Ferulic acid-loaded polymeric nanoparticles prepared from nano-emulsion templates facilitate internalisation across the blood-brain barrier in model membranes.

A hydroxycinnamic acid derivative, namely ferulic acid (FA) has been successfully encapsulated in polymeric nanoparticles (NPs) based on poly(lactic-co-glycolic acid) (PLGA). FA-loaded polymeric NPs were prepared from O/W nano-emulsion templates using the phase inversion composition (PIC) low-energy emulsification method. The obtained PLGA NPs exhibited high colloidal stability, good drug-loading capacity, and particle hydrodynamic diameters in the range of 74 to 117 nm, depending on the FA concentration used. In vitro drug release studies confirmed a diffusion-controlled mechanism through which the amount of released FA reached a plateau at 60% after 6 hours-incubation. Five kinetic models were used to fit the FA release data as a function of time. The Weibull distribution and Korsmeyer-Peppas equation models provided the best fit to our experimental data and suggested quasi-Fickian diffusion behaviour. Moderate dose-response antioxidant and radical scavenging activities of FA-loaded PLGA NPs were demonstrated using the DPPH˙ assay achieving inhibition activities close to 60 and 40%, respectively. Cell culture studies confirmed that FA-loaded NPs were not toxic according to the MTT colorimetric assay, were able to internalise efficiently SH-SY5Y neuronal cells and supressed the intracellular ROS-level induced by H2O2 leading to 52% and 24.7% of cellular viability at 0.082 and 0.041 mg mL-1, respectively. The permeability of the NPs through the blood brain barrier was tested with an in vitro organ-on-a-chip model to evaluate the ability of the FA-loaded PLGA and non-loaded PLGA NPs to penetrate to the brain. NPs were able to penetrate the barrier, but permeability decreased when FA was loaded. These results are promising for the use of loaded PLGA NPs for the management of neurological diseases.

A Free-Market Environmentalist Enquiry on Spain's Energy Transition along with Its Recent Increasing Electricity Prices.

This paper analyzes the Spanish energy transition's general situation and its increasing electricity prices in recent years from a free-market environmentalist (FME) approach. We hypothesize and argue that high taxes, high government subsidies, and government industrial access restrictions breach private property rights, hindering Spain's renewable energy (RE) development. Our paper discovers that Spain's state-interventionist policies have increased the cost of the energy and power industries, leading to electricity prices remaining relatively high before and after the outbreak of the COVID-19 pandemic. After reviewing the literature on the FME approach and Spain's case, a Box-Jenkins (ARIMA) model is used to clarify the economic performance of the Spanish electricity industry with a proposal for forecasting electricity prices. It is observed that Spain fails the EU and its national goal of providing an affordable energy price as a part of the green energy transition. Finally, free-market environmental solutions and policy reforms are proposed to facilitate Spain's energy transition.

Tsunami Effects on the Coast of Mexico by the Hunga Tonga-Hunga Ha'apai Volcano Eruption, Tonga.

The massive explosion by the January 15, 2022 Hunga Tonga-Hunga Ha'apai volcano in Tonga triggered a trans-oceanic tsunami generated by coupled ocean and atmospheric shock waves during the explosion. The tsunami reached first the coast of Tonga, and later many coasts around the world. The shock wave went around the globe, causing sea perturbations as far as the Caribbean and the Mediterranean seas. We present the effects of the January 15, 2022 Tonga tsunami on the Mexican Pacific Coast, Gulf of Mexico, and Mexican Caribbean coast, and discuss the underrated hazard caused by great volcanic explosions, and the role of early tsunami warning systems, in particular in Mexico. The shock wave took about 7.5 h to reach the coast of Mexico, located about 9000 km away from the volcano, and the signal lasted several hours, about 133 h (5.13 days). The shock wave was the only cause for sea alterations on the Gulf of Mexico and Caribbean Sea, while at the Mexican Pacific coast both shock wave and the triggered tsunami by the volcano eruption and collapse affected this coast. The first tsunami waves recorded on the Mexican Pacific coast arrived around 12:35 on January 15, at the Lázaro Cárdenas, Michoacán tide gauge station. The maximum tsunami height exceeded 2 m at the Ensenada, Baja California, and Manzanillo, Colima, tide gauge stations. Most tsunami warning advisories, with two exceptions, reached communities via social media (Twitter and Facebook), but did not clearly state that people must stay away from the shore. We suggest that, although no casualties were reported in Mexico, tsunami warning advisories of far-field tsunamis and those triggered non-seismic sources, such as landslides and volcanic eruptions, should be included and improved to reach coastal communities timely, explaining the associated hazards on the coast. Supplementary Information: The online version contains supplementary material available at 10.1007/s00024-022-03017-9.

Monitoring of Caged Bluefin Tuna Reactions to Ship and Offshore Wind Farm Operational Noises.

Underwater noise has been identified as a relevant pollution affecting marine ecosystems in different ways. Despite the numerous studies performed over the last few decades regarding the adverse effect of underwater noise on marine life, a lack of knowledge and methodological procedures still exists, and results are often tentative or qualitative. A monitoring methodology for the behavioral response of bluefin tuna (Thunnus thynnus) when exposed to ship and wind turbine operational noises was implemented and tested in a fixed commercial tuna feeding cage in the Mediterranean sea. Fish behavior was continuously monitored, combining synchronized echosounder and video recording systems. Automatic information extracted from acoustical echograms was used to describe tuna reaction to noise in terms of average depth and vertical dimensions of the school and the indicators of swimming speed and tilt direction. Video recordings allowed us to detect changes in swimming patterns. Different kinds of stimuli were considered during bluefin tuna cage monitoring, such as noise generated by feeding boats, wind farm operational noise, and other synthetic signals projected in the medium using a broadband underwater projector. The monitoring system design was revealed as a successful methodological approach to record and quantify reactions to noise. The obtained results suggested that the observed reactions presented a strong relationship with insonification pressure level and time. Behavioral changes associated with noise are difficult to observe, especially in semi-free conditions; thus, the presented approach offered the opportunity to link anthropogenic activity with possible effects on a given marine species, suggesting the possibility of achieving a more realistic framework to assess the impacts of underwater noise on marine animals.

Correction: Relationship between weight and linear dimensions of Bluefin tuna (Thunnus thynnus) following fattening on western Mediterranean farms.

[This corrects the article DOI: 10.1371/journal.pone.0200406.].

The times they are a-changin': The evolution of prostate cancer screening practices and beliefs among primary care physicians in Victoria, British Columbia.

INTRODUCTION: Prostate cancer screening practices remain controversial among primary care practitioners (PCPs). Inconsistent guidelines and publication of large prostate cancer screening trials have failed to provide definitive guidance. This study investigates the evolution of prostate cancer screening practices and beliefs over 12 years, in Victoria, British Columbia. METHODS: Questionnaires were delivered to 119 randomly selected PCPs in 2019. Descriptive analysis together with exploratory graphs and Pearson Chi-squared test for independence was calculated. The 2008 data was compared by determining if their value fell within the 2019 data's 95% confidence interval. RESULTS: Response rate was 69.8% (83/119); 30.1% of PCPs reported regularly screening asymptomatic men with prostate-specific antigen (PSA) testing and 37.3% reported regularly performing digital rectal exam (DRE). The combination of PSA and DRE was the most used (48.2 %) screening modality. Most (73.5%) reported that guidelines influence their screening practices, with the most popular choice being those published by The Canadian Task Force on Preventive Health Care (CTF) (32.5%). CONCLUSIONS: The results demonstrate a movement away from prostate cancer screening among PCPs when compared to 2008. PCPs believe that DRE and PSA are less valuable as screening tools and that there is insufficient evidence to support their use. The most used initial screening modality was the combination of PSA/DRE, however, we found a decrease in their use between the two study periods. Clinical guidelines continue to influence PCPs screening practices, but the shift of more PCPs following the CTF guidelines since 2008 has likely led to the reciprocal decrease in prostate cancer screening.

Automatic Bluefin Tuna Sizing with a Combined Acoustic and Optical Sensor.

A proposal is described for an underwater sensor combining an acoustic device with an optical one to automatically size juvenile bluefin tuna from a ventral perspective. Acoustic and optical information is acquired when the tuna are swimming freely and the fish cross our combined sensor's field of view. Image processing techniques are used to identify and classify fish traces in acoustic data (echogram), while the video frames are processed by fitting a deformable model of the fishes' ventral silhouette. Finally, the fish are sized combining the processed acoustic and optical data, once the correspondence between the two kinds of data is verified. The proposed system is able to automatically give accurate measurements of the tuna's Snout-Fork Length (SFL) and width. In comparison with our previously validated automatic sizing procedure with stereoscopic vision, this proposal improves the samples per hour of computing time by 7.2 times in a tank with 77 juveniles of Atlantic bluefin tuna (Thunnus thynnus), without compromising the accuracy of the measurements. This work validates the procedure for combining acoustic and optical data for fish sizing and is the first step towards an embedded sensor, whose electronics and processing capabilities should be optimized to be autonomous in terms of the power supply and to enable real-time processing.

New Insights into the Design and Application of a Passive Acoustic Monitoring System for the Assessment of the Good Environmental Status in Spanish Marine Waters.

Passive acoustic monitoring systems allow for non-invasive monitoring of underwater species and anthropogenic noise. One of these systems has been developed keeping in mind the need to create a user-friendly tool to obtain the ambient noise indicators, while at the same time providing a powerful tool for marine scientists and biologists to progress in studying the effect of human activities on species and ecosystems. The device is based on a low-power processor with ad-hoc electronics, ensuring that the system has efficient energy management, and that the storage capacity is large enough to allow deployments for long periods. An application is presented using data from an acoustic campaign done in 2018 at El Gorguel (Cartagena, Spain). The results show a good agreement between theoretical maps created using AIS data and the ambient noise level indicators measured in the frequency bands of 63 Hz and 125 Hz specified in the directive 11 of the EU Marine Strategy Framework Directive. Using a 2D representation, these ambient noise indicators have enabled repetitive events and daily variations in boat traffic to be identified. The ship noise registered can also be used to track ships by using the acoustic signatures of the engine propellers' noise.

The effect of low frequency noise on the behaviour of juvenile Sparus aurata.

Anthropogenic activities are causing increased noise levels in the marine environment. To date, few studies have been undertaken to investigate the effects of different noise frequencies on the behaviour of juvenile fish. In this study, the behavioural changes of juvenile gilthead seabream (Sparus aurata) are evaluated when exposed to white noise filtered in third-octave bands centred at 63, 125, 500, and 1000 Hz (sound pressure level, 140-150 dB re 1 µΡa) for 7 h. The group dispersion, motility, and swimming height of the fish were analysed before and during the acoustic emission. Dispersion of the fish was found to reduce immediately upon application of low frequency sound (63 and 125 Hz) with a return to control condition after 2 h (indicative of habituation), whereas at 1 kHz, dispersion increased after 2 h without any habituation. The motility decreased significantly at 63 Hz throughout the 7 h of sound exposure. The swimming height decreased significantly for all frequencies other than 125 Hz. The results of this study highlight significant variations in the behavioural responses of juvenile fish that could have consequences on their fitness and survival.

Ozonation of the algaecide irgarol: Kinetics, transformation products, and toxicity.

The degradation of irgarol, a frequently detected algaecide in the aquatic environment, by ozonation was investigated in this study. The second-order rate constants for the reaction of irgarol with ozone (O3) and hydroxyl radical (OH) were determined to be 505 M-1 s-1 and 4.96 × 109 M-1 s-1, respectively. During ozonation, sixteen transformation products (TPs) of irgarol were proposed using an electrospray ionization quadrupole time-of-flight mass spectrometer. Most of the TPs are ozone-refractory compounds and therefore could only be further transformed by oxidation with OH generated from O3 decomposition during ozonation. Toxicity analysis using the ecological structure activity relationship class program indicates that some of the TPs (e.g., irgarol sulfoxide) still exhibit high acute or chronic toxicity to aquatic organisms (fish, daphnia, and algae) as the parent compound. With a typical ozone dose applied in water treatment (2 mg/L, corresponding to a specific ozone dose of 0.8 mg O3/mg dissolved organic carbon), irgarol could be completely abated in a selected surface water by ozonation. However, most of the TPs persisted in the ozonation effluent because of their low ozone reactivity. The results of this study suggest that ozonation with typical ozone doses applied in water treatment may not be able to sufficiently reduce the ecotoxicological effects of irgarol on aquatic organisms. More effective treatment processes such as ozone-based advanced oxidation processes may be required to enhance the removal of toxic TPs of irgarol in water treatment.

Relationship between weight and linear dimensions of Bluefin tuna (Thunnus thynnus) following fattening on western Mediterranean farms.

This study presents various models based on formulae relating weight and dimensions (length, height and width) of Bluefin tuna, Thunnus thynnus (L.), fattened in captivity. The main aim of establishing these expressions is to design tools for indirectly predicting the weight of a Bluefin tuna from measurements of one or more dimensions obtained using non-invasive methods such as stereoscopic cameras. Measurements of maximum length, height and width following slaughter were taken of fish fattened in captivity (n = 2078). Different relationships drawn from the dimensions of the tuna against their weight are fitted with part of the data collection and later checked against a reserved sample set. The resulting formulae are compared with the formulae most commonly used in the case of wild tuna. The results of this study confirm that, for tuna fattened in cages, the availability of more than one dimension to estimate weight improves the predictive power of the model and reduces error in the estimate.

Structural and energetic basis for the molecular recognition of dual synthetic vs. natural inhibitors of EGFR/HER2.

Activation of EGFR starts by ligand binding at the extracellular domain which results in homo and heterodimerization, leading to phosphorylation, activation of downstream signaling pathways which upregulate expression of genes, proliferation and angiogenesis. Abnormalities in the expression of EGFR play a critical role in the development of different types of cancer. HER2 is the preferred heterodimerization partner for EGFR; this biological characteristic together with the high percentage of structural homology has been exploited in the design of dual synthetic inhibitors against EGFR/HER2. Herein we combined structural data and molecular dynamics (MD) simulations coupled to an MMGBSA approach to provide insight into the binding mechanism between two dual synthetics (lapatinib and TAK-285) and one dual natural inhibitor (EGCG) which target EGFR/HER2. In addition, we proposed some EGCG derivatives which were filtered through in silico screening. Structural analysis demonstrated that the coupling of synthetic, natural or newly designed compounds impacts the conformational space of EGFR and HER2 differently. Energetic analysis points out that lapatinib and TAK-285 have better affinity for inactive EGFR than the active EGFR state or HER2, whereas some EGCG derivatives seem to form binding affinities similar to those observed for lapatinib or TAK-285.

Binding free energy calculations using MMPB/GBSA approaches for PAMAM-G4-drug complexes at neutral, basic and acid pH conditions.

Dendrimers are synthetic macromolecules with a highly-branched structure and high concentration of surface groups. Among dendrimers, Poly(amidoamine) (PAMAM) has received substantial attention as a novel drug carrier and delivery system. Depending on the generation and type of terminal groups, dendrimer toxicity could change and include cytotoxicity. Although PAMAM is water soluble, molecular modeling of the dendrimer-drug complex is considered challenging for exploring the conformational mobility of dendrimers and atomic specific interactions during the dendrimer-drug association. However, conventional protocols for predicting binding affinities have been designed for small protein molecules or protein-protein complexes that can be applied to study the dendrimer-drug association. In this work, we performed docking calculations for a set of 94 previously reported compounds on PAMAM of fourth generation (G4-PAMAM) to select six compounds, cromoglicic acid (CRO) - a mast cell stabilizer, Fusidic acid (FUS) - a bacteriostatic antibiotic, and Methotrexate (MTX) - a chemotherapy agent and immune system suppressant, which have the highest affinities for G4-PAMAM, and Lidocaine (LDC) - used to numb tissue in a specific area and for ventricular tachycardia treatment, Metoprolol (MET) - a ß1 receptor blocker, and Pindolol (PIN) - a ß blocker, which have the lowest affinities for the G4-PAMAM dendrimer, to perform MD simulations combined with the molecular mechanics generalized/Poisson-Boltzmann surface area MMGBSA/MMPBSA approach to investigate the interactions of generating 4 charge-neutral, charge-basic and charge-acid G4-PAMAM dendrimers. In addition, to validate these theoretical G4-PAMAM-drug complexes, the complexes were experimentally conjugated to determine their stability in aqueous solubility studies immediately and over one year. Our results show that among the different commercial drugs, both charged and neutral PAMAM have the most favorable binding free energies for CRO, MTX, and FUS, which appears to be due to a complex counterbalance of electrostatics and van der Waals interactions. These theoretical and aqueous solubility studies supported the high affinity of methotrexate for the G4-PAMAM-drug due to its carboxyl and aryl moieties that favor its accommodation by noncovalent interactions.

Using straw hydrolysate to cultivate Chlorella pyrenoidosa for high-value biomass production and the nitrogen regulation for biomass composition.

Heterotrophic cultivation of Chlorella pyrenoidosa based on straw substrate was proposed as a promising approach in this research. The straw pre-treated by ammonium sulfite method was enzymatically hydrolyzed for medium preparation. The highest intrinsic growth rate of C. pyrenoidosa reached to 0.097h-1 in hydrolysate medium, which was quicker than that in glucose medium. Rising nitrogen concentration could significantly increase protein content and decrease lipid content in biomass, meanwhile fatty acids composition kept stable. The highest protein and lipid content in microalgal biomass reached to 62% and 32% under nitrogen excessive and deficient conditions, respectively. Over 40% of amino acids and fatty acids in biomass belonged to essential amino acids (EAA) and essential fatty acids (EFA), which were qualified for high-value uses. This research revealed the rapid biomass accumulation property of C. pyrenoidosa in straw hydrolysate medium and the effectiveness of nitrogen regulation to biomass composition at heterotrophic condition.

Pediatric Inflammatory Bowel Disease Among South Asians Living in British Columbia, Canada: A Distinct Clinical Phenotype.

BACKGROUND: Inflammatory bowel disease (IBD) incidence is increasing among low-risk populations. This study examined a cohort of Canadian South Asian (SA) children with IBD to determine if their disease course differed from non-SA (NSA) children. METHODS: Children of SA ethnicity diagnosed with IBD between 1997 and 2012 were identified and compared with NSA children. Data on duration and the type of presenting symptoms, disease phenotype, corticosteroid exposure (CS), exclusive enteral nutrition use, time to commencement of immunomodulator (IM), biologic therapy, and surgical intervention were extracted. RESULTS: Overall, 160 SA children were identified and compared with 783 NSA patients (Crohn's disease [CD]: 44% versus 72%; ulcerative colitis [UC]: 43% versus 21%; IBD-Unclassified: 13% versus 7%; P < 0.001). SA patients were predominantly second-generation Canadians (92%) and had shorter symptom duration (2 versus 4 months; P < 0.001). SA CD patients were less likely to have a parent with IBD (1% versus 14%; P = 0.003). SA patients had more extensive colonic disease (CD: 55% versus 35%; P = 0.005; UC: 77% versus 58%; P = 0.006); SA CD patients presented with more complicated disease (B2/B3: 39% versus 27%; P = 0.006) and UC patients presented with more severe disease (49% versus 23%; P < 0.001). In SA CD patients, CS use was higher (70% versus 58%; P = 0.045), and IM and biologic therapy were commenced earlier (P = 0.027; P = 0.047). SA UC patients were more likely to need CS and IM (P = 0.024; P < 0.001). CONCLUSIONS: These data describe an ethnically unique clinical phenotype, where SA children have a higher proportion of UC, shorter symptom duration, more extensive colonic disease, and are more likely to require earlier escalation of therapy.

Home-based screening for biliary atresia using infant stool colour cards: a large-scale prospective cohort study and cost-effectiveness analysis.

OBJECTIVE: Biliary atresia (BA), a leading cause of paediatric liver failure and liver transplantation, manifests by three weeks of life as jaundice with acholic stools. Poor outcomes due to delayed diagnosis remain a problem worldwide. We evaluated and assessed the cost-effectiveness of methods of introducing a BA Infant Stool Colour Card (ISCC) screening programme in Canada. SETTING AND METHODS: A prospective study at BC Women's Hospital recruited consecutive healthy newborns through six incrementally more intensive screening approaches. Under the baseline "passive" strategy, families received ISCCs at maternity, with instructions to monitor infant stool colour daily and return the ISCC by mail at age 30 days. Additional strategies were: ISCC mailed to family physician; reminder letters or telephone calls to families or physicians. Random telephone surveys of ISCC non-returners assessed total card utilization. Primary outcome was ISCC utilization rate expressed as a composite outcome of the ISCC return rate and non-returned ISCC use. Markov modelling was used to predict incremental costs and life years gained from screening (passive and reminder), compared with no screening, over a 10-year time horizon. RESULTS: 6,187 families were enrolled. Card utilization rates in the passive screening strategy were estimated at 60-94%. For a Canadian population, the increase in cost for passive screening, compared with no screening, is $213,584 and the gain in life years is 9.7 ($22,000 per life-year gained). CONCLUSIONS: A BA ISCC screening programme targeting families of newborns is feasible in Canada. Passive distribution of ISCC at maternity is potentially effective and highly cost-effective.

Tumores benignos de vulva: revisión y caso clínico de acrocordón / Benign tumors of vulva: review and case report of achrocordon

La región vulvovaginal es una zona muy compleja por todos los elementos que la conforma y puede ser origen de un gran número de tumores benignos y en menor frecuencia de tumores malignos. En las últimas décadas, los tumores vulvovaginales han tenido un avance significativo en cuanto a su diagnóstico y tratamiento, dado por las aportaciones de la biología celular y molecular. El presente artículo pretende ser una referencia práctica para el diagnóstico clínico e histopatológico de estos tumores benignos así como en el tratamiento ambulatorio de algunos de ellos y su vigilancia.

The vulvovaginal region is a very complex area because of its anatomy and the fact that it can be source of a large number of benign tumors and less frequent malignant tumors. In recent decades, there have been significant gains in the diagnosis and treatment of vulvovaginal tumors, thanks to the contributions of cellular and molecular biology. The purpose of this review article is to serve as a practical reference for clinical and pathological diagnosis as well as in the outpatient treatment and monitoring of these benign tumors.

World Federation of Pediatric Intensive Care and Critical Care Societies: Global Sepsis Initiative.

BACKGROUND: According to World Health Organization estimates, sepsis accounts for 60%-80% of lost lives per year in childhood. Measures appropriate for resource-scarce and resource-abundant settings alike can reduce sepsis deaths. In this regard, the World Federation of Pediatric Intensive Care and Critical Care Societies Board of Directors announces the Global Pediatric Sepsis Initiative, a quality improvement program designed to improve quality of care for children with sepsis. OBJECTIVES: To announce the global sepsis initiative; to justify some of the bundles that are included; and to show some preliminary data and encourage participation. METHODS: The Global Pediatric Sepsis Initiative is developed as a Web-based education, demonstration, and pyramid bundles/checklist tool (http://www.pediatricsepsis.org or http://www.wfpiccs.org). Four health resource categories are included. Category A involves a nonindustrialized setting with mortality rate <5 yrs and >30 of 1,000 children. Category B involves a nonindustrialized setting with mortality rate <5 yrs and <30 of 1,000 children. Category C involves a developing industrialized nation. In category D, developed industrialized nation are determined and separate accompanying administrative and clinical parameters bundles or checklist quality improvement recommendations are provided, requiring greater resources and tasks as resource allocation increased from groups A to D, respectively. RESULTS: In the vanguard phase, data for 361 children (category A, n = 34; category B, n = 12; category C, n = 84; category D, n = 231) were successfully entered, and quality-assurance reports were sent to the 23 participating international centers. Analysis of bundles for categories C and D showed that reduction in mortality was associated with compliance with the resuscitation (odds ratio, 0.369; 95% confidence interval, 0.188-0.724; p < .0004) and intensive care unit management (odds ratio, 0.277; 95% confidence interval, 0.096-0.80) bundles. CONCLUSIONS: The World Federation of Pediatric Intensive Care and Critical Care Societies Global Pediatric Sepsis Initiative is online. Success in reducing pediatric mortality and morbidity, evaluated yearly as a measure of global child health care quality improvement, requires ongoing active recruitment of international participant centers. Please join us at http://www.pediatricsepsis.org or http://www.wfpiccs.org.

Early outcomes and improvement of patients with juvenile idiopathic arthritis enrolled in a Canadian multicenter inception cohort.

OBJECTIVE: To determine early outcomes and early improvements in a prospective inception cohort of children with juvenile idiopathic arthritis (JIA) treated with current standard therapies. METHODS: Patients selected were enrolled in an inception cohort of JIA, the Research in Arthritis in Canadian Children Emphasizing Outcomes Study. The juvenile rheumatoid arthritis core criteria set measures were completed at enrollment and 6 months later. Frequencies of normal values for each of the core set measures and the American College of Rheumatology (ACR) Pediatric 30, 50, and 70 (Pedi 70) criteria response rates achieved at 6 months after enrollment were calculated for each JIA-onset subtype group. RESULTS: Among 354 patients in the study, the median interval between diagnosis and enrollment was 0.7 months. At 6 months after enrollment, median values of active joint counts were highest in patients with rheumatoid factor (RF)-positive polyarthritis (4) and RF-negative polyarthritis (2), but were 0 or 1 for other subtypes. Fifty percent or more of patients with oligoarthritis, systemic arthritis, enthesitis-related arthritis, and undifferentiated arthritis had no active joints, and the ACR Pedi 70 criteria response rate was 48% or more in those with oligoarthritis, RF-negative polyarthritis, and systemic arthritis. CONCLUSION: With current management strategies in clinical practice, improvement in disease activity was noted in considerable proportions of patients in all of the JIA subtype groups, but low levels of disease activity persisted in many. We expect that these early outcomes will prove to be significant predictors of long-term outcomes.

Bistable and dynamic states of parametrically excited ultrasound in a fluid-filled interferometer.

In this paper the problem of parametric sound generation in an acoustic resonator filled with a fluid is considered, taking explicitly into account the influence of the nonlinearly generated second harmonic. A simple model is presented, and its stationary solutions were obtained. The main feature of these solutions is the appearance of bistable states of the fundamental field resulting from the coupling to the second harmonic. An experimental setup was designed to check the predictions of the theory. The results are consistent with the predicted values for the mode amplitudes and parametric thresholds. At higher driving values a self-modulation of the amplitudes is observed. This phenomenon is identified with a secondary instability previously reported in the frame of the theoretical model.