Undesirable Effects Research Articles

Familiarity analysis and time-advance experimental study of LP-NGD RC-circuit intended to operate with Unity-normalized gain

Purpose The purpose of this paper is to develop a familiarity analysis of resistive-capacitive (RC) network active circuit operating with unfamiliar low-pass (LP) type negative group delay (NGD) behavior. The design method of NGD circuit is validated by simulation with commercial tool and experimental measurement. Design/methodology/approach The present research work methodology is structured in three main parts. The familiarity theory of RC-network LP-NGD circuit is developed. The LP-NGD circuit parameters are expressed in function of the targeted time-advance. Then, the feasibility study is based on the theory, simulation and measurement result comparisons. Findings The RC-network based LP-NGD proof of concept is validated with −1 and −0.5 ms targeted time-advances after design, simulation, test and characterized. The LP-NGD circuit unity gain prototype presents NGD cut-off frequencies of about 269 and 569 Hz for the targeted time-advances, −1 and −0.5 ms, respectively. Bi-exponential and arbitrary waveform signals were tested to verify the targeted time-advance. Research limitations/implications The performance of the unfamiliar LP-NGD topology developed in the present study is limited by the parasitic elements of constituting lumped components. Practical implications The NGD circuit enables to naturally reduce the undesired delay effect from the electronic and communication systems. The NGD circuit can be exploited to reduce the delay induced by electronic devices and system. Social implications As social impacts of the NGD circuit application, the NGD function is one of prominent solutions to improve the technology performances of future electronic device in term of communication aspect and the transportation system. Originality/value The originality of the paper concerns the theoretical approach of the RC-network parameters in function of the targeted time-advance and the input signal bandwidth. In addition, the experimental results are also particularly original.

Optimising the hygiene of a liquid feeding system to improve the quality of liquid feed for pigs

Poor feeding system hygiene may contribute to uncontrolled spontaneous fermentation in liquid pig feed and its associated undesirable effects. This study aimed to determine the effects of an intensive sanitisation programme in a grow-finisher liquid feeding system by monitoring microbiological and physico-chemical parameters of liquid feed and microbial colonisation of the feeding system surfaces. The sanitisation programme involved a combination of physical and chemical cleaning between batches of grow-finisher pigs, combined with nightly rinsing of the system with an organic acid blend. Improved hygiene of the internal surfaces of the mixing tank and feed pipeline, particularly until week 5 post-cleaning, was evidenced by reduced counts of lactic acid bacteria, total aerobes, Enterobacteriaceae, yeasts and moulds and decreased adenosine triphosphate concentrations. Enterobacteriaceae and moulds remained undetectable on pipeline surfaces for 10 weeks. Scanning electron microscopy of the feed pipelines confirmed these findings. Conversely, the impact on liquid feed microbiology was minimal and short-lived. However, acetic acid, ethanol and biogenic amine concentrations decreased in the feed post-cleaning and no gross energy losses were observed. Therefore, by controlling surface microbial communities on liquid feeding systems via implementation of the sanitisation programme developed in the current study, on-farm liquid feed quality should be improved.

Light‐activated Nanocatalyst for Precise In‐situ Antimicrobial Synthesis via Photoredox‐Catalytic Click Reaction

The excessive and prolonged use of antibiotics contributes to the emergence of drug‐resistant S. aureus strains and potential dysbacteriosis‐related diseases, necessitating the exploration of alternative therapeutic approaches. Herein, we present a light‐activated nanocatalyst for synthesizing in‐situ antimicrobials through photoredox‐catalytic click reaction, achieving precise, site‐directed elimination of S. aureus skin infections. Methylene blue (MB), a commercially available photosensitizer, was encapsulated within the CuII‐based metal‐organic framework, MOF‐199, and further enveloped with Pluronic F‐127 to create the light‐responsive nanocatalyst MB@PMOF. Upon exposure to red light, MB participates in a photoredox‐catalytic cycle, driven by the 1,3,5‐benzenetricarboxylic carboxylate salts (BTC−) ligand presented in the structure of MOF‐199. This light‐activated MB then catalyzes the reduction of CuII to CuI through a single‐electron transfer (SET) process, efficiently initiating the click reaction to form active antimicrobial agents under physiological conditions. Both in vitro and in vivo results demonstrated the effectiveness of MB@PMOF‐catalyzed drug synthesis in inhibiting S. aureus, including their methicillin‐resistant strains, thereby accelerating skin healing in severe bacterial infections. This study introduces a novel design paradigm for controlled, on‐site drug synthesis, offering a promising alternative to realize precise treatment of bacterial infections without undesirable side effects.

Light-activated Nanocatalyst for Precise In-situ Antimicrobial Synthesis via Photoredox-Catalytic Click Reaction.

The excessive and prolonged use of antibiotics contributes to the emergence of drug-resistant S. aureus strains and potential dysbacteriosis-related diseases, necessitating the exploration of alternative therapeutic approaches. Herein, we present a light-activated nanocatalyst for synthesizing in-situ antimicrobials through photoredox-catalytic click reaction, achieving precise, site-directed elimination of S. aureus skin infections. Methylene blue (MB), a commercially available photosensitizer, was encapsulated within the CuII-based metal-organic framework, MOF-199, and further enveloped with Pluronic F-127 to create the light-responsive nanocatalyst MB@PMOF. Upon exposure to red light, MB participates in a photoredox-catalytic cycle, driven by the 1,3,5-benzenetricarboxylic carboxylate salts (BTC-) ligand presented in the structure of MOF-199. This light-activated MB then catalyzes the reduction of CuII to CuI through a single-electron transfer (SET) process, efficiently initiating the click reaction to form active antimicrobial agents under physiological conditions. Both in vitro and in vivo results demonstrated the effectiveness of MB@PMOF-catalyzed drug synthesis in inhibiting S. aureus, including their methicillin-resistant strains, thereby accelerating skin healing in severe bacterial infections. This study introduces a novel design paradigm for controlled, on-site drug synthesis, offering a promising alternative to realize precise treatment of bacterial infections without undesirable side effects.

The Increase in the Plasticity of Microcrystalline Cellulose Spheres’ When Loaded with a Plasticizer

Compaction pressure can induce an undesirable solid-state polymorphic transition in drugs, fragmentation, loss of coated pellet integrity, and the decreased viability and vitality of microorganisms. Thus, the excipients with increased plasticity can be considered as an option to decrease the undesirable effects of compaction pressure. This study aims to increase the plasticity (to reduce the mean yield pressure; Py) of dried microcrystalline cellulose (MCC) by loading it with a specially selected plasticizer. Diethyl citrate (DEC), water, and glycerol were the considered plasticizers. Computation of solubility parameters was used to predict the miscibility of MCC with plasticizers (possible plasticization effect). Plasticizer-loaded MCC spheres with 5.0 wt.% of water, 5.2 wt.% of DEC, and 4.2 wt.% glycerol were obtained via the solvent method, followed by solvent evaporation. Plasticizer-loaded formulations were characterised by TGA, DSC, pXRD, FTIR, pressure-displacement profiles, and in-die Heckel plots. Py was derived from the in-die Heckel analysis and was used as a plasticity parameter. In comparison with non-plasticized MCC (Py = 136.5 MPa), the plasticity of plasticizer-loaded formulations increased (and Py decreased) from DEC (124.7 MPa) to water (106.6 MPa) and glycerol (99.9 MPa), and that was in full accordance with the predicted miscibility likeliness order based on solubility parameters. Therefore, water and glycerol were able to decrease the Py of non-plasticized MCC spheres by 16.3 and 30.0%, respectively. This feasibility study showed the possibility of modifying the plasticity of MCC by loading it with a specially selected plasticizer.

On direct estimation of density parameters and Hubble constant for ΛCDM universe using Hubble measurements

The set of cosmological density parameters ( Ω0mh02 , Ω0kh02 , Ω0Λh02 ) and Hubble constant ( hˆ0 ) are useful for fundamental understanding of the Universe from many perspectives. In this article, we propose a new procedure to estimate these parameters for Λ cold dark matter (ΛCDM) universe in the Friedmann-Robertson-Walker (FRW) background. We generalize the two-point statistics first proposed by Sahni et al (2008) to the three point case and estimate the parameters using currently available Hubble parameter (H(z)) values in the redshift range 0.07 ≤ z ≤ 2.36 measured by differential age (DA) and baryon acoustic oscillation (BAO) techniques. All the parameters are estimated assuming the general case of non-flat universe. Using both DA and BAO data we obtain Ω0mh02=0.1485±0.0065 , Ω0kh02=−0.0137±0.017 , Ω0Λh02=0.3126±0.0145 and hˆ0=0.6689±0.0021 . These results are in satisfactory agreement with the Planck results. An important advantage of our method is that to estimate the value of any one of the independent cosmological parameters one does not need to use the values for the rest of them. Each parameter is obtained solely from the measured values of Hubble parameters at different redshifts without any need to use values of other parameters. Such a method is expected to be less susceptible to the undesired effects of degeneracy issues between cosmological parameters during their estimations. Moreover, there is no requirement of assuming spatial flatness in our method.

Effect of Presodiation Additive on Structural and Interfacial Stability of Hard Carbon | P2‐Na0.66Mn0.75Ni0.2Mg0.05O2 Full Cell

The compatibility between a corncob‐derived hard carbon anode and a layered oxide cathode (Na0.66Mn0.75Ni0.2Mg0.05O2), as well as the effect of presodiation via cathode additive (Na2C4O4), are investigated in a sodium‐ion full cell. Extensive physicochemical and electrochemical characterizations are performed to deeply investigate the structural and interfacial evolution of the materials in the presodiated cell, either within the single cycle or upon long‐term cycling. The use of sacrificial cathode additives is generally regarded as a method to improve full cell performance, especially when using sodium‐deficient materials. However, undesired effects upon decomposition of the sacrificial salt may arise due to the complexity of the system. In this study, it is evidenced that the presodiation changes the properties of the electrodes causing a worsening of the electrochemical performance of the cell during long‐term cycling. The surface morphology of the cathode is negatively affected by the formation of holes/cracks, while redox processes associated with structural transformations are suppressed in the voltage window of interest, with partial structural deformations occurring during activation cycles. The SEI and CEI are also affected by the formation of insulating organic species, which lead to an increased thickness and interphase resistance hampering the charge transfer kinetics of the cell.

An insight into the therapeutic effects of isoliquiritigenin in breast cancer.

Breast cancer ranks as the most widespread malignant condition in women, emerging as a primary contributor to mortality. The primary challenges in cancer treatments involve undesirable side effects. Therefore, exploring natural compounds as additional therapy could provide valuable insights. Isoliquiritigenin (ILN), an isoflavonoid featuring a chalcone moiety primarily sourced from Glycyrrhiza species, has garnered increasing interest in breast cancer research. This review aims to provide a comprehensive understanding of ILN's mechanisms of action in breast cancer, drawing from a range of in vitro and in vivo studies. ILN primarily acts by inhibiting angiogenesis, aromatase, inflammation, and cell proliferation, and preventing invasion and metastasis. Mechanistically, it downregulates miR-374a, phosphoinositide-3-kinase-protein kinase B/Akt, maternal embryonic leucine zipper kinase, vascular endothelial growth factor, and estrogen receptor protein levels, and causes enhancement of Wnt inhibitory factor-1, and Unc-51-like kinase 1 expression to treat breast cancer. ILN emerges as a promising natural option, offering therapeutic advantages with minimal side effects. However, it is important to note that current research on ILN is primarily limited to preclinical models, underscoring the need for further investigation to validate its potential efficacy.

Anthocyanin-Rich Berry Extracts Affect SN-38-Induced Response: A Comparison of Non-Tumorigenic HCEC-1CT and HCT116 Colon Carcinoma Cells

Chemotherapy with irinotecan (CPT-11), the pro-drug of the highly cytotoxic SN-38, is among the standard-of-care treatments for colorectal cancer. To counteract undesired toxic side effects on healthy tissue such as the intestinal epithelium, the use of preparations rich in polyphenols with anti-oxidative and anti-inflammatory properties such as anthocyanins has been proposed. In the present study, the question of whether non-tumorigenic human epithelium cells (HCEC-1CT) can be protected against the cytotoxic impact of SN-38 by anthocyanin-rich polyphenol extracts without compromising the desired therapeutic effect against tumor cells (HCT-116) was addressed. Hence, single and combinatory effects of anthocyanin-rich polyphenol extracts of elderberry (EB), bilberry (Bil), blackberry (BB) and black currant (BC) with the chemotherapeutic drug SN-38 were investigated. Out of the extracts, BB showed the most potent concentration-dependent cytotoxicity alone and in combination with SN-38, with even stronger effects in non-tumorigenic HCEC-1CT cells. In cytotoxic concentrations, BB decreased the level of DNA/topoisomerase I covalent complexes in HCEC-1CT cells below base level but without concomitant reduction in SN-38-induced DNA strand breaks. The herein reported data argue towards an interference of anthocyanins with successful treatment of cancer cells and a lack of protective properties in healthy cells.

Transforming Red Phosphorus Photocatalysis: Dual Roles of Pre-Anchored Ru Single Atoms in Defect and Interface Engineering.

Crystalline red phosphorus(CRP), known for its promising photocatalytic properties, faces challenges in photocatalytic hydrogen evolution(PHE) due to undesired inherent charge deep trapping and recombination effects induced by defects. This study overcomes these limitations through an innovative strategy in integrating ruthenium single atoms(Ru1) within CRP to simultaneously repair the intrinsic undesired vacancy defects and serve as the uniformly distributed anchoring sites for a controllable growth into ruthenium nanoparticles(RuNP). Hence, a highly functionalized CRP with Ru1 and RuNP(Ru1-NP/CRP) with concerted effects in regulating electronic structures and promoting interfacial charge transfer has been achieved. Advanced characterizations unveil the pioneering dual role of pre-anchored Ru1in transforming CRP photocatalysis. The regulations of vacancy defects on the surface of CRP minimize the detrimental deep charge trapping, resulting in the prolonged lifetime of charges. With the well-distributed in-situ growth of RuNP on Ru1 sites, the constructed robust "bridge" that connects CRP and RuNP facilitates constructive interfacial charge transfer. Ultimately, the synergistic effect induced by the pre-anchored Ru1 endows Ru1-NP/CRP with an exceptional PHE rate of 3175μmolh-1g-1, positioning it as one of the most efficient elemental-based photocatalysts. This breakthrough underscores the crucial role of pre-anchoring metal single atoms at defect sites of catalysts in enhancing hydrogen production.

Transforming Red Phosphorus Photocatalysis: Dual Roles of Pre‐Anchored Ru Single Atoms in Defect and Interface Engineering

Crystalline red phosphorus(CRP), known for its promising photocatalytic properties, faces challenges in photocatalytic hydrogen evolution(PHE) due to undesired inherent charge deep trapping and recombination effects induced by defects. This study overcomes these limitations through an innovative strategy in integrating ruthenium single atoms(Ru1) within CRP to simultaneously repair the intrinsic undesired vacancy defects and serve as the uniformly distributed anchoring sites for a controllable growth into ruthenium nanoparticles(RuNP). Hence, a highly functionalized CRP with Ru1 and RuNP(Ru1‐NP/CRP) with concerted effects in regulating electronic structures and promoting interfacial charge transfer has been achieved. Advanced characterizations unveil the pioneering dual role of pre‐anchored Ru1 in transforming CRP photocatalysis. The regulations of vacancy defects on the surface of CRP minimize the detrimental deep charge trapping, resulting in the prolonged lifetime of charges. With the well‐distributed in‐situ growth of RuNP on Ru1 sites, the constructed robust “bridge” that connects CRP and RuNP facilitates constructive interfacial charge transfer. Ultimately, the synergistic effect induced by the pre‐anchored Ru1 endows Ru1‐NP/CRP with an exceptional PHE rate of 3175μmolh‐1g‐1, positioning it as one of the most efficient elemental‐based photocatalysts. This breakthrough underscores the crucial role of pre‐anchoring metal single atoms at defect sites of catalysts in enhancing hydrogen production.

Pitfalls and complications in the treatment of clubfoot by the Ponseti method: A literature review

BACKGROUND: At every step of clubfoot treatment using the Ponseti method, pitfalls leading to complications, both minor and potentially dangerous, may occur. Any doctor involved in the treatment of clubfoot may encounter similar difficulties in their practice; however, publications devoted to this problem are limited, and in some cases, experts cannot reach a consensus regarding the interpretation of actions that entail undesirable consequences. AIM: This study aimed to analyze pitfalls and complications associated with the Ponseti method for the treatment of clubfoot using modern literature data. MATERIALS AND METHODS: Articles were searched for in PubMed, Science Direct, Google Scholar, and eLibrary databases using the following keywords: idiopathic clubfoot, Ponseti method, serial casting, bracing, Achilles tenotomy, pitfalls, and complications. The search was performed without language restrictions. Most of the studies included were published no more than 10 years ago. RESULTS: Current literature data present on the pitfalls and complications encountered in the treatment of clubfoot using the Ponseti method. The review also covered associated complications and unfavorable prognostic factors. The restrictive measures during the COVID-19 pandemic have affected the treatment of clubfoot. CONCLUSIONS: Analysis of the causes of pitfalls and complications and control of unfavorable prognostic factors will help reduce complications of clubfoot treatment using the Ponseti method and optimize orthopedic care for children.

Evaluation of fluoride exposure using disability-adjusted life years and health risk assessment in south-western Iran: A novel Monte Carlo simulation

Consumption of fluoride-contaminated water is a worldwide concern, especially in developing countries, including Iran. However, there are restricted studies of non-single-value health risk assessment and the disease burden regarding fluoride intake nationwide. Prolonged exposure to excessive fluoride has been linked to adverse health effects such as dental and skeletal fluorosis. This can lead to under-mineralization of hard tissues, causing aesthetic concerns for teeth and changes in bone structure, increasing the risk of fractures. As such, we aimed to implement probability-based frameworks using Monte Carlo methods to explore the potential adverse effects of fluoride via the ingestion route. This platform consists of two sectors: 1) health risk assessment of various age categories coupled with a variance decomposition technique to measure the contributions of predictor variables in the outcome of the health risk model, and 2) implementing Monte Carlo methods in dose-response curves to explore the fluoride-induced burden of diseases of dental fluorosis and skeletal fractures in terms of disability-adjusted life years (DALYs). For this purpose, total water samples of 8053 (N=8053) from 57 sites were analyzed in Fars and Bushehr Provinces. The mean fluoride concentrations were 0.75 mg/L and 1.09 mg/L, with maximum fluoride contents of 6.5 mg/L and 3.22 mg/L for the Fars and Bushehr provinces, respectively. The hazard quotient of the 95th percentile (HQ>1) revealed that all infants and children in the study area were potentially vulnerable to over-receiving fluoride. Sobol’ sensitivity analysis indices, including first-order, second-order, and total order, disclosed that fluoride concentration (Cw), ingestion rate (IRw), and their mutual interactions were the most influential factors in the health risk model. DALYs rate of dental fluorosis was as high as 981.45 (uncertainty interval: UI 95 % 353.23–1618.40) in Lamerd, and maximum DALYs of skeletal fractures occurred in Mohr 71.61(49.75–92.71), in Fars Province, indicated severe dental fluorosis but mild hazard regarding fractures. Residents of the Tang-e Eram in Bushehr Province with a DALYs rate of 3609.40 (1296.68–5993.73) for dental fluorosis and a DALYs rate of 284.67 (199.11–367.99) for skeletal fractures were the most potentially endangered population. By evaluating the outputs of the DALYs model, the gap in scenarios of central tendency exposure and reasonable maximum exposure highlights the role of food source intake in over-receiving fluoride. This research insists on implementing defluoridation programs in fluoride-endemic zones to combat the undesirable effects of fluoride. The global measures presented in this research aim to address the root causes of contamination and help policymakers and authorities mitigate fluoride's harmful impacts on the environment and public health.

Promising the potential of β-caryophyllene on mercury chloride-induced alteration in cerebellum and spinal cord of young Wistar albino rats.

Mercury chloride (ME) is a chemical pollutant commonly found in the environment, which can contribute to undesirable health consequence worldwide. The current study investigated the detrimental impact of ME on the cerebellum and spinal cord tissues in 6-8-week-old female rats. We also evaluated the neuroprotective efficacy of β-caryophyllene (BC) against spinal and cerebellar changes caused by ME. Thirty-five young Wistar albino rats were randomly chosen and assigned into five groups: control (CO), olive oil (OI), ME, BC, ME + BC. All samples were analysed by means of unbiased stereological, biochemical, immunohistochemical, and histopathological methods. Our biochemical findings showed that SOD level was significantly increased in the ME group compared to the CO group (p < 0.05). We additionally detected a statistically significant decrease in the number of cerebellar Purkinje cells and granular cells, as well as spinal motor neuron in the ME group compared to the CO group (p < 0.05). In the ME + BC group, the number of Purkinje cells, granular cells, and spinal motor neurons was significantly higher compared to the ME group (p < 0.05). Decreased SOD activity in the ME + BC group was also detected than the ME group (p < 0.05). Immunohistochemical (the tumour necrosis factor-alpha (TNF-α)) and histopathological examinations also exhibited crucial information in each of the group. Taken together, ME exposure was associated with neurotoxicity in the cerebellum and spinal cord tissues. BC treatment also mitigated ME-induced neurological alteration, which may imply its potential therapeutic benefits.

Histopathology imaging and clinical data including remission status in pediatric inflammatory bowel disease

The incidence of inflammatory bowel disease (IBD) is increasing annually. Children with IBD often suffer significant morbidity due to physical and emotional effects of the disease and treatment. Corticosteroids, often a component of therapy, carry undesirable side effects with long term use. Steroid-free remission has become a standard for care-quality improvement. Anticipating therapeutic outcomes is difficult, with treatments often leveraged in a trial-and-error fashion. Artificial intelligence (AI) has demonstrated success in medical imaging classification tasks. Predicting patients who will attain remission will help inform treatment decisions. The provided dataset comprises 951 tissue section scans (167 whole-slides) obtained from 18 pediatric IBD patients. Patient level structured data include IBD diagnosis, 12- and 52-week steroid use and name, and remission status. Each slide is labelled with biopsy site and normal or abnormal classification per the surgical pathology report. Each tissue section scan from an abnormal slide is further classified by an experienced pathologist. Researchers utilizing this dataset may select from the provided outcomes or add labels and annotations from their own institutions.

Use of allopurinol to manage skewed 6-mercaptopurine metabolism in pediatric maintenance acute lymphoblastic leukemia treatment.

6-mercaptopurine is a cornerstone of maintenance therapy for pediatric ALL. Response to 6MP is typically determined by the ANC. Therapeutic ANC range while receiving 6MP is between 500 and 1500/μL. In addition to desired myelosuppression, 6MP is associated with multiple adverse drug effects. Increased doses of 6MP can lead to therapeutic ANC values; however, patients may experience adverse effects before obtaining therapeutic myelosuppression, often deemed "skewed metabolism." Allopurinol may potentially correct skewed 6MP metabolism. Pediatric patients with ALL with 6MMP and 6TGN metabolites drawn during maintenance therapy were analyzed for allopurinol use. The primary outcome evaluated the percentage of time spent in therapeutic ANC range before and after allopurinol initiation. In addition, the difference in 6MMP:6TGN ratios before and after allopurinol initiation, incidence of hepatotoxicity, and rates of relapse, were analyzed. Ninety-five patients were included for analysis. Thirty-two (34%) patients received allopurinol. There were no significant differences in baseline demographics between the patients who received allopurinol and those who did not. When comparing ANC values pre- and post-allopurinol initiation, a statistically significant increase in the percentage of time spent in therapeutic range was observed (27% vs. 43%; p = .03). In addition, when comparing metabolite ratios pre- and post-allopurinol initiation, a statistically significant decrease in 6MMP:6TGN metabolite ratio values was observed (86.7 vs. 3.6; p < .0001). Allopurinol significantly increased the percent time in therapeutic ANC range and can be safely utilized to significantly lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable side effects of 6MMP, and optimizing the anti-leukemic effects associated with 6TGN.

Expanding the Availability of Scalp Cooling to All Patients at Risk of Chemotherapy-Induced Alopecia

Alopecia is an undesirable side effect of cancer chemotherapy. The mitigation of alopecia is a desirable adjunct treatment for patients with cancer. FDA-cleared scalp cooling (SC) devices have been successfully used to prevent or reduce chemotherapy-induced alopecia (CIA). This paper provides an understanding of the implementation and value of the new Insurance-Based Billing Model used in the USA for SC and its benefits compared with the original self-pay model. This improved compensation change will result in all patients in need, including underserved and disadvantaged populations, receiving equitable healthcare by allowing access to this valuable supportive care technology.

Upscaling miscanthus production in the United Kingdom: The benefits, challenges, and trade‐offs

AbstractThe UK sixth carbon budget has recommended domestic biomass supply should increase to meet growing demand, planting a minimum of 30,000 hectares of perennial energy crops a year by 2035, with a view to establishing 700,000 hectares by 2050 to meet the requirements of the balanced net zero pathway. Miscanthus is a key biomass crop to scale up domestic biomass production in the United Kingdom. A cohesive land management strategy, based on robust evidence, will be required to ensure upscaling of miscanthus cultivation maximizes the environmental and economic benefits and minimizes undesirable consequences. This review examines research into available land areas, environmental impacts, barriers to uptake, and the challenges, benefits, and trade‐offs required to upscale miscanthus production on arable land and grassland in the United Kingdom. Expansion of perennial biomass crops has been considered best restricted to marginal land, less suited to food production. The review identifies a trade‐off between avoiding competition with food production and a risk of encroaching on areas containing high‐biodiversity or high‐carbon stocks, such as semi‐natural grasslands. If areas of land suitable for food production are needed to produce the biomass required for emission reduction, the review indicates there are multiple strategies for miscanthus to complement long‐term food security rather than compete with it. On arable land, a miscanthus rotation with a cycle length of 10–20 years can be employed as fallow period for fields experiencing yield decline, soil fatigue, or persistent weed problems. On improved grassland areas, miscanthus presents an option for diversification, flood mitigation, and water quality improvement. Strategies need to be developed to integrate miscanthus into farming systems in a way that is profitable, sensitive to local demand, climate, and geography, and complements rather than competes with food production by increasing overall farm profitability and resilience.

Spatial Competition Models in Health Care Markets: A Review

AbstractThrough time, spatial competition has become the natural environment for studying a number of problems, ranging from product differentiation to mail order versus traditional business, to service provision under various assumptions about the institutional setting. Health economics research has greatly benefited from the intuitions that underlie the Hotelling model and several authors have contributed to the literature on the architecture of the market for health care by proposing models within this framework. In this paper we explore how spatial competition has been used in health economics to improve the knowledge of the mechanisms of the market for health care through the derivation of significant policy implications. One of the most important messages is that in spite of competition, the regulator still should have a central role in the architecture of the market and policies have to be carefully tailored in order to avoid the onset of perverse, undesired effects on quality and welfare.

Identification of Psychoplastogenic Tropanes Lacking Muscarinic Activity.

Tropane-containing small molecules like scopolamine are a promising class of psychoplastogens. However, their potent antagonism of all muscarinic receptor subtypes presents the potential for undesirable anticholinergic side effects. In an effort to decouple their neuroplasticity-promoting effects from their muscarinic activity, we performed phenotypic structure-activity relationship studies across a variety of structurally distinct subclasses of tropanes. We discovered several novel tropanes capable of significantly increasing cortical neuronal growth while exhibiting drastically reduced activity at all muscarinic receptor subtypes compared to scopolamine.