1. A method for migrating clinical medical data, comprising:

constructing a verification environment having a first configuration that is the same as a formal environment;

copying first formal data in the formal environment with the first configuration into the verification environment as first verification data, wherein the first formal data and the first verification data both meet the requirements of the first configuration;

modifying the first configuration to a second configuration in the verification environment;

performing data migration on the first verification data in the verification environment to form second verification data, wherein the second verification data meets the requirement of the second configuration;

verifying whether the second verification data is correct in the verification environment;

if the second verification data is correct, taking the second configuration as a latest configuration, and modifying the first configuration into the latest configuration in the formal environment; and

and performing data migration on the first formal data in the formal environment to form second formal data, wherein the second formal data meets the requirement of the latest configuration.

2. The migration method according to claim 1, wherein if the second verification data is incorrect, the second configuration is modified so that the second verification data formed by the data migration meets the requirements of the modified second configuration, and whether the second verification data is correct is verified in the verification environment.

3. The migration method of claim 1, further comprising, after the step of modifying the first configuration to a second configuration in the verification environment: upgrading the version of the verification environment from a first version to a second version.

4. The migration method of claim 3, further comprising, after the step of modifying the first configuration to the latest configuration in the formal environment: and upgrading the version of the formal environment from the first version to the latest version.

5. The migration method of claim 1, wherein the first formal data comprises data populated in a case report table, the case report table including a first configuration item, the first configuration including the first configuration item.

6. The migration method of claim 5, wherein the first formal data further includes a logical check corresponding to the case report table, the first configuration further including a second configuration item corresponding to the logical check.

7. The migration method according to claim 5, wherein the first formal data further includes automatically calculated contents corresponding to the case report table, and the first configuration further includes a third configuration item corresponding to the automatically calculated contents, the third configuration item including data and a calculation formula to which the automatically calculated contents relate.

8. The migration method of claim 1, wherein the first configuration further comprises a user permission setting for setting user access permissions to the first formal data.

9. The migration method of claim 1, wherein the step of modifying the first configuration to the latest configuration in the formal environment is preceded by: executing a standard operating program in the formal environment to determine whether the modification is allowed to be performed.

10. The migration method of claim 1, wherein the verification environment comprises a sandbox environment.

11. A migration apparatus of clinical medical data, comprising:

a memory for storing instructions executable by the processor;

a processor for executing the instructions to implement the method of any one of claims 1-10.

12. A computer-readable medium having stored thereon computer program code which, when executed by a processor, implements the method of any of claims 1-10.

Background

In the course of conducting clinical trial studies, it is necessary to store the collected case information in a storage medium for subsequent calculation and analysis. Clinical medical Data is currently collected using an Electronic Data Capture (EDC) system for clinical research, which includes a Case Report Form (CRF) designed for clinical trial projects to fill in and record relevant information about subjects. As clinical trials progress, trial protocols may be adjusted, and accordingly the structure of the CRF form may also require modification, e.g., adding or deleting items to be entered, some of which were originally mandatory and later updated to optional. As the structure of the CRF form changes, the original data needs to be migrated to the new CRF form. However, since the items in the CRF form have a certain logical relationship, after data migration, a logical relationship error may be caused, so that data in a new CRF form is in error. At present, before data migration is needed, a programmer considers various logic relationships as much as possible and then performs the data migration, but the migrated data still cannot be guaranteed to completely meet the current business scenario. If the data is tested in a formal environment, various audit trails are left, which may lead to the destruction of the integrity of the data and the authenticity of the trails, and finally may lead to the delay of research projects or flow problems.

Disclosure of Invention

The technical problem to be solved by the invention is to provide a method, a device and a computer readable medium for migrating clinical medical data, which can maintain the integrity and authenticity of the data.

The present invention is directed to a method for transferring clinical medical data, including: constructing a verification environment having a first configuration that is the same as a formal environment; copying first formal data in the formal environment with the first configuration into the verification environment as first verification data, wherein the first formal data and the first verification data both meet the requirements of the first configuration; modifying the first configuration to a second configuration in the verification environment; performing data migration on the first verification data in the verification environment to form second verification data, wherein the second verification data meets the requirement of the second configuration; verifying whether the second verification data is correct in the verification environment; if the second verification data is correct, taking the second configuration as a latest configuration, and modifying the first configuration into the latest configuration in the formal environment; and performing data migration on the first formal data in the formal environment to form second formal data, wherein the second formal data meets the requirement of the latest configuration.

In an embodiment of the present invention, if the second verification data is incorrect, the second configuration is modified, so that the second verification data formed through data migration meets the requirement of the modified second configuration, and whether the second verification data is correct is verified in the verification environment.

In an embodiment of the present invention, after the step of modifying the first configuration into the second configuration in the verification environment, the method further includes: upgrading the version of the verification environment from a first version to a second version.

In an embodiment of the present invention, after the step of modifying the first configuration into the latest configuration in the formal environment, the method further includes: and upgrading the version of the formal environment from the first version to the latest version.

In an embodiment of the invention, the first formal data comprises data filled in a case report table, the case report table comprising a first configuration item, the first configuration comprising the first configuration item.

In an embodiment of the invention, the first formal data further comprises a logical check corresponding to the case report table, and the first configuration further comprises a second configuration item corresponding to the logical check.

In an embodiment of the present invention, the first formal data further includes automatically calculated contents corresponding to the case report table, the first configuration further includes a third configuration item corresponding to the automatically calculated contents, and the third configuration item includes data and a calculation formula to which the automatically calculated contents relate.

In an embodiment of the present invention, the first configuration further includes a user right setting, where the user right setting is used to set an access right of a user to the first formal data.

In an embodiment of the present invention, before the step of modifying the first configuration to the latest configuration in the formal environment, the method further includes: executing a standard operating program in the formal environment to determine whether the modification is allowed to be performed.

In one embodiment of the invention, the verification environment comprises a sandbox environment.

The present invention further provides a device for transferring clinical medical data, which comprises: a memory for storing instructions executable by the processor; a processor for executing the instructions to implement the method as described above.

The present invention also provides a computer readable medium storing computer program code, which when executed by a processor implements the method as described above.

According to the data migration method, the verification of the data migration result is moved to the verification environment to be executed, the formal data in the formal environment cannot be influenced, and the authenticity and integrity of the formal data and data traces are prevented from being damaged.

Drawings

In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with figures are described in detail below, wherein:

FIG. 1 is an exemplary flow chart of a method for migration of clinical medical data according to an embodiment of the present invention;

FIG. 2 is an exemplary flow chart of a method of migrating clinical medical data according to another embodiment of the present invention;

fig. 3 is a system block diagram of a clinical medical data migration apparatus according to an embodiment of the present invention.

Detailed Description

In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with figures are described in detail below.

In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described herein, and thus the present invention is not limited to the specific embodiments disclosed below.

As used in this application and the appended claims, the terms "a," "an," "the," and/or "the" are not intended to be inclusive in the singular, but rather are intended to be inclusive in the plural unless the context clearly dictates otherwise. In general, the terms "comprises" and "comprising" merely indicate that steps and elements are included which are explicitly identified, that the steps and elements do not form an exclusive list, and that a method or apparatus may include other steps or elements.

The relative arrangement of the components and steps, the numerical expressions, and numerical values set forth in these embodiments do not limit the scope of the present application unless specifically stated otherwise. Meanwhile, it should be understood that the sizes of the respective portions shown in the drawings are not drawn in an actual proportional relationship for the convenience of description. Techniques, methods, and apparatus known to those of ordinary skill in the relevant art may not be discussed in detail but are intended to be part of the specification where appropriate. In all examples shown and discussed herein, any particular value should be construed as merely illustrative, and not limiting. Thus, other examples of the exemplary embodiments may have different values. It should be noted that: like reference numbers and letters refer to like items in the following figures, and thus, once an item is defined in one figure, further discussion thereof is not required in subsequent figures.

It should be noted that the terms "first", "second", and the like are used to define the components, and are only used for convenience of distinguishing the corresponding components, and the terms have no special meanings unless otherwise stated, and therefore, the scope of protection of the present application is not to be construed as being limited. Further, although the terms used in the present application are selected from publicly known and used terms, some of the terms mentioned in the specification of the present application may be selected by the applicant at his or her discretion, the detailed meanings of which are described in relevant parts of the description herein. Further, it is required that the present application is understood not only by the actual terms used but also by the meaning of each term lying within.

Flow charts are used herein to illustrate operations performed by systems according to embodiments of the present application. It should be understood that the preceding or following operations are not necessarily performed in the exact order in which they are performed. Rather, various steps may be processed in reverse order or simultaneously. Meanwhile, other operations are added to or removed from these processes.

Fig. 1 is an exemplary flowchart of a migration method of clinical medical data according to an embodiment of the present invention. Referring to fig. 1, the migration method of this embodiment includes the steps of:

step S110: constructing a verification environment, wherein the verification environment has a first configuration which is the same as that of the formal environment;

step S120: copying first formal data in a formal environment with a first configuration into a verification environment to serve as first verification data, wherein the first formal data and the first verification data both meet the requirements of the first configuration;

step S130: modifying the first configuration to a second configuration in the verification environment;

step S140: performing data migration on the first verification data in a verification environment to form second verification data, wherein the second verification data meets the requirement of second configuration;

step S150: verifying whether the second verification data is correct in the verification environment;

step S160: if the second verification data is correct, the second configuration is used as the latest configuration, and the first configuration is modified into the latest configuration in the formal environment; and

step S170: and performing data processing on the first formal data in the formal environment to form second formal data, wherein the second formal data meets the latest configuration requirement.

The above steps S110 to S170 are explained in detail below.

In step S110, the verification environment and the formal environment refer to an operating environment of the clinical study electronic data collection system, the verification environment being independent of the formal environment. Typically, a user records and uses clinical study electronic data collection systems in a formal environment, and when changes occur to a CRF form, the CRF form is also modified in the formal environment, and the original clinical medical data is migrated to a new CRF form.

The present invention constructs an authentication environment having the same first configuration as the formal environment in step S110. This step S110 may be performed by a programmer. The programmer may choose any software environment and hardware environment to construct the verification environment as long as the verification environment is independent of the formal environment, i.e., operations performed in the verification environment do not affect settings and data in the formal environment.

In step S120, the first formal data refers to data in a formal environment, and the first formal data meets the requirements of the first configuration. Step S120 may be performed by a programmer.

In some embodiments, the first formal data includes data populated in a case report table that includes a first configuration item for determining a specific item to be populated in the case report table. The first configuration in step S110 may include the first configuration item.

In some embodiments, the first formal data further includes a logical check corresponding to the case report table, and the first configuration further includes a second configuration item corresponding to the logical check. In the case report table, the logical check refers to checking the data in the first formal data according to the second configuration item. For example: the case report table includes the item "sex", and the item is configured as the indispensable item in the second configuration item, but the subject a does not fill the item, so the sex data of the subject a is not included in the first formal data, and the data of the subject a is questioned according to the logical check. The challenge may be presented in various ways. For example, in a page provided to a data administrator or clinical staff, a list of a plurality of subjects is included, a question icon is displayed next to the name of subject a, data representing the subject a is in question, and the data administrator or clinical staff is prompted to manually check the data. In this example, the unfilled data may be supplemented via verification. The first configuration in step S110 may include the second configuration item.

In some embodiments, the first formal data further includes automatically calculated content corresponding to the case report table, the first configuration further includes a third configuration item corresponding to the automatically calculated content, the third configuration item including data and a calculation formula to which the automatically calculated content relates. For example, the case report table will fill in the height and weight of the subject, and the case report table also includes a "body mass index BMI" calculated from the height H and the weight W according to the formula, and the BMI is W/H²This data can be obtained by simply filling in height and weight. The third configuration item of the automatic calculation content includes the data related to setting the BMI, i.e. height H and weight W, and the calculation formula is BMI W/H². The first configuration in step S110 may include the third configuration item.

In some embodiments, the first configuration further comprises a user permission setting for setting a user's access permission to the first formal data. For example, the user a is a data administrator, and the authority of the user a is that all first formal data can be browsed and edited; the user B is a clinical medical staff and has the authority of browsing and editing a part of the first formal data; the user C is a subject and has the authority to browse the data belonging to the user C in the first formal data. The first configuration in step S110 may include the user authority setting.

In step S120, the programmer may perform the copy operation using data migration functionality in the clinical research electronic acquisition system. Assuming that data is migrated from an original environment to a target environment, the original environment having an original configuration and the target environment having a target configuration, the data migrated into the target environment may be made to conform to the target configuration of the target environment using a data migration function. According to steps S110 and S120, the authentication environment and the formal environment have the same first configuration, so that the first authentication data and the first formal data are identical after the data migration. That is, in a formal environment, the first configuration is used to define configuration content of the first formal data; in the authentication environment, the first configuration is used to define configuration content of the first authentication data.

In step S130, the first configuration is modified to a second configuration in the verification environment. As the business requirements change, for example, the first configuration item of the case report table changes, the first configuration needs to be modified to the second configuration. The first configuration is modified in the verification environment, and the first configuration in the formal environment is not changed and has no influence on the first formal data.

For example, assuming that the first configuration includes first configuration items of a case report table including 10 test items, test results of the 10 test items of the subject are required to be filled in the case report table. The 10 test items are displayed in 10 rows in the case report table, the first column of each row is a title column, and the name of the test item is displayed in the title column. In step S130, the first configuration item of the case report table is modified, and 1 test item is added to become a new first configuration item. The added check item is located at a predetermined position in the 10 check items, for example, added on line 5. Obviously, the display mode of the case report table is changed due to the change of the first configuration item, a new line of test items is added on the 5 th line, and the data below the original 4 th line need to be translated downwards.

In some embodiments, after step S130, the method may further include: the version of the verification environment is upgraded from the first version to the second version. Assuming that the version of the verification environment having the first configuration is 1.0, the version of the verification environment having the second configuration may be modified to 2.0 after step S130. In these embodiments, the version of the formal environment having the first configuration may be consistent with the version of the verification environment having the first configuration, also 1.0.

In step S140, in the verification environment, the programmer may use the data migration function to migrate the first verification data into second verification data, which meets the requirements of the second configuration.

Still by way of example, in the verification environment V1.0, according to the first configuration, the case report table includes 10 test items, and the first verification data includes only data of 10 test items. After step S130, the verification environment V1.0 is upgraded to the verification environment V2.0, and 11 verification items are included in the case report table according to the second configuration of the verification environment V2.0. In step S140, the first validation data is reorganized and then populated into a new case report table conforming to the second configuration in the validation environment V2.0.

In step S150, in the verification environment, it is verified whether the second verification data is correct. As the configuration changes, the amount of data contained in a clinical trial is often large, and some errors may occur during the data migration process. Step S150 may be performed by the programmer verifying the second verification data to find out whether there is an error therein.

Still by way of example, in the verification environment V2.0, since a new verification item is added to the 5 th line of the case report table, the first 4 lines of data in the second verification data are the same as the first 4 lines of data in the first verification data, while the last 6 lines of data in the first verification data are located in the 6 th to 11 th lines of the second verification data, and the 5 th line is used to fill in the data of the newly added verification item. And if the problems of wrong rows, omission and the like of the data are found, the correctness and the integrity of the second verification data are questioned.

In some embodiments, after step S150 is executed, if the second verification data is found to be incorrect, the second configuration is modified, the second verification data formed through the data migration is made to meet the requirement of the modified second configuration, and whether the second verification data is correct is verified in the verification environment. This step may be performed in a loop, continuously modifying the second configuration, until the second verification data matches the latest second configuration. The present invention does not limit the number of times this step is performed.

According to the above embodiments, each modified configuration may correspond to a version of a separate verification environment. Assuming that the initial version of the authentication environment is V1.0, the second configuration and the second authentication data are given the same version number for the convenience of explanation. And modifying the first configuration into a second configuration V1.0 in the verification environment V1.0, obtaining second verification data V1.0 after data migration, if the second verification data V1.0 is incorrect, modifying the second configuration V1.0 into a second configuration V2.0 in the verification environment V1.0, upgrading the version of the verification environment V1.0 to V2.0, obtaining second verification data V2.0 after data migration, if the second verification data V2.0 is incorrect, continuously modifying the second configuration into V3.0, and so on. Assuming that the second verification data V3.0 is correct after the 3 modifications, the second configuration V3.0 is the latest configuration, and the version of the verification environment is V3.0.

In step S160, when the second verification data is correct, the second configuration is regarded as the latest configuration, and the first configuration is modified to the latest configuration in the formal environment.

In some embodiments, the version of the formal environment and the version of the verification environment are consistent. Although the above steps S130 to S150 are all executed in the verification environment, the configuration of the verification environment is modified many times, and the version is changed many times. The setting of the formal environment is also the first configuration, and the first configuration of the formal environment is not modified until the latest configuration for making the second verification data correct is obtained in the verification environment, and the version of the formal environment is also upgraded to the latest version. In the above example, i.e., the version of the formal environment is also upgraded to V3.0. Obviously, the formal environment is not upgraded to the V2.0 version, but is upgraded directly from V1.0 to V3.0.

In step S160, before the step of modifying the first configuration to the latest configuration in the formal environment, the method includes: a standard operating program is executed in the formal environment to determine whether modifications are allowed to be performed. A Standard Operation Procedure (SOP) is a Standard that clinical medical software must follow, and includes a series of Operation procedures. Clinical medical software in a formal environment must go through standard operating procedures to modify its configuration, perform data migration, and release new versions.

Accordingly, since formal data is not affected, it is not necessary to follow a standard operation procedure before performing operations such as modification of settings, data migration, and version update under a verification environment, so that verification of verification data can be performed conveniently.

In step S170, the first main data is subjected to data migration to form second main data, and the second main data meets the requirement of the latest configuration.

Since the correctness and integrity of the second verification data have been verified in the previous step, in step S170, only data migration needs to be directly performed on the first formal data, and the obtained second formal data have corresponding correctness and integrity.

According to the data migration method, the verification of the data migration result is moved to the verification environment to be executed, the formal data in the formal environment is not influenced, the damage to the authenticity and the integrity of the formal data and the data trace is avoided, and therefore the normal and ordered progress of the clinical test project is guaranteed.

Fig. 2 is an exemplary flowchart of a method for migrating clinical medical data according to another embodiment of the present invention. Referring to fig. 2, this embodiment includes the following specific steps:

step S210: constructing a verification environment V1.0, wherein the verification environment V1.0 has a first configuration which is the same as the formal environment V1.0;

step S212: copying the first formal data into the verification environment V1.0 as first verification data;

step S214: modifying the CRF form in the verification environment V1.0;

step S216: upgrading the verification environment V1.0 to a verification environment V2.0;

step S218: migrating the first verification data in a verification environment V2.0 to form second verification data;

step S220: storing second verification data by using a CRF form of the V2.0 version;

step S222: verifying whether the second verification data is correct or not, and if so, finishing the verification;

step S224: modifying a CRF form in a formal environment V1.0;

step S226: upgrading the formal environment V1.0 to a formal environment V2.0;

step S228: migrating the first formal data to form second formal data in the formal environment V2.0;

step S230: the second formal data is stored using the CRF form of formal environment V2.0.

The first configuration in the embodiment of FIG. 2 includes a first configuration item of a CRF form, the modification to the configuration of which includes only the modification to the CRF form. After one time of verification in the verification environment V2.0, the second verification data is correct, that is, the CRF form is modified in the formal environment V1.0, and data migration is performed to obtain the formal environment V2.0 and the second formal data in the environment.

The invention also includes a device for migrating clinical medical data, comprising a memory and a processor. Wherein the memory is to store instructions executable by the processor; the processor is configured to execute the instructions to implement the method for migrating clinical medical data as described above.

Fig. 3 is a system block diagram of a clinical medical data migration apparatus according to an embodiment of the present invention. Referring to fig. 3, the migration apparatus 300 may include an internal communication bus 301, a processor 302, a Read Only Memory (ROM)303, a Random Access Memory (RAM)304, and a communication port 305. When used on a personal computer, the migration apparatus 300 may also include a hard disk 306. The internal communication bus 301 may enable data communication among the components of the migration apparatus 300. Processor 302 may make the determination and issue a prompt. In some embodiments, processor 302 may be comprised of one or more processors. The communication port 305 may enable data communication between the migration apparatus 300 and the outside. In some embodiments, the migration device 300 may send and receive information and data from a network through the communication port 305. The migration apparatus 300 may also include various forms of program storage units and data storage units, such as a hard disk 306, Read Only Memory (ROM)303 and Random Access Memory (RAM)304, capable of storing various data files for computer processing and/or communication, as well as possible program instructions for execution by the processor 302. The processor executes these instructions to implement the main parts of the method. The results processed by the processor are communicated to the user device through the communication port and displayed on the user interface.

The migration method may be implemented as a computer program, stored in the hard disk 306, and loaded into the processor 302 for execution, so as to implement the operation method of the present application.

The invention also comprises a computer readable medium having stored thereon computer program code which, when executed by a processor, implements the method of migrating clinical medical data as described above.

The method of migrating clinical medical data, when implemented as a computer program, may also be stored as an article of manufacture in a computer-readable storage medium. For example, computer-readable storage media can include but are not limited to magnetic storage devices (e.g., hard disk, floppy disk, magnetic strips), optical disks (e.g., Compact Disk (CD), Digital Versatile Disk (DVD)), smart cards, and flash memory devices (e.g., electrically Erasable Programmable Read Only Memory (EPROM), card, stick, key drive). In addition, various storage media described herein can represent one or more devices and/or other machine-readable media for storing information. The term "machine-readable medium" can include, without being limited to, wireless channels and various other media (and/or storage media) capable of storing, containing, and/or carrying code and/or instructions and/or data.

It should be understood that the above-described embodiments are illustrative only. The embodiments described herein may be implemented in hardware, software, firmware, middleware, microcode, or any combination thereof. For a hardware implementation, the processor may be implemented within one or more Application Specific Integrated Circuits (ASICs), Digital Signal Processors (DSPs), Digital Signal Processing Devices (DSPDs), Programmable Logic Devices (PLDs), Field Programmable Gate Arrays (FPGAs), processors, controllers, micro-controllers, microprocessors, and/or other electronic units designed to perform the functions described herein, or a combination thereof.

Aspects of the present application may be embodied entirely in hardware, entirely in software (including firmware, resident software, micro-code, etc.) or in a combination of hardware and software. The above hardware or software may be referred to as "data block," module, "" engine, "" unit, "" component, "or" system. The processor may be one or more Application Specific Integrated Circuits (ASICs), Digital Signal Processors (DSPs), digital signal processing devices (DAPDs), Programmable Logic Devices (PLDs), Field Programmable Gate Arrays (FPGAs), processors, controllers, microcontrollers, microprocessors, or a combination thereof. Furthermore, aspects of the present application may be represented as a computer product, including computer readable program code, embodied in one or more computer readable media. For example, computer-readable media may include, but are not limited to, magnetic storage devices (e.g., hard disk, floppy disk, magnetic strips … …), optical disks (e.g., Compact Disk (CD), Digital Versatile Disk (DVD) … …), smart cards, and flash memory devices (e.g., card, stick, key drive … …).

The computer readable medium may comprise a propagated data signal with the computer program code embodied therein, for example, on a baseband or as part of a carrier wave. The propagated signal may take any of a variety of forms, including electromagnetic, optical, and the like, or any suitable combination. The computer readable medium can be any computer readable medium that can communicate, propagate, or transport the program for use by or in connection with an instruction execution system, apparatus, or device. Program code on a computer readable medium may be propagated over any suitable medium, including radio, electrical cable, fiber optic cable, radio frequency signals, or the like, or any combination of the preceding.

Having thus described the basic concept, it will be apparent to those skilled in the art that the foregoing disclosure is by way of example only, and is not intended to limit the present application. Various modifications, improvements and adaptations to the present application may occur to those skilled in the art, although not explicitly described herein. Such modifications, improvements and adaptations are proposed in the present application and thus fall within the spirit and scope of the exemplary embodiments of the present application.

Also, this application uses specific language to describe embodiments of the application. Reference throughout this specification to "one embodiment," "an embodiment," and/or "some embodiments" means that a particular feature, structure, or characteristic described in connection with at least one embodiment of the present application is included in at least one embodiment of the present application. Therefore, it is emphasized and should be appreciated that two or more references to "an embodiment" or "one embodiment" or "an alternative embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, some features, structures, or characteristics of one or more embodiments of the present application may be combined as appropriate.

Numerals describing the number of components, attributes, etc. are used in some embodiments, it being understood that such numerals used in the description of the embodiments are modified in some instances by the use of the modifier "about", "approximately" or "substantially". Unless otherwise indicated, "about", "approximately" or "substantially" indicates that the number allows a variation of ± 20%. Accordingly, in some embodiments, the numerical parameters used in the specification and claims are approximations that may vary depending upon the desired properties of the individual embodiments. In some embodiments, the numerical parameter should take into account the specified significant digits and employ a general digit preserving approach. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the range are approximations, in the specific examples, such numerical values are set forth as precisely as possible within the scope of the application.