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#1 Providing
Legal Information to Rural Markets
The Qianxi Women's Legal Centre, funded by the County Women's Federation, was established in 1995 with eight full-time women lawyers. The Centre provides free legal information for all women, and free legal support for those who are poor. Of 400 cases from 1995 to 1998, one third concerned violence against women.
To raise rural women's awareness of their individual rights as citizens, staff at the Centre looked for ways to take their services to places where rural people go to regularly. They decided to open a "legal desk" (actually a stall) at the main local markets, a public place where people meet once a week to buy and sell goods. At the stall, staff distribute printed materials on the Law Protecting the Rights and Interests of Women, and answer queries from rural women regarding the legal implications of divorce, property rights or domestic violence.
Since early 1998, the Centre has organized a series of activities on violence against women and legal training workshops, which are held in the markets every second week. These activities have become extremely popular among rural women, as they can buy and sell goods and learn about their legal rights in areas such as marriage and property at the same time.
#2 Addressing Stereotypes
in the Media
Chinese media, including newspapers, television commercials, television series and popular magazines, is full of stereotyped portrayals of women. To change this situation, a Media Watch Network was established in 1996 to promote more balanced images of women, and eliminate sexual discrimination in the media. The volunteer members are women journalists from mainstream newspapers, news agencies, magazines, journals and television and radio stations.
In 1998, research by the Network on eight mainstream newspapers indicated that men were the focus of 83% of prime news stories, while women only comprised 17%. In the sample of over 18,500 news items, only 0.5% were about women's issues or movements. The stories tended to emphasise the importance of women's virginity, to portray women as weak and passive members of society, and to suggest that the primary role of women was to be mothers and wives. Cases of violence against women were mostly treated as social stories that over-emphasised the masculinity of the abuser, and lacked a gender perspective.
Based on these findings, the Network implemented a series of interventions. Firstly it conducted gender sensitivity training for all members to sharpen their consciousness of the issues. Secondly, members shared information and resources on violence against women, especially on legal aid, hotline and counselling services that could be passed on to their audience. They also increased gender-sensitive coverage of violence against women in the media in order to raise general awareness of the issue.
#3 Solving Financial
Constraints in a Non-Government Organization
The Maple Women's Psychological Counselling Centre, Beijing, is a non-government, non-profit voluntary women's organization. It was founded in 1988 by a group of female intellectuals who provided some seed funding. While it was hoped that the Centre could raise operational funds by selling products for women and children, this strategy failed. Eventually the Centre solved its financial difficulties by identifying a fee-paying service to raise revenue for its other activities.
The opportunity came after the 1989 elections in China. The number of elected women officials had dropped quite considerably, which caused a lot of concern. The Centre identified a need to enhance the skills and qualifications of women leaders participating in politics, and collaborated with the Women of China magazine to offer a training seminar for women officials nationwide. The seminar introduced very different viewpoints and perspectives than the traditional training seminars for officials, and included courses such as "Special Difficulties and Problems for Female Officials", and "Psychological Barriers to the Success of Female Officials". The courses were designed to meet the needs of the women cadres, and were warmly received by the participants.
Over the following years the Centre organized similar seminars, as well as conducting training courses for officials working in front posts in rural areas, and education on women's legal rights and interests. A moderate tuition fee was charged, which covered the daily operations of the Centre. The training also provided opportunities to conduct surveys and discussions with women officials to further understand the particular problems facing women cadres, and the reality of women's participation in politics. This led to a book entitled "Action of Chinese Women's Participation in Politics" which enabled institutions in other cities and provinces to carry out similar training programs.
In spite of the success of this approach, the Centre believes that the orientation of a social welfare institution should not be to earn revenues through this sort of activities. Recently, it has been successful in raising most of its funds through donations from foreign and domestic funding organizations, social institutions and individuals.
#4 Providing Telephone
Hotline Services to Women
The first Women's Hotline in China was established in Beijing in 1992. As the first Women's Hotline in China, an important part of its work has been training counsellors for hotlines across the country.
In 1996, advanced hotline counselling training was provided to 27 counsellors from nine provinces, municipalities and autonomous regions. In 1998, the Centre worked with the Cultural and Education Section of the British Embassy to provide a Sino-British Hotline Supervision Seminar to train administrators and supervisors of 38 hotlines from 13 provinces and municipalities.
In the five years 1993 to 1997, the Hotline assisted just under 35,000 callers. The main issues raised by the women were sex (22%), marriage (21%), women and children's health (20%), love (15%), legal matters (8%), psychological problems (8%), family upbringing (2%), work-related problems (2%), domestic violence (1%), and sexual harassment (1%).
#5 Integrating Research,
Teaching and legal Services
The Centre of Women's Law Studies and Legal Services was founded by the Law Department of Peking University in 1995 to provide legal services, and to study and promote women's rights in the Chinese legal system. The Centre seeks to promote women's consciousness of their legal rights, to increase legal protection for women's rights, and to improve the treatment of women by the legal system.
The Centre has become an
integrated institution of research, teaching and legal services. In
addition to providing free legal counseling, the Centre researches and
publishes analyses of legal problems facing China's women. It is staffed
by law department faculty staff, graduate students and full- and part-time
lawyers, and receives help from some of China's most noted pioneers in the
fields of women's issues and women's law.
#6 Promoting Awareness
through University Student Activities
Since 1992, the Student Union at Peking University has held a two-week Women Students Cultural Festival each year. More than 5000 students and staff members of 50 faculties take part in activities such as lectures, public forums, movies, and theatres regarding issues of concern to women students.
In 1998, the organizers
decided to incorporate a public forum on the topic "Women's Bodies as
basic Human Rights". More than 150 male and female students and four
female professors exchanged views and argued points. The forum began at
6:30 in the evening, and only ended five hours later when the lights had
to be turned off.
#7 Training Adolescent
Boys and Girls
In 1993, the Jinglun Family Centre of the China Association of Social Workers began offering classes for adolescent boys and girls to address the lack of education on gender roles and sexual relationships in formal middle schooling. The training is designed as workshops and covers gender awareness, gender equality and gender relations. The trainers have specialist qualifications in psychology and sociology. In total, one hundred thousand middle school students have participated in the training.
In 1997, the Centre
recognised the need to re-focus its violence against women efforts towards
prevention. It began to incorporate material on violence against women in
the classes through story telling, drawings and group discussion. The
content was expanded to include basic human rights, implying that any form
of violence against girls and women is a violation of human rights, and
appropriate sexual behaviour including equality and mutual respect between
#8 Educating Police,
Prosecutors, Judges and Counsellors
While domestic violence
accounts for only 1% of phone calls to the Women's Hotline in Xian City,
the counsellors regard it as a serious problem. In 1996, they decided to
conduct a survey of female criminals in the provincial women's jail, and
discovered that some of the prisoners had killed their husband or
boyfriend because they were victims of domestic violence. Even when
police, prosecutors and judges had been aware of the violence, they had
not intervened because they regarded domestic violence as a family matter.
Dated: 2Nov2001


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Featured MNV Articles:
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This module provides code coverage metrics for Perl. Code coverage metrics describe how thoroughly tests exercise code. By using Devel::Cover you can discover areas of code not exercised by your tests and determine which tests to create to increase c...PJCJ/Devel-Cover-1.23 5 (16 reviews) - 24 Apr 2016 14:44:13 GMT - Search in distribution
- Devel::Cover::Op - B::Concise with coverage data
- Devel::Cover::DB - Code coverage metrics for Perl
- Devel::Cover::Pod - Code coverage metrics for Perl
- 42 more results from Devel-Cover »
This module generates a Clover compatible coverage xml file which can be used in a variety of continuous integration software offerings. It is designed to be called from the "cover" program distributed with Devel::Cover....DBARTLE/Devel-Cover-Report-Clover-0.35 - 12 Mar 2012 09:28:05 GMT - Search in distribution
Devel::Cover::Report::Codecov is coverage reporter for Codecov <https://codecov.io>. CI Companies Supported Many CI services supported. You must set CODECOV_TOKEN environment variables if you don't use Travis CI, Circle CI and AppVeyor. * Travis CI <...PINE/Devel-Cover-Report-Codecov-0.14 - 01 May 2016 18:12:05 GMT - Search in distribution
This task module lets you easily install Devel::Cover 1.20 and all its recommended dependencies....VPIT/Task-Devel-Cover-Recommended-v1.200.0 - 31 Jul 2015 17:57:38 GMT - Search in distribution
<https://coveralls.io/> is service to publish your coverage stats online with a lot of nice features. This module provides seamless integration with Devel::Cover in your perl projects....MIKIHOSHI/Devel-Cover-Report-Coveralls-0.11 - 08 Oct 2014 09:14:01 GMT - Search in distribution
Post test coverage summary to selected service...PJFL/Devel-Cover-Report-OwnServer-0.3.1 - 26 Dec 2015 01:27:46 GMT - Search in distribution
By default, this module generates a "phabricator.json" file in Devel::Cover's output directory. This file can then be parsed and used to provide coverage information as part of a unit test report to a Phabricator <http://phabricator.org> server. Phab...MCARTMELL/Devel-Cover-Report-Phabricator-0.01 - 07 Jan 2013 14:38:49 GMT - Search in distribution
KENTNL/Devel-Cover-Report-Json_detailed-0.001000 - 15 Nov 2014 23:12:17 GMT - Search in distribution
The following program sets up the coverage hook on "use" and dumps a report (to "/tmp" by default) at the end of execution. use Devel::QuickCover; my $x = 1; my $z = 1 + $x; The following program sets up the coverage hook on "start()" and dumps a rep...GONZUS/Devel-QuickCover-0.700000 - 04 Jul 2016 07:08:51 GMT - Search in distribution
- lib/Devel/QuickCover/Report.pm
- Devel::QuickCover::Report::Html - Simple Devel::QuickCover report generator
- lib/Devel/QuickCover/Report/Fetcher/Git.pm
This module provides advanced reports based on Devel::Cover database....NATANAEL/Devel-CoverReport-0.05 - 17 May 2012 03:56:55 GMT - Search in distribution
- Devel::CoverReport::App::CoverReport - implement the cover_report command line utility.
- Devel::CoverReport::VCS::Git - Git VCS plugin for Devel::CoverReport.
- Devel::CoverReport::VCS::SVN - Subversion plugin for Devel::CoverReport.
- 10 more results from Devel-CoverReport »
DOMM/App-ArchiveDevelCover-1.002 - 21 Nov 2012 21:03:00 GMT - Search in distribution
- archive_devel_cover.pl - script to archive Devel::Cover reports
Dealing with large code bases and large test suites When a test suite grows as a team of developers implement new features, knowing exactly which test files provide test coverage for which parts of the application becomes less and less obvious. This ...JOHANL/Devel-CoverX-Covered-0.016 - 11 Oct 2014 12:36:58 GMT - Search in distribution
- Devel::CoverX::Covered::Db - Covered database collection and reporting
- covered - Command line interface to Devel::CoverX::Covered
: This command is like "prove" or "make test", running the test suite for the current namespace....BRUMMETT/UR-0.45 - 22 Sep 2016 20:09:37 GMT - Search in distribution
This module is an experiment in functional programming in perl. It uses nothing but a combination of; subroutines, the @_ array and a few built in operators to implement a style of functional programming. None of the code above is all that interestin...STEVAN/fp-0.03 - 28 Sep 2005 22:27:52 GMT - Search in distribution
Sim is a general-purpose discrete event simulator engine written in pure Perl. It was originally developed as the run-core of a sequential/conbinational logic circuit simulator named Tesla. The Sim class is just a static class wrapping around a Sim::...AGENT/Sim-0.03 - 02 Jun 2007 11:35:36 GMT - Search in distribution
Method modifiers are handy, but they are not Devel::Cover friendly. This is because Perl makes package-level anonymous subroutines invisible to Devel::Cover, and the modifiers are often anonymous subroutines. MooseX::CoverableModifiers names the subr...CLKAO/MooseX-CoverableModifiers-0.30 - 16 Feb 2012 16:58:09 GMT - Search in distribution
This module provide a lightweight IOC or Inversion of Control framework. Inversion of Control, sometimes called Dependency Injection, is a component management style which aims to clean up component configuration and provide a cleaner, more flexible ...STEVAN/IOC-0.29 - 27 Apr 2007 00:57:28 GMT - Search in distribution
- IOC::Proxy - Proxy for the IOC Framework
- IOC::Service - An IOC Service object
- IOC::Registry - Registry singleton for the IOC Framework
- 17 more results from IOC »
The DBI is a database access module for the Perl programming language. It defines a set of methods, variables, and conventions that provide a consistent database interface, independent of the actual database being used. It is important to remember th...TIMB/DBI-1.636 5 (27 reviews) - 24 Apr 2016 22:20:56 GMT - Search in distribution
This is a list of wishes for Perl. The most up to date version of this file is at <http://perl5.git.perl.org/perl.git/blob_plain/HEAD:/Porting/todo.pod> The tasks we think are smaller or easier are listed first. Anyone is welcome to work on any of th...RJBS/perl-5.24.0 4.5 (6 reviews) - 09 May 2016 11:35:29 GMT - Search in distribution
- perlobj - Perl object reference
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This is meant to be a full-featured N-ary tree representation with configurable error-handling and a simple events system that allows for transparent persistence to a variety of datastores. It is derived from Tree::Simple, but has a simpler interface...RSAVAGE/Tree-1.10 - 15 Sep 2016 09:51:56 GMT - Search in distribution


text:
LETTER: Media creates hype to shield president
John B. Williams, Evansville
People used to say of old cars on the road that they were an accident looking for a place to happen.
That is what I believe Ferguson Missouri was all about. The residents were not the problem, the people who came into Ferguson were the problem.
I can't help but believe that it was all a diversion to focus the media's attention away from the president and whatever he was doing behind the scenes.
Since we cannot count on the mainstream media to inform the American public of what bills are being passed into law and how the progressive liberal agenda to change the way we govern our country is unfolding, we are stuck with the sensationalism out of the mainstream media circus.
Were it not for conservative media counterparts, conservative state officeholders, party representatives and newsletters from our senators, we probably never would get the truth out of Washington under the president.?
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Man charged with aggravated assault of a police officerOctober 06,2013Staff Report
CHITTENDEN - A local man is expected in court Monday to answer charges after he allegedly struck a state trooper with his car.
Friday night, state police responded to a wooded area between Mountain Top Road and Dam Road for a report of an underage drinking party. As police approached what they described as a large gathering, several people fled on foot and in automobiles.
According to police, one of those drivers was 19-year-old Cody J. Dion, who ignored commands to stop and instead accelerated directly at two police officers. Police said Dion's car struck the hand of one of the officers as he dove out of the way.
Police said neither trooper was seriously injured.
According to police, Dion then struck a parked police cruiser, causing damage to both vehicles.
Police later found Dion's car abandoned on Wildcat Road, and found Dion at his home on Dam Road. He was arrested and held in Rutland jail on $25,000 bail.
He is scheduled to be arraigned Monday in Rutland criminal court on charges of aggravated assault of a police officer and leaving the scene of an accident.MORE IN This Just InPolice: Drunk driver crashes
HARTFORD A Hartland man was cited for drunk driving after... Full StoryBENNINGTON A local man was charged with two felony counts of forgery on Monday in Bennington... Full StoryBENNINGTON Two Pownal residents were arraigned on a felony charge of cultivating marijuana on... Full Story
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text:
Pathology Consultation on Vitamin D Testing
The last decade has seen a substantial increase in clinical interest in vitamin D deficiency and of laboratory testing for vitamin D status. Many clinical laboratories in the United States have seen requests for vitamin D testing increase 100% or more in the last 5 years. The most common laboratory test to assess vitamin D nutritional status is total 25-hydroxyvitamin D serum concentrations. Laboratory professionals are often confronted with challenges related to vitamin D testing, including controversy over optimal and target vitamin D concentrations, variable reference ranges across marketed assays and reference laboratories, lack of standardization of vitamin D assays, and misordering of 1,25-dihydroxyvitamin D testing. This article presents a common clinical case scenario regarding vitamin D and an up-to-date discussion and review of the literature on vitamin D testing.
- Calcitriol
- Calcium metabolism disorders
- Osteoporosis
- Reference standards
- Reference values
- Vitamin D
Case Scenario
A 62-year-old woman was seen in an internal medicine clinic at an academic medical center. She is concerned about osteoporosis, especially because her older sister recently had a hip fracture at the age of 64 years. She is additionally concerned about vitamin D deficiency, having heard this topic discussed on a daytime television talk show. The patient had laboratory testing for vitamin D status 12 months earlier at a community hospital; the test was done by a commercial laboratory and showed a total 25-hydroxyvitamin D serum concentration determined by liquid chromatography/tandem mass spectrometry (LC/MS/MS) of 26 ng/mL (65 nmol/L; >25 ng/mL [62 nmol/L] defined as "optimal" in the reference range).
At the internal medicine clinic, the physician ordered laboratory tests using the hospital computer order system. To check vitamin D status, the physician selected a vitamin D panel that includes 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels. The 25-hydroxyvitamin D serum concentration was determined at the medical center central clinical laboratory by enzyme immunoassay, and results were 29 ng/mL (72 nmol/L), which is in the "insufficiency" range according to the reference ranges on the package insert for the assay. The 1,25-dihydroxyvitamin serum concentration was determined by a reference laboratory by LC/MS/MS, and results were 55 pg/mL (143 pmol/L; reference range, 18–72 pg/mL [47–187 pmol/L]). The internal medicine physician is perplexed about the results of the laboratory testing and contacts the clinical chemistry director for consultation.
What testing is appropriate for assessment of vitamin D nutritional status, and which patients should have vitamin D testing?
What do the data in the published literature show with regard to association of vitamin D deficiency with disease? What laboratory values raise concern for risk of serious complications such as secondary hyperparathyroidism or osteoporosis-related bone fractures?
How are 25-hydroxyvitamin D reference ranges (or target values) established, and how do they vary across marketed assays and reference laboratories?
If 25-hydroxyvitamin D2 and D3 serum concentrations are separately measured and reported as compared with receiving only a total 25-hydroxyvitamin D concentration, how do the additional fractionated data for vitamin D2 and D3 aid clinical interpretation?
What are the methods for measuring 25-hydroxyvitamin D serum concentrations, and how do they differ from one another? Is there standardization across assays?
When is measurement of a 1,25-dihydroxyvitamin D serum concentration clinically indicated?
What are the clinical implications of misordering 1,25-dihydroxyvitamin D in place of 25-hydroxy-vitamin D?
Vitamin D is an essential fat-soluble vitamin that affects nearly every organ system via interactions with the vitamin D receptor, a nuclear hormone receptor that acts as a transcriptional regulator of diverse physiologic processes.1 In the last 2 decades, there has been increasing interest in the biology of vitamin D and a growing recognition that vitamin D insufficiency is common throughout the world.2–4 One consequence of the growing clinical attention to vitamin D has been a substantial increase in laboratory testing for vitamin D. In the United States, many clinical laboratories have experienced increases in vitamin D testing of 100% or more in the last 5 years.5 This increase produces challenges for clinical laboratories, as will be discussed in this review.
Vitamin D was first recognized as a vitamin in the early 20th century as a factor in cod liver oil that prevented the development of rickets, a syndrome of bone weakening in children that can lead to fractures and permanent skeletal deformity.6 The "classic" actions of vitamin D are in the regulation of mineral metabolism, primarily by influencing renal reabsorption of calcium and phosphate and intestinal absorption of calcium.2 Vitamin D and parathyroid hormone (PTH) together serve as the most important physiologic regulators of calcium and phosphorus. Abnormal vitamin D serum or plasma concentrations trigger compensatory changes in PTH levels.7 For example, prolonged vitamin D deficiency can lead to a sustained increase in PTH secretion, a condition known as secondary hyperparathyroidism.
To complement the well-known role of vitamin D in mineral metabolism, research has demonstrated an increasing list of "nonclassic" vitamin D actions, including effects on immune modulation, cell cycle proliferation, and brain health.8,9 Vitamin D deficiency has now been associated with increased risk of multiple sclerosis, certain cancers (especially breast, colorectal, and prostate), and chronic respiratory infections (eg, tuberculosis).2 Consequently, vitamin D deficiency has health implications that extend well beyond skeletal abnormalities.
The term vitamin D usually refers collectively to vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol), together known as the calciferols.2 Vitamins D2 and D3 are hydroxylated by the enzyme vitamin D 25-hydroxylase in the liver to form 25-hydroxyvitamin D2 or D3. 25-Hydroxyvitamin D (calcidiol) is the main storage form of vitamin D and also the analyte typically measured in serum or plasma to assess vitamin D stores. 25-Hydroxyvitamin D is further hydroxylated in the kidney by 25-hydroxyvitamin D 1α-hydroxylase to form 1,25-dihydroxyvitamin D (calcitriol), which represents the biologically most active form of vitamin D in terms of effects at the vitamin D receptor. 1,25-Dihydroxyvitamin D varies day-to-day much more than 25-hydroxyvitamin D and is, in fact, not a good marker of overall vitamin D nutritional status.2 In fact, it is possible to be profoundly deficient in overall stores of vitamin D yet have a 1,25-dihydroxyvitamin D serum or plasma concentration within the reference range owing to higher levels of PTH that cause greater conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D.10 As will be discussed, there are few clinical indications to assay serum or plasma 1,25-dihydroxyvitamin D concentration.
Reasons for Vitamin D Deficiency
A number of factors contribute to vitamin D deficiency. The first is decreased endogenous production.11 UV-B rays in sunlight convert 7-dehydrocholesterol in the skin to previtamin D3, which then rapidly converts to vitamin D3. This process requires a UV-B index of greater than 3. In practical terms, optimal endogenous vitamin D3 production in response to sunlight in the northern latitudes requires sunlight exposure in the warmer months and during peak sunlight hours (approximately 10:00 am to 3:00 pm). In the Northern Hemisphere above 35° latitude (roughly that of Atlanta, GA, in the United States), essentially no vitamin D3 is produced endogenously from November to March, even with direct sunlight exposure. Consequently, for many people in the United States during the winter months, the only substantial source of vitamin D is from the diet. Even in climates in lower latitudes that have abundant sunlight, people who reside predominantly indoors during peak daylight hours produce very little vitamin D endogenously. Sunscreen use also dramatically decreases vitamin D production.11 Sunscreens with a sun protection factor of 15 or higher block 99% or more of vitamin D production. The ability to produce vitamin D also decreases as part of the aging process, mainly related to decreased availability of 7-dehydrocholesterol. Skin damage (eg, burns) can also reduce vitamin D production, depending on the extent of injury.12
The second main factor underlying vitamin D deficiency is low dietary intake.2 There are a relatively small number of foods that naturally contain high amounts of vitamin D.13 These include oily fish (eg, mackerel), eggs, and shiitake mushrooms. Animal sources of vitamin D generally contain vitamin D3 (the endogenous compound); however, farmraised animals may be fed vitamin D2-enriched diets and, thus, have appreciable amounts of vitamin D2 in their tissues.14 Sun-dried shiitake mushrooms contain substantial amounts of vitamin D2, especially when exposed to UV light. The amount of vitamin D in supplements varies considerably.2 Most multivitamins contains 400 IU of vitamin D2 or D3. Vitamin D3 supplements generally contain 400, 800, 1,000, or 2,000 IU. There is a liquid supplement of vitamin D2 that contains 8,000 IU/mL and a vitamin D2 capsule containing 50,000 IU.
To enhance vitamin D intake on a population-wide basis, dairy products (eg, milk, butter) may be supplemented with vitamin D2 or D3.13 Nearly all of the milk sold in the United States is voluntarily fortified with 100 IU vitamin D2 or D3 per cup. With the decreasing intake of milk by children, the list of foods supplemented with vitamin D has expanded to include orange juice, cereals, and some other foods. Canada and the United States mandate fortification of infant formula with vitamin D. It is important to keep in mind that dietary intake of vitamin D is often much less than could be achieved with 30 minutes of direct sunlight.11,15 For example, sunlight equivalent to 1 minimal erythemal dose (just enough to achieve redness of skin in 24 hours) in the summertime can result in 20,000 IU of vitamin D3 production. In contrast, 3.5 ounces of fresh wild salmon contains 600 to 1,000 IU of vitamin D3, while most fortified beverages and foods (eg, milk, orange juice) contain only 100 IU per serving. Breast milk also contains low concentrations of vitamin D, especially in lactating women who themselves are vitamin D–insufficient.2
The third main factor that can contribute to vitamin D deficiency is malabsorption.2 Conditions that can reduce vitamin D absorption include use of bile acid sequestrants (eg, cholestyramine, colesevelam), cystic fibrosis, celiac disease, Whipple disease, Crohn disease, and gastric bypass surgery. Patients with these conditions are also at risk for deficiency in other fat-soluble vitamins (A, E, and K). In patients with these conditions, increased vitamin D supplementation may be indicated. Alternatively, use of tanning beds at subtanning intensities can be highly effective in increasing vitamin D production in the skin.2
Last, a number of other factors can lead to vitamin D deficiency. A group of drugs (eg, carbamazepine, phenobarbital, phenytoin, rifampin, and St John's wort) increase liver expression of cytochrome P-450 enzymes that accelerate clearance of the active forms of vitamin D.16 Vitamin D supplementation is advised in patients receiving extended therapy with such medications, as may occur in conditions such as epilepsy and tuberculosis. Severe liver deficiency impairs 25-hydroxylation of vitamin D2 and D3. Not surprisingly, liver transplant recipients have a high prevalence of severe vitamin D deficiency.17 In nephrotic syndrome, vitamin D binding protein can be lost in the urine along with the bound vitamin D.2 There are also rare inborn errors of the vitamin D synthetic pathway or of the vitamin D binding protein that can cause vitamin D deficiency.18 In primary hyperparathyroidism, increased synthesis of 1,25-dihydroxyvitamin D leads to accelerated catabolism of 25-hydroxyvitamin D.19
Methods for Measuring 25-Hydroxyvitamin D
There are a number of methods for measuring 25-hydroxyvitamin D in serum or plasma, including enzyme immunoassay, radioimmunoassay, high-performance liquid chromatography (HPLC), liquid chromatography–mass spectrometry (LC/MS), and LC/MS/MS.10,20 Radioimmunoassay represented the first reliable technology for measuring total 25-hydroxyvitamin D, although enzyme immunoassay and LC/MS techniques have become more common. LC/MS/MS can readily distinguish 25-hydroxyvitamin D2 and D3, and clinical laboratories using this method can individually quantitate and report both analytes, in addition to providing a total 25-hydroxyvitamin D concentration. The clinical advantages of obtaining "fractionated" 25-hydroxyvitamin D2 and D3 measurements include the ability to assess endogenous vitamin D3 production and to determine compliance with vitamin D2 therapy. For example, a severe deficiency of vitamin D3 indicates lack of endogenous production and dietary intake. However, for most clinical situations, a total 25-hydroxyvitamin D concentration is sufficient.
The explosion of interest in monitoring vitamin D levels has revealed a number of challenges and controversies related to the various methods of determining 25-hydroxyvitamin D serum or plasma concentrations.10,20 One of the main challenges is the need to measure 25-hydroxyvitamin D2 and D3, which is particularly critical in a country such as the United States that heavily uses vitamin D2 in dietary supplements and to fortify food. Most immunoassay methods measure total 25-hydroxyvitamin D owing to antibody cross-reactivity with both 25-hydroxyvitamin D2 and D3.10,20 For these methods, the antibody or antibodies used in the assay ideally would cross-react equally with 25-hydroxyvitamin D2 and D3 (and not with other vitamin D compounds in the serum or plasma) and thereby produce an accurate measurement of total 25-hydroxyvitamin D. In practice, this is challenging to achieve, as revealed by comparisons of immunoassay and mass spectrometry–based measurements.21–23 For example, in 1 study, 2 commercial immunoassays showed significant deviation from linearity and highly variable results in comparison with the reference method of LC/MS/MS.22
Other factors contributing to interassay variability include lack of standardization between methods, varying preanalytic purification schemes, the C-3 epimer issue, and interlaboratory differences in operating procedures.20 Standardization of 25-hydroxyvitamin D measurements has been aided by the development of standard reference material by the National Institute of Standards and Technology (United States)24 and ongoing efforts to standardize immunoassay and LC/MS/MS methods.20 One challenging issue is the discovery that certain patients, mainly infants (younger than 12 months), have high concentrations of a 25-hydroxyvitamin D3 isomer with epimeric variation at carbon-3 (C-3).25 The C-3 epimer can produce considerable problems with vitamin D measurements in infants, and currently only a limited number of reference laboratories have validated LC/MS/MS methods to deal with infant samples. Expert panels associated with the United Kingdom Food Standards Agency26 and the US National Health and Nutrition Examination Survey27 have recommended LC/MS/MS as the reference method for measuring 25-hydroxyvitamin D, with attention to be given to integrating the available standard reference materials and the ability to discriminate the C-3 epimer of 25-hydroxyvitamin D3. These national efforts will likely spur further improvements in 25-hydroxyvitamin D measurements.
Reference Ranges for 25-Hydroxyvitamin D
One of the major areas of discussion in the vitamin D literature is what should be the appropriate reference/target ranges for 25-hydroxyvitamin D.2 There are a number of challenges here. First, population-based reference ranges are problematic owing to the variability of 25-hydroxyvitamin D levels across different ethnic backgrounds, geographic locations, and seasons. Second, there is substantial evidence that vitamin D deficiency is common in the United States and many other countries, making it difficult to define a "normal" population. Last, what defines normal or optimal with regard to vitamin D status is a matter of debate, with some authorities indicating that many people, even people without signs or symptoms of pathology, are deficient or borderline deficient in vitamin D stores.2,4,28
One physiologic approach to define 25-hydroxyvitamin D ranges is to look at the relationship between 25-hydroxyvitamin D and PTH levels. These show an inverse relationship with PTH concentrations rising as the 25-hydroxyvitamin D concentration decreases.7 This is an important physiologic means to maintain calcium homeostasis. PTH begins to increase substantially when 25-hydroxyvitamin D concentrations drop below 30 to 40 ng/mL, suggesting that 25-hydroxyvitamin D levels below this range are not optimal, even though overt disease (eg, rickets, osteomalacia, bone pain) may not be evident. Secondary hyperparathyroidism can be corrected with an average 25-hydroxyvitamin D serum or plasma level of 32 ng/mL (80 nmol/L), and at least 1 reference laboratory uses this value as the lower limit of optimal 25-hydroxyvitamin D serum and plasma concentrations Table 1.4,7.28–41
An alternative approach to vitamin D reference ranges is to define clinical decision values for 25-hydroxyvitamin D serum and plasma concentrations such as the concentrations below which adverse health outcomes (especially osteoporotic-related bone fractures) increase significantly. This is the approach underlying the World Health Organization definition of vitamin D deficiency as a 25-hydroxyvitamin D serum or plasma concentration less than 20 ng/mL (50 nmol/L), which occurs in approximately 1 billion people worldwide.2 Some reference laboratories define optimal and deficient ranges for 25-hydroxyvitamin D concentrations, often with an insufficient or borderline deficient range in between. Some clinical decision values further delineate a "severe deficiency" range (often ≥10 ng/mL [10 nmol/L]) that have a high risk of serious skeletal abnormalities and, thus, warrant immediate treatment (Table 1).
The lack of consensus on 25-hydroxyvitamin D target ranges results in substantial variation in the reference ranges or target values used by reference laboratories and manufacturers of 25-hydroxyvitamin D assays. Table 1 lists the ranges for 4 large reference laboratories in the United States and for 3 marketed immunoassays. Some of the ranges in Table 1 include a toxic concentration threshold that varies from 80 to 180 ng/mL (50–450 nmol/L). Combined with analytic variability in 25-hydroxyvitamin D concentrations across different laboratories and methods (discussed later), the lack of consistency of reference ranges makes it challenging for clinicians to assess multiple 25-hydroxyvitamin D concentrations for a given patient if performed at different laboratories. For example, a 25-hydroxyvitamin serum or plasma concentration of 26 ng/mL (65 nmol/L) could be interpreted as in the lower end of the "optimum" range in one laboratory but could result in the "insufficiency" range for another laboratory. The variety of Table 1 does not include reference ranges used by individual clinical laboratories that have developed their own method (eg, HPLC or LC/MS/MS) and set a reference range based on published literature or some other approach.
Vitamin D Toxic Ranges
Like vitamin A, vitamin D can cause toxic symptoms if taken in overdose.32 Indeed, high doses of vitamin D2 and D3 are used as rodenticides, and hypervitaminosis D can be seen in patients ingesting such compounds.42 However, vitamin D toxicity in humans appears to be rare, especially compared with the frequency of vitamin D deficiency, leading some to argue that the fear of vitamin D toxicity has prevented adoption of more extensive vitamin D supplementation throughout the population.43 Hypervitaminosis D is usually associated with prolonged exposure to very high doses of vitamin D (eg, >10,000 IU/d),32 with a number of case reports documenting vitamin D toxicity from frequent ingestion of supplements containing very high amounts of vitamin D.44–46 Excessive sunlight or exposure to tanning beds does not cause vitamin D toxicity because prolonged UV light exposure degrades vitamin D precursors, preventing excessive formation of vitamin D3.2
A 25-hydroxyvitamin D concentration of 80 ng/mL (200 nmol/L) is the lowest level reported to cause toxicity in patients without primary hyperparathyroidism,32 and some reference laboratories use this value as the lower limit of a potentially toxic 25-hydroxyvitamin D concentration range (Table 1). Patients with renal failure can have 25-hydroxyvitamin D concentrations higher than 80 ng/mL (200 nmol/L) without signs or symptoms of toxicity because conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D is impaired.2 Other reference laboratories have adopted higher limits for toxicity up to 150 ng/mL (Table 1).
1,25-Dihydroxyvitamin D
Although 1,25-dihydroxyvitamin D is the biologically active form of vitamin D, this analyte is not a good marker of overall vitamin D status for multiple reasons.10 First, the circulating half-life of 1,25-dihydroxyvitamin D is only 4 to 6 hours, contributing to variability in 1,25-dihydroxyvitamin D serum and plasma levels at different times. Second, the concentrations of 1,25-dihydroxyvitamin D in serum and plasma are about 1,000-fold less than 25-hydroxyvitamin D and, thus, can be difficult to measure. Third, and perhaps most important, overall vitamin D deficiency leads to decreased intestinal calcium absorption and a lower ionized calcium level, which, in turn, stimulates increased secretion of PTH. Ultimately, PTH increases the ionized calcium level by multiple mechanisms, including increased renal production of 1,25-dihydroxyvitamin D. Thus, overall vitamin D deficiency can actually lead to an increased 1,25-dihydroxyvitamin D concentration.
Measurement of 1,25-dihydroxyvitamin D is useful in some clinical circumstances, including renal failure (failure to 1α-hydroxylate 25-hydroxyvitamin D), granulomatous disease (eg, sarcoidosis, histoplasmosis), and workup of rare inborn errors of vitamin D metabolism. In granulomatous disease, there is increased conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D that can lead to hypercalcemia. Studies have shown an association of lower 1,25-dihydroxyvitamin D serum and plasma concentrations and higher mortality in patients with cardiac disease,47,48 HIV,49 and renal failure,50 although it is unclear how to translate this information to clinical decision making.
A survey of vitamin D ordering indicated that many clinical laboratories in the United States have also seen an increase in recent years in 1,25-dihydroxyvitamin D orders, although not usually as dramatic as for 25-hydroxyvitamin D.5 Given the relatively narrow clinical value of measuring 1,25-dihydroxyvitamin D serum and plasma concentrations, this raises the possibility that 1,25-dihydroxyvitamin D levels may be ordered in error. Two possible reasons for misordering include confusion of the 2 forms of vitamin D or a mistaken notion that monitoring the "active" form of vitamin D should be done to assess nutritional status. In addition, clinicians may request measurement of both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D (perhaps thinking more information from this "panel" is helpful) when measuring only 25-hydroxyvitamin D alone is all that is needed for routine assessment of nutritional stores.
The growing clinical interest in vitamin D has led to dramatic increases in vitamin D testing. Consequently, laboratory professionals are confronted with the dual challenge of increasing testing volumes and helping clinicians navigate the complexities of vitamin D assays. Table 2 summarizes some of the preanalytic, analytic, and postanalytic issues related to vitamin D testing. Clinical laboratory professionals can guide clinicians in appropriate indications for ordering 25-hydroxyvitamin D and also develop strategies to prevent inappropriate ordering of 1,25-dihydroxyvitamin D. Education on 25-hydroxyvitamin D reference ranges can help place the results in a clinical context that can guide therapy and counseling of patients. Last, awareness of the limitations of the various 25-hydroxyvitamin D assays is especially important in comparing results across different assays, especially with the expected marketing of higher-throughput homogeneous immunoassays for 25-hydroxyvitamin D for automated instruments in the near future.
Case Summary
The patient had 2 measurements of 25-hydroxyvitamin D levels approximately 12 months apart, one by LC/MS/MS at a reference laboratory and the other by enzyme immunoassay at a medical center clinical laboratory. The 2 values (26 and 29 ng/mL [65 and 72 nmol/L]) essentially show no change in the patient's overall vitamin D nutritional status, especially considering the known variability between 25-hydroxyvitamin D assay methods and fluctuations in the 25-hydroxyvitamin D level that may occur over time for any given person. The confusion for clinicians and the patient is mostly related to the different reference ranges associated with the 2 results. Although the first assay result fell (barely) into an "optimal" range in the reference range, the literature shows that 25-hydroxyvitamin D levels between 20 and 30 ng/mL (50–75 nmol/L) fit into a borderline category, more than the recognized deficiency threshold of 20 ng/mL (50 nmol/L) but less than the 25-hydroxyvitamin D levels that avoid a compensatory increase in the PTH level that can lead to secondary hyperparathyroidism. One approach to communicate with clinicians is to say that the patient's 25-hydroxyvitamin D level is not ideal but not yet in the range associated with severe deficiency.
The ordering of 1,25-dihydroxyvitamin D in this case was unnecessary and potentially misleading. For this patient, the 1,25-dihydroxyvitamin D level was within the reference range despite borderline deficient 25-hydroxyvitamin D levels, a situation that can result from increases in the PTH level. The discussion with the clinician can include some information on the lack of necessity of 1,25-dihydroxyvitamin D measurement in many patients and the narrow list of situations that warrant measurement of this active form of vitamin D. If 1,25-dihydroxyvitamin D misordering seems to be common, education of clinicians and, perhaps, review of electronic or paper order sets that allow for ordering of 1,25-dihydroxyvitamin D may be warranted.
Upon completion of this activity you will be able to:
describe the potential health consequences of vitamin D deficiency or excess.
analyze the 2 main methods (immunoassay, liquid chromatography/tandem mass spectrometry) used for measuring 25-hydroxyvitamin D serum/plasma concentrations and how they may produce different results (including obtaining fractionated vs total 25-hydroxyvitamin D concentrations).
define the indications for assessing 1,25-dihydroxyvitamin D (most biologically active form of vitamin D).
The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit ™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module.
The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.
Questions appear on p 653. Exam is located at www.ascp.org/ajcpcme.
- © American Society for Clinical Pathology


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Candy Flip were a British electronic dance band associated with the Madchester music scene in the early 1990s. They are best remembered for their cover version of The Beatles hit "Strawberry Fields Forever", which was a #3 hit in the UK Singles Chart.
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