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BackgroundSTAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL).Methods and findingsPatients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively.ConclusionsProstate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC.Trial registrationClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544.

Background STAMPEDE previously reported adding upfront docetaxel improved overall survival for prostate cancer patients starting long-term androgen deprivation therapy. We report long-term results for non-metastatic patients using, as primary outcome, metastatic progression-free survival (mPFS), an externally demonstrated surrogate for overall survival. Methods Standard of care (SOC) was androgen deprivation therapy with or without radical prostate radiotherapy. A total of 460 SOC and 230 SOC plus docetaxel were randomly assigned 2:1. Standard survival methods and intention to treat were used. Treatment effect estimates were summarized from adjusted Cox regression models, switching to restricted mean survival time if non-proportional hazards. mPFS (new metastases, skeletal-related events, or prostate cancer death) had 70% power (α = 0.05) for a hazard ratio (HR) of 0.70. Secondary outcome measures included overall survival, failure-free survival (FFS), and progression-free survival (PFS: mPFS, locoregional progression). Results Median follow-up was 6.5 years with 142 mPFS events on SOC (3 year and 54% increases over previous report). There was no good evidence of an advantage to SOC plus docetaxel on mPFS (HR = 0.89, 95% confidence interval [CI] = 0.66 to 1.19; P = .43); with 5-year mPFS 82% (95% CI = 78% to 87%) SOC plus docetaxel vs 77% (95% CI = 73% to 81%) SOC. Secondary outcomes showed evidence SOC plus docetaxel improved FFS (HR = 0.70, 95% CI = 0.55 to 0.88; P = .002) and PFS (nonproportional P = .03, restricted mean survival time difference = 5.8 months, 95% CI = 0.5 to 11.2; P = .03) but no good evidence of overall survival benefit (125 SOC deaths; HR = 0.88, 95% CI = 0.64 to 1.21; P = .44). There was no evidence SOC plus docetaxel increased late toxicity: post 1 year, 29% SOC and 30% SOC plus docetaxel grade 3-5 toxicity. Conclusions There is robust evidence that SOC plus docetaxel improved FFS and PFS (previously shown to increase quality-adjusted life-years), without excess late toxicity, which did not translate into benefit for longer-term outcomes. This may influence patient management in individual cases.

Chronic kidney disease (CKD) constitutes a major public health challenge, with a global prevalence of 15-74.7 cases /million children. Preventing CKD in children, slowing its progression and management of complications are essential, especially in challenged health systems in low middle income countries (LMIC). We conducted a retrospective review to assess the underlying cause and stage of CKD at presentation and clinical outcomes in children and adolescents at the Indus Hospital and Health Network (IHHN) in Karachi, Pakistan. Children 0-16 years with CKD stage 1 and/or higher at presentation were included. Data including demographics, clinical status and lab results at presentation and during follow-up, surgical intervention if any, kidney function at last visit and outcome at last follow-up was recorded. A total of 229 children diagnosed with CKD are included in our study. The median age at diagnosis was 10 years with male: female ratio of 1.8:1. Only 5% children presented in stage 1 CKD. The rate of adverse outcomes is 4.5 times higher in children with CKD stage 3-5 compared to early CKD. Congenital anomaly of kidney and urinary tract (CAKUT) was the underlying cause in 49% children. Children with glomerular disease had comparatively worse outcome. Proteinuria, hypertension, anemia and bone disease were associated with high morbidity and mortality. The true epidemiology of childhood CKD is unknown in Pakistan. Our cohort showed better CKD outcomes in children diagnosed early with appropriate surgical and medical follow-up. Prompt diagnosis, treatment and prevention of progression can be life-saving in our setting. CKD registry data can inform policy changes that can prevent poor outcomes.

Underwater Wireless Sensor Networks (UWSNs) are an enabling technology for many applications in commercial, military, and scientific domains. In some emergency response applications of UWSN, data dissemination is more important, therefore these applications are handled differently as compared to energy-focused approaches, which is only possible when propagation delay is minimized and packet delivery at surface sinks is assured. Packet delivery underwater is a serious concern because of harsh underwater environments and the dense deployment of nodes, which causes collisions and packet loss. Resultantly, re-transmission causes energy loss and increases end-to-end delay ( D E 2 E ). In this work, we devise a framework for the joint optimization of sink mobility, hold and forward mechanisms, adoptive depth threshold ( d t h ) and data aggregation with pattern matching for reducing nodal propagation delay, maximizing throughput, improving network lifetime, and minimizing energy consumption. To evaluate our technique, we simulate the three-dimensional (3-D) underwater network environment with mobile sink and dense deployments of sensor nodes with varying communication radii. We carry out scalability analysis of the proposed framework in terms of network lifetime, throughput, and packet drop. We also compare our framework to existing techniques, i.e., Mobicast and iAMCTD protocols. We note that adapting varying d t h based on node density in a range of network deployment scenarios results in a reduced number of re-transmissions, good energy conservation, and enhanced throughput. Furthermore, results from extensive simulations show that our proposed framework achieves better performance over existing approaches for real-time delay-intolerant applications.

Stock market forecasting is one of the most challenging problems in today’s financial markets. According to the efficient market hypothesis, it is almost impossible to predict the stock market with 100% accuracy. However, Machine Learning (ML) methods can improve stock market predictions to some extent. In this paper, a novel strategy is proposed to improve the prediction efficiency of ML models for financial markets. Nine ML models are used to predict the direction of the stock market. First, these models are trained and validated using the traditional methodology on a historic data captured over a 1-day time frame. Then, the models are trained using the proposed methodology. Following the traditional methodology, Logistic Regression achieved the highest accuracy of 85.51% followed by XG Boost and Random Forest. With the proposed strategy, the Random Forest model achieved the highest accuracy of 91.27% followed by XG Boost, ADA Boost and ANN. In the later part of the paper, it is shown that only classification report is not sufficient to validate the performance of ML model for stock market prediction. A simulation model of the financial market is used in order to evaluate the risk, maximum draw down and returns associate with each ML model. The overall results demonstrated that the proposed strategy not only improves the stock market returns but also reduces the risks associated with each ML model.

Prostate cancer might have high radiation-fraction sensitivity that would give a therapeutic advantage to hypofractionated treatment. We present a pre-planned analysis of the efficacy and side-effects of a randomised trial comparing conventional and hypofractionated radiotherapy after 5 years follow-up. CHHiP is a randomised, phase 3, non-inferiority trial that recruited men with localised prostate cancer (pT1b–T3aN0M0). Patients were randomly assigned (1:1:1) to conventional (74 Gy delivered in 37 fractions over 7·4 weeks) or one of two hypofractionated schedules (60 Gy in 20 fractions over 4 weeks or 57 Gy in 19 fractions over 3·8 weeks) all delivered with intensity-modulated techniques. Most patients were given radiotherapy with 3–6 months of neoadjuvant and concurrent androgen suppression. Randomisation was by computer-generated random permuted blocks, stratified by National Comprehensive Cancer Network (NCCN) risk group and radiotherapy treatment centre, and treatment allocation was not masked. The primary endpoint was time to biochemical or clinical failure; the critical hazard ratio (HR) for non-inferiority was 1·208. Analysis was by intention to treat. Long-term follow-up continues. The CHHiP trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN97182923. Between Oct 18, 2002, and June 17, 2011, 3216 men were enrolled from 71 centres and randomly assigned (74 Gy group, 1065 patients; 60 Gy group, 1074 patients; 57 Gy group, 1077 patients). Median follow-up was 62·4 months (IQR 53·9–77·0). The proportion of patients who were biochemical or clinical failure free at 5 years was 88·3% (95% CI 86·0–90·2) in the 74 Gy group, 90·6% (88·5–92·3) in the 60 Gy group, and 85·9% (83·4–88·0) in the 57 Gy group. 60 Gy was non-inferior to 74 Gy (HR 0·84 [90% CI 0·68–1·03], pNI=0·0018) but non-inferiority could not be claimed for 57 Gy compared with 74 Gy (HR 1·20 [0·99–1·46], pNI=0·48). Long-term side-effects were similar in the hypofractionated groups compared with the conventional group. There were no significant differences in either the proportion or cumulative incidence of side-effects 5 years after treatment using three clinician-reported as well as patient-reported outcome measures. The estimated cumulative 5 year incidence of Radiation Therapy Oncology Group (RTOG) grade 2 or worse bowel and bladder adverse events was 13·7% (111 events) and 9·1% (66 events) in the 74 Gy group, 11·9% (105 events) and 11·7% (88 events) in the 60 Gy group, 11·3% (95 events) and 6·6% (57 events) in the 57 Gy group, respectively. No treatment-related deaths were reported. Hypofractionated radiotherapy using 60 Gy in 20 fractions is non-inferior to conventional fractionation using 74 Gy in 37 fractions and is recommended as a new standard of care for external-beam radiotherapy of localised prostate cancer. Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

This study aimed to determine the potentially toxic metal contents in soil and spinach samples in areas irrigated with industrial wastewater and to evaluate the potentially toxic metal accumulation in spinach samples according to pollution indices. Water, soil and spinach samples were analysed using atomic absorption spectrophotometer (Perkin-Elmer AAS-300). In this study, it was determined that the potentially toxic metal values ​​in the spinach samples irrigated with groundwater and sugar industry wastewater varied between 1.59 and 1.84, 0.22–0.68, 0.56–1.14, 1.41–1.56, 1.62–3.23, 0.57–1.02, 0.86–1.33, 0.20–0.32 and 0.35–2.10 mg/kg for Cd, Co, Cr, Cu, Fe, Ni, Pb, Zn and Mn, respectively. It was concluded that the difference between the metal values ​​in the spinach samples according to the irrigation sources was statistically significant, except for Cu and Pb (p > 0.05). According to the results of this study, there is no health risk for Pb, Co and Cr with HRI values ​​below 1.0, while there is a risk for Cd, Cu, Fe, Ni, Mn and Zn. The much higher HRI values ​​of Cd than 1 (196.8 and 169.6) suggested that this metal is likely to cause significant health problems in the region.

In this paper, a modified form of the Proportional Integral Derivative (PID) controller known as the Integral- Proportional Derivative (I-PD) controller is developed for Automatic Generation Control (AGC) of the two-area multi-source Interconnected Power System (IPS). Fitness Dependent Optimizer (FDO) algorithm is employed for the optimization of proposed controller with various performance criteria including Integral of Absolute Error (IAE), Integral of Time multiplied Absolute Error (ITAE), Integral of Time multiplied Square Error (ITSE), and Integral Square Error (ISE). The effectiveness of the proposed approach has been assessed on a two-area network with individual source including gas, hydro and reheat thermal unit and then collectively with all three sources. Further, to validate the efficacy of the proposed FDO based PID and I-PD controllers, comprehensive comparative performance is carried and compared with other controllers including Differential Evolution based PID (DE-PID) controller and Teaching Learning Based Optimization (TLBO) hybridized with Local Unimodal Sampling (LUS-PID) controller. The comparison of outcomes reveal that the proposed FDO based I-PD (FDO-I-PD) controller provides a significant improvement in respect of Overshoot (Osh), Settling time (Ts), and Undershoot (Ush). The robustness of an I-PD controller is also verified by varying parameter of the system and load variation.

Background & Objectives India is considered a region with intermediate to high endemicity for the carriage of Hepatitis B surface antigen (HBsAg). Epidemiological updates are crucial to monitor the progress towards the global commitment to eliminate hepatitis by 2030. This study was designed to analyse the demographic, epidemiological, laboratory, virological, clinical, and genotypic characteristics of the patients with Chronic Hepatitis B (CHB) in North India. Methods One hundred and eighty-three HBsAg-positive patients were enrolled in the study between October 2019 and October 2022. Inclusion criteria required patients to have HBsAg detectable in serum for more than six months. The genotype of Hepatitis B virus (HBV) was determined by using polymerase chain reaction (PCR)- based method. To validate the findings, 20 samples were selected for HBV DNA polymerase genes (S/POL) sequencing, which is crucial for accurately classifying of the virus and its genotypic characteristics. Sequences were manually edited with the BioEdit Sequence Editor (version 7.2.5) and analysed via BLAST. Results Among 183 HBsAg-positive chronic liver disease patients, 77.5 per cent clinically presented as HBeAg negative chronic hepatitis. The identified genotypes were predominantly D (170; 92.2%), followed by A (11; 6%) and C (2; 1.1%). Of the total patients, 102 (55.7%) were male, with the majority within the 0-45 years age group (83.4%). The most common risk factor was surgical intervention (77; 42.1%), followed by tattooing and body piercing (39; 21.3%), blood transfusion (14; 7.7%), dialysis (33; 18%), mother-to-child transmission (4; 2.2%), IV drug abuse (10; 5.5%), and dental procedures (3; 1.6%). Familial transmission was observed in 11.8 per cent of spouses. Interpretation & conclusions The study highlighted that genotype D was the most prevalent and acquired commonly through the parenteral routes, with severe disease phase, while genotype A was the next frequent genotype associated with vertical or familial spread, with the most patients seen in the immune-tolerant phase.

Widespread acceptance of COVID-19 vaccines is crucial for achieving sufficient immunization coverage to end the global pandemic, yet few studies have investigated COVID-19 vaccination attitudes in lower-income countries, where large-scale vaccination is just beginning. We analyze COVID-19 vaccine acceptance across 15 survey samples covering 10 low- and middle-income countries (LMICs) in Asia, Africa and South America, Russia (an upper-middle-income country) and the United States, including a total of 44,260 individuals. We find considerably higher willingness to take a COVID-19 vaccine in our LMIC samples (mean 80.3%; median 78%; range 30.1 percentage points) compared with the United States (mean 64.6%) and Russia (mean 30.4%). Vaccine acceptance in LMICs is primarily explained by an interest in personal protection against COVID-19, while concern about side effects is the most common reason for hesitancy. Health workers are the most trusted sources of guidance about COVID-19 vaccines. Evidence from this sample of LMICs suggests that prioritizing vaccine distribution to the Global South should yield high returns in advancing global immunization coverage. Vaccination campaigns should focus on translating the high levels of stated acceptance into actual uptake. Messages highlighting vaccine efficacy and safety, delivered by healthcare workers, could be effective for addressing any remaining hesitancy in the analyzed LMICs.