High life satisfaction reported among small-scale societies with low incomes.

Global polls have shown that people in high-income countries generally report being more satisfied with their lives than people in low-income countries. The persistence of this correlation, and its similarity to correlations between income and life satisfaction within countries, could lead to the impression that high levels of life satisfaction can only be achieved in wealthy societies. However, global polls have typically overlooked small-scale, nonindustrialized societies, which can provide an alternative test of the consistency of this relationship. Here, we present results from a survey of 2,966 members of Indigenous Peoples and local communities among 19 globally distributed sites. We find that high average levels of life satisfaction, comparable to those of wealthy countries, are reported for numerous populations that have very low monetary incomes. Our results are consistent with the notion that human societies can support very satisfying lives for their members without necessarily requiring high degrees of monetary wealth.

Repeat expansions nested within tandem CNVs: a unique structural change in GLS exemplifies the diagnostic challenges of non-coding pathogenic variation.

Glutaminase deficiency has recently been associated with ataxia and developmental delay due to repeat expansions in the 5'UTR of the glutaminase (GLS) gene. Patients with the described GLS repeat expansion may indeed remain undiagnosed due to the rarity of this variant, the challenge of its detection and the recency of its discovery. In this study, we combined advanced bioinformatics screening of ~3000 genomes and ~1500 exomes with optical genome mapping and long-read sequencing for confirmation studies. We identified two GLS families, previously intensely and unsuccessfully analyzed. One family carries an unusual and complex structural change involving a homozygous repeat expansion nested within a quadruplication event in the 5'UTR of GLS. Glutaminase deficiency and its metabolic consequences were validated by in-depth biochemical analysis. The identified GLS patients showed progressive early-onset ataxia, cognitive deficits, pyramidal tract damage and optic atrophy, thus demonstrating susceptibility of several specific neuron populations to glutaminase deficiency. This large-scale screening study demonstrates the ability of bioinformatics analysis-validated by latest state-of-the-art technologies (optical genome mapping and long-read sequencing)-to effectively flag complex repeat expansions using short-read datasets and thus facilitate diagnosis of ultra-rare disorders.

Dihydropyrimidine dehydrogenase gene variants for predicting grade 4-5 fluoropyrimidine-induced toxicity: FUSAFE individual patient data meta-analysis.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) deficiency is the main known cause of life-threatening fluoropyrimidine (FP)-induced toxicities. We conducted a meta-analysis on individual patient data to assess the contribution of deleterious DPYD variants *2A/D949V/*13/HapB3 (recommended by EMA) and clinical factors, for predicting G4-5 toxicity. METHODS: Study eligibility criteria included recruitment of Caucasian patients without DPD-based FP-dose adjustment. Main endpoint was 12-week haematological or digestive G4-5 toxicity. The value of DPYD variants *2A/p.D949V/*13 merged, HapB3, and MIR27A rs895819 was evaluated using multivariable logistic models (AUC). RESULTS: Among 25 eligible studies, complete clinical variables and primary endpoint were available in 15 studies (8733 patients). Twelve-week G4-5 toxicity prevalence was 7.3% (641 events). The clinical model included age, sex, body mass index, schedule of FP-administration, concomitant anticancer drugs. Adding *2A/p.D949V/*13 variants (at least one allele, prevalence 2.2%, OR 9.5 [95%CI 6.7-13.5]) significantly improved the model (p < 0.0001). The addition of HapB3 (prevalence 4.0%, 98.6% heterozygous), in spite of significant association with toxicity (OR 1.8 [95%CI 1.2-2.7]), did not improve the model. MIR27A rs895819 was not associated with toxicity, irrespective of DPYD variants. CONCLUSIONS: FUSAFE meta-analysis highlights the major relevance of DPYD *2A/p.D949V/*13 combined with clinical variables to identify patients at risk of very severe FP-related toxicity.

CIAO1 and MMS19 deficiency: A lethal neurodegenerative phenotype caused by cytosolic Fe-S cluster protein assembly disorders.

PURPOSE: The functionality of many cellular proteins depends on cofactors; yet, they have only been implicated in a minority of Mendelian diseases. Here, we describe the first 2 inherited disorders of the cytosolic iron-sulfur protein assembly system. METHODS: Genetic testing via genome sequencing was applied to identify the underlying disease cause in 3 patients with microcephaly, congenital brain malformations, progressive developmental and neurologic impairments, recurrent infections, and a fatal outcome. Studies in patient-derived skin fibroblasts and zebrafish models were performed to investigate the biochemical and cellular consequences. RESULTS: Metabolic analysis showed elevated uracil and thymine levels in body fluids but no pathogenic variants in DPYD, encoding dihydropyrimidine dehydrogenase. Genome sequencing identified compound heterozygosity in 2 patients for missense variants in CIAO1, encoding cytosolic iron-sulfur assembly component 1, and homozygosity for an in-frame 3-nucleotide deletion in MMS19, encoding the MMS19 homolog, cytosolic iron-sulfur assembly component, in the third patient. Profound alterations in the proteome, metabolome, and lipidome were observed in patient-derived fibroblasts. We confirmed the detrimental effect of deficiencies in CIAO1 and MMS19 in zebrafish models. CONCLUSION: A general failure of cytosolic and nuclear iron-sulfur protein maturation caused pleiotropic effects. The critical function of the cytosolic iron-sulfur protein assembly machinery for antiviral host defense may well explain the recurrent severe infections occurring in our patients.

Hereditary Alpha Tryptasemia: Validation of a Single-Well Multiplex Digital Droplet PCR Assay in a Cohort of Symptomatic Patients.

BACKGROUND: Hereditary alpha tryptasemia (HαT) has significant prevalence and potential morbidity in the general population. However, it remains largely undiagnosed in routine clinical diagnostics due to low availability of efficient assessment methods. To address this issue, we developed a reliable and efficient single-well multiplex digital droplet PCR assay. METHODS: The assay was based on the reconstruction of the TPSAB1 gene through quantification of the ratio of α- and ß-tryptase copy number variants (CNV) in a single-well measurement. We performed analytical validation by determining CNV measurement clustering around the expected copy numbers in 281 cases and determined the diagnostic accuracy of basal serum tryptase (BST) to predict HαT and HαT subtypes in 141 symptomatic patients. RESULTS: The assay determined α- and ß-tryptase CNVs with an overall accuracy, expressed as a 99% prediction interval, of 0.03 ± 0.27 copy numbers. The optimal BST cutoff level to predict HαT in symptomatic patients, who had no other explanation for relatively high tryptase levels (i.e., no diagnosis of systemic mastocytosis, myeloid neoplasm, or end-stage renal failure), was 9.2 ng/mL (sensitivity: 98.1%; specificity: 96.6%). HαT showed a linear gene-dose effect, with an average gene-dose increase of 7.5 ng/mL per extra α-tryptase gene. CONCLUSION: Our single-well multiplex digital droplet PCR assay accurately determined HαT and could be implemented as a state-of-the-art routine diagnostic test. The assay demonstrated a strong correlation with BST and the optimal threshold for identifying HαT in symptomatic patients with unexplained high tryptase concentrations was at a BST level of 9.2 ng/mL.

CLOCK gene circannual expression in cluster headache.

BACKGROUND: Cluster headache is a primary headache disorder characterized by bouts with circadian and circannual patterns. The CLOCK gene has a central role in regulating circadian rhythms. Here, we investigate the circannual CLOCK expression in a population of cluster headache patients in comparison to matched controls. METHODS: Patients with cluster headache were sampled two to four times over at least one year, both in or outside bouts, one week after each solstice and equinox. The expression of CLOCK was measured by quantitative real-time polymerase chain reaction (RT-PCR) in the peripheral blood. RESULTS: This study included 50 patients and 58 matched controls. Among the patient population, composed of 42/50 males (84%) with an average age of 44.6 years, 45/50 (90%) suffered from episodic cluster headache. Two to four samples were collected from each patient adding up to 161 samples, 36 (22.3%) of which were collected within a bout. CLOCK expression for cluster headache patients was considerably different from that of the control population in winter (p-value mean = 0.006283), spring (p-value mean = 0.000006) and summer (p-value mean = 0.000064), but not in autumn (p-value mean = 0.262272). For each season transition, the variations in CLOCK expression were more pronounced in the control group than in the cluster headache population. No statistically significant differences were found between bout and non-bout samples. No individual factors (age, sex, circadian chronotype, smoking and coffee habits or history of migraine) were related to CLOCK expression. CONCLUSIONS: We observed that CLOCK expression in cluster headache patients fluctuates less throughout the year than in the control population. Bout activity and lifestyle factors do not seem to influence CLOCK expression.

Analysis of microscopy techniques to measure segregation in continuous-cast steel slabs.

The accurate characterisation of centreline segregation requires precise measurements of composition variations over large length scales (10 - 1 $^{-1}$ m ${\rm {m}}$ ) across the centreline of the cast product, while having high resolution, sufficient to quantify the significant composition variations between dendrites due to microsegregation at very small length scales (10 - 5 m $^{-5}{\rm {m}}$ ). This study investigates the potential of a novel microscopy technique, named Synchrotron Micro X-ray Flurorescence (SMXRF), to generate large-scale high-resolution segregation maps from a steel sample taken from a thin slab caster. Two methods, Point Analysis and Regression Analysis, are proposed for SMXRF data calibration. By comparing with the traditional Laser-Induced Breakdown Spectroscopy (LIBS), and Electron Probe Micro Analyser (EPMA) techniques, we show that SMXRF is successful in quantitative characterisation of centreline segregation. Over large areas (e.g. 12 × $\times$ 16 mm 2 ${\rm {mm}}^2$ ) and at high resolution (10-50 µ m $\mu\text{m}$ pixel size) various techniques yield comparable outcomes in terms of composition maps and solute profiles. The findings also highlight the importance of both high spatial resolution and large field of view to have a quantitative, accurate, and efficient measurement tool to investigate segregation phenomena.

Presence and abundance of malaria vector species in Miami-Dade County, Florida.

BACKGROUND: Malaria outbreaks have sporadically occurred in the United States, with Anopheles quadrimaculatus serving as the primary vector in the eastern region. Anopheles crucians, while considered a competent vector, has not been directly implicated in human transmission. Considering the locally acquired Plasmodium vivax cases in Sarasota County, Florida (7 confirmed cases), Cameron County, Texas (one confirmed case), and Maryland (one confirmed case) in the summer of 2023. The hypothesis of this study is that major cities in the United States harbour sufficient natural populations of Anopheles species vectors of malaria, that overlap with human populations that could support local transmission to humans. The objective of this study is to profile the most abundant Anopheles vector species in Miami-Dade County, Florida-An. crucians and An. quadrimaculatus. METHODS: This study was based on high-resolution mosquito surveillance data from 2020 to 2022 in Miami-Dade County, Florida. Variations on the relative abundance of An. crucians and An. quadrimaculatus was assessed by dividing the total number of mosquitoes collected by each individual trap in 2022 by the number of mosquitoes collected by the same trap in 2020. In order to identify influential traps, the linear distance in meters between all traps in the surveillance system from 2020 to 2022 was calculated and used to create a 4 km buffer radius around each trap in the surveillance system. RESULTS: A total of 36,589 An. crucians and 9943 An. quadrimaculatus were collected during this study by the surveillance system, consisting of 322 CO2-based traps. The findings reveal a highly heterogeneous spatiotemporal distribution of An. crucians and An. quadrimaculatus in Miami-Dade County, highlighting the presence of highly conducive environments in transition zones between natural/rural and urban areas. Anopheles quadrimaculatus, and to a lesser extent An. crucians, pose a considerable risk of malaria transmission during an outbreak, given their high abundance and proximity to humans. CONCLUSIONS: Understanding the factors driving the proliferation, population dynamics, and spatial distribution of Anopheles vector species is vital for implementing effective mosquito control and reducing the risk of malaria outbreaks in the United States.

Plant-based diets benefit aerobic performance and do not compromise strength/power performance: a systematic review and meta-analysis.

Plant-based diets have emerged as athletic performance enhancers for various types of exercise. Therefore, the present study evaluated the effectiveness of plant-based diets on aerobic and strength/power performances, as well as on BMI of physically active individuals. This systematic review and meta-analysis was conducted and reported according to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. A systematic search of electronic databases, including PubMed, Web of Science and SPORTDiscus, was performed. On the basis of the search and inclusion criteria, four and six studies evaluating the effects of plant-based diets on aerobic and strength/power performances in humans were, respectively, included in the systematic review and meta-analysis. Plant-based diets had a moderate but positive effect on aerobic performance (0·55; 95 % CI 0·29, 0·81) and no effect on strength/power performance (-0·30; 95 % CI -0·67, 0·07). The altogether analyses of both aerobic and strength/power exercises revealed that athletic performance was unchanged (0·01; 95 % CI -0·21, 0·22) in athletes who adopted plant-based diets. However, a small negative effect on BMI (-0·27; 95 % CI -0·40, -0·15) was induced by these diets. The results indicate that plant-based diets have the potential to exclusively assist aerobic performance. On the other hand, these diets do not jeopardise strength/power performance. Overall, the predicted effects of plant-based diets on physical performance are impactless, even though the BMI of their adherents is reduced.

Mental Health of School-Aged Children Treated with Propranolol or Atenolol for Infantile Hemangioma and Their Parents.

BACKGROUND: Infants with infantile hemangioma (IH) have been effectively treated with propranolol or atenolol. Concerns were raised about the mental health of these children at school age, due to central nervous system effects of propranolol and visible nature of IH. OBJECTIVE: This study aimed to compare the mental health at school age of children treated with propranolol to children treated with atenolol for IHs and their parents. METHODS: This two-centered cross-sectional study included children aged ≥6 years and treated with either propranolol or atenolol for IH during infancy. Children's outcomes were performance-based affect recognition (Dutch version of the Developmental Neuropsychological Assessment-II [NEPSY-II-NL]), parent-reported emotional and behavioral functioning (Child Behavioral Checklist [CBCL]), and health-related quality of life (KIDSCREEN-27). Parents' outcome was parenting stress (Parenting Stress Questionnaire [OBVL]). RESULTS: Data of 105 children (36 propranolol, 69 atenolol; 6.0-11.8 years) were analyzed. Mental health outcomes did not differ between both ß-blocker groups. Although overall functioning was in line with norms, children presented specific problems concerning affect recognition, parent-reported attention, and social quality of life. Parents showed increased physical symptoms, depressive symptoms, and parent-child relationship problems. CONCLUSION: No difference in mental health at school age was found between children treated with propranolol or atenolol for IH. Although few overall mental health problems were found, specific problems require follow-up. Follow-up of children should be directed toward affect recognition, attention, and social functioning in daily life. Problems reported by parents could be ameliorated by mental health support during and after their infant's ß-blocker treatment.

Minimally invasive surgical approach in children treated for oesophageal atresia is associated with attention problems at school age: a prospective cohort study.

The long-term neurodevelopment of children born with oesophageal atresia (OA) is unclear. Therefore, we assessed the neurocognitive domains and their predictors. Patients born with OA between February 2006 and December 2014, who were routinely seen at eight years as part of a structured prospective longitudinal follow-up program, were included. Main outcome measures were need for school support, performance in various neurocognitive domains and potential predictors of neurocognitive problems. We analysed data of 65 children with a mean (SD) age of 8.1 (0.2) years, of whom 89% with OA type C. Thirty-five (54%) surgical corrections were minimally invasive; the median (interquartile range) duration of exposure to anaesthetics in the first 24 months was 398 (296 - 710) minutes. Forty-four (68%) attended regular education without extra support and intelligence was within normal range (99-108). More than 50% had z-scores ≤ -2 on one or more neurocognitive domains, of which attention was the most frequently affected domain. The speed on the sustained attention task was significantly below normal (z-score -1.48 (2.12), p < .001), as was fluctuation of sustained attention (z-score -3.19 (3.80), p < .001). The minimally invasive approach and a lower socio-economic status (both p = 0.006) proved significant predictors for sustained attention problems in multivariable analyses.  Conclusion: Children who undergo minimally invasive surgery for OA correction are at risk for sustained attention problems at school age. Future studies unravelling the effects of perioperative events on neurodevelopment should lead to optimal surgical, anaesthesiological, and intensive care management in the neonatal period. What is Known: • School-aged children born with oesophageal atresia have normal intelligence but problems with sustained attention at eight years. What is New: • Oesophageal atresia patients, who undergo minimally invasive surgery or who have a background of lower socioeconomic status are at serious risk for sustained attention problems at school age. • Moreover, those who have been intubated for a longer period are at risk for stronger fluctuations in sustained attention.

Paternal morphine exposure in rats reduces social play in adolescent male progeny without affecting drug-taking behavior in juvenile males or female offspring.

The ongoing opioid addiction crisis necessitates the identification of novel risk factors to improve prevention and treatment of opioid use disorder. Parental opioid exposure has recently emerged as a potential regulator of offspring vulnerability to opioid misuse, in addition to heritable genetic liability. An understudied aspect of this "missing heritability" is the developmental presentation of these cross-generational phenotypes. This is an especially relevant question in the context of inherited addiction-related phenotypes, given the prominent role of developmental processes in the etiology of psychiatric disorders. Paternal morphine self-administration was previously shown to alter the sensitivity to the reinforcing and antinociceptive properties of opioids in the next generation. Here, phenotyping was expanded to include the adolescent period, with a focus on endophenotypes related to opioid use disorders and pain. Paternal morphine exposure did not alter heroin or cocaine self-administration in male and female juvenile progeny. Further, baseline sensory reflexes related to pain were unaltered in morphine-sired adolescent rats of either sex. However, morphine-sired adolescent males exhibited a reduction in social play behavior. Our findings suggest that, in morphine-sired male offspring, paternal opioid exposure does not affect opioid intake during adolescence, suggesting that this phenotype does not emerge until later in life. Altered social behaviors in male morphine-sired adolescents indicate that the changes in drug-taking behavior in adults sired by morphine-exposed sires may be due to more complex factors not yet fully assessed.

Bone-marrow mononuclear cells and acellular human amniotic membrane improve global cardiac function without inhibition of the NLRP3 Inflammasome in a rat model of heart failure.

Recent studies have suggested that therapies with stem cells and amniotic membrane can modulate the inflammation following an ischemic injury in the heart. This study evaluated the effects of bone-marrow mononuclear cells (BMMC) and acellular human amniotic membrane (AHAM) on cardiac function and NLRP3 complex in a rat model of heart failure.On the 30th day,the echocardiographic showed improvements on ejection fraction and decreased pathological ventricular remodeling on BMMC and AHAM groups.Oxidative stress analysis was similar between the three groups,and the NLRP3 inflammasome activity were not decreased with the therapeutic use of both BMMC and AHAM,in comparison to the control group.

Characterization of the vocal behavior of the miniature and transparent fish model, Danionella cerebruma).

Danionella cerebrum has recently been proposed as a promising model to investigate the structure and function of the adult vertebrate brain, including the development of vocal-auditory neural pathways. This genetically tractable and transparent cypriniform is highly vocal, but limited information is available on its acoustic behavior and underlying biological function. Our main goal was to characterize the acoustic repertoire and diel variation in sound production of D. cerebrum, as well as to investigate the relationship between vocal behavior and reproduction. Sound recordings demonstrated high vocal activity, with sounds varying from short sequences of pulses known as "bursts" (comprising up to 15 pulses) to notably longer sounds, termed "long bursts", which extended up to 349 pulses with over 2.7 s. Vocal activity peaked at midday and it was very low at night with only a few bursts. While the number of pulses was higher during the daytime, the interpulse interval was longer at night. In addition, calling time was positively associated with the number of viable eggs, suggesting that acoustic communication is important for reproduction. These preliminary findings reveal the potential of using D. cerebrum to investigate vocal plasticity and the implications for sexual selection and reproduction in a novel vertebrate model for neuroscience.

Comparing Video Analysis to Computerized Detection of Limb Position for the Diagnosis of Movement Control during Back Squat Exercise with Overload.

Incorrect limb position while lifting heavy weights might compromise athlete success during weightlifting performance, similar to the way that it increases the risk of muscle injuries during resistance exercises, regardless of the individual's level of experience. However, practitioners might not have the necessary background knowledge for self-supervision of limb position and adjustment of the lifting position when improper movement occurs. Therefore, the computerized analysis of movement patterns might assist people in detecting changes in limb position during exercises with different loads or enhance the analysis of an observer with expertise in weightlifting exercises. In this study, hidden Markov models (HMMs) were employed to automate the detection of joint position and barbell trajectory during back squat exercises. Ten volunteers performed three lift movements each with a 0, 50, and 75% load based on body weight. A smartphone was used to record the movements in the sagittal plane, providing information for the analysis of variance and identifying significant position changes by video analysis (p < 0.05). Data from individuals performing the same movements with no added weight load were used to train the HMMs to identify changes in the pattern. A comparison of HMMs and human experts revealed between 40% and 90% agreement, indicating the reliability of HMMs for identifying changes in the control of movements with added weight load. In addition, the results highlighted that HMMs can detect changes imperceptible to the human visual analysis.

Development of a Smart Wireless Multisensor Platform for an Optogenetic Brain Implant.

Implantable cell replacement therapies promise to completely restore the function of neural structures, possibly changing how we currently perceive the onset of neurodegenerative diseases. One of the major clinical hurdles for the routine implementation of stem cell therapies is poor cell retention and survival, demanding the need to better understand these mechanisms while providing precise and scalable approaches to monitor these cell-based therapies in both pre-clinical and clinical scenarios. This poses significant multidisciplinary challenges regarding planning, defining the methodology and requirements, prototyping and different stages of testing. Aiming toward an optogenetic neural stem cell implant controlled by a smart wireless electronic frontend, we show how an iterative development methodology coupled with a modular design philosophy can mitigate some of these challenges. In this study, we present a miniaturized, wireless-controlled, modular multisensor platform with fully interfaced electronics featuring three different modules: an impedance analyzer, a potentiostat and an optical stimulator. We show the application of the platform for electrical impedance spectroscopy-based cell monitoring, optical stimulation to induce dopamine release from optogenetically modified neurons and a potentiostat for cyclic voltammetry and amperometric detection of dopamine release. The multisensor platform is designed to be used as an opto-electric headstage for future in vivo animal experiments.

Understanding the impact of tuberous sclerosis complex: development and validation of the TSC-PROM.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare and complex genetic disorder, associated with tumor growth in various organ systems, epilepsy, and a range of neuropsychiatric manifestations including intellectual disability. With improving patient-centered care and targeted therapies, patient-reported outcome measures (PROMs) are needed to measure the impact of TSC manifestations on daily functioning. The aim of this study was to develop a TSC-specific PROM for adults that captures the impact of TSC on physical functions, mental functions, activity and participation, and the social support individuals with TSC receive, called the TSC-PROM. METHODS: COSMIN methodology was used to develop a self-reported and proxy-reported version. Development and validation consisted of the following studies: PROM development, content validity, structural validity, internal consistency, and construct validity. The International Classification of Functioning and Disability was used as a framework. Content validity was examined by a multidisciplinary expert group and cognitive interview study. Structural and construct validity, and internal consistency were examined in a large cohort, using confirmatory factor analysis, hypotheses testing, and Cronbach's alpha. RESULTS: The study resulted in an 82-item self version and 75-item proxy version of the TSC-PROM with four subscales (physical functions 18 and 19 items, mental functions 37 and 28 items, activities and participation 13 and 14 items, social support 13 items, for self version and proxy version respectively). Sufficient results were found for structural validity with sufficient unidimensionality for each subscale. With regard to construct validity, 82% of the hypotheses were met for the self version and 59% for the proxy version. The PROM showed good internal consistency (Cronbach's alpha 0.78-0.97). CONCLUSIONS: We developed a PROM for adults with TSC, named TSC-PROM, showing sufficient evidence for reliability and validity that can be used in clinical and research settings to systematically gain insight into their experiences. It is the first PROM in TSC that addresses the impact of specific TSC manifestations on functioning, providing a valuable, patient-centered addition to the current clinical outcomes.

Landscape-scale forest cover drives the predictability of forest regeneration across the Neotropics.

Abandonment of agricultural lands promotes the global expansion of secondary forests, which are critical for preserving biodiversity and ecosystem functions and services. Such roles largely depend, however, on two essential successional attributes, trajectory and recovery rate, which are expected to depend on landscape-scale forest cover in nonlinear ways. Using a multi-scale approach and a large vegetation dataset (843 plots, 3511 tree species) from 22 secondary forest chronosequences distributed across the Neotropics, we show that successional trajectories of woody plant species richness, stem density and basal area are less predictable in landscapes (4 km radius) with intermediate (40-60%) forest cover than in landscapes with high (greater than 60%) forest cover. This supports theory suggesting that high spatial and environmental heterogeneity in intermediately deforested landscapes can increase the variation of key ecological factors for forest recovery (e.g. seed dispersal and seedling recruitment), increasing the uncertainty of successional trajectories. Regarding the recovery rate, only species richness is positively related to forest cover in relatively small (1 km radius) landscapes. These findings highlight the importance of using a spatially explicit landscape approach in restoration initiatives and suggest that these initiatives can be more effective in more forested landscapes, especially if implemented across spatial extents of 1-4 km radius.

Organocatalyzed Visible Light-Mediated gem-Borosilylcyclopropanation.

The borosilylcyclopropanation of styrene derivatives using a (diiodo(trimethylsilyl)methyl)boronic ester carbene precursor is reported herein. The key reagent was synthesized in a 4-step sequence using inexpensive and commercially available starting materials. This method enabled the preparation of novel 1,1,2-tri- and 1,1,2,2-tetrasubstituted borosilylcyclopropanes up to excellent yields and diastereoselectivity. The reaction is organocatalyzed by eosin Y in the presence of visible light. A mechanism consistent with the experimental observations was postulated based on density functional theory calculations. The versatility of these entities was highlighted through post-functionalization reactions.

Optimising urinary catecholamine metabolite diagnostics for neuroblastoma.

INTRODUCTION: The analysis of urinary catecholamine metabolites is a cornerstone of neuroblastoma diagnostics. Currently, there is no consensus regarding the sampling method, and variable combinations of catecholamine metabolites are being used. We investigated if spot urine samples can be reliably used for analysis of a panel of catecholamine metabolites for the diagnosis of neuroblastoma. METHODS: Twenty-four-hour urine or spot urine samples were collected from patients with and without neuroblastoma at diagnosis. Homovanillic acid (HVA), vanillylmandelic acid (VMA), dopamine, 3-methoxytyramine, norepinephrine, normetanephrine, epinephrine and metanephrine were measured by high-performance liquid chromatography coupled with fluorescence detection (HPLC-FD) and/or ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC-MS/MS). RESULTS: Catecholamine metabolite levels were measured in urine samples of 400 neuroblastoma patients (24-hour urine, n = 234; spot urine, n = 166) and 571 controls (all spot urine). Excretion levels of catecholamine metabolites and the diagnostic sensitivity for each metabolite were similar in 24-hour urine and spot urine samples (p > .08 and >.27 for all metabolites). The area under the receiver-operating-characteristic curve (AUC) of the panel containing all eight catecholamine metabolites was significantly higher compared to that of only HVA and VMA (AUC = 0.952 vs. 0.920, p = .02). No differences were observed in metabolite levels between the two analysis methods. CONCLUSION: Catecholamine metabolites in spot urine and 24-hour urine resulted in similar diagnostic sensitivities. The Catecholamine Working Group recommends the implementation of spot urine as standard of care. The panel of eight catecholamine metabolites has superior diagnostic accuracy over VMA and HVA.