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The U2AF1 gene is a core part of mRNA splicing machinery and frequently contains somatic mutations that contribute to oncogenesis in myelodysplastic syndrome, acute myeloid leukemia, and other cancers. A change introduced in the GRCh38 version of the human reference build prevents detection of mutations in this gene, and others, by variant calling pipelines. This study describes the problem in detail and shows that a modified GRCh38 reference build with unchanged coordinates can be used to ameliorate the issue.

Anxiety disorders are among the most common psychiatric disorders in children and adolescents. As reviewed in this guideline, both cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitor (SSRI) medication have considerable empirical support as safe and effective short-term treatments for anxiety in children and adolescents. Serotonin norepinephrine reuptake inhibitor (SNRI) medication has some empirical support as an additional treatment option. In the context of a protracted severe shortage of child and adolescent-trained behavioral health specialists, research demonstrating convenient, efficient, cost-effective, and user-friendly delivery mechanisms for safe and effective treatments for child and adolescent anxiety disorders is an urgent priority. The comparative effectiveness of anxiety treatments, delineation of mediators and moderators of effective anxiety treatments, long-term effects of SSRI and SNRI use in children and adolescents, and additional evaluation of the degree of suicide risk associated with SSRIs and SNRIs remain other key research needs.

Intellectual disability (intellectual developmental disorder) (ID/IDD) is both a psychiatric disorder and a risk factor for co-occurring psychiatric disorders in children and adolescents. DSM-5 introduced important changes in the conceptualization and diagnosis of ID/IDD, and current research studies clarify assessment and treatment of co-occurring psychiatric disorders in this population. Optimal assessment and treatment of psychiatric illness in children and adolescents with ID/IDD includes modifications in diagnostic and treatment techniques, appreciation of variations in the clinical presentation of psychiatric disorders, an understanding of the spectrum of etiologies of behavioral disturbance, and knowledge of psychosocial and medical interventions.

Subduction of oceanic lithosphere transports surface H2O into the mantle. Recent studies show that dense SiO2 in the form of stishovite, an abundant mineral in subducted oceanic crust at depths greater than ∼270 km, has the potential to host and transport a considerable amount of H2O into the lower mantle, but the H2O storage capacity of SiO2 phases at high pressure and temperature remains uncertain. We investigate the hydration of stishovite and its higher-pressure polymorphs, β-stishovite and seifertite, with in situ X-ray diffraction experiments at high pressures and temperatures. The H2O contents in SiO2 phases are quantified based on observed increases in unit cell volume relative to the anhydrous SiO2 system. Density functional theory (DFT) computations permit calibration of water content as a function of volume change based on interstitial substitution of H2O. Regression of our experimental data indicates an H2O storage capacity in stishovite of ∼3.5 wt% in the transition zone and shallow lower mantle, decreasing to about 0.8 wt% at the base of the mantle. We find that SiO2-bearing subducted oceanic crust can accommodate all the H2O in slab lithosphere that survives sub-arc dehydration. Hydration of silica phases in subducted oceanic crust and their unparalleled capacity to host significant amounts of H2O even at high mantle temperatures provides a unique mechanism for transport and storage of water in the deepest mantle.

Velocity and density jumps across the 410-km seismic discontinuity generally indicate olivine contents of ∼30 to 50 vol.% on the basis of the elastic properties of anhydrous olivine and wadsleyite, which is considerably less than the ∼60% olivine in the widely accepted pyrolite model for the upper mantle. A possible explanation for this discrepancy is that water dissolved in olivine and wadsleyite affects their elastic properties in ways that can reconcile the pyrolitic model with seismic observations. In order to more fully constrain the olivine content of the upper mantle near the 410-km discontinuity, and to place constraints on the mantle water content at this depth, we determined the full elasticity of hydrous wadsleyite at the P-T conditions of the discontinuity based on density functional theory calculations. Together with previous determinations for the effect of water on olivine elasticity, we simultaneously modeled the density and seismic velocity jumps (Δρ, Δ V P , Δ V S ) across the olivine-wadsleyite transition. Our models allow for several scenarios that can well reproduce the density and seismic velocity jumps across the 410-km discontinuity when compared to globally averaged seismic models. When the water content of olivine and wadsleyite is assumed to be equal as in a simple binary system, our modeling indicates a best fit for low water contents (

Retroperitoneal sarcomas (RPS) are rare mesenchymal tumours. Their rarity challenges our ability to understand expected outcomes. The aim of this systematic review was to examine 30-day morbidity and mortality, overall survival rates and prognostic predictors from population-based studies for patients undergoing curative resection for primary RPS. A systematic literature review of EMBASE, MEDLINE, PUBMED and the Cochrane library was performed using PRISMA for population-based studies reporting from nationally registered databases on primary RPS surgical resections in adults. The main outcomes evaluated were 30-day morbidity and mortality and overall survival rates. The use of additional treatment modalities and predictors of overall survival were also examined. Fourteen studies (n = 12 834 patients) reporting from 3 national databases, (Surveillance, Epidemiology and End Results (SEER), the United States National Cancer Database (US NCDB) and the American College of Surgeons’ National Surgical Quality Improvement Program (ACS NSQIP)) were analysed. The reported overall 30-day morbidity and mortality were 23% (n = 191/846) and 3% (n = 278/10 181) respectively. Reported use of perioperative radiotherapy was 28%. No study reported loco-regional recurrence rates. Overall reported 5-year survival ranged from 52% to 62%. Independent predictors of overall survival were age of the patient, resection margin, tumour grade and size, histological subtype and receipt of radiotherapy. This review of population-based data demonstrated relatively low 30-day morbidity rates in patients undergoing curative surgical resections for primary RPS. Thirty-day mortality rates were similar to other abdominal tumour groups. There remains a paucity of data reporting recurrence rates, however 5-year survival rates ranged from 52 to 62%.

Readiness to change (RTC) indicates an individual's recognition of a problem as well as confidence in their ability to change (Gaume, Bertholet, & Daeppen, 2016), and is hypothesized to play an important role in therapeutic processes aimed at changing offending behaviors (Polaschek & Ross, 2010). However, prior research has generally failed to consider RTC among severe offender subgroups ( Hodge & Renwick, 2002 ; Howells & Day, 2007) such as those with psychopathic personality features whom have often been characterized as resistant to treatment (Harris & Rice, 2006; Salekin, 2002). In the current sample of formerly incarcerated persons (N = 70), we explore the relationship between psychopathic personality traits, as measured by the Triarchic Psychopathy Measure (TriPM; Patrick, 2010), and the unique components of RTC, as measured by an originally constructed assessment called the Change Readiness Scale (CRS). Each item of the CRS has been empirically supported and combined to form five subscales of change readiness (recognition, action, social bonds, human agency, and self-efficacy). Results show unique associations between the subscales of the TriPM and aspects of the RTC construct, yielding it necessary to further explore these relationships to better understand how these factors may contribute to treatment and justice system outcomes.

We report on laser-heated diamond anvil cell (LHDAC) experiments in the FeO–MgO–SiO2–CO2 (FMSC) and CaO–MgO–SiO2–CO2 (CMSC) systems at lower mantle pressures designed to test for decarbonation and diamond forming reactions. Sub-solidus phase relations based on synthesis experiments are reported in the pressure range of ∼35 to 90 GPa at temperatures of ∼1600 to 2200 K. Ternary bulk compositions comprised of mixtures of carbonate and silica are constructed such that decarbonation reactions produce non-ternary phases (e.g. bridgmanite, Ca-perovskite, diamond, CO2–V), and synchrotron X-ray diffraction and micro-Raman spectroscopy are used to identify the appearance of reaction products. We find that carbonate phases in these two systems react with silica to form bridgmanite ±Ca-perovskite + CO2 at pressures in the range of ∼40 to 70 GPa and 1600 to 1900 K in decarbonation reactions with negative Clapeyron slopes. Our results show that decarbonation reactions form an impenetrable barrier to subduction of carbonate in oceanic crust to depths in the mantle greater than ∼1500 km. We also identify carbonate and CO2–V dissociation reactions that form diamond plus oxygen. On the basis of the observed decarbonation reactions we predict that the ultimate fate of carbonate in oceanic crust subducted into the deep lower mantle is in the form of refractory diamond in the deepest lower mantle along a slab geotherm and throughout the lower mantle along a mantle geotherm. Diamond produced in oceanic crust by subsolidus decarbonation is refractory and immobile and can be stored at the base of the mantle over long timescales, potentially returning to the surface in OIB magmas associated with deep mantle plumes.

Previous work has shown that Mo isotopes measurably fractionate between metal and silicate liquids, even at temperatures appropriate for core formation. However, the effect of variations in the structural environment of Mo in the silicate liquid, especially as a function of valence state, on Mo isotope fractionation remained poorly explored. We have investigated the role of valence state in metal-silicate experiments in a gas-controlled furnace at 1400 °C and at oxygen fugacities between 10−12.7 and 10–9.9, i.e. between three and 0.2 log units below the iron-wüstite buffer. Two sets of experiments were performed, both with a silicate liquid in the CaO-Al2O3-SiO2 system. One set used molybdenum metal wire loops as the metal source, the other liquid gold alloyed with 2.5 wt% Mo contained in silica glass tubes. X-ray absorption near-edge spectroscopy analysis indicates that Mo6+/ΣMo in the silicate glasses varies between 0.24 and 0.77 at oxygen fugacities of 10–12.0 and 10–9.9 in the wire loop experiments and between 0.15 and 0.48 at 10–11.4 and 10–9.9 in the experiments with Au-Mo alloys. Double-spiked analysis of Mo isotope compositions furthermore shows that Mo isotope fractionation between metal and silicate is a linear function of Mo6+/ΣMo in the silicate glasses, with a difference of 0.51‰ in 98Mo/95Mo between purely Mo4+-bearing and purely Mo6+-bearing silicate liquid. The former is octahedrally and the latter tetrahedrally coordinated. Our study implies that previous experimental work contained a mixture of Mo4+ and Mo6+ species in the silicate liquid. Our refined parameterisation for Mo isotope fractionation between metal and silicate can be described as Δ98/95Mometal–silicate=[Formula presented] Molybdenum isotope ratios therefore have potential as a proxy to constrain the oxygen fugacity during core formation on planetary bodies if the parameterisation of Mo6+/ΣMo variation with oxygen fugacity is expanded, for instance to include iron-bearing systems. On Earth literature data indicate that the upper mantle is depleted in heavy Mo isotopes relative to the bulk Earth, as represented by chondrites. As previously highlighted, this difference is most likely not caused by core formation, which either enriches the mantle in heavy Mo isotopes or causes no significant fractionation, depending on temperature and, as we determined here, Mo6+ content. We reaffirm that core formation does not account for the Mo isotope composition of the modern upper mantle, which may instead reflect the effect of fractionation during subduction as part of global plate recycling.

We report ab initio atomistic simulations of hydrous silicate melts under deep upper mantle to shallow lower mantle conditions and use them to parameterise density and viscosity across the ternary system MgO-SiO2-H2O (MSH). On the basis of phase relations in the MSH system, primary hydrous partial melts of the mantle have 40-50 mol% H2O. Our results show that these melts will be positively buoyant at the upper and lower boundaries of the mantle transition zone except in very iron-rich compositions, where ≳ 75% Mg is substituted by Fe. Hydrous partial melts will also be highly inviscid. Our results indicate that if melting occurs when wadsleyite transforms to olivine at 410 km, melts will be buoyant and ponding of melts is unexpected. Box models of mantle circulation incorporating the upward mobility of partial melts above and below the transition zone suggest that the upper mantle becomes efficiently hydrated at the expense of the transition zone such that large differences in H2O concentration between the upper mantle, transition zone and lower mantle are difficult to maintain on timescales of mantle recycling. The MORB source mantle with ∼0.02-0.04 wt% H2O may be indicative of the H2O content of the transition zone and lower mantle, resulting in a bulk mantle H2O content of the order 0.5 to 1 ocean mass, which is consistent with geochemical constraints and estimates of subduction ingassing.

Organic−inorganic hybrid perovskites have created significant opportunities for low-cost and high-performance solar cells. The electron transporting layer (ETL) is one of the main components of the solar cell, which selectively transports electrons and at the same time acts as a barrier for holes. This paper focuses on the ETL composed of titanium dioxide deposited by sol-gel method. In particular, perovskite solar cells with ETL from aged titanium sol revealed significant differences of short circuit current which is 8% higher than their counterpart with ETL from fresh sol. Analysis of ETL morphology by atomic force microscopy combined with electrochemical impedance spectroscopy and optical properties measurements enabled to determine the source of this diversity. Additionally, the role of roughness of transparent electrode was indicated. The in-depth material analysis revealed some disadvantages of the ETL material, originally considered as supporting higher photovoltaic performance. The results indicated several problems associated with hardly controlled aging conditions, defects and presence of residual water, strongly advocate for TiO2 ETL form the fresh sol, which after optimization can guarantee the same good solar cell performance.

Inland salt meadows are particularly valuable ecosystems, because they support a variety of salt-adapted species (halophytes). They can be found throughout Europe; including the peatlands of the glacial lowlands in northeast Germany. These German ecosystems have been seriously damaged through drainage. To assess and ultimately limit the damages, temporal monitoring of soil salinity is essential, which can be conducted by geoelectrical techniques that measure the soil electrical conductivity. However, there is limited knowledge on how to interpret electrical conductivity surveys of peaty salt meadows. In this study, temporal and spatial monitoring of dissolved salts was conducted in saline peatland soils using different geoelectrical techniques at different scales (1D: conductivity probe, 2D: conductivity cross-sections). Cores and soil samples were taken to validate the geoelectrical surveys. Although the influence of peat on bulk conductivity is large, the seasonal dynamics of dissolved salts within the soil profile could be monitored by repeated geoelectrical measurements. A close correlation is observed between conductivity (~ salinity) at different depths and temperature, precipitation and corresponding groundwater level. The conductivity distribution between top- and subsoil during the growing season reflected the leaching of dissolved salts by precipitation and the capillary rise of dissolved salts by increasing temperature (~ evaporation). Groundwater levels below 0.38 cm resulted in very low conductivities in the topsoil, which is presumably due to limited soil moisture and thus precipitation of salts. Therefore, to prevent the disappearance of dissolved salts from the rooting zone, which are essential for the halophytes, groundwater levels should be adjusted to maintain depths of between 20 and 35 cm. Lower groundwater levels will lead to the loss of dissolved salts from the rooting zone and higher levels to increasing dilution with fresh rainwater. The easy-to-handle conductivity probe is an appropriate tool for salinity monitoring. Using this probe with regressions adjusted for sandy and organic substrates (peat and organic gyttja) additional influences on bulk conductivity (e.g. cation exchange capacity, water content) can be compensated for and the correlation between salinity and electrical conductivity is high.

Geophysical and geochemical evidence suggests that Earth's core is predominantly made of iron (or iron-nickel alloy) with several percent of light elements. However, Earth's solid inner core transmits shear waves at a much lower velocity than expected from mineralogical models that are consistent with geochemical constraints. Here we investigate the effect of hydrogen on the elastic properties of iron and iron-silicon alloys using ab initio molecular dynamic simulations. We find that these H-bearing alloys maintain a superionic state under inner-core conditions and that their shear moduli exhibit a strong shear softening due to the superionic effect, with a corresponding reduction in V S . Several hcp-iron-silicon-hydrogen compositions can explain the observed density, V P , V S , and Poisson's ratio of the inner core simultaneously. Our results indicate that hydrogen is a significant component of the Earth's core, and that it may contain at least four ocean masses of water. This indicates that the Earth may have accreted wet and obtained its water from chondritic and/or nebular materials before or during core formation.

SUMMARY Somatic mutations in spliceosome genes are found in ~50% of patients with myelodysplastic syndromes (MDS), a myeloid malignancy associated with low blood counts. Expression of the mutant splicing factor U2AF1(S34F) alters hematopoiesis and mRNA splicing in mice. Our understanding of the functionally relevant alternatively spliced target genes that cause hematopoietic phenotypes in vivo remains incomplete. Here, we demonstrate that reduced expression of H2afy1.1, an alternatively spliced isoform of the histone H2A variant gene H2afy, is responsible for reduced B cells in U2AF1(S34F) mice. Deletion of H2afy or expression of U2AF1(S34F) reduces expression of Ebf1 (early B cell factor 1), a key transcription factor for B cell development, and mechanistically, H2AFY is enriched at the EBF1 promoter. Induced expression of H2AFY1.1 in U2AF1(S34F) cells rescues reduced EBF1 expression and B cells numbers in vivo. Collectively, our data implicate alternative splicing of H2AFY as a contributor to lymphopenia induced by U2AF1(S34F) in mice and MDS., Graphical Abstract, In brief Kim et al. demonstrate that H2AFY is a functional target of U2AF1(S34F)-induced alternative splicing, a common spliceosome gene mutation in myelodysplastic syndromes. H2afy−/− and U2AF1(S34F) mice have similar defective B cell development. H2AFY occupies the Ebf1 promoter, a key B cell differentiation transcription factor, providing a potential mechanism to regulate its expression.

Invasive plants may display age or genotype-specific defenses against herbivory. Thus, the importance of herbivory for preventing or mitigating plant invasions may depend on genetics and age-structure of invader populations. We used an excised-leaf experiment to test whether constitutive herbivore defenses in Butomus umbellatus L. (flowering rush) plants decline with age between colonizing (1st year) and established (2nd year) plants and whether the decline was parallel between introduced diploid and triploid genotypes. Leaves from colonizing and established plants were fed to the generalist herbivore fall armyworm (FAW; Spodoptera frugiperda) and then short-term FAW development was measured. Additionally, leaf dry matter content (DMC), % carbon (%C), % nitrogen (%N), carbon:nitrogen (C:N) ratio, and total leaf phenolics were determined for leaves from a subset of test plants. FAW fed leaves from diploid plants grew 27 % less than those fed leaves from triploid plants but were only 1 % smaller when fed leaves from second-year versus first-year plants of either cytotype. DMC of diploid leaves was 11 % greater overall (11 % DMC) but the difference in cytotypes depended on age (1 % difference in colonizing plants vs. 21 % difference in established plants). In general, diploid plants were characterized by 29 % higher total phenolics, 17 % less leaf nitrogen, and 21 % higher C:N ratio, regardless of age. Measured traits were, on average, 27 % more variable for diploid than triploid plants, possibly a reflection of increased genetic diversity of diploid flowering rush populations used in the study. These results demonstrate that diploid B. umbellatus plants are, overall, better defended against generalist herbivory than triploid plants. Differences in herbivore performance on B. umbellatus lineages, and to a lesser extent plants of varying ages, may therefore contribute to spatial or temporal heterogeneity in the dominance of genotypes in areas where they grow together.

In terrestrial ecosystems, changes in soil nutrient availability, plant growth or natural enemies can generate important shifts in abundance of organisms at various trophic levels. In agroecosystems the performance of (invasive) herbivores and their impacts on crops is of particular concern. Scientists are presently challenged with making reliable inferences on invader success, natural enemy performance and efficacy of biological control, particularly in tropical agroecosystems. In this study, we assess how trophic regulatory forces (bottom-up vs. top down) influence the success of three globally important pests of cassava. We examine the mealybug species (Hemiptera: Pseudococcidae) of differing host breadth and invasion history: Phenacoccus manihoti, Paracoccus marginatus, and Pseudococcus jackbeardsleyi. Potted plant fertilizer trials were combined with a regional survey in Vietnam, Laos and Cambodia of 65 cassava fields of similar size and age, but with varying soil fertility. Relative abundance of each mealybug invader was mapped along a soil fertility gradient, and contrasted with site-specific measures of parasitism. Potted plant trials revealed strong bottom-up effects for P. manihoti, such that impacts of nitrogen and potassium additions were propagated through to higher trophic levels and substantially boost development and fitness of its specialist parasitoid, Anagyrus lopezi (Hymenoptera: Encyrtidae). Field surveys indicate that mealybug performance is highly species-specific and context-dependent. For example, field-level abundance of P. jackbeardsleyi and P. marginatus, was related to measures of soil fertility parameters, soil texture and plant disease incidence. Furthermore, for P. manihoti, in-field abundance is equally associated with soil texture (i.e., silt content). Principal component analysis (PCA) and regression suggested that P. manihoti and P. marginatus are disproportionately favored in low-fertility conditions, while P. jackbeardsleyi prospers in settings with high organic carbon and phosphorus. Parasitism of P. manihoti by A. lopezi varied greatly with field and soil fertility conditions, and was highest in soils with intermediate fertility levels and where management practices include the addition of fertilizer supplements. Our characterization of the relative performance of invasive mealybugs and strength of parasitism across variable soil fertility conditions will help guide parasitoid release programs and soil management practices that enhance mealybug biological control.

Eutectic melting curves in the system MgO–SiO2 have been experimentally determined at lower mantle pressures using laser-heated diamond anvil cell (LH-DAC) techniques. We investigated eutectic melting of bridgmanite plus periclase in the MgO–MgSiO3 binary, and melting of bridgmanite plus stishovite in the MgSiO3–SiO2 binary, as analogues for natural peridotite and basalt, respectively. The melting curve of model basalt occurs at lower temperatures, has a shallower d T / d P slope and slightly less curvature than the model peridotitic melting curve. Overall, melting temperatures detected in this study are in good agreement with previous experiments and ab initio simulations at ∼25 GPa ( Liebske and Frost, 2012 ; de Koker et al., 2013 ). However, at higher pressures the measured eutectic melting curves are systematically lower in temperature than curves extrapolated on the basis of thermodynamic modelling of low-pressure experimental data, and those calculated from atomistic simulations. We find that our data are inconsistent with previously computed melting temperatures and melt thermodynamic properties of the SiO2 endmember, and indicate a maximum in short-range ordering in MgO–SiO2 melts close to Mg2SiO4 composition. The curvature of the model peridotite eutectic relative to an MgSiO3 melt adiabat indicates that crystallization in a global magma ocean would begin at ∼100 GPa rather than at the bottom of the mantle, allowing for an early basal melt layer. The model peridotite melting curve lies ∼ 500 K above the mantle geotherm at the core–mantle boundary, indicating that it will not be molten unless the addition of other components reduces the solidus sufficiently. The model basalt melting curve intersects the geotherm at the base of the mantle, and partial melting of subducted oceanic crust is expected.

Despite potential to structure ecosystem food webs through top-down effects, the trophic interactions of the American Eel Anguilla rostrata remain largely understudied. All previous research on the trophic ecology of American Eel in inland aquatic ecosystems has been conducted in temperate continental regions of the species' range. These studies have led to a paradigm that American Eel is a nocturnally active benthic predator, which most commonly consumes benthic invertebrates. Tropical island streams and rivers have habitats and communities that are distinct from temperate counterparts, but comprise a large portion of the adult habitat in the American Eel's range. We documented a previously undescribed diurnal feeding behavior by American Eel in a Caribbean river and demonstrate that this behavior, and a shift toward more frequent daytime feeding, is linked to periodic mass migrations of postlarvae of amphidromous fish taxa, including the Sicydiine goby Sicydium spp. Our findings indicate that periodic mass migrations of amphidromous postlarvae could function as a potentially important food source for American Eel in tropical regions of its distribution, despite the intermittence of availability. Furthermore, this suggests that the American Eel plays an important role in the structure of tropical lotic food webs through top-down effects that are potentially augmented by instream barriers.

The trace element compositions of inclusions in sub-lithospheric diamonds from the Juina-5 kimberlite, Brazil, are presented. Literature data for mineral/melt partition coefficients were collated, refitted and employed to interpret inclusion compositions. As part of this process an updated empirical model for predicting the partitioning behaviour of trivalent cations for garnet–melt equilibrium calibrated using data from 73 garnet-melt pairs is presented. High levels of trace element enrichment in inclusions interpreted as former calcium silicate perovskite and majoritic garnet preclude their origin as fragments of an ambient deep mantle assemblage. Inclusions believed to represent former bridgmanite minerals also display a modest degree of enrichment relative to mantle phases. The trace element compositions of ‘NAL’ and ‘CF phase’ minerals are also reported. Negative Eu, Ce, and Y/Ho anomalies alongside depletions of Sr, Hf and Zr in many inclusions are suggestive of formation from a low-degree carbonatitic melt of subducted oceanic crust. Observed enrichments in garnet and ‘calcium perovskite’ inclusions limit depths of melting to less than ~ 600 km, prior to calcium perovskite saturation in subducting assemblages. Less enriched inclusions in sub-lithospheric diamonds from other global localities may represent deeper diamond formation. Modelled source rock compositions that are capable of producing melts in equilibrium with Juina-5 ‘calcium perovskite’ and majorite inclusions are consistent with subducted MORB. Global majorite inclusion compositions suggest a common process is responsible for the formation of many superdeep diamonds, irrespective of geographic locality. Global transition zone inclusion compositions are reproduced by fractional crystallisation from a single parent melt, suggesting that they record the crystallisation sequence and melt evolution during this interaction of slab melts with ambient mantle. All observations are consistent with the previous hypothesis that many superdeep diamonds are created as slab-derived carbonatites interact with peridotitic mantle in the transition zone.

Diamonds from the Machado River alluvial deposit have been characterised on the basis of external morphology, internal textures, carbon isotopic composition, nitrogen concentration and aggregation state and mineral inclusion chemistry. Variations in morphology and features of abrasion suggest some diamonds have been derived directly from local kimberlites, whereas others have been through extensive sedimentary recycling. On the basis of mineral inclusion compositions, both lithospheric and sublithospheric diamonds are present at the deposit. The lithospheric diamonds have clear layer-by-layer octahedral and/or cuboid internal growth zonation, contain measurable nitrogen and indicate a heterogeneous lithospheric mantle beneath the region. The sublithospheric diamonds show a lack of regular sharp zonation, do not contain detectable nitrogen, are isotopically heavy (δ13CPDB predominantly − 0.7 to − 5.5) and contain inclusions of ferropericlase, former bridgmanite, majoritic garnet and former CaSiO3-perovskite. This suggests source lithologies that are Mg- and Ca-rich, probably including carbonates and serpentinites, subducted to lower mantle depths. The studied suite of sublithospheric diamonds has many similarities to the alluvial diamonds from Kankan, Guinea, but has more extreme variations in mineral inclusion chemistry. Of all superdeep diamond suites yet discovered, Machado River represents an end-member in terms of either the compositional range of materials being subducted to Transition Zone and lower mantle or the process by which materials are transferred from the subducted slab to the diamond-forming region.

This Practice Parameter is a revision of a previous Parameter addressing reactive attachment disorder that was published in 2005. It reviews the current status of reactive attachment disorder (RAD) and disinhibited social engagement disorder (DESD) with regard to assessment and treatment. Attachment is a central component of social and emotional development in early childhood, and disordered attachment is defined by specific patterns of abnormal social behavior in the context of "insufficient care" or social neglect. Assessment requires direct observation of the child in the context of his or her relationships with primary caregivers. Treatment requires establishing an attachment relationship for the child when none exists and ameliorating disturbed social relatedness with non-caregivers when evident.

The genomic events responsible for the pathogenesis of relapsed adult B-lymphoblastic leukemia (B-ALL) are not yet clear. We performed integrative analysis of whole-genome, whole-exome, custom capture, whole-transcriptome (RNA-seq), and locus-specific genomic assays across nine time points from a patient with primary de novo B-ALL. Comprehensive genome and transcriptome characterization revealed a dramatic tumor evolution during progression, yielding a tumor with complex clonal architecture at second relapse. We observed and validated point mutations in EP300 and NF1, a highly expressed EP300-ZNF384 gene fusion, a microdeletion in IKZF1, a focal deletion affecting SETD2, and large deletions affecting RB1, PAX5, NF1, and ETV6. Although the genome analysis revealed events of potential biological relevance, no clinically actionable treatment options were evident at the time of the second relapse. However, transcriptome analysis identified aberrant overexpression of the targetable protein kinase encoded by the FLT3 gene. Although the patient had refractory disease after salvage therapy for the second relapse, treatment with the FLT3 inhibitor sunitinib rapidly induced a near complete molecular response, permitting the patient to proceed to a matched-unrelated donor stem cell transplantation. The patient remains in complete remission more than 4 years later. Analysis of this patient's relapse genome revealed an unexpected, actionable therapeutic target that led to a specific therapy associated with a rapid clinical response. For some patients with relapsed or refractory cancers, this approach may indicate a novel therapeutic intervention that could alter outcome.