Earth is (mostly) flat: Apportionment of the flux of continental sediment over millennial time scales Comment

10.1130/G34846C.1Geology421e316-GLGY

Optimal search strategies for identifying sound clinical prediction studies in EMBASE

BACKGROUND: Clinical prediction guides assist clinicians by pointing to specific elements of the patient's clinical presentation that should be considered when forming a diagnosis, prognosis or judgment regarding treatment outcome. The numbers of validated clinical prediction guides are growing in the medical literature, but their retrieval from large biomedical databases remains problematic and this presents a barrier to their uptake in medical practice. We undertook the systematic development of search strategies ("hedges") for retrieval of empirically tested clinical prediction guides from EMBASE. METHODS: An analytic survey was conducted, testing the retrieval performance of search strategies run in EMBASE against the gold standard of hand searching, using a sample of all 27,769 articles identified in 55 journals for the 2000 publishing year. All articles were categorized as original studies, review articles, general papers, or case reports. The original and review articles were then tagged as 'pass' or 'fail' for methodologic rigor in the areas of clinical prediction guides and other clinical topics. Search terms that depicted clinical prediction guides were selected from a pool of index terms and text words gathered in house and through request to clinicians, librarians and professional searchers. A total of 36,232 search strategies composed of single and multiple term phrases were trialed for retrieval of clinical prediction studies. The sensitivity, specificity, precision, and accuracy of search strategies were calculated to identify which were the best. RESULTS: 163 clinical prediction studies were identified, of which 69 (42.3%) passed criteria for scientific merit. A 3-term strategy optimized sensitivity at 91.3% and specificity at 90.2%. Higher sensitivity (97.1%) was reached with a different 3-term strategy, but with a 16% drop in specificity. The best measure of specificity (98.8%) was found in a 2-term strategy, but with a considerable fall in sensitivity to 60.9%. All single term strategies performed less well than 2- and 3-term strategies. CONCLUSION: The retrieval of sound clinical prediction studies from EMBASE is supported by several search strategies

Validation of the Ottawa Ankle Rules in Iran: A prospective survey

BACKGROUND: Acute ankle injuries are one of the most common reasons for presenting to emergency departments, but only a small percentage of patients – approximately 15% – have clinically significant fractures. However, these patients are almost always referred for radiography. The Ottawa Ankle Rules (OARs) have been designed to reduce the number of unnecessary radiographs ordered for these patients. The objective of this study was to validate the OARs in the Iranian population. METHODS: This prospective survey was done among 200 patients with acute ankle injury from January 2004 to April 2004 in the Akhtar Orthopedics Hospital Emergency Department. Main outcome measures of this survey were: sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios (positive and negative) of the OARs. RESULTS: Sensitivity of the OARs for detecting 37 ankle fractures (23 in the malleolar zone and 14 in the midfoot zone) was 100% for each of the two zones, and 100% for both zones. Specificity of the OARs for detecting fractures was 40.50% for both zones, 40.50% for the malleolar zone, and 56.00% for the midfoot zone. Implementation of the OARs had the potential for reducing radiographs by 33%. CONCLUSION: OARs are very accurate and highly sensitive tools for detecting ankle fractures. Implementation of these rules would lead to significant reduction in the number of radiographs, costs, radiation exposure and waiting times in emergency departments

Evaluation of the safety of C-spine clearance by paramedics: design and methodology

<p>Abstract</p> <p>Background</p> <p>Canadian Emergency Medical Services annually transport 1.3 million patients with potential neck injuries to local emergency departments. Less than 1% of those patients have a c-spine fracture and even less (0.5%) have a spinal cord injury. Most injuries occur before the arrival of paramedics, not during transport to the hospital, yet most patients are transported in ambulances immobilized. They stay fully immobilized until a bed is available, or until physician assessment and/or X-rays are complete. The prolonged immobilization is often unnecessary and adds to the burden of already overtaxed emergency medical services systems and crowded emergency departments.</p> <p>Methods/Design</p> <p>The goal of this study is to evaluate the safety and potential impact of an active strategy that allows paramedics to assess very low-risk trauma patients using a validated clinical decision rule, the Canadian C-Spine Rule, in order to determine the need for immobilization during transport to the emergency department.</p> <p>This cohort study will be conducted in Ottawa, Canada with one emergency medical service. Paramedics with this service participated in an earlier validation study of the Canadian C-Spine Rule. Three thousand consecutive, alert, stable adult trauma patients with a potential c-spine injury will be enrolled in the study and evaluated using the Canadian C-Spine Rule to determine the need for immobilization. The outcomes that will be assessed include measures of safety (numbers of missed fractures and serious adverse outcomes), measures of clinical impact (proportion of patients transported without immobilization, key time intervals) and performance of the Rule.</p> <p>Discussion</p> <p>Approximately 40% of all very low-risk trauma patients could be transported safely, without c-spine immobilization, if paramedics were empowered to make clinical decisions using the Canadian C-Spine Rule. This safety study is an essential step before allowing all paramedics across Canada to selectively immobilize trauma victims before transport. Once safety and potential impact are established, we intend to implement a multi-centre study to study actual impact.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01188447">NCT01188447</a></p

Anti-proliferative activity of the quassinoid NBT-272 in childhood medulloblastoma cells

BACKGROUND: With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to correlate with anaplasia and unfavorable prognosis. In neuroblastoma – an embryonal tumor with biological similarities to MB – the quassinoid NBT-272 has been demonstrated to inhibit cellular proliferation and to down-regulate c-MYC protein expression. METHODS: To study MB cell responses to NBT-272 and their dependence on the level of c-MYC expression, DAOY (wild-type, empty vector transfected or c-MYC transfected), D341 (c-MYC amplification) and D425 (c-MYC amplification) human MB cells were used. The cells were treated with different concentrations of NBT-272 and the impact on cell proliferation, apoptosis and c-MYC expression was analyzed. RESULTS: NBT-272 treatment resulted in a dose-dependent inhibition of cellular proliferation (IC50 in the range of 1.7 – 9.6 ng/ml) and in a dose-dependent increase in apoptotic cell death in all human MB cell lines tested. Treatment with NBT-272 resulted in up to 90% down-regulation of c-MYC protein, as demonstrated by Western blot analysis, and in a significant inhibition of c-MYC binding activity. Anti-proliferative effects were slightly more prominent in D341 and D425 human MB cells with c-MYC amplification and slightly more pronounced in c-MYC over-expressing DAOY cells compared to DAOY wild-type cells. Moreover, treatment of synchronized cells by NBT-272 induced a marked cell arrest at the G1/S boundary. CONCLUSION: In human MB cells, NBT-272 treatment inhibits cellular proliferation at nanomolar concentrations, blocks cell cycle progression, induces apoptosis, and down-regulates the expression of the oncogene c-MYC. Thus, NBT-272 may represent a novel drug candidate to inhibit proliferation of human MB cells in vivo

Therapy Insight: Parenteral Estrogen treatment for Prostate Cancer—a new dawn for an old therapy

Oral estrogens were the treatment of choice for carcinoma of the prostate for over four decades, but were abandoned because of an excess of cardiovascular and thromboembolic toxicity. It is now recognized that most of this toxicity is related to the first pass portal circulation, which upregulates the hepatic metabolism of hormones, lipids and coagulation proteins. Most of this toxicity can be avoided by parenteral (intramuscular or transdermal) estrogen administration, which avoids hepatic enzyme induction. It also seems that a short-term but modest increase in cardiovascular morbidity (but not mortality) is compensated for by a long-term cardioprotective benefit, which accrues progressively as vascular remodeling develops over time. Parenteral estrogen therapy has the advantage of giving protection against the effects of andropause (similar to the female menopause), which are induced by conventional androgen suppression and include osteoporotic fracture, hot flashes, asthenia and cognitive dysfunction. In addition, parenteral estrogen therapy is significantly cheaper than contemporary endocrine therapy, with substantive economic implications for health providers

Patient-Reported Measures for Person-Centered Coordinated Care: A Comparative Domain Map and Web-Based Compendium for Supporting Policy Development and Implementation

BACKGROUND: Patient-reported measure (PRM) questionnaires were originally used in research to measure outcomes of intervention studies. They have now evolved into a diverse family of tools measuring a range of constructs including quality of life and experiences of care. Current health and social care policy increasingly advocates their use for embedding the patient voice into service redesign through new models of care such as person-centered coordinated care (P3C). If chosen carefully and used efficiently, these tools can help improve care delivery through a variety of novel ways, including system-level feedback for health care management and commissioning. Support and guidance on how to use these tools would be critical to achieve these goals. OBJECTIVE: The objective of this study was to develop evidence-based guidance and support for the use of P3C-PRMs in health and social care policy through identification of PRMs that can be used to enhance the development of P3C, mapping P3C-PRMs against an existing model of domains of P3C, and integration and organization of the information in a user-friendly Web-based database. METHODS: A pragmatic approach was used for the systematic identification of candidate P3C-PRMs, which aimed at balancing comprehensiveness and feasibility. This utilized a number of resources, including existing compendiums, peer-reviewed and gray literature (using a flexible search strategy), and stakeholder engagement (which included guidance for relevant clinical areas). A subset of those candidate measures (meeting prespecified eligibility criteria) was then mapped against a theoretical model of P3C, facilitating classification of the construct being measured and the subsequent generation of shortlists for generic P3C measures, specific aspects of P3C (eg, communication or decision making), and condition-specific measures (eg, diabetes, cancer) in priority areas, as highlighted by stakeholders. RESULTS: In total, 328 P3C-PRMs were identified, which were used to populate a freely available Web-based database. Of these, 63 P3C-PRMs met the eligibility criteria for shortlisting and were classified according to their measurement constructs and mapped against the theoretical P3C model. We identified tools with the best coverage of P3C, thereby providing evidence of their content validity as outcome measures for new models of care. Transitions and medications were 2 areas currently poorly covered by existing measures. All the information is currently available at a user-friendly web-based portal (p3c.org.uk), which includes all relevant information on each measure, such as the constructs targeted and links to relevant literature, in addition to shortlists according to relevant constructs. CONCLUSIONS: A detailed compendium of P3C-PRMs has been developed using a pragmatic systematic approach supported by stakeholder engagement. Our user-friendly suite of tools is designed to act as a portal to the world of PRMs for P3C, and have utility for a broad audience, including (but not limited to) health care commissioners, managers, and researchers.BACKGROUND: Patient-reported measure (PRM) questionnaires were originally used in research to measure outcomes of intervention studies. They have now evolved into a diverse family of tools measuring a range of constructs including quality of life and experiences of care. Current health and social care policy increasingly advocates their use for embedding the patient voice into service redesign through new models of care such as person-centered coordinated care (P3C). If chosen carefully and used efficiently, these tools can help improve care delivery through a variety of novel ways, including system-level feedback for health care management and commissioning. Support and guidance on how to use these tools would be critical to achieve these goals. OBJECTIVE: The objective of this study was to develop evidence-based guidance and support for the use of P3C-PRMs in health and social care policy through identification of PRMs that can be used to enhance the development of P3C, mapping P3C-PRMs against an existing model of domains of P3C, and integration and organization of the information in a user-friendly Web-based database. METHODS: A pragmatic approach was used for the systematic identification of candidate P3C-PRMs, which aimed at balancing comprehensiveness and feasibility. This utilized a number of resources, including existing compendiums, peer-reviewed and gray literature (using a flexible search strategy), and stakeholder engagement (which included guidance for relevant clinical areas). A subset of those candidate measures (meeting prespecified eligibility criteria) was then mapped against a theoretical model of P3C, facilitating classification of the construct being measured and the subsequent generation of shortlists for generic P3C measures, specific aspects of P3C (eg, communication or decision making), and condition-specific measures (eg, diabetes, cancer) in priority areas, as highlighted by stakeholders. RESULTS: In total, 328 P3C-PRMs were identified, which were used to populate a freely available Web-based database. Of these, 63 P3C-PRMs met the eligibility criteria for shortlisting and were classified according to their measurement constructs and mapped against the theoretical P3C model. We identified tools with the best coverage of P3C, thereby providing evidence of their content validity as outcome measures for new models of care. Transitions and medications were 2 areas currently poorly covered by existing measures. All the information is currently available at a user-friendly web-based portal (p3c.org.uk), which includes all relevant information on each measure, such as the constructs targeted and links to relevant literature, in addition to shortlists according to relevant constructs. CONCLUSIONS: A detailed compendium of P3C-PRMs has been developed using a pragmatic systematic approach supported by stakeholder engagement. Our user-friendly suite of tools is designed to act as a portal to the world of PRMs for P3C, and have utility for a broad audience, including (but not limited to) health care commissioners, managers, and researchers

The Whereabouts of an Ancient Wanderer: Global Phylogeography of the Solitary Ascidian Styela plicata

Genetic tools have greatly aided in tracing the sources and colonization history of introduced species. However, recurrent introductions and repeated shuffling of populations may have blurred some of the genetic signals left by ancient introductions. Styela plicata is a solitary ascidian distributed worldwide. Although its origin remains unclear, this species is believed to have spread worldwide by travelling on ship's hulls. The goals of this study were to infer the genetic structure and global phylogeography of S. plicata and to look for present-day and historical genetic patterns. Two genetic markers were used: a fragment of the mitochondrial gene Cytochrome Oxidase subunit I (COI) and a fragment of the nuclear gene Adenine Nucleotide Transporter/ADP-ATP Translocase (ANT). A total of 368 individuals for COI and 315 for ANT were sequenced from 17 locations worldwide. The levels of gene diversity were moderate for COI to high for ANT. The Mediterranean populations showed the least diversity and allelic richness for both markers, while the Indian, Atlantic and Pacific Oceans had the highest gene and nucleotide diversities. Network and phylogenetic analyses with COI and ANT revealed two groups of alleles separated by 15 and 4 mutational steps, respectively. The existence of different lineages suggested an ancient population split. However, the geographic distributions of these groups did not show any consistent pattern, indicating different phylogeographic histories for each gene. Genetic divergence was significant for many population-pairs irrespective of the geographic distance among them. Stochastic introduction events are reflected in the uneven distribution of COI and ANT allele frequencies and groups among many populations. Our results confirmed that S. plicata has been present in all studied oceans for a long time, and that recurrent colonization events and occasional shuffling among populations have determined the actual genetic structure of this species