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1.
Heliyon ; 10(5): e25408, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38439843

RESUMEN

In this paper, an innovative transactive energy approach is proposed as viable option for coordinated distribution system planning across a certain horizon. The proposed approach is evaluated across a multi-looped (meshed) test system and is implemented with load growth having prosumers participating in the electrical market in transactive energy system aiming at evaluation on techno-economic basis. Apart from prosumer sensitivity analysis, evaluations have been carried across reducing total production cost of energy, reduction in per unit price, active power losses. Whereas improving voltage profile, cost of scheduling and consumer per kWh purchase and sales in comparison with traditional counterpart. The proposed framework includes optimization algorithm aiming at sources scheduling and IEEE 69 system for validation. The algorithm minimizes cost, maximizes energy efficiency, increases renewable energy mix and reduces consumers cost of energy purchase. Reduction of 51.44 % in cost of energy is achieved, whereas loss reduction of 12.6% is achieved. The comparison of IEEE 69-bus base case with the 10 %, 15% and 20% transactive energy applied with simulations to evaluate performance parameters that will directly benefit both prosumers and utility alike in-terms of low bills and further reduction of stress on the grid amid load growth across multiple years.

2.
Heliyon ; 8(10): e10123, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35974961

RESUMEN

COVID-19 is a severe global pandemic that has caught the whole world unprepared. In the absence of a clear timeline for this pandemic to end, it is need of the hour to investigate the effect of this pandemic on both previous and anticipated investments. Global economic unrest has hindered the ramping deployment of Renewable energy projects. The most quick actions that may be taken to mitigate the effects and to up-rise the investment portfolio policies are a very critical tool in hands of government for a very immediate effect have also been made without keeping the context of COVID-19 into account. New variants of diff rent nature are being discovered and every now and then new lock downs are happening. In this context different policies have to be evaluated under the pandemic scenario. A case study of a large scale renewable energy project for a higher education institute in Pakistan is being used to measure the difference during COVID and pre COVID times. This paper provides a framework to investigate the impact of COVID on renewable energy system projects under current net-metering, net-billing and self-consumption policies. A recent investment in a photovoltaic system is assessed based on previously projected financial benefits versus the pandemic effected ones. This research concludes that investing in photovoltaic systems are still a viable option even in an extreme pandemic situation with less than 0.5 years increase in payback period, and the government can still provide a stimulus for investing in green energy by implementing net-metering policies on a larger scale.

3.
Int J Radiat Oncol Biol Phys ; 114(4): 792-802, 2022 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-35896145

RESUMEN

PURPOSE: The oligometastatic state is observed in patients across many malignancies, with increased recognition regarding improved outcomes after local therapies. However, there is limited data specifically regarding pancreatic ductal adenocarcinoma. We hypothesized that an oligometastatic pancreatic ductal adenocarcinoma (OPanc) phenotype would benefit from stereotactic ablative radiation therapy (SABR) to all active metastatic sites. Here, we report our institutional experience of SABR-treated OPanc to evaluate the feasibility of the approach. METHODS AND MATERIALS: A retrospective review of patients with synchronous or metachronous OPanc (1 to 5 metastases) who received SABR to all active metastatic sites was performed. We identified a comparable group of patients with similar metastatic burden, range of CA19-9 levels, and no progression for at least 5 months who did not receive SABR. We compared overall survival as the primary outcome, and polyprogression-free survival and time off chemotherapy as the secondary exploratory assessments. A third group presenting with stage IV pancreatic ductal adenocarcinoma and more than 5 distant lesions (polymetastatic) was identified to help define expected outcomes after polyprogression. RESULTS: Our study included 20 patients with OPanc receiving SABR and 21 who did not. SABR was delivered to 38 metastatic tumors. Out of the 20 SABR-treated OPanc patients, 17 (85%) had 6 or more months of time off chemotherapy, compared with 7 patients (33.3%) among the chemotherapy-treated group. Median polyprogression-free survival was 40 and 14 months (hazard ratio = 0.2; 95% confidence interval, 0.07-0.54; P = .0009), and overall survival was 42 and 18 months (hazard ratio = 0.21; 95% confidence interval, 0.08-0.53; P = .0003), for SABR- and chemotherapy-treated cohorts, respectively. CONCLUSIONS: Management of OPanc with SABR as local regional therapy could improve outcomes in a selected population and warrants prospective evaluation.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Radiocirugia , Antígeno CA-19-9 , Humanos , Neoplasias Pancreáticas/radioterapia , Radiocirugia/métodos , Neoplasias Pancreáticas
4.
J Natl Cancer Inst ; 114(5): 775-778, 2022 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-35134211

RESUMEN

The incidence and mortality of early onset colorectal cancer (EOCRC) is rising; outcomes appear to differ by race and ethnicity. We aimed to assess differences in mutational landscape and gene expression of EOCRC by racial and ethnic groups (non-Hispanic Asian, non-Hispanic Black, non-Hispanic White, White Hispanic) using data from the American Association for Cancer Research Project GENIE (10.2) and University of Texas Southwestern, the latter enriched in Hispanic patients. All statistical tests were 2-sided. Of 1752 EOCRC patients, non-Hispanic Black patients had higher rates of KRAS mutations (60.9%; P = .001, q = 0.015), and non-Hispanic White and non-Hispanic Black patients had higher rates of APC mutations (77.1% and 76.6% among non-Hispanic White and non-Hispanic Black patients, respectively; P = .001, q = 0.015) via the Fisher exact test with Benjamini-Hochberg correction. Using R packages DESeq2 and clusterProfiler, we found that White Hispanic patients had increased expression of genes involved in oxidative phosphorylation (P < .001, q = 0.025). Genomic profiling has the potential to identify novel diagnostics and influence individualized treatment options to address the currently limited prognosis of EOCRC.


Asunto(s)
Neoplasias Colorrectales , Etnicidad , Población Negra , Neoplasias Colorrectales/genética , Etnicidad/genética , Genómica , Hispánicos o Latinos/genética , Humanos , Estados Unidos/epidemiología
5.
J Pak Med Assoc ; 68(8): 1281-1284, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30108407

RESUMEN

A cross sectional study was conducted in a private medical university among undergraduate MBBS and BDS students, to ascertain their opinion regarding various teaching methods. Convenience sampling technique was utilized with data collection spanning over March to August 2015 on a sample of 398 students. A self-administered questionnaire was used for the purpose. Descriptive analysis was applied for numerical data while chi square was used for categorical data. P value under 0.05 was considered significant. Our results showed that around 120 (30%) of the participants supported PBL as the most effective teaching method while 64(16%) considered clinical rotations, and 60(15%) voted for lectures. According to undergraduate students Problem-based Learning is the most significant tool for learning. Integrated method of teaching was endorsed by both MBBS and BDS students.


Asunto(s)
Educación Médica/métodos , Estudiantes de Medicina/psicología , Enseñanza , Estudios Transversales , Humanos , Pakistán , Facultades de Medicina/estadística & datos numéricos , Estudiantes de Medicina/estadística & datos numéricos , Encuestas y Cuestionarios
6.
Dis Model Mech ; 10(2): 105-118, 2017 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-28067622

RESUMEN

A consanguineous family from Pakistan was ascertained to have a novel deafness-dystonia syndrome with motor regression, ichthyosis-like features and signs of sensory neuropathy. By applying a combined strategy of linkage analysis and whole-exome sequencing in the presented family, a homozygous nonsense mutation, c.4G>T (p.Glu2*), in FITM2 was identified. FITM2 and its paralog FITM1 constitute an evolutionary conserved protein family involved in partitioning of triglycerides into cellular lipid droplets. Despite the role of FITM2 in neutral lipid storage and metabolism, no indications for lipodystrophy were observed in the affected individuals. In order to obtain independent evidence for the involvement of FITM2 in the human pathology, downregulation of the single Fitm ortholog, CG10671, in Drosophila melanogaster was pursued using RNA interference. Characteristics of the syndrome, including progressive locomotor impairment, hearing loss and disturbed sensory functions, were recapitulated in Drosophila, which supports the causative nature of the FITM2 mutation. Mutation-based genetic counseling can now be provided to the family and insight is obtained into the potential impact of genetic variation in FITM2.


Asunto(s)
Trastornos Sordoceguera/genética , Proteínas de Drosophila/genética , Distonía/genética , Ictiosis/genética , Discapacidad Intelectual/genética , Proteínas de la Membrana/genética , Actividad Motora , Mutación/genética , Atrofia Óptica/genética , Células Receptoras Sensoriales/patología , Adiposidad , Animales , Audiometría de Tonos Puros , Secuencia de Bases , Niño , Codón sin Sentido/genética , Trastornos Sordoceguera/sangre , Trastornos Sordoceguera/fisiopatología , Modelos Animales de Enfermedad , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Distonía/sangre , Distonía/fisiopatología , Femenino , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células HEK293 , Pérdida Auditiva/genética , Homocigoto , Humanos , Ictiosis/complicaciones , Ictiosis/fisiopatología , Discapacidad Intelectual/sangre , Discapacidad Intelectual/fisiopatología , Gotas Lipídicas/metabolismo , Hígado/metabolismo , Locomoción , Masculino , Proteínas de la Membrana/metabolismo , Atrofia Óptica/sangre , Atrofia Óptica/fisiopatología , Linaje , Secuenciación del Exoma , Adulto Joven
7.
Clin Appl Thromb Hemost ; 23(7): 800-806, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27313202

RESUMEN

Polymorphisms in cytochrome P450 (CYP) 2C9 (CYP2C9) gene result in interindividual variability in warfarin dose requirement. There is a need for characterization of genotype frequency distribution in different populations for construction of customized dosing algorithms to enhance the efficacy and reduce the toxicity of warfarin therapy. This study was carried out in Pakistani population to evaluate the contribution of common CYP2C9 polymorphisms to warfarin therapy. A total of 550 stable patients taking warfarin were enrolled after medical history, physical examination, and laboratory investigations. Single blood sample was collected after informed consent. Genomic DNA was extracted, and genotype analysis for CYP2C9*2 and CYP2C9*3 polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism assay. A number of samples were also analyzed by direct DNA sequencing for validation of the results. Data were analyzed using SPSS version 20. Genotype frequency distribution of CYP2C9*2 and CYP2C9*3 was found to be different from other populations. Of these 2 polymorphisms, CYP2C9*2 did not demonstrate significant effect on warfarin dose requirement, whereas CYP2C9*3 did show significant effect ( P value = .012). It is concluded that there is a need to study genotype frequency distribution and their effect on warfarin dose variability among different populations due to diversity in outcome.


Asunto(s)
Citocromo P-450 CYP2C9/genética , Frecuencia de los Genes , Polimorfismo Genético , Warfarina/administración & dosificación , Adolescente , Adulto , Anciano , Cálculo de Dosificación de Drogas , Humanos , Persona de Mediana Edad , Pakistán/epidemiología , Farmacogenética/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Adulto Joven
8.
Virol J ; 10: 352, 2013 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-24321105

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma and infects about 3% world population. Response to interferon therapy depends upon the genotype of the virus and factors associated with the host. Despite a good response to interferon therapy, a considerable number of genotype 3a infected patients remains unalleviated. RESULTS: In total forty-nine patients including twenty-five non-responders (non-SVR) and twenty-four responders (SVR) were recruited. Patients were tested for viral status at different intervals and the isolated RNA was sequenced for the NS5A region in both groups. The comparison of PKRBD of HCV between the SVR and non-SVR patients did not confirm any significant difference in the number of mutations. However, when the sequence downstream to the PKRBD of NS5A was compared, two important statistically significant mutations were observed; at positions 2309 (Ala to Ser) and 2326 (Gly to Ala). These mutations were then analysed for tertiary protein structure and important structural changes were observed. Statistically significant difference was also observed when age groups of patients were compared; younger patients showed better response than the older ones. CONCLUSIONS: The region between PKRBD and IRRDR may be important for prediction of response to IFN therapy for genotype 3a. ISDR and PKRBD have not shown any involvement in treatment response. Further functional analyses of these findings can help in understanding the involvement of the NS5A region in interferon treatment of HCV-3a infected patients.


Asunto(s)
Antivirales/uso terapéutico , Variación Genética , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Interferones/uso terapéutico , Dominios y Motivos de Interacción de Proteínas , Proteínas no Estructurales Virales/genética , Adulto , Animales , Genotipo , Hepacivirus/aislamiento & purificación , Humanos , Persona de Mediana Edad , Pakistán , Análisis de Secuencia de ADN , Resultado del Tratamiento , Adulto Joven
9.
J Hum Genet ; 58(12): 819-21, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24172246

RESUMEN

Bjørnstad syndrome is an extremely rare condition characterized by pilitorti and nerve deafness. Only few large families have been reported worldwide. Here we describe a large Pakistani family with five affected individuals. The hair fibers of all the patients were twisted around their axis and devoid of any pigment. In addition the patients had a moderate-to-severe degree of hearing impairment. Genotyping with high-density single-nucleotide polymorphism arrays showed homozygosity in two intervals on chromosome 2. Linkage with one of these regions (genomic position 218745685-221025443, hg19) was confirmed. This region encompasses the BCS1L gene. Mutations in this gene have previously been associated with Bjørnstad's syndrome. We sequenced the BCS1L gene for identification of the causative mutation in the family. A novel homozygous missense mutation c.901T>A was identified, which segregated with the disease in the family. This mutation results in the amino acid change p.Tyr301Asn and was predicted to be pathogenic by bioinformatics tools.


Asunto(s)
Complejo III de Transporte de Electrones/genética , Enfermedades del Cabello/genética , Pérdida Auditiva Sensorineural/genética , Enfermedades Mitocondriales/congénito , Mutación/genética , Polimorfismo de Nucleótido Simple/genética , ATPasas Asociadas con Actividades Celulares Diversas , Niño , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Mitocondriales/genética , Pakistán
10.
ScientificWorldJournal ; 2013: 203492, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24381514

RESUMEN

BACKGROUND: Tumor necrosis factor-alpha (TNF- α ) gene polymorphisms have been implicated in the manifestation of atherosclerosis. Controversy exists regarding the link between the cytokine's variant genotype and CHD among different ethnic groups. There have been fewer studies on the TNF- α gene -1031T>C and -863C>A polymorphisms in relation to CHD. Therefore, the current study was designed to investigate the association of the TNF- α gene -1031T>C and -863C>A polymorphisms with CHD in a Pakistani population. METHODS: Patients with CHD (n = 310) and healthy individuals (n = 310) were enrolled in this study. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A significant difference was observed in the -863C>A polymorphism between patients with CHD and control subjects (P < 0.0001). CHD risk was positively associated with the variant allele -863A (P < 0.0001) in the study subjects. There was no significant link between the -1031T>C polymorphism and CHD risk in the study population. Haplotypes A-T and A-C of the TNF-alpha gene loci at -863 and -1031 showed higher frequency in the patient group compared with controls (P < 0.05). CONCLUSION: The TNF- α -863C>A gene polymorphism was associated with the pathogenesis of CHD while the -1031T>C polymorphism did not show any link with the disease in a Pakistani population.


Asunto(s)
Enfermedad Coronaria/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Factor de Necrosis Tumoral alfa/genética , Adulto , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Pakistán , Polimorfismo de Longitud del Fragmento de Restricción
11.
Diagn Mol Pathol ; 16(2): 108-11, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17525681

RESUMEN

Ewing sarcoma, along with peripheral primitive neuroectodermal tumor, belongs to a tumor family that shares clinicopathologic and molecular genetic features, including the characteristic chromosomal translocation that results in the fusion of the EWS gene on 22q12 to either the FLI1 gene on 11q24 or other Ets family transcription factor gene, such as the ERG gene on 21q22. In contrast, such translocations are not found in central primitive neuroectodermal tumors (cPNETs), such as medulloblastoma and supratentorial PNET. Ewing sarcoma has only rarely been noted to primarily involve the central nervous system-extraosseous Ewing sarcoma (CNS-EES). We report a case of a 7-year-old girl with an anterior cranial fossa mass. Pathology showed a primitive small blue cell tumor with focal Homer Wright rosette formation. The positive membranous immunostaining for CD99 and the EWS-FLI1 fusion demonstrated by fluorescence in situ hybridization studies confirmed the diagnosis of CNS-EES. Although CNS-EES may look identical to cPNETs, these tumors differ in histogenesis, molecular characteristics, and clinical behavior. Demonstration of characteristic translocations by molecular studies differentiates CNS-EES from cPNET and help clinicians make informed decisions regarding therapy.


Asunto(s)
Neoplasias Encefálicas/patología , Tumores Neuroectodérmicos Periféricos Primitivos/patología , Sarcoma de Ewing/patología , Antígeno 12E7 , Antígenos CD/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Moléculas de Adhesión Celular/metabolismo , Niño , Terapia Combinada , Diagnóstico Diferencial , Femenino , Reordenamiento Génico , Humanos , Hibridación Fluorescente in Situ , Proteína Proto-Oncogénica c-fli-1/genética , Proteína Proto-Oncogénica c-fli-1/metabolismo , Proteína EWS de Unión a ARN/genética , Proteína EWS de Unión a ARN/metabolismo , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/terapia , Translocación Genética
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