In this paper, a generalized class of estimators for the estimation of population median are proposed under simple random sampling without replacement (SRSWOR) through robust measures of the auxiliary variable. Three robust measures, decile mean, Hodges–Lehmann estimator, and trimean of an auxiliary variable, are used. Mathematical properties of the proposed estimators such as bias, mean squared error (MSE), and minimum MSE are derived up to first order of approximation. We considered various real-life datasets and a simulation study to check the potentiality of the proposed estimators over the competitors. Robustness is also examined through a real dataset. Based on the fascinating results, the researchers are encouraged to use the proposed estimators for population median under SRSWOR.

β-Thalassemia is a genetic disorder caused by defects in the β-globin gene resulting in the absence or reduced synthesis of adult hemoglobin (HbA). Hydroxyurea is an effective drug to increase fetal γ-globin (HbF) expression, replacing the missing adult β-globin. The mechanism of HbF induction by hydroxyurea and improvement in clinical symptoms are still poorly understood. In the present study we performed comparative analysis of plasma proteome in pre- and post-hydroxyurea-treated β-thalassemia major transfusion-dependent children (n = 10, mean age = 3.2 years) as well as responders versus nonresponders to hydroxyurea treatment. Plasma was collected before and after 6 months of hydroxyurea treatment, with patients subcategorized on the basis of their response to hydroxyurea. Among 400 identified proteins using a label-free quantitative proteomics approach, 28 proteins were found to be significantly different in pre- versus post-hydroxyurea-treated groups, with transferrin receptor protein-1 being most downregulated and hemopexin and haptoglobin the most upregulated proteins after treatment. In responder versus nonresponder comparison, 26 proteins were found to be differentially expressed, with carbonic anhydrase 1, hemoglobin subunit γ-1, and peroxiredoxin-2 showing the significant changes. The mechanism of hydroxyurea treatment in β-thalassemia patients appears to be complex, requiring a large sample size and a longer period of treatment to reveal its details.

Transfusion-related complications and lack of resources in low-to-middle-income countries have led to a search for novel therapies to reduce the need for blood transfusions in β-thalassemia patients. Hydroxyurea (HU) has demonstrated promising outcomes; additionally, thalidomide has also shown improvement in hemoglobin (Hb) levels for patients with β-thalassemia in some studies. This study presents the findings of a single-arm non-randomized trial to evaluate the efficacy of combination therapy of HU and thalidomide in children with β -thalassemia. A total of 135 patients [median age 6 (IQR 3-10) years], 77 (57%) males and 58 (43%) females were followed first using HU alone, for six months, and then using the combination of HU and thalidomide for another six months. The primary outcome was a response to therapy, as measured by the number of transfusions required and hemoglobin levels, for patients while receiving HU alone and then while using the combination therapy. Study findings showed a significant decline in blood transfusion volume (p < 0.001) and a significant increase in median Hb levels within 3 and 6 months of the combination therapy (p < 0.001). Eighty-nine (65.93%) participants were good responders, 16 (11.85%) were responders, and 30 (22.22%) were non-responders; whereas, the responders had variable genetic mutations. A total of 38 adverse events were reported which resolved on supportive treatment or temporary hold of the intervention. The combination therapy demonstrated promising results and could be considered for a diverse patient population with β-thalassemia. This trial was registered at www.clinicaltrial.gov as # NCT 05132270.

β-Thalassemia is the most common hereditary disorder characterized by reduced production of β-globin chains of hemoglobin A (HbA). In recent years, hydroxyurea (HU) has shown promising therapeutic benefits in patients with β-thalassemia by fetal hemoglobin augmentation. We have analyzed effects of hydroxyurea treatment on oxidative stress in β-thalassemia patients by assessing activities of paraoxonase (PON) and arylesterase along with malondialdehyde (MDA) and total reactive oxygen species (ROS) concentrations. Blood samples from 159 individuals including 56 HU-treated and 58 untreated β-thalassemia patients and 45 healthy controls were analyzed. PON activity was found to be highest in healthy individuals (177.76 ± 4.44 U/mL) as compared to treated (52.67 ± 3.65 U/mL) and untreated (55.11 ± 3.26 U/mL) patients. A similar trend was observed in the case of arylesterase activity in normal, β-thalassemia-treated, and untreated (210.0 ± 11.25 U/mL, 163.03 ± 9.04 U/mL, 139.77 ± 10.10 U/mL) subjects. Serum MDA concentrations (2.59 ± 0.09 nmol/mL, 2.45 ± 0.08 nmol/mL, and 1.15 ± 0.05 nmol/mL) and total ROS concentrations (3.73 ± 0.20 nmol/mL, 3.54 ± 0.23 nmol/mL, and 2.45 ± 0.14 nmol/mL) were significantly elevated in both groups (untreated and treated) as compared to healthy individuals (P < .01). Oxidative stress was found to be markedly elevated in β-thalassemia patients as compared to healthy controls. Insignificant differences were, however, observed in mean concentrations of PON1 paraoxonase and arylesterase activities, serum MDA concentration and total ROS concentrations between HU-treated and untreated patients. We propose that HU therapy alone seems to be ineffective in managing oxidative stress and is likely to offer a better clinical outcome when supplemented with efficient iron chelation therapy and antioxidants.

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Mainly determination focused on examining the 'underemployment 'via exploring its relationship with 'turnover intention'. Furthermore, the other variable 'job deprivation' was analyzed as a mediator for said relationship. In addition, the moderating role of 'job stress' was also premeditated for underemployment and job deprivation. Our targeted audience for this research article was "Traffic Police Wardens" (TPW). We have collected sample data from three cities of Punjab province (1) Lahore, (2) Multan, & (3) Bahawalpur. The population was the whole of Pakistan. Data was collected with the help of a questionnaire via cross-sectional data. 600 were distributed and received N= 499 which were completed by all aspects. The CFA was carried out in SEM (Structural Equation Model), whereas the data was analyzed in SPSS, on the 22nd version. The statistical analysis of this research article retrospection that Cronbach alpha (α) > 0.72 among all variables which are presenting the highest reliability. Further, we check the correlation of the variables among each other, and we found that the dependent variable (DV) is positively correlated to independent variables (IV) because 'underemployment in turnover intention is positively correlated with job deprivation and job stresses. Results of this research article demonstrate that correlation values were r = >0.5 and Regression’s values p = <0.01. It indicates that there was a positive and significant effect of underemployment on turnover intention. The findings also support job deprivation as an intervening mechanism for the relation of underemployment and turnover intention. In addition, job stress acts as a moderator for the relationship between underemployment and job deprivation. The study concludes with a discussion, limitations, and future research directions including implications both for theory and practitioners. JEL Classification Codes:  O15.

Despite high prevalence and incidence of β-thalassemia in Pakistan, there is very limited work on the use of hydroxyurea (HU) in thalassemia patients in the country. This is the first insight regarding genetic profiling of BCL11A and HU responses in Pakistani β-thalassemia. It correlates single-nucleotide polymorphisms on BCL11A (rs4671393, rs766432) and HBG2 (XmnI), age at first transfusion, and β-globin mutations with HU response in β-thalassemia major (BTM). Of 272 patients treated with HU, 98 were complete responders, 55 partial responders, and 119 nonresponders. Our analysis shows that HU response was significantly associated with patients having IVSI-1 or CD 30 mutation (P < 0.001), age at first transfusion > 1 year (P < 0.001), and with the presence of XmnI polymorphism (P < 0.001). The single-nucleotide polymorphisms of BCL11A were more prevalent among responders, but could not show significant association with HU response (P > 0.05). Cumulative effect of all 5 predicting factors through simple binary scoring indicates that the likelihood of HU response increases with the number of primary and secondary genetic modifiers (P < 0.001). Predictors scoring is a pragmatic tool to foresee HU response in patients with BTM. The authors recommend a score of ≥ 2 for starting HU therapy in Pakistani patients with BTM.

Long-standing research efforts have enabled the widespread introduction of organic field-effect transistors (OFETs) in next-generation technologies. Concurrently, environmental and operational stability is the major bottleneck in commercializing OFETs. The underpinning mechanism behind these instabilities is still elusive. Here we demonstrate the effect of ambient air on the performance of p-type polymer field-effect transistors. After exposure to ambient air, the device showed significant variations in performance parameters for around 30 days, and then relatively stable behaviour was observed. Two competing mechanisms influencing environmental stability are the diffusion of moisture and oxygen in the metal–organic interface and the active organic layer of the OFET. We measured the time-dependent contact and channel resistances to probe which mechanism is dominant. We found that the dominant role in the degradation of the device stability is the channel resistance rather than the contact resistance. Through time-dependent Fourier transform infrared (FTIR) analysis, we systematically prove that moisture and oxygen cause performance variation in OFETs. FTIR spectra revealed that water and oxygen interact with the polymer chain and perturb its conjugation, thus resulting in degraded performance of the device upon prolonged exposure to ambient air. Our results are important in addressing the environmental instability of organic devices.