Invasive grasses increase fire occurrence and frequency across US ecoregions.

Fire-prone invasive grasses create novel ecosystem threats by increasing fine-fuel loads and continuity, which can alter fire regimes. While the existence of an invasive grass-fire cycle is well known, evidence of altered fire regimes is typically based on local-scale studies or expert knowledge. Here, we quantify the effects of 12 nonnative, invasive grasses on fire occurrence, size, and frequency across 29 US ecoregions encompassing more than one third of the conterminous United States. These 12 grass species promote fire locally and have extensive spatial records of abundant infestations. We combined agency and satellite fire data with records of abundant grass invasion to test for differences in fire regimes between invaded and nearby "uninvaded" habitat. Additionally, we assessed whether invasive grass presence is a significant predictor of altered fire by modeling fire occurrence, size, and frequency as a function of grass invasion, in addition to anthropogenic and ecological covariates relevant to fire. Eight species showed significantly higher fire-occurrence rates, which more than tripled for Schismus barbatus and Pennisetum ciliare. Six species demonstrated significantly higher mean fire frequency, which more than doubled for Neyraudia reynaudiana and Pennisetum ciliare Grass invasion was significant in fire occurrence and frequency models, but not in fire-size models. The significant differences in fire regimes, coupled with the importance of grass invasion in modeling these differences, suggest that invasive grasses alter US fire regimes at regional scales. As concern about US wildfires grows, accounting for fire-promoting invasive grasses will be imperative for effectively managing ecosystems.

Low-dose ipilimumab plus nivolumab combined with IL-2 and hyperthermia in cancer patients with advanced disease: exploratory findings of a case series of 131 stage IV cancers - a retrospective study of a single institution.

The 3-year overall survival (OS) rate of patients with previously treated or untreated stage III or IV melanoma has by now reached 63% using ipilimumab and nivolumab therapy. However, immune-related adverse events (irAEs) of grade 3 or 4 occurred in 59% of patients leading to discontinuation of therapy in 24.5% of patients and one death. Therapy with checkpoint inhibitors could be safer and more effective in combination with hyperthermia and fever inducing therapies. We conducted a retrospective analysis to test the safety and efficacy of a new combination immune therapy in 131 unselected stage IV solid cancer patients with 23 different histological types of cancer who exhausted all conventional treatments. Treatment consisted of locoregional- and whole-body hyperthermia, individually dose adapted interleukin 2 (IL-2) combined with low-dose ipilimumab (0.3 mg/kg) plus nivolumab (0.5 mg/kg). The objective response rate (ORR) was 31.3%, progression-free survival (PFS) was 10 months, survival probabilities at 6 months was 86.7% (95% CI, 81.0-92.8%), at 9 months was 73.5% (95% CI, 66.2-81.7%), at 12 months was 66.5% (95% CI, 58.6-75.4%), while at 24 months survival was 36.6% (95% CI:28.2%; 47.3%). irAEs of World Health Organization (WHO) Toxicity Scale grade 1, 2, 3, and 4 were observed in 23.66%, 16.03%, 6.11%, and 2.29% of patients, respectively. Our results suggest that the irAEs profile of the combined treatment is safer than that of the established protocols without compromising efficacy.

Trimethylamine-N-oxide is present in human follicular fluid and is a negative predictor of embryo quality.

STUDY QUESTION: Are levels of trimethylamine-N-oxide (TMAO) in human follicular fluid (FF) related to IVF outcomes? SUMMARY ANSWER: Higher levels of TMAO are a negative predictor of oocyte fertilization and embryo quality. WHAT IS KNOWN ALREADY: TMAO is a metabolic product of dietary choline and l-carnitine produced via subsequent enzymatic modifications by the intestinal microbiota and hepatocytes. TMAO promotes inflammatory and oxidative stress pathways and has been characterized as a causative biomarker for the development of cardiometabolic disease. STUDY DESIGN, SIZE, DURATION: For the present cross-sectional study, samples (FF and plasma) from 431 modified natural cycle (MNC)-IVF cycles of 132 patients were collected prospectively between October 2014 and March 2018 in a single academic medical center. PARTICIPANTS/MATERIALS, SETTING, METHODS: TMAO and its precursors (choline, l-carnitine and gamma-butyrobetaine) were measured by ultra-high-performance liquid chromatography/mass spectrometry in (i) matched FF and plasma from 63 MNC-IVF cycles, in order to compare metabolite levels in the two matrices and (ii) FF from 232 MNC-IVF cycles in which only one oocyte was retrieved at follicular puncture. The association between metabolite levels and oocyte fertilization, embryo fragmentation percentage, embryo quality and the occurrence of pregnancy was analyzed using multilevel generalized estimating equations with adjustment for patient and cycle characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: The level of choline was higher in FF as compared to matched plasma (P < 0.001). Conversely, the levels of TMAO and gamma-butyrobetaine were lower in FF as compared to plasma (P = 0.001 and P = 0.075, respectively). For all metabolites, there was a positive correlation between FF and plasma levels. Finally, levels of TMAO and its gut-derived precursor gamma-butyrobetaine were lower in FF from oocytes that underwent normal fertilization (TMAO: odds ratio [OR] 0.66 [0.49-0.90], P = 0.008 per 1.0-µmol/L increase; gamma-butyrobetaine: OR 0.77 [0.60-1.00], P = 0.047 per 0.1-µmol/L increase) and developed into top-quality embryos (TMAO: OR 0.56 [0.42-0.76], P < 0.001 per 1.0-µmol/L increase; gamma-butyrobetaine: OR 0.79 [0.62-1.00], P = 0.050 per 0.1-µmol/L increase) than in FF from oocytes of suboptimal development. LIMITATIONS, REASONS FOR CAUTION: The individual contributions of diet, gut bacteria and liver to the metabolite pools have not been quantified in this analysis. WIDER IMPLICATIONS OF THE FINDINGS: More research on the contribution of diet and the effect of gut bacteria on FF TMAO is warranted. Since TMAO integrates diet, microbiota and genetic setup of the person, our results indicate potential important clinical implications for its use as biomarker for lifestyle interventions to improve fertility. STUDY FUNDING/COMPETING INTEREST(S): No external funding was received for this project. The Department of Obstetrics and Gynecology of the University Medical Center Groningen received an unrestricted educational grant of Ferring Pharmaceutical BV, the Netherlands. The authors have no other conflicts of interest. TRIAL REGISTRATION NUMBER: Netherlands Trial Register number NTR4409.

Human-started wildfires expand the fire niche across the United States.

The economic and ecological costs of wildfire in the United States have risen substantially in recent decades. Although climate change has likely enabled a portion of the increase in wildfire activity, the direct role of people in increasing wildfire activity has been largely overlooked. We evaluate over 1.5 million government records of wildfires that had to be extinguished or managed by state or federal agencies from 1992 to 2012, and examined geographic and seasonal extents of human-ignited wildfires relative to lightning-ignited wildfires. Humans have vastly expanded the spatial and seasonal "fire niche" in the coterminous United States, accounting for 84% of all wildfires and 44% of total area burned. During the 21-y time period, the human-caused fire season was three times longer than the lightning-caused fire season and added an average of 40,000 wildfires per year across the United States. Human-started wildfires disproportionally occurred where fuel moisture was higher than lightning-started fires, thereby helping expand the geographic and seasonal niche of wildfire. Human-started wildfires were dominant (>80% of ignitions) in over 5.1 million km2, the vast majority of the United States, whereas lightning-started fires were dominant in only 0.7 million km2, primarily in sparsely populated areas of the mountainous western United States. Ignitions caused by human activities are a substantial driver of overall fire risk to ecosystems and economies. Actions to raise awareness and increase management in regions prone to human-started wildfires should be a focus of United States policy to reduce fire risk and associated hazards.

Spatiotemporal prediction of wildfire size extremes with Bayesian finite sample maxima.

Wildfires are becoming more frequent in parts of the globe, but predicting where and when wildfires occur remains difficult. To predict wildfire extremes across the contiguous United States, we integrate a 30-yr wildfire record with meteorological and housing data in spatiotemporal Bayesian statistical models with spatially varying nonlinear effects. We compared different distributions for the number and sizes of large fires to generate a posterior predictive distribution based on finite sample maxima for extreme events (the largest fires over bounded spatiotemporal domains). A zero-inflated negative binomial model for fire counts and a lognormal model for burned areas provided the best performance. This model attains 99% interval coverage for the number of fires and 93% coverage for fire sizes over a six year withheld data set. Dryness and air temperature strongly predict extreme wildfire probabilities. Housing density has a hump-shaped relationship with fire occurrence, with more fires occurring at intermediate housing densities. Statistically, these drivers affect the chance of an extreme wildfire in two ways: by altering fire size distributions, and by altering fire frequency, which influences sampling from the tails of fire size distributions. We conclude that recent extremes should not be surprising, and that the contiguous United States may be on the verge of even larger wildfire extremes.

Polyclonal RB1 mutations and acquired resistance to CDK 4/6 inhibitors in patients with metastatic breast cancer.

Background: While deregulation of the cyclin D1-CDK4/6-retinoblastoma pathway is common in hormone receptor positive (HR+) breast cancer, Rb is usually intact in HR+ breast cancer, and targeted CDK 4/6 inhibitors that act upstream of Rb, are routinely being utilized in clinical practice. However, factors that can lead to clinical resistance to CDK 4/6 inhibitors are not known. Patients and methods: We identified patients who had pre- and post-genotyping in tissue and peripheral blood samples after receiving CDK 4/6 inhibitors. Genotyping was carried out in tumor tissue or blood collected before start of CDK 4/6 inhibitor and after disease progression on CDK 4/6 inhibitor, covering more than 90% of the coding region in RB1. Results: We identified detectable acquired RB1 mutations in circulating tumor DNA (ctDNA) after exposure to CDK4/6 inhibitor (palbociclib, palbociclib, ribociclib) for 5, 8, and 13 months, respectively, in three patients. The RB1 mutations included substitution in donor splicing site of exon 8 of the RB1 gene in patient #1; substitution in donor splicing site of exon 22 of RB1 gene, exon 19 deletion, exon 3 insertion in patient #2; and RB1 exon 16 H483Y mutation in patient #3. None of these RB1 mutations were present in the pre-CDK 4/6 specimen highlighting these molecular alterations, which lead to functional loss of Rb1, likely emerged under selective pressure from the CDK4/6 inhibitor potentially confering therapeutic resistance. Conclusion: This is the first clinical report to describe the emergence of somatic RB1 mutations after exposure to palbociclib or ribociclib, in patients with metastatic breast cancer. Further research is needed to validate these findings, identify how these mutations temporally emerge under selective pressure of CDK 4/6 inhibitor, and develop rational therapeutic strategies.

Extension of the phenotype of biallelic loss-of-function mutations in SLC25A46 to the severe form of pontocerebellar hypoplasia type I.

Biallelic mutations in SLC25A46, encoding a modified solute transporter involved in mitochondrial dynamics, have been identified in a wide range of conditions such as hereditary motor and sensory neuropathy with optic atrophy type VIB (OMIM: *610826) and congenital lethal pontocerebellar hypoplasia (PCH). To date, 18 patients from 13 families have been reported, presenting with the key clinical features of optic atrophy, peripheral neuropathy, and cerebellar atrophy. The course of the disease was highly variable ranging from severe muscular hypotonia at birth and early death to first manifestations in late childhood and survival into the fifties. Here we report on 4 patients from 2 families diagnosed with PCH who died within the first month of life from respiratory insufficiency. Patients from 1 family had pathoanatomically proven spinal motor neuron degeneration (PCH1). Using exome sequencing, we identified biallelic disease-segregating loss-of-function mutations in SLC25A46 in both families. Our study adds to the definition of the SLC25A46-associated phenotypic spectrum that includes neonatal fatalities due to PCH as the severe extreme.

Nutrient limitation in tropical secondary forests following different management practices.

Secondary forests now make up more than one-half of all tropical forests, and constraints on their biomass accumulation will influence the strength of the terrestrial carbon (C) sink in the coming decades. However the variance in secondary tropical forest biomass for a given stand age and climate is high and our understanding of why is limited. We constructed a model of terrestrial C, nitrogen (N), and phosphorus (P) cycling to examine the influence of disturbance and management practices on nutrient limitation and biomass recovery in secondary tropical forests. The model predicted that N limited the rate of forest recovery in the first few decades following harvest, but that this limitation switched to P approximately 30-40 yr after abandonment, consistent with field data on N and P cycling from secondary tropical forest chronosequences. Simulated biomass recovery agreed well with field data of biomass accumulation following harvest (R2  = 0.80). Model results showed that if all biomass remained on site following a severe disturbance such as blowdown, regrowth approached pre-disturbance biomass in 80-90 yr, and recovery was faster following smaller disturbances such as selective logging. Field data from regrowth on abandoned pastures were consistent with simulated losses of nutrients in soil organic matter, particularly P. Following any forest disturbance that involved the removal of nutrients (i.e., except blowdown), forest regrowth produced reduced biomass relative to the initial state as a result of nutrient loss through harvest, leaching and/or sequestration by secondary minerals. Differences in nutrient availability accounted for 49-94% of the variance in secondary forest biomass C at a given stand age. Management lessons from this study are the importance of strategies that help retain nutrients on site, recognizing the role of coarse woody debris in immobilization and subsequent release of nutrients, and the potential for nutrient additions to enhance biomass growth and recovery in secondary tropical forests.

Citrobacter freundii as a test platform for recombinant cellulose degradation systems.

Cellulosic biomass represents a huge reservoir of renewable carbon, but converting it into useful products is challenging. Attempts to transfer cellulose degradation capability to industrially useful micro-organisms have met with limited success, possibly due to poorly understood synergy between multiple cellulases. This is best studied by co-expression of many combinations of cellulases and associated proteins. Here, we describe the development of a test platform based on Citrobacter freundii, a cellobiose-assimilating organism closely related to Escherichia coli. Standard E. coli cloning vectors worked well in Cit. freundii. Expression of cellulases CenA and Cex of Cellulomonas fimi in Cit. freundii gave recombinant strains which were able to grow at the expense of cellulosic filter paper or microcrystalline cellulose (Avicel) in a mineral medium supplemented with a small amount of yeast extract. Periodic physical agitation of the cultures was highly beneficial for growth at the expense of filter paper. This provides a test platform for the expression of combinations of genes encoding biomass-degrading enzymes to develop effective genetic cassettes for degradation of different biomass streams. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofuels have been shown to be the best sustainable and alternative source of fuel to replace fossil fuels. Of the different types of feedstocks used for producing biofuels, lignocellulosic biomass is the most abundant. Converting this biomass to useful products has met with little success. Different approaches are being used and microbial platforms are the most promising and sustainable method. This study shows that Citrobacter freundii is a better test platform than Escherichia coli for testing various combinations of cellulases for the development of microbial systems for biomass conversion.

Presence of bile acids in human follicular fluid and their relation with embryo development in modified natural cycle IVF.

STUDY QUESTION: Are bile acids (BA) and their respective subspecies present in human follicular fluid (FF) and do they relate to embryo quality in modified natural cycle IVF (MNC-IVF)? SUMMARY ANSWER: BA concentrations are 2-fold higher in follicular fluid than in serum and ursodeoxycholic acid (UDCA) derivatives were associated with development of top quality embryos on Day 3 after fertilization. WHAT IS KNOWN ALREADY: Granulosa cells are capable of synthesizing BA, but a potential correlation with oocyte and embryo quality as well as information on the presence and role of BA subspecies in follicular fluid have yet to be investigated. STUDY DESIGN, SIZE, DURATION: Between January 2001 and June 2004, follicular fluid and serum samples were collected from 303 patients treated in a single academic centre that was involved in a multicentre cohort study on the effectiveness of MNC-IVF. PARTICIPANTS/MATERIALS, SETTING, METHODS: Material from patients who underwent a first cycle of MNC-IVF was used. Serum was not stored from all patients, and the available material comprised 156 follicular fluid and 116 matching serum samples. Total BA and BA subspecies were measured in follicular fluid and in matching serum by enzymatic fluorimetric assay and liquid chromatography-mass spectrometry, respectively. The association of BA in follicular fluid with oocyte and embryo quality parameters, such as fertilization rate and cell number, presence of multinucleated blastomeres and percentage of fragmentation on Day 3, was analysed. MAIN RESULTS AND THE ROLE OF CHANCE: Embryos with eight cells on Day 3 after oocyte retrieval were more likely to originate from follicles with a higher level of UDCA derivatives than those with fewer than eight cells (P < 0.05). Furthermore, follicular fluid levels of chenodeoxycholic derivatives were higher and deoxycholic derivatives were lower in the group of embryos with fragmentation compared with those without (each P < 0.05). Levels of total BA were 2-fold higher in follicular fluid compared with serum (P < 0.001), but had no predictive value for oocyte and embryo quality. LIMITATIONS, REASONS FOR CAUTION: Only samples originating from first cycle MNC-IVF were used, which resulted in 14 samples only from women with an ongoing pregnancy, therefore further prospective studies are required to confirm the association of UDCA with IVF pregnancy outcomes. The inter-cycle variability of BA levels in follicular fluid within individuals has yet to be investigated. We checked for macroscopic signs of contamination of follicular fluid by blood but the possibility that small traces of blood were present within the follicular fluid remains. Finally, although BA are considered stable when stored at -20°C, there was a time lag of 10 years between the collection and analysis of follicular fluid and serum samples. WIDER IMPLICATIONS OF THE FINDINGS: The favourable relation between UDCA derivatives in follicular fluid and good embryo development and quality deserves further prospective research, with live birth rates as the end-point. STUDY FUNDING/COMPETING INTERESTS: This work was supported by a grant from the Netherlands Organisation for Scientific Research (VIDI Grant 917-56-358 to U.J.F.T.). No competing interests are reported.

Structure and composition of altered riparian forests in an agricultural Amazonian landscape.

Deforestation and fragmentation influence the microclimate, vegetation structure, and composition of remaining patches of tropical forest. In the southern Amazon, at the frontier of cropland expansion, forests are converted and fragmented in a pattern that leaves standing riparian forests whose dimensions are mandated by the Brazilian National Forest Code. These altered riparian forests share many characteristics of well-studied upland forest fragments, but differ because they remain connected to larger areas of forest downstream, and because they may experience wetter soil conditions because reduction of forest cover in the surrounding watershed raises groundwater levels and increases stream runoff. We compared forest regeneration, structure, composition, and diversity in four areas of intact riparian forest and four areas each of narrow, medium, and wide altered riparian forests that have been surrounded by agriculture since the early 1980s. We found that seedling abundance was reduced by as much as 64% and sapling abundance was reduced by as much as 67% in altered compared to intact riparian forests. The most pronounced differences between altered and intact forest occurred near forest edges and within the narrowest sections of altered riparian forests. Woody plant species composition differed and diversity was reduced in altered forests compared to intact riparian forests. However, despite being fragmented for several decades, large woody plant biomass and carbon storage, the number of live or dead large woody plants, mortality rates, and the size distribution of woody plants did not differ significantly between altered and intact riparian forests. Thus, even in these relatively narrow forests with high edge: area ratios, we saw no evidence of the increases in mortality and declines in biomass that have been found in other tropical forest fragment studies. However, because of the changes in both species community and reduced regeneration, it is unclear how long this relative lack of change will be sustained. Additionally, Brazil recently passed a law in their National Forest Code allowing narrower riparian buffers than those studied here in restored areas, which could affect their long-term sustainability.

BAHA Attract to Osia conversion patients: comparison of the two systems and long-term outcomes.

OBJECTIVE: Osia is a new, transcutaneous, active bone-conduction implant. This study aimed to compare the BAHA Attract and the first-generation Osia system after BAHA Attract to Osia conversion surgery. METHOD: Five patients who had previously used the BAHA Attract system were converted to the first generation of the Osia system. Surgical aspects of the two different systems, audiological performance and subjective opinions of the patients were investigated. Pure tone audiometry and speech audiometry in quiet was performed with each patient's BAHA 5 sound processor on Attract, and the test battery was repeated six weeks after the Attract to Osia conversion and at different time points after the first fitting. Details of the surgery and patients' feedback were analysed. RESULTS: Audiology tests showed significant improvement when using either system; however, the Osia system performance was better. Based on patient feedback, all the five implantees preferred the Osia system. CONCLUSION: The study results suggest that the Osia system is a safe and powerful hearing implant that provides good clinical outcomes.

Microcephalic osteodysplastic primordial dwarfism type I with biallelic mutations in the RNU4ATAC gene.

Microcephalic osteodysplastic primordial dwarfism type I (MOPD I) is a rare autosomal recessive developmental disorder characterized by extreme intrauterine growth retardation, severe microcephaly, central nervous system abnormalities, dysmorphic facial features, skin abnormalities, skeletal changes, limb deformations, and early death. Recently, mutations in the RNU4ATAC gene, which encodes U4atac, a small nuclear RNA that is a crucial component of the minor spliceosome, were found to cause MOPD I. MOPD I is the first disease known to be associated with a defect in small nuclear RNAs. We describe here the clinical and molecular data for 17 cases of MOPD I, including 15 previously unreported cases, all carrying biallelic mutations in the RNU4ATAC gene.

Water resources and land use and cover in a humid region: the southeastern United States.

It is widely recognized that forest and water resources are intricately linked. Globally, changes in forest cover to accommodate agriculture and urban development introduce additional challenges for water management. The U.S. Southeast typifies this global trend as predictions of land-use change and population growth suggest increased pressure on water resources in coming years. Close attention has long been paid to interactions between people and water in arid regions; however, based on information from regions such as the Southeast, it is evident that much greater focus is required to sustain a high-quality water supply in humid areas as well. To that end, we review hydrological, physicochemical, biological, and human and environmental health responses to conversion of forests to agriculture and urban land uses in the Southeast. Commonly, forest removal leads to increased stream sediment and nutrients, more variable flow, altered habitat and stream and riparian communities, and increased risk of human health effects. Although indicators such as the percentage of impervious cover signify overall watershed alteration, the threshold to disturbance, or the point at which effects can been observed in stream and riparian parameters, can be quite low and often varies with physiographic conditions. In addition to current land use, historical practices can greatly influence current water quality. General inferences of this study may extend to many humid regions concerning climate, environmental thresholds, and the causes and nature of effects.

Risky Development: Increasing Exposure to Natural Hazards in the United States.

Losses from natural hazards are escalating dramatically, with more properties and critical infrastructure affected each year. Although the magnitude, intensity, and/or frequency of certain hazards has increased, development contributes to this unsustainable trend, as disasters emerge when natural disturbances meet vulnerable assets and populations. To diagnose development patterns leading to increased exposure in the conterminous United States (CONUS), we identified earthquake, flood, hurricane, tornado, and wildfire hazard hotspots, and overlaid them with land use information from the Historical Settlement Data Compilation data set. Our results show that 57% of structures (homes, schools, hospitals, office buildings, etc.) are located in hazard hotspots, which represent only a third of CONUS area, and ∼1.5 million buildings lie in hotspots for two or more hazards. These critical levels of exposure are the legacy of decades of sustained growth and point to our inability, lack of knowledge, or unwillingness to limit development in hazardous zones. Development in these areas is still growing more rapidly than the baseline rates for the nation, portending larger future losses even if the effects of climate change are not considered.

Polymorphisms of beta defensins are associated with the risk of severe acute pancreatitis.

AIMS: Bacterial translocation from the intestinal tract plays an important role in severe acute pancreatitis (AP). Human ß-defensins are a family of antimicrobial peptides present at the mucosal surface. The aim of this study was to investigate the relevance of single nucleotide polymorphisms (SNPs) in the DEFB1 gene and copy number polymorphisms of the DEFB4 genes in AP. METHODS: 124 AP patients (30 with mild and 94 with severe disease) and 100 healthy controls were enrolled in the study. Three SNPs of the DEFB1 gene [G-20A (c.-20G→A), C-44G (c.-44C→G) and G-52A (c.-52G→A)] were genotyped by Custom TaqMan assay. The DEFB4 gene copy number was determined by means of a TaqMan real-time PCR assay. RESULTS: Significantly higher frequencies of the AA genotype of G-20A (c.-20G→A) and the AA genotype of G-52A (c.-52G→A) were observed among the patients with severe AP (SAP) compared with the healthy controls (38 vs. 20 and 41 vs. 18%, respectively). The GG protective genotype of C-44G (c.-44C→G) SNP was much less frequent (1%) among the patients than among the controls (9%). A higher frequency of a lower (<4) copy number of the DEFB4 gene was observed in the patients with SAP compared with the healthy controls (62 vs. 24%, respectively). CONCLUSIONS: The variations in the genes encoding human ß-defensin-1 and -2 may be associated with the risk of SAP. and IAP.

First Trimester Ultrasound Diagnosis of Right Aortic Arch (RAA).

OBJECTIVES: In the present research we proposed to evaluate the cases diagnosed in the first trimester of pregnancy by ultrasound with RAA, knowing the fact that although, in most cases the disease is isolated and asymptomatic, in some cases the presence of RAA can be associated with other fetal structural abnormalities that must be detected and monitored during pregnancy. We established correlations between the postnatal or anatomopathological examination (in cases ended by therapeutic abortion) and the presence of RAA detected in the first trimester. MATERIAL AND METHOD: We conducted a retrospective analytical study that investigated the role of the RAA early detection (isolated or associated with other cardiac abnormalities) for a correct pregnancy monitoring and postpartum management. Between 2012 and 2018, patients admitted in the first Obstetrics and Gynecology Clinic-the Prenatal Diagnostic Unit-of the Emergency County Hospital from Craiova, were evaluated in the first trimester of pregnancy for genetic abnormalities and early morphology. The study material was represented by the patient's medical records (observation sheets, surgical protocol records, anatomopathological diagnostic records). The obtained information was stored in Microsoft Excel files and statistically processed. RESULTS: During the study period, 14 cases with right aortic arch were diagnosed in the first and second trimester of pregnancy. 4 cases were detected in the first trimester: 2 cases (50%) presented left ductus arteriosus (DA)-RAA type 2 ("U" sign) and 2 cases (50%) presented right DA-RAA type 1 (mirror image-"V" sign). RAA type 1 associated Tetralogy of Fallot in one case (25%) and in another one case (25%) the anomaly was isolated. RAA type 2 associated atrio-ventricular septal defect (AVSD) in one case (25%) and in another one case (25%) the anomaly was isolated. There were no fetal extracardiac structural abnormalities associated with the RAA diagnosis in the first trimester. CONCLUSIONS: Over a seven years study period (2012-2018), 14 cases with RAA in the first and second trimester of pregnancy were detected. In the low-risk pregnancies group, the first trimester incidence of the RAA was 0.11% and the association of congenital heart abnormalities was 50%.

Soil Carbon Dynamics in Soybean Cropland and Forests in Mato Grosso, Brazil.

Climate and land use models predict that tropical deforestation and conversion to cropland will produce a large flux of soil carbon (C) to the atmosphere from accelerated decomposition of soil organic matter (SOM). However, the C flux from the deep tropical soils on which most intensive crop agriculture is now expanding remains poorly constrained. To quantify the effect of intensive agriculture on tropical soil C, we compared C stocks, radiocarbon, and stable C isotopes to 2 m depth from forests and soybean cropland created from former pasture in Mato Grosso, Brazil. We hypothesized that soil disturbance, higher soil temperatures (+2°C), and lower OM inputs from soybeans would increase soil C turnover and deplete C stocks relative to nearby forest soils. However, we found reduced C concentrations and stocks only in surface soils (0-10 cm) of soybean cropland compared with forests, and these differences could be explained by soil mixing during plowing. The amount and Δ14C of respired CO2 to 50 cm depth were significantly lower from soybean soils, yet CO2 production at 2 m deep was low in both forest and soybean soils. Mean surface soil δ13C decreased by 0.5‰ between 2009 and 2013 in soybean cropland, suggesting low OM inputs from soybeans. Together these findings suggest the following: (1) soil C is relatively resistant to changes in land use and (2) conversion to cropland caused a small, measurable reduction in the fast-cycling C pool through reduced OM inputs, mobilization of older C from soil mixing, and/or destabilization of SOM in surface soils.

Acquired Resistance to Poly (ADP-ribose) Polymerase Inhibitor Olaparib in BRCA2-Associated Prostate Cancer Resulting From Biallelic BRCA2 Reversion Mutations Restores Both Germline and Somatic Loss-of-Function Mutations.

PARP1/2 inhibitors are effective against BRCA2-deficient tumors. The PARP inhibitor (PARPi) olaparib received FDA breakthrough designation for treatment of metastatic castration-resistant prostate cancers (CRPC) carrying mutations in BRCA1/2 or ATM genes. Emergent resistance to PARPi has been associated with tumor-specific BRCA2 mutations that revert the normal open reading frame rescuing homologous recombination. We describe a case of metastatic CRPC with germline BRCA2 mutation with acquired resistance to olaparib related to biallelic BRCA2 reversion mutations of both the germline and somatic loss of function alleles detected by circulating tumor DNA testing. We also summarize a retrospective analysis of 1,534 prostate cancer cases with ctDNA analysis showing a 1.6% incidence of germline BRCA2 mutations. Within the germline BRCA2-positive cases exposed to platinum chemotherapy or PARP inhibition, the prevalence of reversion mutations was 40%. This report documents the frequency of reversion mutations in a large cohort of prostate cancer patients carrying of BRCA mutations. It also shows the potential utility of ctDNA analyses for early detection of reversion mutation driving tumor resistance.