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Background Due to the lack of complexity and variety of stimuli, conventional housing conditions of laboratory mice do not allow these animals to fully express their behavioral repertoire, including manipulative and cognitive activities. Therefore, we designed mechanical puzzles, so-called lockboxes, for mice that can be provided in their home cages. We investigated the impact of the lockbox enrichment on their phenotype and affective state when compared to conventional housing (CH) and super-environmental enrichment (SEE). Methods Young adult female C57BL/6JCrl mice were examined before and after 2-month exposure to the different types of enrichment in a phenotyping test battery, including tests for trait and state anxiety-related behavior, calorimetric measurements, body weight measurements, the analysis of stress hormone metabolite concentrations, and sequential problem-solving abilities with a novel lockbox. At the end of the study, adrenal gland weights were determined and pathohistological evaluation was performed. For all continuous variables, the relative variability was calculated. Results While the different types of enrichment affected trait anxiety-related behavior, neither state anxiety-related behavior nor physiological variables (i.e., bodyweight, resting metabolic rate, stress hormone metabolite concentrations, adrenal gland weights) were influenced. LE improved sequential problem-solving (i.e., solving novel lockboxes) when compared to SEE. Regardless of the housing condition, the relative variability increased in most variables over time, although the coefficient of variation decreased for some variables, especially in animals with access to LE. There was no evidence of toxicopathological effects associated with the material from which the lockboxes were made. Conclusions All lockboxes are available as open-source tool. LE revealed beneficial effects on the affective state of laboratory mice and their performance in solving novel lockboxes. Neither relevant phenotype of the mice nor reproducibility of the data were compromised by LE, similar to SEE. The lockboxes may also be used as novel approach for assessing cognition in mice.

Abstract Objective We estimate annual hospital expenditures to achieve high emergency department (ED) pediatric readiness (HPR), that is, weighted Pediatric Readiness Score (wPRS) ≥ 88 (0–100 scale) across EDs with different pediatric volumes of children, overall and after accounting for current levels of readiness. Methods We calculated the annual hospital costs of HPR based on two components: (1) ED pediatric equipment and supplies and (2) labor costs required for a Pediatric Emergency Care Coordinator (PECC) to perform pediatric readiness tasks. Data sources to generate labor cost estimates included: 2021 national salary information from U.S. Bureau of Labor Statistics, detailed patient and readiness data from 983 EDs in 11 states, the 2021 National Pediatric Readiness Project assessment; a national PECC survey; and a regional PECC survey. Data sources for equipment and supply costs included: purchasing costs from seven healthcare organizations and equipment usage per ED pediatric volume. We excluded costs of day‐to‐day ED operations (ie, direct clinical care and routine ED supplies). Results The total annual hospital costs for HPR ranged from $77,712 (95% CI 54,719–100,694) for low volume EDs to $279,134 (95% CI 196,487–362,179) for very high volume EDs; equipment costs accounted for 0.9–5.0% of expenses. The total annual cost‐per‐patient ranged from $3/child (95% CI 2–4/child) to $222/child (95% CI 156–288/child). After accounting for current readiness levels, the cost to reach HPR ranged from $23,775 among low volume EDs to $145,521 among high volume EDs, with costs per patient of $4/child to $48/child. Conclusions Annual hospital costs for HPR are modest, particularly when considered per child.

Abstract Background Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside of their home cages at selected time points. However, the outcome of such tests can be influenced by various factors and valuable information may be missed when the animals are only monitored for short periods. These issues can be overcome by longitudinally monitoring mice and rats in their home cages. To shed light on the development of home cage monitoring (HCM) and the current state-of-the-art, a systematic review was carried out on 521 publications retrieved through PubMed and Web of Science. Results Both the absolute (~ × 26) and relative (~ × 7) number of HCM-related publications increased from 1974 to 2020. There was a clear bias towards males and individually housed animals, but during the past decade (2011–2020), an increasing number of studies used both sexes and group housing. In most studies, animals were kept for short (up to 4 weeks) time periods in the HCM systems; intermediate time periods (4–12 weeks) increased in frequency in the years between 2011 and 2020. Before the 2000s, HCM techniques were predominantly applied for less than 12 h, while 24-h measurements have been more frequent since the 2000s. The systematic review demonstrated that manual monitoring is decreasing in relation to automatic techniques but still relevant. Until (and including) the 1990s, most techniques were applied manually but have been progressively replaced by automation since the 2000s. Independent of the year of publication, the main behavioral parameters measured were locomotor activity, feeding, and social behaviors; the main physiological parameters were heart rate and electrocardiography. External appearance-related parameters were rarely examined in the home cages. Due to technological progress and application of artificial intelligence, more refined and detailed behavioral parameters have been investigated in the home cage more recently. Conclusions Over the period covered in this study, techniques for HCM of mice and rats have improved considerably. This development is ongoing and further progress as well as validation of HCM systems will extend the applications to allow for continuous, longitudinal, non-invasive monitoring of an increasing range of parameters in group-housed small rodents in their home cages.

Abstract Fusion oncoproteins (FOs) arise from chromosomal translocations in ~17% of cancers and are often oncogenic drivers. Although some FOs can promote oncogenesis by undergoing liquid-liquid phase separation (LLPS) to form aberrant biomolecular condensates, the generality of this phenomenon is unknown. We explored this question by testing 166 FOs in HeLa cells and found that 58% formed condensates. The condensate-forming FOs displayed physicochemical features distinct from those of condensate-negative FOs and segregated into distinct feature-based groups that aligned with their sub-cellular localization and biological function. Using Machine Learning, we developed a predictor of FO condensation behavior, and discovered that 67% of ~3000 additional FOs likely form condensates, with 35% of those predicted to function by altering gene expression. 47% of the predicted condensate-negative FOs were associated with cell signaling functions, suggesting a functional dichotomy between condensate-positive and -negative FOs. Our Datasets and reagents are rich resources to interrogate FO condensation in the future.

The mechanisms underlying the formation and retrieval of memories are still an active area of research and discussion. Manifold models have been proposed and refined over the years, with most assuming a dichotomy between memory processes involving non-conscious and conscious mechanisms. Despite our incomplete understanding of the underlying mechanisms, tests of memory and learning count among the most performed behavioral experiments. Here, we will discuss available protocols for testing learning and memory using the example of the most prevalent animal species in research, the laboratory mouse. A wide range of protocols has been developed in mice to test, e.g., object recognition, spatial learning, procedural memory, sequential problem solving, operant- and fear conditioning, and social recognition. Those assays are carried out with individual subjects in apparatuses such as arenas and mazes, which allow for a high degree of standardization across laboratories and straightforward data interpretation but are not without caveats and limitations. In animal research, there is growing concern about the translatability of study results and animal welfare, leading to novel approaches beyond established protocols. Here, we present some of the more recent developments and more advanced concepts in learning and memory testing, such as multi-step sequential lockboxes, assays involving groups of animals, as well as home cage-based assays supported by automated tracking solutions; and weight their potential and limitations against those of established paradigms. Shifting the focus of learning tests from the classical experimental chamber to settings which are more natural for rodents comes with a new set of challenges for behavioral researchers, but also offers the opportunity to understand memory formation and retrieval in a more conclusive way than has been attainable with conventional test protocols. We predict and embrace an increase in studies relying on methods involving a higher degree of automatization, more naturalistic- and home cage-based experimental setting as well as more integrated learning tasks in the future. We are confident these trends are suited to alleviate the burden on animal subjects and improve study designs in memory research.

Abstract Breast cancer is a heterogeneous disease classified into four main subtypes with different clinical outcomes, such as patient survival, prognosis, and relapse. Current genetic tests for the differential diagnosis of BC subtypes showed a poor reproducibility. Therefore, an early and correct diagnosis of molecular subtypes is one of the challenges in the clinic. In the present study, we identified differentially expressed genes, long non-coding RNAs and RNA binding proteins for each BC subtype from a public dataset applying bioinformatics algorithms. In addition, we investigated their interactions and we proposed interacting biomarkers as potential signature specific for each BC subtype. We found a network of only 2 RBPs (RBM20 and PCDH20) and 2 genes (HOXB3 and RASSF7) for luminal A, a network of 21 RBPs and 53 genes for luminal B, a HER2-specific network of 14 RBPs and 30 genes, and a network of 54 RBPs and 302 genes for basal BC. We validated the signature considering their expression levels on an independent dataset evaluating their ability to classify the different molecular subtypes with a machine learning approach. Overall, we achieved good performances of classification with an accuracy >0.80. In addition, we found some interesting novel prognostic biomarkers such as RASSF7 for luminal A, DCTPP1 for luminal B, DHRS11, KLC3, NAGS, and TMEM98 for HER2, and ABHD14A and ADSSL1 for basal. The findings could provide preliminary evidence to identify putative new prognostic biomarkers and therapeutic targets for individual breast cancer subtypes.

Interferon lambdas (IFNλ) (also known as type III IFNs) are critical cytokines that combat infection predominantly at barrier tissues, such as the lung, liver, and gastrointestinal tract. Humans have four IFNλs (1–4), where IFNλ1–3 show ~80%–95% homology, and IFNλ4 is the most divergent displaying only ~30% sequence identity. Variants in IFNλ4 in humans are associated with the outcome of infection, such as with hepatitis C virus. However, how IFNλ4 variants impact cytokine signalling in other tissues and how well this is conserved is largely unknown. In this study, we address whether differences in antiviral signalling exist between IFNλ4 variants in human hepatocyte and intestinal cells, comparing them to IFNλ3. We demonstrate that compared to IFNλ3, wild-type human IFNλ4 induces a signalling response with distinct magnitudes and kinetics, which is modified by naturally occurring variants P70S and K154E in both cell types. IFNλ4’s distinct antiviral response was more rapid yet transient compared to IFNλ1 and 3. Additionally, divergent antiviral kinetics were also observed using non-human primate IFNλs and cell lines. Furthermore, an IFNλ4-like receptor-interacting interface failed to alter IFNλ1’s kinetics. Together, our data provide further evidence that major functional differences exist within the IFNλ gene family. These results highlight the possible tissue specialisation of IFNλs and encourage further investigation of the divergent, non-redundant activities of IFNλ4 and other IFNλs.

Photothermal spectroscopy (PTS) is a promising sensing technique for the measurement of gases and aerosols. PTS systems using a Fabry–Pérot interferometer (FPI) are considered particularly promising owing to their robustness and potential for miniaturization. However, limited information is available on viable procedures for signal improvement through parameter tuning. In our work, we use an FPI-based PTS configuration, in which the excitation laser irradiates the target collinearly to the flowing gas. We demonstrate that the generated thermal wave, and thus the signal intensity, is significantly affected by the ratio between excitation modulation frequency and gas flow velocity towards another. We provide an analytical model that predicts the signal intensity with particular considerations of these two parameter settings and validate the findings experimentally. The results reveal the existence of an optimal working regime, depending on the modulation frequency and flow velocity.

Ageing causes an inability to replace damaged tissue. Here, the authors perform proteomics analyses of human haematopoietic stem cells and other cells in the bone marrow niche at different ages and show changes in central carbon metabolism, reduced bone marrow niche function, and enhanced myeloid differentiation.

Introduction Serotonin syndrome is caused by an accumulation of serotonin in the body from drug interactions or overdose of serotonergic medications, including commonly used antidepressants. Symptoms can be life-threatening and encompass both neurologic and cardiovascular toxicity, including agitation, seizure, tachycardia, rhabdomyolysis, and hyperthermia. Methods This simulation case was developed for pediatric emergency medicine fellows and emergency medicine residents in the pediatric emergency department and can be altered to accommodate other learners. The case involved a 16-year-old male, represented by a low- or high-fidelity manikin, who presented with altered mental status/agitation after an overdose of antidepressant medication. The team of learners was required to perform a primary and a secondary assessment; manage airway, breathing, and circulation; and recognize and initiate treatment for serotonin syndrome. The patient had a seizure resulting in airway compromise requiring advanced airway support, as well as developed rhabdomyolysis requiring aggressive fluid hydration. We created a debriefing guide and a participant evaluation form. Results Fifty-seven participants across five institutions completed this simulation, which included residents, fellows, faculty, and students. The scenario was rated by participants using a 5-point Likert scale and was generally well received. Participants rated the simulation case as effective in learning how to both recognize (M = 4.9) and manage (M = 4.8) serotonin syndrome. Discussion This pediatric emergency simulation scenario can be tailored for a range of learner backgrounds and simulation environments. We used the participant evaluation form to improve future iterations of the simulation.

Summary: Recent evidence indicates that specific RNAs promote the formation of ribonucleoprotein condensates by acting as scaffolds for RNA-binding proteins (RBPs). We systematically investigated RNA-RBP interaction networks to understand ribonucleoprotein assembly. We found that highly contacted RNAs are structured, have long UTRs, and contain nucleotide repeat expansions. Among the RNAs with such properties, we identified the FMR1 3′ UTR that harbors CGG expansions implicated in fragile X-associated tremor/ataxia syndrome (FXTAS). We studied FMR1 binding partners in silico and in vitro and prioritized the splicing regulator TRA2A for further characterization. In a FXTAS cellular model, we validated the TRA2A-FMR1 interaction and investigated implications of its sequestration at both transcriptomic and post-transcriptomic levels. We found that TRA2A co-aggregates with FMR1 in a FXTAS mouse model and in post-mortem human samples. Our integrative study identifies key components of ribonucleoprotein aggregates, providing links to neurodegenerative disease and allowing the discovery of therapeutic targets. : Cid-Samper et al. analyze protein-RNA networks and identify properties of RNA scaffolds within biological condensates. They find that CGG repeats in the 3′ UTR of FMR1 attract several proteins, including the splicing factor TRA2A that co-aggregates in fragile X-associated tremor/ataxia syndrome (FXTAS). Keywords: phase separation, scaffolding RNA, CGG repeat expansion, FMR1 premutation, fragile X-associated tremor/ataxia syndrome, FXTAS, RNA aggregates, RNA binding proteins, RBP, TRA2A splicing regulator, neurodegeneration

The discovery of 3C 273 in 1963, and the emergence of the Kerr solution shortly thereafter, precipitated the current era in astrophysics focused on using black holes to explain active galactic nuclei (AGN). But while partial success was achieved in separately explaining the bright nuclei of some AGN via thin disks, as well as powerful jets with thick disks, the combination of both powerful jets in an AGN with a bright nucleus, such as in 3C 273, remained elusive. Although numerical simulations have taken center stage in the last 25 years, they have struggled to produce the conditions that explain them. This is because radiatively efficient disks have proved a challenge to simulate. Radio quasars have thus been the least understood objects in high energy astrophysics. But recent simulations have begun to change this. We explore this milestone in light of scale-invariance and show that transitory jets, possibly related to the jets seen in these recent simulations, as some have proposed, cannot explain radio quasars. We then provide a road map for a resolution.

Precise control of protein turnover is essential for cellular homeostasis. The ubiquitin-proteasome system is well established as a major regulator of protein degradation, but an understanding of how inherent structural features influence the lifetimes of proteins is lacking. We report that yeast, mouse, and human proteins with terminal or internal intrinsically disordered segments have significantly shorter half-lives than proteins without these features. The lengths of the disordered segments that affect protein half-life are compatible with the structure of the proteasome. Divergence in terminal and internal disordered segments in yeast proteins originating from gene duplication leads to significantly altered half-life. Many paralogs that are affected by such changes participate in signaling, where altered protein half-life will directly impact cellular processes and function. Thus, natural variation in the length and position of disordered segments may affect protein half-life and could serve as an underappreciated source of genetic variation with important phenotypic consequences.

Sensors for the reliable measurement of nitrogen dioxide concentrations are of high interest due the adverse health effects of this pollutant. This work employs photothermal spectroscopy to measure nitrogen dioxide concentrations at the parts per billion level. Absorption induced temperature changes are detected by means of a fiber-coupled Fabry−Pérot interferometer. The small size of the interferometer enables small detection volumes, paving the way for miniaturized sensing concepts as well as fast response times, demonstrated down to 3 s. A normalized noise equivalent absorption of 7.5 × 10 − 8 cm−1W/ Hz is achieved. Additionally, due to the rigid structure of the interferometer, the sensitivity to mechanical vibrations is shown to be minor.

Background: The impact of neoadjuvant chemotherapy (NACT) on surgical outcomes following immediate breast reconstruction (IBR) remains unclear. While it is generally considered safe practice to perform an IBR post NACT, reported complication rates in published data are highly variable with the majority of studies including fewer than 50 patients in the NACT and IBR arm. To evaluate this further, we conducted a systematic review and meta-analysis on the effect of NACT on autologous and implant based immediate breast reconstructions. We aimed to assess for differences in the post-operative course following IBR between patients who received NACT with those who did not. Methods: PubMed, EMBASE, and Cochrane Library were searched from 1995 to Sept 2, 2020 to identify articles that assessed the impact of NACT on IBR. All included studies assessed outcomes following IBR. Only studies comparing reconstructed patients receiving NACT to a control group of women who did not receive NACT were included. Unadjusted relative risk of outcomes between patients who received or did not receive NACT were synthesized using a fixed-effect meta-analysis. The evidence was assessed using the Newcastle Ottawa Scale scores and GRADE. Primary effect measures were risk ratios (RRs) with 95% confidence intervals. Results: A total 17 studies comprising 3249 patients were included in the meta-analyses. Overall, NACT did not increase the risk of complications after immediate breast reconstructions (risk ratio [RR]: 0.91, 95% CI 0.74 to 1.11, p = 0.34). There was a moderate, but not significant, increase in flap loss following NACT compared with controls (RR: 1.23, 95% CI 0.70 to 2.18, p = 0.47; I2 = 0%). Most notably, there was a statistically significant increase in implant/expander loss after NACT (RR: 1.54, 95% CI 1.04 to 2.29, p = 0.03; I2 = 34%). NACT was not shown to significantly increase the incidence of hematomas, seromas or wound complications, or result in a significant delay to commencing adjuvant therapy (RR: 1.59, 95% CI 0.66 to 3.87, p = 0.30). Conclusion: Immediate breast reconstruction after NACT is a safe procedure with an acceptable post-operative complication profile. It may result in a slight increase in implant loss rates, but it does not delay commencing adjuvant therapy.

Introduction Noma is a significant yet neglected disease which affects some of the least developed countries in the world. The long-term benefit and safety of Noma surgical reconstructive missions have recently been under scrutiny due to a perceived lack of measurable outcomes and appropriate follow-up. This study analyses and reports on classifications, outcome measurement tools and follow-up for reconstructive surgery after Noma disease.Methods This systematic review was undertaken following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The three medical databases Medline, EMBASE and Web of Sciences were searched, articles published between 1 January 1983 and 15 April 2020 were included. All primary evidence on reconstructive surgery following Noma disease, reporting data on outcome after surgery, follow-up time and complications were included. Extracted data were aggregated to generate overall and population corrected mean outcomes and complication rates.Results Out of 1393 identified records, 31 studies including 1110 Noma patients were analysed. NOITULP and Montandon/WHO were the most commonly used classification systems. Mouth opening (MO) and complication rates were the two most often reported outcomes. Overall mean complication rate was 44%, reported by 24 studies. Postoperative MO was reported by eight publications, of which, five reported long-term outcomes (>12 months). Mean MO improved by 20 mm when compared with mean population weighted preoperative MO (7 mm). At long-term follow-up, MO decreased to 20 mm.Conclusions Studies reporting on neglected diseases in developing countries often lack methodological rigour. Surgeons should be mindful during patient examination by using a classification system that allows to compare preoperative versus postoperative state of disease. Short-term mission surgery is a vital part of healthcare delivery to underdeveloped and poor regions. Future missions should aim at sustainable partnerships with local healthcare providers to ensure postoperative care and long-term patient-oriented follow-up. A shift towards a diagonal treatment delivery approach, whereby local surgeons and healthcare staff are educated and empowered, should be actively promoted.PROSPERO registration number CRD42020181931.

Immunotherapy targeting the CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint axis has emerged as a promising treatment strategy for various cancers. Experimental evidence suggests that phosphatidylinositol-4,5-bisphosphonate 3-kinase (PI3K) signaling may upregulate CD274 expression. Thus, we hypothesized that PIK3CA mutation, PTEN loss, or their combined status might be associated with CD274 overexpression in colorectal carcinoma. We assessed tumor CD274 and PTEN expression by immunohistochemistry and assessed PIK3CA mutation by pyrosequencing in 753 patients among 4,465 incident rectal and colon cancer cases that had occurred in two U.S.-wide prospective cohort studies. To adjust for potential confounders and selection bias due to tissue availability, inverse probability weighted multivariable ordinal logistic regression analyses used the 4,465 cases and tumoral data including microsatellite instability, CpG island methylator phenotype, KRAS and BRAF mutations. PIK3CA mutation and loss of PTEN expression were detected in 111 of 753 cases (15%) and 342 of 585 cases (58%), respectively. Tumor CD274 expression was negative in 306 (41%), low in 195 (26%), and high in 252 (33%) of 753 cases. PTEN loss was associated with CD274 overexpression [multivariable odds ratio (OR) 1.83; 95% confidence interval (CI), 1.22–2.75; P = .004]. PIK3CA mutation was statistically-insignificantly (P = .036 with the stringent alpha level of 0.005) associated with CD274 overexpression (multivariable OR, 1.54; 95% CI, 1.03–2.31). PIK3CA-mutated PTEN-lost tumors (n = 33) showed higher prevalence of CD274-positivity (82%) than PIK3CA-wild-type PTEN-lost tumors (n = 204; 70% CD274-positivity) and PTEN-expressed tumors (n = 147; 50% CD274-positivity) (P = .003). Our findings support the role of PI3K signaling in the CD274/PDCD1 pathway.

Urban, peri-urban forests and other natural areas provide a wide range of material and non-material benefits to people known as ecosystem services. Access to these areas has been linked to benefits for physical and mental health of local populations. In the spring of 2020, the COVID-19 global pandemic forced many governments to impose a set of restrictions including the closure of businesses, cancelation of public events and schooling, social distancing, limitations on the size of social gatherings, and travel restrictions. During this period of restrictions, we conducted a study assessing the importance of urban and peri-urban forests and other natural areas to people living in and around the city of Burlington, Vermont, USA. We evaluated the self-reported use and changes in personal importance related to these natural areas before and during the period of restrictions. We received over 400 responses to our field survey. The results show that 69.0% of the respondents had increased or greatly increased their visitation rate to our natural areas and urban forests, and 80.6% of respondents considered that the importance of these areas, and access to them, either increased or greatly increased. Moreover 25.8% of the sample had either never, or very rarely accessed their local natural areas before the pandemic, but 69.2% of the first time or infrequent visitors reported that having access to these areas during COVID-19 as 'very important'. People reported that these areas were important for a wide range of activities from exercise to birding, but also reported values related to reducing stress in a time of global chaos. Our results indicate the increasing demand and value of such areas in times of crisis such as COVID-19. Experts in zoonotic disease predict the potential for more frequent pandemic events, thus predicating the importance for continued funding for, maintenance of, and improved access to, natural areas to our largely urban civilization.

In this work, a secure wireless sensor network (WSN) for the surveillance, monitoring and protection of critical infrastructures was developed. To guarantee the security of the system, the main focus was the implementation of a unique security concept, which includes both security on the communication level, as well as mechanisms that ensure the functional safety during its operation. While there are many theoretical approaches in various subdomains of WSNs—like network structures, communication protocols and security concepts—the construction, implementation and real-life application of these devices is still rare. This work deals with these aforementioned aspects, including all phases from concept-generation to operation of a secure wireless sensor network. While the key focus of this paper lies on the security and safety features of the WSN, the detection, localization and classification capabilities resulting from the interaction of the nodes’ different sensor types are also described.

OBJECTIVES: One of the most referenced theoretical frameworks to measure Health Related Quality of Life (HRQoL) is the Wilson and Cleary framework. With some adaptions this framework has been validated in the adult population, but has not been tested in pediatric populations. Our goal was to empirically investigate it in children. METHODS: The contributory factors to Health Related Quality of Life that we included were symptom status (presence of chronic disease or hospitalizations), functional status (developmental status), developmental aspects of the individual (social-emotional) behavior, and characteristics of the social environment (socioeconomic status and area of education). Structural equation modeling was used to assess the measurement structure of the model in 214 German children (3-5 years old) participating in a follow-up study that investigates pediatric health outcomes. RESULTS: Model fit was χ2 = 5.5; df = 6; p = 0.48; SRMR = 0.01. The variance explained of Health Related Quality of Life was 15%. Health Related Quality of Life was affected by the area education (i.e. where kindergartens were located) and development status. Developmental status was affected by the area of education, socioeconomic status and individual behavior. Symptoms did not affect the model. CONCLUSIONS: The goodness of fit and the overall variance explained were good. However, the results between children' and adults' tests differed and denote a conceptual gap between adult and children measures. Indeed, there is a lot of variety in pediatric Health Related Quality of Life measures, which represents a lack of a common definition of pediatric Health Related Quality of Life. We recommend that researchers invest time in the development of pediatric Health Related Quality of Life theory and theory based evaluations.

We consider the quantized free massive Dirac field on oriented and globally hyperbolic ultrastatic slab spacetimes with compact spatial section and demonstrate how a gauge invariant, pure and quasifree state on the C*-completion of the self-dual CAR-algebra can be extracted from the fermionic projector construction of Finster and Reintjes. This state is analogous to the ‘SJ-state’ of the free scalar field recently discussed in the literature. We prove that this state generically fails to be Hadamard. However, we also show how a modified version of the construction, inspired by the work of Brum and Fredenhagen, yields states that are Hadamard. We also relate the Hadamard condition to the finiteness of fluctuations of Wick polynomials. [ABSTRACT FROM AUTHOR]