by about a factor two with respect to standard mTiO₂. Taking advantage of the absorption coefficient dispersion, the MAPI layer morphology is probed, along the thickness, finding that the MAPI embedded in the ETL composed by G+mTiO₂ plus GO‐Li brings to a very good crystalline quality of the MAPI layer with a trap density about one order of magnitude lower than that found with the other ETLs. In addition, this ETL freezes MAPI at the tetragonal phase, regardless of the temperature. Graphene‐based ETLs can open the way to significant improvement of perovskite solar cells.