Miracle-dz/UniFAR-FTUs huggingface dataset:
QALYs: some challenges.

In the preceding article, Weinstein et al. [1] explain the QALYconcept, its methods, and their underlying assumptions. Anumber of interesting themes for discussion arise from thisfactual presentation. We restrict ourselves to addressing fourissues that we deem particularly challenging.As a general background for our selection of issues, we reit-erate a basic point about valuation perspectives: StandardQALYs are meant to express the personal utility of health out-comes as judged ex ante and “on average” by the general publicfrom behind a veil of ignorance about future health (so-called“decision utility”). Standard QALYs thus express value in termsof ex ante self-interest. There are, however, possible alternatives.First, health state utilities may in principle be elicited ex postrather than ex ante, i.e., from people who have or have had directexperience with the health states that are the object of the valu-ation (so-called “experienced utility”). Second, QALYs may beconstructed to express society’s valuation of health outcomeswhen not only self-interest but also concerns for fairness aretaken into account. The choice of approach depends on thequestion one wishes to answer, and the choice of health statevaluation techniques depends on the choice of perspective.The issues we address in the following reﬂect the aboveplurality in possible valuation perspectives and are in part inde-pendent of each other. One issue is intermethod variation in theestimation of ex ante health state utilities. A second is the exist-ence of unwillingness to trade lifetime in elicitations of experi-enced utility. A third is the discrepancy between aggregateindividual utility of health programs on the one hand and, on theother hand, societal valuations that include concerns for fairness.A fourth is a hitherto much overlooked distinction betweenhealthy individuals’ valuations of states of illness (which
Enhancement of Adenovirus-Mediated Gene Delivery to Rheumatoid Arthritis Synoviocytes and Synovium by Fiber Modifications: Role of Arginine-Glycine-Aspartic Acid (RGD)- and Non-RGD-Binding Integrins1

Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) do not express the coxsackie-adenovirus (Ad) receptor and are poorly permissive to Ad serotype 5 (Ad5). Genetically modified, coxsackie-Ad receptor-independent Ad5 vectors were studied for gene delivery in human RA FLS and synovium explants and murine collagen-induced arthritis. Short-fiber Ad5 vectors with seven fiber shaft repeats Ad5GFP-R7-knob, Ad5GFP-R7-arginine-glycine-aspartic acid (RGD) (RGD-liganded), and Ad5GFPΔknob (knob-deleted) were compared with Ad5GFP-FiWT, a conventional wild-type (WT) Ad5 vector. Gene transfer by Ad5GFP-R7-knob and Ad5GFP-R7-RGD was 40- to 50-fold and 25-fold higher, respectively, than Ad5GFP-FiWT in FLS. Ad5GFPΔknob was more efficacious than its knob-bearing version Ad5GFP-R7-knob in FLS transduction. Virus attachment and entry required RGD- and LDV-binding integrins including αv, αvβ3, avβ5, and β1. Ad5GFP-R7-knob infection of FLS was partially neutralized by synovial fluid (SF), but remained 30- to 40-fold higher than Ad5GFP-FiWT in the presence of SF. Ad5GFPΔknob was partially neutralized by SF at low virus input, but escaped viral neutralization by SF at higher virus input. Gene transfer to human synovium ex vivo explants and murine collagen-induced arthritis in vivo was also more efficient with short fiber-modified vectors (with and without the knob domain) than Ad5GFPFiWT. Gene transfer by short fiber-modified vectors was enhanced by inflammatory cytokines in vitro and in the presence of inflammation in murine synovium in vivo. Our data indicated that the highly efficient gene delivery RA was mediated by RGD- and non-RGD-binding integrins and enhanced by inflammation. Short fiber modifications with knob ablation may be a strategy to enhance gene delivery, reducing vector dose and vector-induced inflammation and toxicity.
Protein microarrays: high-throughput tools for proteomics

Protein microarrays are versatile tools for parallel, miniaturized screening of binding events involving large numbers of immobilized proteins in a time- and cost-effective manner. They are increasingly applied for high-throughput protein analyses in many research areas, such as protein interactions, expression profiling and target discovery. While conventionally made by the spotting of purified proteins, recent advances in technology have made it possible to produce protein microarrays through in situ cell-free synthesis directly from corresponding DNA arrays. This article reviews recent developments in the generation of protein microarrays and their applications in proteomics and diagnostics.
Optimal timing of surgical decompression in acute spinal cord injury

Objective: To evaluate the clinical evidence and determine recommendations regarding the optimal timing of decompression surgery following acute cervical spinal cord injury. Methods: A MEDLINE search of the English literature was performed using the search terms spinal cord injury, SCI, quadriplegia and paraplegia, which were paired with the terms surgery, decompression, and timing. To focus on the most recent and relevant evidence, only articles published in the last 15 years were considered for review. Results: Recent studies classifying early decompression surgery as outcomes. However, studies where the decompression surgery occurred resulted in significant improvement. Conclusion: There is a benefit to performing decompression surgery in concerted efforts to operate within eight hours of injury are needed to further advance our understanding of the optimal timing for decompression surgery.
A Study of the Impact of Organizational Learning on Information System Effectiveness

Past studies on system effectiveness capture the underlying factors (top management support, communication effectiveness, firm size, and user training) as well as different dimensions (system quality, information quality, use, user satisfaction, individual impact, and organizational impact) necessary to evaluate the effectiveness of a system. Although the framework of system effectiveness from DeLone and McLean [1992, 2003] is well established, some recent studies on organizational learning (OL), which is a more intrinsic concept, drive us to revisit the issue of system effectiveness. With a strong learning culture, companies can face the challenges of new things. It is hypothesized that an organization with good learning orientation will facilitate the implementation and use of a new system. A survey was conducted among those firms implementing an electronic document management system (EDMS). It is found that management support is still the most important factor and may improve an organization's performance in different ways. Other than that, organizational learning does impact the performance of employees and their satisfaction with new technology implementation. Its influence on EDMS effectiveness is stronger on employees than on the organization.
Quality of warfarin control affects the incidence of stroke in elderly patients with atrial fibrillation.

OBJECTIVE Adjusted-dose warfarin therapy can prevent stroke in patients with atrial fibrillation. However, the quality of the warfarin control may be considered to be important for elderly patients. methods: We followed 188 patients (age > or =70 years) with atrial fibrillation (warfarin, 120 patients; non-warfarin, 68 patients) for 2 years. Their warfarin control was assessed by time in therapeutic range (TTR) for an international normalized ratio of prothrombin time of 1.6-2.6, based on the Japanese guidelines of anticoagulation for elderly patients with atrial fibrillation. RESULTS Stroke occurred in 23 patients (12.2%). In warfarin-treated patients, receiver-operator characteristic (ROC) curves suggested that patients with TTR >68% had anticoagulation benefit. In the ROC curves for prediction of stroke, the area under the curve of TTR was 0.709 (95% confidence interval, 0.585 to 0.834; p=0.02). The sensitivity and specificity of TTR < or =68% were 91.7% and 54.0%, respectively. Kaplan-Meier curves showed that the event-free ratio of stroke was significantly higher in patients who achieved this cut-off of TTR. CONCLUSION The results suggest that the quality of warfarin control is directly associated with the incidence of stroke in elderly patients.
Resistance to influenza virus infection of Mx transgenic mice expressing Mx protein under the control of two constitutive promoters

Transgenic mice constitutively expressing in the brain the influenza virus resistance protein Mx1 controlled by the HMG (3-hydroxy-3-methylglutaryl coenzyme A reductase) promoter showed specific resistance against the neurotropic influenza A virus strain NWS. Control mice of the A2G strain express Mx1 protein in all organs, but only after induction by interferon type I upon or without viral infection. The extent of specific resistance in transgenic mice of the best-expressing line reached about two-thirds that of controls, most likely because of considerably less total-body Mx protein activity in the transgenic mice. Thus, the theoretical advantage in these mice of the continuous presence of Mx protein with early inhibitory potential to viral replication was apparently offset by restricted organ expression. Strong evidence that the Mx1 protein on its own is a specific anti-influenza A virus agent and that its efficiency in the experimental setting is independent of interferon actions could be derived from the treatment of experimental and control mice with anti-interferon antibodies at the time of virus tests. Whereas in A2G mice, Mx1 mRNA and Mx1 protein synthesis were abolished and viral resistance was markedly reduced or abolished, resistance in the transgenic mice persisted to almost the same degree. Transgenic mice generated with a mouse albumin/Mx1 cDNA construct showed liver-specific expression. However, in two expressing transgenic lines, Mx1 protein synthesis was suppressed after a few months. The mechanism of suppression could not be elucidated, but increasing methylation of the transgene's coding region was not the cause. It is possible that continuous Mx1 protein expression in the liver is less well tolerated than that in the brain. Whether this partial suppression and, with the HMG promoter, restricted organ expression are the organism's responses to interference of Mx1 with normal cellular activities such as nucleocytoplasmic transport of RNA and proteins cannot be determined until the molecular mechanisms of antiviral activity of Mx1 protein are understood.
Trust in product review blogs: the influence of self-disclosure and popularity

Many modern consumers use blogs as important information sources, which they evaluate on the basis of blog-specific cues. Using the theory of self-disclosure, this study posits that bloggers' product evaluation self-disclosures, social self-disclosures, and blog popularity are key determinants of readers' cognitive and affective trust. Readers' trust in turn should affect their product attitudes and feedback intentions towards the blog. With a survey study involving seven blog articles about dining experience and a structural equation model, this research confirms the positive influences of product evaluation self-disclosures and popularity on readers' cognitive trust and of social self-disclosures on readers' affective trust. Both cognitive and affective forms of trust enhance product attitudes. Affective trust also increases readers' feedback intentions towards the blog. With these findings, this study offers suggestions for bloggers and companies that use blogs as marketing tools.
Clinical review 156: Recombinant human thyrotropin and thyroid cancer management.

The initial use of exogenous TSH to augment radioiodine uptake in thyroid cancer patients, using extracts from bovine pituitary glands, occurred over 50 yr ago (1–3). This ap-proach fell out of favor due to the frequent development of neutralizing antibodies (4) and allergic reactions with subsequent exposures (5). The availability of bovine TSH ceased in the mid-1980s, resulting in the routine use of thyroid hormone withdrawal to stimulate radioiodine uptake in thyroid cancer patients between 1985 and 2000. Pioneering work from the laboratories of Weintraub and colleagues (6) and Kourides and colleagues (7) in the late 1980s provided the primary sequence of the (cid:1) -subunit of human TSH. The human pituitary (cid:2) -glycoprotein subunit and the human TSH (cid:1) -subunit were then separately cloned and coexpressed in human embryonal cells with the recovery of recombinant human TSH (rhTSH) from the culture me-dium (8). Purified rhTSH was first shown to have biological activity in rat FRTL-5 cells by Thotakura et al. (9). Bioactivity was then documented in human fetal thyroid cells (10) and in rhesus monkeys (11). Early studies demonstrated that compared with TSH extracted from human pituitaries, rhTSH produced in Chinese hamster ovary cells had higher levels of sialic acid, lower binding affinity for porcine TSH receptors, reduced potency to stimulate cAMP in mamma-lian thyroid membranes, and slower metabolic clearance. Most of these differences were eliminated by enzymatic de-sialylation (9). The process of rhTSH production was mod-ified and scaled up in Chinese hamster ovary cells with the assistance of scientists at Genzyme Genetics (Framingham, MA) with the
Soluble tumor necrosis factor receptor p55 predicts cytokinemia and systemic inflammatory response after cardiopulmonary bypass

ObjectivesTo examine the behavior of soluble tumor necrosis factor (TNF) receptors in circulation before and after cardiopulmonary bypass and the relationship to the development of cytokinemia and acute complications comprising systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). The predictive value of soluble TNF receptor is assessed herein. DesignProspective study comparing prebypass and postbypass levels in patients with and without complications indicative of SIRS and MODS. SettingCardiac surgical intensive care unit in a tertiary care hospital. PatientsA total of 20 pediatric patients who underwent cardiopulmonary bypass during open heart surgery. InterventionsBlood samples were collected from catheters before and 2 hrs and 24 hrs after the onset of bypass. Measurements and Main ResultsWe measured plasma levels of soluble TNF receptors by using enzyme-linked immunosorbent assay in 20 patients before and after cardiopulmonary bypass. Clinical data, including duration of bypass and tests or signs indicative of SIRS/MODS, were collected. Soluble TNF receptor I (p55 sR), significantly increased (2241 ± 312 pg/mL) at 2 hrs after bypass (p < .0005) and remained elevated (2826 ± 695 pg/mL) at 1 day after bypass (p < .005) when compared with prebypass levels (725 ± 130 pg/mL). Patients with the acute complications of SIRS/MODS had a higher ratio of postbypass to prebypass p55 sR levels (5.0-fold, p < .001) when compared with patients with no SIRS/MODS (1.75-fold). Remarkably, before surgery, levels of TNF p55 sR predict both cytokinemia (r = .67 to .73, p < .05) and SIRS/MODS (p < .01). The prebypass levels of TNF p55 sR were consistently higher (range, 1000–1400 pg/mL) in patients who subsequently developed SIRS/MODS than the levels (range, 400–570 pg/mL) in patients who did not develop SIRS/MODS. Hypotension, respiratory dysfunctions, and coagulopathy were particularly more prevailing (p < .005) among the complications that were associated with high prebypass levels of TNF p55 sR. ConclusionsSoluble TNF receptor p55 can be employed as a predictive marker for cytokinemia and the development of SIRS/MODS that may arise from a major insult to the body such as cardiopulmonary bypass.
VOLATILE CONSTITUENTS FROM THE FLOWERS OF TWO SPECIES OF HONEYSUCKLE ( LONICERA JAPONICA AND LONICERA CAPRIFOLIUM )

The aim of this paper was to evaluate the chemical composition of volatile oil isolated from the flowers of Lonicera japonica and Lonicera caprifolium cultivated in Romania. One oil sample from Lonicera caprifolium and two oil samples from Lonicera japonica obtained by hidrodistillation were analysed by gas chromatography mass spectrometry (GC-MS). The main compounds found belong to sesquiterpene hydrocarbons (germacrene D 11.26 33.09%) and sesquiterpene alcohols (farnesol 26.16 50.98%, nerolidol 1.28 2.63%, α-cadinol 0.68 2.86%). The monoterpene alcohol linalool was identified in our samples from 1.93% in Lonicera caprifolium oil to 11.64% in Lonicera japonica oil. Other quantitatively important compounds were the esters: 3-hexenyl tiglate 2.62 6.79%, 3-hexenyl benzoate 0.57 5.24%, farnesyl acetate 0.11 5.23%. Cis-jasmone was detected in reduced, but apreciable quantities (0.58 0.85%) in oil samples from Lonicera japonica.
Effects of dietary fiber levels on cecal microbiota composition in geese

Objective This study shows the effects of dietary fiber levels on cecal microbiota composition in geese at day 70 according to pyrosequencing of the 16S ribosomal RNA gene. Methods A total of 468 1-day-old healthy male Yangzhou goslings with similar body weight were randomly divided into 3 groups with 6 replicates per group and 26 geese per replicate. Geese were fed diets with fiber levels of 2.5% (low fiber level diet, Group I) and 6.1% (Group III) during days 1–70, respectively, or 4.3% for days 1–28 and 6.1% for days 29–70 (Group II). Results Low fiber level diet decreased body weight, average daily gain during, increased lower feed conversation rate of geese during day 1 to 70 (p<0.05). Low fiber level diet decreased the total operational taxonomic units, Chao1 index and Shannon index, whereas increased the Simpson index of cecal microbiota in geese at day 70. Low fiber level diet decreased the relative abundance of Bacteroidetes, Firmicutes, Bacteroides, and Paraprevotella in cecum of geese at day 70. The similarity of cecal microbiota between low fiber level diet group and other groups was smaller. Conclusion This study indicates that the low fiber level diet decreased diversity of microbiota, and relative abundance of some beneficial microbiota in cecum of geese at day 70, implying that the low fiber level diet has negative influence on performance by altering the diversity and population of cecal microbiota in geese.
Expression of Nucleoprotein Gene of CTN Strain Rabies Virus from China in E. coli with Antigenicity

The nucleoprotein (NP) gene of rabies CTN strain isolated from China was recombined into pMal-c2x. The antigenicity of the recombined MBP-NP fusion proteins was examined by western blotting and by enzyme linked immunosorbent assay (ELISA). The results demonstrated that the recombined protein possesses predominant antigenicity.
Morphological, physiological and biochemical responses of different plant species to Cd stress

Naturally plants exposed with many adverse environmental conditions like biotic and a biotic stress. Despite all others stresses heavy metal stress is one of great importance which has a notable adverse effects on crop productivity and growth, heavy metal stress triggers different responses in plants, ranging from biochemical responses to crop yield. Understanding the biochemical and molecular responses to Cd stress is essential for a holistic opinion of plant resistance mechanisms to heavy metal stress. This review illustrates some aspects of Cd stress that make changes in morphological, physiological and biochemical changes of plants. Cd stress gradually declines photosynthetic rate due to limited access of CO2 which decrease gas exchange results triggers in reduction of plant growth and productivity. It also reduce leaf size, stems extension and root proliferation and decrease water absorption and transportation by causing turgor loss through decreasing the cell wall elasticity. Exposure to Cd stress increase reactive oxygen species (ROS) production which is harmful for the cell components and toxicity of cadmium is responsible for alterations in the antioxidant systems and increase of lipid peroxidation can be strongly limited at both production and consumption level by increasing antioxidative systems. This review focuses on the ability and strategies of higher plants to respond adapt and overcome the Cd stress.
When does the K4‐free process stop?

The K4‐free process starts with the empty graph on n vertices and at each step adds a new edge chosen uniformly at random from all remaining edges that do not complete a copy of K4. Let G be the random maximal K4‐free graph obtained at the end of the process. We show that for some positive constant C, with high probability as n→∞ , the maximum degree in G is at most Cn3/5logn5 . This resolves a conjecture of Bohman and Keevash for the K4‐free process and improves on previous bounds obtained by Bollobás and Riordan and by Osthus and Taraz. Combined with results of Bohman and Keevash this shows that with high probability G has Θ(n8/5logn5) edges and is ‘nearly regular’, i.e., every vertex has degree Θ(n3/5logn5) . This answers a question of Erdős, Suen and Winkler for the K4‐free process. We furthermore deduce an additional structural property: we show that whp the independence number of G is at least Ω(n2/5(logn)4/5/loglogn) , which matches an upper bound obtained by Bohman up to a factor of Θ(loglogn) . Our analysis of the K4‐free process also yields a new result in Ramsey theory: for a special case of a well‐studied function introduced by Erdős and Rogers we slightly improve the best known upper bound.Copyright © 2012 Wiley Periodicals, Inc. Random Struct. Alg. , 44, 355‐397, 2014
Pharmacological profile of BMS 180,291: a potent, long-acting, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist.

180,291 1S-(1 alpha, 2 alpha, 3 alpha, 4 alpha)-2-[[3-[4- [(pentylamino)carbonyl]-2-oxazolyl]-7-oxabicyclo[2.2. 1]hept- 2- yl]methyl]benzenepropanoic acid (BMS) is a potent and highly selective antagonist of thromboxane A2/prostaglandin endoperoxide (TP) receptors. In human platelet-rich plasma, BMS 180,291 inhibited platelet aggregation induced by arachidonate (800 microM) and U-46,619 (10 microM) with respective IC50 values of 7 +/- 1 (S.E.M.) and 21 +/- 2 nM. Inhibition of both the rate and full extent of 11,9-epoxymethano-prostaglandin H2 (U-46,619)-induced platelet aggregation were insurmountable at antagonist concentrations > 10 nM, but BMS 180,291 antagonized U-46,619-induced platelet shape change competitively with a KB of 11 +/- 2 nM. BMS 180,291 concentrations < or = 1 mM did not inhibit platelet aggregation induced by high concentrations of ADP (20 microM) or human alpha-thrombin (1 U/ml). BMS 180,291 inhibited binding of [3H]1S-[1 alpha,2 alpha(5Z),3 alpha,4 alpha]-7-[3-[[2- [(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2. 1]-hept-2- yl]-5-heptenoic acid to human platelet membranes with a kd of 4.0 +/- 1.0 nM and slope factor of 1.06 +/- 0.13. U-46,619-induced concentrations of rat aortae were competitively antagonized by BMS 180,291 with a KB of 0.6 +/- 0.1 nM. Aortic responses to norepinephrine, serotonin and angiotensin II were not inhibited by BMS 180,291 at 1 microM. U-46,619-induced contractions of guinea pig tracheal rings were antagonized in an almost all-or-none manner, with maximal blockade at > or = 1 nM BMS 180,291, but little effect at lower concentrations. (ABSTRACT TRUNCATED AT 250 WORDS)