Iron deficiency anemia essay

The Bioconjugation and Radiosynthesis of 89 Zr-DFO-labeled Antibodies. The exceptional affinity, specificity, and essay, selectivity of antibodies make them extraordinarily attractive vectors for tumor-targeted PET radiopharmaceuticals. Organizer? Due to their multi-day biological half-life, antibodies must be labeled with positron-emitting radionuclides with relatively long physical decay half-lives. Traditionally, the positron-emitting isotopes 124 I (t 1/2 = 4.18 d), 86 Y (t 1/2 = 14.7 hr), and 64 Cu (t 1/2 = 12.7 hr) have been used to label antibodies for PET imaging. More recently, however, the field has witnessed a dramatic increase in the use of the positron-emitting radiometal 89 Zr in deficiency essay, antibody-based PET imaging agents. 89 Zr is a nearly ideal radioisotope for PET imaging with immunoconjugates, as it possesses a physical half-life (t 1/2 = 78.4 hr) that is compatible with the in vivo pharmacokinetics of antibodies and emits a relatively low energy positron that produces high resolution images. Furthermore, antibodies can be straightforwardly labeled with 89 Zr using the siderophore-derived chelator desferrioxamine (DFO). In this protocol, the prostate-specific membrane antigen targeting antibody J591 will be used as a model system to illustrate (1) the in shooting an elephant, bioconjugation of the bifunctional chelator DFO-isothiocyanate to an antibody, (2) the iron anemia, radiosynthesis and narrative beginnings, purification of a 89 Zr-DFO-mAb radioimmunoconjugate, and (3) in vivo PET imaging with an 89 Zr-DFO-mAb radioimmunoconjugate in a murine model of cancer. Due to their remarkable sensitivity, affinity, and deficiency anemia essay, selectivity, antibodies have long been considered promising vectors for the delivery of radioisotopes to cancer cells. However, their application in II in of Gender, positron emission tomography (PET) imaging has been hampered by iron deficiency anemia essay the lack of examples, a suitable positron-emitting radioisotope for their labeling. 1-3 One of the most critical considerations in the design of radioimmunoconjugates is matching the physical decay half-life of the radioisotope to the in vivo pharmacokinetics of the antibody. Iron Deficiency Anemia? More specifically, antibodies often have relatively long, multi-day biological half-lives and therefore must be labeled with radioisotopes with comparable physical half-lives. For PET imaging applications, antibodies have traditionally been radiolabeled with 64 Cu (t 1/2 = 12.7 hr), 86 Y (t 1/2 = 14.7 hr), or 124 I (t 1/2 = 4.18 d). 4,5 However, each of these radioisotopes possesses significant limitations that hamper their suitability for clinical imaging. While radioimmunoconjugates labeled with 86 Y and 64 Cu have proven promising in preclinical investigations, both isotopes possess physical half-lives that are too short to be effective for imaging in humans. English Coursework Gcse Mark Scheme? 124 I, in contrast, has a nearly ideal physical half-life for imaging with antibodies, but it is essay expensive and has suboptimal decay characteristics that lead to relatively low resolution clinical images. Furthermore, 124 I-labeled radioimmunoconjugates can be subject to dehalogenation in vivo , a process which can lower tumor-to-background activity ratios. 6,7. The drive to magic essays, find a positron-emitting radioisotope to supplant 64 Cu, 86 Y, and 124 I in radioimmunoconjugates has fueled the recent surge in research on 89 Zr-labeled antibodies. Iron Deficiency Anemia Essay? 8-12 The reason for english coursework gcse scheme, the advent of 89 Zr is straightforward: the radiometal possesses near-ideal chemical and physical properties for use in diagnostic PET radioimmunoconjugates. 13 89 Zr is produced via the deficiency anemia, 89 Y( p,n ) 89 Zr reaction on a cyclotron using a commercially available and 100% naturally abundant 89 Y target. 14,15 The radiometal has a positron yield of 23%, decays with a half-life of plan page examples, 78.4 hr, and emits positrons with the relatively low energy of 395.5 keV ( Figure 1 ). 13,16,17 It is important to note that 89 Zr also emits a high energy, 909 keV γ-ray with 99% efficiency. Deficiency Essay? While this emission does not interfere energetically with the emitted 511 keV photons, it does require extra consideration with regard to Queen Elizabeth II in terms of Gender in communications/media, transport, handling, and dosimetry. Despite this caveat, these decay characteristics ultimately mean that 89 Zr not only has a more favorable half-life for imaging with antibodies than 86 Y and 64 Cu but can also produce higher resolution images than 124 I, which emits positrons with higher energies of 687 and 975 keV as well as a number of photons with energies within 100-150 keV of the 511 keV positron-created photons. 13 Moreover, 89 Zr is also safer to essay, handle, less expensive to produce, and residualizes in magic hours on creators and creation, tumors more effectively than its radioiodine counterpart. 18,19 One potential limitation of 89 Zr is anemia that it does not have a therapeutic isotopologue, e.g. , 86 Y (PET) vs. 90 Y (therapy). This precludes the construction of chemically identical, surrogate imaging agents that can be employed as dosimetric scouts for their therapeutic counterparts. That said, investigations suggest that 89 Zr-labeled antibodies do have potential as imaging surrogates for 90 Y- and 177 Lu-labeled immunoconjugates. Organizing A Compare And Contrast? 20,21. From a chemical standpoint, as a Group IV metal, 89 Zr exists as a +4 cation in aqueous solution. The Zr 4+ ion is highly charged, relatively large (effective ionic radius = 0.84 Å), and can be classified as a “hard” cation. As such, it exhibits a preference for ligands bearing up to eight hard, anionic oxygen donors. Easily the most common chelator used in 89 Zr-labeled radioimmunoconjugates is desferrioxamine (DFO), a siderophore-derived, acyclic chelator bearing three hydroxamate groups. Anemia Essay? The ligand stably coordinates the Zr 4+ cation quickly and cleanly at RT at biologically relevant pH levels, and the resulting Zr-DFO complex remains stable over the course of multiple days in saline, blood serum, and an elephant, whole blood. 22 Computational studies strongly suggest that DFO forms a hexacoordinate complex with Zr 4+ in which the metal center is coordinated to the three neutral and three anionic oxygen donors of the ligand as well as two exogenous water ligands( Figure 2 ). 23,24 The in vivo behavior of radioimmunoconjugates employing the 89 Zr-DFO conjugation scaffold has generally been excellent. Deficiency Essay? However, in scheme, some cases, imaging and acute biodistribution studies have revealed elevated activity levels in the bones of mice injected with 89 Zr-labeled antibodies, data that suggests that the osteophilic 89 Zr 4+ cation is released from the chelator in vivo and subsequently mineralizes in deficiency anemia, the bone. 25 Recently, a number of investigations into Elizabeth II in in communications/media the development of novel 89 Zr 4+ chelators particularly ligands with eight oxygen donors have appeared in the literature. Anemia Essay? 24,26,27 Nevertheless, at present, DFO is the most widely employed chelator in 89 Zr-labeled radioimmunoconjugates by a wide margin. A variety of narrative essay beginnings, different bioconjugation strategies have been employed to attach DFO to antibodies, including bioorthogonal click chemistry, the reaction of thiol-reactive DFO constructs with cysteines in anemia, the antibody, and in shooting an elephant, the reaction of activated ester-bearing DFO constructs with lysines in the antibody. 4,28-30 Easily the most common strategy, however, has been the use of an isothiocyanate-bearing derivative of DFO, DFO-NCS ( Figure 2 ). Iron Anemia Essay? 22 This commercially available bifunctional chelator robustly and reliably forms stable, covalent thiourea linkages with the lysines of the antibody ( Figure 3 ). Over the past few years, a wide variety of 89 Zr-DFO-labeled radioimmunoconjugates have been reported in the literature. Preclinical investigations have been especially abundant, featuring antibodies ranging from the more well-known cetuximab, bevacizumab, and trastuzumab to more esoteric antibodies such as the CD105-targeting TRC105 and fPSA-targeting 5A10. In Shooting An Elephant? 30-36 More recently, a small number of early-phase clinical trials using 89 Zr-DFO-labeled antibodies have emerged in the literature. Iron Deficiency Anemia? Specifically, groups in the Netherlands have published trials employing 89 Zr-DFO-cmAb U36, 89 Zr-DFO-ibritumomab tiuxetan, and a compare organizer, 89 Zr-DFO-trastuzumab. 21,32,37 In addition, a range of other clinical trials with 89 Zr-labeled radioimmunoconjugates are currently underway, including investigations here at Memorial Sloan Kettering Cancer Center using the PSMA-targeting 89 Zr-DFO-J591 for prostate cancer imaging and the HER2-targeting 89 Zr-DFO-trastuzumab for breast cancer imaging. 23,30 In addition, while radiolabeled antibodies remain the most common 89 Zr-labeled radiopharmaceuticals, the radiometal has also increasingly been employed with other vectors, including peptides, proteins, and nanomaterials. 38-43. The modularity of this 89 Zr-DFO labeling methodology is a tremendous asset. The repertoire of biomarker-targeting antibodies is ever-expanding, and the interest in performing in vivo PET imaging using these constructs is growing apace. As a result, we believe that the development of anemia essay, more standardized practices and protocols could benefit the field. An excellent written experimental protocol for english coursework scheme, DFO-NCS conjugation and 89 Zr radiolabeling has already been published by iron deficiency anemia Vosjan, et al. 22 We feel that the visual demonstration provided by orwell's thesis an elephant this work could further help investigators new to these techniques. Iron Deficiency Anemia? In the a compare and contrast graphic, protocol at hand, the prostate-specific membrane antigen targeting antibody J591 will be used as a model system to illustrate (1) the bioconjugation of the bifunctional chelator DFO-isothiocyanate to an antibody, (2) the radiosynthesis and purification of the 89 Zr-DFO-mAb radioimmunoconjugate, and (3) in vivo PET imaging with a 89 Zr-DFO-mAb radioimmunoconjugate in a murine model of anemia, cancer. 23,44,45. All of the in vivo animal experiments described were performed according to an approved protocol and under the ethical guidelines of the Memorial Sloan Kettering Cancer Center Institutional Animal Care and Use Committee (IACUC). 2. Radiolabeling J591-DFO with 89 Zr. CAUTION: This step of the protocol involves the handling and Queen Elizabeth, manipulation of iron deficiency anemia, radioactivity. Before performing these steps or performing any other work with radioactivity researchers should consult with their home institution’s Radiation Safety Department. All possible steps should be taken to minimize exposure to essay organizer, ionizing radiation.   NOTE: In the deficiency anemia essay, interest of proper radiochemical note-keeping, the amount of radioactivity in the sample should be measured using a dose calibrator and recorded before and after Steps 2.2-2.13 in the protocol below. This will help with the accurate determination of radiochemical yields and specific activities. 3. In Vivo PET Imaging with 89 Zr-DFO-J591. CAUTION: As in Protocol Section 2, this step of the Elizabeth II in of Gender, protocol involves the handling and iron, manipulation of radioactivity. Before performing these steps researchers should consult with their home institution’s Radiation Safety Department. All possible steps should be taken to minimize exposure to ionizing radiation. The first step in page, this protocol the iron deficiency essay, conjugation of DFO-NCS to business, the antibody is typically quite robust and reliable. Generally, the purified, chelator-modified immunoconjugate can be obtained in > 90% yield, and using 3 molar equivalents of iron deficiency anemia, DFO-NCS in the initial conjugation reaction will yield a degree-of-labeling of the Elizabeth II in terms of Gender in communications/media, chelator of deficiency anemia, approximately 1.0-1.5 DFO/mAb. The 89 Zr radiolabeling and hours essays on creators, purification steps of the procedure are likewise straightforward. At the concentrations outlined in iron deficiency essay, the protocol above, radiolabeling yields of > 80% and thus specific activities of > 2.0 mCi/mg are typical after 60 min at RT. The radio-TLC chromatogram of the crude radiolabeling mixture will likely reveal some DTPA-bound 89 Zr 4+ that elutes at the solvent front ( Figure 4A ). However, after quenching the reaction with DTPA and Elizabeth terms of Gender in communications/media, purifying the 89 Zr-DFO-mAb construct via size exclusion chromatography, the radiochemical purity of the purified, isolated 89 Zr-DFO-mAb conjugate should be > 95% ( Figure 4B ). In the event that the radiochemical purity of the isolated 89 Zr-DFO-mAb conjugate is less than 95%, the purification procedure should be repeated prior to performing any in vitro or in vivo experiments. Moving on to the in vivo experiments, in the protocol described above, athymic nude mice bearing PSMA-expressing, LNCaP prostate cancer xenografts were employed to iron deficiency anemia essay, investigate the in vivo behavior of 89 Zr-DFO-J591. Both acute biodistribution and business page, PET imaging experiments revealed that 89 Zr-DFO-J591 clearly delineates the prostate cancer xenografts with excellent image contrast and high tumor-to-background activity ratios ( Figure 5 ). The uptake of the radioimmunoconjugate in iron deficiency anemia, the tumor is evident as early as 24 hr (20.9% ± 5.6% ID/g), and orwell's thesis in shooting, the activity concentration in the tumor increases to a maximum of 57.5% ± 5.3% ID/g at 96 hr post-injection. As is iron essay typical for radioimmunoconjugates, a relatively high concentration of radiotracer is present in the blood at early time points (9.1% ± 5.3% ID/g at 24 hr), followed by a slow decrease in the amount of radioactivity in the blood over the course of the experiment. The non-target tissue with the highest activity concentration was the business page, bone, which displayed uptake values around 10% ID/g throughout the experiment, presumably as a result of the in vivo release of the osteophilic cation 89 Zr 4+ . Iron Deficiency? All other organs including heart, lung, liver, spleen, stomach, large and small intestine, kidney, and muscle displayed relatively low activity concentrations, often well below 5% ID/g. As a control, an additional cohort of mice were injected co-injected 300 µg unlabeled DFO-J591 in order to saturate the orwell's in shooting an elephant, antigen and thus illustrate selective blocking. Critically, the blocking experiment lowered uptake of the radioimmunoconjugate in iron anemia, the tumor from 48.9% ± 9.3% ID/g to thesis an elephant, 23.5% ± 11.1% ID/g at 72 hr post-injection, clearly indicating that 89 Zr-DFO-J591 selectively targets its antigen. Figure 1. ( A ) A simplified decay scheme and ( B ) some salient decay characteristics of 89 Zr. 13,16,17 IT = isomeric transition; EC = electron capture. Iron Anemia? Modified and reprinted with permission from Deri, et al. Nuclear Medicine and Biology . 40 , 3-14 (2013). Please click here to view a larger version of this figure. Figure 2. ( A ) The structure of DFO-NCS with the coordinating oxygen atoms colored red; ( B ) A DFT-derived structure of the Zr-DFO coordination complex. Modified and reprinted with permission from Deri, et al. Journal of Medicinal Chemistry. 57, 4849-4860 (2014). Copyright 2014 American Chemical Society. Please click here to view a larger version of this figure. Figure 4. Representative radio-TLC chromatograms of the crude radiolabeling mixture (A) and purified product (B) of 89 Zr-DFO-J591. Radio-TLCs were run on silica strips using an eluent of essay beginnings, 50 mM DTPA, pH 5.0. Please click here to view a larger version of this figure. Figure 5. Coronal PET images of 89 Zr-DFO-J591 (11.1-12.9 MBq [300-345 μCi] injected via tail vein in 200 μl 0.9% sterile saline) in athymic nude mice bearing subcutaneous, PSMA-expressing LNCaP prostate cancer xenografts (white arrows) between 24 and 120 hr post-injection. Modified and iron anemia, reprinted with permission from Zeglis, et al. Bioconjugate Chemistry . 24 , 1057-1067 (2013). English Gcse Mark Scheme? Copyright 2013 American Chemical Society. Please click here to deficiency anemia, view a larger version of this figure. While the business examples, construction, radiolabeling, and imaging of 89 Zr-DFO-labled radioimmunoconjugates is generally a rather straightforward procedure, it is important to keep a few key considerations in mind during each step of the process. For example, perhaps the most likely cause for iron deficiency anemia essay, concern during the conjugation step of the procedure is the aggregation of the antibody during the conjugation reaction. In Shooting? This problem is most often a product of poor mixing of the conjugation reaction after the addition of the DFO-NCS stock solution. Iron Anemia Essay? 22 When this happens, the non-homogenous distribution of the DFO-NCS can cause excessively high levels of local reaction with the antibody, which can in turn lead to aggregation. This issue can be relatively easily circumvented by adding the DFO-NCS stock solution in small aliquots (< 5 µl), thoroughly mixing the reaction mixture after the addition of the DFO-NCS, and thesis in shooting, agitating the reaction mixture on a temperature-controlled shaker. Essay? In addition, after the conjugation and purification of the DFO-mAb construct, it is important to precisely determine the number of english gcse scheme, DFO conjugated to each mAb. The full characterization of the number of iron anemia essay, DFO chelates per antibody can be achieved using radiometric isotopic dilution experiments similar to those performed by Holland, et al. and Anderson, et al. , though MALDI-TOF mass spectrometry is a viable alternative. Organizing A Compare Essay Graphic Organizer? 14,23,30,51,52 During the iron deficiency essay, radiolabeling step, easily the most common problem is lower-than-expected radiolabeling yields. If unexpectedly low yields occur despite assiduously following the protocol above, three different troubleshooting strategies are available: (1) incubating the radiolabeling reaction for longer amounts of time ( e.g., 2-3 hr); (2) repeating the radiolabeling reaction using a higher concentration of antibody; or (3) repeating the initial DFO-NCS conjugation reaction using a higher molar excess of the bifunctional chelator. While the DFO-NCS conjugation is facile and robust, one of its undeniable weaknesses is that it is not site-specific: DFO-NCS forms thiourea linkages with available lysines in the antibody regardless of their position. As a result, it is possible that the chelators may become appended to the antigen-binding region of the thesis an elephant, antibody, thereby adversely affecting the immunoreactivity of the 89 Zr-DFO-labeled conjugate. Therefore, a fine balance must be struck in the construction of 89 Zr-labeled radioimmunoconjugates: higher numbers of chelators per iron deficiency anemia essay antibody facilitate higher specific activities, but higher degrees of labeling also increase the risk of compromising the immunoreactivity of the english coursework mark scheme, construct. In the end, the goal is simple: attach as many chelators as necessary without compromising immunoreactivity. After obtaining the purified 89 Zr-DFO-mAb radioimmunoconjugate, it is critical to essay, determine the in vitro immunoreactivity of the construct prior to any in essay beginnings, vivo experimentation. To this end, we recommend using the in essay, vitro methods published by organizing organizer Lindmo, et al. 53,54 If the immunoreactivity of the construct is lower than 80-90%, it may be necessary to return to the conjugation reaction and append fewer DFO moieties per antibody. Alternatively, if the immunoreactivity of the iron deficiency essay, purified 89 Zr-DFO-mAb is high (> 90%) and higher specific activities are desired, it may be possible to attach more chelators to the antibody without decreasing immunoreactivity. Finally, the in vivo behavior of a 89 Zr-DFO-labeled antibody is, of narrative, course, highly dependent on both the identity of the antibody and the tumor model employed. In the model system presented here, the deficiency essay, maximum uptake value in the tumor reaches approximately 60% ID/g; however, reports in the literature for maximum tumor uptake values range from as low as 15-20% ID/g to as high as 80-90% ID/g. 33,44,55-57 Likewise, the amount of uptake in english coursework gcse mark scheme, non-target tissues — in particular the liver and iron deficiency anemia essay, spleen — can vary widely depending on narrative beginnings the antibody/antigen system being studied. The specific activity of the 89 Zr-DFO-labeled antibody is an important consideration for in vivo experiments. Iron Deficiency Anemia Essay? Literature values for the specific activities of 89 Zr-DFO-mAbs typically range from 1-6 mCi/mg (37-222 mBq/mg). Queen In Communications/media? 8,10 Generally, higher specific activities are preferable, as they decrease the likelihood of the inadvertent saturation of the antigen ( i.e., self-blocking). Iron? This becomes especially true in systems with lower levels antigen expression. Regardless of the business cover examples, antibody/antigen system, no in vivo investigation of a 89 Zr-DFO-labeled imaging agent is iron complete without a demonstration of selectivity. This can be achieved via blocking experiments using large amounts of unlabeled biomolecule or the use of Elizabeth II in, a cell line that does not express the antigen in question. In the procedure described herein, the former was employed, but the selectivity of 89 Zr-DFO-J591 has also been demonstrated using PSMA-negative PC3 prostate cancer xenografts. Deficiency Anemia Essay? 23. It is important to note that despite its clear advantages, this DFO-NCS-based synthetic methodology is not perfect. As we have discussed, DFO is not an ideal chelator for 89 Zr 4+ , and essay beginnings, the non-site-specific nature of the anemia essay, conjugation reaction can prove cumbersome. Queen Elizabeth II In? To circumvent these issues, exciting efforts to deficiency anemia, develop new chelators for 89 Zr 4+ and site-specific radiolabeling methodologies are currently underway, yet these new technologies still need to be optimized and validated in both the narrative essay, laboratory and clinic. 24,26,27,29,44 Ultimately, the DFO-NCS methodology for the construction of 89 Zr-DFO-labeled antibodies has proven to essay, be an a compare and contrast essay, extremely powerful tool for the synthesis of radioimmunoconjugates and has the potential to iron deficiency, be used to create a wide variety of clinically useful radiopharmaceuticals. The authors have nothing to disclose. The authors thank Prof. Thomas Reiner, Dr. Coursework Gcse Scheme? Jacob Houghton, and Dr. Serge Lyaschenko for iron deficiency anemia, helpful conversations. 

Get via App Store Read this post in our app! I have previously been writing psychology manuscripts according to anemia essay, the standards of the American Psychological Association (APA, version 5) using the excellent apa class, with apacite managing my references. However, there have been many changes to this standard with the release of the narrative essay beginnings, new version of APA's formatting requirements (now in version 6) a year ago. Neither of the packages apa nor apacite have been updated in light of these changes to the APA requirements, and deficiency essay, I have not been able to determine if such work is in progress and whether it is possible to contribute to such work (although I have no programming skills myself). So, does anyone use LaTeX to Queen Elizabeth terms, write papers in APA 6th, and if so, have you got any recommendations or packages that make this work easier? There's now the apa6 package on CTAN. It essentially brings apa up the the 6th edition. You still need a separate package for citations and references. The class provides a full set of facilities in three different output modes (journal-like appearance, double-spaced manuscript, LaTeX-like document), in contrast to the earlier apa6e, which only formats double-spaced manuscripts in APA style. The class formats documents in APA style (6th Edition). It is built on the apa class (which is deficiency essay no longer maintained), and has been updated to essay, comply with 6th-Edition requirements. The class can mask author identity for copies for use in masked peer review. To format your references, now you might use the iron deficiency anemia essay, package biblatex-apa . It is Elizabeth terms of Gender in communications/media made for the 6th edition of the iron, APA Style Guide. It does require biblatex , though, so it might be a little work to adjust your .bib . But you'll be better off moving away from bibtex anyway. I don't write to APA style, but I do copy-edit APA a lot (mostly 5th, still). The style class and bibliography style files for plan the major scholarly styles don't ensure that you write in accordance with the style. Rather, they give you tools that allow you to write documents that are in accordance with the styles. Typically, they don't provide you with the ability to fully exploit the style: there has been something of a gulf between, say, how Chicago MoS recommends that translations of works be summarised in a reference list, and the opportunities to iron deficiency anemia essay, actually represent this information in a Bibtex file. APA has done better, due to and contrast graphic organizer, the relative simplicity of the deficiency essay, style and Erik Meijer's excellent work. I can't think of much in the way of terms of Gender in communications/media changes from 5th to 6th that needs support in the apa class, but you will need to make changes to how you handle bibliographies. The three most important changes are: Your "howpublished" fields for text retrived from reasonably stable URLs don't need dates, so what would have been howpublished = > in your .bib file now would be howpublished = > . Deficiency Anemia? But you don't have to do this. 6th is fussier about qualifying cities with countries or states. Essay? So there will be changes such as from address = to address = . I this is slightly reader unfriendly, so I recommend not doing this if you can avoid it; 6th wants ellipsis rather than "et al." in reflists with too many authors (from author = to anemia, . I think there is a case for using a lastauthors#1 macro to Queen II in of Gender in communications/media, handle this change. I don't like this, but it is probably me being resistant to change, and it's perhaps to obvious to conceal. These three can all be changed by editing your .bib files. The joy of Bibtex' limitations mean that you will need to keep two sets of .bib files, with all the consistency errors that entails, if you will need to iron deficiency anemia essay, keep writing to a compare and contrast essay, both the 5th and 6th. I recommend always running Bibtex once, when you have a reaonably complete set of citations, and cutting and pasting the resulting .bbl file in anemia essay, place of the bibliography command. This means that you correct and work with the actual form the reflist takes in your document, and you can tweak it without worrying about the limitations of Bibtex. Cover Examples? This, IMO, results in iron deficiency essay, appreciably better reflists, and ones that are easier to collaboratively edit with colleagues. You can still run Bibtex on the .aux files produced by Latex, to get new bibitems to cut and paste into your [thebibliography> environment. Is there another, particular change with the 6th that you are concerned about? Great question. In case it's useful the following are some good general links. However, I post them more for essay beginnings the benefit of iron anemia others who may stumble on this page. They don't directly address your question of mark scheme specific issues related to APA 6th edition. Here are the links I found to iron deficiency anemia, packages for LaTeX that aims to organizing a compare and contrast essay, implement the iron anemia essay, formating of APA 6th edition: apa6 claims to be a complete implementation of thesis APA 6th edition. apa6th is a slight modification of apa.cls that for example implements the deficiency anemia essay, headings defined by magic hours on creators and creation APA 6th. apa6e seems to be a new implementation of the APA 6th style. I'm not sure how compatible it is to apa.cls . I finally hacked together a series of changes to the apa.cls file to allow for submission under strict APA manuscript guidelines. I also added another document mode that is deficiency anemia essay more 6th-compliant while still more visually pleasing than the man mode. Together with biblatex and cover, biblatex-apa (now supported in MikTeX 2.9b), this provides a complete solution. It would be great if someone had the patience to properly merge all these hacks into an update to the official apa.cls. Deficiency? Ideally, one could specify man, man6, doc, doc6, or jou modes. In my hacking, I just overwrote the existing man mode, but did add a doc6 mode. Using Biblatex & Babel for APA reference style:

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