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Previous studies have shown that modulating neural activity can affect rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. Low-intensity transcranial ultrasound stimulation (TUS) can effectively modulate neural activity. However, the modulation effect of TUS on REM and NREM sleep is still unclear. In this study, we used ultrasound to stimulate motor cortex and hippocampus, respectively, and found the following: (i) In healthy mice, TUS increased the NREM sleep ratio and decreased the REM sleep ratio, and altered the relative power and sample entropy of the delta band and spindle in NREM sleep and that of the theta and gamma bands in REM sleep. (ii) In sleep-deprived mice, TUS decreased the ratio of REM sleep or the relative power of the theta band during REM sleep. (iii) In sleep-disordered Alzheimer's disease (AD) mice, TUS increased the total sleep time and the ratio of NREM sleep and modulated the relative power and the sample entropy of the delta and spindle bands during NREM and that of the theta band during REM sleep. These results demonstrated that TUS can effectively modulate REM and NREM sleep and that modulation effect depends on the sleep state of the samples, and can improve sleep in sleep-disordered AD mice.
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Sono REM , Sono de Ondas Lentas , Camundongos , Animais , Sono REM/fisiologia , Eletroencefalografia/métodos , Sono/fisiologia , Sono de Ondas Lentas/fisiologia , Hipocampo/fisiologiaRESUMO
The traditional methods for the synthesis of phosphinate esters use phosphorus trichloride (PCl3) as the phosphorous source, resulting in procedures that are often highly polluting and energy intensive. The search for an alternative approach that is both mild and environmentally friendly is a challenging, yet highly rewarding task in modern chemistry. Herein, we use an inorganic phosphorous-containing species, NaH2PO2, to serve as the source of phosphorous that participates directly in the nickel-catalyzed selective alkyne hydrophosphonylation reaction. The transformation was achieved in a multicomponent fashion and at room temperature, and most importantly, the H-phosphinate product generated is an advanced intermediate which can be readily converted into diverse phosphinate derivatives, including those bearing new P-C, P-S, P-N, P-Se, and P-O bonds, thus providing a complimentary method to classic phosphinate ester synthesis techniques.
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Rapid and on-site qualitative and quantitative analysis of small molecules (including bioflavonoids) in biofluids are of great importance in biomedical applications. Herein, we have developed two deep learning models based on the 3D fluorescence spectra of gold nanoclusters as a single probe for rapid qualitative and quantitative analysis of eight bioflavonoids in serum. The results proved the efficiency and stability of the random forest-bidirectional long short-term memory (RF-BLSTM) model, which was used only with the most important features after deleting the unimportant features that might hinder the performance of the model in identifying the selected bioflavonoids in serum at very low concentrations. The optimized model achieves excellent overall accuracy (98-100%) in the qualitative analysis of the selected bioflavonoids. Next, the optimized model was transferred to quantify the selected bioflavonoids in serum at nanoscale concentrations. The transferred model achieved excellent accuracy, and the overall determination coefficient (R2) value range was 99-100%. Furthermore, the optimized model achieved excellent accuracies in other applications, including multiplex detection in serum and model applicability in urine. Also, LOD in serum at nanoscale concentration was considered. Therefore, this approach opens the window for qualitative and quantitative analysis of small molecules in biofluids at nanoscale concentrations, which may help in the rapid inclusion of sensor arrays in biomedical and other applications.
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Líquidos Corporais , Nanopartículas Metálicas , Ouro , Flavonoides , Espectrometria de Fluorescência/métodosRESUMO
Vitamin B6 derivatives (VB6Ds) are of great importance for all living organisms to complete their physiological processes. However, their excess in the body can cause serious problems. What is more, the qualitative and quantitative analysis of different VB6Ds may present significant challenges due to the high similarity of their chemical structures. Also, the transfer of deep learning model from one task to a similar task needs to be present more in the fluorescence-based biosensor. Therefore, to address these problems, two deep learning models based on the intrinsic fingerprint of 3D fluorescence spectra have been developed to identify five VB6Ds. The accuracy ranges of a deep neural network (DNN) and a convolutional neural network (CNN) were 94.44-97.77% and 97.77-100%, respectively. After that, the developed models were transferred for quantitative analysis of the selected VB6Ds at a broad concentration range (1-100 µM). The determination coefficient (R2) values of the test set for DNN and CNN were 93.28 and 97.01%, respectively, which also represents the outperformance of CNN over DNN. Therefore, our approach opens new avenues for qualitative and quantitative sensing of small molecules, which will enrich fields related to deep learning, analytical chemistry, and especially sensor array chemistry.
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Aprendizado Profundo , Fluorescência , Ouro , Vitamina B 6 , VitaminasRESUMO
A 2-year-old girl was diagnosed as Weill-Marchesani syndrome with typical systemic features of short stature, short and stubby hands and feet, language disorders and mental retardation. He developed bilateral angle closure glaucoma, ectopia lentis and suffered visual loss from the ocular features of Weill-Marchesani syndrome. The child was successfully treated by combined CO2 laser-assisted sclerectomy surgery and trabeculectomy.
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Glaucoma , Trabeculectomia , Síndrome de Weill-Marchesani , Dióxido de Carbono , Criança , Pré-Escolar , Feminino , Glaucoma/etiologia , Glaucoma/cirurgia , Humanos , Lasers , MasculinoRESUMO
Objective To observe the role of ultrasound biomicroscopy(UBM)in two-year post-operative follow-up for primary open-angle glaucoma patients with modified CO2 laser-assisted sclerectomy surgery(CLASS).Methods This was a case series study.A combination of modified CLASS and preoperative laser iris management was administered to 28 eyes.Visual acuity,intraocular pressure(IOP),and slit-lamp examinations,visual field testing,and gonioscopy were carried out at baseline and until 24 months postoperatively.UBM examination was performed at 1,3,12 and 24 months postoperatively.Results Compared with the mean preoperative IOP [(30.61±10.59)mmHg],the IOP at each time point after operation was significantly lowered [(15.15±5.87),(12.56±3.24),(13.15±2.73),(13.75±2.55)and(13.75±2.46)mmHg at 1,3,6,12 and 24 months,respectively;all P<0.001].Complete success rates and qualified success rates at 12 months and 24 months were 60.71%,89.29% and 53.57%,85.71%,respectively.UBM images can present "dolphin head sign" after successful CLASS.The thickness of trabeculo-Descemet's window was(0.13±0.03)mm,which had no significant correlation with postoperative IOP at 12(r=-0.278,P=0.144)and 24 months(r=0.026,P=0.895).UBM examination revealed a severe scleral lake diminution(a change > 50%)in 1 eye(3.57%)at 12 months and 3 eyes(10.71%)at 24 months.There was no statistical significance detected between the size of the scleral lake and IOP after CLASS.Non-founctional blebs were found in 16 eyes(57.14%)at 12 months and 25 eyes(89.28%)at 24 months.Two eyes(7.14%)demonstrated severe peripheral anterior synechiae at 24 months,requiring surgical intervention.Conclusions UBM can effectively observe the morphology of the scleral lake,anterior chamber angle and filtering blebs in post-operative follow-up after modified CLASS,and give early warning of complications.It plays an important role in ensuring the success of CLASS.
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Glaucoma de Ângulo Aberto , Dióxido de Carbono , Seguimentos , Glaucoma de Ângulo Aberto/diagnóstico por imagem , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Microscopia Acústica , Esclera/diagnóstico por imagem , Resultado do TratamentoRESUMO
We outline a conceptual blueprint that provides direct and atom economical access to a wide range of complex polyheterocycles. Our method capitalizes on the ambiphilic reactivity of rhodacyclopentanones that arise upon exposure of cyclopropanes to Rh(I) catalysts and CO. Using this approach, a wide array of polycyclizations are achieved, including variants that involve powerful dearomatizations and medium ring formations.
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Temporary directing groups (TDGs) underpin a range of C-C bond activation methodologies; however, the use of TDGs for the regiocontrolled activation of cyclopropane C-C bonds is underdeveloped. In this report, we show how an unusual ring contraction process can be harnessed for TDG-based carbonylative C-C bond activations of cyclopropanes. The method involves the transient installation of an isocyanate-derived TDG, rather than relying on carbonyl condensation events as used in previous TDG-enabled C-C bond activations.
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It is found that catechol inhibits the oxidase-mimicking activity of chitosan-protected platinum nanoparticles (Chit-PtNPs) by competing with the substrate for the active site of the Ch-PtNPs. The inhibition mechanism of catechol is different from that of ascorbic acid in that it neither reacts with O2â¢- nor reduces the oxidized 3,3',5,5'-tetramethylbenzidine (TMB). Tyrosinase (TYRase) catalyzes the oxidation of catechol, thus restoring the activity of oxidase-mimicking Chit-PtNPs. By combining the Chit-PtNP, catechol, and TYRase interactions with the oxidation of TMB to form a yellow diamine (maximal absorbance at 450 nm), a colorimetric analytical method was developed for TYRase determination and inhibitor screening. The assay works in the 0.5 to 2.5 U·mL-1 TYRase activity range, and the limit of detection is 0.5 U·mL-1. In our perception, this new assay represents a powerful approach for determination of TYRase activity in biological samples. Graphical abstract Schematic representation of a colorimetric method for tyrosinase (TYRase) detection and inhibitor screening. It is based on the fact that catechol can inhibit the oxidase-like activity of chitosan-stabilized platinum nanoparticles (Ch-PtNPs) by competing with the substrate for the active sites and TYRase can catalyze the oxidation of catechol.
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Materiais Biomiméticos/química , Catecóis/farmacologia , Quitosana/química , Colorimetria/métodos , Nanopartículas Metálicas/química , Monofenol Mono-Oxigenase/metabolismo , Platina/química , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Oxirredutases/metabolismoRESUMO
Platinum nanoparticles (Pt NPs) covered with a bovine serum albumin scaffold and a particle size of 1.5 nm (BSA-PtS NPs) are shown to display enhanced multiple enzyme-mimicking activities including peroxidase, oxidase, and catalase-like activities. The peroxidase-like activity is characterized by robustness and low signal background. BSA-PtS NPs were used to design colorimetric assays for H2O2 and glucose. H2O2 latter reacts with 3,3',5,5'-tetramethylbenzidine in the presence of BSA-PtS NPs to form a blue product with an absorption maximum at 652 nm. The assay works in the 5-250 µM H2O2 concentration range. The glucose assay is based on its glucose oxidase-catalyzed oxidation to produce gluconic acid and H2O2 which then is colorimetrically quantified. Response is linear in the 10-120 µM glucose concentration range, and the detection limit is 2 µM (at S/N = 3). The method correlates well with the glucose standard method (R2 = 0.997 in the 95% confidence interval) which confirms that glucose in human serum has been successfully detected. Graphical abstractImproved enzymatic assay for hydrogen peroxide and glucose by exploiting the enzyme-mimicking properties of BSA-coated platinum nanoparticles.
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Glicemia/análise , Colorimetria/métodos , Peróxido de Hidrogênio/análise , Nanopartículas Metálicas/química , Animais , Benzidinas/química , Catálise , Bovinos , Corantes/química , Glucose Oxidase/química , Humanos , Peróxido de Hidrogênio/química , Limite de Detecção , Oxirredução , Oxirredutases/química , Tamanho da Partícula , Platina/química , Soroalbumina Bovina/químicaRESUMO
Aminocyclopropanes equipped with pendant nucleophiles undergo carbonylative heterocyclization triggered by C-C bond activation to generate eight-membered N-heterocycles. In these processes, intramolecular "capture" of a rhodacyclopentanone intermediate by an aryl or N-based nucleophile is followed by C-C or C-N bond-forming "collapse" to the targets. These studies demonstrate how the combination of cyclopropane strain release and the templating effect of catalytically generated metallacycles can be harnessed to enable otherwise challenging medium ring closures.
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A modular Rh-catalyzed entry to azepines is outlined. Under a CO atmosphere, protecting group directed C-C bond activation of aminocyclopropanes provides rhodacyclopentanones. These intermediates are effective for intramolecular C-H metalation of either an N-aryl or N-vinyl unit en route to azepine ring systems. Thus, byproduct-free heterocyclizations are enabled by sequential C-C activation and C-H functionalization steps.
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Under carbonylative conditions, neutral Rh(I)-systems modified with weak donor ligands (AsPh3 or 1,4-oxathiane) undergo N-Cbz, N-benzoyl, or N-Ts directed insertion into the proximal C-C bond of aminomethylcyclopropanes to generate rhodacyclopentanone intermediates. These are trapped by N-tethered alkenes to provide complex perhydroisoindoles.
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A facile approach is proposed for the growth of platinum nanoparticles on graphene oxide (PtNPs/GO). The resulting PtNPs/GO hybrid has been proved to function as peroxidase mimics that can catalyze the oxidation of peroxidase substrates in the presence of hydrogen peroxide (H2O2). Kinetic studies indicate that the PtNPs/GO nanocomposite has a considerably higher affinity for both 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 than those of other platinum-based peroxidase mimics. Furthermore, colorimetric recognition and sensing of L-cysteine with high sensitivity and selectivity is presented based on target-induced shielding against the peroxidase-like activity of PtNPs/GO. We envision that this material will be an ideal candidate for a wide range of potential applications in the fields of biomedicine and environmental chemistry.
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Cisteína/análise , Grafite/química , Nanopartículas Metálicas/química , Óxidos/química , Peroxidase/química , Benzidinas/química , Catálise , Colorimetria/métodos , Peróxido de Hidrogênio/química , Cinética , Limite de Detecção , Nanopartículas Metálicas/ultraestrutura , Modelos Moleculares , OxirreduçãoRESUMO
Given the importance of hydrogen peroxide (H2O2) in many biological processes and its wide application in various industries, the demand for sensitive, accurate, and economical H2O2 sensors is high. In this study, we used Fenton reaction-stimulated fluorescence quenching of N-acetyl-L-cysteine-protected gold nanoclusters (NAC-AuNCs) as a reporter system for the determination of H2O2. After the experimental conditions were optimized, the sensing platform enabled the analysis of H2O2 with a limit of detection (LOD) as low as 0.027 µM. As the glucose oxidase cascade leads to the generation of H2O2 and catalase catalyzes the decomposition of H2O2, these two biocatalytic procedures can be probed by the Fenton reaction-mediated quenching of NAC-AuNCs. The LOD for glucose was found to be 0.18 µM, and the linear range was 0.39-27.22 µM. The LOD for catalase was 0.002 U mL(-1), and the linear range was 0.01-0.3 U mL(-1). Moreover, the proposed sensing methods were successfully applied for human serum glucose detection and the non-invasive determination of catalase activity in human saliva, demonstrating their great potential for practical applications.
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Acetilcisteína/química , Técnicas Biossensoriais/métodos , Glicemia/análise , Catalase/análise , Peróxido de Hidrogênio/análise , Ferro/química , Nanopartículas Metálicas/química , Glucose/análise , Humanos , Peróxido de Hidrogênio/química , Limite de Detecção , Modelos Moleculares , Saliva/química , Saliva/enzimologiaRESUMO
The powerful parallel computation ability of a graphics processing unit (GPU) makes it feasible to perform dynamic receive beamforming However, a real time GPU-based beamformer requires high data rate to transfer radio-frequency (RF) data from hardware to software memory, as well as from central processing unit (CPU) to GPU memory. There are data compression methods (e.g. Joint Photographic Experts Group (JPEG)) available for the hardware front end to reduce data size, alleviating the data transfer requirement of the hardware interface. Nevertheless, the required decoding time may even be larger than the transmission time of its original data, in turn degrading the overall performance of the GPU-based beamformer. This article proposes and implements a lossless compression-decompression algorithm, which enables in parallel compression and decompression of data. By this means, the data transfer requirement of hardware interface and the transmission time of CPU to GPU data transfers are reduced, without sacrificing image quality. In simulation results, the compression ratio reached around 1.7. The encoder design of our lossless compression approach requires low hardware resources and reasonable latency in a field programmable gate array. In addition, the transmission time of transferring data from CPU to GPU with the parallel decoding process improved by threefold, as compared with transferring original uncompressed data. These results show that our proposed lossless compression plus parallel decoder approach not only mitigate the transmission bandwidth requirement to transfer data from hardware front end to software system but also reduce the transmission time for CPU to GPU data transfer.
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Compressão de Dados/métodos , Processamento de Imagem Assistida por Computador/métodos , Processamento de Sinais Assistido por Computador , Ultrassonografia/métodos , Algoritmos , Imagens de FantasmasRESUMO
An easily prepared platinum nanoparticle (PtNP) probe for the sensitive and selective detection of Hg(2+) ions is developed here. The PtNPs with an average size of approximately 2.5 nm were prepared by a reduction method with sodium borohydride and trisodium citrate serving as reductant and stabilizer, respectively. The resulting PtNPs could catalyze the reduction of Hg(2+) by surface-capping citrate. The effect of Hg(2+) uptake implies amalgam formation, which leads to remarkable inhibition of the peroxidase-like activity of citrate-capped PtNPs. On the basis of this effect, a colorimetric mercury sensor was established through the use of citrate-capped PtNPs to catalyze the colorimetric system of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2. The high specificity of the Hg-Pt interaction provides the excellent selectivity for Hg(2+) over interfering metal ions. The sensitivity of this smart probe to Hg(2+) is extremely excellent with a limit of detection (LOD) as low as 8.5 pM. In view of these advantages, as well as the cost-effectiveness, minimized working steps, and naked-eye observation, we expect that this colorimetric sensor will be a promising candidate for the field detection of toxic Hg(2+) ions in environmental, biological, and food samples.
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Citratos/química , Mercúrio/análise , Nanopartículas Metálicas/química , Platina/química , Limite de Detecção , Microscopia Eletrônica de TransmissãoRESUMO
The harmful effects of microplastics (MPs) on male fertility are receiving more and more attention. However, the impact of low-dose MPs exposure on the reproductive function of male mice is still unclear. In this study, we exposed male mice to low-dose MPs (25-30 µg/kg body weight/day) or low-dose MPs combined with high-fat diet (HFD) feeding. Our results showed that low-dose MPs exposure or HFD feeding significantly reduced sperm quality and the number of offspring born, while low-dose MPs exposure combined with HFD feeding further enhanced the above effects. The combination of low-dose MPs exposure and HFD feeding resulted in a notable elevation of inflammatory level within the prostate of mice and induced apoptosis of prostate epithelium and a decrease in nutrients (zinc, citrate) in seminal plasma fluid. Our findings in this study could provide valuable clues for better understanding the influence of low-dose MPs exposure on the reproductive system under metabolic disorders and facilitate the development of the prevention of reproductive toxicity caused by MPs exposure.
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Microplásticos , Poliestirenos , Masculino , Humanos , Poliestirenos/toxicidade , Microplásticos/toxicidade , Plásticos , Dieta Hiperlipídica/efeitos adversos , Próstata , Sêmen , Fertilidade , ObesidadeRESUMO
Background: Adrenocortical carcinoma (ACC) is an extremely rare and highly invasive malignant tumor. However, there is currently no reliable method to predict the prognosis of ACC. Our objective is to construct a nomogram and a risk classification system to predict the 1-year, 3-year, and 5-year overall survival (OS) of ACC. Methods: We retrieved clinicopathological data of patients diagnosed with ACC in The Surveillance, Epidemiology, and End Results (SEER) database and divided them into training and validation cohorts with a 7:3 ratio. Simultaneously, we collected an external validation cohort from The First Affiliated Hospital of Naval Medical University (Shanghai, China). Univariate and multivariate Cox analyses were performed to identify relevant risk factors, which were then combined to develop a correlation nomogram. The predictive performance of the nomogram was evaluated using the concordance index (C-index), receiver-operating characteristic curve (ROC), and calibration curves. Decision curve analysis (DCA) was applied to assess the clinical utility of the nomogram. In addition, Kaplan-Meier survival curves were generated to demonstrate the variation in OS between groups. Results: The final nomogram consisted of five factors: age, T, N, M, and history of chemotherapy. Our prognostic model demonstrated significant discriminative ability, with C-index and the area under the receiver operating characteristic (AUC) values exceeding 0.70. Additionally, DCA validated the clinical utility of the nomogram. In the entire cohort, the median OS for patients in the low- and high-risk groups was 70 and 10 months, respectively. Conclusions: A nomogram and a corresponding risk classification system were developed in order to predict the OS of patients diagnosed with ACC. These tools have the potential to provide valuable support for patient counseling and assist in the decision-making process related to treatment options.
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BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS: High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.