Long-term post-treatment stability of the Herbst appliance

The Herbst appliance is an adjunctive treatment for the correction of Class II malocclusions. Previous studies have indicated that the correction following the end of treatment frequently relapses. The purpose of this study was to assess the cephalometric changes during and following a treatment protocol of 12 months of Herbst appliance treatment followed by fixed appliance treatment, and 12 months of retention. The changes from the end of treatment to the retention recall were, on average, very small. The only statistically significant changes (Mixed linear model; P<0.05) observed were relapse in the ANB angle (-0.31 degrees;sd=0.88 ), overjet (0.49mm;sd=0.94) and overbite (0.55mm;sd=0.98). These changes were considered not clinically significant. The Class II correction effected by this treatment protocol appears stable one year out of treatment

Association Between Buprenorphine Use and Weight Gain in Pregnancy

Many pregnant women in the Appalachian Highlands region utilize buprenorphine as medication-assisted treatment (MAT) for opioid use disorder. This treatment is a tool used by medical teams to minimize patients’ drug cravings and optimize chances for a healthy pregnancy. Providers in our region have posited a relationship between MAT use and poor pregnancy weight gain based on clinical experience and observation. Appropriate weight gain in pregnancy is a critical determinant of pregnancy health; without it, pregnant mothers will possibly need nutritional supplementation. Therefore, understanding the association between buprenorphine use and weight gain may contribute to healthier pregnancies. In order to evaluate the association between buprenorphine use and weight gain in pregnant women using MAT, we conducted a retrospective chart review. A list of potential participants was generated by ETSU Population Health using ICD-10 codes. We enrolled patients who were cared for by ETSU Health and delivered babies between July 1, 2019 and June 30, 2021: a total of 504 patients. Of these, 96 were participants in the ETSU low-dose MAT clinic (Group 1), 109 were receiving MAT from other community clinics (Group 2), 97 were non-smoking women in the regular OB clinic (Group 3), and 202 were smoking women in the regular OB clinic (Group 4). Participants’ medical records were screened for inclusion and exclusion criteria. All patients were over age 18 with singleton pregnancies, had pregnancy care initiated in the first trimester, and delivered at or after 37 weeks’ gestation. Patients with confounding medical conditions including (but not limited to) Crohn’s disease, diabetes, heart disease, hypertension, fetal anomalies, or IUFD were excluded. In addition, patients were also excluded with BMI \u3e30 or undocumented BMI, prenatal care initiated after the first trimester, transfer to another practice or lost to follow up, or other documented drug abuse other than opiate use disorder. After consideration of the above criteria, 262 patients were excluded and 242 patients remained in the study. Of these, 53 were in Group 1, 53 in Group 2, 45 in Group 3, and 90 in Group 4. All protected health information was stored in the ETSU HIPAA-compliant REDCap server. At this time, the project is in the data analysis stage, with results expected by the end of March 2023. If an association between buprenorphine use and lower weight gain in pregnancy is discovered, these results can be used to recommend additional measures such as nutritional supplementation to optimize maternal and fetal health during pregnancy. Final conclusions will be drawn after data analysis is complete and associations, or lack thereof, can be fully evaluated. Based on observations of obstetric providers in the region, some association between lower weight gain and buprenorphine use is anticipated

LIPID MEDIATORS IN IMMUNE REGULATION AND RESOLUTION

We are all too familiar with the events that follow a bee sting – heat, redness, swelling and pain. These are Celsus’ four cardinal signs of inflammation that are driven by very well defined signals and hormones; in fact targeting the factors that drive this onset phase is the basis upon which most current anti‐inflammatory therapies were developed. We are also very well aware that within a few hours these cardinal signs normally disappear. In other words, inflammation resolves. When it does not, inflammation persists resulting in damaging chronic conditions. While inflammatory onset is actively driven so also is its resolution – years of research has identified novel internal counter‐regulatory signals that work together to switch off inflammation. Among these signals, lipids are potent signaling molecules that regulate an array of immune responses including vascular hyper reactivity and pain as well as leukocyte trafficking and clearance, so‐called resolution. Here, we collate bioactive lipid research to date and summarise the major pathways involved in their biosynthesis and their role in inflammation as well as resolution

Influence of cognitive reserve on neuropsychological functioning in bipolar disorder: Findings from a 5‐year longitudinal study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136365/1/bdi12470_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136365/2/bdi12470.pd

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.

Glioblastoma is the most common primary malignant brain tumor in adults and is associated with poor survival. The Ivy Foundation Early Phase Clinical Trials Consortium conducted a randomized, multi-institution clinical trial to evaluate immune responses and survival following neoadjuvant and/or adjuvant therapy with pembrolizumab in 35 patients with recurrent, surgically resectable glioblastoma. Patients who were randomized to receive neoadjuvant pembrolizumab, with continued adjuvant therapy following surgery, had significantly extended overall survival compared to patients that were randomized to receive adjuvant, post-surgical programmed cell death protein 1 (PD-1) blockade alone. Neoadjuvant PD-1 blockade was associated with upregulation of T cell- and interferon-γ-related gene expression, but downregulation of cell-cycle-related gene expression within the tumor, which was not seen in patients that received adjuvant therapy alone. Focal induction of programmed death-ligand 1 in the tumor microenvironment, enhanced clonal expansion of T cells, decreased PD-1 expression on peripheral blood T cells and a decreasing monocytic population was observed more frequently in the neoadjuvant group than in patients treated only in the adjuvant setting. These findings suggest that the neoadjuvant administration of PD-1 blockade enhances both the local and systemic antitumor immune response and may represent a more efficacious approach to the treatment of this uniformly lethal brain tumor

Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma.

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated protein CD79B

The SPARC water vapour assessment II: comparison of annual, semi-annual and quasi-biennial variations in stratospheric and lower mesospheric water vapour observed from satellites

In the framework of the second SPARC (Stratosphere-troposphere Processes And their Role in Climate) water vapour assessment (WAVAS-II), the amplitudes and phases of the annual, semi-annual and quasi-biennial variation in stratospheric and lower mesospheric water were compared using 30 data sets from 13 different satellite instruments. These comparisons aimed to provide a comprehensive overview of the typical uncertainties in the observational database which can be considered in subsequent observational and modelling studies. For the amplitudes, a good agreement of their latitude and altitude distribution was found. Quantitatively there were differences in particular at high latitudes, close to the tropopause and in the lower mesosphere. In these regions, the standard deviation over all data sets typically exceeded 0.2 ppmv for the annual variation and 0.1 ppmv for the semi-annual and quasi-biennial variation. For the phase, larger differences between the data sets were found in the lower mesosphere. Generally the smallest phase uncertainties can be observed in regions where the amplitude of the variability is large. The standard deviations of the phases for all data sets were typically smaller than a month for the annual and semi-annual variation and smaller than 5 months for the quasi-biennial variation. The amplitude and phase differences among the data sets are caused by a combination of factors. In general, differences in the temporal variation of systematic errors and in the observational sampling play a dominant role. In addition, differences in the vertical resolution of the data, the considered time periods and influences of clouds, aerosols as well as non-local thermodynamic equilibrium (NLTE) effects cause differences between the individual data sets

Validation of MIPAS HNO3 operational data

Nitric acid (HNO3) is one of the key products that are operationally retrieved by the European Space Agency (ESA) from the emission spectra measured by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) onboard ENVISAT. The product version 4.61/4.62 for the observation period between July 2002 and March 2004 is validated by comparisons with a number of independent observations from ground-based stations, aircraft/balloon campaigns, and satellites. Individual HNO3 profiles of the ESA MIPAS level-2 product show good agreement with those of MIPAS-B and MIPAS-STR (the balloon and aircraft version of MIPAS, respectively), and the balloon-borne infrared spectrometers MkIV and SPIRALE, mostly matching the reference data within the combined instrument error bars. In most cases differences between the correlative measurement pairs are less than 1 ppbv (5-10%) throughout the entire altitude range up to about 38 km (similar to 6 hPa), and below 0.5 ppbv (15-20% or more) above 30 km (similar to 17 hPa). However, differences up to 4 ppbv compared to MkIV have been found at high latitudes in December 2002 in the presence of polar stratospheric clouds. The degree of consistency is further largely affected by the temporal and spatial coincidence, and differences of 2 ppbv may be observed between 22 and 26 km (similar to 50 and 30 hPa) at high latitudes near the vortex boundary, due to large horizontal inhomogeneity of HNO3. Similar features are also observed in the mean differences of the MIPAS ESA HNO3 VMRs with respect to the ground-based FTIR measurements at five stations, aircraft-based SAFIRE-A and ASUR, and the balloon campaign IBEX. The mean relative differences between the MIPAS and FTIR HNO3 partial columns are within +/- 2%, comparable to the MIPAS systematic error of similar to 2%. For the vertical profiles, the biases between the MIPAS and FTIR data are generally below 10% in the altitudes of 10 to 30 km. The MIPAS and SAFIRE HNO3 data generally match within their total error bars for the mid and high latitude flights, despite the larger atmospheric inhomogeneities that characterize the measurement scenario at higher latitudes. The MIPAS and ASUR comparison reveals generally good agreements better than 10-13% at 20-34 km. The MIPAS and IBEX measurements agree reasonably well (mean relative differences within +/- 15%) between 17 and 32 km. Statistical comparisons of the MIPAS profiles correlated with those of Odin/SMR, ILAS-II, and ACE-FTS generally show good consistency. The mean differences averaged over individual latitude bands or all bands are within the combined instrument errors, and generally within 1, 0.5, and 0.3 ppbv between 10 and 40 km (similar to 260 and 4.5 hPa) for Odin/SMR, ILAS-II, and ACE-FTS, respectively. The standard deviations of the differences are between 1 to 2 ppbv. The standard deviations for the satellite comparisons and for almost all other comparisons are generally larger than the estimated measurement uncertainty. This is associated with the temporal and spatial coincidence error and the horizontal smoothing error which are not taken into account in our error budget. Both errors become large when the spatial variability of the target molecule is high.Peer reviewe

The SPARC water vapour assessment II: biases and drifts of water vapour satellite data records with respect to frost point hygrometer records

Satellite data records of stratospheric water vapour have been compared to balloon-borne frost point hygrometer (FP) profiles that are coincident in space and time. The satellite data records of 15 different instruments cover water vapour data available from January 2000 through December 2016. The hygrometer data are from 27 stations all over the world in the same period. For the comparison, real or constructed averaging kernels have been applied to the hygrometer profiles to adjust them to the measurement characteristics of the satellite instruments. For bias evaluation, we have compared satellite profiles averaged over the available temporal coverage to the means of coincident FP profiles for individual stations. For drift determinations, we analysed time series of relative differences between spatiotemporally coincident satellite and hygrometer profiles at individual stations. In a synopsis we have also calculated the mean biases and drifts (and their respective uncertainties) for each satellite record over all applicable hygrometer stations in three altitude ranges (10–30 hPa, 30–100 hPa, and 100 hPa to tropopause). Most of the satellite data have biases <10 % and average drifts <1 % yr−1 in at least one of the respective altitude ranges. Virtually all biases are significant in the sense that their uncertainty range in terms of twice the standard error of the mean does not include zero. Statistically significant drifts (95 % confidence) are detected for 35 % of the ≈ 1200 time series of relative differences between satellites and hygrometers

Evaluating modelled tropospheric columns of CH4_4 , CO, and O3_3 in the Arctic using ground-based Fourier transform infrared (FTIR) measurements

This study evaluates tropospheric columns of methane, carbon monoxide, and ozone in the Arctic simulated by 11 models. The Arctic is warming at nearly 4 times the global average rate, and with changing emissions in and near the region, it is important to understand Arctic atmospheric composition and how it is changing. Both measurements and modelling of air pollution in the Arctic are difficult, making model validation with local measurements valuable. Evaluations are performed using data from five high-latitude ground-based Fourier transform infrared (FTIR) spectrometers in the Network for the Detection of Atmospheric Composition Change (NDACC). The models were selected as part of the 2021 Arctic Monitoring and Assessment Programme (AMAP) report on short-lived climate forcers. This work augments the model–measurement comparisons presented in that report by including a new data source: column-integrated FTIR measurements, whose spatial and temporal footprint is more representative of the free troposphere than in situ and satellite measurements. Mixing ratios of trace gases are modelled at 3-hourly intervals by CESM, CMAM, DEHM, EMEP MSC-W, GEM- MACH, GEOS-Chem, MATCH, MATCH-SALSA, MRI-ESM2, UKESM1, and WRF-Chem for the years 2008, 2009, 2014, and 2015. The comparisons focus on the troposphere (0–7 km partial columns) at Eureka, Canada; Thule, Greenland; Ny Ålesund, Norway; Kiruna, Sweden; and Harestua, Norway. Overall, the models are biased low in the tropospheric column, on average by −9.7 % for CH$_4$, −21 % for CO, and −18 % for O$_3$. Results for CH$_4$ are relatively consistent across the 4 years, whereas CO has a maximum negative bias in the spring and minimum in the summer and O$_3$ has a maximum difference centered around the summer. The average differences for the models are within the FTIR uncertainties for approximately 15 % of the model–location comparisons