Marginal Response Research Articles

The effects of different densities of Asparagopsis armata (Harvey, 1855) seaweed on the clam Ruditapes philippinarum (A. Adams and Reeve, 1850): Insights from a laboratory assessment

Several invasive species can occupy the same geographic area. Interaction between species depends on several factors, and the results of such interactions can be highly diverse. Asparagopsis armata is a invasive red seaweed whose exudates contain a cocktail of toxic halogenated compounds. In this study, the impact of high and low levels of A. armata on the bivalve Ruditapes philippinarum was assessed in a laboratory experiment. Both are prominent invasive species in Europe and could share the same habitats. The effects of the algae were measured at different biological levels, framed by an integrated approach: bioturbation as a proxy for organismal activity and behaviour within the sediment, and several subcellular biomarkers related to oxidative stress and damage, energy metabolism, detoxification, and neurotransmission. While bioturbation revealed the effects of exudates on the bivalve, with a decrease in most parameters when exposed to the different amounts of algae, only marginal responses were found for biomarkers, suggesting a possible temporal decoupling between the behavioural response and the intrinsic biochemical environment. These results denote that despite the recognized potential of biomarkers to address a myriad of situations, a proxy for higher levels of biological organization, such as behaviour, for its integration of lower-level effects, is a robust tool to address complex and lesser-known mixtures of stressors.

Numerical investigation of lean methane flame response to NRP discharges actuation

This study investigates the response of a laminar methane-air flame to Nanosecond Repetitively Pulsed (NRP) discharges in a canonical wall-stabilized burner using a combined experimental and numerical approach. The flow and flame behaviors were modeled using Direct Numerical Simulation (DNS) with an Analytically Reduced Chemistry for a precise chemical description. A phenomenological model incorporating detailed plasma kinetics and experimental observations was developed to simulate plasma effects. Zero-dimensional plasma reactor simulations were used to build up a reduced-order model describing discharge energy distribution in the specific conditions studied. Experimental measurements of electrical profiles identified two discharge regimes: a low-energy Corona discharge and a higher-energy Glow discharge, characterized by distinct spatial energy distributions. Experimental flame response analysis revealed three major phases: marginal response up to 100 pulses, a downstream shift of the flame tip, and stabilization after 400 pulses. Numerical simulations indicated that the Corona regime is crucial for explaining initial flame responses, while the Glow regime influences later stages. Adjustments in the Vibrational-Translational (VT) energy relaxation time and energy deposition ratios between fresh and burnt gases were necessary to match experimental observations. Additionally, an accurate modeling of the transient and steady-state flame responses requires integrating both the specificity of the Corona and the Glow discharge regimes. Future work should focus on measuring or theoretically calculating N2(v) relaxation times in CH4-H2O-CO2 mixtures and analyzing the spatial energy distribution of discharges interacting with flames to enhance plasma-combustion coupled models.Novelty and significanceIn this work, a phenomenological plasma-assisted combustion model has been developed, to investigate a laminar premixed stagnation plate burner, focusing on VT energy relaxation time and spatio-temporal energy distribution modeling. For the first time, not only O2, N2 and O but also the fuel and combustion intermediates and products have been considered in the VT relaxation model. It revealed their strong influence on the overall flame response in a case where the discharge crosses a flame front, highlighting the strong beneficial effect of energy deposited in vibrational form. The study questions and investigates the energy distribution from fresh to burnt gases, challenging the conventional uniform energy distribution assumption. The experimental identification of two specific plasma regimes was necessary to predict the transient flame response. Additionally, energy deposited downstream of the flame, in fresh gases, was found to more efficient than in hot gases to enhance combustion.

The predicting value of post neoadjuvant treatment magnetic resonance imaging: a meta-analysis.

Neoadjuvant therapy has become standard of care for locally advanced rectal cancer patients. It is correlated with improved clinical and pathological outcomes, including significant tumor downstaging and organ preservation in certain patients. Magnetic resonance imaging (MRI), which has become the standard for pre-operative staging, is also used for clinical and pre-operative restaging following pre-operative treatment. In this meta-analysis, we aimed to evaluate the concordance between restaging MRI (following the completion of neoadjuvant therapy) and postoperative pathology result. We conducted a meta-analysis following the PRISMA 2020 guidelines. Two independent reviewers searched PubMed and Google Scholar for studies reporting restaging MRI results compared to pathological outcomes. Outcomes included tumor and nodal staging, circumferential resection margin (CRM) and pathological complete response (pCR). Out of 25,000 studies found on the initial search; 33 studies were included. The studies were published between 2005 and 2023 and included 4100 patients (57.14% males). The median age was 62.45 years. The median interval between the conclusion of neoadjuvant treatment and the subsequent restaging MRI was 6 weeks (range 4.14-8.8 weeks). The pooled concordance rates between the restaging MRI and the pathological outcomes for ypT stage and ypN stage were 63.9% (54.5%-73.3%, I2 = 96.02%) and 60.9% (42.9%-78.9%, I2 = 98.96%), respectively. The pooled concordance for predicting pathological complete response was 70.4% (53.6%-87.1%, I2 = 98.21%). As for the circumferential resection margin (CRM), the pooled concordance was 78.2.% (71.6%-84.8%, I2 = 83.76%). Our findings suggest that the concordance rates between restaging MRI and pathological outcomes in rectal cancer patients following neoadjuvant therapy are limited. Caregivers should take these results into consideration when making clinical decisions about these patients. More data should be gathered about the predictive value of MRI after total neoadjuvant therapy as well as immunotherapy in rectal cancer patients.

Magnetic excitations in strained infinite-layer nickelate PrNiO2 films

Strongly correlated materials respond sensitively to external perturbations such as strain, pressure, and doping. In the recently discovered superconducting infinite-layer nickelates, the superconducting transition temperature can be enhanced via only ~ 1% compressive strain-tuning with the root of such enhancement still being elusive. Using resonant inelastic x-ray scattering (RIXS), we investigate the magnetic excitations in infinite-layer PrNiO2 thin films grown on two different substrates, namely SrTiO3 (STO) and (LaAlO3)0.3(Sr2TaAlO6)0.7 (LSAT) enforcing different strain on the nickelates films. The magnon bandwidth of PrNiO2 shows only marginal response to strain-tuning, in sharp contrast to the enhancement of the superconducting transition temperature Tc in the doped superconducting samples. These results suggest the bandwidth of spin excitations of the parent compounds is similar under strain while Tc in the doped ones is not, and thus provide important empirics for the understanding of superconductivity in infinite-layer nickelates.

Progressive demyelinating polyneuropathy after hematopoietic cell transplantation in metachromatic leukodystrophy: a case series

Metachromatic leukodystrophy (MLD) is a neuro-metabolic disorder due to arylsulfatase A deficiency, causing demyelination of the central and peripheral nervous system. Hematopoietic cell transplantation (HCT) can provide a symptomatic and survival benefit for pre-symptomatic and early symptomatic patients by stabilizing CNS disease. This case series, however, illustrates the occurrence of severely progressive polyneuropathy shortly after HCT in two patients with late-infantile, one with late-juvenile, and one with adult MLD, leading to the inability to walk or sit without support. The patients had demyelinating polyneuropathy before HCT, performed at the ages of 2 years in the first two patients and at 14 and 23 years in the other two patients. The myeloablative conditioning regimen consisted of busulfan, fludarabine and, in one case, rituximab, with anti-thymocyte globulin, cyclosporine, steroids, and/or mycophenolate mofetil for GvHD prophylaxis. Polyneuropathy after HCT progressed parallel with tapering immunosuppression and paralleled bouts of infection and graft-versus-host disease (GvHD). Differential diagnoses included MLD progression, neurological GvHD or another (auto)inflammatory cause. Laboratory, electroneurography and pathology investigations were inconclusive. In two patients, treatment with immunomodulatory drugs led to temporary improvement, but not sustained stabilization of polyneuropathy. One patient showed recovery to pre-HCT functioning, except for a Holmes-like tremor, for which a peripheral origin cannot be excluded. One patient showed marginal response to immunosuppressive treatment and died ten months after HCT due to respiratory failure. The extensive diagnostic and therapeutic attempts highlight the challenge of characterizing and treating progressive polyneuropathy in patients with MLD shortly after HCT. We advise to consider repeat electro-neurography and possibly peripheral nerve biopsy in such patients. Nerve conduction blocks, evidence of the presence of T lymphocytes and macrophages in the neuronal and surrounding nerve tissue, and beneficial effects of immunomodulatory drugs may indicate a partially (auto)immune-mediated pathology. Polyneuropathy may cause major residual disease burden after HCT. MLD patients with progressive polyneuropathy could potentially benefit from a more intensified immunomodulatory drug regime following HCT, especially at times of immune activation.

Abstract 3963: Indoleamine 2,3-dioxygenase 1 (IDO1) regulates immune evasion in lymphoma

Abstract Recently, anti-programmed death (anti-PD) therapy has been at the forefront of cancer therapy. However, the clinical efficacy of anti-PD therapy in DLBCL remains obscure. The marginal response to anti-PD therapy in DLBCL indicates that different mechanisms of immune evasion other than the PD-1/PD-L1 pathway may be present. To investigate the mechanisms of resistance to anti-PD therapy in DLBCL, we assessed gene expression in patients with DLBCL in public database. Accordingly, we found indoleamine 2,3-dioxygenase 1 (IDO1), a key enzyme responsible for tryptophan catabolism, is highly expressed in DLBCL. IDO1 expression is upregulated by IFN-gamma produced by T cells in tumor microenvironments (TMEs) of various cancer types. Upregulated IDO1 leads to the production of kynurenine, which creates an immunosuppressive TMEs. However, it remains unknown whether IDO1 induces immune evasion in DLBCL and if so, which subsets of IDO1 expressing cells are responsible for immune evasion in DLBCL. To address these questions, we first determined the intrinsic role of IDO1 in lymphoma cells. We knocked down IDO1 expression (IDO1 KD) in a human DLBCL RC-K8 cell line using short hairpin RNA. We observed decreased cell proliferation in IDO KD lymphoma cells compared with control cells. We also found increased susceptibility to apoptosis in IDO1 KD RC-K8 cells compared with IDO1 WT control, when these were co-cultured with THP-1-derived macrophages or activated Jurkat T lymphocytes. These data suggest that lymphoma IDO1 has an intrinsic role of lymphoma progression and makes lymphoma sensitive to cytotoxic immune cells. To validate the anti-tumor effect of IDO1 deficiency in immune cells, we assessed EL4 lymphoma growth and immune TME of lymphoma in syngeneic wild type (WT) and Ido1 knock-out (KO) mice. The growth of EL4 lymphoma tumor was significantly suppressed in Ido1 KO mice compared to WT mice (Ido1 KO: 621.9mm3 vs WT: 1228mm3, N=22, P<0.001). Immune TME assessment revealed a decreased frequency of regulatory T cells, yet, the increased proportions of B cells, MHC II+ antigen-presenting cells, monocytes, and NK cells in Ido1 KO tumors compared with WT control. In summary, IDO1 is highly expressed in DLBCL. IDO1 up-regulation may drive lymphoma progression both intrinsically and extrinsically (immune evasion). This data suggests that IDO1 overexpression may be one of the mechanisms of resistance to anti-PD therapy. We will extend our studies to determine a combination effect of IDO1 inhibitors with immune checkpoint inhibitors including anti-PD therapy in DLBCL. Citation Format: Jihyun Park, Seung-Joo Yoo, Qianni Hu, Carly M. Fielder, Hyundong Yoon, Junshik Hong, Byung-Su Kim, Youngil Koh, Tae Kon Kim, Sung-Soo Yoon, Chi Yan. Indoleamine 2,3-dioxygenase 1 (IDO1) regulates immune evasion in lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3963.

Identifying the Depreciation Rate of Durables from Marginal Spending Responses

AbstractThis paper presents a new method to estimate the depreciation rate of durable goods using a combination of identified marginal and average spending shares. We apply our method to Chinese spending responses to disposable income changes induced by monetary policy in 2008–09. The marginal total spending response is 0.40. About 46% of this marginal spending response is due to durable goods. By combining this marginal spending share on durables with an average spending share of 14%, we estimate the annual depreciation rate of durables in China to be 0.17.

A critical analysis of physical activity's promising function in the management of Type 2 Diabetes Mellitus

Physical activity (PA) has been demonstrated to have negative correlations with type 2 diabetes mellitus. Considering provided the establishment of the dose‒response interactions still additionally undiscovered. For investigating the association involving extra cases of type 2-diabetes and PA, the study utilizes model nonlinearity. Implementing together study findings from multidemographic long-term studies. A metric that exclusively considers energy employed above resting metabolic rate was used to translate PA exposures through reduced metabolic equivalent of task (MET) and the physiological equivalent of task hours per the previous week. The association involving radiation and illness was modeled utilizing restricted quadratic splices. The results point to a general nonlinear association; utilizing the rectangular spline model, we discovered a probability decrease for type 2 diabetes of twenty-six percent among people who attained eleven twenty-five MET hours per month. A risk decrease of 36% was shown when this quantity of PA was doubled, and more significant reductions were seen at higher dosages. For moderate-intensity PA the power source marginal MET week dose‒response curve's findings revealed comparable. However, the advantages of higher-intensity PA were more significant, and those of lower-intensity activity substantially decreased. Among the overall population, higher levels of has been connected to a significantly decreased risk of type 2 diabetes. The relationships between type’s two diabetics with LTPA were curved. At quantities far higher than those recommended by the health department standards, however, further benefits may be possible. The most significant insufficient quantities of exercise result in relative improvements.

Targeted In Vivo Generation of CAR T and NK Cells Utilizing an Engineered Lentiviral Vector Platform

CAR T cell therapies have revolutionized the treatment of B cell malignancies. Ex vivo CAR manufacturing is complex, costly, and cumbersome, prompting efforts that develop shorter manufacturing and allogeneic or “universal donor” strategies. Conventional ex vivo CAR T cell therapy is not widely accessible and financial burdens to patients further hinder access to care. Furthermore, recent data show that CAR T product efficacy is correlated with reduced ex vivo manipulation of cells. Here, we have designed a gene delivery system to transduce effector cells inside the body to generate autologous CAR cells, circumventing ex vivo cell manipulation, avoiding patient conditioning chemotherapy, and providing a low cost, “off-the-shelf” therapy. The product, INT2104, is an intravenously administered lentiviral vector encoding an anti-CD20 CAR transgene. INT2104 was rationally designed with an engineered fusogen and a novel binder to enable targeted transduction of CD7 + T and NK cells. The CAR20 molecule encoded by INT2104 is constructed of fully human domains, including a human and NHP cross-reactive anti-CD20 scFv, enabling preclinical studies in both humanized mouse and NHP models (Figure 1). Prior to animal studies, INT2104 was extensively assessed in vitro for targeting specificity and the ability to generate functional effector cells. Incubating INT2104 with activated primary human PBMCs confirmed transduction of CD4 and CD8 T cells as well as NK cells. No B cell transduction was seen across a wide range of MOIs when INT2104 was used to inoculate a large panel of B cell tumor lines and primary PBMCs isolated from patients with B cell malignancies and healthy donors. INT2104-treated PBMCs cocultured with B cell tumor targets resulted in dose-dependent tumor cell killing. In vivo evaluation of INT2104 has been conducted in three humanized mouse models. In CD34-engrafted NSG mice, delivery of INT2104 via tail vein injection resulted in B cell depletion within 7 days, with CAR + cells detectable in blood coincident with B cell ablation. In an established B cell tumor NSG model, INT2104 administration also resulted in B cell aplasia. In this tumor model, complete tumor ablation was seen in all treated mice across a 15-fold range in dosing, including a dose matching the proposed FIH dose in TU/kg. Protection from a re-challenge with tumor cells was also demonstrated. Finally, transgenic hIL15-expressing CD34-engrafted NSG mice were used to demonstrate in vivo generation of both CAR NK cells and CAR T cells in animals having B cell depletion. In preclinical studies, 15 of 16 cynomolgus macaques receiving the CAR20 vector achieved at least a 75% reduction in circulating B cells following vector infusion. Some animals experienced a variable return of circulating B cells that was associated with immune responses to the CAR protein (anti-CAR responses). One animal (with a marginal immune response to the CAR) has shown complete and prolonged B cell depletion associated with persistence of the CAR transgene in peripheral blood and bone marrow (Figure 2). Taken together, these data suggest that intravenous delivery of INT2104 will be both safe and effective, providing a faster, cheaper, and more accessible option for treatment of B cell malignancies. Ongoing efforts include a GLP Toxicology study to enable IND submission in 2Q2024.

Selection on Welfare Gains: Experimental Evidence from Electricity Plan Choice

We study a problem in which policymakers need to screen self-selected individuals by unobserved heterogeneity in social welfare gains from a policy intervention. In our framework, the marginal treatment effects and marginal treatment responses arise as key statistics to characterize social welfare. We apply this framework to a randomized field experiment on electricity plan choice. Consumers were offered welfare-improving dynamic pricing with randomly assigned take-up incentives. We find that price-elastic consumers—who generate larger welfare gains—are more likely to self-select. Our counterfactual simulations quantify the optimal take-up incentives that exploit observed and unobserved heterogeneity in selection and welfare gains. (JEL C93, D12, L11, L94, L98)

Interactive effects of a stimbiotic supplementation and wheat bran inclusion in corn- or wheat-based diets on growth performance, ileal digestibility, and expression of nutrient transporters of broilers chickens

A 42-day experiment was conducted to investigate the interactive effects of a stimbiotic (STB) and wheat bran (WB) in broiler chickens receiving diets (DT) based on corn or wheat. A total of 960 Cobb 500 male broiler chicks at zero-day old were allocated to 64 pens with 8 treatments, 8 replicates per treatment, and 15 birds per replicate. The treatments were arranged in a randomized complete block design with 2×2×2 factorial, with the factors as diet (corn-soybean meal or wheat-soybean meal), STB (with or without), and WB (0 or 50 g/kg). Body weight gain (BWG), feed intake (FI), and mortality-corrected FCR data were collected for the starter (d 0-10), grower (d 10-28), and finisher (d 28-42) phases. Ileal digesta and jejunal tissue were collected on d 18 and 42. Data were analyzed as a 2×2×2 factorial using a mixed model of JMP. There was no significant 3-way interaction for growth performance and expression of nutrient transporters. There was a significant SB×WB for FCR (P < 0.05) in the grower phase. Stimbiotic supplementation and WB inclusion individually improved (P < 0.05) FCR regardless of cereal type, but this effect was not observed when the two were combined. In the overall phase (d 0-42), birds receiving corn-based diets had higher (P < 0.05) FI and BWG than those receiving wheat-based diets. There was a significant 3-way interaction for ileal digestible energy (IDE) (P < 0.05) and N digestibility (ND) on d 18 and 42 (P < 0.05). There was no effect of STB or WB in corn-based diets, whereas WB inclusion decreased IDE in wheat-based diets, but STB supplementation increased IDE with or without WB. In corn-based diets, WB inclusion increased ND, whereas ND was decreased in wheat-based diets. Supplementation with STB had no effect on ND, but STB increased ND in wheat-based diets with and without WB. Ileal DE was greater (P < 0.05) for wheat- than corn-based diets on d 42. Wheat bran inclusion increased ND in corn-based diets whereas, with STB supplementation, there was no difference in ND with or without WB. There was no difference in ND with or without STB or WB in wheat-based diets. There was a significant STB×DT on the expression of GLUT-1 (P < 0.05). In corn-based diets, STB produced an upward expression of GLUT-1, whereas in wheat-based diets, STB supplementation had no effect. On d 42, stimbiotic supplementation produced upward (P < 0.05) expression of SGLT-1. In conclusion, STB supplementation in wheat- or corn-based diets and with WB inclusion improved energy digestibility. On the other hand, WB inclusion in wheat-based diets decreased nutrient digestibility especially on d 18, thus making room for a positive response to STB supplementation in wheat-based diets compared to the marginal response to STB supplementation observed in corn-based diets.

Predicting Positive Radial Margin on Restaging MRI of Patients with Low Rectal Cancer: Can We Do Better?

Objective The aim of this study was to characterize the tissue involving the margin and study if this information will affect margin prediction on restaging magnetic resonance imaging (MRI) in low rectal adenocarcinoma (LRC) patients treated with neoadjuvant long-course chemoradiotherapy (LCCRT). Methods In this retrospective study of nonmetastatic LRC (distal margin <5 cm from the anal verge) treated with LCCRT followed by surgery, a radiologist blinded to outcome reread the restaging MRI and documented if the radial margin was involved by tumor, fibrosis, or mucin reaction using T2 high-resolution (HR) and diffusion-weighted imaging (DWI). The diagnostic performance of tumor-involving margin on restaging MRI was assessed using surgical histopathology as a reference. Interobserver agreement between three independent radiologists was assessed in a subset. Results We included 133 patients (80 males and 53 females) with a mean (range) age of 44.7 (21-86) years and 82% of them had well or moderately differentiated adenocarcinoma. Baseline MRI showed T3 ( n = 58) or T4 ( n = 60) disease in 89% of the patients. The pathological margin was positive in 21% ( n = 28) cases. In restaging MRI, the circumferential resection margin (CRM) ≤1 mm in 75.1% ( n = 100) cases and MRI predicted tumor, fibrosis, and mucin reaction at the margin in 60, 34, and 6%, respectively, and histopathology showed tumor cells in 33, 14.7, and 16.6% of them, respectively. LRC with tumor-involving margin and bad response (MR tumor regression grade [mr-TRG] 3-5) on restaging MRI had fourfold increased risk of positive pathological circumferential resection margin (pCRM). There was moderate and fair inter-reader agreement for the tissue type involving the CRM ( κ = 0.471) and mr-TRG ( κ = 0.266), p < 0.05. The use of both distance criteria and tumor-involving margins improved the diagnostic accuracy for margin prediction from 39 to 66% on restaging MRI. Conclusions Margin prediction on restaging MRI can be improved by characterizing the tissue type involving the margin in low rectal cancer patients. The inter-reader agreement was moderate for determining the tissue type.

The efficacy of low-level laser therapy for the healing of second-degree burn wounds on lower limbs of glucocorticoid-dependent patients.

This study was designed to investigate the effect of 630 ~ 650-nm red light on treating second-degree burns on lower limbs of glucocorticoid-dependent patients. Sixty-two glucocorticoid-dependent patients with the second-degree burns on lower limbs were divided into the control group (n = 25) and the observation group (n = 37) according to the treatment sequence and the patients' willingness. The patients in both groups were conventionally treated with 1% sulfadiazine silver cream dressing, with the only difference that the observation group received an additional 630-650-nm red light irradiation for 20min before dressing. Each group was observed for 21days, and observation ended if the wound healing was terminated. The wound healing rates, wound secretions, marginal response, and pain/itching levels were monitored and assessed. Compared with the control group, the observation group showed higher wound healing rate, fewer wound secretions, and more relief in marginal response. Clinical observation showed that 630-650-nm red light could effectively reduce wound purulent drainage/discharge, relieve the marginal response as well as pain, and promote wound healing.

Farm-level Hydroeconomic Analysis of Alternative Water Tariff Charges Using a Hybrid Solution Method

This paper's main objective is to develop a farm-level water programming model to realistically model extensive margin and intensive margin responses resulting from deficit irrigation to the implementation of volumetric water charges. The highly complex programming model that uses the FAO56 water budget calculations to simulate crop water use while using relative evapotranspiration to estimate crop yield is solved using a hybrid procedure. The hybrid solution procedure uses a genetic algorithm to simplify the optimization model by fixing the irrigation schedule of each crop and then solving for the optimal water allocation amongst crops subject to water constraints. The area-based charges results showed that when irrigation application efficiency is low, irrigators could apply more water per hectare to sustain high crop yields without being held accountable if water quotas are exceeded. In contrast, irrigators with higher application efficiency could use less water than the area-based estimated water use. The results also showed that volumetric water charges cause both intensive margin and extensive margin responses. The conclusion of whether a volumetric-based water charging system will be better than area-based water charges is not straightforward because of differentiated impacts on profitability and hydrology. While irrigators will use irrigation water more efficiently and adopt more efficient irrigation technologies, their changed behavior could impact the hydrology of the water system through reduced return flows.

Future Physical and Biogeochemical Ocean Conditions under Climate Change along the British Columbia Continental Margin

ABSTRACT Climate change impacts coastal ecosystems through large scale changes in temperature, stratification, circulation and ocean acidification. Here, the potential response of the British Columbia continental margin to climate change is investigated using a regional ocean circulation-biogeochemical model to downscale climate change projections from the Canadian regional and global climate models (CanRCM4/CanESM2) under two Intergovernmental Panel on Climate Change emission scenarios (RCP 4.5 and RCP 8.5). Projections of future physical and biogeochemical conditions for the 2041–2070 period are compared to the recent past (1981–2010). We found an overall annual average warming of >1.6°C in sea surface temperature, increase in stratification in the upper layer, and decrease in surface pH of as much as 0.21. Increasing stratification and changing winds have a limited impact on nitrate availability, phytoplankton biomass and primary production, whilst ocean warming increases primary production by up to 30% in most of the model domain. Increased atmospheric CO2 contributes to acidification over the model domain with a decrease in pH and aragonite saturation (Ωarag) at all depths resulting in an increase of 20 to 32% of the volume of Ωarag ≤1 in the upper 100 m of the continental shelf depending on the climate scenario. Our projected results, therefore, show that future climate change may alter the amount of food available for higher trophic levels and the habitat of benthic species, since bottom waters on the shelf will be undersaturated with respect to aragonite for 2–3 months in mid-summer. Both climate change scenarios results in a similar pattern of changes but projected changes were stronger and more extensive under RCP 8.5 showing the benefit of mitigation efforts in reducing the effect of climate change on marine ecosystem stressors.

Cost-Utility Comparison of Bevacizumab and Aflibercept in the Treatment of Central or Hemiretinal Vein Occlusion in the SCORE2 Trial

Retinal vein occlusion is the second most common retinal vascular disease. Bevacizumab was demonstrated in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) to be noninferior to aflibercept with respect to visual acuity in study participants with macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) following 6 months of therapy. In this study, the cost-utility of bevacizumab vs aflibercept for treatment of CRVO is evaluated. To investigate the relative cost-effectiveness of bevacizumab vs aflibercept for treatment of macular edema associated with CRVO or HRVO. This economic evaluation study used a microsimulation cohort of patients with clinical and demographic characteristics similar to those of SCORE2 participants and a Markov process. Parameters were estimated and validated using a split-sample approach of the SCORE2 population. The simulated cohort included 5000 patients who were evaluated 100 times, each with a different set of characteristics randomly selected based on the SCORE2 trial. SCORE2 data were collected from September 2014 October 2019, and data were analyzed from October 2019 to July 2021. Bevacizumab (followed by aflibercept among patients with a protocol-defined poor or marginal response to bevacizumab at month 6) vs aflibercept (followed by a dexamethasone implant among patients with a protocol-defined poor or marginal response to aflibercept at month 6). Incremental cost-utility ratio. The simulation demonstrated that patients treated with aflibercept will have an expected cost $18 127 greater than those treated with bevacizumab in the year following initiation. When coupled with the lack of clinical superiority over bevacizumab (ie, patients treated with bevacizumab had a gain over aflibercept in visual acuity letter score of 4 in the treated eye and 2 in the fellow eye), these results demonstrate that first-line treatment with bevacizumab dominated aflibercept in the simulated cohort of SCORE2 participants. At current price levels, aflibercept would be considered the preferred cost-effective option only if treatment restored the patient to nearly perfect health. While there will be some patients with CRVO-associated or HRVO-associated macular edema who will benefit from first-line treatment with aflibercept rather than bevacizumab, given the minimal differences in visual acuity outcomes and large cost differences for bevacizumab vs aflibercept, first-line treatment with bevacizumab is cost-effective for this condition.

High Step-Up Gain Converter Based on Two-Phase Interleaved Coupled Inductor Without Right-Hand Plane Zero

This paper proposed a novel two-phase interleaved Coupled Inductor (CI) based high step-up gain converter without Right Half Plane (RHP) zeros for a wide operating range of duty cycle. A coupled inductor between input and output is used in the proposed converter to eliminate RHP zero. The energy of CI is transferred to output capacitor when switch is ON to eliminate RHP zero. Furthermore, the converter has a wide operating range to eliminate RHP zero with a coefficient coupling of CI near one. Thus, the converter achieves higher bandwidth and a wide range of control over output voltage. The small-signal model of proposed converter is derived to verify the proposed claim. The single loop voltage control is sufficient to regulate output voltage of the converter with a good stability margin and faster dynamic response for a wide range of load changes. In addition, proposed converter has a high voltage step-up gain and low voltage stress on switching devices compared to the boost converter. Moreover, interleaved operation at input side reduces ripple and increases power density. All theoretical findings are verified by simulation and experimental results. Experimental results are provided from implemented laboratory prototype of input voltage of 24 V to output voltage of 100 V and 200 W power.

Optimizing rice in-season nitrogen topdressing by coupling experimental and modeling data with machine learning algorithms

The modern in-season crop N recommendation approaches should have high reliability in promoting agricultural sustainability. These approaches are relevant to soil properties, meteorological conditions, management practices, and crop in-season growing status. This study aims to use machine learning (ML) algorithms to incorporate the above variables as well as the field reactive nitrogen (N) losses (i.e., N damage cost) simulated by a DeNitrification–DeComposition (DNDC) model to develop a new strategy for optimizing rice in-season topdressing N (TN) usage. Rice field experiments with multiple N treatments and rice varieties were carried out during 2015–2021 at four study sites in eastern China. Four ML algorithms, namely random forest regression (RFR), support vector regression (SVR), lasso regression (LSR), and partial least square regression (PLSR) were used to develop in-season prediction models of yield and reactive N losses by combining soil, meteorological, and management data with crop remote sensing data. The observed in-season agronomic optimum N rates (AONR) that can maximize rice yield at different sites were in the range of 116.5 to 177.4 kg N ha−1, while the in-season economic optimum N rates (EONR) that can maximize marginal revenue (i.e., yield income minus N fertilizer costs and N damage costs) were in the range of 97.4 to 163.6 kg N ha−1. The developed ML models were further used to simulate yield and marginal revenue responses to a series of assumed TN rates (0–300 kg N ha−1, gradient = 20 kg N ha−1). Comparably, RFR model and SVR model were more suitable for determining optimum TN rates, because their simulated response curves of yield and marginal revenue fit the normal regulation (linear plus plateau or single-peak shapes). Independent validation results showed that the in-season AONR and EONR predicted by RFR and SVR well accorded with the observed values (R2 ≥ 0.64, RRMSE ≤ 18.3 %), and the accuracy of ML models containing both historical and in-season meteorological information is superior to ML models that contain in-season meteorological information only. The proposed ML-based strategy is expected to help the regional rice production systems precisely manage N use, improve net profits, and reduce environmental footprints.

Constructing Sexual Victimization: A Thematic Analysis of Reader Responses to A Literary Female-on-Male Rape Story on Goodreads

ABSTRACT Τhe aim of this study was to provide a detailed understanding of unprompted audience responses to a literary story of female-on-male rape on Goodreads. Thematic analysis of 429 reviews revealed 5 key themes and 16 sub-themes, which evolved around appraising the social function of the book, evaluating its literary features, assessing the depiction of female-on-male rape especially in terms of its perceived realism, as well as around a variety of explicitly emotional and cognitive responses. The esthetic features of the story proved to be of particular importance for shaping reader engagement. Reflective elaborations on the female rapist were found to constitute a marginal response pattern. Findings identified the existence of an overarching cognitive schema that construes sexual victimization as feminized and is linked to a tripartite pattern of comprehending female on- male rape (female-focused, gender-inclusive, gender-neutral). The study highlights the persistence of gendered rape myths structured around an “ideal victim” – “ideal offender” paradigm, which, however, co-exist with alternative responses oriented toward de-gendering sexual victimization. These findings suggest the importance of addressing audience responses in future investigations of female sexual violence (hands-on and hands-off behaviors) and pursuing an interventional agenda of more inclusive conceptualizations of victimization.

Flexural Response to Erosional Unloading of Continental Margins: An Example From the Bering Sea, USA

AbstractThe geodynamic response of continental margins to erosion may reveal current and past changes in the location of the continental slope. We model the three‐dimensional isostatic response to erosion along the retreating Beringian Margin to test the hypothesis that the margin and its canyons were dominantly eroded during the Pleistocene. Our results predict 900 m of flexural uplift, though evidence for this magnitude of uplift is not observed in Pleistocene and younger deposits, suggesting a substantial amount of margin erosion occurred pre‐Pleistocene. Uplift of this magnitude may be represented by a Late Miocene unconformity across the Bering Shelf and upwarped subsurface units at the base of the Beringian Margin. The distribution of uplift from varying canyon incision and margin retreat scenarios has implications for the extent of geodynamic response during erosional periods.