text: AOSIS OpenJournals http://www.openjournals.net firstname.lastname@example.com http://www.ojvr.org 0030-2465 2219-0635 The African buffalo: A villain for inter-species spread of infectious diseases in southern Africa The African buffalo (Syncerus caffer) is a large wild bovid which until recently ranged across all but the driest parts of sub-Saharan Africa, and their local range being limited to about 20 km from surface water. They are of high ecological value due to their important role as bulk feeders in the grazing hierarchy. They also have high economic value, because they are one of the sought after 'Big Five' in the eco-tourism industry. In Africa, buffaloes have been recognised for some time as an important role player in the maintenance and transmission of a variety of economically important livestock diseases at the wildlife and/or livestock interface. These include African strains of foot-and-mouth disease (FMD), Corridor disease (theileriosis), bovine tuberculosis and bovine brucellosis. For a number of other diseases of veterinary importance, African buffaloes may also serve as amplifier or incidental host, whereby infection with the causative pathogens may cause severe clinical signs such as death or abortion as in the case of anthrax and Rift Valley fever, or remain mild or subclinical for example heartwater. The long term health implications of most of those infections on the buffalo at a population level is usually limited, and they do not pose a threat on the population's survival. Because of their ability to harbour and transmit important diseases to livestock, their sustainable future in ecotourism, trade and transfrontier conservation projects become complex and costly and reliable diagnostic tools are required to monitor these infections in buffalo populations. Anita L. Michel1 1Department of Veterinary Tropical Diseases, University of Pretoria, South Africa Roy G. Bengis2 2Directorate Veterinary Services, Skukuza, South AfricaAnita Michel firstname.lastname@example.com Private Bag X04, Onderstepoort 0110, South Africa 45379210.4102/ojvr.v79i2.453 Michel, A.L. & Bengis, R.G., 2012, 'The African buffalo: A villain for inter-species spread of infectious diseases in southern Africa', Onderstepoort Journal of Veterinary Research 79(2), Art. #453, 5 pages. http://dx.doi.org/10.4102/ojvr.v79i2.453 Proceedings of the Conference of the Southern African Centre for Infectious Disease Surveillance 'One Health' held at the National Institute for Communicable Diseases, Johannesburg, July 2011. © 2012.The Authors. Licensee: AOSIS OpenJournals. This work is licensed under the Creative Commons Attribution License. Introduction The transmission and spread of infectious diseases amongst and between domestic and wild animals can occur directly through contact (foot-and-mouth disease [FMD], bovine tuberculosis and brucellosis), or indirectly through the agency of haematophagous arthropod vectors such as mosquitoes, tsetse flies and Ixodid ticks (Kock 2005). In addition, environmental contamination with infected ticks (theileriosis) or fomites (anthrax) can infect livestock even when the habitat is not shared at the same time. Some of these diseases can affect a variety of wildlife hosts, but only very few species play a decisive role in disease maintenance and transmission at the wildlife and/or livestock interface. The increasing competition for land available for livestock – based agriculture or wildlife ranching and conservation has highlighted the need for an integrated approach to sustainable livestock and wildlife health, use and management. In this debate the African buffalo features as a villain to those who wish to protect livestock populations from devastating diseases, as they undermine national and international disease eradication schemes, which have been implemented and executed with significant success, and at great cost in the past (Munag'andu et al. 2006). On the other hand, conservationists and wildlife ranchers take on a distinctly different attitude towards controlling livestock diseases transmitted by wildlife (Bengis, Kock & Fischer 2002). In this overview the role of the African buffalo, both as a victim and asymptomatic carrier in the transmission of the most important livestock diseases at the wildlife and/or livestock interface, is reviewed. Links between disease ecology and buffaloes' ecology are examined in an attempt to reveal why buffaloes are successful maintenance hosts for several of those diseases. Status of African buffaloes Since the early days of European settlement in southern and eastern Africa, African buffaloes have attracted the admiration of hunters and have consequently been a highly sought after trophy animal for the past three centuries (Prins 1996). In addition, they gained extraordinary value for other ecotourism related purposes during the past decades (Van der Merwe, Saayman & Krugell 2004). The African buffalo (Syncerus caffer) is one of the most ubiquitous large herbivores which can tolerate a wide range of climatic conditions and habitats as long as it is provided with access to an abundant supply of water (Grimsdell 1969; Sinclair 1977). Ecologically, the African buffalo is a bulk grazer and occupies an important niche through opening up habitats that are preferred by short-grass grazers (De Vos & Bengis 1994). Currently the conservation status of the African buffalo is satisfactory with no immediate threat of extinction (Friedmann & Daly 2004). Infectious diseases transmitted by African buffaloes African buffaloes have been recognised for some time for various roles in disease transmission amongst wildlife species and at the interface with livestock. Amongst the best known diseases are foot-and-mouth disease, caused by the African strains SAT 1, 2 and 3 (FMD viruses) and Corridor disease (theileriosis, caused by Theileria parva), owing to the disastrous, large scale clinical outbreaks they may cause in livestock (Anonymous 2007; Norval, Perry & Young 1992). However, African buffaloes have been implicated in a number of other epidemiological roles involving both indigenous and alien livestock diseases. Diseases which originated in Africa and co-evolved with African wildlife species including African buffaloes are defined as indigenous. They generally do not pose a threat on the survival of their hosts' populations because of the evolutionary development of unique coping mechanisms. Well known indigenous diseases maintained by African buffaloes include FMD caused by the SAT strain viruses (Thomson 1995), Corridor disease and African trypanosomosis (Anonymous 2007, 2009; De Vos & Bengis 1994; Norval et al. 1992). In contrast, foreign, so-called alien livestock diseases, such as bovine tuberculosis (Mycobacterium bovis) and bovine brucellosis (Brucella abortus), have been introduced and successfully established themselves in buffaloes which serve as wildlife maintenance host (De Vos et al. 2001). Rinderpest falls within the same grouping of alien diseases but its extreme pathogenicity and high mortality precluded the development of a wildlife reservoir (De Vos & Bengis 1994). The devastating effect of rinderpest on many cloven hoofed African ungulate species and African buffaloes (as an epidemic end host) in particular at a local or regional population level was more important ecologically and epidemiologically than their potential role in transmission of the disease to livestock. In 2011, rinderpest was officially eradicated from the world (Morens et al. 2011) and therefore its significance for interspecies transmission no longer exists. Due to their wide geographical range and distribution, African buffaloes have been furthermore implicated as amplifiers or incidental hosts in the epidemiology of a number of other indigenous infectious agents, including those confined to specific localised geographic areas, for example trypanosomes is limited to certain savannah and forested areas endemic for tsetse flies, and buffalo are one of the preferred hosts for these flies and develop a symptomatic carrier state for this parasite (Molooa et al. 1999). Anthrax, caused by Brucella anthracis is limited to certain anthrax endemic areas of the African continent (Anonymous 2009). For Rift Valley fever little is known about the precise mechanisms of virus maintenance and transmission. However, buffaloes have been associated with a possible sentinel role during epidemics and a possible maintenance role during interepidemic periods, respectively (Bengis et al. 2010; LaBeaud et al. 2011). Factors related to African buffaloes in disease transmission The epidemiology of infectious diseases is determined by factors related to the host, the environment and the causative pathogen. In the case of African buffaloes a number of intrinsic behavioural characteristics are instrumental to its role in hosting and transmitting livestock diseases. They are a highly social species living in large herds of up to 1000 animals, whose gregarious behaviour provides ideal conditions for direct pathogen transmission via aerosol and body secretions (Grimsdell 1969; Michel et al. 2006). Individual or small groups of buffaloes have also been shown to migrate over large distances within short periods of time, either in response to drought or as a result of the dispersal strategies for heifers or bachelor bulls. These events, like fission and fusion events driven by changes in the seasonal availability of grazing, take place on a regular basis and constitute a powerful vehicle for pathogen dispersal across herds (Cross, Lloyd-Smith & Getz 2005; Halley, Vandewalle & Taolo 2002). Factors related to the pathogen As regards the chronic, slow alien livestock diseases, such as bovine tuberculosis and bovine brucellosis, the lack of coping mechanisms in naïve African buffaloes may result in deleterious long term effect on certain buffalo populations. Some pathogens exhibit a very strict and narrow host range, for example T. parva, whilst M. bovis is capable of causing disease in a very broad spectrum of domestic and wild animal species. Amongst its wildlife hosts, maintenance host potential has been confirmed for African buffaloes and is suspected for greater kudu and possibly others (Michel et al. 2006). Indirect transmission of pathogens via environmental contamination is more effective if the organism can survive for significant periods of time outside of its host(s). Whilst the survival of most viruses outside the host is very short, M. bovis has been shown to survive for between five days and four weeks in the environment (Tanner & Michel 1999) and the spore forming Bacillus anthracis bacterium is ideally equipped for long term (years) survival outside of a host (De Vos 2004). Factors related to the environment African buffaloes occur in many different habitats including woodlands, grasslands, swamps, floodplains and thickets, at a range of altitudes, provided they have access to an abundant supply of water and good quality grazing. This species' ability to survive in all but the more arid habitats, allows it to host a variety of pathogens under diverse environmental conditions. For example, the abundance of the Aedine mosquitoes, the endemic vector of the Rift Valley fever virus, is influenced by wet climatic shifts which are frequently associated with increased virus transmission to domestic and wild ruminants (Bengis et al. 2010). In addition, African buffaloes spend a considerable percentage of their time in and near water (Ryan, Knechtel & Getz 2006) which further increases their risk of exposure to vectors. In addition, African buffaloes are a preferred host for certain ixodid tick species, the vectors of various protozoal and rickettsial parasites of bovids. The modern wildlife industry grows at an average annual rate of 5.6% in terms of area exempted for game ranching and is mainly based on ecotourism, hunting and live game trade (Cloete, Taljaard & Grove 2007). This rapid growth rate in conjunction with the historical iconic role of the African buffalo as a member of the 'Big Five' for viewing, photographing and hunting has lead to an increase in the numbers and distribution of buffaloes on private land. In certain parts of South Africa the number of game farms registered for keeping buffaloes has equalled or exceeded that of livestock, resulting in an expansion of the wildlife and/or live stock interface and hence a risk in bi-directional disease transmission. High population densities and frequent translocation of African buffaloes between private game properties for commercial gain are contributing to cumulative risk of African buffalo to contract or transmit livestock diseases. For this reason, in South Africa buffaloes and cattle may not be kept together on shared rangeland. However, pathogens do not generally respect fences. Against the background of the establishment of large wildlife conservation areas and transfrontier parks in southern Africa, the potential role of buffaloes in the transmission of infectious diseases at the wildlife and/or livestock interface cannot be ignored. High expectations have been linked to the creation of large conservation areas in terms of improved and sustainable livelihoods for the communities in and around those wildlife areas. However, increased numbers of livestock and buffaloes, in the absence of game deterrent fences and often a lack of effective livestock vaccines, will inevitably increase the risk of disease transmission, and make disease eradication from livestock virtually impossible (Kock 2005). Impact of infectious diseases on African buffaloes and their environment Amongst the infectious diseases, FMD and Corridor disease and African trypanosomosis are truly asymptomatic in African buffaloes, which act as biological reservoirs of infection in an endemic cycle. The FMD infection occasionally escapes into other sympatric wild cloven-hoofed species, and where livestock are in contact with African buffaloes, they may become infected resulting in devastating outbreaks with a high socio-economic impact (Vosloo et al. 2005). Rift Valley fever, is a seasonal vector born disease and viremia and abortions have been reported in African buffaloes (Evans et al. 2008). Their exact role in the epidemiology of Rift Valley fever is however, still unknown but results of serological investigations in Kenya and South Africa indicated that African buffaloes become infected with the virus (Evans et al. 2008; LaBeaud et al. 2011). Bovine tuberculosis in African buffaloes has been well documented and can be described as a chronic, progressively debilitating condition (De Vos et al. 2001). It has spread throughout the buffalo population of the Kruger National Park and spilled into more than a dozen other wildlife species. There is a continuous risk for spillback into livestock and an associated zoonotic risk for animal owners, which is undetermined (Berg et al. 2011; Michel, Müller & Van Helden 2010). Anthrax is a sporadic, usually fatal disease affecting buffaloes in numerous endemic areas in sub-Saharan Africa (De Vos 1990; Mohan & Gotts 1970). Herbivores are known to be more susceptible to anthrax than omnivores and carnivores, and losses in African buffaloes, greater kudu, nyala and waterbuck have been significant in outbreaks of this disease in southern and eastern Africa (De Vos 2004). When buffaloes are affected by anthrax, they serve as highly effective multipliers of B. anthracis, which can contaminate the soil and run-off water, and carcasses become amplifiers for blowflies. Anthrax may be transmitted to neighbouring livestock farms and initiate an outbreak amongst cattle, and the converse has also been experienced when an outbreak in cattle spilled over into wildlife in an adjoining conservation area (Malilangwe – Zimbabwe) (De Vos 1990). It has been speculated that African buffaloes are the species with the highest susceptibility to rinderpest, which decimated the buffalo populations all over Africa during the rinderpest epidemic between 1888 and 1899 (De Vos & Bengis 1994). Diagnosis and control of infectious diseases in African buffaloes Availability of diagnostic tests for wildlife species is very often the biggest limitation in diagnosing infectious diseases in target wildlife species which are taxonomically far removed from the closest livestock counterparts. The African buffalo falls into the subfamily Bovinae together with domestic cattle, which is helpful and provides a basis for adapting and developing diagnostic tests for relevant infections in buffaloes. However, it needs to be emphasised that all tests applied in buffaloes still require validation to prove fitness for purpose as stated by the World Organisation for Animal Health (OIE) (OIE 2009). The question whether infectious diseases in buffaloes require controlling is a contentious one and is best discussed per disease grouping. Since the causative agents of certain indigenous diseases, namely FMD viruses, trypanosomes and theilerias, are widely maintained by African buffaloes and generally do not pose a threat to these population's existence, diagnostic testing is usually applied for monitoring and surveillance activities at population level. For movement purposes and international trade, the same tests (including direct pathogen detection for Corridor disease and trypanosomosis) are applied at individual animal level in conjunction with herd testing records. It is accepted that FMD can at best be contained in wildlife areas that have buffaloes, but eradication will not be achievable (Vosloo et al. 2005). The situation is essentially the same for indigenous diseases detected less frequently in African buffaloes, such as Rift Valley fever and anthrax, where outbreaks are monitored strictly for epidemiological information and analyses. A very different scenario is presented in the cases of bovine tuberculosis and bovine brucellosis, which are both alien diseases introduced into the buffalo population most likely through contact with infected cattle. Following their successful establishment in African buffaloes as their wildlife reservoir or maintenance host, the state veterinary and conservation authorities have been faced with a set of previously unknown challenges. Apart from the need to prevent spillover of the diseases to neighbouring livestock, these diseases may spread uncontrolled within infected conservation areas. Although our current knowledge on the impact of bovine tuberculosis and bovine brucellosis does not indicate an immediate threat on buffalo survival at the population level, it would be premature to make any prediction about the long term impact at this point in time. As no effective vaccine exists for bovine tuberculosis in animals and given the extremely broad host spectrum of the causative organism, the real threat goes beyond buffalo conservation but concerns severely affected sympatric species such as lions and kudus (Michel et al. 2009). It is fair to speculate that African buffaloes will not remain the only maintenance host in an endemically infected ecosystem such as the Kruger National Park and disease management and control strategies are urgently called for. Two effective vaccines are registered for the control of bovine brucellosis in cattle, but their efficacy and safety in African buffaloes has not been tested, as the disease is currently considered to have little effect on African buffaloes and the ecosystem (Godfroid 2004). Pre-movement testing of buffaloes for both bovine tuberculosis and brucellosis is an absolute requirement to minimise the risk of disease transmission to uninfected populations. In the case of bovine tuberculosis serological tests are not useful to detect infection and the intradermal tuberculin test (skin test) is applied in conjunction with the interferon gamma assay (Michel et al. 2011; Michel & Simoes 2009). ConclusionIt is clear that disease transmission at the interface is bi-directional and African buffaloes are culprits or villains in respect of some diseases, whilst they have fallen victim to alien diseases transmitted from cattle. As the wildlife and/or livestock and/or human interface is rapidly expanding and gaining in intensity and complexity, there should be no room for a blaming game, but it must be appreciated that African buffaloes form an integral part of the indigenous fauna of Africa and are inseparable from their indigenous pathogens. A strictly separate approach is needed for the alien diseases which may directly affect the health of buffaloes or indirectly the conservation of wildlife by turning infected areas into 'conservation islands' and making them unavailable for conservation in the bigger sense. To enable ecologists, veterinary researchers and conservation biologists to correctly assess and predict the long term dynamics of significant livestock diseases at this growing and intensifying disease interface, an understanding of the host-parasite interactions at population level in cattle and African buffaloes is crucial to finding solutions and to attempt achieve compatibility between traditional livestock farming and wildlife conservation-based ecotourism. It should also be emphasised that host-parasite interactions are not limited to the processes guiding infection and immunopathogenesis, but they must include the external determinants of the environment, including climate change, human interventions and other ecosystem drivers. 1.Anonymous, 2007, 'Institutional strategies and economic impacts of alternative FMD prevention and control strategies in Southern Africa', in B.D. Perry & K.R. Sones (eds.), International Livestock Research Institute, p. 56, Nairobi, Kenya.2.Anonymous, 2009, 'African animal trypanosomiasis', Center for Food Security and Public Health, Iowa State University, Iowa.3.Bengis, R.G., Kock, R.A. & Fischer, J., 2002, 'Infectious animal diseases: The wildlife/livestock interface', Revue Scientifique et Technique 21, 53–65. 4.Bengis, R.G., Swanepoel, R., De Klerk, L-M., Pienaar, N.J. & Prinsloo, G., 2010, 'Rift Valley fever: Current concepts and recent findings', paper presented at the 9th Annual Conference of the 'Southern African Society for Veterinary Epidemiology and Preventive Medicine', The Farm Inn, Pretoria, South Africa, 18–20 August.5.10.1128/JB.00750-10210976086.10.3957/0379-4369-37.1.717.10.1016/j.anbehav.2004.08.0068.De Vos, V., 2004, 'Anthrax', in J.A.W Coetzer & R.C Tustin (eds.), Infectious diseases of livestock, n.p., Oxford University Press, Cape Town. 9.De Vos, V., 1990, 'The ecology of anthrax in the Kruger National Park, South Africa', Salisbury Medical Bulletin 68, 19–23.10.De Vos, V., Bengis, R.G., Kriek, N.P., Michel, A., Keet, D.F., Raath, J.P. & Huchzermeyer, H.F., 2001, 'The epidemiology of tuberculosis in free-ranging African buffalo (Syncerus caffer) in the Kruger National Park, South Africa', Onderstepoort Journal of Veterinary Research 68, 119–130.1158508911.De Vos, V. & Bengis, R.G., 1994, 'The disease status of African buffalo in South Africa', in W. Van Hoven, H. Ebedes & A. Conroy (eds.), Wildlife ranching: A celebration of diversity Proceedings of the 3rd International Wildlife Ranching Symposium, Centre for Wildlife Management, University of Pretoria, Pretoria, October, 1992, n.p.12.10.1017/S095026880700980613.Friedmann, Y. & Daly, B., 2004, Red Data book of mammals of South Africa: A conservation assessment, Conservation Breeding Specialist Group Southern Africa, South Africa.14.Godfroid, J., 2004, 'Brucellosis in wildlife', in J.A.W. Coetzer & R.C. Tustin (eds.), Infectious Diseases of Livestock, Oxford University Press.15.Grimsdell, J.J.R., 1969, 'Ecology of the buffalo, Syncerus caffer in western Uganda', PhD thesis, Cambridge University.16.10.1046/j.0141-6707.2001.00336.x17.Kock, R.A., 2005, 'What is the infamous wildlife/livestock disease interface? A review of current knowledge', Southern and East African Experts Panel on Designing Successful Conservation and Development Interventions at the Wildlife/Livestock Interface: Implications for Wildlife, Livestock, and Human Health. AHEAD Animal Health for the Environment And Development Forum. IUCN/SSC Veterinary Specialist Group, Southern Africa Sustainable Use Specialist Group et al., IUCN, Gland, Switzerland and Cambridge, UK, 14–15 September 2003.18.10.4269/ajtmh.2011.10-01872146002419.10.1016/j.vetmic.2005.11.0351634381920.10.1016/j.vetmic.2008.07.0231878678521.10.1016/j.prevetmed.2010.10.0162112293222.10.1016/j.vetmic.2009.08.0291977313423.10.1016/j.vetimm.2008.09.0251900799924.Mohan, R.N. & Gotts, M.G., 1970, 'Diseases and parasites of the African buffalo (Syncerus caffer)', Veterinary Bulletin 40, 157–166.25.Molooa, S.K., Orindab, G.O., Sabwaa, C.L., Minjaa, S.H. & Masakea, R.A., 1999, 'Study on the sequential tsetse-transmitted Trypanosoma congolense, T. brucei brucei and T. vivax infections to African buffalo, eland, waterbuck, N'Dama and Boran cattle', Veterinary Parasitology 80, 197–213. 995034426.10.1093/infdis/jir3272165323027.Munag'andu, H.M., Siamudaala, V.M., Nambota, A., Bwalya, J.M., Munyeme, M., Mweene, A.S. et al., 2006, 'Disease constraints for utilization of the African buffalo (Syncerus caffer) on game ranches in Zambia', Japanese Journal of Veterinary Research 54, 3–13.1678697328.Norval, R.A.I., Perry, B.D. & Young, A.S. (eds.), 1992, The epidemiology of theileriosis in Africa, American Press, London.29.OIE, 2009, 'Standard Operating Procedure (SOP) for OIE Validation and Certification of Diagnostic Assays', Version 2.1.30.Prins, H.H.T., 1996, 'Ecology and behaviour of the African buffalo - Social inequality and decision making', PhD thesis, Chapman & Hall, London.31.10.2193/0022-541X(2006)70[764:RAHSOA]2.0.CO;232.Sinclair, A.R.E., 1977, 'The African buffalo - a study of resource limitations of populations', PhD thesis, University of Chicago Press.33.Tanner, M. & Michel, A.L., 1999, 'Investigation of the viability of Mycobacterium bovis under different environmental conditions in the Kruger National Park', Onderstepoort Journal of Veterinary Research 66, 185–190.1063170834.Thomson, G.R., 1995, 'Overview of foot and mouth disease in southern Africa', Revue Scientifique et Technique 14, 503–520.859338635.Van der Merwe, P., Saayman, M. & Krugell, W., 2004, 'Factors that determine the price of game', Koedoe 47, 105–113.36.Vosloo, W., Bastos, A.D.S., Sahle, M., Sangare, O. & Dwarka, R.M., 2005, 'Virus topotypes and the role of wildlife in foot and mouth disease in Africa', Southern and East African Experts Panel on Designing Successful Conservation and Development Interventions at the Wildlife/Livestock Interface: Implications for Wildlife, Livestock, and Human Health. AHEAD Animal Health for the Environment And Development, Forum. IUCN/SSC Veterinary Specialist Group, Southern Africa Sustainable Use Specialist Group et al., IUCN, Gland, Switzerland and Cambridge, UK, 14–15 September 2003.


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Custom 1990 Mazda B2200 - Plane Jane
A Mini-Trucker's Salute
This truck is definitely a little different than the average mini-truck built today. In fact the story behind Plane Jane and us here at MT is an interesting one in itself. The owner, Shawn Arcidino, wanted to keep the truck under tight wraps, so we didn't even get wind of it until right before we headed off to Showfest. We got a few snapshot photos and a little write-up and didn't put too much thought into the truck after that, and it got filed away in the Readers' Rides section - what a mistake that was! Showfest is such a huge show that we only came upon Plane Jane in person the very last day. Unfortunately, we missed the mark and a few other magazines beat us to the punch, so we waited patiently for our turn to have a crack at her. But this truck is not just a one- or two-feature mini, so we decided to go all-out and show our readers what really went into the buildup of this truck. Instead of hearing us ramble on and on about how cool both the truck and the owner are, we wanted you to hear the story behind the scenes and the reason for the build straight from the source. So, enjoy the story of all that is Plane Jane told by none other than Shawn "Sick Side" Arcidino. For more information or to get some killer custom work done, call Sick Side Kustoms at (816) 525-4421.
If you have attended any major national shows this year, you have probably seen a truck in the distance that might not strike you as something that necessarily belongs in a mini-truck show, something you would expect to see at an air show or behind a chain-link fence on a federal military base. Intrigued, you probably walked over to the truck and after a good long walk around her (if you paid close enough attention) you might have noticed that you were looking at one of the most heartfelt trucks that you've ever laid your eyes on. I am not just saying that because she's mine. I'm saying that because this one particular truck is Plane Jane, the P-51 Mazda truck built with my own two hands as owner and operator of Sick Side Kustoms. This truck was built and is driven with all my heart and soul, solidly committed to supporting the troops, the men and women of the Armed Forces (most of them are around our age), and showing them the best way I can how much they are appreciated. While we are kicked back checking out rides and wondering where the next party is, they are half a world away fighting for the rights we are enjoying, even as you're reading this magazine. Take a second and think about all the freedoms you enjoy each and every single day, and if you ever get a chance thank the troops in your own special way for those very same freedoms. Many of you reading this who I've met this show season, and even those I haven't, know someone overseas fighting or who died to fight for our country. And for them, I give the one gift I can, Plane Jane. This truck will honor all who have died and all who still stand to serve this great country of ours. Well, thanks for checking out my truck and don't forget to support the troops.
Shawn Arcidino, Sick Side Kustoms
History of Big, Beautiful Doll
With the call sign 472218, it was coded WZ-I while flown in the European Theatre of Operations and carried the nose art of Big, Beautiful Doll. This P-51 was flown by Colonel John Landers (pictured here), commanding officer of the 78th Fighter Group, who flew a series of P-38s and P-51s, all of which were named Big, Beautiful Doll. Col. Landers finished the war with 14.5 victories, plus 20 additional ground victories. It's interesting to note that the top row of Kill markings are for six Japanese aircraft, and Col. Landers flew in both the PTO and ETO and was an ACE in both.
The Interior
Just like every nut and bolt on Plane Jane, the interior was built the way it was for a reason. The inside of the P-51 Mustangs (used in WWII) were in no way, shape, or form pretty; they were bare and not really all that comfortable. The structure in those planes were much like the confines that we find in our trucks once we have stripped all the stuff that can catch fire during our buildups. It's just painted olive drab green with some dirt here and there. So for that reason, the interior of Plane Jane is afforded no comforts, such as a stereo or carpet. In the center of the two custom bomber seats, which were made of metal in the actual planes to keep the pilots awake during long missions, you will find a small canvas military-surplus bag. This houses the battery and serves as a good place to rest your arm. The dash is very simple, with not much of the cool gadgetry of today, just gauges that you would find on your early-day airplane. The gear selector is comprised of the leftover parts of a lawn mower, but to me, it looked like the yoke of a plane. The gauges in the dash and every other part in the truck were actually never attached to a P-51. I had to replicate all of that on my own.
Moving to the front, you will notice a flat bumper and an unusual grille shell. The reason there is no fancy grille or shiny bumper is because P-51s were not made for looks, but for speed and war. The radiator that cools Jane down on long missions to the gas station for smokes and more gas is suspended by two 2-inch straps, a detail that would not be on a P-51 because it was air-cooled. I just thought it looked cool and industrial. If you take a bullet in this one, unstrap it, put a new one on, and come right back, ready for action before your motor cools.
The paintjob mimics that of the Big, Beautiful Doll (one of the 151 P-51 flying survivors still around today), call number WZ I 472218. I had to put my own spin on it, and what better way than with a thin, well-endowed blonde named Plane Jane? Besides, I wanted people to ask what kind of truck I had and I could say a "plane" old Mazda. Every rivet on the bed was done by hand, just like the old times. The rest were painted on. I love to see people touch them and expect them to be real. The markings were changed from WZ-I to P-51 out of the respect for people and history. I also had to change the Kill signs so I wouldn't offend anyone.
Engine Bay
The front engine bay was designed from pictures that I received from the Revell model of the plane that I purchased from Wally World (Wal-Mart, in case you didn't know). The pictures were simple structure shapes, so I was able get a good idea of the composition. The flat-black piece of American steel in the center is King of all Hotrods, a small-block Chevrolet, all-black just like the planes. I wrapped all the hoses and wires with cloth bandage tape and used a product I am sure your mom has right now, Old English wood cleaner, to give it that worn-out look and even put part numbers on them. The motor shoots out its "go-gases" through the pipes that run directly under my floor (which also serves as my heater in the winter) to six exhaust pipes that exit right behind the door. Many have stated that the exhaust sounds much like an early airplane. That was just luck!
Often-Overlooked Details
The most common details that people miss are listed here so you can find them for yourself at the next show. Take notes. There's oil coming out of the bullet hole on the passenger side of the bed. There is a pinup picture on the driver-side B-pillar that I got from a swap meet. I weathered it and had my girl sign it for good luck, just like the pilots used to do. As for the door locks inside the cockpit, you just push the locks down to open the door. There's an actual bullet hole that I shot with my 9mm on the passenger-side floor with airbrushed smoke trails. The soot on the hood has been swiped to look as if it will smear when you wipe it down. The dirt that is coming out of the cracks of the plane's seams is not rust; P-51s were made of aluminum, so they didn't rust. The screw chips on the Kill signs were painted to actually look like the paint has been chipped during access to a maintenance hatch. Check out Plane Jane's feet closely. Now, I know what you're thinking, Why look at her feet when there is so much more of her to see? When you're done with your little pervert session, look down at her toes - they're backwards. We did that just to see who pays attention and to bust all the foot-fetish people. The cooler in the bed between the louvered panels lifts up, and you can fill it with all sorts of goodies. In the paint on the sides of the truck, you can see the wing lines and the gun barrels.
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Is Tilda Swinton's Nap Bad for Art?
Another day, another nap for the actress/cultural oddity at the Museum of Modern Art. Not everyone's so excited this time, including a high-profile art critic, but maybe they should be.
Another day, another nap for Tilda Swinton at the Museum of Modern Art. Yes, the actress/cultural oddity was back at MoMA in her glass box in New York again Monday after creating a sensation this weekend when she, unannounced, began performing her piece "The Maybe," originally devised in collaboration with Cornelia Parker, at the preeminent museum. "The Maybe" consists of Swinton sleeping in a glass box. And while museum visitors and culture critics around the world continuing to freak out Swinton's appearance, it was also slammed today by one of the most high profile art critics on Earth: New York magazines's Jerry Saltz, who sees the Swinton thing as more self-serving stunt than performance art—even if there's something to that.
Swinton-mania is still definitely going strong. There's now a Tumblr dedicated to answering the question "Is Tilda Swinton Sleeping in a Box?" The answer today was of course "Yes."
According to Gothamist, Swinton moved upstairs today to a second floor gallery, after she was on display Saturday in the Agnes Gund Garden Lobby. She also apparently got some celebrity visitors: Sarah Jessica Parker and Matthew Broderick stopped by, according to People. James Franco has also been reported at the scene, but that should surprise absolutely no one—he once stared at performance artist Marina Abramovic from a chair at MoMA, and is, well, James Franco.
And, yet, the Swinton performance has not impressed everyone. Saltz wrote that Swinton's performance is yet another example of MoMA—which recently and famously staged Abramović's "The Artist is Present," the exhibition that drew the attention of celebrities aside from Franco—using a living art gimmick to draw in visitors. He calls the Swinton piece the "latest twist on whatever-it-takes to get them in the doors while presumably showing a little intellectual leg." Saltz continues:
I'm a sourpuss, so I think this is just a hokey artsy strategy to disguise the fact that the place doesn't have enough room to show its tremendous collection. Visiting there now is unpleasant because the museum has been so overcrowded since its 2004 makeover. The event also has inner content: MoMA is narcissistically puffing its celebrity feathers, playing at being avant-garde. And then the atrium itself is a problem: It's such a weirdly proportioned disembodied non-space that almost all efforts to hang traditional artworks there have been a bust.
Saltz questions MoMA's relationship to celebrity and what it costs a museum with so much else to offer. The quandary of the relationship of celebrity to museum culture is not a new one, and in fact was recently the basis of critique against gallerist-turned-MOCA director Jeffrey Deitch. In October of last year Guy Trebay wrote of Deitch's tenure in the New York Times:
There have been missteps over the two years since Mr. Deitch moved west, specifically a handful of shows that took celebrity as their focus. Yet while there have been measurable and even outstanding successes, these have been purged from the narrative.
But, as Saltz points out himself, there is also some good to the project in "the wonderful possibility that museum visitors might come here, see a movie star asleep in a case, accept it as some kind of art, get super excited, and wonder how on Earth something this strange got started. And they'd rush upstairs to the greatest collection of modern art in the world, let themselves go, and add their thinking to the group mind." Even if the idea itself borders on sell-out, there is some purpose served by the undoubtedly attention-grabbing piece: More people should see what MoMA has to offer, even if it's surrounded by the seemingly random stunt piece. And since she was napping a bit closer to some actual art rather than a staircase just beyond the museum entrance on Monday, well, maybe there's hope for this ridiculous thing yet. Just don't get too excited for back-to-back performances. MoMA is closed on Tuesdays.


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Reviewed by: Rootman (Audio Enthusiast)
Review Date June 28, 2010
Overall Rating 5 of 5
Value Rating 5 of 5
Used product for More than 1 year
This is my third McCormack amp. I've gone from the DNA-1 Deluxe, to the DNA-225 and now this. The other two were toys compared to this. I call this one the Velvet Hammer from Steve. It's being used to drive a pair of Magnepan 3.6r's through a VTL 5.5. It's like the Energize bunny; just keeps going and going and going….until you stop or blow those Maggies up!!! It even makes Maggies have bottom end, contrary to what everyone believes about a lack of bass with 3.5′s.
The one thing I do notice, is that when a recording is bad, it's really bad with this amp because those etchy highs are really etched with this much current driving your speakers. On the other hand, there's so much control and reserve headroom available, it takes you to places on recordings that you'll never hear with the other two amps I've owned, or other amps that I've borrowed because of the power reserves it has. Initially when I bought it made me want to play all my favorite albums in one night when I started hearing Jimi Hendrix or Stevie Ray Vaughn like they really played, rather than what I thought they sounded like.
So where does it really shine. I would guess I would say that the mids and highs are really pristine with this amp. The more you listen to female vocalists, like Patricia Barber, Sheryl Crow, Diana Krall or Bonnie Raitt you just can't hear enough of them. Male singer like Jackson Browne and Elton John, really sound like themselves, instead of like listening through a glass of water like with other amps.
I know Magnepan says that Bryston amps match up well with their speakers, but I'm telling you after having had this DNA-500 for 3 years, that their Mono Block 7′s can't hang with the Velvet Hammer, and as good as the Conrad Johnson 350 SS amp is, it gives up long before this girl decides to stop partying no matter what kind of music you're feeding her. The Bryston's sound edgy and brittle after a few weeks, and the CJ is a great piece, but dollar for dollar, just plain isn't as good a value as Steve's top of the line. Funny that CJ now is manufacturing the McCormack line in 2010…..
If you can find one of these amps for around $4000 and are looking for something in this class that's solid state, then you should give this one a listen. As with everything in this business, it might be for you and it might not. Different ears hear different things when they sit down to give things a listen. I find all of Steve's amps to be very musical to my ears. They're not tubes, but they sure have a lot of those tube like characteristics that I love in tubes. Why don't I use tubes versus something like a DNA-500 you might ask? Convenience and power. You have to spend a lot more money on tubes and more time to get what I feel is an equivalent sound for the buck. To my ears that's probably twice the investment to get the return I feel I'm getting for my buck. That's a lot of bang for me……..
Good listening….Trust you own ears, not someones review!!!!!!
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Evangelical United Brethren Church
Evangelical United Brethren Church, Protestant denomination created (1946) by the union of the Evangelical Church and the United Brethren in Christ. Both denominations originated early in the 19th cent. and had similarities in organization and polity. The Evangelical Church was begun by the evangelical, pietistic efforts of Jacob Albright, a Lutheran convert to Methodism, who preached among his fellow Pennsylvania Germans. The United Brethren in Christ came into being as a result of the evangelistic preaching of Philip William Otterbein of the German Reformed Church and Martin Boehm, a Mennonite bishop. These two ministers conducted revivals among the German-speaking people of Pennsylvania, Maryland, and Virginia. The methods of Albright, Otterbein, and Boehm were similar: after evangelistic meetings, converts were encouraged to form classes or societies for strengthening their spiritual life. The groups formed under Albright held a general conference in 1807 at which he was elected bishop; in 1816 the name Evangelical Association was adopted. In 1891 a group that became the United Evangelical Church seceded from the Evangelical Association, but in 1922 the two bodies reunited as the Evangelical Church. The societies formed under Otterbein and Boehm took shape as a distinct ecclesiastical body, to be known as the United Brethren in Christ, at a conference in 1800, at which the two ministers were elected bishops. The United Brethren in Christ (Old Constitution) parted from the main body in 1889; from that time they have maintained a separate church. Members of the Moravian Church are also sometimes called the United Brethren. In earlier years the membership of the Evangelical Church and of the United Brethren in Christ included few who were not German in speech, but later the German-speaking element formed only a small proportion. Extension W of the Alleghenies was rapid. The newly combined church supported publishing houses in the United States and abroad, four theological seminaries, a number of colleges, and foreign missions. It had an episcopal form of government. In doctrine it was Arminian. Particular emphasis was laid on prayer, a life of devotion to Christ, and the responsibility of the individual. Having long maintained a close relationship with the Methodist Church, it merged with it to found (1968) the United Methodist Church, U.S.A.
See R. W. Albright, History of the Evangelical Church (1942, repr. 1956); J. W. Owen, A Short History of the Church of the United Brethren in Christ (1944).
The Columbia Electronic Encyclopedia, 6th ed. Copyright © 2023, Columbia University Press. All rights reserved.
See more Encyclopedia articles on: Protestant Denominations


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While implementing Edulinq, I only focused on two implementations: .NET 4.0 and Edulinq. However, I was aware that there were other implementations available, notably LinqBridge and the one which comes with Mono. Obviously it's interesting to see how other implementations behave, so I've now made a few changes in order to make the test code run in these different environments.
The test environments
I'm using Mono 2.8 (I can't remember the minor version number offhand) but I tend to think of it as "Mono 3.5" or "Mono 4.0" depending on which runtime I'm using and which base libraries I'm compiling against, to correspond with the .NET versions. Both runtimes ship as part of Mono 2.8. I will use these version numbers for this post, and ask forgiveness for my lack of precision: whenever you see "Mono 3.5" please just think "Mono 2.8 running against the 2.0 runtime, possibly using some of the class libraries normally associated with .NET 3.5".
LinqBridge is a bit like Edulinq – a clean room implementation of LINQ to Objects, but built against .NET 2.0. It contains its own Func delegate declarations and its own version of ExtensionAttribute for extension methods. In my experience this makes it difficult to use with the "real" .NET 3.5, so my build targets .NET 2.0 when running against LinqBridge. This means that tests using HashSet had to be disabled. The version of LinqBridge I'm running against is 1.2 – the latest binary available on the web site. This has AsEnumerable as a plain static method rather than an extension method; the code has been fixed in source control, but I wanted to run against a prebuilt binary, so I've just disabled my own AsEnumerable tests for LinqBridge. Likewise the tests for Zip are disabled both for LinqBridge and the "Mono 3.5" tests as Zip was only introduced in .NET 4.
The other issue of not having .NET 4 available in the tests is that the string.Join<T>(string, IEnumerable<T>) overload is unavailable – something I'd used quite a lot in the test code. I've created a new static class called "StringEx" and replaced string.Join with StringEx.Join everywhere.
There are batch files under a new "testing" directory which will build and run:
- Microsoft's LINQ to Objects and Edulinq under .NET
- LinqBridge, Mono 3.5's LINQ to Objects and Edulinq under Mono 3.5
- Mono 4.0's LINQ to Objects and Edulinq under Mono 4.0
Although I have LinqBridge running under .NET 2.0 in Visual Studio, it's a bit of a pain building the tests from a batch file (at least without just calling msbuild). The failures running under Mono 3.5 are the same as those running under .NET 2.0 as far as I can tell, so I'm not too worried.
Note that while I have built the Mono tests under both the 3.5 and 4.0 profiles, the results were the same other than due to generic variance, so I've only included the results of the 4.0 profile below.
What do the tests cover?
Don't forget that the Edulinq tests were written in the spirit of investigation. They cover aspects of LINQ's behaviour which are not guaranteed, both in terms of optimization and simple correctness of behaviour. I have included a test which demonstrates the "issue" with calling Contains on an ICollection<T> which uses a non-default equality comparer, as well as the known issue with OrderByDescending using a comparer which returns int.MinValue. There are optimizations which are present in Edulinq but not in LINQ to Objects, and I have tests for those, too.
The tests which fail against Microsoft's implementation (for known reasons) are normally marked with an [Ignore] attribute to prevent them from alarming me unduly during development. NUnit categories would make more sense here, but I don't believe ReSharper supports them, and that's the way I run the tests normally. Likewise the tests which take a very long time (such as counting more than int.MaxValue elements) are normally suppressed.
In order to truly run all my tests, I now have a horrible hack using conditional compilation: if the ALL_TESTS preprocessor symbol is defined, I build my own IgnoreAttribute class in the Edulinq.Tests namespace, which effectively takes precedence over the NUnit one… so NUnit will ignore the [Ignore], so to speak. Frankly all this conditional compilation is pretty horrible, and I wouldn't use it for a "real" project, but this is a slightly unusual situation.
EDIT: It turns out that ReSharper does support categories. I'm not sure how far that support goes yet, but at the very least there's "Group by categories" available. I may go through all my tests and apply a category to each one: optimization, execution mode, time-consuming etc. We'll see whether I can find the energy for that :)
So, let's have a look at what the test results are…
Unsurprisingly, Edulinq passes all its own tests, with the minor exception of CastTest.OriginalSourceReturnedDueToGenericCovariance running under Mono 3.5, which doesn't include covariance. Arguably this test should be conditionalised to not even run in that situation, as it's not expected to work.
Microsoft's LINQ to Objects
8 failures, all expected:
- Contains delegates to the ICollection<T>.Contains implementation if it exists, rather than using the default comparer for the type. This is a design and documentation issue which I've discussed in more detail in the Contains part of this series.
- Optimization: ElementAt and ElementAtOrDefault don't validate the specified index eagerly when the input sequence implements ICollection<T> but not IList<T>.
- Optimization: OfType always uses an intermediate iterator even when the input sequence already implements IEnumerable<T> and T is a non-nullable value type.
- Optimization: SequenceEqual doesn't compare the counts of the sequences eagerly even when both sequences implement ICollection<T>
- Correctness: OrderByDescending doesn't work if you use a key comparer which returns int.MinValue
- Consistency: Single and SingleOrDefault (with a predicate) don't throw InvalidOperationException as soon as they encounter a second element matching the predicate; the predicate-less overloads do throw as soon as they see a second element.
All of these have been discussed already, so I won't go into them now.
LinqBridge had a total of 33 failures. I haven't looked into them in detail, but just going from the test output I've broken them down into the following broad categories:
- Optimization:
- Cast never returns the original source, presumably always introducing an intermediate iterator.
- All three of Microsoft's "missed opportunities" listed above are also missed in LinqBridge
- Use of input sequences:
- Except and Intersect appear to read the first sequence first (possibly completely?) and then the second sequence. Edulinq and LINQ to Objects read the second sequence completely and then stream the first sequence. This behaviour is undocumented.
- Join, GroupBy and GroupJoin appear not to be deferred at all. If I'm right, this is a definite bug.
- Aggregation accuracy: both Average and Sum over an IEnumerable<float> appear to use a float accumulator instead of a double. This is probably worth fixing for the sake of both range and accuracy, but isn't specified in the documentation.
- OrderBy (etc) appears to apply the key selector multiple times while sorting. The behaviour here isn't documented, but as I mentioned before, it could produce performance issues unnecessarily.
- Exceptions:
- ToDictionary should throw an exception if you give it duplicate keys; it appears not to – at least when a custom comparer is used. (It's possible it's just not passing the comparer along.)
- The generic Max and Min methods don't return the null value for the element type when that type is nullable. Instead, they throw an exception – which is the normal behaviour if the element type is non-nullable. This behaviour isn't well documented, but is consistent with the behaviour of the non-generic overloads. See the Min/Max post for more details.
- General bugs:
- The generic form of Min/Max appears not to ignore null values when the element type is nullable.
- OrderByDescending appears to be broken in the same way as Microsoft's implementation
- Range appears to be broken around its boundary testing.
- Join, GroupJoin, GroupBy and ToLookup break when presented with null keys
Mono 4.0 (and 3.5, effectively)
Mono failed 18 of the tests. There are fewer definite bugs than in LinqBridge, but it's definitely not perfect. Here's the breakdown:
- Optimization:
- Mono misses the same three opportunities that LinqBridge and Microsoft miss.
- Contains(item) delegates to ICollection<T> when it's implemented, just like in the Microsoft implementation. (I assume the authors would call this an "optimization", hence its location in this section.) I believe that LinqBridge has the same behaviour, but that test didn't run in the LinqBridge configuration as it uses HashSet.
- Average/Sum accumulator types:
- Mono appears to use float when working with float values, leading to more accumulator error than is necessary.
- Average overflow for integer types
- Mono appears to use checked arithmetic when summing a sequence, but not when taking the average of a sequence. So the average of { long.MaxValue, long.MaxValue, 2 } is 0. (This originally confused me into thinking it was using floating point types during the summation, but I now believe it's just a checked/unchecked issue.)
- Bugs:
- Count doesn't overflow either with or without a predicate
- The Max handling of double.NaN isn't in line with .NET. I haven't investigated the reason for this yet.
- OrderByDescending is broken in the same way as for LinqBridge and the Microsoft implementation.
- Range is broken for both Range(int.MinValue, 0) and Range(int.MaxValue, 1). Test those boundary cases, folks :)
- When reversing a list, Mono doesn't buffer the current contents. In other words, changes made while iterating over the reversed list are visible in the returned sequence. The documentation isn't very clear about the desired behaviour here, admittedly.
- GroupJoin and Join match null keys, unlike Microsoft's implementation.
How does Edulinq fare against other unit tests?
It didn't seem fair to only test other implementations against the Edulinq tests. After all, it's only natural that my tests should work against my own code. What happens if we run the Mono and LinqBridge tests against my code?
The LinqBridge tests didn't find anything surprising. There were two failures:
- I don't have the "delegate Contains to ICollection<T>.Contains" behaviour, which the tests check for.
- I don't optimize First in the case of the collection implementing IList<T>. I view this as a pretty dubious optimization to be honest – I doubt that creating an iterator to get to the first item is going to be much slower than checking for IList<T>, fetching the count, and then fetching the first item via the indexer… and it means that all non-list implementations also have to check whether the sequence implements IList<T>. I don't intend to change Edulinq for this.
The Mono tests picked up the same two failures as above, and two genuine bugs:
- By implementing Take via TakeWhile, I was iterating too far: in order for the condition to become false, we had to iterate to the first item we wouldn't return.
- ToLookup didn't accept null keys – a fault which propagated to GroupJoin, Join and GroupBy too. (EDIT: It turns out that it's more subtle than that. Nothing should break, but the MS implementation ignores null keys for Join and GroupJoin. Edulinq now does the same, but I've raised a Connect issue to suggest this should at least be documented.)
I've fixed these in source control, and will add an addendum to each of the relevant posts (Take, ToLookup) when I have a moment spare.
There's one additional failure, trying to find the average of a sequence of two Int64.MaxValue values. That overflows on both Edulinq and LINQ to Objects – that's the downside of using an Int64 to sum the values. As mentioned, Mono suffers a degree of inaccuracy instead; it's all a matter of trade-offs. (A really smart implementation might use Int64 while possible, and then go up to using Double where necessary, I suppose.)
Unfortunately I don't have the tests for the Microsoft implementation, of course… I'd love to know whether there's anything I've failed with there.
This was very interesting – there's a mixture of failure conditions around, and plenty of "non-failures" where each implementation's tests are enforcing their own behaviour.
I do find it amusing that all three of the "mainstream" implementations have the same OrderByDescending bug though. Other than that, the clear bugs between Mono and LinqBridge don't intersect, which is slightly surprising.
It's nice to see that despite not setting out to create a "production-quality" implementation of LINQ to Objects, that's mostly what I've ended up with. Who knows – maybe some aspects of my implementation or tests will end up in Mono in the future :)
Given the various different optimizations mentioned in this post, I think it's only fitting that next time I'll discuss where we can optimize, where it's worth optimizing, and some more tricks we could still pull out of the bag…


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aIn July 2008, the 1600-IU/d group was discontinued because 93% of infants developed plasma 25-hydroxyvitamin D concentrations of 250 mmol/L or greater by age 3 months.
Error bars indicate 95% CIs. 25(OH)D indicates 25-hydroxyvitamin D. * P < .05 vs 400-IU/d group.
Black data markers indicate means; error bars indicate 95% CIs. 25(OH)D indicates 25-hydroxyvitamin D. Data for each participant are shown as a spaghetti plot underlying the summary estimates.
Gallo S, Comeau K, Vanstone C, et al. Effect of different dosages of oral vitamin D supplementation on vitamin D status in healthy, breastfed infants: a randomized trial. JAMA. doi:10.1001/jama.2013.3404
eTable 1. Changes Over Time
eTable 2. Completers vs Dropouts
eTable 3. Logistic Regression Model for Main Objective
eFigure 1. Mean [95% CI] Plasma 25(OH)D Concentrations by Enzyme Immunoassay (A) and Radioimmunoassay (B)
eFigure 2. Mean [95% CI] Plasma 3-Epimer-25(OH)D (A) and 24,25(OH)2D3 (B) Concentrations by LC-MS/MS
eFigure 3. Mean [95% CI] Lumbar Spine BMC (A) and Accretion (B); Femur BMC (C) and Accretion (D); Whole Body BMC (E) and Accretion (F)
eFigure 4. Mean [95% CI] Safety Parameters for Mineral Status and Growth by Age and Treatment Weight-for-Age Z-Score (A), Length-for-Age Z-Score (B), Head Circumference-for-Age Z-Score (C), Ionized Calcium (D), Urinary Calcium:Creatinine (E), Plasma PTH (F)
Customize your JAMA Network experience by selecting one or more topics from the list below.
Gallo S, Comeau K, Vanstone C, et al. Effect of Different Dosages of Oral Vitamin D Supplementation on Vitamin D Status in Healthy, Breastfed Infants: A Randomized Trial. JAMA. 2013;309(17):1785–1792. doi:10.1001/jama.2013.3404
© 2023
Author Affiliations: School of Dietetics and Human Nutrition, McGill University (Mss Gallo, Comeau, Vanstone, and Agellon and Drs Rodd and Weiler), Montreal Children's Hospital, McGill University Health Centre (Drs Sharma and Rodd), and Europharm International Canada Inc (Dr Khamessan), Montréal, Québec, Canada; Departments of Biomedical and Molecular Sciences and Medicine, Queen's University, Kingston, Ontario, Canada (Dr Jones); and Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada (Dr L'Abbé).
Importance Vitamin D supplementation in infancy is required to support healthy bone mineral accretion. A supplement of 400 IU of vitamin D per day is thought to support plasma 25-hydroxyvitamin D (25[OH]D) concentrations between 40 and 50 nmol/L; some advocate 75 to 150 nmol/L for bone health.
Objective To investigate the efficacy of different dosages of vitamin D in supporting 25(OH)D concentrations in infants.
Design, Setting, and Participants Double-blind randomized clinical trial conducted among 132 one-month-old healthy, term, breastfed infants from Montréal, Québec, Canada, between March 2007 and August 2010. Infants were followed up for 11 months ending August 2011 (74% completed study).
Intervention Participants were randomly assigned to receive oral cholecalciferol (vitamin D3) supplements of 400 IU/d (n=39), 800 IU/d (n=39), 1200 IU/d (n=38), or 1600 IU/d (n=16).
Main Outcomes and Measures The primary outcome was a plasma 25(OH)D concentration of 75 nmol/L or greater in 97.5% of infants at 3 months. Secondary outcomes included 25(OH)D concentrations of 75 nmol/L or greater in 97.5% of infants at 6, 9, and 12 months; 25(OH)D concentrations of 50 nmol/L or greater across all times; growth; and whole body and regional bone mineral content. Data were analyzed by intention to treat using available data, logistic regression, and mixed-model analysis of variance.
Results By 3 months, 55% (95% CI, 38%-72%) of infants in the 400-IU/d group achieved a 25(OH)D concentration of 75 nmol/L or greater vs 81%(95% CI, 65%-91%) in the 800-IU/d group, 92% (95% CI, 77%-98%) in the 1200-IU/d group, and 100% in the 1600-IU/d group. This concentration was not sustained in 97.5% of infants at 12 months in any of the groups. The 1600-IU/d dosage was discontinued prematurely because of elevated plasma 25(OH)D concentrations. All dosages established 25(OH)D concentrations of 50 nmol/L or greater in 97% (95% CI, 94%-100%) of infants at 3 months and sustained this in 98% (95% CI, 94%-100%) to 12 months. Growth and bone mineral content did not differ by dosage.
Conclusions and Relevance Among healthy, term, breastfed infants, only a vitamin D supplement dosage of 1600 IU/d (but not dosages of 400, 800, or 1200 IU/d) increased plasma 25(OH)D concentration to 75 nmol/L or greater in 97.5% of infants at 3 months. However, this dosage increased 25(OH)D concentrations to levels that have been associated with hypercalcemia.
Trial Registration clinicaltrials.gov Identifier: NCT00381914
Quiz Ref IDVitamin D is important during periods of rapid bone mineral accrual. Nursing infants are susceptible to vitamin D deficiency because vitamin D in breast milk is limited.1 Pediatric societies in the United States2 and Canada3 recommend 400 IU (10 μg) per day based on maintenance of 25-hydroxyvitamin D (25[OH]D) concentrations in the range of 75 to 150 nmol/L (30-60 ng/mL). Similarly, the Institute of Medicine's health policy recommendation for infants in North America is 400 IU/d but targets lower 25(OH)D concentrations, between 40 and 50 nmol/L (16-20 ng/mL).4 This policy also established a healthy range of 50 to 125 nmol/L for 25(OH)D concentrations.4
Several functional outcomes have been used to systematically assess the adequacy of vitamin D, including 25(OH)D at various target concentrations (50 and 75 nmol/L), parathyroid hormone concentrations, and bone health.4 However, there is a paucity of such data in infants. In one study,5 bone mineral content (BMC) was lower in infants receiving a supplement of 400 IU/d compared with placebo. The effects of doses higher than 400 IU on bone health are unknown. While France6 and Finland7 recommend vitamin D intakes greater than 1000 IU/d for infants, the lack of well-defined recommendations supports the need for dose-response studies.
The objective of this study was to investigate the efficacy of different dosages of oral vitamin D in supporting 25(OH)D concentrations in infants.
The study was a single-center, double-blind, randomized dose-response trial conducted among 132 infants who were randomly assigned at 1 month of age to receive 400, 800, 1200, or 1600 IU/d of oral cholecalciferol (vitamin D3) for 11 months. The primary objective was to establish a dosage of oral vitamin D supplementation that would support 25(OH)D concentrations of 75 nmol/L or greater in 97.5% of breastfed infants by 3 months of age. Secondary objectives were to evaluate the dosages that would support plasma concentrations of 25(OH)D of 50 nmol/L or greater in 97.5% of infants at 3 months, as well as to evaluate whether concentrations were sustained at 12 months with any dosage, to evaluate growth, and to measure bone mineral accrual from 1 to 12 months of age. Quiz Ref IDThe primary outcome was assessed at 3 months of age because most infants are still predominantly breastfed at this age,8 other sources of vitamin D are limited, and bone modeling is rapid.9 The objectives were designed to provide data to help establish a Recommended Dietary Allowance value, which is defined as the intake level that meets the nutrient requirements of nearly all individuals (97%-98%) in a life-stage group.4 For vitamin D, this recommendation considers 25(OH)D concentration and bone health outcomes. The secondary outcomes, including 25(OH)D concentration, growth, and BMC, were monitored at 5 study visits conducted at 1 (baseline), 3, 6, 9, and 12 months of age. Growth and safety end points were evaluated at each visit and at an additional visit at 2 months. The study was carried out between March 2007 and August 2011 at the Mary Emily Clinical Nutrition Research Unit of McGill University, Montréal, Québec, Canada, and was approved by the institutional review board of McGill University and Health Canada. Parents provided written informed consent and received compensation for travel.
Newborns (≤1 month of age) were referred from Lakeshore General Hospital and 5 pediatric clinics located in greater Montréal between March 2007 and August 2010 (Figure 1). The final study measures were obtained in August 2011, when the last infant reached 12 months of age. Infants who were healthy, term, singleton, appropriate size for gestational age, and breastfeeding (consuming ≥80% of total milk volume) were eligible to participate. Exclusion criteria included infants of mothers with gestational diabetes, hypertension in pregnancy, chronic alcohol use, or malabsorption syndromes. Parents self-identified race/ethnicity, using Canadian Census criteria, to assist in interpretation of vitamin D status10 and bone health assessments.11 Other demographic information including education and income were reported by the mothers.
Supplements containing 400, 800, 1200, or 1600 IU of vitamin D3 were formulated by Europharm International Canada Inc and administered in 2-mL/d volume using a standardized dropper; all had similar taste, smell, and appearance. Supplements were provided in precoded bottles of 60-mL volume. Parents and researchers were blinded to treatment dosage. All dosages were proven to be within 10% of target dosage, with an 18-month shelf life. Adherence evaluation included weighing bottles before and after use and recording number of missed doses reported by mothers.
Following enrollment into the study and baseline measurements, the infants were randomly assigned to 1 of the 4 groups in a 1:1:1:1 allocation ratio. Randomization was stratified by sex in equal blocks of 4. The randomization list was generated using http://www.randomization.com and blinded supplement codes. The codes were revealed only after the statistical analysis was complete.
An independent safety monitoring officer reviewed unblinded data. Stopping rules included hypercalcemia or evidence of plasma 25(OH)D concentrations of 250 nmol/L or greater because such values may be associated with hypercalcemia.3 In July 2008, the 1600-IU/d group was discontinued because 93% of infants (n = 15/16) developed plasma 25(OH)D concentrations of 250 nmol/L or greater by 3 months of age based on an enzyme immunoassay. The protocol was amended and those receiving 1600 IU/d (n = 10; 6-9 months of age) were subsequently switched to the standard-of-care dosage (400 IU/d) until 12 months of age; their data were analyzed by intention to treat (ie, 1600-IU/d group). Those recruited at 1 month of age after July 2008 (n = 17) were randomized in a 1:1:1 ratio to the remaining 3 groups12 and analyzed in their respective group (Figure 1).
Potential for endogenous synthesis of vitamin D through exposure to sunlight was assessed by questionnaire and sun index (hours per week of sun exposure multiplied by percentage body surface area exposed).13 Vitamin D in breast milk was estimated from the volume of breast milk consumed over a 24-hour period.14 Vitamin D from other foods was assessed using 3-day dietary records completed by parents after each visit. Nutrient intake was generated using Nutritionist Pro software version 4.7.0 (Axxya Systems LLC) and the 2010b Canadian Nutrient File database (Health Canada).
Capillary plasma samples from heel or finger were stored frozen at −80°C for batch analysis. Samples were screened for safety assessments for plasma 25(OH)D at McGill University using an enzyme immunoassay (Octeia, Immunodiagnostic Systems Ltd). A commonly used15 radioimmunoassay for measurement of 25(OH)D (DiaSorin Inc) and liquid chromatography tandem mass spectrometry (LC-MS/MS)16 were used to measure the primary outcome. The immunoassays quantify total 25(OH)D, whereas the LC-MS/MS assay separately quantifies 25(OH)D isomers (25[OH]D2 + 25[OH]D3), as well as the 3-epimer-25(OH)D17 and 24,25-dihydroxyvitamin D (24,25[OH]2D) which may interfere in immunoassays.18 Plasma 25(OH)D, 3-epimer-25(OH)D, and 24,25(OH)2D were quantified (Warnex Bioanalytical Services) based on internal standards: 25(OH)D3-d(6) (Chemaphor Inc), 25(OH)D2-d(3) (Isosciences), and 3-epi-25(OH)D3-d(6) and 24,25(OH)2D3-d(6) (Toronto Research Chemicals). Briefly, following liquid-liquid extraction, vitamin D metabolites were derivatized using a substituted triazolinedione in a Diels-Alder addition,19,20 separated on a high-performance liquid chromatograph system, and detected using an API-4000 (ABSciex ON) or a TSQ-Vantage LC-MS/MS instrument (Thermo Scientific). All infants had vitamin D2 metabolites below the limit of quantification. The intra-assay coefficient of variation was less than 15% for all vitamin D metabolites across all assays; the laboratories were certified by the Vitamin D External Quality Assessment Scheme to facilitate comparison with other laboratories.
The safety end points were selected to comprehensively examine calcium homeostasis and risk of soft tissue calcification.3,4 Blood-ionized calcium (ABL 725 series blood gas analyzer; Radiometer America) and plasma total calcium, phosphorus, alkaline phosphatase, and urinary calcium:creatinine were measured (Beckman Coulter DxC600) within 4 hours of collection. Parathyroid hormone was measured using an enzyme-linked immunosorbent assay (Immutopics International). Intra-assay coefficient of variation was less than 5%. Without normative reference limits for ionized calcium and urinary calcium:creatinine in healthy infants, these were extrapolated from hospitalized older children. Any safety measures with results outside the normal range were repeated; if confirmed as such, the infant was switched to the standard of care (400 IU/d vitamin D3) but analyzed per intention to treat.
The proportion of infants who maintained plasma 25(OH)D concentrations of 75 nmol/L or greater at 6, 9, and 12 months of age were explored as secondary outcomes, as was the proportion who maintained 25(OH)D concentrations of 50 nmol/L or greater. At each visit, nude weight (infant scale model SB 32000, Mettler-Toledo Inc), length (O'Learly Length Board, Ellard Instrumentation Ltd), and head circumference (nonstretchable tape) were measured and reported as absolute units, and z scores were calculated using World Health Organization growth standards.21 Bone mineral content and bone mineral density (BMD) were measured at each of the 5 study visits using dual-energy x-ray absorptiometry (Hologic 4500A Discovery, APEX software version 13.2:1, Hologic Inc). Infants were scanned in array mode to obtain BMC of the whole body, lumbar spine vertebrae 1 to 4, and whole femur while sleeping (nonsedated) as previously described.10,22 Change in BMC was calculated between visits. The coefficient of variation was 1% for BMC and 0.3% for BMD using a spine phantom (Hologic phantom No. 14774).
The primary objective was to determine which dosage met the plasma 25(OH)D threshold of 75 nmol/L in at least 97.5% of infants at 3 months of age. The sample estimate assumed that 50% of the infants in the 400-IU/d group would be able to achieve a 25(OH)D concentration of 75 nmol/L or greater by 3 months. To achieve our target, this would require a change of 47.5% from the 400-IU/d group. Using a χ2 statistic to compare proportions, 23 infants per group gave the study greater than 90% power at the .05 significance level. Assuming 20% dropout and an additional 20% to compensate for early weaning from breastfeeding, 32 participants per group would be necessary at 3 months.
Baseline differences among groups were tested using analysis of variance (ANOVA) for continuous variables and χ2 (with Fisher exact tests for small sample sizes) for categorical variables (including recruitment site); characteristics with differences among groups were included as covariates in regression modeling. Group differences in breastfeeding status and adherence (proportion of treatments taken) were analyzed using χ2 at each time point. Infant anthropometry, dietary intake, and sun exposure variables were tested across treatments and time (repeated-measures mixed-model analysis of variance). In evaluating 25(OH)D concentrations at each time, differences among treatments were tested using the existing data and logistic regression without imputing the small number of missing observations. Careful comparisons of participants with missing and fully observed data were consistent with data missing at random. The effects of vitamin D dosage on plasma 25(OH)D concentration, safety biochemistry, growth, and bone mineral accretion were also explored and tested using repeated-measures mixed-model analysis of variance with time-treatment interactions. The mixed-model analysis of variance estimates the effect size based on available data (Figure 1 and Figure 2), and participants with missing data are not dropped, mitigating the need for imputation.23 Post hoc tests (estimate statements) were used to test for differences between the 400-IU/d and higher dosage groups (800 and 1200 IU/d). The 1600-IU/d group was not included in the statistical models because of its discontinuation; data are presented descriptively. Statistical significance was set at P ≤.05 with 2-tailed testing. Data were analyzed using SAS version 9.2 statistical software (SAS Institute Inc).
Of 937 referred infants, 275 were excluded, 530 did not consent, and 132 were enrolled (Figure 1), of whom 84% were taking a vitamin D supplement (400 IU/d). Maternal and infant baseline characteristics were similar among groups except for mother's race (P = .03); thus, race was included as a covariate in all analyses (Table). There were no differences in attrition rates (Figure 1), referring center, or reported
adherence (eTable 1) across treatment groups. Overall, 88% of infants received breast milk up to 6 months of age and 35% up to 12 months. Time, but not group, differences were observed in nutrient intakes, including dietary vitamin D and sun exposure (eTable 1). Maternal education and infant baseline 25(OH)D concentrations were lower in dropouts vs completers, and more dropouts were nonwhite (eTable 2).
The percentage of infants achieving the primary outcome of 75 nmol/L of 25(OH)D differed at 3 months by group (for 400 IU/d, 55% [95% CI, 38%-72%]; for 800 IU/d, 81% [95% CI, 65%-91%]; for 1200 IU/d, 92% [95% CI, 77%-98%]; and for 1600 IU/d, 100%) (Figure 2A). The percentage of infants at 6, 9, and 12 months who met or exceeded the target cutoff of 75 nmol/L of 25(OH)D declined with time. The crude and adjusted logistic regression models (eTable 3) indicate that at 3 months and after adjusting for race only (model 1), the 800-IU/d had an odds ratio of 3.5 (95% CI, 1.1-11.0) vs the 400-IU/d group for achieving a 25(OH)D concentration of 75 nmol/L or greater, whereas the odds ratio for achieving this in the 1200-IU/d vs 400-IU/d group was 9.7 (95% CI, 1.9-49.7). Adjusting for sex and period of birth (model 2) did not change these results.
Overall, 97% (95% CI, 94%-100%) of infants in all treatment groups achieved the secondary outcome of 50 nmol/L or greater of plasma 25(OH)D by 3 months of age, with no differences among groups (for 400 IU/d, 97% [95% CI, 91%-100%]; 800 IU/d, 97% [95% CI, 91%-100%]; 1200 IU/d, 96% [95% CI, 89%-100%]; and 1600 IU/d, 100%) (Figure 2B). This concentration was sustained in 98% (95% CI, 94%-100%) of infants at 12 months. The 25(OH)D concentrations in all groups peaked at approximately 3 months with mean concentrations of 78 (95% CI, 71-84) nmol/L in the 400-IU/d group, 102 (95% CI, 90-114) nmol/L in the 800-IU/d group, 134 (95% CI, 118-150) nmol/L in the 1200-IU/d group, and 180 (95% CI, 154-207) nmol/L in the 1600-IU/d group (Figure 3).
Differences were observed in the values of plasma 25(OH)D obtained using different methods (eFigure 1); the enzyme immunoassay tended to overestimate and the radioimmunoassay to underestimate 25(OH)D concentrations vs LC-MS/MS. The 3-epimer-25(OH)D, measured by LC-MS/MS, was present in 98% of all samples tested. In proportion to plasma 25(OH)D, 3-epimer-25(OH)D was equivalent to 30% to 40% of plasma 25(OH)D at baseline and declined to approximately 10% by 12 months (eFigure 2A). Plasma 24,25(OH)2D, measured by LC-MS/MS, was equivalent to approximately 15% of plasma 25(OH)D
concentration (eFigure 2B). Concentrations of both 3-epimer-25(OH)D and 24,25(OH)2D3 were different only at 2 and 3 months and only in the 400-IU/d vs 1200-IU/d groups.
Bone mineral concentration increased over time for lumbar spine, femur, and whole body (eFigure 3) but did not differ by group. Similarly, lumbar spine BMD did not differ by group or time. Infants grew in an age-appropriate way over time, with no differences by group (eFigure 4A-C).
Ionized calcium and urinary calcium:creatinine values (eFigure 4D-E) declined over time, with no treatment interaction. Plasma parathyroid hormone values increased over time without treatment or interaction effects (eFigure 4F). Over the 11 months, total plasma calcium (median, 2.52 [interquartile range {IQR}, 2.47-2.57] mmol/L), alkaline phosphatase (median, 240 [IQR, 193-289] U/L), and phosphate (median, 1.89 [IQR, 1.74-2.01] mmol/L) differed over time, but no differences among groups were noted. Forty-two infants were retested because the results of their safety measurements were outside the normal range (n = 9 in the 400-IU/d, n = 10 in the 800-IU/d, n = 17 in 1200-IU/d, and n = 6 in the 1600-IU/d groups). Based on these results and suspected hypercalcemia (n = 2 in the 800-IU/d, n = 2 in the 1200-IU/d, and n = 2 in the 1600-IU/d groups) or suspected hypercalciuria (n = 1 in the 800-IU/d, n = 1 in the 1200-IU/d, and n = 1 in the 1600-IU/d groups), additional safety procedures (electrocardiogram or renal ultrasound) were conducted at the Montreal Children's Hospital; all results were normal.
Quiz Ref IDOur primary objective was to establish a vitamin D dosage that would support a plasma concentration of 25(OH)D of 75 nmol/L or greater in 97.5% of infants at 3 months of age. Only the 1600-IU/d dosage of vitamin D met this criterion; however, this dosage was discontinued because most infants in that group developed elevated plasma 25(OH)D concentrations that have been associated with hypercalcemia.4 Although a higher percentage of infants in the 800-IU/d and 1200-IU/d groups achieved 75 nmol/L of 25(OH)D (81% and 92%, respectively), only 55% of infants did so in the 400-IU/d group at 3 months. Thus, the primary outcome was not achieved at 3 months, when plasma 25(OH)D concentrations were highest; all dosages failed except the highest dosage, which appears to be too high. Furthermore, in none of the groups was this concentration sustained in 97.5% of infants at 12 months. In contrast, regardless of vitamin D dosage, 97% of our infant population achieved the secondary outcome of a 25(OH)D concentration of 50 nmol/L at 3 months and 98% from 6 to 12 months.
Quiz Ref IDA dose-response study of vitamin D intake and bone health has been lacking in infants.4 Despite our demonstration of a dose-response relationship in plasma 25(OH)D concentrations relative to vitamin D dosage, no such response was observed in BMC or accrual. Similarly, older studies did not find improvements in bone mineral accretion5 or content25 over 26 weeks with 400 IU/d of vitamin D vs placebo. Bone mineral accretion in breastfed infants is likely optimal and less affected by vitamin D supplementation unless an underlying deficiency exists. Alternatively, the sensitivity of dual-energy x-ray absorptiometry to detect small changes in infants over an 11-month period may not be sufficient. Possible benefits to bone may take longer to present, as shown in prospective studies.26
The safety of vitamin D dosages greater than 400 IU/d has not been tested in infants. The tolerable upper intake levels for infants aged 0 to 6 months of 1000 IU/d and for those aged 6 to 12 months of 1500 IU/d were established based on a no-observed-adverse-effect level of 1800 IU/d.4 This level was established from data collected in 193827 showing that vitamin D greater than 1800 IU/d for 6 months impaired linear growth. Our data did not demonstrate abnormalities in growth or calcium homeostasis. Although the 1600-IU/d group was discontinued, this was based on 25(OH)D concentrations exceeding the normal range.3 The other safety procedures were designed to monitor safety end points at the individual level and were thus not powered to test for safety at the population level. Reassuringly, a cohort of 10 060 Finnish infants followed up prospectively7 for 31 years showed that dosages up to 2000 IU/d did not alter linear growth. A randomized clinical trial28 found similar increases in circulating 25(OH)D concentrations with dosages up to 1600 IU/d for 3 months; however, uncertainty still remains about this high dosage.
Concentrations of 25(OH)D declined from 3 to 12 months of age in all groups although dietary vitamin D sources increased. This decline in all groups may be due to decreased adherence, but it is more likely that the changes reflect the relative intake over time. For example, infants in the 400-IU/d group at 3 months would have received 64 IU/kg, whereas this declined to 42 IU/kg at 12 months. Whether the lower values may reflect increased requirements based on larger size and hepatic maturity is unclear.
During the study, several methods were examined to measure vitamin D metabolites in a selective, sensitive, and accurate manner. Even though the radioimmunoassay has been widely used,15,29 we chose LC-MS/MS to interpret our key observations because it is now considered a gold-standard assay.30 Discrepancies among antibody-based methods in cross-method comparisons31,32 and our findings question the usefulness of antibody-based methods for infant assessments.33 In agreement with others,17 an abundance of 3-epimer-25(OH)D was observed during the first year of life, although its biological significance is unclear. In addition, 24,25(OH)2D was equivalent to 15% of the 25(OH)D pool in infant samples. To our knowledge, the present study represents the first analyses of the several key vitamin D metabolites during infancy; these metabolite concentrations mirror vitamin D intake.
Even though this study has many strengths, including rigorous methods, the data may not represent all Canadian infants because the sample consisted of a large proportion of well-educated, high-income mothers, and baseline plasma 25(OH)D concentrations at 1 month of age were robust, with an average of 59 nmol/L (95% CI, 55-63 nmol/L). The population studied was underrepresented in participants with darker skin pigmentation, who are at higher risk of deficiency.3,4 Moreover, the study may have been underpowered to test for some secondary outcomes and too short to assess for benefits to bone. A larger, more heterogeneous group would need to be studied.
In conclusion, only the 1600-IU/d dosage of vitamin D met the 25(OH)D concentration target of 75 nmol/L or greater, confirming the guidelines of the Endocrine Society.2 However, it also led to plasma 25(OH)D concentrations that exceeded the healthy population target range of 50 to 125 nmol/L.4Quiz Ref IDFurthermore, dosages of vitamin D exceeding 400 IU/d provide no additional benefits for bone mineral accretion up to 1 year of age. Additional studies are required before conclusions can be made regarding higher targets or the needs of high-risk groups.
Corresponding Author: Hope Weiler, RD, PhD, School of Dietetics and Human Nutrition, McGill University, 21111 Lakeshore Rd, Ste-Anne-de-Bellevue, Québec H9X 3V9, Canada (email@example.com).
Author Contributions: Drs Rodd and Weiler, the senior authors of this article, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Sharma, Jones, L'Abbé, Khamessan, Rodd, Weiler.
Acquisition of data: Gallo, Comeau, Vanstone, Agellon, Jones, Weiler.
Analysis and interpretation of data: Gallo, Sharma, Jones, L'Abbé, Rodd, Weiler.
Drafting of the manuscript: Gallo, Vanstone, Rodd, Weiler.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Gallo, Sharma, Rodd, Weiler.
Obtained funding: Jones, Rodd, Weiler.
Administrative, technical, or material support: Gallo, Comeau, Vanstone, Agellon, Jones, Khamessan, Rodd, Weiler.
Study supervision: Gallo, Vanstone, Agellon, L'Abbé, Rodd, Weiler.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Ms Gallo reports travel support from CIHR Human Development Child and Youth Health and the American Society for Bone and Mineral Research. Dr Sharma reports consulting fees for analyses prepared for Drs Weiler and Rodd. Dr Jones reports that he is cofounder and scientific advisory board member for Cytochroma Inc and has received payment for speakers bureaus from Genzyme/Sanofi. No other disclosures were reported.
Funding/Support: This work was supported by funding from the Canadian Institutes for Health Research, Nutricia Research Foundation, and the Canadian Foundation for Innovation and in-kind support from Europharm International Canada Inc for provision of the supplements. Fonds de la Recherche en Santé du Québec provided personal funding for the doctoral student (Ms Gallo) and the Canada Research Chairs provided a salary award to Dr Weiler.
Role of the Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.
Previous Presentations: This work was presented at the Experimental Biology meeting on April 21, 2012; at the Canadian Nutrition Society meeting on May 25, 2012; at the Canadian Paediatric Society conference on June 8, 2012; and at the British Columbia Children's Hospital and Montreal Children's Hospital Grand Rounds on March 23, 2012, and May 2, 2012, respectively.
Online-Only Material: The Author Audio Interview is available here.
Additional Contributions: We thank John Mitchell, MD, FRCPC, Montreal Children's Hospital, for his unpaid role as safety officer, the Montreal Children's Hospital clinical laboratory for mineral analyses, and all of the pediatricians as well as Lakeshore General Hospital maternity ward for help with recruitment. We thank McGill University graduate students Samira Bou Raad, MSc, Saja Al Saleh, MSc, Sonia Jean-Philippe, RD, MSc, and Anna Phan, RD, MSc, for help with study measurements. Mss Jean-Philippe and Phan received financial remuneration for their assistance in dietary assessment. Finally, we thank all of the families who agreed to participate in this study and the Mary Emily Clinical Nutrition Research Unit of the School of Dietetics and Human Nutrition.


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Release Date: 06/12/2012
Contact Information: James Pinkney, (404) 562-9183, email@example.com
(Atlanta - June 12, 2012) - The U.S. Environmental Protection Agency (EPA) Deputy Regional Administrator, Stan Meiburg, will recognize the cities of Greenville, Havelock, and Wilson, NC as the recipients of brownfields grants for assessment and cleanup of contaminated properties on Thursday, June 14, 2012 at the Reade Ventures Redevelopment Site in Greenville, NC.
The city of Havelock will receive a $400,000 assessment grant and the cities of Wilson and Greenville will receive a $200,000 assessment grant.
Grants funded by EPA's brownfields program will help recipients to conduct assessment and cleanup activities, and secure funding to eliminate delays in moving from assessment to cleanup. The investments will continue to provide communities with necessary funding to help clean up America's land, boost local economies and create jobs while protecting public health.
Who: EPA Deputy Regional Administrator, Stan Meiburg, city of Greenville Mayor, Allen M. Thomas, city of Havelock Mayor, Jimmy Sanders, city of Wilson Mayor, C. Bruce Rose
What: EPA Brownfields Check Presentations to the City of Greenville, City of Havelock and City of Wilson, NC
When: Thursday, June 14, 2012 at 11:00 a.m.
Where: Reade Ventures Redevelopment Site
629 Dickinson Avenue
Greenville, NC 27834
Since inception in 1995, EPA's brownfields investments have leveraged more than $18.3 billion in cleanup and redevelopment funding from a variety of public and private sources and have resulted in approximately 75,500 jobs. In 2012, EPA awarded $69.3 million to 245 grantees in 39 states across the country to assess and clean up abandoned industrial and commercial properties.
More information on brownfields grants by state: https://cfpub.epa.gov/bf_factsheets/
More information on EPA's Brownfields program: https://www.epa.gov/brownfields/
Search this collection of releases | or search all news releases
View selected historical press releases from 1970 to 1998 in the EPA History website.


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I asked Yu Kai what inspired him to open up Kai Lin Shop, here is is response:
Here are some of my favorites:
Jarno Kettunen, a chic fashion illustrator from Finland who creates art using make up and has illustrated many fashion shows from the top designers from Dior to Chanel. Personally I have the one on the far right, it is an illustration of a Comme des Garcons piece, and I call her my cotton candy drag queen (not the hair.)
Mr Soggs Creatures made by an artist named Joelle Medici from Tennessee. Her fun whimsical plush dolls are adorable! I am thinking of these little guys for a friend who just had a baby and one who is preggo--super cute shower gift!
Alex Leopold, a Nashville artist who creates beautiful resin pieces of illustrated and animal imagery. I love these.
Mike Lowery who is a professor at SCAD of Illustration and his pieces are quirky, light-hearted, and child-like.
Viva Greetings which is a local greeting card, wrapping paper, t-shirts and toymaker who makes really great products. So you can walk out of there with a card and wrap it all up too! He has thought of everything...besides, who doesn't love a greeting card in Spanish. I know I do!
The gallery and shop have items that range in price from $2-$250 so you can really find something for everyone. The shop hours are the same as the gallery hours, Tuesday through Friday 10-6pm and Saturday 11-6pm. They are also open by appointment.
Ready for more after you hit up Kai Lin? Try these other favorite places for more Holiday Happiness (all within walking distance of the shop, btw):
Lush Life: Beautiful store for great flower arrangements, fab books and gifts. Great Mother/Sister-In-Law or Hostess Gifts--or Niki gifts.
Mitchell Gold+Bob Williams: Great home accessories, art, books, candles, pillows, frames, throw pillows, perfect for anyone who has a new home/condo/apartment and needs a little style. Ask for Hayley, she's amazing.
Sage: Fab woman's boutique with great clothes, jewelry, bags, all around awesome for any female you need to shop for.
Pieces: A.m.a.z.i.n.g. home boutique, Lee is a doll and you will just want to lick everything in there.
And when you are all done, go get yourself a cupcake from Piece of Cake, because you deserve it.
The moral of the story is shop local, shop smart and shop small businesses! They need our support and the stuff you'll get from them is going to be way cooler then anything you find at the mall.


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Bruce Coulter: Backlogged claims still an issue for VA
"The VA system is confusing, overwhelming and is not at all friendly to veterans."
Reading the words of Gulf War veteran David Bohan, who testified before a house subcommittee last month brought on a feeling of déjà vu for me.
Been there, done that, threw away the T-shirt.
Bohan appeared before the House Veterans' Affairs Disability Assistance and Memorial Affairs Subcommittee, which heard testimony on the growing backlog at the Veterans Benefits Administration (VBA).
According to a release issued by Bob Filner, chairman of the House Committee on Veterans Affairs, the hearing, led by Congressman John Hal, D-N.Y., was held to examine the record number of claims – nearly 1 million – the Department of Veterans Affairs is dealing with.
Just how well the VA deals with that backlog has been the subject of discussion for years, during which the numbers have only climbed.
Michael Walcoff, VA's deputy undersecretary for benefits said the VBA has made progress in improving the timeliness of its decisions. According to Walcoff, the waiting game for rating claims has improved from 178.9 days at close of fiscal 2008 to 161.8 days as of the end of May.
But Walcoff also told the committee the term for claims awaiting decisions is not a "claims backlog," which he said is an incorrect description. Rather, he added, the inventory is dynamic rather than static.
"It includes all claims received, whether pending for just a few hours or as long as six months," he told the committee. "Completed claims are continuously removed from the inventory while new claims are added. This year we are averaging over 80,000 new claims added to the inventory each month."
For the record Mr. Walcoff, and this is an old complaint of mine – we're veterans – not "inventory." Further, if a veteran is waiting for a decision on a claim, it's a backlog. Particularly when the VA has nearly 21 percent of its cases pending for more than 180 days. Add to that the fact that Appeals Management Center (AMC) recently completed it final case – for 2003 – and still has 40 cases pending from 2004. Moreover, AMC and the Board of Veterans Appeals takes on average nearly 18 months to complete a case.
Veterans understand claims aren't processed and approved overnight. Cases taking five and six years to complete are another story.
Larry Scott, founder of VA Watchdog, said hiring additional claims processors and training them is the simplest answer to the backlog of claims.
"Training is a two-year process ... and, right now, training is a joke," Scott wrote in an e-mail. "New employees are told to read the manuals ... go to a class or two ... and then thrown into the mix."
Scott also said the VA lacks a system requiring the training needed and verifying it was completed.
"It's a mess. I really feel that a top-notch management team from the insurance industry (they know about claims) should re-design the entire process from the bottom up."
But giving the devil its due, the VA is attempting to speed up fully developed compensation and pensions claims no more than 90 days after those claims are submitted under a one-year pilot program.
A second pilot program would assess the feasibility and advisability of providing a claimant and his/her representative (if any) a checklist containing information or evidence required to substantiate the claim.
The programs are part of the Veterans Benefits Improvement Act (P.L. 110-389), which hopes to modernize the VA's disability benefits claims processing system by, among other things, authorizing temporary ratings and claimant substitution. The law also calls for additional training and certification of VBA employees to speed the claims process along.
Bruce Coulter is a retired, disabled veteran. He may be reached at 978-371-5775 or by e-mail at firstname.lastname@example.com.