Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term safety and tolerability of glatiramer acetate 20 mg/ml in the treatment of relapsing forms of multiple sclerosis

ABSTRACT Introduction: Glatiramer acetate (GA) is a first-line therapy for the treatment of relapsing-remitting multiple sclerosis (RRMS). It has a well-characterized long-term safety profile and established efficacy, with over 2 million patient-years of exposure. Areas covered: To present long-term safety and tolerability findings for GA 20 mg/mL daily in the management of patients with multiple sclerosis (MS). A database analysis of all patients with MS who have ever been exposed to GA 20 mg/mL daily in clinical trials, including patients with up to 20 years of continuous treatment.Total exposure to GA in the clinical trials analyzed was 10,017 patient-years, and treatment duration ranged from 0 to 23.1 years (median 1.8 years). No unexpected adverse events (AEs) were recorded. The most common AEs were injection-site related (ISR), affecting 49% of patients receiving GA in clinical trials. Development of erythema at the injection site was the most common ISR, affecting 29.2% of study patients. Immediate post-injection reactions (IPIRs) were experienced by 24.0% of study patients; dyspnea was the most common IPIR, affecting 12.1% of patients. Expert opinion: The results of this analysis are consistent with long-term studies showing GA to be safe and generally well tolerated.
Variation at multiple trophic levels mediates a novel seagrass-grazer interaction

Herbivores can have highly variable effects across their ranges, sometimes with unanticipated effects on trophic dynamics that in turn affect management and conservation programs. In seagrass beds, small invertebrate grazers (mesograzers) are expected to benefit the habitat-forming plants by removing competing algae; however, harm by mesograzers has been documented increasingly in a number of regions. In San Francisco Bay, California, USA, a gammaridean amphipod (Ampithoe valida), native to the US East Coast and putatively introduced to Pacific coastlines, reaches outbreak densities and consumes large quantities of eelgrass Zostera marina, while it is not known to do so elsewhere in its range. Using a series of mesocosm experiments, we manipulated predator (fish) identity and density, herbivore assemblage, and habitat complexity to test how variation at multiple trophic levels influences the abundance and role of A. valida. Reductions in A. valida abundance by native San Francisco Bay shiner surfperch and bay pipefish were less pronounced than by a pinfish brought in from North Carolina, USA; however, the former 2 predators enhanced eelgrass biomass, while consumption of both amphipods and eelgrass by pinfish netted limited benefits to eelgrass. Increasing density of the surfperch in a separate experiment did not further reduce A. valida abundance but nonetheless strengthened positive effects on eelgrass, presumably through behavioral response to increased threat. The presence of a second (introduced) grazer reduced predation pressure on A. valida, weakening the trophic cascade to the detriment of eelgrass. Increasing habitat complexity by substituting flowering shoots reduced predation success, leading to higher A. valida abundances. Our results point to the importance of predator control of A. valida to reduce eelgrass damage; however, the strength of the trophic cascade across this grazer’s range is likely to be modulated by composition of predator and grazer assemblages as well as flowering rates and phenology.
Molecular diversity within clones of cv. Tannat (Vitis vinifera)

DNAs from 9 clones of cv. Tannat ( Vitis vinifera ) were analyzed at 89 microsatellite loci. Only one, VMCNg 1d12, showed a differential pattern that separated the clones in two groups. The statistical analysis of concentrations for aroma compounds from microvinifications also resulted in the same two groupings of clones. Many analyzed microsatellite loci amplified only one allele, implying that Tannat is a highly homozygous variety. For a given set of 15 microsatellites the level of homozygosity was 53 % for Tannat, in contrast to 6 % for Pinot, 20 % for both Cabernet Franc and Chardonnay and 33 % for Cabernet Sauvignon. We provide molecular data for Tannat, originating from southwestern France and nowadays becoming the emblematic cultivar of Uruguayan fine red wines. We also report a correlation between aroma-related compounds and molecular markers within clones of a cultivar.
Prognostic significance of cell cycle parameters in infiltrative ductal breast carcinoma

Flow‐cytometric DNA analysis was performed retrospectively from paraffin‐embedded blocks in 158 consecutive ductal infiltrative breast carcinoma patients grades I–III. Normal breast tissue was used as control. Tumor proliferative activity, cell ploidy, and DNA index (DI) were related to age of patients, histological grade of tumor, tumor size, axillary lymph node status, estrogen and progesterone receptor status, menopausal status, TNM clinical classification, and survival. There was a significant association between DNA aneuploidy and a high cellular proliferative activity, increased DI, poor differentiation of tumor, primary tumor size, number of positive lymph nodes, and postmenopausal state. Increased proportion of cells in S‐phase was associated with positive lymph node status and higher number of positive lymph nodes. The cell cycle parameters had no prognostic value either for overall survival of disease‐free survival of the patients. J. Clin. Lab. Anal. 12:131–136, 1998. © 1998 Wiley‐Liss, Inc.
Response to immunization with measles, tetanus, and Haemophilus influenzae type b vaccines in children who have human immunodeficiency virus type 1 infection and are treated with highly active antiretroviral therapy.

OBJECTIVE To assess the level of immunity to measles, tetanus, and Haemophilus influenzae type b (Hib) in previously immunized children who have human immunodeficiency virus (HIV) infection and were treated with highly active antiretroviral therapy (HAART) and to determine the response to reimmunization. METHODS Retrospective review of clinical data from children who have HIV-1 infection and were treated with HAART. Children were included in the analysis when they had a history of immunizations before treatment with HAART; had specific immunoglobulin G levels to tetanus, measles, or Hib measured after starting HAART but before the receipt of additional immunizations; were reimmunized while on HAART; and had postimmunization immunoglobulin G levels available. RESULTS Nineteen children (median age: 7 years; range: 3-14 years) who were treated with 3 to 5 drug HAART regimens for a median of 20 months (range: 8-37) met the criteria for at least 1 antigen and were included in this review. Fifteen (79%) of the 19 had plasma RNA levels <50 copies/mL. The median CD4% before HAART was 26% (range: 1-41) and at the time of immunization, 35% (range: 20-54). Before reimmunization, 1 (5%) of 18 children had detectable antibody levels to measles, 6 (35%) of 17 had detectable antibody levels to tetanus, and 14 (78%) of 18 had detectable antibody levels to Hib. After immunization, 15 (83%) of 18, 10 (90%) of 11, and 3 (75%) of 4 seroconverted to measles, tetanus, and Hib, respectively. Antibody levels remained detectable after 1 year in the majority of children tested. CONCLUSIONS Consideration should be given to readministering childhood immunizations to children who have HIV infection and are treated successfully with combination antiretroviral therapy.
On the evolutionary pathway of parental care in mouth–brooding cichlid fishes

Evolutionary theory predicts that differences in parental care patterns among species arose from interspecific differences in the costs and benefits of care for each sex. In Galilee St Peter's fish, Sarotherodon galilaeus (Cichlidae), male care, female care and biparental care all occur in the same population. We exploit this unusual variability to isolate conditions favouring biparental versus uniparental mouth–brooding by males or females. We first review a game–theoretic model of parental care evolution, predictions of which we test experimentally in this paper. Manipulations of the operational sex ratio show that males and females desert their offspring more frequently when the costs of care are high (in terms of lost mating opportunities). Breeding trials with males of different sizes show that small fathers desert more frequently than large fathers. We attribute this to the associated difference in the fitness benefit of biparental care relative to female–only care. Our experimental results confirm that in St Peter's fish the probability of caring is determined facultatively according to current conditions at each spawn. The experiments and model together suggest that interspecific variation in remating opportunities and clutch size may be responsible for differences in care patterns within the sub–family Tilapiini. Our results support the hypothesis that biparental mouth–brooding was the ancestral state of both male and female uniparental mouth–brooding in cichlid fishes.
CORRELATION OF SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS WITH VISUAL ACUITY IN EYES WITH SUBFOVEAL SCARRING AFTER TREATMENT FOR WET AGE-RELATED MACULAR DEGENERATION

Purpose: Correlating spectral domain optical coherence tomography characteristics with final best-corrected visual acuity (BCVA) in eyes with subfoveal scarring after treatment for wet age-related macular degeneration. Methods: Seventy-nine eyes from 64 subjects, who developed subfoveal scarring after treatment of wet age-related macular degeneration, were retrospectively studied. Spectral domain optical coherence tomography characteristics were analyzed, including percentage disruption of inner segment/outer segment junction and external limiting membrane, central macular thickness, subfoveal scar thickness, subretinal scar area, and proximity of retina with intact outer structures to the fovea. A multivariate stepwise regression analysis was performed with the final BCVA logarithm of minimum angle of resolution as a response and the above-identified spectral domain optical coherence tomography variables as predictors. Results: There was no correlation between the final BCVA and any of the demographic data, treatment modality received, and central macular thickness. The final BCVA was significantly correlated with the percentage of inner segment/outer segment disruption (P = 0.011), external limiting membrane disruption (P = 0.005), and scar area on spectral domain optical coherence tomography (P = 0.018). Multivariate analysis showed that the baseline BCVA and distance between the fovea and nearest retina with intact outer structures are the most predictive of the final BCVA (R2 = 0.52). Conclusion: Baseline BCVA and integrity of outer retinal structures are good predictors of the final BCVA of wet age-related macular degeneration patients developing scarring after treatment.
Small group treatments: Introduction to special section

A brief state of the art overview introduces this special section followed by a commentary on how the three articles herein contribute to our current knowledge base. It is heartening to see an increasing number of group articles being published in Psychotherapy Research that test specific group interventions, explore mechanisms of change and evaluate analytic issues for group treatments. But before going to the specifics of the articles in this special section, I’d like return to a framework introduced in the Handbook of psychotherapy and behavior change (Burlingame, Mackenzie, & Strauss, 2004) to discuss recent advances and issues. There is general agreement that sufficient empirical evidence exists to conclude that group is an effective modality when compared to the individual format (McRoberts, Burlingame, & Hoag, 1998) and when used to treat diverse populations (DeLucia-Waack, Gerrity, Kalodner, & Riva, 2004). Based on this, we introduced a model to describe frequently used influences that might explain the therapeutic benefits of group interventions. The model introduced five sources that have been linked to group outcomes. Tests of formal change theory reflect the source with the largest number of articles in the literature followed by small group process research that tests putative mechanisms of change (e.g., cohesion, participation in a social microcosm, giving/receiving interpersonal feedback, etc.). The client and leader domains reflect extra-therapy (e.g., pre-therapy expectations, attachment style) and in-session characteristics and behavior (e.g., warmth, interpersonal style, empathy, etc.) and the structural source describe treatment characteristics (dosage, sequencing of sessions, group size, etc.). Recent advances and concerns in the first two sources are summarized to set a context for this special section.
Evaluating measurement error in estimates of worker exposure assessed in parallel by personal and biological monitoring.

BACKGROUND While studies indicate that the attenuating effects of imperfectly measured exposure can be substantial, they have not had the requisite data to compare methods of assessing exposure for the same individuals monitored over common time periods. METHODS We examined measurement error in multiple exposure measures collected in parallel on 32 groups of workers. Random-effects models were applied under both compound symmetric and exponential correlation structures. Estimates of the within- and between-worker variances were used to contrast the attenuation bias in an exposure-response relationship that would be expected using an individual-based exposure assessment for different exposure measures on the basis of the intra-class correlation coefficient (ICC). RESULTS ICC estimates ranged widely, indicative of a great deal of measurement error in some exposure measures while others contained very little. There was generally less attenuation in the biomarker data as compared to measurements obtained by personal sampling and, among biomarkers, for those with longer half-lives. The interval ICC estimates were often-times wide, suggesting a fair amount of imprecision in the point estimates. Ignoring serial correlation tended to over estimate the ICC values. CONCLUSIONS Although personal sampling results were typically characterized by more intra-individual variability than inter-individual variability when compared to biological measurements, both types of data provided examples of exposure measures fraught with error. Our results also indicated substantial imprecision in the estimates of exposure measurement error, suggesting that greater emphasis needs to be given to studies that collect sufficient data to better characterize the attenuating effects of an error-prone exposure measure.
Aspergillus Fumigatus Biofilm on Primary Human Sinonasal Epithelial Culture

Background Bacterial biofilms have been implicated in chronic rhinosinusitis (CRS). However, direct evidence in support of fungal biofilms in sinus disease is lacking in the literature. This study was designed to develop and characterize an in vitro Aspergillus fumigatus biofilm model on primary human sinonasal epithelial cell culture. Methods Sinonasal biopsy specimens harvested during endoscopic sinus surgery of six CRS patients and three pituitary tumor (control) patients were cultured in Dulbecco's modified Eagle media (DMEM; Invitrogen)/Hams F12 airway media to encourage epithelial cell proliferation. Epithelial cells separated by immunomagnetic beads were seeded in tissue culture-treated Y-shaped microslides. At confluence the primary cultures were inoculated with A. fumigatus spores. Fungus was allowed to germinate and form biofilms under two in vitro conditions: (1) static (no flow through of media) and (2) continuous flow coculture (continuous flow movement of media). At regular intervals cocultures were stained with FUN-1, concanavalin A–alexa fluor 488, and examined by confocal scanning laser microscopy. Comstat software was used to assess biomass and thickness. Results A. fumigatus formed three-dimensional biofilm structures with parallel-packed, cross-linked hyphae and channels/passages. Metabolically active hyphae showed orange–red fluorescing intravacuolar structures. Extracellular matrix (ECM) between/around the hyphae fluoresced intense green. A. fumigatus biofilms development occurred in five stages: (1) conidial attachment to epithelial cells, (2) hyphal proliferation, (3) ECM production, (4) hyphal parallel packing and cross-linking, and (5) channel/pores formation. Mature biofilms showed basal conidial, middle hyphal, and superficial ECM layers. Biofilms formed underflow conditions displayed more robust and faster growth kinetics when compared with that under static conditions, with a thick, stocky, wrinkly/undulating hyphal growth and extensive ECM production. The differences in biomass and average thickness of the cocultures under static and flow conditions were statistically significant after similar periods of incubation (p = 0.0002; p < 0.0001, respectively. Conclusion To our knowledge, this is the first article of an in vitro model characterizing A. fumigatus biofilm formation using primary human sinonasal epithelium under different growth conditions.
Iron homeostasis and its disruption in mouse lung in iron deficiency and overload

What is the central question of this study? The aim was to explore the role and hitherto unclear mechanisms of action of iron proteins in protecting the lung against the harmful effects of iron accumulation and the ability of pulmonary cells to mobilize iron in iron deficiency. What is the main finding and its importance? We show that pulmonary hepcidin appears not to modify cellular iron mobilization in the lung. We propose pathways for supplying iron to the lung in iron deficiency and for protecting the lung against iron excess in iron overload, mediated by the co‐ordinated action of iron proteins, such as divalent metal transporter 1, ZRT‐IRE‐like‐protein 14, transferrin receptor, ferritin, haemochromatosis‐associated protein and ferroportin.
Inhaled corticosteroids and the growth of lung function in children

This month's edition of the European Respiratory Journal contains two papers that address the important topic of the effect of inhaled corticosteroids (ICS) on lung development in childhood 1, 2. The papers are important because: 1) they raise important methodological issues concerning the design of outcome studies in children; 2) they illustrate different approaches to the measurement of lung function in different age groups (preschool children and teenagers, respectively); 3) they raise questions about the relationship between the structure and function in the developing lung; and 4) they fuel the debate about the appropriate choice of outcomes in managing ICS therapy in children. These points, in turn, are considered below. First, the design of the two studies is quite different. Devulapalli et al. 1 carried out a longitudinal observational study of a population sample in which young children who were prescribed ICS for “recurrent bronchial obstruction” (undefined) were compared with untreated symptomatic and symptom-free groups. Although the design is justified as being “based upon … real life”, it suffers from the shortfall that an independent effect of ICS on functional outcome cannot be deduced from the results presented. At best, it is possible to conclude that both treated and untreated young children with recurrent bronchial obstruction appear functionally to return towards normal by 2 yrs of age. Multivariate analysis might have added strength to the assumption that this process was indeed related in someway to ICS therapy, rather than being simply …
Relationship between Mental Toughness and Physical Endurance

This study tested the criterion validity of the inventory, Mental Toughness 48, by assessing the correlation between mental toughness and physical endurance for 41 male undergraduate sports students. A significant correlation of . 34 was found between scores for overall mental toughness and the time a relative weight could be held suspended. Results support the criterion-related validity of the Mental Toughness 48.
Repainting the ceiling: Do patient safety and satisfaction initiatives make things safer or more satisfying?

‘‘I think the symptoms ﬁrst began when I bent over to adjust the backyard sprinkler head. I was distinctly uncomfortable, unable to get enough air, or so it felt; as if my belt were cinched too tight or my pants too small. ’’ This is how Jerry Jurkovich began the 1997 Western Trauma Association (WTA) Presidential Address, ‘‘Paint the Ceiling. ’’ 1 He chronicled his life as a patient, his triumph over lymphoma, and his tribulations negotiating the mid-1900s health care system. He gave us the patient’s perspective, lying in bed. In his case, he stared at the peeling paint. Hence, the title, ‘‘Paint the Ceiling. ’’ It was inspiring. All were touched. After everyone else left, the glow of his address surrounded me. It was perfect, heartfelt, and transparent; it evoked real emotion, and everybody left better for the experience. Using a sports metaphor, he left everything on the ﬁeld. Being President of the AASTand the WTA simultaneously was a huge honor. As I walked off the stage after delivering my address at the AAST, people began asking me about the subject of my WTA presidential address. I had no idea. It had to be intensely personal and new, but the things that were important to me had not changed. I was emotionally spent. I needed time to decompress, to recharge, and frankly, to actually do my day job.
Developmental trajectories of psychotic-like experiences across adolescence: impact of victimization and substance use

Background Research suggests that psychotic-like experiences (PLEs) in the general population are common, but can reflect either transitory or persistent developmental phenomena. Using a general adolescent population it was examined whether different developmental subtypes of PLEs exist and whether different trajectories of PLEs are associated with certain environmental risk factors, such as victimization and substance use. Method Self-reported PLEs were collected from 409 adolescents (mean age 14 years 7 months) at four time points, each 6 months apart. General growth mixture modelling was utilized to identify classes of adolescents who followed distinct trajectories of PLEs across this period. Predictors of class membership included demographics, personality, victimization, depression, anxiety and substance use. Results We identified the following three developmental subgroups of PLEs: (1) persistent; (2) increasing; (3) low. Adolescents on the persistent trajectory reported frequent victimization and consistent elevated scores in depression and anxiety. Adolescents on the increasing trajectory were engaging in cigarette use prior to any increases in PLEs and were engaging in cocaine, cannabis and other drug use as PLEs increased at later time points. Conclusions The findings suggest that different developmental subgroups of PLEs exist in adolescence and are differentially related to victimization and substance use.