Developing Bayesian EWMA chart for change detection in the shape parameter of Inverse Gaussian process.

Bayesian Control charts are emerging as the most efficient statistical tools for monitoring manufacturing processes and providing effective control over process variability. The Bayesian approach is particularly suitable for addressing parametric uncertainty in the manufacturing industry. In this study, we determine the monitoring threshold for the shape parameter of the Inverse Gaussian distribution (IGD) and design different exponentially-weighted-moving-average (EWMA) control charts based on different loss functions (LFs). The impact of hyperparameters is investigated on Bayes estimates (BEs) and posterior risks (PRs). The performance measures such as average run length (ARL), standard deviation of run length (SDRL), and median of run length (MRL) are employed to evaluate the suggested approach. The designed Bayesian charts are evaluated for different settings of smoothing constant of the EWMA chart, different sample sizes, and pre-specified false alarm rates. The simulative study demonstrates the effectiveness of the suggested Bayesian method-based EWMA charts as compared to the conventional classical setup-based EWMA charts. The proposed techniques of EWMA charts are highly efficient in detecting shifts in the shape parameter and outperform their classical counterpart in detecting faults quickly. The proposed technique is also applied to real-data case studies from the aerospace manufacturing industry. The quality characteristic of interest was selected as the monthly industrial production index of aircraft from January 1980 to December 2022. The real-data-based findings also validate the conclusions based on the simulative results.

The 3-component mixture of power distributions under Bayesian paradigm with application of life span of fatigue fracture.

Mixture distributions are naturally extra attractive to model the heterogeneous environment of processes in reliability analysis than simple probability models. This focus of the study is to develop and Bayesian inference on the 3-component mixture of power distributions. Under symmetric and asymmetric loss functions, the Bayes estimators and posterior risk using priors are derived. The presentation of Bayes estimators for various sample sizes and test termination time (a fact of time after that test is terminated) is examined in this article. To assess the performance of Bayes estimators in terms of posterior risks, a Monte Carlo simulation along with real data study is presented.

Radicalisation studies: An emerging interdisciplinary field.

This research note provides an overview of Radicalisation Studies as an emerging interdisciplinary field aimed at developing more holistic understandings of how and why individuals and groups turn to extreme ideologies and political violence. It traces the evolution of radicalisation research across core social science disciplines, including sociology, psychology, anthropology, and political science. While this burgeoning scholarship has expanded knowledge, persistent gaps remain due to studying radicalisation in disciplinary silos. To address this fragmentation, the research note proposes an integrated Radicalisation Studies approach grounded in critical social theory and reflexivity. This paradigm synthesises concepts and mechanisms from across disciplines to investigate the complex interplay between individual vulnerabilities, group dynamics, and broader socio-political contexts in generating radicalisation. The note outlines theoretical foundations, guiding research questions, and methodological strategies for this new field focused on mixed-methods, multi-level analysis. Radicalisation Studies holds promise for advancing theoretical integration, contextualised explanations, critical perspectives on radicalisation discourse, and evidence-based preventative policies. While challenges remain in institutionalising this emerging field, Radicalisation Studies has the potential to steer research towards greater interdisciplinarity and the nuanced understandings necessary to elucidate this complex phenomenon. The research note aims to spur debate on constructing Radicalisation Studies as a viable scholarly enterprise.

Liver Metastases and Immune Checkpoint Inhibitor Efficacy in Patients With Refractory Metastatic Colorectal Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Immune checkpoint inhibitors (ICIs) have limited activity in microsatellite-stable (MSS) or mismatch repair-proficient (pMMR) colorectal cancer. Recent findings suggest the efficacy of ICIs may be modulated by the presence of liver metastases (LM). Objective: To investigate the association between the presence of LM and ICI activity in advanced MSS colorectal cancer. Design, Setting, and Participants: In this secondary analysis of the Canadian Cancer Trials Group CO26 (CCTG CO.26) randomized clinical trial, patients with treatment-refractory colorectal cancer were randomized in a 2:1 fashion to durvalumab plus tremelimumab or best supportive care alone between August 10, 2016, and June 15, 2017. The primary end point was overall survival (OS) with 80% power and 2-sided α = .10. The median follow-up was 15.2 (0.2-22.0) months. In this post hoc analysis performed from February 11 to 14, 2022, subgroups were defined based on the presence or absence of LM and study treatments. Intervention: Durvalumab plus tremelimumab or best supportive care. Main Outcomes and Measures: Hazard ratios (HRs) and 90% CIs were calculated based on a stratified Cox proportional hazards regression model. Plasma tumor mutation burden at study entry was determined using a circulating tumor DNA assay. The primary end point of the study was OS, defined as the time from randomization to death due to any cause; secondary end points included progression-free survival (PFS) and disease control rate (DCR). Results: Of 180 patients enrolled (median age, 65 [IQR, 36-87] years; 121 [67.2%] men; 19 [10.6%] Asian, 151 [83.9%] White, and 10 [5.6%] other race or ethnicity), LM were present in 127 (70.6%). For patients with LM, there was a higher proportion of male patients (94 of 127 [74.0%] vs 27 of 53 [50.9%]; P = .005), and the time from initial cancer diagnosis to study entry was shorter (median, 40 [range, 8-153] vs 56 [range, 14-181] months; P = .001). Plasma tumor mutation burden was significantly higher in patients with LM. Patients without LM had significantly improved PFS with durvalumab plus tremelimumab (HR, 0.54 [90% CI, 0.35-0.96]; P = .08; P = .02 for interaction). Disease control rate was 49% (90% CI, 36%-62%) in patients without LM treated with durvalumab plus tremelimumab, compared with 14% (90% CI, 6%-38%) in those with LM (odds ratio, 5.70 [90% CI, 1.46-22.25]; P = .03). On multivariable analysis, patients without LM had significantly improved OS and PFS compared with patients with LM. Conclusions and Relevance: In this secondary analysis of the CCTG CO.26 study, the presence of LM was associated with worse outcomes for patients with advanced colorectal cancer. Patients without LM had improved PFS and higher DCR with durvalumab plus tremelimumab. Liver metastases may be associated with poor outcomes of ICI treatment in advanced colorectal cancer and should be considered in the design and interpretation of future clinical studies evaluating this therapy.

Evaluation of nanoceria on cadmium uptake in Triticum aestivum (L.) and its implications for dietary health risk.

In recent times, significant attention has been directed toward the synthesis and application of nanoparticles (NPs) in agriculture sector. In current study, nanoceria (CeO2 NPs) synthesized by green method were employed to address cadmium (Cd) accumulation in wheat (Triticum aestivum L.) cultivated in field with excess Cd. The application of CeO2 NPs was carried out through foliar spraying, performed twice during the growth of T. aestivum. Four levels of CeO2 NPs were used: T0, T1, T2, and T3 as 0, 50, 75, and 100 mgL-1, respectively. Results highlighted the positive effects of CeO2 NPs on various growth parameters, including plant height, spike length, photosynthetic related attributes, as well as straw and grain of grains in comparison to T1 (control group). Furthermore, CeO2 NPs led to a reduction in oxidative stress in the leaves and enhanced in enzyme activities in comparison to T1. Notably, Cd concentrations in straw, roots, and grains exhibited a decline following the treatment with CeO2 NPs, in contrast to the control group. In terms of health implications, the calculated health risk index associated with dietary consumption of grains by adults remained below the defined threshold with supply of nanoparticles. Foliar application of CeO2 NPs proved to be an effective approach in reducing cadmium content in wheat grains. This reduction holds significant potential for minimizing the risk of cadmium exposure to human health through the food chain. Employing the green synthesis method amplifies the potential for extensive production and a wide array of environmental applications for CeO2 NPs. This dual capacity makes them proficient in tackling environmental stresses while concurrently mitigating adverse ecological effects.

Comparative efficacy of silicon and iron oxide nanoparticles towards improving the plant growth and mitigating arsenic toxicity in wheat (Triticum aestivum L.).

Nano-enabled agriculture has emerged as an attractive approach for facilitating soil pollution mitigation and enhancing crop production and nutrition. In this study, we conducted a greenhouse experiment to explore the efficacy of silicon oxide nanoparticles (SiONPs) and iron oxide nanoparticles (FeONPs) in alleviating arsenic (As) toxicity in wheat (Triticum aestivum L.) and elucidated the underlying mechanisms involved. The application of SiONPs and FeONPs at 25, 50, and 100 mg kg-1 soil concentration significantly reduced As toxicity and concurrently improved plant growth performance, including plant height, dry matter, spike length, and grain yield. The biochemical analysis showed that the enhanced plant growth was mainly due to stimulated antioxidative enzymes (catalase, superoxide dismutase, peroxidase) and reduced reactive oxygen species (electrolyte leakage, malondialdehyde, and hydrogen peroxide) in wheat seedlings under As stress upon NPs application. The nanoparticles (NPs) exposure also enhanced the photosynthesis efficiency, including the total chlorophyll and carotenoid contents as compared with the control treatment. Importantly, soil amendments with 100 mg kg-1 FeONPs significantly reduced the acropetal As translocation in the plant root, shoot and grains by 74%, 54% and 78%, respectively, as compared with the control treatment under As stress condition, with relatively lower reduction levels (i.e., 64%, 37% and 58% for the plant root, shoot and grains, respectively) for SiONPs amendment. Overall, the application of NPs especially the FeONPs as nanoferlizers for agricultural crops is a promising approach towards mitigating the negative impact of HMs toxicity, ensuring food safety, and promoting future sustainable agriculture.

Effect of green synthesized cerium oxide nanoparticles on fungal disease of wheat plants: A field study.

Recently, there has been considerable attention towards the production of environmentally friendly nanoparticles (NPs). In this investigation, the successful synthesis of cerium oxide nanoparticles (CeO2 NPs) was achieved by employing an eco-friendly technique that utilized an extract from the leaves of local plant quinoa (Chenopodium quinoa L.). The synthesized CeO2 NPs were subjected to characterization using state-of-the-art methods. The prepared CeO2 NPs contained a round shape with clusters and have a size of 7-10 nm. To assess how effective CeO2 NPs derived from C. quinoa were against Ustilago tritici, a fungal disease that negatively affects wheat crop globally, a study was performed on two varieties of wheat crop comprised of Arooj (V1) and Akber (V2), cultivated under field conditions. CeO2 NPs were applied foliarly twice to the wheat crop at four different concentrations: T0 (0 mg/L), T1 (50 mg/L), T2 (75 mg/L), and T3 (100 mg/L). The results revealed that the control group (T0) exhibited the highest disease severity index (DSI) with a value of 75% compared to the other concentrations of CeO2 NPs on both varieties. At a concentration of 100 mg/L of CeO2 NPs, the DSI dropped to a minimum of 35% and 37% on both V1 and V2 respectively. These findings indicated that an increase in the concentration of CeO2 NPs has a beneficial impact on disease severity. Similar patterns have also been observed with disease incidence (DI), with the greatest efficacy observed at a concentration of 100 mg/L of CeO2 NPs. Our investigation has shown that CeO2 NPs exhibitd significant antifungal potential against U. tritici which may be a promising strategy to mitigate fungal disease and crop losses globally.

Performance evaluation of DEWMA3 in phase-II for capturing changes in simple linear profiles based on run rule mechanism.

In Statistical Process Control, many techniques exist for monitoring the stability of a process over time. In this work, we study the relationship of the response variable with explanatory variables in the form of linear profiles for detecting changes in slope and intercept of the linear quality profiles. We used the transformation of explanatory variables approach used for make the regression estimates independent of each other to have zero average. A comparative study of three phase-II methods using DEWMA statistics in monitoring and capturing undesirable deviations in the slope, intercept, and variability is also studied by applying different proposed run rules schemes i.e., R1/1, R2/3, R3/3. Monte Carlo simulations were carried out on R-Software for finding the results of proposed schemes by taking various levels of shifts for intercept, slope, and standard deviation in identifying the false alarm rate of a process. The simulation results based on the average run length criterion show that the proposed run rule schemes improve the detection ability of the control structure. Among all the proposed schemes R2/3 is found to be the best one because of its quick detection ability of false alarm rate. The proposed scheme also shows superiority in comparison to other schemes. The simulation results are further justified with a real data application.

Effect of soil texture and zinc oxide nanoparticles on growth and accumulation of cadmium by wheat: a life cycle study.

Cadmium (Cd) is getting worldwide attention due to its continuous accumulation in agricultural soils which is due to anthropogenic activities and finally Cd enters in food chain mainly through edible plants. Cadmium free food production on contaminated soils is great challenge which requires some innovative measures for crop production on such soils. The current study evaluated the efficiency of zinc oxide nanoparticles (ZnONPs) (0, 150 and 300 mg/kg) on the growth of wheat in texturally different soils including clay loam (CL), sandy clay loam (SCL), and sandy loam (SL) which were contaminated with were contaminated with 25 mg/kg of Cd before crop growth. Results depicted that doses of ZnONPs and soil textures significantly affected the biological yields, Zn and Cd uptake in wheat plants. The application of 300 mg/kg ZnONPs caused maximum increase in dry weights of shoot (66.6%), roots (58.5%), husk (137.8%) and grains (137.8%) in CL soil. The AB-DTPA extractable Zn was increased while Cd was decreased with doses of NPs depending upon soil textures. The maximum decrease in AB-DTPA extractable Cd was recorded in 300 mg/kg of ZnONPs treatment which was 58.7% in CL, 33.2% in SCL and 12.1% in SL soil as compared to respective controls. Minimum Cd concentrations in roots, shoots, husk and grain were found in 300 mg/kg ZnONPs amended CL soil which was 58%, 76.7%, 58%, and 82.6%, respectively. The minimum bioaccumulation factor (0.14), translocation index (2.46) and health risk index (0.05) was found in CL soil with the highest dose of NPs. The results concluded that use of ZnONPs significantly decreased Cd concentration while increased Zn concentrations in plants depending upon doses of NPs and soil textures.

Patient and Physician Satisfaction with Telemedicine in Cancer Care in Saskatchewan: A Cross-Sectional Study.

Background: Telemedicine is a useful tool that connects patients to their care team remotely and improves access to medical care for rural residents. This study aimed to determine the telemedicine experience of both rural patients with cancer and their physicians, and to explore factors associated with a positive patient experience. Methods: In this cross-sectional study, cancer patients and physicians in Saskatchewan completed a paper-based survey composed of 32 items or an electronic survey of 18 items, respectively. Logistic regression analysis was performed to assess patient satisfaction in relation to various sociodemographic and cancer-related factors. Results: Overall, 25 physicians and 165 patients participated in the study. Among the physicians, 94% were confident in their telemedicine assessment, 58% agreed that telemedicine improved clinical efficiency, and 73% agreed that doctor−patient rapport was unimpaired with telemedicine. Of 165 patients, 61% had used telemedicine for the first time, 81% felt that their needs were met, 83% were satisfied with the quality of their care, and 88% had a positive experience. Overall, 83% patients vs. 45% physicians preferred telemedicine to a face-to-face clinic visit (p = 0.005). On univariate analysis, patients ≥ 65 years old had a greater positive telemedicine experience compared to patients < 65 years old (odds ratio 4.1 [1.2−13.8], p = 0.02). Conclusion: Both patients and physicians have a high rate of positive experiences with telemedicine. However, patients have a higher preference for telemedicine over face-to-face visits compared to physicians. In addition, elderly patients have more positive telemedicine experiences compared to younger patients.

Effect of Combined Immune Checkpoint Inhibition vs Best Supportive Care Alone in Patients With Advanced Colorectal Cancer: The Canadian Cancer Trials Group CO.26 Study.

Importance: Single-agent immune checkpoint inhibition has not shown activities in advanced refractory colorectal cancer (CRC), other than in those patients who are microsatellite-instability high (MSI-H). Objective: To evaluate whether combining programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition improved patient survival in metastatic refractory CRC. Design, Setting, and Participants: A randomized phase 2 study was conducted in 27 cancer centers across Canada between August 2016 and June 2017, and data were analyzed on October 18, 2018. Eligible patients had histologically confirmed adenocarcinoma of the colon or rectum; received all available standard systemic therapies (fluoropyrimidines, oxaliplatin, irinotecan, and bevacizumab if appropriate; cetuximab or panitumumab if RAS wild-type tumors; regorafenib if available); were aged 18 years or older; had adequate organ function; had Eastern Cooperative Oncology Group performance status of 0 or 1, and measurable disease. Interventions: We randomly assigned patients to receive either 75 mg of tremelimumab every 28 days for the first 4 cycles plus 1500 mg durvalumab every 28 days, or best supportive care alone (BSC) in a 2:1 ratio. Main Outcomes and Measures: The primary end point was overall survival (OS) and a 2-sided P<.10 was considered statistically significant. Circulating cell-free DNA from baseline plasma was used to determine microsatellite instability (MSI) and tumor mutation burden (TMB). Results: Of 180 patients enrolled (121 men [67.2%] and 59 women [32.8%]; median [range] age, 65 [36-87] years), 179 were treated. With a median follow-up of 15.2 months, the median OS was 6.6 months for durvalumab and tremelimumab and 4.1 months for BSC (hazard ratio [HR], 0.72; 90% CI, 0.54-0.97; P = .07). Progression-free survival was 1.8 months and 1.9 months respectively (HR, 1.01; 90% CI, 0.76-1.34). Grade 3 or 4 adverse events were significantly more frequent with immunotherapy (75 [64%] patients in the treatment group had at least 1 grade 3 or higher adverse event vs 12 [20%] in the BSC group). Circulating cell-free DNA analysis was successful in 168 of 169 patients with available samples. In patients who were microsatellite stable (MSS), OS was significantly improved with durvalumab and tremelimumab (HR, 0.66; 90% CI, 0.49-0.89; P = .02). Patients who were MSS with plasma TMB of 28 variants per megabase or more (21% of MSS patients) had the greatest OS benefit (HR, 0.34; 90% CI, 0.18-0.63; P = .004). Conclusions and Relevance: This phase 2 study suggests that combined immune checkpoint inhibition with durvalumab plus tremelimumab may be associated with prolonged OS in patients with advanced refractory CRC. Elevated plasma TMB may select patients most likely to benefit from durvalumab and tremelimumab. Further confirmation studies are warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02870920.

Crowd of Oz: A Crowd-Powered Social Robotics System for Stress Management.

Coping with stress is crucial for a healthy lifestyle. In the past, a great deal of research has been conducted to use socially assistive robots as a therapy to alleviate stress and anxiety related problems. However, building a fully autonomous social robot which can deliver psycho-therapeutic solutions is a very challenging endeavor due to limitations in artificial intelligence (AI). To overcome AI's limitations, researchers have previously introduced crowdsourcing-based teleoperation methods, which summon the crowd's input to control a robot's functions. However, in the context of robotics, such methods have only been used to support the object manipulation, navigational, and training tasks. It is not yet known how to leverage real-time crowdsourcing (RTC) to process complex therapeutic conversational tasks for social robotics. To fill this gap, we developed Crowd of Oz (CoZ), an open-source system that allows Softbank's Pepper robot to support such conversational tasks. To demonstrate the potential implications of this crowd-powered approach, we investigated how effectively, crowd workers recruited in real-time can teleoperate the robot's speech, in situations when the robot needs to act as a life coach. We systematically varied the number of workers who simultaneously handle the speech of the robot (N = 1, 2, 4, 8) and investigated the concomitant effects for enabling RTC for social robotics. Additionally, we present Pavilion, a novel and open-source algorithm for managing the workers' queue so that a required number of workers are engaged or waiting. Based on our findings, we discuss salient parameters that such crowd-powered systems must adhere to, so as to enhance their performance in response latency and dialogue quality.

Diabetes in Pakistan: A systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was assess the time trend of the prevalence of prediabetes and diabetes and risk factors associated with diabetes in Pakistan by using a systematic review and meta-analysis. METHODS: A systematic literature search of Embase, PubMed, and the Cochrane library was carried out between January 1, 1995 and August 30, 2018. Diabetes and prediabetes prevalence estimates were combined by the random-effects model. The existence of publication bias was tested by Egger regression. This systematic review was reported following the PRISMA guidelines. RESULTS: The search conceded a total of 635 studies, only 14 studies were considered for meta-analysis. The prevalence of diabetes in Pakistan was revealed 14.62% (10.651%-19.094%; 14 studies) based on 49,418 people using the inverse-variance random-effects model. The prevalence of prediabetes was 11.43% (8.26%-15.03%; 10 studies) based on a total sample of 26,999 people. The risk factors associated with diabetes were mean age (ß = 0.48%, 95% CI: 0.21-0.78, p<0.001), the proportion of participants with a family history of diabetes (ß = 0. 45%, 95% CI: 0.08-0.82, p =0.018, p<0.001), hypertension (ß = 0.40%, 95% CI: 0.06-0.75, p = 0.022), weight (BMI) (ß = 0.21%, 95% CI: 0.02-0.4, p=0.030). CONCLUSIONS: There has been a continuous increase in the prevalence of prediabetes and diabetes in Pakistan. All parts of the country have been affected, with the highest in Sindh and lowest in Khyber Pakhtunkhwa. The main factors include growing age, family history, hypertension and obesity. A nationwide diabetes care survey on risk factors and prevention policy is highly recommended.

Cardiac tamponade induced by dabrafenib and trametinib combination therapy for melanoma: Case report.

RATIONALE: BRAF and MEK inhibitors (BRAF/MEKi) are targeted therapy for proto-oncogene BRAF mutated metastatic unresectable melanoma. Compared to monotherapy, an increased cardiovascular toxicity is reported with the combination of Dabrafenib and Trametinib. This case report documents Grade 4 cardiac treatment emergent adverse effect of pericardial effusion and cardiac tamponade induced by this combination therapy. PATIENT CONCERNS: A 52 year old man presented with clinical stage II unresectable melanoma with BRAF mutation, was initiated on treatement with Dabrafenib and Trametinib. He complained of generalised edema and increased his weight by 27 kg. This progressed to shortness of breath and he underwent echocardiogram which revealed cardiac tamponade. DIAGNOSES: Emergent pericardiocentesis was performed. No definited pathology was demonstrated in laboratory analysis of pericardial fluid. Re- initiating treatment resulted in cardiac tamponade and pericardiotomy was performed by video-assisted thoracic surgical (VATS). Pericardial biopsy revealed nonspecific chronic inflammation. INTERVENTIONS: Discontinuation of treatment with Dabrafenib and Trametinib and diuretics resolved peripheral edema. Cardiac function normalized after pericardiocentesis and pericardiotomy. OUTCOMES: Treatment with Dabrafenib and Trametinib caused significant peripheral edema and pericardial effusion resulting in cardiac tamponade. Naranjo score suggests probable association of treatment induced pericardial effusion and cardiac tamponade. LESSONS: This is the first documented report of pericardial effusion and cardiac tamponade induced by Dabrafenib and Trametinib. Cardiac toxicity of BRAF/MEK inhibitors is rare but clinicans must monitor for treatment emergent adverse effects.

Effect of biochar on alleviation of cadmium toxicity in wheat (Triticum aestivum L.) grown on Cd-contaminated saline soil.

Soil degradation by salinity and accumulation of trace elements such as cadmium (Cd) in the soils are expected to become one of the most critical issues hindering sustainable production and feeding the increasing population. Biochar (BC) has been known to protect the plants against soil salinity and heavy metal stress. A soil culture study was performed to evaluate the effect of BC on wheat (Triticum aestivum L.) growth, biomass, and reducing Cd and sodium (Na) uptake grown in Cd-contaminated saline soil under ambient conditions. Soil salinity decreased the plant growth, biomass, grain yield, chlorophyll contents, and gas exchange parameters and caused oxidative stress in plants compared with Cd stress alone. Salt stress increased Cd and Na uptake and reduced the potassium (K) and zinc (Zn) uptake by plants. AB-DTPA-extractable Cd and soil electrical conductivity (ECe) increased under salt stress compared to the soil without NaCl stress. Biochar application improved the plant growth and reduced the Cd and Na uptake except in plants treated with higher BC and salt stress (5.0% BC + 50 mM NaCl). Biochar application reduced the oxidative stress in plants and modified the antioxidant enzyme activities, and reduced the bioavailable Cd under salt stress. The positive effects of BC under lower salt stress while the negative effects of BC under higher BC and salt levels indicated that BC doses should be used with great care in higher soil salinity levels simultaneously contaminated with Cd to avoid the negative effects of BC on growth and metal uptake.

Biochar application increased the growth and yield and reduced cadmium in drought stressed wheat grown in an aged contaminated soil.

Cadmium (Cd) and drought stress in plants is a worldwide problem, whereas little is known about the effect of biochar (BC) under combined Cd and drought stress. The current study was conducted to determine the impact of BC on Cd uptake in wheat sown in Cd-contaminated soil under drought stress. Wheat was grown in a soil after incubating the soil for 15 days with three levels of BC (0%, 3.0% and 5.0% w/w). Three levels of drought stress (well-watered, mild drought and severe drought containing 70%, 50%, and 35% of soil water holding capacity respectively) were applied to 45-d-old wheat plants. Drought stress decreased plant height, spike length, chlorophyll contents, gas exchange parameters, root and shoot dry biomasses and grain yields. Drought stress also caused oxidative stress and decreased the antioxidant enzymes activities whereas increased the Cd concentration in plants. Biochar increased morphological and physiological parameters of wheat under combined drought and Cd stress and reduced the oxidative stress and Cd contents and increased antioxidant enzymes activities. The decrease in Cd concentration with BC application in drought-stressed plant might be attributed to BC-induced increase in crop biomass production and reduction in oxidative stress. These results indicate that BC could be used as an amendment in metal contaminated soil for improving wheat growth and reducing Cd concentrations under semiarid conditions.

Residual effects of biochar on growth, photosynthesis and cadmium uptake in rice (Oryza sativa L.) under Cd stress with different water conditions.

Soil cadmium (Cd) contamination and drought stress are among the main issues hindering global food security. Biochar has been used to reduce metal uptake by plants and water stress mitigation, but long-term residual effects of biochar under Cd stress at different moisture levels needs to be investigated. A following rice (Oryza sativa L.) was grown after wheat on Cd-contaminated soil amended with different levels of biochar (0, 3.0, and 5.0%, w/w). Thirty five days old plants were irrigated with three moisture levels including zero drought as a control (1-2 cm water layer on soil), mild drought (MD, 50% of soil water holding capacity, WHC), and severe drought (SD, 35% of soil WHC) for an accompanying 35 days. Plant height, biomass and photosynthesis were reduced whereas oxidative stress increased under MD and SD than control in un-amended soil while opposite trends were observed in plants grown in biochar amended soil. At the same biochar addition, Cd concentrations in seedlings were lower in continuous flooding than MD and SD treatments. The biochar supply reduced the bioavailable Cd in the soil whereas increased the soil EC and pH than the control treatment. In conclusion, continuous flooding plus residual biochar can be strategized in mitigating Cd-contamination in paddy soils and decreased Cd concentrations in rice which may reduce the potential risks to humans.

Outcomes and Drug Costs of Sunitinib Regimens for Metastatic Renal Cell Carcinoma: A Provincial Population-Based Study.

BACKGROUND: Conventional sunitinib dosing in metastatic renal cell carcinoma (mRCC) administers 50 mg daily on a 4 weeks on/2 weeks off (4/2) schedule. Not all patients tolerate this regimen and many undergo modifications to schedule, dose, or both. MATERIAL AND METHODS: All patients with mRCC treated with sunitinib by the Saskatchewan Cancer Agency between January 1, 2006, and January 1, 2013, were included. Regimens were categorized as standard intermittent dosing (SID), modified intermittent schedule (MIS), modified intermittent dosing (MID), combination of modified schedule and dosing (MSD), or continuous dosing (CD). The primary objective was to compare overall survival (OS) between regimens. Secondary outcomes included progression-free survival (PFS), discontinuation due to adverse effects (AE), and medication cost. RESULTS: Among 161 patients, 18.0%, 51.6%, and 30.4% had favorable, intermediate, and poor Heng risk prognoses, respectively. A total of 140 (87.0%) received sunitinib as first-line therapy. MID was associated with longer OS compared with SID (estimated median 28.4 vs. 11.2 months). PFS was longer for MID, MSD, and CD compared with SID (estimated median 12.0, 9.0, and 8.0 months vs. 3.0 months, respectively). Adjustment for potential confounders did not negate these associations. SID also had higher average monthly drug costs than MIS, MID, and MSD. Overall discontinuation rate due to AE was high (24%). CONCLUSION: An adjusted-dose sunitinib regimen is associated with improved OS and PFS over SID, with lower costs. The development of toxicities requiring dose reductions serves as a predictive biomarker for better outcomes.

Effect of biochar on cadmium bioavailability and uptake in wheat (Triticum aestivum L.) grown in a soil with aged contamination.

Cadmium (Cd) is a well-known and widespread toxic heavy metal while the effects of biochar (BC) on Cd bioavailability and toxicity in wheat, especially in soils with aged contamination are largely unknown. In the present study, the effect of rice straw BC on Cd immobilization in soil and uptake by wheat in an agricultural contaminated-soil was investigated. Different levels of rice straw BC (0%, 1.5%, 3.0% and 5% w/w) were incorporated into the soil and incubated for two weeks. After this, wheat plants were grown in the amended soil until maturity. The results show that the BC treatments increased the soil and soil solution pH and silicon contents in the plant tissues and in the soil solution while decreased the bioavailable Cd in soil. The BC application increased the plant-height, spike-length, shoot and root dry mass and grain yield in a dose additive manner when compared with control treatment. As compared to control, BC application increased the photosynthetic pigments and gas exchange parameters in leaves. Biochar treatments decreased the oxidative stress while increased the activities of antioxidant enzymes in shoots compared to the control. The BC treatments decreased the Cd and Ni while increased Zn and Mn concentrations in shoots, roots, and grains of wheat compared to the control. As compared to the control, Cd concentration in wheat grains decreased by 26%, 42%, and 57% after the application of 1.5%, 3.0%, and 5.0% BC respectively. Overall, the application of rice straw BC might be effective in immobilization of metal in the soil and reducing its uptake and translocation to grains.