Key Points• The inhibitor incidence in nonsevere hemophilia A patients with certain F8 mutations approaches the inhibitor incidence in severe patients.• These findings are highly relevant for clinical practice, as they facilitate identification of high-risk patients based on F8 genotype.Neutralizing antibodies (inhibitors) toward factor VIII form a severe complication in nonsevere hemophilia A, profoundly aggravating the bleeding pattern. Identification of high-risk patients is hampered by lack of data that take exposure days to therapeutic factor VIII concentrates into account. In the INSIGHT study, we analyzed the association between F8 mutation and inhibitor development in patients with nonsevere hemophilia A (factor VIII 2-40 IU/dL). This analysis included 1112 nonsevere hemophilia A patients from 14 centers in Europe and Australia that had genotyped at least 70% of their patients. Inhibitor risk was calculated as KaplanMeier incidence with cumulative number of exposure days as the time variable. During 44 800 exposure days (median, 24 exposure days per patient; interquartile range [IQR], 7-90), 59 of the 1112 patients developed an inhibitor; cumulative incidence of 5.3% (95% confidence interval [CI], 4.0-6.6) after a median of 28 exposure days (IQR,. The inhibitor risk at 50 exposure days was 6.7% (95% CI, 4.5-8.9) and at 100 exposure days the risk further increased to 13.3% (95% CI, 9.6-17.0). Among a total of 214 different F8 missense mutations 19 were associated with inhibitor development. These results emphasize the importance of F8 genotyping in nonsevere hemophilia A. (Blood. 2013; 122(11):1954-1962 IntroductionPatients with hemophilia A who are treated with factor VIII concentrates are at risk of developing factor VIII neutralizing alloantibodies (inhibitors).1,2 Inhibitor development is one of the most challenging complications in the treatment of hemophilia A, as it increases the bleeding tendency while it renders treatment with therapeutic factor VIII concentrates ineffective. Although inhibitor development is less frequently observed in patients with nonsevere hemophilia A (baseline factor VIII activity of 2-40 IU/dL), the clinical impact can be profound. In these patients, inhibitors may also interact with their endogenous factor VIII, resulting in a decrease of the factor VIII plasma level below 1 IU/dL 1 and major bleeding complications. 4 Identification of patients at risk of developing inhibitors may help to prevent this serious complication. However, currently there are no tools available to predict individual inhibitor risk in nonsevere hemophilia patients.The type of mutation in the factor VIII gene (F8) is an important risk factor for inhibitor development. [5][6][7] Nonsevere hemophilia A is generally caused by F8 missense mutations.8 Despite information on large numbers of F8 mutations associated with nonsevere hemophilia A that is collected in international databases, 9,10 it is not possible to calculate the inhibitor risk for specific F8 mutations, as data on exposure days to thera...

Abstract. The Plasma Wave Instrument on the Polar spacecraft is designed to provide measurements of plasma waves in the Earth's polar regions over the frequency range from 0.l Hz to 800 kHz. Three orthogonal electric dipole antennas are used to detect electric fields, two in the spin plane and one aligned along the spacecraft spin axis. A magnetic loop antenna and a triaxial magnetic search coil antenna are used to detect magnetic fields. Signals from these antennas are processed by five receiver systems: a wideband receiver, a high-frequency waveform receiver, a low-frequency waveform receiver, two multichannel analyzers; and a pair of sweep frequency receivers. Compared to previous plasma wave instruments, the Polar plasma wave instrument has several new capabilities. These include (1) an expanded frequency range to improve coverage of both low-and high-frequency wave phenomena, (2) the ability to simultaneously capture signals from six orthogonal electric and magnetic field sensors, and (3) a digital wideband receiver with up to 8-bit resolution and sample rates as high as 249k samples s -_ .

Summary. Background: The life expectancy of non-severe hemophilia A (HA) patients equals the life expectancy of the non-hemophilic population. However, data on the effect of inhibitor development on mortality and on hemophilia-related causes of death are scarce. The development of neutralizing factor VIII antibodies in non-severe HA patients may dramatically change their clinical outcome due to severe bleeding complications. Objectives: We assessed the association between the occurrence of inhibitors and mortality in patients with non-severe HA. Methods: In this retrospective cohort study, clinical data and vital status were collected for 2709 non-severe HA patients (107 with inhibitors) who were treated between 1980 and 2011 in 34 European and Australian centers. Mortality rates for patients with and without inhibitors were compared. Results: During 64 200 patient-years of follow-up, 148 patients died (mortality rate, 2.30 per 1000 person-years; 95% confidence interval (CI), 1.96-2.70) at a median age of 64 years (interquartile range [IQR], 49-76). In 62 patients (42%) the cause of death was hemophilia related. Sixteen inhibitor patients died at a median age of 71 years (IQR,. In ten patients the inhibitor was present at time of death; seven of them died of severe bleeding complications. The all-cause mortality rate in inhibitor patients was > 5 times increased compared with that for those without inhibitors (ageadjusted mortality rate ratio, 5.6). Conclusion: Inhibitor development in non-severe hemophilia is associated with increased mortality. High rates of hemophilia-related mortality in this study indicate that non-severe hemophilia is not mild at all and stress the importance of close follow-up for these patients.

BackgroundAcquired myasthenia gravis (MG) in cats most commonly causes generalized weakness without megaesophagus and is more often associated with a cranial mediastinal mass, compared to dogs.Hypothesis/ObjectivesTo extend the clinical findings described in the report of 2000 on MG in cats (J Am Vet Med Assoc 215:55–57).AnimalsTwo hundred and thirty‐five cats with MG.MethodsRetrospective case study to evaluate the long‐term outcome and incidence of spontaneous remission in myasthenic cats. Information including signalment, clinical presentation, presence of and type of cranial mediastinal mass, treatment including surgical versus medical, survival time, and outcome including spontaneous remissions was collected and analyzed in cats diagnosed at the Comparative Neuromuscular Laboratory, University of California San Diego by detection of acetylcholine receptor antibody titers >0.3 nmol/L by immunoprecipitation radioimmunosassay.ResultsAcquired MG in cats is associated with a euthanasia rate of 58%. Abyssinian and Somali cats had an increased incidence of MG compared to mixed breed cats or cats of other breeds. A cranial mediastinal mass, most commonly thymoma, was observed in 52% of the cats, which is higher than in the previous report. Spontaneous remission is not a characteristic of MG in cats.Conclusions and clinical importanceMyasthenia gravis in cats is a chronic disease associated with a high incidence of a cranial mediastinal mass. Spontaneous remission is not common and clinicians should warn owners of the necessity for long‐term treatment. The clinical outcome with a cranial mediastinal mass did not differ between surgical or medical treatment.

Background Screening has become one of our best tools for early detection and prevention of cancer. The group-randomized trial is the most rigorous experimental design for evaluating multilevel interventions. However, identifying the proper sample size for a group-randomized trial requires reliable estimates of intraclass correlation (ICC) for screening outcomes, which are not available to researchers. We present crude and adjusted ICC estimates for cancer screening outcomes for various levels of aggregation (physician, clinic, and county) and provide an example of how these ICC estimates may be used in the design of a future trial. Methods Investigators working in the area of cancer screening were contacted and asked to provide crude and adjusted ICC estimates using the analysis of variance method estimator. Results Of the 29 investigators identified, estimates were obtained from 10 investigators who had relevant data. ICC estimates were calculated from 13 different studies, with more than half of the studies collecting information on colorectal screening. In the majority of cases, ICC estimates could be adjusted for age, education, and other demographic characteristics, leading to a reduction in the ICC. ICC estimates varied considerably by cancer site and level of aggregation of the groups. Conclusions Previously, only two articles had published ICCs for cancer screening outcomes. We have complied more than 130 crude and adjusted ICC estimates covering breast, cervical, colon, and prostate screening and have detailed them by level of aggregation, screening measure, and study characteristics. We have also demonstrated their use in planning a future trial and the need for the evaluation of the proposed interval estimator for binary outcomes under conditions typically seen in GRTs.