Phototrophic Fe(II) oxidation benefits from light/dark cycles.

Phototrophic Fe(II)-oxidizers use Fe(II) as electron donor for CO2 fixation thus linking Fe(II) oxidation, ATP formation, and growth directly to the availability of sunlight. We compared the effect of short (10 h light/14 h dark) and long (2-3 days light/2-3 days dark) light/dark cycles to constant light conditions for the phototrophic Fe(II)-oxidizer Chlorobium ferrooxidans KoFox. Fe(II) oxidation was completed first in the setup with constant light (9 mM Fe(II) oxidised within 8.9 days) compared to the light/dark cycles but both short and long light/dark cycles showed faster maximum Fe(II) oxidation rates. In the short and long cycle, Fe(II) oxidation rates reached 3.5 ± 1.0 and 2.6 ± 0.3 mM/d, respectively, compared to 2.1 ± 0.3 mM/d in the constant light setup. Maximum Fe(II) oxidation was significantly faster in the short cycle compared to the constant light setup. Cell growth reached roughly equivalent cell numbers across all three light conditions (from 0.2-2.0 × 106 cells/mL to 1.1-1.4 × 108 cells/mL) and took place in both the light and dark phases of incubation. SEM images showed different mineral structures independent of the light setup and 57 Fe Mössbauer spectroscopy confirmed the formation of poorly crystalline Fe(III) oxyhydroxides (such as ferrihydrite) in all three setups. Our results suggest that periods of darkness have a significant impact on phototrophic Fe(II)-oxidizers and significantly influence rates of Fe(II) oxidation.

Quaternary glucocorticoid receptor structure highlights allosteric interdomain communication.

The glucocorticoid receptor (GR) is a ligand-activated transcription factor that binds DNA and assembles co-regulator complexes to regulate gene transcription. GR agonists are widely prescribed to people with inflammatory and autoimmune diseases. Here we present high-resolution, multidomain structures of GR in complex with ligand, DNA and co-regulator peptide. The structures reveal how the receptor forms an asymmetric dimer on the DNA and provide a detailed view of the domain interactions within and across the two monomers. Hydrogen-deuterium exchange and DNA-binding experiments demonstrate that ligand-dependent structural changes are communicated across the different domains in the full-length receptor. This study demonstrates how GR forms a distinct architecture on DNA and how signal transmission can be modulated by the ligand pharmacophore, provides a platform to build a new level of understanding of how receptor modifications can drive disease progression and offers key insight for future drug design.

Is GPR146 really the receptor for proinsulin C-peptide?

Proinsulin C-peptide has previously been proposed to interact with a G-protein coupled receptor (GPCR), specifically the orphan receptor GPR146. To investigate the potential of C-peptide in treating complications of diabetes, such as kidney damage, it is necessary to understand its mode of action. We used CHO-K1 cells expressing human GPR146 to study human and murine C-peptide in dynamic mass redistribution and GPCR ß-arrestin assays, as well as with fluorescence confocal microscopy. Neither assay revealed any significant intracellular response to C-peptide at concentrations of up to 33 µM. We observed no internalisation of C-peptide by fluorescence microscopy. Our results do not support GPR146 as the receptor for C-peptide, but suggest that further investigations of the mode of action of C-peptide should be undertaken.

Cell banking for pharmaceutical research.

The provision of high-quality eukaryotic cells through robust cell banking processes is essential for the progression of drug discovery projects throughout the pharmaceutical research process. Numerous models exist to meet this aim, and this review describes many of the underlying principles, challenges and opportunities as well as detailing how these have been addressed within AstraZeneca. Crucial aspects discussed include cell line acquisition, cell bank generation, cryopreservation, storage, tracking and distribution. Because quality assurance underpins much of the process, quality control (QC) testing including mycoplasma screening and cell line authentication are also discussed in detail. Furthermore, because many of the underlying principles of cell banking are applicable in non-pharmaceutical settings, it is hoped that this review will prove a useful resource across the wider scientific community.

Multiple deficits in ADHD: executive dysfunction, delay aversion, reaction time variability, and emotional deficits.

BACKGROUND: The notion that ADHD constitutes a heterogeneous disorder is well accepted. However, this study contributes with new important knowledge by examining independent effects of a large range of neuropsychological deficits. In addition, the study investigated whether deficits in emotional functioning constitute a dissociable component of ADHD. METHOD: The study included children with ADHD (n = 102; 7-13 years) and a control sample individually matched with regard to age and gender. The administered tasks were designed to tap into three different neuropsychological domains: executive functions (i.e., working memory, inhibition, and shifting), delay aversion, and reaction time variability. Parent ratings of emotion regulation and a test of emotion recognition were also included. RESULTS: Children with ADHD differed significantly from controls on all measures, except for delay aversion and recognition of disgust. No main effects of gender or interaction effects of gender and group were found. More importantly, executive functioning, reaction time variability, and emotional functioning all contributed independently to distinguishing between children with ADHD and controls. CONCLUSIONS: The current study supports the view of ADHD as a heterogeneous disorder related to multiple neuropsychological deficits. In addition, emotional functioning appears to be an area of importance for ADHD that needs to be incorporated into future theoretical models.

Implementing teams in a patient-centered medical home residency practice: lessons learned.

INTRODUCTION: The "new model of care" calls for a new approach for primary care delivery that focuses on patient centeredness, quality, safety, effective and efficient care, and interdisciplinary teamwork. Medical education needs to parallel this health care reorganization. Implementing a team approach in a residency practice, especially in ambulatory settings, poses unique challenges. METHODS: We introduced interdisciplinary teams in a family medicine residency site, integrating clinical and educational objectives. RESULTS: We report our challenges and successes in the transformational journey to a patient-centered medical home, for which a team approach is critical to achieving high quality care. CONCLUSION: Establishing high-functioning interdisciplinary teams takes leadership commitment; the engagement of everyone in the practice; investment in staff, resident, and faculty development; and clear communication of vision and goals. Integration of clinical and educational objectives can be powerfully synergistic. Clinical, organizational, and educational outcomes are needed to evaluate impact.

Effects of implementation of a team model on physician and staff perceptions of a clinic's organizational and learning environments.

BACKGROUND AND OBJECTIVES: Although teamwork is widely promoted by the Institute of Medicine, the American Academy of Family Physicians, and the Future of Family Medicine project, the health care literature does not provide clear direction on how to create or maintain high-functioning teams in ambulatory residency education. In 2004, we reorganized the clinical operation of our family medicine residency clinic into teams, each consisting of faculty, residents, and nursing and administrative staff. We hypothesized that operating within teams would have a positive effect on employees' job satisfaction and perceptions of our clinic's organizational and learning environments. METHODS: We administered a confidential survey to faculty, residents, and staff annually over 5 years (2002-2006). Using questionnaire data from 2002-2003 as a baseline and data from 2004-2006 as a post-intervention measurement, we performed Mann-Whitney tests to assess the effect of the implementation of teams on employees' ratings of job satisfaction, individual autonomy, organizational commitment, goal attainment, physical characteristics and personnel arrangements within the clinic, learning opportunities for residents, teaching behaviors of faculty, roles of staff, and learning organization characteristics. RESULTS: After the implementation of teams, there was an improvement in ratings of learning opportunities and quality of teaching, job satisfaction, employee autonomy, staff roles, and staff attitudes toward residents. CONCLUSIONS: Implementing a team approach in a residency clinic can improve measures of physician and staff satisfaction and organizational function.

Insights from practice-based researchers to develop family medicine faculty as scholars.

BACKGROUND AND OBJECTIVES: National mandates call for accelerating scholarly development of family medicine faculty. One strategy to address these mandates is training more faculty to participate in practice-based research (PBR). We need to determine competencies that enable faculty to conduct PBR, methods for training faculty in PBR, and strategies to streamline PBR operations in clinics. METHODS: Through a qualitative literature review process, we identified faculty knowledge, attitudes, and skills thought to promote PBR. We then conducted structured interviews with a sample of PBR experts to explore their experience with and opinions about PBR: What knowledge, attitudes, and skills support PBR? What types of training will prepare family physicians to participate in and conduct PBR? What factors in the ambulatory clinical setting facilitate the success of PBR? What are the most important barriers to conducting PBR? RESULTS: Recommendations for PBR teaching and learning fell within the topic areas of scope of training, teaching methods, essential knowledge, and organizational environment. The most frequent expert recommendation was that all clinical practice and teaching settings should offer participatory research training for faculty, learners, and staff on an ongoing basis. Lack of funding and scarcity of time are the greatest impediments to conducting PBR. Additional barriers include lack of interest, lack of motivation, and lack of PBR knowledge and skills. Success in PBR often begins with an enthusiastic PBR champion whose characteristics include passion, initiative, and reflectiveness. Through organizational development, PBR champions can foster enthusiasm and commitment on the part of colleagues, administrators, and staff. It is important to continue to enhance PBR skill development opportunities at national meetings and to foster dissemination of PBR findings through presentations and publications. CONCLUSIONS: To foster growth and success of practice-based researchers, we should implement and sustain comprehensive multi-level training in PBR and nurture a culture of ongoing inquiry in family medicine. A culture conducive to PBR offers opportunities for continual development of enthusiastic, informed, and skilled faculty whose interdisciplinary teams conduct PBR and develop physicians in training as future practice-based researchers.

Exploring physician and staff perceptions of the learning environment in ambulatory residency clinics.

BACKGROUND AND OBJECTIVES: Investigations of teaching quality in ambulatory clinics have generally focused on faculty and medical student perspectives. We investigated the association of learning and organizational environment variables with faculty, resident, and nursing staff perceptions of quality of teaching and with a measure of resident learning in ambulatory residency clinics. METHODS: Annually over 5 years (1998-2002), we distributed learning and organizational environment surveys to faculty, residents, and staff in three ambulatory clinics of the Wayne State University Department of Family Medicine. We assessed internal reliability of the surveys' 11 scales and then compared responses of employee groups across sites. We then conducted a multiple regression analysis to determine the association of learning and organizational environment variables with faculty, resident, and staff perceptions of quality of teaching. We also compared the mean change in residents' In-training Examination (ITE) scores at our clinic teaching sites over the years of the study. RESULTS: Nine of 11 survey scales demonstrated acceptable internal reliability. Staff views were significantly lower than residents' views on all scales and were significantly lower than faculty's on all but one scale. Opinions about availability of learning opportunities for residents explained the most variance (35.2%) in the overall assessment of teaching quality. The addition of job satisfaction brought the explained variance up to 46.4%. The mean change in ITE scores was higher for residents at the site with higher learning and organizational environment assessment scores but not significantly so. CONCLUSIONS: Nine learning and organizational environment scales were found internally reliable and useful to measure faculty, resident, and staff perspectives on ambulatory teaching sites. Two areas of focus for improvement were found. First, learning opportunities should be structured so that residents are oriented to the ambulatory clinic, have their knowledge assessed regularly, are helped to meet individual goals, are given appropriate levels of responsibility, and see an adequate number, mix, and continuity of patients. Second, prioritizing efforts to improve job satisfaction for all employees is important because of the association between job satisfaction and employee perceptions of quality of teaching. We recommend that research into the educational climate in ambulatory clinics include perspectives of the full range of clinic personnel who can contribute to resident learning.

Synchronous distance learning as an effective and feasible method for delivering residency didactics.

BACKGROUND AND OBJECTIVES: Providing effective multisite didactic teaching in residency programs remains a challenge. There is limited evidence regarding the educational equivalency of the traditional and distance learning methods for delivery of didactics. We introduced a synchronous two-way audio and video Internet-transmitted distance learning methodology in two sites. The study assessed both residents' satisfaction and knowledge gain at the face-to-face lecture site as compared with the distance learning site. METHODS: The study was conducted over 1 year at the Wayne State University family medicine residency program, involving all 36 residents. Seventeen distance learning sessions were conducted, and the results from the lecture and distance learning sites were evaluated. RESULTS: The didactic sessions were rated highly by both groups, with no significant differences on the resident satisfaction survey. The distance learning method was received positively by learners. The residents in both groups scored higher on posttests compared to the pretests, and there was no statistical difference in knowledge gain between the lecture and the distance learning group. CONCLUSIONS: Synchronous interactive instructor-led distance learning is an effective method for delivering residency didactics at more than one site. The new technology is well accepted by learners and is a promising approach to multi-site education.

Scholarly development of clinician faculty using evidence-based medicine as an organizing theme.

While scholarship is a critical component of the mission of all academic departments, little is known about how to approach the scholarly development of clinician faculty. The authors developed a thematically based faculty development curriculum with two primary components: evidence-based clinical practice and critical appraisal of current clinical research. They took a task management approach to reducing anticipated barriers to program success by instituting a regularly scheduled seminar series, providing evidence-based reading materials, recruiting clinician faculty as speakers for the clinical presentations, and providing continuing medical education credits for seminar attendance. This case study illustrates a faculty development curriculum that stimulated scholarly discussion and research activities in the authors' clinician faculty.

E-conferencing for delivery of residency didactics.

OBJECTIVE: While didactic conferences are an important component of residency training, delivering them efficiently is a challenge for many programs, especially when residents are located in multiple sites, as they are at Wayne State University School of Medicine in the Department of Family Medicine. Our residents find it difficult to travel from our hospitals or rotation sites to a centralized location for conferences. In order to overcome this barrier, we implemented distance learning and electronically delivered the conferences to the residents. DESCRIPTION: We introduced an Internet-delivered, group-learning interactive conference model in which the lecturer is in one location with a group of residents and additional residents are in multiple locations. We launched the project in July 2001 using external company meeting services to schedule, coordinate, support, and archive the conferences. Equipment needed in each location consisted of a computer with an Internet connection, a telephone line, and a LCD projector (a computer monitor sufficed for small groups). We purposely chose simple distance-learning technology and used widely available equipment. Our e-conferencing had two components: (1) audio transmission via telephone connection and (2) visual transmission of PowerPoint presentations via the Internet. The telephone connection was open to all users, allowing residents to ask questions or make comments. Residents chose a conference location depending on geographic proximity to their rotation locations. Although we could accommodate up to 50 sites, we focused on a small number of locations in order to facilitate interaction among residents and faculty. Each conference session is archived and stored on the server for one week so those residents whose other residency-related responsibilities precluded attendance can view any conferences they have missed. DISCUSSION: E-conferencing proved to be an effective method of delivering didactics in our residency program. Its many advantages included ease of use, cost-efficiency, and wide availability of equipment. Residents had the advantage of both geographic and temporal independence. Our e-conferences were interactive, and in addition to a PowerPoint presentation, faculty provided Web sites and hyperlinks for references. Initial problems included slow-speed connection, the requirement for digital materials, and the need for residents and faculty to adjust to a new learning method. There was also a need for increased coordination at the sites and reliance on electronic communication. To assess the effectiveness of the program, residents completed knowledge pre- and post-tests and a conference evaluation form. We also monitored conference attendance rates. Preliminary results indicated positive resident attitudes toward distance learning and significant increases in conference attendance. To objectively evaluate this instructional delivery method, we will compare residents' knowledge gains in the face-to-face instructor group with those of the group to which the lecture is broadcast. Ultimately, we are hoping to offer this educational opportunity to other family practice residency programs in the area, to medical students interested in family medicine, and to community family physicians for continuing medical education. We are considering the addition of streaming video to the presentations in the future, once the bandwidth of the Internet connections is sufficient.