Range Restricted Interpolation Using Cubic Bézier Triangles.

A range restricted C1 interpolation local scheme to scattered data is derived. Each macro triangle of the triangulated domain is split into three mini triangles and the interpolating surface on each mini triangle is a cubic Bézier triangle. Sufficient conditions derived for the non-negativity of these cubic Bézier triangles are expressed as lower bounds to the Bézier ordinates. The non-negativity preserving interpolation scheme extends to the construction of a range restricted interpolating surface with lower or upper constraints which are polynomial surfaces of degree up to three. The scheme is illustrated with graphical examples

Development and characterisation study of liposomes-encapsulated piroxicam

The objective of present work was to develop a novel liposomes-based drug delivery system for a lipophilic non-steroidal anti-inflammatory drug, piroxicam. The system was prepared using proliposomes method and optimised for different preparation parameters including type of proliposomes, concentration of drug, duration of hydration and type of particle size reduction treatment used. All prepared liposomal samples were extensively characterized for their drug-entrapment and size profile using various in-vitro techniques. Present work showed that the most optimum formulation (Pro-lipoTM Duo; 12mg piroxicam per gram Pro-lipoTM; 10 hours hydration time) produced highest amount of actual drug been entrapped in liposomes (800.4 mg/g Pro-lipoTM) with a satisfactory entrapment efficiency of 15.36%. This formulation had also produced liposomal samples with a homogenous (polydispersity index = 0.45) and small particle size (359.95nm). Extrusion technique was found to cause significant reduction in drug-entrapment and size profile of drug-loaded liposomes. A 4-weeks storage study showed that drug-entrapment and size profile of liposomal samples were stable in both refrigerated and room temperature. Electron microscopy revealed that prepared liposomal samples were spherical-shaped and showed concentric lamellae. In conclusion, present work successfully demonstrated a simple, reproducible and practical method of preparation for liposomes-encapsulated piroxicam.Keywords: Proliposomes; Liposomes; Piroxicam; Encapsulation; Particle size; Transmission electron microscop

Indication, Safety and Clinical Impact of Cardiovascular Magnetic Resonance: A Pilot Run of the First National CMR Registry for Malaysia

Background: Cardiovascular magnetic resonance (CMR) is a rapidly emerging noninvasive imaging technique providing high resolution images without any application of radiation. It has broad range of clinical applications and is increasingly been used in clinical practice in Malaysia. A national CMR Registry is needed to assess its practice in Malaysia. Objective: To evaluate indications, safety and impact on patient management of CMR in Sarawak Heart Centre. Materials Methods: A pilot run of CMR Registry in single centre with consecutive patients who underwent clinical CMR from January-June 2015. Retrospective data collection from CMR database and case notes. Results: A total of 169 patients underwent clinical CMR, with 20 did not complete scan; 25% due to claustrophobia. 94% of patients received gadolinium-based contrast agent. Most important indications were viability assessment (54.4%), cardiomyopathy (28.2%), and risk stratification in suspected coronary artery disease (CAD) (4.7%). 6.7% of patients underwent stress MR (adenosine or dobutamine). Severe complications only occurred in 0.7% of the cases (anaphylactic reaction secondary to contrast agent). No mortality during/due to CMR. There was direct impact of CMR on the clinical management by confirming suspected diagnosis (59.1%), excluding suspected diagnosis (21.5%), providing additional information for suspected diagnosis which is confirmed or excluded (18.1%) and providing unsuspected completely new diagnosis (1.3%). Invasive coronary angiogram was avoided and diagnosis were excluded in all patients referred for risk stratification of suspected coronary artery disease. Invasive therapeutic procedures such as PCI, CABG, valve surgerywere triggered in 49.6 % of patients after CMR was done, regardless of indication. Out of 81 patients who underwent CMR for viability study, 76.5% were planned for revascularisation (CABG or PCI) with the restwere planned for optimalmedical therapy only after the CMR. Conclusions: The top indications of CMR in Sarawak are viability assessment, cardiomyopathy and risk stratification in suspected CAD, which differs from the EuroCMR registry results. This demonstrated the importance of establishing a national multicentre CMR registry in Malaysia, and subsequently substudy on specific conditions. With appropriate medical personnel training and patient selection, CMR is safe and has strong impact on clinical management

LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast cancer

Deletion of 11q23-q24 is frequent in a diverse variety of malignancies, including breast and colorectal carcinoma, implicating the presence of a tumor suppressor gene at that chromosomal region. We show here that LARG, from 11q23, has functional characteristics of a tumor suppressor. We examined a 6-Mb region on 11q23 by high-resolution deletion mapping, utilizing both loss of heterozygosity (LOH) analysis and microarray comparative genomic hybridization (CGH). LARG (also called ARHGEF12), identified from the analyzed region, was underexpressed in 34% of primary breast carcinomas and 80% of breast cancer cell lines including the MCF-7 line. Multiplex ligation-dependent probe amplification on 30 primary breast cancers and six breast cancer cell lines showed that LARG had the highest frequency of deletion compared to the BCSC-1 and TSLC1 genes, two known candidate tumor suppressor genes from 11q. In vitro analysis of breast cancer cell lines that underexpress LARG showed that LARG could be reactivated by trichostatin A, a histone deacetylase inhibitor, but not by 5-Aza-2{prime}-deoxycytidine, a demethylating agent. Bisulfite sequencing and quantitative high-throughput analysis of DNA methylation confirmed the lack of CpG island methylation in LARG in breast cancer. Restoration of LARG expression in MCF-7 cells by stable transfection resulted in reduced proliferation and colony formation, suggesting that LARG has functional characteristics of a tumor suppressor gene

Comparison of Resting PD/PA with Fractional Flow Reserve Using a Monorail Pressure Catheter

Background: The RXi™ system (ACIST Medical Systems, MN, USA) is a new Fractional Flow Reserve (FFR) technology utilising an ultrathinmonorail microcatheter (Navvus®; ACIST Medical Systems) with an optical pressure sensor located close to the distal catheter tip. FFR measurement using monorail microcatheter is comparable to the conventional pressure wires. However, the predictive value of resting distal coronary artery pressure/aortic pressure (Pd/Pa) on hyperemic FFR value in the real world practice is unknown. Objective: To explore the diagnostic accuracy of resting Pd/Pa in relation to hyperemic FFR using the monorail pressure catheter. Methods: Resting Pd/Pa and FFR were measured using monorail pressure catheter in 67 consecutive patients with intermediate coronary artery lesions (30% to 80% diameter stenoses) between 01-03-2016 to 17-01-2017. Of 121 studied lesions, 29 (23.97%) were excluded because of no hyperemic FFR due to postive resting Pd/Pa (n=17), severe or non-critical stenosis (n=11) and suboptimal acquisition (n=1), leaving 92 lesions for final analysis. Hyperemic FFR was induced with intracoronary adenosine. The selection of coronary wire and the dose of intracoronary nitroglycerine were at the operators’ discretions. Results: Bland-Altman plots showed a moderate degree of scatter between Pd/Pa and FFR value. On average, Pd/Pa exceeded FFR by 0.066 (-0.09 to +0.22). Receiver-operating characteristic curves of the resting Pd/Pa with FFR≤0.80 as the reference variable showed an area under the curve of 0.78 (95% confidence intervals 0.680 to 0.881, pb0.001), with a diagnostic accuracy of 79.3% when the resting Pd/Pa was ≤0.86. Certain cutoff values of Pd/Pa can reliably predict whether hyperemic FFR was positive or negative (FFR cutoff≤0.80). Resting Pd/Pa value of N0.96 had a negative predictive value (NPV) of 100% and sensitivity of 100%; the resting Pd/Pa value of ≤0.82 had a positive predictive value (PPV) of 100% and specificity of 98.3%. These were consistent regardless of coronary vessel, location of lesion or degree of diameter stenosis. Conclusions: Certain range of resting Pd/Pa measured by monorail pressure catheter had excellent NPV and sensitivity or excellent PPV and specificity to predict hyperemic FFR. Clinical outcome studies are required to determine whether the results might obviate the need for hyperemia in selected patients

Prognostic Value of N-terminal B-type Natriuretic Peptide in Patients with Acute Myocardial Infarction: A Multicenter Study

Background: Several models have been developed to help the clinician in risk stratification for Acute Coronary Syndrome (ACS),such as the TIMI and GRACE risk scores. However, there is conflicting evidence for the prognostic value of NT-ProBNP in acute myocardial infarction (AMI). Objective: (1) To explore the association of NT-proBNP with 30-day clinical outcome in AMI patients. (2) To compare the prognostic value of NT-proBNP with TIMI and GRACE risk scores in AMI patients. Methods: We conducted a multicenter, prospective observational study recruiting patients presented with AMI between 29-October-2015 and 14-January-2017, involving 1 cardiology referral centre and 4 non-cardiology hospitals. NT-proBNP level (Alere Triage®, US)was measured within 24 hours fromthe diagnosis of AMI. Patientswere followed-up for 1 month. Results: A total of 186 patients were recruited, 143 from tertiary cardiology centre and 43 from non-cardiology hospitals. Mean age was 54.7±10.0 years, 87.6% male and 64% were STEMI. The NT-proBNP level ranged from 60 to 16700pg/ml, with a median of 714pg/ml. Using the 75th centile as the cutoff, Kaplan-Meier survival analysis for the 30-day cardiac related mortality was significantly higher for patient with NT-proBNP level of ≥1600pg/ml (6.4% vs. 0.7%, p=0.02). Cox-regression analysis showed that NT-proBNP level of ≥1600pg/ml was an independent predictor of 30-day cardiac related mortality, regardless of TIMI risk score, GRACE score, LV ejection fraction and study hospitals (HR 9.274, p=0.054, 95%CI 0.965, 89.161). Readmission for heart failure at 30-day was also higher for patient with NT-proBNP level of ≥1600pg/ml (HR 9.308, p=0.053, 95%CI 0.969, 89.492). NT-proBNP level was not associated with all-cause mortality, risk of readmission for ACS, arrhythmia and stroke (pN0.05). By adding 50 score to GRACE risk score for NT-proBNP level of ≥1600pg/ml, combination of GraceNT-proBNP scores of more than 200 appeared to be a better independent predictor for 30-day cardiac related mortality (HR:28.28, p=0.004, 95%CI 2.94, 272.1). ROC analysis showed that this new score had 75% sensitivity and 91.2% specificity in predicting 30-day cardiac related mortality (AUC 0.791, p=0.046). Conclusions: NT-proBNP is a useful point-of-care risk stratification biomarker in AMI. It can be combined to the current risk score model for better risk stratification in AMI patients

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

FUT2 Variants Confer Susceptibility to Familial Otitis Media

Non-secretor status due to homozygosity for the common FUT2 variant c.461G>A (p.Trp154∗) is associated with either risk for autoimmune diseases or protection against viral diarrhea and HIV. We determined the role of FUT2 in otitis media susceptibility by obtaining DNA samples from 609 multi-ethnic families and simplex case subjects with otitis media. Exome and Sanger sequencing, linkage analysis, and Fisher exact and transmission disequilibrium tests (TDT) were performed. The common FUT2 c.604C>T (p.Arg202∗) variant co-segregates with otitis media in a Filipino pedigree (LOD = 4.0). Additionally, a rare variant, c.412C>T (p.Arg138Cys), is associated with recurrent/chronic otitis media in European-American children (p = 1.2 × 10−5) and US trios (TDT p = 0.01). The c.461G>A (p.Trp154∗) variant was also over-transmitted in US trios (TDT p = 0.01) and was associated with shifts in middle ear microbiota composition (PERMANOVA p 20 were combined, FUT2 variants were over-transmitted in trios (TDT p = 0.001). Fut2 is transiently upregulated in mouse middle ear after inoculation with non-typeable Haemophilus influenzae. Four FUT2 variants—namely p.Ala104Val, p.Arg138Cys, p.Trp154∗, and p.Arg202∗—reduced A antigen in mutant-transfected COS-7 cells, while the nonsense variants also reduced FUT2 protein levels. Common and rare FUT2 variants confer susceptibility to otitis media, likely by modifying the middle ear microbiome through regulation of A antigen levels in epithelial cells. Our families demonstrate marked intra-familial genetic heterogeneity, suggesting that multiple combinations of common and rare variants plus environmental factors influence the individual otitis media phenotype as a complex trait