Решение задач многокритериальной оптимизации с использованием генетических алгоритмов

В данной работе представлены существующие подходы и методы применения генетических алгоритмов для решения задач многокритериальной оптимизации. Предложены математическая модель и алгоритмы решения многокритериальной задачи выбора стратегии развития производственной системы. Представлены также результаты применения для решения этой задачи метода присваивания рангов Голдберга и гибридного генетического алгоритма.Представлені існуючи підходи і методи застосування генетичних алгоритмів для рішення залач багатокритеріальної оптимізації. Запропоновано математичну модель і алгоритми розв’язку багатокритеріальної задачі вибору стратегії розвитку виробничої системи. Навелено результати застосування для розв’язку цієї задачі методу надання рангів Голдберга і гібридного генетичного алгоритму.This paper describes the existing approaches and methods of application of genetic algorithms for multiobjective optimization. The mathematical model and algorithms for solving multiobjective optimization problems in management have been proposed. Experimental results of application of the hybrid genetic algorithms for solving combinatorial optimization problems have been presented

Dietary Liberalization in Tetrahydrobiopterin-Treated PKU Patients:Does It Improve Outcomes?

Purpose: this systematic review aimed to assess the effects of dietary liberalization following tetrahydrobiopterin (BH4) treatment on anthropometric measurements, nutritional biomarkers, quality of life, bone density, mental health and psychosocial functioning, and burden of care in PKU patients. Methods: the PubMed, Cochrane, and Embase databases were searched on 7 April 2022. We included studies that reported on the aforementioned domains before and after dietary liberalization as a result of BH4 treatment in PKU patients. Exclusion criteria were: studies written in a language other than English; studies that only included data of a BH4 loading test; insufficient data for the parameters of interest; and wrong publication type. Both within-subject and between-subject analyses were assessed, and meta-analyses were performed if possible. Results: twelve studies containing 14 cohorts and 228 patients were included. Single studies reported few significant differences. Two out of fifteen primary meta-analyses were significant; BMI was higher in BH4-treated patients versus controls (p = 0.02; standardized mean difference (SMD) (95% confidence interval (CI)) = −0.37 (−0.67, −0.06)), and blood cholesterol concentrations increased after starting BH4 treatment (p = 0.01; SMD (CI) = −0.70 (−1.26, −0.15)). Conclusion: there is no clear evidence that dietary liberalization after BH4 treatment has a positive effect on anthropometric measurements, nutritional biomarkers, or quality of life. No studies could be included for bone density, mental health and psychosocial functioning, and burden of care

Prenatal reflective functioning in primiparous women with a high-risk profile

The concept of maternal reflective functioning (RF) has been gaining increasing interest as a possible intermediate mechanism in associations between a wide range of psychosocial risk factors and poor child outcomes. The purpose of the present study was to determine which psychosocial risk factors are linked to prenatal RF in a high-risk (HR) group of primiparous women. Differences in prenatal RF between the HR group and a low-risk (LR) control group also were examined. The sample consisted of 162 women (M = 22.22 years, SD = 2.39; 83 classified as HR). RF was coded from the Pregnancy Interview (A. Slade, 2007a). Risk status was assessed by means of the Mini-International Neuropsychiatric Interview-plus (M.I.N.I.-plus; D.V. Sheehan et al., 1997) and several questionnaires. HR women demonstrated significantly lower RF quality than did the LR group. Regression analyses indicated that maternal education, size of social support network, and substance use during pregnancy were the strongest predictors of prenatal RF for the HR group. The results suggest that maternal RF potentially could be an important target for those prevention and intervention programs that aim to reduce adverse psychosocial development in offspring of HR mothers

Social-cognitive functioning and social skills in patients with early treated phenylketonuria: a PKU-COBESO study

Objective: Early treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still show cognitive and mood problems. In this study, it was investigated whether ET-PKU-patients have specific phenylalanine (Phe-)related problems with respect to social-cognitive functioning and social skills. Methods: Ninety five PKU-patients (mean age 21.6 ± 10.2 years) and 95 healthy controls (mean age 19.6 ± 8.7 years) were compared on performance of computerized and paper-and-pencil tasks measuring social-cognitive abilities and on parent- and self-reported social skills, using multivariate analyses of variance, and controlling for general cognitive ability (IQ-estimate). Further comparisons were made between patients using tetrahydrobiopterin (BH4, N = 30) and patients not using BH4. Associations with Phe-levels on the day of testing, during childhood, during adolescence and throughout life were examined. Results: PKU-patients showed poorer social-cognitive functioning and reportedly had poorer social skills than controls (regardless of general cognitive abilities). Quality of social-cognitive functioning was negatively related to recent Phe-levels and Phe-levels between 8 and 12 years for adolescents with PKU. Qu

Development of international consensus recommendations using a modified Delphi approach

Funding Information: This work was supported by BioMarin Pharmaceutical Inc . Funding Information: The content of this manuscript was based on preparatory pre-meeting activities and presentations and discussions during two advisory board meetings that were coordinated and funded by BioMarin Pharmaceutical Inc. All authors or their institutions received funding from BioMarin to attend at least one or both meetings. Additional disclosures: BKB received consulting payments from BioMarin, Shire, Genzyme, Alexion, Horizon Therapeutics, Denali Therapeutics, JCR Pharma, Moderna, Aeglea BioTherapeutics, SIO Gene Therapies, Taysha Gene Therapy, Ultragenyx, and Inventiva Pharma, participated as clinical trial investigator for BioMarin, Shire, Denali Therapeutics, Homology Medicines, Ultragenyx, and Moderna as well as received speaker fees from BioMarin, Shire, Genzyme, and Horizon Therapeutics. AH received consulting payments from BioMarin, Chiesi, Shire, Genzyme, Amicus, and Ultragenyx, participated as clinical trial investigator for Ultragenyx as well as received speaker fees from Alexion, Amicus, BioMarin, Genzyme, Nutricia, Sobi, and Takeda. ABQ received consulting payments from BioMarin, speaker fees from BioMarin, Nutricia, Vitaflo, Sanofi, Takeda, Recordati, and travel support from Vitaflo . SEC received consulting payments and speaker fees from BioMarin as well as consulting payments from Synlogic Therapeutics. COH was clinical trial investigator for BioMarin and received consulting and speaker payments from BioMarin. SCJH received consulting payments and travel support from BioMarin and Homology Medicines. NL received consulting payments from Alnylam, Amicus, Astellas, BioMarin, BridgeBio, Chiesi, Genzyme/Sanofi, HemoShear, Horizon Therapeutics, Jaguar, Moderna, Nestle, PTC Therapeutics, Reneo, Shire, Synlogic, and Ultragenyx, participated as clinical trial investigator for Aeglea, Amicus, Astellas, BioMarin, Genzyme/Sanofi, Homology, Horizon, Moderna, Pfizer, Protalix, PTC Therapeutics, Reneo, Retrophin/Travere therapeutics, Shire, and Ultragenyx, as well as received speaker fees from Cycle Pharmaceuticals, Leadiant and Recordati. MCM II received consulting payments from BioMarin, Horizon Therapeutics, Rhythm Pharmaceuticals, Applied Therapeutics, Cycle Therapeutics, and Ultragenyx. ALSP received speaker fees from BioMarin. JCR received consulting payments from Applied Pharma Research, Merck Serono, BioMarin, Vitaflo, and Nutricia, speaker fees from Applied Pharma Research, Merck Serono, BioMarin Pharmaceutical, Vitaflo, Cambrooke, PIAM, LifeDiet, and Nutricia, as well as travel support from Applied Pharma Research, Merck Serono, BioMarin, Vitaflo, Cambrooke, PIAM, and Nutricia. SS received consulting payments, research grants, speaker fees, and travel support from BioMarin and participated as clinical trials investigator for BioMarin. ASV received consulting payments from BioMarin, Horizon Therapeutics, and Ultragenyx and participated as clinical trial investigator for Acadia, Alexion, BioMarin, Genzyme, Homology Medicines, Kaleido, Mallinckrodt, and Ultragenyx. JV received consulting payments from BioMarin, LogicBio Pharmaceuticals, Sangamo Therapeutics, Orphan Labs, Synlogic Therapeutics, Sanofi, Axcella Health, Agios Pharmaceuticals, and Applied Therapeutics as well as travel grants from BioMarin and LogicBio Pharmaceuticals. MW received consulting payments, speaker fees, and travel support from BioMarin, and participated as clinical trial investigator for Mallinckrodt, Roche, Wave, Cycle Therapeutics, and Intrabio. ACM participated in strategic advisory boards and received honoraria as a consultant and as a speaker for Merck Serono, BioMarin, Nestlé Health Science (SHS), Applied Pharma Research, Actelion, Retrophin, Censa, PTC Therapeutics, and Arla Food. Funding Information: Ideally, access to (neuro)psychological/psychiatric support should assist adolescents with identifying, understanding, and reporting of PKU-specific challenges (Table 3), offering individualized recommendations on managing these challenges. Although there is no replacement for mental health services for patients with identified needs, psychosocial support from PKU peers, e.g., through PKU camps, virtual social events, etc., can at least in the short-term help to improve metabolic control by providing individuals an opportunity to participate in supportive PKU-related educational activities potentially reducing perceived social isolation [91]. In addition to PKU camps, which may be very specific to certain regions or countries, HCPs should consider encouraging involvement in local, regional, national and international PKU patient/family advocacy and social support organizations, introducing adolescents and young adults to national/international patient registries [92,93]. Besides support from PKU peers, patients can benefit from non-PKU peer support, although some adolescents and young adults with PKU may not disclose to others and may avoid eating in with others or eating in public due to potential feelings of anxiety or feelings of being ashamed of their disease. In addition, patients with PKU of all ages, but particularly vulnerable adolescents and young adults, can benefit from having the opportunity to learn about and practice strategies that help promote feelings of empowerment and self-efficacy that can be used in both familiar and unfamiliar environments where they may experience peer pressure and feel the need to ‘fit in’. For example, a role-play approach involving behavioral rehearsal, self-monitoring, goal setting, and training in problem-solving skills with emphasis on initiation and inhibition (i.e., how to say no) could be provided by parents, PKU peers, or even members of the PKU team. These types of activities can be used to teach adolescents with PKU how to react in social situations, such as dining out, helping to avoid indulging and increased risk-taking behavior, a hallmark of the adolescent period [94].This work was supported by BioMarin Pharmaceutical Inc.The content of this manuscript was based on preparatory pre-meeting activities and presentations and discussions during two advisory board meetings that were coordinated and funded by BioMarin Pharmaceutical Inc. All authors or their institutions received funding from BioMarin to attend at least one or both meetings. Additional disclosures: BKB received consulting payments from BioMarin, Shire, Genzyme, Alexion, Horizon Therapeutics, Denali Therapeutics, JCR Pharma, Moderna, Aeglea BioTherapeutics, SIO Gene Therapies, Taysha Gene Therapy, Ultragenyx, and Inventiva Pharma, participated as clinical trial investigator for BioMarin, Shire, Denali Therapeutics, Homology Medicines, Ultragenyx, and Moderna as well as received speaker fees from BioMarin, Shire, Genzyme, and Horizon Therapeutics. AH received consulting payments from BioMarin, Chiesi, Shire, Genzyme, Amicus, and Ultragenyx, participated as clinical trial investigator for Ultragenyx as well as received speaker fees from Alexion, Amicus, BioMarin, Genzyme, Nutricia, Sobi, and Takeda. ABQ received consulting payments from BioMarin, speaker fees from BioMarin, Nutricia, Vitaflo, Sanofi, Takeda, Recordati, and travel support from Vitaflo. SEC received consulting payments and speaker fees from BioMarin as well as consulting payments from Synlogic Therapeutics. COH was clinical trial investigator for BioMarin and received consulting and speaker payments from BioMarin. SCJH received consulting payments and travel support from BioMarin and Homology Medicines. NL received consulting payments from Alnylam, Amicus, Astellas, BioMarin, BridgeBio, Chiesi, Genzyme/Sanofi, HemoShear, Horizon Therapeutics, Jaguar, Moderna, Nestle, PTC Therapeutics, Reneo, Shire, Synlogic, and Ultragenyx, participated as clinical trial investigator for Aeglea, Amicus, Astellas, BioMarin, Genzyme/Sanofi, Homology, Horizon, Moderna, Pfizer, Protalix, PTC Therapeutics, Reneo, Retrophin/Travere therapeutics, Shire, and Ultragenyx, as well as received speaker fees from Cycle Pharmaceuticals, Leadiant and Recordati. MCM II received consulting payments from BioMarin, Horizon Therapeutics, Rhythm Pharmaceuticals, Applied Therapeutics, Cycle Therapeutics, and Ultragenyx. ALSP received speaker fees from BioMarin. JCR received consulting payments from Applied Pharma Research, Merck Serono, BioMarin, Vitaflo, and Nutricia, speaker fees from Applied Pharma Research, Merck Serono, BioMarin Pharmaceutical, Vitaflo, Cambrooke, PIAM, LifeDiet, and Nutricia, as well as travel support from Applied Pharma Research, Merck Serono, BioMarin, Vitaflo, Cambrooke, PIAM, and Nutricia. SS received consulting payments, research grants, speaker fees, and travel support from BioMarin and participated as clinical trials investigator for BioMarin. ASV received consulting payments from BioMarin, Horizon Therapeutics, and Ultragenyx and participated as clinical trial investigator for Acadia, Alexion, BioMarin, Genzyme, Homology Medicines, Kaleido, Mallinckrodt, and Ultragenyx. JV received consulting payments from BioMarin, LogicBio Pharmaceuticals, Sangamo Therapeutics, Orphan Labs, Synlogic Therapeutics, Sanofi, Axcella Health, Agios Pharmaceuticals, and Applied Therapeutics as well as travel grants from BioMarin and LogicBio Pharmaceuticals. MW received consulting payments, speaker fees, and travel support from BioMarin, and participated as clinical trial investigator for Mallinckrodt, Roche, Wave, Cycle Therapeutics, and Intrabio. ACM participated in strategic advisory boards and received honoraria as a consultant and as a speaker for Merck Serono, BioMarin, Nestlé Health Science (SHS), Applied Pharma Research, Actelion, Retrophin, Censa, PTC Therapeutics, and Arla Food. Publisher Copyright: © 2022 The AuthorsBackground: Early treated patients with phenylketonuria (PKU) often become lost to follow-up from adolescence onwards due to the historical focus of PKU care on the pediatric population and lack of programs facilitating the transition to adulthood. As a result, evidence on the management of adolescents and young adults with PKU is limited. Methods: Two meetings were held with a multidisciplinary international panel of 25 experts in PKU and comorbidities frequently experienced by patients with PKU. Based on the outcomes of the first meeting, a set of statements were developed. During the second meeting, these statements were voted on for consensus generation (≥70% agreement), using a modified Delphi approach. Results: A total of 37 consensus recommendations were developed across five areas that were deemed important in the management of adolescents and young adults with PKU: (1) general physical health, (2) mental health and neurocognitive functioning, (3) blood Phe target range, (4) PKU-specific challenges, and (5) transition to adult care. The consensus recommendations reflect the personal opinions and experiences from the participating experts supported with evidence when available. Overall, clinicians managing adolescents and young adults with PKU should be aware of the wide variety of PKU-associated comorbidities, initiating screening at an early age. In addition, management of adolescents/young adults should be a joint effort between the patient, clinical center, and parents/caregivers supporting adolescents with gradually gaining independent control of their disease during the transition to adulthood. Conclusions: A multidisciplinary international group of experts used a modified Delphi approach to develop a set of consensus recommendations with the aim of providing guidance and offering tools to clinics to aid with supporting adolescents and young adults with PKU.publishersversionpublishe

Neurobiological and behavioral stress reactivity in children prenatally exposed to tobacco

This study examined neurobiological and behavioral stress reactivity in children who had been prenatally exposed to tobacco. Neurobiological stress reactivity was measured using salivary cortisol and alpha-amylase levels at five different time points throughout a stressful neuropsychological test session, which involved a competition against a videotaped opponent. Participants (mean age: 10.6 years, SD 1.3) were 14 prenatally exposed (PE) children, 9 children with disruptive behavior problems (DBD), and 15 normal controls (NC). For cortisol responses, no significant differences between the three groups were observed. Normal controls, however, had significantly higher alpha-amylase levels than PE-children throughout the test session, and their alpha-amylase levels also increased throughout the session, whereas these remained low and stable for PE-children. Alpha-amylase levels and trajectory of PE-children were similar to those observed for DBD-children. PE-children also showed significantly increased behavioral stress reactivity compared to NC-children, and neurobiological and behavioral stress reactivity were inversely related in PE-children, again similar to what was observed for DBD-children. These results support the hypothesis that prenatal smoking may lead to long-lasting neurobiological and behavioral changes in exposed offspring

Functional Connectivity Changes and Executive and Social Problems in Neurofibromatosis Type I

Neurofibromatosis type 1 (NF1) has regularly been associated with cognitive, social, and behavioral problems. The fact that many different cognitive and behavioral impairments have been observed in NF1 suggests that networks of brain regions are involved rather than specific brain regions. Here, we examined whether functional connectivity was different in NF1 and, if so, whether associations were present with cognitive, social, and behavioral outcomes. Fourteen NF1 patients (8 male, age: M=12.49, SD=2.65) and 30 healthy controls (HC; 23 male, age: M=12.30, SD=2.94; p=0.835) were included. Functional connectivity was assessed using functional resting-state scanning. We analyzed brain regions that have been associated with cognitive and social functions: the bilateral ventral anterior cingulate cortex (vACC), the bilateral amygdala, the bilateral orbitofrontal cortex (OFC), and the posterior cingulate cortex (PCC). For NF1 patients, connection strengths between brain regions showing HC-NF1 differences were correlated with parent reports of cognitive, social, and behavioral functioning. Compared to HC, patients showed differences in functional connectivity between the left vACC and the frontal cortex, insula, and subcortical areas (caudate, putamen), between the left amygdala and the frontal cortex, insula, supramarginal gyrus, and PCC/precuneus, and between the left OFC and frontal and subcortical areas (caudate, pallidum). In patients, indications were found for associations between increased frontofrontal and temporofrontal functional connectivity with cognitive, social, and behavioral deficits (r-range=0.536–0.851). NF1 patients showed differences in functional connectivity between areas associated with cognitive and social functioning when compared to controls. This, plus the fact that connectivity strengths in these networks were associated with worse cognitive, social, and behavioral outcomes, suggests a neuropathological basis for the widespread deficits observed in NF1

Device and method for generating a plasma discharge for patterning the surface of a substrate

Device for generating a plasma discharge near a substrate for patterning the surface of the substrate, comprising a first electrode having a first discharge portion and a second electrode having a second discharge portion, a high voltage source for generating a high voltage difference between the first and the second electrode, and positioning means for positioning the first electrode with respect to the substrate. The device is further provided with an intermediate structure that is, in use, arranged in between the first electrode and the substrate while allowing for positioning the first electrode with respect to the substrate

The impact of metabolic control and tetrahydrobiopterin treatment on health related quality of life of patients with early-treated phenylketonuria: A PKU-COBESO study

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