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Aboveground biomass density (AGBD) estimates from Earth Observation (EO) can be presented with the consistency standards mandated by United Nations Framework Convention on Climate Change (UNFCCC). This article delivers AGBD estimates, in the format of Intergovernmental Panel on Climate Change (IPCC) Tier 1 values for natural forests, sourced from National Aeronautics and Space Administration’s (NASA’s) Global Ecosystem Dynamics Investigation (GEDI) and Ice, Cloud and land Elevation Satellite (ICESat-2), and European Space Agency’s (ESA’s) Climate Change Initiative (CCI). It also provides the underlying classification used by the IPCC as geospatial layers, delineating global forests by ecozones, continents and status (primary, young (≤20 years) and old secondary (>20 years)). The approaches leverage complementary strengths of various EO-derived datasets that are compiled in an open-science framework through the Multi-mission Algorithm and Analysis Platform (MAAP). This transparency and flexibility enables the adoption of any new incoming datasets in the framework in the future. The EO-based AGBD estimates are expected to be an independent contribution to the IPCC Emission Factors Database in support of UNFCCC processes, and the forest classification expected to support the generation of other policy-relevant datasets while reflecting ongoing shifts in global forests with climate change.

Background: The application of different approaches calculating the anthropogenic carbon net flux from land, leads to estimates that vary considerably. One reason for these variations is the extent to which approaches consider forest land to be “managed” by humans, and thus contributing to the net anthropogenic flux. Global Earth Observation (EO) datasets characterising spatio-temporal changes in land cover and carbon stocks provide an independent and consistent approach to estimate forest carbon fluxes. These can be compared against results reported in National Greenhouse Gas Inventories (NGHGIs) to support accurate and timely measuring, reporting and verification (MRV). Using Brazil as a primary case study, with additional analysis in Indonesia and Malaysia, we compare a Global EO-based dataset of forest carbon fluxes to results reported in NGHGIs. Results: Between 2001 and 2020, the EO-derived estimates of all forest-related emissions and removals indicate that Brazil was a net sink of carbon (− 0.2 GtCO2yr−1), while Brazil’s NGHGI reported a net carbon source (+ 0.8 GtCO2yr−1). After adjusting the EO estimate to use the Brazilian NGHGI definition of managed forest and other assumptions used in the inventory’s methodology, the EO net flux became a source of + 0.6 GtCO2yr−1, comparable to the NGHGI. Remaining discrepancies are due largely to differing carbon removal factors and forest types applied in the two datasets. In Indonesia, the EO and NGHGI net flux estimates were similar (+ 0.6 GtCO2 yr−1), but in Malaysia, they differed in both magnitude and sign (NGHGI: -0.2 GtCO2 yr−1; Global EO: + 0.2 GtCO2 yr−1). Spatially explicit datasets on forest types were not publicly available for analysis from either NGHGI, limiting the possibility of detailed adjustments. Conclusions: By adjusting the EO dataset to improve comparability with carbon fluxes estimated for managed forests in the Brazilian NGHGI, initially diverging estimates were largely reconciled and remainin

Earth Observation data are uniquely positioned to estimate forest aboveground biomass density (AGBD) in accordance with the United Nations Framework Convention on Climate Change (UNFCCC) principles of ‘transparency, accuracy, completeness, consistency and comparability’. However, the use of space-based AGBD maps for national-level reporting to the UNFCCC is nearly non-existent as of 2023, the end of the first global stocktake (GST). We conduct an evidence-based comparison of AGBD estimates from the NASA Global Ecosystem Dynamics Investigation and ESA Climate Change Initiative, describing differences between the products and National Forest Inventories (NFIs), and suggesting how science teams must align efforts to inform the next GST. Between the products, in the tropics, the largest differences in estimated AGBD are primarily in the Congolese lowlands and east/southeast Asia. Where NFI data were acquired (Peru, Mexico, Lao PDR and 30 regions of Spain), both products show strong correlation to NFI-estimated AGBD, with no systematic deviations. The AGBD-richest stratum of these, the Peruvian Amazon, is accurately estimated in both. These results are remarkably promising, and to support the operational use of AGB map products for policy reporting, we describe targeted ways to align products with Intergovernmental Panel on Climate Change (IPCC) guidelines. We recommend moving towards consistent statistical terminology, and aligning on a rigorous framework for uncertainty estimation, supported by the provision of open-science codes for large-area assessments that comprehensively report uncertainty. Further, we suggest the provision of objective and open-source guidance to integrate NFIs with multiple AGBD products, aiming to enhance the precision of national estimates. Finally, we describe and encourage the release of user-friendly product documentation, with tools that produce AGBD estimates directly applicable to the IPCC guideline methodologies. With these steps, spac

Changes in cellular bioenergetics such as mitochondrial respiration and glycolysis may play a role in the pathogenesis of various diseases including type 1 diabetes (T1D). We used Seahorse extracellular flux technology to analyse the efficiency of glycolysis and mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells (PBMCs) obtained from fresh blood samples from fifteen long-term T1D individuals with albuminuria (five females) with an average (±SD) age of 58 (±14) years and 15 age and sex-matched healthy non-diabetic controls. In T1D PBMCs, mitochondrial proton leak was higher (T1D: 21,3 ± 1,46 pmol/min; controls: 17,3 ± 1,24 pmol/min; p = 0,049) and glucose (5 mM) suppressed mitochondrial proton leak more than in healthy controls. Further, PBMCs from T1D individuals had higher glycolysis compared with healthy controls (T1D: 9,68 ± 0,94 mpH/min; controls: 7,07 ± 0,64 mpH/min; p = 0,032). Correlation analysis of circulating inflammatory factors identified Leukaemia Inhibitor factor 1 (LIF) being negatively correlated with PBMC glycolysis. Our results suggest that mitochondrial and glycolytic pathways of PBMCs from long-term T1D individuals with albuminuria might be dysfunctional, possibly due to increased cellular metabolic load and/or oxidative stress in which inflammatory factors could play a role.

Changes in cellular bioenergetics such as mitochondrial respiration and glycolysis may play a role in the pathogenesis of various diseases including type 1 diabetes (T1D). We used Seahorse extracellular flux technology to analyse the efficiency of glycolysis and mitochondrial oxidative phosphorylation in peripheral blood mononuclear cells (PBMCs) obtained from fresh blood samples from fifteen long-term T1D individuals with albuminuria (five females) with an average (±SD) age of 58 (±14) years and 15 age and sex-matched healthy non-diabetic controls. In T1D PBMCs, mitochondrial proton leak was higher (T1D: 21,3 ± 1,46 pmol/min; controls: 17,3 ± 1,24 pmol/min; p = 0,049) and glucose (5 mM) suppressed mitochondrial proton leak more than in healthy controls. Further, PBMCs from T1D individuals had higher glycolysis compared with healthy controls (T1D: 9,68 ± 0,94 mpH/min; controls: 7,07 ± 0,64 mpH/min; p = 0,032). Correlation analysis of circulating inflammatory factors identified Leukaemia Inhibitor factor 1 (LIF) being negatively correlated with PBMC glycolysis. Our results suggest that mitochondrial and glycolytic pathways of PBMCs from long-term T1D individuals with albuminuria might be dysfunctional, possibly due to increased cellular metabolic load and/or oxidative stress in which inflammatory factors could play a role.

This article uses the concept of performance to think about four fourteenth-century Portuguese monuments with effigies of elite women holding open books in their hands. It proposes looking at them as builders of a reading/praying experience aimed at engaging their viewers by converting the dead into undying performers who in turn encourage their audiences to imitate their performance. The sculpted women operate as activators of a mediation between the artwork and its audiences, the terrestrial and the celestial, the bodily and the spiritual, timelessness and mortality, the personal and the social, presence and absence, the word and silence, the contemplative and the performative.

Purpose: To develop a genotype assay to assess associations with common and rare age-related macular degeneration (AMD) risk variants, to calculate an overall genetic risk score (GRS), and to identify potential misdiagnoses with inherited macular dystrophies that mimic AMD. Design: Case-control study. Participants: Individuals (n = 4740) from 5 European cohorts. Methods: We designed single-molecule molecular inversion probes for target selection and used next generation sequencing to sequence 87 single nucleotide polymorphisms (SNPs), coding and splice-site regions of 10 AMD-(related) genes (ARMS2, C3, C9, CD46, CFB, CFH, CFI, HTRA1, TIMP3, and SLC16A8), and 3 genes that cause inherited macular dystrophies (ABCA4, CTNNA1, and PRPH2). Genetic risk scores for common AMD risk variants were calculated based on effect size and genotype of 52 AMD-associated variants. Frequency of rare variants was compared between late AMD patients and control individuals with logistic regression analysis. Main Outcome Measures: Genetic risk score, association of genetic variants with AMD, and genotype-phenotype correlations. Results: We observed high concordance rates between our platform and other genotyping platforms for the 69 successfully genotyped SNPs (>96%) and for the rare variants (>99%). We observed a higher GRS for patients with late AMD compared with patients with early/intermediate AMD (P < 0.001) and individuals without AMD (P < 0.001). A higher proportion of pathogenic variants in the CFH (odds ratio [OR] = 2.88; P = 0.006), CFI (OR = 4.45; P = 0.005), and C3 (OR = 6.56; P = 0.0003) genes was observed in late AMD patients compared with control individuals. In 9 patients, we identified pathogenic variants in the PRPH2, ABCA4, and CTNNA1 genes, which allowed reclassification of these patients as having inherited macular dystrophy. Conclusions: This study reports a genotype assay for common and rare AMD genetic variants, which can identify individuals at intermediate to high

Purpose: To develop a genotype assay to assess associations with common and rare age-related macular degeneration (AMD) risk variants, to calculate an overall genetic risk score (GRS), and to identify potential misdiagnoses with inherited macular dystrophies that mimic AMD. Design: Case-control study. Participants: Individuals (n = 4740) from 5 European cohorts. Methods: We designed single-molecule molecular inversion probes for target selection and used next generation sequencing to sequence 87 single nucleotide polymorphisms (SNPs), coding and splice-site regions of 10 AMD-(related) genes (ARMS2, C3, C9, CD46, CFB, CFH, CFI, HTRA1, TIMP3, and SLC16A8), and 3 genes that cause inherited macular dystrophies (ABCA4, CTNNA1, and PRPH2). Genetic risk scores for common AMD risk variants were calculated based on effect size and genotype of 52 AMD-associated variants. Frequency of rare variants was compared between late AMD patients and control individuals with logistic regression analysis. Main Outcome Measures: Genetic risk score, association of genetic variants with AMD, and genotype-phenotype correlations. Results: We observed high concordance rates between our platform and other genotyping platforms for the 69 successfully genotyped SNPs (>96%) and for the rare variants (>99%). We observed a higher GRS for patients with late AMD compared with patients with early/intermediate AMD (P < 0.001) and individuals without AMD (P < 0.001). A higher proportion of pathogenic variants in the CFH (odds ratio [OR] = 2.88; P = 0.006), CFI (OR = 4.45; P = 0.005), and C3 (OR = 6.56; P = 0.0003) genes was observed in late AMD patients compared with control individuals. In 9 patients, we identified pathogenic variants in the PRPH2, ABCA4, and CTNNA1 genes, which allowed reclassification of these patients as having inherited macular dystrophy. Conclusions: This study reports a genotype assay for common and rare AMD genetic variants, which can identify individuals at intermediate to high

Background: Inhibitors of the sodium-glucose cotransporter 2 (SGLT2) slow the progression of diabetic kidney disease, possibly by reducing the proximal tubule transport workload with subsequent improvement of renal oxygenation. We aimed to test this hypothesis in individuals with type 1 diabetes and albuminuria. Methods: A randomised, double-blind, placebo-controlled, crossover trial with a single 50 mg dose of the SGLT2 inhibitor dapagliflozin and placebo in random order, separated by a two-week washout period. Magnetic resonance imaging (MRI) was used to assess renal R2* (a low value corresponds to a high tissue oxygenation), renal perfusion (arterial spin labelling) and renal artery flow (phase contrast imaging) at baseline, three- and six hours from tablet ingestion. Exploratory outcomes, including baroreflex sensitivity, peripheral blood oxygen saturation, peripheral blood mononuclear cell mitochondrial oxygen consumption rate, and biomarkers of inflammation were evaluated at baseline and 12 h from medication. The study is registered in the EU Clinical Trials Register (EudraCT 2019–004,557–92), on ClinicalTrials.gov (NCT04193566), and is completed. Findings: Between February 3, 2020 and October 23, 2020, 31 individuals were screened, and 19 eligible individuals were randomised. Three dropped out before receiving any of the interventions and one dropped out after receiving only placebo. We included 15 individuals (33% female) in the per-protocol analysis with a mean age of 58 (SD 14) years, median urinary albumin creatinine ratio of 46 [IQR 21–58] mg/g and an eGFR of 73 (32) ml/min/1·73m2. The mean changes in renal cortical R2* from baseline to six hours were for dapagliflozin -1·1 (SD 0·7) s−1 and for placebo +1·3 (0·7) s−1, resulting in a difference between interventions of -2·3 s−1 [95% CI -4·0 to -0·6]; p = 0·012. No between-intervention differences were found in any other MRI outcomes, phy

Background: Inhibitors of the sodium-glucose cotransporter 2 (SGLT2) slow the progression of diabetic kidney disease, possibly by reducing the proximal tubule transport workload with subsequent improvement of renal oxygenation. We aimed to test this hypothesis in individuals with type 1 diabetes and albuminuria. Methods: A randomised, double-blind, placebo-controlled, crossover trial with a single 50 mg dose of the SGLT2 inhibitor dapagliflozin and placebo in random order, separated by a two-week washout period. Magnetic resonance imaging (MRI) was used to assess renal R2* (a low value corresponds to a high tissue oxygenation), renal perfusion (arterial spin labelling) and renal artery flow (phase contrast imaging) at baseline, three- and six hours from tablet ingestion. Exploratory outcomes, including baroreflex sensitivity, peripheral blood oxygen saturation, peripheral blood mononuclear cell mitochondrial oxygen consumption rate, and biomarkers of inflammation were evaluated at baseline and 12 h from medication. The study is registered in the EU Clinical Trials Register (EudraCT 2019–004,557–92), on ClinicalTrials.gov (NCT04193566), and is completed. Findings: Between February 3, 2020 and October 23, 2020, 31 individuals were screened, and 19 eligible individuals were randomised. Three dropped out before receiving any of the interventions and one dropped out after receiving only placebo. We included 15 individuals (33% female) in the per-protocol analysis with a mean age of 58 (SD 14) years, median urinary albumin creatinine ratio of 46 [IQR 21–58] mg/g and an eGFR of 73 (32) ml/min/1·73m2. The mean changes in renal cortical R2* from baseline to six hours were for dapagliflozin -1·1 (SD 0·7) s−1 and for placebo +1·3 (0·7) s−1, resulting in a difference between interventions of -2·3 s−1 [95% CI -4·0 to -0·6]; p = 0·012. No between-intervention differences were found in any other MRI outcomes, phy

Purpose: To develop a genotype assay to assess associations with common and rare age-related macular degeneration (AMD) risk variants, to calculate an overall genetic risk score (GRS), and to identify potential misdiagnoses with inherited macular dystrophies that mimic AMD. Design: Case-control study. Participants: Individuals (n = 4740) from 5 European cohorts. Methods: We designed single-molecule molecular inversion probes for target selection and used next generation sequencing to sequence 87 single nucleotide polymorphisms (SNPs), coding and splice-site regions of 10 AMD-(related) genes (ARMS2, C3, C9, CD46, CFB, CFH, CFI, HTRA1, TIMP3, and SLC16A8), and 3 genes that cause inherited macular dystrophies (ABCA4, CTNNA1, and PRPH2). Genetic risk scores for common AMD risk variants were calculated based on effect size and genotype of 52 AMD-associated variants. Frequency of rare variants was compared between late AMD patients and control individuals with logistic regression analysis. Main Outcome Measures: Genetic risk score, association of genetic variants with AMD, and genotype–phenotype correlations. Results: We observed high concordance rates between our platform and other genotyping platforms for the 69 successfully genotyped SNPs (>96%) and for the rare variants (>99%). We observed a higher GRS for patients with late AMD compared with patients with early/intermediate AMD (P < 0.001) and individuals without AMD (P < 0.001). A higher proportion of pathogenic variants in the CFH (odds ratio [OR] = 2.88; P = 0.006), CFI (OR = 4.45; P = 0.005), and C3 (OR = 6.56; P = 0.0003) genes was observed in late AMD patients compared with control individuals. In 9 patients, we identified pathogenic variants in the PRPH2, ABCA4, and CTNNA1 genes, which allowed reclassification of these patients as having inherited macular dystrophy. Conclusions: This study reports a genotype assay for common and rare AMD genetic variants, which can identify individuals at interm

Purpose To develop a genotype assay to assess associations with common and rare age-related macular degeneration (AMD) risk variants, to calculate an overall genetic risk score (GRS), and to identify potential misdiagnoses with inherited macular dystrophies that mimic AMD. Design Case-control study. Participants Individuals (n = 4740) from 5 European cohorts. Methods We designed single-molecule molecular inversion probes for target selection and used next generation sequencing to sequence 87 single nucleotide polymorphisms (SNPs), coding and splice-site regions of 10 AMD-(related) genes (ARMS2, C3, C9, CD46, CFB, CFH, CFI, HTRA1, TIMP3, and SLC16A8), and 3 genes that cause inherited macular dystrophies (ABCA4, CTNNA1, and PRPH2). Genetic risk scores for common AMD risk variants were calculated based on effect size and genotype of 52 AMD-associated variants. Frequency of rare variants was compared between late AMD patients and control individuals with logistic regression analysis. Main Outcome Measures Genetic risk score, association of genetic variants with AMD, and genotype–phenotype correlations. Results We observed high concordance rates between our platform and other genotyping platforms for the 69 successfully genotyped SNPs (>96%) and for the rare variants (>99%). We observed a higher GRS for patients with late AMD compared with patients with early/intermediate AMD (P < 0.001) and individuals without AMD (P < 0.001). A higher proportion of pathogenic variants in the CFH (odds ratio [OR] = 2.88; P = 0.006), CFI (OR = 4.45; P = 0.005), and C3 (OR = 6.56; P = 0.0003) genes was observed in late AMD patients compared with control individuals. In 9 patients, we identified pathogenic variants in the PRPH2, ABCA4, and CTNNA1 genes, which allowed reclassification of these patients as having inherited macular dystrophy. Conclusions This study reports a genotype assay for common and rare AMD genetic variants, which can identify individuals at intermediate to high genetic

Medieval tombs are a privileged source for the exploration of women’s reality and its dynamics in relation to the categories of memory, power and gender. Through the effigy and the iconographies of the chest but also through setting, sepulchers provide a nuanced “portrait” of medieval women. While showing them as pious and devout individuals, committed to the communitarian (matrimonial, family) and patriarchal circumstances of their lives, tombs often celebrate women in their own existence and mirror their power. In this article, I focus on seven tombs, all produced for or by the initiative of elite women linked to the Portuguese medieval context, which allow us to observe the real possibilities they were granted to craft (and embody) an image of power., A tumulária medieval oferece uma fonte privilegiada para o perscrutar do universo feminino e das suas dinâmicas, na relação com as categorias da memória, do poder e do género. O “retrato” que os sepulcros nos comunicam —através dos jacentes e das iconografias da arca, mas também da localização e disposição do túmulo— é de mulheres tão pias e devotas quanto comprometidas com as dinâmicas comunitárias (matrimoniais, linhagísticas) e patriarcais em que se inserem, sem por isso lhes ser negada a possibilidade de afirmação pessoal e muito menos se mostrarem isentas de poder. Neste artigo tomo como objecto de análise sete sepulcros medievais, produzidos para ou por iniciativa de mulheres de elite ligadas ao contexto medieval português e que nos permitem observar as reais possibilidades de que dispõem para a construção (e a vivência) de uma imagem de poder

Medieval tombs are a privileged source for the exploration of women’s reality and its dynamics in relation to the categories of memory, power and gender. Through the effigy and the iconographies of the chest but also through setting, sepulchers provide a nuanced “portrait” of medieval women. While showing them as pious and devout individuals, committed to the communitarian (matrimonial, family) and patriarchal circumstances of their lives, tombs often celebrate women in their own existence and mirror their power. In this article, I focus on seven tombs, all produced for or by the initiative of elite women linked to the Portuguese medieval context, which allow us to observe the real possibilities they were granted to craft (and embody) an image of power., A tumulária medieval oferece uma fonte privilegiada para o perscrutar do universo feminino e das suas dinâmicas, na relação com as categorias da memória, do poder e do género. O “retrato” que os sepulcros nos comunicam —através dos jacentes e das iconografias da arca, mas também da localização e disposição do túmulo— é de mulheres tão pias e devotas quanto comprometidas com as dinâmicas comunitárias (matrimoniais, linhagísticas) e patriarcais em que se inserem, sem por isso lhes ser negada a possibilidade de afirmação pessoal e muito menos se mostrarem isentas de poder. Neste artigo tomo como objecto de análise sete sepulcros medievais, produzidos para ou por iniciativa de mulheres de elite ligadas ao contexto medieval português e que nos permitem observar as reais possibilidades de que dispõem para a construção (e a vivência) de uma imagem de poder

A tumulária medieval oferece uma fonte privilegiada para o perscrutar do universo feminino e das suas dinâmicas, na relação com as categorias da memória, do poder e do género. O “retrato” que os sepulcros nos comunicam —através dos jacentes e das iconografias da arca, mas também da localização e disposição do túmulo— é de mulheres tão pias e devotas quanto comprometidas com as dinâmicas comunitárias (matrimoniais, linhagísticas) e patriarcais em que se inserem, sem por isso lhes ser negada a possibilidade de afirmação pessoal e muito menos se mostrarem isentas de poder. Neste artigo tomo como objecto de análise sete sepulcros medievais, produzidos para ou por iniciativa de mulheres de elite ligadas ao contexto medieval português e que nos permitem observar as reais possibilidades de que dispõem para a construção (e a vivência) de uma imagem de poder.

Deletions within chromosome 11q22-23, are considered among the most common chromosomal aberrations in chronic lymphocytic leukemia (CLL), and are associated with a poor outcome. In addition to the ataxia telangiectasia mutated (ATM) gene, the baculoviral IAP repeat-containing 3 (BIRC3) gene is also located in the region. BIRC3 encodes a negative regulator of the non-canonical nuclear factor.-light-chain-enhancer of activated B cells (NF-kappa B) protein. Disruption of BIRC3 is known to be restricted to CLL fludarabine-refractory patients. The aim of the present study was to determine the frequency of copy number changes of BIRC3 and to assess its association with two known predictors of negative CLL outcome, ATM and tumor protein 53 (TP53) gene deletions. To evaluate the specificity of BIRC3 alterations to CLL, BIRC3 copy numbers were assessed in 117 CLL patients in addition to 45 B-cell acute lymphocytic leukemia (B-ALL) patients. A commercially available multiplex ligation dependent probe amplification kit, which includes four probes for the detection of TP53 and four probes for ATM gene region, was applied. Interphase-directed fluorescence in situ hybridization was used to apply commercially available probes for BIRC3, ATM and TP53. High resolution array-comparative genomic hybridization was conducted in selected cases. Genetic abnormalities of BIRC3 were detected in 23/117 (similar to 20%) of CLL and 2/45 (similar to 4%) of B-ALL cases. Overall, 20 patients with CLL and 1 with B-ALL possessed a BIRC3 deletion, whilst 3 patients with CLL and 1 with B-ALL harbored a BIRC3 duplication. All patients with an ATM deletion also carried a BIRC3 deletion. Only 2 CLL cases possessed deletions in BIRC3, ATM and TP53 simultaneously. Evidently, the deletion or duplication of BIRC3 may be observed rarely in B-ALL patients. BIRC3 duplication may occur in CLL patients, for which the prognosis requires additional studies in the future. The likelihood that TP53 deletions occur si

Deletions within chromosome 11q22-23, are considered among the most common chromosomal aberrations in chronic lymphocytic leukemia (CLL), and are associated with a poor outcome. In addition to the ataxia telangiectasia mutated (ATM) gene, the baculoviral IAP repeat-containing 3 (BIRC3) gene is also located in the region. BIRC3 encodes a negative regulator of the non-canonical nuclear factor.-light-chain-enhancer of activated B cells (NF-kappa B) protein. Disruption of BIRC3 is known to be restricted to CLL fludarabine-refractory patients. The aim of the present study was to determine the frequency of copy number changes of BIRC3 and to assess its association with two known predictors of negative CLL outcome, ATM and tumor protein 53 (TP53) gene deletions. To evaluate the specificity of BIRC3 alterations to CLL, BIRC3 copy numbers were assessed in 117 CLL patients in addition to 45 B-cell acute lymphocytic leukemia (B-ALL) patients. A commercially available multiplex ligation dependent probe amplification kit, which includes four probes for the detection of TP53 and four probes for ATM gene region, was applied. Interphase-directed fluorescence in situ hybridization was used to apply commercially available probes for BIRC3, ATM and TP53. High resolution array-comparative genomic hybridization was conducted in selected cases. Genetic abnormalities of BIRC3 were detected in 23/117 (similar to 20%) of CLL and 2/45 (similar to 4%) of B-ALL cases. Overall, 20 patients with CLL and 1 with B-ALL possessed a BIRC3 deletion, whilst 3 patients with CLL and 1 with B-ALL harbored a BIRC3 duplication. All patients with an ATM deletion also carried a BIRC3 deletion. Only 2 CLL cases possessed deletions in BIRC3, ATM and TP53 simultaneously. Evidently, the deletion or duplication of BIRC3 may be observed rarely in B-ALL patients. BIRC3 duplication may occur in CLL patients, for which the prognosis requires additional studies in the future. The likelihood that TP53 deletions occur si

BACKGROUND: Recently, a number of patients have been described with structural rearrangements at 3q13.31, delineating a novel microdeletion syndrome with common clinical features including developmental delay and other neurodevelopmental disorders (NDD). A smallest region of overlapping deletions (SRO) involved five RefSeq genes, including the transcription factor gene ZBTB20 and the dopamine receptor gene DRD3, considered as candidate genes for the syndrome.METHODS AND RESULTS: We used array comparative genomic hybridization and next-generation mate-pair sequencing to identify key structural rearrangements involving ZBTB20 in two patients with NDD. In a patient with developmental delay, attention-deficit hyperactivity disorder, psychosis, Tourette's syndrome and autistic traits, a de novo balanced t(3;18) translocation truncated ZBTB20. The other breakpoint did not disrupt any gene. In a second patient with developmental delay and autism, we detected the first microdeletion at 3q13.31, which truncated ZBTB20 but did not involve DRD3 or the other genes within the previously defined SRO. Zbtb20 directly represses 346 genes in the developing murine brain. Of the 342 human orthologous ZBTB20 candidate target genes, we found 68 associated with NDD. Using chromatin immunoprecipitation and quantitative PCR, we validated the in vivo binding of Zbtb20 in evolutionary conserved regions in six of these genes (Cntn4, Gad1, Nrxn1, Nrxn3, Scn2a, Snap25).CONCLUSIONS: Our study links dosage imbalance of ZBTB20 to a range of neurodevelopmental, cognitive and psychiatric disorders, likely mediated by dysregulation of multiple ZBTB20 target genes, and provides new knowledge on the genetic background of the NDD seen in the 3q13.31 microdeletion syndrome.

Our goal is to make the critique of the family concept presented in the guidelines of the National Policy for Social Assistance-PNAS, approved in 2004, and still until today. Considered as an advance in the complex relationship of concession-conquest, PNAS, through the implementation of the Social Assistance Unique System (SUAS), tries to organize social assistance such as social security right, outstanding the matricialidade family member on the centrality of this policy. Focusing on the family brings aims proposing full protection from the state, which cares for social individuals, taking into account the social and familiar sphere, to put an end to the culture of the fragmentation in the service of social demands through public policies. In order to accomplish that goal, public policy of social assistance should strive for a social protection that ensures survival security "(of income and autonomy); of protectio; and conviviality or family experience "(PNAS 2004). However, a denial to the materialization of constitutional rights, through the deployment of SUAS guidelines, PNAS rescues the conservative principles and values for the understanding of the family. In this manner, it becomes an instrument of accountability for poor families, seeking, through the fault of social individuals, the "solutions" of the refractions of the "social question", that are resized as individual and family problems., Resumen Nuestro objetivo es realizar la crítica al concepto de familia que está presente en las directrices de la Política Nacional de Asistencia Social (PNAS), aprobada en el año 2004, y todavía vigente. Considerada como avance en la compleja relación de concesión-conquista, la PNAS, a través de la implantación del Sistema Único de Asistencia Social (SUAS), propone dar organicidad a la Asistencia Social como derecho de la Seguridad Social, destacando la matriz socio familiar en la centralidad de esta política. La centralidad en la familia trae como propuesta la protección integral por parte del Estado, que atienda a los individuos sociales, considerando el espacio socio familiar, para romper con la cultura de la fragmentación en la atención a las demandas sociales vía políticas públicas. Para lo cual, la política pública de asistencia social debe preocuparse por una protección social que garantice la “seguridad de sobrevivencia (de renta y de autonomía); de amparo; y convivio o vivencia familiar” (PNAS 2004). Sin embargo, en un movimiento de negación en la materialización de los derechos Constitucionales, a través de las orientaciones para la implantación del SUAS, la PNAS rescata los principios y valores conservadores en la comprensión de la familia. Así se vuelve instrumento que responsabiliza a los miembros de las familias pobres, para que busquen a través de culpabilizarlos, las “soluciones” a las secuelas de la “cuestión social”, que son redimensionadas como problemas individuales y da familia. AbstractOur goal is to make the critique of the family design presented in the guidelines of the National Policy for Social Assistance-PNAS, approved in 2004, and still valid. How to advance in the complex relationship of concession-conquest, PNAS, through the implementation of the Social Assistance Unique System (SUAS), proposes giving organize social assistance such as social security right, outstanding the matricialidade family member on the centrality of this policy

Our goal is to make the critique of the family concept presented in the guidelines of the National Policy for Social Assistance-PNAS, approved in 2004, and still until today. Considered as an advance in the complex relationship of concession-conquest, PNAS, through the implementation of the Social Assistance Unique System (SUAS), tries to organize social assistance such as social security right, outstanding the matricialidade family member on the centrality of this policy. Focusing on the family brings aims proposing full protection from the state, which cares for social individuals, taking into account the social and familiar sphere, to put an end to the culture of the fragmentation in the service of social demands through public policies. In order to accomplish that goal, public policy of social assistance should strive for a social protection that ensures survival security "(of income and autonomy); of protectio; and conviviality or family experience "(PNAS 2004). However, a denial to the materialization of constitutional rights, through the deployment of SUAS guidelines, PNAS rescues the conservative principles and values for the understanding of the family. In this manner, it becomes an instrument of accountability for poor families, seeking, through the fault of social individuals, the "solutions" of the refractions of the "social question", that are resized as individual and family problems., Resumen Nuestro objetivo es realizar la crítica al concepto de familia que está presente en las directrices de la Política Nacional de Asistencia Social (PNAS), aprobada en el año 2004, y todavía vigente. Considerada como avance en la compleja relación de concesión-conquista, la PNAS, a través de la implantación del Sistema Único de Asistencia Social (SUAS), propone dar organicidad a la Asistencia Social como derecho de la Seguridad Social, destacando la matriz socio familiar en la centralidad de esta política. La centralidad en la familia trae como propuesta la protección integral por parte del Estado, que atienda a los individuos sociales, considerando el espacio socio familiar, para romper con la cultura de la fragmentación en la atención a las demandas sociales vía políticas públicas. Para lo cual, la política pública de asistencia social debe preocuparse por una protección social que garantice la “seguridad de sobrevivencia (de renta y de autonomía); de amparo; y convivio o vivencia familiar” (PNAS 2004). Sin embargo, en un movimiento de negación en la materialización de los derechos Constitucionales, a través de las orientaciones para la implantación del SUAS, la PNAS rescata los principios y valores conservadores en la comprensión de la familia. Así se vuelve instrumento que responsabiliza a los miembros de las familias pobres, para que busquen a través de culpabilizarlos, las “soluciones” a las secuelas de la “cuestión social”, que son redimensionadas como problemas individuales y da familia. AbstractOur goal is to make the critique of the family design presented in the guidelines of the National Policy for Social Assistance-PNAS, approved in 2004, and still valid. How to advance in the complex relationship of concession-conquest, PNAS, through the implementation of the Social Assistance Unique System (SUAS), proposes giving organize social assistance such as social security right, outstanding the matricialidade family member on the centrality of this policy

Our goal is to make the critique of the family concept presented in the guidelines of the National Policy for Social Assistance-PNAS, approved in 2004, and still until today. Considered as an advance in the complex relationship of concession-conquest, PNAS, through the implementation of the Social Assistance Unique System (SUAS), tries to organize social assistance such as social security right, outstanding the matricialidade family member on the centrality of this policy. Focusing on the family brings aims proposing full protection from the state, which cares for social individuals, taking into account the social and familiar sphere, to put an end to the culture of the fragmentation in the service of social demands through public policies. In order to accomplish that goal, public policy of social assistance should strive for a social protection that ensures survival security "(of income and autonomy); of protectio; and conviviality or family experience "(PNAS 2004). However, a denial to the materialization of constitutional rights, through the deployment of SUAS guidelines, PNAS rescues the conservative principles and values for the understanding of the family. In this manner, it becomes an instrument of accountability for poor families, seeking, through the fault of social individuals, the "solutions" of the refractions of the "social question", that are resized as individual and family problems., Resumen Nuestro objetivo es realizar la crítica al concepto de familia que está presente en las directrices de la Política Nacional de Asistencia Social (PNAS), aprobada en el año 2004, y todavía vigente. Considerada como avance en la compleja relación de concesión-conquista, la PNAS, a través de la implantación del Sistema Único de Asistencia Social (SUAS), propone dar organicidad a la Asistencia Social como derecho de la Seguridad Social, destacando la matriz socio familiar en la centralidad de esta política. La centralidad en la familia trae como propuesta la protección integral por parte del Estado, que atienda a los individuos sociales, considerando el espacio socio familiar, para romper con la cultura de la fragmentación en la atención a las demandas sociales vía políticas públicas. Para lo cual, la política pública de asistencia social debe preocuparse por una protección social que garantice la “seguridad de sobrevivencia (de renta y de autonomía); de amparo; y convivio o vivencia familiar” (PNAS 2004). Sin embargo, en un movimiento de negación en la materialización de los derechos Constitucionales, a través de las orientaciones para la implantación del SUAS, la PNAS rescata los principios y valores conservadores en la comprensión de la familia. Así se vuelve instrumento que responsabiliza a los miembros de las familias pobres, para que busquen a través de culpabilizarlos, las “soluciones” a las secuelas de la “cuestión social”, que son redimensionadas como problemas individuales y da familia. AbstractOur goal is to make the critique of the family design presented in the guidelines of the National Policy for Social Assistance-PNAS, approved in 2004, and still valid. How to advance in the complex relationship of concession-conquest, PNAS, through the implementation of the Social Assistance Unique System (SUAS), proposes giving organize social assistance such as social security right, outstanding the matricialidade family member on the centrality of this policy

Our goal is to make the critique of the family concept presented in the guidelines of the National Policy for Social Assistance-PNAS, approved in 2004, and still until today. Considered as an advance in the complex relationship of concession-conquest, PNAS, through the implementation of the Social Assistance Unique System (SUAS), tries to organize social assistance such as social security right, outstanding the matricialidade family member on the centrality of this policy. Focusing on the family brings aims proposing full protection from the state, which cares for social individuals, taking into account the social and familiar sphere, to put an end to the culture of the fragmentation in the service of social demands through public policies. In order to accomplish that goal, public policy of social assistance should strive for a social protection that ensures survival security "(of income and autonomy); of protectio; and conviviality or family experience "(PNAS 2004). However, a denial to the materialization of constitutional rights, through the deployment of SUAS guidelines, PNAS rescues the conservative principles and values for the understanding of the family. In this manner, it becomes an instrument of accountability for poor families, seeking, through the fault of social individuals, the "solutions" of the refractions of the "social question", that are resized as individual and family problems., Resumen Nuestro objetivo es realizar la crítica al concepto de familia que está presente en las directrices de la Política Nacional de Asistencia Social (PNAS), aprobada en el año 2004, y todavía vigente. Considerada como avance en la compleja relación de concesión-conquista, la PNAS, a través de la implantación del Sistema Único de Asistencia Social (SUAS), propone dar organicidad a la Asistencia Social como derecho de la Seguridad Social, destacando la matriz socio familiar en la centralidad de esta política. La centralidad en la familia trae como propuesta la protección integral por parte del Estado, que atienda a los individuos sociales, considerando el espacio socio familiar, para romper con la cultura de la fragmentación en la atención a las demandas sociales vía políticas públicas. Para lo cual, la política pública de asistencia social debe preocuparse por una protección social que garantice la “seguridad de sobrevivencia (de renta y de autonomía); de amparo; y convivio o vivencia familiar” (PNAS 2004). Sin embargo, en un movimiento de negación en la materialización de los derechos Constitucionales, a través de las orientaciones para la implantación del SUAS, la PNAS rescata los principios y valores conservadores en la comprensión de la familia. Así se vuelve instrumento que responsabiliza a los miembros de las familias pobres, para que busquen a través de culpabilizarlos, las “soluciones” a las secuelas de la “cuestión social”, que son redimensionadas como problemas individuales y da familia. AbstractOur goal is to make the critique of the family design presented in the guidelines of the National Policy for Social Assistance-PNAS, approved in 2004, and still valid. How to advance in the complex relationship of concession-conquest, PNAS, through the implementation of the Social Assistance Unique System (SUAS), proposes giving organize social assistance such as social security right, outstanding the matricialidade family member on the centrality of this policy