236 research outputs found
Three novel F8 mutations in sporadic haemophilia A cases
No full textLetter to the editorRashid Hussain, Noman Bin Abid, Sajjad Hussain, Zeeshan Shaukat, Mudassir Altaf, Sara Altaf, and Gulzar Niaz
sj-docx-2-cpc-10.1177_10556656231225573 - Supplemental material for Management of Velopharyngeal Dysfunction (VPD) Following Cleft Palate Repair: A Comprehensive Decision-Making Process Based on Severity and Structural Deficiencies
No full textSupplemental material, sj-docx-2-cpc-10.1177_10556656231225573 for Management of Velopharyngeal Dysfunction (VPD) Following Cleft Palate Repair: A Comprehensive Decision-Making Process Based on Severity and Structural Deficiencies by Syed Altaf Hussain, Charanya Vijayakumar, Subramaniyan Balasubramanian, Sara Rahavi-Ezabadi, Vishnu Sundar, Deborah Sybil and Zaid Hussain in The Cleft Palate Craniofacial Journal</p
sj-docx-3-cpc-10.1177_10556656231225573 - Supplemental material for Management of Velopharyngeal Dysfunction (VPD) Following Cleft Palate Repair: A Comprehensive Decision-Making Process Based on Severity and Structural Deficiencies
No full textSupplemental material, sj-docx-3-cpc-10.1177_10556656231225573 for Management of Velopharyngeal Dysfunction (VPD) Following Cleft Palate Repair: A Comprehensive Decision-Making Process Based on Severity and Structural Deficiencies by Syed Altaf Hussain, Charanya Vijayakumar, Subramaniyan Balasubramanian, Sara Rahavi-Ezabadi, Vishnu Sundar, Deborah Sybil and Zaid Hussain in The Cleft Palate Craniofacial Journal</p
sj-docx-1-cpc-10.1177_10556656231225573 - Supplemental material for Management of Velopharyngeal Dysfunction (VPD) Following Cleft Palate Repair: A Comprehensive Decision-Making Process Based on Severity and Structural Deficiencies
No full textSupplemental material, sj-docx-1-cpc-10.1177_10556656231225573 for Management of Velopharyngeal Dysfunction (VPD) Following Cleft Palate Repair: A Comprehensive Decision-Making Process Based on Severity and Structural Deficiencies by Syed Altaf Hussain, Charanya Vijayakumar, Subramaniyan Balasubramanian, Sara Rahavi-Ezabadi, Vishnu Sundar, Deborah Sybil and Zaid Hussain in The Cleft Palate Craniofacial Journal</p
A Study of Reduced Order 4D-VAR with a Finite Element Shallow Water Model
No full textForecast models often depend on unknown parameters, such as model initial and boundary conditions, or other tunable parameters not necessarily having any physical meaning. Calibration of these parameters to minimize errors between forecasted and observed states is called data assimilation. A common approach in this context are variational methods, of which four dimensional data variation (4D-VAR) is studied in this thesis. In 4D-VAR, a cost function is defined that penalizes misfits between observations and the corresponding numerical model results, obtained by running the model with the chosen configuration. Performing optimization with regard to this cost function yields an improved initial parameter set. Associated with this type of methods, however, are difficulties in connection with programming the adjoint model, which is needed to compute the exact gradient of the cost function. Additionally, having to integrate the adjoint model backwards in time adds significantly to the computational cost of the data assimilation process. To avoid manual implementation of adjoint code and to reduce computational complexity, approximation of the gradient calculation is considered through the use of proper orthogonal decomposition (POD), a flexible data-driven order reduction method. To facilitate this, a finite element model of the shallow water equations is tested with both the full adjoint 4D-VAR method and two different POD-reduced approaches. Twin experiments are performed and comparisons are made in terms of accuracy, computational complexity and sensitivity to perturbation and number of observation points.Applied mathematicsElectrical Engineering, Mathematics and Computer Scienc
Model reduced variational data assimilation for shallow water flow models
No full textIdentifying uncertain parameters in large-scale numerical flow models can be done using the variational method. However, for implementing the variational method the adjoint model have to be available, which requires highly complex computer code and maintenance and thus hampers its applications. To ease this problem, this thesis has explored several methods for efficiently identifying uncertain parameters in a large-scale tidal model of the entire European continental shelf which does not require the implementation of these complex adjoint code. In this study, as a first step an estimation method based on model reduction is developed and investigated for the estimation of diffusion coefficient in a simple 2D-advection diffusion model. Two projection based model reduction methods were considered, namely proper orthogonal decomposition (POD) and Balanced proper orthogonal decomposition (BPOD). In the POD based estimation method an ensemble of forward model simulations is used to determine an approximation of the covariance matrix of the model variability and a small number of the leading eigenvectors of this matrix is used to define a model subspace. By projecting the original model onto this subspace an approximate linear reduced model is obtained. Once the reduced model is available its adjoint can be implemented easily and the minimization problem is solved completely in reduced space with very low computational cost. BPOD is also a model reduction method which considers both inputs and outputs of the system while determining the reduce subspace. The estimation method has been extended by including BPOD procedure into the estimation procedure. Numerical results from a simple pollution model demonstrate that the POD based estimation approach successfully estimate the diffusion coefficient for both advection dominated problems as for diffusion dominated problems. Another important message in this study, although lots of effort had been made in constructing a reduced order model by the BPOD method, the minimization results demonstrated that both the POD and the BPOD methods performed similarly. Preliminary results showed the validity of the POD based model reduction methods for parameter estimation. As a next step, the POD based estimation method is used to calibrate numerical tidal models. Results from (twin) numerical experiments showed that the POD based calibration method performed very efficiently to estimate depth values in the selected regions of the model domain. The computational costs of the POD based calibration method are dominated by the generation of an ensemble of forward model simulations where the simulation period of the ensemble is equivalent to the timescale of the original model. It has also been found in the study that it is not needed to use a full simulations of the original model for the generation of the ensemble. The POD based calibration method has also been implemented for the estimation of the water depth and space varying bottom friction coefficient values in a very large-scale DCSM model. The recently designed large-scale spherical grid based water level model for the northwest European continental shelf (around 1000000 computational grid points) has been used for this purpose. This has been the first application of the POD based calibration method to a very large-scale model and with real data. Results from numerical experiments showed that the calibration method performs very efficiently. An overall improvement of more than 50\% was observed after the calibration in comparison with the initial model. The results also demonstrated that the POD based calibration method offered a very efficient minimization technique compared to the classical adjoint method without the burden of implementation of the adjoint. As a concluding step, to estimate depth values in the model DCSM, a Simultaneous perturbation stochastic approximation (SPSA) method has been used. The method uses stochastic simultaneous perturbation of all model parameters to generate a search at each iteration. SPSA is based on a highly efficient and easily implemented simultaneous perturbation approximation to the gradient. This gradient approximation for the central difference method uses only two objective function evaluations independent of the number of parameters being optimized. The results from experiments showed that SPSA has a lower convergence rate than POD based calibration method, however the computational cost in each iteration of the SPSA method is usually far less then the POD based calibration method. The results also demonstrated that the SPSA algorithm proved to be a promising optimization algorithm for model calibration for cases where adjoint code is not available for computing the gradient of the objective function.Applied mathematicsElectrical Engineering, Mathematics and Computer Scienc
Investigation of the Genetic Link Between the Metabolic Diseases Gout and Type 2 Diabetes
No full textGout is associated with various co-morbidities including insulin resistance and type 2 diabetes. Gout and type 2 diabetes are strongly linked to the individual components of metabolic syndrome. There may be shared pathogenic pathways between gout and type 2 diabetes in which insulin resistance, obesity, hypertension and hyperuricaemia play a central role.
Genetic and environmental factors play a crucial role in the development of these diseases. Genetic factors that are associated with type 2 diabetes and metabolic syndrome may be shared with gout. It was hypothesised in this study that genetic variants that influence type 2 diabetes and metabolic syndrome also influence gout. The aim of the study was to find a genetic link between the two diseases by finding novel associations with gout and testing whether or not the effect is independent of diabetes and metabolic syndrome.
The case-control study approach was used in this study. In this study 19 variants from 11 genes were examined in a multi-ethnic sample of 1003 gout cases and 1244 controls from the NZ gout population. Two reference datasets were added to provide a comparative group: Framingham Heart Study (FHS) and Atherosclerosis Risk in Communities Study (ARIC). A combined meta-analysis was performed to increase the overall power of the association. Haplotype analysis was also performed and gene-gene interactions were also investigated.
The results chapter is divided into three sections. The first section focuses on variants associated with type 2 diabetes. The KCNJ11 gene variant rs2285676 G allele was associated with a reduced risk of gout in the New Zealand European Caucasian (P=0.04, OR=0.73[0.54-0.99]) and Western Polynesian (P=0.03, OR=0.65[0.44-0.96]) sample sets. The miRNA16A gene variant rs2910164 C allele was found to be associated with reduced risk of gout in the New Zealand European Caucasian (P=0.02, OR=0.60[0.39-0.92]) and Eastern Polynesian (P=0.02, OR=0.38[0.16-0.89]) sample sets. All variants either showed weak or non-significant associations with gout. In order to establish a positive link between gout and type 2 diabetes, replication is needed in larger cohorts.
The second section is focused on variants associated with obesity. The MC3R gene variant, rs3827103 A allele was significantly associated with a reduced risk of gout in the New Zealand European Caucasian (P=0.0004, OR= 0.30 [0.18-0.50]) and in the mixed Eastern and Western Polynesian (P=0.04, OR=0.01[0.001-0.89]) sample sets. The MC4R gene variant rs17782313 C allele in the Western Polynesian sample set was found to be associated with a reduced risk of gout (P=0.01, OR=0.53[0.32-0.89]). When combined in meta-analysis, the Polynesian sample set was also found to be associated with a reduced risk of gout (P=0.03, OR= 0.73[0.55-0.98]). Another MC4R gene variant, rs17700633 (A allele), showed a significant association (P=0.04, OR=0.60[0.37-0.98]) with a reduced risk of gout in the Western Polynesian sample set. The haplotype analysis of MC4R gene variants rs17782313 and rs921971 showed that minor alleles were associated with an increased risk of gout and the major alleles were associated with a decreased risk of gout. The FTO gene variant rs9922047 C allele was associated (P=0.002, OR=2.23[145-3.43]) with an increased risk of gout in the Western Polynesian sample. When combined in meta-analysis, the Polynesian sample set also showed an increased risk for gout (P=0.003, OR=1.33[1.10-1.59]). One particular haplotype, GAG, of the FTO gene variants rs9922047, rs17817288 and rs9923233 was consistently protective against gout, independent of BMI. The results of this study indicate that obesity-associated variants also influence gout in a manner that is independent of obesity. These genes are expressed in the hypothalamus of the brain and are thought to possibly influence gout by modulating eating behaviour. A high intake of a diet rich in purine and fructose increases serum urate levels, which can ultimately lead to gout.
The third section is about PDZK1 gene variants that influence serum urate levels and metabolic syndrome. The T allele of rs1284300 was found to be associated with a reduced risk of gout (P=0.04, OR=0.44[0.20-0.99]) in the New Zealand European Caucasian sample set. Combined meta-analysis of the Caucasian sample set was found to be associated with a reduced risk of gout (P=0.009, OR=0.71[0.56-0.92]). The rs11576685 variant showed a reduced risk for gout in the combined meta-analysis of the Polynesian sample set (P=0.007, OR=0.26[0.10-0.68]). The results of the association analysis suggest that PDZK1 gene variants influence gout. PDZK1 was also tested for gene-gene interactions with urate transporters such as URAT1, ABCG2, OAT4 and NPT1, but this study did not find any significant interactions.
This is the first study that has directly investigated the association of type 2 diabetes, obesity and metabolic syndrome variants with gout. This study has found some novel associations with gout, particularly with regard to the MC3R, MC4R and FTO genes, which suggests that metabolic syndrome variants also influence gout independent of type 2 diabetes, obesity and metabolic syndrome. However, to confirm these findings, these variants need to be genotyped in large association studies, as this will be important in exploring the role of common risk variants between gout and type 2 diabetes
Distinct gene mutations, their prognostic relevance and molecularly targeted therapies in Acute Myeloid Leukemia (AML)
No full textAcquired genetic alterations which include balanced and unbalanced chromosome aberrations and submicroscopic gene mutations and changes in gene expression strongly influenced by pretreatment clinical features and prognosis of adults patients with acute myeloid leukemia (AML). Cytogenetic profiling separate AML patients into three broad prognostic groups: favorable, intermediate and adverse. The cytogenetic risk classifications vary to some extent for younger adult patients and for those aged 60 years or older. In many cases, patients with specific cytogenetic rearrangement such as those with a normal karyotype or those with either RUNX1-RUNX1T1 or CBFB-MYH11 feature of core-binding factor (CBF) can be further subdivided into prognostic categories depend on the presence or absence of specific gene mutations or changes in gene expression. Advancement in the understanding of cancer genetic and discovery of recurrent mutations in AML provide opportunity to develop targeted therapies and improve the clinical outcome. The identified gene mutations, mainly targetable lesions are gain of function mutations of JAK2 and cKIT and FLT3 in APL have been associated with clinical features and/ or outcome of patients with these AML subtypes. These data emphasize the significance of genetic testing for common translocations for diagnosis, prognosis and increasingly targeted therapy in acute leukemia. Notably, these several molecular genetic alterations constitute a variety of diverse new targets for salvage therapies. These approaches intend to develop targeted treatment concepts that depend on interference with molecular genetics or epigenetic mechanisms. This report provides an overview on characteristic gene mutations, discuss their biological functions and Prognostic significance, which serve as basis for selected therapy approaches now or might represent options for such approaches in the future and expected to have a role in treating AML subtypes with characteristic molecular alterationsMuhammad Tayyab, Mahwish Khan, Zafar Iqbal, Sara Altaf, Zain Noor, Nida Noor, and Tanveer Akhta
Harpactus Shuckard 1837
No full textGenus Harpactus Shuckard, 1837 Arpactus Jurine, 1807: 192, junior homonym of Arpactus Panzer, 1805, and of Arpactus Panzer, 1806 (both junior synonyms of Gorytes Latreille, 1804). Type species: Arpactus formosus Jurine, 1807, designated by Shuckard 1837: 220. Harpactus Shuckard 1837: 221. Emendation of Arpactus Jurine, 107 on linguistic grounds, thus an available new name, with its own date and author (Articles 19 and 33.2). Since Harpactus is an emendation, it has the same type-species as Arpactus Jurine (Article 67.8). Harpactes Dahlbom 1843: 147, junior homonym of Harpactes Swainson, 1837 (Aves), and of Harpactes Templeton, 1834 (Arachnida). Emendation of Harpactus Shuckard. Dienoplus W.J. Fox 1894: 548. Type species: Dienoplus pictifrons Fox, 1894, by monotypy. Key to Harpactus species of India and adjacent territories 1. Head and mesosoma without distinct punctures............................................................. 2 - Head, mesosoma, [and T2] distinctly foveolate-punctate, with scattered foveae. [Kashmir].......... H. pulawskii sp. nov. 2. Propodeum with oblique and irregular striae................................................................ 3 - Propodeum with distinct coarse, longitudinal striae [Pakistan].................................. H. vividus (Turner) 3. Fore wing with fuscous patch in radial and cubital cells; propodeal enclosure red. [Northern India; Myanmar]................................................................................................. H. ornatus (Smith) - Fore wing usually without fuscous patch in radial and cubital cells; propodeal enclosure black. [Oriental India].............................................................................................. H. impudens (Nurse)Published as part of Binoy, C., Kumar, P. Girish, Monks, Joseph & Sheikh, Altaf Hussain, 2022, A review of digger wasp genus Harpactus Shuckard, 1837 (Hymenoptera Crabronidae) of the Indian subcontinent, with description of a new species and rediscovery of Harpactus impudens (Nurse, 1903), pp. 531-542 in Zootaxa 5190 (4) on page 532, DOI: 10.11646/zootaxa.5190.4.3, http://zenodo.org/record/713847
High-prevalence and high-estimated incidence of HIV infection among new injecting drug users in Estonia: need for large scale prevention programs.
No full textOBJECTIVE: To examine HIV risk behavior and HIV infection among new injectors in Tallinn, Estonia. Design and methods Data from two cross-sectional surveys of injecting drug users (IDUs) recruited from a syringe exchange program (N = 162, Study 1) or using respondent driven sampling (N = 350, Study 2). Behavioral surveys were administered; serum samples were collected for HIV testing. Subjects were categorized into new injectors (injecting 3 years). RESULTS: Twenty-eight of 161 (17%, Study 1) and 73/350 (21%, Study 2) of the study subjects were new injectors. HIV infection was substantial among the newer injectors: HIV prevalence was 50% (Study 1) and 34% (Study 2), and estimated HIV incidence 31/100 PY and 21/100 PY, respectively. In Study 2, new injectors were more likely to be female and ethnic Estonian and less likely to be injecting daily compared with long-term injectors. No significant difference was found among two groups on sharing injecting equipment or reported number of sexual partners. CONCLUSIONS: A continuing HIV epidemic among new injectors is of critical public health concern. Interventions to prevent initiation into injecting drug use and scaling up HIV prevention programs for IDUs in Estonia are of utmost importance
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