Background Hepatocellular carcinoma is a common malignancy for which chronic hepatitis B infection has been defined as the most common etiologic factor. The most frequent metastatic sites are the lung, bone, lymphatics, and brain, respectively. Metastases to the chest wall have been reported only rarely.
Background
Hepatocellular carcinoma is a common malignancy for which chronic hepatitis B infection has been defined as the most common etiologic factor. The most frequent metastatic sites are the lung, bone, lymphatics, and brain, respectively. Metastases to the chest wall have been reported only rarely.Case presentation We report a patient with hepatocellular carcinoma who presented with an isolated metastatic mass on the left anterolateral chest wall in the axillary region.
Case presentation
We report a patient with hepatocellular carcinoma who presented with an isolated metastatic mass on the left anterolateral chest wall in the axillary region.Conclusions Metastasis of HCC should be included in the differential diagnosis of rapidly growing lesions in unusual localizations, particularly in patients with chronic liver disease even if a primary tumor can not be radiologically identified.
Conclusions
Metastasis of HCC should be included in the differential diagnosis of rapidly growing lesions in unusual localizations, particularly in patients with chronic liver disease even if a primary tumor can not be radiologically identified.

Background Hepatocellular carcinoma (HCC) is the most frequent primary malignant tumor of the liver [ 1 ]. It is usually seen in the 6 th  and 7 th  decades of life, and the most common etiologic factor is chronic viral hepatitis, particularly in the presence of cirrhosis. Chronic hepatitis B has been described as the most frequent cause [ 2 - 4 ]. Hematogeneous extrahepatic metastases are common, with lungs, regional lymph nodes, kidneys, bone marrow and adrenals being the most frequent sites [ 3 , 4 ]. Rarely HCC may present as a mass without a primary liver tumor being identified [ 5 - 7 ]. This report presents an unusual metastasis of HCC which presented as a mass on the left chest wall in the axillary region.
Background
Hepatocellular carcinoma (HCC) is the most frequent primary malignant tumor of the liver [ 1 ]. It is usually seen in the 6 th  and 7 th  decades of life, and the most common etiologic factor is chronic viral hepatitis, particularly in the presence of cirrhosis. Chronic hepatitis B has been described as the most frequent cause [ 2 - 4 ]. Hematogeneous extrahepatic metastases are common, with lungs, regional lymph nodes, kidneys, bone marrow and adrenals being the most frequent sites [ 3 , 4 ]. Rarely HCC may present as a mass without a primary liver tumor being identified [ 5 - 7 ].This report presents an unusual metastasis of HCC which presented as a mass on the left chest wall in the axillary region.Case presentation A 71-year-old male was admitted to our clinic with complaints of left shoulder pain, swelling in the left anterolateral chest wall, jaundice, weight loss, dyspnea and weakness. At three months prior to admission, he had noticed a less movable mass approximately 2 cm in diameter and then the tumor had grown rapidly, becoming increasingly painful during exertion. There was no history of expectoration, fever, or night sweats. The patient's physical examination revealed yellow discoloration of the sclerae, pitting edema up to the knees and a 5 cm × 6 cm fixed mass in the left axillary region. There was mild splenomegaly but no hepatomegaly, liver masses or ascites. Laboratory findings were as follows: sedimentation rate: 90 mm/hr; Hb: 11.5 mg/dL; WBC: 3900/mm 3 ; Plt: 126 000/mm 3 ; PT: 15.6 sec; INR:1.3; total protein: 6.5 g/dL (N: 6.4–8.5 g/dL); albumin: 2.2 g/dL (N: 3.4–4.8 g/dL); AST: 124 iu/L (N: 15–40); ALT: 52 iu/L (N: 10–40); ALP: 173 iu/L (N: 37–147); GGT: 213 iu/L (N:0–40); total bilirubin: 3.8 mg/dL (N: 0.1–1.2), and direct bilirubin: 1.57 mg/dL (N: 0–0.3). Hepatitis B virus surface antigen, IgG antibody to the core antigen, anti-HBe and HBV DNA with polymerase chain reaction were positive. HBe antigen, anti-Delta and serological markers of hepatitis C were negative. Abdominal ultrasonography showed ascites, splenomegaly and diffusely nodular and heterogeneous echogenic patterns in the liver. There was no history of chronic liver disease. Upper gastrointestinal endoscopy was normal except for esophageal varices. Computerized tomography of the thorax revealed a mass on the left anterolateral chest wall (Figure  1 ). Cytological examination of a fine needle aspirate taken from the mass was consistent with metastatic hepatocellular carcinoma (Figure  2 ). Abdominal computerized tomography detected thrombosis in the right portal vein. The liver parenchyma was diffusely heterogeneous with irregular borders and without a clear mass or infiltrating lesion. There was no lymphadenopathy on thoracic, abdominal or pelvic computerized tomography. The patient had an elevated serum alpha-feto protein (AFP) level of 60 000 ng/mL (0 – 13.6 ng/ml). Cytological examination of the liver confirmed the diagnosis of hepatocellular carcinoma. The patient was discharged on palliative treatment, and he died 21 days later.
Case presentation
A 71-year-old male was admitted to our clinic with complaints of left shoulder pain, swelling in the left anterolateral chest wall, jaundice, weight loss, dyspnea and weakness. At three months prior to admission, he had noticed a less movable mass approximately 2 cm in diameter and then the tumor had grown rapidly, becoming increasingly painful during exertion. There was no history of expectoration, fever, or night sweats. The patient's physical examination revealed yellow discoloration of the sclerae, pitting edema up to the knees and a 5 cm × 6 cm fixed mass in the left axillary region. There was mild splenomegaly but no hepatomegaly, liver masses or ascites. Laboratory findings were as follows: sedimentation rate: 90 mm/hr; Hb: 11.5 mg/dL; WBC: 3900/mm 3 ; Plt: 126 000/mm 3 ; PT: 15.6 sec; INR:1.3; total protein: 6.5 g/dL (N: 6.4–8.5 g/dL); albumin: 2.2 g/dL (N: 3.4–4.8 g/dL); AST: 124 iu/L (N: 15–40); ALT: 52 iu/L (N: 10–40); ALP: 173 iu/L (N: 37–147); GGT: 213 iu/L (N:0–40); total bilirubin: 3.8 mg/dL (N: 0.1–1.2), and direct bilirubin: 1.57 mg/dL (N: 0–0.3). Hepatitis B virus surface antigen, IgG antibody to the core antigen, anti-HBe and HBV DNA with polymerase chain reaction were positive. HBe antigen, anti-Delta and serological markers of hepatitis C were negative.Abdominal ultrasonography showed ascites, splenomegaly and diffusely nodular and heterogeneous echogenic patterns in the liver. There was no history of chronic liver disease. Upper gastrointestinal endoscopy was normal except for esophageal varices. Computerized tomography of the thorax revealed a mass on the left anterolateral chest wall (Figure  1 ). Cytological examination of a fine needle aspirate taken from the mass was consistent with metastatic hepatocellular carcinoma (Figure  2 ). Abdominal computerized tomography detected thrombosis in the right portal vein. The liver parenchyma was diffusely heterogeneous with irregular borders and without a clear mass or infiltrating lesion. There was no lymphadenopathy on thoracic, abdominal or pelvic computerized tomography. The patient had an elevated serum alpha-feto protein (AFP) level of 60 000 ng/mL (0 – 13.6 ng/ml). Cytological examination of the liver confirmed the diagnosis of hepatocellular carcinoma. The patient was discharged on palliative treatment, and he died 21 days later.Discussion Although extrahepatic metastasis of HCC was reported in 18% of untreated patients in a retrospective study, metastatic lesions were found at a higher incidence in an autopsy study of deaths related to primary liver cancer [ 8 , 9 ]. The most common sites of extrahepatic involvement are the lungs, lymph nodes, adrenal glands, and bones [ 3 , 8 , 10 - 12 ]. Metastasis of HCC occurs frequently by way of intrahepatic blood vessels, lymphatic permeation, or direct infiltration. Hematogenous spread occurs with the involvement of hepatic or portal veins or the vena cava. Metastases have also been found in collaterals and varices, and this appears to have been the route of metastasis in the patient reported here. His right portal vein was thrombosed, most likely due to tumoral infiltration. Tumor cells might have passed through the left thoracic wall via portosystemic collaterals, the azygous system and finally intercostal veins. Another possible route is through subcutaneous collaterals communicating to thoracoepigastric veins and draining into the axillary vein. Although bone metastases are seen in 10% of HCC patients [ 13 ], it infrequently appears as the first manifestation of HCC. The most common sites are the vertebra and pelvis [ 14 ]. Isolated metastases of HCC to the ribs have been rarely reported [ 5 , 6 , 15 - 17 ]. The establishment of the diagnosis of metastatic HCC can occasionally be problematic, particularly when the primary tumor has not been identified. To the best of our knowledge there are only two reports in the literature describing cases of solitary metastasis to the chest wall from an unknown primary HCC. One patient had an HCC metastasis involving the sternum, and the other patient had a metastasis on the right 4 th  rib [ 5 , 6 ]. In the present patient, the etiology of HCC was due to chronic hepatitis B, and the HCC was diffuse in nature. Yuki et al. reported an association between HBs antigen positivity and diffuse-type HCC. Intrahepatic, hematogenous and lymphogenous metastases have been frequently observed in diffuse-type HCC [ 18 ]. Nevertheless, diffuse-type HCC is often difficult to detect on imaging studies because of its permeative appearance and heterogeneity of background chronic liver disease [ 19 ]. In our patient, although HCC was of the diffuse type, metastasis involvement was isolated. There was also no regional lymph node infiltration. AFP, when elevated, usually correlates with tumor size. AFP doubling time is also closely related to tumor doubling time. A rapidly growing axillary mass, diffuse tumoral infiltration of the liver and a very high level of AFP in our patient are consistent with these observations. However, nearly one-fourth of patients with HCC may have normal AFP values [ 19 ]. The need for liver biopsy might be questionable in the our patient. The presence of chronic liver disease with a very high AFP level was highly suggestive for HCC. However, there are several reports in the literature describing ectopic HCC without a liver origin. These patients can be treated with surgical resection and have a good prognosis [ 7 , 20 ]. Furthermore, several reports have claimed that ectopic livers are particularly predisposed to developing HCC [ 20 - 22 ]. In conclusion, metastasis of HCC should be included in the differential diagnosis of rapidly growing lesions in unusual localizations, particularly in patients with chronic liver disease even if a primary tumor cannot be radiologically identified.
Discussion
Although extrahepatic metastasis of HCC was reported in 18% of untreated patients in a retrospective study, metastatic lesions were found at a higher incidence in an autopsy study of deaths related to primary liver cancer [ 8 , 9 ]. The most common sites of extrahepatic involvement are the lungs, lymph nodes, adrenal glands, and bones [ 3 , 8 , 10 - 12 ]. Metastasis of HCC occurs frequently by way of intrahepatic blood vessels, lymphatic permeation, or direct infiltration. Hematogenous spread occurs with the involvement of hepatic or portal veins or the vena cava. Metastases have also been found in collaterals and varices, and this appears to have been the route of metastasis in the patient reported here. His right portal vein was thrombosed, most likely due to tumoral infiltration. Tumor cells might have passed through the left thoracic wall via portosystemic collaterals, the azygous system and finally intercostal veins. Another possible route is through subcutaneous collaterals communicating to thoracoepigastric veins and draining into the axillary vein.Although bone metastases are seen in 10% of HCC patients [ 13 ], it infrequently appears as the first manifestation of HCC. The most common sites are the vertebra and pelvis [ 14 ]. Isolated metastases of HCC to the ribs have been rarely reported [ 5 , 6 , 15 - 17 ].The establishment of the diagnosis of metastatic HCC can occasionally be problematic, particularly when the primary tumor has not been identified. To the best of our knowledge there are only two reports in the literature describing cases of solitary metastasis to the chest wall from an unknown primary HCC. One patient had an HCC metastasis involving the sternum, and the other patient had a metastasis on the right 4 th  rib [ 5 , 6 ].In the present patient, the etiology of HCC was due to chronic hepatitis B, and the HCC was diffuse in nature. Yuki et al. reported an association between HBs antigen positivity and diffuse-type HCC. Intrahepatic, hematogenous and lymphogenous metastases have been frequently observed in diffuse-type HCC [ 18 ]. Nevertheless, diffuse-type HCC is often difficult to detect on imaging studies because of its permeative appearance and heterogeneity of background chronic liver disease [ 19 ]. In our patient, although HCC was of the diffuse type, metastasis involvement was isolated. There was also no regional lymph node infiltration.AFP, when elevated, usually correlates with tumor size. AFP doubling time is also closely related to tumor doubling time. A rapidly growing axillary mass, diffuse tumoral infiltration of the liver and a very high level of AFP in our patient are consistent with these observations. However, nearly one-fourth of patients with HCC may have normal AFP values [ 19 ].The need for liver biopsy might be questionable in the our patient. The presence of chronic liver disease with a very high AFP level was highly suggestive for HCC. However, there are several reports in the literature describing ectopic HCC without a liver origin. These patients can be treated with surgical resection and have a good prognosis [ 7 , 20 ]. Furthermore, several reports have claimed that ectopic livers are particularly predisposed to developing HCC [ 20 - 22 ].In conclusion, metastasis of HCC should be included in the differential diagnosis of rapidly growing lesions in unusual localizations, particularly in patients with chronic liver disease even if a primary tumor cannot be radiologically identified.Competing interest The author(s) declare that they have no competing interests.
Competing interest
The author(s) declare that they have no competing interests.Authors contributions SC, involved in the patient active management and preparation of the figures. OY, carried out the literature search. SK, revised it for scientific content. KC, performed the cytological examination. MB, involved in the patient active management. AD, edited the manuscript and coordinated the submission. All authors contributed to the preparation of the manuscript. All authors read and approved the final version of the manuscript.
Authors contributions
SC, involved in the patient active management and preparation of the figures. OY, carried out the literature search. SK, revised it for scientific content. KC, performed the cytological examination. MB, involved in the patient active management. AD, edited the manuscript and coordinated the submission. All authors contributed to the preparation of the manuscript. All authors read and approved the final version of the manuscript.Pre-publication history The pre-publication history for this paper can be accessed here:
Pre-publication history
The pre-publication history for this paper can be accessed here:


Background Alignment and comparison of related genome sequences is a powerful method to identify regions likely to contain functional elements. Such analyses are data intensive, requiring the inclusion of genomic multiple sequence alignments, sequence annotations, and scores describing regional attributes of columns in the alignment. Visualization and browsing of results can be difficult, and there are currently limited software options for performing this task.
Background
Alignment and comparison of related genome sequences is a powerful method to identify regions likely to contain functional elements. Such analyses are data intensive, requiring the inclusion of genomic multiple sequence alignments, sequence annotations, and scores describing regional attributes of columns in the alignment. Visualization and browsing of results can be difficult, and there are currently limited software options for performing this task.Results The Application for Browsing Constraints (ABC) is interactive Java software for intuitive and efficient exploration of multiple sequence alignments and data typically associated with alignments. It is used to move quickly from a summary view of the entire alignment via arbitrary levels of resolution to individual alignment columns. It allows for the simultaneous display of quantitative data, (e.g., sequence similarity or evolutionary rates) and annotation data (e.g. the locations of genes, repeats, and constrained elements). It can be used to facilitate basic comparative sequence tasks, such as export of data in plain-text formats, visualization of phylogenetic trees, and generation of alignment summary graphics.
Results
The Application for Browsing Constraints (ABC) is interactive Java software for intuitive and efficient exploration of multiple sequence alignments and data typically associated with alignments. It is used to move quickly from a summary view of the entire alignment via arbitrary levels of resolution to individual alignment columns. It allows for the simultaneous display of quantitative data, (e.g., sequence similarity or evolutionary rates) and annotation data (e.g. the locations of genes, repeats, and constrained elements). It can be used to facilitate basic comparative sequence tasks, such as export of data in plain-text formats, visualization of phylogenetic trees, and generation of alignment summary graphics.Conclusions The ABC is a lightweight, stand-alone, and flexible graphical user interface for browsing genomic multiple sequence alignments of specific loci, up to hundreds of kilobases or a few megabases in length. It is coded in Java for cross-platform use and the program and source code are freely available under the General Public License. Documentation and a sample data set are also available  .
Conclusions
The ABC is a lightweight, stand-alone, and flexible graphical user interface for browsing genomic multiple sequence alignments of specific loci, up to hundreds of kilobases or a few megabases in length. It is coded in Java for cross-platform use and the program and source code are freely available under the General Public License. Documentation and a sample data set are also available  .

Background Functional elements in a genome accumulate inter-specific substitutions more slowly than neutral DNA throughout evolution [ 1 ]. Therefore, comparing orthologous genomic sequences from related species is useful for the identification of elements that play important roles in the biology of an organism [ 2 - 7 ]. While the statistical and computational methods for extracting comparative information are variable, the types of data involved are generally quite similar. First, a multiple sequence alignment is necessary. Second, a vector of quantitative scores is produced that describes the similarity of the nucleotides observed in small windows, or individual columns, of the alignment; percent identity is the metric used by the popular program VISTA [ 8 ], while a variety of other scoring methods also exist [ 9 - 12 ]. Third, annotations are generated that highlight regions of the alignment that are under constraint or meet some other quantitative threshold. Fourth, annotations of features like transcripts, promoters, coding exons, and repeats provide functional context. Finally, the phylogenetic tree that relates the aligned sequences is important for both performing comparative analyses and for interpreting their results. Simultaneous visualization of complex data such as these is of utmost importance both for experimentalists and for computational biologists. Several options currently exist for such visualization, but there are a variety of characteristics that distinguish the ABC from them. VISTA, for example, generates a static image that is not interactive [ 8 ]. Other popular browsers such as phylo-VISTA [ 13 ] and PipMaker [ 14 , 15 ] require the use of a particular alignment program and scoring scheme. Also, the ABC is not suited for genome-wide visualization. Other tools exist for this and are quite useful for the browsing of very large genomic intervals and major evolutionary events such as genomic rearrangements [ 16 - 19 ]. However, these programs are generally part of larger, more complex interfaces that are not necessarily ideal for targeted analysis of an individual alignment or genomic locus. Finally, we note that the ABC allows many annotation types and colors, is not web-based and can be used on a local machine as intensively as necessary, and the source code is open and freely available allowing users to modify and add features if desired.
Background
Functional elements in a genome accumulate inter-specific substitutions more slowly than neutral DNA throughout evolution [ 1 ]. Therefore, comparing orthologous genomic sequences from related species is useful for the identification of elements that play important roles in the biology of an organism [ 2 - 7 ]. While the statistical and computational methods for extracting comparative information are variable, the types of data involved are generally quite similar. First, a multiple sequence alignment is necessary. Second, a vector of quantitative scores is produced that describes the similarity of the nucleotides observed in small windows, or individual columns, of the alignment; percent identity is the metric used by the popular program VISTA [ 8 ], while a variety of other scoring methods also exist [ 9 - 12 ]. Third, annotations are generated that highlight regions of the alignment that are under constraint or meet some other quantitative threshold. Fourth, annotations of features like transcripts, promoters, coding exons, and repeats provide functional context. Finally, the phylogenetic tree that relates the aligned sequences is important for both performing comparative analyses and for interpreting their results.Simultaneous visualization of complex data such as these is of utmost importance both for experimentalists and for computational biologists. Several options currently exist for such visualization, but there are a variety of characteristics that distinguish the ABC from them. VISTA, for example, generates a static image that is not interactive [ 8 ]. Other popular browsers such as phylo-VISTA [ 13 ] and PipMaker [ 14 , 15 ] require the use of a particular alignment program and scoring scheme. Also, the ABC is not suited for genome-wide visualization. Other tools exist for this and are quite useful for the browsing of very large genomic intervals and major evolutionary events such as genomic rearrangements [ 16 - 19 ]. However, these programs are generally part of larger, more complex interfaces that are not necessarily ideal for targeted analysis of an individual alignment or genomic locus. Finally, we note that the ABC allows many annotation types and colors, is not web-based and can be used on a local machine as intensively as necessary, and the source code is open and freely available allowing users to modify and add features if desired.Implementation The ABC requires Java 1.4 or later and has been successfully tested on Windows, Linux, and OS X. There is no specific upper limit in the size of potential data sets, but system memory usage can be high on large alignments. The ABC can efficiently handle a 2 Mb alignment of 29 sequences on a machine with a 1 GHz processor and 1 Gb of RAM. Details about file formats and instructions for use are available in the documentation that is available along with the source code  . The file formats used by the ABC are quite similar, with only minor modifications, to other standard formats, such as fasta-formatted sequence files and standard parenthesis notation for phylogenetic tree descriptions. A sample data set is available, and is the source of the screenshot depicted in Figure  1 . The sequence data are derived from a previously published analysis [ 20 ]; it includes ~300 kb of sequence from 9 mammals, centered around the  ST7  gene in the human genome, near the  CFTR  gene. Repeats were identified in the human sequence using RepeatMasker [ 21 ] and genes identified using RefSeq annotations from the UCSC genome browser [ 17 ]. The alignment was generated using MLAGAN [ 22 ], and has been compressed so that the human sequence is ungapped; annotation of human sequence features is thus identical to the alignment annotations shown in Figure  1 . A description of the method used to score the alignment columns and identify constrained elements, along with Perl scripts that facilitate this method, including export of results in ABC-ready formats, will be described elsewhere (in preparation). Please note that the ABC will not translate coordinates from alignment to sequence coordinates (or vice versa); the annotations that the user supplies must be appropriate to the alignment being analyzed.
Implementation
The ABC requires Java 1.4 or later and has been successfully tested on Windows, Linux, and OS X. There is no specific upper limit in the size of potential data sets, but system memory usage can be high on large alignments. The ABC can efficiently handle a 2 Mb alignment of 29 sequences on a machine with a 1 GHz processor and 1 Gb of RAM. Details about file formats and instructions for use are available in the documentation that is available along with the source code  . The file formats used by the ABC are quite similar, with only minor modifications, to other standard formats, such as fasta-formatted sequence files and standard parenthesis notation for phylogenetic tree descriptions. A sample data set is available, and is the source of the screenshot depicted in Figure  1 . The sequence data are derived from a previously published analysis [ 20 ]; it includes ~300 kb of sequence from 9 mammals, centered around the  ST7  gene in the human genome, near the  CFTR  gene. Repeats were identified in the human sequence using RepeatMasker [ 21 ] and genes identified using RefSeq annotations from the UCSC genome browser [ 17 ]. The alignment was generated using MLAGAN [ 22 ], and has been compressed so that the human sequence is ungapped; annotation of human sequence features is thus identical to the alignment annotations shown in Figure  1 . A description of the method used to score the alignment columns and identify constrained elements, along with Perl scripts that facilitate this method, including export of results in ABC-ready formats, will be described elsewhere (in preparation). Please note that the ABC will not translate coordinates from alignment to sequence coordinates (or vice versa); the annotations that the user supplies must be appropriate to the alignment being analyzed.ST7CFTRResults and discussion By default, the ABC displays graphical summaries of the quantitative information associated with the alignment. Scores are summarized regionally in consecutive non-overlapping windows. The size of these windows depends on the resolution, defined as the number of alignment columns summarized per pixel. The ABC has three distinct display modes, chosen automatically depending on the density of the information. At very low resolution, a histogram is displayed that plots the number of data points in each window that are at or below a specified value; note that regions containing many low scores will stand out as peaks in the histogram, as demonstrated by the clear association of peaks and the location of exons (Figure  1 , top panel). At intermediate resolutions, a 'wiggly plot' is displayed, in which the average score for each regional window is plotted; in this case, regions containing many low scores will appear as valleys in the plot (Figure  1 ; middle panels). Finally, at very high resolution, the user may view the sequence data directly, along with the sequence names and a tree relating the sequences (Figure  1 ; lower panel). A mobile and scalable zoom window allows for exploration of the summary views (Figure  1 ; upper panels). The user may drag and resize this rectangle, and when a desired region is selected a more detailed view can be obtained. This region will be expanded immediately below the parent display, with the resolution, score plot, and annotation adjusted accordingly (Figure  1 ; compare the start and stop coordinates of the black rectangle in the top panel to the start and stop coordinates of the entire panel immediately below). At all resolutions, annotation tracks are displayed immediately above the score/sequence display (Figure  1 ; all panels). An arbitrary number of tracks may be displayed, but the bottom two tracks are reserved for displaying information about transcripts with exons and introns. Colors for features can be specified individually using standard RGB notation. Other key features of the ABC include: • Mouse-over highlighting to reveal annotations, scores, coordinates, etc • Exporting of sequence, score, and annotation data • Searching sequence data for particular nucleotide strings • GoTo feature to quickly bring up a desired region The ABC is flexible in that is has the ability to visualize diverse quantitative information and it has the capacity to display an arbitrary number of annotation types. It does not have a built-in scoring function; all data needs to be generated and formatted prior to being displayed in the ABC. While this may seem to be a drawback, it is in fact the intended function for an interface that has no preconceptions about the methodology that generated the data. Finally, the ABC is interactive, allowing the user to zoom in quickly from summary views of the comparative data to individual alignment columns. Zoom levels remain in the display, allowing the user to keep a birds-eye view of a large genomic region while focusing at much higher resolution on a small section within it.
Results and discussion
By default, the ABC displays graphical summaries of the quantitative information associated with the alignment. Scores are summarized regionally in consecutive non-overlapping windows. The size of these windows depends on the resolution, defined as the number of alignment columns summarized per pixel. The ABC has three distinct display modes, chosen automatically depending on the density of the information. At very low resolution, a histogram is displayed that plots the number of data points in each window that are at or below a specified value; note that regions containing many low scores will stand out as peaks in the histogram, as demonstrated by the clear association of peaks and the location of exons (Figure  1 , top panel). At intermediate resolutions, a 'wiggly plot' is displayed, in which the average score for each regional window is plotted; in this case, regions containing many low scores will appear as valleys in the plot (Figure  1 ; middle panels). Finally, at very high resolution, the user may view the sequence data directly, along with the sequence names and a tree relating the sequences (Figure  1 ; lower panel).A mobile and scalable zoom window allows for exploration of the summary views (Figure  1 ; upper panels). The user may drag and resize this rectangle, and when a desired region is selected a more detailed view can be obtained. This region will be expanded immediately below the parent display, with the resolution, score plot, and annotation adjusted accordingly (Figure  1 ; compare the start and stop coordinates of the black rectangle in the top panel to the start and stop coordinates of the entire panel immediately below). At all resolutions, annotation tracks are displayed immediately above the score/sequence display (Figure  1 ; all panels). An arbitrary number of tracks may be displayed, but the bottom two tracks are reserved for displaying information about transcripts with exons and introns. Colors for features can be specified individually using standard RGB notation. Other key features of the ABC include:• Mouse-over highlighting to reveal annotations, scores, coordinates, etc• Exporting of sequence, score, and annotation data• Searching sequence data for particular nucleotide strings• GoTo feature to quickly bring up a desired regionThe ABC is flexible in that is has the ability to visualize diverse quantitative information and it has the capacity to display an arbitrary number of annotation types. It does not have a built-in scoring function; all data needs to be generated and formatted prior to being displayed in the ABC. While this may seem to be a drawback, it is in fact the intended function for an interface that has no preconceptions about the methodology that generated the data. Finally, the ABC is interactive, allowing the user to zoom in quickly from summary views of the comparative data to individual alignment columns. Zoom levels remain in the display, allowing the user to keep a birds-eye view of a large genomic region while focusing at much higher resolution on a small section within it.Conclusions The ABC is stand-alone alignment browsing software that is relatively easy to use and customize. While it was not designed as a genome-wide browser, it is well-suited for tasks associated with comparative sequence analysis: exploration of alignments of individual genomic loci; analyzing the relationship between known biological features and quantitative comparative data; visualizing results for researchers who develop and test methods for comparative sequence analysis; isolating sequence elements in a genomic locus for downstream applications like motif-discovery or primer design; generating graphics that characterize a multiple sequence alignment or region of an alignment; and potentially more applications that we have not yet considered. In our own research, for example, we have used it to display SNPs between different mouse strains in the context of a comparative alignment (not shown). This flexibility should be beneficial to researchers whose primary interest is comparative sequence analysis, but should also be valuable to those who use comparative analyses in support of other types of projects, such as experimental characterization of constrained elements. We also note that this flexibility distinguishes the ABC from other browsers that require built-in or specific types of score data and/or the use of a particular alignment program. The software is written in Java for cross-platform support, and the source code is freely available under the General Public License (GPL).
Conclusions
The ABC is stand-alone alignment browsing software that is relatively easy to use and customize. While it was not designed as a genome-wide browser, it is well-suited for tasks associated with comparative sequence analysis: exploration of alignments of individual genomic loci; analyzing the relationship between known biological features and quantitative comparative data; visualizing results for researchers who develop and test methods for comparative sequence analysis; isolating sequence elements in a genomic locus for downstream applications like motif-discovery or primer design; generating graphics that characterize a multiple sequence alignment or region of an alignment; and potentially more applications that we have not yet considered. In our own research, for example, we have used it to display SNPs between different mouse strains in the context of a comparative alignment (not shown). This flexibility should be beneficial to researchers whose primary interest is comparative sequence analysis, but should also be valuable to those who use comparative analyses in support of other types of projects, such as experimental characterization of constrained elements. We also note that this flexibility distinguishes the ABC from other browsers that require built-in or specific types of score data and/or the use of a particular alignment program. The software is written in Java for cross-platform support, and the source code is freely available under the General Public License (GPL).Availability and requirements Project name: Application for Browsing Constraints (ABC) Project home page:  Operating system: Platform independent Programming language: Java Other requirements: Java 1.4 or later License: GPL
Availability and requirements
Project name: Application for Browsing Constraints (ABC)Project home page:Operating system: Platform independentProgramming language: JavaOther requirements: Java 1.4 or laterLicense: GPLAbbrevations ABC: Application for Browsing Constraints GUI: Graphical User Interface GPL: General Public License SNP: Single Nucleotide Polymorphism UCSC: University of California, Santa Cruz RGB: Red-Green-Blue
Abbrevations
ABC: Application for Browsing ConstraintsGUI: Graphical User InterfaceGPL: General Public LicenseSNP: Single Nucleotide PolymorphismUCSC: University of California, Santa CruzRGB: Red-Green-BlueAuthors' contributions GMC and AS conceived of the project, organized the feel and design of the browser, generated the underlying data, and wrote the manuscript. SAGS wrote the Java code and provided comments on the manuscript. All authors read and approved the final manuscript.
Authors' contributions
GMC and AS conceived of the project, organized the feel and design of the browser, generated the underlying data, and wrote the manuscript. SAGS wrote the Java code and provided comments on the manuscript. All authors read and approved the final manuscript.


Beginning two years ago, the US Dept of Health and Human Services began "special reviews" of all current research grants that involved harm reduction, sex and drugs, and continues its ban on funding of needle exchange. With Bush's second term, the campaign was extended to all US funded international programs that dealt with these issues and populations. And, most recently, the US has again undertaken to dominate the discourse within international organizations charged with drug control and AIDS policies – especially those of the UN. But the international harm reduction and human rights community is fighting back in several important ways, including "An Open Letter to the delegates of the Forty-eighth session of the Commission on Narcotic Drugs (CND) of the UN" prepared by a group of 334 well respected public health experts and human rights advocates, protesting U.S. pressure on the U.N. to withdraw its support from harm reduction. This editorial includes the letter and signatures as well as French, Spanish, and Russian versions of the letter as additional files.

"This is a sharp time, now, a precise time - we live no longer in the dusky afternoon when evil mixed itself with good and befuddled the world. Now, by God's grace, the shining sun is up, and them that fear not light will surely praise it." Arthur Miller, The Crucible, Act III "I do not believe that the meaning of our Eighth Amendment, any more than the meaning of other provisions of our Constitution, should be determined by the subjective views of five members of this court and like-minded foreigners" Justice Antonin Scalia, in his dissent from the US Supreme Court majority decision barring capital punishment for crimes committed by minors . It is indeed "a sharp time" in the US for those of us who agree with "like-minded foreigners". This is especially so regarding matters of drug and AIDS policies based on harm reduction (HR) and public health – decriminalization of drug users, the need for safer injections, low thresholds for access to care, sex education and social supports that work to reduce risk. Today more people are imprisoned for drug use in the US than are incarcerated in the European Union for all crimes. US conservatives have, in the same lethal moralistic tradition of our Salem witch-hunts of the 1600's and the McCarthy era, effectively obstructed and undermined our HR efforts at home for two decades. But now the Bush administration, emboldened by its re-election and in full warrior mode, has undertaken a newly invigorated global jihad against harm reduction. Americans who support HR are now to be made to feel "foreign", their moral compass, patriotism, and loyalty to "American core – values" placed in doubt. Parallels to the death penalty are not casual: the failed punitive drug policies of the war on drugs are also official "death sentences", with many more lives lost to them each year than to all the judicially sanctioned executions of all the countries on earth. And, because preventable death is more then an analogy when it comes to public health, we can learn a lot from this Supreme Court case. Justice Anthony M. Kennedy, writing for the courts majority, recognized the "evolving standards of decency" that should shape our judgment of what constitutes a violation of our Constitution's Eighth Amendment and its prohibition against cruel and unusual punishments: "it is fair to say that the United States now stands alone in a world that has turned its face against the juvenile death penalty." But Justice Scalia, significant as the most likely nominee for Chief Justice with the ailing incumbents imminent departure, saw it differently, the NY Times reporting that he reserved "his strongest dissent for (the majority's) reference to international developments that have left the United States alone in supporting juvenile executions". For while the majority opinion said the court was not bound by foreign developments, "it is proper that we acknowledge the overwhelming weight of international opinion" for its "respected and significant confirmation for our own conclusions", Scalia objected that this position implied that "the views of our own citizens are essentially irrelevant," and had wrongly given "center stage" to the "so-called international community." Assumedly this would be that same " international community" that our Declaration of Independence refers to in its famous opening paragraph where, attempting to justify our nations throwing off British rule, we are told that " a decent respect to the opinions of mankind requires that " we explain our course of action. But as the worlds "sole super- power" (tell China that) it appears that we no longer have to show a decent respect for any other nations opinions about human rights, nor it would seem for the relentlessly insistent biology of HIV. The US harm maximization drug policies, which violate both human rights and the realities of infectious diseases, are immoral and dangerously misguided – sustained by demagogic politicians and mad moralists now in near absolute power in our country. As surely as capital punishment, these policies mete out death sentences on a massive scale to our most vulnerable citizens. These failed policies account for the continued annual incidence of 40,000 new HIV infections in the US. Beginning two years ago, the US Dept of Health and Human Services (the parent agency of our National Institutes of Health, which funds most AIDS and drug research in the world) began "special reviews" of all current research grants that involved sex and drugs. Washington re-asserted the drive for mandated "abstinence only" and "faith based" programs, and continues the Federal ban on funding of needle exchange. Don't even bother applying for work on gay sex. With Bush's second term, the campaign was extended to all US funded international programs that dealt with these issues and populations. And, most recently, the US has again undertaken to dominate the discourse within international organizations charged with drug control and AIDS policies – especially those of the UN. Now the US seeks to impose them as extra judicial capital punishment on the rest of the world. But the international harm reduction and human rights community is not going quietly – it is fighting back in several important ways and we can cite many successes that have already saved hundreds of thousands of lives. Henceforth we will chronicle this struggle in this journal. As a start we are publishing An Open Letter to the delegates of the Forty-eighth session of the Commission on Narcotic Drugs (CND) of the UN prepared by a group of well respected public health experts and human rights advocates, protesting U.S. pressure on the U.N. to withdraw its support from harm reduction (see  Additional file 1 ). The letter garnered 334 individual and organizational endorsements from fifty-six countries. The organizers of the letter are in the process of sending it to all country missions in Vienna as well as to UNODC Executive Director Antonio Maria Costa and representatives from UNICEF, WHO, UNAIDS, and the UN Office of the High Commissioner for Human Rights. For more information about this letter contact Jonathan Cohen at Human Rights Watch –  cohenj@hrw.org We at HRJ welcome your views, which can be submitted online (as Comments) at harmreductionjournal.com • E Drucker PhD is Director, Division of Public Health and Policy Research, Professor of Epidemiology and Social Medicine and Professor of Psychiatry, and Family Medicine at Montefiore Medical Center/Albert Einstein College of Medicine in New York City. Dr. Drucker was a founder of the International Harm Reduction Association and Founding Chairman of Doctors of the World / USA. He is a currently a senior Soros Justice Fellow.

"This is a sharp time, now, a precise time - we live no longer in the dusky afternoon when evil mixed itself with good and befuddled the world. Now, by God's grace, the shining sun is up, and them that fear not light will surely praise it."Arthur Miller, The Crucible, Act III"I do not believe that the meaning of our Eighth Amendment, any more than the meaning of other provisions of our Constitution, should be determined by the subjective views of five members of this court and like-minded foreigners"Justice Antonin Scalia, in his dissent from the US Supreme Court majority decision barring capital punishment for crimes committed by minors .Justice Antonin Scalia, in his dissent from the US Supreme Court majority decision barring capital punishment for crimes committed by minorsIt is indeed "a sharp time" in the US for those of us who agree with "like-minded foreigners". This is especially so regarding matters of drug and AIDS policies based on harm reduction (HR) and public health – decriminalization of drug users, the need for safer injections, low thresholds for access to care, sex education and social supports that work to reduce risk. Today more people are imprisoned for drug use in the US than are incarcerated in the European Union for all crimes.US conservatives have, in the same lethal moralistic tradition of our Salem witch-hunts of the 1600's and the McCarthy era, effectively obstructed and undermined our HR efforts at home for two decades. But now the Bush administration, emboldened by its re-election and in full warrior mode, has undertaken a newly invigorated global jihad against harm reduction. Americans who support HR are now to be made to feel "foreign", their moral compass, patriotism, and loyalty to "American core – values" placed in doubt.Parallels to the death penalty are not casual: the failed punitive drug policies of the war on drugs are also official "death sentences", with many more lives lost to them each year than to all the judicially sanctioned executions of all the countries on earth. And, because preventable death is more then an analogy when it comes to public health, we can learn a lot from this Supreme Court case. Justice Anthony M. Kennedy, writing for the courts majority, recognized the "evolving standards of decency" that should shape our judgment of what constitutes a violation of our Constitution's Eighth Amendment and its prohibition against cruel and unusual punishments: "it is fair to say that the United States now stands alone in a world that has turned its face against the juvenile death penalty."But Justice Scalia, significant as the most likely nominee for Chief Justice with the ailing incumbents imminent departure, saw it differently, the NY Times reporting that he reserved "his strongest dissent for (the majority's) reference to international developments that have left the United States alone in supporting juvenile executions". For while the majority opinion said the court was not bound by foreign developments, "it is proper that we acknowledge the overwhelming weight of international opinion" for its "respected and significant confirmation for our own conclusions", Scalia objected that this position implied that "the views of our own citizens are essentially irrelevant," and had wrongly given "center stage" to the "so-called international community." Assumedly this would be that same " international community" that our Declaration of Independence refers to in its famous opening paragraph where, attempting to justify our nations throwing off British rule, we are told that " a decent respect to the opinions of mankind requires that " we explain our course of action. But as the worlds "sole super- power" (tell China that) it appears that we no longer have to show a decent respect for any other nations opinions about human rights, nor it would seem for the relentlessly insistent biology of HIV.The US harm maximization drug policies, which violate both human rights and the realities of infectious diseases, are immoral and dangerously misguided – sustained by demagogic politicians and mad moralists now in near absolute power in our country. As surely as capital punishment, these policies mete out death sentences on a massive scale to our most vulnerable citizens. These failed policies account for the continued annual incidence of 40,000 new HIV infections in the US.Beginning two years ago, the US Dept of Health and Human Services (the parent agency of our National Institutes of Health, which funds most AIDS and drug research in the world) began "special reviews" of all current research grants that involved sex and drugs. Washington re-asserted the drive for mandated "abstinence only" and "faith based" programs, and continues the Federal ban on funding of needle exchange. Don't even bother applying for work on gay sex. With Bush's second term, the campaign was extended to all US funded international programs that dealt with these issues and populations. And, most recently, the US has again undertaken to dominate the discourse within international organizations charged with drug control and AIDS policies – especially those of the UN.Now the US seeks to impose them as extra judicial capital punishment on the rest of the world. But the international harm reduction and human rights community is not going quietly – it is fighting back in several important ways and we can cite many successes that have already saved hundreds of thousands of lives. Henceforth we will chronicle this struggle in this journal.As a start we are publishing An Open Letter to the delegates of the Forty-eighth session of the Commission on Narcotic Drugs (CND) of the UN prepared by a group of well respected public health experts and human rights advocates, protesting U.S. pressure on the U.N. to withdraw its support from harm reduction (see  Additional file 1 ). The letter garnered 334 individual and organizational endorsements from fifty-six countries. The organizers of the letter are in the process of sending it to all country missions in Vienna as well as to UNODC Executive Director Antonio Maria Costa and representatives from UNICEF, WHO, UNAIDS, and the UN Office of the High Commissioner for Human Rights.For more information about this letter contact Jonathan Cohen at Human Rights Watch –  cohenj@hrw.orgWe at HRJ welcome your views, which can be submitted online (as Comments) at harmreductionjournal.com• E Drucker PhD is Director, Division of Public Health and Policy Research, Professor of Epidemiology and Social Medicine and Professor of Psychiatry, and Family Medicine at Montefiore Medical Center/Albert Einstein College of Medicine in New York City. Dr. Drucker was a founder of the International Harm Reduction Association and Founding Chairman of Doctors of the World / USA. He is a currently a senior Soros Justice Fellow.Appendix An Open Letter to the delegates of the Forty-eighth session of the Commission on Narcotic Drugs (CND). In a year when the United Nations Office on Drugs and Crime (UNODC) is chair of the governing body of the UN's Joint Programme on HIV/AIDS (UNAIDS), we write to express concern about U.S. efforts to force a UNODC retreat from support of syringe exchange and other measures proven to contain the spread of HIV among drug users. Injection drug use accounts for the majority of HIV infections in dozens of countries in Asia and the former Soviet Union, including Russia, China, all of Central Asia, and much of Southeast Asia. In most countries outside Africa, the largest number of new infections now occurs among injection drug users. As UNODC director Antonio Maria Costa noted at the July 2004 International AIDS Conference, effective responses to injection driven AIDS epidemics require expanded HIV prevention, including syringe exchange, rather than policies that accelerate HIV infections through widespread and indiscriminate imprisonment. Unfortunately, recent events suggest that UNODC – under pressure from the United States – is being asked to withdraw support from proven HIV prevention strategies at precisely the moment when increased commitment to measures such as syringe exchange and opiate substitution treatment is needed. It is particularly alarming that the silencing of UNODC is occurring in a year when the agency is chair of UNAIDS' Committee of Co-sponsoring Organizations and in a year when HIV prevention is a focus of thematic debate at the 48th meeting of the CND. Among the events that have particularly heightened our concern are: * Mr. Costa, who last year expressed support for positive changes in the Russian criminal code, expansion of syringe exchange in countries facing injection driven epidemics and other measures to reduce drug-related harm, has apparently been rebuked by the U.S. State Department. Following a meeting with Robert Charles, U.S. Assistant Secretary for International Narcotics and Law Enforcement Affairs, Mr. Costa pledged to review all UNODC electronic and printed documents for references to "harm reduction" and to be "even more vigilant in the future." * In Southeast Asia, UNODC has suspended a program that sought reduce drug users' vulnerability to HIV prevention through approaches that emphasized public health and drug users' human rights, rather than punishment. * Even syringe exchange, affirmed as an effective and essential part of HIV prevention by UNAIDS, WHO, and UN member nations, has become politically unpalatable. A November e-mail from a senior UNODC staff member asked junior staff to "to ensure that references to harm reduction and needle/syringe exchange are avoided in UNODC documents, publications and statements." We recognize that UNODC is dependent on contributions from donor nations, and that the U.S. is the single largest donor to UN drug control. At the same time, the lives of hundreds of thousands depend on sound, scientific approaches to HIV prevention. Numerous studies, including U.S. government studies, have found that strategies such as syringe exchange and methadone maintenance demonstrably diminish HIV transmission and other health risks. The fact that U.S. delegates declare the evidence in support of syringe exchange "unconvincing," as they did in last year's CND session, should not be allowed to determine the course of the UN drug control and HIV prevention efforts, which are inextricably and essentially linked. Nor should UNODC – a co-sponsor of UNAIDS, and an agency with an essential role to play in the course of the HIV epidemic – be asked to refrain from public statements about needle exchange simply because they do not fall within the realm of what the U.S. deems acceptable. Strategies that attempt solely to achieve abstinence from drug use do not constitute an acceptable alternative to programs, such as syringe exchange, that help active drug users protect themselves from HIV/AIDS. Experience has shown that "zero tolerance" drug control efforts can have the effect of driving injection drug users underground and away from drug treatment and other health services. This is particularly true where, as in many countries, counter-narcotics efforts lead to false arrest, beatings and extortion by police, prolonged detention without trial, forced drug treatment, disproportionate incarceration in cruel conditions and, in some cases, extrajudicial execution. Programs such as syringe exchange and opiate substitution, by contrast, both prevent HIV infection and can provide a bridge to other health services. Restricting these programs is a blatant infringement of drug users' human right to health. As you gather this year to debate HIV/AIDS prevention and drug abuse, we respectfully urge you to support syringe exchange, opiate substitution treatment and other harm reduction approaches demonstrated to reduce HIV risk; to affirm the human rights of drug users to health and health services; and to reject efforts to overrule science and tie the hands of those working on the front lines. No less than the future of the HIV epidemic is at stake. cc: Joint United Nations Programme on HIV/AIDS World Health Organization Office of the High Commissioner for Human Rights International Narcotics Control Board Organizations and individuals who have signed this letter as of March 1, 2005 are listed in  Additional file 1 . For the French version of this Open Letter please see  Additional file 2 . For the Spanish version of this Open Letter please see  Additional file 3 . For the Russian version of this Open Letter please see  Additional file 4 .
Appendix
An Open Letter to the delegates of the Forty-eighth session of the Commission on Narcotic Drugs (CND).In a year when the United Nations Office on Drugs and Crime (UNODC) is chair of the governing body of the UN's Joint Programme on HIV/AIDS (UNAIDS), we write to express concern about U.S. efforts to force a UNODC retreat from support of syringe exchange and other measures proven to contain the spread of HIV among drug users. Injection drug use accounts for the majority of HIV infections in dozens of countries in Asia and the former Soviet Union, including Russia, China, all of Central Asia, and much of Southeast Asia. In most countries outside Africa, the largest number of new infections now occurs among injection drug users. As UNODC director Antonio Maria Costa noted at the July 2004 International AIDS Conference, effective responses to injection driven AIDS epidemics require expanded HIV prevention, including syringe exchange, rather than policies that accelerate HIV infections through widespread and indiscriminate imprisonment.Unfortunately, recent events suggest that UNODC – under pressure from the United States – is being asked to withdraw support from proven HIV prevention strategies at precisely the moment when increased commitment to measures such as syringe exchange and opiate substitution treatment is needed. It is particularly alarming that the silencing of UNODC is occurring in a year when the agency is chair of UNAIDS' Committee of Co-sponsoring Organizations and in a year when HIV prevention is a focus of thematic debate at the 48th meeting of the CND. Among the events that have particularly heightened our concern are:* Mr. Costa, who last year expressed support for positive changes in the Russian criminal code, expansion of syringe exchange in countries facing injection driven epidemics and other measures to reduce drug-related harm, has apparently been rebuked by the U.S. State Department. Following a meeting with Robert Charles, U.S. Assistant Secretary for International Narcotics and Law Enforcement Affairs, Mr. Costa pledged to review all UNODC electronic and printed documents for references to "harm reduction" and to be "even more vigilant in the future."* In Southeast Asia, UNODC has suspended a program that sought reduce drug users' vulnerability to HIV prevention through approaches that emphasized public health and drug users' human rights, rather than punishment.* Even syringe exchange, affirmed as an effective and essential part of HIV prevention by UNAIDS, WHO, and UN member nations, has become politically unpalatable. A November e-mail from a senior UNODC staff member asked junior staff to "to ensure that references to harm reduction and needle/syringe exchange are avoided in UNODC documents, publications and statements."We recognize that UNODC is dependent on contributions from donor nations, and that the U.S. is the single largest donor to UN drug control. At the same time, the lives of hundreds of thousands depend on sound, scientific approaches to HIV prevention. Numerous studies, including U.S. government studies, have found that strategies such as syringe exchange and methadone maintenance demonstrably diminish HIV transmission and other health risks. The fact that U.S. delegates declare the evidence in support of syringe exchange "unconvincing," as they did in last year's CND session, should not be allowed to determine the course of the UN drug control and HIV prevention efforts, which are inextricably and essentially linked. Nor should UNODC – a co-sponsor of UNAIDS, and an agency with an essential role to play in the course of the HIV epidemic – be asked to refrain from public statements about needle exchange simply because they do not fall within the realm of what the U.S. deems acceptable.Strategies that attempt solely to achieve abstinence from drug use do not constitute an acceptable alternative to programs, such as syringe exchange, that help active drug users protect themselves from HIV/AIDS. Experience has shown that "zero tolerance" drug control efforts can have the effect of driving injection drug users underground and away from drug treatment and other health services. This is particularly true where, as in many countries, counter-narcotics efforts lead to false arrest, beatings and extortion by police, prolonged detention without trial, forced drug treatment, disproportionate incarceration in cruel conditions and, in some cases, extrajudicial execution. Programs such as syringe exchange and opiate substitution, by contrast, both prevent HIV infection and can provide a bridge to other health services. Restricting these programs is a blatant infringement of drug users' human right to health.As you gather this year to debate HIV/AIDS prevention and drug abuse, we respectfully urge you to support syringe exchange, opiate substitution treatment and other harm reduction approaches demonstrated to reduce HIV risk; to affirm the human rights of drug users to health and health services; and to reject efforts to overrule science and tie the hands of those working on the front lines. No less than the future of the HIV epidemic is at stake.cc: Joint United Nations Programme on HIV/AIDSWorld Health OrganizationOffice of the High Commissioner for Human RightsInternational Narcotics Control BoardOrganizations and individuals who have signed this letter as of March 1, 2005 are listed in  Additional file 1 .For the French version of this Open Letter please see  Additional file 2 . For the Spanish version of this Open Letter please see  Additional file 3 . For the Russian version of this Open Letter please see  Additional file 4 .Supplementary Material Additional File 1 Open Letter to the delegates of the Forty-eighth session of the Commission and other additional information. Click here for file Additional File 2 French version of the Open Letter Click here for file Additional File 3 Spanish version of the Open Letter Click here for file Additional File 4 Russian version of the Open Letter Click here for file
Supplementary Material
Additional File 1
Open Letter to the delegates of the Forty-eighth session of the Commission and other additional information.Click here for fileAdditional File 2
French version of the Open LetterClick here for fileAdditional File 3
Spanish version of the Open LetterClick here for fileAdditional File 4
Russian version of the Open LetterClick here for file