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The activity and safety profile of selective B-cell depletion with rituximab, an anti-CD20 monoclonal antibody, were evaluated in 10 patients with acquired hemophilia. Rituximab was given intravenously at the dose of 375 mg/m(2) once weekly for 4 consecutive weeks. Infusion-related side effects were observed in 3 patients but were of mild intensity and did not require discontinuation of treatment. Eight patients with Factor VIII (FVIII) inhibitor titers between 4 and 96 Bethesda units per milliliter (BU/mL) achieved a complete remission, which was defined as a return to normal FVIII activity and undetectable FVIII inhibitor titers. Two more patients with inhibitor levels greater than 100 BU/mL experienced only a partial transient decrease of the inhibitor after rituximab alone, but they achieved a complete response after being challenged with a combination of rituximab plus pulse intravenous cyclophosphamide. With a median follow-up of 28.5 months (range, 12-41 months), 3 patients have thus far relapsed. Retreatment with the monoclonal antibody at the same dose and schedule resulted in a new sustained response in all these patients. In conclusion, rituximab appears an effective and well-tolerated treatment for patients with acquired hemophilia and low inhibitor titers. A reinforcement of therapy with other agents seems to be required to achieve a full and durable response in those patients with high inhibitor levels.
This document, EPUB Accessibility Techniques, provides informative guidance on how to understand andapply the discovery and accessibility requirements defined in the EPUB Accessibility 1.1specification [epub-a11y-11] that are unique to EPUB publications.
The accessibility techniques described in this document are advisory in nature. They are intended to helpEPUB creators create EPUB publications that conform to therequirements in [epub-a11y-11], but they are not all applicable in all situations and there may beother ways to meet the requirements of that specification. As a result, this document should not be readas providing prescriptive requirements.
As an example of setting sufficient access modes, consider an EPUB publication that contains graphicsand charts, as well as descriptions for all these images. The publication has both textual andvisual content, so the EPUB creator willinclude the following schema:accessMode metadata entries to indicate this:
This metadata does not make clear whether a textual access mode is sufficient to read the entirepublication, or whether a visual one is, only that the user requires the ability to read in thosetwo modes by default. This discrepancy is why sufficiency is also important to know.
Setting the correct access modes and sufficient access modes for EPUB 3 publications that containsynchronized text-audio playback requires evaluating whether playback is essential to reading thepublication or an additional feature.
If an EPUB publication does not meet the requirements for content accessibility in [epub-a11y-11],the reason(s) it fails should be noted in the summary. Similarly, if an EPUB creator is hesitant tomake a formal claim of conformance, the reasons why can be explained in the summary.
As EPUB allows two EPUB contentdocuments to be rendered together in a synthetic spread [epub-3], the order of content within a single document cannotalways be evaluated in isolation. Content may span visually from one document to the next. Forexample, a sidebar might span the bottom of two pages.
[wcag2] Success Criterion 2.4.5 requires there be morethan one way to locate a web page within a set of web pages. By default, EPUB publications meet this WCAGrequirement so long as EPUB creatorsfollow the EPUB requirements to include allEPUB content documents in the spine and ensure access to all non-lineardocuments [epub-3].
The reason an EPUB publication passes by meeting these requirements has to do with differences inhow a user interacts with the set of documents in an EPUB publication. In particular, althoughan EPUB publication typically consists of many EPUB content documents, reading systems automaticallyprovide the ability for the user to move seamlessly from one document to the next, so long asthey are listed in the spine [epub-3]. To the user, an EPUB publication is a single document they have completeaccess to, not a set of disconnected pages that they need links to move through.
The required table of contents provides a second method to access the major headings of thepublication. The user can jump to any heading and continue to navigate from there, regardless ofhow the publication is chunked.
A common question about the EPUB table of contents is what completeness it needs to have withrespect to the headings of the publication. Although the obvious answer seems like it shouldbe a simple aggregation of all headings for all sections, practically there are severalusability challenges to this approach.
When EPUB creators choose not to provide links to all the headings, however, they shouldoptimize the linking they do provide for the best overall reading experience. Someconsiderations on how to achieve this include:
Although visually these restructuring decisions can be hidden from readers, they impact thefunctionality of assistivetechnologies. In the case of [wai-aria] roles, the result is that only the subset presentin the currently-loaded EPUB content document are exposed to users. An assistive technologycannot provide a list of landmarks for the whole publication, as it cannot see outside thecurrent document.
[wai-aria] landmarks are similar in nature to EPUB landmarks [epub-3]: both aredesigned to provide users with quick access to the major structures of a document, such aschapters, glossaries and indexes. ARIA landmarks are compiled automatically by assistive technologies from the roles that have been applied to the markup, so EPUB creators only need to followthe requirement to include roles for the landmarks to be made available to users.
Although automatic generation of ARIA landmarks simplifies authoring, it also means that ARIAlandmarks are limited to how the EPUB publication has been chunked up into EPUB content documents. Anassistive technology can only present the landmarks available in the currently-loaded document;it cannot provide a complete picture of all the landmarks in a multi-document publication (seethe previous section for more discussion about content chunking).
EPUB landmarks, on the other hand, are compiled by the EPUB creator prior to distribution, andare not directly linked to the use of the type attribute [epub-3] in the content. They are designed to simplifylinking to major sections of the publication in a machine-readable way, as reading systems do not scanthe entire publication for landmarks, either. EPUB landmarks are typically not as numerous asARIA landmarks, as reading systems only expose so many of these navigation aids.
Consequently, it is necessary to provide the language of all text content in the package documentto conform with these WCAG success criteria. The easiest way to meet this requirement is to addan xml:lang attribute on the root package element[epub-3].
Although it is not strictly required to set this information to meet [wcag2] Success Criterion 3.1.1, as it is non-normative, itshould be considered a best practice to always set this field with the proper languageinformation. (Note that EPUB3 requires the language always be specified, so omitting will failvalidation requirements.)
The [epub-multi-rend-11] specification defines a set of features for creating these types of EPUBpublications. It specifies a set of attributes that allow a reading system to automaticallyselect a preferred rendition for the user or to provide the user the option to manually selectbetween the available options. This functionality technically meets the requirements of [wcag2] interms of ensuring the user can access the accessible version.
In practice, however, the [epub-multi-rend-11] specification is not broadly supported in readingsystems at the time of publication. As a result, a user who obtains an EPUB publication thatcontains more than one rendition will only have access to the default. Unless this rendition is theaccessible one, the EPUB publication might not be readable by them.
EPUB creators therefore need to use theirbest discretion when implementing this functionality to meet accessibility requirements. EPUBpublications that contain multiple renditions are conformant to the [epub-a11y-11] specificationif at least one rendition meets all the content requirements, but EPUB creators at a minimum need tonote that a reading system that supports multiple renditions is required in their accessibility summary. Any other methods the EPUB creator can use to makethis dependence known is advisable (e.g., in the distribution metadata).
Both the EPUB Structural Semantics Vocabulary [epub-ssv] and Digital Publishing WAI-ARIA 1.0Module [dpub-aria-1.0] include a semantic for static page breaks: pagebreak and doc-pagebreak, respectively.
Users typically want to know the source of the page break markers included in an EPUB publication when they arederived from a static media. Considerations like which printing, by which publisher or imprint,and whether the pagination comes from the hard or soft cover edition will affect decisions aboutits usefulness (e.g., does it exactly match the pagination of a print book used in aclassroom).
Ensuring the complete text of an EPUBpublication is synchronized with audio is key to allowing users who require fullsynchronized playback, or even audio-only playback, have access to the same information as userswho do not require synchronized playback.
The primary consideration for this objective is what constitutes the text content of an EPUBpublication. The minimal candidates for synchronization with audio are all the elements withvisible text content.
The media overlays textelement is used to reference these elements, either to play back the pre-recorded audioin a sibling audioelement [epub-3] or to initiate playback of an audio or video element if theaudio element is missing (e.g., for embedded audio and video in thedocument). 153554b96e
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