Task-related hemodynamic responses contribute prominently to functional magnetic resonance imaging (fMRI) recordings. They reflect behaviorally important brain states, such as arousal and attention, and can dominate stimulus-evoked responses, yet they remain poorly understood. To help characterize these responses, we present a method for parametrically estimating both stimulus-evoked and task-related components of hemodynamic responses from subjects engaged in temporally predictable tasks. The stimulus-evoked component is modeled by convolving a hemodynamic response function (HRF) kernel with spiking. The task-related component is modeled by convolving a Fourier-series task-related function (TRF) kernel with task timing. We fit this model with simultaneous electrode recordings and intrinsic-signal optical imaging from the primary visual cortex of alert, task-engaged monkeys. With high [Formula: see text], the model returns HRFs that are consistent across experiments and recording sites for a given animal and TRFs that entrain to task timing independent of stimulation or local spiking. When the task schedule conflicts with that of stimulation, the TRF remains locked to the task emphasizing its behavioral origins. The current approach is strikingly more robust to fluctuations than earlier ones and gives consistently, if modestly, better fits. This approach could help parse the distinct components of fMRI recordings made in the context of a task.

Hydroxyl radical footprinting (HRF) of proteins with mass spectrometry (MS) is a widespread approach for assessing protein structure. Hydroxyl radicals react with a wide variety of protein side chains, and the ease with which radicals can be generated (by radiolysis or photolysis) has made the approach popular with many laboratories. As some side chains are less reactive and thus cannot be probed, additional specific and nonspecific labeling reagents have been introduced to extend the approach. At the same time, advances in liquid chromatography and MS approaches permit an examination of the labeling of individual residues, transforming the approach to high resolution. Lastly, advances in understanding of the chemistry of the approach have led to the determination of absolute protein topologies from HRF data. Overall, the technology can provide precise and accurate measures of side-chain solvent accessibility in a wide range of interesting and useful contexts for the study of protein structure and dynamics in both academia and industry. Expected final online publication date for the Annual Review of Biophysics Volume 47 is May 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Plant XPD homolog UVH6 is the protein involved in the repair of strand breaks, and the excision repair and uvh6 mutant is not impaired in transgenerational increase in HRF. While analyzing the transgenerational response to stress in plants, we found that the promoter and gene body of Arabidopsis thaliana (Arabidopsis) XPD homolog UVH6 underwent hypomethylation and showed an increase in the level of transcript. Here, we analyzed the mutant of this gene, uvh6-1, by crossing it to two different reporter lines: one which allows for analysis of homologous recombination frequency (HRF) and another which makes it possible to analyze the frequency of point mutations. We observed that uvh6-1 plants exhibited lower rate of spontaneous homologous recombination but higher frequencies of spontaneous point mutations. The analysis of strand breaks using ROPS and Comet assays showed that the mutant had a much higher level of strand breaks at non-induced conditions. Exposure to stresses such as UVC, heat, cold, flood and drought showed that the mutant was not impaired in an increase in somatic HRF. The analysis of spontaneous HRF in the progeny of control plants compared to that of the progeny of stressed plants demonstrated that uvh6-1 was mildly affected in response to temperature, UV and drought. Our data suggest that UVH6 may be involved in the repair of strand breaks and excision repair, but it is unlikely that UVH6 is required for transgenerational increase in HRF.

Issue addressed Smoking, risky drinking, overweight and obesity, and physical inactivity are health-risk factors (HRFs) that contribute significantly to morbidity worldwide. Several initiatives have been introduced over the past two decades to reduce these HRFs. This paper examines changes in the prevalence of HRFs in young women (aged 18-23 years) between 1996 and 2013, overall and within demographic groups. Methods Data from two cohorts of the Australian Longitudinal Study on Women's Health, born in 1973-78 (n=14247) and 1989-95 (n=17012) were weighted to provide national estimates. Prevalence ratios were used to compare HRFs in 2013 relative to 1996. Results In 1996, 32% were current smokers, 38% were risky drinkers, 22% were overweight or obese and 7% were physically inactive. In 2013, corresponding estimates were 19%, 35%, 33% and 6%. Between 1996 and 2013, overall smoking prevalence decreased, but remained over 43% among least educated women. Overweight and obesity increased in all demographic groups. Conclusions The findings suggest that only smoking, which has been the subject of changes in taxation, legislation and regulation, declined significantly, in all except the least educated women. In contrast, the prevalence of overweight and obesity, which has largely been addressed through awareness campaigns and voluntary actions by the food industry, increased markedly in all demographic sub-groups. So what? The findings show that comprehensive health promotion interventions, such as those for tobacco control, are successful (but may still be ineffective among less educated women). In contrast the measures to control population weight gain among young women have been futile so far.

Background: To evaluate the earliest retinal morphological and functional changes in diabetic eyes without or with early signs of diabetic retinopathy (DR).

Methods: Twenty-two eyes with no DR (noDR group), 22 eyes with mild DR (DR group), and 18 healthy nondiabetic eyes (controls) were enrolled. All eyes were studied by means of spectral domain optical coherence tomography (OCT), OCT angiography (OCTA), and multifocal electroretinogram (mfERG).

Results: A significantly higher number of OCT hyperreflective intraretinal foci (HRF) was found in both noDR and DR groups versus controls, but not between DR groups. The OCTA parameters of the superficial vascular plexus (SVP) were significantly reduced in the noDR group both versus controls and DR group (p < 0.05). The OCTA parameters of the intermediate capillary plexus (ICP) were significantly reduced in the DR group versus controls. An increased number of altered hexagons on mfERG was found in the noDR versus the DR group (p = 0.0192).

Conclusions: Retinal vascular and functional parameters are differently involved in diabetic eyes; major vascular changes in the SVP and functional alterations of the mfERG are present in diabetic eyes with no clinical microvascular signs of DR, while ICP is mainly involved when early ophthalmoscopic signs of DR are present. The integrated use of mfERG and OCTA provides new significant insights into the pathogenesis of diabetic related retinal disease.

Keywords: diabetic retinopathy; early stages; hyperreflective intraretinal spots; microaneurysms; morpho-functional correlation; multifocal electroretinography; optical coherence tomography; optical coherence tomography angiography; retinal layers; vascular plexuses.

Our aim is to determine indicators of survival in children with severe hypoxic respiratory failure (HRF) after transition to high-frequency oscillatory ventilation (HFOV). Single-center retrospective examination of children with HRF transitioned to HFOV. Blood gases and ventilator settings 24 hours prior to and 48 hours after HFOV in survivors and nonsurvivors were evaluated. Sixty-two children with mean age of 7 years and mean weight of 26 kg were included with an observed mortality of 29%. Mean airway pressures (Paw), oxygenation index (OI), arterial oxygen partial pressure (PaO₂)/fraction of inspired oxygen (FiO₂) (P/F) ratio, pH, bicarbonate, and arterial carbon dioxide partial pressure were similar prior to HFOV in survivors and nonsurvivors. During HFOV, mean OI and P/F ratio improved in both groups with an average Paw increase of ∼10 cm H₂O. Survivors had lower OI than nonsurvivors (21 ± 0.9 vs. 26.5 ± 2.2; p < 0.01) beginning 24 hours after HFOV. P/F ratio appears to diverge by 36 hours, with survivors having P/F ratio >200. Survivors had higher pH than nonsurvivors at 36 hours (7.40 ± 0.01 vs. 7.32 ± 0.02; p < 0.05), higher bicarbonate levels (27.1 ± 0.7 vs. 23.9 ± 1.3 mEq/L), and similar arterial carbon dioxide partial pressure with less oscillatory support (i.e., hertz and amplitude). Inhaled nitric oxide was used in 53% of patients with improvements in oxygenation but with no effect on mortality. HFOV improves oxygenation in children with severe HRF. Nonsurvivors can be distinguished from survivors at 24 to 36 hours during HFOV by higher OI, metabolic acidosis, and higher oscillatory support. These data may assist in prognostication or timing of initiating alternative therapies, such as extracorporeal membrane oxygenation.

Optical coherence tomography (OCT) allows us to identify, into retinal layers, new morphological entities, which can be considered clinical biomarkers of retinal diseases. According to the literature, solitary, small (<30 µm), medium level hyperreflective (similar to retinal fiber layer) retinal foci (HRF) may represent aggregates of activated microglial cells and an in vivo biomarker of retinal inflammation. The identification and quantification of this imaging biomarker allows for estimating the level and possibly the amount of intraretinal inflammation in major degenerative retinal disorders, whose inflammatory component has already been demonstrated (diabetic retinopathy, age-related macular degeneration, radiation retinopathy). Currently, diabetic retinopathy (DR) probably represents the best clinical model to apply this analysis in the definition of this clinical biomarker. However, the main limitation to the clinical use of HRF is related to the technical difficulty of counting them: a time-consuming methodology, which also needs trained examiners. To contribute to solve this limitation, we developed and validated a new method for the semi-automatic detection of HRF in OCT scans. OCT scans of patients affected by DR, were analyzed. HRF were manually counted in High Resolution spectral domain OCT images. Then, the same OCT scans underwent semi-automatic HRF counting, using an ImageJ software with four different settings profiles. Statistical analysis showed an excellent intraclass correlation coefficient (ICC) between the manual count and each of the four semi-automated methods. The use of the second setting profile allows to obtain at the Bland-Altman graph a bias of -0.2 foci and a limit of agreement of ±16.3 foci. This validation approach opens the way not only to the reliable and daily clinical applicable quantification of HRF, but also to a better knowledge of the inflammatory component-including its progression and regression changes-of diabetic retinopathy.

Keywords: OCT; automatic detection; biomarker; diabetic retinopathy; hyperreflective retinal foci; inflammation.

OBJECTIVE

Macula segmentation and fovea localization is one of the primary tasks in retinal analysis as they are responsible for detailed vision. Existing approaches required segmentation of retinal structures viz. optic disc and blood vessels for this purpose.

METHODS

This work avoids knowledge of other retinal structures and attempts data mining techniques to segment macula. Unsupervised clustering algorithm is exploited for this purpose. Selection of initial cluster centres has a great impact on performance of clustering algorithms. A heuristic based clustering in which initial centres are selected based on measures defining statistical distribution of data is incorporated in the proposed methodology. The initial phase of proposed framework includes image cropping, green channel extraction, contrast enhancement and application of mathematical closing. Then, the pre-processed image is subjected to heuristic based clustering yielding a binary map. The binary image is post-processed to eliminate unwanted components. Finally, the component which possessed the minimum intensity is finalized as macula and its centre constitutes the fovea.

RESULTS

The proposed approach outperforms existing works by reporting that 100%,of HRF, 100% of DRIVE, 96.92% of DIARETDB0, 97.75% of DIARETDB1, 98.81% of HEI-MED, 90% of STARE and 99.33% of MESSIDOR images satisfy the 1R criterion, a standard adopted for evaluating performance of macula and fovea identification.

CONCLUSIONS

The proposed system thus helps the ophthalmologists in identifying the macula thereby facilitating to identify if any abnormality is present within the macula region.

Background: Radiographic changes after stereotactic body radiation therapy (SBRT) have not been well studied. The purpose of this study was to investigate the computed tomography (CT) appearance pattern of radiation-induced lung injury (RILI) and recurrence after SBRT in patients with early stage non-small cell lung cancer (NSCLC).

Methods: We retrospectively analyzed clinical data of inoperable early stage NSCLC patients undergoing SBRT treatment from February 2012 to June 2018. All patients had undergone serial CT scanning before SBRT and after completion of SBRT. An experienced radiation oncologist and radiologist reviewed all CT images, and identified the RILI and CT high-risk features (HRFs).

Results: A total of 60 patients were enrolled in this study; 55 patients had RILI (91.67%) and 7 patients had local failure. In the early CT findings of observers 1 and 2, there were diffuse ground glass opacities (GGOs) in 3 and 4 patients, diffuse consolidation in 10 and 12 patients, patchy consolidation in 22 and 15 patients, patchy GGOs in 19 and 24 patients, and no changes in 5 and 4 patients, respectively (kappa =0.706). In the late CT findings of observer 1 and 2, there were modified conventional patterns in 37 and 37 patients, mass-like patterns in 10 and 9 patients, scar-like patterns in 7 and 8 patients, and no changes in 5 and 5 patients, respectively (kappa =0.726). In the results of the CT-based HRFs of disease local failure, there were ≥1 HRFs in 7 patients, ≥2 HRFs in 7 patients, ≥3 HRFs in 6 patients, ≥4 HRFs in 5 patients, and ≥5 HRFs in 3 patients, respectively. Patients with only 1 HRF showed high sensitivity (100%) and low specificity (52.80%), with the specificity increasing and the sensitivity decreasing as the number of HRFs increased.

Conclusions: The agreement of the CT appearance on RILI between 2 observers was good. Regular follow-up and attention to HRFs are vital for better identifying RILI and local disease failure.

Keywords: Radiation-induced lung injury (RILI); early stage non-small cell lung cancer; stereotactic body radiation therapy (SBRT); tumor recurrence.

BACKGROUND

Hemodiafiltration (HFR) with on-line regeneration of the ultrafiltrate, a technique of hemodiafiltration in which the ultrafiltrate passes through a cartridge containing uncoated charcoal, has been shown to be safe, simple, and well tolerated and has been claimed to improve nutritional status or to prevent its deterioration while decreasing the inflammatory response via a reduced production of proinflammatory cytokines. The purpose of the present prospective study was to ascertain whether HRF improves the nutritional status, reduces microinflammation, and decreases serum beta2-microglobulin levels in patients with end-stage renal disease (ESRD).

METHODS

Eight patients, four males and four females, with a mean age of 49.4 +/- 16.8 years, stable on hemodialysis over a period of 8.7 +/- 6.1 years and on standard 4-4.5 h three-times-a-week bicarbonate hemodialysis, were switched to three-times-a-week, 4-h HFR. At baseline and every two months for 12 months at mid-week, serum levels of urea, creatinine, albumin, total cholesterol, C-reactive protein, fibrinogen, complement, ferritin, beta2-microglobulin, intact parathyroid hormone (PTH), hemoglobin concentrations, and hematocrit and the EPO weekly dose were determined. At baseline and at the end of the study, the Malnutrition Inflammatory Score (MIS) was calculated.

RESULTS

Nutritional and inflammatory parameters remained constant during the 12-month period of the study. After 12 months of HFR, the MIS trended to be lower, but the difference was not statistically significant. Serum beta2-microglobulin and PTH levels remained constant during all time intervals. Neither hematocrit nor hemoglobin changed over the course of the study as well as the weekly EPO dose.

CONCLUSIONS

The change from bicarbonate hemodialysis to HFR was safe and well tolerated but was not associated with an improvement of nutritional and inflammatory parameters or a reduction of serum beta2-microglobulin levels.

Inhaled nitric oxide (iNO) was approved for use in critically ill term and near-term neonates (>34 weeks gestational age) in 1999 for hypoxic respiratory failure (HRF) with evidence of pulmonary hypertension. In 2011 and 2014, the National Institutes of Health and American Academy of Pediatrics respectively recommended against the use of iNO in preterm infants <34 weeks. However, these guidelines were based on trials conducted with varying inclusion criteria and outcomes. Recent guidelines from the American Thoracic Society/American Heart Association, the Pediatric Pulmonary Hypertension Network (PPHNet) and European Pediatric Pulmonary Vascular Disease Network recommend the use of iNO in preterm neonates with HRF with confirmed pulmonary hypertension. This review discusses the available evidence for off-label use of iNO. Preterm infants with prolonged rupture of membranes and pulmonary hypoplasia appear to respond to iNO. Similarly, preterm infants with physiology of pulmonary hypertension with extrapulmonary right-to-left shunts may potentially have an oxygenation response to iNO. An overview of relative and absolute contraindications for iNO use in neonates is provided. Absolute contraindications to iNO use include a ductal dependent congenital heart disease where systemic circulation is supported by a right-to-left ductal shunt, severe left ventricular dysfunction and severe congenital methemoglobinemia. In preterm infants, we do not recommend the routine use of iNO in HRF due to parenchymal lung disease without pulmonary hypertension and prophylactic use to prevent bronchopulmonary dysplasia. Future randomized trials evaluating iNO in preterm infants with pulmonary hypertension and/or pulmonary hypoplasia are warranted. (233/250 words).

Regulatory focus (i.e., focus on motivation to achieve gains or avoid losses and non-gains) is used to tailor health behavior change interventions, improving efficacy, but is currently assessed by scales that are not health-specific and may capture a version of the construct that is not ideally matched to the rationale for tailoring.

We developed and validated a Health Regulatory Focus Scale (HRFS), which assesses tendencies to avoid negative health consequences (prevention focus) or achieve positive health outcomes (promotion focus).

Across four studies (and a scale development study in supplementary online materials), we established convergent, discriminant, and predictive validity for the HRFS. In studies examining predictive validity, main outcome measures were health behavior intentions, including intentions to reduce alcohol use, quit smoking, eat a healthy diet, exercise, be screened for cancer, and engage in general cancer preventive behaviors.

The promotion and prevention sub-scales performed well in confirmatory factor analyses. Single-factor models had significantly poorer fit than models delineating promotion and prevention. The sub-scales were differentially (and only modestly) correlated with related constructs (anxiety, optimism, information avoidance, ambiguity/fatalism). Higher HRFS-Promotion focus generally corresponded with greater health behavior intentions. Conversely, higher HRFS-Prevention focus corresponded with lower health behavior intentions. Associations were largely maintained even when controlling for established regulatory focus measures, supporting the assertion that the HRFS would predict unique variance in health behavior intentions.

The HRFS has the potential to improve the precision with which framed health messages change behavior, as it may assess a version of regulatory focus that is more ideally matched to rationale for tailoring interventions.

OBJECTIVE

This study investigated the diagnostic and prognostic value of cardiac magnetic resonance (CMR) imaging in chronic aortic regurgitation (AR).

BACKGROUND

Accurate quantification of AR severity by echocardiography frequently remains difficult. CMR is recommended as the complementary method; however, its accuracy and prognostic utility remain unknown.

METHODS

A total of 232 consecutive patients (34.5% were females 55.5 ± 19.8 years of age) with chronic AR (including 40 with moderate to severe and 44 with severe AR on echocardiography) underwent CMR within 4 weeks of echocardiography. CMR included phase-contrast velocity-encoded imaging for the measurement of regurgitant volume and fraction at the sinotubular junction and assessment of holodiastolic retrograde flow (HRF) in the descending aorta. Significant AR was defined as the presence of HRF on CMR. Patients were followed prospectively, and multivariate Cox regression was applied for outcome analysis using a combination of heart failure, hospitalization, and cardiovascular death as primary endpoint.

RESULTS

AR severity on the basis of echo was reclassified in a significant number of patients according to CMR: 6.8% with mild AR on echo had HRF on CMR, whereas 34.1% with severe AR on echo did not have HRF on CMR and were reclassified as having nonsignificant AR. In 40 patients with uncertain AR severity (moderate to severe) on echo, 45.0% had HRF on CMR, indicating severe AR. Patients were followed for 35.3 ± 26.6 months. During that period, 63 patients (27.2%) reached the combined endpoint, including 43 (18.5%) with heart failure hospitalizations and 20 (8.6%) with cardiovascular deaths. By multivariate regression analysis, including clinical as well as imaging parameters, only N-terminal pro-B-type natriuretic peptide concentration (hazard ratio: 2.184 [95% confidence interval: 1.468 to 3.248]; p < 0.001) and HRF on CMR (hazard ratio: 2.774 [95% confidence interval: 1.131 to 6.802]; p = 0.026) remained significantly associated with outcome.

CONCLUSIONS

In chronic AR, CMR has the potential to add important diagnostic and prognostic information.

UNASSIGNED

Chronic hypercapnic respiratory failure (HRF) in obesity hypoventilation syndrome (OHS) is commonly treated using non-invasive ventilation (NIV). We hypothesised that treatment of OHS would improve neural respiratory drive index (NRDI) and cardiac function.

UNASSIGNED

Fourteen patients (8 females) with OHS, who were admitted for initiation of domiciliary NIV, were prospectively studied. Patients had (mean ± SD): age (53±10 years), body mass index (BMI) (50.1±10.8 kg/m2), and pCO2 (7.3±0.9 kPa). NRDI was assessed by surface electromyogram of the parasternal intercostals. Cardiac function was assessed by transthoracic echocardiography (TTE). All measurements were performed at baseline, 6 weeks, and 3 months.

UNASSIGNED

NRDI improved on day one following NIV set-up comparing to baseline (484.2±214.8 vs. 316.5±106.5 AU) and this improvement was maintained at 6 weeks (369.1±173.2 AU) and at 3 months (351.2±167.1 AU) (P=0.004). No significant differences were identified in terms of cardiac function between baseline and 3 months [tricuspid annular plane systolic excursion (TAPSE) (24.6±5.8 vs. 23.0±4.0 mm, P=0.317); systolic pulmonary artery (PA) pressures (36.7±15.2 vs. 44.5±23.9 mmHg, P=0.163].

UNASSIGNED

NIV improves NRDI in patients with OHS, while the cardiac function over a three-month period remains unchanged.

In the present paper we report the results of a study in which we compared 2 different approaches to the computation of biological age (BA) in a sample of 322 Japanese men (age range 20 to 79 years). In the first approach, 4 commonly used measures of health-related fitness (VO2peak, trunk flexion from a standing position, body fat, and grip strength) were reduced to a single BA score (HRF Age) using principal component analysis. In contrast, in the second approach, 3 commonly used measures of skilled motor performance and agility (vertical jump, stepping side-to-side, and balancing on one leg with eyes closed) were reduced to a single BA score (SMP Age) using similar multivariate procedures. The criterion-related validity of both of the BA measures was examined by assessing each measure's ability to discriminate between healthy and active groups of subjects. This was achieved by classifying the original subject pool into regularly active (ACT; n = 108) and healthy (HLTH; n = 169) subgroups on the basis of self-reported activity levels. Analyses revealed that HRF Age was a more powerful discriminator between the two activity groups than SMP Age. While HRF Age of HLTH subjects was very close to their chronological age (CA), in the ACT group, HRF Age was on average 15 years less than their CA (P < 0.05). In a separate analysis, we assessed the HRF Age of patients with ischemic heart disease, hypertension, obesity, or diabetes (PAT; n = 45). The HRF Age of these subjects averaged 10 years above their CA. Our data suggest that commonly used measures of health-related fitness can be usefully employed as indices of BA which differentiate between individuals of similar ages but differing health and physical activity status. In contrast, measures of skilled motor performance were found to be less valuable measures of BA. The implication of our findings for future experimental design in exercise and aging research is discussed.

OBJECTIVE

To evaluate outcome predictors of aflibercept in neovascular age-related macular degeneration pretreated with ranibizumab based on a treat-and-extend regimen (TER).

METHODS

We performed a retrospective evaluation of 18-month follow-up of 45 consecutive patients with limited response to ranibizumab.

RESULTS

At month 18, mean central retinal thickness and intraretinal fluid (IRF) height were significantly reduced. The recurrence-free treatment interval (RFTI) increased from 7.0 ± 1.8 to 8.5 ± 2.4 weeks (p = 0.01); visual acuity remained stable. At month 18, 58.1% of patients showed a longer RFTI. At month 12, eyes with baseline subretinal fluid (SRF) had a shorter RFTI than those without SRF (p = 0.032). Eyes with baseline IRF showed a longer RFTI than those without IRF (p = 0.037). Baseline hyperreflective foci (HRF) presence indicated improvement in SRF (p = 0.024) and IRF at month 12 (p = 0.049).

CONCLUSIONS

Baseline HRF presence predicted better morphological outcome, while SRF predicted a shorter RFTI and IRF a longer RFTI after switching from ranibizumab to aflibercept within a TER.

BACKGROUND

The use of opiates, particularly heroin, remains an important cause of morbidity and mortality. Half of the deaths among heroin consumers are attributed to overdose. In response to this problem, overdose prevention programs (OPPs) were designed. The objective of our study was to assess coverage of OPPs among the target population in a specific Spanish region (Catalonia) and to identify characteristics related to attendance.

METHODS

A cross-sectional survey recruited individuals from outpatient treatment centers (OTCs), therapeutic communities (ThCs), and harm reduction facilities (HRFs) in Catalonia. From 513 participants, 306 opiate users and/or injectors were selected for this study. Coverage was calculated as the proportion of subjects who declared having participated in an OPP. A Poisson regression with robust variance was used to assess factors (socio-demographic aspects and psychoactive substance use patterns) associated to OPP participation, taking into account recruitment strategy.

RESULTS

Average age of the 306 subjects was 39.7 years (s.d.: 7.7); 79% were male; 79.2% lived in urban areas and 56.3% were unemployed or had never worked. Overall OPP coverage was 43.5% (95% CI: 37%-49%). Training was received mostly in HRF (60%), followed by OTC (24.4%), prison (19%), and ThC (16%). OPP sessions were attended by 41% of Spanish-born study participants and by 63.3% of foreigners; 92.2% of the participants lived in urban areas. The Poisson regression analysis adjusted by age, sex, and type of recruitment center showed that OPP participation rates were higher for individuals with foreign nationality (PR = 1.3; 95% CI: 1.04-1.72), for those living in municipalities with more than 100,000 inhabitants (PR = 2.0; 95% CI: 1.37-2.81) or the Barcelona conurbation (PR = 2.5; 95% CI: 1.68-3.77), and for those having ever been in prison (PR = 1.6; 95% CI: 1.41-1.81) and had first consumption when they were less than 12 years old (PR = 1.2; 95% CI: 1.06-1.45).

CONCLUSIONS

Coverage as a whole can be considered high. However, in Catalonia, new strategies ought to be developed in order to attract opiate users and injectors not currently participating, by expanding OPP offer to services and regions where coverage is poor.

We synthesized a cDNA library from the intertidal copepod Tigriopus japonicus, converted it to phagemids and sequenced expressed sequence tags (ESTs). Of these, Tigriopus translationally controlled tumor protein/histamine releasing factor (TCTP/HRF) was further characterized. The Tigriopus TCTP/HRF gene encoded 172 amino acid residues and showed high similarity to Drosophila but moderate similarity to other annelids (e.g. Brugia, Wuchereria and C. elegans). The Tigriopus TCTP/HRF gene appeared in the same clade as the annelids. Here, we describe the analysis of the Tigriopus TCTP/HRF gene.

Small interfering RNAs (siRNAs) are involved in the regulation of plant development and response to stress. We have previously shown that mutants impaired in Dicer-like 2 (DCL2), DCL3 and DCL4, RDR2, RDR6 and NPRD1 are partially impaired in their response to stress and dcl2 and dcl3 plants are also impaired in transgenerational response to stress, including changes in homologous recombination frequency (HRF). Here, we have analyzed genome stability of dcl2, dcl3, dcl4, dcl2 dcl3, dcl2 dcl3 dcl4 and rdr6 mutants by measuring the non-induced and the stress-induced recombination frequency. We found that all mutants had the lower spontaneous HRF. The analysis of strand breaks showed that all tested Arabidopsis mutants had a higher level of spontaneous strand breaks, suggesting that the lower HRF is not due to the unusually low level of breaks. Exposure to methyl methane sulfonate (MMS) resulted in an increase in the level of strand breaks in wild-type plants and a decrease in mutants. All mutants had the higher methylation of cytosines at CpG sites under non-induced conditions. Exposure to MMS resulted in a decrease in methylation level in wild-type plants and an increase in methylation in all dcl mutants. The expression of several DNA repair genes was altered in dcl4 plants under non-induced and induced conditions. Our data suggest that siRNA biogenesis may be essential for the maintenance of the genome stability and stress response in Arabidopsis.

The role of ventral versus dorsolateral prefrontal regions in instantiating proactive and reactive cognitive control remains actively debated, with few studies parsing cue versus probe-related activity. Rapid sampling (460 ms), long cue-probe delays, and advanced analytic techniques (deconvolution) were therefore used to quantify the magnitude and variability of neural responses during the AX Continuous Performance Test (AX-CPT; N = 46) in humans. Behavioral results indicated slower reaction times during reactive cognitive control (AY trials) in conjunction with decreased accuracy and increased variability for proactive cognitive control (BX trials). The anterior insula/ventrolateral prefrontal cortex (aI/VLPFC) was commonly activated across comparisons of both proactive and reactive cognitive control. In contrast, activity within the dorsomedial and dorsolateral prefrontal cortex was limited to reactive cognitive control. The instantiation of proactive cognitive control during the probe period was also associated with sparse neural activation relative to baseline, potentially as a result of the high degree of neural and behavioral variability observed across individuals. Specifically, the variability of the hemodynamic response function (HRF) within motor circuitry increased after the presentation of B relative to A cues (i.e., late in HRF) and persisted throughout the B probe period. Finally, increased activation of right aI/VLPFC during the cue period was associated with decreased motor circuit activity during BX probes, suggesting a possible role for the aI/VLPFC in proactive suppression of neural responses. Considered collectively, current results highlight the flexible role of the VLPFC in implementing cognitive control during the AX-CPT task but suggest large individual differences in proactive cognitive control strategies.

Nasal washings (NW) have been used by many investigators as a readily available biologic fluid for studying the mechanism of allergic reactions. These fluids have been analyzed for the presence of various mediators, including cytokines. Recently, histamine releasing factors (HRF) have been detected in the NW. The objective of this study was to investigate the effect of treatment with topical corticosteroids on the recovery of these cytokines from the NW obtained from patients with allergic rhinitis. A group of 30 patients with ragweed pollen allergy were given either beclomethasone dipropionate (BDP) or placebo for 1 wk in a double-blind randomized manner. NW were performed twice before the start of the treatment period and were repeated twice at the end of the study. HRF activity was measured in the NW. Patients maintained a daily symptom score. The activity of HRF decreased significantly (mean +/- SD, pre = 37.2 +/- 21.3% versus post = 23.8 +/- 20.1%; p less than 0.01) in the BDP group, as did the mean symptom score (5.1 +/- 1.4 versus 1.5 +/- 1.5, p less than 0.01) at the end of the treatment period. In contrast, there was no significant change in HRF recovery (32.8 +/- 25.6% versus 33.8 +/- 25.3%; p less than 0.05) or symptom score (4.8 +/- 1.8 versus 5.4 +/- 1.9; p greater than 0.05) in the placebo group. There was a significant correlation between the net changes in symptom scores and the net differences in HRF activity. We speculate that the reduction in HRF in the nasal mucosa may contribute to the clinical efficacy of topical corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)