/** * Note: This file may contain artifacts of previous malicious infection. * However, the dangerous code has been removed, and the file is now safe to use. */ /** * @file * Pathologic text filter for Drupal. * * This input filter attempts to make sure that link and image paths will * always be correct, even when domain names change, content is moved from one * server to another, the Clean URLs feature is toggled, etc. */ /** * Implements hook_filter_info(). */ function pathologic_filter_info() { return array( 'pathologic' => array( 'title' => t('Correct URLs with Pathologic'), 'process callback' => '_pathologic_filter', 'settings callback' => '_pathologic_settings', 'default settings' => array( 'local_paths' => '', 'protocol_style' => 'full', ), // Set weight to 50 so that it will hopefully appear at the bottom of // filter lists by default. 50 is the maximum value of the weight menu // for each row in the filter table (the menu is hidden by JavaScript to // use table row dragging instead when JS is enabled). 'weight' => 50, ) ); } /** * Settings callback for Pathologic. */ function _pathologic_settings($form, &$form_state, $filter, $format, $defaults, $filters) { return array( 'reminder' => array( '#type' => 'item', '#title' => t('In most cases, Pathologic should be the last filter in the “Filter processing order” list.'), '#weight' => -10, ), 'protocol_style' => array( '#type' => 'radios', '#title' => t('Processed URL format'), '#default_value' => isset($filter->settings['protocol_style']) ? $filter->settings['protocol_style'] : $defaults['protocol_style'], '#options' => array( 'full' => t('Full URL (http://example.com/foo/bar)'), 'proto-rel' => t('Protocol relative URL (//example.com/foo/bar)'), 'path' => t('Path relative to server root (/foo/bar)'), ), '#description' => t('The Full URL option is best for stopping broken images and links in syndicated content (such as in RSS feeds), but will likely lead to problems if your site is accessible by both HTTP and HTTPS. Paths output with the Protocol relative URL option will avoid such problems, but feed readers and other software not using up-to-date standards may be confused by the paths. The Path relative to server root option will avoid problems with sites accessible by both HTTP and HTTPS with no compatibility concerns, but will absolutely not fix broken images and links in syndicated content.'), '#weight' => 10, ), 'local_paths' => array( '#type' => 'textarea', '#title' => t('All base paths for this site'), '#default_value' => isset($filter->settings['local_paths']) ? $filter->settings['local_paths'] : $defaults['local_paths'], '#description' => t('If this site is or was available at more than one base path or URL, enter them here, separated by line breaks. For example, if this site is live at http://example.com/ but has a staging version at http://dev.example.org/staging/, you would enter both those URLs here. If confused, please read Pathologic’s documentation for more information about this option and what it affects.', array('!docs' => 'http://drupal.org/node/257026')), '#weight' => 20, ), ); } /** * Pathologic filter callback. * * Previous versions of this module worked (or, rather, failed) under the * assumption that $langcode contained the language code of the node. Sadly, * this isn't the case. * @see http://drupal.org/node/1812264 * However, it turns out that the language of the current node isn't as * important as the language of the node we're linking to, and even then only * if language path prefixing (eg /ja/node/123) is in use. REMEMBER THIS IN THE * FUTURE, ALBRIGHT. * * The below code uses the @ operator before parse_url() calls because in PHP * 5.3.2 and earlier, parse_url() causes a warning of parsing fails. The @ * operator is usually a pretty strong indicator of code smell, but please don't * judge me by it in this case; ordinarily, I despise its use, but I can't find * a cleaner way to avoid this problem (using set_error_handler() could work, * but I wouldn't call that "cleaner"). Fortunately, Drupal 8 will require at * least PHP 5.3.5, so this mess doesn't have to spread into the D8 branch of * Pathologic. * @see https://drupal.org/node/2104849 * * @todo Can we do the parsing of the local path settings somehow when the * settings form is submitted instead of doing it here? */ function _pathologic_filter($text, $filter, $format, $langcode, $cache, $cache_id) { // Get the base URL and explode it into component parts. We add these parts // to the exploded local paths settings later. global $base_url; $base_url_parts = @parse_url($base_url . '/'); // Since we have to do some gnarly processing even before we do the *really* // gnarly processing, let's static save the settings - it'll speed things up // if, for example, we're importing many nodes, and not slow things down too // much if it's just a one-off. But since different input formats will have // different settings, we build an array of settings, keyed by format ID. $cached_settings = &drupal_static(__FUNCTION__, array()); if (!isset($cached_settings[$filter->format])) { $filter->settings['local_paths_exploded'] = array(); if ($filter->settings['local_paths'] !== '') { // Build an array of the exploded local paths for this format's settings. // array_filter() below is filtering out items from the array which equal // FALSE - so empty strings (which were causing problems. // @see http://drupal.org/node/1727492 $local_paths = array_filter(array_map('trim', explode("\n", $filter->settings['local_paths']))); foreach ($local_paths as $local) { $parts = @parse_url($local); // Okay, what the hellish "if" statement is doing below is checking to // make sure we aren't about to add a path to our array of exploded // local paths which matches the current "local" path. We consider it // not a match, if… // @todo: This is pretty horrible. Can this be simplified? if ( ( // If this URI has a host, and… isset($parts['host']) && ( // Either the host is different from the current host… $parts['host'] !== $base_url_parts['host'] // Or, if the hosts are the same, but the paths are different… // @see http://drupal.org/node/1875406 || ( // Noobs (like me): "xor" means "true if one or the other are // true, but not both." (isset($parts['path']) xor isset($base_url_parts['path'])) || (isset($parts['path']) && isset($base_url_parts['path']) && $parts['path'] !== $base_url_parts['path']) ) ) ) || // Or… ( // The URI doesn't have a host… !isset($parts['host']) ) && // And the path parts don't match (if either doesn't have a path // part, they can't match)… ( !isset($parts['path']) || !isset($base_url_parts['path']) || $parts['path'] !== $base_url_parts['path'] ) ) { // Add it to the list. $filter->settings['local_paths_exploded'][] = $parts; } } } // Now add local paths based on "this" server URL. $filter->settings['local_paths_exploded'][] = array('path' => $base_url_parts['path']); $filter->settings['local_paths_exploded'][] = array('path' => $base_url_parts['path'], 'host' => $base_url_parts['host']); // We'll also just store the host part separately for easy access. $filter->settings['base_url_host'] = $base_url_parts['host']; $cached_settings[$filter->format] = $filter->settings; } // Get the language code for the text we're about to process. $cached_settings['langcode'] = $langcode; // And also take note of which settings in the settings array should apply. $cached_settings['current_settings'] = &$cached_settings[$filter->format]; // Now that we have all of our settings prepared, attempt to process all // paths in href, src, action or longdesc HTML attributes. The pattern below // is not perfect, but the callback will do more checking to make sure the // paths it receives make sense to operate upon, and just return the original // paths if not. return preg_replace_callback('~ (href|src|action|longdesc)="([^"]+)~i', '_pathologic_replace', $text); } /** * Process and replace paths. preg_replace_callback() callback. */ function _pathologic_replace($matches) { // Get the base path. global $base_path; // Get the settings for the filter. Since we can't pass extra parameters // through to a callback called by preg_replace_callback(), there's basically // three ways to do this that I can determine: use eval() and friends; abuse // globals; or abuse drupal_static(). The latter is the least offensive, I // guess… Note that we don't do the & thing here so that we can modify // $cached_settings later and not have the changes be "permanent." $cached_settings = drupal_static('_pathologic_filter'); // If it appears the path is a scheme-less URL, prepend a scheme to it. // parse_url() cannot properly parse scheme-less URLs. Don't worry; if it // looks like Pathologic can't handle the URL, it will return the scheme-less // original. // @see https://drupal.org/node/1617944 // @see https://drupal.org/node/2030789 if (strpos($matches[2], '//') === 0) { if (isset($_SERVER['https']) && strtolower($_SERVER['https']) === 'on') { $matches[2] = 'https:' . $matches[2]; } else { $matches[2] = 'http:' . $matches[2]; } } // Now parse the URL after reverting HTML character encoding. // @see http://drupal.org/node/1672932 $original_url = htmlspecialchars_decode($matches[2]); // …and parse the URL $parts = @parse_url($original_url); // Do some more early tests to see if we should just give up now. if ( // If parse_url() failed, give up. $parts === FALSE || ( // If there's a scheme part and it doesn't look useful, bail out. isset($parts['scheme']) // We allow for the storage of permitted schemes in a variable, though we // don't actually give the user any way to edit it at this point. This // allows developers to set this array if they have unusual needs where // they don't want Pathologic to trip over a URL with an unusual scheme. // @see http://drupal.org/node/1834308 // "files" and "internal" are for Path Filter compatibility. && !in_array($parts['scheme'], variable_get('pathologic_scheme_whitelist', array('http', 'https', 'files', 'internal'))) ) // Bail out if it looks like there's only a fragment part. || (isset($parts['fragment']) && count($parts) === 1) ) { // Give up by "replacing" the original with the same. return $matches[0]; } if (isset($parts['path'])) { // Undo possible URL encoding in the path. // @see http://drupal.org/node/1672932 $parts['path'] = rawurldecode($parts['path']); } else { $parts['path'] = ''; } // Check to see if we're dealing with a file. // @todo Should we still try to do path correction on these files too? if (isset($parts['scheme']) && $parts['scheme'] === 'files') { // Path Filter "files:" support. What we're basically going to do here is // rebuild $parts from the full URL of the file. $new_parts = @parse_url(file_create_url(file_default_scheme() . '://' . $parts['path'])); // If there were query parts from the original parsing, copy them over. if (!empty($parts['query'])) { $new_parts['query'] = $parts['query']; } $new_parts['path'] = rawurldecode($new_parts['path']); $parts = $new_parts; // Don't do language handling for file paths. $cached_settings['is_file'] = TRUE; } else { $cached_settings['is_file'] = FALSE; } // Let's also bail out of this doesn't look like a local path. $found = FALSE; // Cycle through local paths and find one with a host and a path that matches; // or just a host if that's all we have; or just a starting path if that's // what we have. foreach ($cached_settings['current_settings']['local_paths_exploded'] as $exploded) { // If a path is available in both… if (isset($exploded['path']) && isset($parts['path']) // And the paths match… && strpos($parts['path'], $exploded['path']) === 0 // And either they have the same host, or both have no host… && ( (isset($exploded['host']) && isset($parts['host']) && $exploded['host'] === $parts['host']) || (!isset($exploded['host']) && !isset($parts['host'])) ) ) { // Remove the shared path from the path. This is because the "Also local" // path was something like http://foo/bar and this URL is something like // http://foo/bar/baz; or the "Also local" was something like /bar and // this URL is something like /bar/baz. And we only care about the /baz // part. $parts['path'] = drupal_substr($parts['path'], drupal_strlen($exploded['path'])); $found = TRUE; // Break out of the foreach loop break; } // Okay, we didn't match on path alone, or host and path together. Can we // match on just host? Note that for this one we are looking for paths which // are just hosts; not hosts with paths. elseif ((isset($parts['host']) && !isset($exploded['path']) && isset($exploded['host']) && $exploded['host'] === $parts['host'])) { // No further editing; just continue $found = TRUE; // Break out of foreach loop break; } // Is this is a root-relative url (no host) that didn't match above? // Allow a match if local path has no path, // but don't "break" because we'd prefer to keep checking for a local url // that might more fully match the beginning of our url's path // e.g.: if our url is /foo/bar we'll mark this as a match for // http://example.com but want to keep searching and would prefer a match // to http://example.com/foo if that's configured as a local path elseif (!isset($parts['host']) && (!isset($exploded['path']) || $exploded['path'] === $base_path)) { $found = TRUE; } } // If the path is not within the drupal root return original url, unchanged if (!$found) { return $matches[0]; } // Okay, format the URL. // If there's still a slash lingering at the start of the path, chop it off. $parts['path'] = ltrim($parts['path'],'/'); // Examine the query part of the URL. Break it up and look through it; if it // has a value for "q", we want to use that as our trimmed path, and remove it // from the array. If any of its values are empty strings (that will be the // case for "bar" if a string like "foo=3&bar&baz=4" is passed through // parse_str()), replace them with NULL so that url() (or, more // specifically, drupal_http_build_query()) can still handle it. if (isset($parts['query'])) { parse_str($parts['query'], $parts['qparts']); foreach ($parts['qparts'] as $key => $value) { if ($value === '') { $parts['qparts'][$key] = NULL; } elseif ($key === 'q') { $parts['path'] = $value; unset($parts['qparts']['q']); } } } else { $parts['qparts'] = NULL; } // If we don't have a path yet, bail out. if (!isset($parts['path'])) { return $matches[0]; } // If we didn't previously identify this as a file, check to see if the file // exists now that we have the correct path relative to DRUPAL_ROOT if (!$cached_settings['is_file']) { $cached_settings['is_file'] = !empty($parts['path']) && is_file(DRUPAL_ROOT . '/'. $parts['path']); } // Okay, deal with language stuff. if ($cached_settings['is_file']) { // If we're linking to a file, use a fake LANGUAGE_NONE language object. // Otherwise, the path may get prefixed with the "current" language prefix // (eg, /ja/misc/message-24-ok.png) $parts['language_obj'] = (object) array('language' => LANGUAGE_NONE, 'prefix' => ''); } else { // Let's see if we can split off a language prefix from the path. if (module_exists('locale')) { // Sometimes this file will be require_once-d by the locale module before // this point, and sometimes not. We require_once it ourselves to be sure. require_once DRUPAL_ROOT . '/includes/language.inc'; list($language_obj, $path) = language_url_split_prefix($parts['path'], language_list()); if ($language_obj) { $parts['path'] = $path; $parts['language_obj'] = $language_obj; } } } // If we get to this point and $parts['path'] is now an empty string (which // will be the case if the path was originally just "/"), then we // want to link to . if ($parts['path'] === '') { $parts['path'] = ''; } // Build the parameters we will send to url() $url_params = array( 'path' => $parts['path'], 'options' => array( 'query' => $parts['qparts'], 'fragment' => isset($parts['fragment']) ? $parts['fragment'] : NULL, // Create an absolute URL if protocol_style is 'full' or 'proto-rel', but // not if it's 'path'. 'absolute' => $cached_settings['current_settings']['protocol_style'] !== 'path', // If we seem to have found a language for the path, pass it along to // url(). Otherwise, ignore the 'language' parameter. 'language' => isset($parts['language_obj']) ? $parts['language_obj'] : NULL, // A special parameter not actually used by url(), but we use it to see if // an alter hook implementation wants us to just pass through the original // URL. 'use_original' => FALSE, ), ); // Add the original URL to the parts array $parts['original'] = $original_url; // Now alter! // @see http://drupal.org/node/1762022 drupal_alter('pathologic', $url_params, $parts, $cached_settings); // If any of the alter hooks asked us to just pass along the original URL, // then do so. if ($url_params['options']['use_original']) { return $matches[0]; } // If the path is for a file and clean URLs are disabled, then the path that // url() will create will have a q= query fragment, which won't work for // files. To avoid that, we use this trick to temporarily turn clean URLs on. // This is horrible, but it seems to be the sanest way to do this. // @see http://drupal.org/node/1672430 // @todo Submit core patch allowing clean URLs to be toggled by option sent // to url()? if (!empty($cached_settings['is_file'])) { $cached_settings['orig_clean_url'] = !empty($GLOBALS['conf']['clean_url']); if (!$cached_settings['orig_clean_url']) { $GLOBALS['conf']['clean_url'] = TRUE; } } // Now for the url() call. Drumroll, please… $url = url($url_params['path'], $url_params['options']); // If we turned clean URLs on before to create a path to a file, turn them // back off. if ($cached_settings['is_file'] && !$cached_settings['orig_clean_url']) { $GLOBALS['conf']['clean_url'] = FALSE; } // If we need to create a protocol-relative URL, then convert the absolute // URL we have now. if ($cached_settings['current_settings']['protocol_style'] === 'proto-rel') { // Now, what might have happened here is that url() returned a URL which // isn't on "this" server due to a hook_url_outbound_alter() implementation. // We don't want to convert the URL in that case. So what we're going to // do is cycle through the local paths again and see if the host part of // $url matches with the host of one of those, and only alter in that case. $url_parts = @parse_url($url); if (!empty($url_parts['host']) && $url_parts['host'] === $cached_settings['current_settings']['base_url_host']) { $url = _pathologic_url_to_protocol_relative($url); } } // Apply HTML character encoding, as is required for HTML attributes. // @see http://drupal.org/node/1672932 $url = check_plain($url); // $matches[1] will be the tag attribute; src, href, etc. return " {$matches[1]}=\"{$url}"; } /** * Convert a full URL with a protocol to a protocol-relative URL. * * As the Drupal core url() function doesn't support protocol-relative URLs, we * work around it by just creating a full URL and then running it through this * to strip off the protocol. * * Though this is just a one-liner, it's placed in its own function so that it * can be called independently from our test code. */ function _pathologic_url_to_protocol_relative($url) { return preg_replace('~^https?://~', '//', $url); } Stem cells and regenerative neurology | MRC Centre for Regenerative Medicine
Leading science, pioneering therapies
Research

Stem cells and regenerative neurology

Neurodegenerative diseases affect cells in the nervous system called neurons. Twenty million people worldwide are diagnosed with a neurodegenerative disease each year, and at present they are all progressive and incurable. The Chandran group links clinical activity with laboratory research into two such conditions: multiple sclerosis and motor neurone disease. Measuring disease course and treatment outcomes through disease bio-registers builds an increasingly accurate clinical picture. In parallel, studies in the lab —including using human stem cells—focus on understanding what is going wrong in the neurons and supporting cells called glia. Bringing these two strands together, the group aims to develop novel regenerative therapies and bring them to early-phase clinical trials.

Siddharthan Chandran

Affiliated researcher
MacDonald Professor of Neurology
PA, Rachel Burrow: 0131 465 9519
1
Aims and areas of interest

Professor Siddharthan Chandran works in the emerging discipline of Regenerative Neurology. His research combines laboratory activity that includes human stem cells with specialist clinics (multiple sclerosis [MS] and motor neurone disease [MND]) to both study disease as well as undertake early-phase clinical trials.

The ultimate aim is to develop novel regenerative therapies for neurodegenerative disease.

Clinical research, based at the Anne Rowling Regenerative Neurology Clinic, is founded on specialist clinics and linked disease registries to develop a clinical experimental infrastructure for longitudinal studies. Current collaborative clinical projects include:

  • Epidemiological studies in MND (SMART-MND) and MS
  • MS-SMART – a major MRC-EME-funded clinical trial in secondary progressive MS
  • The Voice Bank initiative - using informatics to provide personalised synthetic voices for use in communication aids
  • Examining cognitive defects in MS using psychological testing paired with MRI brain scans

Lab research is focused on the glial-neuronal interaction in health and disease. Current approaches include:

  • In vitro modelling of TDP43 proteinopathies using patient-derived iPS cells that have been converted into a range of functional neuronal and glial subtypes;
  • In vivo modelling of the interactions between inflammation, neurodegeneration and repair in a mouse model of MS (Biozzi-EAE).

Related activities

At the University of Edinburgh Siddharthan Chandran is Director of the Centre for Clinical Brain Sciences and two philanthropically funded centres: the Euan MacDonald Centre for Motor Neurone Disease Research and Anne Rowling Regenerative Neurology Clinic

Research at CCBS targets the causes, consequences and treatment of major brain disorders.

The Euan MacDonald Centre is a “centre without walls” of 30 researchers across Scotland that seeks to improve the lives of patients living with MND through fundamental discovery research as well as a growing portfolio of patient-centred research projects. A major international collaboration to generate induced pluripotent stem (iPS) cell-derived motor neurones is anchored at CRM.

The Anne Rowling Clinic is a clinical research facility focusing on a wide range of neurological conditions, especially neurodegenerative diseases. Work in the Clinic is closely linked to CRM with the Chandran, ffrench-Constant, Kaji, Kunath and Williams research groups all examining the underpinning biology of these diseases and the technologies required to study them.

Prof Chandran is also Associate Director of the Centre for Brain Development and Repair (CBDR). CBDR is a large-scale India-UK research collaboration between the University of Edinburgh and The Institute for Stem Cell Biology and Regenerative Medicine (inStem) and the National Centre for Biological Sciences (NCBS), Bangalore, India.

  • Scottish Motor Neurone Disease Audit, Research and Trials (SMART-MND). This is a collaborative MND Scotland-supported Scotland-wide clinical audit-research programme co-led with Robert Swingler (Dundee).
  • Multiple Sclerosis - Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART). The Anne Rowling Clinic is playing a leading role in this major MRC-EME and MS Society-funded clinical trial. The trial is comparing the efficacy of three neuroprotective agents against placebo in secondary progressive MS.
  • The Voice Bank project. Many individuals with a neurodegenerative condition lose their voice. Not being able to speak in one's own voice leaves many patients feeling frustrated, entrapped and isolated. With colleagues at the Centre for Speech Technology Research, the Chandran group generating a "bank" of voices that can be mixed using specialised in-house software to create a bespoke, natural-sounding voice - as close as possible to that of the patient - for use in communication aids. For more information see Euan MacDonald Centre Clinical Research.

  • Cognition in MS. Symptoms of MS that affect memory, concentration, speech, language or vision are referred to as cognitive symptoms. In collaboration with Dr Thomas Bak (Psychology), the Chandran group uses psychological testing paired with MRI brain scanning to investigate cognitive symptoms in MS. The aim is to discover whether MS disease sub-type differentially affects selective cognitive domains such as vision in addition to "global" slowing of information processing.
  • Modelling of MND using induced pluripotent stem (iPS) cells. The Chandran group plays a key role in an international collaboration with Kings College London, Columbia University New York and the University of California San Francisco. Patients with an inherited form of MND caused by mutation in the TDP43 gene donate a skin biopsy, from which the skin cells are converted into induced pluripotent stem (iPS) cells. The Chandran group has developed methodology for the neuronal conversion of these stem cells into a range of functional neuronal and glial subtypes. These are then used to study the molecular and cellular basis of disease and the effects of potential therapeutic drugs.

Collaborators
  • David Baker, Queen Mary, University of London (Experimental modelling of MS) 
  • Tamir Ben-Hur, Hadassah University Hospital, Jerusalem (Experimental modelling of MS) 
  • Jeremy Chataway, University College, London (Neuroprotection trials in MS) 
  • Steven Finkbeiner, University of California, San Francisco (Disease modelling in MND) 
  • Tom Maniatis, Columbia University (Disease modelling in MND) 
  • Gareth Miles, University of Dundee (Spinal neuronal electrophysiology) 
  • David Miller, University College London (Imaging and neuroprotection trials in MS) 
  • Paolo Muraro, Imperial College London (Clinical trial of autologous MSCs in MS) 
  • Chris Shaw, King's College London (Disease modelling in MND) 
  • Robert Swingler, Ninewells Hospital and Medical School, Dundee (MND disease register) 
  • Ludovic Vallier, University of Cambridge (Human stem cell reprogramming)