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1.
J Forensic Sci ; 69(4): 1364-1376, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38602046

RESUMO

Forensic clinicians are often called upon to help courts determine the likelihood that someone will continue to commit sexually violent acts in the future. The utility of these evaluations depends largely on how effectively the results are communicated to and understood by the trier of fact. Actuarial results, such as those commonly reported in sexual offense risk assessments, appear particularly challenging for laypersons to understand. Using a representative sample of 206 U.S. adults, this study examines three methods of communicating actuarial risk via simulated expert testimony on participants' ratings of a hypothetical evaluee's risk of sexual re-offending. The results suggested that all participants, regardless of how results were communicated, over-estimated the examinee's risk level relative to the expert's probabilistic findings, but tended to agree with the expert's categorical predictions. Participants who were only shown actuarial data consistently rated the evaluee as more dangerous and likely to commit future sexually violent acts. Additionally, it was found that gender significantly impacted participants' perceptions, such that women found the evaluee more dangerousness and desired greater social distance from him. This study has implications for best practices regarding expert communication of actuarial results in cases involving sexual violence.


Assuntos
Comunicação , Delitos Sexuais , Humanos , Masculino , Feminino , Adulto , Medição de Risco , Adulto Jovem , Sexismo , Pessoa de Meia-Idade , Adolescente , Prova Pericial , Análise Atuarial , Idoso , Comportamento Perigoso
2.
Respir Res ; 24(1): 215, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37649012

RESUMO

RATIONALE: X-ray velocimetry (XV) has been utilized in preclinical models to assess lung motion and regional ventilation, though no studies have compared XV-derived physiologic parameters to measures derived through conventional means. OBJECTIVES: To assess agreement between XV-analysis of fluoroscopic lung images and pitot tube flowmeter measures of ventilation. METHODS: XV- and pitot tube-derived ventilatory parameters were compared during tidal breathing and with bilevel-assisted breathing. Levels of agreement were assessed using the Bland-Altman analysis. Mixed models were used to characterize the association between XV- and pitot tube-derived values and optimize XV-derived values for higher ventilatory volumes. MEASUREMENTS AND MAIN RESULTS: Twenty-four healthy volunteers were assessed during tidal breathing and 11 were reassessed with increased minute ventilation with bilevel-assisted breathing. No clinically significant differences were observed between the two methods for respiratory rate (average Δ: 0.58; 95% limits of agreement: -1.55, 2.71) or duty cycle (average Δ: 0.02; 95% limits of agreement: 0.01, 0.03). Tidal volumes and flow rates measured using XV were lower than those measured using the pitot tube flowmeter, particularly at the higher volume ranges with bilevel-assisted breathing. Under these conditions, a mixed-model based adjustment was applied to the XV-derived values of tidal volume and flow rate to obtain closer agreement with the pitot tube-derived values. CONCLUSION: Radiographically obtained measures of ventilation with XV demonstrate a high degree of correlation with parameters of ventilation. If the accuracy of XV were also confirmed for assessing the regional distribution of ventilation, it would provide information that goes beyond the scope of conventional pulmonary function tests or static radiographic assessments.


Assuntos
Pulmão , Respiração , Adulto , Humanos , Raios X , Radiografia , Volume de Ventilação Pulmonar , Pulmão/diagnóstico por imagem
3.
Front Med (Lausanne) ; 10: 1160292, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37261124

RESUMO

Dynamic heterogeneity in lung ventilation is an important measure of pulmonary function and may be characteristic of early pulmonary disease. While standard indices like spirometry, body plethysmography, and blood gases have been utilized to assess lung function, they do not provide adequate information on regional ventilatory distribution nor function assessments of ventilation during the respiratory cycle. Emerging technologies such as xenon CT, volumetric CT, functional MRI and X-ray velocimetry can assess regional ventilation using non-invasive radiographic methods that may complement current methods of assessing lung function. As a supplement to current modalities of pulmonary function assessment, functional lung imaging has the potential to identify respiratory disease phenotypes with distinct natural histories. Moreover, these novel technologies may offer an optimal strategy to evaluate the effectiveness of novel therapies and therapies targeting localized small airways disease in preclinical and clinical research. In this review, we aim to discuss the features of functional lung imaging, as well as its potential application and limitations to adoption in research.

4.
Assessment ; 30(6): 1985-1997, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36341535

RESUMO

The Psychological Inventory of Criminal Thinking Styles-Short Form (PICTS-SF) is an abbreviated 35-item version of the PICTS, a measure of cognitions that support a criminal lifestyle. Despite use in research and clinical work, the PICTS-SF's psychometric properties have not been tested. Using two archival datasets, we analyzed the PICTS-SF's reliability and structural validity in multiply imputed data from adult males and females on probation in a residential treatment facility (n = 514). We also tested the PICTS-SF's reliability and discriminant and postdictive validities among adult males in administrative segregation in prison (n = 95). We found evidence for the PICTS-SF's internal consistency (α and ω ≥ .89), structural validity (CFI = .90, RMSEA = .05), discriminant validity (.22 ≤ r ≤ .39), and postdictive validity for receiving disciplinary infractions (incident rate ratio = 1.04). These results support the PICTS-SF's use in research, and qualified use in clinical applications.


Assuntos
Criminosos , Masculino , Adulto , Feminino , Humanos , Criminosos/psicologia , Psicometria , Reprodutibilidade dos Testes , Pensamento , Cognição
5.
BMJ Open ; 12(7): e053606, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35820740

RESUMO

OBJECTIVES: Recurrent symptomatic effusions can be durably managed with pleurodesis or placement of indwelling pleural catheters. Recent pleurodesis trials have largely relied on lung re-expansion on post-thoracentesis radiograph as an inclusion criterion rather than pleural elastance as determined by manometry, which is an important predictor of successful pleurodesis. We investigated the association between lung re-expansion on post-pleural drainage chest imaging and pleural physiology, with particular attention to pleural elastance over the final 200 mL aspirated. DESIGN: Post-hoc analysis of a recent randomised trial. SETTING AND PARTICIPANTS: Post-results analysis of 61 subjects at least 18 years old with symptomatic pleural effusions estimated to be at least of 0.5 L in volume allocated to manometry-guided therapeutic thoracentesis in a recent randomised trial conducted at two major university hospitals in the USA. PRIMARY OUTCOME MEASURES: The primary outcome was concordance of radiographic with normal terminal pleural elastance over the final 200 mL aspirated. We label this terminal elastance 'visceral pleural recoil', or the tendency of the maximally expanded lung to withdraw from the chest wall. RESULTS: Post-thoracentesis chest radiograph and thoracic ultrasound indicated successful lung re-expansion in 69% and 56% of cases, respectively. Despite successful radiographic lung re-expansion, visceral pleural recoil was abnormal in 71% of subjects expandable by radiograph and 77% expandable by ultrasound. The sensitivity and positive predictive value of radiographic lung re-expansion for normal visceral pleural recoil were 44% and 24%, respectively. CONCLUSION: Radiographic lung re-expansion by post-thoracentesis chest radiograph or thoracic ultrasound is a poor surrogate for normal terminal pleural elastance. Clinical management of patients with recurrent symptomatic pleural effusions guided by manometry rather than post-thoracentesis imaging might produce better outcomes, which should be investigated by future clinical trials. TRIAL REGISTRATION NUMBER: NCT02677883; Post-results.


Assuntos
Derrame Pleural , Toracentese , Adolescente , Adulto , Humanos , Pulmão , Pleura/diagnóstico por imagem , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/terapia , Pleurodese
6.
Psychol Serv ; 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35617236

RESUMO

Recent studies have indicated variable reductions in criminal thinking for justice-involved persons with mental illness exposed to cognitive-behavioral treatments. To date, however, no studies have identified risk factors for limited response or modeled observed disparities in responsivity to interventions aimed at reducing criminal thinking. Using an archival data set of 162 probationers with a dual diagnosis who were exposed to changing lives and changing outcomes, a latent profile analysis modeled unobserved heterogeneity in treatment response per observed changes in criminal thinking. Most participants endorsed significant changes in self-reported reactive criminal thinking with minimal changes in proactive criminal thinking. Neither self-reported pretreatment severity of psychopathology nor self-reported compliance with psychotropic medication predicted response to treatment. Although diagnosis also did not predict responsiveness, more favorable views of treatment predicted greater decreases in criminal thinking. Moreover, those expressing fewer levels of criminal thinking after treatment were also found to express a decrease in attitudes supportive of violence. Limitations and treatment recommendations are discussed, including the need for correctional treatments to improve responsiveness to individual treatment needs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

7.
Respiration ; : 1-8, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33550284

RESUMO

BACKGROUND: Digital fluoroscopic tomosynthesis-guided electromagnetic navigational bronchoscopy (F-ENB) is a novel adjunct to ENB associated with higher diagnostic yield. The likelihood of F-ENB allowing accurate placement of a biopsy needle within a target remains unclear. OBJECTIVE: This study intends to determine the accuracy of F-ENB as confirmed by cone-beam computed tomography (CBCT) scan. METHODS: Patients undergoing CBCT-assisted ENB for lung nodule biopsy were prospectively enrolled. ENB was performed followed by digital tomosynthesis correction. Once optimal F-ENB alignment was achieved, and a needle was advanced into the expected location of the nodule followed by CBCT. The primary outcome was the percentage of "needle-in-lesion" hits, defined as needle tip within the nodule in 3 planes. Secondary outcomes were diagnostic yield, procedure and room time, complications, radiation, and distance between the needle tip and nodule. RESULTS: Twenty-six patients with a total of 29 nodules were enrolled. Mean nodule size was 13 mm (±4 mm) in maximal axial dimension, 83% (n = 24) were located in the peripheral third of the chest, and 17% (n = 5) had a bronchus sign. F-ENB guidance resulted in needle-in-lesion in 21 of 29 nodules (72%). Mean needle tip-to-nodule distance for nonhits was 1.75 mm (±1.35 mm). There were no complications. CONCLUSION: F-ENB resulted in a needle-in-lesion biopsy in greater than 70% of nodules despite features traditionally associated with poor diagnostic yield (size, absence of bronchus sign). Mean distance between needle tip and target for nonhits was less than 2 mm. These data suggest F-ENB alignment is accurate for small peripheral nodules.

8.
Psychol Serv ; 18(4): 679-688, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32452691

RESUMO

Research on the effects of restricted housing on inmate well-being indicates mild to moderate psychological effects and barriers opportunities for treatment and positive growth. Yet, there are few interventions tailored both to the needs of this high-risk population and to the institutional constraints of their environment. Given the financial and safety burdens associated with housing someone in segregation compared to the general population, correctional psychology should focus on developing programs that work. Using a prepost design, this study presents findings from a pilot investigation (N = 39) on the effects of a new, largely self-directed program (Stepping Up, Stepping Out [SUSO]) for inmates with mental and behavioral health concerns who are placed in restrictive settings. Results suggest that SUSO is associated with meaningful reductions in overall emotional distress and criminal attitudes; however, improvements in more stable criminal thinking patterns (i.e., distorted cognitions that are used to justify and support antisocial behavior; see Walters, 2012) were not observed. Overall, posttreatment working alliance was rated favorably by program participants. Demographic and preintervention comparisons between program completers and dropouts are also reported. Though preliminary findings suggest SUSO is a promising intervention for alleviating distress and aspects of criminal risk for inmates placed in restricted housing, future research should assess fidelity and engagement leading to a randomized controlled trial to determine the effectiveness of this program. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Habitação , Humanos , Desenvolvimento de Programas
10.
J Community Psychol ; 48(7): 2156-2173, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32779794

RESUMO

Videoconferencing technology (VCT) is rapidly increasing in the mental healthcare industry and is becoming an attractive option to reach justice-involved populations. This paper first highlights the need for alternative service delivery solutions and reviews current literature on the use of VCT for correctional clients. We then outline the specific timeline, procedures, and barriers associated with the initiation of a virtual, multidisciplinary telemental health clinic for jailed and community-released offenders in a rural Mississippi county aimed at reducing criminogenic and psychiatric risks. Finally, we summarize generalizable recommendations for establishing community partnerships, developing structural and logistical processes, and delivering VCT while accounting for unique client factors and integrating evidence-based intervention strategies. We hope other community leaders will feel empowered to initiate similar programs that address needs within in their own jurisdictions.


Assuntos
Serviços Comunitários de Saúde Mental/organização & administração , Criminosos/psicologia , Prisioneiros/psicologia , Telemedicina/organização & administração , Adulto , Feminino , Humanos , Masculino , Mississippi , Desenvolvimento de Programas/métodos
11.
IEEE Access ; 8: 181411-181419, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-35198341

RESUMO

The maximum curvature of a steerable needle in soft tissue is highly sensitive to needle shaft stiffness, which has motivated use of small diameter needles in the past. However, desired needle payloads constrain minimum shaft diameters, and shearing along the needle shaft can occur at small diameters and high curvatures. We provide a new way to adjust needle shaft stiffness (thereby enhancing maximum curvature, i.e. "steerability") at diameters selected based on needle payload requirements. We propose helical dovetail laser patterning to increase needle steerability without reducing shaft diameter. Experiments in phantoms and ex vivo animal muscle, brain, liver, and inflated lung tissues demonstrate high steerability in soft tissues. These experiments use needle diameters suitable for various clinical scenarios, and which have been previously limited by steering challenges without helical dovetail patterning. We show that steerable needle targeting remains accurate with established controllers and demonstrate interventional payload delivery (brachytherapy seeds and radiofrequency ablation) through the needle. Helical dovetail patterning decouples steerability from diameter in needle design. It enables diameter to be selected based on clinical requirements rather than being carefully tuned to tissue properties. These results pave the way for new sensors and interventional tools to be integrated into high-curvature steerable needles.

12.
Artigo em Inglês | MEDLINE | ID: mdl-35284151

RESUMO

Bronchoscopic diagnosis and intervention in the lung is a new frontier for steerable needles, where they have the potential to enable minimally invasive, accurate access to small nodules that cannot be reliably accessed today. However, the curved, flexible bronchoscope requires a much longer needle than prior work has considered, with complex interactions between the needle and bronchoscope channel, introducing new challenges in steerable needle control. In particular, friction between the working channel and needle causes torsional windup along the bronchoscope, the effects of which cannot be directly measured at the tip of thin needles embedded with 5 degree-of-freedom magnetic tracking coils. To compensate for these effects, we propose a new torsional deadband-aware Extended Kalman Filter to estimate the full needle tip pose including the axial angle, which defines its steering direction. We use the Kalman Filter estimates with an established sliding mode controller to steer along desired trajectories in lung tissue. We demonstrate that this simple torsional deadband model is sufficient to account for the complex interactions between the needle and endoscope channel for control purposes. We measure mean final targeting error of 1.36 mm in phantom tissue and 1.84 mm in ex-vivo porcine lung, with mean trajectory following error of 1.28 mm and 1.10 mm, respectively.

13.
N Engl J Med ; 380(9): 811-821, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30779528

RESUMO

BACKGROUND: Hypoxemia is the most common complication during tracheal intubation of critically ill adults and may increase the risk of cardiac arrest and death. Whether positive-pressure ventilation with a bag-mask device (bag-mask ventilation) during tracheal intubation of critically ill adults prevents hypoxemia without increasing the risk of aspiration remains controversial. METHODS: In a multicenter, randomized trial conducted in seven intensive care units in the United States, we randomly assigned adults undergoing tracheal intubation to receive either ventilation with a bag-mask device or no ventilation between induction and laryngoscopy. The primary outcome was the lowest oxygen saturation observed during the interval between induction and 2 minutes after tracheal intubation. The secondary outcome was the incidence of severe hypoxemia, defined as an oxygen saturation of less than 80%. RESULTS: Among the 401 patients enrolled, the median lowest oxygen saturation was 96% (interquartile range, 87 to 99) in the bag-mask ventilation group and 93% (interquartile range, 81 to 99) in the no-ventilation group (P = 0.01). A total of 21 patients (10.9%) in the bag-mask ventilation group had severe hypoxemia, as compared with 45 patients (22.8%) in the no-ventilation group (relative risk, 0.48; 95% confidence interval [CI], 0.30 to 0.77). Operator-reported aspiration occurred during 2.5% of intubations in the bag-mask ventilation group and during 4.0% in the no-ventilation group (P = 0.41). The incidence of new opacity on chest radiography in the 48 hours after tracheal intubation was 16.4% and 14.8%, respectively (P = 0.73). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, patients receiving bag-mask ventilation had higher oxygen saturations and a lower incidence of severe hypoxemia than those receiving no ventilation. (Funded by Vanderbilt Institute for Clinical and Translational Research and others; PreVent ClinicalTrials.gov number, NCT03026322.).


Assuntos
Estado Terminal/terapia , Hipóxia/prevenção & controle , Intubação Intratraqueal/efeitos adversos , Oxigênio/sangue , Respiração Artificial/instrumentação , Adulto , Idoso , Feminino , Humanos , Hipóxia/etiologia , Unidades de Terapia Intensiva , Intubação Intratraqueal/métodos , Máscaras Laríngeas , Masculino , Pessoa de Meia-Idade
14.
BMJ Open ; 8(8): e022139, 2018 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-30099400

RESUMO

INTRODUCTION: Hypoxaemia is the most common complication during endotracheal intubation of critically ill adults, and it increases the risk of cardiac arrest and death. Manual ventilation between induction and intubation has been hypothesised to decrease the incidence of hypoxaemia, but efficacy and safety data are lacking. METHODS AND ANALYSIS: The Preventing Hypoxemia with Manual Ventilation during Endotracheal Intubation trial is a prospective, multicentre, non-blinded randomised clinical trial being conducted in seven intensive care units in the USA. A total of 400 critically ill adults undergoing endotracheal intubation will be randomised 1:1 to receive prophylactic manual ventilation between induction and endotracheal intubation using a bag-valve-mask device or no prophylactic ventilation. The primary outcome is the lowest arterial oxygen saturation between induction and 2 min after successful endotracheal intubation, which will be analysed as an unadjusted, intention-to-treat comparison of patients randomised to prophylactic ventilation versus patients randomised to no prophylactic ventilation. The secondary outcome is the incidence of severe hypoxaemia, defined as any arterial oxygen saturation of less than 80% between induction and 2 min after endotracheal intubation. Enrolment began on 2 February 2017 and is expected to be complete in May 2018. ETHICS AND DISSEMINATION: The trial was approved by the institutional review boards or designees of all participating centres. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. TRIAL REGISTRATION NUMBER: NCT03026322; Pre-results.


Assuntos
Estado Terminal/terapia , Hipóxia/prevenção & controle , Intubação Intratraqueal/métodos , Respiração Artificial/métodos , Adulto , Protocolos Clínicos , Feminino , Humanos , Intubação Intratraqueal/efeitos adversos , Masculino , Resultado do Tratamento
15.
J Sch Health ; 84(10): 661-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25154530

RESUMO

BACKGROUND: Several states have implemented childhood obesity surveillance programs supported by legislation. Representatives from Idaho wished to develop a model for childhood obesity surveillance without the support of state legislation, and subsequently report predictors of overweight and obesity in the state. METHODS: A coalition comprised of the Idaho State Department of Education and 4 universities identified a randomized cluster sample of schools. After obtaining school administrator consent, measurement teams traveled to each school to measure height and weight of students. Sex and race/ethnicity data were also collected. RESULTS: The collaboration between the universities resulted in a sample of 6735 students from 48 schools and 36 communities. Overall, 29.2% of the youth in the sample were classified as overweight or obese, ranging from 24.0% for grade 1 to 33.8% for grade 5. The prevalence of overweight and obesity across schools was highly variable (31.2 ± 7.58%). Hierarchical logistic regression indicated that sex, age, race/ethnicity, socioeconomic status, and region were all significant predictors of overweight and obesity, whereas school was not. CONCLUSIONS: This coalition enabled the state of Idaho to successfully estimate the prevalence of overweight and obesity on a representative sample of children from all regions of the state, and subsequently identify populations at greatest risk.


Assuntos
Índice de Massa Corporal , Sobrepeso/epidemiologia , Vigilância de Evento Sentinela , Adolescente , Pesos e Medidas Corporais , Criança , Feminino , Humanos , Idaho/epidemiologia , Masculino , Obesidade Infantil/epidemiologia , Prevalência , Instituições Acadêmicas , Fatores Sexuais , Fatores Socioeconômicos
16.
Environ Monit Assess ; 186(8): 4779-91, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24729180

RESUMO

Heavy metals are persistent environmental contaminants, and transport of metals into the environment poses a threat to ecosystems, as plants and wildlife are susceptible to long-term exposure, bioaccumulation, and potential toxicity. We investigated the distribution and cascading extent of heavy metal accumulation in southwestern song sparrows (Melospiza melodia fallax), a resident riparian bird species that occurs along the US/Mexico border in Arizona's upper Santa Cruz River watershed. This study had three goals: (1) quantify the degree of heavy metal accumulation in sparrows and determine the distributional patterns among study sites, (2) compare concentrations of metals found in this study to those found in studies performed prior to a 2009 international wastewater facility upgrade, and (3) assess the condition of song sparrows among sites with differing potential levels of exposure. We examined five study sites along with a reference site that reflect different potential sources of contamination. Body mass residuals and leukocyte counts were used to assess sparrow condition. Birds at our study sites typically had higher metal concentrations than birds at the reference site. Copper, mercury, nickel, and selenium in song sparrows did exceed background levels, although most metals were below background concentrations determined from previous studies. Song sparrows generally showed lower heavy metal concentrations compared to studies conducted prior to the 2009 wastewater facility upgrade. We found no cascading effects as a result of metal exposure.


Assuntos
Monitoramento Ambiental , Poluentes Ambientais/metabolismo , Metais Pesados/metabolismo , Pardais/metabolismo , Animais , Arizona , Ecossistema , Poluição Ambiental/estatística & dados numéricos , Metais Pesados/análise , México , Rios/química
17.
Bioorg Med Chem ; 18(7): 2602-10, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-20299229

RESUMO

Natural products serve as a great reservoir for chemical diversity and are the greatest source for antibacterial agents. Recent discoveries of platensimycin and platencin as inhibitors of bacterial fatty acid biosynthesis enzymes supplied new chemical scaffolds for potential antibacterial agents to overcome resistant pathogens. Discovery of natural congeners augment chemical modification in understanding of structure-activity relationship (SAR). Chemical and biological screening of the extracts led to isolation of three hydroxylated analogs of platencin. The C-12, C-14 and C-15 hydroxylated analogs showed attenuated activities which provided significant understanding of functional tolerance in the diterpenoid portion of the molecule. A truncated and oxidized C-13 natural congener was isolated which suggested direct intermediacy of ent-copalyl diphosphate for the biosynthesis of platensimycins and platencins.


Assuntos
Adamantano/análogos & derivados , Aminobenzoatos/química , Aminofenóis/química , Antibacterianos/química , Compostos Policíclicos/química , Streptomyces/química , Adamantano/química , Adamantano/farmacologia , Aminobenzoatos/farmacologia , Aminofenóis/farmacologia , Antibacterianos/farmacologia , Cromatografia Líquida de Alta Pressão , Fermentação , Haemophilus influenzae/efeitos dos fármacos , Hidroxilação , Indicadores e Reagentes , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Modelos Moleculares , Conformação Molecular , Compostos Policíclicos/farmacologia , Espectrofotometria Ultravioleta , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
18.
Bioprocess Biosyst Eng ; 32(4): 443-58, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18853195

RESUMO

A pilot-scale fermentation was developed for an antifungal compound produced by a filamentous fungus. Replacement of galactose with lactose (20-fold cost savings) and a threefold phosphate reduction (15 to 5 g/L) improved productivity 2.5-fold. Addition of supplements--glycine, cobalt chloride, and trace elements--resulted in a further twofold productivity increase, greater process robustness, and less foaming which reduced antifoam addition tenfold (30 to <3 mL/L). Mid-cycle lactose limitations were addressed by raising initial lactose levels (40 to 120 g/L) resulting in another twofold productivity increase. Overall, peak titers increased tenfold from 45 +/- 9 to 448 +/- 39 mg/L, and productivities improved from 3 to 25 mg/L day. Despite its high productivity, process scale up was challenged by high broth viscosity (5,000-6,000 cP at 16.8 s(-1)). Gassed power requirements at the 600 L scale (4.7 kW/1,000 L) exceeded available power at the 15,000 L scale (3.0 kW/1,000 L), and broth transfer to the downstream isolation facility was hindered. Mid-cycle broth dilution with up to five 10 vol% additions of 12 wt% lactose solution or whole medium-reduced viscosity three- to fivefold (1,000-1,500 cP at 16.8 s(-1)), gassed power within scale-up limits (2.5 kW/1,000 L), and peak titer by up to 45%. The process was scaled up to the 15,000 L working volume based on constant aeration rate (vvm) and peak impeller tip speed, raising superficial velocities at similar shear. This strategy maximized mass transfer rates at target gassed power per unit volume levels, and along with controlled broth viscosity, precluded multiple dilution additions. A final titer of 333 mg/L with one dilution addition was achieved, somewhat lower than expected, likely owing to inhibition from some unmeasured volatile compound (not believed to be carbon dioxide) during an extended period of high back-pressure in the early production phase.


Assuntos
Antifúngicos/isolamento & purificação , Antifúngicos/metabolismo , Ascomicetos/crescimento & desenvolvimento , Ascomicetos/metabolismo , Engenharia Biomédica , Reatores Biológicos , Meios de Cultura , Fermentação , Galactose/metabolismo , Glicerol/metabolismo , Lactose/metabolismo , Fosfatos/metabolismo , Projetos Piloto , Viscosidade
19.
Bioprocess Biosyst Eng ; 30(5): 313-26, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17566786

RESUMO

The feasibility of in situ measurement device for bubble size and distribution was explored. A novel in situ probe measurement system, the EnviroCam, was developed. Where possible, this probe incorporated strengths, and minimized weaknesses of historical and currently available real-time measurement methods for bubbles. The system was based on a digital, high-speed, high resolution, modular camera system, attached to a stainless steel shroud, compatible with standard Ingold ports on fermenters. Still frames and/or video were produced, capturing bubbles passing through the notch of the shroud. An LED light source was integral with the shroud. Bubbles were analyzed using customized commercially available image analysis software and standard statistical methods. Using this system, bubble sizes were measured as a function of various operating parameters (e.g., agitation rate, aeration rate) and as a function of media properties (e.g., viscosity, antifoam, cottonseed flour, and microbial/animal cell broths) to demonstrate system performance and its limitations. For selected conditions, mean bubble size changes qualitatively compared favorably with published relationships. Current instrument measurement capabilities were limited primarily to clear solutions that did not contain large numbers of overlapping bubbles.


Assuntos
Biotecnologia/instrumentação , Biotecnologia/métodos , Microscopia/instrumentação , Reatores Biológicos , Calibragem , Computadores , Meios de Cultura/química , Desenho de Equipamento , Fermentação , Microscopia/métodos , Distribuição Normal , Tamanho da Partícula , Software , Temperatura , Fatores de Tempo , Gravação em Vídeo , Água/química
20.
J Biosci Bioeng ; 102(4): 251-68, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17116571

RESUMO

Facility experience primarily in drug-oriented fermentation equipment (producing small molecules such as secondary metabolites, bioconversions, and enzymes) and, to a lesser extent, in biologics-oriented fermentation equipment (producing large molecules such as recombinant proteins and microbial vaccines) in an industrial fermentation pilot plant over the past 15 years is described. Potential approaches for equipment design and maintenance, operational procedures, validation/verification testing, medium selection, culture purity/sterility analysis, and contamination investigation are presented, and those approaches implemented are identified. Failure data collected for pilot plant operation for nearly 15 years are presented and best practices for documentation and tracking are outlined. This analysis does not exhaustively discuss available design, operational and procedural options; rather it selectively presents what has been determined to be beneficial in an industrial pilot plant setting. Literature references have been incorporated to provide background and context where appropriate.


Assuntos
Reatores Biológicos/microbiologia , Descontaminação/métodos , Contaminação de Equipamentos/prevenção & controle , Análise de Falha de Equipamento/métodos , Fermentação , Microbiologia Industrial/instrumentação , Manutenção/métodos , Descontaminação/instrumentação , Análise de Falha de Equipamento/instrumentação , Microbiologia Industrial/métodos , Projetos Piloto
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