Open Access Pub publishes peer-reviewed, free-to-read open-access articles. Showing
articles matching selection — open any to read the full text,
or download the PDF or XML.
Feb 2023 DOI 10.14302/issn.2639-3166.jar-22-4403
The major a biotic stresses affecting chickpea production are high and low temperature, drought and salinity. Heat stress is a major a biotic stress factor, constraining chickpea production worldwide. This study was conducted to identifying chickpea genotypes combining heat tolerance and high yield potential and to study correlation among the heat tolerance indices. The genotypes were tested under different field-growing conditions, normal sown (non – heat stress) and late sown (heat stress) at two locations, Merowe and Gezira during winter season 2018/2019. The trials were laid out in alpha lattice design with three replications. Eight heat tolerance indices, which were most frequently used in plant breeding including, geometric mean productivity (GMP), yield index (YI), mean productivity (MP), stress susceptibility index (SSI), stress tolerance index (STI), tolerance index (TOL), sensitivity heat index (SHI) and relative heat index (RHI) were calculated based on seed yield under heat stress (Ys) and non – heat stress (Yp) conditions. Under both environments, the results from combined analysis of variance showed that there were highly significant differences among the genotypes for all traits studies. There were highly significant differences observed among the tested chickpea genotypes response to heat stress. Seed yield in stress (Ys) condition was positive and highly significant correlated with geometric mean productivity, yield index, stress tolerance index and relative heat index. The Ys was negative and highly significant correlated with stress susceptibility index and sensitivity heat index. Seed yield in non-stress (Yp) condition was positive and significant correlated with geometric mean productivity, yield index, stress tolerance index and tolerance index. The results of this research showed that the six indices, GMP, YI, SSI, STI, SHI and RHI can be used as optimal indicators for screening heat tolerant chickpea genotypes. Nine genotypes including four released improved varieties (Shiekh Mohamed, Wad Hamid, Salwa and Hwata) and five genotypes (no. 11, 4, 26, 30 and 34) are most stable chickpea genotypes for heat tolerance and can be further used in breeding program. These genotypes can be used in the chickpea national breeding program to develop varieties with improved heat tolerance in Sudan. Genotype no. 11 (FLIP 08-59 C) was release by Sudan national variety release committee for commercial production under the name Elbarkal in September 2022 to will be grown in Gezira, River Nile and Northern States of Sudan.
Jan 2022 DOI 10.14302/issn.2379-8572.joa-21-3964
Back ground and Objectives The inferior conchae have important role in the maintenance of nasal airflow via providing the nasal valve mechanism but increase of inferior turbinate bulk may result in significant nasal obstruction. Therefore, this may need further surgical intervention to deal with these bulky conchae but it is very necessary to balance between the mechanical as well as the functional patency of the nose. Thus, through this surgery it become difficult to decide whether the patient is a candidate for surgery and which technique is suitable for that particular patient. Patients and Methods Two- thousands three- hundreds and six patients aged 3-65 years of hypertrophied inferior conchae, had been diagnosed as a cases of mechanical nasal obstruction due to hypertrophied inferior conchae (HIC). The patients operated by two techniques of inferior conchae surgery, which are sub-mucosal diathermy (SMD) and partial inferior turbinectomy (PIT). The outcomes were correlated to different factors to assess as much as possible the clear conclusion for this significant issue in rhinology. Results and Conclusion The proper selection of patient for this pattern of surgery is considered as one of main aspects of this issue and one of significant steps toward the resolving of this dilemma it is very necessary to select the most suitable candidate for this surgery. On the other hand, the type of the technique for this surgery is needed to be selected probably.
Dec 2019 DOI 10.14302/issn.2694-1198.jge-19-3079
The problem of natural selection against recessive homozygotes in a population is investigated. It is shown that natural selection of mutant alleles linked with the Х-chromosome in a population at women is described by the nonlinear differential equation of the third order. The order of the differential equation characterizes a power of selection. It is marked that the high order of the differential equation of natural selection allows level all mutational processes in Earth populations.
Jul 2018 DOI 10.14302/issn.2639-3166.jar-18-2083
This study was conducted to determine drought tolerant indices of some sugar beet genotypes under water stress and non-stress conditions. Nine sugar beet (Beta Vulgaris L.) genotypes were tested in a Split-plot experiment based on a randomized complete block design in three replications under three levels of water stress 100%, 75% and 50% from plant requirements at the experimental farm Faculty of Agriculture, Suez Canal University, Ismailia, Egypt during 2015/ 2016 and 2016 / 2017 seasons. Twelve drought tolerance indices were used in this study, stress sensitivity index (SSI), stress tolerance (TOL), mean productivity (MP), geometric mean (GMP), harmonic mean (HM),yield stability index (YSI), yield index (YI), stress tolerance index (STI), sensitivity drought index (SDI), relative drought index (RDI), drought response index (DI) and stress susceptibility percentage index (SSPI). GMP, MP and STI were more informative towards classification of better or superior genotypes with respect to tolerant and sensitive groups. The results showed that the genotypes with high STI, GMP and MP values were suitable for cultivation under drought stress and non-stress environments. Both Yp and Ys of root yield in the control-50% analysis had significantly positive correlated (P value<0.05) with MP, GMP, YI, HM and DI, This indicates that these indices were more effective in identifying high yielding genotypes under drought stress as well as non-stress conditions.Principal components analysis showed that the first two components in the control-50% analysis, genotype Bts 1237 and Temar were identified as the most stable high yielding genotypes in both environments
Jun 2018 DOI 10.14302/issn.2689-4602.jes-18-2128
Natural selection is a buzzword used to describe the main driving force of evolution. Its creative role is believed to be based on: a) an unlimited variety of organisms caused by hereditary variation and b) a direct connection between hereditary changes and their phenotypic expression. These are the two requirements that can lead to the genetically based changing modalities of characters through “iterations” of natural selection in the series of successive generations. Are these two requirements fulfilled in the nature, however? The present study focuses on the analysis of these two “foundation stones” of natural selection. Firstly, hereditary variation is shown to be essentially non-homogenous. New hereditary characteristics of individuals fall onto a narrow “strip of land” in the sea of potential possibilities. Secondly, the consequences of changes in the genotype of an organism are involved into a system of hierarchical multiple compensation, from the molecular to the biocenotic level. In a way, the signal of hereditary change passes through a series of “system filters” at epigenetic, ontogenetic, physiological, behavioural, populational and biocenotic level. Each filter is represented by multiple feedbacks maintaining the integrity of systems at each level and at all the hierarchical levels taken together. It is in these “system filters” the adaptive nature of characters is formed representing the every individual as a subject to the Law of Multilevel Self-Organization. The emerging understanding of this provides a strong reason to change the evolutionary paradigm from the mainly selectogenetic to the mainly orthogenetic one.
Jul 2016 DOI 10.14302/issn.2576-2818.jfb-16-1035
Female fertility is an economically important trait in the dairy industry, and the fertility selection index has been developed as a method of including female fertility in the breeding goals of this industry. This index considers a combination of factors, including days open, number of inseminations per lactation, success after first insemination, and pregnancy within 70 d, 90 d, and 110 d after parity. Based on a genome-wide association study of the fertility selection index using 442 Holsteins, we found that the index is influenced by a variation in the thioredoxin fold region of the family with the sequence similarity 213, member A (FAM213A) protein. FAM213A is a CXXC motif-containing peroxiredoxin 2-like protein that regulates cellular redox status. A replacement of isoleucine with valine in FAM213A was associated with poor fertility in cows. The overexpression of FAM213AVal in bovine endometrial epithelial cells reduced reactive oxygen species to a lesser extent relative to the overexpression of FAM213AIle and caused a decrease in cyclooxygenase-2 expression. Downregulation of cyclooxygenase-2 led to a decline in prostaglandin E2, which is critical for implantation because it protects the conceptus from the maternal immune system. Cows with FAM213AVal showed lower levels of prostaglandin E2 than did cows with FAM213AIle, suggesting that cows with FAM213AVal are less fertile than cows with FAM213AIle because of their reduced uterine environment. Thus, the present study found that FAM213A unexpectedly modulates female fertility in cattle.
May 2026 DOI 10.14302/issn.2641-4538.jphi-26-6161
Objectives Motor fluctuations and non-motor disorders not manageable by first-line treatments in advanced Parkinson's disease require continuous dopaminergic stimulation strategies such as subcutaneous infusions of apomorphine (APO) or foslevodopa/foscarbidopa (FLD/FCD). A Budget Impact Analysis (BIA) was performed to estimate the cost difference between both treatments assuming equivalent clinical efficacy and safety. Material and methods The efficacy results of pivotal clinical trials at 12 and 52 weeks of treatment and the safety profile of APO vs FLD/FCD were compared, based on latest scientific publications and other available clinical data. A comparative BIA was performed, based on estimated annual drug treatment costs at Spanish published prices. Results The efficacy of APO (16 h/day) and FLD/FCD (24 h/day) in reduction of OFF hours (2.47 vs 2.75, 12 weeks; 3.66 vs 3.50, 52 weeks; respectively) and increase of ON hours without disabling dyskinesias (2.77 vs 2.72, 12 weeks; 3.31 vs 3.80, 52 weeks; respectively) could be considered clinically equivalent, as well as their safety profiles. However, a significant discrepancy is observed in the costs of the aforementioned alternatives. Considering published prices and the average dose reported in the literature, in Spain the annual cost of APO would be €13,980 compared to €55,198 for FLD/FCD. Consequently, the financial resources required for the treatment of FLD/FCD would enable the treatment of approximately three to four patients with APO. The BIA indicated the potential for annual savings in more than €2,500 million, considering a total target population of over 60,000 patients per year. Finally, an univariant sensitivity analysis was performed, considering a scenario in which the hospital acquisition cost of FLD/FCD decreased between 20%-30% (€44,159- €38,638/year). In this scenario, the total annual savings range between €1,875-€1,532 million per year. Conclusions Overall APO is more efficient than FLD/FCD, as it provides similar clinical efficacy at a lower treatment cost. The selection of an appropriate treatment option is to be determined by clinical criteria and patient characteristics, but cost evaluation should be considered to select the most cost-effective therapeutic option.
Feb 2026 DOI 10.14302/issn.2689-4602.jes-25-5926
The impact of ionizing radiation on genetic change is well established, yet the extent to which naturally occurring radiation fields have influenced evolutionary trajectories remains incompletely understood. This study examined correlations between microbial evolution and the radiation and geochemical environments associated with natural fission reactors, with emphasis on the Oklo–Bangombé system in present-day Gabon, Africa. The current paper compares plausible doserate regimes adjacent to reactor zones with published observations of radiationinduced phenotypes, geneexpression changes, and repair strategies in model organisms and complex biotas. This study further considers indirect mechanisms (e.g., water radiolysis, redox restructuring, tracemetal mobilization) by which natural reactors could have modulated ecological selection pressures over long timescales. The synthesis supports the plausibility of three interacting pathways: (i) increased mutation supply under low, chronic dose rates; (ii) selection in oxidantrich, redoxstratified niches; and (iii) metabolic subsidies (e.g., H₂) from radiolysis that support chemotrophic guilds. Although temporal–spatial associations exist between reactor activity and biological innovations preserved in Paleoproterozoic strata of Gabon, current evidence remains correlational rather than demonstrably causal. The study further outlines testable predictions and experimental designs capable of discriminating among these mechanisms.
Aug 2025 DOI 10.14302/issn.3070-1937.ijbt-25-5408
Background and Objectives Platelets are small, anucleate blood cells produced in the bone marrow, primarily involved in blood coagulation. Platelet concentrate is a vital blood product with extensive applications. However, its short lifespan and limited donor availability pose global challenges. This study aimed to follow the trend of platelets 5 during days of storage. Material and Methods We studied on 40 platelet bags and analyzed glucose levels, lactate dehydrogenase (LDH), bacterial culture, and apoptosis using flow cytometry with Annexin V-PI over three consecutive days (first, third, and fifth) post-blood collection. Data were analyzed using SPSS. Results No significant correlations were found between age, blood group, or gender and the variables studied. No bacterial growth was detected. Glucose levels decreased significantly from day 1 (382 mg/dl) to day 5 (298 mg/dl). The average platelet apoptosis increased significantly from 3.65% on day 1 to 9.06% on day 5. Significant correlations were observed between glucose levels and apoptosis on days 3 (p<0.05) and 5 (p<0.01). No correlation found between LDH and apoptosis or necrosis, although a significant relationship between necrosis and apoptosis was noted on day 5 (p=0.003). Conclusion These findings suggest that while demographic factors do not influence the studied variables, the significant decrease in glucose levels correlates with increased platelet apoptosis over time, highlighting potential metabolic interactions that warrant further investigation. Highlights 1. The study revealed subtle variations in metabolic markers related to donor demographics, particularly gender and age. Understanding these differences can inform targeted donor selection strategies to optimize platelet quality. 2. A significant negative correlation was found between glucose levels and apoptosis rates, indicating that as glucose decreases, platelet viability declines. This relationship highlights the need for careful monitoring of glucose levels during storage to maintain platelet function. 3. Fluctuations in lactate dehydrogenase (LDH) levels were correlated with increasing rates of apoptosis, suggesting that LDH could serve as a valuable biomarker for assessing platelet quality throughout the storage period. This finding could lead to improved storage protocols and enhanced transfusion safety.
Dec 2024 DOI 10.14302/issn.2474-9273.jbtm-24-5317
Adolescence in Cameroon, as in many parts of sub-Saharan Africa, is often marked by early childbearing. Studies have shown a national prevalence of adolescent deliveries to be around 14.2% - 14.4%, a higher rate than the average for sub-Saharan Africa This presents a unique challenge for young mothers, who must navigate the complex process of identity reorganization while still navigating their own adolescence with its multiple changes. This article explores the experiences of primiparous (first-time) Cameroonian adolescents as they transition from daughters to mothers. The objective of this article is to understand how identity reorganization takes place among primiparous Cameroonian adolescents who pass without transition from the status of daughter to the status of mother. Drawing on qualitative data from semi-structured interviews, with seven participants chosen on the basis of selection criteria, the article examines the psychological, social, and cultural factors that shape this identity shift. An interview guide with three main themes made it possible to collect verbatim comments from the participants. The thematic analysis highlights the challenges faced by these young mothers, such as navigating social stigma, managing emotional upheaval, and balancing motherhood with their own developmental needs. The findings of this study highlight the complex and multifaceted nature of identity reorganization among primiparous Cameroonian adolescents. The social stigma associated with early childbearing, coupled with the emotional and practical demands of motherhood, can pose significant challenges to these young women. However, a study on a larger sample could reveal the resilience and resourcefulness of some adolescents, who find support within their communities and employ various coping mechanisms to navigate this transition. Finally, the article discusses the implications of these findings for adolescent maternal health interventions and social policy in Cameroon.
Sep 2024 DOI 10.14302/issn.2689-4602.jes-24-5245
Charles Darwin's exploration of the Galápagos Islands in 1835 and his subsequent formulation of the theory of evolution in 1839 were significantly influenced by his observations of land-birds, including finches, larks, owls, and mockingthrushes. Despite a primary focus on geology during his voyage on the HMS Beagle, Darwin meticulously documented various species in his field notebooks. Early observations during his youth at Edinburgh University and the Beagle expedition reflected Darwin's growing curiosity about species variation. However, it was not until his return to England and his interaction with ornithologist John Gould that Darwin began to recognize the significance of the finches he had observed in the Galápagos. This review synthesizes existing literature on Darwin's transition from geological interests to his groundbreaking insights into evolution. By examining primary sources, historical interpretations, and contemporary analyses, this paper highlights how Darwin's observations and Gould's influence shaped his revolutionary theory of species transmutation—the gradual transformation of one species into another over time. The review aims to provide a comprehensive understanding of Darwin's contributions, illustrating how his Galápagos observations and collaboration with Gould laid the foundation for modern evolutionary biology and continue to influence scientific thought on species adaptation and natural selection.
Jun 2024 DOI 10.14302/issn.2641-4538.jphi-24-5106
Introduction Compared to their heterosexual counterparts, cisgender LGBTQ+ youth are more likely to experience numerous mental health conditions, for instance, suicidal ideation, stress, and anxiety. This study aimed to explore mental health disparities among LGBTQ+ youth while identifying strategies to promote their well-being. Methodology Incorporating a systematic approach, studies were selected according to the predefined inclusion criteria, ensuring recentness and relevance. Five databases were systematically searched while the PRISMA flowchart was employed for illustrating the systematic selection process. The PEO framework directed the study selection. Thematic analysis was applied to identify themes that were related to the study aim. Results Five themes were emerged including policy changes and legal frameworks, contextual and cultural factors, family and social support, underlying factors of mental health, and healthcare services access. The synthesis of the literature uncovers the multifaceted relationship between cultural and contextual factors and policy changes, social and family support and healthcare services. The study also underlines the importance of implementing an intersectional minority stress model for comprehensively understanding mental health disparities among LGBTQ+ youth. Conclusion The results emphasize the importance of ongoing research in policy alterations, accessibility to healthcare, and creating supportive surroundings to tackle differences in mental health. Recognizing the complexity of these issues, this paper requires an in-depth examination that considers intersecting factors, promotes inclusivity, and involves long-term studies in providing mental health support to enhance the well-being of LGBTQ+ young individuals.
Mar 2024 DOI 10.14302/issn.2689-4602.jes-24-4956
A new type of mutations-dominant lethals with a facultative manifestation -were discovered in D. melanogaster in 2000. These mutations were named conditional mutations. Under restrictive genetic conditions, the mutations manifest themselves as dominant lethals, whereas dominant lethality disappears under permissive conditions, displaying a set of other manifestations. The genes responsible for the emergence of conditional mutations were named ontogenes. The experiments with mutations in ontogenes have revealed the following processes: (1) genome editing in germline cells; (2) induction of high mutagenesis rates in germline cells of the mutants for ontogenes; (3) zygotic selection; (4) isolation of mutants; and (5) alterations in the lethality of mutants with time. The specific features in the manifestation of ontogenes together with the listed processes formed the background for construction of the model of speciation named the regeneration model. The event of speciation is represented as the regeneration of the working state of a genetic system disturbed by the emergence of a mutation in an ontogene. According to the model, it is ontogenes that are in charge of speciation and, eventually, the structure of living matter in the form of individual species. The significance of Mendelian protein-coding genes and Darwinian selection of the fittest according to these genes are doubtless but not paramount.
Sep 2023 DOI 10.14302/issn.2381-862X.jwrh-23-4505
Background Many women feel physical or mood changes in the days before menstruation. Previous studies in other areas of Ethiopia have not looked at factors that could be related to the premenstrual syndrome. As a result, this study aims to fill these gaps by determining the prevalence and behavioral, reproductive, and menstrual factors that affect premenstrual syndrome in Arba Minch town. Methods An institution-based cross-sectional survey was conducted in Arba Minch town from April 1 to April 25, 2021. Participants were chosen using computerized simple random selection from a list of female students' registration numbers that had been transformed into unique codes. SPSS for Windows version 25.0 was used to analyze and interpret the data. Bivariate analysis was used to fit variables with a P-value of less than 0.2 for multivariable analysis. In multivariable logistic regression, variables with a P-value less than 0.05 are considered statistically significant. Result This study has revealed that 59.8% (95% CI: 55.8%–63.8%) of students have premenstrual syndrome. Dysmenorrhea (AOR = 3.172, 95% CI: 2.032, 4.952), family history of PMS (AOR = 3.155, 95% CI: 2.119, 4.697), normal body mass index (AOR = 0.244, 95% CI: 0.161, 0.37), and overweight (AOR = 3.739, 95% CI: 1.763, 7.931) were significantly associated with premenstrual syndrome. This study has revealed that 59.8% (95% CI: 55.8%–63.8%) of students have premenstrual syndrome. Dysmenorrhea (AOR = 3.172, 95% CI: 2.032, 4.952), family history of PMS (AOR = 3.155, 95% CI: 2.119, 4.697), normal body mass index (AOR = 0.244, 95% CI: 0.161, 0.37), and overweight (AOR = 3.739, 95% CI: 1.763, 7.931) were significantly associated with premenstrual syndrome. Conclusion Six out of ten Arba Minch town secondary school students had premenstrual syndrome. Dysmenorrhea, a family history of premenstrual syndrome, and body mass index were found to be significantly associated.
Jul 2023 DOI 10.14302/issn.2639-3166.jar-23-4606
St. Augustinegrass (Stenotaphrum secundatum (Walt.) Kuntze) generally has poor cold tolerance yet good to excellent shade tolerance. As mostly hot summers follow cold winters in USDA Hardiness Zone 7, severely damaging tall fescue (Lolium arundinaceum (Schreb.) Darbysh.) and centipedegrass (Eremochloa ophiuroides (Munro) Hack.), a St. Augustinegrass cultivar cold tolerant enough to be grown for shady lawns would greatly benefit home owners, recreational sites, and sod growers in the “transition zone.” Eight St. Augustinegrass samples were selected, including industry standards ‘Raleigh’ and ‘Palmetto’, plus ‘Palisades’ zoysiagrass (Zoysia japonica Steud.) for further testing from an established germplasm collection of material collected from lawns grown in USDA Hardiness Zone 7. Overall, based on 8-week greenhouse studies, the experimental lines had similar shade tolerance compared to commercial standards ‘Raleigh’ ‘Palmetto’ and ‘Palisades’ zoysiagrass. Field studies may be warranted to validate greenhouse studies to help further evaluate shade tolerance of experimental and commercial lines. Information generated supports the use of certain St. Augustinegrass selection in a wider environmental conditions such as reduced light environments (RLE).
Feb 2023 DOI 10.14302/issn.2379-7835.ijn-23-4441
A practical review compares growth chart standards and references for pediatric monitoring after the COVID era. It advises on selection, interpretation, and equity considerations in diverse populations.
Mar 2022 DOI 10.14302/issn.2692-1537.ijcv-22-4117
Several mRNA vaccines are used on the population in the U.S. I started predicting the dangers of mRNA vaccines before March 2021 and update my findings periodically. My prior model study enabled me to identify many flaws in clinical trials, side-effect evaluation methods and mechanism studies, and I also considered consistent failure in predicting drug side effects in the past and systematic failure of FDA in keeping out dangerous drugs from market. I found that the risks of vaccination cannot be determined by experiments alone and must be determined by using a combination of methods. By studying mRNA expression dynamics and kinetics, I predict that vaccination with mRNA vaccines may increase cancer risks, multiple organ failure risks, earlier death risks, genome alteration speeds by one or more mechanisms, alter the normal selection process for viral evolution resulting in more virulent viruses, and aggravate chronic diseases or cause healed diseases to relapse. Two root problems are practical inability to control expression sites and severe adverse reactions from repeated vaccination. Based on mRNA bio-distribution, the mRNA mainly strikes the liver and other vital organs, and poses grave dangers to persons whose vascular functional reserves are relatively small, or whose vascular systems are temporarily burdened by other causes such as viral infections or life activities. If an mRNA vaccine is administered on a pregnant woman by second or booster shots, spike protein synthesis in fetus brain disrupts the highly regulated protein synthesis processes, resulting in potential brain damages. In less than a year, most of my early predicted damages are being materialized or are on the track to hit the population. In this update, I present a benefits-and-risks map to show how the number of deaths caused by mRNA vaccines is grossly underestimated and why claimed benefits like 95% effectiveness rate and 90% death rate reduction are meaningless and misleading.
Nov 2021 DOI 10.14302/issn.2575-1212.jvhc-21-3973
This review focused on the various methods for controlling estrous cycles in well-managed dairy cows. Because up to 70% of dairy cows may stay non-pregnant after an AI procedure, an effective approach for identifying and reinseminating open cows is essential for dairy herds to achieve optimal reproductive performance. Overall, well-managed dairy farms with effective estrus detection programs inseminate 50% or more of non-pregnant cows after behavioral estrus is detected. Cows not detected in estrus are admitted in a resynchronization of ovulation procedure to receive a timed AI (TAI) service to avoid a long interbreeding interval. In Egypt, a widely used program involves starting the Ovsynch protocol (GnRH-7 d-PGF2-56 h-GnRH-16 to 20 h-TAI) 32 days after an initial AI, regardless of pregnancy status. Previous studies have proven that there was no difference in pregnancy/artificial insemination (P/AI) between Ovsynch+P4 and Presynch-Ovsynch, both protocols were equally effective in improving the fertility of cows with a CL 15 mm. The review also addressed different methods for synchronization of ovulation and different factors affecting the selection of the management program.
Oct 2021 DOI 10.14302/issn.2639-3166.jar-21-3875
Repair and maintenance cost is considered as one of important items for machinery management and selection. The present study was carried out in Dongola area for tractor repair and maintenance costs estimation. The data was collected from records of Elshimalya Company for Agricultural Inputs. Forty four tractors rep resenting two sizes of tractors, 75hp and 150hp used in the area were selected for this study. Based on the data collected, regression correlation analysis was carried out and mathematical models were derived to predict the accumulated repair and maintenance (R and M) costs as percent of purchase price in relation to accumulated hours of use and age (years) for each tractor size, and also for the two sizes collectively. Five model forms (linear, logarithmic, polynomial, power and exponential) were derived and the power function was found the best fit to explain the relation. The accumulated Rand M costs as percent of purchase price (Y) was increased as the accumulated hours of use (x) and age (g) of the tractor in years were increased. A high correlation was found between the accumulated R and M cost and both accumulated hours of use and tractor age in years (Average R2 = 0.93). It was concluded that the power function was the best fit for repair and maintenance cost estimations and the following relations may be used as an average for estimation of the accumulated R and M costs as percent of purchase price (Y) with accumulated hours of use (x) and age (g) of the tractor: Y=0.028x0.662 (mean) Y=12.294g1.276 (mean).
Aug 2021 DOI 10.14302/issn.2643-6655.jcap-21-3888
The number of children with SEN is continuously growing, leading to pressure on the few special schools available in the USA. Furthermore, the adoption of a special school system has been criticized on the basis that it isolates and discriminates against children with special educational needs and disabilities. Even though inclusive education can address such limitations, the application of the most appropriate pedagogical approaches for SEN learners is still a challenge. The presented study focused on critically appraising the pedagogical approaches for SEN learners in the 21st century and beyond. In order to achieve this goal, a systematic review of the literature approach was adopted. The literature search process was conducted on three databases: Education Full Text, Linguistics and Language Behavior Abstracts, and PsycINFO. The selection of these databases was influenced by their reputation of hosting high quality and up-to-date literature about special education. The initial literature search process generated 6129 hits, but only ten studies were finally selected for review after the application of inclusion and exclusion criteria. A critical review of the evidence presented in the selected studies generated eight themes describing various pedagogical approaches for special education, within both blended and mainstream learning environment. Knowledge generated in this systematic review can be used by the special education sector of the U.S to develop pedagogical approaches for SEN students, leading to improved performance and social skill development.
Mar 2021 DOI 10.14302/issn.2692-1537.ijcv-21-3756
In contributing to the initiative to address the COVID-19 pandemic and in order to enhance the knowledge on driving forces shaping the evolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (isolated from Tunisian patients), a comparison in relation to other coronaviruses infecting humans (SARS-CoV-1, MERS-CoV, HCoV/229E, HCoV/NL63, HCoV/OC43, and HCoV/HKU1) as well as animals (SARS-CoVs in tiger, bats, civet, pangolin, bovine, and MERS-CoV in dromedary/camel), was conducted. In-depth analysis was carried out involving 115 sequences of spike glycoprotein-coding gene extracted from the international databases. Phylogeny inference allowed the reconstruction of a bifurcating tree where four distinct groups were delineated and at the same time, three animal accessions (SARS-CoV-2/tiger, MERS-CoV/camel, and SARS-CoV/bovine) shifted from the animal group and integrated the human coronaviruses clades. Nonetheless, in the presence of reticulate events such as recombination, networks described better the phylogenetic relationships rather than the classic dendrogram. Thus, networks were produced and identified four clusters containing sharply demarcated subgroups (eight subdivisions). Except networked phylogenies of SARS-CoV-1, SARS-CoV-2, and HCoV/HKU1, all the others showed edges and boxes illustrating the occurrence of incompatibilities related to the sequences of spike glycoprotein-coding gene. Thereby and consolidating this result, three methods (RDP package, GARD, and RECCO) were used to detect breakpoints in aligned sequences. Except the clades SARS-CoV-1 and SARS-CoV-2, all the remaining phylogenetic subdivisions were subject to recombination. Furthermore, the screening of selection pressure in all studied sequences by various statistics-based models of the HyPhy package, showed that, similarly, the lineages belonging to the clades SARS-CoV-1 and SARS-CoV-2 were not under selection. In contrast, all members of the remaining clades underwent, to different extents, adaptive selection as well as purifying selection.
Nov 2020 DOI 10.14302/issn.2381-862X.jwrh-20-3501
Background A well-functioning drug supply management is the corner stone for any meaningful health service. However, Pharmaceutical supply systems in many developing countries have severe problems, including inefficient selection, procurement and use of drugs. The magnitude and extent of the problem is huge and chronic in the Ethiopian health care system for a long time. Objective To evaluate auditable pharmaceutical transaction service process in Seka primary hospital, Jimma zone south west Ethiopia. Evaluation Methodology Case study design involving both quantitative and qualitative methods was conducted in Seka primary hospital. The focus of this evaluation was on the process of Auditable pharmaceutical transaction service. The evaluation was focused on process part of the program with dimensions; availability, compliance and client satisfaction in the dimension of accommodation. Resource inventory, document review; key informant interviews and observations were conducted. Client satisfaction was assessed through exit interview; with sample size of 326. The qualitative data was analyzed manually using thematic analysis and quantitative data were analyzed by using SPSS version 23 software. Results In Seka primary hospital, percentage availability of the 32 selected Key medicinewas 10.7(82.0%) and there were no expired drugs found on their shelves. The availability of 17 of the required 20(85%) professionals was adequate according the Auditable pharmaceutical transaction service. The average lead time was found to be less than five days. The average counselling and dispensing time were 5:43 minutes and 1:17 minutes, respectively. The average number of drugs per prescription was 2.0. The 1154(97.9%) of drugs prescribed by generic name and 1175(99.7%) of prescribed drugs on Essential Drug List indicates prescribers ‘adherence to facility specific List. Conclusion This evaluation revealed that (based on the pre-set judgment criteria) the achievement of the Auditable pharmaceutical transaction service in Seka primary Hospital was GOOD 82.6 % (achieved 355.2 of 430 weight given), i.e. even though it is Good achievement ,there are areas that needs improvement. Areas for improvement identified were: Pre- and in-service training for all health workers involved in store room and dispensary to improve on the medium counselling time, poor record keeping and the extremely poor labelingof drugs which this all improve the overall client satisfaction.
Oct 2020 DOI 10.14302/issn.2379-7835.ijn-20-3418
Isolation methods that employ readily-available inexpensive supplies on the open market, which are reliable, as well as economical, such as nucleic acid amplification techniques (NAAT) based on microfluidic technology in low-resource research settings (LRRS) that meets the ASSURED guidelines are essential to develop a noninvasive diagnostic colon cancer screen in stool using micro(mi)RNA molecules. A combination of a microfluidic-based MiRNA stool test with a reliable rolling circle amplification/detection method applied to the quantification of miRNA molecules, result in an affordable sensitive and specific isothermal method for the noninvasive quantitative detection of miRNAs in LRRS. Scientists and engineers have become interested in miRNAs, and they have intensified their efforts to apply emerging simple detection tools to the important bioanalytical challenge of quantifying these small 18-26 nt long molecules. Some of the proposed approaches incorporate novel material, such as simple centrifuges and methods based on microfluidic technology, while others utilize the interesting biological properties of these molecules, such as forming branched RCA structures, allowing for the detection of these biomarker molecules at an attomolar "aM" concentration level, using low cost extraction and isothermal amplification methods in LRRS. We have been interested in studying colorectal cancer (CRC) because it is the 3rd most common malignancy worldwide, and stool can be obtained noninvasively from the patients. We have focused in this research on colon cancer (CC) because it is more common in the USA than rectal cancer (RC). The innovation of our approach lies in the exploratory use of an affordable, quantitative miRNA profiling in noninvasive stool samples in LRRS, whose extracted fragile total RNA is stabilized shortly after excretion from stool by commercially available kits, so it does not ever fragment, followed by quantitative standardized analytical tests that are neither labor intensive, nor require expensive instrumentation, in order to develop apanel of novel miRNA genes for the noninvasive diagnostic screening of early left and right sporadic colon cancers, more economically, and with higher sensitivity and specificity than any other colon cancer screening test currently available on the market. To show the clinical sensitivity and specificity of the proposed quantitative miRNA test using simple methodologies in LRRS,the miRNA results are to be correlated with FOBT, colonoscopy, and pathology data. Standardization establishes test’s performance criteria (sample selection, optimal sample running conditions, preservation and storage), in order to ensure that the assay will perform the same way in any laboratory, by any trained personnel, anywhere in low-resource laboratory settings worldwide.
Jun 2020 DOI 10.14302/issn.2379-7835.ijn-19-3123
Isolation methods that employ readily-available inexpensive supplies on the open market, which are reliable, as well as economical, such as nucleic acid amplification techniques (NAAT) based on microfluidic technology in low-resource research settings (LRRS) that meets the ASSURED guidelines are essential to develop a noninvasive diagnostic colon cancer screen in stool using micro(mi)RNA molecules. A combination of a microfluidic-based MiRNA stool test with a reliable rolling circle amplification/detection method applied to the quantification of miRNA molecules, result in an affordable sensitive and specific isothermal method for the noninvasive quantitative detection of miRNAs in LRRS. Scientists and engineers have become interested in miRNAs, and they have intensified their efforts to apply emerging simple detection tools to the important bioanalytical challenge of quantifying these small 18-26 nt long molecules. Some of the proposed approaches incorporate novel material, such as simple centrifuges and methods based on microfluidic technology, while others utilize the interesting biological properties of these molecules, such as forming branched RCA structures, allowing for the detection of these biomarker molecules at an attomolar "aM" concentration level, using low cost extraction and isothermal amplification methods in LRRS. We have been interested in studying colorectal cancer (CRC) because it is the 3rd most common malignancy worldwide, and stool can be obtained noninvasively from the patients. We have focused in this research on colon cancer (CC) because it is more common in the USA than rectal cancer (RC). The innovation of our approach lies in the exploratory use of an affordable, quantitative miRNA profiling in noninvasive stool samples in LRRS, whose extracted fragile total RNA is stabilized shortly after excretion from stool by commercially available kits, so it does not ever fragment, followed by quantitative standardized analytical tests that are neither labor intensive, nor require expensive instrumentation, in order to develop apanel of novel miRNA genes for the noninvasive diagnostic screening of early left and right sporadic colon cancers, more economically, and with higher sensitivity and specificity than any other colon cancer screening test currently available on the market. To show the clinical sensitivity and specificity of the proposed quantitative miRNA test using simple methodologies in LRRS,the miRNA results are to be correlated with FOBT, colonoscopy, and pathology data. Standardization establishes test’s performance criteria (sample selection, optimal sample running conditions, preservation and storage), in order to ensure that the assay will perform the same way in any laboratory, by any trained personnel, anywhere in low-resource laboratory settings worldwide.
Mar 2020 DOI 10.14302/issn.2694-1198.jge-20-3206
On the basis of Hardy – Weinberg’s law the problem of inbreeding in a family tree and a population was investigated. With use of an inbreeding factor are received the discrete equation for a family tree and differential equation for a population. The numerical solution of the differential equation for a population was found and analyzed at various values of the inbreeding factor. Migration of inbred population is investigated in view of natural selection. It was shown that velocity of migration falls with increase of the inbreeding factor. Interrelation of the recessive allele frequency at woman for a migrating population with inbreeding factor and standard parameter of selection was found.
Jan 2020 DOI 10.14302/issn.2694-1198.jge-19-3141
On the basis of Hardy – Weinberg law the problem of migration from the genetic point of view is considered. It is proved the linear differential equation of migratory process of a panmictic population. The phase of the solution of this equation is investigated. On the basis of the carried out analysis the dependence of migration velocity of a population on average time of alternation of generations is found. It is shown that migration of primitive people from Africa to Europe needed alternation the several hundred generations. The dependence of migration velocity of a population on the average area developed by a population for year is investigated. Lacks of the carried out analysis owing to absence of the account of natural selection and inbreeding are marked.
Dec 2019 DOI 10.14302/issn.2641-5518.jcci-19-3133
To demonstrate that percutaneous coronary intervention (PCI) may in some cases be a safe option for patients with a high-risk surgical category, we report a complex clinical case of revascularization of multivessel coronary artery disease including left main coronary artery (LMCA) quadrifurcation. Methods For safety reasons, PCI was done in 2 separate sessions (staged PCI). Stenting of the LMCA quadrifurcation was performed using different stenting techniques in combination: modified balloon mini crush stenting technique was used - for LMCA and intermediate artery (IMA) stenting; modified balloon crush stenting technique was used for LMCA, circumflex artery (CX) and first obtuse marginal branch (OM1) stenting; provisional stenting technique was used for CX stenting, followed by sequential kissing balloon post-dilatation technique between LMCA and every branch; proximal optimization technique (POT) was performed in the LMCA. Left anterior descending artery (LAD), intermediate artery, circumflex artery, first obtuse marginal branch, left main coronary artery and its quadrifurcation were stented with 5 drug-eluting stents (DES) (Resolute Integrity, Medtronic); right coronary artery (RCA) was stented with 3 bare-metal stents (BMS) (Rebel, Boston Scientific). Results The interventions ended without complications, the ejection fraction increased from 35% to 48%, congestive heart failure functional class decreased to class I. Subsequent coronary angiography, eight months after the last PCI, revealed patent stents with mild, nonsignificant restenosis. More than three years after the intervention, the patient has no complaints (according to MACE). Conclusions It should be considered that in case of the selection of suitable patients and the use of the appropriate revascularization technique, LMCA quadrifurcation lesion can be successfully treated with PCI.
Oct 2019 DOI 10.14302/issn.2641-5518.jcci-19-3039
Chronic total occlusion (CTO) of the left main coronary artery (LMCA) is rare on the angiograms; Coronary Artery Bypass Grafting is the standard method of its revascularization. To demonstrate that PCI may in some cases be a safe option for patients with a high-risk surgical category, we report a complex clinical case of revascularization of chronic total occlusion of the LMCA, left anterior descending artery (LAD), and circumflex artery (CX). Methods Recanalization of the occluded LMCA and LAD was performed by utilizing the support-balloon technique, and CTO wires (Miracle 3™ wire, Abbott Vascular; Runthrough® NS Intermediate wire, Terumo); LAD, CX, LMCA, and its bifurcation, were stented with 3 drug-eluting stents (Resolute Integrity DES, Medtronic); the "Culotte Stenting " technique was used for bifurcation stenting, followed by "Kissing Balloon" post-dilatation technique; proximal optimization technique was performed in the LMCA. Results The intervention ended without complications. 2 months after stenting, the ejection fraction increased from 20% to 38%, improved almost all parameters of the heart, Congestive Heart Failure functional class decreased to class I. Conclusions It should be considered that LMCA CTO lesions can be successfully revascularized with PCI in case of the selection of the suitable patient and appropriate revascularization technique.
Sep 2019 DOI 10.14302/issn.2689-4602.jes-19-2990
There is hardly anything more central to our universe than conservation. Many scientific fields and disciplines view the law of conservation as one of the most fundamental universal laws. The Darwinian model pivots the process of evolution on variability, reproduction, and natural selection. Conservation plays a marginal role in this model and is not really universal, as the model allows exceptions to conservation, i.e. non-conservation, to play an equally important role in evolution. This anomalous role of conservation in the Darwinian model raises questions: What is the reason for this anomaly? Is conservation really universal, as we tend to believe or is it not, as the Darwinian model suggests? This contribution proposes a new model of evolution that focuses on levels of organization, rather than of species, organisms, or populations. It argues that conservation is central to evolution. Not only does this new model restores the universal status of conservation but it also makes possible to resolve some outstanding problems and controversies that continue to plague the Darwinian model. The article tries to advance the broad Darwinian project that seeks to explain the process of evolution as a product of the spontaneous processes in nature.
Aug 2019 DOI 10.14302/issn.2572-3030.jcgb-19-2597
In other to present a series of stochastic models from population dynamics capable of describing rudimentary aspects of genetic evolution, we studied two-allele Wright–Fisher and the Moran models for evolution of the relative frequencies of two alleles at a diploid locus under random genetic drift in a population of fixed size “simplest form, selection, and random mutation”. Principal results were presented in qualitative terms, illustrated by Monte Carlo simulations from R and http://www.radford.edu/~rsheehy/Gen_flash/popgen. Moran and the Wright-Fisher Models exhibited the same fixation probabilities, only that the Moran model runs twice as fast as the Wright-Fisher Model. A clue that can help us to understand this result is provided by the variance in reproductive success in the two models. Genetic changes due to drift were neither directional nor predictable in any deterministic way. Nonetheless, genetic drift led to evolutionary change in the absence of mutation (P=0.5), natural selection or gene flow. In general, alleles drift to fixation is significantly faster in smaller populations. Probability of fixation of an allele A was approximately equivalent to the initial frequency of that allele. With the inclusion of selection in our model, probability of fixation of a favoured allele due to natural selection increased with increase in fitness advantage and population size. The time taken to reach fixation is much slower, in case of no selective advantage, than a fixation under mutation with selective advantage.
Apr 2019 DOI 10.14302/issn.2377-2549.jndc-19-2736
Antibody phage display has become a useful technique for discovering and optimizing target-specific monoclonal antibodies suitable for many applications, including therapeutic ligands, which may act as direct pharmacological compounds or may be used as targeting ligands for controlled drug delivery. Recently, the D2-5-HT1A heteromer, which is formed by the dopamine D2 and serotonin 5-HT1A receptors has attracted attention as a potential target of antipsychotic drugs. Therefore, the aim of the study was to identify scFv monoclonal antibodies that are able to specifically recognize epitopes formed within the heteromer structure. Because both receptors are membrane proteins, it is important to conduct bio-panning experiments in the most natural conditions, in which the presented antigens (D2-5-HT1A heteromers) are in their native form and possibly in their best-preserved spatial structure. It has been shown here that phage display methodology can be successfully used in the preparation of monoclonal antibodies against dimers of membrane proteins. To separate phages specifically binding the D2-5-HT1A heteromer, the selection process using CHO+ cells with overexpression of both receptors was conducted. Phages that were bound to receptor monomers or other CHO-K1 cell surface proteins were eliminated as a result of negative selection by using CHO- cells expressing separate receptor monomers.
Feb 2019 DOI 10.14302/issn.2689-4602.jes-18-2431
The existing hypotheses on speciation rely on Mendelian genes and mutations in them. However, genome-wide sequencing demonstrates that the Mendelian genes account less than one-tenth of the entire genome DNA. This means that a greater part of the genome has not yet been subject to large-scale evolutionary consideration. This paper deals with the conditional mutations in drosophila, which are mutations of the genes belonging to a special category (ontogenes) controlling the program of individual development. The ontogenes presumably reside in the DNA of intergenic spaces and introns. Conditional mutations display a number of properties absent in the mutations of Mendelian genes. These specific properties allow three key problems in speciation to be solved: (1) the possibility of emergence of new traits as a result of sequential mutagenesis; (2) selection of mutants; and (3) establishment of isolation. We have shown that (1) the mutations in ontogenes are able to form new multigenic regulatory blocks that escape selection during their creation; (2) mutations in ontogenes allow for existence of constantly acting zygotic selection, which is by no means less important for speciation than Darwinian selection; and (3) owing to their conditionally lethal effect, the mutations in ontogenes are able to create biological isolation barrier. This gives the grounds for assuming that the emergence of mutations in ontogenes is a necessary condition for speciation.
Feb 2019 DOI 10.14302/issn.2471-7061.jcrc-18-2526
There is currently no validated micro(mi)RNA diagnostic stool test to screen for colon cancer (CC) on the market because of the complexity of fecal density, vulnerability of stool to daily changes, and the presence of three sources of miRNAs in stool (cell-free from fecal homogenates, exsosomal miRNAs from fecal exosomes, and fecal colonocytes). To address these complexities, we have first carried out a microarray miRNA experiment, using Affymetrix GeneChip miRNA 2.0 Arrays, on immunocaptured and enriched stool colonocytes of 15 subjects (three healthy controls and twelve colon cancer patients [three TNM stage 0-1 (e.g., polyps◻ ³ 1 cm, villous or tubvillous, or with high grade dysplasia), three stage 2, three stage 3, and three stage 4 in triplicates to select a smaller panel of 14 preferentially expressed mature miRNAs associated with colon cancer (12 Up-Regulated, miR-19a, miR-20a, miR-21, miR-31, miR-34a, miR-96, miR-106a, miR-133a, miR-135b, miR-206, miR-224 and miR-302; and 2 Down-Regulated, miR-143 and miR-145). In a subsequent validation study carried out on total small RNA extracted by immunocapture, followed by RT that employed TaqMan® miRNA Reverse Transcription (RT) Kit and a Custom TaqMan RT Primer Pool, absolute quantification of miRNAs, in copies/µl, was measured using a chip-based Absolute QuantStudio 3D Digital PCR analysis. To ensure that we have chosen human and not bacterial small total RNA, we have carried out coextraction protocols with E. coli K1 strain RS18, compare Agilent electrophoretic patterns, and also sequenced random samples throughout this research using mRNA/miRNA sequencing. Our initial quantitative dPCR miRNA data presented herein showe that the quantitative changes in the expression of a few mature miRNA genes in stool, which are associated with right and left colon cancer, would provide for a more convenient, sensitive and specific diagnostic screening markers thatare more useful than those test markers currently available on the market, such as the low-sensitivity (<15%) fecal occult blood test (FOBT); result in better compliance; and is more economical than the invasive and expensive colonoscopy exam in colon cancer, which can be cured if that cancer is detected at the early TNM stages, and that becomes incurable and deadly if not diagnosed before metastasis. Initial test performance characteristics of the miRNA approach showed that the test has a high numerical predictive value in colon cancer. Moreover, underpinning of the miRNA markers as a function of total RNA showed that the test can numerically differentiate between control subjects and colon cancer patients, particularly at the early stages of that curable cancer. We propose to extend our initial research results to a larger prospective and randomized five-years nested case-control study, to validate the expression of the above 14 miRNAs, in stool of 180 individuals in an epidemiologically designed study, using (30 controls and 150 colon cancer patients (thirty precancerous polyps (stage 0-1), forty five stage 2, and seventy-five colon cancer stages 3 or 4). chosen randomly by an epidemiological method from 900 control and CC subjects to allow for an adequate time to collect the required 900 stool samples, as well as allowing for statistically valid analysis, standardized test conditions, and to provide a mean for determining the true sensitivity and specificity of a miRNA-screening approach in noninvasive human stool. Power-analysis has indicated that a total of 180 individuals, which will take us 5 years to enroll in testing, is an appropriate number of subjects to standardize and validate our proposed miRNA screening test. We may find out at the end of the proposed validation study in stool that fewer miRNAs, or even one miRNA, may suffice to serve as an efficient and a quantitative marker for the non-invasive diagnostic screening of colon cancer in human stool. The above approach when combined with bioinformatics analysis, to correlate miRNA seed data with our previously published messenger (m)RNA target data in stool, allows for a thorough mechanistic understanding of how miRNA genes regulate mRNA expression, and would offer a better comprehensive diagnostic screening test for the non-invasive early detection stage (0-1) of colon cancer. In order to show the clinical sensitivity and specificity of the proposed miRNA test, the absolute miRNA PCR values, in copies/µl, will be correlated with FOBT, colonoscopy, and pathology data. Standardization will establish test’s performance characteristics (sample selection, optimal sample running conditions, preservation and storage) to ensure that the assay will perform the same way in any laboratory, by any trained personnel, anywhere in the World. Ultimately, a smaller number of selected validated miRNAs (<10) showing increased and reduced expression could suffice to give quantitative miRNAs colon cancer expression values, useful for the early diagnostic screening of that curable cancer.
Jan 2019 DOI 10.14302/issn.2379-7835.ijn-18-2469
Background Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are categorized as omega-3 poly unsaturated fatty acids (PUFAs) that are present in fish oil, etc. DHA and EPA omega-3 PUFAs have a well-established fasting serum triglycerides (TG) lowering effect that may result in normal lipidemia in hyperlipidemic patients. In general, omega-3 PUFAs, such as DHA and EPA, can be ingested easily, and because they are highly safe, they are assumed to be suitable for controlling fasting serum TG in the serum of those who do not require drug treatment. To the best of our knowledge, however, almost all systematic reviews on the effects of omega-3 PUFAs on lowering fasting serum TG are directed at patients fulfilling the diagnostic criteria of dyslipidemia. Objectives To review and confirm the preventive effect of omega-3 PUFAs against hypertriglyceridemia or the effect on nondrug treatment in patients with a mild disease, a systematic review was conducted to determine whether there was a fasting serum TG-lowering effect in subjects without disease and those with a slightly higher triglyceride level who consumed DHA and/or EPA orally compared to those with placebo or no intake of DHA and/or EPA. Search Methods We evaluated articles from searches of PubMed (1946-February 2016), Ichushi-Web (1977-February 2016), and J Dream III (JST Plus, 1981-February 2016; JMED Plus, 1981-February 2016). The keywords were set as follows: “DHA” or “docosahexaenoic acid” or “EPA” or “eicosapentaenoic acid” and “TG” or “triglyceride” or “triglycerol” or “triacylglycerol” or “neutral lipid.”. In addition to the literature group obtained by the database search, we included participants not suffering from any disease (i.e., excluding mild hypertriglyceridemia). Eligibility Criteria Before the test selection process, the following inclusion criteria were defined. Participants were healthy men and women including those with mild hypertriglyceridemia (fasting serum TG level, 150-199 mg/dL [1.69-2.25 mmol/L)). Intervention was defined as orally ingested DHA and/or EPA. Comparison was made to placebo intake or no intake of DHA and/or EPA. Results were measured for the fasting serum TG level. The test design was RCT, and quasi-RCT. Data Abstraction Various characteristics were extracted from original reports using a standardized data extraction form, including the author of the study, research year, research design, subject characteristics (sex, age, sample size), period, dose of DHA and/or EPA (mg/day), and comparison group. Main Results We identified 37 documents for review. Among the 37 reports used to integrate literature results, 25 revealed a decrease in fasting serum TG level due to the oral ingestion of DHA and/or EPA. Sixteen studies on subjects without disease and 21 on subjects with slightly higher fasting serum TG levels were separated and stratified analysis was conducted. Ten of the 16 (normal TG participant) and 15 of the 21 studies (slightly higher TG participant) respectively, indicated that at least 133 mg/day of DHA and/or EPA intervention provided a statistically significant decrease in the fasting serum TG level between an intervention group versus a placebo group.
Jan 2019 DOI 10.14302/issn.2572-3030.jcgb-18-2527
As remarkable advances have been made in immunotherapies, the overall goal of immunotherapy has become the selection of patients and evaluating the benefits of treatment. One of the major obstacles to develop immunotherapies is the lack of effective immune monitoring. Monitoring of key changes in the immune system during immunotherapy (immunomonitoring) provides important insights into efficacy as well as the immune mechanisms of response at the molecular and cellular levels. Immunomonitoring techniques include traditional immunoassays that use specific antibodies to recognize the analytes of interest, new high-throughput immunoassays that target immune cells and nucleic acids, and less classical immunogenomic approaches that rely on genome-wide profiling and computational analysis on various types of clinical samples. Substantial progress has been made in the application of immunomonitoring strategies to pre-clinical and clinical studies, especially for patients with cancer and infectious diseases. Current and emerging immunoassays performed in clinical practice will be examined herein, and immunogenomic approaches that complement these techniques will be highlighted and compared with traditional methods. Finally, we will discuss several new computational methods for analyzing gene signatures for immunomonitoring, including gene expression data profiling by microarray, the nCounter technique, regular RNA-seq, and single-cell RNA-seq. Novel immunomonitoring techniques, especially immunogenomic approaches, will continue to be developed to facilitate assessment of immunotherapeutic response and predict patient outcomes in cancer and infectious disease.
Dec 2018 DOI 10.14302/issn.2578-8590.ipj-18-2556
Swimming is a human activity that relies heavily on individual physiological capabilities. In fact, the swimming general performance equation, proposed several years ago by di Prampero 1, highlighted the energy expenditure, the propulsive efficiency and the hydrodynamic drag as its main determinants. Therefore, coaches and exercise physiologists have been proposing a number of testing protocols aiming to diagnose the swimmers physiological training status. However, most of these protocols are invasive, time consuming and costly (e.g. the oxygen uptake assessment and the blood lactate concentrations determination). In addition, some of these tests have some constraints, as the use of a cumbersome breathing valve for respiratory data collection (cf. 2) and the selection of an averaged value of blood lactate concentrations as an non individualized index of endurance performance 34.
Nov 2018 DOI 10.14302/issn.2768-0207.jbr-18-2175
Non–information technology (IT) professionals and nonexpert casual users are increasingly adopting self-service business intelligence (SSBI) tools (such as Tableau, Qlik, and Power BI) to create data visualization dashboards. This study identified the most relevant dashboard design principles for SSBI tool users. The research approach included organizing a focus group in which most of the participants were non-IT professionals in health care, extracting recommended principles from the literature, applying these recommended principles by using data on quality of diabetes care to design relevant dashboards, and proposing the following 5S dashboard design principle framework: 1) seeing both the forest and trees, 2) simplicity through self-selection, 3) simplicity through significance, 4) simplicity through synthesis, and 5) storytelling. The third and fourth principles are novel and provide solutions to decision-making problems (such as conflicting results from excessive and discordant indicators) encountered by health care professional in the public sector as well as in other domains. The 5S dashboard design principles are easily memorized and practical and thus enable non-IT professionals and nonexpert casual users to design insightful dashboards efficiently by using SSBI tools.
Oct 2018 DOI 10.14302/issn.2576-6694.jbbs-18-2408
Improved economic and developed people with their lifestyle have created many challenges of health issues (obesity, osteoporosis, cancer, diabetes, allergies and dental problems), due to selection of different food habits (such as consumption of manifold junk foods). It has created number of health problem (development of many diseases) related to nutritional deficiencies food. Nowadays, people have developed the habit for shifting of synthetic food ingredients to organic foods and ingredients, obtained from natural sources. In this regards, nutraceuticals food or its food products can perform important role in controlling the diseases via fulfilling all the health benefits to many people at worldwide. Incredible dietary supplements as nutraceuticals food (involvement in nutritional, immunologic and physiological functions) can help in prevention or treatment of many diseases (mitigating of gastrointestinal (GI) tract problem), as it is synthesized from raw herbals and lots of rapidly growing industries are reported to synthesize these natural products. And around 100 million people are found to take these products (power of plant based materials) for getting health benefits. It can work as drugs as health benefit of nutraceuticals via regulation/ control for diseases. Global nutraceuticals market had been valued for US$ 165.62 billion in 2014 and it would be grow the value of US$ 278.96 billion by 2021 with compound annual growth rate of 7.3%. This proposed paper will discuss the different types of nutraceuticals food or its functional components involved in prevention or treatment of diseases.
Sep 2018
Epilepsy comprises a series of chronic neurological disorders characterized by recurrent seizures. Over 50 million people are affected by epilepsy worldwide. In addition, genetic components capable of predicting epilepsy predisposition and antiepileptic drugs response would lead to the development of promising treatment and a better prognosis of the disease. Several genes and their variants have been investigated whether they could affect the onset of epilepsy. The brain-derived neurotrophic factor gene, the ATP-binding cassette subfamily B member and the cytochrome P450 are the most common polymorphic genes related to epilepsy. Early identification of risk factors for epilepsy should optimize treatment and prognosis. The characterization of genetic polymorphism contribute to the selection of the most promising antiepileptic therapy and avoidance of drug resistance. The development of biomarkers to estimate the risk of epilepsy and drug resistance would have a clinical impact on the treatment of the disease and on anti-epileptic drug therapy.
Aug 2018 DOI 10.14302/issn.2689-4602.jes-18-2229
A historical and conceptual review traces how evolutionary theory has expanded from classical selection to modern syntheses incorporating development, epigenetics, and systems thinking. Implications for research and science communication are discussed.
Aug 2018 DOI 10.14302/issn.2690-4721.ijcm-18-2217
Background Overuse of beta-lactam antibiotics has lead to selection for extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae, a major cause of antibiotic resistant urinary tract infections (UTIs). Standard detection methods are time-consuming, with disputed accuracy. This study describes a novel real-time PCR method to detect CTX-M, SHV, OXA and TEM. Methods 179 Enterobacteriaceae isolates from UTIs were collected from the Leicester Royal Infirmary, UK. A multiplex Plexor®-based real-time PCR assay detected ESBLs using their specific amplicon melting temperature, during each cycle, removing the need for a melt-curve analysis. Validation was achieved by end-point PCR and disk diffusion. Results The method was able to produce rapid and accurate results, achieving a sensitivity and specificity of 94.9% and 72% respectively, and the assay can differentiate between the different ESBL genes, with ease. Conclusions With further investigation, a Plexor®-based assay could form the basis of a high-throughput kit that health services could use to detect ESBLs or other antibiotic resistance genes.
Apr 2018
Heart failure(HF) is a disease with high morbility and mortality. The benefits of current pharmacological and device therapy for survival outcomes of patients with HF are limited. Gene therapy represents a novel promising strategy in treating HF, as it can theoretically normalize the aberrantly expressed genes and their regulatory mechanisms permanently. However, the translation of gene therapy for HF from bench to bedside has been less successful. There are many challenges ahead for gene therapy, especially in the areas of selection of the optimal targets, the needs for developing delivery systems and the improvement in design of clinical trials. In this review, we summarize the most promising gene targets which have been used in experimental and clinical studies for treating HF, highlighting the results from several clinical trials. We also review the latest development in gene therapy vectors and delivery methods, aiming to provide directions for future studies.
Mar 2018
An important use of proteomics data from Mass Spectrometry (MS) is the classification of tumor types with respect to peptides in specific cancer types. It is highly critical to find an optimal set of markers among specific cancer peptides whose expression can be clinically utilized to build assays for the diagnosis or to track the progression of specific cancer types. A number of feature selection algorithms have been proposed to obtain the classification of MS data. In this article, we proposed an improved feature selection algorithm based on feature weighting. Relief algorithm can calculate the weight of different features according to the correlation between their characteristics and categories. F-score is a simple filter-based feature selection method by evaluating how two sets of real numbers discriminate from each other. The main goal of this paper is to introduce a new feature weighting selection algorithm combining score from f-value and weight from relief, which is more accurate when classifying high-resolution MALDI-TOF (matrix-assisted laser desorption and ionization time-of-flight) MS data. We have developed a four-step strategy for data processing based on: (1) Align the study sets by binning of raw MS data, (2) local maximum search(LMS) peak detection, (3) a new combination feature weighting selection algorithm and (4) support vector machines achieve a satisfactory performance of identifying cancer and the healthy. The best parameter set for LMS were achieved with control variable method, which achieve an average accuracy of 97.4167% (sd = 0.0146) and the best accuracy of 98.6111% in 1000 independent 10 -fold cross validations.
Nov 2017 DOI 10.14302/issn.2576-6694.jbbs-17-1748
Neo-Darwinian natural selection theory indicates that sudden, drastic changes in the environment place selective pressure on genetic variants in a population. As time progresses, this pressure sculpts individuals to better fit this new environment. Waddington’s classic experiment was repeated using white-eyed (the w1118strains) flies which produced the crossveinless (cve; disturbed wing crossveins) trait from the parent generation. The F1 generation was split into two selection lines: an Upward Selection Line, that produced more cve in successive generations, and a Downward Selection Line that responded with a consistent but non-linear decline in the percentage of crossveinless. This article will introduce and enlarge observations made on flies with cve; especially the manner in which the Waddington experiment impacts the population. It seems that Waddington evaluated crossveinless just by what it is good for, but not by the price of using it. That is to say, there is an inevitable cost that needs to be paid in order to acquire crossveinless-ness (cve and the associated phenotypes).
Nov 2017 DOI 10.14302/issn.2576-9383.jhhr-17-1768
Antifungal antagonism of different fourteen plant essential oils was examined as natural agents against economic and hygienic effective three yeasts; the preservative efficacy of most potent anti-yeast essential oil in food sanitary was also tested. Study involved oils antifungal bioactivity screening against Saccharomycescerevisiae, Candida albicans,and Candida utilis. Study also included selection and invitro extraction of most bioactive oil, and evaluation of its antifungal minimal inhibitory concentrations (MICs). Control ofjuice spoilage by Saccharomycescerevisiae under the effect of in vitro oil extract different concentrations was also screened. Among the tested essential oils, apricot seed oil was the most bioactive anti-yeast agent. Two MIC values of apricot oil invitro extract, 12.5μgml-1 and 25μgml-1 were recorded. In juice samples, oil extract bioactivity increased gradually up to concentration 100μgml-1.Highest oil preservative ability was observed at oil concentration of and above 125μgml-1. Higher oil concentrations needed for juice preservation were found more than in vitro assay to give the same effect. Applying of apricot oil and some other plant essential oils could be used as an environmental safety mode in osmophilic food preservation and in Candidate diseases biocontrol.
Oct 2017 DOI 10.14302/issn.2381-862X.jwrh-17-1758
Background: The nature of placenta previa can be unpredictable and harsh on the mother and baby. These complications are often unpredictable, unpreventable and often leave the labour ward team in a dilemma. This Obstetricians' nightmare is fortunately a rare complication. The frequency of placenta previa at the time of delivery average 1/200 births i.e. 0.5%. Placenta previa is still an important cause of maternal and fetal death in our country. The risk factors are Advanced Maternal age, Multi parity, Previous Cesarean Section, Multiple gestation, Previous Abortions, Previous intrauterine surgery, placenta previa in previous pregnancy, Smoking. Objective: Identification of risk factors, the feto-maternal outcome and complications of patients having placenta previa with previous caesarean section. Methodology: This cross sectional study was conducted from July 2012 to June 2015 in Obstetrics and Gynaecology department, Dhaka Medical College hospital. 100 patients of placenta previa were included in this study. Non-probability purposive sampling method was used for selection of patients. Results: In this study, Socio-demographic profiles, Identification of risk factors, the feto-maternal outcome and complications of patients having placenta previa were assessed. The frequency of placenta previa associated with previous cesarean section was 61%. In demographic profiles of the patients in this study - with a history of previous caesarean section, 78.7% patients were in the age group 26-35. Multiparity was predominant on scarred uterus group (63.9%). Here, demonstrated that > 2 previous history of caesarean section was associated with 80.3% of placenta previa. Regarding maternal outcome, complications like massive haemorrhage, ureteral injury, bladder injury, wound infection, DIC, maternal and perinatal mortality were more in the scarred patients than in the unscarred patients. In our study, 29.5% of morbid adhesion of placenta observed in scarred uterus. Conclusions: There is significant association of placenta previa with previous cesarean delivery. So, Careful monitoring of high risk pregnancies is of utmost importance. Avoidance of unnecessary caesarean sections and early week’s pregnancy terminations can minimize the Obstetricians' nightmare.
Sep 2017 DOI 10.14302/issn.2474-7785.jarh-17-1727
Background: Healthcare services provided to patients should vary depending on disease severity. However, disease severity bias, a type of selection bias, is a commonly encountered problem in administrative database studies. Herein, we selected chronic obstructive pulmonary disease (COPD), which commonly affects elderly Japanese citizens, for the development and validation of a severity classification system based on a health insurance claims database. Methods: Patients who received COPD-related diagnostic codes in 2011 were selected from a commercially based health insurance claims database. COPD patients were randomly divided into two groups to develop and validate severity scores. A principal component analysis was used to estimate factor loadings used to weight calculations of COPD severity scores. Score validity was evaluated using a linear trend test to predict COPD treatment costs and acute exacerbation events. Results: Using records from 880 patients, ten variables were created: acute exacerbation events, emphysema diagnoses, laboratory test and oxygen therapy procedures, prescribed anticholinergic, inhaled corticosteroid (ICS), short acting beta-agonist, and long acting bronchodilator (LABA) agents, asthma diagnosis and patient birth years. Factor loadings from LABA and ICS prescriptions had the strongest impacts on estimated severity scores (0.50 and 0.49, respectively). Among 300 validation group patients, scores were found to associate with increasing trends of median costs and exacerbation risks (p for trend < 0.05). Conclusions: Estimatedseverity scores would help to predict COPD-related medical costs and exacerbation events. For further clinical implementation, this classification system should be re-evaluated using clinical lung functions information indicative COPD severity and treatment choices.
Aug 2017 DOI 10.14302/issn.2470-5020.jnrt-17-1487
The global popularity of soccer has led to widespread tendency towards this sport. Because of the convenience of using artificial surfaces, the rapid growth of using these surfaces led to concerns about the declining performance of the players. The aim of this comprehensive review is to study the difference between the performance of players on different playing surfaces and the risk factors for use of artificial turf compared to natural grass. A literature search of valid scientific databases such as Science Direct, PubMed and Jstor by searching keywords was performed. In total, more than 6,000 articles were retrieved. After the preliminary selection process, the final analysis was performed on a total of 76 articles. Results: Mechanical properties of artificial grass have a significant effect on the average time of sprinting, the best time of sprinting and maximum speed. The numbers of sliding tackles on artificial turf were lower compared to natural grass. Artificial turfs exposed hardness, elasticity and high friction. The characteristics of artificial grass have changed over time and increased the probability of injuries. There was no significant difference between the overall risks of acute injuries in soccer players performing on artificial turf compared to natural grass. The amateur, young and female soccer players had rated lower injuries on artificial grass. But the rate of injuries in elite soccer players were higher on artificial grass and hence they are not found of playing on such playing surfaces.
Aug 2017 DOI 10.14302/issn.2379-7835.ijn-17-1710
Background: High number of patients suffering from autism spectrum disorders utilize dietary intervention methods, especially gluten-free/casein-free diet. In contrast with its’ extensive usage no sufficient and consistent data exist to support its’ efficiency and safety. Objective: The main aim of this systematic review is to provide a general look to the efficiency and safety of gluten-free/casein-free diet treatment for autism spectrum disorders. Method: Studies used in this systematic review are gathered from 3 online databases (PubMed, Embase and the Cochrane Library). Inclusion criteria are established for study selection. Articles published in a peer-reviewed article between 1990 and 2016 in English about our topic of interest and conducted with patients under the age of eighteen (18) are selected and further analyzed (“Level of Evidence” and “Grade of Recommendation” criteria are utilized). Results: Even though some studies with high values of “Level of Evidence” claim that gluten-free/casein-free diet is beneficial for patients suffering from autism spectrum disorders, studies with lower risk of bias demonstrate otherwise. Since studies such as case reports and cohort studies may contain bias associated with small sample size, absence of clear assessment methods, lack of randomization and short treatment period we suggest that there is no sufficient data to support gluten-free/casein-free diet treatment. Conclusion: Due to controversial outcomes from studies that have different “Level of Evidence” we speculate that efficiency of gluten-free/casein-free diet might be related to individual genetic differences. Therefore, studies conducted with large study groups could not provide statistically significant data to support this treatment option. Further studies should be conducted, especially in the field of genetics, in order to test our hypothesis.
Apr 2017 DOI 10.14302/issn.2644-1101.jhp-17-1460
The objective of this study was to study the selection of seat location by individuals in a group in a confined environment and to identify the factors leading people to prefer one location to another. We analyzed the seating location of students in a lecture hall over the course of two academic programs of different durations (19 days and 44 days). The goal was to determine the rate at which participants would settle into a specific seat location. Unobtrusive photography was used to collect objective data on an hourly basis. Results showed that in both courses participants began to settle into a specific location from the second day of class. Twenty percent of the participants had settled after 4-7 days or 15.5 hours in class. Settling continued for the duration of the shorter course. However, in the longer course settling stopped after 28.5 days on average. The plateau in the number of settlers depended on the number of days, not on the time actually spent in class. At the end of the longer course 52.5% of the participants had settled, compared to 38.9% in the shorter course. Settling into the same seat location can be interpreted as a strategy to establish a personal territory. These results indicate that about half of a cohort expresses the need for establishing a personal territory when in a confined and crowded environment, and this process takes about one month.
Mar 2017
This article examines how HLA‑DRB1 allele mismatching influences outcomes after hematopoietic stem cell transplantation. It reviews graft‑versus‑host disease risk, engraftment, and survival metrics in the context of donor matching strategies. The findings support careful allele‑level typing to optimize donor selection and improve post‑transplant prognosis.
Jan 2017 DOI 10.14302/issn.2574-4372.jesr-16-1395
Calcium (Ca2+) plays a central role in regulating many biological processes in the cell from muscle contraction to neurotransmitter release. The need for reliable fluorescent calcium indicator dyes is of vast importance for studying many aspects of cell biology as well as screening compounds using phenotypic high throughput assays. We have assessed two of the latest generation of calcium indicator dyes, FLIPR Calcium 6 and Cal-520 AM for studying calcium transients (CaTs) in induced pluripotent stem cell (iPSC) -derived human cardiomyocytes. FLIPR Calcium 6 and Cal-520 dyes both displayed robust CaTs with a high signal-to-noise ratio (SNR) and were non-toxic to the cells. The analysis showed that CaT amplitudes were stable between measurements, but CaT duration was more variable and tended to increase between reads. Two methods were compared for drug-screening hit-selection; difference in average (unstandardized) and standardized difference. The unstandardized difference was better for assessing CaT amplitude, whereas standardized difference was equal to or better for assessing CaT duration. In summary, FLIPR Calcium 6 and Cal-520 are suitable dyes for drug-screening using iPSC-derived human cardiomyocytes.
Jul 2016 DOI 10.14302/issn.2574-4372.jesr-16-1055
Human-induced pluripotent stem cells (HiPSCs) demonstrate promise in their ability to differentiate into neural cells and ultimately replace the cell types and thereby brain tissue damaged by stroke. This may diminish cognitive impairment due to stroke. Prior to transplantation, an appropriate scaffold must be determined to allow for heightened accuracy by facilitating proper adhesion, differentiation, and proliferation, increasing the likelihood of success, as will be defined in this review, in vivo. This paper aims to provide a review of available biocompatible scaffolds and their efficacy, to provide insight for future research utilizing clinical trials to study stem cell therapy as a form of post-stroke recovery. A systematic review of scaffolds outlined in full-text, peer-reviewed articles with unique experimental data, available on PubMed, will be conducted to determine an ideal scaffold, based on article and scaffold selection criteria best suited for the transplantation of human-induced pluripotent stem cells.
May 2016 DOI 10.14302/issn.2574-450X.jom-16-1039
Over the last three decades, an epidemic of obesity has markedly affected patients suffering from mental illnesses such as schizophrenia. Antipsychotic medications used to treat schizophrenia are considered as major culprits. The aim of this review is to first consider risk factors, to then outline negative sequelae of obesity for this population, and finally to address timing and content of recommended clinical interventions. Medical databases were searched with the terms “”weight,” “obesity,” and “schizophrenia.” Selection of articles was guided by date of publication; recent papers are preferentially cited. The main findings were that, in addition to antipsychotic medications, socio-economics, lifestyle, immune factors, and circadian rhythms also contribute to obesity risk. A barrier to effective health promotion within psychiatry has been the concern that fears about gaining weight might stop individuals with schizophrenia from taking needed antipsychotic medication. Recommendations, therefore, are to keep the dose of antipsychotic medication as low as possible, avoid polypharmacy, encourage healthy eating and physical activity, address sleep problems and substance use, monitor weight, blood pressure, and metabolic parameters regularly, utilize motivational interviewing techniques and peer support, pay special attention to special needs such as those of women during pregnancy, and include bariatric surgery as a potential intervention. Conclusion: Besides careful attention to medication regimens, the literature supports the active encouragement and support of patient self-management strategies to both prevent and manage obesity in schizophrenia.
Feb 2016 DOI 10.14302/issn.2575-7881.jdrr-15-849
Reverse Transcription Polymerase Chain Reaction (RT-PCR) using new designed primers pair for Heat Shock Protein70 homologue (HSP70h) of Olive leaf yellowing-associated virus revealed 667 amplified product of 10 olive accessions collected from various olive-growing regions in Tunisia. Amplicons were cloned and sequenced. The sequences were deposited in the international databases. Pairwise sequence comparisons among 10 Tunisian isolates along with a reference sequence (AJ440010) extracted from GenBank revealed a nucleotide identity of 86.06-99.40 and an amino acid similarity of 91.89-99.55. Sequence multiple alignments were searched for evidence of recombination using three methods, ie. Differences of Sums of Squares (DSS) implemented in TOPALi v2.5 software and Single Breakpoint (SBP) along with GARD, a genetic algorithm, both incorporated in HyPhy package. All used methods pointed out the presence of putative breaking points in partially sequenced HSP70h-coding gene. Since failing to account for recombination can mislead the phylogeny inference and can elevate the false positive error rate in positive selection assessment, the use of GARD resulted in the reconstruction of different phylogenies on the left as well as on the right sides of putative recombination breaking points, and the 11 accessions were distributed into at least three clusters compared to MEGA6 software which delineated only two clades. Nonetheless, by dividing the aligned sequences at breakpoints into separate sequence sets, MEGA6 delineated a clustering pattern different from the former two. As a result, recombination reshuffled the affiliation of the different accessions to the clusters. Analysis of selection pressures exerted on HSP70h encoded protein using different models (SLAC, IFEL, FEL, REL, PARRIS, FUBAR, MEME, GA Branch, and PRIME) taking into account recombination, and implemented in HyPhy package, revealed that it underwent predominantly purifying selection as confirmed by Tajima’s D, Fu and Li’s D and F tests, and SNAP algorithm. However, a few sites were also under positive selection as assessed by various models such as FEL, IFEL, REL, MEME, and PRIME.
Oct 2014 DOI 10.14302/issn.2329-9487.jhc-14-404
This review discusses causes of lower‑limb bypass graft failure and strategies to improve durability. It considers patient selection, conduit choice, surveillance, and re‑intervention options.