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In this study, we have investigated the ionospheric responses on the August 2017 solar eclipse event by using a three-dimensional tomography algorithm with the ground-based GNSS (Global Navigation Satellite System) total electron content observations around Northern America. This three-dimensional ionospheric electron density structure from the tomography can provide us more information regarding the density variations and propagations of disturbances. Results show that the ionospheric electron density depletion triggered by the solar eclipse started from the higher ionosphere and then extended to lower altitudes. The maximum electron density depletion is around 40% compared with the previous day of solar eclipse. After around 30 min of the totality, the electron density continuously returned to the normal level. We further conduct a procedure of Fourier analyses to derive the vertical phase and group velocities of the electron density propagations. Results show that the opposite directions of the vertical phase and group velocities around 220–240 km altitude imply the energy/oscillation source by the solar eclipse. Graphical Abstract

Background Dementia risk and benefit of lipid lowering in individuals with severe hypercholesterolemia has not been well studied. The aim of this study was to evaluate the risk of dementia and effect of lipid lowering in this population using nationwide cohort. Methods This study was performed using the National Health Insurance Service database of Korea. Among individuals who took health check-up and were followed-up, 1,584,401 were enrolled and analyzed. Study population were categorized to three groups with severe hypercholesterolemia according to LDL-C levels, >260, 225–259, and 190–224 mg/dL groups, and a control group (130 mg/dL). Results In the median follow-up of 6.1 years, all dementia occurred up to 5.41/1000 person-year in the groups with severe hypercholesterolemia. Adjusted hazard ratios (aHRs) of all dementia in the groups ranged from 1.05 to 1.34 (p=0.023) and were dependent of LDL-C categories. Alzheimer's disease developed up to 4.94/1000 person-year and aHRs ranged from 1.04 to 1.38 (p=0.040) with the same pattern to all dementia. Vascular dementia occurred up to 0.59/100 person-year and aHRs ranged from 1.03 to 1.57 without significant difference according to LDL-C categories. In the median follow-up of 6.2 years in new statin users, aHRs were 0.69 to 0.92 for all dementia and 0.74 to 0.92 for Alzheimer's disease, and 0.53 to 1.15 for vascular dementia according to post-treatment LDL-C levels. However, the risk was not significantly related to the levels. Conclusions This study newly showed elevated risk of dementia, particularly Alzheimer's disease, in patients with severe hypercholesterolemia. The benefit of active lipid lowering on this neurological disease needs to be proven by further studies. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Korean Society of Lipid and Atherosclerosis; National Research Foundation of Korea

Background Frailty is known to be an important prognostic indicator in heart failure (HF). The Korean version of the frail scale for Koreans (K-FRAIL) has been developed and verified. The purpose of this study is to analyze the relationship between the K-FRAIL scale and physical performance, including muscular fitness and aerobic capacity in patients with HF. Methods This study included 143 HF patients aged over 65 years from a single tertiary hospital. In these subjects, muscular fitness was assessed using the handgrip test and knee extensor strength measurement, and aerobic capacity was assessed by cardiopulmonary exercise test and 6-minute walk test. Frailty status was measured using the K-FRAIL questionnaire and was classified as robust (K-FRAIL scale: 0), prefrail (1–2), and frail (3–5). Results Mean age of participants with robust (N=37), prefrail (N=75), and frail (N=31) were 72.5, 73.5, and 76.3 years, respectively. There was no difference in sex and left ventricular ejection fraction (LVEF) among groups, but the estimated glomerular filtration rate (eGFR) was significantly lower as frailty status increased (75.6±17.2 vs. 70.0±20.5 vs. 56.1±23.7 mL/min/1.73 m2; P Conclusion In elderly HF patients, physical performance differs according to frailty status, peak VO2 and 6-min walk distance correlates with the K-FRAIL scale better than muscular fitness. Funding Acknowledgement Type of funding sources: None.

Introduction Although the hypothesis that metformin is beneficial for diabetic patients with heart failure (HF) has been steadily raised, there have been no solid data on the efficacy of metformin in acute HF patients. Purpose We investigated the impact of metformin on all-cause mortality in hospitalized acute HF patients with type 2 diabetes. Methods The Korean Acute Heart Failure registry enrolled patients hospitalized for acute HF from 2011 to 2014. Among this cohort, we analyzed patients with diabetes. We investigated all-cause mortality at 1 year after discharge. Propensity score matching (1:1 matching) and Cox proportional hazard models were used to assess difference in all-cause mortality. Results The study analyzed 1,976 diabetic patients (median age 72 years, mean left ventricular ejection fraction (LVEF) 34%, 54.5% male). Among them, 712 (36%) patients were on metformin. After 1:1 propensity score matching, 1,424 patients (712 metformin users vs. 712 non-users) were analyzed. During the median follow-up period of 11 months, 146 (21%) metformin non-users died and 108 (15%) metformin users died. Kaplan-Meier curves showed a higher all-cause mortality rate in non-users than in metformin users (Log-rank P=0.0025). After adjustment for clinically relevant variables, metformin was associated with lower risk for all-cause mortality (HR 0.713, 95% CI 0.551–0.922, P=0.01). In subgroup analyses, metformin use was significantly associated with a lower all-cause mortality in higher eGFR group (≥60 ml/min/1.73 m2, HR 0.531, 95% CI 0.357–0.790, P=0.002), but not in lower eGFR group (40% (P-for-interaction=0.906). Conclusion Metformin use was associated with a lower risk for 1-year all-cause mortality in diabetic acute HF patients, especially in high eGFR group. Funding Acknowledgement Type of funding sources: None.

Background High-sensitivity troponin assays allow for accurate and rapid rule-in or rule-out of myocardial infarction (MI) among patients with acute-onset chest pain. However, prognostic implications of serial high-sensitivity troponin concentrations are unknown. Purpose To determine short- and long-term prognostic implications of high-sensitivity troponin T (hsTnT) concentrations and their changes from baseline, in patients with suspected acute coronary syndrome. Methods Retrospective cohort study based on Danish national registries. We identified all patients discharged from the hospital with either MI, unstable angina, suspected MI, or chest pain from January 2012 through December 2019 and merged these individuals with all records of two serial hsTnT measurements obtained ≤7 hours apart during the same hospitalization. The primary outcome was death at days 0–30 and 31–365. Prognostic implications of serial hsTnT were examined in accordance with the 2012 ESC algorithm stratifying patients for normal baseline concentrations and relative changes of 20% and 50% from baseline. In case of a normal baseline concentration, 20% and 50% of the upper reference level (14 ng/l) were used as thresholds instead, i.e., 3 ng/l and 7 ng/l, respectively. Absolute risks were calculated through multivariable logistic regression with average treatment effect modeling (G-formula). Results Complete data were available in 28,902 individuals (median age [25th-75th percentile] 65.2 [53.4–75.4] years, 11,632 [40.2%] women). Of these, 11,116 (38.5%) had a final diagnosis of MI, 1518 (5.3%) of unstable angina, and 16,268 (56.3%) of either suspected MI or chest pain. Median baseline hsTnT was 18 ng/l (25th-75th percentile, 10–69), second hsTnT 21 ng/l (25th-75th percentile, 10–248), relative hsTnT change 3.6% (25th-75th percentile, 0–66.7), and time between samples 4.0 hours (25th-75th percentile, 3.2–5.4). Most patients had either two normal hsTnT concentrations (9483, 32.8%) or two elevated hsTnT concentrations (18,235, 63.1%). At 30 days, 796 (2.8%) individuals had died, while an additional 1287 (4.6% of 30-day survivors) died between days 31–365. Baseline hsTnT and the relative hsTnT change both displayed a significant, non-linear association with death and interacted with each other (P Conclusions This is the first study to assess both short- and long-term outcomes as a function of both baseline hsTnT and its change from first to second measurement. In general, patients with two normal hsTnT concentrations have an excellent prognosis while those with two elevated concentrations require scrutiny. Funding Acknowledgement Type of funding sources: None.

Background Non-ischemic dilated cardiomyopathy (NIDCM) is a genetic disorder that causes heart failure and life-threatening arrhythmia. However, there has been no study about the up-to-date genetic analysis for NIDCM in Korean. Therefore, we performed the genetic analysis of Korean NIDCM patients (pts) using next generation sequencing (NGS). Methods We analyzed clinical and echocardiographic data of 203 NIDCM in a single center from July 2017 to May 2020. All pts underwent NGS analysis with customized panel including 369 genes. Genetic variants were classified as pathogenic, likely pathogenic mutations or variants of uncertain significance regarding American College of Medical Genetics guideline. Results A total of 203 NIDCM pts (57±15 years old, 32.0% male, LVEF 28%) had NGS analysis. Thirty-seven (18.2%) pts had pathogenic or likely pathogenic mutations. The most prevalent mutated genes were TTN (n=16, 43.2%). TNNT2 (n=6, 16.2%), MYBPC3 (n=6, 16.2%) and MYH7 (n=3, 8.1%) mutated genes were common in the following order. The patients with positive panel mutation had no significant difference in initial LVEF (27% vs. 28%, p=0.216) and prevalence of atrial fibrillation (37.8% vs. 44.6%, p=0.454) compared with patients with negative panel mutation. During the median follow-up period of 40 months, there was no significant difference in composite outcome (all-cause death, heart transplantation, LVAD, heart failure re-admission, fatal arrhythmia) (35.3% vs. 32.2%, p=0.729) or presence of improved EF (≥10 points increase from baseline LVEF, and a second measurement of LVEF >40%) (41.2% vs. 50.0%, p=0.354) between the two groups. Conclusion This is the first study of NGS analysis in Korean NIDCM pts. We could find disease-related pathogenic or likely pathogenic mutations in 18.2% NIDCM patients. Further prospective, large study should be warranted to elucidate the effect of genetic mutation in clinical manifestation and prognosis of NIDCM in Korean population. Funding Acknowledgement Type of funding sources: None.

Introduction Glycemic variability (GV) is known to be a poor prognostic marker in various diseases including cardiovascular disease. Purpose We investigated the association of GV with all-cause mortality in patients with acute heart failure (HF). Methods The Korean Acute Heart Failure registry enrolled patients hospitalized for acute HF from 2011 to 2014. Among survivors of the index hospitalization, we analyzed those who had ≥3 blood glucose measurements before discharge. Patients were divided into two groups based on their coefficient of variation (%CV) as an indicator of GV. We investigated all-cause mortality at 6 month and 1 year after discharge. Results The study analyzed 2,617 patients (median age 72 years, 53% male). During the median follow-up period of 11 months, 583 (22%) patients died. Compared to alive patients, patients who died had a significantly higher diabetes prevalence (46% vs. 41%, P=0.035) and higher %CV (31.0% vs. 27.5%, P21%) was associated with lower cumulative survival to all-cause death compared with a low GV (%CV ≤21%) (log-rank P Conclusion A high GV (%CV >21%) before discharge was associated with all-cause mortality within 1 year, especially in non-diabetic acute HF patients. Funding Acknowledgement Type of funding sources: None.

The Human Genome Project marked a major milestone in the scientific community as it unravelled the ~3 billion bases that are central to crucial aspects of human life. Despite this achievement, it only scratched the surface of understanding how each nucleotide matters, both individually and as part of a larger unit. Beyond the coding genome, which comprises only ~2% of the whole genome, scientists have realized that large portions of the genome, not known to code for any protein, were crucial for regulating the coding genes. These large portions of the genome comprise the 'non-coding genome'. The history of gene regulation mediated by proteins that bind to the regulatory non-coding genome dates back many decades to the 1960s. However, the original definition of 'enhancers' was first used in the early 1980s. In this Review, we summarize benchmark studies that have mapped the role of cardiac enhancers in disease and development. We highlight instances in which enhancer-localized genetic variants explain the missing link to cardiac pathogenesis. Finally, we inspire readers to consider the next phase of exploring enhancer-based gene therapy for cardiovascular disease.

Unusual and discrepant ABO phenotypes are often due to genetic variants that lead to altered levels or activity of ABO transferases and consequently to altered expression of ABO antigens. This report describes eight genetic alterations found in 15 cases with reduced or undetectable expression of ABO antigens. Forward and reverse ABO grouping was performed by standard gel or tube methods. Adsorption-heat elution and saliva testing for H and A substances followed the AABB technical manual procedures. Genomic DNA extracted from whole blood was PCR-amplified to cover the entireUnusual and discrepant ABO phenotypes are often due to genetic variants that lead to altered levels or activity of ABO transferases and consequently to altered expression of ABO antigens. This report describes eight genetic alterations found in 15 cases with reduced or undetectable expression of ABO antigens. Forward and reverse ABO grouping was performed by standard gel or tube methods. Adsorption-heat elution and saliva testing for H and A substances followed the AABB technical manual procedures. Genomic DNA extracted from whole blood was PCR-amplified to cover the entire

RATIONALE: The attempt at direct liberation from mechanical ventilation (MV) using open-circuit oxygen in the tracheostomized patients with prolonged MV might carry a substantial failure rate. Frequent switching between closed-circuit MV support and open-circuit oxygen, such as a T-piece during the liberation attempt, might also carry a risk of dispersing aerosol particles to the care environment, especially during the pandemic era. We aimed to analyze the feasibility and predictability of adding a screening test with automated tube compensation (ATC) or airway resistance compensation (ARC) mode before the attempt of an open-circuit oxygen trial. METHODS: We conducted a retrospective analysis of tracheostomized patients admitted to a medical center's dedicated weaning unit in Taiwan. Because of coronavirus's global pandemic, the unit implemented a universal process to apply ATC/ARC screening tests to patients since April 2020. Before starting the MV liberation trial with continuous spontaneous breathing via open-circuit oxygen (T-piece), the patients received a screening test consisting of 12 hours of ATC/ARC the first day followed by 72 hours of continuous ATC/ARC. Those who passed the test then proceeded to the open-circuit liberation trial. Those who failed the test would receive repeated ATC/ARC or open circuit trials. RESULTS: A total of 79 (51% of the admitted) patients, including 54 male, aged 69 [18-95] years, and averaged 32 days of MV before admission to the weaning unit, received the screening test (59 for ATC;20 for ARC) after MV settings reduction. Of the 79 patients, 48 (61%) succeeded in the test. Upon discharge from the unit, 49 (62%) were liberated from MV, and 43 (54%) were MV-free status 30 days after the ATC/ARC test. Of the 31 who failed ATC/ARC, 22 (71%) remained MV-dependent at 30 days after the ATC/ARC test. Therefore, the sensitivity, specificity, positive predictive value, and negative predictive values of the ATC/ARC test for outcomes of MV-liberation upon discharge from the unit were 90%, 87%, 92%, and 84%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive values of the ATC/ARC test for outcomes of MV-free status 30 days after the test were 93%, 78%, 83%, and 90%, respectively. CONCLUSION: Before proceeding with open-circuit oxygen, a screening test with ATC/ARC provides an optimal prediction for the 30-day outcomes of MV liberation.

High-resolution X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) were used to characterize IrO

Introduction The purpose of this study was to delineate the anatomic relationship between the anterior articular capsule and the adjacent subscapularis by measuring the dimensions of the anterior articular capsule attachment and the subscapularis footprint on the humerus, as well as investigating the interface between the two structures. Materials and methods Three shoulder specimens underwent histological analysis; for histological analysis, cross-sections through the subscapularis-capsule complex were harvested at the tendinous and muscular insertion sites. The dimensions of the anterior articular capsule attachment and the subscapularis footprint (including the tendinous and muscular insertions) were measured in thirteen cadaveric shoulder specimens. Results Histologically, the articular capsule has thin and loosely arranged collagen fibers with many interspersing fibroblast nuclei, whereas the outer layer of the articular capsule blends into a layer of more loosely spaced and less organized collagen fibers. This interface between the subscapularis and the underlying articular capsule is filled with more loosely spaced and less organized collagen fibers. The macroscopic evaluation showed that the minimum articular capsule width (4.2 mm, SD 2.2 mm) was located at its initiation 4.9 mm (SD, 2.1 mm) inferior to the superior margin of the subscapularis; the corresponding subscapularis footprint width measured 10.1 mm (SD, 4.9 mm). The maximum articular capsule width was11.1 mm (SD, 3.7 mm) and was located 5 mm distal to the inferior margin of the tendinous footprint. The maximum subscapularis footprint width was 15.8 mm (SD, 2.9 mm); the corresponding articular capsule attachment measured 5.2 mm (SD, 1.8 mm). Conclusions Our results suggest that the anterior articular capsule attachment of the glenohumeral joint complements the footprint of the subscapularis and occupies a larger area of the lesser tubercle and metaphysis of the humerus than previously documented. The histological study confirms the presence of a demarcation between the subscapularis and articular capsule, specifically more significant at the region medial to the tendon insertion and at the muscular insertion of the subscapularis.

The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n=60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n=650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n=45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.

We investigated adsorption of N

Identifying genetic markers for heterogeneous complex diseases such as heart failure has been challenging, and may require prohibitively large cohort sizes in genome-wide association studies (GWAS) in order to meet genome-wide statistical significance. On the other hand, chromatin quantitative trait loci (QTL), elucidated by direct epigenetic profiling of specific human tissues, may contribute towards prioritising sub-threshold variants for disease-association. Here, we captured non-coding genetic variants by performing enhancer H3K27ac ChIP-seq in 70 human control and end-stage failing hearts, mapping out a comprehensive catalogue of 47,321 putative human heart enhancers. 3,897 differential acetylation peaks (FDR 5%) pointed to pathways altered in heart failure (HF). To identify cardiac histone acetylation QTLs (haQTLs), we regressed out confounding factors including HF disease status, and employed the G-SCI test to call out 1,680 haQTLs (FDR 10%). RNA-seq performed on the same heart samples proved a subset of haQTLs to have significant association also to gene expression (expression QTLs), either in cis (180), or through long range interactions (81), identified by Hi-C and Hi-ChIP performed on a subset of hearts. We validated 2 of the haQTLs through base editing to show that the presence of those SNPs indeed affects gene expression in human embryonic stem cells-derived cardiomyocytes. Furthermore, a concordant relationship between the gain or disruption of transcription factor (TF) binding motifs, inferred from alternative alleles at the haQTLs, implied a surprising direct association between these specific TF and local histone acetylation in human hearts. Finally, 62 unique loci were identified by colocalisation of haQTLs with heart-related GWAS datasets. Disease-association for these new loci may indeed be mediated through modification of H3K27-acetylation enrichment and their corresponding gene expression differences.

A large body of evidence demonstrates that strategies that promote student interactions and cognitively engage students with content ( 1 ) lead to gains in learning and attitudinal outcomes for students in science, technology, engineering, and mathematics (STEM) courses ( 1 , 2 ). Many educational and governmental bodies have called for and supported adoption of these student-centered strategies throughout the undergraduate STEM curriculum. But to the extent that we have pictures of the STEM undergraduate instructional landscape, it has mostly been provided through self-report surveys of faculty members, within a particular STEM discipline [e.g., ( 3 – 6 )]. Such surveys are prone to reliability threats and can underestimate the complexity of classroom environments, and few are implemented nationally to provide valid and reliable data ( 7 ). Reflecting the limited state of these data, a report from the U.S. National Academies of Sciences, Engineering, and Medicine called for improved data collection to understand the use of evidence-based instructional practices ( 8 ). We report here a major step toward a characterization of STEM teaching practices in North American universities based on classroom observations from over 2000 classes taught by more than 500 STEM faculty members across 25 institutions.

Ocean Thermal Energy Conversion (OTEC) has garnered international interest as a clean and sustainable source of secondary power generation, without impacting the environment and regardless of seasonal weather conditions, for offshore Oil & Gas (O&G) processing facilities. This is considering the suitability of waste heat extraction from existing offshore deepwater Oil & Gas platforms as a complementary application for integrated OTEC modules (hereafter abbreviated as i-OTEC). Such an application is possible with the availability of cold seawater drawn from extended seawater lift caissons or deepwater intake risers. This study investigates, in detail, the various refrigerants that are feasible alternatives to Ammonia (NH3) for a 1MWe i-OTEC scheme. Anhydrous NH3 or R717 was initially selected as the refrigerant for the aforementioned i-OTEC scheme which is modelled based on an Organic Rankine Cycle (ORC). It is widely accepted that R717 is the ideal refrigerant for this application due to R717's high enthalpy change during expansion. Although R717 is classified toxic, R717 emissions generally do not create environmental problems, and is detrimental to health only upon presence of R717 at a Short Term Exposure Limit (STEL) of 35ppm. For comparison purposes, other alternative refrigerants were also studied; focusing particularly the risks associated with the refrigerants including toxicity, flammability, asphyxiation, reactivity and physical hazards. Hence, the selection of the refrigerant was a major factor in the design as it provides the basis for further investigation. Shortlisted alternatives, which include R1234yf, R410a, R134a, R290 and R32, were additionally assessed on multiple factors including expected enthalpy gain from the Rankine cycle, circulation flowrate, equipment sizing, hazard classification of refrigerants, compliance to international/local exposure standards, handling and storage of refrigerants. It is identified that the aforementioned refrigerants are possible alternatives to R717 - but with some drawbacks from a thermodynamic performance perspective, and the fact that some of these refrigerants would be rendered obsolete in various industries. Consideration of the next generation of refrigerants must balance out factors such as public awareness, manufacturers availability, safety aspects and environmental concerns. The latest refrigerant with minimal environmental impact is R1234yf and it has been slowly accepted in the HVAC and motor industry. Additionally, the turboexpander-generator shaft sealing was identified as the major source of refrigerant emissions during normal operation. Hence, various shaft sealing solutions were also scrutinized to assess the viability of utilizing R717 as a refrigerant whilst still fulfilling safety and emission requirements.

This paper presents a D-band linearized power amplifier (PA) with on-chip current combining transformer using a standard 65nm CMOS process, which covers 114 to 131 GHz. To mitigate the parasitic gate-drain capacitance feedback, each stage consists of common source (CS) amplifier with a neutralization using cross-coupled capacitor (Cc). The PA achieves a small-signal gain of 22.3 dB and 3-dB bandwidth (BW) of 17 GHz, a 1-dB compressed power (P1dB) of 12.2 dBm and a saturated output power (P SAT ) of 14.5 dBm with a peak PAE of 10.2%. The PA chip area is 0.343mm2 including the pads and the core chip area is 0.103mm2.

Recombinant parathyroid hormone (1-34), the drug of choice for treating severe osteoporosis, has a short half-life and requires daily subcutaneous injections. Controlled release formulation of recombinant parathyroid hormone (1-34) might prevent daily injections and improve therapeutic outcome. In this study, recombinant parathyroid hormone (1-34)-loaded poly(D,L-lactic-co-glycolic acid) microspheres using a double emulsion method were prepared. Scanning electron microscopy proved that the microspheres were spherical in shape with 2.0 to 5.0 µm diameter. A loading efficiency up to 84 % was achieved in the optimized formulation. Release study performed using microspheres of 10:1.0 polymer:drug ratio formulation revealed that the release of recombinant parathyroid hormone (1-34) was controlled over 22 days in a biphasic manner with an initial burst and a subsequent slow release. For pharmacokinetic study, recombinant parathyroid hormone (1-34)-loaded poly(D,L-lactic-co-glycolic acid) microspheres were subcutaneously injected to rats at 0.01 mg/kg dose of recombinant parathyroid hormone (1-34). Plasma drug concentration of recombinant parathyroid hormone (1-34)-loaded poly(D,L-lactic-co-glycolic acid) microspheres were maintained for a week whereas free recombinant parathyroid hormone (1-34) was quickly eliminated within a day. These results suggest that recombinant parathyroid hormone (1-34)-loaded poly(D,L-lactic-co-glycolic acid) microspheres appear to have the potential for further clinical development.

The 2D distinct element method was used to investigate the propagation of fault rupture traces through overlying sand during reverse faulting along a range of dip angles and at different vertical throws. Calibrated micromechanical material parameters were used in the numerical simulations, which were validated through a comparison of the simulation results with those obtained from a centrifuge experiment involving acceleration at 80 g. The Gompertz sigmoid function with three parameters provided the best fit to the normalized surface deformation profiles obtained both from the numerical simulation and from centrifuge experiments. The three parameters that characterized the Gompertz sigmoid function were the normalized scarp height, the maximum slope on the scarp, and the location of the reverse fault outcropping. A surface deformation profile slope of 1/150 was used as the setback criterion. The normalized affected width and fault outcrop relative to the fault tip were determined for reverse faults having a variety of dips and throws. The dip angle significantly affected the kinematic mechanism underlying reverse faulting. At a given vertical throw, the scarp height increased as the dip angle decreased in the cases of α 45°. As the dip angle decreased, the location of the fault outcropping shifted toward the footwall and the maximum slope on the scarp increased. The horizontal displacement played a significant role at low dip thrusts (α = 22.5°, 30°, 37.5°), a back-thrust fault developed, and an inverted triangle wedge formed in the subsurface.

This study examined the effects of simple changes in the tank environment on the wellbeing of laboratory-maintained zebrafish Danio rerio. Groups of D. rerio were either housed in stable environments (where they were maintained in the same tanks throughout the study) or in environments subject to change (where they were periodically moved to novel but identical tanks) and the effects of these treatments on morphometry, reproductive success and aggressive behaviour assessed. No effect of simple tank changes was found on body condition, reproductive output or aggression, for the periods of time studied, indicating that more complex scenarios in housing tank conditions are required for significant welfare benefits for captive D. rerio.

Background The American Joint Committee on Cancer 8th Edition (AJCC 8) for oral cavity squamous cell carcinoma (OCSCC) incorporates depth of invasion (DOI) into the pathologic tumor classification (pT) and pathologic extranodal extension (pENE) into the pathologic nodal classification (pN). We sought to evaluate the incidence and prognostic importance of stage migration as a result of these changes on the AJCC 8 staging system. Methods From the National Cancer Database, cohorts were identified from patients with OCSCC undergoing definitive surgery between 2004-2013 for pT (n = 7,184), pN (n = 13,627), and pathologic Stage (pStage; n = 5,580) analysis. Results DOI and pENE were prognostic in all groups except AJCC 7 pN3. Upstaging was seen in 12.4% of patients for pT classification, 13.3% for pN classification, and 24.8% for overall pathologic stage grouping. Notably, upstaging led to similar or improved five-year overall survival (5-YR OS) for every AJCC 8 pT/N classification except pStage IVB. AJCC 7 pT1 tumors upstaged to AJCC 8 pT3 tumors had improved overall survival compared to the remainder of the pT3 group (71.7% vs 43.7%, respectively, P Conclusions Upstaging is common in AJCC 8, and upstaged tumors demonstrate improved survival; these factors that should be kept in mind when interpreting data using the new staging system. Postoperative radiotherapy may reduce death in newly upstaged pT3N0 patients, and further study is needed in this area. Legal entity responsible for the study Yale School of Medicine. Funding Research reported in this publication was supported by the National Institute on Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number T35DK104689 (NCJL). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This publication was made possible by the Yale School of Medicine Medical Student Fellowship (NCJL). Disclosure B. Burtness: Honoraria (self), Research grant / Funding (institution): Advaxis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): IDDI; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy: Celgene; Advisory / Consultancy: Genentech. All other authors have declared no conflicts of interest.