In silico constraint-based strain optimization methods: the quest for optimal cell factories

Shifting from chemical to biotechnological processes is one of the cornerstones of 21st century industry. The production of a great range of chemicals via biotechnological means is a key challenge on the way toward a bio-based economy. However, this shift is occurring at a pace slower than initially expected. The development of efficient cell factories that allow for competitive production yields is of paramount importance for this leap to happen. Constraint-based models of metabolism, together with in silico strain design algorithms, promise to reveal insights into the best genetic design strategies, a step further toward achieving that goal. In this work, a thorough analysis of the main in silico constraint-based strain design strategies and algorithms is presented, their application in real-world case studies is analyzed, and a path for the future is discussed.

Project management under uncertainty: a study on solution methods

Project Management involves onetime endeavors that demand for getting it right the first time. On the other hand, project scheduling, being one of the most modeled project management process stages, still faces a wide gap from theory to practice. Demanding computational models and their consequent call for simplification, divert the implementation of such models in project management tools from the actual day to day project management process. Special focus is being made to the robustness of the generated project schedules facing the omnipresence of uncertainty. An "easy" way out is to add, more or less cleverly calculated, time buffers that always result in project duration increase and correspondingly, in cost. A better approach to deal with uncertainty seems to be to explore slack that might be present in a given project schedule, a fortiori when a non-optimal schedule is used. The combination of such approach to recent advances in modeling resource allocation and scheduling techniques to cope with the increasing flexibility in resources, as can be expressed in "Flexible Resource Constraint Project Scheduling Problem" (FRCPSP) formulations, should be a promising line of research to generate more adequate project management tools. In reality, this approach has been frequently used, by project managers in an ad-hoc way.

On the Hill estimator: a comparison of methods

Extreme value theory (EVT) deals with the occurrence of extreme phenomena. The tail index is a very important parameter appearing in the estimation of the probability of rare events. Under a semiparametric framework, inference requires the choice of a number k of upper order statistics to be considered. This is the crux of the matter and there is no definite formula to do it, since a small k leads to high variance and large values of k tend to increase the bias. Several methodologies have emerged in literature, specially concerning the most popular Hill estimator (Hill, 1975). In this work we compare through simulation well-known procedures presented in Drees and Kaufmann (1998), Matthys and Beirlant (2000), Beirlant et al. (2002) and de Sousa and Michailidis (2004), with a heuristic scheme considered in Frahm et al. (2005) within the estimation of a different tail measure but with a similar context. We will see that the new method may be an interesting alternative.

Comparing different methods to measure biofilm thickness: the techniques are: optical coherence tomography, confocal laser scanning microscopy and low load compression test

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clínica)

Suicide attempts and substance use in an emergency room sample

OBJECTIVE: Describe suicide attempts assisted in an emergency room (ER) and acute substance consumption or dependence on these individuals. METHODS: Descriptive epidemiologic study was carried out during one year, evaluating suicide attempts assisted at Embu das Artes ER, São Paulo, Brazil. Patients were scheduled to a non structured psychiatric interview. Main outcomes measures were: socio demographic data, suicide attempt method, drugs or alcohol acute use in the six hours prior to attempt, patients with ICD-10 substance dependence diagnosis. The descriptive analyses and chi-square test (p < 0.05) were used to verify associations between the variables studied. RESULTS: sample was formed of 80 patients, mean age of 26.9 years (SD = 8.91), predominantly female (72.5%) and 21.2% adolescents. Most suicide attempts were made through medicine ingestion (62.5%). Approximately 21.2% and 7.5% related to have used alcohol and an illicit drug respectively within 6 hours prior to attempt and 10% were found to be substance dependent. All substance dependents had attempted suicide previously (p-value = 0.4). There was a significant association between suicide attempt through medicine ingestion and psychiatric treatment history (p = 0.02). CONCLUSION: More national studies are necessary to consider the role of alcohol and drug in suicide attempts assisted in ER, especially in chemical dependents whose suicidal behavior is relevant.

Finite integration methods for isospectral flows

In this paper we consider the approximate computation of isospectral flows based on finite integration methods( FIM) with radial basis functions( RBF) interpolation,a new algorithm is developed. Our method ensures the symmetry of the solutions. Numerical experiments demonstrate that the solutions have higher accuracy by our algorithm than by the second order Runge- Kutta( RK2) method.

Postpartum depression in Recife - Brazil: prevalence and association with bio-socio-demographic factors

OBJECTIVE:To use a semi-structured interview to detect depression in postpartum women according to the criteria proposed by the DSM in child health care clinics in the city of Recife, together with the proper association of this disorder to bio-socio-demographic data. METHODS: The study used a cross-section method and contained a convenience sample of 400 women that were between 2 and 26 weeks of postpartum in child health care clinics. A bio-socio-demographic questionnaire and the Portuguese version of the Structured Clinical Interview for DSM-IV Axis I Disorders were used. RESULTS: Twenty nine of the mothers (7.2%) were diagnosed as suffering from postpartum depression. Women with a past history of psychiatric disorders, a family history of psychiatric disorder and some sort of clinical complication presented a higher prevalence of depression. The same happened to those with a past history of spontaneous abortion, those who had a transpelvic birth and those over 8 weeks of puerperium. CONCLUSION: The rate of postpartum depression in this sample, 7.2%, was lower than that reported by other Brazilian studies. It probably occurred because the other researchers used screening scales to assess this estimate instead of a clinical interview.

Self-evaluated burden in adults with attention-deficit hyperactivity disorder (ADHD): a pilot study

OBJECTIVES: To investigate feasibility and easiness of administration of a brief and simple instrument addressing impairment associated with adult attention deficit hyperactivity disorder (ADHD) and if ADHD subtypes were correlated to specific profiles of self-reported impairment. METHODS: Thirty-five adults (19 men and 16 women; mean age of 31.74 years) diagnosed with ADHD according to DSM-IV with a semi-structured interview (K-SADS PL) were asked to fill out a Likert scale covering six different functional areas (academic, professional, marital, familiar, social and daily activities). Clinicians questioned patients about their understanding of the questionnaire and investigated their answers in more details to check consistency of their answers. RESULTS: No patient reported difficulties in understanding the questionnaire. Further questioning of patients' answers confirmed their choices in the six areas. Academic burden had the highest average score in the whole sample, followed by professional burden. Social area had the lowest average score in this sample.

Is psychodynamic psychotherapy an effective intervention for individuals at ultra-high risk (UHR) of psychosis?: a case report

OBJECTIVE: To report a case and to discuss the use of psychodynamic psychotherapy (PD-P) to treat individuals at ultra-high risk (UHR) of psychosis. METHODS: An individual at UHR was followed up for 24 months. The baseline evaluation included a psychiatric interview, the Structured Interview for Prodromal Symptoms (SIPS), the Scale of Prodromal Symptoms (SOPS), and neuropsychological assessment. He underwent weekly sessions of PD-P for 12 months and was followed up for 12 months after the end of PD-P. The evaluations were at baseline, after 6-, 12-, and 24-month follow-up. No medication was prescribed during the 24-month follow-up. RESULTS: The prodromal symptoms remitted. The initial total score on the SIPS/SOPS was 37 points. After the first 12 months of PD-P, there was a reduction to 12 points on the SIPS/SOPS score, which stabilized in the 24-month follow-up. There was also a slight improvement in his performance on the neuropsychological evaluations. CONCLUSION: This case report suggests that PD-P can reduce prodromal symptoms; nevertheless, a better understanding of the specificity and efficacy of PD-P as an option of treatment for UHR individuals is needed.

Cross-cultural adaptation to Brazil of Medication Adherence Rating Scale for psychiatric patients

Objective The purpose of this research was to make a cross-cultural adaptation of the Medication Adherence Rating Scale (MARS) for psychiatric patients to the Brazilian context. Methods The procedure consisted of four phases: translation of the original scale, back-translation, review by an Expert Committee and Pre-test study with a patients’ sample. Results The Expert Committee corrected the items’ translation when necessary and modified the scale administration format and its instructions from self-report to face-to-face interview form in order to ensure easy understanding by the target population. During Pre-test, the instructions and most of the items were properly understood by patients, with the exception of three of them which had to be changed in order to ensure better understanding. The Pre-test sample was composed by 30 psychiatric patients, with severe and persistent disorders mainly single (46.7%), female (60.0%), with a mean age of 43.8 years old and an average of five years of education. Conclusion The Brazilian version of MARS scale is now adapted to the Brazilian Portuguese language and culture and is easily understood by the psychiatric target population. It is necessary to do further research to evaluate the scale psychometric qualities of validity and reliability in order to use it in Brazil.

Posttraumatic stress disorder: prevalences, comorbidities and quality of life in a community sample of young adults

Objectives To verify the prevalence of current posttraumatic stress disorder (PTSD) in young adults, the occurrence of comorbidities and its association with quality of life. Methods This is a cross-sectional population-based study. The targeted population consisted on individuals aged 18 to 24 years old, who lived in the urban area of Pelotas-RS, Brazil. Cluster sampling was applied. PTSD and its comorbidities were assessed using the Mini International Neuropsychiatric Interview (MINI 5.0), whereas quality of life was evaluated with the eight domains of the Medical Outcomes Survey Short-form General Health Survey (SF-36). Results A total of 1,762 young adults were selected. The prevalence of PTSD was 2.1% and current episode of depression was the most prevalent comorbidity (71.9%). The individuals with PTSD had lower scores in all domains of quality of life. Conclusion These findings indicate that PTSD is associated with other psychopathologies, especially depression, and it has a substantial impact over quality of life in a sample of young adults.

Development of computational and experimental methods for biomass composition and evaluation of its impact in genome-scale models prediction

The use of genome-scale metabolic models has been rapidly increasing in fields such as metabolic engineering. An important part of a metabolic model is the biomass equation since this reaction will ultimately determine the predictive capacity of the model in terms of essentiality and flux distributions. Thus, in order to obtain a reliable metabolic model the biomass precursors and their coefficients must be as precise as possible. Ideally, determination of the biomass composition would be performed experimentally, but when no experimental data are available this is established by approximation to closely related organisms. Computational methods however, can extract some information from the genome such as amino acid and nucleotide compositions. The main objectives of this study were to compare the biomass composition of several organisms and to evaluate how biomass precursor coefficients affected the predictability of several genome-scale metabolic models by comparing predictions with experimental data in literature. For that, the biomass macromolecular composition was experimentally determined and the amino acid composition was both experimentally and computationally estimated for several organisms. Sensitivity analysis studies were also performed with the Escherichia coli iAF1260 metabolic model concerning specific growth rates and flux distributions. The results obtained suggest that the macromolecular composition is conserved among related organisms. Contrasting, experimental data for amino acid composition seem to have no similarities for related organisms. It was also observed that the impact of macromolecular composition on specific growth rates and flux distributions is larger than the impact of amino acid composition, even when data from closely related organisms are used.

Presence of dual diagnosis between users and non-users of licit and illicit drugs in Brazil

ABSTRACT Objective Investigate the occurrence of dual diagnosis in users of legal and illegal drugs. Methods It is an analytical, cross-sectional study with a quantitative approach, non-probabilistic intentional sampling, carried out in two centers for drug addiction treatment, by means of individual interviews. A sociodemographic questionnaire, the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the Mini-International Neuropsychiatric Interview (MINI) were used. Results One hundred and ten volunteers divided into abstinent users (group 1), alcoholics (group 2) and users of alcohol and illicit drugs (group 3). The substances were alcohol, tobacco, crack and marijuana. A higher presence of dual diagnosis in group 3 (71.8%) was observed, which decreased in group 2 (60%) and 37.1% of drug abstinent users had psychiatric disorder. Dual diagnosis was associated with the risk of suicide, suicide attempts and the practice of infractions. The crack consumption was associated with the occurrence of major depressive episode and antisocial personality disorder. Conclusion It was concluded that the illicit drug users had a higher presence of dual diagnosis showing the severity of this clinical condition. It is considered essential that this clinical reality is included in intervention strategies in order to decrease the negative effects of consumption of these substances and provide better quality of life for these people.

Methods to solve the equations of motion

"Series title: Springerbriefs in applied sciences and technology, ISSN 2191-530X"

Integration methods in dynamic analysis

"Series title: Springerbriefs in applied sciences and technology, ISSN 2191-530X"