Optimal Target Values Research Articles

Adaptive Multi-Objective Optimization of Bionic Shoulder Joint Based on Particle Swarm Optimization

To get the movement mode and driving mechanism similar to human shoulder joint, a six degrees of freedom (DOF) serial-parallel bionic shoulder joint mechanism driven by pneumatic muscle actuators (PMAs) was designed. However, the structural parameters of the shoulder joint will affect various performances of the mechanism. To obtain the optimal structure parameters, the particle swarm optimization (PSO) was used. Besides, the mathematical expressions of indexes of rotation ranges, maximum bearing torque, discrete dexterity and muscle shrinkage of the bionic shoulder joint were established respectively to represent its many-sided characteristics. And the multi-objective optimization problem was transformed into a single-objective optimization problem by using the weighted-sum method. The normalization method and adaptive-weight method were used to determine each optimization index’s weight coefficient; then the particle swarm optimization was used to optimize the integrated objective function of the bionic shoulder joint and the optimal solution was obtained. Compared with the average optimization generations and the optimal target values of many experiments, using adaptive-weight method to adjust weights of integrated objective function is better than using normalization method, which validates superiority of the adaptive-weight method.

Mixed Slip-Deceleration PID Control of Aircraft Wheel Braking System

Aircraft antiskid braking system is designed to prevent the main wheels from locking and additionally seeking the optimal braking performance. Wheel deceleration is the traditional controlled target used in antiskid system, since it can be easily measured by angular velocity transducer. However the optimal target value is hard to find due to the changing of road-surface and aircraft velocity. An alternative controlled target is the wheel longitudinal slip which is more robustly controllable under all conditions. But the wheel slip cannot be measured directly, that will definitely result in control error from the poor estimated aircraft speed. In this work a PID control scheme based on mixed slip-deceleration input variable is proposed for aircraft antiskid braking system. This control algorithm is able to stabilize the wheel slip around any equilibrium point. Moreover, it inherits all the appealing characteristics of slip control, while overcoming its sensitivity to slip measurement errors.

Agricultural Multi-Water Source Allocation Model Based on Interval Two-Stage Stochastic Robust Programming under Uncertainty

Numerous uncertainties and complexities exist in the agricultural irrigation water allocation system, that must be considered in the optimization of water resources allocation. In this paper, an agricultural multi-water source allocation model, consisting of stochastic robust programming and two-stage random programming and introducing interval numbers and random variables to represent the uncertainties, was proposed for the optimization of irrigation water allocation in Jiamusi City of Heilongjiang Province, China. The model could optimize the water allocaton to different crops of groundwater and surface water. Then, the optimal target value and the optimal water allocation of different water sources distributed to different crops could be obtained. The model optimized the economic benefits and stability of the agricultural irrigation water allocation system via the introduction of a the penalty cost variable measurement to the objective function. The results revealed that the total water shortage changed from [18.6, 32.3] × 108 m3 to [15.7, 26.2] × 108 m3 at a risk level ω from zero to five, indicating that the water shortage decreased and the reliability improved in the agricultural irrigation water allocation system. Additionally, the net economic benefits of irrigation changed from [287.21, 357.86] × 108 yuan to [253.23, 301.32] × 108 yuan, indicating that the economic benefit difference was reduced. Therefore, the model can be used by decision makers to develop appropriate water distribution schemes based on the rational consideration of the economic benefit, stability and risk of the agricultural irrigation water allocation system.

Adjunctive Vitamin D in the treatment of non-remitted depression: Lessons from a failed clinical trial

BackgroundMany patients with depression fail to achieve remission after several consecutive treatments. Vitamin D deficiency is prevalent and new research suggests that it may have an impact on mood, primarily through an effect on neurotransmitters. Numerous observational studies suggest a relationship between low levels of vitamin D and increased incidence and severity of mood disorders. A small number of pilot studies have been undertaken but lack rigorous methodology required to draw conclusions about a clinical role for this nutrient in treatment resistant depression. MethodsThis study was designed as a randomized, double-blind, placebo controlled intervention study administering a weekly (bolus) dose of 28 000IU of Vitamin D3 or placebo to 125 patients with non-remitted depression adjunct to current antidepressant medication. Patients were followed weekly for eight weeks plus a one month follow up. Outcomes measured included depression severity, serum vitamin D levels and safety. Due to slow recruitment during the first season, amendments were made. These included extending the age range to 18–75 and removing the requirement for failing to respond to one pharmacologic antidepressant agent. The protocol was amended to reduce the burden on participants by changing the in-office visits to bi-weekly. Three additional tertiary psychiatric clinics were also added as trial sites. ResultsOver three recruitment period years (fall/winter), a total of 148 participants completed screening, 24 (16.2%) of whom qualified to participate in the study. Use of too many or no psychiatric medications, comorbid exclusionary psychiatric conditions, current use of a vitamin D supplement, and lack of participant compensation were the predominant reasons for ineligibility or unwillingness to participate. 9 participants were successfully enrolled in the study, 7 (77.8%) of whom completed the trial as per the protocol. After the third season, futility was declared based on inability to enroll participants. The sample size of enrolled participants (7/125, 5.6%) lacks power to conduct a full assessment of findings. DiscussionHigh accessibility of vitamin D, as well as a growing lack of equipoise in patients and clinicians about the potential ubiquitous benefits of vitamin D for Canadians, not just for mood disorders, resulted in a large proportion of ineligible potential participants. Limited funding provided to studies on natural health products hampered recruitment. The labile and fluctuating nature of non-remitted depression as well as frequent co-morbid conditions creates additional challenges for conducting trials in this population. Future studies assessing vitamin D in depression should consider our experiences in design and conduct of research. Innovations in clinical trial design such as preference trials or accepting patients already using vitamin D but not achieving an optimal target value are potential solutions to some of these challenges.

Formulation Optimization and in Vitro Characterization of Orally Disintegrating Films Using a Factorial Design and Mathematical Modeling for Drug Release.

Even though experimental designs are becoming popular especially for conventional dosage forms, limited studies have been performed to optimize formulations of orally disintegrating films (ODFs). This study aimed to evaluate sildenafil citrate-loaded ODFs for a controlled release with hydroxypropyl methylcellulose as a film-forming polymer. A factorial design was utilized for optimization with three control factors: ethanol ratio, plasticizer ratio, and the type of plasticizer. Tensile strength, disintegration time, water contact angle, and thickness were chosen as responses. For optimization, water contact angle, disintegration time, and thickness were minimized, while the tensile strength was maximized. Based on the conditions, optimal formulations were achieved for each type of plasticizer. Evaluation of desirability indicated that the response values were close to the target. When these optimal formulations were validated, the optimal solutions and target values were similar with small biases. The formulations were characterized using scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, surface pH, in vitro dissolution, and drug release simulation with a mathematical modeling. After the drug was homogenously dispersed throughout the film, the crystalline form of the drug provided strong hydrogen bonds between the drug and the film components. Moreover, it showed a controlled drug release profiles that were well matched with simulated results. This study suggests that the optimized films may present a better alternative to conventional tablets for the treatment of male erectile dysfunction.

Fibrinogen supplementation after cardiac surgery: insights from the Zero-Plasma trial (ZEPLAST)

BackgroundFibrinogen supplementation has been proposed both to prevent and treat postoperative bleeding in cardiac surgery. The optimal fibrinogen concentration trigger and target values and the fibrinogen concentrate dose required remain uncertain. This subanalysis of data from the Zero-Plasma Trial (ZEPLAST) assessed target fibrinogen values and the corresponding fibrinogen concentrate dose for supplementation. MethodsWe performed a post hoc analysis of 116 subjects included in the randomized, placebo-controlled ZEPLAST trail. Data considered were fibrin-based thromboelastometry (FIBTEM) maximum clot firmness (MCF) determined by whole-blood thromboelastometry (ROTEM) before and after placebo or fibrinogen concentrate, Clauss fibrinogen concentration after placebo or fibrinogen concentrate, postoperative bleeding and severe bleeding (SB). The association between FIBTEM MCF and Clauss fibrinogen concentration was tested with linear regression analyses. The predictive value for SB of FIBTEM MCF and Clauss fibrinogen concentration was tested with receiver operating characteristic analyses. ResultsThere was a good association between FIBTEM MCF and Clauss fibrinogen concentration in the baseline study population (r2 + 0.66), which worsened in fibrinogen-supplemented subjects. Both FIBTEM MCF and Clauss fibrinogen concentration yielded a good discriminative power for SB (area under the curve 0.721 and 0.767, respectively). The negative predictive value for SB was 100% for a Clauss fibrinogen concentration of 287 mg dl−1 and 98% for an FIBTEM MCF of 14 mm. Based on these newly defined target values, the dose of fibrinogen concentrate needed would be 3 g lower than the dose used in ZEPLAST. ConclusionsA dose of fibrinogen concentrate rarely exceeding 2 g might be sufficient to prevent bleeding in cardiac surgery.

Optimal Target States for Satellite Cluster Flight Control on Near-Circular Orbits

One of the methods for maintaining a cluster of satellites in long-term bounded relative distances is keeping the satellites on near-circular orbits having the same mean semimajor axes and mean inclinations. This approach allows some freedom in determining the reference mean semimajor axis and reference mean inclination for the cluster. In this paper, this freedom is used to find the optimal target values of the mean semimajor axis and mean inclination, with the optimization criteria being either the total propellant consumption of the cluster or the fuel consumption differences among satellites. The optimization problems are solved analytically, assuming that a fixed-magnitude thruster is used for closed-loop orbit control, and new results are presented, providing simple closed-form expressions for the optimal target states. Simulations are used for validating the results, showing that much propellant can be saved by properly setting the cluster reference orbit.

Clinical Profile of Adults with Long-Standing Type 1 Diabetes: A 30-year-Experience from Theptarin Hospital, Thailand

Objective. To present our 30-year experience with type 1 diabetes in adults treated at Theptarin hospital, Bangkok, Thailand. Methodology. A retrospective study was conducted on medical records of patients with type 1 diabetes in Theptarin hospital between 1983 and 2013. Clinical characteristics, glycemic control, and complications were retrieved and compared between patients who developed complications and those who have remained free of complications. Results. There were 129 T1DM patients who attended our hospital during the three decades. Two patients died from sepsis and leukemia. Only 70 patients are still active on follow-up (median time of follow-up 11.1 years, range 0.3-29.2 years). In the active follow-up cohort, the mean age of onset was 25.3(12.4) years and duration of diabetes was 14.4(10.0) years. The mean HbA 1c and LDL were 7.9(1.4%) and 99(30) mg/dl respectively. Optimal glycemic control (HbA 1c ≤ 7%), LDL control (LDL≤ 100 mg/dl), and target blood pressure (BP ≤ 130/80 mmHg) were achieved in 31%, 54%, and 97% of patients respectively. The optimal combined target values for glucose, LDL, and blood pressure were achieved in only 17% of patients. The cumulative incidence of retinopathy, nephropathy, and cardiovascular disease were 17%, 19%, and 0.4%, respectively. Only longer duration of diabetes was associated with increased risk of development of microvascular complications. Conclusions. Despite advancement in the treatment of diabetes, optimal glycemic control has not been achieved in most adult patients with T1DM. Microvascular complications have been observed in about one fifth of patients. Intensive therapy should be implemented as early as possible in order to ameliorate long-term complications of diabetes

A Novel Experimental Design Method to Optimize Hydrophilic Matrix Formulations with Drug Release Profiles and Mechanical Properties

To investigate the effects of hydrophilic polymers on the matrix system, an experimental design method was developed to integrate response surface methodology and the time series modeling. Moreover, the relationships among polymers on the matrix system were studied with the evaluation of physical properties including water uptake, mass loss, diffusion, and gelling index. A mixture simplex lattice design was proposed while considering eight input control factors: Polyethylene glycol 6000 (x1), polyethylene oxide (PEO) N-10 (x2), PEO 301 (x3), PEO coagulant (x4), PEO 303 (x5), hydroxypropyl methylcellulose (HPMC) 100SR (x6), HPMC 4000SR (x7), and HPMC 105SR (x8). With the modeling, optimal formulations were obtained depending on the four types of targets. The optimal formulations showed the four significant factors (x1, x2, x3, and x8) and other four input factors (x4, x5, x6, and x7) were not significant based on drug release profiles. Moreover, the optimization results were analyzed with estimated values, targets values, absolute biases, and relative biases based on observed times for the drug release rates with four different targets. The result showed that optimal solutions and target values had consistent patterns with small biases. On the basis of the physical properties of the optimal solutions, the type and ratio of the hydrophilic polymer and the relationships between polymers significantly influenced the physical properties of the system and drug release. This experimental design method is very useful in formulating a matrix system with optimal drug release. Moreover, it can distinctly confirm the relationships between excipients and the effects on the system with extensive and intensive evaluations.

Clinically relevant quality measures for risk factor control in primary care: a retrospective cohort study

BackgroundAssessment of the proportion of patients with well controlled cardiovascular risk factors underestimates the proportion of patients receiving high quality of care. Evaluating whether physicians respond appropriately to poor risk factor control gives a different picture of quality of care. We assessed physician response to control cardiovascular risk factors, as well as markers of potential overtreatment in Switzerland, a country with universal healthcare coverage but without systematic quality monitoring, annual report cards on quality of care or financial incentives to improve quality.MethodsWe performed a retrospective cohort study of 1002 randomly selected patients aged 50–80 years from four university primary care settings in Switzerland. For hypertension, dyslipidemia and diabetes mellitus, we first measured proportions in control, then assessed therapy modifications among those in poor control. “Appropriate clinical action” was defined as a therapy modification or return to control without therapy modification within 12 months among patients with baseline poor control. Potential overtreatment of these conditions was defined as intensive treatment among low-risk patients with optimal target values.Results20% of patients with hypertension, 41% with dyslipidemia and 36% with diabetes mellitus were in control at baseline. When appropriate clinical action in response to poor control was integrated into measuring quality of care, 52 to 55% had appropriate quality of care. Over 12 months, therapy of 61% of patients with baseline poor control was modified for hypertension, 33% for dyslipidemia, and 85% for diabetes mellitus. Increases in number of drug classes (28-51%) and in drug doses (10-61%) were the most common therapy modifications. Patients with target organ damage and higher baseline values were more likely to have appropriate clinical action. We found low rates of potential overtreatment with 2% for hypertension, 3% for diabetes mellitus and 3-6% for dyslipidemia.ConclusionsIn primary care, evaluating whether physicians respond appropriately to poor risk factor control, in addition to assessing proportions in control, provide a broader view of the quality of care than relying solely on measures of proportions in control. Such measures could be more clinically relevant and acceptable to physicians than simply reporting levels of control.

Is Subclinical Hypothyroidism a Cardiovascular Risk Factor in the Elderly?

The negative impact of subclinical hypothyroidism (sHT) on cardiovascular risk, widely recognized in young adults (aged <55-60 y), is still debated in the elderly (>65 y), especially in the oldest olds (>80 y). We searched Medline for reports published with the following search terms: "hypothyroidism," "subclinical hypothyroidism," "ageing," "elderly," "L-thyroxin," "thyroid," "guidelines," "treatment," "quality of life," "cardiovascular risk," "heart failure," "coronary heart disease" (CHD), "atherosclerosis," and "endothelial dysfunction." We limited our search to reports in English published after 1980, although we incorporated some reports published before 1980. We supplemented the search with records from personal files, textbooks, and relevant articles. Analyzed parameters included the epidemiology of thyroid failure, the effect of thyroid hormone on the aging process, cardiovascular function, and CHD risk factors. We also included the potential benefits of L-T4 therapy on the quality of life, cardiovascular events, and survival. TSH levels increase with age, even in older people without thyroid disease. Most longitudinal studies show an increased risk for CHD events and mortality in sHT participants. This increase is less evident in the elderly, mainly in cases of serum TSH values above 10 mIU/L. Lower mortality rate in a cohort of the oldest olds (>85 y) has been reported. sHT in older people should be not regarded as a unique condition, and moderately old patients (aged <70-75 y) could be considered clinically similar to the adult population, albeit with a higher optimal TSH target value. Conversely, the oldest old subjects should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. The decision to treat elderly people is still an unresolved clinical challenge--first, due to a lack of appropriately powered randomized controlled trials of L-T4 in sHT patients, examining cardiovascular hard endpoints in various classes of age; and second, because of the negative effects of possible overtreatment.

Experience in Treating Congenital Hypothyroidism: Implications Regarding Free Thyroxine and Thyrotropin Steady-State Concentrations During Optimal Levothyroxine Treatment

A major problem in the treatment of patients with congenital hypothyroidism (CHT) is that the optimal individual target values of thyrotropin (TSH) and free thyroxine (fT(4)) are unknown. We investigated whether patients with CHT have during treatment considered optimal stable fT(4) and TSH steady-state concentrations (SSCs) that can be used as target values, and whether TSH or fT(4) is more useful in guiding decisions regarding therapy. From 60 early-treated patients with CHT, TSH and fT(4) follow-up samples within the age interval 1.5-132 months (postinitial period) and within TSH interval 0.5-10 mU/L were selected. TSH and fT(4) SSCs were estimated by taking the individual mean values of a series of determinations, under the most euthyroid conditions possible (n=1257), for the whole age and TSH intervals, as well as for the age intervals 1.5-24, 25-72, and 73-132 months, as well as, for fT(4), for the two split TSH intervals 0.5-4.49 and 4.5-10 mU/L. For all SSCs, the within-subject coefficient of variation (CV(w)) was determined. Further, fT(4) SSCs were assessed for the first 6 weeks after therapy initiation. For both TSH and fT(4), individual SSCs differed significantly (p<0.001). The 95% confidence interval for TSH SSCs was 1.1-5.7 mU/L and for fT(4) SSCs 16.6-28.7 pmol/L. Mean CV(w) values for TSH and fT(4) SSCs were 60.9% and 13.1%, respectively. Individual fT(4) and TSH SSCs were reproducible when assessed for the three age intervals, both slightly decreasing with age (p≤0.033), and fT(4) SSCs were reproducible for the two split TSH intervals, with a slight fT(4) difference (p<0.001). fT(4) SSCs were largely independent of the administered LT(4) dosage (range 2.4-6.1 μg/kg). fT(4) SSCs of the initial period were comparable to those of postinitial period with a mean±SD difference of 1.0±3.5 pmol/L, p=0.07. Our study suggests that in CHT during therapy considered optimal, stable TSH and fT(4) SSCs can be found slightly decreasing with age and largely independent of the administered LT(4) dosage (range 2.4-6.1 μg/kg). In clinical follow-up, fT(4) SSCs may be more valuable as individual target values than TSH SSCs.

Hypomagnesaemia, the kidney and the vessels

The morbidity and mortality of chronic kidney disease (CKD) and dialysis patients remain excessive, despite increasing knowledge on the role of a multitude of cardiovascular risk factors. As a hallmark of this, randomized controlled trials (RCTs) in these populations failed to demonstrate survival benefit of interventions successfully targeted on well-accepted risk factors in the general population or on dialysis efficiency [1]. Extensive research has confronted the nephrology community with a complex and elusive network of pathophysiological pathways. In contrast, our knowledge of basic elements, such as magnesium, remains surprisingly scarce. Nevertheless, emerging evidence, be it mostly circumstantial, from in vitro and in vivo studies, indicates that hypomagnesaemia, or rather a magnesium deficit per se might convey nephrotoxicity together with negative cardiovascular effects. Alternatively, higher serum magnesium levels might be beneficial. This review aims to further critically appraise and outline this premise. Of importance, the interventional trials targeting magnesium status in CKD and dialysis patients are almost non-existent. Confounding by unmeasured residual subclinical disease and multicollinearity could subsequently hamper the interpretability of the observational evidence. Hypomagnesaemia might merely be considered a 'risk marker' rather than 'risk factor'. Future studies in the CKD and dialysis population therefore should meticulously address causality in order to allow the development of guidelines on optimal target values.

Modeling and Multi-Objective Optimization of Woodblock Gasification Process

In this paper, the LS-SVM model of woodblock gasification process has been established. The test results show that the model has better simulation and prediction effect for woodblock gasification process. On the basis of this model, the multi-objective optimization functions which is during control parameters (gasification temperature and equivalence ratio) and gas heating value and tat content is established, aiming to obtain the optimal target value of control parameters when the gas heating value reach maximum and lowest tar content in the process of woodblock gasification. The Pareto optimal solutions are obtained by optimization calculation. And each group data of the solutions is a compromise selection for gas heating value and percentage of tar heating value in raw material. It is more in line with practice more than a group of optimal solution.

Prognosis value of central venous oxygen saturation in acute decompensated heart failure

Central venous oxygen saturation (ScvO2) provides an estimation of body oxygen consumption/delivery ratio. Its use has been suggested for monitoring treatment of patients admitted for acute decompensated heart failure (ADHF) but the optimal target value has never been clearly reported. We aimed to address the prognostic value of ScvO2 in ADHF requiring inotrope support. ScvO2 was prospectively assessed in 60 patients with ADHF requiring inotrope support (mean age 62±16 years; 45 men; left ventricular ejection fraction 25±7%) and was compared with major adverse cardiac events (MACE), defined as heart transplantation, cardiac assistance and death. MACE occurred in 22 (35%) patients (14 deaths; eight referred for heart transplantation or cardiac assistance). Admission ScvO2 (mean 57±13%) did not differ between patients with and without MACE. At 24 hours ScvO2 (mean 62±7%) increased only in patients without MACE (65±6% vs. 58±7%; p<0.0001) and was associated with urine output, vena cava diameter and oxygen consumption reduction. No correlation was observed between ScvO2 and cardiac output or catecholamine rate. Multivariable analysis showed that ScvO2 at 24 hours remained an independent predictor of MACE. Using the optimal cut-off of 60% derived from receiver operating characteristic curves, MACE were observed in 81% of patients (17/21) with ScvO2≤60% at 24 hours vs. 13% (5/39) with ScvO2>60% at 24 hours. In patients admitted for ADHF requiring inotrope support, ScvO2≤60% despite optimal treatment is a marker of poor outcome and might be an indicator for considering more aggressive therapy.

Effect of mass spectrometric parameters on peptide and protein identification rates for shotgun proteomic experiments on an LTQ‐orbitrap mass analyzer

The success of a shotgun proteomic experiment relies heavily on the performance and optimization of both the LC and the MS systems. Despite this, little consideration has, so far, been given to the importance of evaluating and optimizing the MS instrument settings during data-dependent acquisition mode. Moreover, during data-dependent acquisition, the users have to decide and choose among various MS parameters and settings, making a successful analysis even more challenging. We have systematically investigated and evaluated the effect of enabling and disabling the preview mode for FTMS scan, the number of microscans per MS/MS scan, the number of MS/MS events, the maximum ion injection time for MS/MS, and the automatic gain control target value for MS and MS/MS events on protein and peptide identification rates on an LTQ-Orbitrap using the Saccharomyces cerevisiae proteome. Our investigations aimed to assess the significance of each MS parameter to improve proteome analysis and coverage. We observed that higher identification rates were obtained at lower ion injection times i.e. 50-150 ms, by performing one microscan and 12-15 MS/MS events. In terms of ion population, optimal automatic gain control target values were at 5×10(5) -1×10(6) ions for MS and 3×10(3) -1×10(4) ions for MS/MS. The preview mode scan had a minimal effect on identification rates. Using optimized MS settings, we identified 1038 (±2.3%) protein groups with a minimum of two peptide identifications and an estimated false discovery rate of ∼1% at both peptide and protein level in a 160-min LC-MS/MS analysis.

Belief rule-based methodology for mapping consumer preferences and setting product targets

Rapid and accurate identification of consumer demands and systematic assessment of product quality are essential to success for new product development, in particular for fast moving consumer goods such as food and drink products. This paper reports an investigation into a belief rule-based (BRB) methodology for quality assessment, target setting and consumer preference prediction in retro-fit design of food and drink products. The BRB methodology can be used to represent the relationships between consumer preferences and product attributes, which are complicated and nonlinear. A BRB system can initially be established using expert knowledge and then optimally trained and validated using data generated from consumer or expert panel assessments or from tests and experiments. The established BRBs can then be used to predict the consumer acceptance of new products or set product target values in retro-fit design. The proposed BRB methodology is applied to the design of a lemonade drink product using real data provided by a sensory product manufacturer in the UK. The results show that the BRB methodology can be used to predict consumer preferences with high accuracy and to set optimal target values for product quality improvement.

Diabetes and risk of tumors: oncologic considerations

Type 2 diabetes mellitus and malignant tumors are frequent diseases worldwide. The incidence of these two diseases is growing continuously and causes serious health care problem. Population based epidemiologic studies show that the coexistence of type 2 diabetes and malignant tumors is more frequent than expected by the age-corrected incidence and prevalence of each disease. Epidemiologic studies and meta-analyses show that type 2 diabetes increases the risk and tumor specific mortality of certain cancers. The overlapping risk factors of the diseases suggest a relationship between type 2 diabetes and malignant tumors, with a significant role of obesity as a major risk factor. In the pathophysiology of type 2 diabetes there are several biological processes, which may explain the higher cancer risk in type 2 diabetes. In vitro experiments, and in vivo animal studies show that the mitotic effect of hyperinsulinemia plays an important role in the relationship of cancer and type 2 diabetes mellitus. Recent studies show that the different treatment modalities, antidiabetic drugs and their combinations used for the treatment of type 2 diabetes can modify cancer risk. The majority of the data show that metformin therapy decreases, while insulin secretagog drugs slightly increase the risk of certain types of cancers in type 2 diabetes. Metformin can decrease cell proliferation and induce apoptosis in certain cancer cell lines. Endogenous and exogenous (therapy induced) hyperinsulinemia may be mitogenic and may increase the risk of cancer in type 2 diabetes. Human studies showed that the analogue insulin glargin increases the risk of certain cancers. As a result of conceptual weaknesses in study design, data collection, and statistical methods the results of these studies are questionable. According to present knowledge, obtaining and maintaining optimal metabolic target values with the appropriate choice of treatment modality is the aim of treatment in type 2 diabetes. Presently, study results showing elevated mitogenic potential with some antidiabetic treatment modalities are not taken into account, when considering the choice of antidiabetic treatment in type 2 diabetic patients. In the care of patients with increased cancer risk, oncologic considerations should be taken into account. Well designed, prospective, clinical studies would be necessary to demonstrate the possible correlation between treatment modalities of type 2 diabetes and change of cancer risk in type 2 diabetes mellitus.

Time-oriented experimental design method to optimize hydrophilic matrix formulations with gelation kinetics and drug release profiles

A new experimental design methodology was developed by integrating the response surface methodology and the time series modeling. The major purposes were to identify significant factors in determining swelling and release rate from matrix tablets and their relative factor levels for optimizing the experimental responses. Properties of tablet swelling and drug release were assessed with ten factors and two default factors, a hydrophilic model drug (terazosin) and magnesium stearate, and compared with target values. The selected input control factors were arranged in a mixture simplex lattice design with 21 experimental runs. The obtained optimal settings for gelation were PEO, LH-11, Syloid, and Pharmacoat with weight ratios of 215.33 (88.50%), 5.68 (2.33%), 19.27 (7.92%), and 3.04 (1.25%), respectively. The optimal settings for drug release were PEO and citric acid with weight ratios of 191.99 (78.91%) and 51.32 (21.09%), respectively. Based on the results of matrix swelling and drug release, the optimal solutions, target values, and validation experiment results over time were similar and showed consistent patterns with very small biases. The experimental design methodology could be a very promising experimental design method to obtain maximum information with limited time and resources. It could also be very useful in formulation studies by providing a systematic and reliable screening method to characterize significant factors in the sustained release matrix tablet.

Product design on the basis of fuzzy quality function deployment

In the implementation of quality function deployment (QFD), the determination of the target values of engineering characteristics is a complex decision process with multiple variables and multiple objectives that should trade off, and optimize all kinds of conflicts and constraints. A fuzzy linear programming model (FLP) is proposed. On the basis of the inherent fuzziness of QFD system, triangular fuzzy numbers are used to represent all the relationships and correlations, and then, the functional relationships between the customer needs and engineering characteristics and the functional correlations among the engineering characteristics are determined with the information in the house of quality (HoQ) fully used. The fuzzy linear programming (FLP) model aims to find the optimal target values of the engineering characteristics to maximize the customer satisfaction. Finally, the proposed method is illustrated by a numerical example.