Is juvenile dermatomyositis a different disease in children up to three years of age at onset than in children above three years at onset? A retrospective review of 23 years of a single center’s experience

BACKGROUND: We tested the hypothesis that the course and outcome of juvenile dermatomyositis (JDM) in children seen at one center with the JDM disease onset at or below three years of age is different from that in the children with disease onset at greater than three years of age. METHODS: Institutional Review Board approval was obtained to retrospectively review the charts of 78 patients from age 0–18 years with JDM seen in the pediatric rheumatology clinic at Nationwide Children’s Hospital in Columbus, Ohio over the past 23 years from January 1988. The diagnosis was made by the treating pediatric rheumatologist. Not all the patients met the Bohan and Peter criteria, as muscle biopsy and EMG were not always performed and we utilized a modified JDM criteria. The data regarding disease course and outcome were collected as of the last clinic follow-up or to July 1, 2010. We used the Wilcoxon Two-Sample test to compare numerical variables between two age groups, and used logistic regression to compare categorical variables between two age groups in SAS 9.1.3. Minitab-16 was used to calculate various mean, median, modes, standard deviations and range. For survival analysis, we used Kaplan-Meier method with log-rank test. RESULTS: The mean age of onset in the two groups at Nationwide Children’s Hospital was 27 months and 91 months. The mean times between onset of symptoms to diagnosis in the younger and older age groups was 5.6 months and 4.5 months, respectively, not a statistically significant difference. The younger onset group had more females (p=0.05) and their disease onset occurred less frequently during the typical winter-spring seasons (p=0.031). The younger onset group was more likely to have a preceding fever (p=0.029) and family history of autoimmune diseases (p=0.012). The younger onset group was less likely to have heliotrope rash (p=0.04), Gottron’s sign (p=0.049), capillary loop abnormalities (p=0.010), or elevations in creatine kinase (CK, p=0.022), aspartate aminotransferase (AST, p=0.021) or aldolase (p=0.035). The younger onset group was treated less often with pulse methylprednisolone at diagnosis (p=0.043) and less often with hydroxychloroquine (p=0.035). There were no differences between the two groups regarding initial oral steroid dose (p=0.8017), number of patients who received methotrexate at diagnosis (p=0.709), and the number who ever received other immunosuppressants (p=0.323). The mean and maximum duration (mean duration 24.3 months vs. 35.2 months, maximum duration 51 vs. 124 months in younger and older onset group respectively) of methotrexate therapy, and the mean and maximum duration of oral steroid therapy (Mean duration 16.8 months vs. 33.3 months, maximum duration 50 vs. 151 months in younger and older onset group respectively), was shorter in the younger group. The younger onset patients were less likely to have active disease at 5 years (9% vs. 35.7%, p=0.015) and 10 years post-diagnosis (9% vs. 45.1%, p=0.011, Table 7). The younger patients were less likely to have osteonecrosis (p=0.023). Two disease-related deaths occurred in the younger group, none in the older group. The results of the survival analysis showed that the difference between the age groups was statistically significant (p < 0.012). The sex and race were not significant (p> 0.26 and p>0.95, respectively). CONCLUSIONS: There were significant differences between JDM patients with disease onset at or below age three years at our center, compared to their older counterparts. Younger patients in our cohort had fewer typical findings at diagnosis and a milder disease course without needing as long a duration of corticosteroids and immunosuppression. Patients with a younger onset had a higher mortality rate but mortalities were unusual and numbers small. The younger group had a similar complication rate compared to the older onset patients, except for osteonecrosis which was higher in the older onset group. These findings differ from the previous reports that a younger age of onset in JDM is often associated with a more severe disease, as results at our center suggest that children with younger onset JDM appear to be atypical but may do well compared to the older JDM patients

A study to determine methods of improving the subsonic performance of a proposed Personnel Launch System (PLS) concept

An investigation has been conducted in the Langley 7- by 10-Foot High Speed Wind Tunnel to determine the longitudinal and lateral directional aerodynamic characteristics of a series of personnel launch system concepts. This series of configurations evolved during an effort to improve the subsonic characteristics of a proposed lifting entry vehicle (designated the HL-20). The primary purpose of the overall investigation was to provide a vehicle concept which was inherently stable and trimable from entry to landing while examining methods of improving subsonic aerodynamic performance

Fostering bioinformatics education through skill development of professors: Big Genomic Data Skills Training for Professors.

Bioinformatics has become an indispensable part of life science over the past 2 decades. However, bioinformatics education is not well integrated at the undergraduate level, especially in liberal arts colleges and regional universities in the United States. One significant obstacle pointed out by the Network for Integrating Bioinformatics into Life Sciences Education is the lack of faculty in the bioinformatics area. Most current life science professors did not acquire bioinformatics analysis skills during their own training. Consequently, a great number of undergraduate and graduate students do not get the chance to learn bioinformatics or computational biology skills within a structured curriculum during their education. To address this gap, we developed a module-based, week-long short course to train small college and regional university professors with essential bioinformatics skills. The bioinformatics modules were built to be adapted by the professor-trainees afterward and used in their own classes. All the course materials can be accessed at https://github.com/TheJacksonLaboratory/JAXBD2K-ShortCourse

Helical magnetic structure and the anomalous and topological Hall effects in epitaxial B20 Fe1−y_{1-y}Coy_yGe films

Epitaxial films of the B20-structure alloy Fe$_{1-y}$Co$_y$Ge were grown by molecular beam epitaxy on Si (111) substrates. The magnetization varied smoothly from the bulk-like values of one Bohr magneton per Fe atom for FeGe to zero for non-magnetic CoGe. The chiral lattice structure leads to a Dzyaloshinskii-Moriya interaction (DMI), and the films' helical magnetic ground state was confirmed using polarized neutron reflectometry measurements. The pitch of the spin helix, measured by this method, varies with Co content $y$ and diverges at $y \sim 0.45$. This indicates a zero-crossing of the DMI, which we reproduced in calculations using first principle methods. We also measured the longitudinal and Hall resistivity of our films as a function of magnetic field, temperature, and Co content $y$. The Hall resistivity is expected to contain contributions from the ordinary, anomalous, and topological Hall effects. Both the anomalous and topological Hall resistivities show peaks around $y \sim 0.5$. Our first principles calculations show a peak in the topological Hall constant at this value of $y$, related to the strong spin-polarisation predicted for intermediate values of $y$. Half-metallicity is predicted for $y = 0.6$, consistent with the experimentally observed linear magnetoresistance at this composition. Whilst it is possible to reconcile theory with experiment for the various Hall effects for FeGe, the large topological Hall resistivities for $y \sim 0.5$ are much larger then expected when the very small emergent fields associated with the divergence in the DMI are taken into account

The preservation of erythrocytes at liquid nitrogen temperatures with hydroxyethyl starch: the removal of hydroxyethyl starch from erythrocytes after thawing

Packed human erythrocytes were frozen in liquid nitrogen using hydroxyethyl starch as a cryoprotective agent. Upon thawing, the cells were washed with a balanced salt solution. The washed cells were stable when resuspended in 0.154 n NaCl. The postthaw saline stability approximated the total recovery after washing the cells. Intracellular potassium loss was 15% immediately postthaw, and an additional 15% loss occurred after washing. These results indicate that HES can be removed from frozen-thawed cells by washing, and that freezing erythrocytes protected by HES does not result in significant losses of intracellular potassium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33516/1/0000014.pd

Social Freedom and Self-Actualization: “Normative Reconstruction” as a Theory of Justice

In Freedom's Right Axel Honneth seeks to provide a theory of justice by appropriatingHegel's account of ethical substance in the Philosophy of Right, but hewants to do sowithout endorsingHegel'smore robust idealist commitments. I argue that this project can only succeed if Honneth can offer an alternative, comparatively robust demonstration of the rationality and normative coherence of existing social institutions. I contend that the grounds Honneth provides for this claimare insufficient for his purposes. In particular, I argue that Honneth's claim that "justice and individual self-determination are mutually referential," even were it to be accepted, would be insufficient to underwrite hismore robust identification between the normative foundations of justice, autonomy and reciprocal self-realization. In the final section of the paper, I turn to Honneth's analysis of the "social institution" of friendship,which he, followingHegel, holds up as a paradigmatic instantiation of social freedom understood as, in Hegel's words, "being with oneself in another" (Beisichselbstsein in einem Anderen). I argue that an analysis of the normative import of friendship wholly in terms of mutual recognition misses an important aspect of the kind of self-realization that friendship makes possible

Early Components of the Complement Classical Activation Pathway in Human Systemic Autoimmune Diseases

The complement system consists of effector proteins, regulators, and receptors that participate in host defense against pathogens. Activation of the complement system, via the classical pathway (CP), has long been recognized in immune complex-mediated tissue injury, most notably systemic lupus erythematosus (SLE). Paradoxically, a complete deficiency of an early component of the CP, as evidenced by homozygous genetic deficiencies reported in human, are strongly associated with the risk of developing SLE or a lupus-like disease. Similarly, isotype deficiency attributable to a gene copy number variation, and/or the presence of autoantibodies directed against a CP component or a regulatory protein that result in an acquired deficiency are relatively common in SLE patients. Applying accurate assay methodologies with rigorous data validations, low gene copy numbers of total C4, heterozygous and homozygous deficiencies of C4A have been shown as medium to large effect size risk factors, while high copy numbers of total C4 or C4A as prevalent protective factors, of European and East-Asian SLE. Here, we summarize the current knowledge related to genetic deficiency and insufficiency, and acquired protein alterations for C1q, C1r, C1s, C4A/C4B, and C2 in disease pathogenesis and prognosis of SLE, and, briefly, for other systemic autoimmune diseases. As the complement system is increasingly found to be associated with autoimmune diseases, it has become an attractive therapeutic target. We highlight the recent developments and offer a balanced perspective concerning future investigations and therapeutic applications with a focus on early components of the CP in human systemic autoimmune diseases