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Discovery of new human beta-defensins using a genomics-based approach.

Epithelial beta-defensins are broad-spectrum cationic antimicrobial peptides that also act as chemokines for adaptive immune cells. In the human genome, all known defensin genes cluster to a <1 Mb region of chromosome 8p22-p23. To identify new defensin genes, the DNA sequence from a contig of large-insert genomic clones from the region containing human beta-defensin-2 (HBD-2) was analyzed for the presence of defensin genes. This sequence survey identified a novel beta-defensin, termed HBD-3. The HBD-3 gene contains two exons, is located 13 kb upstream from the HBD-2 gene, and it is transcribed in the same direction. A partial HBD-3 cDNA clone was amplified from cDNA derived from IL-1beta induced fetal lung tissue. The cDNA sequence encodes for a 67 amino acid peptide that is approximately 43% identical to HBD-2 and shares the beta-defensin six cysteine motif. By PCR analysis of two commercial cDNA panels, HBD-3 expression was detected in adult heart, skeletal muscle, placenta and in fetal thymus. From RT-PCR experiments, HBD-3 expression was observed in skin, esophagus, gingival keratinocytes, placenta and trachea. Furthermore, in fetal lung explants and gingival keratinocytes, HBD-3 mRNA expression was induced by IL-1beta. Additional sequence analysis identified the HE2 (human epididymis secretory protein) gene 17 kb upstream from the HBD-3 gene. One splice variant of this gene (HE2beta1) encodes a beta-defensin consensus cysteine motif, suggesting it represents a defensin gene product. HE2beta1 mRNA expression was detected in gingival keratinocytes and bronchial epithelia using RT-PCR analysis. The discovery of these novel beta-defensin genes may allow further understanding of the role of defensins in host immunity at mucosal surfaces.

Adult↗

The use of free resources in a subscription-based digital library: a case study of the North Carolina AHEC Digital Library.

BACKGROUND: The North Carolina (NC) Area Health Education Center's (AHEC) Digital Library (ADL) is a web portal designed to meet the information needs of health professionals across the state by pulling together a set of resources from numerous different sources and linking a pool of users to only the resources for which they have eligibility. Although the ADL was designed with the primary purpose of linking health care professionals to a set of licensed resources, the ADL also contains a significant number of links to free resources. These resources are available to any ADL member logging into their ADL account and to guest visitors to the ADL. While there are regular assessments of the subscription resources in the ADL as to utility and frequency of use, up until this point there has been no systematic analysis of the use of the overall set of free resources. It was decided to undertake an examination of the usage of ADL free resources over a 6-month period to analyze the utility of these resources to both ADL members and guests. METHODS: Each time a resource is accessed through the ADL, it is logged in a table. This study used a SQL query to pull every free resource accessed between November 1, 2005 and April 30, 2006. An additional query also pulled the user information for each free resource accessed. Once the queries of the database were complete, the results were imported into an Excel spreadsheet and analyzed using basic descriptive statistics. RESULTS: The vast majority of resource use through the ADL is to licensed resources. There are 2056 free resource URLs in the ADL, to which 1351 were linked out, meaning there was at least one link out to 65% of the free resources. The single most popular free resource was PubMed with 4803 link outs or nearly 20% of the total link outs to free resources. The breakdown of free resource use by different use groups indicates that the highest percentage of use of free resources was by guests followed by institutional affiliates and AHEC Faculty/Staff. The next 3 highest user groups accessing free resources are: paid members, preceptors, and residents. CONCLUSION: The only free resource capturing a significant number of link outs is the free link to PubMed. This reflects the importance placed on traditional medical literature searching by the ADL clinical user base. Institutional affiliates access free resources through the ADL with the second highest frequency of all the user groups. Finally, in analyzing use of free resources, it is important to note the overall limitations of this survey. While link outs are excellent indicators of frequency of use they do not provide any information about the ultimate usefulness of the resource being accessed. Further studies would need to examine not only the quantitative use of resources, but also their qualitative importance to the user.

Journal Article↗

Health-related quality of life in patients with idiopathic pulmonary fibrosis: a systematic review.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) profoundly affects the quality of patients' lives. A systematic review was performed to evaluate critically the published literature and to examine what is known about health-related quality of life (HRQL) in patients with IPF. METHODS: The MEDLINE, EMBASE, Health and Psychosocial Instruments, and Cochrane Library databases were searched to 1 April 2004. Abstracts and bibliographies of published articles were scanned and contact was made with investigators. Included studies analysed HRQL (or quality of life) in at least 10 patients with IPF. Two reviewers independently selected studies, evaluated their quality according to predetermined criteria, and abstracted data on study design, patients' demographic and clinical characteristics, and quality of life outcome measures. RESULTS: Seven studies met the inclusion criteria. The studies enrolled 512 patients with IPF and used three different instruments to measure HRQL. All studies had important limitations in methodological quality; none measured longitudinal changes in HRQL over time. Patients reported substantially impaired HRQL, especially in domains that measured physical health and level of independence. Patients with IPF appear to have similar impairments in HRQL to those with chronic obstructive pulmonary disease. Measures of dyspnoea were moderately correlated with scores from domains that measured physical health (R2 = 0.03-0.66) and energy/fatigue/pep (R2 = 0.19-0.55), but measures of pulmonary function and gas exchange did not correlate as strongly with these and other domains. CONCLUSION: Studies of HRQL in patients with IPF suggest that, in addition to the obvious effect on physical health, general health, energy level, respiratory symptoms, and level of independence are also impaired. Variability in HRQL among patients is not fully explained by measures of dyspnoea or pulmonary function, suggesting that HRQL measures provide unique information. More research is needed to identify or design appropriate measurement instruments for patients with IPF and to examine changes in HRQL over time or in response to specific treatments.

Aged↗

Genome encyclopedias and their use for comparative analysis of Rhodobacter capsulatus strains.

This paper consists of two components: the use of gene encyclopedias in genomic studies and Rhodobacter capsulatus genome project. A survey of vectors used for encyclopedia construction includes a brief discussion of their relative advantages and limitations. Projects employing various methods of encyclopedia assembly including the comparison of restriction patterns, restriction maps, linking by hybridization, oligonucleotide fingerprinting, sequence tagged site (STS) fingerprinting and encyclopedias derived from genetic maps are listed and briefly described. The R. capsulatus SB 1003 genome project started with the construction of its cosmid encyclopedia, which comprises 192 cosmids covering the chromosome and the 134 kbp plasmid in strain SB 1003, with the exact map coordinates of each cosmid. In a pilot sequencing study, several cosmids were individually subcloned using the vector M13mp18 and merged into one 189 kbp contig. About 160 open reading frames (ORFs) identified by the CodonUse program were subjected to similarity searches. The biological functions of eighty ORFs could be assigned reliably using the WIT (what is there) genome investigation environment. Eighty percent of these recognizable ORFs were organized in functional clusters, which simplified assignment decisions and increased the strength of the predictions. A set of 26 genes for cobalamin biosynthesis, genes for polyhydroxyalkanoic acid metabolism, DNA replication and recombination, and DNA gyrase were among those identified. Recently, another 1.2 Mbp genome fragment of the Rhodobacter genome was sequenced using a slightly modified approach. These results together with some genome investigation tools, have been placed at our web site (http://capsulapedia.uchicago.edu). The sequence of R. capsulatus is expected to be completed by summer 1998. A project to construct a systematic set of deletion strains of R. capsulatus in order to assign functions to unknown ORFs has been started. Preliminary data demonstrate the extreme convenience of the unique gene transfer agent (GTA) system to perform such work.

Animals↗

Health-Related quality of life (HRQoL) and health state utility values (HSUV) in patients with head and neck Cancer: A systematic review and Meta-Analysis.

BACKGROUND: Head and neck cancer (HNC) and its treatment can substantially impair speech, swallowing, eating, appearance, and social functioning, resulting in persistent reductions in health-related quality of life (HRQoL). Although the EuroQol 5-Dimensions questionnaire (EQ-5D) is widely used to assess generic HRQoL and derive health state utility values (HSUVs), EQ-5D-based evidence in HNC has not been comprehensively synthesized. This study aimed to summarize EQ-5D-based HRQoL and HSUVs in HNC, estimate pooled utility and EQ-VAS scores, explore subgroup differences, and identify predictors of poorer HRQoL. METHODS: A systematic review and meta-analysis was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420261307907). PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus were searched from inception to February 10, 2026. Studies reporting baseline EQ-5D utility values and/or EQ-VAS scores in patients with HNC were included. Random-effects meta-analyses using the DerSimonian-Laird (DL) estimator with the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment were performed to pool mean scores. Between-study variance (&#x3c4;2) and 95&#xa0;% prediction intervals (PI) were calculated to capture parameter dispersion. Subgroup analyses were conducted across clinical and methodological vectors. RESULTS: Twenty studies involving 7,403 patients were included. The pooled mean EQ-5D utility score was 0.79 (95&#xa0;% CI: 0.75-0.83; &#x3c4;2&#xa0;=&#xa0;0.0011; 95&#xa0;% PI: 0.72-0.86). The pooled mean EQ-VAS score was 69.36 (95&#xa0;% CI: 65.71-73.01; &#x3c4;2&#xa0;=&#xa0;38.4586; 95&#xa0;% PI: 55.11-83.61). Extreme heterogeneity was observed (I2&#xa0;=&#xa0;96.4&#xa0;% and 97.1&#xa0;%, respectively). Utility values were significantly higher in studies utilizing the EQ-5D-5&#xa0;L than the EQ-5D-3&#xa0;L version (0.82 vs. 0.76). By tumor subsite, nasopharyngeal cancer showed the highest utility value (0.85, exploratory), whereas oral cancer demonstrated the lowest (0.73). Adjusted multivariable models revealed that advanced stage, high treatment intensity, severe pharyngolaryngeal pain, dysphagia, malnutrition, and older age were robust predictors of poorer HRQoL. CONCLUSIONS: Patients with HNC experience substantial and persistent HRQoL impairment, with meaningful variations driven by tumor subsites and instrument versions. In light of the extreme heterogeneity, these pooled findings establish a macro-level, broad reference estimate rather than a fixed target. These parameters directly inform localized survivorship care planning, health technology evaluations, and cost-utility decision-making modeling in head and neck oncology.

Humans↗

Use of quality-adjusted life years for the estimation of effectiveness of health care: A systematic literature review.

OBJECTIVES: The objectives of this study were to identify, in a systematic literature review, published studies having used quality-adjusted life years (QALYs) based on actual measurements of patients' health-related quality of life (HRQoL) and to determine which HRQoL instruments have been used to calculate QALYs. Furthermore, the aims were to characterize studies with regard to medical specialty, intervention studied, results obtained, quality, country of origin, QALY gain observed, and interpretation of results regarding cost-effectiveness. METHODS: Systematic searches of the literature were made using the MEDLINE, Embase, CINAHL, SCI, and Cochrane Library electronic databases. Initial screening of identified articles was based on abstracts read independently by two of the authors; full-text articles were again evaluated by two authors, who made the final decision on which articles should be included. RESULTS: The search identified 3,882 articles; 624 were obtained for closer review. Of the reviewed full-text articles, seventy reported QALYs based on actual before-after measurements using a valid HRQoL instrument. The most frequently used instrument was EuroQol HRQoL instrument (EQ-5D, 47.5 percent). Other instruments used were Health Utilities Index (HUI, 8.8 percent), the Rosser-Kind Index (6.3 percent), Quality of Well-Being (QWB, 6.3 percent), Short Form-6D (SF-6D, 5.0 percent), and 15D (2.5 percent). The rest (23.8 percent) used a direct valuation method: Time Trade-Off (10.0 percent), Standard Gamble (5.0 percent), visual analogue scale (5.0 percent), or rating scale (3.8 percent). The most frequently studied medical specialties were orthopedics (15.5 percent), pulmonary diseases (12.7 percent), and cardiology (9.9 percent). Ninety percent of the studies came from four countries: United Kingdom, United States, Canada, the Netherlands. Approximately half of the papers were methodologically high quality randomized trials. Forty-nine percent of the studied interventions were viewed by the authors of the original studies as being cost-effective; only 13 percent of interventions were deemed not to be cost-effective. CONCLUSIONS: Although QALYs gained are considered an important measure of effectiveness of health care, the number of studies in which QALYs are based on actual measurements of patients' HRQoL is still fairly limited.

Cost-Benefit Analysis↗

Genome-wide analysis of DNA copy-number changes using cDNA microarrays.

Gene amplifications and deletions frequently contribute to tumorigenesis. Characterization of these DNA copy-number changes is important for both the basic understanding of cancer and its diagnosis. Comparative genomic hybridization (CGH) was developed to survey DNA copy-number variations across a whole genome. With CGH, differentially labelled test and reference genomic DNAs are co-hybridized to normal metaphase chromosomes, and fluorescence ratios along the length of chromosomes provide a cytogenetic representation of DNA copy-number variation. CGH, however, has a limited ( approximately 20 Mb) mapping resolution, and higher-resolution techniques, such as fluorescence in situ hybridization (FISH), are prohibitively labour-intensive on a genomic scale. Array-based CGH, in which fluorescence ratios at arrayed DNA elements provide a locus-by-locus measure of DNA copy-number variation, represents another means of achieving increased mapping resolution. Published array CGH methods have relied on large genomic clone (for example BAC) array targets and have covered only a small fraction of the human genome. cDNAs representing over 30,000 radiation-hybrid (RH)-mapped human genes provide an alternative and readily available genomic resource for mapping DNA copy-number changes. Although cDNA microarrays have been used extensively to characterize variation in human gene expression, human genomic DNA is a far more complex mixture than the mRNA representation of human cells. Therefore, analysis of DNA copy-number variation using cDNA microarrays would require a sensitivity of detection an order of magnitude greater than has been routinely reported. We describe here a cDNA microarray-based CGH method, and its application to DNA copy-number variation analysis in breast cancer cell lines and tumours. Using this assay, we were able to identify gene amplifications and deletions genome-wide and with high resolution, and compare alterations in DNA copy number and gene expression.

Chromosomes, Human, Pair 17↗

Expression of nuclear hormone receptors in the rat supraoptic nucleus.

To investigate the role of nuclear hormone receptors on neuropeptide gene expression in the hypothalamo-neurohypophyseal system (HNS) of the rat, a survey was made of members of the nuclear hormone receptor superfamily that are expressed in the supraoptic nucleus (SON). A polymerase chain reaction cloning strategy based on homologies in the DNA-binding domain of AGGTCA-binding factors was devised for the identification of receptors in microdissected SON tissue. Cloning of the amplified products led to the identification of five true receptors, thyroid hormone receptor-alpha (THR alpha), retinoic acid receptor-alpha, retinoic acid receptor-gamma, retinoid X receptor-alpha, and retinoid X receptor-gamma, as well as four orphan receptors, apolipoprotein AI regulatory protein (ARP-1), chicken ovalbumin upstream promoter transcription factor I (COUP-TF I), estrogen-related receptor 2, and testis receptor 4 (TR4). Dot-blot screening of amplified gene fragment analysis showed that THR alpha, ARP-1, TR4, and COUP-TF I were the most abundant factors expressed in the SON region, in the order THR alpha > ARP-1 > TR4 approximately COUP-TF I. THR alpha has previously been localized to HNS neurons. In situ hybridization analysis showed that ARP-1, COUP-TF I, and TR4 were not expressed in magnocellular neurons at appreciable levels, but rather in surrounding structures. Furthermore, in lactating female rats there were no significant differences in the composition of the nine identified nuclear hormone receptors in the SON region compared with control animals. From these experiments, it is concluded that there is a multitude of hypothalamically expressed nuclear hormone receptors, but that only THR alpha is expressed at relatively high abundance in HNS neurons. This indicates that the peptide-producing magnocellular neurons of the SON express a specific set of transcription factors of the nuclear hormone receptor family.

Amino Acid Sequence↗

Neoadjuvant or adjuvant therapy for resectable gastric cancer? A practice guideline.

OBJECTIVE: To make recommendations on the use of neoadjuvant or adjuvant therapy in addition to surgery in patients with resectable gastric cancer (T1-4, N1-2, M0). OPTIONS: Neoadjuvant or adjuvant treatments compared with "curative" surgery alone. OUTCOMES: Overall survival, disease-free survival, and adverse effects. EVIDENCE: The MEDLINE, CANCERLIT and Cochrane Library databases and relevant conference proceedings were searched to identify randomized trials. VALUES: Evidence was selected and reviewed by one member of the Cancer Care Ontario Practice Guidelines Initiative (CCOPGI) Gastrointestinal Cancer Disease Site Group and methodologists. A systematic review of the published literature was combined with a consensus process around the interpretation of the evidence in the context of conventional practice, to develop an evidence-based practice guideline. This report has been reviewed and approved by the Gastrointestinal Cancer Disease Site Group, comprising medical oncologists, radiation oncologists, surgeons, a pathologist and 2 community representatives. BENEFITS, HARMS AND COSTS: When compared with surgery alone, at 3 years adjuvant chemoradiotherapy has been shown to increase overall survival by 9% (50% v. 41%, p = 0.005) and to improve relapse-free survival from 31% to 48% (p = 0.001). At 5 years, it has been shown to increase overall survival by 11.6% (40% v. 28.4%) and to improve relapse-free survival from 25% to 38% (p < 0.001). Treatment has been associated with toxic deaths in 1% of patients. The most frequent adverse effects (> grade 3 [Southwest Oncology Group toxicity scale] are hematologic (54%), gastrointestinal (33%), influenza-like (9%), infectious (6%) and neurologic (4%). The radiation fields used can possibly damage the left kidney, resulting in hypertension and other renal problems. Furthermore, this therapy could increase the demand on radiation resources. Physicians and patients should understand the tradeoffs between survival benefit and toxicity and cost before making treatment decisions. RECOMMENDATIONS: After surgical resection, patients whose tumours have penetrated the muscularis propria or involve regional lymph nodes should be considered for adjuvant combined chemoradiotherapy. The current standard protocol consists of 1 cycle of 5-fluorouracil (5-FU) (425 mg/m2 daily) and leucovorin (20 mg/m2 daily) administered daily for 5 days, followed 1 month later by 45 Gy (1.8 Gy/d) of radiation given with 5-FU (400 mg/m2 daily) and leucovorin (20 mg/m2 daily) on days 1 through 4 and the last 3 days of radiation. One month after completion of radiation, 2 cycles of 5-FU (425 mg/m2 daily) and leucovorin (20 mg/m2 daily) in a daily regimen for 5 days are given at monthly intervals. There is no evidence on which to make a recommendation for patients with node-negative tumours that have not penetrated the muscularis propria. For patients unable to undergo radiation, adjuvant chemotherapy alone may be of benefit, particularly for those with lymph-node metastases. The optimal regimen remains to be defined. There is insufficient evidence from randomized trials to recommend neoadjuvant chemotherapy, or neoadjuvant or adjuvant radiotherapy or immunotherapy, either alone or in combination, outside a clinical trial. VALIDATION: A draft version of this document was circulated to 166 clinicians using a 21-item feedback questionnaire. Ninety-nine (63%) returned the questionnaire, and 74 of these indicated that the guideline was relevant to their clinical practice and completed the survey. Of the 74 clinicians, 52 (70%) agreed that the document should be approved as a practice guideline. SPONSORS: The CCOPGI is supported by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

Chemotherapy, Adjuvant↗

Six Sigma: not for the faint of heart.

Six Sigma is an excellent quality and performance improvement tool. Like any tool, the results of using it are highly dependent on whether you use it with competence and on the right problem. This article will help you decide if your problem is well-suited for a Six Sigma approach and will suggest the optimum approach for planning and implementing Six Sigma methodology. Performance improvement methods can be grouped into two broad categories, based on the problem to be addressed. When the problem is relatively minor and localized, "evolutionary" methods may be suitable (e.g., quality circles, problem-solving staff meetings, continuous quality improvement [CQI], total quality management [TQM]). These tools work best when modest incremental improvements are sought, when major process redesign is not thought to be necessary, and when the avoidance of workplace disruption is desired. Reengineering and Six Sigma are the best-known examples of the "revolutionary" performance improvement methods. These methods should be used when major (drastic, do or die, etc.) improvements are needed. Problems that cross departmental boundaries need these methods. When a process is so dysfunctional that you feel like you need to tear up the standard operating procedure (SOP) and start all over again, you need a revolutionary method. A Six Sigma project requires a major expenditure of money and employee time, and a willingness to make some hard decisions about jobs, employee retention and relationships among stakeholders. An institution's culture should be considered as part of the decision about using Six Sigma. If the institution has a history of making data-driven decisions, or at least has displayed openness to operating in that manner, Six Sigma has a good chance of success. A radiology-driven Six Sigma project should not be undertaken until a comprehensive written description of the scope of the project is approved by the radiology department leadership team and by the appropriate higher-level institutional leaders. This document should address the specific outcomes desired, the resources available, a rough tentative timeline, and any political constraints imposed on the project (e.g., inviolate HR policies, compatibility with enterprise strategic goals). The document should be comprehensive enough and explicit enough to be useful as a major component of the bid package for hiring a consultant or for writing the job description for the hiring of an in-house expert. A full-time project manager should be designated if an in-house expert is not hired. This person should be a senior leader in the department, but not the department director. Leading a Six Sigma project is a full-time job in itself and cannot be performed as an additional duty. Although it may be tempting to appoint a senior staff technologist or nurse, keep in mind that the project manager must have sufficient authority to expect cooperation from departmental supervisors without resorting to frequent appeals to the department director. Contact the institution's CIO and ask that a knowledgeable person on the IT staff be appointed to serve as the IT liaison for the project. This person should have in-depth familiarity with the HIS and the ways that it interfaces with the RIS (if the RIS is not a module within the HIS). Most importantly, this liaison must understand the exact data definitions and the origins of the data that are passed between the HIS and the RIS. The steering committee should consist of at least one physician and one department-level administrator from outside of the radiology department. From within the radiology department, there should be at least one radiologist and one senior modality manager (whose modality is not the primary focus), the project manager, and the manager of a radiology component that is a focus of the project (e.g., the film library manager). The consultant should be an ex officio member without vote. The steering committee should be small enough to be manageable, yet large enough to provide insight from both the radiology department and the rest of the institution. Because of the size of the steering committee and the difficulty of bringing so many people together for meetings, the day-to-day governance of the project will be provided by an informal "operations committee." When we consider "change" in the context of a Six Sigma project, we talk about a wide variety of topics, but they can be summarized usefully as dealing with processes, policies, physical plant and equipment, personnel, and politics (or culture). The first three of these lend themselves to quantitative analysis, or at least rigorously qualitative analysis. The final two, however, are subjective, ill-defined or not readily acknowledged, and fraught with potentially major challenges when it becomes necessary to implement changes in the first three. The Six Sigma process, as taught by GE, consists of five phases summarized by the acronym DMAIC: Define, Measure, Analyze, Improve and Control. This article deals mostly with the time period from first consideration of a possible Six Sigma project through the early part of the Define phase. It also discusses pitfalls that must be considered anytime throughout a project, from first thoughts of conducting a project until recommended changes become ingrained in the department's operations. Six Sigma compares baseline or historical data to data obtained after implementation of Six Sigma-driven changes in order to determine if desired changes in performance have been achieved. When historical data are not available, the Six Sigma team must collect baseline data as one of their earliest tasks. A Six Sigma project can easily last 18 to 24 months or longer. We must be sure that the data we collect during Month 18 are collected identically to the data we collected at baseline. A major performance improvement project is likely to require 12 to 24 months or longer. Upper management initially may be reluctant to appoint the "cream of the crop" to the project teams. Success is predicated on having the most knowledgeable personnel involved in the project. Without them, the chances of success are reduced. A Six Sigma project's length always exceeds the attention span of the vast majority of its participants. The department director and project manager must anticipate this and devote special efforts to maintaining motivation and momentum after the initial flurry of activity. The complexity of a Six Sigma project will be greatly increased, and all of the pitfalls discussed here will be exacerbated, if your facility has multiple sites. At the simplest, the multiple sites will introduce complications in getting personnel to come to project meetings. The complications will escalate if the sites are under different management, such as a confederated health system. The project manager and the consultant will expend additional time and effort dealing with these issues, which likely will lengthen the project unavoidably. The project manager must spend time with the department's external customers who have significant stakes in the project. At a minimum, this should include relatively formal meetings with other department directors or subordinate managers and key physician and nurse leaders, and attendance at their managerial or staff meetings (you may need to ask to be invited). Although paper or e-mail surveys can be helpful, only sustained personal contact with a stakeholder will truly allow you to understand how they interact with radiology and what their concerns are. As with daily operational management, a performance improvement project requires attention to policies, procedures, processes, physical plant and infrastructure, personnel, and perhaps most importantly, to politics.

Efficiency, Organizational↗

Student research projects and theses: should they be a requirement for medical school graduation?

From 1981 to 1994, 69 fourth-year students at the Albert Einstein College of Medicine participated in a 6-month medical school research project (MSRP) with the same mentor. Students could choose an original project or library project, and were required to prepare a written report suitable for submission to a peer-reviewed journal. In this article, it is assessed whether a mandatory fourth-year MSRP might substitute for traditional clinical electives. Student reactions to the experience were ascertained by using the responses to an open- and closed-ended questionnaire regarding skills gained by doing MSRPs, the impact on their careers, and their relationship to the mentor. Eighty-nine percent of the students responded that MSRPs increased their ability to formulate a hypothesis, 91% reported that this project increased their ability to conduct a literature search, 95% felt that MSRPs increased their knowledge of research techniques, and 91% reported having improved data collection skills after completing these projects. Students also reported that MSRPs increased their ability to critically evaluate the literature (95%) or to work independently (93%), and 89% responded that the project improved their ability to evaluate their individual strengths and weaknesses. Eighty-nine percent reported that the project increased their ability to write a research paper (34% of projects were original research, 35% were literature reviews, and 30% both original research and literature reviews). Thirty-three percent of respondents reported having some kind of problem completing their projects, and 90% of project reports were accepted for publication in peer-reviewed journals. Ninety-one percent of students responded that they had received appropriate guidance from their mentor, and 73% met with him at least once a week. Seventy-three percent described a relationship with the mentor that went beyond project advising. Eighty-five percent responded that the project impacted their careers in medicine, 97% felt that the research experience was a useful replacement for fourth-year electives, and 91% felt they were as well prepared for residency training as their classmates who had regular fourth-year electives without research. Fifty percent of students indicated that completion of an independent research project should not be required for graduation, whereas 18% responded it should be a requirement and 32% were undecided. Incorporating an MSRP in the fourth year appears to increase research skills and is considered to be a useful replacement for traditional elective rotations. The MSRP impacts favorably on future careers; however, many students do not think it should be a mandatory requirement for graduation from medical school.

Academic Dissertations as Topic↗

Risk to tourists posed by wild mammals in South Africa.

BACKGROUND: One of South Africa's principal tourist attractions is the opportunity to encounter Africa's large mammals in the wild. Attacks by these mammals can be exceptionally newsworthy with potentially deleterious effects on tourism. Little is known about the risk of injury and death caused by wild mammals to visitors to South Africa's nature reserves. The aim of this study was to determine the incidence of fatal and nonfatal attacks on tourists by wild mammals in South Africa and to ascertain avoidable factors, if any. METHODS: Commercial press records covering all South African Newspapers archived at the Independent Newspapers' central library were systematically reviewed for a 10-year period, January 1988 to December 1997 inclusive, to identify all deaths and injuries to domestic and international tourists resulting from encounters with wild mammals in South Africa. All of these incidents were analyzed to ascertain avoidable factors. RESULTS: During the review period seven tourists, including two students from Thailand and a German traveler, were killed by wild mammals in South Africa. Three of the four deaths ascribed to lions resulted from tourists carelessly approaching prides on foot in lion reserves. A judicial inquiry found that the management of a KwaZulu-Natal Reserve was culpable for the remaining death. Tourist ignorance of animal behavior and flagrant disregard of rules contributed to the two fatalities involving hippopotami. The unusual behavior manifested by the bull elephant responsible for the final death, resulted from discomfort caused by a dental problem to this pachyderm. During the same period there were 14 nonfatal attacks on tourists, including five by hippo, three by buffalo, two by rhino, and one each by a lion, leopard, zebra and musth elephant. Only the latter occurred while the visitor was in a motor vehicle. Tourist ethological naivete and failure to determine the experience of trail guides prior to travel, resulted in inadvertent agonistic behavior, unnecessary risk-taking and avoidable injury. CONCLUSIONS: This retrospective study has shown that attacks on tourists by wild mammals in South Africa are an uncommon cause of injury and death. Sensible precautions to minimize this risk include remaining in a secure motor vehicle or adequately fenced precincts while in the vicinity of large mammals, rigidly observing nature reserve instructions, never approaching animals that appear ill, malnourished, displaying aggressive behavior traits or female wild mammals with young, and demanding adequately trained and experienced game rangers when embarking on walking trails. Any behavior that might be construed as antagonistic and which could provoke an attack by large mammals should be avoided (e.g., driving directly at a lion). Visitors need to be informed of classic signs of aggression, in particular in elephants, which will allow timely avoidance measures to be taken. The risk-enhancing effect of excessive alcohol intake is undesirable in the game reserve setting, as is driving at high speed after dusk in areas where hippos graze. Local advice on personal safety in wildlife reserves and the credentials of trail guides should be obtained from lodge or reserve management, tourism authorities or the travel industry prior to travel to game reserves.

Adolescent↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗