Miracle-dz/UniFAR-FTUs huggingface dataset:
A latex D-dimer reliably excludes venous thromboembolism.

BACKGROUND D-Dimer, a cross-linked fibrin degradation product, has a high sensitivity in patients with suspected venous thrombosis. Traditional latex D-dimer assays, however, have not been sufficiently sensitive to exclude venous thromboembolism. METHODS To determine the clinical utility of a latex D-dimer assay (MDA D-Dimer; Organon Teknika Corporation, Durham, NC) in patients with suspected venous thromboembolism, we conducted a retrospective cohort study involving 595 unselected patients at 4 tertiary care hospitals. Patients had blood drawn for performance of the D-dimer assay and underwent objective testing for venous thromboembolism. Pretest probability was determined using validated models in 571 patients. Patients were classified as venous thromboembolism positive or negative according to results of objective tests and 3-month follow-up. The sensitivities, specificities, predictive values, and negative likelihood ratios of the assay were calculated for all patients and for subgroups of patients with known cancer or a low, moderate, or high pretest probability of venous thromboembolism. RESULTS The prevalence of venous thromboembolism was 19.0% (113/595). Of those who had a pretest probability assessment, 35.9% had a low pretest probability, 49.7% a moderate pretest probability, and 14.4% a high pretest probability. Using a discriminant value of 0.50 microg fibrinogen equivalent units per milliliter, the assay showed an overall sensitivity of 96%, a negative predictive value of 98%, a specificity of 45%, and a negative likelihood ratio of 0.09. In patients with a low or moderate pretest probability, the sensitivity, negative predictive value, and negative likelihood ratio were 97%, 99%, and 0.07, respectively. CONCLUSIONS The MDA D-Dimer assay is the first latex agglutination assay with sufficient sensitivity to be clinically useful in the exclusion of venous thromboembolism. A negative result has the potential to be used as the sole test to exclude venous thromboembolism in patients with a low or moderate pretest probability of disease.
Promoting health care safety through training high reliability teams

Many organizations have been using teams as a means of achieving organizational outcomes (such as productivity and safety). Research has indicated that teams, especially those operating in complex environments, are not always effective. There is a subset of organizations in which teams operate that are able to balance effectiveness and safety despite the complexities of the environment (for example, aviation, nuclear power). These high reliability organizations (HROs) have begun to be examined as a model for those in other complex domains, such as health care, that strive to reach a status of high reliability. In this paper we analyse the components leading to the effectiveness of HROs by examining the teams that comprise them. We use a systems perspective to uncover the behavioral markers by which high reliability teams (HRTs) are able to uphold the values of their parent organizations, thereby promoting safety. Using these markers, we offer guidelines and developmental strategies that will help the healthcare community to shift more quickly to high reliability status by not focusing solely on the organizational level.
Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure.

BACKGROUND The specific resting metabolic rates (K(i); in kcal · kg(-1 )· d(-1)) of major organs and tissues in adults were suggested by Elia (in Energy metabolism: tissue determinants and cellular corollaries. New York, NY: Raven Press, 1992) to be as follows: 200 for liver, 240 for brain, 440 for heart and kidneys, 13 for skeletal muscle, 4.5 for adipose tissue, and 12 for residual organs and tissues. However, Elia's K(i) values have never been fully evaluated. OBJECTIVES The objectives of the present study were to evaluate the applicability of Elia's K(i) values across adulthood and to explore the potential influence of age on the K(i) values. DESIGN A new approach was developed to evaluate the K(i) values of major organs and tissues on the basis of a mechanistic model: REE = Σ(K(i) × T(i)), where REE is whole-body resting energy expenditure measured by indirect calorimetry, and T(i) is the mass of individual organs and tissues measured by magnetic resonance imaging. With measured REE and T(i), marginal 95% CIs for K(i) values were calculated by stepwise univariate regression analysis. An existing database of nonobese, healthy adults [n = 131; body mass index (in kg/m²) <30] was divided into 3 age groups: 21-30 y (young, n = 43), 31-50 y (middle-age, n = 51), and > 50 y (n = 37). RESULTS Elia's K(i) values were within the range of 95% CIs in the young and middle-age groups. However, Elia's K(i) values were outside the right boundaries of 95% CIs in the >50-y group, which indicated that Elia's study overestimated K(i) values by 3% in this group. Age-adjusted K(i) values for adults aged >50 y were 194 for liver, 233 for brain, 426 for heart and kidneys, 12.6 for skeletal muscle, 4.4 for adipose tissue, and 11.6 for residuals. CONCLUSION The general applicability of Elia's K(i) values was validated across adulthood, although age adjustment is appropriate for specific applications.
Treatment of corneal neovascularization with dietary isoflavonoids and flavonoids.

The purpose of this study was to investigate the use of dietary isoflavonoids and flavonoids for the treatment of ocular neovascularization. Corneal blood vessels were induced by intrastromal implantation of pellets containing bFGF. Isoflavonoids and flavonoids (Genistein, Fisetin and Luteolin) were dissolved in a microemulsion to increase bioavailability and applied topically in concentrations between 0.5 and 1 ng ml(-1). Corneal neovascularization was quantified under the microscope. In comparison to control eyes, all three substances significantly inhibited corneal neovascularization (P < or = 0.05). Fisetin had the strongest effect followed by Genistein and Luteolin. No significant topical side effects were observed. We concluded that the isoflavonoid Genistein and two structurally related flavonoids are potent inhibitors of corneal angiogenesis in vivo. The wide distribution of the flavonoids in the plant kingdom together with the presented results suggests that flavonoids may contribute to the preventive effect of a plant-based diet on neovascular disease of the eye.
Anxiety disorders, major depressive disorder and the dynamic relationship between these conditions: treatment patterns and cost analysis

Abstract Objective: To determine the treatment pattern and impact on healthcare costs of anxiety disorders and major depressive disorder (MDD), and influence of their concomitance and subsequence. Methods: A retrospective cohort study was conducted using a US reimbursement claims database. Adult patients with an incident diagnosis of anxiety or MDD (index date) were included. Their sociodemographic data, diagnoses, healthcare resource use and associated costs were collected over the 6 months preceding and 12 months following index date. Results: A total of 599,624 patients were identified and included. Patients with phobia or post-traumatic stress disorder had the highest 12-month costs ($8,442 and $8,383, respectively). Patients with social anxiety disorder had the lowest costs ($3,772); generalized anxiety disorder ($6,472) incurred costs similar to MDD ($7,170). Costs were substantially increased with emergence of anxiety during follow-up in MDD patients ($10,031) or emergence of MDD in anxiety patients ($9,387). This was not observed in patients with both anxiety and MDD at index date ($6,148). Conclusion: This study confirms the high burden of costs of anxiety, which were within the same range as MDD. Interestingly, the emergence of anxiety or MDD in the year following a first diagnosis of MDD or anxiety, respectively, increased costs substantially. Major limitations were short follow-up and lack of absenteeism costs.
Politics as Usual: The Cyberspace `Revolution′

The Normalization of Cyberspace Democracy in Cyberspace A Brief History Parties and Interest Groups Organizing, Lobbying and Electioneering in Cyberspace Elected Officials and Government Bureaucracy in Cyberspace The Internet, Mass Media and Public Opinion Doing Business on the Web New Rules or New Taxes? Gambling on the Internet A Case Study in the Politics of Regulation Criminal Activity in Cyberspace and What to Do About It Democracy and Cyberspace A Peek into the Future
Learning, Termination, and Payout Policy in Dynamic Incentive Contracts

We study a principal-agent setting in which both sides learn about future profitability from output, and the project can be abandoned/terminated if profitability is too low. With learning, shirking by the agent both reduces output and lowers the principal’s estimate of future profitability. The agent can exploit this belief discrepancy and earn information rents, reducing his incentives to exert effort. The optimal contract controls information rents to improve incentives by distorting the termination decision. Our results capture the transition from a young, financially constrained firm to a mature firm that pays dividends. For young firms, poor performance permanently raises the termination threshold, as doing so lowers information rents. Mature firms pay smoothed dividends and have a fixed termination threshold. Dividend smoothing occurs because earnings surprises are used to adjust financial slack in line with profitability. When profitability only reflects the agent’s private ability, a simple equity contract is optimal.
Does contract farming improve smallholder income? The case of avocado farmers in Kenya

Purpose – Contract farming (CF) is seen as a tool for creating new market opportunities hence increasing incomes for smallholder farmers. Critics, however, argue that CF is likely to pass risks to small scale farmers, thus favouring large scale farmers at the expense of smallholder farmers. The purpose of this paper is to examine the effect of CF on smallholder farmers’ income using a case study of avocado farmers in Kandara district in Kenya. Design/methodology/approach – The study uses data collected from 100 smallholder avocado farmers in Kandara district in Kenya and employs an instrumental variable model (Probit-2SLS) to control for endogeneity in participation in the contract and examine the effect of CF on household, farm and avocado income. Findings – The results indicate that participation in CF is not sufficient to improve household, farm and avocado income. Question remains regarding efficient implementation of CF arrangements to promote spill over effects on other household enterprises. Resear.
Docetaxel for platinum-refractory advanced thymic carcinoma.

OBJECTIVE Thymic carcinoma is a rare mediastinal neoplasm. While platinum-based chemotherapy has been reported to be effective for advanced thymic carcinoma in a first-line setting, little information is available regarding the benefits of salvage chemotherapy for platinum-refractory thymic carcinoma. This study assessed the efficacy and safety profiles of docetaxel monotherapy for platinum-refractory thymic carcinoma. METHODS A total of 13 thymic carcinoma patients treated with docetaxel monotherapy in a second- or later-line setting between January 2003 and April 2014 were retrospectively reviewed. The median age was 61 years (range, 41-75 years). RESULTS The overall response rate and disease control rate were 31% [95% confidence interval (CI), 6-56%] and 77% (95% CI, 54-100%), respectively. The median progression-free survival and overall survival after docetaxel monotherapy were 5.5 months (95% CI, 2.3-6.5 months) and 24.0 months (95% CI, 9.4-31.2 months), respectively. The most common Grade ≥3 toxicity was neutropenia (62%). No incidents of febrile neutropenia and no treatment-related deaths were recorded. CONCLUSIONS This retrospective analysis demonstrated that docetaxel was active against platinum-refractory thymic carcinoma with acceptable toxicities. Docetaxel monotherapy might be a promising therapeutic option for patients with platinum-refractory thymic carcinoma.
Restricted gene flow within and between rapidly diverging Neotropical plant species

Speciation involves the evolution of traits and genetic differences that contribute to reproductive isolation and the cessation of gene flow, and studying closely related species and divergent populations gives insight into how these phenomena proceed. Here, we document patterns of gene flow within and between two members of a rapid Neotropical species radiation, Costus pulverulentus and Costus scaber (Costaceae). These species co‐occur in the tropical rainforest and share pollinators, but are reproductively isolated by a series of prezygotic barriers, some of which show evidence of reinforcement at sympatric sites. Here, we genotype microsatellite markers in plants from eight sites that span the geographical range of both species, including four sympatric sites. We also genotype putative hybrids found at two sympatric sites. We find high levels of genetic isolation among populations within each species and low but detectable levels of introgression between species at sympatric sites. Putative hybrids identified by morphology are consistent with F1 or more advanced hybrids. Our results highlight the effectiveness of prezygotic isolating mechanisms at maintaining species boundaries in young radiations and provide empirical data on levels of gene flow consistent with reinforcement.
Clinicopathological characteristics of surgically resected lung cancer associated with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is well known to be associated with lung cancer. It is important to clarify the clinical and pathological features of lung cancer with IPF in understanding the pathogenesis of lung cancer in IPF patients. We compared clinicopathological factors of lung cancer in patients with and without IPF.
Immune Destruction of Larval Taenia crassiceps in Mice

ABSTRACT Immune destruction of larval Taenia crassiceps was examined by first injecting BALB/cJ mice subcutaneously with larval buds and 30 to 60 days later challenging the mice with larvae injected into the peritoneal cavity. The larvae injected intraperitoneally (i.p.) secondarily are killed by host cells that completely encase the larvae in a thick sheath. The peritoneal exudate cells and the cytokines they produced were characterized by flow cytometry, enzyme-linked immunosorbent assays (ELISAs), and reverse transcription PCR (RT-PCR). No changes in percentage of CD4+ T cells, CD8+ T cells, B1 cells, or macrophages were detected in the peritoneal cavities of mice that were killing larvae compared to mice with a primary 7-day infection i.p. Both RT-PCR and ELISA demonstrated a decrease in cytokines including gamma interferon (IFN-γ), interleukin-4 (IL-4), and IL-10 in mice that were killing the larvae compared to control mice infected for 30 to 60 days i.p. alone, although there was little difference compared to mice infected for 7 days i.p. alone. Serum cytokine levels in mice that were killing the larvae showed a decrease in IFN-γ and IL-4, an increase in IL-10 when compared to mice infected for 30 to 60 days i.p. alone, and increases in all cytokines compared to mice infected for 7 days i.p. alone. Inhibition of nitric oxide production did not significantly affect the number or the viability of larvae in the peritoneal cavity of mice that were killing larvae during secondary infection.
Adjuncts in the IVF laboratory: where is the evidence for ‘add-on’ interventions?

Globally, IVF patients are routinely offered and charged for a selection of adjunct treatments and tests or 'add-ons' that they are told may improve their chance of a live birth, despite there being no clinical evidence supporting the efficacy of the add-on. Any new IVF technology claiming to improve live birth rates (LBR) should, in most cases, first be tested in an appropriate animal model, then in clinical trials, to ensure safety, and finally in a randomized controlled trial (RCT) to provide high-quality evidence that the procedure is safe and effective. Only then should the technique be considered as 'routine' and only when applied to the similar patient population as those studied in the RCT. Even then, further pediatric and long-term follow-up studies will need to be undertaken to examine the long-term safety of the procedure. Alarmingly, there are currently numerous examples where adjunct treatments are used in the absence of evidence-based medicine and often at an additional fee. In some cases, when RCTs have shown the technique to be ineffective, it is eventually withdrawn from the clinic. In this paper, we discuss some of the adjunct treatments currently being offered globally in IVF laboratories, including embryo glue and adherence compounds, sperm DNA fragmentation, time-lapse imaging, preimplantation genetic screening, mitochondria DNA load measurement and assisted hatching. We examine the evidence for their safety and efficacy in increasing LBRs. We conclude that robust studies are needed to confirm the safety and efficacy of any adjunct treatment or test before they are offered routinely to IVF patients.
Universities and economic development in lagging regions: ‘triple helix’ policy in Wales

ABSTRACT Universities and economic development in lagging regions: ‘triple helix’ policy in Wales. Regional Studies. This paper considers the applicability and relevance of triple helix-based policy and theory, in the weaker region context of Wales, where the success of such approaches has been questionable. It calls for a broader appreciation of the roles of universities in weaker regions beyond a narrow ‘third mission’ conceptualization, moving away from a normative application of the triple helix in contexts very different from those in which it was originated. Instead, it supports the broadening of the original theory beyond the three key actors of university, government and business, and an increasing focus on diverse regional settings and spaces.
Efficacy and safety of recombinant human nerve growth factor in patients with diabetic polyneuropathy: A randomized controlled trial. rhNGF Clinical Investigator Group.

CONTEXT Nerve growth factor is a neurotrophic factor that promotes the survival of small fiber sensory neurons and sympathetic neurons in the peripheral nervous system. Recombinant human nerve growth factor (rhNGF) has demonstrated efficacy as treatment for peripheral neuropathy in experimental models and phase 2 clinical trials. OBJECTIVE To evaluate the efficacy and safety of a 12-month regimen of rhNGF in patients with diabetic polyneuropathy. DESIGN Randomized, double-blind, placebo-controlled phase 3 trial conducted from July 1997 through May 1999. SETTING Eighty-four outpatient centers throughout the United States. PATIENTS A total of 1019 men and women aged 18 to 74 years with either type 1 or type 2 diabetes and a sensory polyneuropathy attributable to diabetes. INTERVENTIONS Patients were randomly assigned to receive either rhNGF, 0.1 microg/kg (n = 504), or placebo (n = 515) by subcutaneous injection 3 times per week for 48 weeks. Patients were assessed at baseline, 12 weeks, 24 weeks, and 48 weeks. MAIN OUTCOME MEASURES The primary outcome measure was a change in neuropathy between baseline and week 48, demonstrated by the Neuropathy Impairment Score for the Lower Limbs, compared between the 2 groups. Secondary outcome measures included quantitative sensory tests using the CASE IV System, the Neuropathy Symptom and Change questionnaire, the Patient Benefit Questionnaire (PBQ), and a global symptom assessment, as well as nerve conduction studies and occurrence of new plantar foot ulcers. Patients also were evaluated for presence of adverse events. RESULTS Among patients who received rhNGF, 418 (83%) completed the regimen compared with 461 (90%) who received placebo. Administration of rhNGF was safe, with few adverse events attributed to treatment apart from injection site pain/hyperalgesia and other pain syndromes. However, neither the primary end point (P =.25) nor most of the secondary end points demonstrated a significant benefit of rhNGF. Exceptions were the global symptom assessment (P =.03) and 2 of 32 comparisons within the PBQ, which showed a modest but significant benefit of rhNGF (P =.05 for severity of pain in the legs and P =.003 for 6-month symptoms in the feet and legs). CONCLUSION Unlike previous phase 2 trials, this phase 3 clinical trial failed to demonstrate a significant beneficial effect of rhNGF on diabetic polyneuropathy. JAMA. 2000;284:2215-2221.
Addressing the Most Reliable Edge-Disjoint Paths With a Delay Constraint

Recently, multipath solutions have been proposed to improve the quality-of-service of the source to destination (s,t)-path in communication networks (CNs). This paper de scribes the λDP/DR problem to obtain λ ≥ 1 edge-disjoint (s,t)-paths (λDP) such that its reliability is maximized while keeping its delay no longer than a delay constraint D ≥ 1. This problem is NP-hard, and thus this paper proposes an approximate solution using Lagrange-relaxation. Our algorithm generates λDP with δ(λDP) ≤ D, and reliability bounded by |log(R<sub>min</sub>)| ≤ |log(ρ(λDP))| ≤ (1 + k)*|log(R<sub>min</sub>)|, where R<sub>min</sub> is the minimum reliability of any (s, t)-path in the CN, and k ≥ 1. Our simulations on forty random CNs and large grid networks show that our solution produces λDP with delay and reliability comparable to those obtained by the optimal but exponential time algorithm.
Cyclosporine pharmacokinetics and dose monitoring after lung transplantation: comparison between cystic fibrosis and other conditions

Background. In cystic fibrosis (CF), absorption of cyclosporine A (CsA) through the gastrointestinal tract is often impaired because of fat malabsorption. The aim of this study was to compare the steady-state pharmacokinetics of CsA and the inter- and intrasubject variability of CsA exposure in stable lung transplant recipients with and without CF and to determine the best single-time predictors of the area under the curve (AUC). Methods. Ten lung transplant recipients without CF and 10 lung transplant recipients with CF were studied. All patients received Neoral twice daily. Blood samples were obtained predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h postdose on three separate days within a 5-day period. Results. CsA exposure and pharmacokinetic variables were similar in the two groups, although exposure-per-milligram-per-dose was ∼25% lower in CF patients. Coefficients of intersubject variability were numerically higher in CF patients, but the difference between groups did not reach significance. On the other hand, the maximum concentration (Cmax), the concentration 2 hours after administration (C2), AUC0–12, and AUC0–4 showed a twofold greater intrasubject variability in CF patients. CsA trough concentration did not predict accurately the AUC, but C2 was a good predictor of the AUC0–4 in both CF (r2=0.90) and non-CF (r2=0.78) patients. Conclusion. Compared to patients without CF, patients with CF show a lower bioavailability of CsA and a greater intrasubject variability of Cmax, C2, and AUC. C2 is the best single-point predictor of the AUC0–4 in lung transplant recipients with and without CF.