Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics of CAMPATH-1H in BMT patients.

BACKGROUND CAMPATH-1 (CD52)Abs are used in stem-cell transplantation for prevention of GvHD and rejection. The humanized Ab CAMPATH1H has recently replaced the rat Ab CAMPATH-1G. There was a concern whether it might have a longer half-life in vivo and, possibly, cause prolonged immunosuppression post-transplant. METHODS Serum samples were collected pre- and post-transplant from patients receiving CAMPATH-1H at 10 mg/day according to two protocols: (A) from Day -5 to Day +4 (total dose, 100 mg), (B) from Day -10 to Day -6 (total dose, 50 mg). The Ab concentrations were measured using an immunofluorescence assay. RESULTS Lymphocytes were substantially depleted by the second day of treatment and were below 0.1 x 10(9)/L by the day of transplant and for at least 1 month post-transplant. By Day 90 there was a greater recovery in Group B, to a median of 0.32 x 10(9)/L compared with 0.25 x 10(9)/L in Group A. By Day 180, both groups had recovered to approx 0.52 x 10(9)/L. Serum concentrations of CAMPATH-1H on the day of transplant were well above the level necessary for opsonization of lymphocytes. The peak Ab concentration was 6.1 micro g/mL in Group A and 2.5 micro g/mL in Group B. CAMPATH-1H could be detected in Group A for 23 days post-transplant, significantly longer than in Group B (11 days). The terminal half-life in the two groups was similar (range 15-21 days) and contrasts with the half-life of < 1 day previously estimated for CAMPATH-1G. There were no cases of graft failure and the incidence of GvHD was similar in the two groups. DISCUSSION The humanized Ab CAMPATH-1H appears to persist in the circulation for longer than the original rat Ab CAMPATH-1G. This might contribute to delayed lymphocyte recovery and prohibit the use of early donor-lymphocyte infusions. A short course of treatment given early pre-transplant is likely to be preferable to the extended course given both pre- and post-transplant.
Macrophage ADAM17 Deficiency Augments CD36-Dependent Apoptotic Cell Uptake and the Linked Anti-Inflammatory Phenotype

Rationale: Apoptotic cell phagocytosis (efferocytosis) is mediated by specific receptors and is essential for resolution of inflammation. In chronic inflammation, apoptotic cell clearance is dysfunctional and soluble levels of several apoptotic cell receptors are elevated. Reports have identified proteolytic cleavage as a mechanism capable of releasing soluble apoptotic cell receptors, but the functional implications of their proteolysis are unclear. Objective: To test the hypothesis that ADAM17-mediated cleavage of apoptotic cell receptors limits efferocytosis in vivo. Methods and Results: In vivo comparison of macrophage efferocytosis in wild-type and Adam17-null hematopoietic chimeras demonstrates that ADAM17 deficiency leads to a 60% increase in efferocytosis and an enhanced anti-inflammatory phenotype in a model of peritonitis. In vitro uptake of phosphatidylserine liposomes identifies the dual-pass apoptotic cell receptor CD36 as a major contributor to enhanced efferocytosis, and CD36 surface levels are elevated on macrophages from Adam17-null mice. Further, temporal elevation of CD36 expression with inflammation may also contribute to its impact. Soluble CD36 from macrophage-conditioned media comprises 2 species based on Western blotting, and mass spectrometry identifies 3 N-terminal peptides that represent probable cleavage sites. Levels of soluble CD36 are decreased in Adam17-null conditioned media, providing evidence for involvement of ADAM17 in CD36 cleavage. Importantly, enhanced efferocytosis in vivo by macrophages lacking ADAM17 is CD36 dependent and accelerates macrophage clearance from the peritoneum, thus promoting resolution of inflammation and highlighting the impact of increased apoptotic cell uptake. Conclusions: Our studies demonstrate the importance of ADAM17-mediated proteolysis for in vivo efferocytosis regulation and suggest a possible mechanistic link between chronic inflammation and defective efferocytosis.
Compact Loaded PIFA for Multifrequency Applications

A new multifrequency microstrip patch antenna is presented. The antenna can be considered a PIFA since it has a metallic wall on one of its sides. The different bands of operation are independent of each other, and different radiation patterns for each band can be achieved if desired. In addition, a circuital model is introduced to explain the operation of the antenna. This model presents some similarities with composite right left handed models presented in the literature. Some prototypes have been manufactured and measurements of return losses, efficiencies and radiation patterns, have been performed for a thorough characterization of the antenna as well as to validate the simulation results.
Treatment and screening of hypothyroidism in pregnancy: results of a European survey.

BACKGROUND Maternal hypothyroidism in pregnancy is associated with several adverse outcomes. The Endocrine Society Guidelines for the management of thyroid diseases in pregnancy were published in 2007; however, impact of the guidelines in routine clinical practice is unknown. Therefore, we have carried out a survey of members of the European Thyroid Association (ETA) to study current practices relating to the management of hypothyroidism in pregnancy. SUBJECTS AND METHODS In December 2010, we emailed an electronic questionnaire survey based on clinical case scenarios to 605 members of the ETA. Responses from 190 clinician members (from 28 European countries) were analyzed. RESULTS For a pregnant woman with newly diagnosed overt hypothyroidism, most responders initiated a full dose of l-thyroxine (l-T(4)). For a woman with hypothyroidism planning pregnancy, 50% recommended increasing the dose of l-T(4) as soon as pregnancy is confirmed, whilst 43% favored testing thyroid function before adjusting the dose. Responders used diverse combinations of tests to monitor the dose of l-T(4). The target of thyroid function tests that responders aimed to achieve with l-T(4) was also inconsistent. Forty-two percent responders or their institutions screened all pregnant women for thyroid dysfunction, 43% performed targeted screening of only the high-risk group, whilst 17% did not carry out systemic screening. Timing of the screening, tests used, and criteria for starting treatment and monitoring were variable. CONCLUSIONS There is wide variation in the clinical practice relating to the treatment and screening of hypothyroidism during pregnancy in Europe.
Retention of Adult Patients on Antiretroviral Therapy in Low- and Middle-Income Countries: Systematic Review and Meta-analysis 2008–2013

Background:We previously published systematic reviews of retention in care after antiretroviral therapy initiation among general adult populations in sub-Saharan Africa. We estimated 36-month retention at 73% for publications from 2007 to 2010. This report extends the review to cover 2008–2013 and expands it to all low- and middle-income countries. Methods:We searched PubMed, Embase, Cochrane Register, and ISI Web of Science from January 1, 2008, to December 31, 2013, and abstracts from AIDS and IAS from 2008–2013. We estimated retention across cohorts using simple averages and interpolated missing times through the last time reported. We estimated all-cause attrition (death, loss to follow-up) for patients receiving first-line antiretroviral therapy in routine settings in low- and middle-income countries. Results:We found 123 articles and abstracts reporting retention for 154 patient cohorts and 1,554,773 patients in 42 countries. Overall, 43% of all patients not retained were known to have died. Unweighted averages of reported retention were 78%, 71%, and 69% at 12, 24, and 36 months, after treatment initiation, respectively. We estimated 36-month retention at 65% in Africa, 80% in Asia, and 64% in Latin America and the Caribbean. From lifetable analysis, we estimated retention at 12, 24, 36, 48, and 60 months at 83%, 74%, 68%, 64%, and 60%, respectively. Conclusions:Retention at 36 months on treatment averages 65%–70%. There are several important gaps in the evidence base, which could be filled by further research, especially in terms of geographic coverage and duration of follow-up.
Innovative performance with interactions between technological proximity and geographic proximity: evidence from China electronics patents

ABSTRACT A lot of researches have shown that geographic proximity and technological proximity influence firms’ innovative performance. Little work has been done to explore how technological proximity interacts with geographic proximity. Using the theories of recombinant innovation and economic geography, this study develops and tests a theory of how firms’ abilities to reap local benefits and generate innovation are influenced by technological features. Data on technological and geographic proximity of the top 100 firms in China’s electronics industry from 1985 to 2012 are used to test the hypotheses. This study shows that, for a firm with high geographic proximity or located in a dense area of R&D, a low technological proximity in the industry facilitates the process of recombinant innovation.
Activation of human monocyte chemiluminescence response by acylpoly(1,3)galactosides derived from Klebsiella pneumoniae

The stimulating activity of several preparations isolated from a membrane proteoglycan of a nonen‐ capsulated smooth strain of Klebsiella pneumoniae (Kp‐ MPG) on the oxidative burst of human blood monocytes was assessed by luminol‐enhanced chemiluminescence (CL). Five Kp derivatives were studied: a 34‐kd acyl‐ poly(l,3)galactoside (APG), obtained by drastic alkaline hydrolysis and purified by chromatography; an APG preparation subjected to acid hydrolysis that removed the core part and all fatty acids, leaving intact the galactose chain of APG (GC‐APG); an APG preparation subjected to mild oxidation (ox APG); a preparation obtained by mild alkaline hydrolysis of Kp‐MPG, containing additional ester‐linked C14 and C16 fatty acids bound to the APG molecule (EFA‐APG); and a polymer of the latter compound, APG pol. EFA‐APG directly stimulated monocyte CL, whereas Kp‐MPG, APG pol, and the whole bacterial cells had little or no activity. APG itself and ox APG induced a weaker response than EFA‐APG. Polymyxin B sulfate completely inhibited the CL response to bacterial lipopolysaccharide (LPS) but not to EFA‐APG. The stimulating action of EFA‐APG on blood monocytes was dependent on the extracellular levels of both calcium and magnesium. Preincubation of monocytes with monoclonal antibody anti‐Mac‐1 directed against CDllb, the αchain of complement receptor type 3 (CR3; CDllb/CD18), strongly inhibited CL activation by EFA‐APG and to a lesser extent CL activation by un‐ opsonized zymosan and rough LPS. Altogether, these findings provide indirect evidence for the contribution of the CDllb/CD18 integrin in the functional interaction of EFA‐APG with monocyte membranes. They demonstrate the role of fatty acids in the triggering of monocyte oxidative burst, while the polysaccharide chain itself does not contribute to induction of the CL response in this model. In keeping with the effects of EFA‐APG and APG, we show that the monocyte CL response was triggered by bacterial LPS from the rough strain of Salmonella minnesota Re 595 and its lipid A, but not by LPS from smooth strains, again suggesting a critical role for the lipid moiety.
Osteopontin Expression in Cardiovascular Diseases a

Adhesive interactions are recognized requirements for cellular proliferation, migration and differentiation during normal morphogenesis as well as disease. By differential cloning, osteopontin was identified as an adhesive protein upregulated during vascular remodeling and neointima formation in both rat models and human vascular diseases including atherosclerosis and restenosis. In functional studies, purified osteopontin promoted adhesion, focal contact formation, and migration of vascular smooth muscle and endothelial cells. Utilizing neutralizing antibodies, three integrin-type receptors, alpha v beta 3, alpha v beta 1, and alpha v beta 5 were found to support cellular adhesion to osteopontin. In contrast, only cells containing the alpha v beta 3 integrin could migrate towards an osteopontin gradient, demonstrating for the first time that different functions of osteopontin are mediated via distinct receptors. These results suggest a model whereby osteopontin, via its integrin-type receptors, contributes to vascular remodeling during development and disease by facilitating smooth muscle migration and simultaneously promoting endothelial coverage of the affected area.
The effects of direction similarity in visual working memory: Behavioural and event-related potential studies

Object similarity can improve visual working memory (VWM) performance in the change-detection task, but impair the recognition performance when it occurs at retrieval of VWM in the recognition task. The effect of direction similarity is an issue that has not been well resolved. Furthermore, electrophysiological evidence in support of the mechanisms that underlie the effects of similarity is still scarce. In the current study, we conducted three behavioural experiments to examine the effects of direction similarity on memory performance with regard to both the encoding and retrieval phases of VWM and one event-related potential (ERP) experiment to explore the neural signatures of direction similarity in VWM. Our behavioural studies indicated that direction similarity improved performance when it occurred at the encoding phase but impaired performance when it occurred at the retrieval phase. Moreover, the ERP experiment showed that the amplitude of the contralateral delay activity (CDA) increased with the increasing set size for similar but not dissimilar directions. In addition, the CDA amplitude for similar directions was lower than that for dissimilar directions at set size 2. Taken together, these findings suggest that direction similarity at encoding has a positive effect on VWM performance and at retrieval has a negative effect. Given that VWM capacity depends on information load and the number of objects, the positive effect of similarity may be attributed to reduced information load of memory objects.
[Effects of Tai Chi on fall risk factors: a meta-analysis].

PURPOSE This study was done to analyze the effects of Tai Chi on fall-related risk factors through meta-analysis of randomized clinical trials published in English and Korean between 2000 and 2010. METHODS Using health related database and hand search of references and Google, 28 randomized studies were collected from doctoral dissertation and published peer reviewed articles. The Comprehensive Meta-analysis version 2.0 was used for the analysis. RESULTS The effect sizes for Tai Chi for 3 months were significant with ES=0.54 for static balance, ES=0.24 for dynamic balance, ES=0.69 for balance measured by scale, and ES=0.40 for flexibility, ES=0.48 for muscle strength, ES=0.71 for ADL, and ES=0.37 for fear of falling. Also, the effect sizes of Tai Chi for 6 months were significant for most fall-related variables. The 6 month data for flexibility was not analyzed since only one study was published. CONCLUSION The analysis of studies of randomized clinical trials indicate that Tai Chi is effective in improving balance, flexibility, muscle strength, activities of daily living, and fear of falling when applied for 3 or 6 months. The findings provide the objective evidence to apply Tai Chi as a fall preventive intervention.
Deployment-related mental disorders among Canadian Forces personnel deployed in support of the mission in Afghanistan, 2001–2008

Background: The conflict in Afghanistan has exposed more Canadian Forces personnel to a greater degree of adversity than at any time in recent memory. We determined the incidence of Afghanistan deployment–related mental disorders and associated risk factors among personnel previously deployed in support of this mission. Methods: The study population consisted of 30 513 Canadian Forces personnel who began a deployment in support of the mission in Afghanistan before Jan. 1, 2009. The primary outcome was a mental disorder perceived by a Canadian Forces clinician to be related to the Afghanistan deployment. Data on diagnoses and perceptions were abstracted from medical records of a stratified random sample of 2014 personnel. Sample design weights were used in all analyses to generate descriptive statistics for the entire study population. Results: Over a median follow-up of 1364 days, 13.5% (95% confidence interval [CI] 12.1%–14.8%) of the study population had a mental disorder that was attributed to the Afghanistan deployment. Posttraumatic stress disorder was the most common diagnosis (in 8.0%, 95% CI 7.0%–9.0%, of personnel). Deployment to higher-threat locations, service in the Canadian Army and lower rank were independent risk factors associated with an Afghanistan-related diagnosis (e.g., hazard ratio for deployment to Kandahar Province 5.6, 95% CI 2.6–12.5, relative to deployment to the United Arab Emirates). In contrast, sex, Reserve Forces status, multiple deployments and deployment length were not independent risk factors. Interpretation: An important minority of Canadian Forces personnel deployed in support of the Afghanistan mission had a diagnosis of a mental disorder perceived to be related to the deployment. Determining long-term outcomes is an important next step.
Effect of climatic factors on cash crop farming in India: an application of Cobb-Douglas production function model.

Research studies conducted hitherto have shown that climatic factors are changing at global level. Most of the studies have arrived at that climatic factors have a significant influence on cropped area, production and yield of crops in farming. In India, few studies have estimated the association of climatic and non-climatic factors with cropped area, production and yield during different stages of crop growth. Therefore, the present study assesses the influence of climatic factors on cropped area, production and yield of major cash crops in India. Moreover, it estimates the projected production, yield and cropped area of crops using marginal impact analysis technique. Cobb-Douglas production function model has been applied to state-wise panel data for the period 1971-2013. Empirical results of the study show that cropped area of groundnut and sesame crops have decreased by 13.87% and 23.50% respectively. Production of groundnut and cotton crops have also come down by 9.83% and 41.09% respectively; and yield of potato, groundnut, sesame and cotton crops have subsided by 3.71%, 10.31%, 4.51% and 7.20% respectively due to 1% increase in climatic variables. Consequently, climate change has resulted in reduction in farmer's income, job opportunities for rural labourers and raw materials for agro-based industries in India. It provides several policy suggestions to mitigate the adverse effect of climate change on crop farming.
Infliximab or Cyclosporine as Rescue Therapy in Hospitalized Patients with Steroid‐Refractory Ulcerative Colitis: A Retrospective Observational Study

Background: Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid‐refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives. Methods: Outcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid‐refractory moderate to severe UC: 1) a Swedish‐Danish cohort (n = 49) treated with a single infusion of IFX; 2) an Austrian cohort (n = 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy‐free survival at 3 and 12 months. Kaplan–Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy. Results: At 15 days, colectomy‐free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX‐treated patients of 11.2 (95% confidence interval [CI] 2.4–53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1–8.2, P = 0.030) at 12 months in comparison with CsA‐treated patients. There were no opportunistic infections or mortality. Conclusions: Colectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months' follow‐up. The superiority of CsA was seen principally during the first 15 days. (Inflamm Bowel Dis 2011;)
Quantifying Macroeconomic Expectations in Stock Markets Using Google Trends

Among other macroeconomic indicators, the monthly release of U.S. unemployment rate figures in the Employment Situation report by the U.S. Bureau of Labour Statistics gets a lot of media attention and strongly affects the stock markets. I investigate whether a profitable investment strategy can be constructed by predicting the likely changes in U.S. unemployment before the official news release using Google query volumes for related search terms. I find that massive new data sources of human interaction with the Internet not only improves U.S. unemployment rate predictability, but can also enhance market timing of trading strategies when considered jointly with macroeconomic data. My results illustrate the potential of combining extensive behavioural data sets with economic data to anticipate investor expectations and stock market moves.
NF-κB Signaling Regulates Functional Expression of the MHC Class I-Related Neonatal Fc Receptor for IgG via Intronic Binding Sequences1

The neonatal Fc receptor for IgG (FcRn) functions to transport maternal IgG to a fetus or newborn and to protect IgG from degradation. Although FcRn is expressed in a variety of tissues and cell types, the extent to which FcRn expression is regulated by immunological and inflammatory events remains unknown. Stimulation of intestinal epithelial cell lines, macrophage-like THP-1, and freshly isolated human monocytes with the cytokine TNF-α rapidly up-regulated FcRn gene expression. In addition, the TLR ligands LPS and CpG oligodeoxynucleotide enhanced the level of FcRn expression in THP-1 and monocytes. Treatment of TNF-stimulated THP-1 cells with the NF-κB-specific inhibitor or overexpression of a dominant negative mutant inhibitory NF-κB (IκBα; S32A/S36A) resulted in down-regulation of FcRn expression. By using chromatin immunoprecipitation we identified three NF-κB binding sequences within introns 2 and 4 of the human FcRn gene. An EMSA confirmed the p50/p50 and/or p65/p50 complex (s) bound to intron 2- or 4-derived oligonucleotides containing putative NF-κB binding sequences, respectively. The intronic NF-κB sequences in combination with the promoter or alone regulated the expression of a luciferase reporter gene in response to TNF-α stimulation or overexpression of NF-κB p65 and p50. DNA looping interactions potentially occurred after the stimulation between intronic NF-κB sequences and the FcRn promoter as shown by a chromosome conformation capture assay. Finally, TNF-α stimulations enhanced IgG transport across an intestinal Caco-2 epithelial monolayer. Together, these data provide the first evidence that NF-κB signaling via intronic sequences regulates FcRn expression and function.