Lymph node follicles capture and retain antigens to induce germinal centers and long-lived humoral immunity. However, control over antigen retention has been limited. Here we discovered that antigen ...conjugated to nanoparticle carriers of different sizes impacts the intralymph node transport and specific cell interaction. We found that follicular dendritic cell (FDC) networks determine the intralymph node follicle fate of these nanoparticles by clearing smaller ones (5–15 nm) within 48 h and retaining larger ones (50–100 nm) for over 5 weeks. The 50–100 nm-sized nanoparticles had 175-fold more delivery of antigen at the FDC dendrites, 5-fold enhanced humoral immune responses of germinal center B cell formation, and 5-fold more antigen-specific antibody production over 5–15 nm nanoparticles. Our results show that we can tune humoral immunity by simply manipulating the carrier size design to produce effectiveness of vaccines.
Rotavirus is considered a directly transmitted disease due to its high infectivity. Environmental pathways have, therefore, largely been ignored. Rotavirus, however, persists in water sources, and ...both its surface water concentrations and infection incidence vary with temperature. Here, we examine the potential for waterborne rotavirus transmission. We use a mechanistic model that incorporates both direct and waterborne transmission pathways, coupled with a hydrological model, and we simulate rotavirus transmission between two communities with interconnected water sources. To parameterize temperature dependency, we estimated temperature-dependent decay rates in water through a metaanalysis. Our meta-analysis suggests that rotavirus decay rates are positively associated with temperature (n = 39, P < 0.001). This association is stronger at higher temperatures (over 20 °C), consistent with tropical climate conditions. Our model analysis demonstrates that water could disseminate rotavirus between the two communities for all modeled temperatures. While direct transmission was important for disease amplification within communities, waterborne transmission could also amplify transmission. In standing-water systems, the modeled increase in decay led to decreased disease, with every 1 °C increase in temperature leading to up to a 2.4% decrease in incidence. These effect sizes are consistent with prior meta-analyses, suggesting that environmental transmission through water sources may partially explain the observed associations between temperature and rotavirus incidence. Waterborne rotavirus transmission is likely most important in cooler seasons and in communities that use slow-moving or stagnant water sources. Even when indirect transmission through water cannot sustain outbreaks, it can seed outbreaks that are maintained by high direct transmission rates.
Background Consumption of Chinese herbs that contain aristolochic acid (eg, Mu Tong) has been associated with an increased risk of urinary tract cancer. Methods We conducted a population-based ...case–control study in Taiwan to examine the association between prescribed Chinese herbal products that contain aristolochic acid and urinary tract cancer. All patients newly diagnosed with urinary tract cancer (case subjects) from January 1, 2001, to December 31, 2002, and a random sample of the entire insured population from January 1, 1997, to December 31, 2002 (control subjects), were selected from the National Health Insurance reimbursement database. Subjects who were ever prescribed more than 500 pills of nonsteroidal anti-inflammatory drugs and/or acetaminophen were excluded, leaving 4594 case patients and 174 701 control subjects in the final analysis. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multivariable logistic regression models for the association between prescribed Chinese herbs containing aristolochic acid and the occurrence of urinary tract cancer. Models were adjusted for age, sex, residence in a township where black foot disease was endemic (an indicator of chronic arsenic exposure from drinking water a risk factor for urinary tract cancer), and history of chronic urinary tract infection. Statistical tests were two-sided. Results Having been prescribed more than 60 g of Mu Tong and an estimated consumption of more than 150 mg of aristolochic acid were independently associated with an increased risk for urinary tract cancer in multivariable analyses (Mu Tong: at 61–100 g, OR = 1.6, 95% CI = 1.3 to 2.1, and at >200 g, OR = 2.1, 95% CI = 1.3 to 3.4; aristolochic acid: at 151–250 mg, OR = 1.4, 95% CI = 1.1 to 1.8, and at >500 mg, OR = 2.0, 95% CI = 1.4 to 2.9). A statistically significant linear dose–response relationship was observed between the prescribed dose of Mu Tong or the estimated cumulative dose of aristolochic acid and the risk of urinary tract cancer (P < .001 for both). Conclusions Consumption of aristolochic acid–containing Chinese herbal products is associated with an increased risk of cancer of the urinary tract in a dose-dependent manner that is independent of arsenic exposure.
Galanin and galanin receptors (GalRs) have been reported to be involved in the transmission and modulation of nociceptive information in the central nervous system (CNS). However, the underlying ...mechanism of the antinociception of GalRs in neuropathic pain remains unclear. This study investigated the antinociception induced by galanin receptor 1 (GalR1) via protein kinase A (PKA) signaling pathway in the nucleus accumbens (NAc) of rats with neuropathic pain. A mononeuropathy model was replicated by ligation of the left sciatic nerve, following which the expression of phospho-PKA (p-PKA) in the NAc were markedly up-regulated at 14(th) and 28(th) day after ligation of sciatic nerve, and p-PKA expression was down-regulated by intra-NAc injection of GalR1 agonist M617, but the GalR1 antagonist M35 did not have an effect. We also found that M35 in the NAc blocked the M617-induced increase in the hind paw withdrawal latencies (HWLs) of rats with mononeuropathy, but M35 alone had no effect on HWLs, and PKA inhibitor H-89 attenuated the M617-induced an increase in the HWLs. These results suggested that GalR1 induced an antinociception via inhibiting PKA activation, implying that GalR agonists may be potential and potent therapeutic options to treat chronic neuropathic pain.
With possibly incomplete nuclear families, the family based association test (FBAT) method allows one to evaluate any test statistic that can be expressed as the sum of products (covariance) between ...an arbitrary function of an offspring's genotype with an arbitrary function of the offspring's phenotype. We derive expressions needed to calculate the mean and variance of these test statistics under the null hypothesis of no linkage. To give some guidance on using the FBAT method, we present three simple data analysis strategies for different phenotypes: dichotomous (affection status), quantitative and censored (eg, the age of onset). We illustrate the approach by applying it to candidate gene data of the NIMH Alzheimer Disease Initiative. We show that the RC-TDT is equivalent to a special case of the FBAT method. This result allows us to generalise the RC-TDT to dominant, recessive and multi-allelic marker codings. Simulations compare the resulting FBAT tests to the RC-TDT and the S-TDT. The FBAT software is freely available.
Colony-stimulating factor-3 receptor (
)-T618I is a recurrent activating mutation in chronic neutrophilic leukemia (CNL) and to a lesser extent in atypical chronic myeloid leukemia (aCML) resulting ...in constitutive JAK-STAT signaling. We sought to evaluate safety and efficacy of the JAK1/2 inhibitor ruxolitinib in patients with CNL and aCML, irrespective of
mutation status.
We conducted a phase II study of ruxolitinib in 44 patients (21 CNL and 23 aCML). The primary end point was overall hematologic response rate (ORR) by the end of 6 continuous 28-day cycles for the first 25 patients enrolled. We considered a response as either partial (PR) or complete response (CR). We expanded accrual to 44 patients to increase our ability to evaluate secondary end points, including grade ≥ 3 adverse events, spleen volume, symptom assessment, genetic correlates of response, and 2-year survival.
ORR was 32% for the first 25 enrolled patients (8 PR 7 CNL and 1 aCML). In the larger cohort of 44 patients, 35% had a response (11 PR 9 CNL and 2 aCML and 4 CR CNL), and 50% had oncogenic
mutations. The mean absolute allele burden reduction of
-T618I after 6 cycles was greatest in the CR group, compared with the PR and no response groups. The most common cause of death is due to disease progression. Grade ≥ 3 anemia and thrombocytopenia were observed in 34% and 14% of patients, respectively. No serious adverse events attributed to ruxolitinib were observed.
Ruxolitinib was well tolerated and demonstrated an estimated response rate of 32%. Patients with a diagnosis of CNL and/or harboring
-T618I were most likely to respond.
Comparative analysis of RNA sequences is the basis for the detailed and accurate predictions of RNA structure and the determination of phylogenetic relationships for organisms that span the entire ...phylogenetic tree. Underlying these accomplishments are very large, well-organized, and processed collections of RNA sequences. This data, starting with the sequences organized into a database management system and aligned to reveal their higher-order structure, and patterns of conservation and variation for organisms that span the phylogenetic tree, has been collected and analyzed. This type of information can be fundamental for and have an influence on the study of phylogenetic relationships, RNA structure, and the melding of these two fields.
We have prepared a large web site that disseminates our comparative sequence and structure models and data. The four major types of comparative information and systems available for the three ribosomal RNAs (5S, 16S, and 23S rRNA), transfer RNA (tRNA), and two of the catalytic intron RNAs (group I and group II) are: (1) Current Comparative Structure Models; (2) Nucleotide Frequency and Conservation Information; (3) Sequence and Structure Data; and (4) Data Access Systems.
This online RNA sequence and structure information, the result of extensive analysis, interpretation, data collection, and computer program and web development, is accessible at our Comparative RNA Web (CRW) Site http://www.rna.icmb.utexas.edu. In the future, more data and information will be added to these existing categories, new categories will be developed, and additional RNAs will be studied and presented at the CRW Site.
Ehealth is one of the system that use modern technologies that be apply to the healthcare organization. This system allowed the patient to access the system to monitor their health records and else ...by using internet as a platform to communicate. Thus, this project is inspired by Ehealth system to making a hardware device with software application that act as monitoring system to the people. For the hardware, the user only need to grasped the two terminal in the device that contains of all the sensor for doing the testing procedure. Thus, all the data that be contain will be sent to the apps via internet of things for storing them. This will helps physical education and health teacher to do observation and record the data obtain from the apps.Besides, this way also will avoiding any incident to be occur towards the students if they carry on the activities in abnormal condition of their body system. The scope for this project is focusing on monitoring students body condition before they starting their outdoor activities in the field. The way for sensing the parameter including pulse sensor, LM35 and Galvanic Skin Response sensor with arduino as a microcontroller to process the input and output signal.
Both population-based and family-based designs are commonly used in genetic association studies to locate genes that underlie complex diseases. The simplest version of the family-based design--the ...transmission disequilibrium test--is well known, but the numerous extensions that broaden its scope and power are less widely appreciated. Family-based designs have unique advantages over population-based designs, as they are robust against population admixture and stratification, allow both linkage and association to be tested for and offer a solution to the problem of model building. Furthermore, the fact that family-based designs contain both within- and between-family information has substantial benefits in terms of multiple-hypothesis testing, especially in the context of whole-genome association studies.
Abstract
Societal and environmental risks dominated the top 10 risks in both likelihood and impact, according to the surveys conducted by the World Economic Forum. Against this background, there have ...been many cases demonstrating the disastrous financial impact of organisational failure to address societal and environmental risks. As a person whose responsibility is to assess financial risks of the organisation, there is increasing expectation for the Chief Financial Officer (CFO) to lead sustainability strategy and initiatives. This research serves to review the literature which highlights the roles and characteristics of CFOs essential for corporate sustainability. Drawing upon this and related literature examining the influence of CFOs on other accounting practices, it proposes a framework illustrating the potential relationships between CFO characteristics and corporate sustainability.
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