| 1. |
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| 2. |
- Razis, E., et al.
(författare)
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Assessment of the management of carcinomatous meningitis from breast cancer globally: a study by the Breast International Group Brain Metastasis Task Force
- 2022
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carcinomatous meningitis (CM) is a severe complication of breast cancer. The Breast International Group (BIG) carried out a survey to describe the approach to CM internationally. Patients and methods: A questionnaire on the management of CM was developed by the Brain Metastases Task Force of BIG and distributed to its groups, requesting one answer per group site. Results: A total of 241 sites responded, 119 from Europe, 9 from North America, 39 from Central/South America, 58 from Asia, and 16 in Australia/New Zealand, with 24.5% being general hospitals with oncology units, 44.4% university hospitals, 22.4% oncology centers, and 8.7% private hospitals. About 56.0% of sites reported seeing <5 cases annually with 60.6% reporting no increase in the number of cases of CM recently. Nearly 63.1% of sites investigate for CM when a patient has symptoms or radiological evidence, while 33.2% investigate only for symptoms. For diagnosis, 71.8% of sites required a positive cerebrospinal fluid cytology, while magnetic resonance imaging findings were sufficient in 23.7% of sites. Roughly 97.1% of sites treat CM and 51.9% also refer patients to palliative care. Intrathecal therapy is used in 41.9% of sites, mainly with methotrexate (74.3%). As many as 20 centers have a national registry for patients with breast cancer with central nervous system metastases and of those 5 have one for CM. Most (90.9%) centers would be interested in participating in a registry as well as in studies for CM, the latter preferably (62.1%) breast cancer subtype specific. Conclusions: This is the first study to map out the approach to CM from breast cancer globally. Although guidelines with level 1 evidence are lacking, there is a high degree of homogeneity in the approach to CM globally and great interest for conducting studies in this area.
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| 3. |
- Guerova, G., et al.
(författare)
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National Status Reports
- 2020
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Ingår i: Advanced GNSS Tropospheric Products for Monitoring Severe Weather Events and Climate. - Cham : Springer International Publishing. - 9783030139001 ; , s. 403-481
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In this section a summary of the national progress reports is given. GNSS4SWEC Management Committee (MC) members provided outline of the work conducted in their countries combining input from different partners involved. In the COST Action paticipated member from 32 COST countries, 1 Near Neighbour Country and 8 Intrantional Partners from Australia, Canada, Hong Kong and USA. The text reflects the state as of 1 January 2018.
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| 4. |
- Kennedy, K. M., et al.
(författare)
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Questioning the fetal microbiome illustrates pitfalls of low-biomass microbial studies
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 613:7945, s. 639-649
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Tidskriftsartikel (refereegranskat)abstract
- Whether the human fetus and the prenatal intrauterine environment (amniotic fluid and placenta) are stably colonized by microbial communities in a healthy pregnancy remains a subject of debate. Here we evaluate recent studies that characterized microbial populations in human fetuses from the perspectives of reproductive biology, microbial ecology, bioinformatics, immunology, clinical microbiology and gnotobiology, and assess possible mechanisms by which the fetus might interact with microorganisms. Our analysis indicates that the detected microbial signals are likely the result of contamination during the clinical procedures to obtain fetal samples or during DNA extraction and DNA sequencing. Furthermore, the existence of live and replicating microbial populations in healthy fetal tissues is not compatible with fundamental concepts of immunology, clinical microbiology and the derivation of germ-free mammals. These conclusions are important to our understanding of human immune development and illustrate common pitfalls in the microbial analyses of many other low-biomass environments. The pursuit of a fetal microbiome serves as a cautionary example of the challenges of sequence-based microbiome studies when biomass is low or absent, and emphasizes the need for a trans-disciplinary approach that goes beyond contamination controls by also incorporating biological, ecological and mechanistic concepts.
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| 5. |
- Andaji-Garmaroudi, Z., et al.
(författare)
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Elucidating and Mitigating Degradation Processes in Perovskite Light-Emitting Diodes
- 2020
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Ingår i: Advanced Energy Materials. - : Wiley-VCH Verlag. - 1614-6832 .- 1614-6840. ; 10:48
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Tidskriftsartikel (refereegranskat)abstract
- Halide perovskites have attracted substantial interest for their potential as disruptive display and lighting technologies. However, perovskite light-emitting diodes (PeLEDs) are still hindered by poor operational stability. A fundamental understanding of the degradation processes is lacking but will be key to mitigating these pathways. Here, a combination of in operando and ex situ measurements to monitor the performance degradation of (Cs0.06FA0.79MA0.15)Pb(I0.85Br0.15)3 PeLEDs over time is used. Through device, nanoscale cross-sectional chemical mapping, and optical spectroscopy measurements, it is revealed that the degraded performance arises from an irreversible accumulation of bromide content at one interface, which leads to barriers to injection of charge carriers and thus increased nonradiative recombination. This ionic segregation is impeded by passivating the perovskite films with potassium halides, which immobilizes the excess halide species. The passivated PeLEDs show enhanced external quantum efficiency (EQE) from 0.5% to 4.5% and, importantly, show significantly enhanced stability, with minimal performance roll-off even at high current densities (>200 mA cm−2). The decay half-life for the devices under continuous operation at peak EQE increases from <1 to ≈15 h through passivation, and ≈200 h under pulsed operation. The results provide generalized insight into degradation pathways in PeLEDs and highlight routes to overcome these challenges.
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| 6. |
- Dar, Pe'er, et al.
(författare)
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Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome.
- 2022
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 227:1
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Tidskriftsartikel (refereegranskat)abstract
- Prenatal screening has historically focused primarily on detection of fetal aneuploidies. Cell-free DNA (cfDNA) now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (22q11.2DS or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2DS, large cohort studies with postnatal confirmatory testing to assess test performance have not been reported.To assess the performance of SNP-based cfDNA prenatal screening for detection of 22q11.2DS.Patients who had SNP-based cfDNA prenatal screening for 22q11.2DS were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation with chromosomal microarray. The primary outcome was sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cfDNA for detection of all deletions, including the classical deletion and nested deletions that are ≥500kb, in the 22q11.2 low copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2DS and performance of an updated cfDNA algorithm that was evaluated blinded to pregnancy outcome.Of 20,887 women enrolled, genetic outcome was available in 18,289 (87.6%). Twelve 22q11.2DS cases were confirmed in the cohort, including five (41.7%) nested deletions, yielding a prevalence of 1:1524. In the total cohort, cfDNA reported 17,976 (98.3%) as low risk for 22q11.2DS and 38 (0.2%) as high-risk; 275 (1.5%) were non-reportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% CI: 42.8, 94.5); specificity of 99.84% (95% CI: 99.77, 99.89); PPV of 23.7% (95% CI: 11.44, 40.24) and NPV of 99.98% (95% CI: 99.95, 100). None of the cases with a non-reportable result was diagnosed with 22q11.2DS. The updated algorithm detected 10/12 cases (83.3%; 95% CI: 51.6-97.9) with a lower false positive rate (0.05% vs. 0.16%, p<0.001) and a PPV of 52.6% (10/19; 95% CI 28.9-75.6).Noninvasive cfDNA prenatal screening for 22q11.2DS can detect most affected cases, including smaller nested deletions, with a low false positive rate.
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| 7. |
- Dar, Pe'er, et al.
(författare)
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Cell-free DNA screening for trisomies 21, 18 and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation
- 2022
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 227:2
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Tidskriftsartikel (refereegranskat)abstract
- Cell-free DNA (cfDNA) non-invasive prenatal screening for trisomy (T) 21, 18, and 13 has been rapidly adopted into clinical practice. However, prior studies are limited by lack of follow up genetic testing to confirm outcomes and accurately assess test performance, particularly in women at low-risk for aneuploidy.To compare the performance of cfDNA screening for T21, T18 and T13 between women at low and high-risk for aneuploidy in a large, prospective cohort with genetic confirmation of results.A multicenter prospective observational study at 21 centers in 6 countries. Women who had SNP-based cfDNA screening for T21, T18 and T13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. Test performance and test failure (no-call) rates were assessed for the cohort and women with low and high prior risk for aneuploidy were compared. An updated cfDNA algorithm, blinded to pregnancy outcome, was also assessed.20,194 were enrolled at median gestational age of 12.6 weeks (IQR:11.6, 13.9). Genetic outcomes were confirmed in 17,851 (88.4%): 13,043 (73.1%) low-risk and 4,808 (26.9%) high-risk for aneuploidy. Overall, 133 trisomies were diagnosed (100 T21; 18 T18; 15 T13). cfDNA screen positive rate was lower in low- vs. high-risk (0.27% vs. 2.2%, p<0.0001). Sensitivity and specificity were similar between groups. The positive predictive value (PPV) for the low and high-risk groups was 85.7% vs. 97.5%, p=0.058 for T21; 50.0% vs. 81.3%, p=0.283 for T18; and 62.5% vs. 83.3, p=0.58 for T13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. Trisomy rate was higher in the 287 with no-call results than patients with a result on a first draw (2.8% vs. 0.7%, p=0.001). The updated algorithm showed similar sensitivity and specificity to the study algorhitm with a lower no-call rate.In women at low-risk for aneuploidy, SNP-based cfDNA has high sensitivity and specificity, PPV of 85.7% for T21 and 74.3% for the three common trisomies. Patients who receive a no-call result are at increased risk of aneuploidy and require additional investigation.
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| 8. |
- Martin, Kimberly, et al.
(författare)
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Impact of high-risk prenatal screening results for 22q11.2 deletion syndrome on obstetric and neonatal management: Secondary analysis from the SMART study
- 2023
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Ingår i: Prenatal Diagnosis. - 0197-3851 .- 1097-0223. ; 43:13, s. 1574-1580
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Tidskriftsartikel (refereegranskat)abstract
- Objective: One goal of prenatal genetic screening is to optimize perinatal care and improve infant outcomes. We sought to determine whether high-risk cfDNA screening for 22q11.2 deletion syndrome (22q11.2DS) affected prenatal or neonatal management. Methods: This was a secondary analysis from the SMART study. Patients with high-risk cfDNA results for 22q11.2DS were compared with the low-risk cohort for pregnancy characteristics and obstetrical management. To assess differences in neonatal care, we compared high-risk neonates without prenatal genetic confirmation with a 1:1 matched low-risk cohort. Results: Of 18,020 eligible participants enrolled between 2015 and 2019, 38 (0.21%) were high-risk and 17,982 (99.79%) were low-risk for 22q11.2DS by cfDNA screening. High-risk participants had more prenatal diagnostic testing (55.3%; 21/38 vs. 2.0%; 352/17,982, p<0.001) and fetal echocardiography (76.9%; 10/13 vs. 19.6%; 10/51, p<0.001). High-risk newborns without prenatal diagnostic testing had higher rates of neonatal genetic testing (46.2%; 6/13 vs. 0%; 0/51, P<0.001), echocardiography (30.8%; 4/13 vs. 4.0%; 2/50, p=0.013), evaluation of calcium levels (46.2%; 6/13 vs. 4.1%; 2/49, P<0.001) and lymphocyte count (53.8%; 7/13 vs. 15.7%; 8/51, p=0.008). Conclusions: High-risk screening results for 22q11.2DS were associated with higher rates of prenatal and neonatal diagnostic genetic testing and other 22q11.2DS-specific evaluations. However, these interventions were not universally performed, and >50% of high-risk infants were discharged without genetic testing, representing possible missed opportunities to improve outcomes for affected individuals.
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| 9. |
- Martin, Kimberly, et al.
(författare)
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Performance of prenatal cfDNA screening for sex chromosomes.
- 2023
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Ingår i: Genetics in medicine : official journal of the American College of Medical Genetics. - 1530-0366. ; 25:8
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Tidskriftsartikel (refereegranskat)abstract
- To assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCA) in an unselected obstetrical population with genetic confirmation.This was a planned secondary analysis of the multicenter, prospective SMART study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCTs; 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies.17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs and fetal sex was determined in 17,297, 10,333 and 14,486 pregnancies, respectively. Sensitivity, specificity, and PPV of cfDNA were 83.3%, 99.9%, and 22.7% for MX, and 70.4%, 99.9%, and 82.6% for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%.Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, while the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.
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| 10. |
- Norton, Mary E, et al.
(författare)
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Obstetrical, perinatal and genetic outcomes associated with non-reportable prenatal cell free DNA screening results.
- 2023
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 229:3
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Tidskriftsartikel (refereegranskat)abstract
- The clinical implications of non-reportable cfDNA screening results are uncertain, but this may reflect poor placental implantation in some cases and be associated with adverse obstetrical and perinatal outcomes.To assess the outcomes of pregnancies with non-reportable cell-free DNA (cfDNA) screening in a cohort of patients with complete genetic and obstetric outcomes.This was a prespecified secondary analysis of a multicenter prospective observational study of prenatal cfDNA screening for fetal aneuploidy and 22q11.2 deletion syndrome. Participants who underwent cfDNA screening from April 2015 through January 2019 were offered participation. Obstetric outcomes and neonatal genetic testing results were collected from 21 primary care and referral centers in the US, Europe, and Australia. The primary outcome was risk for adverse obstetrical and perinatal outcomes (aneuploidy, preterm birth (PTB) at <28, <34, and <37 weeks' gestation, preeclampsia, small for gestational age (SGA) or birthweight <10th percentile for gestational week, and a composite outcome that included PTB<37 weeks, preeclampsia, SGA, and stillbirth>20 weeks') after non-reportable cfDNA screening due to low fetal fraction or other causes. Multivariable analyses were performed, adjusting for variables known to be associated with obstetrical and perinatal outcomes, non-reportable results, or fetal fraction.In total, 25,199 pregnant individuals were screened, and 20,194 were enrolled. Genetic confirmation was missing in 1165 (5.8%), 1085 (5.4%) were lost to follow-up, and 93 (0.5%) withdrew; the final study cohort included 17,851 (88.4%) participants who had cfDNA, fetal or newborn genetic confirmatory testing, and obstetrical and perinatal outcomes collected. Results were non-reportable in 602 (3.4%). A sample was redrawn and testing again attempted in 427; in 112 (26.2%) results were again non-reportable. Non-reportable results were associated with higher BMI, chronic hypertension, later gestational age, lower fetal fraction, and Black race. Trisomy 13, 18, or 21 was confirmed in 1.6% with non-reportable tests vs. 0.7% with results (p=.013). PTB <28, 34, and 37 weeks, preeclampsia, and the composite outcome were higher after non-reportable results, and further increased with a second non-reportable test, while SGA was not increased. After adjustment for confounders, the aOR for aneuploidy was 2.2 (95% CI 1.1, 4.4) and 2.6 (95% CI 0.6, 10.8) and for the composite outcome was 1.5 (95% CI 1.2, 1.8) and 2.1 (95% CI 1.4, 3.2) after a first and second non-reportable test. In all, 94.9% of patients with non-reportable tests had a livebirth as compared to 98.8% with those with test results obtained (aOR for livebirth: 0.20 [95% CI 0.13-0.30]).Patients with non-reportable cfDNA results are at increased risk for a number of adverse outcomes, including aneuploidy as well as preeclampsia and preterm birth. They should be offered diagnostic genetic testing and clinicians should be aware of the increased risk of pregnancy complications.
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| 11. |
- Norton, Mary E., et al.
(författare)
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Obstetrical, Perinatal, and Genetic Outcomes Associated With Nonreportable Prenatal Cell-Free DNA Screening Results
- 2024
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Ingår i: OBSTETRICAL & GYNECOLOGICAL SURVEY. - 0029-7828 .- 1533-9866. ; 79:3, s. 146-148
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Tidskriftsartikel (refereegranskat)abstract
- Although cell-free DNA (cfDNA) prenatal screening is widely used and has high sensitivity and specificity, there are circumstances in which the screening does not provide an interpretable result. Although this is relatively uncommon, it happens enough that clinical implications and potential reasons for follow-up should be studied and assessed. This study was designed to evaluate outcomes for pregnancies with nonreportable results on cfDNA screening tests. This study was a secondary analysis of the data from a multicenter prospective observational study of cfDNA screening for aneuploidy and 22q11.2 deletion syndrome. All patients were tested for trisomies 13, 18, and 21, as well as the 22q11.2 deletion syndrome, and all patients had confirmatory testing on the newborns in addition to collecting obstetric and perinatal outcomes. Inclusion criteria were women older than 18 years and at greater than 9 weeks of gestation with a singleton pregnancy. Exclusion criteria were having received cfDNA screening results before enrollment, organ transplant, ovum donation, vanishing twin, or being unwilling to provide a newborn sample. The primary outcome was the rate of adverse obstetrical and perinatal outcomes, including aneuploidy; preterm birth at less than 28, 34, or 37 weeks' gestation; preeclampsia; small for gestational age birth; and a composite outcome that included preterm birth before 37 weeks, preeclampsia, stillbirth at greater than 20 weeks, and small for gestational age. Final analyses included 17,851 individuals who had cfDNA screening, confirmatory genetic testing on the newborn, and obstetrical and perinatal outcomes recorded. Nonreportable results were found in 602 individuals (3.4%) after the first draw, with 32.2% of these due to low fetal fraction. Another third of the cohort had patterns where the risk of aneuploidy was uninterpretable but with an adequate fetal fraction, and in the final third, the fetal fraction could not be measured. Of the original 602 cases of nonreportable findings, 427 had a second draw, with 112 of these (26.2%) again having nonreportable results. There were no significant differences in baseline characteristics of age and parity for those with successful versus nonreportable test results; gestational age was significantly higher in individuals with nonreportable results (14.4 vs 13.4 weeks, P < 0.001), as was body mass index (26.2 vs 31.3), and the rate of chronic hypertension (4.0% vs 9.7%). In this cohort, there were 133 genetically confirmed trisomies, with 100 fetuses with trisomy 21, 18 individuals with trisomy 18, and 15 individuals with trisomy 13. Overall, the rate of aneuploidy was 1.7% in individuals with nonreportable results, versus 0.7% in those with reported results (P = 0.013; adjusted odds ratio [aOR] 2.1; 95% confidence interval [CI], 1.1-4.0). Rates of preterm birth were also higher in those with nonreportable test results, with delivery at less than 34 weeks at 1.5% in those with a test result, 4.6% in those with one nonreportable test result and 6.9% in those with a second nonreportable test result (aOR, 2.2 and 2.7; 95% CI, 1.4-3.4 and 1.2-6.0, respectively). Preeclampsia showed a similar trend, with rates climbing from 3.9% in those with a reported result to 9.4% with 1 nonreportable result and 16.8% with 2 (aOR, 1.4 and 2.0; 95% CI, 1.0-1.9 and 1.1-3.7, respectively). Chances of live birth were significantly reduced in pregnancies with a nonreportable results (aOR, 0.20; 95% CI, 0.13-0.30), with the chances decreasing more after a second nonreportable test result (aOR, 0. 11; 95% CI, 0.06-0.23). The study found that nonreportable cfDNA screening results are associated with an increased risk for aneuploidy, preterm birth, and preeclampsia, with a gradient of increased risk with a second failed test. This adds to literature with conflicting findings surrounding obstetrical complications in those with altered cfDNA levels and with most studies largely focused on characteristics that may be predictive of a nonreportable result rather than outcomes associated with nonreportable results. These results can inform clinicians who have patients with nonreportable test results in a way that may help them provide better care; future research should focus on more fully understanding the adverse outcomes associated with nonreportable tests to maximize this ability for clinicians in the future. Further research should also focus on specific populations or diagnoses to understand if there are fundamental differences in different groups of individuals.
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