Development of the Analytical Methodology for Pyrimethamine and Its Application to Studies of Partitioning and Binding in the Subcompartments of Blood

An original HPLC assay was developed for pyrimethamine (PYR) in plasma, RBCs, and buffer for the purpose of studying its plasma protein binding and RBC partitioning. Equilibrium dialysis (ED) was used to study protein binding. Isotonic phosphate buffer used in ED did not prevent small volume shifts. The pH of the plasma affected the protein binding of PYR although it was not significant for the comparison of binding at pH 7.4 vs. 8.0. PYR at 1000 ng/ml averaged 93.1% bound to plasma proteins. Binding to pure human albumin was 86.5% at lower levels of albumin and PYR (350 ng/ml). There was a significant difference (p\u3c.03) in the plasma binding at two levels in the therapeutic range, with more free at higher levels. There was also concentration dependent binding at higher concentrations; the drug did not follow to law of mass action when binding increased at higher concentrations. This is a solubility phenomenon. Linear regression at the effect at albumin concentration on plasma binding yielded the equation percent free = -0.467(albumin g/L) + 23.5. The binding to pure albumin was only slightly above that predicted by this equation (83.1%). The first and second stoichiometric binding constants are K1 = 2.83 x 104 and K2 = 1.74 x 104 M-1 from nonlinear regression at data. There was no binding to normal levels at α1-acid glycoprotein. PYR is preferentially bound to plasma proteins in comparison to RBCss. The mean RBC/plasma ratio was 0.42 (10.2% CV, n=5). when plasma was removed and pH 7.4 isotonic buffer substituted, mean RBC/buffer ratio was 5.2 (11.8% CV, n=2). Mean percent bound to hemolysate was 42.5% (19% CV, n=10). Binding to hemoglobin did not account for all the RBC uptake. Therefore, PYR binds to RBC membranes

Model Bisnis dan Antarmuka Pelanggan E-Commerce pada PT. SMG

PT. SMG is a company which sells music and movies product in CDs, VCDs and DVDs. PT. SMG relies its business on direct selling through its outlets. PT. SMG needs a solution to facilitate the customers\u27 needs in getting product information and online transactions. E-commerce can be use to develop business and provide an alternative solution to customers on how to transact and obtain product information from PT. SMG using the internet. The objective of this study is to design a business model and customer interface of e-commerce website for PT. SMG. The methodology uses e-commerce business model and customer interface design by Rayport and Jaworski. The website interface design uses a 7C framework approach: Context, Content, Communication, Commerce, Connection, Community and Customization. The result achieved is an e-commerce website that helps sales system and enhances the company competitiveness. The conclusions obtained are that PT. SMG can take advantage of e-commerce to support their sales system and the business model online for PT. SMG is the widest-assortment model

Strategi Promosi Melalui Media Sosial Instagram Guna Menarik Generasi Milenial untuk Memilih Produk Tabungan Pada PT Bank Pembangunan Daerah Kalimantan Selatan Cabang Paringin

Tujuan dari penelitian ini adalah untuk mengetahui strategi promosi melalui media sosial Instagram yang selama ini dilakukan Bank Pembangunan Daerah Kalimantan Selatan Cabang Paringin. Mengetahui strategi promosi melalui media sosial Instagram yang dapat dilakukan guna menarik generasi milenial untuk memilih produk Tabungan pada PT Bank Pembangunan Daerah Kalimantan Selatan Cabang Paringin.Metode penelitian yang digunakan dalam penelitian ini adalah metode deskriptif dengan teknik pengumpulan  data yaitu  observasi  dan  wawancara.  Teknik  analisis  data  yang digunakan adalah data non statistic, dimana dalam penelitian ini tidak menggunakan rumus statistic dan untuk menganalisis data yang sudah dikumpulkan digunakan pendekatan library approach.Permasalahan yang dihadapi PT Bank Pembangunan Daerah Kalimantan Selatan Cabang Paringin adalah tidak maksimalnya promosi melalui media sosial Instagram. Untuk mengatasi  permasalahan  yang  dihadapi  PT  Bank  Pembangunan  Daerah  Kalimantan Selatan Cabang Paringin sebaiknya memaksimalkan promosi melalui media sosial Instagram agar lebih mudah mendekati segmentasi milenial yang melek akan teknologi dengan   langkah-langkah   sebagai   berikut  :   (1)   Update   Image,   (2)   Membangun Kepopuleran Akun, (3) Add Follower, (4) Comment, (5) Share Fitur, (6) Local Ads Fitur/Endorse, (7) Instagram Ads, (8) Like Give, (9) Auto Schedule Post,  (10) CSR Image, (11)  Hasgtag(#) + arroba (@)

Peran Organisai Ikatan Keluarga Pasaman Barat Dalam Mempertahankan kebudayaan Minangkabau di Jakarta, Bogor,Depok, Tanggerang, Bekasi ( JABODETABEK)

Penelitian ini bertujuan untuk mengetahui Gambaran atau fenomena Peran Organisasi Ikatan Keluarga Pasaman Barat dalam Mempertahankan kebudayaan Minangkabau di Jakarta, Bogor, Depok, Tanggerang, Bekasi ( JABODETABEK ). Penelitian ini memfokuskan pada hal Deskripsi lokasi penelitian. peran organisasi Ikatan Keluarga Pasaman Barat dalam mempertahankan Kebudayaan Minangkabau di Jabodetabek, dan bagaimana Kontsribusi terhadap perkembangan Pasaman Barat Penelitian ini menggunakan metode kualitatif. Subjek penelitian ini adalah pihak pengurus Organisasi Ikatan Keluarga Pasaman Barat yang terdiri dari Pimpinan organisasi IKPB, Wakil ketua IKPB, Bendahara IKPB, para anggota perantau Pasaman Barat yang tergabung di organisasi IKPB, masyarakat kabupaten Pasaman Barat. Data di kumpulkan melalui pengamatan atau observasi wawancara, dan mendokumentasikan hal-hal mengenai data yang di butuhkan kemudian data di analisis dengan cermat dan baik Hasil penelitian menunjukkan bahwa 1). Berdasarkan hasil penelitian dan data yang peneliti peroleh di lapangan dalam kegiatan aktifitas yang di lakukan oleh Organisasi Ikatan keluarga Pasaman Barat dalam Mempertahankan Kebudayaan Minangkabau di Jabodetabek. Ternyata adanya nilai-nilai kebudayaan Minangkabau yang di gunakan dalam setiap acara kegiatan aktifitas Organisasi Ikatan Keluarga Pasaman Barat dalam mempertahankan kebudayaan Minangkabau di Jabodetabek. 2).Organisasi Ikatan Keluarga Pasaman Barat Dalam mempertahankan kebudayaan Minangkabau di jabodetabek. Organisasi IKPB berperan dalam mempertahankan Kebudayaan Minangkabau dan berkontribusi untuk perkembangan Pasaman Barat, hal tersebut dapat dilihat dari adanya usaha dan keinginan yang besar dari para cendikiawan muda dan tokoh- tokoh masyarakat Minangkabau yang berada di Pasaman Barat dan di perantau untuk menggali dan mempelajari budaya dan adat Minangkabau ini, meskipun menghadapi berbagai kesulitan dan hambatan setiap melaksanakan kegiatan di organisasi. 3).Memberikan Rekomendasi Pasaman Barat dalam kemajuan Pasaman Barat dari persepektik kebudayaan, perekonomian, pariwisata, pertanian, pendiikan dalam melakukan diskusi. Ikpb sebagai mitramemberikan masukan -masukan dan pemikiran itu sangat menambah wawasan masyarakat perantau asal Pasman Barat yang berada di jabodetabek dan masyarakat dalam nagari

Cartera de crédito según categoría de riesgo de MIBANCO, periodo 2017-2019

La presente investigación se realizó un análisis vertical y horizontal de la cartera de crédito por categoría de riesgo con el objetivo principal de determinar la situación financiera actual que presentan tanto los créditos directos e indirectos otorgados a los clientes de MIBANCO - Banco de la Microempresa de los periodos: 2017, 2018 y 2019. El procedimiento que se utilizó fue tomar y examinar los valores presentados en los estados financieros auditados de la entidad y más específicamente en las notas a los estados financieros en el rubro cartera de créditos neto, de esta manera poder obtener los resultados esperados en la investigación. Por lo tanto, se determinó que la cartera de crédito con categoría normal es la más predominante en un valor de 90.69% en los créditos directos; mientras que, los créditos indirectos el 100% corresponde a la categoría normal en los tres años. Esto significa que los deudores que están catalogados en esta categoría realizan los pagos en los tiempos establecidos, es decir la capacidad de generar ingresos que les permitan cumplir con los pagos de las deudas u obligaciones adquiridas para el financiamiento de sus actividades económicas y proyectos

Visible and Near-Infrared Spectrophotometry of the Deep Impact Ejecta of Comet 9P/Tempel 1

We have obtained optical spectrophotometry of the evolution of comet 9P/Tempel 1 after the impact of the Deep Impact probe, using the Supernova Integral Field Spectrograph (SNIFS) at the UH 2.2m telescope, as well as simultaneous optical and infrared spectra using the Lick Visible-to-Near-Infrared Imaging Spectrograph (VNIRIS) spectrograph. The spatial distribution and temporal evolution of the "violet band" CN (0-0) emission and of the 630 nm [OI] emission was studied. We found that CN emission centered on the nucleus increased in the two hours after impact, but that this CN emission was delayed compared to the light curve of dust-scattered sunlight. The CN emission also expanded faster than the cloud of scattering dust. The emission of [OI] at 630 nm rose similarly to the scattered light, but then remained nearly constant for several hours after impact. On the day following the impact, both CN and [OI] emission concentrated on the comet nucleus had returned nearly to pre-impact levels. We have also searched for differences in the scattering properties of the dust ejected by the impact compared to the dust released under normal conditions. Compared to the pre-impact state of the comet, we find evidence that the color of the comet was slightly bluer during the post-impact rise in brightness. Long after the impact, in the following nights, the comet colors returned to their pre-impact values. This can be explained by postulating a change to a smaller particle size distribution in the ejecta cloud, in agreement with the findings from mid-infrared observatons, or by postulating a large fraction of clean ice particles, or by a combination of these two.Comment: 28 pages of text and 8 figures. Paper is accepted for publication in Icaru

Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe

The Extragalactic Background Light (EBL) includes photons with wavelengths from ultraviolet to infrared, which are effective at attenuating gamma rays with energy above ~10 GeV during propagation from sources at cosmological distances. This results in a redshift- and energy-dependent attenuation of the gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts (GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using photons above 10 GeV collected by Fermi over more than one year of observations for these sources, we investigate the effect of gamma-ray flux attenuation by the EBL. We place upper limits on the gamma-ray opacity of the Universe at various energies and redshifts, and compare this with predictions from well-known EBL models. We find that an EBL intensity in the optical-ultraviolet wavelengths as great as predicted by the "baseline" model of Stecker et al. (2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A. Reimer, L.C. Reye

Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial.

BACKGROUND: Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes. METHODS: In this multicentre, open-label, randomised controlled trial, we recruited women aged 18-40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527. FINDINGS: Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference -0·19%; 95% CI -0·34 to -0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight [7%] CGM, five [5%] control) and in three (3%) participants in the planning pregnancy trial (two [4%] CGM and one [2%] control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy). INTERPRETATION: Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use. FUNDING: Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research

Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries

Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20–37) versus 47 (IQR 32–58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11–40]) than in HICs (44/102 [43%, 95% CI 34–53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.</p