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Exploration of phylogenetic data using a global sequence analysis method.

BACKGROUND: Molecular phylogenetic methods are based on alignments of nucleic or peptidic sequences. The tremendous increase in molecular data permits phylogenetic analyses of very long sequences and of many species, but also requires methods to help manage large datasets. RESULTS: Here we explore the phylogenetic signal present in molecular data by genomic signatures, defined as the set of frequencies of short oligonucleotides present in DNA sequences. Although violating many of the standard assumptions of traditional phylogenetic analyses--in particular explicit statements of homology inherent in character matrices--the use of the signature does permit the analysis of very long sequences, even those that are unalignable, and is therefore most useful in cases where alignment is questionable. We compare the results obtained by traditional phylogenetic methods to those inferred by the signature method for two genes: RAG1, which is easily alignable, and 18S RNA, where alignments are often ambiguous for some regions. We also apply this method to a multigene data set of 33 genes for 9 bacteria and one archea species as well as to the whole genome of a set of 16 gamma-proteobacteria. In addition to delivering phylogenetic results comparable to traditional methods, the comparison of signatures for the sequences involved in the bacterial example identified putative candidates for horizontal gene transfers. CONCLUSION: The signature method is therefore a fast tool for exploring phylogenetic data, providing not only a pretreatment for discovering new sequence relationships, but also for identifying cases of sequence evolution that could confound traditional phylogenetic analysis.

Algorithms↗

Evidence-based obstetrics in four hospitals in China: An observational study to explore clinical practice, women's preferences and provider's views.

BACKGROUND: Evidence-based obstetric care is widely promoted in developing countries, but the success of implementation is not known. Using selected childbirth care procedures in four hospitals in Shanghai, we compared practice against evidence-based information, and explored user and provider views about each procedure. METHODS: Observational study. Using the Cochrane Library, we identified six procedures that should be avoided as routine and two that should be encouraged. Procedure rate determined by exit interviews with women, verified using hospital notes. Views of women and providers explored with in depth interviews.The study sites were three hospitals in Shanghai and one in neighbouring province of Jiangsu. 150 women at each centre for procedure rate, and 48 in-depth interviews with women and providers. RESULTS: Vaginal births were 50% (303/599) of the total. Of the six practices where evidence suggests they should be avoided as routine, three were performed with rates above 70%: pubic shaving (3 hospitals), rectal examination (3 hospitals), and episiotomy (3 hospitals). Most women delivered lying down, pain relief was rarely given, and only in the urban district hospital did women routinely have a companion. Most women wanted support or companionship during labour and to be given pain relief; but current practice is insufficient to meet women's needs. CONCLUSION: Obstetric practice is not following best available evidence in the hospitals studied. There is a need to adjust hospital policy to support the use of interventions proven to be of benefit to women during childbirth, and develop approaches that ensure clinical practice changes.

Journal Article↗

A centralised public information resource for randomised trials: a scoping study to explore desirability and feasibility.

BACKGROUND: There are currently several concerns about the ways in which people are recruited to participate in randomised controlled trials, the low acceptance rates among people invited to participate, and the experiences of trial participants. An information resource about on-going clinical trials designed for potential and current participants could help overcome some of these problems. METHODS: We carried out a scoping exercise to explore the desirability and feasibility of establishing such a resource. We sought the views of a range of people including people who were considering taking part in a trial, current trial participants, people who had been asked but refused to participate in a trial, consumer group representatives and researchers who design and conduct trials. RESULTS: There was broad-based support for the concept of a centralised information resource for members of the public about on-going and recently completed clinical trials. Such an information resource could be based on a database containing standardised information for each trial relating to the purpose of the trial; the interventions being compared; the implications of participation for participants; and features indicative of scientific quality and ethical probity. The usefulness of the database could be enhanced if its search facility could allow people to enter criteria such as a disease and geographic area and be presented with all the trials relevant to them, and if optional display formats could allow them to view information in varying levels of detail. Access via the Internet was considered desirable, with complementary supported access via health information services. The development of such a resource is technically feasible, but the collation of the required information would take a significant investment of resources. CONCLUSION: A centralised participant oriented information resource about clinical trials could serve several purposes. A more detailed investigation of its feasibility and exploration of its potential impacts are required.

Databases as Topic↗

Exploring the effects of telehealth on medical human resources supply: a qualitative case study in remote regions.

BACKGROUND: The availability of medical human resource supply is a growing concern for rural and remote communities in many countries. In the last decade, various telehealth experiences in Canada have highlighted the potential impact of this technology on professional practice. The purpose of this study was to explore physicians' and managers' perceptions regarding the potential of telehealth to support recruitment and retention of physicians in remote and rural regions. METHODS: A case study in Eastern Quebec was performed to explore this complex phenomenon. The analytical framework was based on two literature reviews and a Delphi study. Data were collected from semi-structured interviews with 41 physicians and 22 managers. Transcripts were produced and interview content was coded independently by two judges and validated by an expert panel. RESULTS: Interviews have highlighted the potential impact of telehealth on several factors influencing the recruitment and retention of physicians in rural and remote regions. The potential effects of telehealth on physicians' choice of practice location could be seen at the professional, organizational, educational and individual levels. For instance, telehealth could improve work satisfaction by allowing a regional on-call duty system and a better follow-up of patients. However, there are also certain limits related to telehealth, such as the fear that it would eventually replace all continuing medical education activities and onsite specialists in remoteregions. CONCLUSION: Telehealth is likely to have an impact on several factors related to medical workforce supply in remote and rural regions. However, the expected benefits will materialize if and only if this technology is properly integrated into organizations as a support to professional practice.

Administrative Personnel↗

An explorative study to assess the efficacy of toltrazuril-sulfone (ponazuril) in calves experimentally infected with Neospora caninum.

BACKGROUND: Neospora caninum is an important cause of infectious abortion and stillbirth in cattle world-wide. Infection is common and may frequently be passed from mother to calf (vertical transmission) with no signs of disease. Based on our previous observation that N. caninum-infection can be efficiently controlled with toltrazuril-sulfone (ponazuril) in experimentally infected mice, we addressed the question if efficacy could also be obtained in experimentally infected calves. MATERIAL AND METHODS: The study included 19 calves and represents an initial explorative approach to document a basic effectiveness at first. Fifteen animals received each 2 x 10(8) N. caninum trophozoites, half of the dose being injected intravenously and the other half subcutaneously. Efficacy of treatment was assessed using molecular detection of parasite DNA with PCR and pathological alterations by immunohistochemistry in different organs of the animals. Assessment included also clinical, serological and pathophysiological parameters. RESULTS: In those calves medicated with ponazuril (one, or six consecutive days, respectively, starting one day after infection), a complete abrogation of the parasite detectability was obtained in the brain and other organs, while 50% of non-treated calves became PCR-positive in brain and muscles. Clinically, ponazuril chemotherapy of infected calves--in comparison to non-treated infected animals--reduced symptoms (fever), but no differences were observed between treated and non-treated animals with regard to serum enzymes and metabolites. Efficacy of a six-day treatment was also reflected by significantly lower anti-Neospora antibody concentrations developed after infection, when compared to non-treated animals. CONCLUSION: Based on our findings in this initially explorative approach that indicate a basic effectiveness of ponazuril against experimental N. caninum infection in calves, we plan to follow our chemotherapeutical intervention strategy to control bovine neosporosis with a subsequent more extensive field study with naturally infected calves.

Journal Article↗

Urgent abdominal re-explorations.

BACKGROUND: Treatment of a number of complications that occur after abdominal surgeries may require that Urgent Abdominal Re-explorations (UARs), the life-saving and obligatory operations, are performed. The objectives of this study were to evaluate the reasons for performing UARs, outcomes of relaparotomies (RLs) and factors that affect mortality. METHODS: Demographic characteristics; initial diagnoses; information from and complications of the first surgery received; durations and outcomes of UAR(s) performed in patients who received early RLs because of complicated abdominal surgeries in our clinic between 01.01.2000 and 31.12.2004 were investigated retrospectively. Statistical analyses were done using the chi-square and Fisher exact tests. RESULTS: Early UAR was performed in 81 out of 4410 cases (1.8%). Average patient age was 50.46 (13-81) years with a male-to-female ratio of 60/21. Fifty one (62.96%) patients had infection, 41 (50.61%) of them had an accompanying serious disease, 24 (29.62%) of them had various tumors and 57 (70.37%) patients were operated under emergency conditions during first operation. Causes of urgent abdominal re-explorations were as follows: leakage from intestinal repair site or from anostomosis (n:34; 41.97%); hemorrhage (n:15; 18.51%); intestinal perforation (n:8; 9.87%); intraabdominal infection or abscess (n:8; 9.87%); progressive intestinal necrosis (n:7; 8.64%); stomal complications (n:5; 6.17%); and postoperative ileus (n:4; 4.93%). Two or more UARs were performed in 18 (22.22%) cases, and overall mortality was 34.97% (n:30). Interval between the first laparotomy and UAR averaged as 6.95 (1-20) days, and average hospitalization period was 27.1 (3-78) days.Mortality rate was found to be higher among the patients who received multiple UARs. The most common (55.5%) cause of mortality was sepsis/multiple organ failure (MOF). The rates for common mortality and sepsis/MOF-dependent mortality that occured following UAR were significantly higher in patients who received GIS surgery than in those who received other types of surgeries (p:0.000 and 0.010, respectively). CONCLUSION: UARs that are performed following complicated abdominal surgeries have high mortality rates. In particular, UARs have higher mortality rates following GIS surgeries or when infectious complications occur. The possibility of efficiently lowering these high rates depends on the success of the first operations that the patient had received.

Journal Article↗

Exploring shotgun metagenomic data to detect microeukaryotic pathogens in wildlife.

BACKGROUND: Microeukaryotic parasites of the intestinal tract are an understudied group of organisms that infect humans and many other animals. Targeted sequencing methods focused on individual loci are usually employed for detection of these parasites, making comprehensive studies of microeukaryotic parasite diversity within hosts or other systems difficult. Exploratory approaches such as shotgun metagenomic sequencing to survey the diversity of microeukaryotic parasites in new and existing datasets are not well developed. RESULTS: Utilizing existing datasets from 12 goose fecal samples, we explored some of the benefits and challenges of using shotgun metagenome sequencing to detect microeukaryotic parasites. We demonstrated the importance of careful curation of read classification data to avoid erroneously linking pathogens to hosts or environments as unsupported classifications were common in the data and varied widely depending on analysis parameters. However, we were able to establish strong support for the presence of sequences of Eimeria and Enterocytozoon bieneusi. In addition, examination of trichomonad reads indicated that parasite reads mapping to human pathogens unlikely to colonize geese may in fact represent cryptic microeukaryotic species that are not included in existing curated databases opening new potential avenues of study. CONCLUSIONS: Taken together these findings support the idea that exploring microeukaryotic parasite diversity within shotgun metagenomic datasets can be beneficial to our understanding of the presence and diversity of these organisms in wildlife hosts.

Animals↗

Exploring the potential of genetic analysis in historical blood spots for patients with iodine-deficient goiter and thyroid carcinomas in Switzerland and Germany (1929-1989).

Iodine deficiency-induced goiter continues to be a global public health concern, with varying manifestations based on geography, patient's age, and sex. To gain insights into clinical occurrences, a retrospective study analyzed medical records from patients with iodine deficiency-induced goiter or thyroid cancer who underwent surgery at the Community Hospital in Riehen, Switzerland, between 1929 and 1989. Despite today's adequate iodine supplementation, a significant risk for iodine-independent goiter remains in Switzerland, suggesting that genetic factors, among others, might be involved. Thus, a pilot study exploring the feasibility of genetic analysis of blood spots from these medical records was conducted to investigate and enhance the understanding of goiter development, potentially identify genetic variations, and explore the influence of dietary habits and other environmental stimuli on the disease.Blood prints from goiter patients' enlarged organs were collected per decade from medical records. These prints had been made by pressing, drawing, or tracing (i.e., pressed and drawn) the removed organs onto paper sheets. DNA analysis revealed that its yields varied more between the prints than between years. A considerable proportion of the samples exhibited substantial DNA degradation unrelated to sample collection time and DNA mixtures of different contributors. Thus, each goiter imprint must be individually evaluated and cannot be used to predict the success rate of genetic analysis in general. Collecting a large sample or the entire blood ablation for genetic analysis is recommended to mitigate potential insufficient DNA quantities. Researchers should also consider degradation and external biological compounds' impact on the genetic analysis of interest, with the dominant contributor anticipated to originate from the patient's blood.

Humans↗

Exploring the c.406 C > T variant in TNNI3 gene: pathogenic insights into restrictive cardiomyopathy.

BACKGROUND: Restrictive cardiomyopathy (RCM) is a rare cardiac disorder characterized by diastolic dysfunction and myocardial stiffness, frequently associated with genetic variants. We aimed to explore the genetic basis of RCM in a diagnosed patient through comprehensive genetic analysis. METHODS: Whole exome sequencing (WES) was conducted on the proband, followed by Sanger sequencing for variant confirmation and familial segregation analysis. In silico tools and structural protein modeling were employed to assess the functional impact of the identified variant. RESULTS: The c.406 C > T variant, classified as likely pathogenic, results in a truncated TNNI3 protein. Bioinformatics analysis highlighted significant structural disruptions, likely impairing sarcomere function. The patient presented with growth retardation, progressive dyspnea, and echocardiographic findings consistent with RCM. Both parents were heterozygous carriers, supporting an autosomal recessive inheritance pattern. The homozygosity of the novel variant identified in this study is a critical factor in the genotype-phenotype correlation observed in this case. CONCLUSION: This study identified the novel c.406 C > T variant in TNNI3 as a potential pathogenic driver of RCM, emphasizing the critical role of genetic evaluations in early diagnosis and management of inherited cardiomyopathies. Further studies are warranted to explore therapeutic interventions targeting TNNI3-related pathologies.

Humans↗

A qualitative exploration of the experiences of lesbian and heterosexual patients with breast cancer.

PURPOSE/OBJECTIVES: To explore similarities and differences between lesbian and heterosexual survivors of breast cancer regarding cancer experiences, medical interactions related to cancer treatment, and quality of life (QOL). DESIGN: Qualitative study using focus groups. SETTING: Urban, community-based health center. SAMPLE: A convenience sample of lesbians (n = 13) and heterosexual women (n = 28) with a diagnosis of breast cancer within the past five years. Participants were recruited via posted advertisements. METHODS: Focus groups were conducted as part of a larger study exploring coping and adjustment in lesbian survivors of breast cancer. Transcribed focus group data were analyzed through thematic and representative case study methods. MAIN RESEARCH VARIABLES: Broad aspects of medical interactions and the patient-provider relationship that may be associated with improved QOL of lesbian and heterosexual patients with cancer. FINDINGS: Data suggested similarities between lesbians and heterosexual women in their overall QOL. However, differences did emerge between the groups. Lesbians reported higher stress associated with diagnosis, lower satisfaction with care received from physicians, and a trend toward lower satisfaction with the availability of emotional support. CONCLUSIONS: Study findings have important implications for future research on adjustment and coping among lesbian patients with breast cancer and for the improvement of their mental and physical healthcare services. IMPLICATIONS FOR NURSING: Study findings may help improve healthcare services for lesbians with cancer.

Adaptation, Psychological↗

Using the Canadian Code of Ethics for Registered Nurses to explore ethics in palliative care research.

Nursing research in palliative care raises specific and challenging ethical issues. Questions have arisen about whether such research is morally justified, given the low likelihood of direct benefit to dying patients as research participants. The Canadian Code of Ethics for Registered Nurses outlines eight primary values intended to guide nursing practice. We use these values to explore the moral dimensions of research with the palliative care population. Our conclusion is that palliative care research is needed to foster excellent care for these patients and their families, but that nurses must remain constantly vigilant to ensure that participants are protected from resultant harms. Through this exploration we highlight particular considerations that nurse researchers must contemplate when accessing a vulnerable population.

Canada↗

Exploring nursing values in the development of a nurse-led service.

This article considers the development of nurse-led services as a part of a pilot study and explores the therapeutic nature of the role of the nurse. In particular it suggests a need for reconsideration of the fundamental values of nurse-led care in the context of changing organizational culture. Within the UK there has been pressure from policy makers to extend the role of the specialist nurse and create new nursing roles, shifting the boundaries between professional health groups. The philosophy of nurse-led initiatives has therefore been driven mainly from a service redesign and clinical need standpoint rather than necessarily focusing on enhancing patients' experience and the changes in organizational culture required to achieve this. While several studies have focused on the safety, comparative cost and comparative patient outcomes in nurse-led care in relation to traditional or doctor-led care, little attention has been given to the changing organizational values underlying the nursing role. Exploring this context is essential if new nursing roles are to provide more than relief for bottlenecks in the system and also meet their potential for providing patient centred and innovative models of care.

Ethics, Nursing↗

Exploring issues of quality of service in a Next Generation Internet testbed: a case study using PathMaster.

This case study describes a project that explores issues of quality of service (QoS) relevant to the next-generation Internet (NGI), using the PathMaster application in a testbed environment. PathMaster is a prototype computer system that analyzes digitized cell images from cytology specimens and compares those images against an image database, returning a ranked set of "similar" cell images from the database. To perform NGI testbed evaluations, we used a cluster of nine parallel computation workstations configured as three subclusters using Cisco routers. This architecture provides a local "simulated Internet" in which we explored the following QoS strategies: (1) first-in-first-out queuing, (2) priority queuing, (3) weighted fair queuing, (4) weighted random early detection, and (5) traffic shaping. The study describes the results of using these strategies with a distributed version of the PathMaster system in the presence of different amounts of competing network traffic and discusses certain of the issues that arise. The goal of the study is to help introduce NGI QoS issues to the Medical Informatics community and to use the PathMaster NGI testbed to illustrate concretely certain of the QoS issues that arise.

Cell Biology↗

Curiosity and exploration: facilitating positive subjective experiences and personal growth opportunities.

In an effort to expand research on curiosity, we elaborate on a theoretical model that informs research on the design of a new measure and the nomological network of curiosity. Curiosity was conceptualized as a positive emotional-motivational system associated with the recognition, pursuit, and self-regulation of novelty and challenge. Using 5 independent samples, we developed the Curiosity and Exploration Inventory (CEI) comprising 2 dimensions: exploration (appetitive strivings for novelty and challenge) and absorption (full engagement in specific activities). The CEI has good psychometric properties, is relatively unaffected by socially desirable responding, is relatively independent from positive affect, and has a nomological network consistent with our theoretical framework. Predicated on our personal growth facilitation model, we discuss the potential role of curiosity in advancing understanding of various psychological phenomena.

Adult↗

Resolution of hemifacial spasm after posterior fossa exploration without vascular decompression.

A 57-year-old woman who had hemifacial spasm on the left side for 5 years underwent exploration of the cerebellopontine angle region for the purpose of microvascular decompression. At operation, however, no artery, vein, or other abnormality was noted at the facial nerve root exit zone. Consequently, the exploration was completed without additional manipulation or the placement of a protective barrier, but the patient awoke from the operation completely free of the spasm. The cause of the hemifacial spasm in this patient could not be explained by the currently predominating vascular compression theory.

Biomechanical Phenomena↗

Image guidance during abdominal exploration for recurrent colorectal cancer.

BACKGROUND: Real-time intraoperative image guidance has been successfully applied to malignancies of the head, neck and central nervous system. Few attempts have been made to apply this technology to gastrointestinal cancers. Our purpose was to determine if a computer-assisted navigation system could be accurately used at the time of abdominal exploration. METHODS: Fourteen patients with resectable recurrent colorectal cancer underwent computer tomography (CT) imaging of the abdomen and pelvis. The CT images were uploaded to a StealthStation (Medtronic, Inc., Minneapolis, MN), a device that tracks the motion of a handheld probe in the operating field and displays its position, in real time, on the uploaded images. Various anatomic points were utilized to match, or register, the patient to the images in the navigation system. After four or more anatomic points were registered, the accuracy of the registration process was computed by the navigation system and reported as the global error. RESULTS: A total of 23 different anatomic structures were used for registration. The median number of points used for registration per patient was 6.5 (range 5-9). The anatomic sites most commonly used were the anterior superior iliac spines, aortic bifurcation, sacral promontory, symphysis pubis, and iliac artery bifurcation. The median global error was 10.0 mm (range 6.7 mm-27.0 mm). CONCLUSION: Computer-assisted navigation systems can be used to accurately deliver image guidance at the time of abdominal exploration. Future work will be directed at determining the value of this technology in the localization and resection of tumors.

Aged↗

Cell behavior and actomyosin organization in Dictyostelium during substrate exploration.

The behavior of individual Dictyostelium amebae was quantitatively analyzed with the computer-assisted "Dynamic Morphology System" (Soll, Voss, Varnum-Finney and Wessels, (1988) J. Cell. Biochem., 37: 177-192.). The same amoebae were then fixed and analyzed for filamentous (F-) actin and myosin (myosin-II, or "conventional" myosin) by fluorescence microscopy using the "agar-overlay method" (Yumura, and Fukui (1985) Nature, 314: 194-196.). This procedure provides a novel description of the behavior and morphometric changes preceding the static analysis of cytoskeletal organization in the same cell. It is demonstrated that when translocating cells make contact with an etched-smooth glass interface, 14% cross the interface, 20% either reverse direction or migrate along the interface, and the remaining 45% stay at the site. Cells contacting the interface from the smooth or etched side show equivalent behavioral responses. Upon contact with the interface, they project numerous lamellipodia and pseudopodia. While the lamellipodial projections exhibit cycles of spreading and retraction, the pseudopodia show lateral scanning motion, analogous to "substrate exploration" in fibroblasts (Albrecht-Buehler (1976) J. Cell Biol., 69: 275-286.). F-actin is localized in the lamellipodia and pseudopodia of amoebae contacting the interface. There is also discernable cortical F-actin, while conventional myosin appears to be excluded from the cortex and dispersed throughout the cytoplasm. The myosin displays a transient filamentous lattice at the base of newly forming lamellipodia. The ultrastructural study suggests that the new lamellipodia are formed on the dorsal surface and subsequently make contact with the substrate, indicating the dorsoventral sequence of polarity of the motile/sensory cellular organs. The present study demonstrates substrate exploration in Dictyostelium amoebae, and suggests its coupling to dynamic reorganization of the actomyosin cytoskeleton. The possible role of single-headed small myosin(s) (myosin-I, or mini-myosin) is discussed.

Actomyosin↗

Penetrating neck wounds: selective exploration.

This study of 223 patients with penetrating neck wounds justifies individualizing surgical treatment. Twenty-four percent was selected for neck surgery. In spite of selective rather than mandatory neck exploration, the mortality rate related to the neck wound in this series was three percent. This compared favorably with the experience of others employing mandatory exploration. There were no deaths in our series attributable to selective observation.

Ataxia↗