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Advances in health information technology, such as electronic health records (EHRs) and disease registries, promise new sources of evidence on the effectiveness of health interventions. As these data sources become more readily accessible to investigators, they are likely to supplement or even replace clinical trials data in SRs of

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CER. Furthermore, as with other data sources, the potential for bias and confounding will need to be addressed.

The Food and Drug Administration Sentinel Initiative and related activities (e.g., Observational Medical Outcomes Partnership) may be an important new data source for future SRs. When operational, the Sentinel Initiative will be a national, integrated, electronic database built on EHRs and claims records databases for as many as 100 million individuals (HHS, 2010; Platt et al., 2009). Although the principal objective of the system is to detect adverse effects of drugs and other medical products, it may also be useful for SRs of CER questions. A “Mini-Sentinel” pilot is currently under development at Harvard Pilgrim Health Care (Platt, 2010) . The system will be a distributed network, meaning that separate data holders will contribute to the network, but the data will never be put into one common repository. Instead, all database holders will convert their data into a common data model and retain control over their own data. This allows a single “program” to be run (e.g., a statistical analysis in SAS) on all the disparate datasets, generating an estimated relative risk (or other measure) from each database. These then can be viewed as a type of meta-analysis.

The fact that available data are conducive to pooling is not in itself sufficient reason to conduct a meta-analysis (Fu et al., 2010). The meta-analysis should not be undertaken unless the anticipated results are likely to produce meaningful answers that are useful to patients, clinicians, or other decision makers. For example, if the same outcomes are measured differently in the individual studies and the measures cannot be converted to a common scale, doing a meta-analysis may not be appropriate (Cummings, 2004). This situation may occur in studies comparing the effect of an intervention on a variety of important patient outcomes such as pain, mental health status, or pulmonary function.

Conducting the Meta-Analysis

Good statistical analyses quantify the amount of variability in the data in order to obtain estimates of the precision with which estimates may be made. Large amounts of variability reduce our confidence that effects are accurately measured. In meta-analysis,

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variability arises from three sources—clinical diversity, methodological diversity, and statistical heterogeneity—which should be separately considered in presentation and discussion (Fu et al., 2010). Clinical diversity describes variability in study population characteristics, interventions, and outcome ascertainments. Methodological diversity encompasses variability in study design, conduct, and quality, such as blinding and concealment of allocation. Statistical heterogeneity, relating to the variability in observed treatment effects across studies, may occur because of random chance, but may also arise from real clinical and methodological diversity and bias.

Assessing the amount of variability is fundamental to determining the relevance of the individual studies to the SR’s research questions. It is also key to choosing which statistical model to use in the quantitative synthesis. Large amounts of variability may suggest a poorly formulated question or many sources of uncertainty that can influence effects. As noted above, if the individual studies are so diverse in terms of populations, interventions, comparators, outcomes, time lines, and/or settings, summary data will not yield clinically meaningful conclusions about the effect of an intervention for important subgroups of the population (West et al., 2010).

In general, quantifying heterogeneity helps determine whether and how the data may be combined, but specific tests of the presence of heterogeneity can be misleading and should not be used because of their poor statistical properties and because an assumption of complete homogeneity is nearly always unrealistic (Higgins et al., 2003). Graphical representations of among-study variation such as forest plots can be informative ( Catz Print Sweat Dress B933 Love Moschino rgl6zwzPeP
) (Anzures-Cabrera and Higgins, 2010).

When pooling is feasible, investigators typically use one of two statistical techniques—fixed-effects or random-effects models—to analyze and integrate the data, depending on the extent of heterogeneity. Each model has strengths and limitations. A fixed-effects model assumes that the treatment effect is the same for each study. A random-effects model assumes that some heterogeneity is present and acceptable, and the data can be pooled. Exploring the potential sources of heterogeneity may be more important than a decision about the use of fixed- or random-effects models. Although the committee does not believe that any single statistical technique should be a methodological standard, it is essential that the SR team clearly explain and justify the reasons why it chose the technique actually used.

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FIGURE 4-1 Forest plot.

SOURCE: Schriger et al. (2010).

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In meta-analyses, the amount of within- and between-study variation determines how precisely study and aggregate treatment effects are estimated. Estimates of effects without accompanying measures of their uncertainty, such as confidence intervals, cannot be correctly interpreted. A forest plot can provide a succinct representation of the size and precision of individual study effects and aggregated effects. When effects are heterogeneous, more than one summary effect may be necessary to fully describe the data. Measures of uncertainty should also be presented for estimates of heterogeneity and for statistics that quantify relationships between treatment effects and sources of heterogeneity.

PRESS RELEASE June 4, 2018

Charter Communications to Offer AppleTV4K to Spectrum Cable Customers

San Jose, California — Apple today previewed tvOS 12, the powerful operating system designed for enjoying entertainment on the big screen, which takes the cinematic experience of Apple TV 4K to the next level with support for Dolby Atmos audio, convenient new features to easily access the shows and movies you love and breathtaking aerials shot from space.
Apple TV 4K has been a hit since its debut last fall, offering customers the largest collection of 4K HDR movies, including free 4K HDR upgrades to previously purchased movies in customers’ iTunes libraries. This fall, iTunes will be home to the largest collection of Dolby Atmos-supported movies anywhere, and these titles will also include Dolby Atmos audio for free. With tvOS 12, Apple TV 4K will be the only streaming player both Dolby Vision and Dolby Atmos certified, delivering the highest quality cinematic experience of stunning 4K HDR visuals and immersive sound that flows all around in three-dimensional space.
Video providers around the world are choosing Apple TV 4K to deliver their subscription services to customers. Apple today announced that Charter Communications, the second-largest cable operator in the US, will begin offering Apple TV 4K to their customers. Later this year, customers in nearly 50 million households will have access to live channels and tens of thousands of on-demand programs via an all-new Spectrum TV app on their Apple TV 4K, iPhone and iPad, seamlessly integrated with Siri and the Apple TV App. In addition, as part of this collaboration, Charter will be offering iPhone and iPad to customers as they grow their mobile presence. Charter joins ATT’s DirecTV Now in the US, CANAL+ in France and Salt in Switzerland, which have begun offering their customers Apple TV 4K with their services.
The Apple TV App on iPhone, iPad and Apple TV is the single destination to find and watch TV shows and movies from more than 100 participating video apps in 10 countries. Single sign-on for Apple TV and iOS has allowed users to sign in once to get access to all the video apps available through their cable subscription. With tvOS 12, Apple further simplifies the authentication process with zero sign-on. Apple TV simply detects the user’s broadband network and automatically signs them in to all the supported apps they receive through their subscription — no typing required. Zero sign-on begins with Charter later this year and will expand to other providers over time.
Aerial screensavers are a favorite of Apple TV users and reach new heights with tvOS 12. Apple, in collaboration with the International Space Station National Lab and the Center for the Advancement of Science in Space, unveiled brand new aerials shot from space by NASA astronauts, so Apple TV customers can enjoy even more stunning scenes filmed in 4K HDR. Aerial screensavers will also be more interactive, allowing viewers to see the location information and swipe between dozens of beautiful aerials.
Additional tvOS 12 features for Apple TV 4K and Apple TV 4th generation make it even easier for customers to access the shows and movies they love:
Availability
The tvOS developer preview is available for Apple Developer Program members at skull print hitops Black Mastermind Japan Pce32WmQ0
starting today. The new tvOS will be available this fall as a free software update for Apple TV 4K and Apple TV 4th generation. For more information, visit apple.com/apple-tv-4K . Features are subject to change. Some features may not be available in all regions or all languages.

Images of Apple TV 4K and Dolby Atmos

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> Touring prestigious and notable universities in the U.S.

Contents

From Wikivoyage

Many foreign visitors to the Sale Rion Dot Dress Little Remix Little Remix 61tTO4IDk1
, especially those with pre-college-age children thinking about studying abroad , are interested in touring its famous universities. This article is a short overview of university tourism in the U.S., focused on the nation's most prestigious research and educational institutions as well as the most notable and historic campuses.

For more detailed information about visiting the individual schools here, you will find extensive information for visitors on their own websites, which should be considered the most up-to-date source of information, as well as the linked Wikivoyage city articles.

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, which you would often hear Americans talking about, refers to a group of 8 prestigious private universities located near the East Coast. The 8 universities that make up the Ivy League are Harvard University , Brown University , Columbia University , Cornell University , Dartmouth College , Princeton University , University of Pennsylvania and Yale University . While officially a sports confederation, all 8 universities are also very well regarded academically and are considered to be among the most prestigious universities in the world. However, not all prestigious universities in the United States are members of the Ivy League, and there are non Ivy League universities which rank alongside, or even higher than some of the lower ranked Ivies.

Memorial Hall at Harvard

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are home to the densest cluster of the top American universities, and therefore a good place to start the tour—you can cover a lot of institutions without having to spend too much time in transit.

The Great Dome at MIT
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Nassau Hall at Princeton University

Nearly all of the East Coast universities are easily reachable by the Boston-Washington Amtrak Northeast Corridor rail line, although it is much faster to fly between far-flung cities on the Corridor ( Boston to Washington is a 90-minute flight versus an eight-hour train ride on the Northeast Regional or a seven-hour ride on the more expensive Acela Express ). Boston, New York City , Philadelphia , and Washington, D.C. and cities between are also served by commercial bus lines, the cheapest of which are Chinatown bus services, which travel between the Chinatowns in the four major cities (as well as midtown in New York City; Chinatown in NYC is downtown, and so the buses serve both locations). Road travel, whether by bus or by car, may not be the best option for the farthest-flung points. Car travel can be a nightmare in tangled cities like Boston (home to the infamous Big Dig) and New York. Renting or driving, however, does afford one the most freedom of movement.

Most patent systems in the world are based on three general principles. First, patents should be granted only for technical subject matter. Abstract subjects such as discoveries, pure information, aesthetic creations and mathematical theories are not considered to be patentable. Second, a patentable invention must be novel and a creation that goes beyond previous art (that is, everything published or made publicly available before the filing date). Third, it must be industrially applicable (as defined in Europe and Japan) or have utility (in the USA). (See Fig 3 for a breakdown of patent applications by country.)

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Figure 3

Patent applications to the EPO: breakdown by applicants' country residence or place of business.

The first of these principles is often used as an argument against the patenting of nucleic acids and proteins because these already existed in nature and thus were allegedly only discovered and not invented. Apart from the fact that natural products, such as microbial antibiotics, hormones and plant extracts, have been patented for more than a century, it is also important to realize that nucleic acids or proteins do not usually occur in an isolated form in nature. It requires technology and inventive activity to isolate them and make them technically usable, which often requires considerable investment. The patent system was applied to protect the outcome of such endeavour against copying by others and to promote research and development in this area. Furthermore, the concept of novelty in the patent system is not the same as in common usage. 'Novelty' in patent law is defined as everything that has not been made available to the public by means of written or oral description, by use, or in any other way. For example, when a patent application relating to human H2-relaxin was filed, the protein had not previously been described. Moreover, it was not found existing freely in nature, but had to be isolated to be available to the public. It was therefore regarded as an invention and not a mere discovery ( EPO, 1995 ). Another example of the distinction between a discovery and an invention based on the patent concept of novelty is the isolation of an antibiotic producing microorganism from soil. Although the bacterium existed in nature, it was not available to the public because it had never been isolated. Furthermore, its existence was not known before the filing of the patent application. The microorganism is therefore regarded as novel. Nevertheless, the mere isolation of a natural substance is not sufficient for patentability: there must in addition be an inventive activity. With regard to genes, the EC Directive explicitly states that “the human body, at the various stages of its formation and development, and the simple discovery of one of its elements, including the sequence or partial sequence of a gene, cannot constitute patentable inventions,” and that “the industrial application of a sequence or partial sequence must be disclosed in the patent application.”

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