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Down syndrome–associated arthritis (DA) is underrecognized, and current therapies used for juvenile idiopathic arthritis (JIA) appear to be poorly tolerated and less effective in patients with DA. The objective of this study was to characterize clinical manifestations and therapeutic preferences in DA compared to JIA, using the new Childhood Arthritis and Rheumatology Research Alliance (nCARRA) registry. In a case–control study, between July 2015 and March 2019, patients with a diagnosis of JIA and Down syndrome (DS) were identified and matched by age, sex, and JIA subtype to patients who have JIA without DS. Collected data included demographic characteristics, disease characteristics, laboratory results, treatment exposure, and outcome measures. A total of 36 children with DA and 165 with JIA were identified. Most patients presented with polyarticular rheumatoid factor–negative disease. At entry into the nCARRA registry, there were minimal differences between the groups, and at the last visit there were significant differences (P< 0.05) for multiple outcome measures. Patients with DA and those with JIA had similar therapeutic exposure to disease‐modifying antirheumatic drugs (DMARDs) and biologics, but those with DA had more DMARD‐related adverse events (93% versus 25%) and biologic therapy ineffectiveness (60% versus 17%). There was little difference between patients with DA and those with JIA at baseline, and similar therapy was implemented for those in the nCARRA registry; however, at the last visit, the patients with DA had greater disease burden. Additionally, there were more DMARD‐related adverse events and biologic ineffectiveness for those patients with DA. More research is needed to determine differences in pathophysiology and optimal therapeutic approaches.

Much of the Earth’s biosphere has been appropriated for the production of harvestable biomass in the form of food, fuel and fibre. Here we show that the simplification and intensification of these systems and their growing connection to international markets has yielded a global production ecosystem that is homogenous, highly connected and characterized by weakened internal feedbacks. We argue that these features converge to yield high and predictable supplies of biomass in the short term, but create conditions for novel and pervasive risks to emerge and interact in the longer term. Steering the global production ecosystem towards a sustainable trajectory will require the redirection of finance, increased transparency and traceability in supply chains, and the participation of a multitude of players, including integrated ‘keystone actors’ such as multinational corporations.

An important tenet of science is establishing the reproducibility of findings. While long‐term studies may seem ill‐suited to this goal, here we provide an example of reproducible results from repeated nutrient additions to a lake. We added nitrogen and phosphorus to Peter Lake in 9 yr of a 33‐yr study. For seven of these nine additions, phytoplankton biomass, as measured by seasonal mean chlorophyll a, increased in proportion to the rate of nutrient loading. Additionally, for these seven additions, similar nutrient loading rates resulted in mean Chl aconcentrations within a roughly twofold range—an outcome within expectation given uncontrolled sources of variation in a whole‐lake manipulation. However, for two of the nine nutrient additions, Chl aconcentrations were well below expected concentrations. The low chlorophyll responses co‐occurred with years having the highest water color (absorbance of light at 440 nm). The number of years of nutrient additions was too limited to strongly test the influence of color at the scale of seasonal mean values. We, therefore, tested for the effect of phosphorus load and color, on Chl ausing time series models of weekly data. At the weekly scale, there was a strong negative effect of color on chlorophyll concentration. Overall, the repeated nutrient additions provided a confirmation of existing models at the whole‐lake scale and demonstrated an interesting exception to these models. Including repeated manipulations as part of long‐term studies is an important way to test generalizations and to identify unexpected outcomes that raise new questions.

In a dramatic revision of science education in the state, the Kansas Board of Education voted 6-4 last Wednesday to remove almost all mention of evolution from its required curriculum. [...]

Scientists have long struggled to determine how the brain sorts out its jumble of visual information to recognize objects. Many studies have indicated that the brain dedicates separate regions, or [...]

Convulsions triggered by high fevers strike up to 5 percent of infants and young children. Physicians generally regard such episodes as benign because they seldom lead to neurological problems in [...]

Psychologists who study telepathy rejoiced when a 1994 study in a major scientific journal supported the existence of extrasensory perception (ESP), also known as psi. Now, an analysis of other [...]

Heart attacks typically hit men at an earlier age than they do women, but women may not hold the ultimate advantage. Among people stricken during middle age, women are much [...]

In bone marrow, where blood cells are born, a few cells have the unique ability to develop into any type of blood cell, as needed, and to produce offspring that [...]

A stellar explosion rocked Earth's neighborhood about 5 million years ago, according to German researchers who have uprooted the first direct evidence of a supernova recent and so close. Such [...]

The music of Mozart is surely inspiring. However, one seldom hears even the most avid music enthusiast exclaim, 'Ah, the 800-hertz fundamental in those violins is spectacular!' One reason is [...]

For decades, the prevalence of childhood cavities has plummeted, thanks mostly to fluoridated water. But for some children, especially in northeastern U.S. cities and among the most economically disadvantaged, tooth [...]

A sooty haze hovered over the northern Indian Ocean this spring, outstripping the worst expectations of an international team of scientists that spent 6 weeks in the area studying the [...]

Tadpoles have a stinky way of warning each other to hunker down when a predator looms, according to a new study. Like many aquatic species, tadpoles use their keen olfactory [...]

Bearing out researchers' longstanding suspicion of a link between cocaine use and heart attacks, a new study confirms that cocaine users' risk skyrockets within minutes of taking the drug. Cocaine [...]

Randomized controlled trials (RCTs) on pediatric venous thromboembolism (VTE) treatment have been challenged by unsubstantiated design assumptions and/or poor accrual. Pilot/feasibility (P/F) studies are critical to future RCT success.

Abstract: Orectolobicestus n. g. (Cestoda:: Tetraphyllidea) is erected for six cestode species parasitising bamboo sharks (Orectolobiformes: Chiloscyllium). Members of this genus differ from all other phyllobothriid genera in possessing modified maisiform spinitriches on their distal bothridial surfaces. In addition, they are easily recognised in that they share the following unique combination of characters: their vitelline fields are interrupted by the ovary, their necks are scutellate, and their bothridia bear an apical sucker and marginal loculi. Five new species of Orectolobicestus are described, including O. tyleri n. sp. from Chiloscyllium punctatum off Borneo, O. lorettae n. sp. from C. cf. punctatum off Australia, O. mukahensis n. sp. and O. kelleyae n. sp. from C. indicum off Borneo, and O. randyi n.sp. from C. hasselti also from off Borneo. In addition, Phyllobothrium chiloscyllii Subhapradha, 1955 is transferred to the new genus. O. chiloscyllii (Subhapradha, 1955) n. comb. is readily distinguished from all five new species in its greater total length. In addition to a number of proglottid features, O.␣kelleyae n. sp. and O. randyi n. sp. clearly differ from the other three new species in their possession of trifid, rather than fully serrate, spinitriches on their proximal bothridial surfaces. The latter two species conspicuously differ from one another in total number of proglottids (11–21 vs 27–38). O. tyleri n. sp. generally has fewer proglottids than O. lorrettae n. sp. (7–17 vs 13–23) and, like O. mukahensis n. sp., possesses scutes that are spathate rather than elongate. O. tyleri n. sp. is readily distinguished from O. mukahensis n. sp. in its possession of fewer proglottids (7–17 vs. 19–29). The five new species of Orectolobicestus share derived bothridial microthrix features with Phyllobothrium squali Yamaguti, 1952, Thysanocephalum sp., Orygmatobothrium sp., Ruhnkecestus Caira & Durkin, 2006 and species of Paraorygmatobothrium Ruhnke, 1994. Among these taxa, Orectolobicestus most closely resembles Paraorygmatobothrium and Ruhnkecestus in its vitelline fields being interrupted by the ovary and the possession of a scutellate neck.

ABSTRACTWe report here the first Portuguese case of acute fatal granulomatous encephalitis attributed to Balamuthia mandrillaris, initially thought to be a brain tumor, which had a progressive and fatal outcome. Balamuthia mandrillarisis a free-living amoeba recognized as an uncommon agent of granulomatous encephalitis. Infections have been identified in immunocompromised hosts and in immunocompetent pediatric patients. Balamuthiainfections are very rare, with only two reported cases in Europe. The case presented here occurred in a previously healthy boy who died 5 weeks after the onset of the symptoms. No evidence of immunological deficiency was noted, and testing for human immunodeficiency virus antibodies was negative. The symptoms were initially thought to be the result of a tumor, but histopathologic examination showed evidence of amoebic infection. Immunofluorescence staining of brain tissue identified B. mandrillarisas the infectious agent. The diagnosis was confirmed with PCR by detecting BalamuthiaDNA in formalin-fixed brain tissue sections. Despite initiation of empirical antimicrobial therapy for balamuthiasis, the patient died 3 weeks after being admitted to the hospital. No source of infection was readily apparent.

Presents the short story "Journey Inland," by S. S. Carpenter.

We have observed differences in the infrared spectra of viable fibroblast cells depending on whether the cells were in the exponential (proliferating) or plateau (nonproliferating) phase of growth. The spectral changes were observed even after correcting for cell number and volume, ruling out these trivial explanations. Several of the changes occurred for both transformed and normal cell lines and were greater for the normal cell line. The biochemical basis of the spectral changes was estimated by fitting the cell spectra to a linear superposition of spectra for the major biochemical components of mammalian cells (DNA, RNA, protein, lipids, and glycogen). The ratios of RNA/lipid and protein/lipid increased when the cells were in the exponential phase compared to the plateau phase of growth. The fits of cell spectra to individual biochemical components also demonstrated that DNA is a relatively minor spectroscopic component as would be expected biochemically. Contrary to other reports in the literature, our data demonstrate that determining DNA content or structure using Fourier transform infrared spectroscopy data is difficult due to the relatively small amount of DNA and the overlap of DNA bands with the absorption bands of other biochemical components.

Cofacial palladium(II) bisporphyrins anchored by xanthene [Pd2(DPX)] and dibenzofuran [Pd2(DPD)] pillars were prepared, and the dynamics of their triplet excited states were investigated. The phosphorescence quantum yield [Φp = 4.59(121) × 10^-3 in CH2Cl2] and lifetime [τp = 18.2(2) μs in CH2Cl2] of Pd2(DPD) are significantly attenuated compared to those of its Pd2(DPX) congener [Φp = 29.4(5) × 10^-3 and τp = 102(3) μs in CH2Cl2]. Electronic absorption and emission spectroscopy and electrochemical measurements establish that the porphyrin rings of the DPX cofacial analogue are closer to each other than the porphyrin rings of the DPD analogue in fluid solution. These observations are supported by X-ray crystallographic analyses, which show that the metal−metal distance for the dibenzofuran-bridged bisporphyrin in the solid state is almost 3 Å greater than that for bisporphyrins linked by the xanthene spacer. The spectroscopic, photophysical, and structural results suggest that the decreased Φp and τp of Pd2(DPD) are not a consequence of simple interplanar interactions but rather arise from the increased conformational flexibility of the porphyrin rings about the aryl ring of the DPD pillar. In support of this contention, the photophysical properties of monomeric palladium etioporphyrin I [Pd(Etio)] and meso-phenyl-substituted palladium etioporphyrin II [Pd(PhEtio)] were examined and found to be similar to those of Pd2(DPX) and Pd2(DPD), respectively. Density functional theory calculations reveal that torsional motion about the C(meso)−C(aryl bridge) bond induces nonplanar distortion of the porphyrin framework, causing a substantial decrease in the T1−S0 energy gap. This structural perturbation is consistent with the observed results of enhanced deactivation of Pd2(DPD) and Pd(PhEtio) triplet excited states.

An understanding of the relationship between tissue structures and light scattering from tissue will help facilitate the development and acceptance of noninvasive optical diagnostics including elastic scattering spectroscopy, diffuse reflectance, and optical coherence tomography. For example, a quantitative model of the structures that scatter light in epithelial cells would allow determination of what structures control the characteristics of in vivolight transport measurements and subsequently could provide a detailed relationship between cellular structures and optical measurements. We have determined the size distribution of refractive index structure variations in epithelial cells as well as in nuclei isolated from epithelial cells from measurements of the angular dependence of polarized light scattering. The quantitative size distributions we obtained for both whole cells and isolated nuclei include particles with effective radii of 2 m to 10 nm or less and contain orders of magnitude more small particles than large particles. These results demonstrate that not only are biological cells very heterogeneous, but so are the nuclei within them. Light scattering is likely sensitive to structures smaller than those commonly investigated by standard pathology methods. © 2002 Society of Photo-Optical Instrumentation Engineers.

We quantified the spatial and temporal variability of crustacean zooplankton abundance at annual time steps with 261 lake‐years of data from 22 lakes in three regions of central North America. None of these lakes had been experimentally manipulated. Using a nested three‐way analysis of variance, we apportioned variance among years, regions, lakes, and their interactions for 10 functional groups and 4 larger taxonomic aggregates. We proposed that relative variation in the abundance of zooplankton would be greatest among regions and lakes and least among years. We also explored how variability differed among functional groups and changed with taxonomic aggregation. Spatial sources of variation dominated the analysis, but a large interaction between lakes and years indicated that time cannot be ignored. Regional variation was half that found among lakes. Relative variance components differed widely among functional groups, which indicates that species will differ in their response to environmental controls and sensitivity to perturbation. Total explained variation also differed widely among zooplankton and decreased with increasing aggregation of taxa. Whether choosing ecological indicators or designing experiments and monitoring programs, these results clearly show that large‐scale temporal and spatial variability will be an important consideration.

We present a laboratory‐based examination of oviposition preference in the Scottish biting midge, Culicoides impunctatus(Diptera: Ceratopogonidae). A variety of oviposition substrates were screened in no‐choice and choice bioassays for efficacy in eliciting an egg‐laying response. Both upper‐layer photosynthetic Sphagnumspp. moss and Juncus articulatusinfusions were identified as producing increased oviposition under no‐choice conditions. During choice trials against a control of damp cottonwool, upper‐layer Sphagnumspp. moss produced a significantly greater egg‐laying response. These conclusions are interpreted in terms of possible cues involved in oviposition site selection and assessed for future use in colonisation of this troublesome species.

The complexities of genetic data may not be accurately described by any single analytical tool. Phylogenetic analysis is often used to study the genetic relationship among different sequences. Evolutionary models and assumptions are invoked to reconstruct trees that describe the phylogenetic relationship among sequences. Genetic databases are rapidly accumulating large amounts of sequences. Newly acquired sequences, which have not yet been characterized, may require preliminary genetic exploration in order to build models describing the evolutionary relationship among sequences. There are clustering techniques that rely less on models of evolution, and thus may provide nice exploratory tools for identifying genetic similarities. Some of the more commonly used clustering methods perform better when data can be grouped into mutually exclusive groups. Genetic data from viral quasispecies, which consist of closely related variants that differ by small changes, however, may best be partitioned by overlapping groups.

We report the identification and cloning of a unique chick myosin heavy chain (CMHC1) that is expressed exclusively in the heart during embryogenesis. Using primers specific to myosin heavy chains, we used reverse transcriptase-polymerase chain reaction to clone and isolate CMHC1 from embryonic day 10 chicken heart RNA. Sequence analysis indicated that CMHC1 was a novel member of the myosin heavy chain family. Expression of the CMHC1 transcripts was detected in Hamburger Hamilton stage 10 chick embryos in the fusing myocardium. Expression of CMHC1 was maintained at high levels throughout the tubular heart of later stage embryos. Reverse transcriptase-polymerase chain reaction and in situ hybridizations failed to detect CMHC1 transcripts in the developing somites, limb buds, or skeletal musculature at any stage of chick development. Genomic CMHC1 clones have been isolated that contain sequences approximately 5.2 kilobase upstream of the presumptive CMHC1 transcription start site. Portions of the upstream regulatory region induced a 21-fold increase in reporter gene expression in primary cardiomyocytes. Because of its unique cardiac-restricted expression, CMHC1 will provide an excellent model system to study the molecular mechanisms required for the early developmental regulation of heart-specific genes.

Background: Endoscopic ultrasonography (EUS) is highly accurate in the localization of small pancreatic tumors. We determined the cost effectiveness of EUS used early in the preoperative evaluation of pancreatic endocrine tumors. Methods: In a study with a case-control design, 36 patients (19 men, 17 women) who underwent preoperative EUS were matched retrospectively with 36 patients who underwent surgical exploration immediately before the introduction of EUS. The number, cost, and effectiveness of preoperative localization studies, days of hospitalization, and surgical and anesthesia times were assessed. Results: The EUS group had reduced charges for preoperative localization studies: $2620 versus $4846 per patient (p < 0.05), largely because of reductions in the number of diagnostic angiograms and venous sampling procedures performed. Surgical and total anesthesia times were decreased, as were the number of preoperative admissions for angiographic procedures. The cost-effectiveness ratio for the EUS group was $3144 per tumor localized compared with $5628 per tumor localized for the group treated before EUS became available (p < 0.05). Conclusion: EUS is highly accurate in the localization of pancreatic neuroendocrine tumors and is cost effective when used early in the preoperative localization strategy. EUS decreased the need for additional invasive tests and avoided unnecessary morbidity and resource consumption. EUS should play a primary role in preoperative localization of pancreatic neuroendocrine tumors. (Gastrointest Endosc 1999;49:19-25.)

No Abstract.

We investigated the short-lived S2 (¹A1) state of phenol using two-photon resonance-enhanced photoionization coupled with photoelectron spectroscopy. Spectra were obtained by exciting the S2 state with femtosecond laser pulses at various wavelengths near 207 nm and ionizing with pulses at 207 or 414 nm. The spectra feature a strong transition to the ground electronic state of the ion (&Xtilde;) and a very weak transition to the first excited electronic state of the ion (Ã). In comparison, ionization via the longer-lived S1 state using 275 nm pulses generates slightly more à ions. We interpret the relative intensities of the à state signals as a reflection of configuration interactions in the intermediate S2 and S1 states. Time-delayed ionization experiments, as well as experiments with different laser pulse durations, suggest that the S2 state has a lifetime between 150 and 350 fs. Ionization via S1 produces a vibrationally resolved photoelectron spectrum, while ionization via S2 leads to a highly congested spectrum. The envelope of the latter spectrum extends over more than 1 eV and features a long progression, probably in the 6a vibration. This suggests that the S2 state has a geometrical structure that is displaced from the ground state along the 6a coordinate. No vibrational structure could be resolved in the à ion spectrum obtained by ionization via either S2 or S1.

This paper presents the first structural analysis of the cytoplasmic domain of neurofascin, which is highly conserved among the L1CAM family of cell adhesion molecules, and describes sequence requirements for neurofascin-ankyrin interactions in living cells. The cytoplasmic domain of neurofascin dimerizes in solution, has an asymmetric shape, and exhibits a reversible temperature-dependent beta-structure. Residues Ser56-Tyr81 are necessary for ankyrin binding but do not contribute to either dimerization or formation of structure. Transfected neurofascin recruits GFP-tagged 270-kDa ankyrinG to the plasma membrane of human embryo kidney 293 cells. Deletion mutants demonstrate that the sequence Ser56-Tyr81 contains the major ankyrin-recruiting activity of neurofascin. Mutations of the FIGQY tyrosine (Y81H/A/E) greatly impair neurofascin-ankyrin interactions. Mutation of human L1 at the equivalent tyrosine (Y1229H) is responsible for certain cases of mental retardation (Van Camp, G., Fransen, E., Vits, L., Raes, G., and Willems, P. J. (1996) Hum. Mutat. 8, 391). Mutations F77A and E73Q greatly impair ankyrin binding activity, whereas mutation D74N and a triple mutation of D57N/D58N/D62N result in less loss of ankyrin binding activity. These results provide evidence for a highly specific interaction between ankyrin and neurofascin and suggest that ankyrin association with L1 is required for L1 function in humans.

A model is proposed to explain the effect of precipitation on acoustic emission from dislocation motion in age-hardening systems. The model is based on the hypothesis that a substantial number of dislocations must move rapidly and nearly simultaneously within a small volume of material in order to create detectable acoustic emission. In alloy systems where cross slip is difficult, precipitates, if they are not too strong, can serve as breakable pins and lead to the formation of dislocation avalanches and thereby increase acoustic emission near the onset of plastic flow. In easy cross slip systems, dislocations tend to cross slip around precipitates rather than form pile-ups, so the precipitates do not lead to increased acoustic emission. These considerations do not apply if the pins are Cottrell atmospheres, and high levels of acoustic emission may be observed in either easy or difficult cross slip systems when solute atmospheres provide the pinning. Acoustic emission measurements have been made as a function of heat treatment in several age-hardening systems with various stacking fault energies, elastic moduli, and precipitate strengths. For easy cross slip systems, including 7075 aluminium, 6061 aluminium, 2219 aluminium, and sterling silver, the acoustic emission was greatest in the solution-treated condition and was lowered by precipitation. For more difficult cross slip systems, including JBK–75, Incoloy 903, and an experimental beryllium-hardened austenitic stainless steel, the acoustic emission increased with increased aging times, for relatively short aging times, and then declined for longer aging times. No acoustic emission peak was observed in 17–10P, a stainless steel hardened by M23C6carbides. A relatively high acoustic emission peak was observed in 5083–0 and also in solution-treated 7075 and 6061, where serrated yielding indicated pinning by solute atmospheres.

Abstract: Detailed measurements are reported of acoustic emission (AE) produced during theδ → α phase transformation in plutonium-gallium alloys. During thermal cycling, the number of AE signals produced decreased with each thermal cycle more rapidly than the amount of additional material transformed. Thus, some portion of the transformation does not produce detectable AE. The average amplitude of the signals produced during quenching was not appreciably dependent on gallium content or cooling cycle. The amplitude of the signals is greater for rapid cooling than for slow cooling. The AE behavior is consistent with an isothermal, nonthermoelastic martensitic transformation.

Budgets for chlorophyll a and selected degradation products were constructed during summer stratification in 1984 and 1985 in two lakes. In Paul Lake, the reference ecosystem, pigment sedimentation showed no significant interannual differences. In Tuesday Lake, fish manipulations in May 1985 changed the zooplankton from an assemblage of Bosmina and small cyclopoids to one of large cladoceran grazers. Sedimentation of pigments, especially the grazing indicator pheophorbide a, increased significantly as the grazer assemblage changed. Mean grazer size was positively related to pheophorbide deposition rate in both lakes. Results of this whole-lake experiment indicate that major changes in lake food webs alter pigment deposition rates.

Article abstract An unusual neurovisceral lipid storage disorder in two unrelated juvenile patients manifested itself by dystonia and involuntary movements, with facial grimacing, dysarthria, gait difficulty, and impaired manual dexterity. Supranuclear paresis of vertical gaze and splenomegaly were present. Absent were seizures, major intellectual deterioration, spasticity, or blindness. Histiocytes showed lysosomal storage of various phospholipids, cholesterol, neutral lipids, and autofluorescent material. Appendiceal neurons showed only an increase of phospholipids by histochemistry. Neuronal deposits differed ultrastructurally from these in histiocytes. Leukocyte sphingomyelinase activity was normal. The nosology of this disease and its relationship to so-called juvenile types of Niemann-Pick disease is discussed. The primaly metabolic defect in these patients remains unknown.