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2.
Eur J Hum Genet ; 31(3): 257-261, 2023 03.
Article in English | MEDLINE | ID: mdl-36631541

ABSTRACT

A Community Genetics carrier screening program for the Jewish community has operated on-site in high schools in Sydney (Australia) for 25 years. During 2020, in response to the COVID-19 pandemic, government-mandated social-distancing, 'lock-down' public health orders, and laboratory supply-chain shortages prevented the usual operation and delivery of the annual testing program. We describe development of three responses to overcome these challenges: (1) pivoting to online education sufficient to ensure informed consent for both genetic and genomic testing; (2) development of contactless telehealth with remote training and supervision for collecting genetic samples using buccal swabs; and (3) a novel patient and specimen identification 'GeneTrustee' protocol enabling fully identified clinical-grade specimens to be collected and DNA extracted by a research laboratory while maintaining full participant confidentiality and privacy. These telehealth strategies for education, consent, specimen collection and sample processing enabled uninterrupted delivery and operation of complex genetic testing and screening programs even amid pandemic restrictions. These tools remain available for future operation and can be adapted to other programs.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Pandemics , Specimen Handling/methods , Informed Consent , Genetic Testing
3.
Phytochemistry ; 201: 113265, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35660549

ABSTRACT

The most abundant monoterpenoid indole alkaloids (MIAs) in Catharanthus roseus roots include lochnericine and (+)-echitovenine. The formation of (+)-echitovenine involves a 3-step pathway including (+)-vincadifformine-19-hydroxylase (V19H) that differentiates it from a parallel pathway involved in the formation of lochnericine, hörhammericine and its O-acetylated derivative. Homology based modeling and docking experiments in the present study show that (+) and (-) vincadifformine can occupy the V19H active site and is proven experimentally by showing that (-)-vincadifformine is a competitive inhibitor of V19H. Comparative modeling of V19H with tabersonine 3-oxidase (T3O) and tabersonine 19-hydroxylase (T19H) that accept (-)-aspidosperma MIAs identified four conserved amino acid residues in T3O and T19H that were different in the V19H binding site and were used to generate a series of single-, double-, or four-point mutations in V19H. While all mutants retained their ability to convert (+)-vincadifformine to (+)-minovincinine only the four-point mutant gained T3O activity enabling it to convert (-)-tabersonine to tabersonine 2,3-epoxide. The gain of T3O-like activity following mutagenesis without the loss of V19H activity supports the hypothesis that V19H shares a common ancestor to T3O which is involved in vindoline biosynthesis in C. roseus leaves.


Subject(s)
Catharanthus , Alkaloids , Catharanthus/genetics , Catharanthus/metabolism , Indole Alkaloids/chemistry , Mixed Function Oxygenases/metabolism , Mutagenesis, Site-Directed , Oxidoreductases/metabolism , Plant Proteins/metabolism
4.
BMC Med Educ ; 21(1): 221, 2021 Apr 20.
Article in English | MEDLINE | ID: mdl-33879139

ABSTRACT

BACKGROUND: The Covid pandemic and associated lockdown forced medical schools globally not only to deliver emergency remote teaching, but to consider alternative methods of high stakes assessment. Here we outline our approach to the resit virtual OSCE ("VOSCE") for final year medical students that we undertook during "lockdown" in the current pandemic. METHODS: The original 'pre Covid' examination blueprint was reviewed and modified for the virtual environment in both format and content. In anticipation of the new format delivery, a number of pre-training sessions took place for all parties, and standardised templates were developed. RESULTS: A total of 9 students undertook the VOSCE, which took the form of a two-part exam (a communication and clinical examination component, and a practical procedures component). The VOSCE was completed by all students, examiners, simulated patients and invigilators on an online digital platform with no issues with regards to technical problems. CONCLUSIONS: A total of 6 students passed the VOSCE and as such progressed to graduation. The limitation of assessing some particular types of skills across the remote format (such as practical procedures) was recognised. The training and the templates developed were helpful in case the VOSCE format needs to be adopted in future at short notice and/or expanded in future.


Subject(s)
Academic Performance , COVID-19 , Education, Distance/organization & administration , Students, Medical , Clinical Competence , Communicable Disease Control , Humans , Pandemics
5.
Cultur Divers Ethnic Minor Psychol ; 27(2): 234-244, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32271044

ABSTRACT

Objective: Racial discrimination is a common experience for African Americans, but no research has examined how discrimination reported in daily-life moments influences concurrent negative emotions and psychosocial resources. Method: Emerging adult African Americans (N = 54) reported hourly on momentary racial discrimination, negative emotions, and psychosocial resources across two days. Results: Controlling for past discrimination and trait emotion, momentary racial discrimination was associated with greater negative emotions and lower psychosocial resources (ps < .05). The relationship between momentary racial discrimination and negative emotions was stronger among individuals residing in areas with fewer African Americans (simple slope p < .0001). The relationship between momentary racial discrimination and psychosocial resources was stronger among individuals reporting greater past discrimination (simple slope p < .0001). Vicarious discrimination (exposure to discrimination experienced by another person) was associated with higher negative emotions (p < .01), but not with psychosocial resources. Conclusion: These results are the first to demonstrate that personal and vicarious racial discrimination are associated with negative emotions and lower coping resources in daily-life moments and that contextual factors modify these associations. Results refine our understanding of the immediate sequelae of discrimination in daily life and point to possible targets for ecological momentary interventions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Subject(s)
Racism , Adult , Black or African American , Emotions , Humans
6.
Anal Bioanal Chem ; 412(5): 1123-1128, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31900537

ABSTRACT

Since its introduction, gas chromatography (GC) coupled to vacuum ultraviolet spectrophotometry (VUV) has been shown to complement mass spectrometry (MS) for materials such as petrochemicals, explosives, pesticides, and drugs. In forensic chemistry, opioids are commonly encountered but rarely are the samples pure. This work focuses on GC-VUV analysis applied to naturally occurring (e.g., morphine), semi-synthetic (e.g., heroin), and synthetic (fentanyl) opioids as well as common adulterants and diluents (e.g., lidocaine and quinine). The specificity of the VUV spectra were examined visually as well as via descriptive statistical methods (e.g., correlation coefficients and sums of square residuals). Multivariate pattern recognition techniques (principal component analysis and discriminant analysis (DA)) were used to prove the opioid spectra can be reliably differentiated. The accuracy of the DA model was 100% for a test set of VUV spectra. Finally, three "street" heroin samples were analyzed to show "real-world" performance for forensic analyses. These samples contained adulterants such as caffeine, as well as by-products of heroin manufacture.


Subject(s)
Chromatography, Gas/methods , Opiate Alkaloids/analysis , Spectrophotometry, Ultraviolet/methods , Discriminant Analysis , Forensic Medicine , Principal Component Analysis , Reproducibility of Results
7.
Soc Sci Res ; 71: 11-18, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29514753

ABSTRACT

For over 30 years, researchers have examined social influence using status characteristics theory (Berger and Conner, 1974). While research has investigated beauty and attractiveness as status characteristics (e.g., Webster and Driskell, 1983), there is a dearth of research that examines whether obesity has status value using status characteristics theory. The current paper reviews the literature on, demonstrating how they are related to status characteristics. Next, this paper demonstrates how the effects of both gender and obesity can be explained by considering them as status characteristics, which have the potential to create subsequent status beliefs and stigma. Finally, this study reports empirical findings that support obesity as a status characteristic. We find an effect for obesity on ratings of diffuse status, and effects for both obesity and gender on ratings of influence.

8.
J Child Adolesc Psychopharmacol ; 25(10): 783-98, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26682999

ABSTRACT

OBJECTIVE: The purpose of this study was to investigate the clinical effect and safety of a broad spectrum, 36 ingredient micronutrient (vitamins and minerals) in treating children with attention-deficit/hyperactivity disorder (ADHD). METHODS: This open-label, on-off-on-off (reversal design) study followed 14 participants (8-12 years of age) with ADHD, diagnosed using standardized instruments, for 6 months with no dropouts. Following baseline assessment, including hematology and biochemistry screening, participants began an 8 week treatment phase with micronutrients titrated up to maximum dose (15 capsules/day). Treatment was withdrawn for 4 weeks, reinstated for a further 8 weeks, and then withdrawn for 4 weeks. Primary outcomes included the Conners' Parent Rating Scale, the Clinical Global Impressions Scale (CGI), and the Strengths and Difficulties Questionnaire - Parent version (SDQ). Secondary outcomes were mood and global functioning. RESULTS: Modified Brinley plots revealed a reduction in ADHD symptoms, improved mood, and improved overall functioning during intervention phases, and deterioration in ADHD symptoms, mood, and overall functioning during the withdrawal phases. Reliable change analyses, Cohen's d and percent superiority effect sizes, 95% confidence intervals and t tests confirmed clinically and statistically significant change between the intervention and withdrawal phases, with large effect sizes observed pre- to post-exposure of micronutrients (d = 1.2-2.2) on ADHD symptoms during intervention phases. Seventy-one percent of participants showed at least a 30% decrease in ADHD symptoms by the end of the second treatment phase, and 79% were identified as "much improved" or "very much improved" at the end of the second phase (5 months) based on the clinician-rated CGI when considering functioning generally. The SDQ showed that these benefits occurred across other areas of functioning including emotional symptoms, conduct problems, and prosocial behaviours. The children's self-reports confirmed the improvements. Excellent adherence to treatment occurred throughout, side effects were mild and transitory, and no safety issues were identified through blood analyses. CONCLUSIONS: This study demonstrates the clinical benefit, feasibility, and safety of broad-spectrum micronutrients in the treatment of childhood ADHD. Replications utilizing double-blind placebo-controlled studies are warranted. Trial is registered with the Australia and New Zealand Clinical Trial Registry: ACTRN12612000645853.


Subject(s)
Affect/drug effects , Attention Deficit Disorder with Hyperactivity/drug therapy , Micronutrients/therapeutic use , Child , Double-Blind Method , Female , Humans , Male , Micronutrients/pharmacology , Neuropsychological Tests/statistics & numerical data , Parents
9.
Biochim Biophys Acta ; 1837(8): 1362-75, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24747069

ABSTRACT

The axial ligands of the acceptor chlorophylls, A(0A) and A(0B), in Photosystem I are the Met sulfur atoms of M688(PsaA) and M668(PsaB). To determine the role of the Met, His variants were generated in Synechocystis sp. PCC 6803. Molecular dynamics simulations on M688H(PsaA) show that there exist low energy conformations with the His coordinated to A(0A) and possibly H-bonded to A(1A). Transient EPR studies on M688H(PsaA) indicate a more symmetrical electron spin distribution in the A(1A) phyllosemiquinone ring consistent with the presence of an H-bond to the C1 carbonyl. Ultrafast optical studies on the variants show that the 150fs charge separation between P700 and A(0) remains unaffected. Studies on the ns timescale show that 57% of the electrons are transferred from A(0A)(-) to A(1A) in M688H(PsaA) and 48% from A(0B)(-) to A(1B) in M668H(PsaB); the remainder recombine with P700(+) with 1/e times of 25ns and 37ns, respectively. Those electrons that reach A(1A) and A(1B) in the branch carrying the mutation are not transferred to FX, but recombine with P700(+) with 1/e times of ~15µs and ~5µs, respectively. Hence, the His is coordinated to A0 in all populations, but in a second population, the His may be additionally H-bonded to A(1). Electron transfer from A(0) to A(1) occurs only in the latter, but the higher redox potentials of A(0) and A(1) as a result of the stronger coordination bond to A(0) and the proposed second H-bond to A(1) preclude electron transfer to the Fe/S clusters.


Subject(s)
Chlorophyll/chemistry , Photosynthesis/genetics , Photosystem I Protein Complex/chemistry , Synechocystis/genetics , Chlorophyll/genetics , Chlorophyll/metabolism , Electron Spin Resonance Spectroscopy , Electron Transport , Histidine , Hydrogen Bonding , Kinetics , Ligands , Mutation , Photosystem I Protein Complex/genetics , Synechocystis/chemistry , Synechocystis/growth & development
10.
Hum Psychopharmacol ; 29(3): 230-43, 2014 May.
Article in English | MEDLINE | ID: mdl-24554519

ABSTRACT

OBJECTIVE: We investigated whether micronutrients given acutely following the Christchurch earthquakes continued to confer benefit 1 year following the treatment. METHODS: Sixty-four adults from the original 91 participants experiencing heightened anxiety or stress 2-3 months following the 22nd February 2011 earthquake and who had been randomized to receive three different doses of micronutrients completed on-line questionnaires assessing mood, anxiety, stress, and symptoms associated with post-traumatic stress disorder 1 year after completing the initial study. Twenty-one out of 29 nonrandomized controls who did not receive the treatment also completed the questionnaires. RESULTS: Both the treated and control groups experienced significant improvement in psychological functioning compared with end-of-trial. However, treated participants had better long-term outcomes on most measures compared with controls (ES=0.69-1.31). Those who stayed on micronutrients through to follow-up or stopped all treatment reported better psychological functioning than those who switched to other treatments including medications. About 10% of the sample continued to have post-traumatic stress disorder symptoms. CONCLUSIONS: Disaster survivors improve psychologically over time regardless of receiving intervention; however, those taking micronutrients during the acute phase following a disaster show better outcomes, identifying micronutrients as a viable treatment for acute stress following a natural disaster with maintenance of benefits 1 year later. ACTRN 12611000460909


Subject(s)
Anxiety Disorders/drug therapy , Anxiety Disorders/etiology , Earthquakes , Micronutrients/administration & dosage , Stress Disorders, Post-Traumatic/drug therapy , Adult , Depression/drug therapy , Depression/etiology , Female , Follow-Up Studies , Humans , Male , New Zealand , Psychiatric Status Rating Scales , Regression Analysis , Surveys and Questionnaires , Treatment Outcome
11.
RNA Biol ; 10(11): 1714-25, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24157614

ABSTRACT

hnRNP A2 is a cellular protein that is important for nucleocytoplasmic and cytosolic trafficking of the HIV-1 genomic RNA. Both hnRNP A2's interaction with HIV-1 RNA and its expression levels influence the activities of Rev in mediating nucleocytoplasmic export of the HIV-1 genomic RNA. While the lack of Rev expression during HIV-1 gene expression results in nuclear retention of HIV-1 genomic RNA, we show here by fluorescence in situ hybridization and fractionation studies that the genomic RNA translocates to the cytoplasm when hnRNP A2/B1 are depleted from cells. Polyribosome analyses revealed that the genomic RNA was shunted into a cytoplasmic, dense polyribosomal fraction. This fraction contained several RNA-binding proteins involved in viral gene expression and RNA trafficking but did not contain the translation initiation factor, eIF4G1. Amino acid incorporation into nascent polypeptides in this fraction was also greatly reduced, demonstrating that this fraction contains mRNAs that are poorly translated. These results demonstrate that hnRNP A2/B1 expression plays roles in the nuclear retention of the HIV-1 genomic RNA in the absence of Rev and in the release of the genomic RNA from translationally inactive, cytoplasmic RNP complexes.


Subject(s)
HIV-1/genetics , HIV-1/metabolism , Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism , RNA Transport/physiology , RNA, Viral/metabolism , rev Gene Products, Human Immunodeficiency Virus/metabolism , Cell Nucleus/physiology , Cytoplasm/genetics , Cytoplasm/metabolism , Genes, Viral/genetics , HeLa Cells , Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics , Humans , In Situ Hybridization, Fluorescence , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Viral/genetics
12.
J Phys Chem B ; 116(48): 14008-16, 2012 Dec 06.
Article in English | MEDLINE | ID: mdl-23137346

ABSTRACT

The phylloquinone acceptor PhQ(A) in photosystem I binds to the protein through a single H-bond to the backbone nitrogen of PsaA-L722. Here, we investigate the effect of this H-bond on the electron transfer (ET) kinetics by substituting threonine for PsaA-L722. Room temperature spin-polarized transient EPR measurements show that in the PsaA-L722T mutant, the rate of PhQ(A)(-) to F(X) ET increases and the hyperfine coupling to the 2-methyl group of PhQ(A) is much larger than in the wild type. Molecular dynamics simulations and ONIOM type electronic structure calculations indicate that it is possible for the OH group of the Thr side chain to form an H-bond to the carbonyl oxygen atom, O(4) of the phylloquinone, and that this results in an increase in the 2-methyl hyperfine couplings as observed in the transient EPR data. The Arrhenius plot of the PhQ(A)(-) to F(X) ET in the PsaA-L722T mutant suggests that the increased rate is probably the result of a slight change in the electronic coupling between PhQ(A)(-) and F(X). The strong deviation from Arrhenius behavior observed at ∼200 K can be reproduced using a semiclassical model, which takes the zero-point energy of the mode coupled to the ET into account. However, since the change in slope of the Arrhenius plot occurs at the protein glass transition temperature, it is argued that it could be the result of a change in the protein relaxation dynamics at this temperature rather than quantum mechanical effects.


Subject(s)
Chlamydomonas reinhardtii/metabolism , Photosystem I Protein Complex/metabolism , Plant Proteins/metabolism , Threonine/metabolism , Vitamin K 1/metabolism , Chlamydomonas reinhardtii/chemistry , Chlamydomonas reinhardtii/genetics , Electron Spin Resonance Spectroscopy , Electron Transport , Hydrogen Bonding , Kinetics , Molecular Dynamics Simulation , Mutation , Photosystem I Protein Complex/chemistry , Photosystem I Protein Complex/genetics , Plant Proteins/chemistry , Plant Proteins/genetics , Threonine/chemistry , Vitamin K 1/chemistry
13.
Hum Psychopharmacol ; 27(5): 440-54, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22782571

ABSTRACT

OBJECTIVE: To compare two micronutrient (vitamins and minerals) formulas (Berocca™ and CNE™) and assess their impact on emotions and stress related to the 6.3 earthquake on February 22(nd) 2011 in Christchurch, New Zealand. METHODS: 91 adults experiencing heightened anxiety or stress 2-3 months following the earthquake were randomized to Berocca™, CNE™ low dose (CNE4), or CNE™ high dose (CNE8), for 28 days and monitored weekly via on-line questionnaires and followed 1 month post-trial. A nonrandomized control group (n = 25) completed questionnaires at baseline and 4 weeks. RESULTS: All treatment groups experienced significant declines in psychological symptoms (p < .001). CNE™ groups experienced greater reduction in intrusive thoughts as compared with Berocca™ (p = .05), with no group differences on other measures of psychological symptoms. However, CNE8 group reported greater improvement in mood, anxiety, and energy (p < .05) with twice as many reporting being "much" to "very much" improved and five times more likely to continue taking CNE™ post-trial than Berocca™ group. Treated participants had better outcomes on most measures over 4 weeks as compared to controls. CONCLUSIONS: This study supports micronutrients as an inexpensive and practical treatment for acute stress following a natural disaster with a slight advantage to higher doses ACTRN 12611000460909.


Subject(s)
Earthquakes , Micronutrients/therapeutic use , Stress, Psychological/therapy , Adult , Female , Fenoterol , Follow-Up Studies , Humans , Male , Middle Aged , Minerals , New Zealand , Stress, Psychological/etiology , Treatment Outcome , Vitamins/therapeutic use , Young Adult
14.
Can Assoc Radiol J ; 63(3 Suppl): S33-6, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22277803

ABSTRACT

INTRODUCTION: To assess the incidence and clinical significance of pneumoperitoneum after radiologic percutaneous gastrojejunostomy (PGJ) tube insertion. METHODS: Sixteen subjects were prospectively assessed after imaging-guided PGJ tube insertion to discern the incidence of pneumoperitoneum related to specific clinical signs and symptoms. Computed tomography of the abdomen and the pelvis was performed immediately after PGJ insertion. A clinical evaluation, including history, general and abdominal physical examination, temperature, complete blood cell count, abdominal pain, and abdominal tension, was performed on days 1 and 3, and at the discretion of the nutritional support team on day 7 after PGJ insertion. RESULTS: Fifteen of the 16 subjects demonstrated imaging findings of pneumoperitoneum after the PGJ-tube insertion. Only a small amount of pneumoperitoneum was demonstrated in 10 of the subjects, whereas a large volume of gas was detected in 2 of the subjects. The only altered clinical findings encountered were increased white blood cell count and fever. These abnormal clinical data were most frequently seen immediately after feeding-tube placement. DISCUSSION: Pneumoperitoneum was a common finding after PGJ-tube placement in our study population. There were no statistically significant abnormal clinical parameters, in the presence or absence of pneumoperitoneum, for any of the subjects after PGJ-tube insertion. Conservative management of pneumoperitoneum after PGJ is warranted.


Subject(s)
Gastric Bypass/adverse effects , Pneumoperitoneum/diagnostic imaging , Pneumoperitoneum/etiology , Radiography, Interventional , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Aged, 80 and over , Female , Fluoroscopy , Humans , Incidence , Male , Middle Aged , Pneumoperitoneum/epidemiology , Prospective Studies , Risk Factors , Treatment Outcome
15.
Brain Cogn ; 77(1): 113-9, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21683500

ABSTRACT

Responses to threat occur via two known independent processing routes. We propose that early, reflexive processing is predominantly tuned to the detection of congruent combinations of facial cues that signal threat, whereas later, reflective processing is predominantly tuned to incongruent combinations of threat. To test this prediction, we examined responses to threat-gaze expression pairs (anger versus fear expression by direct versus averted gaze). We report on two functional magnetic resonance imaging (fMRI) studies, one employing prolonged presentations (2s) of threat-gaze pairs to allow for reflective processing (Study 1), and one employing severely restricted (33 ms), backward masked presentations of threat-gaze pairs to isolate reflexive neural responding (Study 2). Our findings offer initial support for the conclusion that early, reflexive responses to threat are predominantly tuned to congruent threat-gaze pairings, whereas later reflective responses are predominantly tuned to ambiguous threat-gaze pairings. These findings highlight a distinct dual function in threat perception.


Subject(s)
Aggression/psychology , Awareness/physiology , Cerebral Cortex/physiology , Discrimination, Psychological/physiology , Neural Pathways/physiology , Adult , Brain Mapping , Escape Reaction/physiology , Facial Expression , Fixation, Ocular , Humans , Magnetic Resonance Imaging , Male , Perceptual Masking , Reaction Time/physiology , Reflex/physiology , Time Factors , Young Adult
16.
Interdiscip Sci ; 3(1): 1-16, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21369882

ABSTRACT

Polyglutamine is a naturally occurring peptide found within several proteins in neuronal cells of the brain, and its aggregation has been implicated in several neurodegenerative diseases, including Huntington's disease. The resulting aggregates have been demonstrated to possess ß-sheet structure, and experimental evidence has demonstrated that aggregation begins with a nucleus composed of a single peptide. In this paper, we computationally examined the structural tendencies of mutant polyglutamine peptides that were studied experimentally, and found to aggregate with varying efficiencies. Low-energy structures were generated for each peptide by simulated annealing molecular dynamics, and were analyzed quantitatively by various geometry-based methods. In all simulations, the carboxy-terminal end of each peptide was constrained to a ß-turn-ß-strand structure to simulate a situation in which ß-structure formation has initiated due to interaction with a seed or a growing oligomer/aggregate. Our results suggest the experimentally-observed inhibition of aggregation to be due to localized conformational restraint on the peptide backbone, which in turn confines the peptide to native coil structure, discouraging transition towards the ß-sheet structure required for aggregation.


Subject(s)
Peptides/chemistry , Models, Molecular , Molecular Dynamics Simulation , Mutation , Peptides/genetics , Protein Structure, Secondary
17.
J Chem Phys ; 131(22): 225102, 2009 Dec 14.
Article in English | MEDLINE | ID: mdl-20001084

ABSTRACT

Given the principal component analysis (PCA) of a molecular dynamics (MD) conformational trajectory for a model protein, we perform orthogonal Procrustean rotation to "best fit" the PCA squared-loading matrix to that of a target matrix computed for a related but different molecular system. The sum of squared deviations of the elements of the rotated matrix from those of the target, known as the error of fit (EOF), provides a quantitative measure of the dissimilarity between the two conformational samples. To estimate precision of the EOF, we perform bootstrap resampling of the molecular conformations within the trajectories, generating a distribution of EOF values for the system and target. The average EOF per variable is determined and visualized to ascertain where, locally, system and target sample properties differ. We illustrate this approach by analyzing MD trajectories for the wild-type and four selected mutants of the beta1 domain of protein G.


Subject(s)
Bacterial Proteins , Models, Molecular , Molecular Dynamics Simulation , Amino Acid Sequence , Bacterial Proteins/chemistry , GTP-Binding Proteins/chemistry , Molecular Conformation , Molecular Sequence Data , Principal Component Analysis
18.
Acta bioeth ; 15(2): 184-192, nov. 2009.
Article in English | LILACS | ID: lil-581957

ABSTRACT

Purpose: To describe and evaluate priority setting in an Acute Care hospital in Argentina, using Accountability for Reasonableness, an ethical framework for fair priority setting. Methods: Case Study involving key informant interviews and document review. Thirty respondents were identified using a snowball sampling strategy. A modified thematic approach was used in analyzing the data. Results: Priorities are primarily determined at the Department of Health. The committee which is supposed to set priorities within the hospital was thought not to have much influence. Decisions were based on government policies and objectives, personal relationships, economic, political, historical and arbitrary reasons. Decisions at the DOH were publicized through internet; however, apart from the tenders and a general budget, details of hospital decisions were not publicized. CATA provided an accessible but ineffective forum for appeals. There were no clear mechanisms for appeals and leadership to ensure adherence to a fair process. Conclusions: In spite of their efforts to ensure fairness, Priority setting in the study hospital did not meet all the four conditions of a fair process. Policy discussions on improving legitimacy and fairness provided an opportunity for improving fairness in the hospital and Accountability for Reasonableness might be a useful framework for analysis and for identifying and improving strategies.


Propósito: Describir y evaluar el establecimiento de prioridades en un hospital de cuidados intensivos en Argentina, empleando la Administración Razonable como marco ético para una justa asignación. Métodos: Estudio de un Caso que incluía entrevistas a un informante y revisión de documentos. Se identificó a treinta participantes empleando la estrategia de muestras tipo "bola de nieve". Al analizar los datos, se empleó un enfoque temático modificado. Resultados: Las prioridades se determinan principalmente en el Departamento de Salud. El comité que, se supone, debe establecer las prioridades dentro del hospital no tiene mayor influencia. Las decisiones se basan en políticas y objetivos gubernamentales, relaciones personales, razones económicas, políticas, históricas e, incluso, arbitrarias. Las decisiones del Departamento de Salud se publicitan a través de Internet; sin embargo, fuera de las propuestas y del presupuesto general, no se publicitan las decisiones del hospital. CATA proporciona un foro accesible pero ineficaz para apelar. No existen mecanismos claros para apelar ni para un liderazgo que asegure un proceso justo. Conclusiones: A pesar de los esfuerzos por asegurar la equidad, el establecimiento de prioridades del hospital no cumple las cuatro condiciones de un proceso justo. Las discusiones acerca de políticas de mejoramiento, legitimidad y equidad dan oportunidad para mejorar la equidad en el hospital, y el marco ético "Administración Razonable" podría constituir un marco útil para el análisis así como para identificar y mejorar las estrategias.


Propósito: Descrever e avaliar o estabelecimento de prioridades em um hospital de cuidados intensivos na Argentina, empregando a Administração Razoável como marco ético para uma justa destinação de recursos. Métodos: Estudo de um caso que incluía entrevistas a um informante e revisão de documentos. Foram identificados trinta participantes empregando a estratégia de amostras tipo bola de neve. Ao analisar os dados, se empregou um enfoque temático modificado. Resultados: As prioridades são determinadas principalmente no Departamento de Saúde. O comitê que, se supõe, deve estabelecer as prioridades dentro do hospital não tem maior influência. As decisões se baseiam em políticas e objetivos governamentais, relações pessoais, razões econômicas, políticas, históricas e, inclusive, arbitrárias. As decisões do Departamento de Saúde são divulgadas por meio da Internet; no entanto, além das propostas e do orçamento geral, não se divulgam as decisões do hospital. CATA proporciona uma instância acessível, porém ineficaz para apelar. Não existem mecanismos claros para apelar nem para uma liderança que assegure um processo justo. Conclusões: Apesar dos esforços para assegurar a equidade, o estabelecimento de prioridades do hospital não cumpre as quatro condições de um processo justo. As discussões sobre políticas de melhoria, legitimidade e equidade dão oportunidade para melhorar a equidade no hospital e no marco ético "Administração Razoável" poderia constituir um marco útil para a análise assim como para identificar e melhorar as estratégias.


Subject(s)
Humans , Bioethics , Critical Care , Emergency Service, Hospital , Health Priorities , Health Systems , Public Health , Argentina , Qualitative Research
19.
Disabil Rehabil ; 31(11): 906-13, 2009.
Article in English | MEDLINE | ID: mdl-19191059

ABSTRACT

PURPOSE: To evaluate the use of quality of life and participation measures in routine rehabilitation practice, determine the relationship between two scales and investigate their ability to evaluate change in a general outpatient population over a time of rehabilitation. METHODS: This cohort study consisted of 55 patients admitted consecutively to an outpatient rehabilitation centre. All participants completed the WHOQOL-BREF and the London Handicap Scale (LHS) at admission and discharge. RESULTS: Non-parametric statistical analysis demonstrated a significant change in the total scores of both the WHOQOL-BREF and LHS over time (Z = -4.33, P < 0.001 and Z = -4.40, P < 0.001 respectively) with 'better' scores on completion of rehabilitation. A strong correlation existed between the total WHOQOL-BREF and LHS scores both cross-sectionally (admission and discharge p > 0.7), and longitudinally (p = 0.63). CONCLUSIONS: Our study demonstrated a strong relationship between quality of life and participation, with change shown using both scales over a period of outpatient rehabilitation. Given the findings, it seems appropriate to use only one of these measures. The WHOQOL-BREF has a wider scope, being useful both to evaluate service delivery in a diverse outpatient population or when measuring an individual over time.


Subject(s)
Outpatients , Patient Participation , Quality of Life , Rehabilitation Centers , Adolescent , Adult , Aged , Disability Evaluation , Female , Humans , Male , Middle Aged , Statistics, Nonparametric , Surveys and Questionnaires
20.
J Cogn Neurosci ; 20(12): 2167-74, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18457504

ABSTRACT

The human amygdala robustly activates to fear faces. Heightened response to fear faces is thought to reflect the amygdala's adaptive function as an early warning mechanism. Although culture shapes several facets of emotional and social experience, including how fear is perceived and expressed to others, very little is known about how culture influences neural responses to fear stimuli. Here we show that the bilateral amygdala response to fear faces is modulated by culture. We used functional magnetic resonance imaging to measure amygdala response to fear and nonfear faces in two distinct cultures. Native Japanese in Japan and Caucasians in the United States showed greater amygdala activation to fear expressed by members of their own cultural group. This finding provides novel and surprising evidence of cultural tuning in an automatic neural response.


Subject(s)
Amygdala/physiology , Cross-Cultural Comparison , Face , Fear/physiology , Adolescent , Adult , Amygdala/blood supply , Analysis of Variance , Female , Functional Laterality , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Oxygen/blood , Pattern Recognition, Visual , Photic Stimulation/methods , Reaction Time/physiology , Young Adult
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