GONG p-Mode Parameters Through Two Solar Cycles.

We investigate the parameters of global solar p-mode oscillations, namely damping width Γ , amplitude A , mean squared velocity 〈 v 2 〉 , energy E , and energy supply rate d E / d t , derived from two solar cycles' worth (1996 - 2018) of Global Oscillation Network Group (GONG) time series for harmonic degrees l = 0 - 150 . We correct for the effect of fill factor, apparent solar radius, and spurious jumps in the mode amplitudes. We find that the amplitude of the activity-related changes of Γ and A depends on both frequency and harmonic degree of the modes, with the largest variations of Γ for modes with 2400 µ Hz ≤ ν ≤ 3300 µ Hz and 31 ≤ l ≤ 60 with a minimum-to-maximum variation of 26.6 ± 0.3 % and of A for modes with 2400 µ Hz ≤ ν ≤ 3300 µ Hz and 61 ≤ l ≤ 100 with a minimum-to-maximum variation of 27.4 ± 0.4 % . The level of correlation between the solar radio flux F 10.7 and mode parameters also depends on mode frequency and harmonic degree. As a function of mode frequency, the mode amplitudes are found to follow an asymmetric Voigt profile with ν max = 3073.59 ± 0.18 µ Hz . From the mode parameters, we calculate physical mode quantities and average them over specific mode frequency ranges. In this way, we find that the mean squared velocities 〈 v 2 〉 and energies E of p modes are anticorrelated with the level of activity, varying by 14.7 ± 0.3 % and 18.4 ± 0.3 % , respectively, and that the mode energy supply rates show no significant correlation with activity. With this study we expand previously published results on the temporal variation of solar p-mode parameters. Our results will be helpful to future studies of the excitation and damping of p modes, i.e., the interplay between convection, magnetic field, and resonant acoustic oscillations.

Successful Treatment of ANCA-Associated Vasculitis in the Setting of Common Variable Immunodeficiency Using Rituximab.

Autoimmune diseases such as idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia have a high reported prevalence in patients with common variable immunodeficiency (CVID). We describe the case of a 36-year-old Hispanic man with CVID treated with intravenous immunoglobulin, who developed antineutrophilic cytoplasmic antibodies (ANCA)-associated vasculitis 15 years after immunodeficiency diagnosis. After failing first-line immunosuppressive therapy, the patient was successfully treated with rituximab. Although autoimmunity in the setting of CVID is well documented, this is the first report to describe a case of ANCA-associated vasculitis associated with CVID. Moreover, we report effective and safe use of rituximab in a patient with primary immunodeficiency.

Bladder Injury From Penetrating Trauma of the Inner Thigh.

This is a unique case of bladder injury from a penetrating upper leg wound. The patient's initial presentation did not suggest genitourinary injury, however the patient had a relatively late episode of gross hematuria that prompted further investigation. Based on findings of bladder laceration, the patient was managed conservatively and did well. To our knowledge an injury with this particular trajectory and mechanism has not been described previously in the literature. It stands as a reminder that genitourinary trauma can have many points of origin and that a high index of suspicion is necessary during evaluation of these patients.

Dr. Peter Emil Becker and the Third Reich.

In 1985 the physician after whom Becker Muscular Dystrophy is named, German neurologist Dr. Peter Emil Becker (1908-2000), published an autobiographical article in the American Journal of Medical Genetics in which he disavowed any association with the Nazi Party. A closer look at the evidence, however, suggests otherwise. Review of war records and related sources raise concern for Dr. Becker's affiliation with the Nazi Party and his contributions to its ideology.

The impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients; results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI.

BACKGROUND: The MRC UKALLXI trial tested the efficacy of different central nervous system (CNS) directed therapies in childhood acute lymphoblastic leukaemia (ALL). To evaluate morbidity 555/1826 randomised children underwent prospective psychological evaluations. Full Scale, verbal and performance IQs were measured at 5 months, 3 years and 5 years. Scores were compared in; (1) all patients (n = 555) versus related controls (n = 311), (2) low-risk children (presenting white cell count (WCC) < 50 × 10(9)/l) randomised to intrathecal methotrexate (n = 197) versus intrathecal and high-dose intravenous methotrexate (HDM) (n = 202), and (3) high-risk children (WCC ≥ 50 × 10(9)/l, age ≥ 2 years) randomised to HDM (n = 79) versus cranial irradiation (n = 77). RESULTS: There were no significant differences in IQ scores between the treatment arms in either low- or high-risk groups. Despite similar scores at baseline, results at 3 and 5 years showed a significant reduction of between 3.6 and 7.3 points in all three IQ scores in all patient groups compared to controls (P < 0.002) with a higher proportion of children with IQs < 80 in the patient groups (13% vs. 5% at 3 years p = 0.003). CONCLUSION: Children with ALL are at risk of CNS morbidity, regardless of the mode of CNS-directed therapy. Further work needs to identify individuals at high-risk of adverse CNS outcomes. TRIAL REGISTRATION: ISRCTN: ISRCTN16757172.

The impact of bleeding history, von Willebrand factor and PFA-100(®) on the diagnosis of type 1 von Willebrand disease: results from the European study MCMDM-1VWD.

The relationships between the Platelet Function Analyzer (PFA)-100 and von Willebrand factor (VWF) levels and bleeding score (BS) were evaluated within a multicentre project on Molecular and Clinical Markers for the Diagnosis and Management of type 1 von Willebrand disease (MCMDM-1VWD). PFA-100 closure time, either with epinephrine (EPI) or adenosine diphosphate (ADP)-cartridges, was measured in 107 index cases, 105 affected and 71 unaffected family members, and 79 healthy controls. By regression analysis VWF levels were strongly related to both closure times, with a non-linear progression. In a multiple stepwise regression model, age- and sex-adjusted PFA-100 ADP and VWF ristocetin cofactor activity (VWF:RCo) were independently associated with BS. Most of the variation of BS was predicted by PFA-100 ADP and VWF:RCo alone. In the subgroup of patients with subtle abnormalities of the multimeric pattern, VWF was invariably reduced and closure time prolonged in almost all of them. Neither PFA-100 ADP nor EPI closure times appeared to significantly improve the diagnostic capability of VWF antigen (VWF:Ag) measurement. Thus, in an unselected population a normal PFA-100 would be useful to exclude VWD, but whether it could replace the more specific VWF assay in patients with significant mucocutaneous bleeding symptoms remains to be investigated prospectively.

Relationship between HLA-DP supertype and survival in childhood acute lymphoblastic leukaemia: evidence for selective loss of immunological control of residual disease?

We recently reported that two of six HLA-DP supertypes (DP1-4, 6, 8) were associated with susceptibility (DP2) and resistance (DP1) to childhood acute lymphoblastic leukaemia (ALL). To determine whether DP supertypes are associated with childhood ALL prognosis, we compared treatment outcomes in a cohort (n = 798) of DPB1-typed ALL cases in the UK Medical Research Council UKALL XI trial. No differences in clinical characteristics and outcome between DPB1-typed and untyped (n = 1292) cases suggest no selection bias. Event-free survival (EFS) rates in patients with DP1 and DP3 supertypes were significantly worse than in patients with DP2, DP4, DP6 and DP8 [10-year EFS: 55%; 95% confidence interval (CI) = 49-61%; compared with 64% (61-68%), P = 0.006]. Ten-year EFS in DP1/DP3 heterozygous patients [30% (2-58%)] was significantly worse than in patients with DP1, DP3 or neither allele [56% (50-62%); P = 0.02]. Lack of evidence that DP1 or DP3 are associated with known prognostic factors leads us to suggest that these two supertypes exert an independent effect on prognosis. This may involve abrogation of DP1/3-restricted T-cell control of residual disease due to selective effects of chemotherapy. Further studies of HLA supertypes in relation to outcome in recent childhood ALL trials may resolve this question.

Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD).

The decreased survival of von Willebrand factor (VWF) in plasma has been implicated as a mechanism in a subset of type 1 von Willebrand disease (VWD) patients. We have previously reported that the ratio of plasma levels of VWF and its propeptide (VWFpp) can be used to identify patients with reduced VWF survival. In this study, we report the assay of VWFpp and VWF:Ag in 19 individuals recruited from 6 European centers within the MCMDM-1VWD study. Eight individuals had a VWF:Ag level less than 30 IU/dL. Seven of these patients had a robust desmopressin response and significantly reduced VWF half-life that was predicted by a markedly increased steady-state plasma VWFpp/VWF:Ag ratio. VWF mutations previously associated with reduced VWF survival were identified in each of the 7 individuals. Thus, a substantially increased ratio of steady-state VWFpp/VWF:Ag predicted a reduced VWF half-life in patients with markedly decreased VWF:Ag levels. These data indicate that a reduced VWF survival is found in a subpopulation of patients with type 1 VWD. The systematic assay of both plasma VWF and the VWF propeptide in moderately severe type 1 VWD patients may identify patients with a reduced VWF survival phenotype.

Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD.

We have prospectively evaluated the biologic response to desmopressin in 77 patients with type 1 von Willebrand disease (VWD) enrolled within the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD project. Complete response to desmopressin was defined as an increase of both ristocetin cofactor activity (VWF:RCo) and factor VIII coagulant activity (FVIII:C) to 50 IU/dL or higher and partial response as VWF:RCo or FVIII:C lower than 50 IU/dL after infusion, but at least 3-fold the basal level. Complete response was observed in 83% of patients; partial in 13%; and no response in 4%. Patients with some abnormality of VWF multimeric pattern had significantly lower basal FVIII:C and VWF, lower VWF:RCo/Ag ratio, and less complete responses to desmopressin than patients with a normal multimeric pattern (P=.002). Patients with mutations at codons 1130 and 1205 in the D'-D3 domain had the greatest relative increase, but shortest FVIII and VWF half-lives after infusion. Most partial and nonresponsive patients had mutations in the A1-A3 domains. Response to desmopressin in these VWD patients seemed to be associated with the location of the causative mutation. The presence of subtle multimeric abnormalities did not hamper potential clinically useful responses, as in typical type 1 VWD.

Incision and drainage followed by mattress suture repair of auricular hematoma.

OBJECTIVE: Auricular hematoma is a condition requiring early and effective management to prevent pathogenesis of the unsightly cauliflower ear. The objective of this study is to review cases of auricular hematoma and present incision and drainage followed by through-and-through whip-type absorbable mattress sutures without bolsters as an effective treatment. STUDY DESIGN: Retrospective chart review of auricular hematoma cases. METHODS: A 5-year retrospective evaluation of auricular hematomas presenting to an otolaryngology group was performed. Patients' charts were reviewed and data regarding the treatment and follow-up of auricular hematomas were assembled and analyzed. RESULTS: Twenty-two patients were found to present with auricular hematoma. One patient was lost to follow-up. Twenty-eight treatments were performed on 23 ears. Seven hematomas were treated with needle aspiration, two were treated with incision and drainage with iodoform wick placement, and 19 were treated with incision and drainage followed by absorbable mattress sutures. There were five hematoma reaccumulations requiring an additional procedure after treatment by an otolaryngologist. Three followed needle drainage; one followed incision and drainage with wick placement, and one followed incision and drainage with absorbable mattress sutures. CONCLUSION: Incision and drainage followed by through-and-through absorbable mattress sutures appears to be a superior method of treatment with rare reaccumulation of hematoma. This method of treatment was shown to be simple and well tolerated, and it had few complications.

Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV.

Since the 1970s, mortality in the hemophilia population has been dominated by human immunodeficiency virus (HIV) and few reports have described mortality in uninfected individuals. This study presents mortality in 6018 people with hemophilia A or B in the United Kingdom during 1977 to 1998 who were not infected with HIV, with follow-up until January 1, 2000. Given disease severity and factor inhibitor status, all-cause mortality did not differ significantly between hemophilia A and hemophilia B. In severe hemophilia, all-cause mortality did not change significantly during 1977 to 1999. During this period, it exceeded mortality in the general population by a factor of 2.69 (95% confidence interval [CI]: 2.37-3.05), and median life expectancy in severe hemophilia was 63 years. In moderate/mild hemophilia, all-cause mortality did not change significantly during 1985 to 1999, and median life expectancy was 75 years. Compared with mortality in the general population, mortality from bleeding and its consequences, and from liver diseases and Hodgkin disease, was increased, but for ischemic heart disease it was lower, at only 62% (95% CI: 51%-76%) of general population rates, and for 14 other specific causes it did not differ significantly from general population rates. There was no evidence of any death from variant Creutzfeldt-Jakob disease or from conditions that could be confused with it.

Ciprofloxacin/dexamethasone drops decrease the incidence of physician and patient outcomes of otorrhea after tube placement.

OBJECTIVE: To evaluate ciprofloxacin 0.3%/dexamethasone 0.1% (CIPRODEX, Alcon, Ft. Worth, TX) for the prevention of early post-operative otorrhea following TT placement. METHODS: This was a single-center, randomized, evaluator-blinded, parallel-group study. Two hundred children undergoing bilateral TT placement were categorized as having unilateral ("wet/dry"), bilateral ("wet/wet"), or no ("dry/dry") effusion at the time of surgery. All patients received Ciprodex or no treatment for 5 days post-operatively and returned at 2 weeks. RESULTS: Physician-observed otorrhea was reported in 5 (4.95%) patients receiving Ciprodex and 39 (39.39%) patients receiving no treatment (p<0.0001). Treatment decreased otorrhea in all groups, while the greatest benefit was observed in patients with bilateral effusion (93% reduction). Ciprodex treatment also decreased the rate of clinically diagnosed otitis media (OM) and effusion following TT placement (p< or =0.0006). CONCLUSION: Ciprodex reduced early post-operative otorrhea, clinically diagnosed OM and effusion following TT insertion. The greatest reduction in otorrhea was observed in patients with bilateral effusion at the time of surgery.

Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD).

Type 1 von Willebrand disease (VWD) is characterized by a personal and family history of bleeding coincident with reduced levels of normal plasma von Willebrand factor (VWF). The molecular basis of the disorder is poorly understood. The aims of this study were to determine phenotype and genotype and their relationship in patients historically diagnosed with type 1 VWD. Families were recruited in 9 European countries based on previous type 1 VWD diagnosis. Bleeding symptoms were recorded, plasma phenotype analyzed, and VWF mutation analysis performed in all index cases (ICs). Phenotypic and molecular analysis stratified patients into those with or without phenotypes suggestive of qualitative VWF defects (abnormal multimers) and with or without mutations. A total of 105 of 150 ICs (70%) had mutations identified. A subgroup with abnormal multimers (38% of ICs, 57 of 150) showed a high prevalence of VWF gene mutations (95% of ICs, 54 of 57), whereas in those with qualitatively normal VWF, fewer mutations were identified (55% of ICs, 51 of 93). About one third of the type 1 VWD cases recruited could be reconsidered as type 2. The remaining group could be considered "true" type 1 VWD, although mutations were found in only 55%.

An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease.

Forty families diagnosed by UK centres to have type 1 VWD were recruited. Following review, six families were re-diagnosed to have type 2 VWD, one to have a platelet storage pool disorder, and one family was determined to be unaffected. Direct DNA sequencing of the promoter region and all exons and intronic boundaries of the VWF gene identified six mutations likely to be causative of VWD in index cases of nine of the 32 (28%) confirmed type 1 VWD families. These included R1205H (3614G > A) VWD Vicenza, P1648fsX45 (4944delT), D141G (422A > G) and three splice site mutations: 3108 + 5G > A, 7437 + 1G > A and 3379 + 1G > A. The Y1584C (4751A > G) polymorphism was present in eight additional families. No significant VWF gene mutation or polymorphism was identified in 15 of the 32 type 1VWD index cases (47%). Haplotype studies were performed using a panel of VWF polymorphisms to investigate the segregation in families of VWD phenotype with the VWF gene. In 13 of the 32 families it was likely that VWD segregated with the VWF gene. In eight families (25%) VWD clearly did not segregate with the VWF gene. We suggest that mutation screening of the VWF gene has limited general utility in genetic diagnostic and family studies in type 1 VWD. If genetic studies are performed, the incomplete penetrance and variable expressivity of type 1 VWD must be taken into account. Unless linkage of VWD phenotype with the VWF gene can be clearly demonstrated, the results of any genetic family studies should be interpreted with caution.