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This study evaluates the effectiveness of KMnO4, MK3 and 1-butanol inhibitors on corrosion of AISI 314 and AISI 304 stainless steels using linear and potentiodynamic polarization in 0.1 M HNO3. The metrics like corrosion potential (Ecorr), current density (jcorr) and polarization resistance (Rp) influence the inhibitor efficacy. The inhibitors improved electrochemical parameters significantly, indicating strong anti-corrosive properties. 1-Butanol had the strongest effect, enhancing corrosion potential and drastically reducing corrosion current density, demonstrating superior protection. The results indicated that without inhibitors, both steels showed higher corrosion rates and more negative potentials, reflecting their susceptibility to corrosion. The introduction of inhibitors markedly improved these parameters, particularly with 1-butanol, which significantly enhanced the polarization resistance and shifted the corrosion potential towards less negative values. The potentiodynamic results highlighted the dynamic effectiveness of inhibitors, reinforcing their role in mitigating corrosion under varied conditions. The study underscores the importance of selecting the appropriate inhibitors to enhance the durability and longevity of stainless steels in acidic environments, with 1-butanol showing the potential for industrial applications requiring high corrosion resistance. This necessitates comprehensive testing to accurately measure inhibitor capabilities in different conditions.

Production of various traditional dairy products, particularly cheese, has a long history in Montenegro. White-brined cheeses are the most well-known. One of them is Kučki cheese, with distinct flavor and higher level of proteolysis. The aim of this research was to analyze the proteolysis process during ripening of Kučki cheese. The cheese is produced using traditional technology. FTIR Spectrophotometry was used to calculate the amount of total protein in cheese (IDF141C: 2000). The degree of proteolysis was determined by SDS PAGE (Laemmli, 1970). The cheese was examined for their water-soluble nitrogen (WSN) content using Kuchroo and Fox’s method from 1982, as well as their 5% phosphotungstic acid soluble nitrogen (PTAN) content using Stadhouser’s method from 1960. The results were expressed as percentages of WSN and PTAN of the total nitrogen matter (WSN/TN and PTAN/TN), as well as PTAN as a percentage of WSN (PTAN/WSN). All analyses were done on 10th, 20th and 30th day of cheese ripening. Four samples of cheese were analyzed for each ripening period. The content of proteins increased during the ripening period. The parameters that determine the process of proteolysis increased during the first 30 days of ripening. The WSN/TN ranged from 13.33 to 44.32%. Also, PTAN/WSN varied from 3.79 to 21.57%. The initial results show that uneven ripening conditions have a direct impact on how proteolytic changes develop throughout ripening. Due to the absence of established cheese-making procedures, Kučki cheese has a considerable degree of heterogeneity in their protein content and proteolysis parameters. However, it is not possible to strictly define the optimal values of the degree of ripening for Kučki cheese. In order to reach certain conclusions, it is necessary to carry out further studies focusing on analyzing a larger number of samples.

The Six-Day War of 1967 was a war conflict almost unanimously defined in the scientific literature as a school example of preemptive war. The conflict was initiated with Israel's attack on Egypt and Syria, after prolonged concentration of strong military forces on their common borders by the two countries. In order to prevent joint and coordinated attack on two fronts, Israel destroyed the Egyptian and Syrian Air Force with a carefully planned airstrike in the matter of hours. Since the founding of the State, the Israeli political and military elite have been guided by a collective narrative in addressing serious security threats. This narrative is based on drawing historical parallels with the experience of collective political violence against Jews as a political community in the past. It dictates proactivity in the protection of national interests and national security, and over time it has manifested itself in various ways. The Israeli army, as well as other security branches, have acted preemptively and preventively many times whenever the need to protect the lives and property of Israeli citizens arose. In the eyes of the Israeli political and military elite each of the mentioned above security threats was placed in the context of the German attempt to exterminate the Jews in WW2. Regardless of our attitudes towards the Middle East conflict, the fact remains that Israel's survival was most threatened in 1948 and 1973, that is, the only two times when Israel was not the first to attack its enemies who grouped against it.

Introduction: Neurofibromas are benign tumors of neuronal origin, occurring most commonly in young adults, with no gender predilection. The connection of neurofibroma with disorders on a general level as von Recklinghausen’s disease makes its diagnosis critical. Case report: A 32-old female patient was administered to the Clinic of Plastic surgery, Clinical Center of Montenegro in Podgorica, with a 10-year history of painless, subcutaneous tumor of the right upper arm that grew in size over the last ten years. The patient reported progressive pain and tingling in her right forearm and right hand for the last 12 months. An MRI showed a non-homogenous tumor of the middle third portion of the triceps muscle, in close contact with the humerus but without infiltrating it. The tumor was removed, with a definitive histopathological result of a solitary benign neurofibroma. Conclusions: This example of successful treatment of solitary neurofibroma may serve to increase the awareness of surgeons and radiologists in small countries regarding benign peripheral nerve sheath tumors. The patient is under observation for two years with no signs of relapse and no other features indicative of neurofibromatosis type 1.

Introduction/Objective. The increased presence of lipid particles in blood is one of most common reasons that transfusion units are unusable. The risk factors for lipemic plasma in donated blood are not completely known. The aim of this study is to identify the factors that influence plasma to be fatty so that we can prevent further storage costs and eliminate unusable transfusion units. Methods. This case–control study was conducted in 2017, and 1552 respondents were included in the study. The control group included 1502 subjects whose blood was not lipemic, while 50 patients with lipemic blood were selected for the case group. The presence of lipemic blood was assessed by inspection, while data were collected by clinical laboratory tests and a questionnaire. Results. Our findings show that multiple blood donors with lipemic blood were significantly older (p < 0.0005) and have higher systolic and diastolic pressure (p < 0.0005), high triglyceride levels (p < 0.0005), and lower levels of hemoglobin (p < 0.0005). Additionally, the presence of lipemic plasma was associated with female sex (p = 0.002), blood type (p = 0.016), heart disease (p < 0.0005), smoking (p < 0.005), diabetes (p = 0.001), lipid intake prior to blood donation (p < 0.005) and venipuncture therapy (p < 0.0005). Systolic pressure is a reliable predictor of lipemic blood (AUROC = 0.901, p < 0.0005). Conclusion. Our study provided a rational explanation and identified some of the risk factors that may help identify potential donors with lipemic blood.

Pharmaceutically active compounds (PhACs), in particular, nonsteroidal antiinflammatory drugs (NSAIDs) are in increasingly wider usage, and as such are more and more frequently part of the organic matter of recipient rivers, especially in their lower courses. To indicate their significance as pollutants, as well as the significant role that the presence of autochthonous microflora plays in solving this issue, we undertook to perform this experiment. The experiment, titled “Application of the model of cylindrical reactor in self-purification by indigenous microorganisms”, was conducted during a one-year period at the location of Vukovci, in the lower course of the Morača river. Assuming that the concentration of NSAIDs and PhACs in water can be reduced through selfpurification, it has been proven that such processes result in a modification of phenotype in the indigenous microbiological population. Having the abovementioned premise in mind, we constructed the experiment model, which entails kineticism of water, whereas the defined volume flow rate per unit time was 0.005 m/s, through the known distance of 432 m. Over one year of application of the model of the cylindrical reactor for enhancing self-purification capacity by indigenous microorganisms, auto-purification increased by 28.05%, the phenotype of the indigenous microorganisms changed by 24.62%, whereas the total concentration of particular PhACs, micropollutants, and NSAIDs decreased by 4.19%.

Determining the presence of pharmaceuticals and endocrine-disrupting compounds in fish tissues has been carried out in Montenegro for the first time in Moraca river and Skadar lake. Skadar lake, Montenegro, is the largest of the Balkan lakes and has a surface area which fluctuates seasonally from approximately 370 to 600 km2. During the spring time of 2016, in the time of high water levels of the lake, fish were fetched in triplets and identified. Determining the presence of pharmaceuticals and endocrine-disrupting compounds in fish tissues has been carried out in Montenegro for the first time. Their muscle tissue was separated, grinded, feezed, and then lyophilized. Prepared samples were analyzed with liquid chromatography coupled to tandem mass spectrometry to determine the presence of pharmaceuticals and endocrine-disrupting compounds. Obtained results are under the border of detection, out of 38 tested distributes, only the tissue of Alburnus scoranza showed the presence of triclosan.

The selection of the appropriate pricing concept is one of the most important business decisions an Internet service provider (ISP) has to make. An efficient pricing concept implies that price reflects the quality of service (QoS) obtained by a service provider. In this paper, we propose four billing scenarios, each with applied user-centric QoS-based pricing concept, which is focused on users' demands, defined through QoS and price requirements, as well as delivered QoS. The main issue of this research is to analyse how much ISP's revenue will vary depending on the applied billing scenario. For this purpose, we propose a novel discrete event simulation model. Тhe proposed simulation model is implemented using a newly created programming library based on the event scheduling strategy. This model can be helpful to an ISP in the process of decision making which billing scenario to choose in order to maximize its revenue. Output parameters obtained through the simulation analysis are ISP's revenue and service prices for different billing scenarios.

Introduction/Objective. The aim of this study was to determine the effects of the estrogen and progesterone receptor status on angiogenesis, proliferation, and apoptosis of myoma cells in premenopausal (PreM) and postmenopausal (PostM) women. Methods. This was a cross section; clinical-experimental, retrospective, non-interventional study in the field of the study of fundamental pathogenesis mechanisms of disease using pathohistological materials from the existing archive. The research included 76 patients diagnosed with uterine leiomyomas, operatively treated in the Clinic for Gynecology and Obstetrics, Clinical Centre Kragujevac, Serbia. According to the menstrual status, we formed two experimental subgroups. The first group was PreM women (n = 35; 46.2 ± 5.02 years old), and the second group was PostM women (n = 41; 60.25 ± 5.41 years old). Hematoxylin-eosin staining for myoma and myometrium was conducted, as well as immunohistochemistry for ERα, ERβ, PRа, vascular endothelial growth factor, endoglin, Ki67, and caspase-3. Results. Progesterone receptor was overexpressed in myoma and myometrium of PreM compared to myoma and myometrium of PostM women. Expression of caspase-3 was a statistically significant increase in PostM women compared to PreM group. ERα and ERβ were not changed among groups neither in myoma nor in myometrium samples. Conclusion. According to our data, PRа had higher influence on apoptosis and cell growth than estrogen receptors. Since PRа was increased in PreM in both myoma and myometrium, probably this expression led further to lower expression of apoptotic marker in PreM women.

The paper describes the mechanical properties and the corrosion behaviour of three Al–Si alloys in 0.5 M NaCl solution. The alloys have exhibited similar values of hardness, but the highest tensile strength and the lowest elongation have shown the specimens of alloy with 11.38 % of silicon. Higher content of both copper and magnesium has contributed to better tensile strength and lower elongation of as-cast hypoeutectic alloys. The harmful effects of iron on mechanical properties of all alloys have been reduced to some extent by nickel and cobalt addition. The differences in the values of the open circuit potential of the examined alloys were insignificant. The thickness of the protective oxide layer has increased over time, and the layer has become very compact. Slight differences in the values of the corrosion potential of the alloys were determined, whereas the lowest value of the corrosion current was indicated for the hypereutectic alloy. The presence of intermetallic phases in the alloys has shown that the oxide film was not consistent. The severe pits have not been found at the surface of the corroded samples. Based on the obtained results, the examined alloys may be used for the manufacturing of the internal combustion engine parts.

Introduction: Studies have shown improved tolerability with once-weekly versus three-weekly docetaxel in the second-line treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the tolerability of nintedanib plus weekly docetaxel in patients with NSCLC., Methods: This phase I, open-label, dose-escalation study (NCT02668393) enrolled patients with locally advanced/metastatic adenocarcinoma NSCLC that had progressed on first-line platinum chemotherapy. The primary endpoint was to determine the maximum tolerated dose of nintedanib (up to 200 mg twice daily [BID]) combined with weekly docetaxel (35 mg/m2) on days 1, 8, and 15 based on the occurrence of dose-limiting toxicities (DLTs) over a 28-day treatment cycle. Adverse events (AEs) were also evaluated., Results: The trial terminated prematurely due to recruitment challenges. At termination, seven patients had received nintedanib 150 mg BID and seven nintedanib 200 mg BID, in combination with weekly docetaxel. In the first treatment cycle, DLTs were reported for 1/6 evaluable patients (16.7%) in each group. The disease control rates were 57.1% and 42.9%, respectively. Grade ≥3 treatment-related AEs affected three patients in each group (42.9%); neutropenia was reported in one patient (14.3%) in each group. Treatment-related serious AEs were reported in three patients (42.9%) receiving nintedanib 150 mg, and two patients (28.6%) receiving nintedanib 200 mg., Conclusions: Overall, nintedanib plus weekly docetaxel was well-tolerated in patients with locally advanced or metastatic lung adenocarcinoma who progressed on first-line platinum-based chemotherapy, without loss of efficacy. DLTs were manageable., Competing Interests: Virginie Westeel’s institution received support from Boehringer Ingelheim for the present manuscript; grants to her institution from AbbVie, Bristol Myers Squibb, Roche, Lilly, Fresenius, Boehringer Ingelheim, Novartis, and Merck Sharp & Dohme; honoraria from Bristol Myers Squibb, AstraZeneca, Roche, and Merck Sharp & Dohme, travel support for attending meetings from Roche, Pfizer, Bristol Myers Squibb, AstraZeneca, and Sanofi; and participation on a data safety monitoring board or advisory board from Merck Sharp & Dohme, Takeda, Bristol Myers Squibb, Amgen, and Novartis. Wolfgang Schütte received honoraria for lectures from Boehringer Ingelheim. Thierry Urban received honoraria for Speaker’s bureaus from AstraZeneca and Novartis; travel support for attending meetings from Roche and Takeda; and participated on advisory boards for AstraZeneca, Bristol Myers Squibb, and Takeda. Dejan Radonjic, Ute von Wangenheim, and Robert M. Lorence are employees of Boehringer Ingelheim. Robert M. Lorence also received consulting fees from Boehringer Ingelheim. Martin Reck received consulting fees from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Beigene, Merck, Merck Sharp & Dohme, Novartis and Pfizer; honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Merck, Beigene, Merck Sharp & Dohme, Novartis, Pfizer, Roche and Sanofi; travel support for attending meetings from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Merck, Beigene, Merck Sharp & Dohme, Novartis, Pfizer, Roche and Sanofi; and participation on a data safety monitoring board or advisory board from Sanofi. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Westeel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The implementation of immune checkpoint inhibitors (ICIs), with or without chemotherapy, as first-line treatment for patients who do not have actionable mutations has proved to be a major paradigm shift in the management of advanced non-small cell lung cancer (NSCLC). However, the transition of ICIs, such as pembrolizumab and nivolumab, to a first-line setting has left an unmet need for effective second-line treatment options, which is an area of intense research. In 2020, we reviewed the biological and mechanistic rationale for anti-angiogenic agents in combination with, or following, immunotherapy with the aim of eliciting a so called 'angio-immunogenic' switch in the tumor microenvironment. Here, we review the latest clinical evidence of the benefits of incorporating anti-angiogenic agents into treatment regimens. While there is a paucity of prospective data, several recent observational studies indicate that the marketed anti-angiogenic drugs, nintedanib or ramucirumab, are effective in combination with docetaxel following immuno-chemotherapy. Addition of anti-angiogenics, like bevacizumab, have also demonstrated clinical benefit when combined with first-line immuno-chemotherapy regimens. Ongoing clinical trials are assessing these agents in combination with ICIs, with encouraging early results (e.g., ramucirumab plus pembrolizumab in LUNG-MAP S1800A). Also, several emerging anti-angiogenic agents combined with ICIs are currently being assessed in phase III trials following immunotherapy, including lenvatinib (LEAP-008), and sitravatinib (SAPPHIRE) It is hoped that these trials will help expand second-line treatment options in patients with NSCLC. Areas of focus in the future will include further molecular dissection of the mechanisms of resistance to immunotherapy and the various response-progression profiles to immunotherapy observed in the clinic and the monitoring of the dynamics of immunomodulation over the course of treatment. Improved understanding of these phenomena may help identify clinical biomarkers and inform the optimal use of anti-angiogenics in the treatment of individual patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Martin Reck received fees for honoraria, consulting/advisory roles and speaker’s bureau from Boehringer Ingelheim. Sanjay Popat received personal fees from Bristol Myers Squibb, Roche, Takeda, AstraZeneca, Pfizer, Merck Sharp & Dohme, EMD Serono, Guardant Health, AbbVie, Boehringer Ingelheim, Tesaro, OncLive, Medscape. Christian Grohé has received sponsorship or research funding and payment or other financial remuneration from AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, F. Hoffmann-La Roche; and payment or other financial remuneration from Lilly. Silvia Novello received personal fees for advisor/speaker’s bureaus from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Takeda, Pfizer, Roche, Merck Sharp & Dohme, Eli Lilly, AbbVie. Wolfgang M. Brueckl received lecture and educational event (personal) fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Lilly, Merck Sharp & Dohme, Pfizer, Roche Pharmaceuticals, Takeda; congress (personal) fees from Boehringer Ingelheim, AstraZeneca, Roche Pharmaceuticals; and advisory board fees (personal) from AstraZeneca, Boehringer Ingelheim, Novartis, Merck Sharp & Dohme, Lilly Pharma, Bristol Myers Squibb, Roche. Dejan Radonjic and Rolf Kaiser are employees of Boehringer Ingelheim. Rolf Kaiser also has a patent EP 2994125 issued. John Heymach received fees for advisory roles from AstraZeneca, EMD Serono, Boehringer Ingelheim, Catalyst, Genentech, GlaxoSmithKline, Hengrui Therapeutics, Eli Lilly, Spectrum, Sanofi, Takeda, Mirati Therapeutics, Bristol Myers Squibb, BrightPath Biotherapeutics, Janssen Global Services, Nexus Health Systems, Pneuma Respiratory, RefleXion, Chugai Pharmaceuticals; fees for a Board of Directors role from Rexanna Foundation; corporate-sponsored research fees from AstraZeneca, Boehringer Ingelheim, Spectrum, Takeda; and royalties and licensing fees from Spectrum. Jesus Corral and Maya Gottfried report no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the effectiveness and safety of nintedanib plus docetaxel in patients with advanced adenocarcinoma non-small cell lung cancer (NSCLC) previously treated with both chemo- and immunotherapy., Materials and Methods: LUME-BioNIS is a European, prospective, multicenter, non-interventional study of patients with advanced adenocarcinoma NSCLC, who initiated nintedanib plus docetaxel after first-line chemotherapy in routine practice according to the approved nintedanib EU label. The primary objective is to explore whether molecular biomarkers can predict overall survival (OS). Information on clinical or radiologic progression and death, and adverse drug reactions (ADRs)/fatal adverse events (AEs) was collected during follow-up. Here, we report a subgroup analysis evaluating outcomes in immunotherapy-pretreated patients., Results: Of 260 enrolled patients, 67 (25.8%) had prior immunotherapy and were included in this subgroup analysis. Prior immunotherapy was administered in first-line in 20 patients (29.9%; combined with chemotherapy in 4 patients [6.0%]) and later-lines in 47 patients (70.1%), and most commonly comprised nivolumab (39 patients; 58.2%), atezolizumab (14 patients; 20.9%) and pembrolizumab (11 patients; 16.4%). Nintedanib plus docetaxel was given in second-line in 10 patients (14.9%) and in later-lines in 57 patients (85.1%). Median OS was 8.8 months (95% confidence interval [CI]: 7.0-11.5) and median progression-free survival (PFS) was 4.6 months (95% CI: 3.5-5.7). Among 55 patients with available data, rates of objective response and disease control were 18.2% and 78.2%, respectively. In 65 patients evaluable for safety, the most common on-treatment ADRs/AEs were malignant neoplasm progression (19 patients; 29.2%), diarrhea (21 patients; 32.3%) and nausea (10 patients; 15.4%)., Conclusions: Used according to the approved nintedanib label in routine practice, nintedanib plus docetaxel demonstrated clinical effectiveness, with no unexpected safety findings, in patients with prior chemotherapy and first- or later-line immunotherapy. These data add to the real-world evidence that can inform clinical decisions in the changing therapeutic landscape., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The introduction of licensed front-line immunotherapies has heralded a new era for the treatment of non-oncogene-addicted, advanced non-small cell lung cancer (NSCLC). Yet as with all evolutions in clinical management, changes in practice can outpace the availability of the clinical evidence needed to inform subsequent therapeutic decision making. At the time of writing, there is limited available evidence on the optimum therapeutic options after progression on immunotherapy. Further research is needed to define mechanisms of immunotherapy resistance in patients with advanced NSCLC, and to understand the implications for subsequent treatment response. Pending the availability of robust clinical data and proven therapeutic options to underpin an optimized therapeutic pathway after progression on immunotherapy, attention must turn to the potential utility of currently licensed agents and any available supporting clinical data in this setting. Within this context we review the mechanistic arguments and supporting evidence for the use of anti-angiogenic agents as a means of targeting immunosuppression within the tumor microenvironment. We consider whether VEGF inhibition may help to normalize the tumor vasculature and to address immunosuppression - reinstating, and potentially enhancing, the effect of subsequent therapies. We also highlight evidence needs and signpost ongoing trials that should enable current clinical opinion in this area to be replaced by robust, evidence-based guidance., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To retrospectively assess the incidence of radiation dermatitis in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) who received primary radiotherapy in combination with cetuximab in a curative intent., Patients and Methods: A total of 112 consecutively treated patients who received cetuximab in combination with radiotherapy at the Departments of Radiotherapy at the Medical University in Vienna and the Hospital Hietzing (Vienna) were analyzed. Radiotherapy was administered either as conventional radiotherapy (70 Gy in 7 weeks) or using a concomitant boost protocol (72 Gy in 6 weeks). The incidence of dermatitis and mucositis within the radiation portals in 103 eligible patients was compared with a historical control group treated at the Medical University of Vienna as well as with published data., Results: The incidence of grade 1/2, 3, and 4 dermatitis was 57%, 29%, and 1% in the radiotherapy plus cetuximab treated collective. The incidence of grade 1/2, 3, and 4 mucositis was 37%, 47%, and 4%, respectively. The incidence of grade 3 dermatitis during concurrent radiotherapy plus cetuximab was 29% in our patient collective. Only one case of grade 4 dermatitis was observed., Conclusion: These results do not statistically differ significantly from the incidence reported in the Bonner trial and indicate that cetuximab in combination with radiotherapy is well tolerated.

1. Slow cortical potential shifts such as the late terminal E-wave component of the CNV appear to be determined mainly by the level of motor preparation and as such it was employed to investigate the degree of cortical involvement in schizophrenics exhibiting abnormal motor phenomena induced by prolonged treatment with neuroleptics. 2. The basic experimental task was a constant foreperiod warned reaction time task consisting of a brief warning tone (S1) followed 4 sec later by a light, the imperative stimulus (S2), upon which the subject was instructed to release a response key. The task was presented twice, in a randomized order, under neutral and fast set instructions, to tardive (TD) and non-tardive dyskinesia (NTD) groups. 3. Computer EEG analysis identified and analysed on early O-wave measured as the average amplitude 500-1000 msec post S1, and the latter E-wave measured as the average amplitude 500 msec prior to S2. Two additional epochs of PINV activity were also analysed. 4. The results indicated that the TD group exhibited significantly larger PINV activity, but unlike NTD patients, the TD group failed to exhibit any significant increases in E-wave amplitude concommitant with improved behavioral reaction times. The results are discussed in relation to a disinhibitory theory of tardive dyskinesia.