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PURPOSE: The Co-HCW study is a prospective, longitudinal, single-center observational study that aims to assess the SARS-CoV-2 seroprevalence and infection status in staff members of Jena University Hospital (JUH) in Jena, Germany. METHODS: This follow-up study covers the observation period from 19th May 2020 to 22nd June 2021. At each of the three voluntary study visits, participants filled out a questionnaire regarding their SARS-CoV-2 exposure and provided serum samples to detect specific SARS-CoV-2 antibodies. Participants who were tested positive for antibodies against nucleocapsid and/or spike protein without previous vaccination and/or reported a positive SARS-CoV-2 PCR test were regarded to have been infected with SARS-CoV-2. Multivariable logistic regression modeling was applied to identify potential risk factors for infected compared to non-infected participants. RESULTS: Out of 660 participants that were included during the first study visit, 406 participants (61.5%) were eligible for the final analysis as their COVID-19 risk area (high-risk n = 76; intermediate-risk n = 198; low-risk n = 132) did not change during the study. Forty-four participants [10.8%, 95% confidence interval (95%CI) 8.0-14.3%] had evidence of a current or past SARS-CoV-2 infection detected by serology (n = 40) and/or PCR (n = 28). No association between SARS-CoV-2 infection and the COVID-19 risk group according to working place was detected. However, exposure to a SARS-CoV-2 positive household member [adjusted OR (AOR) 4.46, 95% CI 2.06-9.65] or colleague (AOR 2.30, 95%CI 1.10-4.79) was found to significantly increase the risk of a SARS-CoV-2 infection. CONCLUSION: Our results demonstrate that non-patient-related SARS-CoV-2 exposure posed the highest infection risk for hospital staff members of JUH.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/diagnóstico , Estudios de Seguimiento , Estudios Seroepidemiológicos , Estudios Prospectivos , Personal de Hospital , Anticuerpos Antivirales , Hospitales Universitarios , Personal de SaludRESUMEN
Historically, observational information about atmospheric temperature has been limited due to a lack of suitable measurements. Recent advances in satellite observations provide new insight into the fine structure of the free atmosphere, with the upper troposphere and lower stratosphere comprising essential components of the climate system. This is a prerequisite for understanding the complex processes of this part of the atmosphere, which is also known to have a large impact on surface climate. With unprecedented resolution, latest climate observations reveal a dramatic warming of the atmosphere. The tropical upper troposphere has already warmed about 1 K during the first two decades of the 21st century. The tropospheric warming extends into the lower stratosphere in the tropics and southern hemisphere mid-latitudes, forming a prominent hemispheric asymmetry in the temperature trend structure. Together with seasonal trend patterns in the stratosphere, this indicates a possible change in stratospheric circulation.
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During the COVID-19 pandemic, healthcare workers have a high workload and have been exposed to various psychosocial stressors. This study aimed to evaluate health workers during the COVID-19 pandemic in the world. The method used in this research is qualitative with a literature review approach. The data sources in this study were taken from the Scopus database using the keywords "health workers," "burnout," AND "coronavirus" from the time range of 2020 to April 25, 2022. From the determination of the time range, 150 documents emerged. This study revealed that the Pearson correlation between total burnout scale scores on healthcare workers, professionals, exhaustion, mental, stress, personal, depression, symptoms, emergency, system, job, and impact indicated that overall burnout scores were associated with depression and anxiety. Stress symptoms had correlation values ranging from 0.84 to 0.73. Job burnout had a significant relationship with exhaustion at 0.89; depression r = 0.73), impacting a score of 0.66. At the same time, the fulfillment of professional and interpersonal disengagement showed a Pearson correlation between the total burnout scale scores on health workers, professionals, exhaustion, mental, stress, personal, depression, symptoms, emergency, system, job, and impact. Overall, the participants in health care workers worldwide experienced high levels of psychological distress. We also found that health workers dealing with COVID-19 pandemic patients were more likely to experience depression, stress, and burnout than health staff who were not personally involved in medical work. Furthermore, this study will be a follow-up study using the Work Ability Index (WAI) to measure work ability and work satisfaction.
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The annual influenza vaccination has been officially recommended for medical staff in Germany since 1988. Nevertheless, the vaccination rate among medical staff is still low. The present study deals with the influenza vaccination rate of staff at a German University hospital over time as well as with the reasons that led to a positive vaccination decision and the barriers to acceptance of vaccination. For this purpose, the staff members received questionnaires in which they were asked about influenza vaccination and the reasons for or against vaccination. In addition, the questionnaire contains information on gender, age group, occupational group and presence of a chronic co-morbidity. Logistic regression analysis was used to investigate which of these predictors most strongly influenced the vaccination decision. It was shown that the reasons for or against vaccination differ significantly between the occupational groups and that the occupational group affiliation has the greatest influence on the vaccination decision in the comparison of the investigated predictors. In order to achieve a positive influence on vaccination acceptance, future measures should focus on increasing confidence in vaccination and on increasing the perception of risk from influenza illness. The findings may contribute to future targeted strategies to increase vaccination rates and suggest occupational group-specific interventions.
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The majority of risk loci identified by genome-wide association studies (GWAS) are in non-coding regions, hampering their functional interpretation. Instead, transcriptome-wide association studies (TWAS) identify gene-trait associations, which can be used to prioritize candidate genes in disease-relevant tissue(s). Here, we aimed to systematically identify susceptibility genes for coronary artery disease (CAD) by TWAS. We trained prediction models of nine CAD-relevant tissues using EpiXcan based on two genetics-of-gene-expression panels, the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) and the Genotype-Tissue Expression (GTEx). Based on these prediction models, we imputed gene expression of respective tissues from individual-level genotype data on 37,997 CAD cases and 42,854 controls for the subsequent gene-trait association analysis. Transcriptome-wide significant association (i.e. P < 3.85e-6) was observed for 114 genes. Of these, 96 resided within previously identified GWAS risk loci and 18 were novel. Stepwise analyses were performed to study their plausibility, biological function, and pathogenicity in CAD, including analyses for colocalization, damaging mutations, pathway enrichment, phenome-wide associations with human data and expression-traits correlations using mouse data. Finally, CRISPR/Cas9-based gene knockdown of two newly identified TWAS genes, RGS19 and KPTN, in a human hepatocyte cell line resulted in reduced secretion of APOB100 and lipids in the cell culture medium. Our CAD TWAS work (i) prioritized candidate causal genes at known GWAS loci, (ii) identified 18 novel genes to be associated with CAD, and iii) suggested potential tissues and pathways of action for these TWAS CAD genes.
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Enfermedad de la Arteria Coronaria , Estudio de Asociación del Genoma Completo , Animales , Enfermedad de la Arteria Coronaria/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo/métodos , Ratones , Polimorfismo de Nucleótido Simple , TranscriptomaRESUMEN
The Co-HCW study is a prospective cohort study among hospital staff, including healthcare workers (HCWs) and administration staff, at the Jena University Hospital (JUH), Germany. The objectives of this study were to assess SARS-CoV-2 IgG seroprevalence, individual exposure risk factors and compliance of HCWs to wear personal protective equipment (PPE). After the first nosocomial COVID-19 outbreak at JUH, mandatory masking was implemented on 20th March 2020. We evaluated point seroprevalence using two IgG detecting immunoassays and issued a questionnaire to assess COVID-19 exposure, clinical symptoms and compliance to wear PPE. Antibody retesting was offered to participants with a divergent result of both immunoassays 5-10 weeks after the first test. Between 19th May and 19th June 2020, we analysed 660 participants [out of 3,228; 20.4%]. Among them, 212 participants (32.1%) had received a previous COVID-19 test. Four of them (1.9%) reported a positive test result. After recruitment, 18 participants (2.7%) had SARS-CoV-2 antibodies in at least one immunoassay. Overall, 21 participants (3.2%) had any evidence of a past or current SARS-CoV-2 infection. Among them, 13 (61.9%) were not aware of direct COVID-19 exposure and 9 (42.9%) did not report any clinical symptoms. COVID-19 exposure at home (adjusted OR (aOR) with 95% CI: 47.82 (5.49, 416.62)) was associated with SARS-CoV-2 seroprevalence. We observed no evidence for an association between seroprevalence and exposure at work (aOR 0.48 (0.13, 1.70)) or with COVID-19 risk area according to the working place (aOR for intermediate-risk vs. high-risk: 1.97 (0.42, 9.22), aOR for low-risk versus high-risk: 2.10 (0.40, 11.06); p = .655). Reported compliance of HCWs to wear PPE differed (p < .001) between working in high-risk (98.3%) and in intermediate-risk areas (69.8%). In conclusion, compared to administration staff, we observed no additional risk to acquire SARS-CoV-2 infections by patient care, probably due to high compliance to wear PPE.
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COVID-19 , Animales , COVID-19/epidemiología , COVID-19/veterinaria , Personal de Salud , Hospitales , Humanos , Personal de Hospital , Estudios Prospectivos , Factores de Riesgo , SARS-CoV-2 , Estudios SeroepidemiológicosRESUMEN
Tropopause height (H) is a sensitive diagnostic for anthropogenic climate change. Previous studies showed increases in H over 19802000 but were inconsistent in projecting H trends after 2000. While H generally responds to temperature changes in the troposphere and stratosphere, the relative importance of these two contributions is uncertain. Here, we use radiosonde balloon observations in the Northern Hemisphere (NH) over 20°N to 80°N to reveal a continuous rise of H over 19802020. Over 20012020, H increases at 50 to 60 m/decade, which is comparable to the trend over 19802000. The GPS radio occultation measurements from satellites and homogenized radiosonde records are in good agreement with those results. The continuous rise of the tropopause in the NH after 2000 results primarily from tropospheric warming. A large trend in H remains after major natural forcings for H are removed, providing further observational evidence for anthropogenic climate change.
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Wildfires are expected to become more frequent and intense in the future. They not only pose a serious threat to humans and ecosystems, but also affect Earth's atmosphere. Wildfire plumes can reach into the stratosphere, but little is known about their climate impact. Here, we reveal observational evidence that major wildfires can have a severe impact on the atmospheric temperature structure and short-term climate in the stratosphere. Using advanced satellite observation, we find substantial warming of up to 10 K of the lower stratosphere within the wildfire plumes during their early development. The short-term climate signal in the lower stratosphere lasts several months and amounts to 1 K for the Northern American wildfires in 2017, and up to striking 3.5 K for the Australian wildfires in 2020. This is stronger than any signal from recent volcanic eruptions. Such extreme events affect atmospheric composition and climate trends, underpinning their importance for future climate.
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To confirm discrepant SARS-CoV-2-IgG results in four standard assays we applied for the first time a prototype of a coronavirus IgG-line-blot which employs antigens from seasonal coronaviruses, SARS-1 and SARS-CoV-2 combined with avidity testing as a confirmatory tool in a follow-up of five cases including pre-pandemic samples.
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Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Inmunoglobulina G/sangre , Pandemias , SARS-CoV-2 , Adulto , Anticuerpos Antivirales/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
A detailed analysis of double tropopause (DT) occurrences requires vertically well resolved, accurate, and globally distributed information on the troposphere-stratosphere transition zone. Here, we use radio occultation observations from 2001 to 2018 with such properties. We establish a connection between El Niño-Southern Oscillation (ENSO) phases and the distribution of DTs by analyzing the global and seasonal DT characteristics. The seasonal distribution of DTs reveals several hotspot locations, such as near the subtropical jet stream and over high mountain ranges, where DTs occur particularly often. In this study, we detect a higher number of DTs during the cold La Niña state while warmer El Niño events result in lower DT rates, affecting the structure of the tropopause region. Close to the Niño 3 region, this relates to a much lower first lapse rate tropopause altitude during La Niña and corresponds to an apparent narrowing of the tropical belt there.
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Sequence variants of the microglial expressed TREM2 (triggering receptor expressed on myeloid cells 2) are a major risk factor for late onset Alzheimer's disease. TREM2 requires a stable interaction with DAP12 in the membrane to initiate signaling, which is terminated by TREM2 ectodomain shedding and subsequent intramembrane cleavage by γ-secretase. To understand the structural basis for the specificity of the intramembrane cleavage event, we determined the solution structure of the TREM2 transmembrane helix (TMH). Caused by the presence of a charged amino acid in the membrane region, the TREM2-TMH adopts a kinked structure with increased flexibility. Charge removal leads to TMH stabilization and reduced dynamics, similar to its structure in complex with DAP12. Strikingly, these dynamical features match with the site of the initial γ-secretase cleavage event. These data suggest an unprecedented cleavage mechanism by γ-secretase where flexible TMH regions act as key determinants of substrate cleavage specificity.
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Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Membrana Celular/metabolismo , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/metabolismo , Receptores Inmunológicos/química , Receptores Inmunológicos/metabolismo , Proteínas Adaptadoras Transductoras de Señales/química , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/genética , Secretasas de la Proteína Precursora del Amiloide/genética , Dicroismo Circular , Células HEK293 , Humanos , Espectroscopía de Resonancia Magnética , Glicoproteínas de Membrana/genética , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Microglía/metabolismo , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Mutación , Conformación Proteica en Hélice alfa , Dominios Proteicos , Receptores Inmunológicos/genética , Factores de Riesgo , Transducción de Señal/genéticaRESUMEN
A membrane protein's oligomeric state modulates its functionality in various cellular processes. Since membrane proteins have to be solubilized in an appropriate membrane mimetic, the use of classical biophysical methods to analyze protein oligomers is challenging. We here present a method to determine the number of membrane proteins inserted into lipid nanodiscs. It is based on the ability to selectively quantify the amount of a small and robust fusion protein that can be proteolytically cleaved off from a membrane protein after incorporation into lipid nanodiscs. A detailed knowledge of the number of membrane proteins per nanodisc at defined assembly conditions is essential to estimate the tendency for oligomerization, but also for guiding sample optimization for structural investigations that require the presence of a homogenous oligomeric state. We show that this method can efficiently be used to determine the number of VDAC1 channels in nanodiscs at various assembly conditions, as confirmed by negative stain EM. The presented method is suitable in particular for membrane proteins that cannot be probed easily by other methods such as single span transmembrane helices. This assay can be applied to any membrane protein that can be incorporated into a nanodisc without the requirement for special instrumentation and will thus be widely applicable and complementary to other methods that quantify membrane protein insertion in lipid nanodiscs.
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Membrana Dobles de Lípidos/química , Proteínas de la Membrana/química , Nanoestructuras/química , Canal Aniónico 1 Dependiente del Voltaje/genética , Fenómenos Biofísicos , Membrana Celular/química , Membrana Celular/genética , Humanos , Proteínas de la Membrana/genética , Fosfolípidos/química , Estructura Secundaria de Proteína , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Canal Aniónico 1 Dependiente del Voltaje/química , Proteína bcl-X/química , Proteína bcl-X/genéticaRESUMEN
Small volcanic eruptions and their effects have recently come into research focus. While large eruptions are known to strongly affect stratospheric temperature, the impacts of smaller eruptions are hard to quantify because their signals are masked by natural variability. Here, we quantify the temperature signals from small volcanic eruptions between 2002 and 2016 using new vertically resolved aerosol data and precise temperature observations from radio occultation. We find characteristic space-time signals that can be associated with specific eruptions. In the lower stratosphere, robust warming signals are observed, while in the midstratosphere also cooling signals of some eruptions appear. We find that the volcanic contribution to the temperature trend is up to 20%, depending on latitude and altitude. We conclude that detailed knowledge of the vertical structure of volcanic temperature impacts is crucial for comprehensive trend analysis in order to separate natural from anthropogenic temperature changes.
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The domestication of the fowl resulted in a large diversity of integumental structures in chicken breeds. Several integumental traits have been investigated from a developmental genetics perspective. However, their distribution among breeds and their developmental morphology remain unexplored. We constructed a discrete trait-breed matrix and conducted a disparity analysis to investigate the variation of these structures in chicken breeds; 20 integumental traits of 72 chicken breeds and the red junglefowl were assessed. The analyses resulted in slight groupings of breed types comparable to standard breed classification based on artificial selection and chicken type use. The red junglefowl groups together with bantams and European breeds. We provide new data on the red junglefowl and four chicken breeds, demonstrating where and when variation arises during embryonic development. We document variation in developmental timing of the egg tooth and feather formation, as well as other kinds of developmental patterning as in the anlagen of different type of combs. Changes in epithelial-mesenchymal signaling interactions may drive the highly diverse integument in chickens. Experimental and comparative work has revealed that the cranial neural crest mesenchyme mediates its interactions with the overlying epithelium and is the likely source of patterning that generates diversity in integumental structures.
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Cruzamiento , Pollos/fisiología , Desarrollo Embrionario/fisiología , Fenotipo , Carácter Cuantitativo Heredable , Animales , Embrión de Pollo , DomesticaciónRESUMEN
Ric-8A is a 530-amino acid cytoplasmic molecular chaperone and guanine nucleotide exchange factor (GEF) for i, q, and 12/13 classes of heterortrimeric G protein alpha subunits (Gα). We report the 2.2-Å crystal structure of the Ric-8A Gα-binding domain with GEF activity, residues 1-452, and is phosphorylated at Ser435 and Thr440. Residues 1-429 adopt a superhelical fold comprised of Armadillo (ARM) and HEAT repeats, and the C terminus is disordered. One of the phosphorylated residues potentially binds to a basic cluster in an ARM motif. Amino acid sequence conservation and published hydrogen-deuterium exchange data indicate repeats 3 through 6 to be a putative Gα-binding surface. Normal mode modeling of small-angle X-ray scattering data indicates that phosphorylation induces relative rotation between repeats 1-4, 5-6, and 7-9. 2D 1H-15N-TROSY spectra of [2H,15N]-labeled Gαi1 in the presence of R452 reveals chemical shift perturbations of the C terminus and Gαi1 residues involved in nucleotide binding.
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Subunidades alfa de la Proteína de Unión al GTP Gi-Go/química , Factores de Intercambio de Guanina Nucleótido/química , Proteínas Nucleares/química , Proteínas Recombinantes de Fusión/química , Secuencia de Aminoácidos , Animales , Sitios de Unión , Clonación Molecular , Cristalografía por Rayos X , Escherichia coli/genética , Escherichia coli/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/genética , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Factores de Intercambio de Guanina Nucleótido/genética , Factores de Intercambio de Guanina Nucleótido/metabolismo , Guanosina Trifosfato , Histidina/genética , Histidina/metabolismo , Modelos Moleculares , Mutación , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Oligopéptidos/genética , Oligopéptidos/metabolismo , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Multimerización de Proteína , Ratas , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
The impact of atmospheric blocking on European heat waves (HWs) and cold spells (CSs) is investigated for present and future conditions . A 50-member ensemble of the second generation Canadian Earth System Model is used to quantify the role of internal variability in the response to blocking. We find that the present blocking-extreme temperature link is well represented compared to ERA-Interim, despite a significant underestimation of blocking frequency in most ensemble members. Our results show a strong correlation of blocking with northern European HWs in summer, spring, and fall. However, we also find a strong anticorrelation between blocking and HW occurrence in southern Europe in all seasons. Blocking increases the CS frequency particularly in southern Europe in fall, winter, and spring but reduces it in summer. For the future we find that blocking will continue to play an important role in the development of both CSs and HWs in all seasons.
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Spring frosts, as experienced in Europe in April 2016 and 2017, pose a considerable risk to agricultural production, with the potential to cause significant damages to agricultural yields. Meteorological blocking events (stable high-pressure systems) have been shown to be one of the factors that trigger cold spells in spring. While current knowledge does not allow for drawing conclusions as to any change in future frequency and duration of blocking episodes due to climate change, the combination of their stable occurrence with the biological system under a warming trend can lead to economic damage increases. To evaluate future frost risk for apple producers in south-eastern Styria, we combine a phenological sequential model with highly resolved climate projections for Austria. Our model projects a mean advance of blooming of -1.6 ± 0.9 days per decade, shifting the bloom onset towards early April by the end of the 21st century. Our findings indicate that overall frost risk for apple cultures will remain in a warmer climate and potentially even increase due to a stronger connection between blocking and cold spells in early spring that can be identified from observational data. To prospectively deal with frost risk, measures are needed that either stabilize crop yields or ensure farmers' income by other means. We identify appropriate adaptation measures and relate their costs to the potential frost risk increase. Even if applied successfully, the costs of these measures in combination with future residual damages represent additional climate change related costs.
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Clima , Producción de Cultivos , Congelación , Malus , Modelos Teóricos , Aclimatación , Austria , Producción de Cultivos/economía , Flores , Predicción , Malus/fisiología , RiesgoRESUMEN
Simulated stratospheric temperatures over the period 1979-2016 in models from the Chemistry-Climate Model Initiative (CCMI) are compared with recently updated and extended satellite observations. The multi-model mean global temperature trends over 1979- 2005 are -0.88 ± 0.23, -0.70 ± 0.16, and -0.50 ± 0.12 K decade-1 for the Stratospheric Sounding Unit (SSU) channels 3 (~40-50 km), 2 (~35-45 km), and 1 (~25-35 km), respectively. These are within the uncertainty bounds of the observed temperature trends from two reprocessed satellite datasets. In the lower stratosphere, the multi-model mean trend in global temperature for the Microwave Sounding Unit channel 4 (~13-22 km) is -0.25 ± 0.12 K decade-1 over 1979-2005, consistent with estimates from three versions of this satellite record. The simulated stratospheric temperature trends in CCMI models over 1979-2005 agree with the previous generation of chemistry-climate models. The models and an extended satellite dataset of SSU with the Advanced Microwave Sounding Unit-A show weaker global stratospheric cooling over 1998-2016 compared to the period of intensive ozone depletion (1979-1997). This is due to the reduction in ozone-induced cooling from the slow-down of ozone trends and the onset of ozone recovery since the late 1990s. In summary, the results show much better consistency between simulated and satellite observed stratospheric temperature trends than was reported by Thompson et al. (2012) for the previous versions of the SSU record and chemistry-climate models. The improved agreement mainly comes from updates to the satellite records; the range of simulated trends is comparable to the previous generation of models.