Predicting Successful Tapering of Biologic Therapy for Patients with Rheumatoid Arthritis in Remission – Why are we still using clinical remission criteria to inform decisions?

Remission is the optimum treatment target for patients with rheumatoid arthritis. With the advent of biologic therapies, and the use of treat to target strategies, many more patients are achieving remission. Once a patient has achieved a period of sustained remission, there is little to guide subsequent management and patients usually continue treatment long-term. This may be inappropriate. Recent evidence suggests that some patients may be able to reduce or even stop therapy however, the ideal patient profile is yet to be determined. Potential predictors have been identified, however have not entered routine clinical practice. There is a need for robust biomarkers to facilitate the prediction of successful tapering

Acute stress response in gilthead sea bream (Sparus aurata L.) is time-of-day dependent: Physiological and oxidative stress indicators

Since fish show daily rhythms in most physiological functions, it should not be surprising that stressors may have different effects depending on the timing of exposure. In this study, we investigated the influence of time of day on the stress responses, at both physiological and cellular levels, in gilthead sea bream (Sparus aurataL.) submitted to air exposure for 30 s and then returned to their tank. One hour after air exposure, blood, hypothalamus and liver samples were taken. Six fish per experimental group (control and stressed) were sampled every 4 h during a 24-h cycle. Fish were fed in the middle of the light cycle (ML) and locomotor activity rhythms were recorded using infrared photocells to determine their daily activity pattern of behaviour, which showed a peak around feeding time in all fish. In the control group, cortisol levels did not show daily rhythmicity, whereas in the stressed fish, a daily rhythm of plasma cortisol was observed, being the average values higher than in the control group, with increased differences during the dark phase. Blood glucose showed daily rhythmicity in the control group but not in the stressed one which also showed higher values at all sampling points. In the hypothalamus of control fish, a daily rhythm ofcorticotropin-releasing hormone(crh) gene expression was observed, with the acrophase at the beginning of the light phase. However, in the stressed fish, this rhythm was abolished. The expression ofcrh-binding protein(crhbp) showed a peak at the end of the dark phase in the control group, whereas in the stressed sea bream, this peak was found at ML. Regarding hepatic gene expression of oxidative stress biomarkers: (i)cytochrome c oxidase 4showed daily rhythmicity in both control and stressed fish, with the acrophases located around ML, (ii)peroxiredoxin(prdx) 3 and5(prdx5) only presented daily rhythmicity of expression in the stressed fish, with the acrophase located at the beginning of the light cycle and (iii)uncoupling protein 1showed significant differences between sampling points only in the control group, with significantly higher expression at the beginning of the dark phase. Taken together, these results indicate that stress response in gilthead sea bream is time-dependent as cortisol level rose higher at night, and that different rhythmic mechanisms interplay in the control of neuroendocrine and cellular stress responses

Major depression, fibromyalgia and labour force participation: A population-based cross-sectional study

BACKGROUND: Previous studies have documented an elevated frequency of depressive symptoms and disorders in fibromyalgia, but have not examined the association between this comorbidity and occupational status. The purpose of this study was to describe these epidemiological associations using a national probability sample. METHODS: Data from iteration 1.1 of the Canadian Community Health Survey (CCHS) were used. The CCHS 1.1 was a large-scale national general health survey. The prevalence of major depression in subjects reporting that they had been diagnosed with fibromyalgia by a health professional was estimated, and then stratified by demographic variables. Logistic regression models predicting labour force participation were also examined. RESULTS: The annual prevalence of major depression was three times higher in subjects with fibromyalgia: 22.2% (95% CI 19.4 – 24.9), than in those without this condition: 7.2% (95% CI 7.0 – 7.4). The association persisted despite stratification for demographic variables. Logistic regression models predicting labour force participation indicated that both conditions had an independent (negative) effect on labour force participation. CONCLUSION: Fibromyalgia and major depression commonly co-occur and may be related to each other at a pathophysiological level. However, each syndrome is independently and negatively associated with labour force participation. A strength of this study is that it was conducted in a large probability sample from the general population. The main limitations are its cross-sectional nature, and its reliance on self-reported diagnoses of fibromyalgia

A randomized controlled trial investigation of a non-stimulant in attention deficit hyperactivity disorder (ACTION): Rationale and design

<p>Abstract</p> <p>Background</p> <p>The ACTION study (<it>Attention deficit hyperactivity disorder Controlled Trial Investigation Of a Non-stimulant) </it>is a multi-center, double-blind, randomized cross-over trial of the non-stimulant medication, Atomoxetine, in children and adolescents with attention deficit hyperactivity disorder (ADHD). The primary aims are to examine the efficacy of atomoxetine for improving cognition and emotional function in ADHD and whether any improvements in these outcomes are more pronounced in participants with comorbid anxiety; and to determine if changes in these outcomes after atomoxetine are more reliable than changes in diagnostic symptoms of ADHD. This manuscript will describe the methodology and rationale for the ACTION study.</p> <p>Methods</p> <p>Children and adolescents aged 6 - 17 y with ADHD will be enrolled. Clinical interview and validated scales will be used to confirm diagnosis and screen for exclusion criteria, which include concurrent stimulant use, and comorbid psychiatric or neurological conditions other than anxiety. Three assessment sessions will be conducted over the 13-week study period: Session 1 (Baseline, pre-treatment), Session 2 (six weeks, atomoxetine or placebo), and Session 3 (13 weeks, cross-over after one-week washout period). The standardized touch-screen battery, "IntegNeuro™", will be used to assess cognitive and emotional function. The primary measure of response will be symptom ratings, while quality of life will be a secondary outcome. Logistic regression will be used to determine predictors of treatment response, while repeated measures of analysis will determine any differences in effect of atomoxetine and placebo.</p> <p>Results</p> <p>The methodology for the ACTION study has been detailed.</p> <p>Conclusions</p> <p>The ACTION study is the first controlled trial to investigate the efficacy of atomoxetine using objective cognitive and emotional function markers, and whether these objective measures predict outcomes with atomoxetine in ADHD with and without comorbid anxiety. First enrollment was in March 2008. The outcomes of this study will be a significant step towards a 'personalized medicine' (and therefore a more efficient) approach to ADHD treatment.</p> <p>Trial registration</p> <p>Australian and New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ANZCTRN12607000535471.aspx">ANZCTRN12607000535471</a>.</p

Iron and phosphorus co-limit nitrogen fixation in the eastern tropical North Atlantic

The role of iron in enhancing phytoplankton productivity in high nutrient, low chlorophyll oceanic regions was demonstrated first through iron-addition bioassay experiments1 and subsequently confirmed by large-scale iron fertilization experiments2. Iron supply has been hypothesized to limit nitrogen fixation and hence oceanic primary productivity on geological timescales3, providing an alternative to phosphorus as the ultimate limiting nutrient4. Oceanographic observations have been interpreted both to confirm and refute this hypothesis5, 6, but direct experimental evidence is lacking7. We conducted experiments to test this hypothesis during the Meteor 55 cruise to the tropical North Atlantic. This region is rich in diazotrophs8 and strongly impacted by Saharan dust input9. Here we show that community primary productivity was nitrogen-limited, and that nitrogen fixation was co-limited by iron and phosphorus. Saharan dust addition stimulated nitrogen fixation, presumably by supplying both iron and phosphorus10, 11. Our results support the hypothesis that aeolian mineral dust deposition promotes nitrogen fixation in the eastern tropical North Atlantic

Young patients', parents', and survivors' communication preferences in paediatric oncology: Results of online focus groups

Contains fulltext : 51596.pdf ( ) (Open Access)BACKGROUND: Guidelines in paediatric oncology encourage health care providers to share relevant information with young patients and parents to enable their active participation in decision making. It is not clear to what extent this mirrors patients' and parents' preferences. This study investigated communication preferences of childhood cancer patients, parents, and survivors of childhood cancer. METHODS: Communication preferences were examined by means of online focus groups. Seven patients (aged 8-17), 11 parents, and 18 survivors (aged 8-17 at diagnosis) participated. Recruitment took place by consecutive inclusion in two Dutch university oncological wards. Questions concerned preferences regarding interpersonal relationships, information exchange and participation in decision making. RESULTS: Participants expressed detailed and multi-faceted views regarding their needs and preferences in communication in paediatric oncology. They agreed on the importance of several interpersonal and informational aspects of communication, such as honesty, support, and the need to be fully informed. Participants generally preferred a collaborative role in medical decision making. Differences in views were found regarding the desirability of the patient's presence during consultations. Patients differed in their satisfaction with their parents' role as managers of the communication. CONCLUSION: Young patients' preferences mainly concur with current guidelines of providing them with medical information and enabling their participation in medical decision making. Still, some variation in preferences was found, which faces health care providers with the task of balancing between the sometimes conflicting preferences of young cancer patients and their parents

Can Geographical Factors Determine the Choices of Farmers in the Ethiopian Highlands to Trade in Livestock Markets?

Proximity and affiliation to the local market appear to be two of the most relevant factors to explain farmer's choices to select a particular trading point. Physical barriers may limit the options , especially in developing countries. A network of villages linked by traders/farmer-traders sharing livestock markets was built with field data collected in 75 villages from 8 kebelles in the Wassona Werna wereda of the Ethiopian Highlands. Two exponential random graph models were fitted with various geographical and demographic attributes of the nodes (dyadic independent model) and three internal network structures (dyadic dependent model). Several diagnostic methods were applied to assess the goodness of fit of the models. The odds of an edge where the distance to the main market Debre Behran and the difference in altitude between two connected villages are both large increases significantly so that villages far away from the main market and at different altitude are more likely to be linked in the network than randomly. The odds of forming an edge between two villages in Abamote or Gudoberet kebelles are approximately 75% lower than an edge between villages in any other kebelles (p<0.05). The conditional log-odds of two villages forming a tie that is not included in a triangle, a 2-star or a 3-star is extremely low, increasing the odds significantly (p<0.05) each time a node is in a 2-star structure and decreasing it when a node is in a 3-star (p<0.05) or in a triangle formation (p<0.05)), conditional on the rest of the network. Two major constraining factors, namely distance and altitude, are not deterrent for the potential contact of susceptible small ruminant populations in the Highlands of Ethiopia

TgICMAP1 Is a Novel Microtubule Binding Protein in Toxoplasma gondii

The microtubule cytoskeleton provides essential structural support for all eukaryotic cells and can be assembled into various higher order structures that perform drastically different functions. Understanding how microtubule-containing assemblies are built in a spatially and temporally controlled manner is therefore fundamental to understanding cell physiology. Toxoplasma gondii, a protozoan parasite, contains at least five distinct tubulin-containing structures, the spindle pole, centrioles, cortical microtubules, the conoid, and the intra-conoid microtubules. How these five structurally and functionally distinct sets of tubulin containing structures are constructed and maintained in the same cell is an intriguing problem. Previously, we performed a proteomic analysis of the T. gondii apical complex, a cytoskeletal complex located at the apical end of the parasite that is composed of the conoid, three ring-like structures, and the two short intra-conoid microtubules. Here we report the characterization of one of the proteins identified in that analysis, TgICMAP1. We show that TgICMAP1 is a novel microtubule binding protein that can directly bind to microtubules in vitro and stabilizes microtubules when ectopically expressed in mammalian cells. Interestingly, in T. gondii, TgICMAP1 preferentially binds to the intra-conoid microtubules, providing us the first molecular tool to investigate the intra-conoid microtubule assembly process during daughter construction

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres