Full Period Research Articles

Dynamics of the return and volatility connectedness among green finance markets during the COVID-19 pandemic

This paper examines the return and volatility connectedness among green finance markets including the green bonds, clean energy and socially responsible stocks, especially focusing on the connectedness changes induced by the COVID-19 pandemic. Specially, by employing the TVP-VAR extended joint connectedness approach, five representative time series, i.e., S&P Green Bond index (GBI), S&P Global Clean Energy index (GCEI), S&P Global 1200 ESG index (ESGI), S&P Global 1200 Carbon Efficient index (CEI) and S&P Global 1200 Fossil Fuel Free index (FFFI), are used to measure the connectedness among the markets over the sample period spanning from 1 January 2014 to 31 December 2021. The empirical results show that GBI is the main net receiver of return spillovers, followed by ESGI, CEI and FFFI, whereas GCEI is the main net transmitter of return spillovers during the full sample period. The dynamic total connectedness of five indices' returns is strongly fluctuating and especially exhibits a significant spike after the outbreak of COVID-19 pandemic. Interestingly, the findings of volatility connectedness indicate that ESGI, CEI, and FFFI are net transmitters of volatility spillovers during the full, pre-COVID-19 and post-COVID-19 periods. In addition, the network connectedness analysis highlights the role of GCEI in facilitating the transmission of financial contagion during the full and pre-COVID-19 periods, while that during the post-COVID-19 period shows that GBI receives more spillovers from others, indicating that the connections of the five indices tend to be stronger during market downturn periods caused by extreme events. Our results provide implications for investors and policymakers.

Abrocitinib efficacy and safety in patients with moderate-to-severe atopic dermatitis: Results from phase 3 studies, including the long-term extension JADE EXTEND study.

Abrocitinib improved signs and symptoms of moderate-to-severe atopic dermatitis (AD) at 12 or 16 weeks in phase 3 studies with a manageable safety profile. Further understanding of the abrocitinib long-term efficacy and safety profile is important for its appropriate use in treating chronic AD. To evaluate the abrocitinib efficacy up to 48 weeks and long-term safety in patients with moderate-to-severe AD. JADE EXTEND (NCT03422822) is an ongoing, phase 3, long-term extension study that enrolled patients from previous abrocitinib AD trials. This analysis focusses on patients from the phase 3 JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871) and JADE COMPARE (NCT03720470) studies who completed the full treatment period of placebo or abrocitinib (200 mg or 100 mg once daily) and subsequently entered JADE EXTEND. Efficacy endpoints included the proportion of patients achieving skin clearance (Investigator's Global Assessment [IGA] 0/1 [clear/almost clear]; ≥75% improvement in Eczema Area and Severity Index [EASI-75]) and itch response (Peak Pruritus Numerical Rating Scale [PP-NRS] severity ≥4-point improvement). Safety endpoints included treatment-emergent adverse events (TEAEs), serious TEAEs and TEAEs leading to discontinuation. Data cut-off: April 22, 2020. As of the data cut-off, ~70% and ~45% of patients received abrocitinib for ≥36 and ≥48 weeks, respectively. Nasopharyngitis, atopic dermatitis, nausea and upper respiratory tract infections were the most frequent TEAEs. Serious TEAEs occurred in 7% and 5% and TEAEs leading to study discontinuation occurred in 9% and 7% of patients receiving abrocitinib 200 mg and 100 mg, respectively. Week 48 efficacy responses with abrocitinib 200 mg and 100 mg were as follows: IGA 0/1 52% and 39%; EASI-75 82% and 67%, and PP-NRS severity ≥4-point improvement 68% and 51%. In patients with moderate-to-severe AD, long-term abrocitinib treatment resulted in clinically meaningful skin and pruritus improvement. The long-term safety profile was manageable and consistent with previous reports.

Dynamic 3D morphology of chick embryos and allantois depicted nondestructively by 3.0T clinical magnetic resonance imaging

Driven by a global trend of applying replace-reduce-refine or 3Rs' guidance for experimental animals in life sciences, chick embryo and particularly allantois with its chorioallantoic membrane have been increasingly utilized to substitute laboratory animals, which call for more extensive and updated knowledge about this novel experimental setup. In this study, being noninvasive, nonionizing, and super-contrasting with high spatiotemporal resolutions, magnetic resonance imaging (MRI) was chosen as an imaging modality for in ovo monitoring morphologic evolution of the chick embryo, allantois, and chorioallantoic membrane longitudinally throughout embryonic day (ED) 1 until ED20. Cooled in 0°C ice bath for 60 min to reduce MRI motion artifacts, 3 chick embryos (n=60 in total) on each ED were scanned by a clinical 3.0T MRI scanner to demonstrate 3D images of both T2- and T1-weighted imaging (T2WI, T1WI) sequences at axial, sagittal, and coronal slices. The volumes of both the entire chick embryo and allantois were semi-automatically segmented based on intensity-based thresholding and region-growing algorithms. The morphometries or quantified 3D structures were achieved by refined segmentation, and confirmed by histological analyses (one for each ED). After MRI, the rest of chick embryos (n=40) continued for incubation. The images from ED2 to ED4 could demonstrate the structural changes of latebra, suggesting its transition into a nutrient supplying channel of yolk sac. The allantois could be recognized by MRI, and its relative volumes on each ED revealed an evolving profile peaked on ED12, with a statistically significant difference from those of earlier and later EDs (P < 0.01). The hypointensity of the yolk due to the susceptibility effect of its enriched iron content overshadowed the otherwise hyperintensity of its lipid components. The chick embryos survived prior cooling and MRI till hatching on ED21. The results could be further developed into a 3D MRI atlas of chick embryo. Clinical 3.0T MRI proved effective as a noninvasive approach to study in ovo 3D embryonic development across the full period (ED1-ED20), which can complement the present knowhow for poultry industry and biomedical science.

The natural history of periodontal disease: The Java study-Origin, implementation, and results 35 years on.

This review describes the origin and results of the prospective longitudinal study to test potential prognostic indicators for periodontal breakdown in a population deprived of regular dental care. Experimental gingivitis studies in individuals highly susceptible or highly resistant to periodontitis showed that bleeding on probing developed quite differently: 50% versus 18% bleeding, respectively, after 18 days of no oral hygiene. This formed, together with other clinical and microbiological parameters, the basis for the 15-year prospective study in the Java tea worker population to test potential prognostic indicators for periodontal breakdown. Evaluation showed that during the 15-year observation period of this population aged 15-25 years at baseline, the number of teeth decreased and the periodontal condition deteriorated. Gingival recession showed no increase during the first 7 years of observation, whereas a sixfold increase had occurred thereafter. Attachment loss doubled during the first 7 years, but almost tripled thereafter. Risk markers for disease onset/progression during the first 7 years of observation were age, the number of sites with subgingival calculus, and the subgingival presence of Aggregatibacter actinomycetemcomitans. Over the full period of 15 years the number of sites with a pocket depth of at least 5 mm and the number of sites with recession were identified as risk markers and male gender as a risk determinant. The prevalence of severe periodontitis amounted to 20% in 2002. Analysis showed that, already at baseline and throughout the study period, the periodontal condition in these individuals was more severe compared with the other participants. In conclusion, characteristics of susceptibility to periodontitis are already apparent in young adulthood.

The influence of weather and climate parameters on the winter rapeseed productivity

Purpose. To study the influence of hydrothermal resources on the productivity of winter rapeseed. Methods. Field (conducting phenological observations and records), measuring and weighting (for recording productivity and yield), mathematical, statistical and correlational analysis (objective assessment of the obtained experimental data). Results. Varieties of winter rapeseed of different ecological and geographical origin were taken as research material. For the analysis, the conditions of the full vegetation period, “seedlings-termination of vegetation”, “restoration of vegetation-beginning of ripening” and “flowering-beginning of ripening” were chosen as the most critical ones. The importance of using the hydrothermal coefficient as an integral indicator in determining the cumulative effect of climatic factors on the yield characteristics of winter rapeseed plants has been proven. It has been established that the following factors have the greatest influence on the formation of rapeseed productivity: duration of the growing season, the sum of active temperatures and the sum of precipitation under a above +10°C temperature regime, especially during the “flowering-beginning of ripening” period. Conclusions. Hydrothermal conditions affect the productivity of winter rapeseed plants. During the entire vegetation period, the following factors had the greatest positive influence: the length of the vegetation period (in particular, when tfact &gt;0o to +5oC and &gt;+10oC), the sum of temperatures tfact &gt;0o to +5oC, the amount of precipitation. From the beginning of germination to the entry into a state of rest and after the resumption of vegetation in the spring, the following factors have the strongest effect on plants: duration of the vegetation period at tfact &gt;0o to +5oC and &gt;+10oC, the availability of moisture at temperatures from 0o to +10oC. During the flowering-ripening period, the length of the growing season had a positive effect, in particular at air temperature &gt;+10°C against the background of a fairly high sum of active temperatures. The yield of winter rapeseed depends on many abiotic factors, which always provide optimal conditions for the sufficient plant development in autumn and spring, but can negatively affect the flowering of plants, and, accordingly, reduce their productivity.

High-definition Cathodal Direct Current Stimulation for Treatment of Acute Ischemic Stroke

Cathodal transcranial direct current stimulation (C-tDCS) provides neuroprotection in preclinical models of acute ischemic stroke (AIS) by inhibiting peri-infarct excitotoxic effects and enhancing collateral perfusion due to its vasodilatory properties. To report the first-in-human pilot study using individualized high-definition (HD) C-tDCS as a treatment of AIS. This randomized clinical trial was sham controlled with 3 + 3 dose escalation design, and was conducted at a single center from October 2018 to July 2021. Eligible participants were treated for AIS within 24 hours from onset, had imaging evidence of cortical ischemia with salvageable penumbra, and were ineligible for reperfusion therapies. HD C-tDCS electrode montage was selected for each patient to deliver the electric current to the ischemic region only. Patients were followed for 90 days. Primary outcomes were feasibility, assessed as time from randomization to study stimulation initiation; tolerability, assessed by rate of patients completing the full study stimulation period; and safety, assessed by rates of symptomatic intracranial hemorrhage at 24 hours. The efficacy imaging biomarkers of neuroprotection and collateral enhancement were explored. A total of 10 patients with AIS were enrolled, 7 were randomized to active treatment and 3 to sham. Patient age was mean (SD) 75 (10) years old, 6 (60%) were female, and National Institutes of Health Stroke Scale score was mean (SD) 8 (7). Two doses of HD C-tDCS (1 milliamp [mA] for 20 minutes and 2 mA for 20 minutes) were studied. The speed of HD C-tDCS implementation was a median (IQR) 12.5 minutes (9-15 minutes) in the last 4 patients. Patients tolerated the HD C-tDCS with no permanent stimulation cessation. The hypoperfused region was reduced by a median (IQR) 100% (46% to 100%) in the active group vs increased by 325% (112% to 412%) in sham. Change in quantitative relative cerebral blood volume early poststimulation was a median (IQR) 64% (40% to 110%) in active vs -4% (-7% to 1%) sham patients and followed a dose-response pattern. Penumbral salvage in the active C-tDCS group was median (IQR) 66% (29% to 80.5%) vs 0% (IQR 0% to 0%) in sham. In this randomized, first-in-human clinical trial, HD C-tDCS was started efficiently and well tolerated in emergency settings, with signals of beneficial effect upon penumbral salvage. These results support advancing HD C-tDCS to larger trials. ClinicalTrials.gov Identifier: NCT03574038.

944-P: Continuous Glucose Monitoring (CGM) Sampling Duration to Estimate Long-Term Glycemic Control in Adults with T2D Not Using Insulin

Objective: Current consensus is that 10-14 days of continuous glucose monitoring (CGM) sampling time is adequate to assess long-term glycemic control in T1D and insulin-using T2D populations. Optimal CGM sampling duration has not been widely studied in people with T2D not using insulin. We studied the relationship between true and estimated long-term (90-day) glycemic control in people with T2D not using insulin. Methods: The study population (N = 829) was composed of adults with T2D enrolled in Level2, a virtual specialty clinic, with CGM data on 75% (68) of the 90 days preceding an A1c lab result and no insulin fills during this period. The mean age and A1c were 56 years and 6.7% respectively. We computed the median absolute percentage error (MAPE) and Pearson correlations (R) between glycemic metrics from sampling periods of increasing duration and the full 90-day period. Because this population was at low risk for hypoglycemia glucose management indicator (GMI) and time above range (&amp;gt;180 mg/dL, TAR) were the primary outcomes of interest. We also assessed the correlations between GMI and A1c. Results: GMI and TAR from 14-day measurements were highly correlated (R = 0.92) with 90-day values, increasing to R = 0.94 with 30-day measurements. Correlations of GMI and A1c were high with 14 and 30 days (R = 0.79, R = 0.82) but did not exceed R = 0.85 with longer sampling periods. MAPE was 2.2 (SD = 2.6) and 1.5 (SD = 2.1) for GMI with 14- and 30-day measurements, respectively, and 29.2 (SD = 47.4) and 21.2 (SD = 27.1) for TAR. Conclusion: In the T2D population not using insulin, 14 days of CGM data is sufficient to estimate long-term mean glucose and the discordance with A1c is consistent with previous studies of people with T1D and insulin-using T2D. TAR is subject to greater error than in previous studies of people with T1D and insulin-using T2D and more work is needed to understand this discrepancy. Disclosure S.Bacon: Employee; Optum Labs, Research Support; Level2. N.Thompson: Employee; Level2, Stock/Shareholder; UnitedHealth Group. D.Ferrell: Stock/Shareholder; Level2, Medexpress Urgent Care. J.Fung: Employee; Level2.

The complex shape of the outer edge of Saturn’s B ring, as observed in Cassini occultation data

We determine the time-variable shape of the outer edge of Saturn’s B ring using the complete set of Cassini radio and stellar occultation data obtained between mid-2005 and the End-of-Mission in late 2017, considerably expanding the range and number of individual ring edge measurements used in previous analyses (Spitale and Porco, 2010; Nicholson et al., 2014a). During this 12-year interval, the dominant m=2 pattern driven by the Mimas 2:1 inner Lindblad resonance completed just over two rotations relative to Mimas, with a circulation period of 5.362 yr, while its radial amplitude varied from a minimum of 4 km to a maximum of 71 km. This circulation pattern has remained essentially unchanged over the full period of the observations. We confirm the existence of four additional perturbations with azimuthal wavenumbers m=1, 3, 4 and 5 and mean amplitudes ranging from 5 to 24 km, which we interpret as normal or edge modes, possibly triggered by viscous overstabilities in the dense B ring (Borderies et al., 1985; Longaretti, 2018). Fits of a simple WKB model to the observed pattern speeds of the edge modes with m≠1 suggest an average surface mass density in the outer 30 km of the B ring of ∼100 g cm−2, somewhat greater than the 50–70 g cm−2 inferred from density and bending waves in most other regions of this ring (Hedman and Nicholson, 2016). The m=1 mode, which extends further into the B ring, yields a more typical value of 60 g cm−2. Surprisingly, all four of these modes exhibit significant librations in their amplitudes and phases, with periods between 2.3 and 8.6 yr and amplitudes of 1.6 to 7.4 km. The origin of these librations is unknown and it is unclear if they are truly periodic and will maintain their amplitudes, periods, and phases over timescales of centuries. Their frequencies do not match those expected for interference between edge modes with varying numbers of radial nodes. Instead, they may represent periodic oscillations in the amplitudes of individual normal modes or nonlinear, non-resonant coupling between normal modes with different values of m, leading to long-term quasi-periodic variations in the mode amplitudes.

Firing mechanism and benefit evaluation of high-strength fired water permeable brick containing vanadium-titanium iron ore tailings

Introduction: The vanadium-titanium iron ore tailings (VTIOTs) has a significant amount of discharge, and serious pollution, which makes it difficult to use directly as a resources resource.Methods: High-strength fired water permeable brick (HSFWPB) was prepared using VTIOTs as the main raw material. The orthogonal test, X-ray diffraction analysis (XRD), scanning electron microscope (SEM), energy dispersive spectrometry (EDS), and synthetic precipitation leaching procedure (SPLP) were obtained to study the basic properties and firing mechanism of HSFWPB containing VTIOTs, and an economic benefit evaluation was conducted on the project investment of HSFWPB containing VTIOTs.Results: The results show that when the content of VTIOTs in HSFWPB is 78%, the firing temperature (FT) is 1080°C and the holding time is 120 min, the compressive strength and permeability coefficient of the fired product reach 70.4 MPa and 0.055 cmˑs−1, respectively, which meet the requirements of Cc60 grade products in Water permeable brick (JC/T 945–2005). The products of HSFWPB containing VTIOTs after firing are diopside (CaMgSi2O6) and augite (Ca (Mg, Fe, Al) (Si, Al)2O6), with the increase of FT and the extension of HT, the low melting point elements of P, Na, K dissolve out, and the content of Fe and Al in the firing products increases, most of Ca2+ in diopside is replaced by Fe3+, so that augite becomes the main crystal phase. With the increase of FT, the pores in the fired products are changed from: closed pores with different sizes→ connected pores with irregular diameters→ irregular collapse pores→ small and uniform circular pores, which provides a guarantee for the permeability of HSFWPB containing VTIOTs.Discussion: The full investment payback period of the project of HSFWPB containing VTIOTs is 1.77 years. When the production reaches 48.585% of the design output, it reaches a breakeven point, and the project has strong risk resistance ability. The research has improved the utilization rate of VTIOTs and provided a new approach for the large-scale application of VTIOTs.

ROSUVASTATINE TREAMENT IN A BIG UKRAINIAN COHORT OF PATIENTS WITH TYPE 2 DIABETES

Objective: Diabetes mellitus (DM) remains one of the most important cardiovascular risk factors significantly worsening the prognosis in patients with hypertension and dyslipidemia. The leading role among drugs for the treatment of such patients is played by statins with their powerful influence on the development and progression of atherosclerosis and its complications. We used the OZIRKA study database and performed additional subanalysis to study the effects of rosuvastatin in patients with diabetes and dyslipidemia. To study the effect of Ozalex (rosuvastatin) on lipid and cholesterol levels in patients with lipid metabolism disorders and hypercholesterolemia and DM. Design and method: A prospective open population study on a primary care level. Recruitment of patients was conducted from March to December 2019. The analysis of the study data was conducted from June to November 2020. All patients attended in total 3 visits. Results: A total of 20,000 patients from all over Ukraine were included in the study. The full follow-up period was completed by 18,100 patients, of whom 17,530 had all the necessary data, and they were included in the final analysis. The mean follow-up period was 2.2 months. Approximately 13% of patients included in the study had DM type 2. We observed a significant reduction in total cholesterol, LDL and triglyceride levels in patients with diabetes. In addition, there was a tendency to increase the level of HDL in this group of patients. In general, it can be noted that there was a significant improvement in lipid profile in patients with diabetes - the level of total cholesterol decreased by 28%, LDL cholesterol by 34%, and triglycerides by 24%. Administration of rosuvastatin did not impair glucose control in any way in the group of patients with DM, moreover, even in the group of people without DM there was no negative effect of rosuvastatin on fasting glucose level. Conclusions: In general, we can recommend rosuvastatin in a dose of 10 to 20 mg as an optimal start of statin therapy at the stage of primary care for patients with DM.

Imaging the innermost gaseous layers of the Mira star R Car with GRAVITY-VLTI

Context. The mass-loss mechanisms in M-type asymptotic giant branch (AGB) stars are still not well understood; these include, in particular, the formation of dust-driven winds from the innermost gaseous layers around these stars. One way to understand the gas-dust interaction in these regions and its impact on the mass-loss mechanisms is through the analysis of high-resolution observations of the stellar surface and its closest environment. Aims. We aim to characterize the inner circumstellar environment (~3 R*) of the M-type Mira star R Car in the near-infrared at different phases of a pulsation period. Methods. We used GRAVITY interferometric observations in the K band obtained during two different epochs over 2018. Those data were analyzed using parametric models and image reconstruction of both the pseudo-continuum and the CO band heads observed. The reported data are the highest angular resolution observations on the source in the K band. Results. We determined sizes of R Car’s stellar disk of 16.67 ± 0.05 mas (3.03 au) in January 2018 and 14.84 ± 0.06 mas (2.70 au) in February, 2018, respectively. From our physical model, we determined temperatures and size ranges for the innermost CO layer detected around R Car. The derived column density of the CO is in the ~9.18×1018–1×1019 cm−2 range, which is sufficient to permit dust nucleation and the formation of stable dust-driven winds. We find that magnesium composites, Mg2SiO4 and MgSiO3, have temperatures and condensation distances consistent with the ones obtained for the CO layer model and pure-line reconstructed images, which are the dust types most likely to be responsible for wind formation. Our reconstructed images show evidence of asymmetrical and inhomogeneous structures, which might trace a complex and perhaps clumpy structure of the CO molecule distribution. Conclusions. Our work demonstrates that the conditions for dust nucleation and thus for initialising dust-driven winds in M-type AGB stars are met in R Car, and we identify magnesium composites as the most probable candidates. We find structural changes between two observing epochs (which are separated by ~10% of the full pulsation period of the star) and evidence of the effects of asymmetries and clumpiness. This observational evidence is crucial to constraining the role of convection and pulsation in M-type stars.

Event-free survival (EFS) in patients with high-risk neuroblastoma (HRNB) receiving eflornithine (DFMO) maintenance treatment based on a retrospective, blinded independent central review (BICR) of imaging during long-term follow-up.

e22007 Background: BICR methodology can evaluate investigator bias in open label studies. Here (BICR W2218), we address potential investigator bias in the open-label evaluation of EFS in a subset of NMTRC003B patients selected for comparison to patients from ANBL0032 (COG trial; NCT00026312) using imaging and clinical assessments. BICR results were then compared to the propensity-score (PS)-matched external control (NO DFMO) patients from ANBL0032. Methods: NMTRC003B DFMO-treated patients (≤2 years, 750 ±250 mg/m2 BID) on (n = 87) or per (n = 5) ANBL0032 and in remission post-dinutuximab completion were selected for inclusion in the BICR. Imaging evaluations (incl. anatomical [CT/MRI] and nuclear [MIBG and/or PET]) were determined at end of immunotherapy (baseline; to confirm remission); at 3, 6, 9, 12, 18, and 24 months; and, per Standard of Care after 24 months. While only required for the 2-year on-therapy period, imaging data were collected during follow up and also evaluated by BICR. All available imaging data (per patient at each visit; baseline via long-term follow up) from NMTRC003B patients were evaluated by two independent radiologists (IR) with adjudication by a third independent radiologist. BICR data from DFMO patients (N = 92) were used to evaluate BICR-EFS vs. EFS in DFMO-treated patients (N = 92) meeting selection criteria (demographic and risk characteristics) for PS-matched comparison (1:3 ratio for DFMO:NO-DFMO) to ANBL0032 (N = 270). ANBL0032 had enrolled N = 1328 HNRB patients assigned to dinutuximab and follow up (≤10 years)1 and required similar imaging evaluations that were unavailable for the BICR. Concordance was evaluated with Cohen’s Kappa coefficient analysis, and EFS using Kaplan-Meier and Cox regression analyses. Results: All 92 patients had adequate imaging at baseline and were included in the BICR. N = 21/92 (22.8%) cases were adjudicated with a final outcome of unequivocal EFS event in N = 15. Despite discordance in n = 2 patients, concordance was very high during the on-treatment (2 years) and full follow-up (≤7) periods with near perfect agreement. In line with previously reported data1, DFMO treatment was associated with significant improvement in relapse events in BICR-DFMO cases vs. PS-matched, external NO DFMO patients over the full BICR period [hazard ratio, HR 0.54 (95% CI: 0.31, 0.95), p = 0.0337] with 2- and 4-year BICR-EFS for DFMO vs. NO DFMO of 88% vs. 80%, and 84% vs. 73%, respectively. Conclusions: This BICR indicates minimal, if any, bias in imaging evaluations in the original NMTRC003B study, providing confidence in the finding that DFMO treatment in HNRB patients in remission post upfront dinutuximab approximately halves the risk of relapse compared to matched control patients.

Feasibility and Acceptability of Community-Based Telehealth to Prevent Long-Term Care Readmission.

Transitioning to community living after long-term care requires multiple complex individualized interventions to prevent readmission. The current focus of home and community-based services (HCBS) is on increasing consumer engagement and individualizing care. Telehealth interventions provide additional services without the burden of face-to-face encounters and have yet to be evaluated for feasibility and acceptability in rural HCBS. West Virginia Bureau for Medical Services and West Virginia University implemented and evaluated a telehealth intervention with 26 Aged and Disabled Waiver or Traumatic Brain Injury Waiver participants who were transitioning back into their communities from a long-term care facility. Feasibility was assessed through recruitment process, fidelity to planned intervention, number of people eligible for participation, number of individuals enrolling in the intervention, enrollment process, completed enrollment, engagement in the intervention, number of weeks participating in the intervention, type of devices provided, attrition, and fidelity to original intervention. Satisfaction with services was used as a marker of acceptability for both participants and providers. Half (n = 12) of the enrolled population completed the full 24-week telehealth monitoring period and modification of the original intervention was necessary for most. Provider and participant satisfaction was high. Recruitment and enrollment may have been affected by COVID-19. Future implementation will continue to track recruitment and retention efforts. Individualized care plans, demonstration and practice with equipment, family or direct-care worker presence, and live technical support through the phone are needed. Primary care provider and in-home direct-care worker satisfaction workflow planning and evaluation are required.

Recent reduced abyssal overturning and ventilation in the Australian Antarctic Basin

Dense water formed near Antarctica, known as Antarctic bottom water (AABW), drives deep ocean circulation and supplies oxygen to the abyssal ocean. Observations show that AABW has freshened and contracted since the 1960s, yet the drivers of these changes and their impact remain uncertain. Here, using observations from the Australian Antarctic Basin, we show that AABW transport reduced by 4.0 Sv between 1994 and 2009, during a period of strong freshening on the continental shelf. An increase in shelf water salinity between 2009 and 2018, previously linked to transient climate variability, drove a partial recovery (2.2 Sv) of AABW transport. Over the full period (1994 to 2017), the net slowdown of −0.8 ± 0.5 Sv decade−1 thinned well-oxygenated layers, driving deoxygenation of −3 ± 2 μmol kg−1 decade−1. These findings demonstrate that freshening of Antarctic shelf waters weakens the lower limb of the abyssal overturning circulation and reduces deep ocean oxygen content.

Optimal Statistical Estimation and Dynamic Adaptive Control of Airline Seat Protection Levels for Several Nested Fare Classes under Parametric Uncertainty of Customer Demand Models

Assigning seats in the same compartment to different fare classes of passengers is a major problem of airline seat allocation. Airlines sell the same seat at different prices according to the time at which the reservation is made and other conditions. Thus the same seat can be sold at different prices. The problem is to find an optimal policy that maximizes total expected revenue. To solve the above problem, this paper presents the novel computational approach to optimization and dynamic adaptive prediction of airline seat protection levels for multiple nested fare classes of single-leg flights under parametric uncertainty. It is assumed that time T (before the flight is scheduled to depart) is divided into h periods, namely a full fare period and h-1 discounted fare periods. The fare structure is given. An airplane has a seat capacity of N. For the sake of simplicity, but without loss of generality, we consider (for illustration) the case of nonstop flight with two fare classes (business and economy). The proposed airline's inventory management policy is based on the use of the proposed computational models. These models emphasize pivotal quantities and ancillary statistics relevant for obtaining statistical predictive limits for anticipated quantities under parametric uncertainty and are applicable whenever the statistical problem is invariant under a group of transformations that acts transitively on the parameter space. The proposed technique is based on a probability transformation and pivotal quantity averaging. It is conceptually simple and easy to use. Finally, we give illustrative examples, where the proposed analytical methodology is illustrated in terms of the two-parameter exponential distribution. Applications to other log-location-scale distributions could follow directly.

Network connectedness of the term structure of yield curve and global Sukuks

This paper explores the connectedness between the returns and volatilities of the conventional and Islamic bond markets. We use the level, slope, and curvature of the US yield curve and estimate the connectedness of these factors with the Dow Jones Islamic indices (of 3 to 10 years of maturity) as well as the minimum connectedness portfolio. The static analysis shows that level and slope of the conventional yield curve are the net transmitters of shocks while the Islamic indices have been mostly at the receiving end. The dynamic connectedness analysis shows a varying degree of the connectedness over the full sample period characterized by distinctive trajectories of booms and busts. The pairwise connectedness analysis also confirms that level and slope are the net transmitters in the system with an exception in most recent times of Covid-19 pandemic. The findings have implications for the researchers, policy makers, regulators, shariah boards, investors, and fund managers.

Long-term ambient air pollution and venous thromboembolism in a population-based Swedish cohort

Air pollution is a major contributor to the global burden of disease and has been linked to several diseases and conditions, including cardiovascular disease. The biological mechanisms are related to inflammation and increased coagulability, factors that play an important role in the pathogenesis of venous thromboembolism (VTE, i.e., deep vein thrombosis or pulmonary embolism). This study investigates if long-term exposure to air pollution is associated with increased VTE incidence. The study followed 29 408 participants from the Malmö Diet and Cancer (MDC) cohort, which consists of adults aged 44–74 recruited in Malmö, Sweden between 1991 and 1996. For each participant, annual mean residential exposures to particulate matter <2.5 μg (PM2.5) and <10 μg (PM10), nitrogen oxides (NOx) and black carbon (BC) from 1990 up to 2016 were calculated. Associations with VTE were analysed using Cox proportional hazard models for air pollution in the year of the VTE event (lag0) and the mean of the prior 1–10 years (lag1-10). Annual air pollution exposures for the full follow-up period had the following means: 10.8 μg/m3 for PM2.5, 15.8 μg/m3 for PM10, 27.7 μg/m3 for NOx, and 0.96 μg/m3 for BC. The mean follow-up period was 19.5 years, with 1418 incident VTE events recorded during this period. Exposure to lag1-10 PM2.5 was associated with an increased risk of VTE (HR 1.17 (95%CI 1.01–1.37)) per interquartile range (IQR) of 1.2 μg/m3 increase in PM2.5 exposure. No significant associations were found between other pollutants or lag0 PM2.5 and incident VTE. When VTE was divided into specific diagnoses, associations with lag1-10 PM2.5 exposure were similarly positive for deep vein thrombosis but not for pulmonary embolism. Results persisted in sensitivity analyses and in multi-pollutant models. Long-term exposure to moderate concentrations of ambient PM2.5 was associated with increased risks of VTE in the general population in Sweden.

Secondary Prevention of Esophageal Variceal Bleeding Is Often Imperfect: A National, Population-Based Cohort Study of 3592 Patients

Secondary prevention of esophageal variceal bleeding is important to improve prognosis, but uptake of guidelines is unknown in a real-world setting. Here, we determined the proportion of patients receiving appropriate nonselective beta-blocker treatment and repeat upper endoscopy after a first episode of esophageal variceal bleeding within a reasonable time frame. Population-based registers were used to identify all patients with a first episode of esophageal variceal bleeding in Sweden from 2006 to 2020. Crosslinkage between registers was performed to receive information on the cumulative incidence of patients with a dispensation of nonselective beta-blockers and repeat upper endoscopy within 120 days from baseline. Overall mortality was investigated using Cox regression. In total, 3592 patients were identified, with a median age of 63 (interquartile range, 54-71) years. The cumulative incidence of a dispensation of nonselective beta-blockers and a repeat endoscopy within 120 days was 33%. A total of 77% received either of these treatments. Overall mortality was high, with 65% of patients dying after esophageal variceal bleeding during the full follow-up period (median 1.7 years). We observed an improved overall mortality during the later years of the study period (adjusted hazard ratio for the 2016-2020 period compared with the 2006-2010 period, 0.80; 95% confidence interval, 0.71-0.89). Patients with receipt of nonselective beta-blockers and repeat upper endoscopy had better overall survival compared with those without (adjusted hazard ratio, 0.80; 95% confidence interval, 0.72-0.90). Secondary prevention of esophageal variceal bleeding has not been widely undertaken, with many patients not receiving guideline-supported interventions within a reasonable time frame. This highlights a need to raise awareness on appropriate prevention strategies to clinicians and patients.

Use of a Prophylactic Retrograde-Flushing Device in High-Risk Pediatric Patients with Ventriculoperitoneal Shunts: A Technical Note

Introduction: Ventriculoperitoneal shunt (VPS) malfunction rates are as high as 40% in the first year with posthemorrhagic hydrocephalus (PHH) patients having the highest proximal occlusion risk. Debris, protein, and cellular ingrowth most commonly obstruct the proximal ventricular catheter and/or valve. Historically, no preventative methods have demonstrated efficacy. We present a technical note and case series describing the use of a retrograde proximal flushing device and prophylactic flushing protocol to maintain ventricular catheter patency and reduce proximal shunt occlusions. Methods: We present our 2.8–4-year follow-up data on the first 9 pediatric cases of ReFlow (Anuncia Inc, Scottsdale, AZ) device implantation combined with routine prophylactic flushing. Rationale for device implantation, patient selection, surgical procedure details, postoperative follow-up, and prophylactic flushing protocol are discussed as well as pre- and postimplantation ventricular catheter obstruction rates. We include a technical note on the device setup and prophylactic flushing protocol. Results: Patient average age was 5.6 years and all patients had PHH. Minimal follow-up was 2.8 years (range 2.8–4 years). Prophylactic flushing was initiated between 2 and 14 days after ReFlow implantation and has continued as of the last follow-up. In 7 patients, ReFlow implantation occurred during the revision of an existing shunt and in two, implantation was coincident with initial VPS placement. In the 2 years preceding ReFlow and prophylactic flushing, 14 proximal shunt failures occurred in the 7 patients with existing VPS. This was reduced to only one proximal shunt failure in all 9 patients during the full follow-up period after ReFlow and prophylactic flushing. Conclusion: Pediatric VPS placement carries high rates of proximal catheter occlusion, often leading to emergency surgery, morbidity, or even death. The ReFlow device along with routine prophylactic flushing may reduce proximal obstruction and need for revision surgery. Higher patient numbers and longer follow-up periods are necessary to further elucidate the safety and effect of such a device on longer term shunt failures and revision surgery.

Export of organic carbon, nutrients and metals by the mid-sized Pechora River to the Arctic Ocean

In contrast to good knowledge of export fluxes of carbon and metals from mainland to the Arctic Ocean by large Arctic Rivers, information on mid-sized rivers is limited, which prevents determining current status and foreseeing future changes in riverine export induced by climate change. Here we focused on one of the ‘middle eight’ Arctic rivers. The Pechora River (Swatershed = 322,000 km2) is the second largest European Arctic river draining through boreal forest and peatlands with partial (∼ 40%) permafrost coverage. Over 4 consecutive years (2015–2019), we measured weekly to monthly concentrations of carbon, major nutrients, and 40 major and trace elements in filtered (< 0.45 μm) river water at the terminal gauging stations for the Pechora River. The dependences between dissolved element concentration and river discharge over the full period of observation revealed 3 groups of major and trace solutes according to their seasonal behavior. Group 1 was comprised of Dissolved Inorganic Carbon (DIC), major anions (Cl, SO4), alkalis (Li, Na, K, Rb), alkaline-earth metals (Mg, Ca, Sr, Ba), elements present in the form of labile anions and neutral molecules (B, Si, Ge, Mo, Sb) and U. It demonstrated minimal concentrations during spring flooding and autumn high flow events, and maximal concentrations during winter base flow. Concentrations of these element negatively correlated with discharge. These elements primarily reflected the dominant sedimentary lithology of the Pechora catchment and were controlled by influx of underground waters hosted in carbonate rocks. Group 2 included DOC and low-mobility trivalent and tetravalent hydrolysates (Be, Al, Ga, Y, REEs, Ti, Zr, Hf, Th) and some trace metals (V, Cr, Cs, Nb). The transport of these elements to the river from the catchment likely occurred via surface and shallow subsurface waters due to leaching from organic-rich litter layer, and their concentrations positively correlated with discharge. Finally, group 3 involved major- (P, N, K) and micro-nutrients (Fe, Mn, Cu, Zn, Mo) and demonstrated features of both the 1st and 2nd groups as these elements originated from surface (organic-rich) and underground (sedimentary rock-hosted) sources and were removed by autochthonous biotic processes in the water column. As a result, the concentration of these nutrients exhibited a winter maximum and a summer minimum.Similar to other Arctic and subarctic rivers, the spring flood, which lasted from May to June, accounted for >50% of the annual export of DOC and generally insoluble trace metals. However, the winter baseflow provided sizable proportions of mobile elements such as DIC, major anions, cations, alkaline-earth elements, trace oxyanions and uranium. The size distribution of riverine solutes demonstrated 20–50% of DOC in the colloidal (3 kDa – 0.45 μm) form, dominance of low molecular forms (< 3 kDa) of soluble elements (alkali, alkaline earths, anions and neutral molecules) and essentially colloidal status of divalent metals (Cu, Zn, Cd, Pb, Ni), trivalent and tetravalent hydrolysates and U (from 30 to 93%). Seasonal variations in colloidal fractions of riverine solutes were consistent with the main mechanisms of element mobilization from the watershed to the Pechora River, as reflected in the 3 groups of elements according to their concentration – discharge relationship. Based on the present study and results of other mid-sized Arctic rivers (Severnaya Dvina, Taz), we demonstrate that mean discharges and solute concentrations in August can be used to adequately (± 20%) approximate mean annual values, hence allowing annual flux assessment via single month sampling campaign. A comparison of contemporary yields of Ca, Mg, Cl, SO4, DIC and DOC against historical data for the Pechora River basin demonstrated reasonable agreement within the inter-annual variations that is consistent with long-term data series on other Arctic rivers.