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Project portfolio selection and scheduling problem under material supply uncertainty
No full textIntegrated decision-making across project portfolio selection, scheduling, and material ordering is essential to avoid suboptimal outcomes, including delays, cost overruns, and missed opportunities. However, existing literature overlooks this integration, as well as the significant impact of uncertainty in material supply on decision-making processes. To address these gaps, we propose a robust methodology for integrating these aspects while accounting for uncertainties in material supply. Initially, we present a deterministic optimization model that integrates key decisions of project portfolio selection, project scheduling, and material ordering to maximize the net present value (NPV). We then enhanced this approach by incorporating various sources of uncertainty in material supply, resulting in a robust model. Given the NP-hard nature of the problem, a modified genetic algorithm was employed to solve it efficiently for larger sizes. Results demonstrate that the modified genetic algorithm enhances computational efficiency while maintaining solution quality compared to exact methods. Specifically, it reduces solution time by over 90% for medium-scale problems with an optimality gap of 1%. Implemented on a road construction project in Australia, sensitivity analysis highlights the pivotal role of supplier capacity in project profitability. A potential 20% increase in capacity correlates with a notable 32% increase in NPV, underlining the importance of considering uncertainty in this parameter. Findings demonstrate that the proposed robust approach ensures feasibility and high-quality solutions across various scenarios, offering decision-makers confidence in unpredictable conditions. This study provides a practical roadmap for integrating decision-making processes and managing uncertainty in project management, enhancing adaptability in dynamic environments.Integrated decision-making across project portfolio selection, scheduling, and material ordering is essential to avoid suboptimal outcomes, including delays, cost overruns, and missed opportunities. However, existing literature overlooks this integration, as well as the significant impact of uncertainty in material supply on decision-making processes. To address these gaps, we propose a robust methodology for integrating these aspects while accounting for uncertainties in material supply. Initially, we present a deterministic optimization model that integrates key decisions of project portfolio selection, project scheduling, and material ordering to maximize the net present value (NPV). We then enhanced this approach by incorporating various sources of uncertainty in material supply, resulting in a robust model. Given the NP-hard nature of the problem, a modified genetic algorithm was employed to solve it efficiently for larger sizes. Results demonstrate that the modified genetic algorithm enhances computational efficiency while maintaining solution quality compared to exact methods. Specifically, it reduces solution time by over 90% for medium-scale problems with an optimality gap of 1%. Implemented on a road construction project in Australia, sensitivity analysis highlights the pivotal role of supplier capacity in project profitability. A potential 20% increase in capacity correlates with a notable 32% increase in NPV, underlining the importance of considering uncertainty in this parameter. Findings demonstrate that the proposed robust approach ensures feasibility and high-quality solutions across various scenarios, offering decision-makers confidence in unpredictable conditions. This study provides a practical roadmap for integrating decision-making processes and managing uncertainty in project management, enhancing adaptability in dynamic environments.A
How dialysis frequency and duration impact uremic toxin and fluid removal : a pediatric perspective
No full textThree-weekly 4-h hemodialysis/hemodiafiltration (HD/HDF) per week has become the “standard HD/HDF” regimen in children across the globe, although increasingly criticized, since crucial determinants such as residual kidney function and patient preferences are not considered. As a consequence, several children fail to achieve adequate dialysis while on a “standard HD/HDF.” In these circumstances, an extended dialysis prescription such as short daily (2–3 h/session, 5–7 days a week) or nocturnal HD/HDF (6–9 h/session, 3–5 days a week), either at home or in a dialysis center, may be considered. The purpose of this educational review is to summarize the impact of dialysis duration and frequency on uremic toxin and fluid removal. Moreover, we aim to summarize the existing literature on HD/HDF strategies with extended dialysis duration and/or increased frequency (> 12 h dialysis time per week) in pediatrics. Dialysis duration and frequency plays a crucial role in uremic toxin removal, in particular for uremic toxins with retarded transport in patients, such as phosphate, β2-microglobulin (β2m), and protein-bound uremic toxins. Also, increasing dialysis duration and/or frequency decreases the gap between plasma refilling and ultrafiltration volume), thereby decreasing the need for a high ultrafiltration rate. Observational studies in children demonstrate a beneficial effect of extended dialysis regimens (i.e., more frequent or longer duration) on blood pressure control, left ventricular hypertrophy, growth, and quality of life. PTH levels tend to decrease in the majority of studies, while hypocalcemia or suppressed PTH levels were also reported. Dietary restrictions were decreased or stopped, along with tapering of phosphate binders and potassium chelators. Extended HD/HDF regimens are beneficial in a particular group of children. Pediatric-specific international guidelines are needed to support pediatric nephrologists in determining for which children extended HD regimens are beneficial, along with increasing efforts to decrease the financial, organizational, and psychosocial barriers that are present in extended HD/HDF.Three-weekly 4-h hemodialysis/hemodiafiltration (HD/HDF) per week has become the “standard HD/HDF” regimen in children across the globe, although increasingly criticized, since crucial determinants such as residual kidney function and patient preferences are not considered. As a consequence, several children fail to achieve adequate dialysis while on a “standard HD/HDF.” In these circumstances, an extended dialysis prescription such as short daily (2–3 h/session, 5–7 days a week) or nocturnal HD/HDF (6–9 h/session, 3–5 days a week), either at home or in a dialysis center, may be considered. The purpose of this educational review is to summarize the impact of dialysis duration and frequency on uremic toxin and fluid removal. Moreover, we aim to summarize the existing literature on HD/HDF strategies with extended dialysis duration and/or increased frequency (> 12 h dialysis time per week) in pediatrics. Dialysis duration and frequency plays a crucial role in uremic toxin removal, in particular for uremic toxins with retarded transport in patients, such as phosphate, β2-microglobulin (β2m), and protein-bound uremic toxins. Also, increasing dialysis duration and/or frequency decreases the gap between plasma refilling and ultrafiltration volume), thereby decreasing the need for a high ultrafiltration rate. Observational studies in children demonstrate a beneficial effect of extended dialysis regimens (i.e., more frequent or longer duration) on blood pressure control, left ventricular hypertrophy, growth, and quality of life. PTH levels tend to decrease in the majority of studies, while hypocalcemia or suppressed PTH levels were also reported. Dietary restrictions were decreased or stopped, along with tapering of phosphate binders and potassium chelators. Extended HD/HDF regimens are beneficial in a particular group of children. Pediatric-specific international guidelines are needed to support pediatric nephrologists in determining for which children extended HD regimens are beneficial, along with increasing efforts to decrease the financial, organizational, and psychosocial barriers that are present in extended HD/HDF.A
Dynamics of SARS-CoV-2 IgG in nursing home residents in Belgium throughout three BNT162b2 vaccination rounds : 19-month follow-up
No full textBackground/Objectives: This study mapped antibody dynamics across three COVID-19 vaccination rounds (primary course, first, and second booster with BNT162b2) in Belgian nursing home residents (NHRs). Methods: Within a national SARS-CoV-2 serosurveillance study (February 2021-September 2022) across Belgian nursing homes, dried blood spots were collected, on which anti-spike SARS-CoV-2 IgG antibodies were quantified by ELISA in international units/mL (IU/mL). Sociodemographic data were collected at the study start and infection history and vaccination data at each sampling round. Results: Infection-na & iuml;ve NHRs had low antibody levels after primary course vaccination (geometric mean concentration (GMC) 292 IU/mL, 95% confidence interval (95% CI): 197-432), but increased tenfold after first booster (GMC 2168 IU/mL, 95% CI: 1554-3027). While antibodies among NHRs significantly declined within six months after primary vaccination (p 0.05). Among primary vaccine non-responders, 92% (95% CI: 82-97%) developed antibodies after the first booster (GMC 594 IU/mL, 95% CI: 416-849), though tenfold lower than initial responders (GMC 4642 IU/mL, 95% CI: 3577-6022). Conclusions: These findings demonstrate that NHRs require tailored vaccination, prioritizing repeated immunization to improve serological outcomes in poor responders such as infection-naive NHRs. Regular immune monitoring could aid in implementing evidence-based vaccine strategies, ensuring optimal protection for vulnerable populations against SARS-CoV-2 and other infectious threats.Background/Objectives: This study mapped antibody dynamics across three COVID-19 vaccination rounds (primary course, first, and second booster with BNT162b2) in Belgian nursing home residents (NHRs). Methods: Within a national SARS-CoV-2 serosurveillance study (February 2021-September 2022) across Belgian nursing homes, dried blood spots were collected, on which anti-spike SARS-CoV-2 IgG antibodies were quantified by ELISA in international units/mL (IU/mL). Sociodemographic data were collected at the study start and infection history and vaccination data at each sampling round. Results: Infection-na & iuml;ve NHRs had low antibody levels after primary course vaccination (geometric mean concentration (GMC) 292 IU/mL, 95% confidence interval (95% CI): 197-432), but increased tenfold after first booster (GMC 2168 IU/mL, 95% CI: 1554-3027). While antibodies among NHRs significantly declined within six months after primary vaccination (p 0.05). Among primary vaccine non-responders, 92% (95% CI: 82-97%) developed antibodies after the first booster (GMC 594 IU/mL, 95% CI: 416-849), though tenfold lower than initial responders (GMC 4642 IU/mL, 95% CI: 3577-6022). Conclusions: These findings demonstrate that NHRs require tailored vaccination, prioritizing repeated immunization to improve serological outcomes in poor responders such as infection-naive NHRs. Regular immune monitoring could aid in implementing evidence-based vaccine strategies, ensuring optimal protection for vulnerable populations against SARS-CoV-2 and other infectious threats.A
Repurposing itraconazole and pyrimethamine with temozolomide as a combinatorial treatment for glioblastoma
No full textBackground: Glioblastoma is marked by a poor median overall survival of 14-16 months, highlighting the need for improving treatment. Drug repurposing leverages existing, safe compounds to provide more effective, cost-efficient cancer treatments. Based on the principle of Multidrug Adjunctive Cancer Treatment (MDACT), this study explores the potential of combining repurposed agents itraconazole and pyrimethamine with low-dose temozolomide as a treatment for glioblastoma.Methods: 2D and 3D CellTiter-Glo assays were used to assess the effects of combination treatments on the viability of different glioblastoma patient-derived stem cell lines (PDSCL) and ex vivo patient-derived tissue fragments (PDTF), respectively. Bulk RNA sequencing was performed on two PDSCL to reveal molecular mechanisms of action. Results: Both itraconazole and pyrimethamine, at clinically relevant concentrations, caused marked reductions in cell viability across a heterogeneous population of primary and recurrent PDSCL. Bliss synergy analysis revealed mainly additive effects between both compounds. A significant decrease in cell viability of PDTF from a recurrent glioblastoma was observed after combinatorial treatment. Combining TMZ with this repurposed regimen led to a significant decrease in cell viability across different PDSCL, compared to TMZ monotherapy. On the molecular level, itraconazole induced upregulation of genes related to apoptosis and cholesterol homeostasis, while pyrimethamine reduced the expression of genes involved in G2/M checkpoint regulation and mitotic spindle assembly. Conclusion: These data demonstrate potent anti-cancer effects when combining itraconazole and pyrimethamine in both in vitro and ex vivo models, highlighting its potential as a combinatorial treatment for glioblastoma. In vivo validation studies are currently ongoing.Background: Glioblastoma is marked by a poor median overall survival of 14-16 months, highlighting the need for improving treatment. Drug repurposing leverages existing, safe compounds to provide more effective, cost-efficient cancer treatments. Based on the principle of Multidrug Adjunctive Cancer Treatment (MDACT), this study explores the potential of combining repurposed agents itraconazole and pyrimethamine with low-dose temozolomide as a treatment for glioblastoma.Methods: 2D and 3D CellTiter-Glo assays were used to assess the effects of combination treatments on the viability of different glioblastoma patient-derived stem cell lines (PDSCL) and ex vivo patient-derived tissue fragments (PDTF), respectively. Bulk RNA sequencing was performed on two PDSCL to reveal molecular mechanisms of action. Results: Both itraconazole and pyrimethamine, at clinically relevant concentrations, caused marked reductions in cell viability across a heterogeneous population of primary and recurrent PDSCL. Bliss synergy analysis revealed mainly additive effects between both compounds. A significant decrease in cell viability of PDTF from a recurrent glioblastoma was observed after combinatorial treatment. Combining TMZ with this repurposed regimen led to a significant decrease in cell viability across different PDSCL, compared to TMZ monotherapy. On the molecular level, itraconazole induced upregulation of genes related to apoptosis and cholesterol homeostasis, while pyrimethamine reduced the expression of genes involved in G2/M checkpoint regulation and mitotic spindle assembly. Conclusion: These data demonstrate potent anti-cancer effects when combining itraconazole and pyrimethamine in both in vitro and ex vivo models, highlighting its potential as a combinatorial treatment for glioblastoma. In vivo validation studies are currently ongoing.C
Insecticide resistance status and vector potential of Bemisia tabaci populations on vegetable crops in Türkiye
No full textThe sweet potato whitefly Bemisia tabaci (Gennadius, 1889) (Hemiptera: Aleyrodidae), is an economically important polyphagous pest species with a global distribution. This pest not only causes direct damage by sucking plant phloem sap but also transmits viruses and excretes honeydew, which can lead to the formation of black sooty mould, thereby intensifying its significance in agricultural regions. Although chemical insecticides have been extensively used for whitefly control, the development of resistance leading to control failures has been frequently documented. Here, we have initially assessed the efficacy of four commonly used insecticides (acetamiprid, sulfoxaflor, spirotetramat, cyantraniliprole) against whitefly populations through greenhouse trials across eight distinct locations. Additionally, we conducted a comprehensive molecular screening of 35 field populations to identify resistance mutations at the insecticide target sites and to detect plant pathogenic viruses. The results revealed that sulfoxaflor and cyantraniliprole exhibited the highest efficacy against nymphal stages of whiteflies, whereas acetamiprid was determined to be the most effective insecticide against adult stages. Several well-known target-site mutations in acetylcholinesterase (F331W), voltage-gated sodium channel (VGSC; M918L, L925I, T929V), and acetyl-CoA carboxylase (A2083V) were found to be widespread in Turkish B. tabaci populations. Additionally, two mutations, I936V and I936F, previously associated with pyrethroid resistance, were identified for the first time in the VGSC of B. tabaci. Conversely, no amino acid substitutions were detected in the amplified fragments of the ryanodine and nicotinic acetylcholine receptors. Furthermore, tomato chlorosis virus (ToCV) was detected in five field populations from Antalya. The widespread distribution of whitefly populations with multiple resistance mutations underscores the necessity of implementing integrated pest management programs in Turkish vegetable production areas.The sweet potato whitefly Bemisia tabaci (Gennadius, 1889) (Hemiptera: Aleyrodidae), is an economically important polyphagous pest species with a global distribution. This pest not only causes direct damage by sucking plant phloem sap but also transmits viruses and excretes honeydew, which can lead to the formation of black sooty mould, thereby intensifying its significance in agricultural regions. Although chemical insecticides have been extensively used for whitefly control, the development of resistance leading to control failures has been frequently documented. Here, we have initially assessed the efficacy of four commonly used insecticides (acetamiprid, sulfoxaflor, spirotetramat, cyantraniliprole) against whitefly populations through greenhouse trials across eight distinct locations. Additionally, we conducted a comprehensive molecular screening of 35 field populations to identify resistance mutations at the insecticide target sites and to detect plant pathogenic viruses. The results revealed that sulfoxaflor and cyantraniliprole exhibited the highest efficacy against nymphal stages of whiteflies, whereas acetamiprid was determined to be the most effective insecticide against adult stages. Several well-known target-site mutations in acetylcholinesterase (F331W), voltage-gated sodium channel (VGSC; M918L, L925I, T929V), and acetyl-CoA carboxylase (A2083V) were found to be widespread in Turkish B. tabaci populations. Additionally, two mutations, I936V and I936F, previously associated with pyrethroid resistance, were identified for the first time in the VGSC of B. tabaci. Conversely, no amino acid substitutions were detected in the amplified fragments of the ryanodine and nicotinic acetylcholine receptors. Furthermore, tomato chlorosis virus (ToCV) was detected in five field populations from Antalya. The widespread distribution of whitefly populations with multiple resistance mutations underscores the necessity of implementing integrated pest management programs in Turkish vegetable production areas.A
Novel flow cytometric antibody panel and dedicated analysis algorithm for automated fully standardized minimal residual disease detection in chronic lymphocytic leukemia
No full textA
Impact of low-protein feeding strategies and on performance and SID lysine efficiency in weaned piglets
No full textFeeding a low-protein (LP) diet to weaned pigs can improve gut health but may also impair growth performance. This study investigated the effects of protein level and feeding duration before transitioning to a common starter diet. A total of 101 weaned piglets (26-28 days, 7.02 ± 0.09 kg) were assigned to four dietary treatments: (1) HP10: high-protein (HP) diet (18.8% crude protein (CP), 12.4% standardized ileal digestible lysine (SID Lys)) for 10 days, followed by a common starter diet (17.9% CP, 11.8% SID Lys) until day 39; (2) HP18: HP for 18 days, then the starter diet; (3) LP10: low-protein (16.2% CP, 10.6% SID Lys) for 10 days, then the starter diet; (4) LP18: LP for 18 days, followed by the starter diet. Feed intake and body weight (BW) were monitored using electronic feeders and weighing stations. Lysine retention was calculated assuming a fixed lysine content per kg BW. And lysine efficiency was calculated as the ratio of lysine retention to SID Lys intake. LP18 showed a 17.7% reduction in average daily gain (ADG) compared to HP18 during days 0-18 (P = 0.009), with lower gain-to-feed in both LP groups than HP18 (P = 0.017). Both LP and HP10 had a higher lysine efficiency compared to HP18 during days 18-39 and 0-39 (P = 0.003 and P = 0.002, respectively). Additionally, lysine efficiency decreased as SID Lys intake per BW0.75 increased during most periods (e.g., y = 1.06 - 0.32 x, P < 0.001, R² = 0.351 for days 18-39), except days 0-10. In summary, prolonged LP feeding (18 days) reduced ADG and feed efficiency, whereas lower SID Lys intake improved lysine efficiency, except in early post-weaning when low ADG impaired efficiency.Feeding a low-protein (LP) diet to weaned pigs can improve gut health but may also impair growth performance. This study investigated the effects of protein level and feeding duration before transitioning to a common starter diet. A total of 101 weaned piglets (26-28 days, 7.02 ± 0.09 kg) were assigned to four dietary treatments: (1) HP10: high-protein (HP) diet (18.8% crude protein (CP), 12.4% standardized ileal digestible lysine (SID Lys)) for 10 days, followed by a common starter diet (17.9% CP, 11.8% SID Lys) until day 39; (2) HP18: HP for 18 days, then the starter diet; (3) LP10: low-protein (16.2% CP, 10.6% SID Lys) for 10 days, then the starter diet; (4) LP18: LP for 18 days, followed by the starter diet. Feed intake and body weight (BW) were monitored using electronic feeders and weighing stations. Lysine retention was calculated assuming a fixed lysine content per kg BW. And lysine efficiency was calculated as the ratio of lysine retention to SID Lys intake. LP18 showed a 17.7% reduction in average daily gain (ADG) compared to HP18 during days 0-18 (P = 0.009), with lower gain-to-feed in both LP groups than HP18 (P = 0.017). Both LP and HP10 had a higher lysine efficiency compared to HP18 during days 18-39 and 0-39 (P = 0.003 and P = 0.002, respectively). Additionally, lysine efficiency decreased as SID Lys intake per BW0.75 increased during most periods (e.g., y = 1.06 - 0.32 x, P < 0.001, R² = 0.351 for days 18-39), except days 0-10. In summary, prolonged LP feeding (18 days) reduced ADG and feed efficiency, whereas lower SID Lys intake improved lysine efficiency, except in early post-weaning when low ADG impaired efficiency.C
A survey on measurement and reporting of total testosterone, sex hormone-binding globulin and free testosterone in clinical laboratories in Europe
No full textLike birds of a feather? A multi-case study on the connections between cannabis, tobacco, alcohol and pharmaceutical companies in legalized cannabis markets
No full textBackground: As of 2024, cannabis legalization in Northern American countries has spurred industry growth, intersecting with alcohol, tobacco, and pharmaceuticals. This study examines the investments and employee movement between five cannabis companies and alcohol, tobacco and pharmaceutical companies in order to explore the connections between the industries. While these relationships may bolster cannabis businesses, they also pose risks such as profit-driven practices that could undermine public health protections. Method: An exploratory and descriptive approach was used to analyze business investments and employee flow between five cannabis companies (Canopy Growth, Aurora Cannabis, Tilray, Cronos Group, and Organigram) and alcohol, tobacco, and pharmaceutical companies. Data was collected through Nexis Uni, corporate reports, press releases, and LinkedIn, documenting financial transactions and management transitions. Results: The results reveal investment relationships between the five cannabis companies and companies from the alcohol, tobacco, and pharmaceutical sectors. Some cannabis companies have secured substantial investments from alcohol and tobacco firms, which view cannabis as both a competitor and an opportunity for market expansion. These investments often come with influence, allowing industries to shape the cannabis market. Additionally, employee flows indicate cross-industry expertise transfer, particularly in management, finance, and strategy. This suggests that traditional companies are strategically positioning themselves within the cannabis sector, while cannabis companies are leveraging expertise form other sectors to drive innovation. Conclusion: The connections between cannabis and traditional industries raise concerns over market dynamics and public health risks by importing profit-driven tactics that weaken regulations and public safety. By drawing on lessons from established industries, future studies can help navigate the balance between industry growth and societal well-being, ensuring that cannabis commercialization does not come at the expense of consumer health.Background: As of 2024, cannabis legalization in Northern American countries has spurred industry growth, intersecting with alcohol, tobacco, and pharmaceuticals. This study examines the investments and employee movement between five cannabis companies and alcohol, tobacco and pharmaceutical companies in order to explore the connections between the industries. While these relationships may bolster cannabis businesses, they also pose risks such as profit-driven practices that could undermine public health protections. Method: An exploratory and descriptive approach was used to analyze business investments and employee flow between five cannabis companies (Canopy Growth, Aurora Cannabis, Tilray, Cronos Group, and Organigram) and alcohol, tobacco, and pharmaceutical companies. Data was collected through Nexis Uni, corporate reports, press releases, and LinkedIn, documenting financial transactions and management transitions. Results: The results reveal investment relationships between the five cannabis companies and companies from the alcohol, tobacco, and pharmaceutical sectors. Some cannabis companies have secured substantial investments from alcohol and tobacco firms, which view cannabis as both a competitor and an opportunity for market expansion. These investments often come with influence, allowing industries to shape the cannabis market. Additionally, employee flows indicate cross-industry expertise transfer, particularly in management, finance, and strategy. This suggests that traditional companies are strategically positioning themselves within the cannabis sector, while cannabis companies are leveraging expertise form other sectors to drive innovation. Conclusion: The connections between cannabis and traditional industries raise concerns over market dynamics and public health risks by importing profit-driven tactics that weaken regulations and public safety. By drawing on lessons from established industries, future studies can help navigate the balance between industry growth and societal well-being, ensuring that cannabis commercialization does not come at the expense of consumer health.A