Computer discrimination between diseases of the brain based on MR image features

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Simple relationships between residence time and annual nutrient retention, export, and loading for estuaries

Simple mathematical models are derived from mass balances for water and transported substance to provide insight into the relationships between import, export, transport, and internal removal for nonconservative sub-stances in an estuary. Extending previous work, our models explicitly include water and substance inputs from the ocean and are expressed in terms of timescales (i.e., mean residence time and the timescale for net removal). Steady-state, timescale-based expressions for ratios of export to import, retention to import, and net export to loading, as well as for loading and annually averaged concentration, are provided. The net export:loading model explains the underlying mechanisms for a well-known empirical relationship between fractional net export and residence time derived by other authors. Although our simplified models are first-order approximations, the relative importance of physical and biochemical processes influencing export or retention of a substance can be assessed using mean residence time and the timescale for net removal. Assumptions employed in deriving the simplified models(e.g., well-mixed, dynamic steady state) may not be met for real estuaries. However, model application to Chesapeake Bay for 1985–2012 demonstrates that interannual variations in total nitrogen (TN)net export:loading can be evaluated, and annual nutrient loadings can be well estimated using numerically modeled time-varying mean residence time, observation-based mean concentration, freshwater inflow, and an appropriately estimated removal timescale. Our model shows that net fractional export of TN loading ranges from 0.3 to 0.5 over the 28-yr period.The models can be employed for other substances and water bodies if the underlying assumptions are applicable

Barriers to hydroxyurea use in sickle cell disease: perspectives of providers, families, and adults

PURPOSE: Sickle cell disease (SCD) is an inherited blood disorder that affects the hemoglobin protein of red blood cells and has a significant impact on morbidity, mortality, and quality of life. Hydroxyurea has been FDA approved since 1998 as a disease-modifying therapy for SCD. However, hydroxyurea has not been optimally utilized for those with SCD. The purpose of this study was to evaluate reasons for hydroxyurea use, from the perspectives of providers, adults with SCD, and parents/caregivers of children with SCD, as well as perceived barriers to its use. We examined indications and reasons for being “on hydroxyurea,” defined by patients as currently taking hydroxyurea, and reported on pain frequency, perceptions of barriers, hydroxyurea adherence, and health care access for patients with SCD who were either on and not on hydroxyurea. METHODS: We conducted a cross sectional analysis of data collected within the Pacific Sickle Cell Regional Collaborative (PSCRC), a consortium of nine western U.S. states. Individuals were eligible for this study if they 1) had a confirmed diagnosis of SCD, 2) were followed at one of the PSCRC sites, and 3) were eligible for hydroxyurea therapy. Parents/caregivers of children with SCD less than 18 years and adults with SCD 18 years and older completed a brief survey about hydroxyurea use, indications, side effects, pain frequency, number of hospital and emergency department (ED) admissions per year, and individual and family perceptions of barriers to hydroxyurea use. Participants completed a follow-up survey annually, but we reported only on baseline data. Data collection occurred between February 2016 and May 2018. RESULTS: Individuals with SCD (n = 413) included 1) children (n=178; 6.7 ± 3.4 years), 2) adolescents (n=66; 15.0 ± 1.4 years), 3) young adults (n=57; 21.4 ± 2.6 years), and 4) adults (n=112; 39.2 ± 10.6 years). The majority were predominantly female (51.6%), African American (93.2%), and had HgbSS (74.1%) genotype. The majority of children (65.2%), adolescents (62.1%), and young adults (54.4%) were on hydroxyurea; fewer adults (39.3%) were on hydroxyurea. The majority with HgbSS (65.5%) were adherent to hydroxyurea. There was no significant difference in hospitalizations for pain, ED visits, and pain severity in the previous 12 months between individuals who were and were not on hydroxyurea, and between individuals who were and were not adherent to hydroxyurea. For those with a current prescription for hydroxyurea, the majority (66.5%) were receiving hydroxyurea for recurrent pain episodes or acute chest syndrome (19.9%). Hydroxyurea was discontinued because of patient/family preference (34.5%), chronic transfusions (31.1%), and side effects (24.1%). Patients prescribed hydroxyurea for empiric use (n=21) had fewer hospitalizations for pain, ED visits, and severe pain interfering with daily activities. The major barriers to hydroxyurea use, from the perspective of individuals with SCD or their caregivers, were 1) forgetting to take the medicine (19.4%), 2) worried about side effects (16.4%), and 3) lack of knowledge about hydroxyurea (13.6%). Fewer young adults (49.1%) and adults (50.0%) had primary care providers than children (78.1%) and adolescents (65.2%). CONCLUSIONS: Barriers to hydroxyurea use persist with emerging solutions to alleviate these barriers. For this sample, while hydroxyurea prescription rates by sickle cell specialists were similar to what has been seen in some other studies, neither hydroxyurea use nor adherence were associated with decreased frequency of hospitalizations for pain, ED visits, and severe acute pain episodes in the previous 12 months. Future studies need to evaluate hydroxyurea prescription patterns, duration on hydroxyurea, and adherence to hydroxyurea. Healthcare providers are recommended to prescribe hydroxyurea for eligible individuals who may benefit from it, such as those HgbSS or HgbS-β0 thalassemia genotype, and prescribe for empiric use to minimize complications. Provider and patient education about hydroxyurea could reduce common barriers experienced by individuals with SCD. It is important to customize educational resources to specific concerns for different age groups. Individuals 18 years and older with SCD have been documented with more ED visits and hospitalizations due to pain, most likely because they did not have a primary care provider and an adult hematologist with expertise in SCD. Future studies need to evaluate whether primary care providers who receive SCD education may promote hydroxyurea use and adherence. Dedicating time and resources for shared decision making between providers and patients/families can address concerns about hydroxyurea and increase patient/family confidence when deciding about hydroxyurea. As more disease-modifying therapies become available for individuals with SCD, strategies for shared decision making facilitate standardization and optimize the use of hydroxyurea and emerging therapies

Extreme precipitation on consecutive days occurs more often in a warming climate

Extreme precipitation occurring on consecutive days may substantially increase the risk of related impacts, but changes in such events have not been studied at a global scale. Here we use a unique global dataset based on in situ observations and multimodel historical and future simulations to analyze the changes in the frequency of extreme precipitation on consecutive days (EPCD). We further disentangle the relative contributions of variations in precipitation intensity and temporal correlation of extreme precipitation to understand the processes that drive the changes in EPCD. Observations and climate model simulations show that the frequency of EPCD is increasing in most land regions, in particular, in North America, Europe, and the Northern Hemisphere high latitudes. These increases are primarily a consequence of increasing precipitation intensity, but changes in the temporal correlation of extreme precipitation regionally amplify or reduce the effects of intensity changes. Changes are larger in simulations with a stronger warming signal, suggesting that further increases in EPCD are expected for the future under continued climate warming.We acknowledge support from the National Key R&D Program of China (2019YFC0409101), Science and Technology Development Plan of Jilin Province (20190201291JC), the Joint Fund of National Natural Science Foundation of China (U19A2023), the Fundamental Research Funds for the Central Universities (2412020FZ002), and 2236 Co-Funded Brain Circulation Scheme2 (CoCirculation2) of TÜBİTAK (121C054). M.G.D. acknowledges support by the Horizon 2020 EUCP project under Grant Agreement 776613 and by the Spanish Ministry for the Economy, Industry and Competitiveness Ramón y Cajal 2017 Grant Reference RYC-2017-22964.Peer Reviewed"Article signat per 28 autors/es: Haibo Du, Markus G. Donat, Shengwei Zong, Lisa V. Alexander, Rodrigo Manzanas, Andries Kruger, Gwangyong Choi, Jim Salinger, Hong S. He, Mai-He Li, Fumiaki Fujibe, Banzragch Nandintsetseg, Shafiqur Rehman, Farhat Abbas, Matilde Rusticucci, Arvind Srivastava, Panmao Zhai, Tanya Lippmann, Ibouraïma Yabi, Michael C. Stambaugh, Shengzhong Wang, Altangerel Batbold, Priscilla Teles de Oliveira, Muhammad Adrees, Wei Hou, Claudio Moises Santos e Silva, Paulo Sergio Lucio, and Zhengfang Wu "Postprint (published version

Formulation of an anti-tuberculosis drug delivery system

ABSTRACT:Tuberculosis (TB) is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. A number of novel drug delivery systems incorporating the principle anti-tuberculosis (anti-TB) agents have been fabricated that either target the site of TB infection or reduce the dosing frequency with the aim of improving patient outcomes; however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin (RIF) bioavailability recently reported in a number of fixed-dose combinations (FDCs). There is an urgent need to segregate the delivery of RIF and isoniazid (INH) upon co-administration, such that INH is not released in the stomach owing to the induction of accelerated hydrolysis of RIF in acidic medium to the poorly absorbed insoluble 3-formyl rifamycin SV in the presence of INH. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-TB drugs, which attains segregated delivery of RIF and INH for improved RIF bioavailability, could be a step in the right direction in addressing issues of treatment failure due to administration of poor quality FDCs and patient non-compliance. Novel approaches were implemented for the fabrication of an oral multiparticulate system for differentiated release of RIF and INH in the gastrointesinal tract. The envisaged system comprised INH-loaded enterosoluble multiparticulate entities for targeted delivery of the INH to the small intestine and reconstitutable multiparticulate entities incorporating the poorly water-soluble RIF and appropriate gel-forming hydrophilic suspending agents, which were required to disintegrate rapidly in tepid water to form a gel network suspending RIF and the INH-loaded enterosoluble multiparticulates. The dry dispersible multiparticulate system may be reconstituted immediately prior to administration to the patient for once-daily dosing as a compliancepromoting tool. The design of a novel anti-TB drug delivery system hinged on preformulatory investigations and preliminary experimental activities to yield a sufficient database to allow for the selection of the qualitative composition of a prototype formulation. The aforementioned activities initiated the systematic identification of an innovative method for formulating enterosoluble multiparticulates demonstrating the required enteric-release properties. The novelly-formed multiparticulates, referred to as ‘enterospheres’, were obtained by inducing separation (‘salting-out’) of a pH-sensitive poly (methacrylic acid-co-ethylacrylate) copolymer as a polymer-rich enteric film and ionotropically cross-linking the internal enterosphere matrix. Rational selection of appropriate suspending agents for design of reconstitutable multiparticulates resolved in the identification of a synergistic hydrophilic sodium starch glycolate-kappa carrageenan combination, duly characterised by physicomechanical analyses. The gel-forming composite system attained ease of dispersal and the formation of a three-dimensional supporting network possessing the essential properties for extemporaneous use. Statistical experimental design, implementing response surface methodology, was pivotally instituted on the multiparticulate forms for the identification of critical formulation and processing variables for the development of the optimum enterosoluble and reconstitutable multiparticulate systems for delivery to the patient as the preferred multiparticulate two-drug FDC. Because there was an unequivocal relationship between the properties of a cross-linked enterospheres and their structure in such a way that both characteristics could not be considered in an isolated way, in-depth analyses on drug-free and drug-loaded enterospheres was systematically undertaken. Of principle concern in this study was the attainment of segregated gastrointestinal delivery of RIF and INH in order to address issues of unacceptable RIF bioavailability on co-administration with INH. The proposed United States Pharmacopoeial (USP) high performance liquid chromatographic (HPLC) and colorimetric method, and a proposed regressional analysis of ultraviolet (UV) spectrophotometric absorbance data were employed to resolve RIF and INH release from the optimum multiparticulate system at simulated gastric pH for comparison with the release profiles of anti-TB FDCs commercially available in South Africa. Ultimately, in keeping up to speed with future trends, this dissertation addressed innovations in nanotechnology, with particular reference to anti-TB nanosystems. The novelly identified method for enterosphere manufacture was adapted with a view to nanosizing the salted-out and cross-linked architecture, for controlled delivery of anti-TB drugs to the patient, in the bid to promote patient adherence

Extending the generalizability and pragmatic contributions to solve privacy paradox

Privacy issue has increasingly become an integral part of organizations and businesses that operate within the digital era. However, heretofore, there is a lack of a systematic literature review to help scholars to integrate what has been done in previous studies when privacy issues were addressed especially the privacy paradox that still perplexes both academia and practitioners alike. Furthermore, with the inconsistency of findings regarding the privacy paradox, there is also a need to support researchers in recognizing the substantial constructs to improve the results of their empirical papers. Therefore, this paper aims to serve as an integrated review to congregate constructs that can help scholars to improve the generalizability and pragmatic contributions when addressing privacy paradox issue. Besides the conclusion that there is a lack of empirical papers on privacy paradox published in the business, management and marketing journal publications, we also synthesize constructs such as the population of the study, methodology, cross-cultural aspect and context of the study to improve the extent of the generalizability and practical contributions of empirical paper related to the privacy paradox. The limitations and implications of this study are also discussed at the end of this paper

Design and Characterization of Endostatin-Loaded Nanoparticles for In Vitro Antiangiogenesis in Squamous Cell Carcinoma

The aim of this study is to effectively enhance antitumor activities of endostatin by preparing polymeric nanocarriers. NMR and FT-IR spectra confirmed the successful grafting of the CHT-g-PEI and CHT-g-PEI-PEG-NH2 conjugates. SEM micrographs confirmed the shape of endostatin-loaded nanoparticles to be spherical while both TEM and zeta size results showed nanoparticle’s average size to be 100.6 nm having a positively charged surface with zeta potential of 7.95 mV. The concentrations of CHT and TPP as well as the changing pH conditions account for the increased swelling pattern of endostatin-loaded nanoparticles and influenced endostatin release in vitro. PEI increased the overall amine protonation while PEG aggravated endostatin encapsulation and release. Nanoparticles swell and release endostatin at acidic tumor pH of 6.8 compared to physiological pH of 7.4. The native CHT-g-PEI-PEG-NH2 conjugate showed high cytocompatibility above 80% cell viability across tested formulations. Endostatin-loaded nanoparticles showed a significant reduction in cell viability across tested formulations, with 5.32% cell death at 125 μg/mL and 13.36% at 250 μg/mL following 24 hours’ incubation period. Interestingly, more than a fourfold (61.68%) increment in cytotoxicity was observed at nanoparticle concentration of 1000 μg/mL. It was concluded that CHT-g-PEI-PEG-NH2 is an effective cargo for endostatin delivery with antiangiogenic effect in squamous cell carcinoma

Potential Antioxidative Effects of Kolaviron on Reproductive Function in Streptozotocin-Induced Diabetic Wistar Rats

The present study investigated the effects of Kolaviron (KV) on the testicular and epididymal tissue antioxidant status in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ at 50 mg/kg body weight. The antioxidant status was studied by evaluating epididymal and testicular levels of malondialdehyde (MDA), a lipid peroxidation (LPO) marker, and the activities of catalase (CAT) glutathione peroxidase (GPX) and superoxide dismutase (SOD) were also assessed using biochemical techniques. Diabetes induction resulted in testicular and epididymal LPO and adversely affected the activities of antioxidant enzymes evident by a noticeable decrease in enzyme activity in both tissues. The potential antioxidative effects of KV in the testicular and epididymal tissues of STZ-induced diabetes were revealed by its ability to mitigate against LPO and increase the activity of antioxidant defense enzymes in the reproductive tissues studied. KV might potentially be used as an antioxidant as well as antidiabetic treatment; however, further studies are needed