Protein interaction mapping: a Drosophila case study

The Drosophila (fruit fly) model system has been instrumental in our current understanding of human biology, development, and diseases. Here, we used a high-throughput yeast two-hybrid (Y2H)-based technology to screen 102 bait proteins from Drosophila melanogaster, most of them orthologous to human cancer-related and/or signaling proteins, against high-complexity fly cDNA libraries. More than 2300 protein-protein interactions (PPI) were identified, of which 710 are of high confidence. The computation of a reliability score for each protein-protein interaction and the systematic identification of the interacting domain combined with a prediction of structural/functional motifs allow the elaboration of known complexes and the identification of new ones. The full data set can be visualized using a graphical Web interface, the PIMRider (http://pim.hybrigenics.com), and is also accessible in the PSI standard Molecular Interaction data format. Our fly Protein Interaction Map (PIM) is surprisingly different from the one recently proposed by Giot et al. with little overlap between the two data sets. Analysis of the differences in data sets and methods suggests alternative strategies to enhance the accuracy and comprehensiveness of the post-genomic generation of broad-scale protein interaction maps.     

A phenomenological analysis of doctor-patient interaction: a case study

The fact that the biomedical model has been very successful in practice does not preclude that some health issues can be understood by way of other health care perspectives. Acquiring skills in meeting patients requires theories that structure other fields of knowledge than the biomedical sciences. An old man, who experiences himself as deeply misunderstood by the medical profession, is interviewed, his personal life-story is gone into and his case records and other available data are analysed. A phenomenological method is used, i.e. disciplined and rigorous reflection upon available data, remaining close to the particular pieces of the patient's narrative as they stand forth in their contextual relationships. The study shows that the doctors involved did not relate to the patient but to a biomedical image of him. His efforts to make himself understood were converted into instrumentally manageable disorders. Finally, dialogue medicine is briefly introduced as a model for counselling patients, especially when they need assistance to abandon the notion that they have been afflicted with a disease, a perception that might serve the purpose of keeping a threatening self-image out of consciousness.     

Patient-by-treatment context interaction in chronic disease: a conceptual framework for the study of patient adherence

OBJECTIVE: Previous reviews have concluded that there is little or no evidence supporting a predictable association between patient characteristics and regimen adherence in chronic illness. The primary objective of this article is to propose an alternative conceptual framework for the interpretation and design of adherence research. METHODS: The author's research involving adherence among patients with end-stage renal disease is reviewed and used to illustrate the patient-by-context interactive framework. RESULTS: Adherence is most favorable when the patient's characteristic or preferred style of coping with illness and treatment-related experiences is congruent with the contextual features or demands of the particular type of medical intervention the patient is undergoing. Among patients with end-stage renal disease, a more vigilant or active style of coping is associated with more favorable adherence only for patients undergoing home-based dialysis treatment modalities that are highly patient directed. Among patients receiving hospital-based, provider-controlled treatment, a less vigilant or more passive coping style is associated with more favorable dialysis regimen adherence. CONCLUSIONS: The patient-by-context interactive perspective can provide a useful framework for the interpretation and design of adherence research.     

Accomplishments of the thought disordered person: a case study in psychiatrist-patient interaction

Background

The research and clinical literature portrays the thought disordered person as incapable of meaningful social interaction. This model views thought disorder exclusively as a brain dysfunction, evidenced by dysfunctions in speech.

Aims

The study seeks to address this deficit model by investigating the interactional accomplishments of thought disordered people in clinical interviews.

Method

An analysis of clinical interview data.

Results

We investigate (1) what thought disordered people actually accomplish in interaction, and (2) how thought disordered people and their psychiatrists routinely communicate on matters consequential for treatment.

Conclusions

This paper introduces a new perspective on the interactional achievements of people with thought disorder. The skills required by both parties during routine clinical interviews have not previously been recognised or described.     

一例社交焦虑认知行为咨询的案例概念化

目的:应用Boschen等所提出的模型制订一例社交焦虑认知行为咨询的案例概念化咨询方案。方法:首先按照案例概念化的流程和要求将个案的内容以模式图的形式呈现给来访者,然后根据每一部分的具体问题按照相对应的咨询方法进行干预。结果:综合评价结果显示,来访者的社交焦虑症状减轻,社交回避程度下降。结论:社交焦虑认知行为咨询的案例概念化有助于有社交焦虑问题的来访者对自身问题的理解,在心理咨询中具有实际应用价值。     

Fractographic analysis of a dental zirconia framework: A case study on design issues

Fractographic analysis of clinically failed dental ceramics can provide insights as to the failure origin and related mechanisms. One anterior 6-unit all-ceramic zirconia fixed partial denture (FPD) (Cercon^®) has been clinically recovered and examined using qualitative fractography. The purpose was to identify the fracture origin and to state the reasons for failure. The recovered parts of the zirconia FPD were microscopically examined to identify classic fractographic patterns such as arrest lines, hackle, twist hackle and wake hackle. The direction of crack propagation was mapped and interpreted back to the origin of failure at the interface of the occlusal–palatal tip of the core and the veneering ceramic. An inappropriate core drop design favoring localized stress concentration combined with a pore cluster in the veneering ceramic at the core tip interface were the reasons for this premature through-the-core thickness failure.     

Organizational factors affecting successful adoption of innovative eHealth services: a case study employing the FITT framework

Objective

The paper presents an application of the “Fit between Individuals, Task and Technology” (FITT) framework to analyze the socio-organizational-technical factors that influence IT adoption in the healthcare domain.

Method

The FITT framework was employed as the theoretical instrument for a retrospective analysis of a 15-year effort in implementing IT systems and eHealth services in the context of a Regional Health Information Network in Crete. Quantitative and qualitative research methods, interviews and participant observations were employed to gather data from a case study that involved the entire region of Crete.

Results

The detailed analysis of the case study based on the FITT framework, showed common features, but also differences of IT adoption within the various health organizations. The emerging picture is a complex nexus of factors contributing to IT adoption, and multi-level interventional strategies to promote IT use.

Conclusion

The work presented in this paper shows the applicability of the FITT framework in explaining the complexity of aspects observed in the implementation of healthcare information systems. The reported experiences reveal that fit management can be viewed as a system with a feedback loop that is never really stable, but ever changing based on external factors or deliberate interventions. Management of fit, therefore, becomes a constant and complex task for the whole life cycle of IT systems.     

Psychopathology, GABA, and the Rubinstein-Taybi syndrome: a review and case study

An adult female with congenital Rubinstein-Taybi syndrome (RTS) and severe mental retardation is described, who presented with symptoms of severe over-activity, short attention span, mood lability, and aggressive outbursts in a cyclical pattern, suggestive of recurrent manic-like episodes. These symptoms improved significantly with divalproex (Depakote) monotherapy. Review of the existing studies showed that 10-76% of persons with RTS may be identified with similar behavioral symptoms. We postulate other persons with RTS may respond to divalproex, and there may be some relationship between the chromosome 16p13.3 deletion and gamma-aminobutyric acid (GABA) receptor or neurotransmitter abnormalities. Recent molecular genetic studies suggest a linkage of this region to bipolar mood disorder and autism, both of which were diagnosed in this patient. Further prospective study is needed of RTS persons regarding behavioral problems, comorbid psychiatric diagnoses, and treatment responses, correlated with genetic abnormalities.     

An evaluation of the mode of action framework for mutagenic carcinogens case study: Cyclophosphamide

In response to the 2005 revised US Environmental Protection Agency (EPA) Cancer Guidelines, a Risk Assessment Forum's Technical Panel has devised a strategy in which genetic toxicology data combined with other information are assessed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent adjustment factors (ADAFs) should be applied to the cancer risk assessment. A decision tree has been developed as a part of this approach and outlines the critical steps for analyzing a compound for carcinogenicity through a mutagenic MOA (e.g., data analysis, determination of mutagenicity in animals and in humans). Agents, showing mutagenicity in animals and humans, proceed through the Agency's framework analysis for MOAs. Cyclophosphamide (CP), an antineoplastic agent, which is carcinogenic in animals and humans and mutagenic in vitro and in vivo, was selected as a case study to illustrate how the framework analysis would be applied to prove that a carcinogen operates through a mutagenic MOA. Consistent positive results have been seen for mutagenic activity in numerous in vitro assays, in animals (mice, rats, and hamsters) and in humans. Accordingly, CP was processed through the framework analysis and key steps leading to tumor formation were identified as follows: metabolism of the parent compound to alkylating metabolites, DNA damage followed by induction of multiple adverse genetic events, cell proliferation, and bladder tumors. Genetic changes in rats (sister chromatid exchanges at 0.62 mg/kg) can commence within 30 min and in cancer patients, chromosome aberrations at 35 mg/kg are seen by 1 hr, well within the timeframe and tumorigenic dose range for early events. Supporting evidence is also found for cell proliferation, indicating that mutagenicity, associated with cytotoxicity, leads to a proliferative response, which occurs early (48 hr) in the process of tumor induction. Overall, the weight of evidence evaluation supports CP acting through a mutagenic MOA. In addition, no data were found that an alternative MOA might be operative. Therefore, the cancer guidelines recommend a linear extrapolation for the risk assessment. Additionally, data exist showing that CP induces mutagenicity in fetal blood and in the peripheral blood of pediatric patients; thus, the ADAFs would be applied.     

Postural prioritization defines the interaction between a reaction time task and postural perturbations

Concurrent demands for postural and cognitive control processes are now known to induce interference, e.g., information processing speed may decrease during postural adjustment. It is less clear whether postural control may, at least in many situations, take precedence over cognitive control (“postural prioritization”). The purpose of this study was to determine if postural dual-task effects are the result of a postural prioritization effect. Twelve young subjects (6 female; 24.1 ± 4.1) performed a discrete choice reaction time (RT) task in combination with a platform perturbation. To assess the effect of postural prioritization on RT and center of pressure (COP) parameters, destabilizing perturbations were randomly interspersed with non-destabilizing perturbations. Furthermore, stimulus order and the time interval of the RT stimulus relative to the platform perturbation were manipulated. COP and RT data obtained in these manipulations were compared to single-task baseline data. The results suggested that, irrespective of the degree of threat to postural stability, postural task processes are prioritized. Furthermore, anticipation of a postural stimulus negatively affects RT. However, once a perturbation commences subsequent RTs are speeded. Postural reactions were unaffected by a concurrent RT task, however. The RT stimulus acted as a cue to initiate biomechanical adaptations for an upcoming perturbation.     

Using a contextualized sensemaking model for interaction design: A case study of tumor contouring

Sensemaking theories help designers understand the cognitive processes of a user when he/she performs a complicated task. This paper introduces a two-step approach of incorporating sensemaking support within the design of health information systems by: (1) modeling the sensemaking process of physicians while performing a task, and (2) identifying software interaction design requirements that support sensemaking based on this model. The two-step approach is presented based on a case study of the tumor contouring clinical task for radiotherapy planning. In the first step of the approach, a contextualized sensemaking model was developed to describe the sensemaking process based on the goal, the workflow and the context of the task. In the second step, based on a research software prototype, an experiment was conducted where three contouring tasks were performed by eight physicians respectively. Four types of navigation interactions and five types of interaction sequence patterns were identified by analyzing the gathered interaction log data from those twenty-four cases. Further in-depth study on each of the navigation interactions and interaction sequence patterns in relation to the contextualized sensemaking model revealed five main areas for design improvements to increase sensemaking support. Outcomes of the case study indicate that the proposed two-step approach was beneficial for gaining a deeper understanding of the sensemaking process during the task, as well as for identifying design requirements for better sensemaking support.     

Selecting interventions to promote fruit and vegetable consumption: from policy to action,a planning framework case study in Western Australia

Background

The Department of Health in Western Australia identified access to, and daily consumption of recommended amounts of fruit and vegetables, as priority health determinants. The numerous factors that influence supply and consumption of fruit and vegetables indicated that a comprehensive approach would be required.A government and non-government sector steering group was set up to select priority interventions using the National Public Health Partnership's Framework for Implementing Public Health Strategies. This structured framework was used for developing strategies to improve fruit and vegetable consumption and supply, and to identify implementation priorities.After one year a desktop audit of progress on framework interventions was undertaken.

Results

The structured framework led to a plan for defined actions, partners, costs, and performance indicators for strategies to improve fruit and vegetable consumption and supply. Lead agency custodians for management of the selected interventions were identified.After one year there was significant progress in the implementation of a number of the high-ranking interventions. The exception was interventions that provide the infrastructure support such as research and development capacity, information systems.

Conclusion

A structured framework and stakeholder participation assisted in developing a fruit and vegetable implementation strategy. Engagement and commitment of influential and diverse stakeholders is needed, not just for program support, but particularly in the areas of food and nutrition policy development and providing the infrastructure support required. Further work is required to develop performance outcomes and cost effectiveness measures for many of the strategies that have been proposed to address portfolio objectives.

     

Argyrophil carcinoma of the breast: a cytologic, histochemical, and ultrastructural study of a case

Aspirate from an argyrophil carcinoma ("carcinoid") of the breast showed malignant dispersed epithelial cells. With Diff-Quik, the cytoplasm was seen to be abundant, with prominent eosinophilic granularity. The nuclei were fairly uniform, round or oval, and eccentric and had a finely stippled chromatin pattern. On histology, the tumor appeared typical for argyrophil carcinoma, and staining with Grimelius for argyrophilic granules was positive. Membrane-bound neurosecretory granules were seen on electron microscopy.     

Lean diesel technology and human health: a case study in six Brazilian metropolitan regions

OBJECTIVE:

Due to their toxicity, diesel emissions have been submitted to progressively more restrictive regulations in developed countries. However, in Brazil, the implementation of the Cleaner Diesel Technologies policy (Euro IV standards for vehicles produced in 2009 and low-sulfur diesel with 50 ppm of sulfur) was postponed until 2012 without a comprehensive analysis of the effect of this delay on public health parameters. We aimed to evaluate the impact of the delay in implementing the Cleaner Diesel Technologies policy on health indicators and monetary health costs in Brazil.

METHODS:

The primary estimator of exposure to air pollution was the concentration of ambient fine particulate matter (particles with aerodynamic diameters <2.5 µm, [PM2.5]). This parameter was measured daily in six Brazilian metropolitan areas during 2007-2008. We calculated 1) the projected reduction in the PM2.5 that would have been achieved if the Euro IV standards had been implemented in 2009 and 2) the expected reduction after implementation in 2012. The difference between these two time curves was transformed into health outcomes using previous dose-response curves. The economic valuation was performed based on the DALY (disability-adjusted life years) method.

RESULTS:

The delay in implementing the Cleaner Diesel Technologies policy will result in an estimated excess of 13,984 deaths up to 2040. Health expenditures are projected to be increased by nearly US$ 11.5 billion for the same period.

CONCLUSIONS:

The present results indicate that a significant health burden will occur because of the postponement in implementing the Cleaner Diesel Technologies policy. These results also reinforce the concept that health effects must be considered when revising fuel and emission policies.     

When sound and picture do not fit: Mismatch negativity and sensory interaction.

The Mismatch Negativity (MMN), an index of auditory stimulus representation, was studied in a design of simultaneous auditory and visual stimulus presentation. A counting task drew the attention of participants to picture presentation and was unrelated to the occurring sounds. With the picture of a hammer hitting a nail a standard sound "bang" came along. Rarely, a deviant picture showed the hammer hitting the finger combined with a corresponding deviant sound "ouch." Sometimes this deviant picture was combined with the standard sound. In spite of the absence of a sound deviancy to the standard sounds, also in the latter case a significant MMN was detected, indicating that the actual visual context affected the incoming auditory information leading to a mismatch with the prevailing auditory memory trace. Herewith, MMN gains importance as an index of auditory stimulus representation also in studies of sensory interaction.     

Enhancement of selective attention by tDCS: interaction with interference in a Sternberg task

The amyloid β (Aβ) protein is believed to be the key pathological mediator of Alzheimer's disease (AD) which is the first and most well known type of dementia. Despite a growing body of evidence indicating that Aβ neurotoxicity induces changes in synaptic function, little effort, if any, has been made to investigate the effect of in vivo Aβ treatment on intrinsic neuronal properties. The present study was designed to examine the effects that in vivo Aβ treatment have on the intrinsic repetitive firing properties of CA1 pyramidal neurons, using whole cell patch clamp recording. Protective effect of cannabinoid CB1 receptor activation was also investigated against Aβ-induced alterations in evoked electrophysiological activities. The findings from present study demonstrated that a bilateral injection of Aβ into the prefrontal cortex causes robust changes in activity-dependent electrophysiological responses in hippocampal CA1 pyramidal neurons. The effects of Aβ treatment alone was almost completely prevented by combined treatment with Aβ and ACEA, a selective CB1 receptor agonist. It can be concluded Aβ treatment reduces evoked neuronal activity and activation of CB1 cannabinoid receptors may have beneficial preventative effects on Aβ-induced electrophysiological changes.