Optimization - Science topic

Hello Rahman! HUVECs are primary cells. They have a limitation proliferation. You cannot subculture in a long time (as yours is passage 18). You should use the same passage numbers (in around 3 subculture passages) of HUVEC cells for the whole of your project to maintain similar morphology and properties. Passages 5 and 18 are quite far together. Their characteristics might be changed.

For a project based on "Geometric Mean Optimizer for Solving a Problem of a Real-Life Embedded System Application," here are some of the most promising topics to explore as a basis for your master’s thesis:

Each of these topics provides a strong basis for exploring and demonstrating the value of a geometric mean optimizer in improving specific performance metrics in embedded systems, positioning you well for a deeper thesis project.

I have this type of error

Warning: CPLEX: Q matrix is not positive semi-definite.

Warning: Model status 13: Error no solution, Solver status 9: Error: Setup failure (see message window).

solver is CPLEX 22.1 and model type is MIQCP

确保食品的质量和新鲜度，最大化利润，最小化损失

It sounds like there might be an issue with how the PV generation data is being interpreted or calculated in the optimization process. Here are a few steps to troubleshoot:

Addressing these aspects should help in diagnosing and fixing the issue with the optimization results.

Hort Tandem Repeat (STR) testing, often used in forensic science and genetic analysis, is a powerful tool for identifying individuals based on the number of repeating units at specific locations in their DNA. STR testing can still identify someone with a germ-line mutation by detecting changes in the repeat patterns at specific DNA loci. If a germ-line mutation alters an STR region, the individual’s STR profile may show a new allele or a different number of repeats than expected based on their relatives. This can result in mismatches in parent-child STR profiles, which might indicate a mutation. While STR testing is generally reliable, the results must be carefully interpreted.

Understanding these cost parameters and their relationships will help you optimize your disaster response logistics model effectively.

Your advisor should contact some of the authors whose work you have cited in your thesis. Today, with tools like LinkedIn and Research Gate, contacting experts may not be difficult.

Thank's very lot.

In the realm of C++ development, achieving optimal performance is a constant pursuit. Two powerful tools can significantly improve your code's efficiency: gperftools and Chrono. This blog post will delve into how these tools can be leveraged to streamline your C++ applications.

gperftools, developed by Google, is a collection of open-source performance analysis tools. It provides a comprehensive suite of utilities to pinpoint bottlenecks and optimize your code. Here are some of gperftools' gems:

By incorporating gperftools into your development workflow, you gain valuable insights into your code's performance characteristics. You can then use this knowledge to target specific areas for optimization and make data-driven decisions to enhance your application's speed and efficiency.

Time measurement is fundamental to performance analysis. The Chrono library, part of the C++ standard library (C++11 onwards), provides a robust and versatile framework for measuring time intervals and durations. Here's how Chrono empowers you:

By leveraging Chrono's capabilities, you can meticulously measure the execution time of different parts of your code. This fine-grained analysis empowers you to identify performance bottlenecks and optimize your code for efficiency.

gperftools and Chrono work exceptionally well together. You can use gperftools to identify performance bottlenecks in your code, and then use Chrono's high-precision time measurement to pinpoint the exact source of the issue within that code section. This symbiotic relationship empowers you to make targeted optimizations that yield significant performance improvements.

gperftools (Google Performance Tools) includes several tools to optimize the performance of your code:

Profiling helps to identify which parts of your code take the most time.

Compile your program with profiling support:

g++ -o myprogram myprogram.cpp -lprofiler

Run the program with profiling:

CPUPROFILE=/tmp/myprogram.prof ./myprogram

Analyzing the Profile:

Use pprof for analysis:

pprof --text myprogram /tmp/myprogram.prof

For visualization, use:

pprof --pdf myprogram /tmp/myprogram.prof > output.pdf

2. Using tcmalloc to Speed Up Memory Operations

tcmalloc (Thread-Caching Malloc) improves performance by managing memory more efficiently.

nstall gperftools:

sudo apt-get install google-perftools

Link your program with tcmalloc:

g++ -o myprogram myprogram.cpp -ltcmalloc

3. Using the Heap Profiler

The heap profiler helps identify memory leaks and understand memory usage.

Collecting Heap Information:

Run your program with heap profiling:

HEAPPROFILE=/tmp/myprogram-heap ./myprogram

Use pprof for analysis:

pprof --text myprogram /tmp/myprogram-heap.0001.heap

Optimizing C++ with Chrooo

Currently, there is no known tool named Chrooo associated with C++ optimization. If you meant another tool or if there was a typo, please provide more details so I can give you accurate information.

If you have more specific questions or need assistance with these tools, please let me know.

Best regards, Oleh Chashyn

https://www.researchgate. net/publication/380823913_Optimizing_Fluid_and_Electrolyte_Management_in_the_Intensive_Care_Unit_A_Comprehensive_Review?_sg%5B0%5D=IxlDZHVdSAO32fi2N6CoPJRvHGHCHIRHun5d9s0HImp3HmIQ5XhX0tt2fpfwR9GASb6OpBjsdiJcoae1ZINFpohQTO0gtomXLdp5nOGy.ceojn0eBdHakm_VzPHFlIgbhtbZhZ5G-tJx9bwx4w6QFoTzuXmJsGro2Qy3yaWrj1Dw1SQpi3tWSKFnaQtZWGQ&_tp=eyJjb250ZXh0Ijp7ImZpcnN0UGFnZSI6InByb2ZpbGUiLCJwYWdlIjoicHJvZmlsZSIsInByZXZpb3VzUGFnZSI6InByb2ZpbGUiLCJwb3NpdGlvbiI6InBhZ2VDb250ZW50In19

These should address your questions:

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Found in the National Library of Medicine:

CNS Drugs. 2022; 36(7): 659–679.

Published online 2022 Jun 27. doi: 10.1007/s40263-022-00932-2

PMCID: PMC9243911

PMID: 35759211

A Guideline and Checklist for Initiating and Managing Clozapine Treatment in Patients with Treatment-Resistant Schizophrenia

C. U. Correll,1,2,3 Ofer Agid,4 Benedicto Crespo-Facorro,5 Andrea de Bartolomeis,6 Andrea Fagiolini,7 Niko Seppälä,8 and Oliver D. Howes 9

Author information Article notes Copyright and License information PMC Disclaimer

This article has been corrected. See CNS Drugs. 2022 August 17; 36(9): 1015.

Abstract

Treatment-resistant schizophrenia (TRS) will affect about one in three patients with schizophrenia. Clozapine is the only treatment approved for TRS, and patients should be treated as soon as possible to improve their chances of achieving remission. Despite its effectiveness, concern over side effects, monitoring requirements, and inexperience with prescribing often result in long delays that can expose patients to unnecessary risks and compromise their chances of achieving favorable long-term outcomes. We critically reviewed the literature on clozapine use in TRS, focusing on guidelines, systematic reviews, and algorithms to identify strategies for improving clozapine safety and tolerability. Based on this, we have provided an overview of strategies to support early initiation of clozapine in patients with TRS based on the latest evidence and our clinical experience, and have summarized the key elements in a practical, evidence-based checklist for identifying and managing patients with TRS, with the aim of increasing confidence in prescribing and monitoring clozapine therapy.

Key Points

Early and sustained treatment with clozapine represents the best available strategy for achieving and maintaining remission in patients with treatment-resistant schizophrenia.Common side effects including sialorrhea, constipation and weight gain may result in poor adherence to treatment, while the existence of rare severe adverse events and the associated monitoring burden may result in delays in starting therapy.Strategies for optimizing treatment and managing side effects are summarized and a checklist is provided.

Introduction

Schizophrenia is a serious mental illness involving positive and negative symptoms, as well as cognitive impairment [1]. It has a median incidence of 287 (uncertainty interval 246–331)/100,000 [2] and median standardized mortality ratio of 2.6 [3]. Therapies targeting postsynaptic dopamine receptors are not effective in all cases, especially regarding negative symptoms and in patients with treatment-resistant schizophrenia (TRS). TRS is defined as patients who do not respond sufficiently to sequential trials of at least two different antipsychotics administered at appropriate doses, duration, and with adequate adherence from the patient [4–7].

TRS is a major clinical challenge that can occur early in the treatment pathway or develop later in patients who respond initially to antipsychotic treatment [8–10]. Several lines of evidence indicate that it has a different neurobiology to schizophrenia that responds to dopamine D2 receptor blockers [11, 12]. It has been hypothesized that TRS could represent a neurobiologically distinct sub-type of schizophrenia [13, 14]. Some data point to a sub-type of schizophrenia associated with TRS characterized by unaltered dopamine function [15–17], and glutamate dysregulation [18–20], which would explain why these patients do not respond to dopamine D2 blockers [21]. TRS occurs in 20–50% of patients with schizophrenia [22–24], including in community settings [25]. It is associated with higher disease burden [26, 27] and poorer outcomes [28], especially involving persistent positive symptoms despite adherence with treatment [29].

Clozapine is the only drug approved for TRS by regulators in North America, Europe, and many other jurisdictions. It is a tricyclic dibenzodiazepine derivative that interacts with multiple neuroreceptors, including dopamine, serotonin and muscarinic receptors [30, 31]. Its low affinity for D2 dopamine receptors may explain its relative lack of extrapyramidal side effects [30], whilst its actions to modulate glutamate levels may contribute to its superior efficacy in TRS [32]. Clozapine is more effective than other antipsychotics for TRS [33], and it reduces rates of hospital readmission and all-cause mortality [34–36]. A systematic review and meta-analysis of long-term studies (median follow-up 5.4 years) revealed that continuous clozapine treatment was associated with a significantly lower all-cause mortality rate compared to other antipsychotics (mortality rate ratio = 0.56, 95% confidence interval (CI) = 0.36–0.85, P = 0.007) [37], which may be due to reduced suicidality [38].

________________________________________________________________________________

Found in UpToDate, Wolters Kluwer, The whole article is excellent. Find the complete article at UpToDate

Schizophrenia in adults: Guidelines for prescribing clozapine

CONTRAINDICATIONS AND PRECAUTIONS NeutropeniaDuffy-null associated neutrophil count (DANC) Cardiac disease Seizures Other conditions PHARMACOLOGYPharmacodynamics Pharmacokinetics ADMINISTRATIONPretreatment assessment Dose titration and plasma levels Maintenance dosing Re-initiation after interruption MONITORING Neutrophil countRequired bloodwork and COVID-19 CardiovascularMyocarditis QTc prolongation Metabolic Gastrointestinal ADVERSE EFFECTS

Neutropenia/agranulocytosis Myocarditis/cardiomyopathy QTc interval prolongation Pulmonary embolism Weight gain Insulin resistance and diabetes mellitus Seizures Excessive salivation Urinary incontinence Gastrointestinal hypomotility Sedation Teratogenic and neonatal risks Mortality risk Movement disorders TablesCauses of long QT syndrome AUTHORS:Oliver Freudenreich, MDJoseph McEvoy, MD

SECTION EDITOR:Stephen Marder, MD

DEPUTY EDITOR:Michael Friedman, MDContributor DisclosuresAll topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Apr 2024.This topic last updated: May 22, 2023

Neutropenia —Duffy-null associated neutrophil count (DANC) — Lower neutrophil thresholds were established for starting and treating clozapine in patients with confirmed DANC, a cause of neutropenia not associated with recurrent or severe infection that is most often seen in individuals of African descent and Sephardic Jews [3]. Treatment can be instituted and continued in patients with an ANC of at least 1000/microL. Collaboration with hematology is recommended to manage moderate or severe neutropenia in this patient group. (See "Approach to the adult with unexplained neutropenia", section on 'Normal variants <1500/microL'.)Cardiac disease )Seizures Other conditions —PHARMACOLOGYThe pharmacologic mechanisms underlying clozapine’s superiority for treatment-resistant schizophrenia are not known.Pharmacodynamics — Clozapine binds loosely and transiently to dopamine D2 receptors. Clozapine does not induce catalepsy or inhibit apomorphine-induced stereotypy in animal models as is seen with conventional antipsychotic medications; this may explain its reduced potential for producing movement abnormalities relative to tightly binding dopamine D2 antagonists such as haloperidol. Clozapine also binds to D1, D3, and D5 receptors, and has a high affinity for the D4 receptor, but the implications of these binding activities are unclear.Clozapine also interacts at histamine H1, acetylcholine muscarinic M1 and serotonin 5-HT2A, 5-HT2C, 5-HT6, and 5-HT7 receptors, and at alpha-1-adrenoceptors. Postural dizziness, sedation, and increased appetite may reflect actions of clozapine at alpha-1, H1, and 5-HT2c receptors, respectively. Actions at the 5-HT2A and M1 receptors may reduce movement side effects [4].Pharmacokinetics — Clozapine is well absorbed. First-pass metabolism reduces its bioavailability to 60 to 70 percent of the administered dose; food has little effect on the bioavailability of clozapine. The elimination half-life of clozapine averages approximately 14 hours under steady state conditions, but there is substantial variability across individuals [5].Clozapine is extensively metabolized by the cytochrome P450 system in the liver, and excreted in both the urine and feces. Cytochrome P450 1A2 is primarily responsible for clozapine metabolism; cytochromes 2C19, 2C9, 2D6, and 3A4 play less important roles. Agents that induce cytochrome CYP1A2, such as tobacco cigarette smoke, will increase the metabolism of clozapine. Tobacco smokers may require twice the dose of nonsmokers to achieve similar blood levels. Strong inducers of CYP3A4 (eg, phenobarbital, carbamazepine) will also reduce serum concentrations of clozapine; additive bone marrow toxicity with carbamazepine has been described [6-10]. Agents that inhibit CYP1A2 (eg, ciprofloxacin, fluvoxamine) will decrease the metabolism of clozapine and may produce clinical toxicity at usual doses [11]. Cytochrome-related problems can be avoided by monitoring clozapine plasma levels while gradually increasing clozapine from a low starting dose. (See 'Dose titration and plasma levels' below.)In addition, patients prescribed clozapine should have their medication regimen analyzed for drug interactions when initiating and adjusting therapy; this may be done by use of the drug interactions program.The major metabolite of clozapine, norclozapine (desmethylclozapine), has failed to demonstrate any therapeutic activity in clinical trials. Clozapine and norclozapine plasma levels are both reported by clinical labs, but only the clozapine level is useful for dose optimization [12].

Pretreatment assessment — Assessment prior to treatment with clozapine should include evaluation of the patient’s general and cardiovascular health status. Other components of an evaluation include documentation and testing of:●Complete blood count that includes an absolute neutrophil count (ANC). The minimum ANC required to initiate clozapine is described above [3]. (See 'Neutropenia' above.)●Weight and height (body mass index), waist circumference, fasting blood sugar (or HbA1c), and fasting lipids. (See 'Weight gain' below and 'Insulin resistance and diabetes mellitus' below.)●Drug levels for patients on anticonvulsant medications (need to be in the therapeutic range). (See 'Seizures' below.)●Vital signs.●Electrocardiogram.●An Abnormal Involuntary Movement Scale documenting absence or presence of abnormal motor movements (form 1).●Pregnancy test in women of childbearing age.In addition, consider obtaining measures of inflammation (eg, C-reactive protein) and cardiac muscle damage (eg, troponin levels). (See 'Cardiovascular' below.)Dose titration and plasma levels●Starting dose and titration – For patients initially starting clozapine in nonurgent situations, we prefer a slow titration. As an example, we suggest 12.5 to 25 mg once daily at bedtime for three to four days, then 25 to 50 mg once daily at bedtime for three to four days. We then increase further by 25 mg twice weekly. An initial test dose of 12.5 mg is recommended to confirm tolerability in patients who have never received clozapine.In urgent situations (active aggression/violence or self-injury/suicide) we double the titration rate above. For example, we suggest 50 mg once daily for three or four days, then 100 mg once daily for three to four days followed by increases of 50 mg twice weekly. Sleepiness is the primary clinical ceiling side effect, so as clozapine dose is increasing, we simultaneously taper off other sedating agents. We monitor for seizure risk by asking patients or their families to report myoclonic jerking movements.We adjust dosing for individuals of Asian descent as they require less clozapine to reach therapeutic blood levels.●Initial target dose – The initial target dose for healthy, young adults is 300 mg/day. Older adult patients and patients with cardiac disease may need a lower target dose and a slower titration, particularly if they experience sedation or orthostatic hypotension to avoid falls or worsening cardiac function.●Target plasma levels – Plasma levels can be checked after the initial target dose is reached or earlier (eg, after reaching 100 mg). A clozapine plasma level in the range of 250 to 350 ng/mL is a reasonable target.

Maintenance dosing — A maintenance dose of 300 to 600 mg/day is usually required for efficacy. The average final daily dose in patients with treatment-resistant psychosis is approximately 400 mg daily. Doses higher than 900 mg/day are not recommended.Due to great interindividual variability in clozapine metabolism, in rare instances, levels can reach toxic range with lower doses (eg, 100 mg/day) or fail to achieve therapeutic levels at higher doses (eg, 600 to 900 mg/day). Checking plasma levels is thus important during the titration phase; however, once a target dose is achieved, ongoing plasma level monitoring is not routinely necessary. Regular therapeutic drug monitoring can help detect unsuspected adherence problems early enough to take counter measures. (See 'Dose titration and plasma levels' above.)Once the patient is stabilized on an effective maintenance dose, all or most of the daily dose may be given at bedtime. This will aid patients in getting to sleep and avoiding daytime sedation. Adherence can be improved by taking the medication at the time of routine, consistent behaviors, such as breakfast or bedtime preparations, and by prescribing once or twice daily rather than more frequently. However, some patients require split doses to avoid bed wetting or morning grogginess.Re-initiation after interruption — If clozapine treatment is interrupted for two or more days, we start clozapine at 12.5 mg once or twice daily in order to assess tolerability and decrease the risk of severe cardiovascular effects including orthostatic hypotension, syncope, and cardiac arrest [16]. If well tolerated, however, the previous dose can be achieved more quickly compared with patients who are initially started on clozapine

.MONITORING: Neutrophil count —intervals:●Weekly during the first six months of clozapine administration●Every other week for the second six months●Every four weeks after one year, for the duration of treatment. If neutropenia develops during treatment, clozapine would either need to be monitored more frequently, stopped temporarily, or discontinued, based on the severity of neutropenia [1]:●Mild neutropenia (ANC: 1000 to 1499/microL) – Continue treatment but increase monitoring frequency to three times per week.●Moderate neutropenia (ANC: 500 to 999/microL) – Interrupt clozapine treatment, increase monitoring to daily until ANC is 1000/microL at which point clozapine can be reinstituted.●Severe neutropenia/agranulocytosis (ANC: <500/microL) – Discontinue clozapine. Rechallenge should only occur if the benefits outweigh the risks

)ADVERSE EFFECTS

Neutropenia/agranulocytosis —  )Myocarditis/cardiomyopathy —QTc interval prolongation — Pulmonary embolism — Weight gain — Insulin resistance and diabetes mellitus --Seizures-- Excessive salivation —

SUMMARY AND RECOMMENDATIONS●

Indications – Primary indications for clozapine include schizophrenia or schizoaffective disorder partially or fully resistant to treatment with other antipsychotic drugs, or schizophrenia/schizoaffective accompanied by persistent suicidal or self-injurious behavior. (See 'Indications' above.)●Pretreatment assessment – Prior to beginning clozapine, we do the following baseline evaluation (see 'Pretreatment assessment' above):•General and cardiovascular health status, vital signs, weight, height, body mass index•Complete blood count (absolute neutrophil count [ANC] must be ≥1500/microL to initiate clozapine)•Check for therapeutic drug levels of anticonvulsant medications•Fasting blood sugar or HbA1c, fasting lipids (non-high-density lipoprotein cholesterol if nonfasting)•Electrocardiogram (ECG)•Baseline Abnormal Involuntary Movement Scale test•Pregnancy test in women of childbearing age

●Administration – For patients initially starting clozapine in nonurgent situations, we prefer a slow titration. As an example, we suggest 12.5 to 25 mg once daily at bedtime for three to four days, then 25 to 50 mg once daily at bedtime for three to four days. We increase by 25 mg twice weekly. In urgent situations (active aggression/violence or self-injury/suicide) we double the titration rate above.The initial target dose for healthy, young adults is 300 mg/day. A maintenance dose of 300 to 600 mg/day is usually required for efficacy. Doses higher than 900 mg/day are not recommended. We are cautious with older adults (>65 years) and in individuals with comorbid medical or cardiac disease. Typical maintenance dose may be as low as 100 to 150 mg/day. We titrate slowly in these individuals to avoid adverse effects. We check plasma levels once target dose is reached or earlier (after 100 mg are reached). (See 'Administration' above.)●Monitoring – For all patients taking clozapine in the United States, the US Food and Drug Administration requires regular monitoring and registry reporting of neutrophil counts. Patients taking clozapine should receive routine weekly-to-monthly monitoring and maintain an ANC ≥1500/microL (≥1000/microL for individuals with Duffy-null associated neutrophil count. Lower ANC levels require more frequent monitoring, and possible interruption of clozapine and/or reevaluation of its use. Monitoring frequency is as follows (see 'Monitoring' above):•Weekly during the first six months of clozapine administration•Every other week for the second six months•Every four weeks after one year, for the duration of treatmentIf neutropenia develops during treatment, clozapine we either monitored more frequently, stopped the medication temporarily, or discontinued the medication, based on the severity of neutropenia.●Adverse effects (see 'Adverse effects' above)•Neutropenia/agranulocytosis – Clozapine-induced agranulocytosis occurs at a rate of approximately 0.8 percent. Leukopenia occurs in approximately 3 percent of cases. The peak risks for both occurred early in treatment, between 6 to 18 weeks from initiation. (See 'Neutropenia/agranulocytosis' above.)•Cardiovascular effects – Clozaril is associated with early myocarditis that can lead to the development of cardiomyopathy. Additionally, it can cause a dose dependent QTc prolongation. We obtain an ECG prior to starting clozapine; we repeat the ECG once steady state is obtained. (See 'Myocarditis/cardiomyopathy' above.)•Insulin resistance, weight gain, metabolic dysregulation – Clozapine can cause insulin resistance, metabolic dysregulation and weight gain. While most weight gain occurs during the first 6 to 12 months, some patients continue to gain weight without reaching a plateau. We monitor metabolic parameters at regular intervals. (See 'Insulin resistance and diabetes mellitus' above.)•Seizures – Clozapine is associated with a dose-dependent seizure risk at a rate higher than that seen with most other antipsychotic drugs (See 'Seizures' above.)•Other effects – Treatment with clozapine can cause constipation, sedation, sialorrhea, incontinence, pulmonary embolism. Treatment with antipsychotics including clozapine is associated with increased mortality in individuals with dementia. (See 'Adverse effects' above.)

Antimicrobial resistance (AMR) is a significant global health concern that requires a multifaceted approach to address it effectively. Here are several strategies that can be employed to tackle AMR and promote responsible antibiotic prescribing:

1. Enhance public awareness and education: Educating the public about the appropriate use of antibiotics, the consequences of AMR, and the importance of completing prescribed antibiotic courses is crucial. Public awareness campaigns can be conducted through various channels, including schools, healthcare facilities, media, and community outreach programs.

2. Strengthen surveillance and monitoring: Establish robust surveillance systems to monitor AMR patterns, antibiotic consumption, and the emergence of new resistant strains. This data can guide evidence-based policies and interventions while providing early warning signs for outbreaks or resistance hotspots.

3. Implement antibiotic stewardship programs: These programs aim to optimize antibiotic use by promoting appropriate prescribing practices. They involve guidelines, protocols, and interventions that encourage healthcare professionals to prescribe antibiotics only when necessary, select the right antibiotics, and use the correct dosage and duration.

4. Improve infection prevention and control: Emphasize the importance of infection prevention measures, such as hand hygiene, vaccination, and sanitation practices. Effective infection control measures can reduce the need for antibiotics by preventing infections in the first place.

5. Strengthen healthcare systems: Enhance healthcare infrastructure, especially in resource-limited settings, to ensure access to quality diagnostics, appropriate antibiotics, and effective surveillance. This includes training healthcare professionals in rational antibiotic use, providing access to essential medicines, and improving laboratory capacity for accurate diagnosis.

6. Foster research and development: Encourage research and development for new antibiotics, diagnostics, and alternative treatment options. Incentives can be provided to promote innovation in this field, as the development of new antimicrobial drugs has been limited in recent years.

7. Promote international collaboration: AMR is a global issue that requires international cooperation. Encourage collaboration among countries to share best practices, exchange information, and coordinate efforts to address AMR comprehensively.

8. Regulate antibiotic use in agriculture: Implement regulations and guidelines to ensure responsible use of antibiotics in agriculture and livestock farming. This includes promoting alternatives to antibiotics, restricting the use of antibiotics for growth promotion, and monitoring antibiotic residues in food products.

9. Encourage research on novel therapies: Explore and support research on alternative therapies, such as phage therapy, monoclonal antibodies, and probiotics, which may provide effective alternatives to antibiotics in certain situations.

10. Promote innovation in diagnostics: Develop and promote rapid and accurate diagnostic tools that can identify pathogens and their susceptibility to antibiotics. This can help healthcare professionals prescribe antibiotics more precisely, reducing unnecessary prescriptions.

Various methods, including- 1.Resistance Surveillance 2.Antibiotic Utilization Metrics

3.Clinical outcome

4.Education and Training

5.Adherence to Guidelines

6.Cost Analysis

7.Patient satisfaction

8.Antimicrobial Stewardship Program (ASP) Metrics.

Lack of fit F test is used to test the hypothesis of model correctness: that is whether there is statistically significant model misspecification in not.

In RSM, the Lack of fit test is used to determine whether there is significant curvature in the experimental data: the first order model with interaction term is not able to capture adequate data variation and hence a second order model based design (CCD or Box Behnken type) is needed to fit the data coming from this particular region of the experimental space.

Details about the RSM process and statistical tests associated with it can be found in the following books:

1) Chemometrics: Experimental Design by Ed Morgan

2) Response Surface Methodology by Myers, Montogomery and Cook

Interprofessional collaboration plays a vital role in optimizing outcomes with ivabradine therapy by leveraging the expertise and perspectives of multiple healthcare disciplines to provide comprehensive care and support to patients. Here's how interprofessional collaboration contributes to optimizing outcomes with ivabradine therapy:

Overall, interprofessional collaboration fosters a team-based approach to care delivery, promotes patient-centeredness, and enhances the effectiveness and safety of ivabradine therapy in optimizing outcomes for patients with heart failure.

Healthcare providers should monitor patients receiving ivabradine therapy through several means to ensure treatment efficacy and safety. Monitoring parameters include:

Regular monitoring and communication between healthcare providers and patients are crucial to optimize ivabradine therapy, minimize adverse effects, and ensure patient safety and treatment efficacy.

Contraindications for using ivabradine include:

It's important for healthcare providers to assess patients for these contraindications before initiating ivabradine therapy to ensure patient safety and optimize treatment outcomes.

Ivabradine affects heart rate primarily by selectively inhibiting the If (funny current) channels in the sinoatrial node of the heart. These channels play a crucial role in regulating the heart's pacemaker activity by allowing the influx of sodium and potassium ions during the diastolic phase, which contributes to the spontaneous depolarization of cardiac pacemaker cells.

By blocking the If channels, ivabradine slows down the rate at which these pacemaker cells depolarize, effectively prolonging the duration of the diastolic phase of the cardiac cycle. This action leads to a reduction in heart rate without directly affecting myocardial contractility or the force of cardiac contraction.

In contrast to beta-blockers, which exert their effects on heart rate and contractility by blocking beta-adrenergic receptors, ivabradine specifically targets the If channels in the sinoatrial node, making it a selective and direct modulator of heart rate. This mechanism of action allows ivabradine to lower heart rate without compromising cardiac function, making it particularly useful in conditions such as heart failure and angina where controlling heart rate is beneficial.

Common adverse effects associated with ivabradine therapy include:

It's essential for healthcare providers to monitor patients regularly for these adverse effects during ivabradine therapy and adjust treatment as necessary to minimize discomfort and optimize patient safety.

The mechanism of action of ivabradine involves its selective inhibition of the If (funny current) channels in the sinoatrial node of the heart. These channels play a crucial role in regulating the heart's pacemaker activity by allowing the influx of sodium and potassium ions during the diastolic phase, which contributes to the spontaneous depolarization of cardiac pacemaker cells. By blocking the If channels, ivabradine slows down the heart rate without affecting myocardial contractility, resulting in a reduction in heart rate without negative inotropic effects. This mechanism makes ivabradine particularly useful in managing conditions such as heart failure and angina, where controlling heart rate is beneficial.

Aren't the same structures, but at 3 different orientations?

To me these look the same when mentally rotating them.

Rotation operations reach each other, right?

Maybe you may mean when OH is trans to C=O, not cis as in the 3 structures in the image.

Several emerging therapies and neuroprotective agents are being investigated for the management of traumatic brain injury (TBI). While many of these interventions are still in preclinical or early clinical stages of development, they hold promise for improving outcomes and reducing long-term disability in TBI patients. Here are some examples:

These emerging therapies and neuroprotective agents hold promise for improving outcomes in TBI patients by targeting various aspects of the pathophysiology of TBI, including inflammation, neurodegeneration, axonal injury, and synaptic dysfunction. Further research and clinical trials are needed to evaluate their safety, efficacy, and long-term effects in diverse patient populations with TBI.

Predicting outcomes for patients with severe traumatic brain injury (TBI) poses several challenges due to the complex and heterogeneous nature of TBI and individual variability in patient factors. Some challenges in predicting outcomes for severe TBI patients include:

Addressing these challenges in predicting outcomes for severe TBI patients requires a comprehensive and multidimensional approach that integrates clinical expertise, evidence-based assessments, advanced prognostic tools, and ongoing reassessment throughout the continuum of care. Strategies to improve outcome prediction include:

A multidisciplinary team-based approach is essential for optimizing the care of patients with severe traumatic brain injury (TBI) by leveraging the expertise of various healthcare professionals to address the complex and multifaceted needs of these patients. Here's how a multidisciplinary team-based approach enhances the care of patients with severe TBI:

Overall, a multidisciplinary team-based approach enhances the care of patients with severe TBI by facilitating comprehensive assessment, tailored treatment plans, optimization of medical management, early rehabilitation interventions, psychosocial support, continuity of care, research, and quality improvement initiatives. By working collaboratively, healthcare professionals can provide holistic, patient-centered care that maximizes outcomes and improves quality of life for individuals affected by severe TBI and their families.

Prolonged immobilization in traumatic brain injury (TBI) patients can lead to various complications, both neurological and systemic. Here are some potential complications associated with prolonged immobilization and strategies to prevent them:

Overall, proactive measures to prevent complications associated with prolonged immobilization in TBI patients are crucial for optimizing outcomes and promoting recovery. Multidisciplinary collaboration involving healthcare providers, rehabilitation specialists, and family caregivers is essential to implement preventive strategies effectively and address the unique needs of each patient.

Multimodal monitoring plays a crucial role in traumatic brain injury (TBI) management by providing comprehensive and real-time information about various aspects of cerebral physiology. This approach allows clinicians to tailor treatment strategies based on individual patient needs and optimize outcomes. Several modalities are typically included in multimodal monitoring for TBI:

By integrating data from multiple monitoring modalities, clinicians can obtain a comprehensive understanding of cerebral physiology and tailor treatment strategies to optimize cerebral perfusion, oxygenation, and metabolism in TBI patients. This personalized approach improves the likelihood of favorable outcomes and minimizes the risk of secondary brain injury.

Reducing intracranial pressure (ICP) is a crucial aspect of managing severe traumatic brain injury (TBI) to prevent secondary brain injury and improve outcomes. Several strategies can be employed to lower ICP in these patients:

Overall, a multimodal approach combining pharmacological, surgical, and supportive measures is often necessary to effectively lower ICP and mitigate secondary brain injury in patients with severe TBI. Treatment should be guided by continuous monitoring and frequent reassessment of neurological status.

In severe traumatic brain injury (TBI), computed tomography (CT) imaging plays a crucial role in assessing the extent of injury and guiding management. Some key radiographic findings indicative of severe TBI on CT imaging include:

These radiographic findings are indicative of severe TBI and may necessitate urgent medical or surgical intervention to mitigate further brain injury and improve outcomes. Interpretation of CT imaging should be performed in conjunction with clinical assessment and other diagnostic modalities to guide management effectively.

Pupil reactivity, or the response of the pupils to light, is a crucial aspect of the neurological assessment in traumatic brain injury (TBI). Here's why pupil reactivity is significant:

Overall, pupil reactivity assessment is an integral component of the neurological evaluation in TBI patients, offering valuable insights into brainstem function, early detection of deterioration, prognostication, and guiding clinical management decisions.

Management of traumatic brain injury (TBI) aims to achieve several primary goals:

These goals may vary depending on the severity of the injury, the presence of associated injuries, and individual patient factors. A multidisciplinary approach involving neurosurgeons, intensivists, neurologists, nurses, therapists, and other healthcare professionals is often necessary to optimize outcomes in TBI management.

Improving pharmaceutical supply chains in Sub-Saharan Africa necessitates strategies like local manufacturing promotion, digitalization for transparency (Smith, 2020), and resilient practices (WHO, 2019). Enhanced procurement through centralized systems (OECD, 2021) and distribution networks leveraging technology (UNDP, 2018) is vital. Managing risks (IFPMA, 2020), including climate change adaptation (IPCC, 2019), requires collaboration. Balancing local vs. international manufacturing (UNCTAD, 2020) and in-shoring vs. offshoring depends on cost-effectiveness and quality (UNIDO, 2018). Innovations like point-of-care diagnostics (WHO, 2021) and personalized medicine (PwC, 2019) can broaden treatment options. Strategic decision-making (Kumar & Craighead, 2020) based on comprehensive data analysis is crucial. Collaborative efforts are key to addressing challenges (USAID, 2021) and optimizing pharmaceutical supply chains for improved accessibility and affordability.

Data science

Been years since I used Matlab but as far as I know you can just program it as a new function, it is not a big deal. These might help you do that:

Hi Gueddidi Djihene,

Genetic Algorithms (GAs) are heuristic algorithms widely used for performing optimization especially in complex systems. Indeed, in those circumstances, finding the exaxt solution to the problem at hand could be very hard because of lack of information or mathematical issues. Smart Grids (SGs) are basically groups of modular interconnected electrical grids with many nodes (e.g. residential buildings) and elements (e.g. batteries and PV generators), generally aimed at reaching the minimum operative costs for their users. Therefore, energy flows between nodes have to be optimized with the aforementioned purpose. To sum up, GA optimization is useful for SGs since they are complex systems to be optimized.

Check this link.

Hi, this is not a simple question to answer !

But there are some points to focus on to modify the swarm behavior of PSO core algorithm :

- Initialize population using methods to maximize search space coverage (such as latin hypercubes, sequences, ...)

- try different hyper-parameter values (to poderate inertia vs social behavior)

- try different neighborhood topology.

Then there are other evolutions of the core algorithm, but other evolutions as TRIBES, FIPS, ...

you can find more at :

Clerc, M. et J. Kennedy. 2002, "The particle swarm - explosion, stability, and convergence in a multidimensional complex space"

Mendes, R., J. Kennedy et J. Neves. 2004, "The fully informed particle swarm : simpler, maybe better"

Clerc, M. 2003, "TRIBES - Un exemple d’optimisation par essaim particulaire sans paramètre de contrôle"

El Dor, A. 2012, Perfectionnement des algorithmes d’Optimisation par Essaim Particulaire. Application en segmentation d’images et en électronique (study of topologies, in french)

GOOD LUCK !

Vigorously miracle

hi Hector Marañón-Ledesma

To optimize a multivariable problem with constraints of the form `{0} ∪ [a, b]` using a genetic algorithm, consider implementing custom mutation and crossover functions that increase the likelihood of variables taking on a value of zero, and adjust the fitness function to impose penalties for values within the non-desirable range `(0, a)`. You can also employ a two-part variable representation to handle zeros and non-zeros distinctly, initialize the population with a higher frequency of zeros, or use adaptive fitness scaling to dynamically value solutions with zeros more favorably. Lastly, specialized selection mechanisms can be designed to favor individuals that meet the constraints, ensuring the genetic algorithm efficiently explores and exploits the desired search space within the DEAP framework.

This link

may shed some light.

Most standard cloning vectors have an ampicillin resistant gene (which is beta-lactamase). So those are nearly universal.

Unless you are performing protein purification for biochemical analysis, you don't require an optimized cassette. Most the naturally found genes for resistance will express adequately to confer resistance. So you just PCR out the genes from any plasmid carrying that resistance marker.

Thanks a lot

Thank you Hamza Magaji Makarfi and Alfonsas Misevicius ....still any other...

Well, looks like it is there

!?!

Hi Muhammed,

I can't comment on diethylene glycol but what I've done in the past is to cryopreserve the full brain in 30% sucrose in TBS before sectioning, then store the brain sections free floating in a 1:1 glycerol-TBS solution at -20C. I find this preserves them almost indefinitely for IHC with the exception of some particularly sensitive stains.

I can provide you some open-sourced matlab codes for optimization using CVX 3.1.

You can give a default fitness function value that is very large (in case you are in a minimization problem), the algorithm will automatically avoid such parameters in next iterations

Like this:

If period verified

Fitness = Your evaluation

If not

Fitness= large

End

In general, integer problems are not convex. First of all, due to nonconvexity of the feasible set. However, there are linear integer programming problems possessing properties similar to continuous linear problems. For example, classical transportation, assignment and many network flow problems. The reason is that all vertices of the feasible set have integer components. See more, e.g., in L.Wolsey, Integer Programming.

No, a Pareto front produced by an evolutionary algorithm does not necessarily include both global and local optima. The Pareto front represents the set of non-dominated solutions in multi-objective optimization problems. These solutions are not dominated by any other solution in terms of all the objective functions simultaneously.

In a multi-objective optimization problem, there can be multiple optimal solutions, known as Pareto optimal solutions, that represent trade-offs between conflicting objectives. These solutions lie on the Pareto front and are considered efficient solutions because improving one objective would require sacrificing performance in another objective.

The Pareto front typically contains a mixture of global and local optima. Global optima are solutions that provide the best performance across all objectives in the entire search space. Local optima, on the other hand, are solutions that are optimal within a specific region of the search space but may not be globally optimal.

The evolutionary algorithm aims to explore the search space and find a diverse set of Pareto optimal solutions across the entire front, which may include both global and local optima. However, the algorithm's ability to discover global optima depends on its exploration and exploitation capabilities, the problem complexity, and the specific settings and parameters of the algorithm.

It's important to note that the distribution and representation of global and local optima on the Pareto front can vary depending on the problem and algorithm used. Analyzing the Pareto front and its solutions can provide valuable insights into the trade-offs and optimal solutions available in multi-objective optimization problems.

You may read the articles there on the internet. Here are some links:

1) https://www.dartistics.com/fast-r-code.html

2) https://r.iq.harvard.edu/docs/zelig/3.4-8/How_can_I.html

3) https://bookdown.org/content/d1e53ac9-28ce-472f-bc2c-f499f18264a3/speedtips.html

Thank you so much for your kind response, Dear Mostak.

After some deeper searches, I could find a good example in the Casadi blog which has implemented the Casadi for optimal control of the Vanderpol system. You can catch it up from the following link:

https://web.casadi.org/blog/mpc-simulink/.

I could modify it for my problem (Nonlinear Model predictive control of a Wheeled Mobile Robot), but the tracking performance is not good as expected from an MPC controller. The tracking performance is sensitive to the cost function weighting factors and based I my knowledge the MPC weighting factors tunning is straightforward and should not be a challenging task.

Maybe I make mistakes in modifying the Simulink source file, but I checked the Simulink file over and over.

Moreover, I tried to convert the simulation file of the following code to the Simulink file and call the Casadi using the s-function, I did it but the simulation results is wrong.

https://github.com/MMehrez/MPC-and-MHE-implementation-in-MATLAB-using-Casadi/tree/master/workshop_github/Codes_casadi_v3_5_5/MPC_code.

Any positive experience in converting these examples to the Simulink file could help me.

Regards,

Hossein.

To formulate of this model you need to consider the amount of information included in it:

1.

2.

Tahereh Alavi Hi

I hope you will be fine

I have read your problem, there is two way to find the IP. One is you will perform neutral molecules and visualize the HOMO LUMO energy. A highly occupied orbital shows the maximum energy to donate the electron so HOMO energy is equal to IP similarly LUMO shows maximum energy to accept an electron that is also equal to EA. But in another way, you will perform a neutral molecule and note down the energy of the molecule and again perform that molecule after adding + charge and calculating energy. In the end you can calculate the IP by differentiating energy .