The biggest debate today in the stem cell world is over how much regulation is needed for new, investigational stem cell therapies that are not as yet approved.
Sometimes it feels very lonely being out there publicly advocating for appropriately thorough regulation of stem cell therapies and at times I get a lot of heat for that, especially from stem cell clinics. For instance, I am publicly opposed to the REGROW Act, a piece of legislation that would dangerously weaken oversight of experimental stem cell therapies. Still, I have not yet seen a statement from major stem cell organizations on these issues. It was therefore a great boost to hear just now that the top stem cell biotech industry organization, The Alliance for Regenerative Medicine (ARM), has issued a statement firmly opposing the REGROW Act.
I want to send kudos to ARM and its more than 250 members.
For years in this debate there was a bright line between the academics as well as mainstream organizations in the stem cell arena (together supporting the need for rigorous science-based stem cell medicine and for the FDA, even if some reforms are needed) versus the dubious stem cell clinics out to make a quick buck and wanting as little regulation as possible.
However, in the past year we've seen a troubling seismic shift such that some academics and others who used to support the FDA have begun arguing for dramatically less regulation of experimental stem cell treatments. For more background on these pushes for stem cell deregulation, please see my past posts on the Bipartisan Policy Commission (BPC) report that proposed extreme measures such as conditional approval of experimental stem cell interventions, charging patients to be experimented upon, and eliminating Phase III trials in some cases and also see my post opposing the REGROW Act.
It is a big, positive decision for ARM to oppose the REGROW Act, and I'm encouraged to see that I'm not alone in opposing this overreaching legislation. The reasons for ARM's opposition and my own rationales for being against the bill substantially overlap. We both focus on the dangers posed to patients by inappropriately extreme deregulation. I can't speak for ARM, but my impression is that they like many of us support some changes in how stem cell therapies are regulated. Perhaps there is hope that the REGROW Act could reemerge in a new incarnation in the future that is more balanced and would chart a prudent path forward.
"The Alliance for Regenerative Medicine is appreciative of Senator Kirk's longtime support of the regenerative medicine sector and his belief in the transformative durable treatments and potential cures this field holds for patients. Our organization is committed to our continued cooperation with Senator Kirk and his staff to advance policies supportive of this sector and expediting potentially life-saving cell therapies, gene therapies and other regenerative medicine products.
However, ARM cannot support the REGROW Act. We continue to believe the proposal does not contain critical statutory protections for patients. We look forward to a continuing dialogue with the sponsors of REGROW Act as well as other stakeholders to create alternative approaches to ensure access to safe and effective regenerative medicine therapies without putting patients at risk, disadvantaging American therapeutic developers and potentially damaging a very promising field of medicine.
Note that ARM leaders Michael Werner and Edward Lanphier seem to be the point people on the REGROW issue.
I believe the regrow act accelerate progress too much for people trying to make money in the field of regenerative medicine. When you have a patented therapy you don't want someone else to be able to come up with a better therapy before your patent expire..
I bet they like the allogeneic portion of the bill. It is the free for all created by the device side that they probably have a problem with. It will legalize the wild wild west of the existing autologous stem cell market and expand it by providing an FDA stamp of approval. A marketing bonanza. Can you provide a link?
There will be a webcast on April 12, 2016. I urge everyone to listen and make up their own mind, please. Lots of opinions are floating around without everyone doing proper research on what the new policy would actually mean.
Please research how Japan is getting MSCs to patients faster now, for instance for steroid-refractory GvHD (MSCs= the patient's only chance at life in that instance). This act is very similar to what they are doing in Japan.
I have only seen those in the Pharma sector opposing it so far. Those of us who work daily with MSCs and with Patients who need treatments support it. I assure you I am not after "profits", as a translational research scientist.
Thank you very much for weighing in on this important discussion. I value having a robust debate on the issues that includes diverse viewpoints. While I disagree with the BPC report and cannot support the REGROW Act, I respect the fact that others including you feel differently. One mission for my blog is to provide a forum for healthy dialogue between many different stakeholders and interested parties, even if (and perhaps especially so) some of them disagree with me.
So, those of us wishing to use existing technology to help patients are "dubious" and "out to make a quick buck." I feel slandered.
One of my concerns about the BPC report has been that it did not adequately discuss the likely risks associated with the regulatory reforms it proposes (e.g. the risks mentioned now by ARM) so this makes me somewhat concerned that the upcoming Bipartisan Policy forum tomorrow may similarly not present both sides and encourage diverse view points. I hope I'm wrong on the forum. I'll be curious to see how it goes.
If I understand correctly, there the government is generally paying for the experimental regenerative medicine therapies, but here in the U.S. the patients would have that burden barring some dramatic change in coverage.
But I have not seen any indication that American insurers are interested in paying for experimental stem cell (or other) therapies so that leaves in the proposed model the reality that patients, their families, communities, churches, etc. must to try to raise the often very large sums of money.
Since these therapies are experiments, many are ultimately not going to be effective, so is it fair that the patients paid for them? What if the therapies have unexpected side effects, which is possible since they are again experimental?
There's got to be a better way than the status quo of today, but there's also got to be a better way than what BPC/REGROW are proposing, which I believe poses serious risks to both patients and the stem cell field. Where's the regulatory sweet spot?
Since people would travel around the world to get stem cell therapies anyway, wouldn't make more sense to let them get stem cell therapies in the US where things can be monitored better than in any other country and data can be collected in the interest of science? If a therapy does not work, collecting data properly, would make it clear very soon! While if we let people go around the world the scams will never end.
I agree with Jan on this one. Paul, your paternalism towards patients is distressing. A lot of patients with life threatening conditions don't need protection, they need access to products that offer hope and the possibility of relief. If one looks at the conditions in the Act, they include the requirement for adult cells, cells tested for immunogenicity, preliminary clinical efficacy of safety, some efficacy signals, not gene modified, minimally manipulated for non-homologous use or more than minimally manipulated for homologous or non-homologous use etc..this isn't cowboy stuff here. ART for HIV never went through a placebo controlled trial before it exploded on the scene in late 1996. This law may not be perfect, but it's a good starting point and new pathways need to be developed at FDA for regenerative medicine. AIDS activists found a constipated agency and pushed it to serve patients. Why such hoopla for ARM's timidity?
I believe there needs to be a balance between both protections and access when it comes to still experimental stem cell therapies.
At present the way the FDA is regulating this arena is in my view not working that great and I've advocated for specific FDA reforms (e.g. in my stem cell book) to increase transparency and access, but in my opinion the Regrow Act is far too extreme.
For example, I'm not convinced that conditional approval is a net positive for patients. It would only help patients if the therapies turn out to be proven rigorously to be both safe and effective, but since these are still experimental therapies we cannot know the profile of any given therapy until later when the data is produced and analyzed. Getting either ineffective or unsafe therapies to patients quicker doesn't help those patients. Without data, then faster = riskier.
Regrow seems founded on the dangerous assumption that we already know that these therapies are going to be safe and effective for a particular indication, but we don't until science proves it.
I also think the requirements of the Act are not so clear or robust for therapies in order to get conditional approval. There would also be potential from Regrow for bad actors to take advantage of the more permissive landscape.
The regulatory experiment in Japan with reduced regen med oversight has just started and could end badly so I'm not sure why so many people point to that as a positive example to emulate. I also do not see any evidence that bypassing Phase III is safe or beneficial.
Both in Japan and in the U.S. with the BPC report (many of its supporters also support Regrow), there is also growing pressure to more widely charge patients for experimental therapies, which to me seems highly questionable and I can't see how that is good for patients.
I support change in this area overall, but instead of Regrow or what BPC recommends, I am in favor of a more balanced approach that involves faster and simpler FDA triggering of Fast Track, Accelerated or Priority Review or Breakthrough Therapy Designation for cellular and regen med therapies.
As for ARM, I don't applaud "timidity", which seems like a pejorative way to describe their stand, but rather their firmness on sticking to a science-based framework that is in the best interests of patients. I'm sure they have their own agenda and I'm a realist, but on Regrow I feel they are right.
I think we are also going to see other stem cell leaders and organizations come out against Regrow in the near future. I look forward to continuing the discussion and debate. It seems that we disagree on a number of things related to stem cell regulations here, but having a robust discussion of important issues from diverse perspectives is hopefully something that we can agree upon as valuable.
I strongly support the REGROW Act.
Please Read my full opinion of the REGROW ACT.
Hi Paul, you cannot argue with a straight face that FDA regulation is not massively pushing up the costs of research. For example, Uniqure, whose gene therapy Glybera has already been approved in the EU asked the FDA to approve the drug in the US, and the FDA turned around and asked for two additional stage 3 studies to be conducted. Uniqure decided that it wasn't financially worth it, even though they have a treatment that has been proven to work and is already approved in the EU.
This looks suspiciously like bureaucratic arse covering by the FDA. Is the EMA really that lax that they approved a gene therapy when they actually needed two additional stage 3 trials?
The real problem is that no one at the FDA gets fired for saying no.
The public are getting fed up with this, and politicians are responding.
Paul I think what you are missing here is that thousands of patients and decades of work have demonstrated that MSCs are not "dangerous". After thirty years of researching them (even with gene modification) I have not seen anything that would make me feel that we are "putting patients in danger" by using them. That would be the last thing in the world I would ever want.
This act requires Phase II data, an IND to be filed, and requires the cells to be made GMP. Data is collected during Phase III. In my opinion, this accelerates the entire field and is FAR better than patients going offshore to get something unregulated.
I 100% agree with you. The REGROW ACT requires the sponsor to prepare and submit annual reports and adverse event reports to the Secretary containing all the information required for approved biological products. I believe that if the FDA holds the sponsors to very high safety standards during the conditional approval period, and if the FDA truly monitors any adverse events in the same manner that they currently monitor the adverse events in a phase III clinical trial, then it is my opinion that the increased safety risk of conditional approval can be managed and that the overall benefit of accelerated cellular therapy outweighs the risk.
I agree that the overall safety profile for MSCs is very encouraging and you of course know far more about MSCs than I ever will, but I don't believe we can or should make universal declarations of their (or really any type of stem cell's) safety regardless of important variables such as the particular patient from which they are derived, the derivation source tissue (fat, marrow, etc) how they might be handled in culture (e.g. possibility of contamination in many ways) and for how many passages, and the expertise and facilities of those working with them. So there can be a lot of variability.
For instance, I have zero doubt that the MSCs from our facility are top notch, but Regrow would apply to pretty much any lab and wouldn't require a BLA for years, and some of the other labs out there are frankly not so great.
The nature of the specific applications in which the MSCs are used is also going to make a big difference too and this brings in the important issue of homologous use. Non-homologous uses such as taking adipose MSCs and transplanting them into totally different tissues such as lung, CNS, etc. will have higher relative risks. This doesn't mean that this shouldn't be researched, but it something that should be kept in mind and discussed with the FDA.
The other big issue here goes beyond safety to efficacy.
I believe that Regrow would likely end up catalyzing the transplantation of cell products into hundreds or thousands of patients where those specific cell products are not ultimately going to be proven effective. Often there will be no clear expectation of efficacy based on actual data even before the clinical use begins, but in the new regulatory paradigm some people would go ahead and use them anyway based more on hope or excitement than data. Past experience shows that more generally even when there is supportive preliminary efficacy data for any given experimental drug product, most often those trials fail anyway and with Regrow the "data hurdle" to do such experiments becomes much lower.
For these reasons Regrow actually isn't in the best interest of patients even if giving more liberal access to experimental stem cells seems on the surface to be pro-patient, particularly if as is recommended by BPC the patients are actually charged to be allowed access into clinical trials.
I believe the regrow act accelerate progress too much for people trying to make money in the field of regenerative medicine.
@ Kyle Cetrulo – you say, FDA will monitor adverse events "in the same manner as in a phase III clinical trial", but how can that work? In phase III the patients' responses are compared between carefully selected control and treated groups, whereas after conditional approval it will be more like a phase IV monitoring without controls. It will be impossible to assign any side-effect to the treatment under these circumstances, except perhaps rampant cancer or death.
Unfortunately, the current regulatory framework that has not approved a single cellular therapy in the 15 years of its existence will not help the millions of patients that would benefit from stem cell therapy and these patients are forced to choose stem cell therapies that have zero regulation and oversight. The REGROW ACT might not be perfect but I believe it is light years better then the current system.
The Registry that Arnold Caplan wants to create already exists. The registry is called the CIBMTR (the center for international blood and marrow transplant research) and is administered through HRSA (Health Resources Service Administration), under HHS. .
The CIBMTR already has a voluntary reporting system for cellular therapies. There are forms for the infusion and for product characterization. Safety reporting also occurs through this system. If needed, they could create therapy/disease specific outcomes forms too I imagine.
Caplan describes nothing more than a Phase IV type study of adverse effects after the event, whereas a Phase III tries to identify them before release of product to the mass population.
The difference is identifying safety issues in a controlled way before release or treating patients as lab rats, a privilege they will have to pay for.
There has to be revisions to FDA regulations, but this is going back to the dark ages. As a clinician, I find it outrageous that some unwary patients in need will take barely tested therapies, only to find themselves on Caplan's list of unexpected adverse events.
But what the heck, they served their purpose, is that's what your saying?
@Anne Sonnenberg I understand your point. One of the things that I am afraid about is that these patients would end up in some clinics around the world and their adverse effect will not be reported anywhere. That would cause even more patients to do the same thing and we will learn nothing about even more patients having an adverse effect (but maybe also a positive effect). I am not sure you want that.
As a patient I have seen that happen for more than 10 years and it seems the business of "stem cell clinics" that sell unproven therapies is growing. At the end of the day you have to deal with the whole real world (not just with the clinic /state/ country you live in) and deal with it in a practical way which might be different than an ideal way. I have the impression that your approach would in the end harm more people and prevent progress in the field at te same time. Just my opinion.
As one who works in the regenerative medicine industry and long time adult stem cell industry, I'd take a closer look at ARM to see how many of their people work for Big Pharma. Believe you me, when these stem cell treatments and other regenerative technologies hit the shelves, we'll be seeing a major drop in Big Pharma's power, especially over the FDA.
We need to find a solution yes, but the REGROW Act is not it. I'm hearing more and more that folks supporting it really don't understand the consequences or that the FDA is also moving to revise it's regulatory course and this should provide a more appropriate solution for patients.
Regarding stem cell tourism, it is very naive to assume that these clinics will disappear because of the REGROW. In fact, they will receive a boost by becoming legalized in a sense – all they need to do is to claim they are doing a follow-up as REGROW requires and the bad press goes away. But who will police that in China, Mexico and so on.
In any case, the bottom line is not the FDA or REGROW but the health insurers – will they pay for therapies that are still "on trial", albeit post-marketing? The ones I speak to said that their statutes do not oblige them to reimburse costs incurred through such early approvals and they would wait to see if the therapy in question really is safe and effective. They also said that a Phase IV-like database would not provide this evidence as it is not controlled or independent.
So how does anyone on health insurance afford a therapy after REGROW? Stem cell tourism! "Now a REGROW approved therapy at a price you can afford." Patients will be exposed to higher risks thanks to REGROW!
The REGROW people have not done their homework on so many issues here.
@Anne Sonnenberg I do not expect stem cell clinics will disappear because of the REGROW act. Probably I didn't explain my point very well, but never mind.
What do you think of the points made by the CEO of CIRM in the presentation posted above by Jan Nolta?
Lively discussion! The common theme is that I believe everyone responding to this post has the patients' best interest at heart, and that we all agree that changes need to be made.
The current regulatory system is not keeping pace with the MSC field. How to make changes best and most safely is the only thing debated here!
Please see Dr. Randy Mills' short talk from the recent meeting in DC "Advancing a New Policy Framework for Regenerative Cell Therapy". He makes outstanding points.
I found Randal Mills' presentation very good (as always). He showed the current need for revision and the consequences of inadequately regulated cell therapies.
Somewhat disappointing, and rather shocking, was the lack of understanding and any basic knowledge of clinical testing and of different stem cell practices shown by Andrew Vogt from the Office of Sen. Mark Kirk (First Panel Discussion).
His primary selling point was to strengthen the US position against Europe and Japan – should that really be the yardstick for safe and effective therapeutics?
Vogt clearly stated that approval after phase II plus post-market surveillance will not make for higher risks for patients. That is simply not possible as anyone who knows how Phase II and Phase III testing differs will tell you.
And this really scared me: "If there is an adverse event there is a clear process that there are no liability issues for those who are involved" What? Patients have adverse events but nobody is liable?
Do we really want these people determining clinical regulations?
@Anne Sonnenberg if you have found Randal Mills presentation very good our positions are not very distant. I could be wrong, but l had the impression he was not against the Regrow act.
Anyway, do you think the Regrow could be improved and made good enough or you think it should just be adandoned?
In this case what way forward would you suggest considering Randal Mills presentation?
One last point l would consider is that people in some states have the legal option of assisted suicide, so why should not they have the option of taking an experimental therapy at their own risk?
Yes, many are in favor of regulatory reform – the FDA also – but REGROW is a quick fix without consideration the larger picture and is a political junket for various senators to jump on the proactive health bandwagon. Bad news for patients.
Can REGROW be improved? Only by restricting the potential damage to a compassionate-care type policy for those tested in Phase II – in which case we don't need it because we already have one.
To maintain high safety standards for the mass markets, for health insurers to accept reimbursement, and for integration of later therapies coming from iPSC technology, etc, we need a rigorous and well planned regulatory policy, and the FDA and its advisory committees are doing that right now.
You ask if patients shouldn't be allowed to risk being harmed by an experimental therapy if they chose to do so? Of course, but REGROW gives "approval" to such "experimental therapies" and approval sends a message to patients that it has been rigorously tested. REGROW approval would be like subjecting potentially millions of patients to an experimental therapy. As I said before, that will result in many adverse events.


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This is a good standard property for its category with good location. Rooms have been renovated few years ago and are modern and well equipped. The restaurant is a more traditional room, with old paintings dotted around on the blue walls. Chandeliers provide the lighting. This is a modern 3-storey white stone building surrounded by trees. The lobby is a medium sized, simply-furnished area with a large dark wood reception desk.


text:
Bernhardt, Viola "Pearl"
Mont Amoena friends, c, 1926: Margaret Cline, Lala Correll, Dora Earnhardt, Pearl Bernhardt, Ethel Bernhardt.
Viola Pearl Bernhardt,
Catawba College 1928.
Sisters Pearl Bernhardt Kluttz and Ethel Bernhardt Julian at the wedding of younger sister Catherine Bernhardt Safrit, 1939.
Viola Pearl Bernhardt, Catawba College, 1930.
Birth: Nov. 30, 1908, Salisbury, Rowan County, North Carolina, USA
Death: Oct. 30, 1989, North Carolina, USA
Joseph Clarence Bernhardt (1878 – 1956)
Mary Ann Upright Bernhardt (1882 – 1945)
Julius Dodds Kluttz (1908 – 1988)
Sidney Henderson Bernhardt (1904 – 1972)
Lena Ethel Bernhardt Julian (1906 – 1971)
Catherine L Bernhardt Safrit (1913 – 2001)
Saint Pauls Lutheran Church Cemetery
Source: www.findagrave.com, #123826343.
College photos: www.digitalnc.org.
Glenna Sears (5 Sep 2017): "My beloved aunt, Lena Ethel Bernhardt, graduated in the class of 1926. I wear her 1926 Mont Amoena Seminary class ring every day. She finished her studies at Catawba College, and went on to teach 1st grade in Denton and then in the Rowan County Schools until her retirement. Her sister, my aunt, Pearl Bernhardt, was a member of the class of 1927, which I learned from your website was the last year of operation of the school. Pearl also finished her studies at Catawba College. She taught high school math for a time, and after she married, she and her husband, Julius Kluttz, lived in Greensboro, where Pearl worked for the IRS until her retirement. Pearl and Julius are both buried at St. Paul's Lutheran Church, Salisbury."
Mont Amoena friends and wedding photos courtesy of Glenna Sears.
Greensboro News and Record (Greensboro, NC), November 1, 1989, p. C4.
MRS. PEARL KLUTTZ
Mrs. Pearl Bernhardt Kluttz, 80, of 1309 New Garden Rad died Monday at Moses Cone Memorial Hospital.
Funeral will be at 11 a.m. Thursday at St. Paul Lutheran Church in Salisbury, of which she was a member.
She was a native of Salisbury and taught school in Mont Amena, Mount Pleasant, Catawba College, Thomasville, China Grove and Alamance County. She was a retired auditor for the IRS and a member of the National Association of Retired Federal Employees.
Surviving are daughter, Mrs. Ann Hoffmann of Raleigh; sister, Mrs. Caterine Safrit of Salisbury; brothers, Walter A. Bernhardt of Salisbury,, Carl E. Bernhardt of Lexington.
The family will be at Forbis & Dick Guilford Chaapel Funeral Home 7-9 p.m. today, prayer service will be at 8 p.m.
Memorial contributions may be made to the American Heart Association, 1600 E. Wendover Ave., Greensboro, N. C. 27405.

redpajama_set_name: RedPajamaCommonCrawl


text:
/*
 * eXist Open Source Native XML Database
 * Copyright (C) 2004-2007 The eXist Project
 * http://exist-db.org
 *
 * This program is free software; you can redistribute it and/or
 * modify it under the terms of the GNU Lesser General Public License
 * as published by the Free Software Foundation; either version 2
 * of the License, or (at your option) any later version.
 *
 * This program is distributed in the hope that it will be useful,
 * but WITHOUT ANY WARRANTY; without even the implied warranty of
 * MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE.  See the
 * GNU Lesser General Public License for more details.
 *
 * You should have received a copy of the GNU Lesser General Public License
 * along with this program; if not, write to the Free Software Foundation
 * Inc., 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301, USA.
 *
 *  $Id: Collations.java 6367 2007-08-16 08:53:10Z ellefj $
 */
package org.exist.util;

import java.net.URI;
import java.net.URISyntaxException;
import java.text.CollationElementIterator;
import java.text.Collator;
import java.text.ParseException;
import java.text.RuleBasedCollator;
import java.util.Comparator;
import java.util.Locale;
import java.util.StringTokenizer;

import org.apache.log4j.Logger;
import org.exist.xquery.Constants;
import org.exist.xquery.XPathException;
import org.exist.xquery.XQueryContext;

/**
 * Utility methods dealing with collations.
 *
 * @author wolf
 */
public class Collations {

    private final static Logger LOG = Logger.getLogger(Collations.class);

    /**
     * The default unicode codepoint collation URI as defined by the XQuery
     * spec.
     */
    //public final static String CODEPOINT = "http://www.w3.org/2004/07/xpath-functions/collation/codepoint";
    public final static String CODEPOINT = "http://www.w3.org/2005/xpath-functions/collation/codepoint";

    /**
     * Short string to select the default codepoint collation
     */
    public final static String CODEPOINT_SHORT = "codepoint";

    /**
     * The URI used to select collations in eXist.
     */
    public final static String EXIST_COLLATION_URI = "http://exist-db.org/collation";

    /**
     * Get a {@link Comparator}from the specified URI.
     *
     * The original code is from saxon (@linkplain http://saxon.sf.net).
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     * @param uri
     * @throws XPathException
     */
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            String uri) throws XPathException {
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            try {
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            String query = u.getQuery();
            String strength = null;
            /*
             * Check if the db broker is configured to be case insensitive. If
             * yes, we assume "primary" strength unless the user specified
             * something different.
             *
             * TODO: bad idea: using primary strength as default also ignores
             * German Umlaute.
             */
            // if(!context.getBroker().isCaseSensitive())
            // strength = "primary";
            if (query == null) {
                return getCollationFromParams(null, strength, null);
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                LOG.debug("Loading collation: " + query);
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                        + " could not be found", e);
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        } else if (CODEPOINT.equals(uri)) {
        	return null;
        } else
            throw new XPathException("err:XQST0038: Unknown collation : '" + uri + "'");
    }

    public final static boolean equals(Collator collator, String s1, String s2) {
        if (collator == null)
            return s1.equals(s2);
        else
            return collator.equals(s1, s2);
    }

    public final static int compare(Collator collator, String s1, String s2) {
        if (collator == null)
            return s1==null ? (s2==null ? 0 : -1)  : s1.compareTo(s2);
        else
            return collator.compare(s1, s2);
    }

    public final static boolean startsWith(Collator collator, String s1, String s2) {
        if (collator == null)
            return s1.startsWith(s2);
        else {
            final RuleBasedCollator rbc = (RuleBasedCollator) collator;
            final CollationElementIterator i1 = rbc.getCollationElementIterator(s1);
            final CollationElementIterator i2 = rbc.getCollationElementIterator(s2);
            return collationStartsWith(i1, i2);
        }
    }

    public final static boolean endsWith(Collator collator, String s1, String s2) {
        if (collator == null)
            return s1.endsWith(s2);
        else {
            final RuleBasedCollator rbc = (RuleBasedCollator) collator;
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            final CollationElementIterator i2 = rbc.getCollationElementIterator(s2);
            return collationContains(i1, i2, null, false);
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    }

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            return s1.indexOf(s2);
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            final int offsets[] = new int[2];
            final RuleBasedCollator rbc = (RuleBasedCollator) collator;
            final CollationElementIterator i1 = rbc.getCollationElementIterator(s1);
            final CollationElementIterator i2 = rbc.getCollationElementIterator(s2);
            if (collationContains(i1, i2, offsets, false))
                return offsets[0];
            else
                return Constants.STRING_NOT_FOUND;
        }
    }

    private final static boolean collationStartsWith(CollationElementIterator s0,
            CollationElementIterator s1) {
    	//Copied from Saxon
        while (true) {
            int e0, e1;
            do {
                e1 = s1.next();
            } while (e1 == 0);
            if (e1 == -1) {
                return true;
            }
            do {
                e0 = s0.next();
            } while (e0 == 0);
            if (e0 != e1) {
                return false;
            }
        }
        //End of copy
    }

    private final static boolean collationContains(CollationElementIterator s0,
            CollationElementIterator s1, int[] offsets, boolean matchAtEnd) {
    	//Copy from Saxon
        int e0, e1;
        do {
            e1 = s1.next();
        } while (e1 == 0);
        if (e1 == -1) {
            return true;
        }
        e0 = -1;
        while (true) {
            // scan the first string to find a matching character
            while (e0 != e1) {
                do {
                    e0 = s0.next();
                } while (e0 == 0);
                if (e0 == -1) {
                    // hit the end, no match
                    return false;
                }
            }
            // matched first character, note the position of the possible match
            int start = s0.getOffset();
            if (collationStartsWith(s0, s1)) {
                if (matchAtEnd) {
                    do {
                        e0 = s0.next();
                    } while (e0 == 0);
                    if (e0 == -1) {
                        // the match is at the end
                        return true;
                    }
                    // else ignore this match and keep looking
                } else {
                    if (offsets != null) {
                        offsets[0] = start-1;
                        offsets[1] = s0.getOffset();
                    }
                    return true;
                }
            }
            // reset the position and try again
            s0.setOffset(start);

            // workaround for a difference between JDK 1.4.0 and JDK 1.4.1
            if (s0.getOffset() != start) {
                // JDK 1.4.0 takes this path
                s0.next();
            }
            s1.reset();
            e0 = -1;
            do {
                e1 = s1.next();
            } while (e1 == 0);
            // loop round to try again
        }
        //End of copy
    }

    /**
     * @param lang
     * @param strength
     * @param decomposition
     * @return The collator
     */
    private static Collator getCollationFromParams(String lang,
            String strength, String decomposition) throws XPathException {
        Collator collator = null;
        if (lang == null) {
            collator = Collator.getInstance();
        } else if (lang.equals("sme-SE")) {
            // Collation rules contained in a String object.
            // Codes for the representation of names of languages:
            // http://www.loc.gov/standards/iso639-2/englangn.html
            // UTF-8 characters from:
            // http://chouette.info/entities/table-utf8.php
            String Samisk = "< a,A< \u00E1,\u00C1< b,B< c,C"
                    + "< \u010d,\u010c< d,D< \u0111,\u0110< e,E"
                    + "< f,F< g,G< h,H< i,I< j,J< k,K< l,L< m,M"
                    + "< n,N< \u014b,\u014a< o,O< p,P< r,R< s,S"
                    + "< \u0161,\u0160< t,T< \u0167,\u0166< u,U"
                    + "< v,V< z,Z< \u017e,\u017d";
            try {
                collator = new RuleBasedCollator(Samisk);
            } catch (ParseException pe) {
                return null;
            }
        } else {
            Locale locale = getLocale(lang);
            LOG.debug("Using locale: " + locale.toString());
            collator = Collator.getInstance(locale);
        }

        if (strength != null) {
            if ("primary".equals(strength))
                collator.setStrength(Collator.PRIMARY);
            else if ("secondary".equals(strength))
                collator.setStrength(Collator.SECONDARY);
            else if ("tertiary".equals(strength))
                collator.setStrength(Collator.TERTIARY);
            else if (strength.length() == 0 || "identical".equals(strength))
                // the default setting
                collator.setStrength(Collator.IDENTICAL);
            else
                throw new XPathException(
                        "Collation strength should be either 'primary', 'secondary', 'tertiary' or 'identical");
        }

        if (decomposition != null) {
            if ("none".equals(decomposition))
                collator.setDecomposition(Collator.NO_DECOMPOSITION);
            else if ("full".equals(decomposition))
                collator.setDecomposition(Collator.FULL_DECOMPOSITION);
            else if (decomposition.length() == 0
                    || "standard".equals(decomposition))
                // the default setting
                collator.setDecomposition(Collator.CANONICAL_DECOMPOSITION);
            else
                throw new XPathException(
                        "Collation decomposition should be either 'none', 'full' or 'standard");
        }

        return collator;
    }

    /**
     * @param lang
     * @return The locale
     */
    private static Locale getLocale(String lang) {
        int dashPos = lang.indexOf('-');
        if (dashPos == Constants.STRING_NOT_FOUND)
            return new Locale(lang);
        else
            return new Locale(lang.substring(0, dashPos), lang.substring(dashPos + 1));
    }

}

redpajama_set_name: RedPajamaGithub


text:
Q: HTTP GET Range (partial content) my server can send all file, and part of file.
example of problem file.
<pre>
http://scir.bz/z/GOOD%20TO%20GREAT.mp3
</pre>

so, mozilla can play these audio file, and when we will move on timeline, mozilla plays it from a middle.
but google chrome can't do it. and I can't understand, why?
Example http conversation
mozilla -- server
GET /z/GOOD%20TO%20GREAT.mp3 HTTP/1.1

HTTP/1.1 200 OK
Content-Type: audio/mp3
Content-Length: 489986541
Last-Modified: Thu, 06 Mar 2014 18:02:55 GMT
Etag: "55a3ee720b5551b7fbb0b28318576ae9c9deb1cc1394128975"
Accept-Ranges: bytes

--jump on the middle
GET /z/GOOD%20TO%20GREAT.mp3 HTTP/1.1
Range: bytes=195002368-

HTTP/1.1 206 Partial Content
Content-Range: bytes 195002368-489986540/489986541

--and I can continue to listen a file
chrome--server
GET /z/GOOD%20TO%20GREAT.mp3 HTTP/1.1

HTTP/1.1 200 OK
Content-Type: audio/mp3
Content-Length: 489986541
Last-Modified: Thu, 06 Mar 2014 18:02:55 GMT
Etag: "55a3ee720b5551b7fbb0b28318576ae9c9deb1cc1394128975"
Accept-Ranges: bytes

GET /z/GOOD%20TO%20GREAT.mp3 HTTP/1.1
Range: bytes=0-

HTTP/1.1 206 Partial Content
Content-Range: bytes 0-489986540/489986541

--jump on the middle of afile
GET /z/GOOD%20TO%20GREAT.mp3 HTTP/1.1
Range:bytes=333119449-489986540

HTTP/1.1 206 Partial Content
Content-Range: bytes 333119449-489986540/489986541

chrome canceled it and try
GET /z/GOOD%20TO%20GREAT.mp3 HTTP/1.1
Range:bytes=333119448-489986540

HTTP/1.1 206 Partial Content
Content-Range: bytes 333119448-489986540/489986541

and yet
GET /z/GOOD%20TO%20GREAT.mp3 HTTP/1.1
Range:bytes=333119447-489986540

HTTP/1.1 206 Partial Content
Content-Range: bytes 333119447-489986540/489986541

and yet
GET /z/GOOD%20TO%20GREAT.mp3 HTTP/1.1
Range:bytes=333119446-489986540

HTTP/1.1 206 Partial Content
Content-Range: bytes 333119446-489986540/489986541

PS fiddler  shows no error in http

A: Maybe this helps: Chrome won't play mp3 files?
The solution proposed is this:

Found a solution: I downgraded apache to 2.2.17 - and all of a sudden things started to work. No idea why, but probably something in the new version of apache manifests the mp3 playing bug at chrome.

redpajama_set_name: RedPajamaStackExchange


text:
Archive for the 'African American' Category
Rethink Practice of Governors Filling Vacant U.S. Senate Seats
Barack Obama's U.S. Senate seat was allegedly for sale in Illinois. Then the tarnished Governor made a circus out of appoining a new U.S. Senator and there seemed a strong message in his news conference that the seat was reserved for African Americans. Only.
Why shouldn't the people decide?
Blago's pick said the appointment was legal. Great: but it that how we want one of only 100 national lawmakers to get into office? He's legal? So is a lot of seafood….
Above: Gov. Rod R. Blagojevich, right, named Roland Burris to replace President-elect Barack Obama in the Senate. Photo: Amanda Rivkin for The New York Times
In New York, a lady with a big name and not much to say is the leading contender for the U.S. Senate seat vacated by Hillary Clinton. The lady with the big name and lots of money hasn't shown much interest in politics or issues previously and seems unable to articulate positions on many topics today, you know?
So in New York we have a celebrity auction for the U.S. Senate. Why not decide on "American Idol"?
Why can't the voters decide?
Governors appointing U.S. Senators seems to make a mockery of democrocy and takes away a key right and priviledge of every voter: to see, evaluate and decide for themselves after a "campaign."
What we have now in these two "appointment" capers is a media circus of attention and vote by writers, reporters and pundits of the "high profile" possibilities.
These are the last people on earth I trust with my vote…
And if the voters are not asked to decide then put into place a "caretaker" system that allows a person of stature, wisdom and skill to fill the Senate seat while promising not to run in the next election. At that time we can go back to an elected Senator with unknown wisdom and skill….
John E. Carey
Wakefield Chapel, Virginia
Blagojevich Playing The "Race Card"? Hurting Illinois, Obama, African Americans?
Caroline Kennedy Has "Nothing to Say" (And Says It Badly)
From CNN:
http://www.cnn.com/2008/POLITICS/1
2/31/illinois.senate/index.html
New York Gov. David Paterson speaks during a news conference in Albany, N.Y., Tuesday, Dec. 16, 2008. Caroline Kennedy has told Paterson that she's interested in the U.S. Senate seat being vacated by Hillary Rodham Clinton, making her the highest-profile candidate to express a desire for the job. (AP Photo)
Posted in African American, appointments, Black, David Paterson, democracy, Hillary Clinton, Illinois, Kennedy, New York, news, Obama, politics, Rod Blagojevich, Roland Burris, U.S. Senate, voters | Leave a Comment »
Addressing The Ills of the Black Family — Obama Has A Chance
In the nearly half-century in which we have gone from George Wallace to Barack Obama, America has another, less hopeful story to tell about racial progress, one that may be even harder to reverse.
In 1965, a young assistant secretary of labor named Daniel Patrick Moynihan stumbled upon data that showed a rise in the number of black single mothers. As Moynihan wrote in a now-famous report for the Johnson administration, especially troubling was that the growth in illegitimacy, as it was universally called then, coincided with a decline in black male unemployment. Strangely, black men were joining the labor force more, but they were marrying — and fathering — less.
There were other puzzling facts. In 1950, at the height of the Jim Crow era and despite the shattering legacy of slavery, the great majority of black children — an estimated 85 percent — were born to their two married parents. Just 15 years later, there seemed to be no obvious reason that that would change. With the passage of the Civil Rights Act and the Voting Rights Act, legal barriers to equality were falling. The black middle class had grown substantially, and the first five years of the 1960s had produced 7 million new jobs. Yet 24 percent of black mothers were then bypassing marriage. Moynihan wrote later that he, like everyone else in the policy business, had assumed that "economic conditions determine social conditions." Now it seemed, "what everyone knew was evidently not so."
President-elect Barack Obama, right, with his daughter Malia, 10, wait to greet people at a food bank at St. Columbanus Catholic Church on the South Side of Chicago, Wednesday, Nov. 26, 2008. (AP Photo/Pablo Martinez Monsivais)
By Kay Hymowitz
http://www.washingtonpost.com/wp-dyn/content/
article/2008/12/05/AR2008120503088.html
We at Peace and Freedom salute Bill Cosby for his outspoken remarks on Black society and culture….
As recently as July 1, Cosby hurled himself back into the hot seat by yet again openly criticizing the black community while alongside Jesse Jackson at the Rainbow/PUSH Coalition annual conference.
In response to the charge that he is airing African American's dirty laundry out in the open, Cosby answered critics by saying, "Let me tell you something, your dirty laundry gets out of school at 2;30 every day, it's cursing and calling each other n**** as they're walking up and down the street."
"They can't read, they can't write. They're laughing and giggling, and they're going no where."
Above: The Rev. Jesse Jackson (right) is side by side with Bill Cosby as the entertainer urges the black community to work harder to help their children build better lives and a better future. (AP)
But it was the comedian's first public outburst that really got everyone talking.
On May 17, 2004, at a NAACP celebration that marked the 50th anniversary of the 1954 Brown vs. Board of Education decision that outlawed segregation in schools, 66-year-old Bill Cosby made pointed comments about the way black youth dress, citing their oversized clothes as "ridiculous." He also attacked lower class blacks for not speaking proper English, not raising their kids properly — by instilling corrupt and materialist-based values — and naming them silly names.
His bottom line: black people have to take personal responsibility and own up to the fact that (part of) the reason we have not advanced further is because of squandered opportunities.
From the front page to the Op-Ed section, the African-American press has been filled with commentary on the actor and philanthropist's tirades. The past month has seen Cosby's words rehashed and dissected, with opinions ranging from full on agreement to flat out denial.
Following Cosby's lead, some commentators worry that blacks have not done enough to improve their situation.
Above from New America Media, by Danielle Worthy, Posted: Apr 03, 2005
http://news.ncmonline.com/news/view_article.html?article_id=c3a1cf5b268909dfee0db53722131aee
By Greg Braxton, Baltimore Sun
Bill Cosby has long bristled at suggestions that his pioneering NBC comedy, "The Cosby Show," was somehow unrealistic in its portrayal of a black upper-middle-class family.
So with the Obama family set to take up residence in the White House, Cosby reflected on those statements last week with a chuckle. "For all those people who said they didn't know any black people like the Huxtables," quipped Cosby in a phone interview, "all I can say is, 'Will you watch the show now?' "
The entertainer and comedian, who was promoting Tuesday's release of the 25th anniversary box set of "The Cosby Show," also admitted to being pleased with observations about the role of the so-called "Huxtable factor" in Obama's victory.
Bill Cosby's TV family
Said Karl Rove, a former Bush strategist turned Fox News commentator, on election night: "We've had an African American first family for many years in different forms. When 'The Cosby Show' was on, that was America's family. It wasn't a black family. It was America's family."
http://www.baltimoresun.com/entertainment/news/la-et
-cosby10-2008nov10,0,2182409.story?track=rss
Posted in African American, Barack Obama, Black, crime, culture, family, fathers, news, Obama, parents, politics, Schools, society, unwed mothers | Leave a Comment »
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